Arrhythmias & EP

Cardiovascular complications are uncommon for children and young adults after COVID-19 disease or SARS-CoV-2 infection, according to a new scientific statement from the American Heart Association.

However, the infection can cause some children and young people to experience arrhythmias, myocarditis, pericarditis, or multisystem inflammatory syndrome (MIS-C), a new condition identified during the pandemic, it notes.

The statement details what has been learned about how to treat, manage, and prevent cardiovascular complications associated with COVID-19 in children and young adults and calls for more research, including studies following the short- and long-term cardiovascular effects.

It also reports that COVID-19 vaccines have been found to prevent severe COVID-19 disease and decrease the risk of developing MIS-C by 91% among children ages 12-18 years.

On returning to sports, it says data suggest it is safe for young people with mild or asymptomatic COVID-19 to resume exercise after recovery from symptoms. For those with more serious infections, it recommends additional tests, including cardiac enzyme levels, electrocardiogram, and echocardiogram, before returning to sports or strenuous physical exercise.

The scientific statement was published online on in Circulation.

“Two years into the pandemic and with vast amounts of research conducted in children with COVID-19, this statement summarizes what we know so far related to COVID-19 in children,” said chair of the statement writing group Pei-Ni Jone, MD, from the Children’s Hospital Colorado, Aurora.

Analysis of the latest research indicates children generally have mild symptoms from SARS-CoV-2 infection. In the U.S., as of Feb. 24, 2022, children under 18 years of age have accounted for 17.6% of total COVID-19 cases and about 0.1% of deaths from the virus, the report states.  

In addition, young adults, ages 18-29 years, have accounted for 21.3% of cases and 0.8% of deaths from COVID-19.

Like adults, children with underlying medical conditions such as chronic lung disease or obesity and those who are immunocompromised are more likely to be hospitalized, to be admitted to an intensive care unit, and to die of COVID-19, the statement notes. There are conflicting reports on the risk of severe COVID-19 in children and young adults with congenital heart disease, with some reports suggesting a slightly increased risk of severe COVID-19.

In terms of cardiovascular complications of COVID-19 in children, arrhythmias have included ventricular tachycardia and atrial tachycardia, as well as first-degree atrioventricular block. Although arrhythmias generally self-resolve without the need for treatment, prophylactic antiarrhythmics have been administered in some cases, and death caused by recurrent ventricular tachycardia in an adolescent with hypertrophic cardiomyopathy has been described.

Elevations of troponin, electrocardiographic abnormalities, including ST-segment changes, and delayed gadolinium enhancement on cardiac magnetic resonance imaging have been seen in those with myocardial involvement. Although death is rare, both sudden cardiac death and death after intensive medical and supportive therapies have occurred in children with severe myocardial involvement.

In a large retrospective pediatric case series of SARS-CoV-2–associated deaths in individuals under 21 years of age, the median age at death was 17 years, 63% were male, 28% were Black, and 46% were Hispanic. Of those who died, 86% had a comorbid condition, with obesity (42%) and asthma (29%) being the most common.

But the report concludes that: “Although children with comorbidities are at increased risk for symptomatic SARS-CoV-2 infection, compared with healthy children, cardiovascular complications, severe illness, and death are uncommon.”
 

MIS-C: Rare but severe

The authors of the statement explain that children and some young adults may develop MIS-C, a relatively rare but severe inflammatory syndrome generally occurring 2-6 weeks after infection with SARS-CoV-2 that can affect the heart and multiple organ systems.

In the first year of the pandemic, more than 2,600 cases of MIS-C were reported to the Centers for Disease Control and Prevention, at an estimated rate of 1 case per 3,164 cases of SARS-CoV-2 infection in children, with MIS-C disproportionately affecting Hispanic and Black children.

As many as 50% of children with MIS-C have myocardial involvement, including decreased left ventricular function, coronary artery dilation or aneurysms, myocarditis, elevated troponin and BNP or NT-proBNP, or pericardial effusion. Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C, neutrophil/lymphocyte ratio may be higher, and platelet counts lower than those with non–MIS-C febrile illnesses.

Fortunately, the outcome of MIS-C is generally very good, with resolution of inflammation and cardiovascular abnormalities within 1-4 weeks of diagnosis, the report says.

However, there have been reports of progression of coronary artery aneurysms after discharge, highlighting the potential for long-term complications. Death resulting from MIS-C is rare, with a mortality rate of 1.4%-1.9%.

Compared with children and young adults who died of acute SARS-CoV-2 infection, most of the fatalities from MIS-C were in previously healthy individuals without comorbidities.

The authors recommend structured follow-up of patients with MIS-C because of concern about progression of cardiac complications and an unclear long-term prognosis.

The statement notes that the first-line treatment for MIS-C is typically intravenous immunoglobulin (IVIG) and patients with poor ventricular function may need to have IVIG in divided doses to tolerate the fluid load.  

Supportive treatment for heart failure and vasoplegic shock often requires aggressive management in an ICU for administration of inotropes and vasoactive medications. Antiplatelet therapy with low-dose aspirin is considered in patients with coronary artery involvement, and anticoagulation is added, depending on the degree of coronary artery dilation.
 

COVID-19 vaccination

The statement notes that vaccines can prevent patients from getting COVID-19 and decrease the risk of MIS-C by 91% among children 12-18 years of age.

On vaccine-associated myocarditis, it concludes the benefits of getting the vaccines outweigh the risks.  

For example, for every 1 million doses of the mRNA COVID-19 vaccines in males ages 12-29 years (the highest risk group for vaccine-associated myocarditis), it is estimated that 11,000 COVID-19 cases, 560 hospitalizations, and six deaths would be prevented, whereas 39-47 cases of myocarditis would be expected.

But it adds that the CDC is continuing to follow myocarditis in children and young adults closely, particularly a possible connection to the mRNA COVID-19 vaccines.

The statement says that more research is needed to better understand the mechanisms and optimal treatment approaches for SARS-CoV-2 infection, vaccine-associated myocarditis, the long-term outcomes of both COVID-19 and MIS-C, and the impact of these various conditions on the heart in children and young adults. In addition, any new antiviral therapies need to be tested in clinical trials focused on children.

“Although much has been learned about how the virus impacts children’s and young adult’s hearts, how to best treat cardiovascular complications, and prevent severe illness, continued clinical research trials are needed to better understand the long-term cardiovascular impacts,” Dr. Jone said. “It is also important to address health disparities that have become more apparent during the pandemic. We must work to ensure all children receive equal access to vaccination and high-quality care.”

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

Cardiovascular complications are uncommon for children and young adults after COVID-19 disease or SARS-CoV-2 infection, according to a new scientific statement from the American Heart Association.

However, the infection can cause some children and young people to experience arrhythmias, myocarditis, pericarditis, or multisystem inflammatory syndrome (MIS-C), a new condition identified during the pandemic, it notes.

The statement details what has been learned about how to treat, manage, and prevent cardiovascular complications associated with COVID-19 in children and young adults and calls for more research, including studies following the short- and long-term cardiovascular effects.

It also reports that COVID-19 vaccines have been found to prevent severe COVID-19 disease and decrease the risk of developing MIS-C by 91% among children ages 12-18 years.

On returning to sports, it says data suggest it is safe for young people with mild or asymptomatic COVID-19 to resume exercise after recovery from symptoms. For those with more serious infections, it recommends additional tests, including cardiac enzyme levels, electrocardiogram, and echocardiogram, before returning to sports or strenuous physical exercise.

The scientific statement was published online on in Circulation.

“Two years into the pandemic and with vast amounts of research conducted in children with COVID-19, this statement summarizes what we know so far related to COVID-19 in children,” said chair of the statement writing group Pei-Ni Jone, MD, from the Children’s Hospital Colorado, Aurora.

Analysis of the latest research indicates children generally have mild symptoms from SARS-CoV-2 infection. In the U.S., as of Feb. 24, 2022, children under 18 years of age have accounted for 17.6% of total COVID-19 cases and about 0.1% of deaths from the virus, the report states.  

In addition, young adults, ages 18-29 years, have accounted for 21.3% of cases and 0.8% of deaths from COVID-19.

Like adults, children with underlying medical conditions such as chronic lung disease or obesity and those who are immunocompromised are more likely to be hospitalized, to be admitted to an intensive care unit, and to die of COVID-19, the statement notes. There are conflicting reports on the risk of severe COVID-19 in children and young adults with congenital heart disease, with some reports suggesting a slightly increased risk of severe COVID-19.

In terms of cardiovascular complications of COVID-19 in children, arrhythmias have included ventricular tachycardia and atrial tachycardia, as well as first-degree atrioventricular block. Although arrhythmias generally self-resolve without the need for treatment, prophylactic antiarrhythmics have been administered in some cases, and death caused by recurrent ventricular tachycardia in an adolescent with hypertrophic cardiomyopathy has been described.

Elevations of troponin, electrocardiographic abnormalities, including ST-segment changes, and delayed gadolinium enhancement on cardiac magnetic resonance imaging have been seen in those with myocardial involvement. Although death is rare, both sudden cardiac death and death after intensive medical and supportive therapies have occurred in children with severe myocardial involvement.

In a large retrospective pediatric case series of SARS-CoV-2–associated deaths in individuals under 21 years of age, the median age at death was 17 years, 63% were male, 28% were Black, and 46% were Hispanic. Of those who died, 86% had a comorbid condition, with obesity (42%) and asthma (29%) being the most common.

But the report concludes that: “Although children with comorbidities are at increased risk for symptomatic SARS-CoV-2 infection, compared with healthy children, cardiovascular complications, severe illness, and death are uncommon.”
 

MIS-C: Rare but severe

The authors of the statement explain that children and some young adults may develop MIS-C, a relatively rare but severe inflammatory syndrome generally occurring 2-6 weeks after infection with SARS-CoV-2 that can affect the heart and multiple organ systems.

In the first year of the pandemic, more than 2,600 cases of MIS-C were reported to the Centers for Disease Control and Prevention, at an estimated rate of 1 case per 3,164 cases of SARS-CoV-2 infection in children, with MIS-C disproportionately affecting Hispanic and Black children.

As many as 50% of children with MIS-C have myocardial involvement, including decreased left ventricular function, coronary artery dilation or aneurysms, myocarditis, elevated troponin and BNP or NT-proBNP, or pericardial effusion. Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C, neutrophil/lymphocyte ratio may be higher, and platelet counts lower than those with non–MIS-C febrile illnesses.

Fortunately, the outcome of MIS-C is generally very good, with resolution of inflammation and cardiovascular abnormalities within 1-4 weeks of diagnosis, the report says.

However, there have been reports of progression of coronary artery aneurysms after discharge, highlighting the potential for long-term complications. Death resulting from MIS-C is rare, with a mortality rate of 1.4%-1.9%.

Compared with children and young adults who died of acute SARS-CoV-2 infection, most of the fatalities from MIS-C were in previously healthy individuals without comorbidities.

The authors recommend structured follow-up of patients with MIS-C because of concern about progression of cardiac complications and an unclear long-term prognosis.

The statement notes that the first-line treatment for MIS-C is typically intravenous immunoglobulin (IVIG) and patients with poor ventricular function may need to have IVIG in divided doses to tolerate the fluid load.  

Supportive treatment for heart failure and vasoplegic shock often requires aggressive management in an ICU for administration of inotropes and vasoactive medications. Antiplatelet therapy with low-dose aspirin is considered in patients with coronary artery involvement, and anticoagulation is added, depending on the degree of coronary artery dilation.
 

COVID-19 vaccination

The statement notes that vaccines can prevent patients from getting COVID-19 and decrease the risk of MIS-C by 91% among children 12-18 years of age.

On vaccine-associated myocarditis, it concludes the benefits of getting the vaccines outweigh the risks.  

For example, for every 1 million doses of the mRNA COVID-19 vaccines in males ages 12-29 years (the highest risk group for vaccine-associated myocarditis), it is estimated that 11,000 COVID-19 cases, 560 hospitalizations, and six deaths would be prevented, whereas 39-47 cases of myocarditis would be expected.

But it adds that the CDC is continuing to follow myocarditis in children and young adults closely, particularly a possible connection to the mRNA COVID-19 vaccines.

The statement says that more research is needed to better understand the mechanisms and optimal treatment approaches for SARS-CoV-2 infection, vaccine-associated myocarditis, the long-term outcomes of both COVID-19 and MIS-C, and the impact of these various conditions on the heart in children and young adults. In addition, any new antiviral therapies need to be tested in clinical trials focused on children.

“Although much has been learned about how the virus impacts children’s and young adult’s hearts, how to best treat cardiovascular complications, and prevent severe illness, continued clinical research trials are needed to better understand the long-term cardiovascular impacts,” Dr. Jone said. “It is also important to address health disparities that have become more apparent during the pandemic. We must work to ensure all children receive equal access to vaccination and high-quality care.”

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

Cardiovascular complications are uncommon for children and young adults after COVID-19 disease or SARS-CoV-2 infection, according to a new scientific statement from the American Heart Association.

However, the infection can cause some children and young people to experience arrhythmias, myocarditis, pericarditis, or multisystem inflammatory syndrome (MIS-C), a new condition identified during the pandemic, it notes.

The statement details what has been learned about how to treat, manage, and prevent cardiovascular complications associated with COVID-19 in children and young adults and calls for more research, including studies following the short- and long-term cardiovascular effects.

It also reports that COVID-19 vaccines have been found to prevent severe COVID-19 disease and decrease the risk of developing MIS-C by 91% among children ages 12-18 years.

On returning to sports, it says data suggest it is safe for young people with mild or asymptomatic COVID-19 to resume exercise after recovery from symptoms. For those with more serious infections, it recommends additional tests, including cardiac enzyme levels, electrocardiogram, and echocardiogram, before returning to sports or strenuous physical exercise.

The scientific statement was published online on in Circulation.

“Two years into the pandemic and with vast amounts of research conducted in children with COVID-19, this statement summarizes what we know so far related to COVID-19 in children,” said chair of the statement writing group Pei-Ni Jone, MD, from the Children’s Hospital Colorado, Aurora.

Analysis of the latest research indicates children generally have mild symptoms from SARS-CoV-2 infection. In the U.S., as of Feb. 24, 2022, children under 18 years of age have accounted for 17.6% of total COVID-19 cases and about 0.1% of deaths from the virus, the report states.  

In addition, young adults, ages 18-29 years, have accounted for 21.3% of cases and 0.8% of deaths from COVID-19.

Like adults, children with underlying medical conditions such as chronic lung disease or obesity and those who are immunocompromised are more likely to be hospitalized, to be admitted to an intensive care unit, and to die of COVID-19, the statement notes. There are conflicting reports on the risk of severe COVID-19 in children and young adults with congenital heart disease, with some reports suggesting a slightly increased risk of severe COVID-19.

In terms of cardiovascular complications of COVID-19 in children, arrhythmias have included ventricular tachycardia and atrial tachycardia, as well as first-degree atrioventricular block. Although arrhythmias generally self-resolve without the need for treatment, prophylactic antiarrhythmics have been administered in some cases, and death caused by recurrent ventricular tachycardia in an adolescent with hypertrophic cardiomyopathy has been described.

Elevations of troponin, electrocardiographic abnormalities, including ST-segment changes, and delayed gadolinium enhancement on cardiac magnetic resonance imaging have been seen in those with myocardial involvement. Although death is rare, both sudden cardiac death and death after intensive medical and supportive therapies have occurred in children with severe myocardial involvement.

In a large retrospective pediatric case series of SARS-CoV-2–associated deaths in individuals under 21 years of age, the median age at death was 17 years, 63% were male, 28% were Black, and 46% were Hispanic. Of those who died, 86% had a comorbid condition, with obesity (42%) and asthma (29%) being the most common.

But the report concludes that: “Although children with comorbidities are at increased risk for symptomatic SARS-CoV-2 infection, compared with healthy children, cardiovascular complications, severe illness, and death are uncommon.”
 

MIS-C: Rare but severe

The authors of the statement explain that children and some young adults may develop MIS-C, a relatively rare but severe inflammatory syndrome generally occurring 2-6 weeks after infection with SARS-CoV-2 that can affect the heart and multiple organ systems.

In the first year of the pandemic, more than 2,600 cases of MIS-C were reported to the Centers for Disease Control and Prevention, at an estimated rate of 1 case per 3,164 cases of SARS-CoV-2 infection in children, with MIS-C disproportionately affecting Hispanic and Black children.

As many as 50% of children with MIS-C have myocardial involvement, including decreased left ventricular function, coronary artery dilation or aneurysms, myocarditis, elevated troponin and BNP or NT-proBNP, or pericardial effusion. Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C, neutrophil/lymphocyte ratio may be higher, and platelet counts lower than those with non–MIS-C febrile illnesses.

Fortunately, the outcome of MIS-C is generally very good, with resolution of inflammation and cardiovascular abnormalities within 1-4 weeks of diagnosis, the report says.

However, there have been reports of progression of coronary artery aneurysms after discharge, highlighting the potential for long-term complications. Death resulting from MIS-C is rare, with a mortality rate of 1.4%-1.9%.

Compared with children and young adults who died of acute SARS-CoV-2 infection, most of the fatalities from MIS-C were in previously healthy individuals without comorbidities.

The authors recommend structured follow-up of patients with MIS-C because of concern about progression of cardiac complications and an unclear long-term prognosis.

The statement notes that the first-line treatment for MIS-C is typically intravenous immunoglobulin (IVIG) and patients with poor ventricular function may need to have IVIG in divided doses to tolerate the fluid load.  

Supportive treatment for heart failure and vasoplegic shock often requires aggressive management in an ICU for administration of inotropes and vasoactive medications. Antiplatelet therapy with low-dose aspirin is considered in patients with coronary artery involvement, and anticoagulation is added, depending on the degree of coronary artery dilation.
 

COVID-19 vaccination

The statement notes that vaccines can prevent patients from getting COVID-19 and decrease the risk of MIS-C by 91% among children 12-18 years of age.

On vaccine-associated myocarditis, it concludes the benefits of getting the vaccines outweigh the risks.  

For example, for every 1 million doses of the mRNA COVID-19 vaccines in males ages 12-29 years (the highest risk group for vaccine-associated myocarditis), it is estimated that 11,000 COVID-19 cases, 560 hospitalizations, and six deaths would be prevented, whereas 39-47 cases of myocarditis would be expected.

But it adds that the CDC is continuing to follow myocarditis in children and young adults closely, particularly a possible connection to the mRNA COVID-19 vaccines.

The statement says that more research is needed to better understand the mechanisms and optimal treatment approaches for SARS-CoV-2 infection, vaccine-associated myocarditis, the long-term outcomes of both COVID-19 and MIS-C, and the impact of these various conditions on the heart in children and young adults. In addition, any new antiviral therapies need to be tested in clinical trials focused on children.

“Although much has been learned about how the virus impacts children’s and young adult’s hearts, how to best treat cardiovascular complications, and prevent severe illness, continued clinical research trials are needed to better understand the long-term cardiovascular impacts,” Dr. Jone said. “It is also important to address health disparities that have become more apparent during the pandemic. We must work to ensure all children receive equal access to vaccination and high-quality care.”

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

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

A popular fitness tracker company has received approval from the Food and Drug Administration for a new software algorithm to detect atrial fibrillation (AFib), Fitbit announced on April 11.

The algorithm will be the basis of an upcoming Fitbit feature called Irregular Heart Rhythm Notifications, the company said in a press release.

The approval was based on data from the Fitbit Heart Study, which was conducted entirely virtually in more than 455,000 U.S. adults. Participants who had an irregular heart rhythm detected by the software algorithm were notified and invited to meet with a telehealth doctor. They then received a 1-week ECG patch monitor to wear along with the smartwatch or fitness tracker.

Results, presented at the annual scientific sessions of the American Heart Association in November 2021, showed that the positive predictive value of the Fitbit algorithm for detecting undiagnosed AFib with a range of wearable devices was 98%. Notably, irregular heart rhythm detection occurred in 1% of participants overall and 4% of those older than 65 years.

The algorithm works by using an optical measurement method called photoplethysmography (PPG), along with heart rate input from the Fitbit’s photodetector device.

It operates only when the user is still or at rest, so overnight use is important for detection, the company noted.

The upcoming Irregular Heart Rhythm Notifications feature will complement the existing ECG app, providing two ways to detect AFib. The ECG app provides a “spot-check approach” in which the users can screen themselves, and the PPG-based feature will allow for long-term heart rhythm assessment, the statement explained.

“Undiagnosed atrial fibrillation can lead to strokes, and early detection of atrial fibrillation may allow doctors to prescribe medications that are effective at preventing strokes,” said Steven A. Lubitz, MD, MPH, a cardiologist at Harvard University and Massachusetts General Hospital, both in Boston, at the AHA meeting.

A popular fitness tracker company has received approval from the Food and Drug Administration for a new software algorithm to detect atrial fibrillation (AFib), Fitbit announced on April 11.

The algorithm will be the basis of an upcoming Fitbit feature called Irregular Heart Rhythm Notifications, the company said in a press release.

The approval was based on data from the Fitbit Heart Study, which was conducted entirely virtually in more than 455,000 U.S. adults. Participants who had an irregular heart rhythm detected by the software algorithm were notified and invited to meet with a telehealth doctor. They then received a 1-week ECG patch monitor to wear along with the smartwatch or fitness tracker.

Results, presented at the annual scientific sessions of the American Heart Association in November 2021, showed that the positive predictive value of the Fitbit algorithm for detecting undiagnosed AFib with a range of wearable devices was 98%. Notably, irregular heart rhythm detection occurred in 1% of participants overall and 4% of those older than 65 years.

The algorithm works by using an optical measurement method called photoplethysmography (PPG), along with heart rate input from the Fitbit’s photodetector device.

It operates only when the user is still or at rest, so overnight use is important for detection, the company noted.

The upcoming Irregular Heart Rhythm Notifications feature will complement the existing ECG app, providing two ways to detect AFib. The ECG app provides a “spot-check approach” in which the users can screen themselves, and the PPG-based feature will allow for long-term heart rhythm assessment, the statement explained.

“Undiagnosed atrial fibrillation can lead to strokes, and early detection of atrial fibrillation may allow doctors to prescribe medications that are effective at preventing strokes,” said Steven A. Lubitz, MD, MPH, a cardiologist at Harvard University and Massachusetts General Hospital, both in Boston, at the AHA meeting.

A popular fitness tracker company has received approval from the Food and Drug Administration for a new software algorithm to detect atrial fibrillation (AFib), Fitbit announced on April 11.

The algorithm will be the basis of an upcoming Fitbit feature called Irregular Heart Rhythm Notifications, the company said in a press release.

The approval was based on data from the Fitbit Heart Study, which was conducted entirely virtually in more than 455,000 U.S. adults. Participants who had an irregular heart rhythm detected by the software algorithm were notified and invited to meet with a telehealth doctor. They then received a 1-week ECG patch monitor to wear along with the smartwatch or fitness tracker.

Results, presented at the annual scientific sessions of the American Heart Association in November 2021, showed that the positive predictive value of the Fitbit algorithm for detecting undiagnosed AFib with a range of wearable devices was 98%. Notably, irregular heart rhythm detection occurred in 1% of participants overall and 4% of those older than 65 years.

The algorithm works by using an optical measurement method called photoplethysmography (PPG), along with heart rate input from the Fitbit’s photodetector device.

It operates only when the user is still or at rest, so overnight use is important for detection, the company noted.

The upcoming Irregular Heart Rhythm Notifications feature will complement the existing ECG app, providing two ways to detect AFib. The ECG app provides a “spot-check approach” in which the users can screen themselves, and the PPG-based feature will allow for long-term heart rhythm assessment, the statement explained.

“Undiagnosed atrial fibrillation can lead to strokes, and early detection of atrial fibrillation may allow doctors to prescribe medications that are effective at preventing strokes,” said Steven A. Lubitz, MD, MPH, a cardiologist at Harvard University and Massachusetts General Hospital, both in Boston, at the AHA meeting.

Structural aortic valve deterioration (SVD) at 5 years is lower following repair with a contemporary transcatheter implantation (TAVI) device than with surgery, according to a pooled analysis of major trials.

For healthier patients with a relatively long life expectancy, this is important information for deciding whether to undergo TAVI or surgical aortic valve repair (SAVR), Michael J. Reardon, MD, said at the annual scientific sessions of the American College of Cardiology.

“Every week I get this question about which repair is more durable,” said Dr. Reardon, whose study was not only designed to compare device deterioration but to evaluate the effect of SVD on major outcomes.

In this analysis, the rates of SVD were compared for the self-expanding supra-annular CoreValve Evolut device and SAVR. The SVD curves separated within the first year. At 5 years, the differences were highly significant favoring TAVI (2.57% vs. 4.38%; P = .0095).

As part of this analysis, the impact of SVD was also assessed independent of type of repair. At 5 years, those with SVD relative to those without had an approximately twofold increase in all-cause mortality, cardiovascular mortality, and hospitalization of aortic valve worsening. These risks were elevated regardless of type of valve repair.

The data presented by Dr. Reardon can be considered device specific. The earlier PARTNER 2A study comparing older- and newer-generation TAVI devices with SAVR produced a different result. When a second-generation balloon-expandable SAPIEN XT device and a third-generation SAPIEN 3 device were compared with surgery, neither device achieved lower SVD rates relative to SAVR.

In PARTNER 2A, the SVD rate for the older device was nearly three times greater than SAVR (1.61 vs. 0.58 per 100 patient-years). The numerically higher SVD rates for the newer device (0.68 vs. 0.58 per 100 patient-years) was not statistically different, but the TAVI device was not superior.

More than 4,000 patients evaluated at 5 years

In the analysis presented by Dr. Reardon, data were pooled from the randomized CoreValve U.S. High-Risk Pivotal Trial and the SURTAVI Intermediate Risk Trial. Together, these studies randomized 971 patients to surgery and 1,128 patients to TAVI. Data on an additional 2,663 patients treated with the Evolut valve in two registries were added to the randomized trial data, providing data on 4,762 total patients with 5-year follow-up.

SVD was defined by two criteria. The first was a mean gradient increase of at least 10 mm Hg plus a mean overall gradient of at least 20 mm Hg as measured with echocardiography and assessed, when possible, by an independent core laboratory. The second was new-onset or increased intraprosthetic aortic regurgitation of at least moderate severity.

When graphed over time, the SVD curves separated in favor of TAVI after about 6 months of follow-up. The shape of the curves also differed. Unlike the steady rise in SVD observed in the surgery group, the SVD rate in the TAVI group remained below 1% for almost 4 years before beginning to climb.

There was greater relative benefit for the TAVI device in patients with annular diameters of 23 mm or less. Unlike the rise in SVD rates that began about 6 months after SAVR, the SVD rates in the TAVI patients remained at 0% for more than 2 years. At 5 years, the differences remained significant favoring TAVI (1.39% vs. 5.86%; P = .049).

In those with larger annular diameters, there was still a consistently lower SVD rate over time for TAVI relative to SAVR, but the trend for an advantage at 5 years fell just short of significance (2.48% vs. 3.96%; P = .067).
 

SVD linked to doubling of mortality

SVD worsened outcomes. When all data surgery and TAVI data were pooled, the hazard ratios corresponded with about a doubling of risk for major adverse outcomes, including all-cause mortality (HR, 1.98; P < .001), cardiovascular mortality (HR, 1.82; P = .008), and hospitalization for aortic valve disease or worsening heart failure (HR, 2.11; P = .01). The relative risks were similar in the two treatment groups, including the risk of all-cause mortality (HR, 2.24; P < .001 for TAVI vs. HR, 2.45; P = .002 for SAVR).

The predictors for SVD on multivariate analysis included female sex, increased body surface area, prior percutaneous coronary intervention, and a prior diagnosis of atrial fibrillation.

Design improvements in TAVI devices are likely to explain these results, said Dr. Reardon, chair of cardiovascular research at Houston Methodist Hospital.

“The CoreValve/Evolut supra-annular, self-expanding bioprosthesis is the first and only transcatheter bioprosthesis to demonstrate lower rates of SVD, compared with surgery,” Dr. Reardon said.

This analysis validated the risks posed by the definition of SVD applied in this study, which appears to be a practical tool for tracking valve function and patient risk. Dr. Reardon also said that the study confirms the value of serial Doppler transthoracic echocardiography as a tool for monitoring SVD.

Several experts agreed that this is important new information.

“This is a remarkable series of findings,” said James McClurken, MD, who is a cardiovascular surgeon affiliated with Temple University, Philadelphia, and practices in Doylestown, Penn. By both demonstrating the prognostic importance of SVD and showing differences between the study device and SAVR, this trial will yield practical data to inform patients about relative risks and benefits.

Athena Poppas, MD, the new president of the ACC and a professor of medicine at Brown University, Providence, R.I., called this study “practice changing” for the same reasons. She also thinks it has valuable data for guiding choice of intervention.

Overall, the data are likely to change thinking about the role of TAVI and surgery in younger, fit patients, according to Megan Coylewright, MD, chief of cardiology at Erlanger Cardiology, Chattanooga, Tenn.

“There are patients [in need of aortic valve repair] with a long life expectancy who have been told you have to have a surgical repair because we know they last longer,” she said. Although she said that relative outcomes after longer follow-up remain unknown, “I think this does throw that comment into question.”

Dr. Reardon has financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical. Dr. Poppas and McClurken reported no potential financial conflicts of interest. Dr. Coylewright reported financial relationships with Abbott, Alleviant, Boston Scientific, Cardiosmart, Edwards Lifesciences, Medtronic, and Occlutech. The study received financial support from Medtronic.

Structural aortic valve deterioration (SVD) at 5 years is lower following repair with a contemporary transcatheter implantation (TAVI) device than with surgery, according to a pooled analysis of major trials.

For healthier patients with a relatively long life expectancy, this is important information for deciding whether to undergo TAVI or surgical aortic valve repair (SAVR), Michael J. Reardon, MD, said at the annual scientific sessions of the American College of Cardiology.

“Every week I get this question about which repair is more durable,” said Dr. Reardon, whose study was not only designed to compare device deterioration but to evaluate the effect of SVD on major outcomes.

In this analysis, the rates of SVD were compared for the self-expanding supra-annular CoreValve Evolut device and SAVR. The SVD curves separated within the first year. At 5 years, the differences were highly significant favoring TAVI (2.57% vs. 4.38%; P = .0095).

As part of this analysis, the impact of SVD was also assessed independent of type of repair. At 5 years, those with SVD relative to those without had an approximately twofold increase in all-cause mortality, cardiovascular mortality, and hospitalization of aortic valve worsening. These risks were elevated regardless of type of valve repair.

The data presented by Dr. Reardon can be considered device specific. The earlier PARTNER 2A study comparing older- and newer-generation TAVI devices with SAVR produced a different result. When a second-generation balloon-expandable SAPIEN XT device and a third-generation SAPIEN 3 device were compared with surgery, neither device achieved lower SVD rates relative to SAVR.

In PARTNER 2A, the SVD rate for the older device was nearly three times greater than SAVR (1.61 vs. 0.58 per 100 patient-years). The numerically higher SVD rates for the newer device (0.68 vs. 0.58 per 100 patient-years) was not statistically different, but the TAVI device was not superior.

More than 4,000 patients evaluated at 5 years

In the analysis presented by Dr. Reardon, data were pooled from the randomized CoreValve U.S. High-Risk Pivotal Trial and the SURTAVI Intermediate Risk Trial. Together, these studies randomized 971 patients to surgery and 1,128 patients to TAVI. Data on an additional 2,663 patients treated with the Evolut valve in two registries were added to the randomized trial data, providing data on 4,762 total patients with 5-year follow-up.

SVD was defined by two criteria. The first was a mean gradient increase of at least 10 mm Hg plus a mean overall gradient of at least 20 mm Hg as measured with echocardiography and assessed, when possible, by an independent core laboratory. The second was new-onset or increased intraprosthetic aortic regurgitation of at least moderate severity.

When graphed over time, the SVD curves separated in favor of TAVI after about 6 months of follow-up. The shape of the curves also differed. Unlike the steady rise in SVD observed in the surgery group, the SVD rate in the TAVI group remained below 1% for almost 4 years before beginning to climb.

There was greater relative benefit for the TAVI device in patients with annular diameters of 23 mm or less. Unlike the rise in SVD rates that began about 6 months after SAVR, the SVD rates in the TAVI patients remained at 0% for more than 2 years. At 5 years, the differences remained significant favoring TAVI (1.39% vs. 5.86%; P = .049).

In those with larger annular diameters, there was still a consistently lower SVD rate over time for TAVI relative to SAVR, but the trend for an advantage at 5 years fell just short of significance (2.48% vs. 3.96%; P = .067).
 

SVD linked to doubling of mortality

SVD worsened outcomes. When all data surgery and TAVI data were pooled, the hazard ratios corresponded with about a doubling of risk for major adverse outcomes, including all-cause mortality (HR, 1.98; P < .001), cardiovascular mortality (HR, 1.82; P = .008), and hospitalization for aortic valve disease or worsening heart failure (HR, 2.11; P = .01). The relative risks were similar in the two treatment groups, including the risk of all-cause mortality (HR, 2.24; P < .001 for TAVI vs. HR, 2.45; P = .002 for SAVR).

The predictors for SVD on multivariate analysis included female sex, increased body surface area, prior percutaneous coronary intervention, and a prior diagnosis of atrial fibrillation.

Design improvements in TAVI devices are likely to explain these results, said Dr. Reardon, chair of cardiovascular research at Houston Methodist Hospital.

“The CoreValve/Evolut supra-annular, self-expanding bioprosthesis is the first and only transcatheter bioprosthesis to demonstrate lower rates of SVD, compared with surgery,” Dr. Reardon said.

This analysis validated the risks posed by the definition of SVD applied in this study, which appears to be a practical tool for tracking valve function and patient risk. Dr. Reardon also said that the study confirms the value of serial Doppler transthoracic echocardiography as a tool for monitoring SVD.

Several experts agreed that this is important new information.

“This is a remarkable series of findings,” said James McClurken, MD, who is a cardiovascular surgeon affiliated with Temple University, Philadelphia, and practices in Doylestown, Penn. By both demonstrating the prognostic importance of SVD and showing differences between the study device and SAVR, this trial will yield practical data to inform patients about relative risks and benefits.

Athena Poppas, MD, the new president of the ACC and a professor of medicine at Brown University, Providence, R.I., called this study “practice changing” for the same reasons. She also thinks it has valuable data for guiding choice of intervention.

Overall, the data are likely to change thinking about the role of TAVI and surgery in younger, fit patients, according to Megan Coylewright, MD, chief of cardiology at Erlanger Cardiology, Chattanooga, Tenn.

“There are patients [in need of aortic valve repair] with a long life expectancy who have been told you have to have a surgical repair because we know they last longer,” she said. Although she said that relative outcomes after longer follow-up remain unknown, “I think this does throw that comment into question.”

Dr. Reardon has financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical. Dr. Poppas and McClurken reported no potential financial conflicts of interest. Dr. Coylewright reported financial relationships with Abbott, Alleviant, Boston Scientific, Cardiosmart, Edwards Lifesciences, Medtronic, and Occlutech. The study received financial support from Medtronic.

Structural aortic valve deterioration (SVD) at 5 years is lower following repair with a contemporary transcatheter implantation (TAVI) device than with surgery, according to a pooled analysis of major trials.

For healthier patients with a relatively long life expectancy, this is important information for deciding whether to undergo TAVI or surgical aortic valve repair (SAVR), Michael J. Reardon, MD, said at the annual scientific sessions of the American College of Cardiology.

“Every week I get this question about which repair is more durable,” said Dr. Reardon, whose study was not only designed to compare device deterioration but to evaluate the effect of SVD on major outcomes.

In this analysis, the rates of SVD were compared for the self-expanding supra-annular CoreValve Evolut device and SAVR. The SVD curves separated within the first year. At 5 years, the differences were highly significant favoring TAVI (2.57% vs. 4.38%; P = .0095).

As part of this analysis, the impact of SVD was also assessed independent of type of repair. At 5 years, those with SVD relative to those without had an approximately twofold increase in all-cause mortality, cardiovascular mortality, and hospitalization of aortic valve worsening. These risks were elevated regardless of type of valve repair.

The data presented by Dr. Reardon can be considered device specific. The earlier PARTNER 2A study comparing older- and newer-generation TAVI devices with SAVR produced a different result. When a second-generation balloon-expandable SAPIEN XT device and a third-generation SAPIEN 3 device were compared with surgery, neither device achieved lower SVD rates relative to SAVR.

In PARTNER 2A, the SVD rate for the older device was nearly three times greater than SAVR (1.61 vs. 0.58 per 100 patient-years). The numerically higher SVD rates for the newer device (0.68 vs. 0.58 per 100 patient-years) was not statistically different, but the TAVI device was not superior.

More than 4,000 patients evaluated at 5 years

In the analysis presented by Dr. Reardon, data were pooled from the randomized CoreValve U.S. High-Risk Pivotal Trial and the SURTAVI Intermediate Risk Trial. Together, these studies randomized 971 patients to surgery and 1,128 patients to TAVI. Data on an additional 2,663 patients treated with the Evolut valve in two registries were added to the randomized trial data, providing data on 4,762 total patients with 5-year follow-up.

SVD was defined by two criteria. The first was a mean gradient increase of at least 10 mm Hg plus a mean overall gradient of at least 20 mm Hg as measured with echocardiography and assessed, when possible, by an independent core laboratory. The second was new-onset or increased intraprosthetic aortic regurgitation of at least moderate severity.

When graphed over time, the SVD curves separated in favor of TAVI after about 6 months of follow-up. The shape of the curves also differed. Unlike the steady rise in SVD observed in the surgery group, the SVD rate in the TAVI group remained below 1% for almost 4 years before beginning to climb.

There was greater relative benefit for the TAVI device in patients with annular diameters of 23 mm or less. Unlike the rise in SVD rates that began about 6 months after SAVR, the SVD rates in the TAVI patients remained at 0% for more than 2 years. At 5 years, the differences remained significant favoring TAVI (1.39% vs. 5.86%; P = .049).

In those with larger annular diameters, there was still a consistently lower SVD rate over time for TAVI relative to SAVR, but the trend for an advantage at 5 years fell just short of significance (2.48% vs. 3.96%; P = .067).
 

SVD linked to doubling of mortality

SVD worsened outcomes. When all data surgery and TAVI data were pooled, the hazard ratios corresponded with about a doubling of risk for major adverse outcomes, including all-cause mortality (HR, 1.98; P < .001), cardiovascular mortality (HR, 1.82; P = .008), and hospitalization for aortic valve disease or worsening heart failure (HR, 2.11; P = .01). The relative risks were similar in the two treatment groups, including the risk of all-cause mortality (HR, 2.24; P < .001 for TAVI vs. HR, 2.45; P = .002 for SAVR).

The predictors for SVD on multivariate analysis included female sex, increased body surface area, prior percutaneous coronary intervention, and a prior diagnosis of atrial fibrillation.

Design improvements in TAVI devices are likely to explain these results, said Dr. Reardon, chair of cardiovascular research at Houston Methodist Hospital.

“The CoreValve/Evolut supra-annular, self-expanding bioprosthesis is the first and only transcatheter bioprosthesis to demonstrate lower rates of SVD, compared with surgery,” Dr. Reardon said.

This analysis validated the risks posed by the definition of SVD applied in this study, which appears to be a practical tool for tracking valve function and patient risk. Dr. Reardon also said that the study confirms the value of serial Doppler transthoracic echocardiography as a tool for monitoring SVD.

Several experts agreed that this is important new information.

“This is a remarkable series of findings,” said James McClurken, MD, who is a cardiovascular surgeon affiliated with Temple University, Philadelphia, and practices in Doylestown, Penn. By both demonstrating the prognostic importance of SVD and showing differences between the study device and SAVR, this trial will yield practical data to inform patients about relative risks and benefits.

Athena Poppas, MD, the new president of the ACC and a professor of medicine at Brown University, Providence, R.I., called this study “practice changing” for the same reasons. She also thinks it has valuable data for guiding choice of intervention.

Overall, the data are likely to change thinking about the role of TAVI and surgery in younger, fit patients, according to Megan Coylewright, MD, chief of cardiology at Erlanger Cardiology, Chattanooga, Tenn.

“There are patients [in need of aortic valve repair] with a long life expectancy who have been told you have to have a surgical repair because we know they last longer,” she said. Although she said that relative outcomes after longer follow-up remain unknown, “I think this does throw that comment into question.”

Dr. Reardon has financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical. Dr. Poppas and McClurken reported no potential financial conflicts of interest. Dr. Coylewright reported financial relationships with Abbott, Alleviant, Boston Scientific, Cardiosmart, Edwards Lifesciences, Medtronic, and Occlutech. The study received financial support from Medtronic.

The rates of infection involving cardiac implanted electronic devices (CIEDs), like pacemakers and cardioverter defibrillators (ICDs), are substantial, but only a minority of patients in the United States receive the guideline-directed recommendation of device removal, according to data from a Medicare population.

The study was conducted on the hypothesis that adherence to guidelines were low, “but we were surprised by how low the extraction rates turned out to be,” Sean D. Pokorney, MD, an electrophysiologist at the Duke Clinical Research Institute, Durham, N.C., reported at the annual scientific sessions of the American College of Cardiology.

The major U.S. and European guidelines are uniform in recommending complete extraction for a CIED infection. The American Heart Association and the Heart Rhythm Society and two out of the three other guidelines cited by Dr. Pokorney not only recommend extraction but specify prompt extraction.

Neither complete extraction nor prompt extraction are typical.

Of the 11,619 CIED infection cases identified in the Medicare database, 18.2% underwent extraction within 30 days of diagnosis. Only 13% were extracted within 6 days.
 

Lack of extraction may cause avoidable mortality

The result is likely to be avoidable mortality. Among those with extraction within 30 days, 80% were still alive 1 year later. Survival at 1 year fell to 67.6% in those without an extraction within this time frame.

This translated to a 22% lower rate of death at 1 year (hazard ratio, 0.78; P = .008) in those who underwent extraction within 30 days.

For those in whom the device was extracted within 7 days, the associated HR for death at 1 year was more than 40% lower (HR, 0.59; P < .001), reported Dr. Pokorney, who characterized these reductions as occurring in “a dose-response fashion.”

The very high risk of relapse despite antibiotics is the reason that “there is a class 1 indication for complete hardware removal,” Dr. Pokorney. He cited five studies that addressed this question. With partial device removal or medical therapy alone, relapse was consistently 50% or greater. In one study, it was 67%. In another it was 100%.

With complete removal, the rate of infection relapse was 1% or lower in four. In the fifth, the rate was 4.2%.

Infections can occur early or late after implantation, but cases accumulate over time. In the Medicare data sample, infection rates climbed from 0.3% at 1 year to 0.6% at 2 years and then to 1.1% at 3 years, Dr. Pokorney reported.

Other studies have also shown a steady increase in the proportion of implanted devices associated with infection over time. In a cohort study conducted in Olmstead County, Minnesota, the cumulative probability of a CIED infection reached 6.2% after 15 years and 11.7% after 25 years. While about half of these were infections localized to the device pocket, the others were potentially life-threatening systemic infections, according to Dr. Pokorney, who cited this study.

In his analysis of the Medicare data, all fee-for-service patients receiving a first CIED implant over a period of 14 years were included. The 14-year period ended just before the COVID-19 epidemic.

The more than 11,000 CIED infections were identified in 1,065,549 total CIED patients. Most (72%) had received a pacemaker. Of the others , more than half received an ICD and the others received a cardiac resynchronization device. The median age was 78 years.
 

Female and Black patients even less likely to undergo extraction

About half (49.1%) of the overall study population was female, but females represented only about 40% of those who developed an infection. Blacks represented just under 8% of the population but nearly 16% of the CIED infections. Both females and Blacks were significantly less likely than the overall study population to undergo extraction for their infection (P < .001 for both).

Perhaps predictably, patients with comorbidities were more likely to develop CIED infections. For example, 87% of those with infection, versus only 64.9% of the overall population, were in heart failure at the time of implantation. Diabetes (68.3% vs. 49.3%), ischemic heart disease (91.9% vs. 79.4%), renal disease (70.5% vs. 37.9%), and chronic obstructive pulmonary disease (70.6% vs. 55.0%) were also more common at baseline in those who went on to a CIED infection than in the overall population.

Based on the evidence that there is a large unmet need to improve adherence to the guidelines, Dr. Pokorney called for care pathways and other quality initiatives to address the problem.

The reasons that so many patients are not undergoing prompt device extraction at the time of infection is unclear, but Dr. Pokorney offered some hypotheses.

“There appears to be a false belief in the efficacy of antibiotics for treating CIED infections,” Dr. Pokorney said.
 

Comorbidities shouldn’t delay extraction

It is also possible that clinicians are concerned about performing extractions in patients with multiple comorbidities. If clinicians are delaying extractions for this reason, Dr. Pokorney suggested this behavior is misdirected given the fact that delays appear to increase mortality risk.

Several experts, including Rachel Lambert, MD, an electrophysiologist and professor of medicine at Yale University, New Haven, Conn., agreed that these data deserve a response.

“I was not surprised by the mortality data, but I was surprised at this low extraction rate,” said Dr. Lambert, who concurs with the guidelines. She indicated this study provides teeth to prompt action.

“It is great to have these data about the increased mortality risk to back up the guidelines,” she said.

More information is needed to understand exactly why CIED infection is not now leading to guideline-directed care. Dr. Pokorney said: “Where do we go from here is a key question.”

While several different types of initiatives might be needed, Dr. Pokorney called for regionalization of care to address the fact that not every center that places CIEDs has the capability to perform extractions.

“Extraction is not available at every center, and it probably should not be available at every center, so mechanisms are need to get patients with infection to the specialized centers that provide care,” he said.

Dr. Pokorney has financial relationships with Boston Scientific, Bristol-Myers Squibb, Gilead, Janssen, Medtronic, Pfizer, and Philips. Dr. Lambert reported financial relationships with Abbott, Amgen, and Medtronic.

The rates of infection involving cardiac implanted electronic devices (CIEDs), like pacemakers and cardioverter defibrillators (ICDs), are substantial, but only a minority of patients in the United States receive the guideline-directed recommendation of device removal, according to data from a Medicare population.

The study was conducted on the hypothesis that adherence to guidelines were low, “but we were surprised by how low the extraction rates turned out to be,” Sean D. Pokorney, MD, an electrophysiologist at the Duke Clinical Research Institute, Durham, N.C., reported at the annual scientific sessions of the American College of Cardiology.

The major U.S. and European guidelines are uniform in recommending complete extraction for a CIED infection. The American Heart Association and the Heart Rhythm Society and two out of the three other guidelines cited by Dr. Pokorney not only recommend extraction but specify prompt extraction.

Neither complete extraction nor prompt extraction are typical.

Of the 11,619 CIED infection cases identified in the Medicare database, 18.2% underwent extraction within 30 days of diagnosis. Only 13% were extracted within 6 days.
 

Lack of extraction may cause avoidable mortality

The result is likely to be avoidable mortality. Among those with extraction within 30 days, 80% were still alive 1 year later. Survival at 1 year fell to 67.6% in those without an extraction within this time frame.

This translated to a 22% lower rate of death at 1 year (hazard ratio, 0.78; P = .008) in those who underwent extraction within 30 days.

For those in whom the device was extracted within 7 days, the associated HR for death at 1 year was more than 40% lower (HR, 0.59; P < .001), reported Dr. Pokorney, who characterized these reductions as occurring in “a dose-response fashion.”

The very high risk of relapse despite antibiotics is the reason that “there is a class 1 indication for complete hardware removal,” Dr. Pokorney. He cited five studies that addressed this question. With partial device removal or medical therapy alone, relapse was consistently 50% or greater. In one study, it was 67%. In another it was 100%.

With complete removal, the rate of infection relapse was 1% or lower in four. In the fifth, the rate was 4.2%.

Infections can occur early or late after implantation, but cases accumulate over time. In the Medicare data sample, infection rates climbed from 0.3% at 1 year to 0.6% at 2 years and then to 1.1% at 3 years, Dr. Pokorney reported.

Other studies have also shown a steady increase in the proportion of implanted devices associated with infection over time. In a cohort study conducted in Olmstead County, Minnesota, the cumulative probability of a CIED infection reached 6.2% after 15 years and 11.7% after 25 years. While about half of these were infections localized to the device pocket, the others were potentially life-threatening systemic infections, according to Dr. Pokorney, who cited this study.

In his analysis of the Medicare data, all fee-for-service patients receiving a first CIED implant over a period of 14 years were included. The 14-year period ended just before the COVID-19 epidemic.

The more than 11,000 CIED infections were identified in 1,065,549 total CIED patients. Most (72%) had received a pacemaker. Of the others , more than half received an ICD and the others received a cardiac resynchronization device. The median age was 78 years.
 

Female and Black patients even less likely to undergo extraction

About half (49.1%) of the overall study population was female, but females represented only about 40% of those who developed an infection. Blacks represented just under 8% of the population but nearly 16% of the CIED infections. Both females and Blacks were significantly less likely than the overall study population to undergo extraction for their infection (P < .001 for both).

Perhaps predictably, patients with comorbidities were more likely to develop CIED infections. For example, 87% of those with infection, versus only 64.9% of the overall population, were in heart failure at the time of implantation. Diabetes (68.3% vs. 49.3%), ischemic heart disease (91.9% vs. 79.4%), renal disease (70.5% vs. 37.9%), and chronic obstructive pulmonary disease (70.6% vs. 55.0%) were also more common at baseline in those who went on to a CIED infection than in the overall population.

Based on the evidence that there is a large unmet need to improve adherence to the guidelines, Dr. Pokorney called for care pathways and other quality initiatives to address the problem.

The reasons that so many patients are not undergoing prompt device extraction at the time of infection is unclear, but Dr. Pokorney offered some hypotheses.

“There appears to be a false belief in the efficacy of antibiotics for treating CIED infections,” Dr. Pokorney said.
 

Comorbidities shouldn’t delay extraction

It is also possible that clinicians are concerned about performing extractions in patients with multiple comorbidities. If clinicians are delaying extractions for this reason, Dr. Pokorney suggested this behavior is misdirected given the fact that delays appear to increase mortality risk.

Several experts, including Rachel Lambert, MD, an electrophysiologist and professor of medicine at Yale University, New Haven, Conn., agreed that these data deserve a response.

“I was not surprised by the mortality data, but I was surprised at this low extraction rate,” said Dr. Lambert, who concurs with the guidelines. She indicated this study provides teeth to prompt action.

“It is great to have these data about the increased mortality risk to back up the guidelines,” she said.

More information is needed to understand exactly why CIED infection is not now leading to guideline-directed care. Dr. Pokorney said: “Where do we go from here is a key question.”

While several different types of initiatives might be needed, Dr. Pokorney called for regionalization of care to address the fact that not every center that places CIEDs has the capability to perform extractions.

“Extraction is not available at every center, and it probably should not be available at every center, so mechanisms are need to get patients with infection to the specialized centers that provide care,” he said.

Dr. Pokorney has financial relationships with Boston Scientific, Bristol-Myers Squibb, Gilead, Janssen, Medtronic, Pfizer, and Philips. Dr. Lambert reported financial relationships with Abbott, Amgen, and Medtronic.

The rates of infection involving cardiac implanted electronic devices (CIEDs), like pacemakers and cardioverter defibrillators (ICDs), are substantial, but only a minority of patients in the United States receive the guideline-directed recommendation of device removal, according to data from a Medicare population.

The study was conducted on the hypothesis that adherence to guidelines were low, “but we were surprised by how low the extraction rates turned out to be,” Sean D. Pokorney, MD, an electrophysiologist at the Duke Clinical Research Institute, Durham, N.C., reported at the annual scientific sessions of the American College of Cardiology.

The major U.S. and European guidelines are uniform in recommending complete extraction for a CIED infection. The American Heart Association and the Heart Rhythm Society and two out of the three other guidelines cited by Dr. Pokorney not only recommend extraction but specify prompt extraction.

Neither complete extraction nor prompt extraction are typical.

Of the 11,619 CIED infection cases identified in the Medicare database, 18.2% underwent extraction within 30 days of diagnosis. Only 13% were extracted within 6 days.
 

Lack of extraction may cause avoidable mortality

The result is likely to be avoidable mortality. Among those with extraction within 30 days, 80% were still alive 1 year later. Survival at 1 year fell to 67.6% in those without an extraction within this time frame.

This translated to a 22% lower rate of death at 1 year (hazard ratio, 0.78; P = .008) in those who underwent extraction within 30 days.

For those in whom the device was extracted within 7 days, the associated HR for death at 1 year was more than 40% lower (HR, 0.59; P < .001), reported Dr. Pokorney, who characterized these reductions as occurring in “a dose-response fashion.”

The very high risk of relapse despite antibiotics is the reason that “there is a class 1 indication for complete hardware removal,” Dr. Pokorney. He cited five studies that addressed this question. With partial device removal or medical therapy alone, relapse was consistently 50% or greater. In one study, it was 67%. In another it was 100%.

With complete removal, the rate of infection relapse was 1% or lower in four. In the fifth, the rate was 4.2%.

Infections can occur early or late after implantation, but cases accumulate over time. In the Medicare data sample, infection rates climbed from 0.3% at 1 year to 0.6% at 2 years and then to 1.1% at 3 years, Dr. Pokorney reported.

Other studies have also shown a steady increase in the proportion of implanted devices associated with infection over time. In a cohort study conducted in Olmstead County, Minnesota, the cumulative probability of a CIED infection reached 6.2% after 15 years and 11.7% after 25 years. While about half of these were infections localized to the device pocket, the others were potentially life-threatening systemic infections, according to Dr. Pokorney, who cited this study.

In his analysis of the Medicare data, all fee-for-service patients receiving a first CIED implant over a period of 14 years were included. The 14-year period ended just before the COVID-19 epidemic.

The more than 11,000 CIED infections were identified in 1,065,549 total CIED patients. Most (72%) had received a pacemaker. Of the others , more than half received an ICD and the others received a cardiac resynchronization device. The median age was 78 years.
 

Female and Black patients even less likely to undergo extraction

About half (49.1%) of the overall study population was female, but females represented only about 40% of those who developed an infection. Blacks represented just under 8% of the population but nearly 16% of the CIED infections. Both females and Blacks were significantly less likely than the overall study population to undergo extraction for their infection (P < .001 for both).

Perhaps predictably, patients with comorbidities were more likely to develop CIED infections. For example, 87% of those with infection, versus only 64.9% of the overall population, were in heart failure at the time of implantation. Diabetes (68.3% vs. 49.3%), ischemic heart disease (91.9% vs. 79.4%), renal disease (70.5% vs. 37.9%), and chronic obstructive pulmonary disease (70.6% vs. 55.0%) were also more common at baseline in those who went on to a CIED infection than in the overall population.

Based on the evidence that there is a large unmet need to improve adherence to the guidelines, Dr. Pokorney called for care pathways and other quality initiatives to address the problem.

The reasons that so many patients are not undergoing prompt device extraction at the time of infection is unclear, but Dr. Pokorney offered some hypotheses.

“There appears to be a false belief in the efficacy of antibiotics for treating CIED infections,” Dr. Pokorney said.
 

Comorbidities shouldn’t delay extraction

It is also possible that clinicians are concerned about performing extractions in patients with multiple comorbidities. If clinicians are delaying extractions for this reason, Dr. Pokorney suggested this behavior is misdirected given the fact that delays appear to increase mortality risk.

Several experts, including Rachel Lambert, MD, an electrophysiologist and professor of medicine at Yale University, New Haven, Conn., agreed that these data deserve a response.

“I was not surprised by the mortality data, but I was surprised at this low extraction rate,” said Dr. Lambert, who concurs with the guidelines. She indicated this study provides teeth to prompt action.

“It is great to have these data about the increased mortality risk to back up the guidelines,” she said.

More information is needed to understand exactly why CIED infection is not now leading to guideline-directed care. Dr. Pokorney said: “Where do we go from here is a key question.”

While several different types of initiatives might be needed, Dr. Pokorney called for regionalization of care to address the fact that not every center that places CIEDs has the capability to perform extractions.

“Extraction is not available at every center, and it probably should not be available at every center, so mechanisms are need to get patients with infection to the specialized centers that provide care,” he said.

Dr. Pokorney has financial relationships with Boston Scientific, Bristol-Myers Squibb, Gilead, Janssen, Medtronic, Pfizer, and Philips. Dr. Lambert reported financial relationships with Abbott, Amgen, and Medtronic.

The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.

In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.

The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.

“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”

Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.

The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.

The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.

The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.

In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.

The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.

“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”

Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.

The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.

The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.

The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.

In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.

The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.

“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”

Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.

The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.

The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.

Treatment with a novel myosin-inhibiting agent may improve symptoms and hemodynamics enough in patients with obstructive hypertrophic cardiomyopathy (OHCM) so that they can avoid or at least delay septal reduction therapy (SRT), suggests a randomized trial of modest size and duration.

Of 112 patients with OHCM who were sick enough while receiving standard medications to qualify for SRT, those assigned to take mavacamten (MyoKardia) instead of placebo were far less likely to still be eligible for SRT 16 weeks later.

In other words, their OHCM had improved enough during therapy with mavacamten such that SRT, either surgical septal myectomy or transcatheter alcohol septal ablation, could no longer be recommended per guidelines.

Mavacamten, which lessens myocardial contractility by selective inhibition of cardiac myosin, is the first agent tested in prospective trials to appear as a viable medical option in patients with severe, symptomatic OHCM, observed principal investigator Milind Y. Desai, MD, MBA, of the Cleveland Clinic.

“There’s clearly an unmet need for noninvasive therapies, medical therapies, that work in OHCM,” he said in an interview. Mavacamten “adds to the armamentarium” of OHCM management options and may give patients with symptoms despite conventional medications an alternative to SRT, which is considered definitive but has drawbacks.

The goal of SRT is to alleviate obstruction of the left ventricular outflow tract (LVOT), but surgical SRT requires a sternotomy, with all the risks and recovery time that entails. Catheter-based alcohol septal ablation is a less common alternative for some patients with suitable anatomy, Dr. Desai noted.

But those procedures “are not uniformly available, and even when  available, the outcomes are fairly heterogeneous,” he said. “The guidelines recommend that you should go to a center with a mortality rate of less than 1% with these procedures. Centers like that are very few across the world,” and procedural mortality can be much higher at centers with less SRT experience.

Dr. Desai presented the results of VALOR-HCM at the annual scientific sessions of the American College of Cardiology. Of the 56 patients assigned to mavacamten, 10 (17.9%) decided to undergo SRT by the end of the trial, or otherwise still met guideline-recommended criteria for receiving SRT, the primary endpoint. In comparison, 43 of the 56 patients (76.8%) in the control group (P < .0001) met that endpoint.

More patients receiving mavacamten improved by at least one New York Heart Association (NYHA) functional class during the trial’s 16 weeks: 63% versus 21% for those assigned to placebo. And 27% and 2%, respectively, improved by at least two NYHA classes, Dr. Desai said.

Guidelines recommend that SRT be reserved for patients in NYHA class III or IV heart failure with a resting or provoked LVOT gradient of at least 50 mm Hg.

Of note, Desai said, only two patients in each group elected to undergo SRT during the study. “The primary endpoint was driven by reduction in guideline eligibility for SRT, but 95% of patients in the study chose to continue with medical therapy.”

Speaking as a panelist after Dr. Desai’s presentation, Lynne W. Stevenson, MD, lauded the phase 3 trial’s “brave design,” which featured a highly unusual subjective primary endpoint and framed it as an advantage.

That the trial showed a significant mavacamten effect for that endpoint “answered, in one step, the question of what does this actually mean to the patient – which often takes much longer,” observed Dr. Stevenson, from Vanderbilt University, Nashville, Tenn.

Even so, she added, whether patients still qualified for SRT in the trial at least had to be supported by objective measures of LVOT gradient and NT-proBNP levels.

“My perspective is that of a cardiac surgeon who performs septal myectomies,” said John Cleveland, MD, University of Colorado at Denver, Aurora, who said he was impressed at how few patients receiving mavacamten went on to undergo SRT, while the rest were able to at least defer that decision.

Current recommendations are that patients who go to SRT “should be maximally medically treated and still symptomatic,” Dr. Cleveland observed at a press conference on VALOR-HCM. Should mavacamten be added to the list of agents to use before resorting to invasive therapy? “My answer would be yes,” he said, and patients who remain symptomatic even while receiving the myosin inhibitor and other medications should proceed to SRT.

The trial’s patients had documented OHCM, severe symptoms, and a resting or provoked LVOT gradient of at least 50 mm Hg despite maximally tolerated medications – which could include disopyramide, beta-blockers, and calcium channel blockers. About half the study population was female, and 89% were White. All had been referred for SRT.

Active therapy consisted of mavacamten initiated at 5 mg/day, with up-titrations at 8 and 12 weeks as tolerated, guided by echocardiographic left ventricular ejection fraction and LVOT gradient.  

Most secondary endpoints improved significantly in patients receiving the drug, compared with placebo. They included measures of quality of life, symptom status, ventricular function, natriuretic peptides, and troponin I.

The secondary outcomes are consistent with what was observed in the EXPLORER-HCM trial, which in 2020 suggested that mavacamten could improve measures of quality of life, NYHA functional class, LVOT gradient, peak VO2, and other metrics in patients with OHCM.

Dr. Desai said mavacamten was well tolerated. “There were two patients who had a transient drop in ejection fraction to less than 50%, so the drug was temporarily discontinued, but resumed at a lower dose and they were able to complete the study.”

Dr. Stevenson commented on the “pretty quick” up-titration of mavacamten dosages in a study lasting only 4 months, which could have been a concern given the drug’s limited track record and its mechanism of action targeting contractility. “Fortunately, no serious safety signals” were observed.

Dr. Desai emphasized that mavacamten up-titrations were strictly guided by regular echocardiographic monitoring and assessment of LVOT gradients, in addition to clinical responses. And that, he said, is likely how up-titrations should be carried out if mavacamten is approved for OHCM.

VALOR-HCM was supported by MyoKardia. Dr. Desai disclosed receiving honoraria or consulting fees from Caristo Diagnostics, Medtronic, and MyoKardia. Dr. Stevenson disclosed receiving honoraria or consulting fees from Novartis; serving on a data safety monitoring board for Livanova; and other relationships with Abbott Medical, Biotronik, Boston Scientific, Bristol-Myers Squibb, Endotronic, Gore Medical, and Johnson & Johnson. Dr. Cleveland had no disclosures.

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

Treatment with a novel myosin-inhibiting agent may improve symptoms and hemodynamics enough in patients with obstructive hypertrophic cardiomyopathy (OHCM) so that they can avoid or at least delay septal reduction therapy (SRT), suggests a randomized trial of modest size and duration.

Of 112 patients with OHCM who were sick enough while receiving standard medications to qualify for SRT, those assigned to take mavacamten (MyoKardia) instead of placebo were far less likely to still be eligible for SRT 16 weeks later.

In other words, their OHCM had improved enough during therapy with mavacamten such that SRT, either surgical septal myectomy or transcatheter alcohol septal ablation, could no longer be recommended per guidelines.

Mavacamten, which lessens myocardial contractility by selective inhibition of cardiac myosin, is the first agent tested in prospective trials to appear as a viable medical option in patients with severe, symptomatic OHCM, observed principal investigator Milind Y. Desai, MD, MBA, of the Cleveland Clinic.

“There’s clearly an unmet need for noninvasive therapies, medical therapies, that work in OHCM,” he said in an interview. Mavacamten “adds to the armamentarium” of OHCM management options and may give patients with symptoms despite conventional medications an alternative to SRT, which is considered definitive but has drawbacks.

The goal of SRT is to alleviate obstruction of the left ventricular outflow tract (LVOT), but surgical SRT requires a sternotomy, with all the risks and recovery time that entails. Catheter-based alcohol septal ablation is a less common alternative for some patients with suitable anatomy, Dr. Desai noted.

But those procedures “are not uniformly available, and even when  available, the outcomes are fairly heterogeneous,” he said. “The guidelines recommend that you should go to a center with a mortality rate of less than 1% with these procedures. Centers like that are very few across the world,” and procedural mortality can be much higher at centers with less SRT experience.

Dr. Desai presented the results of VALOR-HCM at the annual scientific sessions of the American College of Cardiology. Of the 56 patients assigned to mavacamten, 10 (17.9%) decided to undergo SRT by the end of the trial, or otherwise still met guideline-recommended criteria for receiving SRT, the primary endpoint. In comparison, 43 of the 56 patients (76.8%) in the control group (P < .0001) met that endpoint.

More patients receiving mavacamten improved by at least one New York Heart Association (NYHA) functional class during the trial’s 16 weeks: 63% versus 21% for those assigned to placebo. And 27% and 2%, respectively, improved by at least two NYHA classes, Dr. Desai said.

Guidelines recommend that SRT be reserved for patients in NYHA class III or IV heart failure with a resting or provoked LVOT gradient of at least 50 mm Hg.

Of note, Desai said, only two patients in each group elected to undergo SRT during the study. “The primary endpoint was driven by reduction in guideline eligibility for SRT, but 95% of patients in the study chose to continue with medical therapy.”

Speaking as a panelist after Dr. Desai’s presentation, Lynne W. Stevenson, MD, lauded the phase 3 trial’s “brave design,” which featured a highly unusual subjective primary endpoint and framed it as an advantage.

That the trial showed a significant mavacamten effect for that endpoint “answered, in one step, the question of what does this actually mean to the patient – which often takes much longer,” observed Dr. Stevenson, from Vanderbilt University, Nashville, Tenn.

Even so, she added, whether patients still qualified for SRT in the trial at least had to be supported by objective measures of LVOT gradient and NT-proBNP levels.

“My perspective is that of a cardiac surgeon who performs septal myectomies,” said John Cleveland, MD, University of Colorado at Denver, Aurora, who said he was impressed at how few patients receiving mavacamten went on to undergo SRT, while the rest were able to at least defer that decision.

Current recommendations are that patients who go to SRT “should be maximally medically treated and still symptomatic,” Dr. Cleveland observed at a press conference on VALOR-HCM. Should mavacamten be added to the list of agents to use before resorting to invasive therapy? “My answer would be yes,” he said, and patients who remain symptomatic even while receiving the myosin inhibitor and other medications should proceed to SRT.

The trial’s patients had documented OHCM, severe symptoms, and a resting or provoked LVOT gradient of at least 50 mm Hg despite maximally tolerated medications – which could include disopyramide, beta-blockers, and calcium channel blockers. About half the study population was female, and 89% were White. All had been referred for SRT.

Active therapy consisted of mavacamten initiated at 5 mg/day, with up-titrations at 8 and 12 weeks as tolerated, guided by echocardiographic left ventricular ejection fraction and LVOT gradient.  

Most secondary endpoints improved significantly in patients receiving the drug, compared with placebo. They included measures of quality of life, symptom status, ventricular function, natriuretic peptides, and troponin I.

The secondary outcomes are consistent with what was observed in the EXPLORER-HCM trial, which in 2020 suggested that mavacamten could improve measures of quality of life, NYHA functional class, LVOT gradient, peak VO2, and other metrics in patients with OHCM.

Dr. Desai said mavacamten was well tolerated. “There were two patients who had a transient drop in ejection fraction to less than 50%, so the drug was temporarily discontinued, but resumed at a lower dose and they were able to complete the study.”

Dr. Stevenson commented on the “pretty quick” up-titration of mavacamten dosages in a study lasting only 4 months, which could have been a concern given the drug’s limited track record and its mechanism of action targeting contractility. “Fortunately, no serious safety signals” were observed.

Dr. Desai emphasized that mavacamten up-titrations were strictly guided by regular echocardiographic monitoring and assessment of LVOT gradients, in addition to clinical responses. And that, he said, is likely how up-titrations should be carried out if mavacamten is approved for OHCM.

VALOR-HCM was supported by MyoKardia. Dr. Desai disclosed receiving honoraria or consulting fees from Caristo Diagnostics, Medtronic, and MyoKardia. Dr. Stevenson disclosed receiving honoraria or consulting fees from Novartis; serving on a data safety monitoring board for Livanova; and other relationships with Abbott Medical, Biotronik, Boston Scientific, Bristol-Myers Squibb, Endotronic, Gore Medical, and Johnson & Johnson. Dr. Cleveland had no disclosures.

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

Treatment with a novel myosin-inhibiting agent may improve symptoms and hemodynamics enough in patients with obstructive hypertrophic cardiomyopathy (OHCM) so that they can avoid or at least delay septal reduction therapy (SRT), suggests a randomized trial of modest size and duration.

Of 112 patients with OHCM who were sick enough while receiving standard medications to qualify for SRT, those assigned to take mavacamten (MyoKardia) instead of placebo were far less likely to still be eligible for SRT 16 weeks later.

In other words, their OHCM had improved enough during therapy with mavacamten such that SRT, either surgical septal myectomy or transcatheter alcohol septal ablation, could no longer be recommended per guidelines.

Mavacamten, which lessens myocardial contractility by selective inhibition of cardiac myosin, is the first agent tested in prospective trials to appear as a viable medical option in patients with severe, symptomatic OHCM, observed principal investigator Milind Y. Desai, MD, MBA, of the Cleveland Clinic.

“There’s clearly an unmet need for noninvasive therapies, medical therapies, that work in OHCM,” he said in an interview. Mavacamten “adds to the armamentarium” of OHCM management options and may give patients with symptoms despite conventional medications an alternative to SRT, which is considered definitive but has drawbacks.

The goal of SRT is to alleviate obstruction of the left ventricular outflow tract (LVOT), but surgical SRT requires a sternotomy, with all the risks and recovery time that entails. Catheter-based alcohol septal ablation is a less common alternative for some patients with suitable anatomy, Dr. Desai noted.

But those procedures “are not uniformly available, and even when  available, the outcomes are fairly heterogeneous,” he said. “The guidelines recommend that you should go to a center with a mortality rate of less than 1% with these procedures. Centers like that are very few across the world,” and procedural mortality can be much higher at centers with less SRT experience.

Dr. Desai presented the results of VALOR-HCM at the annual scientific sessions of the American College of Cardiology. Of the 56 patients assigned to mavacamten, 10 (17.9%) decided to undergo SRT by the end of the trial, or otherwise still met guideline-recommended criteria for receiving SRT, the primary endpoint. In comparison, 43 of the 56 patients (76.8%) in the control group (P < .0001) met that endpoint.

More patients receiving mavacamten improved by at least one New York Heart Association (NYHA) functional class during the trial’s 16 weeks: 63% versus 21% for those assigned to placebo. And 27% and 2%, respectively, improved by at least two NYHA classes, Dr. Desai said.

Guidelines recommend that SRT be reserved for patients in NYHA class III or IV heart failure with a resting or provoked LVOT gradient of at least 50 mm Hg.

Of note, Desai said, only two patients in each group elected to undergo SRT during the study. “The primary endpoint was driven by reduction in guideline eligibility for SRT, but 95% of patients in the study chose to continue with medical therapy.”

Speaking as a panelist after Dr. Desai’s presentation, Lynne W. Stevenson, MD, lauded the phase 3 trial’s “brave design,” which featured a highly unusual subjective primary endpoint and framed it as an advantage.

That the trial showed a significant mavacamten effect for that endpoint “answered, in one step, the question of what does this actually mean to the patient – which often takes much longer,” observed Dr. Stevenson, from Vanderbilt University, Nashville, Tenn.

Even so, she added, whether patients still qualified for SRT in the trial at least had to be supported by objective measures of LVOT gradient and NT-proBNP levels.

“My perspective is that of a cardiac surgeon who performs septal myectomies,” said John Cleveland, MD, University of Colorado at Denver, Aurora, who said he was impressed at how few patients receiving mavacamten went on to undergo SRT, while the rest were able to at least defer that decision.

Current recommendations are that patients who go to SRT “should be maximally medically treated and still symptomatic,” Dr. Cleveland observed at a press conference on VALOR-HCM. Should mavacamten be added to the list of agents to use before resorting to invasive therapy? “My answer would be yes,” he said, and patients who remain symptomatic even while receiving the myosin inhibitor and other medications should proceed to SRT.

The trial’s patients had documented OHCM, severe symptoms, and a resting or provoked LVOT gradient of at least 50 mm Hg despite maximally tolerated medications – which could include disopyramide, beta-blockers, and calcium channel blockers. About half the study population was female, and 89% were White. All had been referred for SRT.

Active therapy consisted of mavacamten initiated at 5 mg/day, with up-titrations at 8 and 12 weeks as tolerated, guided by echocardiographic left ventricular ejection fraction and LVOT gradient.  

Most secondary endpoints improved significantly in patients receiving the drug, compared with placebo. They included measures of quality of life, symptom status, ventricular function, natriuretic peptides, and troponin I.

The secondary outcomes are consistent with what was observed in the EXPLORER-HCM trial, which in 2020 suggested that mavacamten could improve measures of quality of life, NYHA functional class, LVOT gradient, peak VO2, and other metrics in patients with OHCM.

Dr. Desai said mavacamten was well tolerated. “There were two patients who had a transient drop in ejection fraction to less than 50%, so the drug was temporarily discontinued, but resumed at a lower dose and they were able to complete the study.”

Dr. Stevenson commented on the “pretty quick” up-titration of mavacamten dosages in a study lasting only 4 months, which could have been a concern given the drug’s limited track record and its mechanism of action targeting contractility. “Fortunately, no serious safety signals” were observed.

Dr. Desai emphasized that mavacamten up-titrations were strictly guided by regular echocardiographic monitoring and assessment of LVOT gradients, in addition to clinical responses. And that, he said, is likely how up-titrations should be carried out if mavacamten is approved for OHCM.

VALOR-HCM was supported by MyoKardia. Dr. Desai disclosed receiving honoraria or consulting fees from Caristo Diagnostics, Medtronic, and MyoKardia. Dr. Stevenson disclosed receiving honoraria or consulting fees from Novartis; serving on a data safety monitoring board for Livanova; and other relationships with Abbott Medical, Biotronik, Boston Scientific, Bristol-Myers Squibb, Endotronic, Gore Medical, and Johnson & Johnson. Dr. Cleveland had no disclosures.

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

Even very light alcohol intake is associated with an increased risk for cardiovascular disease, compared with not drinking at all, and the risk increases exponentially as alcohol intake rises, even at moderate levels, a new study shows.

“Our findings suggest that the observed benefit in individuals with light to moderate alcohol intake, which is consistently shown in epidemiological studies, is likely due to other positive lifestyle factors that are common in these individuals who drink lightly,” senior author Krishna Aragam, MD, Massachusetts General Hospital, Boston, told this news organization.

“Our results also showed that while all levels of alcohol were linked to increased risk of cardiovascular disease, the association was not linear. Rather, light alcohol intake was associated with rather modest risk increases, but there were exponential increases in cardiovascular risk with increasing amounts of alcohol consumption,” he said.

As the risk gradient appeared to increase quite sharply even between 1 and 2 drinks per day, Dr. Aragam suggested that what might be regarded as safe levels of drinking may trend downward in the future.

Kirby Hamilton/iStockphoto

They also conducted genetic analyses to examine the effect of alcohol and cardiovascular disease.   

Dr. Aragam explained that previous work has shown good evidence, in individuals who choose to drink, that several relevant genetic variants predict levels of alcohol consumption quite accurately.

“Mendelian randomization using these gene variants allows for stronger inferences about potential causality than do observational studies, as they are less affected by confounding factors,” he noted.

Newer techniques in Mendelian randomization in which data on several gene variants linked to alcohol consumption are combined into a score allow for a greater understanding of the risk linked to different amount of alcohol intake, he added.

In these Mendelian randomization analyses, a 1-standard deviation increase in genetically predicted alcohol consumption was associated with 1.3-fold higher risk of hypertension (P < .001) and 1.4-fold higher risk of coronary artery disease (P = .006).

Further analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease; light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.

These results were replicated in a second database of 30,716 individuals from the Mass General Brigham Biobank.

“The findings of this study suggest that the observed cardioprotective effects of light to moderate alcohol intake may be largely mediated by confounding lifestyle factors,” the researchers conclude. “Genetic analyses suggest causal associations between alcohol intake and cardiovascular disease but with unequal and exponential increases in risk at greater levels of intake, which should be accounted for in health recommendations around the habitual consumption of alcohol.”

What is an acceptable level? 

“Specifically, our results suggest that consuming as many as 7 drinks per week is associated with relatively modest increases in cardiovascular risk,” they write.

But they point out that there are unequal increases in cardiovascular risk when progressing from 0 to 7 versus 7 to 14 drinks per week in both men and women.

“Although risk thresholds are inherently somewhat subjective, these findings again bring into question whether an average consumption of 2 drinks per day (14 drinks per week) should be designated a low-risk behavior,” they say.

“Furthermore, as several-fold increases in risk were observed for those consuming 21 or more drinks per week, our results emphasize the importance of aggressive efforts to reduce alcohol intake among heavy drinkers,” they add.

Dr. Aragam elaborated: “Our data suggest that reducing alcohol intake will reduce cardiovascular risk in all individuals, but the extent of the relative risk reduction is quite different depending on the current levels of consumption. For the same absolute reduction in alcohol intake, the gains in terms of reduction in cardiovascular risk will be more pronounced in those who drink heavily and will be more modest in those who drink at a light level.”

The results also suggest that while all levels of alcohol intake increase cardiovascular risk, there are low levels of alcohol consumption that do not carry major elevations in risk, but these are probably lower than those currently recommended, Dr. Aragam pointed out. 

“This doesn’t mean that everyone has to give up drinking alcohol completely, just that you shouldn’t consume with the goal of improving cardiovascular health. In fact, our analyses suggest that in an otherwise healthy person, up to 1 drink per day may not pose outsized risks,” he said. “And, even in a less healthy person who might be smoking, eating poorly, and drinking up to 1 drink per day, it may be a higher priority to focus on smoking cessation and diet than cutting back further on alcohol.”

“Beyond that amount, though, the jury is still out. Our models suggested marked increases in risk even between 1 and 2 drinks per day, and of course even greater risk increases beyond that. So, it’s probably worth revisiting what one might consider a ‘safe’ amount within the moderate drinking categories. The conservative move for now might be to advise a limit of 1 drink per day,” he said.   

Dr. Aragam is supported by grants from the National Institutes of Health and the American Heart Association. He reports receiving speaking fees from the Novartis Institute for Biomedical Research.

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

Even very light alcohol intake is associated with an increased risk for cardiovascular disease, compared with not drinking at all, and the risk increases exponentially as alcohol intake rises, even at moderate levels, a new study shows.

“Our findings suggest that the observed benefit in individuals with light to moderate alcohol intake, which is consistently shown in epidemiological studies, is likely due to other positive lifestyle factors that are common in these individuals who drink lightly,” senior author Krishna Aragam, MD, Massachusetts General Hospital, Boston, told this news organization.

“Our results also showed that while all levels of alcohol were linked to increased risk of cardiovascular disease, the association was not linear. Rather, light alcohol intake was associated with rather modest risk increases, but there were exponential increases in cardiovascular risk with increasing amounts of alcohol consumption,” he said.

As the risk gradient appeared to increase quite sharply even between 1 and 2 drinks per day, Dr. Aragam suggested that what might be regarded as safe levels of drinking may trend downward in the future.

Kirby Hamilton/iStockphoto

They also conducted genetic analyses to examine the effect of alcohol and cardiovascular disease.   

Dr. Aragam explained that previous work has shown good evidence, in individuals who choose to drink, that several relevant genetic variants predict levels of alcohol consumption quite accurately.

“Mendelian randomization using these gene variants allows for stronger inferences about potential causality than do observational studies, as they are less affected by confounding factors,” he noted.

Newer techniques in Mendelian randomization in which data on several gene variants linked to alcohol consumption are combined into a score allow for a greater understanding of the risk linked to different amount of alcohol intake, he added.

In these Mendelian randomization analyses, a 1-standard deviation increase in genetically predicted alcohol consumption was associated with 1.3-fold higher risk of hypertension (P < .001) and 1.4-fold higher risk of coronary artery disease (P = .006).

Further analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease; light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.

These results were replicated in a second database of 30,716 individuals from the Mass General Brigham Biobank.

“The findings of this study suggest that the observed cardioprotective effects of light to moderate alcohol intake may be largely mediated by confounding lifestyle factors,” the researchers conclude. “Genetic analyses suggest causal associations between alcohol intake and cardiovascular disease but with unequal and exponential increases in risk at greater levels of intake, which should be accounted for in health recommendations around the habitual consumption of alcohol.”

What is an acceptable level? 

“Specifically, our results suggest that consuming as many as 7 drinks per week is associated with relatively modest increases in cardiovascular risk,” they write.

But they point out that there are unequal increases in cardiovascular risk when progressing from 0 to 7 versus 7 to 14 drinks per week in both men and women.

“Although risk thresholds are inherently somewhat subjective, these findings again bring into question whether an average consumption of 2 drinks per day (14 drinks per week) should be designated a low-risk behavior,” they say.

“Furthermore, as several-fold increases in risk were observed for those consuming 21 or more drinks per week, our results emphasize the importance of aggressive efforts to reduce alcohol intake among heavy drinkers,” they add.

Dr. Aragam elaborated: “Our data suggest that reducing alcohol intake will reduce cardiovascular risk in all individuals, but the extent of the relative risk reduction is quite different depending on the current levels of consumption. For the same absolute reduction in alcohol intake, the gains in terms of reduction in cardiovascular risk will be more pronounced in those who drink heavily and will be more modest in those who drink at a light level.”

The results also suggest that while all levels of alcohol intake increase cardiovascular risk, there are low levels of alcohol consumption that do not carry major elevations in risk, but these are probably lower than those currently recommended, Dr. Aragam pointed out. 

“This doesn’t mean that everyone has to give up drinking alcohol completely, just that you shouldn’t consume with the goal of improving cardiovascular health. In fact, our analyses suggest that in an otherwise healthy person, up to 1 drink per day may not pose outsized risks,” he said. “And, even in a less healthy person who might be smoking, eating poorly, and drinking up to 1 drink per day, it may be a higher priority to focus on smoking cessation and diet than cutting back further on alcohol.”

“Beyond that amount, though, the jury is still out. Our models suggested marked increases in risk even between 1 and 2 drinks per day, and of course even greater risk increases beyond that. So, it’s probably worth revisiting what one might consider a ‘safe’ amount within the moderate drinking categories. The conservative move for now might be to advise a limit of 1 drink per day,” he said.   

Dr. Aragam is supported by grants from the National Institutes of Health and the American Heart Association. He reports receiving speaking fees from the Novartis Institute for Biomedical Research.

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

Even very light alcohol intake is associated with an increased risk for cardiovascular disease, compared with not drinking at all, and the risk increases exponentially as alcohol intake rises, even at moderate levels, a new study shows.

“Our findings suggest that the observed benefit in individuals with light to moderate alcohol intake, which is consistently shown in epidemiological studies, is likely due to other positive lifestyle factors that are common in these individuals who drink lightly,” senior author Krishna Aragam, MD, Massachusetts General Hospital, Boston, told this news organization.

“Our results also showed that while all levels of alcohol were linked to increased risk of cardiovascular disease, the association was not linear. Rather, light alcohol intake was associated with rather modest risk increases, but there were exponential increases in cardiovascular risk with increasing amounts of alcohol consumption,” he said.

As the risk gradient appeared to increase quite sharply even between 1 and 2 drinks per day, Dr. Aragam suggested that what might be regarded as safe levels of drinking may trend downward in the future.

Kirby Hamilton/iStockphoto

They also conducted genetic analyses to examine the effect of alcohol and cardiovascular disease.   

Dr. Aragam explained that previous work has shown good evidence, in individuals who choose to drink, that several relevant genetic variants predict levels of alcohol consumption quite accurately.

“Mendelian randomization using these gene variants allows for stronger inferences about potential causality than do observational studies, as they are less affected by confounding factors,” he noted.

Newer techniques in Mendelian randomization in which data on several gene variants linked to alcohol consumption are combined into a score allow for a greater understanding of the risk linked to different amount of alcohol intake, he added.

In these Mendelian randomization analyses, a 1-standard deviation increase in genetically predicted alcohol consumption was associated with 1.3-fold higher risk of hypertension (P < .001) and 1.4-fold higher risk of coronary artery disease (P = .006).

Further analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease; light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.

These results were replicated in a second database of 30,716 individuals from the Mass General Brigham Biobank.

“The findings of this study suggest that the observed cardioprotective effects of light to moderate alcohol intake may be largely mediated by confounding lifestyle factors,” the researchers conclude. “Genetic analyses suggest causal associations between alcohol intake and cardiovascular disease but with unequal and exponential increases in risk at greater levels of intake, which should be accounted for in health recommendations around the habitual consumption of alcohol.”

What is an acceptable level? 

“Specifically, our results suggest that consuming as many as 7 drinks per week is associated with relatively modest increases in cardiovascular risk,” they write.

But they point out that there are unequal increases in cardiovascular risk when progressing from 0 to 7 versus 7 to 14 drinks per week in both men and women.

“Although risk thresholds are inherently somewhat subjective, these findings again bring into question whether an average consumption of 2 drinks per day (14 drinks per week) should be designated a low-risk behavior,” they say.

“Furthermore, as several-fold increases in risk were observed for those consuming 21 or more drinks per week, our results emphasize the importance of aggressive efforts to reduce alcohol intake among heavy drinkers,” they add.

Dr. Aragam elaborated: “Our data suggest that reducing alcohol intake will reduce cardiovascular risk in all individuals, but the extent of the relative risk reduction is quite different depending on the current levels of consumption. For the same absolute reduction in alcohol intake, the gains in terms of reduction in cardiovascular risk will be more pronounced in those who drink heavily and will be more modest in those who drink at a light level.”

The results also suggest that while all levels of alcohol intake increase cardiovascular risk, there are low levels of alcohol consumption that do not carry major elevations in risk, but these are probably lower than those currently recommended, Dr. Aragam pointed out. 

“This doesn’t mean that everyone has to give up drinking alcohol completely, just that you shouldn’t consume with the goal of improving cardiovascular health. In fact, our analyses suggest that in an otherwise healthy person, up to 1 drink per day may not pose outsized risks,” he said. “And, even in a less healthy person who might be smoking, eating poorly, and drinking up to 1 drink per day, it may be a higher priority to focus on smoking cessation and diet than cutting back further on alcohol.”

“Beyond that amount, though, the jury is still out. Our models suggested marked increases in risk even between 1 and 2 drinks per day, and of course even greater risk increases beyond that. So, it’s probably worth revisiting what one might consider a ‘safe’ amount within the moderate drinking categories. The conservative move for now might be to advise a limit of 1 drink per day,” he said.   

Dr. Aragam is supported by grants from the National Institutes of Health and the American Heart Association. He reports receiving speaking fees from the Novartis Institute for Biomedical Research.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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