Cardiology News

Moderna says neutralizing antibodies generated by its COVID-19 vaccine against three variants of the virus that causes the disease waned substantially 6 months after the second dose.

Because of this, the company expects an increase in breakthrough infections with a need for boosters before winter.

In an experiment, a 50-mg dose of the vaccine, given as a third shot, boosted levels of antibodies in 20 previously vaccinated people by 32 times against the Beta variant, by 44 times against the Gamma variant, and by 42 times against Delta.

The new data was presented in an earnings call to investors and is based on a small study that hasn’t yet been published in medical literature.

The company also said its vaccine remained highly effective at preventing severe COVID outcomes through 6 months.

Last week, Pfizer released early data suggesting a similar drop in protection from its vaccine. The company also showed a third dose substantially boosted protection, including against the Delta variant.

The new results come just 1 day after the World Health Organization implored wealthy nations to hold off on third doses until more of the world’s population could get a first dose.

More than 80% of the 4 billion vaccine doses given around the world have been distributed to high-income countries.

A version of this article first appeared on WebMD.com.

Moderna says neutralizing antibodies generated by its COVID-19 vaccine against three variants of the virus that causes the disease waned substantially 6 months after the second dose.

Because of this, the company expects an increase in breakthrough infections with a need for boosters before winter.

In an experiment, a 50-mg dose of the vaccine, given as a third shot, boosted levels of antibodies in 20 previously vaccinated people by 32 times against the Beta variant, by 44 times against the Gamma variant, and by 42 times against Delta.

The new data was presented in an earnings call to investors and is based on a small study that hasn’t yet been published in medical literature.

The company also said its vaccine remained highly effective at preventing severe COVID outcomes through 6 months.

Last week, Pfizer released early data suggesting a similar drop in protection from its vaccine. The company also showed a third dose substantially boosted protection, including against the Delta variant.

The new results come just 1 day after the World Health Organization implored wealthy nations to hold off on third doses until more of the world’s population could get a first dose.

More than 80% of the 4 billion vaccine doses given around the world have been distributed to high-income countries.

A version of this article first appeared on WebMD.com.

Moderna says neutralizing antibodies generated by its COVID-19 vaccine against three variants of the virus that causes the disease waned substantially 6 months after the second dose.

Because of this, the company expects an increase in breakthrough infections with a need for boosters before winter.

In an experiment, a 50-mg dose of the vaccine, given as a third shot, boosted levels of antibodies in 20 previously vaccinated people by 32 times against the Beta variant, by 44 times against the Gamma variant, and by 42 times against Delta.

The new data was presented in an earnings call to investors and is based on a small study that hasn’t yet been published in medical literature.

The company also said its vaccine remained highly effective at preventing severe COVID outcomes through 6 months.

Last week, Pfizer released early data suggesting a similar drop in protection from its vaccine. The company also showed a third dose substantially boosted protection, including against the Delta variant.

The new results come just 1 day after the World Health Organization implored wealthy nations to hold off on third doses until more of the world’s population could get a first dose.

More than 80% of the 4 billion vaccine doses given around the world have been distributed to high-income countries.

A version of this article first appeared on WebMD.com.

A retracted study on the safety of blood pressure medications in patients with COVID-19 continues to be cited nearly a year later, new research shows.

Floaria Bicher/iStock/Getty Images Plus

The study in question, published on May 1, 2020, in the New England Journal of Medicine, showed no increased risk for in-hospital death with the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) in hospitalized patients with COVID-19.

Concerns about the veracity of the Surgisphere database used for the study, however, led to a June 4 retraction and to the June 13 retraction of a second study, published in the Lancet, that focused on hydroxychloroquine as a COVID-19 treatment.

Although the Surgisphere scandal caused a global reckoning of COVID-19 scientific studies, the new analysis identified 652 citations of the NEJM article as of May 31.

More than a third of the citations occurred in the first 2 months after the retraction, 54% were at least 3 months later, and 2.8% at least 6 months later. In May, 11 months after the article was retracted, it was cited 21 times, senior author Emily G. McDonald, MD, MSc, McGill University, Montreal, and colleagues reported in a research letter in JAMA Internal Medicine.

“In early May and June there were already more than 200 citations in one of the world’s leading scientific journals, so I do believe it was a highly influential article early on and had an impact on different types of studies or research taking place,” she said in an interview.

Dr. McDonald said she’s also “certain that it impacted patient care,” observing that when there are no guidelines available on how to manage patients, physicians will turn to the most recent evidence in the most reputable journals.

“In the case of ACE [inhibitors] and ARBs, although the study was based on fraudulent data, we were lucky that the overall message was in the end probably correct, but that might not have been the case for another study or dataset,” she said.

Early in the pandemic, concerns existed that ACE inhibitors and ARBs could be harmful, increasing the expression of ACE2 receptors, which the SARS-CoV-2 virus uses to gain entry into cells. The first randomized trial to examine the issue, BRACE CORONA, showed no clinical benefit to interrupting use of the agents in hospitalized patients. An observational study suggested ACE inhibitors may even be protective.

Of two high-profile retractions, McDonald said they chose to bypass the hydroxychloroquine study, which had an eye-popping Altmetric attention score of 23,084, compared with 3,727 for the NEJM paper, because it may have been cited for “other” reasons. “We wanted to focus less on the politics and more on the problem of retracted work.”

The team found that researchers across the globe were citing the retracted ACE/ARB paper (18.7% in the United States, 8.1% in Italy, and 44% other countries). Most citations were used to support a statement in the main text of a study, but in nearly 3% of cases, the data were incorporated into new analyses.

Just 17.6% of the studies cited or noted the retraction. “For sure, that was surprising to us. We suspected it, but our study confirmed it,” Dr. McDonald said.

Although retracted articles can be identified by a watermark or line of text, in some cases that can be easily missed, she noted. What’s more, not all citation software points out when a study has been retracted, a fate shared by the copyediting process.

“There are a lot of mechanisms in place and, in general, what’s happening is rare but there isn’t a perfect automated system solution to absolutely prevent this from happening,” she said. “It’s still subject to human error.”

The findings also have to be taken in the context of a rapidly emerging pandemic and the unprecedented torrent of scientific papers released over the past year.

“That might have contributed to why this happened, but the takeaway message is that this can happen despite our best efforts, and we need to challenge ourselves to come up with a system solution to prevent this from happening in the future,” Dr. McDonald said. “Current mechanisms are probably capturing 95% of it, but we need to do better.”

Limitations of the present analysis are that it was limited to the single retracted study; used only a single search engine, Google Scholar, to identify the citing works; and that additional citations may have been missed, the authors noted.

McDonald and coauthor Todd C. Lee, MD, report being signatories on a public letter calling for the retraction of the Surgisphere papers. Dr. Lee also reported receiving research support from Fonds De Recherche du Quebec-Sante during the conduct of the study.

A version of this article first appeared on Medscape.com.

A retracted study on the safety of blood pressure medications in patients with COVID-19 continues to be cited nearly a year later, new research shows.

Floaria Bicher/iStock/Getty Images Plus

The study in question, published on May 1, 2020, in the New England Journal of Medicine, showed no increased risk for in-hospital death with the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) in hospitalized patients with COVID-19.

Concerns about the veracity of the Surgisphere database used for the study, however, led to a June 4 retraction and to the June 13 retraction of a second study, published in the Lancet, that focused on hydroxychloroquine as a COVID-19 treatment.

Although the Surgisphere scandal caused a global reckoning of COVID-19 scientific studies, the new analysis identified 652 citations of the NEJM article as of May 31.

More than a third of the citations occurred in the first 2 months after the retraction, 54% were at least 3 months later, and 2.8% at least 6 months later. In May, 11 months after the article was retracted, it was cited 21 times, senior author Emily G. McDonald, MD, MSc, McGill University, Montreal, and colleagues reported in a research letter in JAMA Internal Medicine.

“In early May and June there were already more than 200 citations in one of the world’s leading scientific journals, so I do believe it was a highly influential article early on and had an impact on different types of studies or research taking place,” she said in an interview.

Dr. McDonald said she’s also “certain that it impacted patient care,” observing that when there are no guidelines available on how to manage patients, physicians will turn to the most recent evidence in the most reputable journals.

“In the case of ACE [inhibitors] and ARBs, although the study was based on fraudulent data, we were lucky that the overall message was in the end probably correct, but that might not have been the case for another study or dataset,” she said.

Early in the pandemic, concerns existed that ACE inhibitors and ARBs could be harmful, increasing the expression of ACE2 receptors, which the SARS-CoV-2 virus uses to gain entry into cells. The first randomized trial to examine the issue, BRACE CORONA, showed no clinical benefit to interrupting use of the agents in hospitalized patients. An observational study suggested ACE inhibitors may even be protective.

Of two high-profile retractions, McDonald said they chose to bypass the hydroxychloroquine study, which had an eye-popping Altmetric attention score of 23,084, compared with 3,727 for the NEJM paper, because it may have been cited for “other” reasons. “We wanted to focus less on the politics and more on the problem of retracted work.”

The team found that researchers across the globe were citing the retracted ACE/ARB paper (18.7% in the United States, 8.1% in Italy, and 44% other countries). Most citations were used to support a statement in the main text of a study, but in nearly 3% of cases, the data were incorporated into new analyses.

Just 17.6% of the studies cited or noted the retraction. “For sure, that was surprising to us. We suspected it, but our study confirmed it,” Dr. McDonald said.

Although retracted articles can be identified by a watermark or line of text, in some cases that can be easily missed, she noted. What’s more, not all citation software points out when a study has been retracted, a fate shared by the copyediting process.

“There are a lot of mechanisms in place and, in general, what’s happening is rare but there isn’t a perfect automated system solution to absolutely prevent this from happening,” she said. “It’s still subject to human error.”

The findings also have to be taken in the context of a rapidly emerging pandemic and the unprecedented torrent of scientific papers released over the past year.

“That might have contributed to why this happened, but the takeaway message is that this can happen despite our best efforts, and we need to challenge ourselves to come up with a system solution to prevent this from happening in the future,” Dr. McDonald said. “Current mechanisms are probably capturing 95% of it, but we need to do better.”

Limitations of the present analysis are that it was limited to the single retracted study; used only a single search engine, Google Scholar, to identify the citing works; and that additional citations may have been missed, the authors noted.

McDonald and coauthor Todd C. Lee, MD, report being signatories on a public letter calling for the retraction of the Surgisphere papers. Dr. Lee also reported receiving research support from Fonds De Recherche du Quebec-Sante during the conduct of the study.

A version of this article first appeared on Medscape.com.

A retracted study on the safety of blood pressure medications in patients with COVID-19 continues to be cited nearly a year later, new research shows.

Floaria Bicher/iStock/Getty Images Plus

The study in question, published on May 1, 2020, in the New England Journal of Medicine, showed no increased risk for in-hospital death with the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) in hospitalized patients with COVID-19.

Concerns about the veracity of the Surgisphere database used for the study, however, led to a June 4 retraction and to the June 13 retraction of a second study, published in the Lancet, that focused on hydroxychloroquine as a COVID-19 treatment.

Although the Surgisphere scandal caused a global reckoning of COVID-19 scientific studies, the new analysis identified 652 citations of the NEJM article as of May 31.

More than a third of the citations occurred in the first 2 months after the retraction, 54% were at least 3 months later, and 2.8% at least 6 months later. In May, 11 months after the article was retracted, it was cited 21 times, senior author Emily G. McDonald, MD, MSc, McGill University, Montreal, and colleagues reported in a research letter in JAMA Internal Medicine.

“In early May and June there were already more than 200 citations in one of the world’s leading scientific journals, so I do believe it was a highly influential article early on and had an impact on different types of studies or research taking place,” she said in an interview.

Dr. McDonald said she’s also “certain that it impacted patient care,” observing that when there are no guidelines available on how to manage patients, physicians will turn to the most recent evidence in the most reputable journals.

“In the case of ACE [inhibitors] and ARBs, although the study was based on fraudulent data, we were lucky that the overall message was in the end probably correct, but that might not have been the case for another study or dataset,” she said.

Early in the pandemic, concerns existed that ACE inhibitors and ARBs could be harmful, increasing the expression of ACE2 receptors, which the SARS-CoV-2 virus uses to gain entry into cells. The first randomized trial to examine the issue, BRACE CORONA, showed no clinical benefit to interrupting use of the agents in hospitalized patients. An observational study suggested ACE inhibitors may even be protective.

Of two high-profile retractions, McDonald said they chose to bypass the hydroxychloroquine study, which had an eye-popping Altmetric attention score of 23,084, compared with 3,727 for the NEJM paper, because it may have been cited for “other” reasons. “We wanted to focus less on the politics and more on the problem of retracted work.”

The team found that researchers across the globe were citing the retracted ACE/ARB paper (18.7% in the United States, 8.1% in Italy, and 44% other countries). Most citations were used to support a statement in the main text of a study, but in nearly 3% of cases, the data were incorporated into new analyses.

Just 17.6% of the studies cited or noted the retraction. “For sure, that was surprising to us. We suspected it, but our study confirmed it,” Dr. McDonald said.

Although retracted articles can be identified by a watermark or line of text, in some cases that can be easily missed, she noted. What’s more, not all citation software points out when a study has been retracted, a fate shared by the copyediting process.

“There are a lot of mechanisms in place and, in general, what’s happening is rare but there isn’t a perfect automated system solution to absolutely prevent this from happening,” she said. “It’s still subject to human error.”

The findings also have to be taken in the context of a rapidly emerging pandemic and the unprecedented torrent of scientific papers released over the past year.

“That might have contributed to why this happened, but the takeaway message is that this can happen despite our best efforts, and we need to challenge ourselves to come up with a system solution to prevent this from happening in the future,” Dr. McDonald said. “Current mechanisms are probably capturing 95% of it, but we need to do better.”

Limitations of the present analysis are that it was limited to the single retracted study; used only a single search engine, Google Scholar, to identify the citing works; and that additional citations may have been missed, the authors noted.

McDonald and coauthor Todd C. Lee, MD, report being signatories on a public letter calling for the retraction of the Surgisphere papers. Dr. Lee also reported receiving research support from Fonds De Recherche du Quebec-Sante during the conduct of the study.

A version of this article first appeared on Medscape.com.

While cases of pericarditis or myocarditis temporally linked to COVID-19 vaccination remain rare, they may happen more often than reported, according to a large review of electronic medical records (EMRs).

peterschreiber_media/iStock/Getty Images

They also appear to represent two “distinct syndromes,” George Diaz, MD, Providence Regional Medical Center Everett (Washington), said in an interview.

Myocarditis typically occurs soon after vaccination in younger patients and mostly after the second dose, while pericarditis occurs later in older patients, after the first or second dose.

Dr. Diaz and colleagues reported their analysis in a research letter published online August 4 in JAMA.

They reviewed the records of 2,000,287 people who received at least one COVID-19 vaccination at 40 hospitals in Washington, Oregon, Montana, and California that are part of the Providence health care system and use the same EMRs.

The median age of the cohort was 57 years and 59% were women.

A little more than three quarters (77%) received more than one dose; most received the mRNA vaccines made by Pfizer (53%) and Moderna (44%); 3% received the Johnson & Johnson vaccine.

The records showed that 20 people had vaccine-related myocarditis (1.0 per 100,000) and 37 had pericarditis (1.8 per 100,000).

A recent report, based on data from the Centers for Disease Control and Prevention’s Vaccine Adverse Events Reporting System, suggested an incidence of myocarditis of about 4.8 cases per 1 million following receipt of mRNA COVID-19 vaccine.

The new study shows a “similar pattern, although at higher incidence, suggesting vaccine adverse event underreporting. In addition, pericarditis may be more common than myocarditis among older patients,” the study team wrote.

“Our study resulted in higher numbers of cases probably because we searched the EMR, and VAERS requires doctors to report suspected cases voluntarily,” Dr. Diaz said in an interview.

Also, in the governments’ statistics, pericarditis and myocarditis were “lumped together,” he noted.
 

Myocarditis cases

The 20 myocarditis cases occurred a median of 3.5 days after vaccination (11 after the Moderna vaccine and 9 after the Pfizer vaccine), 15 of the patients (75%) were men, and the median age was 36 years.

Four individuals (20%) developed myocarditis symptoms after the first vaccination and 16 (80%) after the second dose. Nineteen of the patients (95%) were admitted to the hospital and all were discharged after a median of 2 days.

None of the 20 patients were readmitted or died. Two received a second vaccination after onset of myocarditis; neither had worsening of symptoms. At last available follow-up (median, 23.5 days after symptom onset), 13 patients (65%) had a resolution of their myocarditis symptoms and seven (35%) were improving.
 

Pericarditis cases

The 37 pericarditis cases occurred a median of 20 days after the most recent COVID-19 vaccination: 23 (62%) with Pfizer, 12 (32%) with Moderna, and 2 (5%) with the J&J vaccine. Fifteen developed pericarditis after the first vaccine dose (41%) and 22 (59%) after the second.

Twenty-seven (73%) of the cases occurred in men; the median age was 59 years.

Thirteen patients (35%) were admitted to the hospital, none to intensive care. The median hospital stay was 1 day. Seven patients with pericarditis received a second vaccination. No patient died.

At last available follow-up (median, 28 days), 7 patients (19%) had resolved symptoms and 23 (62%) were improving.

The researchers also calculate that the average monthly number of cases of myocarditis or myopericarditis during the prevaccine period of January 2019 through January 2021 was 16.9 (95% confidence interval, 15.3-18.6) compared with 27.3 (95% CI, 22.4-32.9) during the vaccine period of February through May 2021 (P < .001).

The mean numbers of pericarditis cases during the same periods were 49.1 (95% CI, 46.4-51.9) and 78.8 (95% CI, 70.3-87.9), respectively (P < .001).

The authors say limitations of their analysis include potential missed cases outside care settings and missed diagnoses of myocarditis or pericarditis, which would underestimate the incidence, as well as inaccurate EMR vaccination information.

“Temporal association does not prove causation, although the short span between vaccination and myocarditis onset and the elevated incidence of myocarditis and pericarditis in the study hospitals lend support to a possible relationship,” they wrote.

In late June, the Food and Drug Administration added a warning to the fact sheets accompanying the Pfizer and Moderna mRNA COVID-19 vaccines, flagging the rare risk of heart inflammation after their use.  

Dr. Diaz cautioned that myocarditis and pericarditis events remain “a rare occurrence” after COVID-19 vaccination.

“When discussing vaccination with patients, [health care providers] can advise them that patients generally recover in the rare event they get pericarditis or myocarditis and no deaths were found, and that the vaccines are safe and effective,” Dr. Diaz said.

The study had no specific funding. Dr. Diaz reported receipt of clinical trial research support from Gilead Sciences, Regeneron, Roche, Boehringer Ingelheim, and Edesa Biotech and scientific advisory board membership for Safeology.

A version of this article first appeared on Medscape.com.

While cases of pericarditis or myocarditis temporally linked to COVID-19 vaccination remain rare, they may happen more often than reported, according to a large review of electronic medical records (EMRs).

peterschreiber_media/iStock/Getty Images

They also appear to represent two “distinct syndromes,” George Diaz, MD, Providence Regional Medical Center Everett (Washington), said in an interview.

Myocarditis typically occurs soon after vaccination in younger patients and mostly after the second dose, while pericarditis occurs later in older patients, after the first or second dose.

Dr. Diaz and colleagues reported their analysis in a research letter published online August 4 in JAMA.

They reviewed the records of 2,000,287 people who received at least one COVID-19 vaccination at 40 hospitals in Washington, Oregon, Montana, and California that are part of the Providence health care system and use the same EMRs.

The median age of the cohort was 57 years and 59% were women.

A little more than three quarters (77%) received more than one dose; most received the mRNA vaccines made by Pfizer (53%) and Moderna (44%); 3% received the Johnson & Johnson vaccine.

The records showed that 20 people had vaccine-related myocarditis (1.0 per 100,000) and 37 had pericarditis (1.8 per 100,000).

A recent report, based on data from the Centers for Disease Control and Prevention’s Vaccine Adverse Events Reporting System, suggested an incidence of myocarditis of about 4.8 cases per 1 million following receipt of mRNA COVID-19 vaccine.

The new study shows a “similar pattern, although at higher incidence, suggesting vaccine adverse event underreporting. In addition, pericarditis may be more common than myocarditis among older patients,” the study team wrote.

“Our study resulted in higher numbers of cases probably because we searched the EMR, and VAERS requires doctors to report suspected cases voluntarily,” Dr. Diaz said in an interview.

Also, in the governments’ statistics, pericarditis and myocarditis were “lumped together,” he noted.
 

Myocarditis cases

The 20 myocarditis cases occurred a median of 3.5 days after vaccination (11 after the Moderna vaccine and 9 after the Pfizer vaccine), 15 of the patients (75%) were men, and the median age was 36 years.

Four individuals (20%) developed myocarditis symptoms after the first vaccination and 16 (80%) after the second dose. Nineteen of the patients (95%) were admitted to the hospital and all were discharged after a median of 2 days.

None of the 20 patients were readmitted or died. Two received a second vaccination after onset of myocarditis; neither had worsening of symptoms. At last available follow-up (median, 23.5 days after symptom onset), 13 patients (65%) had a resolution of their myocarditis symptoms and seven (35%) were improving.
 

Pericarditis cases

The 37 pericarditis cases occurred a median of 20 days after the most recent COVID-19 vaccination: 23 (62%) with Pfizer, 12 (32%) with Moderna, and 2 (5%) with the J&J vaccine. Fifteen developed pericarditis after the first vaccine dose (41%) and 22 (59%) after the second.

Twenty-seven (73%) of the cases occurred in men; the median age was 59 years.

Thirteen patients (35%) were admitted to the hospital, none to intensive care. The median hospital stay was 1 day. Seven patients with pericarditis received a second vaccination. No patient died.

At last available follow-up (median, 28 days), 7 patients (19%) had resolved symptoms and 23 (62%) were improving.

The researchers also calculate that the average monthly number of cases of myocarditis or myopericarditis during the prevaccine period of January 2019 through January 2021 was 16.9 (95% confidence interval, 15.3-18.6) compared with 27.3 (95% CI, 22.4-32.9) during the vaccine period of February through May 2021 (P < .001).

The mean numbers of pericarditis cases during the same periods were 49.1 (95% CI, 46.4-51.9) and 78.8 (95% CI, 70.3-87.9), respectively (P < .001).

The authors say limitations of their analysis include potential missed cases outside care settings and missed diagnoses of myocarditis or pericarditis, which would underestimate the incidence, as well as inaccurate EMR vaccination information.

“Temporal association does not prove causation, although the short span between vaccination and myocarditis onset and the elevated incidence of myocarditis and pericarditis in the study hospitals lend support to a possible relationship,” they wrote.

In late June, the Food and Drug Administration added a warning to the fact sheets accompanying the Pfizer and Moderna mRNA COVID-19 vaccines, flagging the rare risk of heart inflammation after their use.  

Dr. Diaz cautioned that myocarditis and pericarditis events remain “a rare occurrence” after COVID-19 vaccination.

“When discussing vaccination with patients, [health care providers] can advise them that patients generally recover in the rare event they get pericarditis or myocarditis and no deaths were found, and that the vaccines are safe and effective,” Dr. Diaz said.

The study had no specific funding. Dr. Diaz reported receipt of clinical trial research support from Gilead Sciences, Regeneron, Roche, Boehringer Ingelheim, and Edesa Biotech and scientific advisory board membership for Safeology.

A version of this article first appeared on Medscape.com.

While cases of pericarditis or myocarditis temporally linked to COVID-19 vaccination remain rare, they may happen more often than reported, according to a large review of electronic medical records (EMRs).

peterschreiber_media/iStock/Getty Images

They also appear to represent two “distinct syndromes,” George Diaz, MD, Providence Regional Medical Center Everett (Washington), said in an interview.

Myocarditis typically occurs soon after vaccination in younger patients and mostly after the second dose, while pericarditis occurs later in older patients, after the first or second dose.

Dr. Diaz and colleagues reported their analysis in a research letter published online August 4 in JAMA.

They reviewed the records of 2,000,287 people who received at least one COVID-19 vaccination at 40 hospitals in Washington, Oregon, Montana, and California that are part of the Providence health care system and use the same EMRs.

The median age of the cohort was 57 years and 59% were women.

A little more than three quarters (77%) received more than one dose; most received the mRNA vaccines made by Pfizer (53%) and Moderna (44%); 3% received the Johnson & Johnson vaccine.

The records showed that 20 people had vaccine-related myocarditis (1.0 per 100,000) and 37 had pericarditis (1.8 per 100,000).

A recent report, based on data from the Centers for Disease Control and Prevention’s Vaccine Adverse Events Reporting System, suggested an incidence of myocarditis of about 4.8 cases per 1 million following receipt of mRNA COVID-19 vaccine.

The new study shows a “similar pattern, although at higher incidence, suggesting vaccine adverse event underreporting. In addition, pericarditis may be more common than myocarditis among older patients,” the study team wrote.

“Our study resulted in higher numbers of cases probably because we searched the EMR, and VAERS requires doctors to report suspected cases voluntarily,” Dr. Diaz said in an interview.

Also, in the governments’ statistics, pericarditis and myocarditis were “lumped together,” he noted.
 

Myocarditis cases

The 20 myocarditis cases occurred a median of 3.5 days after vaccination (11 after the Moderna vaccine and 9 after the Pfizer vaccine), 15 of the patients (75%) were men, and the median age was 36 years.

Four individuals (20%) developed myocarditis symptoms after the first vaccination and 16 (80%) after the second dose. Nineteen of the patients (95%) were admitted to the hospital and all were discharged after a median of 2 days.

None of the 20 patients were readmitted or died. Two received a second vaccination after onset of myocarditis; neither had worsening of symptoms. At last available follow-up (median, 23.5 days after symptom onset), 13 patients (65%) had a resolution of their myocarditis symptoms and seven (35%) were improving.
 

Pericarditis cases

The 37 pericarditis cases occurred a median of 20 days after the most recent COVID-19 vaccination: 23 (62%) with Pfizer, 12 (32%) with Moderna, and 2 (5%) with the J&J vaccine. Fifteen developed pericarditis after the first vaccine dose (41%) and 22 (59%) after the second.

Twenty-seven (73%) of the cases occurred in men; the median age was 59 years.

Thirteen patients (35%) were admitted to the hospital, none to intensive care. The median hospital stay was 1 day. Seven patients with pericarditis received a second vaccination. No patient died.

At last available follow-up (median, 28 days), 7 patients (19%) had resolved symptoms and 23 (62%) were improving.

The researchers also calculate that the average monthly number of cases of myocarditis or myopericarditis during the prevaccine period of January 2019 through January 2021 was 16.9 (95% confidence interval, 15.3-18.6) compared with 27.3 (95% CI, 22.4-32.9) during the vaccine period of February through May 2021 (P < .001).

The mean numbers of pericarditis cases during the same periods were 49.1 (95% CI, 46.4-51.9) and 78.8 (95% CI, 70.3-87.9), respectively (P < .001).

The authors say limitations of their analysis include potential missed cases outside care settings and missed diagnoses of myocarditis or pericarditis, which would underestimate the incidence, as well as inaccurate EMR vaccination information.

“Temporal association does not prove causation, although the short span between vaccination and myocarditis onset and the elevated incidence of myocarditis and pericarditis in the study hospitals lend support to a possible relationship,” they wrote.

In late June, the Food and Drug Administration added a warning to the fact sheets accompanying the Pfizer and Moderna mRNA COVID-19 vaccines, flagging the rare risk of heart inflammation after their use.  

Dr. Diaz cautioned that myocarditis and pericarditis events remain “a rare occurrence” after COVID-19 vaccination.

“When discussing vaccination with patients, [health care providers] can advise them that patients generally recover in the rare event they get pericarditis or myocarditis and no deaths were found, and that the vaccines are safe and effective,” Dr. Diaz said.

The study had no specific funding. Dr. Diaz reported receipt of clinical trial research support from Gilead Sciences, Regeneron, Roche, Boehringer Ingelheim, and Edesa Biotech and scientific advisory board membership for Safeology.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

A version of this article first appeared on Medscape.com.

John Winkler II was dying of heart failure when doctors came to his hospital bedside, offering a chance to prolong his life. The HeartWare Ventricular Assist Device, or HVAD, could be implanted in Winkler’s chest until a transplant was possible. The heart pump came with disclaimers of risk, but Winkler wanted to fight for time. He was only 46 and had a loving wife and four children, and his second grandchild was on the way.

So, in August 2014, Winkler had surgery to implant the device. A golf-ball–sized rotor was attached to his left ventricle to pump blood through a tube and into his aorta. A cable threading out of a small incision in his waist connected to a battery-powered controller strapped to his body. If something went wrong, an alarm as loud as a fire drill would sound.

Winkler returned home weeks later and, as he regained his strength, became hopeful about the future. He started making plans to visit colleges with his daughter, and was able to host his parents and new grandchild for Christmas. “He was doing so much better,” his wife, Tina Winkler, said. “We thought he was coasting until he got his transplant.”

What John Winkler didn’t know: Months before his implant, the Food and Drug Administration put HeartWare on notice for not properly monitoring or repairing HVAD defects, such as faulty batteries and short circuits caused by static electricity, that had killed patients. The agency issued a warning letter, one of its most serious citations. It demanded fixes within 15 days, but took no decisive action as problems persisted.

Ten days after Christmas of 2014, Winkler’s two teenage children heard the HVAD’s piercing alarm and ran upstairs. They found their father collapsed on his bedroom floor, completely unresponsive. Kelly, 17, dropped to his side and tried to copy how people on television did CPR. She told her brother to call 911, and over the device’s siren did her best to hear instructions from the operator.

When paramedics arrived and assessed her father, one made a passing comment that has haunted Kelly ever since: “Well, his toes are already cold.” He died 2 days later. Medtronic, the company that acquired HeartWare in 2016, settled a lawsuit by the family last year, admitting no fault. Tina Winkler believes her children blamed themselves for their father’s death. “Those two kids have never been the same,” she said. “I think they feel like they didn’t do things they needed to do.”

But it was the FDA that failed to protect Winkler and thousands of other patients whose survival depended on the HVAD, a ProPublica investigation found.

As HeartWare and Medtronic failed inspection after inspection and reports of device-related deaths piled up, the FDA relied on the device makers to fix the problems voluntarily rather than compelling them to do so.

The HVAD was implanted into more than 19,000 patients, the majority of whom got it after the FDA found in 2014 that the device didn’t meet federal standards. By the end of last year, the agency had received more than 3,000 reports of patient deaths that may have been caused or contributed to by the device.

Among them were reports of deaths the company linked to serious device problems: a patient who vomited blood as a family member struggled to restart a defective HVAD; a patient who bled out internally and died after implant surgery because a tube attached to the pump tore open; a patient whose heart tissue was left charred after an HVAD short-circuited and voltage surged through the pump.

The ineffective regulatory oversight of the HVAD is emblematic of larger, more systemic weaknesses.

For decades, the FDA and its Center for Devices and Radiological Health have been responsible for ensuring that high-risk medical devices are safe and effective. Yet they rely mostly on manufacturers to identify and correct problems. The agency says it can seize products, order injunctions against companies, or issue fines, but it rarely does so, preferring instead for companies to make fixes voluntarily.

When federal investigators found repeated manufacturing issues with the HVAD for years, the FDA didn’t penalize the company, even as the company issued 15 serious recalls of the device starting in 2014, the most of any single high-risk device in the FDA’s database. Thousands of patients with recalled models needed to have external HVAD parts replaced or take extra caution while handling their devices and monitor them for signs of malfunctions that could cause injury or death.

Meanwhile, the processes to inform the public through formal FDA notices and messages to health care providers repeatedly failed and left patients in the dark about known problems with the HVAD.

“Patients have no idea, and they rely on the FDA to ensure the safety and effectiveness of high-risk devices,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who studies medical device regulation. “How can you not take action on a warning letter with these serious issues with very sick patients?”

In response to ProPublica’s findings, the FDA said it had been closely monitoring issues with the HVAD. It said that after Medtronic acquired HeartWare in 2016, it met with the company more than 100 times to ensure problems were being fixed and to review safety concerns related to the heart pump. The agency also said it initiated formal reviews of new device modifications and continually tracked whether the HVAD had a “reasonable assurance of safety and effectiveness.”

“Our decisions that we made along the way have always been patient focused,” said Dr. William Maisel, director of product evaluation and quality at the FDA’s device division. He added that more than 80% of companies fix their problems by the time the FDA reinspects.

That did not happen with the HVAD. In 2016 and 2018, inspectors found that issues detailed in the 2014 warning letter remained unresolved. Medtronic told the FDA last year that it had fixed the problems, but, before the agency could verify the claim, inspections were paused because of the coronavirus pandemic.

In June, Medtronic stopped HVAD sales and implants. The company conceded that a competing device was safer after a new study showed the HVAD had higher rates of death and neurological injury. Medtronic also cited a 12-year-old problem with its devices not restarting if they disconnect from power, leaving patients’ hearts without support.

Medtronic declined to make Geoffrey Martha, CEO, or Nnamdi Njoku, president of mechanical heart support, available for interviews. In an email, a spokesperson said, “There is nothing more important to Medtronic than the safety and well-being of patients.”

The email continued: “Medtronic takes this matter very seriously and, over the past five years, we have worked closely with FDA and engaged external experts to resolve the issues noted in the warning letter. FDA is aware of the steps Medtronic has taken to address the underlying concerns.”

The company said it will have a support system in place for the 4,000 patients worldwide and 2,000 in the United States who still rely on the HVAD. Medtronic will station 20 specialists across the globe to help with device maintenance and patient education. A centralized engineering team will provide technical support and troubleshooting for patients and medical staff. Medtronic said it will offer financial assistance if insurance doesn’t fully cover the surgery to replace a device with a competing product, but only if a doctor decides it’s medically necessary.

Patients with HVADs have little choice but to hope the devices keep working: The surgery to remove HVADs is so risky that both Medtronic and the FDA advise against it. The device is meant to be left in place until its wearer gets a heart transplant. Or dies.
 

Warning signs

In late 2012, HeartWare, then an independent company headquartered in Massachusetts, won FDA approval to sell a new device that could keep heart failure patients alive and mobile while awaiting a transplant.

A competing device, the HeartMate, was already gaining attention, with high-profile patients like former Vice President Dick Cheney, a heart attack survivor who eventually got a transplant after using the device for 20 months.

The HVAD offered a smaller option that could even be used in children, and it led to a string of publicized successes. A fitness model was able to return to the gym. A 13-year-old with heart defects could attend school again. Medtronic’s YouTube page features 16 interviews with grateful patients and families.

The patients who received HVADs had already been in grave peril. They had advanced heart failure, serious enough to need blood pumped out of their hearts artificially. Most patients were older than 50, but there were also younger patients with heart defects or other cardiac conditions. The device provided help but brought its own risks. Implanting it required invasive open-heart surgery, and clots could develop inside the pump, which, in the worst cases, led to deadly strokes.

The device also came with a steep price tag. Each HVAD cost about $80,000, and, even though HeartWare never made a profit as an independent company, in 2015 device sales brought in $276 million in revenue.

For many severe heart failure patients, the opportunity to survive longer and return to normal life made the device worth the risks and cost.

But patients were unaware the FDA started finding manufacturing issues at HeartWare’s Miami Lakes, Florida, plant as early as 2011, when the device was still seeking approval.

Among the findings, a federal inspector expressed concerns that engineering staff “were not completely reviewing documents before approving them” and found one employee assigned to monitoring device quality had missed several required monthly trainings. HeartWare leadership promised quick corrective action, according to FDA documents.

Then, in 2014, the FDA found more serious lapses, detailed in federal inspection reports.

For example, HeartWare knew of 119 instances in which batteries failed unexpectedly, which could leave the pump powerless, stopping support for the patient’s heart. But the company didn’t test the batteries in inventory for defects, or the batteries of current patients, even though one person’s death had already been linked to battery failure.

The company also received complaints that static electricity could short-circuit its devices. It learned of at least 27 such cases between 2010 and 2013, including four that resulted in serious injuries and two that led to death. HVAD patients would need to avoid contact with certain household objects like televisions or vacuum cleaners — anything that could create strong static electricity. HeartWare added warnings to the patient manual and redesigned its shield to protect the device controller, but the FDA found that the company didn’t replace shields for devices already being used by current patients or produced and sitting in inventory.

Continuing quality control concerns led to the FDA warning letter in June 2014. The document labeled the HVAD as “adulterated,” meaning the device did not meet federal manufacturing standards. The agency gave HeartWare 15 days to correct the problems or face regulatory action.

Still, investment analysts who followed HeartWare believed the warning posed little risk to the company’s business prospects. One described it as being “as benign as possible.”

The 15-day deadline passed, and the FDA never penalized the company.

The agency told ProPublica it had provided additional time because HeartWare was a relatively new manufacturer and the HVAD was a complicated device. It also said it avoided punitive action to make sure patients with severe heart failure had access to this treatment option. “We’re talking about the sickest of the sick patients who really have very few alternatives,” Maisel, the head of device quality, said.

But the HeartMate, the competing device, was available and already being used by the majority of patients. When Medtronic stopped HVAD sales, both companies said the HeartMate could fill the gap.

Inspectors continued to find problems at HeartWare facilities in 2015, 2016, 2017 and 2018. In the most recent report in 2018, inspectors identified seven separate violations at the HVAD plant, including three previously cited in the 2014 warning letter. The company was still mishandling newly discovered defects like pins connecting the controller to a power source that could bend and become unusable, and controllers built with incompatible parts that could chemically react and “attack” the plastic exterior.

Again, the inspection report said the company “promised to correct” the issues.

“What penalty is there for noncompliance? There isn’t one,” said Madris Kinard, a former public health analyst with the FDA and the CEO of Device Events, a software company that analyzes FDA device data. “There’s nothing the FDA is doing that penalizes, in any true sense of the matter, the manufacturer.”

By the time sales were halted last month, the HVAD had become the subject of 15 company-initiated “Class I” recalls for dangerous device problems that could cause injury or death.

One recall came with a warning sent to health care providers in December that said pumps were failing to start up properly. The pattern of malfunctions was almost as old as the device itself, the company later admitted when it halted device sales in June. But even recent patients were completely unaware of the problem.
 

“A no-brainer”

When children asked Latoya Johnson Keelen about the cable that came out of her side and connected to a controller on her hip, she told them she was Iron Woman.

For a while, she felt invulnerable with the HVAD on her heart.

Johnson Keelen, who lives in the Atlanta suburbs, learned she needed the device after delivering her fourth child, Isaiah, in early 2018. Doctors diagnosed her with postpartum cardiomyopathy, a rare and mysterious form of heart failure that afflicts mothers during pregnancy or after birth. Black mothers in the South have among the highest rates of the illness. Some mothers quickly regain heart function, some only partially recuperate and others never recover.

Tests showed that Johnson Keelen, then 42, was suddenly in end-stage heart failure.

Her body’s immune response at the time was too strong for her to receive a heart transplant. Doctors gave her two choices: an HVAD or end-of-life hospice care.

“It became a no-brainer,” she said. “I just had a baby. I just gave birth. I’m not ready to plan for a funeral.”

Johnson Keelen, a woman of faith, believed God would heal her, either through a medical advancement or a miracle. She thought the HVAD was the answer.

Living with a life-sustaining medical device was difficult at first for the fiercely independent mother. She had to leave her job as a public health communications specialist, ask her older sons to change her bandages and lean heavily on her new husband, only a year into their marriage.

But, for about three years, she found comfort in the soft humming of the HVAD’s spinning rotor at night. It served as a lullaby for her new baby when he lay on her chest.

She said she was never told about the manufacturing problems the FDA repeatedly found at HeartWare’s facilities or about device recalls, including one sent to patients in December 2020. The notice said the device sometimes wouldn’t restart properly, which had led to two patient deaths at that point. It warned that current patients should always keep at least one power source, a battery or an AC or DC adapter, connected at all times to avoid the need for a restart.

Two months after that notice, Johnson Keelen was getting her kids ready for school when the HVAD’s low-battery alarm blared. She had unplugged the battery to replace it without realizing her wall adapter was disconnected.

Once before, Johnson Keelen had simply plugged the charger back into the outlet and her device restarted. But this time it wouldn’t.

As an emergency alarm sounded, she called the ventricular-assist team assigned to her case, and a specialist directed her to switch out the device controller.

Nothing changed, and panic crept into the voice on the phone.

An ambulance took Johnson Keelen to a hospital where medical staff used several backup controllers to try to start the pump.

Still nothing.

Doctors and nurses tried to keep calm, but Johnson Keelen could see fear and shock on their faces. Without the HVAD, her only options were a transplant or a completely new pump.

Doctors scurried to locate a donor heart and airlifted her for an emergency transplant. But while running tests, the medical team was stunned to find that Johnson Keelen’s miracle had occurred: Her heart was once again pumping blood on its own.

She had a new choice. She could avoid the risks of transplant rejection and open heart surgery during the pandemic by leaving the device on her functioning heart, while cutting the wires, removing the external components and sealing the pump.

She chose to trust her newly functioning heart, and leave the decommissioned HVAD inside her.

Three months later, when Medtronic said it was stopping HeartWare sales and implants, its announcement cited the problem with pumps not restarting among the reasons.
 

Company-led oversight

If evidence suggests a medical device may be linked to a serious patient injury or death, hospitals and other health care facilities must submit a report to the manufacturer and the FDA. Device companies must also submit reports if they learn independently of any incidents.

By the end of 2020, roughly 3,000 death reports and 20,000 injury reports related to the HVAD had been filed with the FDA.

Any details that could identify patients, like their age or gender, are removed from the publicly available reports. Most only have limited details about circumstances surrounding deaths or injuries. But it’s clear from the reports on the HVAD that some of these outcomes could be linked to problems previously identified by FDA inspectors.

Doctors attempted CPR for two hours after an electrostatic shock short-circuited one patient’s device in 2014, a few months after the FDA inspection that year. An autopsy revealed voltage had caused “deep charring” of the tissue inside the patient’s chest.

Friends found another patient dead in the kitchen, with groceries still on the counter, in 2018 after their device, which did not have the recommended static shield, short-circuited.

Last year, paramedics found a patient with the device disconnected from power. They struggled to restart the device, but it wouldn’t plug back into the power source because the connector pins were bent. The patient would die at the hospital.

In most cases, the FDA turned to the company to investigate whether a malfunction caused or contributed to the incidents.

But the FDA has long known HeartWare and Medtronic could not be relied on to properly submit HVAD incident reports.

In 2014, the FDA cited HeartWare because in at least 10 cases, there were no documents showing the company attempted to investigate.

In 2016, the agency wrote another citation when the company was late in reporting more than 200 cases, some more than a year past their 30-day reporting deadlines, and failed to report malfunctions that occurred during clinical trials.

The FDA told ProPublica the agency increased its monitoring of HVAD reports, and Medtronic hired new employees to submit timely reports. But by 2018, its backlog had only grown, with 677 late case filings. Again, the FDA did nothing beyond telling the company to fix the problem and further increasing its monitoring.

In an email, Medtronic said it “has robust systems in place to monitor the safety of all of our products, including the HVAD device.”

The email said, “When any potential safety issues are identified, those issues are thoroughly investigated and relevant information is shared with regulators and healthcare providers.” The company didn’t respond to the pattern of late reports and incomplete investigations identified in FDA inspections.

Maisel, the director of FDA device evaluation and quality, once criticized asking companies to investigate their own devices. In 2008, as a practicing cardiologist, he testified to the U.S. House oversight committee about his concerns.

“In the majority of cases, FDA relies on industry to identify, correct and report the problems,” he said. “But there is obviously an inherent financial conflict of interest for the manufacturers, sometimes measured in billions of dollars.”

Maisel has since had a change of heart. When asked about his 2008 testimony, he told ProPublica that he now believes the regulatory system “generally serves patients well” and “most companies are well intentioned.”

HeartWare’s track record of questionable investigations was glaring in John Winkler II’s case.

A report submitted by HeartWare that matches the dates and details of Winkler’s case shows the company decided there was “no indication of any device malfunctions.” It told the FDA that the device couldn’t be removed from the body because the hospital said his family declined an autopsy. HeartWare added that the evidence of the device’s role in Winkler’s death was inconclusive.

Yet little of this appears to be true. Documents reviewed by ProPublica show an autopsy of the heart and lungs was performed a day after the death. Tina Winkler said she was told the pump was removed from her husband’s body and was available for inspection.

A year after John Winkler’s death, HeartWare recalled 18,000 potentially faulty batteries produced between 2013 and 2015. Tina Winkler came across the notice online and found her husband’s battery serial numbers on the list. The company never contacted her about it or any further investigation, she said.
 

Rewards, not penalties

As deaths and recalls mounted, HeartWare and Medtronic touted additional FDA approval to treat more patients and their attempts to develop new cutting-edge devices.

With the company on notice under the 2014 warning letter, HeartWare geared up to begin human trials on a smaller heart pump, called the MVAD or Miniaturized Ventricular Assist Device. It would be powered by a new algorithm to more efficiently pump blood. Industry analysts predicted robust sales.

In July 2015, implantations were set to begin on a select group of 60 patients in Europe and Australia. But they were abruptly stopped less than two months later after only 11 implants. Patients experienced numerous adverse events, including major bleeding, infection and device malfunction, according to published data.

HeartWare’s stock price plummeted from about $85 to $35 by October 2015. The next year, Medtronic bought HeartWare for $1.1 billion, replacing much of the company’s leadership shortly after.

Some former HeartWare investors filed a class action lawsuit in January 2016 alleging deception in the development of the MVAD.

According to the accounts of six anonymous former employees in the lawsuit, the details mirror the scandal surrounding Theranos, the former blood test company charged with fraud for raising more than $700 million by allegedly lying about its technology.

Where Theranos made empty promises of a test that only needed a few drops of blood, the suit alleges HeartWare promoted a life-sustaining medical device that former employees said had many problems and actually worsened blood flow, increasing clotting risks.

“Nothing really worked right,” one former HeartWare manager said in the lawsuit, citing “improper alarms, improper touch screen performance, gibberish on display screens — just so many alerts and problems.”

Leadership proceeded with human testing anyway, the suit alleges.

Months later, at an investor conference, HeartWare leadership acknowledged the pump and algorithm led to multiple adverse events. For two patients in particular, the algorithm would direct the pump to speed up so fast that it would try to suck up more blood than was available inside the heart for prolonged periods of time.

HeartWare and Medtronic settled the investor suit for $54.5 million in 2018, admitting no fault.

None of the allegations slowed the FDA as it gave Medtronic additional approval and support for its heart pump technologies.

In September 2017, the agency approved the HVAD as “destination therapy” for patients who were not heart transplant candidates and would rely on the device for the rest of their lives.

“We’re really excited about our HVAD destination therapy approval,” a Medtronic executive said on an investor earnings call. “That’s a real game changer for us in that market.”

Two years later, Medtronic announced it was developing a fully implantable version of the HVAD that would no longer need a cable coming through the waist to connect to power.

Even though issues with the HeartWare device had been unresolved for five years at that point, the FDA accepted the pitch into its new fast-track approval process for high-risk devices.

“Slipped Through The Cracks”

After Johnson Keelen’s pump failed in February, she found a news story about the recall notice sent to medical providers two months prior.

It said the company had identified a problem with pump restarts that could cause heart attacks or serious patient harm. Nineteen patients had been seriously injured so far, and two people had died. The recall warned that patients should be careful to avoid disconnecting the device’s power sources.

“I kept seeing Medtronic on record saying they notified patients,” Johnson Keelen said. “Who did they contact? No one told me.”

Her doctor later told her she must have “slipped through the cracks,” she said.

The current system for informing patients of new safety concerns with high-risk devices relies on a communication chain that can easily break. The device company contacts the FDA and health care providers that work with device patients. The FDA typically issues a public notice, while health professionals contact their patients.

But the agency admits most patients don’t know to look for formal FDA postings. And, experts say, the medical system can lose track of who needs to be notified, especially if a patient moves or switches primary care physicians.

Tina Winkler still wonders why she was never told about FDA-known safety issues with the HVAD. She said her husband’s medical team “had to teach me how to clean his wound, how to change his batteries and what to do if alarms go off. And they never mentioned any of this.”

She said, “If we had all the facts, there’s no way he would have gotten that device implanted in his heart.”

When FDA inspectors find serious safety issues with a medical device, inspection reports are not posted online or sent to patients. The public can obtain reports through a Freedom of Information Act request, but the agency’s records department has said new requests can be stuck behind a year-long backlog.

Patients can find warning letters online in a searchable database of thousands of letters from different FDA divisions, including the center for devices. But HeartWare’s 2014 letter is no longer available for public review because the website purges letters older than five years.

There are also few documents available in state courts about faulty products, because of restrictions on lawsuits related to medical devices. The restrictions date back to a 2008 Supreme Court decision in a case against Medtronic. The court found that U.S. law bars patients and their survivors from suing device makers in state court, essentially because their products go through such a rigorous FDA approval process.

Two recent patient lawsuits against HeartWare and Medtronic, including one filed by Tina Winkler, were moved from state court to federal court. In both cases, Medtronic filed to dismiss the cases because of the U.S. law that protects device companies. Medtronic and the families reached private settlements soon after.

Winkler and an attorney for the other family said they could not comment on their settlements.

Johnson Keelen, with a decommissioned HVAD still attached to her heart, wonders what that means for her and other patients’ chances of recourse.

“Why isn’t anyone now stepping up for the patient?” she asked. “They are now liable for taking care of us because we relied on them.”
 

“Run its course”

Deserae Cain, 33, is one of the 4,000 patients still relying on a HeartWare device.

She was implanted with the heart pump in late 2017, after suddenly being diagnosed with heart failure. Scans showed her heart was three times normal size. It took time for her to come to terms with needing a life-sustaining device — not long before her diagnosis, she had been going on five-mile runs. In the four years since, though, Cain has built a life around the HVAD with her fiance in their Dayton, Ohio, home.

They know the device can malfunction. In 2019, the pump failed for almost an hour as doctors at a nearby hospital struggled to restart it. Cain just tried to stay calm, knowing anxiety could threaten her unsupported weak heart. Months later, she needed an emergency experimental procedure to clear out blood clots developed within her HVAD.

Then, in 2020, Cain developed a widespread infection. Doctors told her she needed surgery to clean out and replace the pump.

Cain asked her medical team if she could switch to the alternative HeartMate device, which other patients told her presented fewer problems, she said. Doctors said the HVAD was better suited for her smaller frame.

But her new pump had problems soon after the surgery.

The device’s suction alarms, which alert when the pump is trying to pull in more blood than is available within the heart, sounded multiple times a day, for hours at a time, she said. Baffled by the issue for months, her medical team eventually turned off that specific alarm.

Soon after, her ventricular-assist specialist called her about a patient’s death linked to the belt that holds the device controller, she said. The belt had ripped and the equipment had fallen, yanking on the cable that connected the controller to the pump. Cain replaced her belt but it quickly frayed and had to be replaced again within six weeks.

Then, in June, she found out about Medtronic’s decision to stop sales and implants. Cain received a letter from her hospital mentioning a Medtronic support program, but it provided few specifics.

Cain wondered if things would be any different than before. Anxious about her future, she asked: “Are they just going to let it run its course until there is none of us left?”

This article first appeared on Propublica.

John Winkler II was dying of heart failure when doctors came to his hospital bedside, offering a chance to prolong his life. The HeartWare Ventricular Assist Device, or HVAD, could be implanted in Winkler’s chest until a transplant was possible. The heart pump came with disclaimers of risk, but Winkler wanted to fight for time. He was only 46 and had a loving wife and four children, and his second grandchild was on the way.

So, in August 2014, Winkler had surgery to implant the device. A golf-ball–sized rotor was attached to his left ventricle to pump blood through a tube and into his aorta. A cable threading out of a small incision in his waist connected to a battery-powered controller strapped to his body. If something went wrong, an alarm as loud as a fire drill would sound.

Winkler returned home weeks later and, as he regained his strength, became hopeful about the future. He started making plans to visit colleges with his daughter, and was able to host his parents and new grandchild for Christmas. “He was doing so much better,” his wife, Tina Winkler, said. “We thought he was coasting until he got his transplant.”

What John Winkler didn’t know: Months before his implant, the Food and Drug Administration put HeartWare on notice for not properly monitoring or repairing HVAD defects, such as faulty batteries and short circuits caused by static electricity, that had killed patients. The agency issued a warning letter, one of its most serious citations. It demanded fixes within 15 days, but took no decisive action as problems persisted.

Ten days after Christmas of 2014, Winkler’s two teenage children heard the HVAD’s piercing alarm and ran upstairs. They found their father collapsed on his bedroom floor, completely unresponsive. Kelly, 17, dropped to his side and tried to copy how people on television did CPR. She told her brother to call 911, and over the device’s siren did her best to hear instructions from the operator.

When paramedics arrived and assessed her father, one made a passing comment that has haunted Kelly ever since: “Well, his toes are already cold.” He died 2 days later. Medtronic, the company that acquired HeartWare in 2016, settled a lawsuit by the family last year, admitting no fault. Tina Winkler believes her children blamed themselves for their father’s death. “Those two kids have never been the same,” she said. “I think they feel like they didn’t do things they needed to do.”

But it was the FDA that failed to protect Winkler and thousands of other patients whose survival depended on the HVAD, a ProPublica investigation found.

As HeartWare and Medtronic failed inspection after inspection and reports of device-related deaths piled up, the FDA relied on the device makers to fix the problems voluntarily rather than compelling them to do so.

The HVAD was implanted into more than 19,000 patients, the majority of whom got it after the FDA found in 2014 that the device didn’t meet federal standards. By the end of last year, the agency had received more than 3,000 reports of patient deaths that may have been caused or contributed to by the device.

Among them were reports of deaths the company linked to serious device problems: a patient who vomited blood as a family member struggled to restart a defective HVAD; a patient who bled out internally and died after implant surgery because a tube attached to the pump tore open; a patient whose heart tissue was left charred after an HVAD short-circuited and voltage surged through the pump.

The ineffective regulatory oversight of the HVAD is emblematic of larger, more systemic weaknesses.

For decades, the FDA and its Center for Devices and Radiological Health have been responsible for ensuring that high-risk medical devices are safe and effective. Yet they rely mostly on manufacturers to identify and correct problems. The agency says it can seize products, order injunctions against companies, or issue fines, but it rarely does so, preferring instead for companies to make fixes voluntarily.

When federal investigators found repeated manufacturing issues with the HVAD for years, the FDA didn’t penalize the company, even as the company issued 15 serious recalls of the device starting in 2014, the most of any single high-risk device in the FDA’s database. Thousands of patients with recalled models needed to have external HVAD parts replaced or take extra caution while handling their devices and monitor them for signs of malfunctions that could cause injury or death.

Meanwhile, the processes to inform the public through formal FDA notices and messages to health care providers repeatedly failed and left patients in the dark about known problems with the HVAD.

“Patients have no idea, and they rely on the FDA to ensure the safety and effectiveness of high-risk devices,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who studies medical device regulation. “How can you not take action on a warning letter with these serious issues with very sick patients?”

In response to ProPublica’s findings, the FDA said it had been closely monitoring issues with the HVAD. It said that after Medtronic acquired HeartWare in 2016, it met with the company more than 100 times to ensure problems were being fixed and to review safety concerns related to the heart pump. The agency also said it initiated formal reviews of new device modifications and continually tracked whether the HVAD had a “reasonable assurance of safety and effectiveness.”

“Our decisions that we made along the way have always been patient focused,” said Dr. William Maisel, director of product evaluation and quality at the FDA’s device division. He added that more than 80% of companies fix their problems by the time the FDA reinspects.

That did not happen with the HVAD. In 2016 and 2018, inspectors found that issues detailed in the 2014 warning letter remained unresolved. Medtronic told the FDA last year that it had fixed the problems, but, before the agency could verify the claim, inspections were paused because of the coronavirus pandemic.

In June, Medtronic stopped HVAD sales and implants. The company conceded that a competing device was safer after a new study showed the HVAD had higher rates of death and neurological injury. Medtronic also cited a 12-year-old problem with its devices not restarting if they disconnect from power, leaving patients’ hearts without support.

Medtronic declined to make Geoffrey Martha, CEO, or Nnamdi Njoku, president of mechanical heart support, available for interviews. In an email, a spokesperson said, “There is nothing more important to Medtronic than the safety and well-being of patients.”

The email continued: “Medtronic takes this matter very seriously and, over the past five years, we have worked closely with FDA and engaged external experts to resolve the issues noted in the warning letter. FDA is aware of the steps Medtronic has taken to address the underlying concerns.”

The company said it will have a support system in place for the 4,000 patients worldwide and 2,000 in the United States who still rely on the HVAD. Medtronic will station 20 specialists across the globe to help with device maintenance and patient education. A centralized engineering team will provide technical support and troubleshooting for patients and medical staff. Medtronic said it will offer financial assistance if insurance doesn’t fully cover the surgery to replace a device with a competing product, but only if a doctor decides it’s medically necessary.

Patients with HVADs have little choice but to hope the devices keep working: The surgery to remove HVADs is so risky that both Medtronic and the FDA advise against it. The device is meant to be left in place until its wearer gets a heart transplant. Or dies.
 

Warning signs

In late 2012, HeartWare, then an independent company headquartered in Massachusetts, won FDA approval to sell a new device that could keep heart failure patients alive and mobile while awaiting a transplant.

A competing device, the HeartMate, was already gaining attention, with high-profile patients like former Vice President Dick Cheney, a heart attack survivor who eventually got a transplant after using the device for 20 months.

The HVAD offered a smaller option that could even be used in children, and it led to a string of publicized successes. A fitness model was able to return to the gym. A 13-year-old with heart defects could attend school again. Medtronic’s YouTube page features 16 interviews with grateful patients and families.

The patients who received HVADs had already been in grave peril. They had advanced heart failure, serious enough to need blood pumped out of their hearts artificially. Most patients were older than 50, but there were also younger patients with heart defects or other cardiac conditions. The device provided help but brought its own risks. Implanting it required invasive open-heart surgery, and clots could develop inside the pump, which, in the worst cases, led to deadly strokes.

The device also came with a steep price tag. Each HVAD cost about $80,000, and, even though HeartWare never made a profit as an independent company, in 2015 device sales brought in $276 million in revenue.

For many severe heart failure patients, the opportunity to survive longer and return to normal life made the device worth the risks and cost.

But patients were unaware the FDA started finding manufacturing issues at HeartWare’s Miami Lakes, Florida, plant as early as 2011, when the device was still seeking approval.

Among the findings, a federal inspector expressed concerns that engineering staff “were not completely reviewing documents before approving them” and found one employee assigned to monitoring device quality had missed several required monthly trainings. HeartWare leadership promised quick corrective action, according to FDA documents.

Then, in 2014, the FDA found more serious lapses, detailed in federal inspection reports.

For example, HeartWare knew of 119 instances in which batteries failed unexpectedly, which could leave the pump powerless, stopping support for the patient’s heart. But the company didn’t test the batteries in inventory for defects, or the batteries of current patients, even though one person’s death had already been linked to battery failure.

The company also received complaints that static electricity could short-circuit its devices. It learned of at least 27 such cases between 2010 and 2013, including four that resulted in serious injuries and two that led to death. HVAD patients would need to avoid contact with certain household objects like televisions or vacuum cleaners — anything that could create strong static electricity. HeartWare added warnings to the patient manual and redesigned its shield to protect the device controller, but the FDA found that the company didn’t replace shields for devices already being used by current patients or produced and sitting in inventory.

Continuing quality control concerns led to the FDA warning letter in June 2014. The document labeled the HVAD as “adulterated,” meaning the device did not meet federal manufacturing standards. The agency gave HeartWare 15 days to correct the problems or face regulatory action.

Still, investment analysts who followed HeartWare believed the warning posed little risk to the company’s business prospects. One described it as being “as benign as possible.”

The 15-day deadline passed, and the FDA never penalized the company.

The agency told ProPublica it had provided additional time because HeartWare was a relatively new manufacturer and the HVAD was a complicated device. It also said it avoided punitive action to make sure patients with severe heart failure had access to this treatment option. “We’re talking about the sickest of the sick patients who really have very few alternatives,” Maisel, the head of device quality, said.

But the HeartMate, the competing device, was available and already being used by the majority of patients. When Medtronic stopped HVAD sales, both companies said the HeartMate could fill the gap.

Inspectors continued to find problems at HeartWare facilities in 2015, 2016, 2017 and 2018. In the most recent report in 2018, inspectors identified seven separate violations at the HVAD plant, including three previously cited in the 2014 warning letter. The company was still mishandling newly discovered defects like pins connecting the controller to a power source that could bend and become unusable, and controllers built with incompatible parts that could chemically react and “attack” the plastic exterior.

Again, the inspection report said the company “promised to correct” the issues.

“What penalty is there for noncompliance? There isn’t one,” said Madris Kinard, a former public health analyst with the FDA and the CEO of Device Events, a software company that analyzes FDA device data. “There’s nothing the FDA is doing that penalizes, in any true sense of the matter, the manufacturer.”

By the time sales were halted last month, the HVAD had become the subject of 15 company-initiated “Class I” recalls for dangerous device problems that could cause injury or death.

One recall came with a warning sent to health care providers in December that said pumps were failing to start up properly. The pattern of malfunctions was almost as old as the device itself, the company later admitted when it halted device sales in June. But even recent patients were completely unaware of the problem.
 

“A no-brainer”

When children asked Latoya Johnson Keelen about the cable that came out of her side and connected to a controller on her hip, she told them she was Iron Woman.

For a while, she felt invulnerable with the HVAD on her heart.

Johnson Keelen, who lives in the Atlanta suburbs, learned she needed the device after delivering her fourth child, Isaiah, in early 2018. Doctors diagnosed her with postpartum cardiomyopathy, a rare and mysterious form of heart failure that afflicts mothers during pregnancy or after birth. Black mothers in the South have among the highest rates of the illness. Some mothers quickly regain heart function, some only partially recuperate and others never recover.

Tests showed that Johnson Keelen, then 42, was suddenly in end-stage heart failure.

Her body’s immune response at the time was too strong for her to receive a heart transplant. Doctors gave her two choices: an HVAD or end-of-life hospice care.

“It became a no-brainer,” she said. “I just had a baby. I just gave birth. I’m not ready to plan for a funeral.”

Johnson Keelen, a woman of faith, believed God would heal her, either through a medical advancement or a miracle. She thought the HVAD was the answer.

Living with a life-sustaining medical device was difficult at first for the fiercely independent mother. She had to leave her job as a public health communications specialist, ask her older sons to change her bandages and lean heavily on her new husband, only a year into their marriage.

But, for about three years, she found comfort in the soft humming of the HVAD’s spinning rotor at night. It served as a lullaby for her new baby when he lay on her chest.

She said she was never told about the manufacturing problems the FDA repeatedly found at HeartWare’s facilities or about device recalls, including one sent to patients in December 2020. The notice said the device sometimes wouldn’t restart properly, which had led to two patient deaths at that point. It warned that current patients should always keep at least one power source, a battery or an AC or DC adapter, connected at all times to avoid the need for a restart.

Two months after that notice, Johnson Keelen was getting her kids ready for school when the HVAD’s low-battery alarm blared. She had unplugged the battery to replace it without realizing her wall adapter was disconnected.

Once before, Johnson Keelen had simply plugged the charger back into the outlet and her device restarted. But this time it wouldn’t.

As an emergency alarm sounded, she called the ventricular-assist team assigned to her case, and a specialist directed her to switch out the device controller.

Nothing changed, and panic crept into the voice on the phone.

An ambulance took Johnson Keelen to a hospital where medical staff used several backup controllers to try to start the pump.

Still nothing.

Doctors and nurses tried to keep calm, but Johnson Keelen could see fear and shock on their faces. Without the HVAD, her only options were a transplant or a completely new pump.

Doctors scurried to locate a donor heart and airlifted her for an emergency transplant. But while running tests, the medical team was stunned to find that Johnson Keelen’s miracle had occurred: Her heart was once again pumping blood on its own.

She had a new choice. She could avoid the risks of transplant rejection and open heart surgery during the pandemic by leaving the device on her functioning heart, while cutting the wires, removing the external components and sealing the pump.

She chose to trust her newly functioning heart, and leave the decommissioned HVAD inside her.

Three months later, when Medtronic said it was stopping HeartWare sales and implants, its announcement cited the problem with pumps not restarting among the reasons.
 

Company-led oversight

If evidence suggests a medical device may be linked to a serious patient injury or death, hospitals and other health care facilities must submit a report to the manufacturer and the FDA. Device companies must also submit reports if they learn independently of any incidents.

By the end of 2020, roughly 3,000 death reports and 20,000 injury reports related to the HVAD had been filed with the FDA.

Any details that could identify patients, like their age or gender, are removed from the publicly available reports. Most only have limited details about circumstances surrounding deaths or injuries. But it’s clear from the reports on the HVAD that some of these outcomes could be linked to problems previously identified by FDA inspectors.

Doctors attempted CPR for two hours after an electrostatic shock short-circuited one patient’s device in 2014, a few months after the FDA inspection that year. An autopsy revealed voltage had caused “deep charring” of the tissue inside the patient’s chest.

Friends found another patient dead in the kitchen, with groceries still on the counter, in 2018 after their device, which did not have the recommended static shield, short-circuited.

Last year, paramedics found a patient with the device disconnected from power. They struggled to restart the device, but it wouldn’t plug back into the power source because the connector pins were bent. The patient would die at the hospital.

In most cases, the FDA turned to the company to investigate whether a malfunction caused or contributed to the incidents.

But the FDA has long known HeartWare and Medtronic could not be relied on to properly submit HVAD incident reports.

In 2014, the FDA cited HeartWare because in at least 10 cases, there were no documents showing the company attempted to investigate.

In 2016, the agency wrote another citation when the company was late in reporting more than 200 cases, some more than a year past their 30-day reporting deadlines, and failed to report malfunctions that occurred during clinical trials.

The FDA told ProPublica the agency increased its monitoring of HVAD reports, and Medtronic hired new employees to submit timely reports. But by 2018, its backlog had only grown, with 677 late case filings. Again, the FDA did nothing beyond telling the company to fix the problem and further increasing its monitoring.

In an email, Medtronic said it “has robust systems in place to monitor the safety of all of our products, including the HVAD device.”

The email said, “When any potential safety issues are identified, those issues are thoroughly investigated and relevant information is shared with regulators and healthcare providers.” The company didn’t respond to the pattern of late reports and incomplete investigations identified in FDA inspections.

Maisel, the director of FDA device evaluation and quality, once criticized asking companies to investigate their own devices. In 2008, as a practicing cardiologist, he testified to the U.S. House oversight committee about his concerns.

“In the majority of cases, FDA relies on industry to identify, correct and report the problems,” he said. “But there is obviously an inherent financial conflict of interest for the manufacturers, sometimes measured in billions of dollars.”

Maisel has since had a change of heart. When asked about his 2008 testimony, he told ProPublica that he now believes the regulatory system “generally serves patients well” and “most companies are well intentioned.”

HeartWare’s track record of questionable investigations was glaring in John Winkler II’s case.

A report submitted by HeartWare that matches the dates and details of Winkler’s case shows the company decided there was “no indication of any device malfunctions.” It told the FDA that the device couldn’t be removed from the body because the hospital said his family declined an autopsy. HeartWare added that the evidence of the device’s role in Winkler’s death was inconclusive.

Yet little of this appears to be true. Documents reviewed by ProPublica show an autopsy of the heart and lungs was performed a day after the death. Tina Winkler said she was told the pump was removed from her husband’s body and was available for inspection.

A year after John Winkler’s death, HeartWare recalled 18,000 potentially faulty batteries produced between 2013 and 2015. Tina Winkler came across the notice online and found her husband’s battery serial numbers on the list. The company never contacted her about it or any further investigation, she said.
 

Rewards, not penalties

As deaths and recalls mounted, HeartWare and Medtronic touted additional FDA approval to treat more patients and their attempts to develop new cutting-edge devices.

With the company on notice under the 2014 warning letter, HeartWare geared up to begin human trials on a smaller heart pump, called the MVAD or Miniaturized Ventricular Assist Device. It would be powered by a new algorithm to more efficiently pump blood. Industry analysts predicted robust sales.

In July 2015, implantations were set to begin on a select group of 60 patients in Europe and Australia. But they were abruptly stopped less than two months later after only 11 implants. Patients experienced numerous adverse events, including major bleeding, infection and device malfunction, according to published data.

HeartWare’s stock price plummeted from about $85 to $35 by October 2015. The next year, Medtronic bought HeartWare for $1.1 billion, replacing much of the company’s leadership shortly after.

Some former HeartWare investors filed a class action lawsuit in January 2016 alleging deception in the development of the MVAD.

According to the accounts of six anonymous former employees in the lawsuit, the details mirror the scandal surrounding Theranos, the former blood test company charged with fraud for raising more than $700 million by allegedly lying about its technology.

Where Theranos made empty promises of a test that only needed a few drops of blood, the suit alleges HeartWare promoted a life-sustaining medical device that former employees said had many problems and actually worsened blood flow, increasing clotting risks.

“Nothing really worked right,” one former HeartWare manager said in the lawsuit, citing “improper alarms, improper touch screen performance, gibberish on display screens — just so many alerts and problems.”

Leadership proceeded with human testing anyway, the suit alleges.

Months later, at an investor conference, HeartWare leadership acknowledged the pump and algorithm led to multiple adverse events. For two patients in particular, the algorithm would direct the pump to speed up so fast that it would try to suck up more blood than was available inside the heart for prolonged periods of time.

HeartWare and Medtronic settled the investor suit for $54.5 million in 2018, admitting no fault.

None of the allegations slowed the FDA as it gave Medtronic additional approval and support for its heart pump technologies.

In September 2017, the agency approved the HVAD as “destination therapy” for patients who were not heart transplant candidates and would rely on the device for the rest of their lives.

“We’re really excited about our HVAD destination therapy approval,” a Medtronic executive said on an investor earnings call. “That’s a real game changer for us in that market.”

Two years later, Medtronic announced it was developing a fully implantable version of the HVAD that would no longer need a cable coming through the waist to connect to power.

Even though issues with the HeartWare device had been unresolved for five years at that point, the FDA accepted the pitch into its new fast-track approval process for high-risk devices.

“Slipped Through The Cracks”

After Johnson Keelen’s pump failed in February, she found a news story about the recall notice sent to medical providers two months prior.

It said the company had identified a problem with pump restarts that could cause heart attacks or serious patient harm. Nineteen patients had been seriously injured so far, and two people had died. The recall warned that patients should be careful to avoid disconnecting the device’s power sources.

“I kept seeing Medtronic on record saying they notified patients,” Johnson Keelen said. “Who did they contact? No one told me.”

Her doctor later told her she must have “slipped through the cracks,” she said.

The current system for informing patients of new safety concerns with high-risk devices relies on a communication chain that can easily break. The device company contacts the FDA and health care providers that work with device patients. The FDA typically issues a public notice, while health professionals contact their patients.

But the agency admits most patients don’t know to look for formal FDA postings. And, experts say, the medical system can lose track of who needs to be notified, especially if a patient moves or switches primary care physicians.

Tina Winkler still wonders why she was never told about FDA-known safety issues with the HVAD. She said her husband’s medical team “had to teach me how to clean his wound, how to change his batteries and what to do if alarms go off. And they never mentioned any of this.”

She said, “If we had all the facts, there’s no way he would have gotten that device implanted in his heart.”

When FDA inspectors find serious safety issues with a medical device, inspection reports are not posted online or sent to patients. The public can obtain reports through a Freedom of Information Act request, but the agency’s records department has said new requests can be stuck behind a year-long backlog.

Patients can find warning letters online in a searchable database of thousands of letters from different FDA divisions, including the center for devices. But HeartWare’s 2014 letter is no longer available for public review because the website purges letters older than five years.

There are also few documents available in state courts about faulty products, because of restrictions on lawsuits related to medical devices. The restrictions date back to a 2008 Supreme Court decision in a case against Medtronic. The court found that U.S. law bars patients and their survivors from suing device makers in state court, essentially because their products go through such a rigorous FDA approval process.

Two recent patient lawsuits against HeartWare and Medtronic, including one filed by Tina Winkler, were moved from state court to federal court. In both cases, Medtronic filed to dismiss the cases because of the U.S. law that protects device companies. Medtronic and the families reached private settlements soon after.

Winkler and an attorney for the other family said they could not comment on their settlements.

Johnson Keelen, with a decommissioned HVAD still attached to her heart, wonders what that means for her and other patients’ chances of recourse.

“Why isn’t anyone now stepping up for the patient?” she asked. “They are now liable for taking care of us because we relied on them.”
 

“Run its course”

Deserae Cain, 33, is one of the 4,000 patients still relying on a HeartWare device.

She was implanted with the heart pump in late 2017, after suddenly being diagnosed with heart failure. Scans showed her heart was three times normal size. It took time for her to come to terms with needing a life-sustaining device — not long before her diagnosis, she had been going on five-mile runs. In the four years since, though, Cain has built a life around the HVAD with her fiance in their Dayton, Ohio, home.

They know the device can malfunction. In 2019, the pump failed for almost an hour as doctors at a nearby hospital struggled to restart it. Cain just tried to stay calm, knowing anxiety could threaten her unsupported weak heart. Months later, she needed an emergency experimental procedure to clear out blood clots developed within her HVAD.

Then, in 2020, Cain developed a widespread infection. Doctors told her she needed surgery to clean out and replace the pump.

Cain asked her medical team if she could switch to the alternative HeartMate device, which other patients told her presented fewer problems, she said. Doctors said the HVAD was better suited for her smaller frame.

But her new pump had problems soon after the surgery.

The device’s suction alarms, which alert when the pump is trying to pull in more blood than is available within the heart, sounded multiple times a day, for hours at a time, she said. Baffled by the issue for months, her medical team eventually turned off that specific alarm.

Soon after, her ventricular-assist specialist called her about a patient’s death linked to the belt that holds the device controller, she said. The belt had ripped and the equipment had fallen, yanking on the cable that connected the controller to the pump. Cain replaced her belt but it quickly frayed and had to be replaced again within six weeks.

Then, in June, she found out about Medtronic’s decision to stop sales and implants. Cain received a letter from her hospital mentioning a Medtronic support program, but it provided few specifics.

Cain wondered if things would be any different than before. Anxious about her future, she asked: “Are they just going to let it run its course until there is none of us left?”

This article first appeared on Propublica.

John Winkler II was dying of heart failure when doctors came to his hospital bedside, offering a chance to prolong his life. The HeartWare Ventricular Assist Device, or HVAD, could be implanted in Winkler’s chest until a transplant was possible. The heart pump came with disclaimers of risk, but Winkler wanted to fight for time. He was only 46 and had a loving wife and four children, and his second grandchild was on the way.

So, in August 2014, Winkler had surgery to implant the device. A golf-ball–sized rotor was attached to his left ventricle to pump blood through a tube and into his aorta. A cable threading out of a small incision in his waist connected to a battery-powered controller strapped to his body. If something went wrong, an alarm as loud as a fire drill would sound.

Winkler returned home weeks later and, as he regained his strength, became hopeful about the future. He started making plans to visit colleges with his daughter, and was able to host his parents and new grandchild for Christmas. “He was doing so much better,” his wife, Tina Winkler, said. “We thought he was coasting until he got his transplant.”

What John Winkler didn’t know: Months before his implant, the Food and Drug Administration put HeartWare on notice for not properly monitoring or repairing HVAD defects, such as faulty batteries and short circuits caused by static electricity, that had killed patients. The agency issued a warning letter, one of its most serious citations. It demanded fixes within 15 days, but took no decisive action as problems persisted.

Ten days after Christmas of 2014, Winkler’s two teenage children heard the HVAD’s piercing alarm and ran upstairs. They found their father collapsed on his bedroom floor, completely unresponsive. Kelly, 17, dropped to his side and tried to copy how people on television did CPR. She told her brother to call 911, and over the device’s siren did her best to hear instructions from the operator.

When paramedics arrived and assessed her father, one made a passing comment that has haunted Kelly ever since: “Well, his toes are already cold.” He died 2 days later. Medtronic, the company that acquired HeartWare in 2016, settled a lawsuit by the family last year, admitting no fault. Tina Winkler believes her children blamed themselves for their father’s death. “Those two kids have never been the same,” she said. “I think they feel like they didn’t do things they needed to do.”

But it was the FDA that failed to protect Winkler and thousands of other patients whose survival depended on the HVAD, a ProPublica investigation found.

As HeartWare and Medtronic failed inspection after inspection and reports of device-related deaths piled up, the FDA relied on the device makers to fix the problems voluntarily rather than compelling them to do so.

The HVAD was implanted into more than 19,000 patients, the majority of whom got it after the FDA found in 2014 that the device didn’t meet federal standards. By the end of last year, the agency had received more than 3,000 reports of patient deaths that may have been caused or contributed to by the device.

Among them were reports of deaths the company linked to serious device problems: a patient who vomited blood as a family member struggled to restart a defective HVAD; a patient who bled out internally and died after implant surgery because a tube attached to the pump tore open; a patient whose heart tissue was left charred after an HVAD short-circuited and voltage surged through the pump.

The ineffective regulatory oversight of the HVAD is emblematic of larger, more systemic weaknesses.

For decades, the FDA and its Center for Devices and Radiological Health have been responsible for ensuring that high-risk medical devices are safe and effective. Yet they rely mostly on manufacturers to identify and correct problems. The agency says it can seize products, order injunctions against companies, or issue fines, but it rarely does so, preferring instead for companies to make fixes voluntarily.

When federal investigators found repeated manufacturing issues with the HVAD for years, the FDA didn’t penalize the company, even as the company issued 15 serious recalls of the device starting in 2014, the most of any single high-risk device in the FDA’s database. Thousands of patients with recalled models needed to have external HVAD parts replaced or take extra caution while handling their devices and monitor them for signs of malfunctions that could cause injury or death.

Meanwhile, the processes to inform the public through formal FDA notices and messages to health care providers repeatedly failed and left patients in the dark about known problems with the HVAD.

“Patients have no idea, and they rely on the FDA to ensure the safety and effectiveness of high-risk devices,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who studies medical device regulation. “How can you not take action on a warning letter with these serious issues with very sick patients?”

In response to ProPublica’s findings, the FDA said it had been closely monitoring issues with the HVAD. It said that after Medtronic acquired HeartWare in 2016, it met with the company more than 100 times to ensure problems were being fixed and to review safety concerns related to the heart pump. The agency also said it initiated formal reviews of new device modifications and continually tracked whether the HVAD had a “reasonable assurance of safety and effectiveness.”

“Our decisions that we made along the way have always been patient focused,” said Dr. William Maisel, director of product evaluation and quality at the FDA’s device division. He added that more than 80% of companies fix their problems by the time the FDA reinspects.

That did not happen with the HVAD. In 2016 and 2018, inspectors found that issues detailed in the 2014 warning letter remained unresolved. Medtronic told the FDA last year that it had fixed the problems, but, before the agency could verify the claim, inspections were paused because of the coronavirus pandemic.

In June, Medtronic stopped HVAD sales and implants. The company conceded that a competing device was safer after a new study showed the HVAD had higher rates of death and neurological injury. Medtronic also cited a 12-year-old problem with its devices not restarting if they disconnect from power, leaving patients’ hearts without support.

Medtronic declined to make Geoffrey Martha, CEO, or Nnamdi Njoku, president of mechanical heart support, available for interviews. In an email, a spokesperson said, “There is nothing more important to Medtronic than the safety and well-being of patients.”

The email continued: “Medtronic takes this matter very seriously and, over the past five years, we have worked closely with FDA and engaged external experts to resolve the issues noted in the warning letter. FDA is aware of the steps Medtronic has taken to address the underlying concerns.”

The company said it will have a support system in place for the 4,000 patients worldwide and 2,000 in the United States who still rely on the HVAD. Medtronic will station 20 specialists across the globe to help with device maintenance and patient education. A centralized engineering team will provide technical support and troubleshooting for patients and medical staff. Medtronic said it will offer financial assistance if insurance doesn’t fully cover the surgery to replace a device with a competing product, but only if a doctor decides it’s medically necessary.

Patients with HVADs have little choice but to hope the devices keep working: The surgery to remove HVADs is so risky that both Medtronic and the FDA advise against it. The device is meant to be left in place until its wearer gets a heart transplant. Or dies.
 

Warning signs

In late 2012, HeartWare, then an independent company headquartered in Massachusetts, won FDA approval to sell a new device that could keep heart failure patients alive and mobile while awaiting a transplant.

A competing device, the HeartMate, was already gaining attention, with high-profile patients like former Vice President Dick Cheney, a heart attack survivor who eventually got a transplant after using the device for 20 months.

The HVAD offered a smaller option that could even be used in children, and it led to a string of publicized successes. A fitness model was able to return to the gym. A 13-year-old with heart defects could attend school again. Medtronic’s YouTube page features 16 interviews with grateful patients and families.

The patients who received HVADs had already been in grave peril. They had advanced heart failure, serious enough to need blood pumped out of their hearts artificially. Most patients were older than 50, but there were also younger patients with heart defects or other cardiac conditions. The device provided help but brought its own risks. Implanting it required invasive open-heart surgery, and clots could develop inside the pump, which, in the worst cases, led to deadly strokes.

The device also came with a steep price tag. Each HVAD cost about $80,000, and, even though HeartWare never made a profit as an independent company, in 2015 device sales brought in $276 million in revenue.

For many severe heart failure patients, the opportunity to survive longer and return to normal life made the device worth the risks and cost.

But patients were unaware the FDA started finding manufacturing issues at HeartWare’s Miami Lakes, Florida, plant as early as 2011, when the device was still seeking approval.

Among the findings, a federal inspector expressed concerns that engineering staff “were not completely reviewing documents before approving them” and found one employee assigned to monitoring device quality had missed several required monthly trainings. HeartWare leadership promised quick corrective action, according to FDA documents.

Then, in 2014, the FDA found more serious lapses, detailed in federal inspection reports.

For example, HeartWare knew of 119 instances in which batteries failed unexpectedly, which could leave the pump powerless, stopping support for the patient’s heart. But the company didn’t test the batteries in inventory for defects, or the batteries of current patients, even though one person’s death had already been linked to battery failure.

The company also received complaints that static electricity could short-circuit its devices. It learned of at least 27 such cases between 2010 and 2013, including four that resulted in serious injuries and two that led to death. HVAD patients would need to avoid contact with certain household objects like televisions or vacuum cleaners — anything that could create strong static electricity. HeartWare added warnings to the patient manual and redesigned its shield to protect the device controller, but the FDA found that the company didn’t replace shields for devices already being used by current patients or produced and sitting in inventory.

Continuing quality control concerns led to the FDA warning letter in June 2014. The document labeled the HVAD as “adulterated,” meaning the device did not meet federal manufacturing standards. The agency gave HeartWare 15 days to correct the problems or face regulatory action.

Still, investment analysts who followed HeartWare believed the warning posed little risk to the company’s business prospects. One described it as being “as benign as possible.”

The 15-day deadline passed, and the FDA never penalized the company.

The agency told ProPublica it had provided additional time because HeartWare was a relatively new manufacturer and the HVAD was a complicated device. It also said it avoided punitive action to make sure patients with severe heart failure had access to this treatment option. “We’re talking about the sickest of the sick patients who really have very few alternatives,” Maisel, the head of device quality, said.

But the HeartMate, the competing device, was available and already being used by the majority of patients. When Medtronic stopped HVAD sales, both companies said the HeartMate could fill the gap.

Inspectors continued to find problems at HeartWare facilities in 2015, 2016, 2017 and 2018. In the most recent report in 2018, inspectors identified seven separate violations at the HVAD plant, including three previously cited in the 2014 warning letter. The company was still mishandling newly discovered defects like pins connecting the controller to a power source that could bend and become unusable, and controllers built with incompatible parts that could chemically react and “attack” the plastic exterior.

Again, the inspection report said the company “promised to correct” the issues.

“What penalty is there for noncompliance? There isn’t one,” said Madris Kinard, a former public health analyst with the FDA and the CEO of Device Events, a software company that analyzes FDA device data. “There’s nothing the FDA is doing that penalizes, in any true sense of the matter, the manufacturer.”

By the time sales were halted last month, the HVAD had become the subject of 15 company-initiated “Class I” recalls for dangerous device problems that could cause injury or death.

One recall came with a warning sent to health care providers in December that said pumps were failing to start up properly. The pattern of malfunctions was almost as old as the device itself, the company later admitted when it halted device sales in June. But even recent patients were completely unaware of the problem.
 

“A no-brainer”

When children asked Latoya Johnson Keelen about the cable that came out of her side and connected to a controller on her hip, she told them she was Iron Woman.

For a while, she felt invulnerable with the HVAD on her heart.

Johnson Keelen, who lives in the Atlanta suburbs, learned she needed the device after delivering her fourth child, Isaiah, in early 2018. Doctors diagnosed her with postpartum cardiomyopathy, a rare and mysterious form of heart failure that afflicts mothers during pregnancy or after birth. Black mothers in the South have among the highest rates of the illness. Some mothers quickly regain heart function, some only partially recuperate and others never recover.

Tests showed that Johnson Keelen, then 42, was suddenly in end-stage heart failure.

Her body’s immune response at the time was too strong for her to receive a heart transplant. Doctors gave her two choices: an HVAD or end-of-life hospice care.

“It became a no-brainer,” she said. “I just had a baby. I just gave birth. I’m not ready to plan for a funeral.”

Johnson Keelen, a woman of faith, believed God would heal her, either through a medical advancement or a miracle. She thought the HVAD was the answer.

Living with a life-sustaining medical device was difficult at first for the fiercely independent mother. She had to leave her job as a public health communications specialist, ask her older sons to change her bandages and lean heavily on her new husband, only a year into their marriage.

But, for about three years, she found comfort in the soft humming of the HVAD’s spinning rotor at night. It served as a lullaby for her new baby when he lay on her chest.

She said she was never told about the manufacturing problems the FDA repeatedly found at HeartWare’s facilities or about device recalls, including one sent to patients in December 2020. The notice said the device sometimes wouldn’t restart properly, which had led to two patient deaths at that point. It warned that current patients should always keep at least one power source, a battery or an AC or DC adapter, connected at all times to avoid the need for a restart.

Two months after that notice, Johnson Keelen was getting her kids ready for school when the HVAD’s low-battery alarm blared. She had unplugged the battery to replace it without realizing her wall adapter was disconnected.

Once before, Johnson Keelen had simply plugged the charger back into the outlet and her device restarted. But this time it wouldn’t.

As an emergency alarm sounded, she called the ventricular-assist team assigned to her case, and a specialist directed her to switch out the device controller.

Nothing changed, and panic crept into the voice on the phone.

An ambulance took Johnson Keelen to a hospital where medical staff used several backup controllers to try to start the pump.

Still nothing.

Doctors and nurses tried to keep calm, but Johnson Keelen could see fear and shock on their faces. Without the HVAD, her only options were a transplant or a completely new pump.

Doctors scurried to locate a donor heart and airlifted her for an emergency transplant. But while running tests, the medical team was stunned to find that Johnson Keelen’s miracle had occurred: Her heart was once again pumping blood on its own.

She had a new choice. She could avoid the risks of transplant rejection and open heart surgery during the pandemic by leaving the device on her functioning heart, while cutting the wires, removing the external components and sealing the pump.

She chose to trust her newly functioning heart, and leave the decommissioned HVAD inside her.

Three months later, when Medtronic said it was stopping HeartWare sales and implants, its announcement cited the problem with pumps not restarting among the reasons.
 

Company-led oversight

If evidence suggests a medical device may be linked to a serious patient injury or death, hospitals and other health care facilities must submit a report to the manufacturer and the FDA. Device companies must also submit reports if they learn independently of any incidents.

By the end of 2020, roughly 3,000 death reports and 20,000 injury reports related to the HVAD had been filed with the FDA.

Any details that could identify patients, like their age or gender, are removed from the publicly available reports. Most only have limited details about circumstances surrounding deaths or injuries. But it’s clear from the reports on the HVAD that some of these outcomes could be linked to problems previously identified by FDA inspectors.

Doctors attempted CPR for two hours after an electrostatic shock short-circuited one patient’s device in 2014, a few months after the FDA inspection that year. An autopsy revealed voltage had caused “deep charring” of the tissue inside the patient’s chest.

Friends found another patient dead in the kitchen, with groceries still on the counter, in 2018 after their device, which did not have the recommended static shield, short-circuited.

Last year, paramedics found a patient with the device disconnected from power. They struggled to restart the device, but it wouldn’t plug back into the power source because the connector pins were bent. The patient would die at the hospital.

In most cases, the FDA turned to the company to investigate whether a malfunction caused or contributed to the incidents.

But the FDA has long known HeartWare and Medtronic could not be relied on to properly submit HVAD incident reports.

In 2014, the FDA cited HeartWare because in at least 10 cases, there were no documents showing the company attempted to investigate.

In 2016, the agency wrote another citation when the company was late in reporting more than 200 cases, some more than a year past their 30-day reporting deadlines, and failed to report malfunctions that occurred during clinical trials.

The FDA told ProPublica the agency increased its monitoring of HVAD reports, and Medtronic hired new employees to submit timely reports. But by 2018, its backlog had only grown, with 677 late case filings. Again, the FDA did nothing beyond telling the company to fix the problem and further increasing its monitoring.

In an email, Medtronic said it “has robust systems in place to monitor the safety of all of our products, including the HVAD device.”

The email said, “When any potential safety issues are identified, those issues are thoroughly investigated and relevant information is shared with regulators and healthcare providers.” The company didn’t respond to the pattern of late reports and incomplete investigations identified in FDA inspections.

Maisel, the director of FDA device evaluation and quality, once criticized asking companies to investigate their own devices. In 2008, as a practicing cardiologist, he testified to the U.S. House oversight committee about his concerns.

“In the majority of cases, FDA relies on industry to identify, correct and report the problems,” he said. “But there is obviously an inherent financial conflict of interest for the manufacturers, sometimes measured in billions of dollars.”

Maisel has since had a change of heart. When asked about his 2008 testimony, he told ProPublica that he now believes the regulatory system “generally serves patients well” and “most companies are well intentioned.”

HeartWare’s track record of questionable investigations was glaring in John Winkler II’s case.

A report submitted by HeartWare that matches the dates and details of Winkler’s case shows the company decided there was “no indication of any device malfunctions.” It told the FDA that the device couldn’t be removed from the body because the hospital said his family declined an autopsy. HeartWare added that the evidence of the device’s role in Winkler’s death was inconclusive.

Yet little of this appears to be true. Documents reviewed by ProPublica show an autopsy of the heart and lungs was performed a day after the death. Tina Winkler said she was told the pump was removed from her husband’s body and was available for inspection.

A year after John Winkler’s death, HeartWare recalled 18,000 potentially faulty batteries produced between 2013 and 2015. Tina Winkler came across the notice online and found her husband’s battery serial numbers on the list. The company never contacted her about it or any further investigation, she said.
 

Rewards, not penalties

As deaths and recalls mounted, HeartWare and Medtronic touted additional FDA approval to treat more patients and their attempts to develop new cutting-edge devices.

With the company on notice under the 2014 warning letter, HeartWare geared up to begin human trials on a smaller heart pump, called the MVAD or Miniaturized Ventricular Assist Device. It would be powered by a new algorithm to more efficiently pump blood. Industry analysts predicted robust sales.

In July 2015, implantations were set to begin on a select group of 60 patients in Europe and Australia. But they were abruptly stopped less than two months later after only 11 implants. Patients experienced numerous adverse events, including major bleeding, infection and device malfunction, according to published data.

HeartWare’s stock price plummeted from about $85 to $35 by October 2015. The next year, Medtronic bought HeartWare for $1.1 billion, replacing much of the company’s leadership shortly after.

Some former HeartWare investors filed a class action lawsuit in January 2016 alleging deception in the development of the MVAD.

According to the accounts of six anonymous former employees in the lawsuit, the details mirror the scandal surrounding Theranos, the former blood test company charged with fraud for raising more than $700 million by allegedly lying about its technology.

Where Theranos made empty promises of a test that only needed a few drops of blood, the suit alleges HeartWare promoted a life-sustaining medical device that former employees said had many problems and actually worsened blood flow, increasing clotting risks.

“Nothing really worked right,” one former HeartWare manager said in the lawsuit, citing “improper alarms, improper touch screen performance, gibberish on display screens — just so many alerts and problems.”

Leadership proceeded with human testing anyway, the suit alleges.

Months later, at an investor conference, HeartWare leadership acknowledged the pump and algorithm led to multiple adverse events. For two patients in particular, the algorithm would direct the pump to speed up so fast that it would try to suck up more blood than was available inside the heart for prolonged periods of time.

HeartWare and Medtronic settled the investor suit for $54.5 million in 2018, admitting no fault.

None of the allegations slowed the FDA as it gave Medtronic additional approval and support for its heart pump technologies.

In September 2017, the agency approved the HVAD as “destination therapy” for patients who were not heart transplant candidates and would rely on the device for the rest of their lives.

“We’re really excited about our HVAD destination therapy approval,” a Medtronic executive said on an investor earnings call. “That’s a real game changer for us in that market.”

Two years later, Medtronic announced it was developing a fully implantable version of the HVAD that would no longer need a cable coming through the waist to connect to power.

Even though issues with the HeartWare device had been unresolved for five years at that point, the FDA accepted the pitch into its new fast-track approval process for high-risk devices.

“Slipped Through The Cracks”

After Johnson Keelen’s pump failed in February, she found a news story about the recall notice sent to medical providers two months prior.

It said the company had identified a problem with pump restarts that could cause heart attacks or serious patient harm. Nineteen patients had been seriously injured so far, and two people had died. The recall warned that patients should be careful to avoid disconnecting the device’s power sources.

“I kept seeing Medtronic on record saying they notified patients,” Johnson Keelen said. “Who did they contact? No one told me.”

Her doctor later told her she must have “slipped through the cracks,” she said.

The current system for informing patients of new safety concerns with high-risk devices relies on a communication chain that can easily break. The device company contacts the FDA and health care providers that work with device patients. The FDA typically issues a public notice, while health professionals contact their patients.

But the agency admits most patients don’t know to look for formal FDA postings. And, experts say, the medical system can lose track of who needs to be notified, especially if a patient moves or switches primary care physicians.

Tina Winkler still wonders why she was never told about FDA-known safety issues with the HVAD. She said her husband’s medical team “had to teach me how to clean his wound, how to change his batteries and what to do if alarms go off. And they never mentioned any of this.”

She said, “If we had all the facts, there’s no way he would have gotten that device implanted in his heart.”

When FDA inspectors find serious safety issues with a medical device, inspection reports are not posted online or sent to patients. The public can obtain reports through a Freedom of Information Act request, but the agency’s records department has said new requests can be stuck behind a year-long backlog.

Patients can find warning letters online in a searchable database of thousands of letters from different FDA divisions, including the center for devices. But HeartWare’s 2014 letter is no longer available for public review because the website purges letters older than five years.

There are also few documents available in state courts about faulty products, because of restrictions on lawsuits related to medical devices. The restrictions date back to a 2008 Supreme Court decision in a case against Medtronic. The court found that U.S. law bars patients and their survivors from suing device makers in state court, essentially because their products go through such a rigorous FDA approval process.

Two recent patient lawsuits against HeartWare and Medtronic, including one filed by Tina Winkler, were moved from state court to federal court. In both cases, Medtronic filed to dismiss the cases because of the U.S. law that protects device companies. Medtronic and the families reached private settlements soon after.

Winkler and an attorney for the other family said they could not comment on their settlements.

Johnson Keelen, with a decommissioned HVAD still attached to her heart, wonders what that means for her and other patients’ chances of recourse.

“Why isn’t anyone now stepping up for the patient?” she asked. “They are now liable for taking care of us because we relied on them.”
 

“Run its course”

Deserae Cain, 33, is one of the 4,000 patients still relying on a HeartWare device.

She was implanted with the heart pump in late 2017, after suddenly being diagnosed with heart failure. Scans showed her heart was three times normal size. It took time for her to come to terms with needing a life-sustaining device — not long before her diagnosis, she had been going on five-mile runs. In the four years since, though, Cain has built a life around the HVAD with her fiance in their Dayton, Ohio, home.

They know the device can malfunction. In 2019, the pump failed for almost an hour as doctors at a nearby hospital struggled to restart it. Cain just tried to stay calm, knowing anxiety could threaten her unsupported weak heart. Months later, she needed an emergency experimental procedure to clear out blood clots developed within her HVAD.

Then, in 2020, Cain developed a widespread infection. Doctors told her she needed surgery to clean out and replace the pump.

Cain asked her medical team if she could switch to the alternative HeartMate device, which other patients told her presented fewer problems, she said. Doctors said the HVAD was better suited for her smaller frame.

But her new pump had problems soon after the surgery.

The device’s suction alarms, which alert when the pump is trying to pull in more blood than is available within the heart, sounded multiple times a day, for hours at a time, she said. Baffled by the issue for months, her medical team eventually turned off that specific alarm.

Soon after, her ventricular-assist specialist called her about a patient’s death linked to the belt that holds the device controller, she said. The belt had ripped and the equipment had fallen, yanking on the cable that connected the controller to the pump. Cain replaced her belt but it quickly frayed and had to be replaced again within six weeks.

Then, in June, she found out about Medtronic’s decision to stop sales and implants. Cain received a letter from her hospital mentioning a Medtronic support program, but it provided few specifics.

Cain wondered if things would be any different than before. Anxious about her future, she asked: “Are they just going to let it run its course until there is none of us left?”

This article first appeared on Propublica.

The U.S. health care system ranked last overall among 11 high-income countries in an analysis by the nonprofit Commonwealth Fund, according to a report released on Aug. 4.

The report is the seventh international comparison of countries’ health systems by the Commonwealth Fund since 2004, and the United States has ranked last in every edition, David Blumenthal, MD, president of the Commonwealth Fund, told reporters during a press briefing.

Researchers analyzed survey answers from tens of thousands of patients and physicians in 11 countries. They analyzed performance on 71 measures across five categories – access to care, care process, administrative efficiency, equity, and health care outcomes. Administrative data were gathered from the Organisation for Economic Cooperation and Development and the World Health Organization.

Among contributors to the poor showing by the United States is that half (50%) of lower-income U.S. adults and 27% of higher-income U.S. adults say costs keep them from getting needed health care.

“In no other country does income inequality so profoundly limit access to care,” Dr. Blumenthal said.

In the United Kingdom, only 12% with lower incomes and 7% with higher incomes said costs kept them from care.

In a stark comparison, the researchers found that “a high-income person in the U.S. was more likely to report financial barriers than a low-income person in nearly all the other countries surveyed: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the U.K.”

Norway, the Netherlands, and Australia were ranked at the top overall in that order. Rounding out the 11 in overall ranking were the U.K., Germany, New Zealand, Sweden, France, Switzerland, Canada, and the United States.

“What this report tells us is that our health care system is not working for Americans, particularly those with lower incomes, who are at a severe disadvantage compared to citizens of other countries. And they are paying the price with their health and their lives,” Dr. Blumenthal said in a press release.

“To catch up with other high-income countries, the administration and Congress would have to expand access to health care, equitably, to all Americans, act aggressively to control costs, and invest in the social services we know can lead to a healthier population.”
 

High infant mortality, low life expectancy in U.S.

Several factors contributed to the U.S. ranking at the bottom of the outcomes category. Among them are that the United States has the highest infant mortality rate (5.7 deaths per 1,000 live births) and lowest life expectancy at age 60 (living on average 23.1 years after age 60), compared with the other countries surveyed. The U.S. rate of preventable mortality (177 deaths per 100,000 population) is more than double that of the best-performing country, Switzerland.

Lead author Eric Schneider, MD, senior vice president for policy and research at the Commonwealth Fund, pointed out that, in terms of the change in avoidable mortality over a decade, not only did the United States have the highest rate, compared with the other countries surveyed, “it also experienced the smallest decline in avoidable mortality over that 10-year period.”

The U.S. maternal mortality rate of 17.4 deaths per 100,000 live births is twice that of France, the country with the next-highest rate (7.6 deaths per 100,000 live births).
 

U.S. excelled in only one category

The only category in which the United States did not rank last was in “care process,” where it ranked second behind only New Zealand.

The care process category combines preventive care, safe care, coordinated care, and patient engagement and preferences. The category includes indicators such as mammography screening and influenza vaccination for older adults as well as the percentage of adults counseled by a health care provider about nutrition, smoking, or alcohol use.

The United States and Germany performed best on engagement and patient preferences, although U.S. adults have the lowest rates of continuity with the same doctor.

New Zealand and the United States ranked highest in the safe care category, with higher reported use of computerized alerts and routine review of medications.
 

‘Too little, too late’: Key recommendations for U.S. to improve

Reginald Williams, vice president of International Health Policy and Practice Innovations at the Commonwealth Fund, pointed out that the U.S. shortcomings in health care come despite spending more than twice as much of its GDP (17% in 2019) as the average OECD country.

“It appears that the US delivers too little of the care that is most needed and often delivers that care too late, especially for people with chronic illnesses,” he said.

He then summarized the team’s recommendations on how the United States can change course.

First is expanding insurance coverage, he said, noting that the United States is the only one of the 11 countries that lacks universal coverage and nearly 30 million people remain uninsured.

Top-performing countries in the survey have universal coverage, annual out-of-pocket caps on covered benefits, and full coverage for primary care and treatment for chronic conditions, he said.

The United States must also improve access to care, he said.

“Top-ranking countries like the Netherlands and Norway ensure timely availability to care by telephone on nights and weekends, and in-person follow-up at home, if needed,” he said.

Mr. Williams said reducing administrative burdens is also critical to free up resources for improving health. He gave an example: “Norway determines patient copayments or physician fees on a regional basis, applying standardized copayments to all physicians within a specialty in a geographic area.”

Reducing income-related barriers is important as well, he said.

The fear of unpredictably high bills and other issues prevent people in the United States from getting the care they ultimately need, he said, adding that top-performing countries invest more in social services to reduce health risks.

That could have implications for the COVID-19 response.

Responding effectively to COVID-19 requires that patients can access affordable health care services, Mr. Williams noted.

“We know from our research that more than two-thirds of U.S. adults say their potential out-of-pocket costs would figure prominently in their decisions to get care if they had coronavirus symptoms,” he said.

Dr. Schneider summed up in the press release: “This study makes clear that higher U.S. spending on health care is not producing better health especially as the U.S. continues on a path of deepening inequality. A country that spends as much as we do should have the best health system in the world. We should adapt what works in other high-income countries to build a better health care system that provides affordable, high-quality health care for everyone.”

Dr. Blumenthal, Dr. Schneider, and Mr. Williams reported no relevant financial relationships outside their employment with the Commonwealth Fund. 

A version of this article first appeared on Medscape.com.

The U.S. health care system ranked last overall among 11 high-income countries in an analysis by the nonprofit Commonwealth Fund, according to a report released on Aug. 4.

The report is the seventh international comparison of countries’ health systems by the Commonwealth Fund since 2004, and the United States has ranked last in every edition, David Blumenthal, MD, president of the Commonwealth Fund, told reporters during a press briefing.

Researchers analyzed survey answers from tens of thousands of patients and physicians in 11 countries. They analyzed performance on 71 measures across five categories – access to care, care process, administrative efficiency, equity, and health care outcomes. Administrative data were gathered from the Organisation for Economic Cooperation and Development and the World Health Organization.

Among contributors to the poor showing by the United States is that half (50%) of lower-income U.S. adults and 27% of higher-income U.S. adults say costs keep them from getting needed health care.

“In no other country does income inequality so profoundly limit access to care,” Dr. Blumenthal said.

In the United Kingdom, only 12% with lower incomes and 7% with higher incomes said costs kept them from care.

In a stark comparison, the researchers found that “a high-income person in the U.S. was more likely to report financial barriers than a low-income person in nearly all the other countries surveyed: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the U.K.”

Norway, the Netherlands, and Australia were ranked at the top overall in that order. Rounding out the 11 in overall ranking were the U.K., Germany, New Zealand, Sweden, France, Switzerland, Canada, and the United States.

“What this report tells us is that our health care system is not working for Americans, particularly those with lower incomes, who are at a severe disadvantage compared to citizens of other countries. And they are paying the price with their health and their lives,” Dr. Blumenthal said in a press release.

“To catch up with other high-income countries, the administration and Congress would have to expand access to health care, equitably, to all Americans, act aggressively to control costs, and invest in the social services we know can lead to a healthier population.”
 

High infant mortality, low life expectancy in U.S.

Several factors contributed to the U.S. ranking at the bottom of the outcomes category. Among them are that the United States has the highest infant mortality rate (5.7 deaths per 1,000 live births) and lowest life expectancy at age 60 (living on average 23.1 years after age 60), compared with the other countries surveyed. The U.S. rate of preventable mortality (177 deaths per 100,000 population) is more than double that of the best-performing country, Switzerland.

Lead author Eric Schneider, MD, senior vice president for policy and research at the Commonwealth Fund, pointed out that, in terms of the change in avoidable mortality over a decade, not only did the United States have the highest rate, compared with the other countries surveyed, “it also experienced the smallest decline in avoidable mortality over that 10-year period.”

The U.S. maternal mortality rate of 17.4 deaths per 100,000 live births is twice that of France, the country with the next-highest rate (7.6 deaths per 100,000 live births).
 

U.S. excelled in only one category

The only category in which the United States did not rank last was in “care process,” where it ranked second behind only New Zealand.

The care process category combines preventive care, safe care, coordinated care, and patient engagement and preferences. The category includes indicators such as mammography screening and influenza vaccination for older adults as well as the percentage of adults counseled by a health care provider about nutrition, smoking, or alcohol use.

The United States and Germany performed best on engagement and patient preferences, although U.S. adults have the lowest rates of continuity with the same doctor.

New Zealand and the United States ranked highest in the safe care category, with higher reported use of computerized alerts and routine review of medications.
 

‘Too little, too late’: Key recommendations for U.S. to improve

Reginald Williams, vice president of International Health Policy and Practice Innovations at the Commonwealth Fund, pointed out that the U.S. shortcomings in health care come despite spending more than twice as much of its GDP (17% in 2019) as the average OECD country.

“It appears that the US delivers too little of the care that is most needed and often delivers that care too late, especially for people with chronic illnesses,” he said.

He then summarized the team’s recommendations on how the United States can change course.

First is expanding insurance coverage, he said, noting that the United States is the only one of the 11 countries that lacks universal coverage and nearly 30 million people remain uninsured.

Top-performing countries in the survey have universal coverage, annual out-of-pocket caps on covered benefits, and full coverage for primary care and treatment for chronic conditions, he said.

The United States must also improve access to care, he said.

“Top-ranking countries like the Netherlands and Norway ensure timely availability to care by telephone on nights and weekends, and in-person follow-up at home, if needed,” he said.

Mr. Williams said reducing administrative burdens is also critical to free up resources for improving health. He gave an example: “Norway determines patient copayments or physician fees on a regional basis, applying standardized copayments to all physicians within a specialty in a geographic area.”

Reducing income-related barriers is important as well, he said.

The fear of unpredictably high bills and other issues prevent people in the United States from getting the care they ultimately need, he said, adding that top-performing countries invest more in social services to reduce health risks.

That could have implications for the COVID-19 response.

Responding effectively to COVID-19 requires that patients can access affordable health care services, Mr. Williams noted.

“We know from our research that more than two-thirds of U.S. adults say their potential out-of-pocket costs would figure prominently in their decisions to get care if they had coronavirus symptoms,” he said.

Dr. Schneider summed up in the press release: “This study makes clear that higher U.S. spending on health care is not producing better health especially as the U.S. continues on a path of deepening inequality. A country that spends as much as we do should have the best health system in the world. We should adapt what works in other high-income countries to build a better health care system that provides affordable, high-quality health care for everyone.”

Dr. Blumenthal, Dr. Schneider, and Mr. Williams reported no relevant financial relationships outside their employment with the Commonwealth Fund. 

A version of this article first appeared on Medscape.com.

The U.S. health care system ranked last overall among 11 high-income countries in an analysis by the nonprofit Commonwealth Fund, according to a report released on Aug. 4.

The report is the seventh international comparison of countries’ health systems by the Commonwealth Fund since 2004, and the United States has ranked last in every edition, David Blumenthal, MD, president of the Commonwealth Fund, told reporters during a press briefing.

Researchers analyzed survey answers from tens of thousands of patients and physicians in 11 countries. They analyzed performance on 71 measures across five categories – access to care, care process, administrative efficiency, equity, and health care outcomes. Administrative data were gathered from the Organisation for Economic Cooperation and Development and the World Health Organization.

Among contributors to the poor showing by the United States is that half (50%) of lower-income U.S. adults and 27% of higher-income U.S. adults say costs keep them from getting needed health care.

“In no other country does income inequality so profoundly limit access to care,” Dr. Blumenthal said.

In the United Kingdom, only 12% with lower incomes and 7% with higher incomes said costs kept them from care.

In a stark comparison, the researchers found that “a high-income person in the U.S. was more likely to report financial barriers than a low-income person in nearly all the other countries surveyed: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the U.K.”

Norway, the Netherlands, and Australia were ranked at the top overall in that order. Rounding out the 11 in overall ranking were the U.K., Germany, New Zealand, Sweden, France, Switzerland, Canada, and the United States.

“What this report tells us is that our health care system is not working for Americans, particularly those with lower incomes, who are at a severe disadvantage compared to citizens of other countries. And they are paying the price with their health and their lives,” Dr. Blumenthal said in a press release.

“To catch up with other high-income countries, the administration and Congress would have to expand access to health care, equitably, to all Americans, act aggressively to control costs, and invest in the social services we know can lead to a healthier population.”
 

High infant mortality, low life expectancy in U.S.

Several factors contributed to the U.S. ranking at the bottom of the outcomes category. Among them are that the United States has the highest infant mortality rate (5.7 deaths per 1,000 live births) and lowest life expectancy at age 60 (living on average 23.1 years after age 60), compared with the other countries surveyed. The U.S. rate of preventable mortality (177 deaths per 100,000 population) is more than double that of the best-performing country, Switzerland.

Lead author Eric Schneider, MD, senior vice president for policy and research at the Commonwealth Fund, pointed out that, in terms of the change in avoidable mortality over a decade, not only did the United States have the highest rate, compared with the other countries surveyed, “it also experienced the smallest decline in avoidable mortality over that 10-year period.”

The U.S. maternal mortality rate of 17.4 deaths per 100,000 live births is twice that of France, the country with the next-highest rate (7.6 deaths per 100,000 live births).
 

U.S. excelled in only one category

The only category in which the United States did not rank last was in “care process,” where it ranked second behind only New Zealand.

The care process category combines preventive care, safe care, coordinated care, and patient engagement and preferences. The category includes indicators such as mammography screening and influenza vaccination for older adults as well as the percentage of adults counseled by a health care provider about nutrition, smoking, or alcohol use.

The United States and Germany performed best on engagement and patient preferences, although U.S. adults have the lowest rates of continuity with the same doctor.

New Zealand and the United States ranked highest in the safe care category, with higher reported use of computerized alerts and routine review of medications.
 

‘Too little, too late’: Key recommendations for U.S. to improve

Reginald Williams, vice president of International Health Policy and Practice Innovations at the Commonwealth Fund, pointed out that the U.S. shortcomings in health care come despite spending more than twice as much of its GDP (17% in 2019) as the average OECD country.

“It appears that the US delivers too little of the care that is most needed and often delivers that care too late, especially for people with chronic illnesses,” he said.

He then summarized the team’s recommendations on how the United States can change course.

First is expanding insurance coverage, he said, noting that the United States is the only one of the 11 countries that lacks universal coverage and nearly 30 million people remain uninsured.

Top-performing countries in the survey have universal coverage, annual out-of-pocket caps on covered benefits, and full coverage for primary care and treatment for chronic conditions, he said.

The United States must also improve access to care, he said.

“Top-ranking countries like the Netherlands and Norway ensure timely availability to care by telephone on nights and weekends, and in-person follow-up at home, if needed,” he said.

Mr. Williams said reducing administrative burdens is also critical to free up resources for improving health. He gave an example: “Norway determines patient copayments or physician fees on a regional basis, applying standardized copayments to all physicians within a specialty in a geographic area.”

Reducing income-related barriers is important as well, he said.

The fear of unpredictably high bills and other issues prevent people in the United States from getting the care they ultimately need, he said, adding that top-performing countries invest more in social services to reduce health risks.

That could have implications for the COVID-19 response.

Responding effectively to COVID-19 requires that patients can access affordable health care services, Mr. Williams noted.

“We know from our research that more than two-thirds of U.S. adults say their potential out-of-pocket costs would figure prominently in their decisions to get care if they had coronavirus symptoms,” he said.

Dr. Schneider summed up in the press release: “This study makes clear that higher U.S. spending on health care is not producing better health especially as the U.S. continues on a path of deepening inequality. A country that spends as much as we do should have the best health system in the world. We should adapt what works in other high-income countries to build a better health care system that provides affordable, high-quality health care for everyone.”

Dr. Blumenthal, Dr. Schneider, and Mr. Williams reported no relevant financial relationships outside their employment with the Commonwealth Fund. 

A version of this article first appeared on Medscape.com.

When the Delta variant of the coronavirus was first identified in India in December 2020, the threat may have seemed too remote to trigger worry in the United States, although the horror of it ripping through the country was soon hard to ignore.

Within months, the Delta variant had spread to more than 98 countries, including Scotland, the United Kingdom, Israel, and now, of course, the United States. The CDC said this week the Delta variant now accounts for 93% of all COVID cases.

Fueled by Delta, COVID-19 cases, hospitalizations, and deaths are increasing in nearly all states, according to the latest CDC data. After the 7-day average number of cases dipped by June 22 to about 11,000, it rose by Aug. 3 to more than 85,000.

Some experts are heartened by the recent decrease in COVID-19 cases in the United Kingdom and India, both hard-hit with the Delta variant. COVID-19 cases in India peaked at more than 400,000 a day in May; by Aug. 2, that had dropped to about 30,500 daily.

Andy Slavitt, former Biden White House senior adviser for COVID-19 response, tweeted July 26 that, if the Delta variant acted the same in the United Kingdom as in India, it would have a quick rise and a quick drop.

The prediction seems to have come true. As of Aug. 3, U.K. cases have dropped to 7,467, compared with more than 46,800 July 19.

So the question of the summer has become: “When will Delta burn out here?”

Like other pandemic predictions, these are all over the board. Here are five predictions about when COVID cases will peak, then fall. They range from less than 2 weeks to more than 2 months:

• Mid-August: Among the most optimistic predictions of when the Delta-driven COVID-19 cases will decline is from Scott Gottlieb, MD, former FDA director. He told CNBC on July 28 that he would expect cases to decline in 2-3 weeks – so by August 11.
• Mid-August to mid-September: Ali Mokdad, PhD, chief strategy officer for population health at the University of Washington, Seattle, said that, “right now for the U.S. as a country, cases will peak mid-August” and then decline. He is citing projections by the university’s Institute for Health Metrics and Evaluation. In its “most likely” scenario, it predicts COVID deaths will peak at about 1,000 daily by mid-September, then decline. (As of Aug. 3, daily deaths averaged 371.)
• September: “I am hoping we get over this Delta hump [by then],” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape. “But sometimes, I am too much of an optimist.”
• Mid-October: Experts at the COVID-19 Scenario Modeling Hub, a consortium of researchers from leading institutions who consult with the CDC, said the Delta-fueled pandemic will steadily increase through summer and fall, with a mid-October peak.
• Unclear: Because cases are underestimated, “I think it is unclear when we will see a peak of Delta,” says Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore. He predicts a decline in cases as “more people get infected and develop natural immunity.”

The predictions are based on different scenarios, such as most likely or worst case. Factors such as personal behaviors, public mandates, and vaccination rates could all alter the projections.
 

What a difference vaccination may make

An uptick in vaccinations could change all the models and predictions, experts agree. As of Aug. 3, almost half (49.7%) of the total U.S. population was fully vaccinated, the CDC said. (And 80.1% of those 65 and over were.)

But that’s a long way from the 70% or 80% figure often cited to reach herd immunity. Recently, Ricardo Franco, MD, of the University of Alabama at Birmingham, said at a briefing by the Infectious Diseases Society of America that the infectiousness of the Delta variant may mean the herd immunity threshold is actually closer to 90%.

Dr. Mokdad estimates that by Nov. 1, based on the current rate of infections, 64% of people in the United States will be immune to a variant like Delta, taking into account those already infected and those vaccinated against COVID-19.

Justin Lessler, PhD, a University of North Carolina at Chapel Hill epidemiologist involved in the modeling hub, says if enough people get vaccinated, it could stop the Delta variant in its tracks. But that percentage is high.

“I am relatively confident that if we could get 90% or more of the eligible population vaccinated that we would see the epidemic begin to recede,” he says.

It’s a huge leap from 50%, or even 64%, to 90%. Could the Delta surge really motivate that many people to head to a vaccination site?

That’s hard to predict, Dr. Topol said. Some unvaccinated people may feel like soldiers in a foxhole, especially if they are in hard-hit states like Louisiana, and rush to get the vaccine as soon as possible. Others, hearing about the “breakthrough” cases in the vaccinated, may dig in their heels and ask: “Why bother?” as they mistakenly conclude that the vaccine has not done its job.
 

Roles of public policy, individual behavior

Besides an increase in vaccinations, individual behaviors and mandates can change the scenario. Doctors can remind even vaccinated patients that behaviors such as social distancing and masks still matter, experts said.

“Don’t ‘stress test’ your vaccine, “ Dr. Topol said.

The vaccines against COVID are good but not perfect and, he notes, they offer less protection if many months have passed since the vaccines were given.

The best advice now, Dr. Topol said, is: “Don’t be inside without a mask.”

Even if outdoors, depending on how close others are and the level of the conversation, a mask might be wise, he says.

Dr. Mokdad finds that “when cases go up, people put on their best behavior,” such as going back to masks and social distancing.

“Unfortunately, we have two countries,” he said, referring to the way public health measures and mandates vary from state to state.
 

Once the Delta variant subsides, what’s next?

It’s not a matter of if there is another variant on the heels of Delta, but when, Dr. Topol and other experts said. A new variant, Lambda, was first identified in Peru in August 2020 but now makes up about 90% of the country’s infections.

There’s also Delta-plus, just found in two people in South Korea.

Future variants could be even more transmissible than Delta, “which would be a horror show,” Dr. Topol said. “This [Delta] is by far the worst version. The virus is going to keep evolving. It is not done with us.”
 

On the horizon: Variant-proof vaccines

What’s needed to tackle the next variant is another approach to vaccine development, according to Dr. Topol and his colleague, Dennis R. Burton, a professor of immunology and microbiology at Scripps Research Institute.

Writing a commentary in Nature published in 2021, the two propose using a special class of protective antibodies, known as broadly neutralizing antibodies, to develop these vaccines. The success of the current COVID-19 vaccines is likely because of the vaccine’s ability to prompt the body to make protective neutralizing antibodies. These proteins bind to the viruses and prevent them from infecting the body’s cells.

The broadly neutralizing antibodies, however, can act against many different strains of related viruses, Dr. Topol and Mr. Burton wrote. Using this approach, which is already under study, scientists could make vaccines that would be effective against a family of viruses. The goal: to stop future outbreaks from becoming epidemics and then pandemics.

A version of this article first appeared on WebMD.com.

When the Delta variant of the coronavirus was first identified in India in December 2020, the threat may have seemed too remote to trigger worry in the United States, although the horror of it ripping through the country was soon hard to ignore.

Within months, the Delta variant had spread to more than 98 countries, including Scotland, the United Kingdom, Israel, and now, of course, the United States. The CDC said this week the Delta variant now accounts for 93% of all COVID cases.

Fueled by Delta, COVID-19 cases, hospitalizations, and deaths are increasing in nearly all states, according to the latest CDC data. After the 7-day average number of cases dipped by June 22 to about 11,000, it rose by Aug. 3 to more than 85,000.

Some experts are heartened by the recent decrease in COVID-19 cases in the United Kingdom and India, both hard-hit with the Delta variant. COVID-19 cases in India peaked at more than 400,000 a day in May; by Aug. 2, that had dropped to about 30,500 daily.

Andy Slavitt, former Biden White House senior adviser for COVID-19 response, tweeted July 26 that, if the Delta variant acted the same in the United Kingdom as in India, it would have a quick rise and a quick drop.

The prediction seems to have come true. As of Aug. 3, U.K. cases have dropped to 7,467, compared with more than 46,800 July 19.

So the question of the summer has become: “When will Delta burn out here?”

Like other pandemic predictions, these are all over the board. Here are five predictions about when COVID cases will peak, then fall. They range from less than 2 weeks to more than 2 months:

• Mid-August: Among the most optimistic predictions of when the Delta-driven COVID-19 cases will decline is from Scott Gottlieb, MD, former FDA director. He told CNBC on July 28 that he would expect cases to decline in 2-3 weeks – so by August 11.
• Mid-August to mid-September: Ali Mokdad, PhD, chief strategy officer for population health at the University of Washington, Seattle, said that, “right now for the U.S. as a country, cases will peak mid-August” and then decline. He is citing projections by the university’s Institute for Health Metrics and Evaluation. In its “most likely” scenario, it predicts COVID deaths will peak at about 1,000 daily by mid-September, then decline. (As of Aug. 3, daily deaths averaged 371.)
• September: “I am hoping we get over this Delta hump [by then],” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape. “But sometimes, I am too much of an optimist.”
• Mid-October: Experts at the COVID-19 Scenario Modeling Hub, a consortium of researchers from leading institutions who consult with the CDC, said the Delta-fueled pandemic will steadily increase through summer and fall, with a mid-October peak.
• Unclear: Because cases are underestimated, “I think it is unclear when we will see a peak of Delta,” says Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore. He predicts a decline in cases as “more people get infected and develop natural immunity.”

The predictions are based on different scenarios, such as most likely or worst case. Factors such as personal behaviors, public mandates, and vaccination rates could all alter the projections.
 

What a difference vaccination may make

An uptick in vaccinations could change all the models and predictions, experts agree. As of Aug. 3, almost half (49.7%) of the total U.S. population was fully vaccinated, the CDC said. (And 80.1% of those 65 and over were.)

But that’s a long way from the 70% or 80% figure often cited to reach herd immunity. Recently, Ricardo Franco, MD, of the University of Alabama at Birmingham, said at a briefing by the Infectious Diseases Society of America that the infectiousness of the Delta variant may mean the herd immunity threshold is actually closer to 90%.

Dr. Mokdad estimates that by Nov. 1, based on the current rate of infections, 64% of people in the United States will be immune to a variant like Delta, taking into account those already infected and those vaccinated against COVID-19.

Justin Lessler, PhD, a University of North Carolina at Chapel Hill epidemiologist involved in the modeling hub, says if enough people get vaccinated, it could stop the Delta variant in its tracks. But that percentage is high.

“I am relatively confident that if we could get 90% or more of the eligible population vaccinated that we would see the epidemic begin to recede,” he says.

It’s a huge leap from 50%, or even 64%, to 90%. Could the Delta surge really motivate that many people to head to a vaccination site?

That’s hard to predict, Dr. Topol said. Some unvaccinated people may feel like soldiers in a foxhole, especially if they are in hard-hit states like Louisiana, and rush to get the vaccine as soon as possible. Others, hearing about the “breakthrough” cases in the vaccinated, may dig in their heels and ask: “Why bother?” as they mistakenly conclude that the vaccine has not done its job.
 

Roles of public policy, individual behavior

Besides an increase in vaccinations, individual behaviors and mandates can change the scenario. Doctors can remind even vaccinated patients that behaviors such as social distancing and masks still matter, experts said.

“Don’t ‘stress test’ your vaccine, “ Dr. Topol said.

The vaccines against COVID are good but not perfect and, he notes, they offer less protection if many months have passed since the vaccines were given.

The best advice now, Dr. Topol said, is: “Don’t be inside without a mask.”

Even if outdoors, depending on how close others are and the level of the conversation, a mask might be wise, he says.

Dr. Mokdad finds that “when cases go up, people put on their best behavior,” such as going back to masks and social distancing.

“Unfortunately, we have two countries,” he said, referring to the way public health measures and mandates vary from state to state.
 

Once the Delta variant subsides, what’s next?

It’s not a matter of if there is another variant on the heels of Delta, but when, Dr. Topol and other experts said. A new variant, Lambda, was first identified in Peru in August 2020 but now makes up about 90% of the country’s infections.

There’s also Delta-plus, just found in two people in South Korea.

Future variants could be even more transmissible than Delta, “which would be a horror show,” Dr. Topol said. “This [Delta] is by far the worst version. The virus is going to keep evolving. It is not done with us.”
 

On the horizon: Variant-proof vaccines

What’s needed to tackle the next variant is another approach to vaccine development, according to Dr. Topol and his colleague, Dennis R. Burton, a professor of immunology and microbiology at Scripps Research Institute.

Writing a commentary in Nature published in 2021, the two propose using a special class of protective antibodies, known as broadly neutralizing antibodies, to develop these vaccines. The success of the current COVID-19 vaccines is likely because of the vaccine’s ability to prompt the body to make protective neutralizing antibodies. These proteins bind to the viruses and prevent them from infecting the body’s cells.

The broadly neutralizing antibodies, however, can act against many different strains of related viruses, Dr. Topol and Mr. Burton wrote. Using this approach, which is already under study, scientists could make vaccines that would be effective against a family of viruses. The goal: to stop future outbreaks from becoming epidemics and then pandemics.

A version of this article first appeared on WebMD.com.

When the Delta variant of the coronavirus was first identified in India in December 2020, the threat may have seemed too remote to trigger worry in the United States, although the horror of it ripping through the country was soon hard to ignore.

Within months, the Delta variant had spread to more than 98 countries, including Scotland, the United Kingdom, Israel, and now, of course, the United States. The CDC said this week the Delta variant now accounts for 93% of all COVID cases.

Fueled by Delta, COVID-19 cases, hospitalizations, and deaths are increasing in nearly all states, according to the latest CDC data. After the 7-day average number of cases dipped by June 22 to about 11,000, it rose by Aug. 3 to more than 85,000.

Some experts are heartened by the recent decrease in COVID-19 cases in the United Kingdom and India, both hard-hit with the Delta variant. COVID-19 cases in India peaked at more than 400,000 a day in May; by Aug. 2, that had dropped to about 30,500 daily.

Andy Slavitt, former Biden White House senior adviser for COVID-19 response, tweeted July 26 that, if the Delta variant acted the same in the United Kingdom as in India, it would have a quick rise and a quick drop.

The prediction seems to have come true. As of Aug. 3, U.K. cases have dropped to 7,467, compared with more than 46,800 July 19.

So the question of the summer has become: “When will Delta burn out here?”

Like other pandemic predictions, these are all over the board. Here are five predictions about when COVID cases will peak, then fall. They range from less than 2 weeks to more than 2 months:

• Mid-August: Among the most optimistic predictions of when the Delta-driven COVID-19 cases will decline is from Scott Gottlieb, MD, former FDA director. He told CNBC on July 28 that he would expect cases to decline in 2-3 weeks – so by August 11.
• Mid-August to mid-September: Ali Mokdad, PhD, chief strategy officer for population health at the University of Washington, Seattle, said that, “right now for the U.S. as a country, cases will peak mid-August” and then decline. He is citing projections by the university’s Institute for Health Metrics and Evaluation. In its “most likely” scenario, it predicts COVID deaths will peak at about 1,000 daily by mid-September, then decline. (As of Aug. 3, daily deaths averaged 371.)
• September: “I am hoping we get over this Delta hump [by then],” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape. “But sometimes, I am too much of an optimist.”
• Mid-October: Experts at the COVID-19 Scenario Modeling Hub, a consortium of researchers from leading institutions who consult with the CDC, said the Delta-fueled pandemic will steadily increase through summer and fall, with a mid-October peak.
• Unclear: Because cases are underestimated, “I think it is unclear when we will see a peak of Delta,” says Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore. He predicts a decline in cases as “more people get infected and develop natural immunity.”

The predictions are based on different scenarios, such as most likely or worst case. Factors such as personal behaviors, public mandates, and vaccination rates could all alter the projections.
 

What a difference vaccination may make

An uptick in vaccinations could change all the models and predictions, experts agree. As of Aug. 3, almost half (49.7%) of the total U.S. population was fully vaccinated, the CDC said. (And 80.1% of those 65 and over were.)

But that’s a long way from the 70% or 80% figure often cited to reach herd immunity. Recently, Ricardo Franco, MD, of the University of Alabama at Birmingham, said at a briefing by the Infectious Diseases Society of America that the infectiousness of the Delta variant may mean the herd immunity threshold is actually closer to 90%.

Dr. Mokdad estimates that by Nov. 1, based on the current rate of infections, 64% of people in the United States will be immune to a variant like Delta, taking into account those already infected and those vaccinated against COVID-19.

Justin Lessler, PhD, a University of North Carolina at Chapel Hill epidemiologist involved in the modeling hub, says if enough people get vaccinated, it could stop the Delta variant in its tracks. But that percentage is high.

“I am relatively confident that if we could get 90% or more of the eligible population vaccinated that we would see the epidemic begin to recede,” he says.

It’s a huge leap from 50%, or even 64%, to 90%. Could the Delta surge really motivate that many people to head to a vaccination site?

That’s hard to predict, Dr. Topol said. Some unvaccinated people may feel like soldiers in a foxhole, especially if they are in hard-hit states like Louisiana, and rush to get the vaccine as soon as possible. Others, hearing about the “breakthrough” cases in the vaccinated, may dig in their heels and ask: “Why bother?” as they mistakenly conclude that the vaccine has not done its job.
 

Roles of public policy, individual behavior

Besides an increase in vaccinations, individual behaviors and mandates can change the scenario. Doctors can remind even vaccinated patients that behaviors such as social distancing and masks still matter, experts said.

“Don’t ‘stress test’ your vaccine, “ Dr. Topol said.

The vaccines against COVID are good but not perfect and, he notes, they offer less protection if many months have passed since the vaccines were given.

The best advice now, Dr. Topol said, is: “Don’t be inside without a mask.”

Even if outdoors, depending on how close others are and the level of the conversation, a mask might be wise, he says.

Dr. Mokdad finds that “when cases go up, people put on their best behavior,” such as going back to masks and social distancing.

“Unfortunately, we have two countries,” he said, referring to the way public health measures and mandates vary from state to state.
 

Once the Delta variant subsides, what’s next?

It’s not a matter of if there is another variant on the heels of Delta, but when, Dr. Topol and other experts said. A new variant, Lambda, was first identified in Peru in August 2020 but now makes up about 90% of the country’s infections.

There’s also Delta-plus, just found in two people in South Korea.

Future variants could be even more transmissible than Delta, “which would be a horror show,” Dr. Topol said. “This [Delta] is by far the worst version. The virus is going to keep evolving. It is not done with us.”
 

On the horizon: Variant-proof vaccines

What’s needed to tackle the next variant is another approach to vaccine development, according to Dr. Topol and his colleague, Dennis R. Burton, a professor of immunology and microbiology at Scripps Research Institute.

Writing a commentary in Nature published in 2021, the two propose using a special class of protective antibodies, known as broadly neutralizing antibodies, to develop these vaccines. The success of the current COVID-19 vaccines is likely because of the vaccine’s ability to prompt the body to make protective neutralizing antibodies. These proteins bind to the viruses and prevent them from infecting the body’s cells.

The broadly neutralizing antibodies, however, can act against many different strains of related viruses, Dr. Topol and Mr. Burton wrote. Using this approach, which is already under study, scientists could make vaccines that would be effective against a family of viruses. The goal: to stop future outbreaks from becoming epidemics and then pandemics.

A version of this article first appeared on WebMD.com.

A Food and Drug Administration advisory panel struggled to muster support for marketing clearance of the TriGuard 3 (Keystone Heart) device for use during transcatheter aortic valve replacement (TAVR).

The Circulatory Systems Devices Panel of the Medical Devices Advisory Committee took no vote when it met Aug. 3, but weighed evidence for a proposed indication for the device “to minimize the risk of cerebral damage by deflecting embolic debris away from the cerebral circulation” during TAVR.

“While this device may deflect some debris, the data would suggest it may also create issues,” said Keith B. Allen, MD, director of surgical research at the Mid America Heart & Lung Surgeons, Kansas City, Mo. “I am really concerned that our desire and the emotion that surrounds preventing stroke are not being supported by the data.”

TriGuard 3 received CE Mark in Europe in March 2020. It was submitted for 510(k) clearance and seeks to prove substantial equivalence to the predicate Sentinel device (Claret Medical), currently the only approved embolic protection device in the United States.

The device is designed to cover all three major aortic vessels (innominate, left carotid, and left subclavian arteries) and is delivered transfemorally through an 8F sheath, whereas the Sentinel is positioned within the branch vessels, doesn’t cover the left subclavian artery, and is introduced through the radial or brachial artery via a 6F sheath.

TriGuard 3 faced an uphill battle, however, after failing to meet the primary composite efficacy endpoint in the REFLECT phase 2 trial (P = .857), with numeric trends showing higher all-cause mortality or any stroke at 30 days (9.8% vs. 6.7%) than pooled control subjects without embolic protection.

Rates for other components of the endpoint also trended higher with the device: National Institutes of Stroke Stroke Scale score worsening 2-5 days after the procedure, cerebral ischemic lesions on MRI 2-5 days after the procedure, and total cerebral ischemic lesion volume.

The Sentinel device was approved in 2017 after it failed to meet its primary efficacy endpoint of new brain lesion volume on MRI, but death and stroke rates favored the device over control, the panel pointed out.

The sponsor provided additional analyses in the per treatment (PT) population, defined as those with complete three-vessel coverage in at least two of three procedural time points. Compared with pooled control subjects, most of the imaging endpoints favored the TriGuard 3 device, but clinical neurologic event rates continued to favor the control group.

“The data used to demonstrate efficacy are all based on the PT subpopulation of the whole population, and those have to be considered promissory data,” said John Hirshfeld, MD, emeritus professor, University of Pennsylvania, Philadelphia. “This is the group where everything went well and for us to decide that’s achievable in the general population is speculative.”
 

Safety data

The REFLECT trial did meet its primary safety endpoint, with a 30-day major adverse cardiovascular event rate of 15.9%, compared with a performance goal of 34.4% (P < .0001).

Although prespecified, panel members pushed back, saying that the performance goal was unacceptably high, with several members remarking they’d never heard of a trial adding 9% as a “fudge factor” to a 25% historic control rate to get to the 34% performance target.

Keystone health officials noted that REFLECT was not designed to demonstrate a significant difference in the rate of primary safety events, compared with control. Instead, its purpose was to demonstrate that TriGuard 3 did not increase the risk associated with a TAVR procedure.

The TriGuard 3 device was successfully placed and retrieved in 100% of patients, but complete coverage was not uniform, with 72% of 157 as-treated patients having complete three-vessel coverage post TAVR but 15% having no coverage.

Panel members also expressed concern over device interference during TAVR, which was reported in nearly 10% of all TriGuard patients.

The TriGuard 3 group had 11 major vascular complications, 2 directly related to the device, and 3 stage 3 acute kidney injuries, whereas neither complication occurred in the control group.

Throughout the 9-hour hearing, the panel wrestled with what was described as a highly select patient group and small patient numbers that made it difficult to interpret observed differences. The trial involved 157 TriGuard 3 patients (including 41 from the roll-in phase) and 119 control subjects pooled from phase 2 of the trial (n = 57) and from phase 1 using the early-stage TriGuard HDH device (n = 57).

Pieter Stella, MD, PhD, Utrecht (the Netherlands) Medical Center, also presented “real-world” evidence from 75 patients in the Netherlands using the latest iteration of the device available in Europe with updates to the crimper and additional training materials to prevent the device from torquing during delivery. No strokes were reported, one patient had a transient ischemic attack (TIA), and two patients had a dissection, which resolved without sequelae.

Ralph Brindis, MD, MPH, professor of medicine, University of California, San Francisco, countered that there were only three experienced operators from a single center and that the stroke incidence was physician reported, “not data we can really embrace.”

There was much debate over why enrollment in phase 2 of the RHYTHM trial was temporarily paused in February 2019, briefly restarted, and then prematurely stopped in April 2019.

FDA officials said the study was paused at the recommendation of the data monitoring committee (DMC) because rates of safety events were different between patients and control subjects and operational errors called into question the accuracy of the data being reviewed. Ultimately, both the DMC and FDA recommended study suspension.

During the public hearing, TAVR pioneer Alain Cribier, MD, University of Rouen’s Charles Nicolle Hospital, Mont-Saint-Aignan, France, said the TriGuard 3 is of interest because it can be used with minimal need for manipulation and complete coverage of the cerebral vessels that is achieved by diverting rather than capturing debris. “The rapid and exponential growth of TAVR procedures demands safe TAVR interventions and the use of cerebral protection devices is a step in this direction.”

Others took a dim view. “Given that the Sentinel device has not demonstrated benefit on clinical outcomes, there is significant concern about similar devices, such as the TriGuard 3, providing clinical benefit,” Rita Redberg, MD, Sanket Dhruva, MD, and Robin Ji, University of California, San Francisco, wrote in a letter submitted to the panel.

Commenting further, they added: “With the results from the REFLECT II trial demonstrating no evidence for clinical outcome benefit in TAVR patients, and numerically higher rates for stroke risk, mortality, bleeding risk, and other dangerous adverse complications among those treated, it is concerning and dangerous for patient safety that the TriGUARD 3 cerebral embolic protection device is being considered for FDA 510(k) clearance.”

The FDA panel members reported no financial relationships.

A version of this article first appeared on Medscape.com.

A Food and Drug Administration advisory panel struggled to muster support for marketing clearance of the TriGuard 3 (Keystone Heart) device for use during transcatheter aortic valve replacement (TAVR).

The Circulatory Systems Devices Panel of the Medical Devices Advisory Committee took no vote when it met Aug. 3, but weighed evidence for a proposed indication for the device “to minimize the risk of cerebral damage by deflecting embolic debris away from the cerebral circulation” during TAVR.

“While this device may deflect some debris, the data would suggest it may also create issues,” said Keith B. Allen, MD, director of surgical research at the Mid America Heart & Lung Surgeons, Kansas City, Mo. “I am really concerned that our desire and the emotion that surrounds preventing stroke are not being supported by the data.”

TriGuard 3 received CE Mark in Europe in March 2020. It was submitted for 510(k) clearance and seeks to prove substantial equivalence to the predicate Sentinel device (Claret Medical), currently the only approved embolic protection device in the United States.

The device is designed to cover all three major aortic vessels (innominate, left carotid, and left subclavian arteries) and is delivered transfemorally through an 8F sheath, whereas the Sentinel is positioned within the branch vessels, doesn’t cover the left subclavian artery, and is introduced through the radial or brachial artery via a 6F sheath.

TriGuard 3 faced an uphill battle, however, after failing to meet the primary composite efficacy endpoint in the REFLECT phase 2 trial (P = .857), with numeric trends showing higher all-cause mortality or any stroke at 30 days (9.8% vs. 6.7%) than pooled control subjects without embolic protection.

Rates for other components of the endpoint also trended higher with the device: National Institutes of Stroke Stroke Scale score worsening 2-5 days after the procedure, cerebral ischemic lesions on MRI 2-5 days after the procedure, and total cerebral ischemic lesion volume.

The Sentinel device was approved in 2017 after it failed to meet its primary efficacy endpoint of new brain lesion volume on MRI, but death and stroke rates favored the device over control, the panel pointed out.

The sponsor provided additional analyses in the per treatment (PT) population, defined as those with complete three-vessel coverage in at least two of three procedural time points. Compared with pooled control subjects, most of the imaging endpoints favored the TriGuard 3 device, but clinical neurologic event rates continued to favor the control group.

“The data used to demonstrate efficacy are all based on the PT subpopulation of the whole population, and those have to be considered promissory data,” said John Hirshfeld, MD, emeritus professor, University of Pennsylvania, Philadelphia. “This is the group where everything went well and for us to decide that’s achievable in the general population is speculative.”
 

Safety data

The REFLECT trial did meet its primary safety endpoint, with a 30-day major adverse cardiovascular event rate of 15.9%, compared with a performance goal of 34.4% (P < .0001).

Although prespecified, panel members pushed back, saying that the performance goal was unacceptably high, with several members remarking they’d never heard of a trial adding 9% as a “fudge factor” to a 25% historic control rate to get to the 34% performance target.

Keystone health officials noted that REFLECT was not designed to demonstrate a significant difference in the rate of primary safety events, compared with control. Instead, its purpose was to demonstrate that TriGuard 3 did not increase the risk associated with a TAVR procedure.

The TriGuard 3 device was successfully placed and retrieved in 100% of patients, but complete coverage was not uniform, with 72% of 157 as-treated patients having complete three-vessel coverage post TAVR but 15% having no coverage.

Panel members also expressed concern over device interference during TAVR, which was reported in nearly 10% of all TriGuard patients.

The TriGuard 3 group had 11 major vascular complications, 2 directly related to the device, and 3 stage 3 acute kidney injuries, whereas neither complication occurred in the control group.

Throughout the 9-hour hearing, the panel wrestled with what was described as a highly select patient group and small patient numbers that made it difficult to interpret observed differences. The trial involved 157 TriGuard 3 patients (including 41 from the roll-in phase) and 119 control subjects pooled from phase 2 of the trial (n = 57) and from phase 1 using the early-stage TriGuard HDH device (n = 57).

Pieter Stella, MD, PhD, Utrecht (the Netherlands) Medical Center, also presented “real-world” evidence from 75 patients in the Netherlands using the latest iteration of the device available in Europe with updates to the crimper and additional training materials to prevent the device from torquing during delivery. No strokes were reported, one patient had a transient ischemic attack (TIA), and two patients had a dissection, which resolved without sequelae.

Ralph Brindis, MD, MPH, professor of medicine, University of California, San Francisco, countered that there were only three experienced operators from a single center and that the stroke incidence was physician reported, “not data we can really embrace.”

There was much debate over why enrollment in phase 2 of the RHYTHM trial was temporarily paused in February 2019, briefly restarted, and then prematurely stopped in April 2019.

FDA officials said the study was paused at the recommendation of the data monitoring committee (DMC) because rates of safety events were different between patients and control subjects and operational errors called into question the accuracy of the data being reviewed. Ultimately, both the DMC and FDA recommended study suspension.

During the public hearing, TAVR pioneer Alain Cribier, MD, University of Rouen’s Charles Nicolle Hospital, Mont-Saint-Aignan, France, said the TriGuard 3 is of interest because it can be used with minimal need for manipulation and complete coverage of the cerebral vessels that is achieved by diverting rather than capturing debris. “The rapid and exponential growth of TAVR procedures demands safe TAVR interventions and the use of cerebral protection devices is a step in this direction.”

Others took a dim view. “Given that the Sentinel device has not demonstrated benefit on clinical outcomes, there is significant concern about similar devices, such as the TriGuard 3, providing clinical benefit,” Rita Redberg, MD, Sanket Dhruva, MD, and Robin Ji, University of California, San Francisco, wrote in a letter submitted to the panel.

Commenting further, they added: “With the results from the REFLECT II trial demonstrating no evidence for clinical outcome benefit in TAVR patients, and numerically higher rates for stroke risk, mortality, bleeding risk, and other dangerous adverse complications among those treated, it is concerning and dangerous for patient safety that the TriGUARD 3 cerebral embolic protection device is being considered for FDA 510(k) clearance.”

The FDA panel members reported no financial relationships.

A version of this article first appeared on Medscape.com.

A Food and Drug Administration advisory panel struggled to muster support for marketing clearance of the TriGuard 3 (Keystone Heart) device for use during transcatheter aortic valve replacement (TAVR).

The Circulatory Systems Devices Panel of the Medical Devices Advisory Committee took no vote when it met Aug. 3, but weighed evidence for a proposed indication for the device “to minimize the risk of cerebral damage by deflecting embolic debris away from the cerebral circulation” during TAVR.

“While this device may deflect some debris, the data would suggest it may also create issues,” said Keith B. Allen, MD, director of surgical research at the Mid America Heart & Lung Surgeons, Kansas City, Mo. “I am really concerned that our desire and the emotion that surrounds preventing stroke are not being supported by the data.”

TriGuard 3 received CE Mark in Europe in March 2020. It was submitted for 510(k) clearance and seeks to prove substantial equivalence to the predicate Sentinel device (Claret Medical), currently the only approved embolic protection device in the United States.

The device is designed to cover all three major aortic vessels (innominate, left carotid, and left subclavian arteries) and is delivered transfemorally through an 8F sheath, whereas the Sentinel is positioned within the branch vessels, doesn’t cover the left subclavian artery, and is introduced through the radial or brachial artery via a 6F sheath.

TriGuard 3 faced an uphill battle, however, after failing to meet the primary composite efficacy endpoint in the REFLECT phase 2 trial (P = .857), with numeric trends showing higher all-cause mortality or any stroke at 30 days (9.8% vs. 6.7%) than pooled control subjects without embolic protection.

Rates for other components of the endpoint also trended higher with the device: National Institutes of Stroke Stroke Scale score worsening 2-5 days after the procedure, cerebral ischemic lesions on MRI 2-5 days after the procedure, and total cerebral ischemic lesion volume.

The Sentinel device was approved in 2017 after it failed to meet its primary efficacy endpoint of new brain lesion volume on MRI, but death and stroke rates favored the device over control, the panel pointed out.

The sponsor provided additional analyses in the per treatment (PT) population, defined as those with complete three-vessel coverage in at least two of three procedural time points. Compared with pooled control subjects, most of the imaging endpoints favored the TriGuard 3 device, but clinical neurologic event rates continued to favor the control group.

“The data used to demonstrate efficacy are all based on the PT subpopulation of the whole population, and those have to be considered promissory data,” said John Hirshfeld, MD, emeritus professor, University of Pennsylvania, Philadelphia. “This is the group where everything went well and for us to decide that’s achievable in the general population is speculative.”
 

Safety data

The REFLECT trial did meet its primary safety endpoint, with a 30-day major adverse cardiovascular event rate of 15.9%, compared with a performance goal of 34.4% (P < .0001).

Although prespecified, panel members pushed back, saying that the performance goal was unacceptably high, with several members remarking they’d never heard of a trial adding 9% as a “fudge factor” to a 25% historic control rate to get to the 34% performance target.

Keystone health officials noted that REFLECT was not designed to demonstrate a significant difference in the rate of primary safety events, compared with control. Instead, its purpose was to demonstrate that TriGuard 3 did not increase the risk associated with a TAVR procedure.

The TriGuard 3 device was successfully placed and retrieved in 100% of patients, but complete coverage was not uniform, with 72% of 157 as-treated patients having complete three-vessel coverage post TAVR but 15% having no coverage.

Panel members also expressed concern over device interference during TAVR, which was reported in nearly 10% of all TriGuard patients.

The TriGuard 3 group had 11 major vascular complications, 2 directly related to the device, and 3 stage 3 acute kidney injuries, whereas neither complication occurred in the control group.

Throughout the 9-hour hearing, the panel wrestled with what was described as a highly select patient group and small patient numbers that made it difficult to interpret observed differences. The trial involved 157 TriGuard 3 patients (including 41 from the roll-in phase) and 119 control subjects pooled from phase 2 of the trial (n = 57) and from phase 1 using the early-stage TriGuard HDH device (n = 57).

Pieter Stella, MD, PhD, Utrecht (the Netherlands) Medical Center, also presented “real-world” evidence from 75 patients in the Netherlands using the latest iteration of the device available in Europe with updates to the crimper and additional training materials to prevent the device from torquing during delivery. No strokes were reported, one patient had a transient ischemic attack (TIA), and two patients had a dissection, which resolved without sequelae.

Ralph Brindis, MD, MPH, professor of medicine, University of California, San Francisco, countered that there were only three experienced operators from a single center and that the stroke incidence was physician reported, “not data we can really embrace.”

There was much debate over why enrollment in phase 2 of the RHYTHM trial was temporarily paused in February 2019, briefly restarted, and then prematurely stopped in April 2019.

FDA officials said the study was paused at the recommendation of the data monitoring committee (DMC) because rates of safety events were different between patients and control subjects and operational errors called into question the accuracy of the data being reviewed. Ultimately, both the DMC and FDA recommended study suspension.

During the public hearing, TAVR pioneer Alain Cribier, MD, University of Rouen’s Charles Nicolle Hospital, Mont-Saint-Aignan, France, said the TriGuard 3 is of interest because it can be used with minimal need for manipulation and complete coverage of the cerebral vessels that is achieved by diverting rather than capturing debris. “The rapid and exponential growth of TAVR procedures demands safe TAVR interventions and the use of cerebral protection devices is a step in this direction.”

Others took a dim view. “Given that the Sentinel device has not demonstrated benefit on clinical outcomes, there is significant concern about similar devices, such as the TriGuard 3, providing clinical benefit,” Rita Redberg, MD, Sanket Dhruva, MD, and Robin Ji, University of California, San Francisco, wrote in a letter submitted to the panel.

Commenting further, they added: “With the results from the REFLECT II trial demonstrating no evidence for clinical outcome benefit in TAVR patients, and numerically higher rates for stroke risk, mortality, bleeding risk, and other dangerous adverse complications among those treated, it is concerning and dangerous for patient safety that the TriGUARD 3 cerebral embolic protection device is being considered for FDA 510(k) clearance.”

The FDA panel members reported no financial relationships.

A version of this article first appeared on Medscape.com.

Bother me, I’m working 

Although some of us have been comfortably functioning in a virtual work environment, others are now trickling back into the office. And you know what that means? People come to your desk to show you pictures of their cat or tell you about their kid’s birthday party. You may sneer at the interruption, but a study shows you actually like it.

Rawpixel/Thinkstock

A team of researchers at the University of Cincinnati surveyed 111 full-time employees twice a day for 3 weeks about their work experience. They asked about mental exhaustion, workplace interruptions, sense of belonging, and overall job satisfaction. They found that employees had a higher sense of belonging and job satisfaction when interrupted with a social versus work interruption.

“Interruptions can actually benefit individuals from an interpersonal perspective – people feel like they belong when others come and talk to them or ask them questions, even while being distracted from their tasks,” said Heather C. Vough, senior investigator and a former university faculty member.

Chitchatting at work is often seen as a distraction, but this study suggests that it’s not like heating up fish in the breakroom microwave.

So the next time someone hits you with the “Hey, do you have a sec?,” do yourself a favor and enjoy the interruption.
 

A smorgasbord of science

It’s probably difficult to recruit patients for some medical trials. Try this new drug and potentially get all sorts of interesting and unpleasant side effects. Pass. We suggest the approach a group of researchers from the University of Kansas took for a recent study into weight gain: Invite a bunch of 20-something adults to an all-you-can-eat buffet. They’ll be beating down your door in no time.

pxfuel

Their study, published in Appetite, focused on hyperpalatable food – the sort of food you can keep eating – and compared it with high-energy-dense food and ultra processed food. The test patients had their body composition measured, were let loose on the buffet, and were measured again a year later.

The patients who favored salty/carbohydrate-filled hyperpalatable food (such as pretzels or popcorn) were much more likely to gain weight, compared with those who focused on salty/fat-filled food of any variety. As a matter of fact, those who stuck to fatty food during the buffet had no change in weight over the 1-year study period. The researchers noted that those who ate the carb-filled food tended more toward hedonic eating, or the act of eating simply for pleasure.

The study is no doubt helpful in the long battle against obesity and overeating, but it’s also a very helpful guide to getting the most bang for your buck at the buffet. Stay away from the cheap salty snack food. Go for the steak and seafood. Get your money’s worth. In the long run you won’t even gain any weight. No promises about tomorrow though.
 

There’s a cheat code for that

For a large percentage of kids and young adults, and maybe even older adults (we don’t judge), a storm warning means a cozy night in playing video games. Staying inside is probably the safest bet when there’s a storm, and the weatherman never says to avoid playing video games when there’s lightning.

xresch/Pixabay

Maybe he should, though, since a man from Tennessee reportedly got struck by lightning through his game controller. Emergency crews determined that lightning either hit the man’s house or struck near it and went through the controller. The type of console was not revealed, even though some people may want to know the specifics before playing during the next storm.

Luckily, the man was not seriously hurt and did not need to go to the hospital. This is apparently not unheard of, as a professional gamer was shocked through a wired controller last year, causing burns on her hands and a broken controller.

This might be our cue to do less electrical types of activities during thunderstorms, like knitting or reading by candlelight.
 

Freeze, squeeze, and enjoy … cramping

As you were ingesting last week’s installment of the never-ending buffet that is LOTME, you probably wondered: What’s going on? Where’s the latest bodily insult being perpetuated by the gang over at TikTok?

Daria-Yakovleva/Pixabay

Have no fear, good readers. We would never make you go 2 straight weeks without serving up some hyperpalatable TikTok tidbits.

Our bodily insult du jour is frozen honey, and it’s exploding all over TikTok … and a few other places. “The hashtag ‘#FrozenHoney’ has been viewed nearly 600 million times, and the hashtag ‘#FrozenHoneyChallenge’ has been viewed more than 80 million times,” NBC News recently reported.

After a few hours in the freezer, honey can be squeezed out of a plastic bottle as a semisolid, toothpastelike goo – it’s stiff enough to rise out of a container that’s pointed straight up – and bitten off in large chunks. And therein lies the problem.

Some people are overdoing it. “Honey is great, but having it in small amounts to sweeten is really a healthy relationship with food, and using it to get a lot of followers and a lot of attention and having it in excess amounts is crazy,” Kristin Kirkpatrick, a registered dietitian at the Cleveland Clinic, told NBC.

Besides the possible weight gain from eating massive amounts of sugar, experts warned that “gobbling up bottles of frozen honey” could lead to stomach cramping, bloating, and diarrhea. Some TikTokers, NBC noted, said that they “were running for the bathroom.”

As we said, it’s a trend that is exploding.

Be sure to tune in next week, when we learn how TikTokers use ground meat as a skin moisturizer.
 

Bother me, I’m working 

Although some of us have been comfortably functioning in a virtual work environment, others are now trickling back into the office. And you know what that means? People come to your desk to show you pictures of their cat or tell you about their kid’s birthday party. You may sneer at the interruption, but a study shows you actually like it.

Rawpixel/Thinkstock

A team of researchers at the University of Cincinnati surveyed 111 full-time employees twice a day for 3 weeks about their work experience. They asked about mental exhaustion, workplace interruptions, sense of belonging, and overall job satisfaction. They found that employees had a higher sense of belonging and job satisfaction when interrupted with a social versus work interruption.

“Interruptions can actually benefit individuals from an interpersonal perspective – people feel like they belong when others come and talk to them or ask them questions, even while being distracted from their tasks,” said Heather C. Vough, senior investigator and a former university faculty member.

Chitchatting at work is often seen as a distraction, but this study suggests that it’s not like heating up fish in the breakroom microwave.

So the next time someone hits you with the “Hey, do you have a sec?,” do yourself a favor and enjoy the interruption.
 

A smorgasbord of science

It’s probably difficult to recruit patients for some medical trials. Try this new drug and potentially get all sorts of interesting and unpleasant side effects. Pass. We suggest the approach a group of researchers from the University of Kansas took for a recent study into weight gain: Invite a bunch of 20-something adults to an all-you-can-eat buffet. They’ll be beating down your door in no time.

pxfuel

Their study, published in Appetite, focused on hyperpalatable food – the sort of food you can keep eating – and compared it with high-energy-dense food and ultra processed food. The test patients had their body composition measured, were let loose on the buffet, and were measured again a year later.

The patients who favored salty/carbohydrate-filled hyperpalatable food (such as pretzels or popcorn) were much more likely to gain weight, compared with those who focused on salty/fat-filled food of any variety. As a matter of fact, those who stuck to fatty food during the buffet had no change in weight over the 1-year study period. The researchers noted that those who ate the carb-filled food tended more toward hedonic eating, or the act of eating simply for pleasure.

The study is no doubt helpful in the long battle against obesity and overeating, but it’s also a very helpful guide to getting the most bang for your buck at the buffet. Stay away from the cheap salty snack food. Go for the steak and seafood. Get your money’s worth. In the long run you won’t even gain any weight. No promises about tomorrow though.
 

There’s a cheat code for that

For a large percentage of kids and young adults, and maybe even older adults (we don’t judge), a storm warning means a cozy night in playing video games. Staying inside is probably the safest bet when there’s a storm, and the weatherman never says to avoid playing video games when there’s lightning.

xresch/Pixabay

Maybe he should, though, since a man from Tennessee reportedly got struck by lightning through his game controller. Emergency crews determined that lightning either hit the man’s house or struck near it and went through the controller. The type of console was not revealed, even though some people may want to know the specifics before playing during the next storm.

Luckily, the man was not seriously hurt and did not need to go to the hospital. This is apparently not unheard of, as a professional gamer was shocked through a wired controller last year, causing burns on her hands and a broken controller.

This might be our cue to do less electrical types of activities during thunderstorms, like knitting or reading by candlelight.
 

Freeze, squeeze, and enjoy … cramping

As you were ingesting last week’s installment of the never-ending buffet that is LOTME, you probably wondered: What’s going on? Where’s the latest bodily insult being perpetuated by the gang over at TikTok?

Daria-Yakovleva/Pixabay

Have no fear, good readers. We would never make you go 2 straight weeks without serving up some hyperpalatable TikTok tidbits.

Our bodily insult du jour is frozen honey, and it’s exploding all over TikTok … and a few other places. “The hashtag ‘#FrozenHoney’ has been viewed nearly 600 million times, and the hashtag ‘#FrozenHoneyChallenge’ has been viewed more than 80 million times,” NBC News recently reported.

After a few hours in the freezer, honey can be squeezed out of a plastic bottle as a semisolid, toothpastelike goo – it’s stiff enough to rise out of a container that’s pointed straight up – and bitten off in large chunks. And therein lies the problem.

Some people are overdoing it. “Honey is great, but having it in small amounts to sweeten is really a healthy relationship with food, and using it to get a lot of followers and a lot of attention and having it in excess amounts is crazy,” Kristin Kirkpatrick, a registered dietitian at the Cleveland Clinic, told NBC.

Besides the possible weight gain from eating massive amounts of sugar, experts warned that “gobbling up bottles of frozen honey” could lead to stomach cramping, bloating, and diarrhea. Some TikTokers, NBC noted, said that they “were running for the bathroom.”

As we said, it’s a trend that is exploding.

Be sure to tune in next week, when we learn how TikTokers use ground meat as a skin moisturizer.
 

Bother me, I’m working 

Although some of us have been comfortably functioning in a virtual work environment, others are now trickling back into the office. And you know what that means? People come to your desk to show you pictures of their cat or tell you about their kid’s birthday party. You may sneer at the interruption, but a study shows you actually like it.

Rawpixel/Thinkstock

A team of researchers at the University of Cincinnati surveyed 111 full-time employees twice a day for 3 weeks about their work experience. They asked about mental exhaustion, workplace interruptions, sense of belonging, and overall job satisfaction. They found that employees had a higher sense of belonging and job satisfaction when interrupted with a social versus work interruption.

“Interruptions can actually benefit individuals from an interpersonal perspective – people feel like they belong when others come and talk to them or ask them questions, even while being distracted from their tasks,” said Heather C. Vough, senior investigator and a former university faculty member.

Chitchatting at work is often seen as a distraction, but this study suggests that it’s not like heating up fish in the breakroom microwave.

So the next time someone hits you with the “Hey, do you have a sec?,” do yourself a favor and enjoy the interruption.
 

A smorgasbord of science

It’s probably difficult to recruit patients for some medical trials. Try this new drug and potentially get all sorts of interesting and unpleasant side effects. Pass. We suggest the approach a group of researchers from the University of Kansas took for a recent study into weight gain: Invite a bunch of 20-something adults to an all-you-can-eat buffet. They’ll be beating down your door in no time.

pxfuel

Their study, published in Appetite, focused on hyperpalatable food – the sort of food you can keep eating – and compared it with high-energy-dense food and ultra processed food. The test patients had their body composition measured, were let loose on the buffet, and were measured again a year later.

The patients who favored salty/carbohydrate-filled hyperpalatable food (such as pretzels or popcorn) were much more likely to gain weight, compared with those who focused on salty/fat-filled food of any variety. As a matter of fact, those who stuck to fatty food during the buffet had no change in weight over the 1-year study period. The researchers noted that those who ate the carb-filled food tended more toward hedonic eating, or the act of eating simply for pleasure.

The study is no doubt helpful in the long battle against obesity and overeating, but it’s also a very helpful guide to getting the most bang for your buck at the buffet. Stay away from the cheap salty snack food. Go for the steak and seafood. Get your money’s worth. In the long run you won’t even gain any weight. No promises about tomorrow though.
 

There’s a cheat code for that

For a large percentage of kids and young adults, and maybe even older adults (we don’t judge), a storm warning means a cozy night in playing video games. Staying inside is probably the safest bet when there’s a storm, and the weatherman never says to avoid playing video games when there’s lightning.

xresch/Pixabay

Maybe he should, though, since a man from Tennessee reportedly got struck by lightning through his game controller. Emergency crews determined that lightning either hit the man’s house or struck near it and went through the controller. The type of console was not revealed, even though some people may want to know the specifics before playing during the next storm.

Luckily, the man was not seriously hurt and did not need to go to the hospital. This is apparently not unheard of, as a professional gamer was shocked through a wired controller last year, causing burns on her hands and a broken controller.

This might be our cue to do less electrical types of activities during thunderstorms, like knitting or reading by candlelight.
 

Freeze, squeeze, and enjoy … cramping

As you were ingesting last week’s installment of the never-ending buffet that is LOTME, you probably wondered: What’s going on? Where’s the latest bodily insult being perpetuated by the gang over at TikTok?

Daria-Yakovleva/Pixabay

Have no fear, good readers. We would never make you go 2 straight weeks without serving up some hyperpalatable TikTok tidbits.

Our bodily insult du jour is frozen honey, and it’s exploding all over TikTok … and a few other places. “The hashtag ‘#FrozenHoney’ has been viewed nearly 600 million times, and the hashtag ‘#FrozenHoneyChallenge’ has been viewed more than 80 million times,” NBC News recently reported.

After a few hours in the freezer, honey can be squeezed out of a plastic bottle as a semisolid, toothpastelike goo – it’s stiff enough to rise out of a container that’s pointed straight up – and bitten off in large chunks. And therein lies the problem.

Some people are overdoing it. “Honey is great, but having it in small amounts to sweeten is really a healthy relationship with food, and using it to get a lot of followers and a lot of attention and having it in excess amounts is crazy,” Kristin Kirkpatrick, a registered dietitian at the Cleveland Clinic, told NBC.

Besides the possible weight gain from eating massive amounts of sugar, experts warned that “gobbling up bottles of frozen honey” could lead to stomach cramping, bloating, and diarrhea. Some TikTokers, NBC noted, said that they “were running for the bathroom.”

As we said, it’s a trend that is exploding.

Be sure to tune in next week, when we learn how TikTokers use ground meat as a skin moisturizer.
 

Having more diverse gut bacteria (greater microbiome richness) and specifically a greater abundance of 12 types of butyrate-producing bacteria were both associated with less insulin resistance and less type 2 diabetes, in a population-based observational study from the Netherlands.

Several studies have reported that there is less microbiome diversity in type 2 diabetes, Zhangling Chen, MD, PhD, of Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues note.

Their study also identified a dozen types of bacteria that ferment dietary fiber (undigested carbohydrates) in the gut to produce butyrate, a short-chain fatty acid, which may play a role in protection against type 2 diabetes.

“The current study is the first, to our knowledge, to comprehensively investigate the associations between gut microbiome composition [and] type 2 diabetes in a large population-based sample … which we adjusted for a series of key confounders,” the researchers write.

“These findings suggest that higher gut microbial diversity, along with specifically more butyrate-producing bacteria, may play a role in the development of type 2 diabetes, which may help guide future prevention and treatment strategies,” they conclude in their study published online July 29 in JAMA Network Open.
 

Confirmation of previous work, plus some new findings

The study confirms what many smaller ones have repeatedly shown – that low gut microbiome diversity is associated with increased risks of obesity and type 2 diabetes, Nanette I. Steinle, MD, RDN, who was not involved in the research, said in an interview.

A diet rich in fiber and prebiotics promotes gut biome diversity, added Dr. Steinle, chief of the endocrinology and diabetes section at Maryland Veterans Affairs Medical Center in Baltimore.

The findings add to other research, she noted, such as a prospective trial in which a high-fiber diet induced changes in the gut microbe that were linked to better glycemic regulation (Science. 2018;359:1151-6) and a study of a promising probiotic formula to treat diabetes.

“An important next step,” according to Dr. Steinle, “is to provide interventions like healthy diet or specific fiber types to see what can be done to produce lasting shifts in the gut microbiome and if these shifts result in improved metabolic health.”

Natalia Shulzhenko, MD, PhD, said: “Some of associations of taxa [bacteria groupings] with type 2 diabetes reported by this study are new.”

Dr. Shulzhenko and colleagues recently published a review of the role of gut microbiota in type 2 diabetes pathophysiology that summarized evidence from 42 human studies as well as preclinical studies and clinical trials of probiotic treatments (EBioMedicine. 2020;51:102590).

“Besides adding new microbes to the list of potential pathobionts [organisms that can cause harm] and beneficial microbes for type 2 diabetes,” the findings by Dr. Chen and colleagues “support a notion that different members of the gut microbial community may have similar effects on type 2 diabetes in different individuals,” commonly known as “functional redundancy,” Dr. Shulzhenko, associate professor, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, pointed out in an email.

Also “in line with previous studies,” the study shows that butyrate-producing bacteria are associated with type 2 diabetes.

She speculated that “these results will probably contribute to the body of knowledge that is needed to develop microbiota-based therapy and diagnostics.”
 

Which gut bacteria are linked with diabetes?

It is unclear which gut bacteria are associated with the development of type 2 diabetes, Dr. Chen and colleagues write.

To investigate this, they identified 1,418 participants from the Rotterdam Study and 748 participants from the LifeLines-DEEP study enrolled from January 2018 to December 2020. Of these participants, 193 had type 2 diabetes.

The participants provided stool samples that were used to measure gut microbiome composition using the 16S ribosomal RNA method. They also had blood tests to measure glucose and insulin, and researchers collected other demographic and medical data.

Participants in the Rotterdam study were older than in the LifeLines Deep study (mean age, 62 vs. 45 years). Both cohorts included slightly more men than women (58%).

Dr. Chen and colleagues identified 126 (bacteria) genera in the gut microbiome in the Rotterdam study and 184 genera in the LifeLines Deep study.

After correcting for age, sex, smoking, education, physical activity, alcohol intake, daily calories, body mass index, and use of lipid-lowering medication or proton pump inhibitors, higher microbiome diversity was associated with lower insulin resistance and a lower prevalence of type 2 diabetes.

A higher abundance of each of seven types of butyrate-producing bacteria – Christensenellaceae, Christensenellaceae R7 group, Marvinbryantia, Ruminococcaceae UCG-005, Ruminococcaceae UCG-008, Ruminococcaceae UCG-010, and Ruminococcaceae NK4A214 group – was associated with lower insulin resistance, after adjusting for confounders such as diet and medications (all P < .001).

And a higher abundance of each of five other types of butyrate-producing bacteria – Clostridiaceae 1, Peptostreptococcaceae, Clostridium sensu stricto 1, Intestinibacter, and Romboutsia – was associated with less type 2 diabetes (all P < .001). 

Study limitations include that gut microbiome composition was determined from stool (fecal) samples, whereas the actual composition varies in different locations along the intestine, and the study also lacked information about butyrate concentrations in stool or blood, the researchers note.

They call for “future research [to] validate the hypothesis of butyrate-producing bacteria affecting glucose metabolism and diabetes risk via production of butyrate.”

The authors and Dr. Shulzhenko have reported no relevant financial relationships. Dr. Steinle has reported receiving funding from the National Institutes of Health and conducting a study funded by Kowa through the VA.

A version of this article first appeared on Medscape.com.

Having more diverse gut bacteria (greater microbiome richness) and specifically a greater abundance of 12 types of butyrate-producing bacteria were both associated with less insulin resistance and less type 2 diabetes, in a population-based observational study from the Netherlands.

Several studies have reported that there is less microbiome diversity in type 2 diabetes, Zhangling Chen, MD, PhD, of Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues note.

Their study also identified a dozen types of bacteria that ferment dietary fiber (undigested carbohydrates) in the gut to produce butyrate, a short-chain fatty acid, which may play a role in protection against type 2 diabetes.

“The current study is the first, to our knowledge, to comprehensively investigate the associations between gut microbiome composition [and] type 2 diabetes in a large population-based sample … which we adjusted for a series of key confounders,” the researchers write.

“These findings suggest that higher gut microbial diversity, along with specifically more butyrate-producing bacteria, may play a role in the development of type 2 diabetes, which may help guide future prevention and treatment strategies,” they conclude in their study published online July 29 in JAMA Network Open.
 

Confirmation of previous work, plus some new findings

The study confirms what many smaller ones have repeatedly shown – that low gut microbiome diversity is associated with increased risks of obesity and type 2 diabetes, Nanette I. Steinle, MD, RDN, who was not involved in the research, said in an interview.

A diet rich in fiber and prebiotics promotes gut biome diversity, added Dr. Steinle, chief of the endocrinology and diabetes section at Maryland Veterans Affairs Medical Center in Baltimore.

The findings add to other research, she noted, such as a prospective trial in which a high-fiber diet induced changes in the gut microbe that were linked to better glycemic regulation (Science. 2018;359:1151-6) and a study of a promising probiotic formula to treat diabetes.

“An important next step,” according to Dr. Steinle, “is to provide interventions like healthy diet or specific fiber types to see what can be done to produce lasting shifts in the gut microbiome and if these shifts result in improved metabolic health.”

Natalia Shulzhenko, MD, PhD, said: “Some of associations of taxa [bacteria groupings] with type 2 diabetes reported by this study are new.”

Dr. Shulzhenko and colleagues recently published a review of the role of gut microbiota in type 2 diabetes pathophysiology that summarized evidence from 42 human studies as well as preclinical studies and clinical trials of probiotic treatments (EBioMedicine. 2020;51:102590).

“Besides adding new microbes to the list of potential pathobionts [organisms that can cause harm] and beneficial microbes for type 2 diabetes,” the findings by Dr. Chen and colleagues “support a notion that different members of the gut microbial community may have similar effects on type 2 diabetes in different individuals,” commonly known as “functional redundancy,” Dr. Shulzhenko, associate professor, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, pointed out in an email.

Also “in line with previous studies,” the study shows that butyrate-producing bacteria are associated with type 2 diabetes.

She speculated that “these results will probably contribute to the body of knowledge that is needed to develop microbiota-based therapy and diagnostics.”
 

Which gut bacteria are linked with diabetes?

It is unclear which gut bacteria are associated with the development of type 2 diabetes, Dr. Chen and colleagues write.

To investigate this, they identified 1,418 participants from the Rotterdam Study and 748 participants from the LifeLines-DEEP study enrolled from January 2018 to December 2020. Of these participants, 193 had type 2 diabetes.

The participants provided stool samples that were used to measure gut microbiome composition using the 16S ribosomal RNA method. They also had blood tests to measure glucose and insulin, and researchers collected other demographic and medical data.

Participants in the Rotterdam study were older than in the LifeLines Deep study (mean age, 62 vs. 45 years). Both cohorts included slightly more men than women (58%).

Dr. Chen and colleagues identified 126 (bacteria) genera in the gut microbiome in the Rotterdam study and 184 genera in the LifeLines Deep study.

After correcting for age, sex, smoking, education, physical activity, alcohol intake, daily calories, body mass index, and use of lipid-lowering medication or proton pump inhibitors, higher microbiome diversity was associated with lower insulin resistance and a lower prevalence of type 2 diabetes.

A higher abundance of each of seven types of butyrate-producing bacteria – Christensenellaceae, Christensenellaceae R7 group, Marvinbryantia, Ruminococcaceae UCG-005, Ruminococcaceae UCG-008, Ruminococcaceae UCG-010, and Ruminococcaceae NK4A214 group – was associated with lower insulin resistance, after adjusting for confounders such as diet and medications (all P < .001).

And a higher abundance of each of five other types of butyrate-producing bacteria – Clostridiaceae 1, Peptostreptococcaceae, Clostridium sensu stricto 1, Intestinibacter, and Romboutsia – was associated with less type 2 diabetes (all P < .001). 

Study limitations include that gut microbiome composition was determined from stool (fecal) samples, whereas the actual composition varies in different locations along the intestine, and the study also lacked information about butyrate concentrations in stool or blood, the researchers note.

They call for “future research [to] validate the hypothesis of butyrate-producing bacteria affecting glucose metabolism and diabetes risk via production of butyrate.”

The authors and Dr. Shulzhenko have reported no relevant financial relationships. Dr. Steinle has reported receiving funding from the National Institutes of Health and conducting a study funded by Kowa through the VA.

A version of this article first appeared on Medscape.com.

Having more diverse gut bacteria (greater microbiome richness) and specifically a greater abundance of 12 types of butyrate-producing bacteria were both associated with less insulin resistance and less type 2 diabetes, in a population-based observational study from the Netherlands.

Several studies have reported that there is less microbiome diversity in type 2 diabetes, Zhangling Chen, MD, PhD, of Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues note.

Their study also identified a dozen types of bacteria that ferment dietary fiber (undigested carbohydrates) in the gut to produce butyrate, a short-chain fatty acid, which may play a role in protection against type 2 diabetes.

“The current study is the first, to our knowledge, to comprehensively investigate the associations between gut microbiome composition [and] type 2 diabetes in a large population-based sample … which we adjusted for a series of key confounders,” the researchers write.

“These findings suggest that higher gut microbial diversity, along with specifically more butyrate-producing bacteria, may play a role in the development of type 2 diabetes, which may help guide future prevention and treatment strategies,” they conclude in their study published online July 29 in JAMA Network Open.
 

Confirmation of previous work, plus some new findings

The study confirms what many smaller ones have repeatedly shown – that low gut microbiome diversity is associated with increased risks of obesity and type 2 diabetes, Nanette I. Steinle, MD, RDN, who was not involved in the research, said in an interview.

A diet rich in fiber and prebiotics promotes gut biome diversity, added Dr. Steinle, chief of the endocrinology and diabetes section at Maryland Veterans Affairs Medical Center in Baltimore.

The findings add to other research, she noted, such as a prospective trial in which a high-fiber diet induced changes in the gut microbe that were linked to better glycemic regulation (Science. 2018;359:1151-6) and a study of a promising probiotic formula to treat diabetes.

“An important next step,” according to Dr. Steinle, “is to provide interventions like healthy diet or specific fiber types to see what can be done to produce lasting shifts in the gut microbiome and if these shifts result in improved metabolic health.”

Natalia Shulzhenko, MD, PhD, said: “Some of associations of taxa [bacteria groupings] with type 2 diabetes reported by this study are new.”

Dr. Shulzhenko and colleagues recently published a review of the role of gut microbiota in type 2 diabetes pathophysiology that summarized evidence from 42 human studies as well as preclinical studies and clinical trials of probiotic treatments (EBioMedicine. 2020;51:102590).

“Besides adding new microbes to the list of potential pathobionts [organisms that can cause harm] and beneficial microbes for type 2 diabetes,” the findings by Dr. Chen and colleagues “support a notion that different members of the gut microbial community may have similar effects on type 2 diabetes in different individuals,” commonly known as “functional redundancy,” Dr. Shulzhenko, associate professor, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, pointed out in an email.

Also “in line with previous studies,” the study shows that butyrate-producing bacteria are associated with type 2 diabetes.

She speculated that “these results will probably contribute to the body of knowledge that is needed to develop microbiota-based therapy and diagnostics.”
 

Which gut bacteria are linked with diabetes?

It is unclear which gut bacteria are associated with the development of type 2 diabetes, Dr. Chen and colleagues write.

To investigate this, they identified 1,418 participants from the Rotterdam Study and 748 participants from the LifeLines-DEEP study enrolled from January 2018 to December 2020. Of these participants, 193 had type 2 diabetes.

The participants provided stool samples that were used to measure gut microbiome composition using the 16S ribosomal RNA method. They also had blood tests to measure glucose and insulin, and researchers collected other demographic and medical data.

Participants in the Rotterdam study were older than in the LifeLines Deep study (mean age, 62 vs. 45 years). Both cohorts included slightly more men than women (58%).

Dr. Chen and colleagues identified 126 (bacteria) genera in the gut microbiome in the Rotterdam study and 184 genera in the LifeLines Deep study.

After correcting for age, sex, smoking, education, physical activity, alcohol intake, daily calories, body mass index, and use of lipid-lowering medication or proton pump inhibitors, higher microbiome diversity was associated with lower insulin resistance and a lower prevalence of type 2 diabetes.

A higher abundance of each of seven types of butyrate-producing bacteria – Christensenellaceae, Christensenellaceae R7 group, Marvinbryantia, Ruminococcaceae UCG-005, Ruminococcaceae UCG-008, Ruminococcaceae UCG-010, and Ruminococcaceae NK4A214 group – was associated with lower insulin resistance, after adjusting for confounders such as diet and medications (all P < .001).

And a higher abundance of each of five other types of butyrate-producing bacteria – Clostridiaceae 1, Peptostreptococcaceae, Clostridium sensu stricto 1, Intestinibacter, and Romboutsia – was associated with less type 2 diabetes (all P < .001). 

Study limitations include that gut microbiome composition was determined from stool (fecal) samples, whereas the actual composition varies in different locations along the intestine, and the study also lacked information about butyrate concentrations in stool or blood, the researchers note.

They call for “future research [to] validate the hypothesis of butyrate-producing bacteria affecting glucose metabolism and diabetes risk via production of butyrate.”

The authors and Dr. Shulzhenko have reported no relevant financial relationships. Dr. Steinle has reported receiving funding from the National Institutes of Health and conducting a study funded by Kowa through the VA.

A version of this article first appeared on Medscape.com.