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Alpha-blockers deemed safe in heart failure
WASHINGTON – Prescribing alpha-adrenergic blocking agents for treatment of benign prostatic hypertrophy in men with heart failure proved to be not only safe, but also was associated with significantly reduced rates of both heart failure readmission and all-cause mortality in a large retrospective cohort study.
“These findings are associative, not necessarily causative. But the novel association between alpha-blocker treatment and improved outcomes may warrant further study,” Alberta L. Warner, MD, said at the annual meeting of the American College of Cardiology.
Many men with heart failure also have benign prostatic hypertrophy (BPH), for which they receive treatment with an alpha-blocker. Yet little is known about the impact of this drug class on safety and outcomes in the setting of heart failure. Of note, the use of alpha-blockers for treatment of hypertension was associated with increased risk of new-onset heart failure in the ALLHAT study.
To shed light on the safety of alpha-blockers in patients with prevalent heart failure, Dr. Warner and her coinvestigators analyzed data on nearly 170,000 men with a primary diagnosis of heart failure discharged from Veterans Affairs hospitals in 2002-2015. They determined that fully 28% of them left the hospital on an alpha-blocker. From this pool of nearly 48,000 heart failure patients, they were able to propensity-score match 38,991 on the basis of 54 baseline clinical characteristics to an equal number of VA heart failure patients who weren’t on an alpha-blocker. The study outcomes were time to first readmission for heart failure or all-cause mortality during 2 years of follow-up.
Patients on an alpha-blocker had a 38% heart failure readmission rate at 2 years, compared with 40% in nonusers, for a modest, albeit statistically significant, 6% reduction in relative risk. The all-cause mortality rate also was significantly lower in patients on an alpha-blocker: 40% versus 44%, for a 9% relative risk reduction.
In a subanalysis restricted to the heart failure patients on an alpha-blocker, higher-dose therapy was associated with a significantly lower incidence of all-cause mortality than was a lower-dose alpha-blocker during 2 years of follow-up, with a 9% relative risk reduction. A high-dose alpha-blocker, however, wasn’t significantly more effective than lower-dose therapy in terms of reducing heart failure readmissions, said Dr. Warner, a cardiologist at the Veterans Affairs Greater Los Angeles Healthcare System and the University of California, Los Angeles.
Similarly, patients treated with a nonspecific, peripherally vasoactive alpha-blocker had a significantly lower mortality rate than those on an alpha-1a-adrenergic–specific agent, with a highly significant 15% reduction in relative risk. The type of alpha-blocker, however, didn’t make a significant difference in terms of heart failure readmissions, where both types of agents were similarly better than not being on an alpha-blocker at all, she said.
Eighty-five percent of study participants were on a beta-blocker. Heart failure readmissions and all-cause mortality were significantly lower with alpha-blocker therapy, regardless of whether patients were on background beta-blocker therapy.
One audience member, however, noting that the beta-blocker carvedilol possesses some alpha-blocking effects, asked if outcomes differed depending on whether a patient was on carvedilol or metoprolol.
Dr. Warner replied that those numbers are still being crunched, and that the final answer isn’t in yet, but her preliminary impression is that the benefits of alpha-blocker therapy in terms of both heart failure readmissions and all-cause mortality were attenuated in the patients on carvedilol, possibly due to that beta-blocker’s alpha-blocking properties.
She reported having no financial conflicts regarding the study.
WASHINGTON – Prescribing alpha-adrenergic blocking agents for treatment of benign prostatic hypertrophy in men with heart failure proved to be not only safe, but also was associated with significantly reduced rates of both heart failure readmission and all-cause mortality in a large retrospective cohort study.
“These findings are associative, not necessarily causative. But the novel association between alpha-blocker treatment and improved outcomes may warrant further study,” Alberta L. Warner, MD, said at the annual meeting of the American College of Cardiology.
Many men with heart failure also have benign prostatic hypertrophy (BPH), for which they receive treatment with an alpha-blocker. Yet little is known about the impact of this drug class on safety and outcomes in the setting of heart failure. Of note, the use of alpha-blockers for treatment of hypertension was associated with increased risk of new-onset heart failure in the ALLHAT study.
To shed light on the safety of alpha-blockers in patients with prevalent heart failure, Dr. Warner and her coinvestigators analyzed data on nearly 170,000 men with a primary diagnosis of heart failure discharged from Veterans Affairs hospitals in 2002-2015. They determined that fully 28% of them left the hospital on an alpha-blocker. From this pool of nearly 48,000 heart failure patients, they were able to propensity-score match 38,991 on the basis of 54 baseline clinical characteristics to an equal number of VA heart failure patients who weren’t on an alpha-blocker. The study outcomes were time to first readmission for heart failure or all-cause mortality during 2 years of follow-up.
Patients on an alpha-blocker had a 38% heart failure readmission rate at 2 years, compared with 40% in nonusers, for a modest, albeit statistically significant, 6% reduction in relative risk. The all-cause mortality rate also was significantly lower in patients on an alpha-blocker: 40% versus 44%, for a 9% relative risk reduction.
In a subanalysis restricted to the heart failure patients on an alpha-blocker, higher-dose therapy was associated with a significantly lower incidence of all-cause mortality than was a lower-dose alpha-blocker during 2 years of follow-up, with a 9% relative risk reduction. A high-dose alpha-blocker, however, wasn’t significantly more effective than lower-dose therapy in terms of reducing heart failure readmissions, said Dr. Warner, a cardiologist at the Veterans Affairs Greater Los Angeles Healthcare System and the University of California, Los Angeles.
Similarly, patients treated with a nonspecific, peripherally vasoactive alpha-blocker had a significantly lower mortality rate than those on an alpha-1a-adrenergic–specific agent, with a highly significant 15% reduction in relative risk. The type of alpha-blocker, however, didn’t make a significant difference in terms of heart failure readmissions, where both types of agents were similarly better than not being on an alpha-blocker at all, she said.
Eighty-five percent of study participants were on a beta-blocker. Heart failure readmissions and all-cause mortality were significantly lower with alpha-blocker therapy, regardless of whether patients were on background beta-blocker therapy.
One audience member, however, noting that the beta-blocker carvedilol possesses some alpha-blocking effects, asked if outcomes differed depending on whether a patient was on carvedilol or metoprolol.
Dr. Warner replied that those numbers are still being crunched, and that the final answer isn’t in yet, but her preliminary impression is that the benefits of alpha-blocker therapy in terms of both heart failure readmissions and all-cause mortality were attenuated in the patients on carvedilol, possibly due to that beta-blocker’s alpha-blocking properties.
She reported having no financial conflicts regarding the study.
WASHINGTON – Prescribing alpha-adrenergic blocking agents for treatment of benign prostatic hypertrophy in men with heart failure proved to be not only safe, but also was associated with significantly reduced rates of both heart failure readmission and all-cause mortality in a large retrospective cohort study.
“These findings are associative, not necessarily causative. But the novel association between alpha-blocker treatment and improved outcomes may warrant further study,” Alberta L. Warner, MD, said at the annual meeting of the American College of Cardiology.
Many men with heart failure also have benign prostatic hypertrophy (BPH), for which they receive treatment with an alpha-blocker. Yet little is known about the impact of this drug class on safety and outcomes in the setting of heart failure. Of note, the use of alpha-blockers for treatment of hypertension was associated with increased risk of new-onset heart failure in the ALLHAT study.
To shed light on the safety of alpha-blockers in patients with prevalent heart failure, Dr. Warner and her coinvestigators analyzed data on nearly 170,000 men with a primary diagnosis of heart failure discharged from Veterans Affairs hospitals in 2002-2015. They determined that fully 28% of them left the hospital on an alpha-blocker. From this pool of nearly 48,000 heart failure patients, they were able to propensity-score match 38,991 on the basis of 54 baseline clinical characteristics to an equal number of VA heart failure patients who weren’t on an alpha-blocker. The study outcomes were time to first readmission for heart failure or all-cause mortality during 2 years of follow-up.
Patients on an alpha-blocker had a 38% heart failure readmission rate at 2 years, compared with 40% in nonusers, for a modest, albeit statistically significant, 6% reduction in relative risk. The all-cause mortality rate also was significantly lower in patients on an alpha-blocker: 40% versus 44%, for a 9% relative risk reduction.
In a subanalysis restricted to the heart failure patients on an alpha-blocker, higher-dose therapy was associated with a significantly lower incidence of all-cause mortality than was a lower-dose alpha-blocker during 2 years of follow-up, with a 9% relative risk reduction. A high-dose alpha-blocker, however, wasn’t significantly more effective than lower-dose therapy in terms of reducing heart failure readmissions, said Dr. Warner, a cardiologist at the Veterans Affairs Greater Los Angeles Healthcare System and the University of California, Los Angeles.
Similarly, patients treated with a nonspecific, peripherally vasoactive alpha-blocker had a significantly lower mortality rate than those on an alpha-1a-adrenergic–specific agent, with a highly significant 15% reduction in relative risk. The type of alpha-blocker, however, didn’t make a significant difference in terms of heart failure readmissions, where both types of agents were similarly better than not being on an alpha-blocker at all, she said.
Eighty-five percent of study participants were on a beta-blocker. Heart failure readmissions and all-cause mortality were significantly lower with alpha-blocker therapy, regardless of whether patients were on background beta-blocker therapy.
One audience member, however, noting that the beta-blocker carvedilol possesses some alpha-blocking effects, asked if outcomes differed depending on whether a patient was on carvedilol or metoprolol.
Dr. Warner replied that those numbers are still being crunched, and that the final answer isn’t in yet, but her preliminary impression is that the benefits of alpha-blocker therapy in terms of both heart failure readmissions and all-cause mortality were attenuated in the patients on carvedilol, possibly due to that beta-blocker’s alpha-blocking properties.
She reported having no financial conflicts regarding the study.
Key clinical point:
Major finding: The risk of all-cause mortality in heart failure patients on an alpha-blocker was 9% lower than in extensively matched controls during 2 years of follow-up.
Data source: This retrospective cohort study included 38,991 heart failure patients taking an alpha-blocker for benign prostatic hypertrophy who were propensity matched on 54 clinical characteristics to an equal number of heart failure controls not on the medication.
Disclosures: The study presenter reported having no financial conflicts.
New-onset AF boosts bad HFrEF outcomes
WASHINGTON – New onset atrial fibrillation more than doubled the rate of adverse outcomes in patients with heart failure with reduced ejection fraction in a review of more than 15,000 such patients.
In 9,934 patients with heart failure with reduced ejection fraction (HFrEF) and no history of atrial fibrillation (AF), development of new-onset AF was linked with a greater than twofold increased risk of cardiovascular disease death or hospitalization for heart failure during follow-up, compared with HFrEF patients who did not initially have or later develop heart failure, after adjustment for several demographic and clinical variables, John J.V. McMurray, MD, said at the annual meeting of the American College of Cardiology. This difference for the primary endpoint of his analysis was statistically significant.
The 1,645 patients with paroxysmal AF at the start of their follow-up also had a significantly increased rate of cardiovascular death or heart failure hospitalization, but their increased risk when compared with HFrEF patients who didn’t develop AF was a much more modest 20% in his fully adjusted analysis. The patients who began follow-up with paroxysmal AF also had a relatively increased relative stroke rate of 33% when compared with HFrEF patients without AF at baseline who remained AF free, but the all-cause mortality rate among those with paroxysmal AF wasn’t significantly elevated, compared with the comparator group.
The 3,770 patients with persistent or permanent AF at baseline showed no statistically significant spike in their adverse event rates, compared with patients without AF, for any of the examined endpoints. The study group also included 66 patients with an undefined form of AF who weren’t included in these analyses.
“It’s the first episodes and paroxysmal episodes that cause trouble, and the trouble they cause is stroke,” Dr. McMurray said in an interview. Their stroke risk gets exacerbated in clinical practice, because these patients often don’t receive the stroke prevention they need in the form of anticoagulation treatment.
“We find over and over that patients with paroxysmal AF are not anticoagulated as frequently as they should be,” Dr. McMurray said. And HFrEF patients with a first AF episode need anticoagulation, too, as soon as AF is diagnosed, he advised.
He went a step further and speculated that the reason why HFrEF patients with new onset AF did so poorly in his analysis was because they already had several prior, brief AF episodes that had gone undetected. “Many of these patients probably had undiagnosed, clinically unapparent AF episodes” that then resulted in strokes, he suggested.
The upshot is that patients with HFrEF may need more aggressive monitoring for new-onset AF, possibly in the form of small, implanted arrhythmia-detection devices. Dr. McMurray said that he and other researchers are currently testing whether this hypothesis is correct. “We and others are now looking at this because these new data are convincing that new-onset AF is bad news [for HFrEF patients].”
In the analysis, “we looked only at clinically recognized and adjudicated new-onset AF. Goodness knows how many HFrEF patients are having unrecognized paroxysmal AF. Almost certainly there is a lot that is unrecognized” that potentially could be detected using a small implanted arrhythmia monitor, which could then lead to earlier anticoagulant treatment as well as possible treatment with antiarrhythmic drugs or with catheter ablation, Dr. McMurray said. Looking for undetected AF in HFrEF patients “is where the science is moving.”
The findings that Dr. McMurray reported are “something we should act on,” commented Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The comorbidity of AF in HFrEF patients requires “aggressive anticoagulation, and also a review of their heart failure medical treatment to be sure that is optimized, because AF could be a sign of worsening heart failure,” Dr. Hernandez said in an interview. “We may need to more aggressively get HFrEF patients with AF into normal sinus rhythm.”
When Mikhail Kosiborod, MD, treats HFrEF patients with a high risk for AF, such as patients with lower ejection fractions, a dilated left ventricle, or a dilated atrium, “I frequently do 30-day loop recordings in these patients because of their risk for incident AF,” Dr. Kosiborod said in an interview. “We don’t yet have convincing evidence for this, but it makes sense.”
Another finding from his analysis was that the HFrEF patients enrolled in these two trials did not get treatment with a mineralocorticoid receptor antagonist – spironolactone or eplerenone – “as often as they should,” with treatment rates of 44%-48%, compared with use of a beta-blocker in 92%-95% of patients. Treatment with eplerenone (Inspra) “has been shown to reduce the risk for new onset AF, so adding eplerenone or spironolactone is an important step that could be taken to try to prevent AF as well as treat the HFrEF and reduce mortality,” Dr. McMurray said.
PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen. Dr. Hernandez has received honoraria from Amgen, AstraZeneca, Janssen, Merck, and Novartis, and has received research support from Amgen, Bayer, Merck, and Portola. Dr. Kosiborod has been a consultant to several drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Gilead, and Sanofi-Aventis.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – New onset atrial fibrillation more than doubled the rate of adverse outcomes in patients with heart failure with reduced ejection fraction in a review of more than 15,000 such patients.
In 9,934 patients with heart failure with reduced ejection fraction (HFrEF) and no history of atrial fibrillation (AF), development of new-onset AF was linked with a greater than twofold increased risk of cardiovascular disease death or hospitalization for heart failure during follow-up, compared with HFrEF patients who did not initially have or later develop heart failure, after adjustment for several demographic and clinical variables, John J.V. McMurray, MD, said at the annual meeting of the American College of Cardiology. This difference for the primary endpoint of his analysis was statistically significant.
The 1,645 patients with paroxysmal AF at the start of their follow-up also had a significantly increased rate of cardiovascular death or heart failure hospitalization, but their increased risk when compared with HFrEF patients who didn’t develop AF was a much more modest 20% in his fully adjusted analysis. The patients who began follow-up with paroxysmal AF also had a relatively increased relative stroke rate of 33% when compared with HFrEF patients without AF at baseline who remained AF free, but the all-cause mortality rate among those with paroxysmal AF wasn’t significantly elevated, compared with the comparator group.
The 3,770 patients with persistent or permanent AF at baseline showed no statistically significant spike in their adverse event rates, compared with patients without AF, for any of the examined endpoints. The study group also included 66 patients with an undefined form of AF who weren’t included in these analyses.
“It’s the first episodes and paroxysmal episodes that cause trouble, and the trouble they cause is stroke,” Dr. McMurray said in an interview. Their stroke risk gets exacerbated in clinical practice, because these patients often don’t receive the stroke prevention they need in the form of anticoagulation treatment.
“We find over and over that patients with paroxysmal AF are not anticoagulated as frequently as they should be,” Dr. McMurray said. And HFrEF patients with a first AF episode need anticoagulation, too, as soon as AF is diagnosed, he advised.
He went a step further and speculated that the reason why HFrEF patients with new onset AF did so poorly in his analysis was because they already had several prior, brief AF episodes that had gone undetected. “Many of these patients probably had undiagnosed, clinically unapparent AF episodes” that then resulted in strokes, he suggested.
The upshot is that patients with HFrEF may need more aggressive monitoring for new-onset AF, possibly in the form of small, implanted arrhythmia-detection devices. Dr. McMurray said that he and other researchers are currently testing whether this hypothesis is correct. “We and others are now looking at this because these new data are convincing that new-onset AF is bad news [for HFrEF patients].”
In the analysis, “we looked only at clinically recognized and adjudicated new-onset AF. Goodness knows how many HFrEF patients are having unrecognized paroxysmal AF. Almost certainly there is a lot that is unrecognized” that potentially could be detected using a small implanted arrhythmia monitor, which could then lead to earlier anticoagulant treatment as well as possible treatment with antiarrhythmic drugs or with catheter ablation, Dr. McMurray said. Looking for undetected AF in HFrEF patients “is where the science is moving.”
The findings that Dr. McMurray reported are “something we should act on,” commented Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The comorbidity of AF in HFrEF patients requires “aggressive anticoagulation, and also a review of their heart failure medical treatment to be sure that is optimized, because AF could be a sign of worsening heart failure,” Dr. Hernandez said in an interview. “We may need to more aggressively get HFrEF patients with AF into normal sinus rhythm.”
When Mikhail Kosiborod, MD, treats HFrEF patients with a high risk for AF, such as patients with lower ejection fractions, a dilated left ventricle, or a dilated atrium, “I frequently do 30-day loop recordings in these patients because of their risk for incident AF,” Dr. Kosiborod said in an interview. “We don’t yet have convincing evidence for this, but it makes sense.”
Another finding from his analysis was that the HFrEF patients enrolled in these two trials did not get treatment with a mineralocorticoid receptor antagonist – spironolactone or eplerenone – “as often as they should,” with treatment rates of 44%-48%, compared with use of a beta-blocker in 92%-95% of patients. Treatment with eplerenone (Inspra) “has been shown to reduce the risk for new onset AF, so adding eplerenone or spironolactone is an important step that could be taken to try to prevent AF as well as treat the HFrEF and reduce mortality,” Dr. McMurray said.
PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen. Dr. Hernandez has received honoraria from Amgen, AstraZeneca, Janssen, Merck, and Novartis, and has received research support from Amgen, Bayer, Merck, and Portola. Dr. Kosiborod has been a consultant to several drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Gilead, and Sanofi-Aventis.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – New onset atrial fibrillation more than doubled the rate of adverse outcomes in patients with heart failure with reduced ejection fraction in a review of more than 15,000 such patients.
In 9,934 patients with heart failure with reduced ejection fraction (HFrEF) and no history of atrial fibrillation (AF), development of new-onset AF was linked with a greater than twofold increased risk of cardiovascular disease death or hospitalization for heart failure during follow-up, compared with HFrEF patients who did not initially have or later develop heart failure, after adjustment for several demographic and clinical variables, John J.V. McMurray, MD, said at the annual meeting of the American College of Cardiology. This difference for the primary endpoint of his analysis was statistically significant.
The 1,645 patients with paroxysmal AF at the start of their follow-up also had a significantly increased rate of cardiovascular death or heart failure hospitalization, but their increased risk when compared with HFrEF patients who didn’t develop AF was a much more modest 20% in his fully adjusted analysis. The patients who began follow-up with paroxysmal AF also had a relatively increased relative stroke rate of 33% when compared with HFrEF patients without AF at baseline who remained AF free, but the all-cause mortality rate among those with paroxysmal AF wasn’t significantly elevated, compared with the comparator group.
The 3,770 patients with persistent or permanent AF at baseline showed no statistically significant spike in their adverse event rates, compared with patients without AF, for any of the examined endpoints. The study group also included 66 patients with an undefined form of AF who weren’t included in these analyses.
“It’s the first episodes and paroxysmal episodes that cause trouble, and the trouble they cause is stroke,” Dr. McMurray said in an interview. Their stroke risk gets exacerbated in clinical practice, because these patients often don’t receive the stroke prevention they need in the form of anticoagulation treatment.
“We find over and over that patients with paroxysmal AF are not anticoagulated as frequently as they should be,” Dr. McMurray said. And HFrEF patients with a first AF episode need anticoagulation, too, as soon as AF is diagnosed, he advised.
He went a step further and speculated that the reason why HFrEF patients with new onset AF did so poorly in his analysis was because they already had several prior, brief AF episodes that had gone undetected. “Many of these patients probably had undiagnosed, clinically unapparent AF episodes” that then resulted in strokes, he suggested.
The upshot is that patients with HFrEF may need more aggressive monitoring for new-onset AF, possibly in the form of small, implanted arrhythmia-detection devices. Dr. McMurray said that he and other researchers are currently testing whether this hypothesis is correct. “We and others are now looking at this because these new data are convincing that new-onset AF is bad news [for HFrEF patients].”
In the analysis, “we looked only at clinically recognized and adjudicated new-onset AF. Goodness knows how many HFrEF patients are having unrecognized paroxysmal AF. Almost certainly there is a lot that is unrecognized” that potentially could be detected using a small implanted arrhythmia monitor, which could then lead to earlier anticoagulant treatment as well as possible treatment with antiarrhythmic drugs or with catheter ablation, Dr. McMurray said. Looking for undetected AF in HFrEF patients “is where the science is moving.”
The findings that Dr. McMurray reported are “something we should act on,” commented Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The comorbidity of AF in HFrEF patients requires “aggressive anticoagulation, and also a review of their heart failure medical treatment to be sure that is optimized, because AF could be a sign of worsening heart failure,” Dr. Hernandez said in an interview. “We may need to more aggressively get HFrEF patients with AF into normal sinus rhythm.”
When Mikhail Kosiborod, MD, treats HFrEF patients with a high risk for AF, such as patients with lower ejection fractions, a dilated left ventricle, or a dilated atrium, “I frequently do 30-day loop recordings in these patients because of their risk for incident AF,” Dr. Kosiborod said in an interview. “We don’t yet have convincing evidence for this, but it makes sense.”
Another finding from his analysis was that the HFrEF patients enrolled in these two trials did not get treatment with a mineralocorticoid receptor antagonist – spironolactone or eplerenone – “as often as they should,” with treatment rates of 44%-48%, compared with use of a beta-blocker in 92%-95% of patients. Treatment with eplerenone (Inspra) “has been shown to reduce the risk for new onset AF, so adding eplerenone or spironolactone is an important step that could be taken to try to prevent AF as well as treat the HFrEF and reduce mortality,” Dr. McMurray said.
PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen. Dr. Hernandez has received honoraria from Amgen, AstraZeneca, Janssen, Merck, and Novartis, and has received research support from Amgen, Bayer, Merck, and Portola. Dr. Kosiborod has been a consultant to several drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Gilead, and Sanofi-Aventis.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: Adverse outcomes were more than twice as frequent in HFrEF patients with incident atrial fibrillation, compared with those without AF.
Data source: Post hoc analysis of 15,415 heart failure patients enrolled in the PARADIGM-HF and ATMOSPHERE trials.
Disclosures: PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen.
Gliflozins’ heart failure protection in type 2 diabetes confirmed
WASHINGTON – The remarkable and unexpected findings first reported from the EMPA-REG OUTCOME trial in late 2015 – that treatment of type 2 diabetes patients with the SGLT-2 inhibitor empagliflozin led to significantly reduced rates of heart failure hospitalization and all-cause death – received its first major confirmation in an analysis of observational data collected from more than 300,000 patients with type 2 diabetes treated in six countries including the United States.
The new findings also, for the first time, extended the EMPA-REG OUTCOME results (N Engl J Med. 2015 Nov 26;373[22]:2117-28) beyond empagliflozin with evidence that the heart failure and mortality benefit also occurred with other drugs from the sodium glucose cotransporter–2 (SGLT-2) inhibitor class, specifically canagliflozin and dapagliflozin, Mikhail Kosiborod, MD, said at the annual meeting of the American College of Cardiology.
The analysis showed that type 2 diabetes patients who were newly started on treatment with one of these SGLT-2 inhibitors had during follow-up a 39% reduced rate of heart failure hospitalizations, a 51% reduced mortality rate, and a 46% reduced rate of the combined endpoint of heart failure hospitalization or death, compared with patients treated with any other type of oral glucose-lowering drug, reported Dr. Kosiborod. The risk reductions were “remarkably similar to those seen in EMPA-REG OUTCOME,” he noted.
The findings address three “key questions” raised by the EMPA-REG OUTCOME results, Dr. Kosiborod, a cardiologist and professor of medicine at Saint Luke’s Mid America Heart Institute in Kansas City, Mo., said in an interview:
• Is this a class effect? The data “seem to suggest that the benefits seen in the EMPA-REG OUTCOME study are likely a class effect.” The study population of 154,523 patients in the heart failure hospitalization analysis who began treatment with an SGLT-2 inhibitor included 53% who received canagliflozin (Invokana), 42% who received dapagliflozin (Farxiga), and 6% who received empagliflozin (Jardiance) (percentages total 101% because of rounding). Dr. Kosiborod also highlighted that within several of the six countries that contributed data to this analysis – the United States, Denmark, Germany, Norway, Sweden, and the United Kingdom – the percentages of patients on each of these three drugs varied substantially, but despite that the relative reduced risks for heart failure hospitalization and mortality were roughly the same within each country, giving further credence to the notion that a class effect exists.
• Do lower-risk patients benefit? “The benefits of SGLT-2 inhibitor treatment appeared to extend to lower risk patients” than those enrolled in EMPA-REG OUTCOME. In the randomized trial, which enrolled 7,028 patients, more than 99% had established cardiovascular disease. In the new analysis patients had a 13% prevalence of any cardiovascular disease at baseline, and the prevalence of heart failure was 3%.
• Is this relevant to clinical practice? Unlike the highly selected patients entered in the EMPA-REG OUTCOME trial, the patients started on an SGLT-2 inhibitor in the observational study were unselected and came from routine practice situations, “suggesting that the benefits seen in EMPA-REG OUTCOME translate into real-world clinical practice,” Dr. Kosiborod said. “With these data we see for the first time in a large number of patients from multiple countries important evidence suggesting that the SGLT-2 inhibitors may provide in the real world a similar benefit to what was observed in EMPA-REG OUTCOME.”
“The lesson from Dr. Kosiborod’s study is that among patients with type 2 diabetes, treatment with an SGLT-2 inhibitor seems to result in lowered rates of heart failure hospitalizations and mortality, and it’s a safe class of drugs. In the past, we worried about worsening heart failure in patients at risk for developing heart failure” such as patients with type 2 diabetes, said Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The new data make it seem like using an SGLT-2 inhibitor to treat patients with type 2 diabetes “is an appropriate strategy.” But Dr. Hernandez added that in his opinion metformin remains the top drug for type 2 diabetes, while SGLT-2 inhibitors are now “the next drug class to add,” he said in an interview.
Dr. Kosiborod had a somewhat different take. “If a patient with type 2 diabetes did not want to enter a trial or couldn’t get into a trial and fit the profile of a patient who could benefit, I would absolutely treat that patient with an SGLT-2 inhibitor. I’m using these medications clinically as a cardiologist,” he said. “Treatments that have significant benefits for important outcomes should be prioritized over treatments that may reduce hemoglobin A1c but do not have similar benefits.”
The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study used data from adult, previously untreated patients with type 2 diabetes in national registries from the five included European countries. U.S. data were from the Truven Health MarketScan database and from Medicare. This produced a total pool of 160,010 patients who began treatment on an SGLT-2 inhibitor and 1,139,905 patients who began treatment with another oral antidiabetes drug.
Dr. Kosiborod and his associates then performed propensity-score matching to identify 154,523 patients started on an SGLT-2 inhibitor who each closely matched a patient from the other subgroup for baseline demographic and clinical features, producing an analysis dataset of just over 309,000 matched patients. The average age of the included patients was 57 years; 45% were women. During follow-up, 961 patients had a heart failure hospitalization and 1,334 patients died.
Dr. Kosiborod noted that while a potential limitation to his findings is residual confounding not eliminated by the propensity score matching, he was confident about the results because the incidence of other outcomes not expected to be influenced by treatment with SGLT-2 inhibitors were similar in the two study subgroups, suggesting that the linkages between the kind of drug used and differences in heart failure hospitalization rates and in mortality weren’t spurious.
“If there was residual confounding, you’d expect to see similar associations for other endpoints, which we didn’t see,” he said. In addition, the heart failure hospitalization rate differences seen between the SGLT-2 inhibitor recipients and the other patients were consistent in a trio of sensitivity analyses, further buttressing the findings’ plausibility.
CVD-REAL was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Kosiborod has been a consultant to and/or received research funding from AstraZeneca, Boehringer Ingelheim, Sanofi-Aventis and Gilead. Dr. Hernandez has received honoraria and/or research support from AstraZeneca, Amgen, Janssen, Merck, Novartis, and Portola. Several of the coauthors on the CVD-REAL study were AstraZeneca employees.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – The remarkable and unexpected findings first reported from the EMPA-REG OUTCOME trial in late 2015 – that treatment of type 2 diabetes patients with the SGLT-2 inhibitor empagliflozin led to significantly reduced rates of heart failure hospitalization and all-cause death – received its first major confirmation in an analysis of observational data collected from more than 300,000 patients with type 2 diabetes treated in six countries including the United States.
The new findings also, for the first time, extended the EMPA-REG OUTCOME results (N Engl J Med. 2015 Nov 26;373[22]:2117-28) beyond empagliflozin with evidence that the heart failure and mortality benefit also occurred with other drugs from the sodium glucose cotransporter–2 (SGLT-2) inhibitor class, specifically canagliflozin and dapagliflozin, Mikhail Kosiborod, MD, said at the annual meeting of the American College of Cardiology.
The analysis showed that type 2 diabetes patients who were newly started on treatment with one of these SGLT-2 inhibitors had during follow-up a 39% reduced rate of heart failure hospitalizations, a 51% reduced mortality rate, and a 46% reduced rate of the combined endpoint of heart failure hospitalization or death, compared with patients treated with any other type of oral glucose-lowering drug, reported Dr. Kosiborod. The risk reductions were “remarkably similar to those seen in EMPA-REG OUTCOME,” he noted.
The findings address three “key questions” raised by the EMPA-REG OUTCOME results, Dr. Kosiborod, a cardiologist and professor of medicine at Saint Luke’s Mid America Heart Institute in Kansas City, Mo., said in an interview:
• Is this a class effect? The data “seem to suggest that the benefits seen in the EMPA-REG OUTCOME study are likely a class effect.” The study population of 154,523 patients in the heart failure hospitalization analysis who began treatment with an SGLT-2 inhibitor included 53% who received canagliflozin (Invokana), 42% who received dapagliflozin (Farxiga), and 6% who received empagliflozin (Jardiance) (percentages total 101% because of rounding). Dr. Kosiborod also highlighted that within several of the six countries that contributed data to this analysis – the United States, Denmark, Germany, Norway, Sweden, and the United Kingdom – the percentages of patients on each of these three drugs varied substantially, but despite that the relative reduced risks for heart failure hospitalization and mortality were roughly the same within each country, giving further credence to the notion that a class effect exists.
• Do lower-risk patients benefit? “The benefits of SGLT-2 inhibitor treatment appeared to extend to lower risk patients” than those enrolled in EMPA-REG OUTCOME. In the randomized trial, which enrolled 7,028 patients, more than 99% had established cardiovascular disease. In the new analysis patients had a 13% prevalence of any cardiovascular disease at baseline, and the prevalence of heart failure was 3%.
• Is this relevant to clinical practice? Unlike the highly selected patients entered in the EMPA-REG OUTCOME trial, the patients started on an SGLT-2 inhibitor in the observational study were unselected and came from routine practice situations, “suggesting that the benefits seen in EMPA-REG OUTCOME translate into real-world clinical practice,” Dr. Kosiborod said. “With these data we see for the first time in a large number of patients from multiple countries important evidence suggesting that the SGLT-2 inhibitors may provide in the real world a similar benefit to what was observed in EMPA-REG OUTCOME.”
“The lesson from Dr. Kosiborod’s study is that among patients with type 2 diabetes, treatment with an SGLT-2 inhibitor seems to result in lowered rates of heart failure hospitalizations and mortality, and it’s a safe class of drugs. In the past, we worried about worsening heart failure in patients at risk for developing heart failure” such as patients with type 2 diabetes, said Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The new data make it seem like using an SGLT-2 inhibitor to treat patients with type 2 diabetes “is an appropriate strategy.” But Dr. Hernandez added that in his opinion metformin remains the top drug for type 2 diabetes, while SGLT-2 inhibitors are now “the next drug class to add,” he said in an interview.
Dr. Kosiborod had a somewhat different take. “If a patient with type 2 diabetes did not want to enter a trial or couldn’t get into a trial and fit the profile of a patient who could benefit, I would absolutely treat that patient with an SGLT-2 inhibitor. I’m using these medications clinically as a cardiologist,” he said. “Treatments that have significant benefits for important outcomes should be prioritized over treatments that may reduce hemoglobin A1c but do not have similar benefits.”
The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study used data from adult, previously untreated patients with type 2 diabetes in national registries from the five included European countries. U.S. data were from the Truven Health MarketScan database and from Medicare. This produced a total pool of 160,010 patients who began treatment on an SGLT-2 inhibitor and 1,139,905 patients who began treatment with another oral antidiabetes drug.
Dr. Kosiborod and his associates then performed propensity-score matching to identify 154,523 patients started on an SGLT-2 inhibitor who each closely matched a patient from the other subgroup for baseline demographic and clinical features, producing an analysis dataset of just over 309,000 matched patients. The average age of the included patients was 57 years; 45% were women. During follow-up, 961 patients had a heart failure hospitalization and 1,334 patients died.
Dr. Kosiborod noted that while a potential limitation to his findings is residual confounding not eliminated by the propensity score matching, he was confident about the results because the incidence of other outcomes not expected to be influenced by treatment with SGLT-2 inhibitors were similar in the two study subgroups, suggesting that the linkages between the kind of drug used and differences in heart failure hospitalization rates and in mortality weren’t spurious.
“If there was residual confounding, you’d expect to see similar associations for other endpoints, which we didn’t see,” he said. In addition, the heart failure hospitalization rate differences seen between the SGLT-2 inhibitor recipients and the other patients were consistent in a trio of sensitivity analyses, further buttressing the findings’ plausibility.
CVD-REAL was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Kosiborod has been a consultant to and/or received research funding from AstraZeneca, Boehringer Ingelheim, Sanofi-Aventis and Gilead. Dr. Hernandez has received honoraria and/or research support from AstraZeneca, Amgen, Janssen, Merck, Novartis, and Portola. Several of the coauthors on the CVD-REAL study were AstraZeneca employees.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – The remarkable and unexpected findings first reported from the EMPA-REG OUTCOME trial in late 2015 – that treatment of type 2 diabetes patients with the SGLT-2 inhibitor empagliflozin led to significantly reduced rates of heart failure hospitalization and all-cause death – received its first major confirmation in an analysis of observational data collected from more than 300,000 patients with type 2 diabetes treated in six countries including the United States.
The new findings also, for the first time, extended the EMPA-REG OUTCOME results (N Engl J Med. 2015 Nov 26;373[22]:2117-28) beyond empagliflozin with evidence that the heart failure and mortality benefit also occurred with other drugs from the sodium glucose cotransporter–2 (SGLT-2) inhibitor class, specifically canagliflozin and dapagliflozin, Mikhail Kosiborod, MD, said at the annual meeting of the American College of Cardiology.
The analysis showed that type 2 diabetes patients who were newly started on treatment with one of these SGLT-2 inhibitors had during follow-up a 39% reduced rate of heart failure hospitalizations, a 51% reduced mortality rate, and a 46% reduced rate of the combined endpoint of heart failure hospitalization or death, compared with patients treated with any other type of oral glucose-lowering drug, reported Dr. Kosiborod. The risk reductions were “remarkably similar to those seen in EMPA-REG OUTCOME,” he noted.
The findings address three “key questions” raised by the EMPA-REG OUTCOME results, Dr. Kosiborod, a cardiologist and professor of medicine at Saint Luke’s Mid America Heart Institute in Kansas City, Mo., said in an interview:
• Is this a class effect? The data “seem to suggest that the benefits seen in the EMPA-REG OUTCOME study are likely a class effect.” The study population of 154,523 patients in the heart failure hospitalization analysis who began treatment with an SGLT-2 inhibitor included 53% who received canagliflozin (Invokana), 42% who received dapagliflozin (Farxiga), and 6% who received empagliflozin (Jardiance) (percentages total 101% because of rounding). Dr. Kosiborod also highlighted that within several of the six countries that contributed data to this analysis – the United States, Denmark, Germany, Norway, Sweden, and the United Kingdom – the percentages of patients on each of these three drugs varied substantially, but despite that the relative reduced risks for heart failure hospitalization and mortality were roughly the same within each country, giving further credence to the notion that a class effect exists.
• Do lower-risk patients benefit? “The benefits of SGLT-2 inhibitor treatment appeared to extend to lower risk patients” than those enrolled in EMPA-REG OUTCOME. In the randomized trial, which enrolled 7,028 patients, more than 99% had established cardiovascular disease. In the new analysis patients had a 13% prevalence of any cardiovascular disease at baseline, and the prevalence of heart failure was 3%.
• Is this relevant to clinical practice? Unlike the highly selected patients entered in the EMPA-REG OUTCOME trial, the patients started on an SGLT-2 inhibitor in the observational study were unselected and came from routine practice situations, “suggesting that the benefits seen in EMPA-REG OUTCOME translate into real-world clinical practice,” Dr. Kosiborod said. “With these data we see for the first time in a large number of patients from multiple countries important evidence suggesting that the SGLT-2 inhibitors may provide in the real world a similar benefit to what was observed in EMPA-REG OUTCOME.”
“The lesson from Dr. Kosiborod’s study is that among patients with type 2 diabetes, treatment with an SGLT-2 inhibitor seems to result in lowered rates of heart failure hospitalizations and mortality, and it’s a safe class of drugs. In the past, we worried about worsening heart failure in patients at risk for developing heart failure” such as patients with type 2 diabetes, said Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The new data make it seem like using an SGLT-2 inhibitor to treat patients with type 2 diabetes “is an appropriate strategy.” But Dr. Hernandez added that in his opinion metformin remains the top drug for type 2 diabetes, while SGLT-2 inhibitors are now “the next drug class to add,” he said in an interview.
Dr. Kosiborod had a somewhat different take. “If a patient with type 2 diabetes did not want to enter a trial or couldn’t get into a trial and fit the profile of a patient who could benefit, I would absolutely treat that patient with an SGLT-2 inhibitor. I’m using these medications clinically as a cardiologist,” he said. “Treatments that have significant benefits for important outcomes should be prioritized over treatments that may reduce hemoglobin A1c but do not have similar benefits.”
The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study used data from adult, previously untreated patients with type 2 diabetes in national registries from the five included European countries. U.S. data were from the Truven Health MarketScan database and from Medicare. This produced a total pool of 160,010 patients who began treatment on an SGLT-2 inhibitor and 1,139,905 patients who began treatment with another oral antidiabetes drug.
Dr. Kosiborod and his associates then performed propensity-score matching to identify 154,523 patients started on an SGLT-2 inhibitor who each closely matched a patient from the other subgroup for baseline demographic and clinical features, producing an analysis dataset of just over 309,000 matched patients. The average age of the included patients was 57 years; 45% were women. During follow-up, 961 patients had a heart failure hospitalization and 1,334 patients died.
Dr. Kosiborod noted that while a potential limitation to his findings is residual confounding not eliminated by the propensity score matching, he was confident about the results because the incidence of other outcomes not expected to be influenced by treatment with SGLT-2 inhibitors were similar in the two study subgroups, suggesting that the linkages between the kind of drug used and differences in heart failure hospitalization rates and in mortality weren’t spurious.
“If there was residual confounding, you’d expect to see similar associations for other endpoints, which we didn’t see,” he said. In addition, the heart failure hospitalization rate differences seen between the SGLT-2 inhibitor recipients and the other patients were consistent in a trio of sensitivity analyses, further buttressing the findings’ plausibility.
CVD-REAL was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Kosiborod has been a consultant to and/or received research funding from AstraZeneca, Boehringer Ingelheim, Sanofi-Aventis and Gilead. Dr. Hernandez has received honoraria and/or research support from AstraZeneca, Amgen, Janssen, Merck, Novartis, and Portola. Several of the coauthors on the CVD-REAL study were AstraZeneca employees.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: Treatment with an SGLT-2 inhibitor was associated with a significant 39% reduction in heart failure hospitalizations compared with other antidiabetes drugs.
Data source: CVD-REAL, which used observational data collected from 309,046 patients with type 2 diabetes in six countries.
Disclosures: CVD-REAL was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Kosiborod has been a consultant to AstraZeneca and to several other drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Sanofi-Aventis and Gilead. Dr. Hernandez has received honoraria and research support from AstraZeneca and has also received honoraria from Amgen, Janssen, Merck, and Novartis, and has also received research support from Amgen, Bayer, Merck, and Portola. Several of the coauthors on the CVD-REAL study were AstraZeneca employees.
Sacubitril/valsartan enhances glycemic control in diabetic patients with heart failure
Washington – Patients with heart failure with reduced ejection fraction and comorbid diabetes whose heart failure was treated with sacubitril/valsartan experienced significantly enhanced glycemic control in addition to reduced morbidity and mortality due to heart failure in the landmark PARADIGM-HF trial, Jelena P. Seferovic, MD, reported at the annual meeting of the American College of Cardiology.
PARADIGM-HF was a randomized, double-blind clinical trial of oral sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, or ARNI, at 97 mg/103 mg twice daily versus enalapril at 10 mg twice daily in 8,442 patients with heart failure with reduced ejection fraction (HFrEF). The primary results, which demonstrated significant reductions in heart failure morbidity and mortality in the sacubitril/valsartan group, have been published (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The findings led to Food and Drug Administration approval of the drug, marketed as Entresto, for HFrEF, as well as a top level Class I recommendation for the drug’s use in the 2016 ACC/AHA heart failure management guidelines.
Dr. Seferovic presented a new post hoc secondary analysis of PARADIGM-HF focused on the 3,778 participants with HFrEF and diabetes. During the first year of study follow-up, hemoglobin A1c decreased by 0.26% from a baseline of 7.44% in the ARNI group, significantly greater than the 0.16% reduction in enalapril-treated controls. This benefit persisted during years 2 and 3.
Moreover, this effect was accompanied by a 29% reduction in new use of insulin in the ARNI group, 7% of whom began insulin therapy during follow-up compared with 10% of controls. Similarly, a 23% reduction in new use of oral antihyperglycemic drugs was seen in the ARNI group, reported Dr. Seferovic of Brigham and Women’s Hospital, Boston.
“Our post hoc study findings should be considered hypothesis-generating, but they suggest that sacubitril/valsartan, which has already been proven to reduce morbidity and mortality in heart failure, might provide additional metabolic benefits in patients with diabetes. Also, our findings suggest that diabetic patients who are treated with sacubitril/valsartan for their heart failure may require dose adjustment of their antihyperglycemic therapy,” she said.
Dr. Seferovic added that this need for dose adjustment is not just a theoretical concern. It actually occurred during the PARADIGM-HF trial.
The impetus for the post hoc analysis was driven in part by animal studies demonstrating that neprilysin inhibition improves insulin sensitivity. Although the mechanism of metabolic benefit for sacubitril/valsartan is not fully understood, it’s known that neprilysin is expressed in adipocytes, cardiac myocytes, smooth muscle cells, and endothelial cells. Neprilysin increases postprandial lipid oxidation, promotes adiponectin release, and boosts the oxidative capacity of muscle. Moreover, neprilysin is responsible for breakdown of natriuretic peptides as well as glucagon-like peptide 1.
“We hypothesize that the beneficial antihyperglycemic effect of sacubitril/valsartan revealed in this analysis is most probably due to the neprilysin inhibition and modulation of its circulating substrates,” said Dr. Seferovic.
One audience member asked Dr. Seferovic if she deemed the 0.14% greater absolute reduction in HbA1c achieved with the ARNI over the course of 3 years to be clinically meaningful. She responded with an emphatic yes.
“We believe any decrease in HbA1c is clinically important,” she declared.
Comorbid diabetes is present in up to 40% of patients with heart failure and has been shown to be a strong independent risk factor for heart failure progression.
Simultaneously with her presentation of the new PARADIGM-HF analysis at ACC 17, the study results were published online in The Lancet Diabetes & Endocrinology.
In an accompanying editorial, Gregory Giamouzis, MD, and Javed Butler, MD, cited a handful of reasons why the new findings are important and exciting. For example, polypharmacy has been linked to poor treatment adherence in heart failure, so a drug that can simultaneously improve diabetes and heart failure is attractive. Also, beta blockers and diuretics – cornerstones of heart failure therapy – have been implicated in worsening hyperglycemia.
“Thus, any heart failure therapy that is protective against incident diabetes or worsening glycemic control is a welcome addition,” according to Dr. Giamouzis of the University of Thessaly, Greece, and Dr. Butler of Stony Brook (N.Y.) University.
They added that important unresolved questions include whether sacubitril/valsartan will provide meaningful metabolic benefits in patients with heart failure and comorbid metabolic syndrome, as well as the effects of the ARNI in diabetic patients with heart failure with preserved ejection fraction. The latter issue is the focus of the ongoing major multicenter PARAGON-HF trial.
The PARADIGM-HF trial was sponsored by Novartis. Dr. Seferovic reported having no financial conflicts.
Washington – Patients with heart failure with reduced ejection fraction and comorbid diabetes whose heart failure was treated with sacubitril/valsartan experienced significantly enhanced glycemic control in addition to reduced morbidity and mortality due to heart failure in the landmark PARADIGM-HF trial, Jelena P. Seferovic, MD, reported at the annual meeting of the American College of Cardiology.
PARADIGM-HF was a randomized, double-blind clinical trial of oral sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, or ARNI, at 97 mg/103 mg twice daily versus enalapril at 10 mg twice daily in 8,442 patients with heart failure with reduced ejection fraction (HFrEF). The primary results, which demonstrated significant reductions in heart failure morbidity and mortality in the sacubitril/valsartan group, have been published (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The findings led to Food and Drug Administration approval of the drug, marketed as Entresto, for HFrEF, as well as a top level Class I recommendation for the drug’s use in the 2016 ACC/AHA heart failure management guidelines.
Dr. Seferovic presented a new post hoc secondary analysis of PARADIGM-HF focused on the 3,778 participants with HFrEF and diabetes. During the first year of study follow-up, hemoglobin A1c decreased by 0.26% from a baseline of 7.44% in the ARNI group, significantly greater than the 0.16% reduction in enalapril-treated controls. This benefit persisted during years 2 and 3.
Moreover, this effect was accompanied by a 29% reduction in new use of insulin in the ARNI group, 7% of whom began insulin therapy during follow-up compared with 10% of controls. Similarly, a 23% reduction in new use of oral antihyperglycemic drugs was seen in the ARNI group, reported Dr. Seferovic of Brigham and Women’s Hospital, Boston.
“Our post hoc study findings should be considered hypothesis-generating, but they suggest that sacubitril/valsartan, which has already been proven to reduce morbidity and mortality in heart failure, might provide additional metabolic benefits in patients with diabetes. Also, our findings suggest that diabetic patients who are treated with sacubitril/valsartan for their heart failure may require dose adjustment of their antihyperglycemic therapy,” she said.
Dr. Seferovic added that this need for dose adjustment is not just a theoretical concern. It actually occurred during the PARADIGM-HF trial.
The impetus for the post hoc analysis was driven in part by animal studies demonstrating that neprilysin inhibition improves insulin sensitivity. Although the mechanism of metabolic benefit for sacubitril/valsartan is not fully understood, it’s known that neprilysin is expressed in adipocytes, cardiac myocytes, smooth muscle cells, and endothelial cells. Neprilysin increases postprandial lipid oxidation, promotes adiponectin release, and boosts the oxidative capacity of muscle. Moreover, neprilysin is responsible for breakdown of natriuretic peptides as well as glucagon-like peptide 1.
“We hypothesize that the beneficial antihyperglycemic effect of sacubitril/valsartan revealed in this analysis is most probably due to the neprilysin inhibition and modulation of its circulating substrates,” said Dr. Seferovic.
One audience member asked Dr. Seferovic if she deemed the 0.14% greater absolute reduction in HbA1c achieved with the ARNI over the course of 3 years to be clinically meaningful. She responded with an emphatic yes.
“We believe any decrease in HbA1c is clinically important,” she declared.
Comorbid diabetes is present in up to 40% of patients with heart failure and has been shown to be a strong independent risk factor for heart failure progression.
Simultaneously with her presentation of the new PARADIGM-HF analysis at ACC 17, the study results were published online in The Lancet Diabetes & Endocrinology.
In an accompanying editorial, Gregory Giamouzis, MD, and Javed Butler, MD, cited a handful of reasons why the new findings are important and exciting. For example, polypharmacy has been linked to poor treatment adherence in heart failure, so a drug that can simultaneously improve diabetes and heart failure is attractive. Also, beta blockers and diuretics – cornerstones of heart failure therapy – have been implicated in worsening hyperglycemia.
“Thus, any heart failure therapy that is protective against incident diabetes or worsening glycemic control is a welcome addition,” according to Dr. Giamouzis of the University of Thessaly, Greece, and Dr. Butler of Stony Brook (N.Y.) University.
They added that important unresolved questions include whether sacubitril/valsartan will provide meaningful metabolic benefits in patients with heart failure and comorbid metabolic syndrome, as well as the effects of the ARNI in diabetic patients with heart failure with preserved ejection fraction. The latter issue is the focus of the ongoing major multicenter PARAGON-HF trial.
The PARADIGM-HF trial was sponsored by Novartis. Dr. Seferovic reported having no financial conflicts.
Washington – Patients with heart failure with reduced ejection fraction and comorbid diabetes whose heart failure was treated with sacubitril/valsartan experienced significantly enhanced glycemic control in addition to reduced morbidity and mortality due to heart failure in the landmark PARADIGM-HF trial, Jelena P. Seferovic, MD, reported at the annual meeting of the American College of Cardiology.
PARADIGM-HF was a randomized, double-blind clinical trial of oral sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, or ARNI, at 97 mg/103 mg twice daily versus enalapril at 10 mg twice daily in 8,442 patients with heart failure with reduced ejection fraction (HFrEF). The primary results, which demonstrated significant reductions in heart failure morbidity and mortality in the sacubitril/valsartan group, have been published (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The findings led to Food and Drug Administration approval of the drug, marketed as Entresto, for HFrEF, as well as a top level Class I recommendation for the drug’s use in the 2016 ACC/AHA heart failure management guidelines.
Dr. Seferovic presented a new post hoc secondary analysis of PARADIGM-HF focused on the 3,778 participants with HFrEF and diabetes. During the first year of study follow-up, hemoglobin A1c decreased by 0.26% from a baseline of 7.44% in the ARNI group, significantly greater than the 0.16% reduction in enalapril-treated controls. This benefit persisted during years 2 and 3.
Moreover, this effect was accompanied by a 29% reduction in new use of insulin in the ARNI group, 7% of whom began insulin therapy during follow-up compared with 10% of controls. Similarly, a 23% reduction in new use of oral antihyperglycemic drugs was seen in the ARNI group, reported Dr. Seferovic of Brigham and Women’s Hospital, Boston.
“Our post hoc study findings should be considered hypothesis-generating, but they suggest that sacubitril/valsartan, which has already been proven to reduce morbidity and mortality in heart failure, might provide additional metabolic benefits in patients with diabetes. Also, our findings suggest that diabetic patients who are treated with sacubitril/valsartan for their heart failure may require dose adjustment of their antihyperglycemic therapy,” she said.
Dr. Seferovic added that this need for dose adjustment is not just a theoretical concern. It actually occurred during the PARADIGM-HF trial.
The impetus for the post hoc analysis was driven in part by animal studies demonstrating that neprilysin inhibition improves insulin sensitivity. Although the mechanism of metabolic benefit for sacubitril/valsartan is not fully understood, it’s known that neprilysin is expressed in adipocytes, cardiac myocytes, smooth muscle cells, and endothelial cells. Neprilysin increases postprandial lipid oxidation, promotes adiponectin release, and boosts the oxidative capacity of muscle. Moreover, neprilysin is responsible for breakdown of natriuretic peptides as well as glucagon-like peptide 1.
“We hypothesize that the beneficial antihyperglycemic effect of sacubitril/valsartan revealed in this analysis is most probably due to the neprilysin inhibition and modulation of its circulating substrates,” said Dr. Seferovic.
One audience member asked Dr. Seferovic if she deemed the 0.14% greater absolute reduction in HbA1c achieved with the ARNI over the course of 3 years to be clinically meaningful. She responded with an emphatic yes.
“We believe any decrease in HbA1c is clinically important,” she declared.
Comorbid diabetes is present in up to 40% of patients with heart failure and has been shown to be a strong independent risk factor for heart failure progression.
Simultaneously with her presentation of the new PARADIGM-HF analysis at ACC 17, the study results were published online in The Lancet Diabetes & Endocrinology.
In an accompanying editorial, Gregory Giamouzis, MD, and Javed Butler, MD, cited a handful of reasons why the new findings are important and exciting. For example, polypharmacy has been linked to poor treatment adherence in heart failure, so a drug that can simultaneously improve diabetes and heart failure is attractive. Also, beta blockers and diuretics – cornerstones of heart failure therapy – have been implicated in worsening hyperglycemia.
“Thus, any heart failure therapy that is protective against incident diabetes or worsening glycemic control is a welcome addition,” according to Dr. Giamouzis of the University of Thessaly, Greece, and Dr. Butler of Stony Brook (N.Y.) University.
They added that important unresolved questions include whether sacubitril/valsartan will provide meaningful metabolic benefits in patients with heart failure and comorbid metabolic syndrome, as well as the effects of the ARNI in diabetic patients with heart failure with preserved ejection fraction. The latter issue is the focus of the ongoing major multicenter PARAGON-HF trial.
The PARADIGM-HF trial was sponsored by Novartis. Dr. Seferovic reported having no financial conflicts.
At ACC 17
Key clinical point:
Major finding: Sacubitril/valsartan reduced the need for new use of insulin by 29% in diabetic patients with heart failure with reduced ejection fraction.
Data source: A secondary post hoc analysis of the 3,778 participants in the randomized pivotal PARADIGM-HF trial who had heart failure with reduced ejection fraction and comorbid diabetes.
Disclosures: The PARADIGM-HF trial was sponsored by Novartis. The study presenter reported having no financial conflicts.
Digoxin definitively dissed for AF
WASHINGTON – In what could prove to be the final word in the clinical controversy over the safety of prescribing digoxin in patients with atrial fibrillation, a secondary analysis of the roughly 18,000-patient ARISTOTLE trial has come down emphatically on the side of avoiding the venerable drug.
“The clinical implications of our analysis are that in the absence of randomized trial data showing its safety and efficacy, digoxin should generally not be prescribed for patients with atrial fibrillation, particularly if symptoms can be alleviated with other treatments. And in patients with atrial fibrillation already taking digoxin, monitoring its serum concentration may be important, targeting blood levels below 1.2 ng/mL,” Renato D. Lopes, MD, PhD, said at the annual meeting of the American College of Cardiology.
A randomized clinical trial of digoxin in AF is extremely unlikely, added Dr. Lopes, professor of medicine at Duke University in Durham, N.C.
ARISTOTLE was a randomized trial of apixaban (Eliquis) versus warfarin for stroke prevention in AF. The results of this landmark study, previously reported (N Engl J Med. 2011 Sep 15;365[11]:981-92), demonstrated that apixaban was the superior oral anticoagulant in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.
ARISTOTLE had some unique features that rendered the study database an exceptional resource for use in a large observational study of digoxin’s safety in patients with AF. It included a detailed serial assessment of concomitant medications as well as measurements of serum digoxin levels, left ventricular ejection fraction, creatinine clearance, and biomarkers including vasoactive intestinal peptide, troponins T and I, N-terminal pro–brain-type natriuretic peptide, and growth differentiation factor 15. These were among the 48 clinical variables included in multivariate adjusted analyses of mortality risk.
One-third of ARISTOTLE participants were on digoxin at study entry, a prevalence typical of what’s seen in clinical practice. Among the 5,824 subjects with AF already on digoxin at the start of the trial, the risk of death during follow-up proved independently related to baseline serum digoxin concentration. Patients with a level from 0.9 ng/mL to less than 1.2 ng/mL had a 16% increased risk of death during study follow-up, compared with digoxin nonusers, a trend that didn’t reach statistical significance. However, the 11% of AF patients with a serum concentration of 1.2 ng/mL or above were at a significant 56% increased risk for death.
When serum digoxin concentration is looked at as a continuous, rather than dichotomous variable, for each 0.5-ng/mL increase in drug concentration, the adjusted risk of all-cause mortality at 1 year of study follow-up climbed by 19%.
Moreover, among 781 AF patients who initiated digoxin during the study, the risk of death was increased by 78%, compared with that of 2,343 extensively matched controls. The most common cause of this excess mortality was sudden death, and in a closer look at that endpoint, the investigators found that the risk of sudden death was increased fourfold in new users of digoxin. This increased risk occurred early: Most sudden deaths occurred within the first 6 months after going on the drug, suggesting a causal relationship, although not providing definitive proof, Dr. Lopes noted.
Forty-three percent of ARISTOTLE participants had heart failure at enrollment. Interestingly, the increased risk of death associated with on-study initiation of digoxin was of similar magnitude, regardless of whether comorbid heart failure was present. The mortality risk was 58% greater in new users with heart failure, compared with matched nonusers with heart failure, and twofold greater in new users without heart failure than in their matched controls.
The benefits of apixaban over warfarin were consistent regardless of whether or not patients were on digoxin.
Discussant Kristen K. Patton, MD, was effusive in her response to the new ARISTOTLE findings.
“This was a really, truly, beautiful observational analysis,” declared Dr. Patton, an electrophysiologist at the University of Washington, Seattle.
“I think in cardiology, where our hearts have been broken before due to flawed observational studies, it’s really important for people to understand that observational data, when analyzed well, with appropriate propensity matching, with new-user analysis and close attention to clinical variables that are important, can really change practice in a good way. I think that’s what we see here,” she said.
A beaming Dr. Lopes responded that it’s likely that some of the past conflicting studies were marred by survival bias – that is, an inability to account for the fact that patients already on digoxin at the outset of a study have already declared themselves to be more tolerant of the drug. Past studies also didn’t adjust for biomarker levels.
“We could adjust for things we know today are associated with death in atrial fibrillation,” he observed.
Dr. Patton added that the most surprising study finding to her involved the new users of digoxin. She suspects that the reported figure of a 78% increased risk of all-cause mortality during study follow-up actually markedly underestimates the true size of that risk during the initial months on the drug. Dr. Lopes agreed.
She also said she found worrisome and disappointing the increased mortality risk reported with initiation of digoxin in AF patients with heart failure. That hasn’t been seen in other studies.
Dr. Lopes said the investigators utilized multiple means of identifying patients with heart failure and are certain they captured the full population of affected patients.
“We feel very confident that, when you have atrial fibrillation together with heart failure, it might be a different story than without atrial fibrillation,” the cardiologist said.
Discussant Jagmeet P. Singh, MD, associate chief of cardiology at Massachusetts General Hospital and professor of medicine at Harvard Medical School, Boston, said the ARISTOTLE analysis carries an eye-opening take-home message: “If you have to initiate digoxin, you have to follow the serum levels more closely than we ever have before. How frequently, I don’t know – maybe monthly instead of at the 6-monthly intervals that we often do. And I think maybe arrhythmia monitoring in the initial stages of putting patients on digoxin will be key to see if there are any additional proarrhythmic effects.”
The original ARISTOTLE trial was sponsored by Bristol-Myers Squibb and Pfizer. However, the ARISTOTLE digoxin analysis was sponsored by the Duke Clinical Research Institute. Dr. Lopes reported serving as a consultant to and/or receiving research grants from Bristol-Myers Squibb, Pfizer, Bayer, Boehringer Ingleheim, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, and Portola.
WASHINGTON – In what could prove to be the final word in the clinical controversy over the safety of prescribing digoxin in patients with atrial fibrillation, a secondary analysis of the roughly 18,000-patient ARISTOTLE trial has come down emphatically on the side of avoiding the venerable drug.
“The clinical implications of our analysis are that in the absence of randomized trial data showing its safety and efficacy, digoxin should generally not be prescribed for patients with atrial fibrillation, particularly if symptoms can be alleviated with other treatments. And in patients with atrial fibrillation already taking digoxin, monitoring its serum concentration may be important, targeting blood levels below 1.2 ng/mL,” Renato D. Lopes, MD, PhD, said at the annual meeting of the American College of Cardiology.
A randomized clinical trial of digoxin in AF is extremely unlikely, added Dr. Lopes, professor of medicine at Duke University in Durham, N.C.
ARISTOTLE was a randomized trial of apixaban (Eliquis) versus warfarin for stroke prevention in AF. The results of this landmark study, previously reported (N Engl J Med. 2011 Sep 15;365[11]:981-92), demonstrated that apixaban was the superior oral anticoagulant in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.
ARISTOTLE had some unique features that rendered the study database an exceptional resource for use in a large observational study of digoxin’s safety in patients with AF. It included a detailed serial assessment of concomitant medications as well as measurements of serum digoxin levels, left ventricular ejection fraction, creatinine clearance, and biomarkers including vasoactive intestinal peptide, troponins T and I, N-terminal pro–brain-type natriuretic peptide, and growth differentiation factor 15. These were among the 48 clinical variables included in multivariate adjusted analyses of mortality risk.
One-third of ARISTOTLE participants were on digoxin at study entry, a prevalence typical of what’s seen in clinical practice. Among the 5,824 subjects with AF already on digoxin at the start of the trial, the risk of death during follow-up proved independently related to baseline serum digoxin concentration. Patients with a level from 0.9 ng/mL to less than 1.2 ng/mL had a 16% increased risk of death during study follow-up, compared with digoxin nonusers, a trend that didn’t reach statistical significance. However, the 11% of AF patients with a serum concentration of 1.2 ng/mL or above were at a significant 56% increased risk for death.
When serum digoxin concentration is looked at as a continuous, rather than dichotomous variable, for each 0.5-ng/mL increase in drug concentration, the adjusted risk of all-cause mortality at 1 year of study follow-up climbed by 19%.
Moreover, among 781 AF patients who initiated digoxin during the study, the risk of death was increased by 78%, compared with that of 2,343 extensively matched controls. The most common cause of this excess mortality was sudden death, and in a closer look at that endpoint, the investigators found that the risk of sudden death was increased fourfold in new users of digoxin. This increased risk occurred early: Most sudden deaths occurred within the first 6 months after going on the drug, suggesting a causal relationship, although not providing definitive proof, Dr. Lopes noted.
Forty-three percent of ARISTOTLE participants had heart failure at enrollment. Interestingly, the increased risk of death associated with on-study initiation of digoxin was of similar magnitude, regardless of whether comorbid heart failure was present. The mortality risk was 58% greater in new users with heart failure, compared with matched nonusers with heart failure, and twofold greater in new users without heart failure than in their matched controls.
The benefits of apixaban over warfarin were consistent regardless of whether or not patients were on digoxin.
Discussant Kristen K. Patton, MD, was effusive in her response to the new ARISTOTLE findings.
“This was a really, truly, beautiful observational analysis,” declared Dr. Patton, an electrophysiologist at the University of Washington, Seattle.
“I think in cardiology, where our hearts have been broken before due to flawed observational studies, it’s really important for people to understand that observational data, when analyzed well, with appropriate propensity matching, with new-user analysis and close attention to clinical variables that are important, can really change practice in a good way. I think that’s what we see here,” she said.
A beaming Dr. Lopes responded that it’s likely that some of the past conflicting studies were marred by survival bias – that is, an inability to account for the fact that patients already on digoxin at the outset of a study have already declared themselves to be more tolerant of the drug. Past studies also didn’t adjust for biomarker levels.
“We could adjust for things we know today are associated with death in atrial fibrillation,” he observed.
Dr. Patton added that the most surprising study finding to her involved the new users of digoxin. She suspects that the reported figure of a 78% increased risk of all-cause mortality during study follow-up actually markedly underestimates the true size of that risk during the initial months on the drug. Dr. Lopes agreed.
She also said she found worrisome and disappointing the increased mortality risk reported with initiation of digoxin in AF patients with heart failure. That hasn’t been seen in other studies.
Dr. Lopes said the investigators utilized multiple means of identifying patients with heart failure and are certain they captured the full population of affected patients.
“We feel very confident that, when you have atrial fibrillation together with heart failure, it might be a different story than without atrial fibrillation,” the cardiologist said.
Discussant Jagmeet P. Singh, MD, associate chief of cardiology at Massachusetts General Hospital and professor of medicine at Harvard Medical School, Boston, said the ARISTOTLE analysis carries an eye-opening take-home message: “If you have to initiate digoxin, you have to follow the serum levels more closely than we ever have before. How frequently, I don’t know – maybe monthly instead of at the 6-monthly intervals that we often do. And I think maybe arrhythmia monitoring in the initial stages of putting patients on digoxin will be key to see if there are any additional proarrhythmic effects.”
The original ARISTOTLE trial was sponsored by Bristol-Myers Squibb and Pfizer. However, the ARISTOTLE digoxin analysis was sponsored by the Duke Clinical Research Institute. Dr. Lopes reported serving as a consultant to and/or receiving research grants from Bristol-Myers Squibb, Pfizer, Bayer, Boehringer Ingleheim, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, and Portola.
WASHINGTON – In what could prove to be the final word in the clinical controversy over the safety of prescribing digoxin in patients with atrial fibrillation, a secondary analysis of the roughly 18,000-patient ARISTOTLE trial has come down emphatically on the side of avoiding the venerable drug.
“The clinical implications of our analysis are that in the absence of randomized trial data showing its safety and efficacy, digoxin should generally not be prescribed for patients with atrial fibrillation, particularly if symptoms can be alleviated with other treatments. And in patients with atrial fibrillation already taking digoxin, monitoring its serum concentration may be important, targeting blood levels below 1.2 ng/mL,” Renato D. Lopes, MD, PhD, said at the annual meeting of the American College of Cardiology.
A randomized clinical trial of digoxin in AF is extremely unlikely, added Dr. Lopes, professor of medicine at Duke University in Durham, N.C.
ARISTOTLE was a randomized trial of apixaban (Eliquis) versus warfarin for stroke prevention in AF. The results of this landmark study, previously reported (N Engl J Med. 2011 Sep 15;365[11]:981-92), demonstrated that apixaban was the superior oral anticoagulant in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.
ARISTOTLE had some unique features that rendered the study database an exceptional resource for use in a large observational study of digoxin’s safety in patients with AF. It included a detailed serial assessment of concomitant medications as well as measurements of serum digoxin levels, left ventricular ejection fraction, creatinine clearance, and biomarkers including vasoactive intestinal peptide, troponins T and I, N-terminal pro–brain-type natriuretic peptide, and growth differentiation factor 15. These were among the 48 clinical variables included in multivariate adjusted analyses of mortality risk.
One-third of ARISTOTLE participants were on digoxin at study entry, a prevalence typical of what’s seen in clinical practice. Among the 5,824 subjects with AF already on digoxin at the start of the trial, the risk of death during follow-up proved independently related to baseline serum digoxin concentration. Patients with a level from 0.9 ng/mL to less than 1.2 ng/mL had a 16% increased risk of death during study follow-up, compared with digoxin nonusers, a trend that didn’t reach statistical significance. However, the 11% of AF patients with a serum concentration of 1.2 ng/mL or above were at a significant 56% increased risk for death.
When serum digoxin concentration is looked at as a continuous, rather than dichotomous variable, for each 0.5-ng/mL increase in drug concentration, the adjusted risk of all-cause mortality at 1 year of study follow-up climbed by 19%.
Moreover, among 781 AF patients who initiated digoxin during the study, the risk of death was increased by 78%, compared with that of 2,343 extensively matched controls. The most common cause of this excess mortality was sudden death, and in a closer look at that endpoint, the investigators found that the risk of sudden death was increased fourfold in new users of digoxin. This increased risk occurred early: Most sudden deaths occurred within the first 6 months after going on the drug, suggesting a causal relationship, although not providing definitive proof, Dr. Lopes noted.
Forty-three percent of ARISTOTLE participants had heart failure at enrollment. Interestingly, the increased risk of death associated with on-study initiation of digoxin was of similar magnitude, regardless of whether comorbid heart failure was present. The mortality risk was 58% greater in new users with heart failure, compared with matched nonusers with heart failure, and twofold greater in new users without heart failure than in their matched controls.
The benefits of apixaban over warfarin were consistent regardless of whether or not patients were on digoxin.
Discussant Kristen K. Patton, MD, was effusive in her response to the new ARISTOTLE findings.
“This was a really, truly, beautiful observational analysis,” declared Dr. Patton, an electrophysiologist at the University of Washington, Seattle.
“I think in cardiology, where our hearts have been broken before due to flawed observational studies, it’s really important for people to understand that observational data, when analyzed well, with appropriate propensity matching, with new-user analysis and close attention to clinical variables that are important, can really change practice in a good way. I think that’s what we see here,” she said.
A beaming Dr. Lopes responded that it’s likely that some of the past conflicting studies were marred by survival bias – that is, an inability to account for the fact that patients already on digoxin at the outset of a study have already declared themselves to be more tolerant of the drug. Past studies also didn’t adjust for biomarker levels.
“We could adjust for things we know today are associated with death in atrial fibrillation,” he observed.
Dr. Patton added that the most surprising study finding to her involved the new users of digoxin. She suspects that the reported figure of a 78% increased risk of all-cause mortality during study follow-up actually markedly underestimates the true size of that risk during the initial months on the drug. Dr. Lopes agreed.
She also said she found worrisome and disappointing the increased mortality risk reported with initiation of digoxin in AF patients with heart failure. That hasn’t been seen in other studies.
Dr. Lopes said the investigators utilized multiple means of identifying patients with heart failure and are certain they captured the full population of affected patients.
“We feel very confident that, when you have atrial fibrillation together with heart failure, it might be a different story than without atrial fibrillation,” the cardiologist said.
Discussant Jagmeet P. Singh, MD, associate chief of cardiology at Massachusetts General Hospital and professor of medicine at Harvard Medical School, Boston, said the ARISTOTLE analysis carries an eye-opening take-home message: “If you have to initiate digoxin, you have to follow the serum levels more closely than we ever have before. How frequently, I don’t know – maybe monthly instead of at the 6-monthly intervals that we often do. And I think maybe arrhythmia monitoring in the initial stages of putting patients on digoxin will be key to see if there are any additional proarrhythmic effects.”
The original ARISTOTLE trial was sponsored by Bristol-Myers Squibb and Pfizer. However, the ARISTOTLE digoxin analysis was sponsored by the Duke Clinical Research Institute. Dr. Lopes reported serving as a consultant to and/or receiving research grants from Bristol-Myers Squibb, Pfizer, Bayer, Boehringer Ingleheim, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, and Portola.
AT ACC 17
Key clinical point:
Major finding: Patients with atrial fibrillation who initiated digoxin therapy had a fourfold increased risk of sudden death, compared with extensively matched controls.
Data source: This was a secondary observational analysis drawn from the roughly 18,000-patient, randomized, multicenter ARISTOTLE trial.
Disclosures: This ARISTOTLE digoxin analysis was sponsored by the Duke Clinical Research Institute. The study presenter reported serving as a consultant to and/or recipient of research grants from numerous companies, including Bristol-Myers Squibb and Pfizer, which cosponsored the original ARISTOTLE trial.
Moderate exercise benefits hypertrophic cardiomyopathy patients
WASHINGTON – A regimen of moderately intense exercise for 16 weeks produced no adverse effects and led to a clinically meaningful improvement in exercise capacity in a multicenter, randomized trial involving 136 patients with hypertrophic cardiomyopathy.
While finding that regular exercise produced a statistically significant improvement, compared with control patients fulfilled the study’s primary endpoint, it was perhaps as important that patients with hypertrophic cardiomyopathy (HCM) randomized to the exercise arm experienced no ill effects, a finding that bucked conventional wisdom that, once diagnosed, HCM patients must adhere to a largely inactive lifestyle.
“I see patients with HCM who tell me that, when they were first diagnosed, they were told by their physician not to do anything at all,” said Dr. Saberi, a cardiologist at the University of Michigan in Arbor. Although she cautioned that the findings from this modestly sized trial cannot prove that exercise is safe for HMC patients – something that would require randomizing more than 2,000 patients and following them for about 3 years – the findings provide some level of reassurance that regular, moderately intense exercise as simple as walking can benefit patients and likely not cause any problems. “We saw no signal of harm,” she stressed in an interview. “I would recommend moderate-intensity, regular exercise. Physicians can feel comfortable using the exercise prescription” used in the study, she advised.
Concurrently with Dr. Saberi’s report at the meeting, the results also appeared in an article published online (JAMA. 2017 Mar 17. doi: 10.1001/jama.2017.2503).
The Study of Exercise Training in Hypertrophic Cardiomyopathy (RESET-HCM) ran during 2010-2015 at the University of Michigan and Stanford University, and enrolled 136 patients 18-80 years old diagnosed with HCM but without more severe manifestations such as a history of exercise-induced syncope or ventricular arrhythmia, a left ventricular ejection fraction less than 55%, recent clinical decompensation, or a history of a severe hypotensive response to exercise. Enrolled patients averaged about 50 years old, their baseline peak oxygen consumption, VO2, was about 22 mL/kg per min, and their maximal ventricular wall thickness was about 21 mm.
Following a comprehensive baseline heart function and imaging assessment, including a cardiopulmonary exercise test, the 67 patients in the intervention arm received an individualized exercise prescription based on their heart rate reserve. At a minimum, they started with three exercise sessions per week lasting at least 20 minutes on their own, a regimen designed to bring them to 60% of their heart rate reserve. Their prescription gradually increased to four to seven exercise periods weekly lasting up to 60 minutes and designed to bring them to 70% of their heart rate reserve. Although most patients accomplished this through walking, some engaged in activities that included cycling, swimming, jogging, or elliptical training. The researchers told the 69 control patients to continue doing their usual activities. Among the patients who entered the study, 57 in the exercise group and 56 controls remained for the full 16 weeks and had a complete final assessment.
After 16 weeks, the average change in peak VO2, was 1.35 mL/kg per min in the intervention group and 0.08 mL/kg per min in the control patients, a statistically significant difference for the primary endpoint and a 6% increase in exercise capacity, compared with baseline for the intervention group. Dr. Saberi noted that, in a prior study of patients with chronic heart failure, a 6% increase in peak VO2 linked with an 8% decrease in cardiovascular mortality of heart failure hospitalization.
This result is “a glimmer of hope for using exercise in HCM patients,” she said. “There are no other disease-modifying treatments for HCM, so this is the first ‘treatment’ to have any impact on the disease.”
The patients who exercised had no identified major adverse effects or changes in cardiac morphology after 16 weeks. Assessment of physical function quality of life using the SF-36v2 showed an average 8-point improvement in the patients who exercised, compared with the controls. In addition, “a lot of patients in the exercise group told us that they felt better,” Dr. Saberi said.
Because patients with HCM are often advised to limit their activity, the consequence is “we increasingly see HCM patients who are obese and have complications such as sleep apnea and atrial fibrillation. Patients are even fearful of going up and down stairs.” She stressed the simplicity and ease of the intervention she and her colleagues tested, which can involve nothing more than regular, daily walks of 20 minutes or more. Dr. Saberi advised tailoring the intensity and frequency of the exercise intervention to each patient and avoiding having the patient push beyond what they find comfortable.
A multicenter U.S. registry, the Lifestyle and Exercise in Hypertrophic Cardiomyopathy Study (LIVE-HCM), is now enrolling HCM patients that should eventually follow enough patients for a long enough period of time to definitely prove whether moderate exercise is safe for HCM patients, but the results will not be available for several more years, Dr. Saberi said. A recent analysis estimated that one in every 200 adults has HCM (J Am Coll Cardiol. 2015 Mar 31;65[12]:1249-54), which means the disease likely affects more than one million Americans.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – A regimen of moderately intense exercise for 16 weeks produced no adverse effects and led to a clinically meaningful improvement in exercise capacity in a multicenter, randomized trial involving 136 patients with hypertrophic cardiomyopathy.
While finding that regular exercise produced a statistically significant improvement, compared with control patients fulfilled the study’s primary endpoint, it was perhaps as important that patients with hypertrophic cardiomyopathy (HCM) randomized to the exercise arm experienced no ill effects, a finding that bucked conventional wisdom that, once diagnosed, HCM patients must adhere to a largely inactive lifestyle.
“I see patients with HCM who tell me that, when they were first diagnosed, they were told by their physician not to do anything at all,” said Dr. Saberi, a cardiologist at the University of Michigan in Arbor. Although she cautioned that the findings from this modestly sized trial cannot prove that exercise is safe for HMC patients – something that would require randomizing more than 2,000 patients and following them for about 3 years – the findings provide some level of reassurance that regular, moderately intense exercise as simple as walking can benefit patients and likely not cause any problems. “We saw no signal of harm,” she stressed in an interview. “I would recommend moderate-intensity, regular exercise. Physicians can feel comfortable using the exercise prescription” used in the study, she advised.
Concurrently with Dr. Saberi’s report at the meeting, the results also appeared in an article published online (JAMA. 2017 Mar 17. doi: 10.1001/jama.2017.2503).
The Study of Exercise Training in Hypertrophic Cardiomyopathy (RESET-HCM) ran during 2010-2015 at the University of Michigan and Stanford University, and enrolled 136 patients 18-80 years old diagnosed with HCM but without more severe manifestations such as a history of exercise-induced syncope or ventricular arrhythmia, a left ventricular ejection fraction less than 55%, recent clinical decompensation, or a history of a severe hypotensive response to exercise. Enrolled patients averaged about 50 years old, their baseline peak oxygen consumption, VO2, was about 22 mL/kg per min, and their maximal ventricular wall thickness was about 21 mm.
Following a comprehensive baseline heart function and imaging assessment, including a cardiopulmonary exercise test, the 67 patients in the intervention arm received an individualized exercise prescription based on their heart rate reserve. At a minimum, they started with three exercise sessions per week lasting at least 20 minutes on their own, a regimen designed to bring them to 60% of their heart rate reserve. Their prescription gradually increased to four to seven exercise periods weekly lasting up to 60 minutes and designed to bring them to 70% of their heart rate reserve. Although most patients accomplished this through walking, some engaged in activities that included cycling, swimming, jogging, or elliptical training. The researchers told the 69 control patients to continue doing their usual activities. Among the patients who entered the study, 57 in the exercise group and 56 controls remained for the full 16 weeks and had a complete final assessment.
After 16 weeks, the average change in peak VO2, was 1.35 mL/kg per min in the intervention group and 0.08 mL/kg per min in the control patients, a statistically significant difference for the primary endpoint and a 6% increase in exercise capacity, compared with baseline for the intervention group. Dr. Saberi noted that, in a prior study of patients with chronic heart failure, a 6% increase in peak VO2 linked with an 8% decrease in cardiovascular mortality of heart failure hospitalization.
This result is “a glimmer of hope for using exercise in HCM patients,” she said. “There are no other disease-modifying treatments for HCM, so this is the first ‘treatment’ to have any impact on the disease.”
The patients who exercised had no identified major adverse effects or changes in cardiac morphology after 16 weeks. Assessment of physical function quality of life using the SF-36v2 showed an average 8-point improvement in the patients who exercised, compared with the controls. In addition, “a lot of patients in the exercise group told us that they felt better,” Dr. Saberi said.
Because patients with HCM are often advised to limit their activity, the consequence is “we increasingly see HCM patients who are obese and have complications such as sleep apnea and atrial fibrillation. Patients are even fearful of going up and down stairs.” She stressed the simplicity and ease of the intervention she and her colleagues tested, which can involve nothing more than regular, daily walks of 20 minutes or more. Dr. Saberi advised tailoring the intensity and frequency of the exercise intervention to each patient and avoiding having the patient push beyond what they find comfortable.
A multicenter U.S. registry, the Lifestyle and Exercise in Hypertrophic Cardiomyopathy Study (LIVE-HCM), is now enrolling HCM patients that should eventually follow enough patients for a long enough period of time to definitely prove whether moderate exercise is safe for HCM patients, but the results will not be available for several more years, Dr. Saberi said. A recent analysis estimated that one in every 200 adults has HCM (J Am Coll Cardiol. 2015 Mar 31;65[12]:1249-54), which means the disease likely affects more than one million Americans.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – A regimen of moderately intense exercise for 16 weeks produced no adverse effects and led to a clinically meaningful improvement in exercise capacity in a multicenter, randomized trial involving 136 patients with hypertrophic cardiomyopathy.
While finding that regular exercise produced a statistically significant improvement, compared with control patients fulfilled the study’s primary endpoint, it was perhaps as important that patients with hypertrophic cardiomyopathy (HCM) randomized to the exercise arm experienced no ill effects, a finding that bucked conventional wisdom that, once diagnosed, HCM patients must adhere to a largely inactive lifestyle.
“I see patients with HCM who tell me that, when they were first diagnosed, they were told by their physician not to do anything at all,” said Dr. Saberi, a cardiologist at the University of Michigan in Arbor. Although she cautioned that the findings from this modestly sized trial cannot prove that exercise is safe for HMC patients – something that would require randomizing more than 2,000 patients and following them for about 3 years – the findings provide some level of reassurance that regular, moderately intense exercise as simple as walking can benefit patients and likely not cause any problems. “We saw no signal of harm,” she stressed in an interview. “I would recommend moderate-intensity, regular exercise. Physicians can feel comfortable using the exercise prescription” used in the study, she advised.
Concurrently with Dr. Saberi’s report at the meeting, the results also appeared in an article published online (JAMA. 2017 Mar 17. doi: 10.1001/jama.2017.2503).
The Study of Exercise Training in Hypertrophic Cardiomyopathy (RESET-HCM) ran during 2010-2015 at the University of Michigan and Stanford University, and enrolled 136 patients 18-80 years old diagnosed with HCM but without more severe manifestations such as a history of exercise-induced syncope or ventricular arrhythmia, a left ventricular ejection fraction less than 55%, recent clinical decompensation, or a history of a severe hypotensive response to exercise. Enrolled patients averaged about 50 years old, their baseline peak oxygen consumption, VO2, was about 22 mL/kg per min, and their maximal ventricular wall thickness was about 21 mm.
Following a comprehensive baseline heart function and imaging assessment, including a cardiopulmonary exercise test, the 67 patients in the intervention arm received an individualized exercise prescription based on their heart rate reserve. At a minimum, they started with three exercise sessions per week lasting at least 20 minutes on their own, a regimen designed to bring them to 60% of their heart rate reserve. Their prescription gradually increased to four to seven exercise periods weekly lasting up to 60 minutes and designed to bring them to 70% of their heart rate reserve. Although most patients accomplished this through walking, some engaged in activities that included cycling, swimming, jogging, or elliptical training. The researchers told the 69 control patients to continue doing their usual activities. Among the patients who entered the study, 57 in the exercise group and 56 controls remained for the full 16 weeks and had a complete final assessment.
After 16 weeks, the average change in peak VO2, was 1.35 mL/kg per min in the intervention group and 0.08 mL/kg per min in the control patients, a statistically significant difference for the primary endpoint and a 6% increase in exercise capacity, compared with baseline for the intervention group. Dr. Saberi noted that, in a prior study of patients with chronic heart failure, a 6% increase in peak VO2 linked with an 8% decrease in cardiovascular mortality of heart failure hospitalization.
This result is “a glimmer of hope for using exercise in HCM patients,” she said. “There are no other disease-modifying treatments for HCM, so this is the first ‘treatment’ to have any impact on the disease.”
The patients who exercised had no identified major adverse effects or changes in cardiac morphology after 16 weeks. Assessment of physical function quality of life using the SF-36v2 showed an average 8-point improvement in the patients who exercised, compared with the controls. In addition, “a lot of patients in the exercise group told us that they felt better,” Dr. Saberi said.
Because patients with HCM are often advised to limit their activity, the consequence is “we increasingly see HCM patients who are obese and have complications such as sleep apnea and atrial fibrillation. Patients are even fearful of going up and down stairs.” She stressed the simplicity and ease of the intervention she and her colleagues tested, which can involve nothing more than regular, daily walks of 20 minutes or more. Dr. Saberi advised tailoring the intensity and frequency of the exercise intervention to each patient and avoiding having the patient push beyond what they find comfortable.
A multicenter U.S. registry, the Lifestyle and Exercise in Hypertrophic Cardiomyopathy Study (LIVE-HCM), is now enrolling HCM patients that should eventually follow enough patients for a long enough period of time to definitely prove whether moderate exercise is safe for HCM patients, but the results will not be available for several more years, Dr. Saberi said. A recent analysis estimated that one in every 200 adults has HCM (J Am Coll Cardiol. 2015 Mar 31;65[12]:1249-54), which means the disease likely affects more than one million Americans.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: Average exercise capacity, peak VO2, increased by 1.27 mL/kg per min in exercising patients compared with nonexercising controls.
Data source: RESET-HCM, a multicenter, randomized trial with 136 hypertrophic cardiomyopathy patients.
Disclosures: Dr. Saberi had no disclosures.
Cannabis associated with increased risk of heart failure and stroke
Cannabis use was associated with an increased risk of cerebrovascular accidents and heart failure in a retrospective analysis of the Nationwide Inpatient Sample (NIS).
Aditi Kalla, MD, a cardiology fellow at Einstein Medical Center in Philadelphia, and her colleagues analyzed data from nearly 21 million adult patients aged 18-55 years from the NIS 2009-2010 database. Approximately 1.5% (316,397) were diagnosed as cannabis users.
Cannabis users also were more likely to report cardiac risk factors such as hypertension (19.9% vs. 15.7% of nonusers), tobacco use (47.2% vs. 11.4%), alcohol use (28.1% vs 3.8%), and obesity (7% vs. 6.5%). They were older, on average, with a mean age of 33 years, compared with 26 years, and were likely to be male (60%), Dr. Kalla noted during a press briefing held in advance of the annual meeting of the American College of Cardiology.
Using multivariate regression analysis to adjust for these traditional cardiovascular risk factors, the investigators found cannabis remained an independent predictor for heart failure, with an odds ratio of 1.1 (P less than .01) and cerebrovascular accident, with an OR of 1.24 (P less than .001).
“Even when we corrected for known risks, we still found a higher rate of both stroke and heart failure in these patients,” Dr. Kalla said. “That leads us to believe that there is something else going on besides just obesity or diet-related cardiovascular side effects.”
Dr. Kalla noted that an expert analysis published by the ACC in September 2016 linked cannabinoid receptor type 1 with atherogenesis.
Further research is needed on the topic of cannabis and cardiovascular effects, especially as the legalization of medical and recreational cannabis spreads across the country, Dr. Kalla said. “Decriminalization of cannabis has passed in several states, bringing the total count now up to 28 states, plus the District of Columbia. We now need to be more knowledgeable of the risks and benefits of cannabis, as patients in these states may inquire into the use of it, or even ask us for prescriptions for it.”
While the NIS provided a large and strong data set for this analysis, the number of cannabis users likely was underreported because cannabis was legal in just 14 states at the time, Dr. Kalla noted. The study also was limited by a lack of specific information regarding cannabis intake, method of intake (ingestion or smoking), quantity and frequency of use, and whether use was medical or recreational.
The information collected also excluded whether patients used marijuana for medical or recreational purpose and how it was taken, by smoking or ingestion.
ezimmerman@frontlinemedcom.com
On Twitter @EAZTweets
Cannabis use was associated with an increased risk of cerebrovascular accidents and heart failure in a retrospective analysis of the Nationwide Inpatient Sample (NIS).
Aditi Kalla, MD, a cardiology fellow at Einstein Medical Center in Philadelphia, and her colleagues analyzed data from nearly 21 million adult patients aged 18-55 years from the NIS 2009-2010 database. Approximately 1.5% (316,397) were diagnosed as cannabis users.
Cannabis users also were more likely to report cardiac risk factors such as hypertension (19.9% vs. 15.7% of nonusers), tobacco use (47.2% vs. 11.4%), alcohol use (28.1% vs 3.8%), and obesity (7% vs. 6.5%). They were older, on average, with a mean age of 33 years, compared with 26 years, and were likely to be male (60%), Dr. Kalla noted during a press briefing held in advance of the annual meeting of the American College of Cardiology.
Using multivariate regression analysis to adjust for these traditional cardiovascular risk factors, the investigators found cannabis remained an independent predictor for heart failure, with an odds ratio of 1.1 (P less than .01) and cerebrovascular accident, with an OR of 1.24 (P less than .001).
“Even when we corrected for known risks, we still found a higher rate of both stroke and heart failure in these patients,” Dr. Kalla said. “That leads us to believe that there is something else going on besides just obesity or diet-related cardiovascular side effects.”
Dr. Kalla noted that an expert analysis published by the ACC in September 2016 linked cannabinoid receptor type 1 with atherogenesis.
Further research is needed on the topic of cannabis and cardiovascular effects, especially as the legalization of medical and recreational cannabis spreads across the country, Dr. Kalla said. “Decriminalization of cannabis has passed in several states, bringing the total count now up to 28 states, plus the District of Columbia. We now need to be more knowledgeable of the risks and benefits of cannabis, as patients in these states may inquire into the use of it, or even ask us for prescriptions for it.”
While the NIS provided a large and strong data set for this analysis, the number of cannabis users likely was underreported because cannabis was legal in just 14 states at the time, Dr. Kalla noted. The study also was limited by a lack of specific information regarding cannabis intake, method of intake (ingestion or smoking), quantity and frequency of use, and whether use was medical or recreational.
The information collected also excluded whether patients used marijuana for medical or recreational purpose and how it was taken, by smoking or ingestion.
ezimmerman@frontlinemedcom.com
On Twitter @EAZTweets
Cannabis use was associated with an increased risk of cerebrovascular accidents and heart failure in a retrospective analysis of the Nationwide Inpatient Sample (NIS).
Aditi Kalla, MD, a cardiology fellow at Einstein Medical Center in Philadelphia, and her colleagues analyzed data from nearly 21 million adult patients aged 18-55 years from the NIS 2009-2010 database. Approximately 1.5% (316,397) were diagnosed as cannabis users.
Cannabis users also were more likely to report cardiac risk factors such as hypertension (19.9% vs. 15.7% of nonusers), tobacco use (47.2% vs. 11.4%), alcohol use (28.1% vs 3.8%), and obesity (7% vs. 6.5%). They were older, on average, with a mean age of 33 years, compared with 26 years, and were likely to be male (60%), Dr. Kalla noted during a press briefing held in advance of the annual meeting of the American College of Cardiology.
Using multivariate regression analysis to adjust for these traditional cardiovascular risk factors, the investigators found cannabis remained an independent predictor for heart failure, with an odds ratio of 1.1 (P less than .01) and cerebrovascular accident, with an OR of 1.24 (P less than .001).
“Even when we corrected for known risks, we still found a higher rate of both stroke and heart failure in these patients,” Dr. Kalla said. “That leads us to believe that there is something else going on besides just obesity or diet-related cardiovascular side effects.”
Dr. Kalla noted that an expert analysis published by the ACC in September 2016 linked cannabinoid receptor type 1 with atherogenesis.
Further research is needed on the topic of cannabis and cardiovascular effects, especially as the legalization of medical and recreational cannabis spreads across the country, Dr. Kalla said. “Decriminalization of cannabis has passed in several states, bringing the total count now up to 28 states, plus the District of Columbia. We now need to be more knowledgeable of the risks and benefits of cannabis, as patients in these states may inquire into the use of it, or even ask us for prescriptions for it.”
While the NIS provided a large and strong data set for this analysis, the number of cannabis users likely was underreported because cannabis was legal in just 14 states at the time, Dr. Kalla noted. The study also was limited by a lack of specific information regarding cannabis intake, method of intake (ingestion or smoking), quantity and frequency of use, and whether use was medical or recreational.
The information collected also excluded whether patients used marijuana for medical or recreational purpose and how it was taken, by smoking or ingestion.
ezimmerman@frontlinemedcom.com
On Twitter @EAZTweets
FROM ACC 17
Key clinical point:
Major finding: Cannabis users showed 26% increased risk (OR, 1.24) of stroke and 10% increased risk (OR, 1.1) of heart failure.
Data source: Retrospective study of over 20 million patients’ records aged 18-55 years gathered from the Nationwide Inpatient Sample 2009-2010 database.
Disclosures: Researchers reported no relevant conflicts of interest.
Prediction: LVADs will rule end-stage heart failure
SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.
declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.
That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.
Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.
Here’s what Dr. Woo sees as the future of MCS:
Minimally invasive implantation
At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.
“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.
Concomitant valvular surgery
At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.
Enhanced right ventricular management
Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.
Adjunctive biologic therapies
Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).
The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.
These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.
Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.
New technologies
The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.
Dr. Woo reported having no financial conflicts.
bjancin@frontlinemedcom.com
SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.
declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.
That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.
Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.
Here’s what Dr. Woo sees as the future of MCS:
Minimally invasive implantation
At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.
“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.
Concomitant valvular surgery
At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.
Enhanced right ventricular management
Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.
Adjunctive biologic therapies
Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).
The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.
These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.
Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.
New technologies
The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.
Dr. Woo reported having no financial conflicts.
bjancin@frontlinemedcom.com
SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.
declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.
That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.
Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.
Here’s what Dr. Woo sees as the future of MCS:
Minimally invasive implantation
At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.
“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.
Concomitant valvular surgery
At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.
Enhanced right ventricular management
Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.
Adjunctive biologic therapies
Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).
The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.
These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.
Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.
New technologies
The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.
Dr. Woo reported having no financial conflicts.
bjancin@frontlinemedcom.com
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Big changes ahead in heart failure management
SNOWMASS, COLO. – Advances in remote telemedical management show enormous promise as a means of preventing costly heart failure hospitalizations, William T. Abraham, MD, said at the Annual Cardiovascular Conference at Snowmass.
He characterized the decades-old conventional approach to heart failure management as a reactive strategy focused on making medication adjustments based upon weight changes and worsening signs and symptoms. But these physiologic markers of acute decompensation aren’t actionable; that is, they don’t occur until it’s too late to successfully intervene to prevent hospitalization.
It’s now clear that objective, measurable changes in intracardiac and pulmonary artery pressures as well as increases in lung fluid volume precede symptomatic decompensation episodes by several weeks. These early harbingers are reliably detectable by telemedical monitoring via small implantable pressure sensors or, noninvasively, using wearable sensors embedded in a vest.
“By moving upstream, we hope to develop a more proactive preventive approach to managing heart failure patients so that we can implement a medical intervention during this presymptomatic phase of worsening heart failure and avert a heart failure hospitalization,” the cardiologist explained.
That has already been demonstrated in several studies in which remote physicians checked the home monitoring data daily and promptly increased the dose of diuretics when pressure readings or lung fluid volume climbed above normal: The elevated readings quickly retreated and heart failure hospitalizations occurred much less frequently than with conventional management.
“Well-structured outpatient care could reduce the need for hospital admission, facilitate early intervention, prevent crisis management, and avoid complications or disease management in these patients,” Dr. Abraham observed.
Finding best telemedicine options
But this high-tech patient management strategy is not quite ready for prime time use in daily clinical practice.
“We’re still sorting through this field and trying to figure out the best telemedicine options,” according to Dr. Abraham.
He cited several recent large, well-conducted randomized trials that have persuasively shown that there’s no point in applying home telemedicine in order to quickly respond to changes in a heart failure patient’s blood pressure, weight, and symptom status.
“The horse is already out of the barn at that point in time,” according to the cardiologist.
For example, the BEAT-HF (Better Effectiveness After Transition–Heart Failure) trial included 1,437 patients hospitalized for heart failure at eight California academic medical centers who were randomized to usual care or an intervention that combined health-coaching telephone calls and protocols for physician or nurse response to daily telemetric data on patient blood pressure, symptoms, heart rate, weight, and symptoms. The intervention turned out to have absolutely no effect on the 180-day rate of readmissions, which was roughly 50% in both groups (JAMA Intern Med. 2016 Mar;176[3]:310-8).
The PCDM (Patient-Centered Disease Management) trial was a multicenter Veterans Affairs study that randomized heart failure patients to usual care or a comprehensive intervention involving collaborative care by a cardiologist, psychiatrist, primary care physician, and nurse coordinator; screening and treatment for depression; and home telemonitoring of heart failure decompensation symptoms. The multifaceted intervention had no effect on the 1-year readmission rate (JAMA Intern Med. 2015 May;175[5]:725-32).
“To date, I would challenge you to find any adequately powered randomized, controlled trial in heart failure disease management that demonstrates that the way we’ve been doing things really keeps heart failure patients out of the hospital. So, it is time for a paradigm shift and some new technologies in our armamentarium,” Dr. Abraham said.
CardioMEMS system
Several remote telemedical management systems for heart failure, which measure early preclinical harbingers of acute decompensation, have received Food and Drug Administration approval. Many more are in development. Dr. Abraham highlighted two approved systems for which he was a coinvestigator in clinical trials.
The CardioMEMS system uses a pressure sensor the size of a small paper clip that is placed in a branch of the pulmonary artery, where it readily becomes endothelialized. Device implantation can be carried out by any cardiologist who can perform a right heart catheterization, be it an electrophysiologist, interventionalist, heart failure specialist, or general cardiologist. It takes only about an additional 7 minutes to deploy the sensor following a standard diagnostic right heart catheterization. The system doesn’t use a battery and has no moving parts.
“Now, with more than 10 years experience, we have yet to see a sensor failure. It’s a highly reliable system,” according to the cardiologist.
Once a day the patient lies down, pushes a button, and the sensor is simultaneously powered up while the data on pulmonary artery pressure waveforms and systolic and diastolic pressures is extracted using radiofrequency energy.
In the randomized, multicenter, controlled, single-blind CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial, Dr. Abraham and coinvestigators demonstrated that pulmonary artery pressure-guided heart failure management reduced the rate of heart failure hospitalizations in the CardioMEMS group by 33% during the first 18 months of the trial and by 48% in the subsequent 13 months (Lancet. 2016 Jan 30;387[10017]:453-61).
“It’s important to note that the results were positive in diastolic as well as systolic heart failure. Patients with a baseline left ventricular ejection fraction of 40% or more saw a 50% reduction in the risk of heart failure hospitalizations, and those with an LVEF of 50% or more saw a 70% reduction,” Dr. Abraham said.
Other implantable hemodynamic monitors
Numerous other implantable pressure sensors are in development for management of heart failure, including other pulmonary artery pressure sensors as well as left atrial pressure monitors.
“You’re going to hear a lot more about this field of implantable hemodynamic monitors in the future,” the cardiologist predicted.
Dr. Abraham was also a coinvestigator in an observational study of a wearable sensor based upon radar technology developed for the military and subsequently applied to rescue searches through rubble for earthquake survivors. This remote dielectric sensing (ReDS) technology has been miniaturized, with the sensors embedded in an FDA-approved vest. The heart failure patient dons the SensiVest for 90 seconds once per day for measurement of the absolute amount of fluid in the lungs. The data is automatically transmitted to a secured site in the cloud, where the physician can review the results and adjust medications in response to early evidence of fluid buildup.
“The normal lung is composed of 20%-35% fluid. So when that fluid content is elevated, patients with heart failure have wet lungs and they’re decompensating. You increase their diuretics to bring it back down into normal range,” he explained.
In the observational study, conducted in Israel, hospital readmission rates were reduced by 87% through the use of ReDS-guided patient management using the system marketed by Sensible Medical Innovations. Dr. Abraham and his coinvestigators are now seeking to confirm those results in the prospective, multicenter, randomized, controlled U.S. SMILE study.
Dr. Abraham reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
SNOWMASS, COLO. – Advances in remote telemedical management show enormous promise as a means of preventing costly heart failure hospitalizations, William T. Abraham, MD, said at the Annual Cardiovascular Conference at Snowmass.
He characterized the decades-old conventional approach to heart failure management as a reactive strategy focused on making medication adjustments based upon weight changes and worsening signs and symptoms. But these physiologic markers of acute decompensation aren’t actionable; that is, they don’t occur until it’s too late to successfully intervene to prevent hospitalization.
It’s now clear that objective, measurable changes in intracardiac and pulmonary artery pressures as well as increases in lung fluid volume precede symptomatic decompensation episodes by several weeks. These early harbingers are reliably detectable by telemedical monitoring via small implantable pressure sensors or, noninvasively, using wearable sensors embedded in a vest.
“By moving upstream, we hope to develop a more proactive preventive approach to managing heart failure patients so that we can implement a medical intervention during this presymptomatic phase of worsening heart failure and avert a heart failure hospitalization,” the cardiologist explained.
That has already been demonstrated in several studies in which remote physicians checked the home monitoring data daily and promptly increased the dose of diuretics when pressure readings or lung fluid volume climbed above normal: The elevated readings quickly retreated and heart failure hospitalizations occurred much less frequently than with conventional management.
“Well-structured outpatient care could reduce the need for hospital admission, facilitate early intervention, prevent crisis management, and avoid complications or disease management in these patients,” Dr. Abraham observed.
Finding best telemedicine options
But this high-tech patient management strategy is not quite ready for prime time use in daily clinical practice.
“We’re still sorting through this field and trying to figure out the best telemedicine options,” according to Dr. Abraham.
He cited several recent large, well-conducted randomized trials that have persuasively shown that there’s no point in applying home telemedicine in order to quickly respond to changes in a heart failure patient’s blood pressure, weight, and symptom status.
“The horse is already out of the barn at that point in time,” according to the cardiologist.
For example, the BEAT-HF (Better Effectiveness After Transition–Heart Failure) trial included 1,437 patients hospitalized for heart failure at eight California academic medical centers who were randomized to usual care or an intervention that combined health-coaching telephone calls and protocols for physician or nurse response to daily telemetric data on patient blood pressure, symptoms, heart rate, weight, and symptoms. The intervention turned out to have absolutely no effect on the 180-day rate of readmissions, which was roughly 50% in both groups (JAMA Intern Med. 2016 Mar;176[3]:310-8).
The PCDM (Patient-Centered Disease Management) trial was a multicenter Veterans Affairs study that randomized heart failure patients to usual care or a comprehensive intervention involving collaborative care by a cardiologist, psychiatrist, primary care physician, and nurse coordinator; screening and treatment for depression; and home telemonitoring of heart failure decompensation symptoms. The multifaceted intervention had no effect on the 1-year readmission rate (JAMA Intern Med. 2015 May;175[5]:725-32).
“To date, I would challenge you to find any adequately powered randomized, controlled trial in heart failure disease management that demonstrates that the way we’ve been doing things really keeps heart failure patients out of the hospital. So, it is time for a paradigm shift and some new technologies in our armamentarium,” Dr. Abraham said.
CardioMEMS system
Several remote telemedical management systems for heart failure, which measure early preclinical harbingers of acute decompensation, have received Food and Drug Administration approval. Many more are in development. Dr. Abraham highlighted two approved systems for which he was a coinvestigator in clinical trials.
The CardioMEMS system uses a pressure sensor the size of a small paper clip that is placed in a branch of the pulmonary artery, where it readily becomes endothelialized. Device implantation can be carried out by any cardiologist who can perform a right heart catheterization, be it an electrophysiologist, interventionalist, heart failure specialist, or general cardiologist. It takes only about an additional 7 minutes to deploy the sensor following a standard diagnostic right heart catheterization. The system doesn’t use a battery and has no moving parts.
“Now, with more than 10 years experience, we have yet to see a sensor failure. It’s a highly reliable system,” according to the cardiologist.
Once a day the patient lies down, pushes a button, and the sensor is simultaneously powered up while the data on pulmonary artery pressure waveforms and systolic and diastolic pressures is extracted using radiofrequency energy.
In the randomized, multicenter, controlled, single-blind CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial, Dr. Abraham and coinvestigators demonstrated that pulmonary artery pressure-guided heart failure management reduced the rate of heart failure hospitalizations in the CardioMEMS group by 33% during the first 18 months of the trial and by 48% in the subsequent 13 months (Lancet. 2016 Jan 30;387[10017]:453-61).
“It’s important to note that the results were positive in diastolic as well as systolic heart failure. Patients with a baseline left ventricular ejection fraction of 40% or more saw a 50% reduction in the risk of heart failure hospitalizations, and those with an LVEF of 50% or more saw a 70% reduction,” Dr. Abraham said.
Other implantable hemodynamic monitors
Numerous other implantable pressure sensors are in development for management of heart failure, including other pulmonary artery pressure sensors as well as left atrial pressure monitors.
“You’re going to hear a lot more about this field of implantable hemodynamic monitors in the future,” the cardiologist predicted.
Dr. Abraham was also a coinvestigator in an observational study of a wearable sensor based upon radar technology developed for the military and subsequently applied to rescue searches through rubble for earthquake survivors. This remote dielectric sensing (ReDS) technology has been miniaturized, with the sensors embedded in an FDA-approved vest. The heart failure patient dons the SensiVest for 90 seconds once per day for measurement of the absolute amount of fluid in the lungs. The data is automatically transmitted to a secured site in the cloud, where the physician can review the results and adjust medications in response to early evidence of fluid buildup.
“The normal lung is composed of 20%-35% fluid. So when that fluid content is elevated, patients with heart failure have wet lungs and they’re decompensating. You increase their diuretics to bring it back down into normal range,” he explained.
In the observational study, conducted in Israel, hospital readmission rates were reduced by 87% through the use of ReDS-guided patient management using the system marketed by Sensible Medical Innovations. Dr. Abraham and his coinvestigators are now seeking to confirm those results in the prospective, multicenter, randomized, controlled U.S. SMILE study.
Dr. Abraham reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
SNOWMASS, COLO. – Advances in remote telemedical management show enormous promise as a means of preventing costly heart failure hospitalizations, William T. Abraham, MD, said at the Annual Cardiovascular Conference at Snowmass.
He characterized the decades-old conventional approach to heart failure management as a reactive strategy focused on making medication adjustments based upon weight changes and worsening signs and symptoms. But these physiologic markers of acute decompensation aren’t actionable; that is, they don’t occur until it’s too late to successfully intervene to prevent hospitalization.
It’s now clear that objective, measurable changes in intracardiac and pulmonary artery pressures as well as increases in lung fluid volume precede symptomatic decompensation episodes by several weeks. These early harbingers are reliably detectable by telemedical monitoring via small implantable pressure sensors or, noninvasively, using wearable sensors embedded in a vest.
“By moving upstream, we hope to develop a more proactive preventive approach to managing heart failure patients so that we can implement a medical intervention during this presymptomatic phase of worsening heart failure and avert a heart failure hospitalization,” the cardiologist explained.
That has already been demonstrated in several studies in which remote physicians checked the home monitoring data daily and promptly increased the dose of diuretics when pressure readings or lung fluid volume climbed above normal: The elevated readings quickly retreated and heart failure hospitalizations occurred much less frequently than with conventional management.
“Well-structured outpatient care could reduce the need for hospital admission, facilitate early intervention, prevent crisis management, and avoid complications or disease management in these patients,” Dr. Abraham observed.
Finding best telemedicine options
But this high-tech patient management strategy is not quite ready for prime time use in daily clinical practice.
“We’re still sorting through this field and trying to figure out the best telemedicine options,” according to Dr. Abraham.
He cited several recent large, well-conducted randomized trials that have persuasively shown that there’s no point in applying home telemedicine in order to quickly respond to changes in a heart failure patient’s blood pressure, weight, and symptom status.
“The horse is already out of the barn at that point in time,” according to the cardiologist.
For example, the BEAT-HF (Better Effectiveness After Transition–Heart Failure) trial included 1,437 patients hospitalized for heart failure at eight California academic medical centers who were randomized to usual care or an intervention that combined health-coaching telephone calls and protocols for physician or nurse response to daily telemetric data on patient blood pressure, symptoms, heart rate, weight, and symptoms. The intervention turned out to have absolutely no effect on the 180-day rate of readmissions, which was roughly 50% in both groups (JAMA Intern Med. 2016 Mar;176[3]:310-8).
The PCDM (Patient-Centered Disease Management) trial was a multicenter Veterans Affairs study that randomized heart failure patients to usual care or a comprehensive intervention involving collaborative care by a cardiologist, psychiatrist, primary care physician, and nurse coordinator; screening and treatment for depression; and home telemonitoring of heart failure decompensation symptoms. The multifaceted intervention had no effect on the 1-year readmission rate (JAMA Intern Med. 2015 May;175[5]:725-32).
“To date, I would challenge you to find any adequately powered randomized, controlled trial in heart failure disease management that demonstrates that the way we’ve been doing things really keeps heart failure patients out of the hospital. So, it is time for a paradigm shift and some new technologies in our armamentarium,” Dr. Abraham said.
CardioMEMS system
Several remote telemedical management systems for heart failure, which measure early preclinical harbingers of acute decompensation, have received Food and Drug Administration approval. Many more are in development. Dr. Abraham highlighted two approved systems for which he was a coinvestigator in clinical trials.
The CardioMEMS system uses a pressure sensor the size of a small paper clip that is placed in a branch of the pulmonary artery, where it readily becomes endothelialized. Device implantation can be carried out by any cardiologist who can perform a right heart catheterization, be it an electrophysiologist, interventionalist, heart failure specialist, or general cardiologist. It takes only about an additional 7 minutes to deploy the sensor following a standard diagnostic right heart catheterization. The system doesn’t use a battery and has no moving parts.
“Now, with more than 10 years experience, we have yet to see a sensor failure. It’s a highly reliable system,” according to the cardiologist.
Once a day the patient lies down, pushes a button, and the sensor is simultaneously powered up while the data on pulmonary artery pressure waveforms and systolic and diastolic pressures is extracted using radiofrequency energy.
In the randomized, multicenter, controlled, single-blind CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial, Dr. Abraham and coinvestigators demonstrated that pulmonary artery pressure-guided heart failure management reduced the rate of heart failure hospitalizations in the CardioMEMS group by 33% during the first 18 months of the trial and by 48% in the subsequent 13 months (Lancet. 2016 Jan 30;387[10017]:453-61).
“It’s important to note that the results were positive in diastolic as well as systolic heart failure. Patients with a baseline left ventricular ejection fraction of 40% or more saw a 50% reduction in the risk of heart failure hospitalizations, and those with an LVEF of 50% or more saw a 70% reduction,” Dr. Abraham said.
Other implantable hemodynamic monitors
Numerous other implantable pressure sensors are in development for management of heart failure, including other pulmonary artery pressure sensors as well as left atrial pressure monitors.
“You’re going to hear a lot more about this field of implantable hemodynamic monitors in the future,” the cardiologist predicted.
Dr. Abraham was also a coinvestigator in an observational study of a wearable sensor based upon radar technology developed for the military and subsequently applied to rescue searches through rubble for earthquake survivors. This remote dielectric sensing (ReDS) technology has been miniaturized, with the sensors embedded in an FDA-approved vest. The heart failure patient dons the SensiVest for 90 seconds once per day for measurement of the absolute amount of fluid in the lungs. The data is automatically transmitted to a secured site in the cloud, where the physician can review the results and adjust medications in response to early evidence of fluid buildup.
“The normal lung is composed of 20%-35% fluid. So when that fluid content is elevated, patients with heart failure have wet lungs and they’re decompensating. You increase their diuretics to bring it back down into normal range,” he explained.
In the observational study, conducted in Israel, hospital readmission rates were reduced by 87% through the use of ReDS-guided patient management using the system marketed by Sensible Medical Innovations. Dr. Abraham and his coinvestigators are now seeking to confirm those results in the prospective, multicenter, randomized, controlled U.S. SMILE study.
Dr. Abraham reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Nonthoracic MRI safe in patients with cardiac devices
Nonthoracic MRI was safe in patients who had implanted non–MRI-conditional pacemakers or implantable cardioverter defibrillators, as long as they followed a specific safety protocol before and after the imaging procedure, according to a report published online Feb. 23 in the New England Journal of Medicine.
Patients with implanted cardiac devices have long been advised to avoid MRI because of the potential for the magnetic field to induce heating of the cardiac leads, which could in turn produce thermal injury to the myocardium and adversely affect the device’s function. Certain cardiac devices that have been proved to pose no such hazards have been designated by the Food and Drug Administration as “MRI conditional.” However, an estimated 2 million patients in the United States and another 6 million worldwide have devices that are not MRI conditional, and at least half of these patients are predicted to require an MRI during their lifetimes, said Robert J. Russo, MD, PhD, of Scripps Research Institute and the La Jolla (Calif.) Cardiovascular Research Institute, and his associates.
The MagnaSafe Registry was established to monitor device-related clinical events and device alterations among adults undergoing nonthoracic MRIs at 1.5 T. Dr. Russo and his associates analyzed data in this registry from 19 medical centers during a 5-year period. They assessed 1,000 MRIs in 818 patients with pacemakers and 500 MRIs in 428 patients with implantable cardioverter defibrillators who were followed for 6 months after the imaging procedures. Most of these scans involved the brain or spine, and the median duration of exposure to the magnetic field was 44 minutes.
According to the safety protocol, all devices were interrogated immediately before the MRI and, depending on those results, were programmed to no pacing or asynchronous pacing during the scan with all tachycardia and bradycardia therapies inactivated. Immediately after the scan, all devices were reprogrammed to baseline settings, a full device interrogation was repeated, and, if necessary, further reprogramming was performed to maintain adequate pacing and sensing. A physician, nurse practitioner, or physician’s assistant with cardiac expertise attended each scan.
There were no deaths, lead failures requiring immediate replacement, losses of capture, or full electrical resets associated with any of the 1,500 MRI scans.
Four patients developed atrial fibrillation, and two developed atrial flutter, during or after the MRI; three returned to sinus rhythm while still in the scanning room, and the other three did so within 49 hours. There were six cases requiring partial generator electrical resets. “Changes in device settings were common, but relatively few exceeded our prespecified threshold criteria for a clinically important change,” Dr. Russo and his associates wrote (N Engl J Med. 2017;376[8]:755-64).
Four patients reported feeling discomfort at the implant site during MRI, including one who felt a heating sensation and was removed from the scanner before completing the procedure. None of them had any further problems.
Some experts have suggested that to allow patients with cardiac devices to undergo MRI, the generators and leads could be removed before the procedure and replaced afterward. The findings of this study show that undergoing a nonthoracic MRI using this protocol would likely be a safer alternative, the investigators added.
This work was supported by St. Jude Medical, Biotronik, Boston Scientific, the Hewitt Foundation for Medical Research, and several philanthropic gifts. Dr. Russo reported ties to St. Jude Medical, Biotronik, Boston Scientific, and the Hewitt Foundation, and his associates reported ties to numerous industry sources.
Nonthoracic MRI was safe in patients who had implanted non–MRI-conditional pacemakers or implantable cardioverter defibrillators, as long as they followed a specific safety protocol before and after the imaging procedure, according to a report published online Feb. 23 in the New England Journal of Medicine.
Patients with implanted cardiac devices have long been advised to avoid MRI because of the potential for the magnetic field to induce heating of the cardiac leads, which could in turn produce thermal injury to the myocardium and adversely affect the device’s function. Certain cardiac devices that have been proved to pose no such hazards have been designated by the Food and Drug Administration as “MRI conditional.” However, an estimated 2 million patients in the United States and another 6 million worldwide have devices that are not MRI conditional, and at least half of these patients are predicted to require an MRI during their lifetimes, said Robert J. Russo, MD, PhD, of Scripps Research Institute and the La Jolla (Calif.) Cardiovascular Research Institute, and his associates.
The MagnaSafe Registry was established to monitor device-related clinical events and device alterations among adults undergoing nonthoracic MRIs at 1.5 T. Dr. Russo and his associates analyzed data in this registry from 19 medical centers during a 5-year period. They assessed 1,000 MRIs in 818 patients with pacemakers and 500 MRIs in 428 patients with implantable cardioverter defibrillators who were followed for 6 months after the imaging procedures. Most of these scans involved the brain or spine, and the median duration of exposure to the magnetic field was 44 minutes.
According to the safety protocol, all devices were interrogated immediately before the MRI and, depending on those results, were programmed to no pacing or asynchronous pacing during the scan with all tachycardia and bradycardia therapies inactivated. Immediately after the scan, all devices were reprogrammed to baseline settings, a full device interrogation was repeated, and, if necessary, further reprogramming was performed to maintain adequate pacing and sensing. A physician, nurse practitioner, or physician’s assistant with cardiac expertise attended each scan.
There were no deaths, lead failures requiring immediate replacement, losses of capture, or full electrical resets associated with any of the 1,500 MRI scans.
Four patients developed atrial fibrillation, and two developed atrial flutter, during or after the MRI; three returned to sinus rhythm while still in the scanning room, and the other three did so within 49 hours. There were six cases requiring partial generator electrical resets. “Changes in device settings were common, but relatively few exceeded our prespecified threshold criteria for a clinically important change,” Dr. Russo and his associates wrote (N Engl J Med. 2017;376[8]:755-64).
Four patients reported feeling discomfort at the implant site during MRI, including one who felt a heating sensation and was removed from the scanner before completing the procedure. None of them had any further problems.
Some experts have suggested that to allow patients with cardiac devices to undergo MRI, the generators and leads could be removed before the procedure and replaced afterward. The findings of this study show that undergoing a nonthoracic MRI using this protocol would likely be a safer alternative, the investigators added.
This work was supported by St. Jude Medical, Biotronik, Boston Scientific, the Hewitt Foundation for Medical Research, and several philanthropic gifts. Dr. Russo reported ties to St. Jude Medical, Biotronik, Boston Scientific, and the Hewitt Foundation, and his associates reported ties to numerous industry sources.
Nonthoracic MRI was safe in patients who had implanted non–MRI-conditional pacemakers or implantable cardioverter defibrillators, as long as they followed a specific safety protocol before and after the imaging procedure, according to a report published online Feb. 23 in the New England Journal of Medicine.
Patients with implanted cardiac devices have long been advised to avoid MRI because of the potential for the magnetic field to induce heating of the cardiac leads, which could in turn produce thermal injury to the myocardium and adversely affect the device’s function. Certain cardiac devices that have been proved to pose no such hazards have been designated by the Food and Drug Administration as “MRI conditional.” However, an estimated 2 million patients in the United States and another 6 million worldwide have devices that are not MRI conditional, and at least half of these patients are predicted to require an MRI during their lifetimes, said Robert J. Russo, MD, PhD, of Scripps Research Institute and the La Jolla (Calif.) Cardiovascular Research Institute, and his associates.
The MagnaSafe Registry was established to monitor device-related clinical events and device alterations among adults undergoing nonthoracic MRIs at 1.5 T. Dr. Russo and his associates analyzed data in this registry from 19 medical centers during a 5-year period. They assessed 1,000 MRIs in 818 patients with pacemakers and 500 MRIs in 428 patients with implantable cardioverter defibrillators who were followed for 6 months after the imaging procedures. Most of these scans involved the brain or spine, and the median duration of exposure to the magnetic field was 44 minutes.
According to the safety protocol, all devices were interrogated immediately before the MRI and, depending on those results, were programmed to no pacing or asynchronous pacing during the scan with all tachycardia and bradycardia therapies inactivated. Immediately after the scan, all devices were reprogrammed to baseline settings, a full device interrogation was repeated, and, if necessary, further reprogramming was performed to maintain adequate pacing and sensing. A physician, nurse practitioner, or physician’s assistant with cardiac expertise attended each scan.
There were no deaths, lead failures requiring immediate replacement, losses of capture, or full electrical resets associated with any of the 1,500 MRI scans.
Four patients developed atrial fibrillation, and two developed atrial flutter, during or after the MRI; three returned to sinus rhythm while still in the scanning room, and the other three did so within 49 hours. There were six cases requiring partial generator electrical resets. “Changes in device settings were common, but relatively few exceeded our prespecified threshold criteria for a clinically important change,” Dr. Russo and his associates wrote (N Engl J Med. 2017;376[8]:755-64).
Four patients reported feeling discomfort at the implant site during MRI, including one who felt a heating sensation and was removed from the scanner before completing the procedure. None of them had any further problems.
Some experts have suggested that to allow patients with cardiac devices to undergo MRI, the generators and leads could be removed before the procedure and replaced afterward. The findings of this study show that undergoing a nonthoracic MRI using this protocol would likely be a safer alternative, the investigators added.
This work was supported by St. Jude Medical, Biotronik, Boston Scientific, the Hewitt Foundation for Medical Research, and several philanthropic gifts. Dr. Russo reported ties to St. Jude Medical, Biotronik, Boston Scientific, and the Hewitt Foundation, and his associates reported ties to numerous industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Nonthoracic MRI was safe in patients who had implanted non–MRI-conditional pacemakers or ICDs, as long as they followed a specific safety protocol before and after the imaging procedure.
Key numerical finding: No deaths, lead failures requiring immediate replacement, losses of capture, or full electrical resets were tied to any of the 1,500 MRI scans.
Data source: A U.S. registry–based cohort study of 1,000 MRIs involving patients with pacemakers and 500 MRIs involving patients with ICDs, performed during a 5-year period.
Disclosures: This work was supported by St. Jude Medical, Biotronik, Boston Scientific, the Hewitt Foundation for Medical Research, and several philanthropic gifts. Dr. Russo reported ties to St. Jude Medical, Biotronik, Boston Scientific, and the Hewitt Foundation, and his associates reported ties to numerous industry sources.