Cardiology News

The addition of image-guided atrial fibrosis ablation did not significantly reduce the risk of recurrence relative to pulmonary vein isolation (PVI) alone in patients with treatment-resistant atrial fibrillation (AFib), according to results of an intention-to-treat analysis of the randomized DECAAF II trial.

Mitchel L. Zoler/MDedge News

However, there was a significant advantage for the addition of image-guided ablation in the subgroup of patients with stage I or II fibrosis, and this is a clinically meaningful finding, Nassir F. Marrouche, MD, reported at the annual congress of the European Society of Cardiology.

“Patients at early stages [of fibrosis] appear to do well if you do a good job covering the myopathy [with scar formation], and that is an important message,” said Dr. Marrouche, the principal investigator.

The underlying hypothesis of the DECAAF trial was that ablation guided with MRI imaging would prove superior to PVI alone in the treatment of resistant AF. There were 843 participants randomized at 44 centers. At baseline, all underwent a late gadolinium-enhancement MRI, a technique that allows detection of fibrotic tissue.

After randomization, those in the control group underwent standard of care PVI alone. Those in the intervention group underwent ablation of areas of the atrium revealed to be fibrotic on the MRI scan in addition to PVI.
 

Five percent risk reduction not significant

After a median follow-up of 12 months, recurrence of AFib, which was the primary endpoint, was observed in 43% in the intervention group and 46.1% in the control group. The relative 5% reduction for treatment was not statistically significant (hazard ratio, 0.95; 95% confidence interval, 0.778-1.17; P = .63).

As part of the study protocol, MRI was repeated 3 months after treatment in all patients. This permitted the investigators to evaluate the degree of scar formation in relation to the fibrosis covered in the intervention group. Independent reviewers rated this coverage on levels from 1 to 5, with 5 representing complete coverage.

In this analysis, it was found that ablation resulted in higher levels of lesion formation in those with early stages of disease, defined as stage I or II fibrosis, but lower levels in advanced stages.

“The more myopathy, the more disease, the less likelihood of lesion formation,” reported Dr. Marrouche, professor of medicine in the section of cardiology at Tulane University, New Orleans.

Attributed to the greater levels of fibrosis coverage, the risk of AF recurrence over the course of follow-up was significantly reduced in the intervention relative to the control group on as-treated analysis in patients who had stage I or II fibrosis at baseline. (HR 0.841, 95% CI, 0.732-0.968; P < .05).

Subgroup data called clinically meaningful

“This has huge implications going forward,” Dr. Marrouche maintained. In the context of a series of previous trials, including DECAAF I, which associated advanced fibrosis with higher risk of failing ablation, DECAAF II provides the groundwork for “where and how to ablate.”

Taken together, the DECAAF data suggest that there is no value in ablating advanced fibrosis. Due to the poor scar formation needed to reduce risk of AF recurrence, there are no benefits to outweigh the slightly greater risk of strokes and other adverse events observed among the intervention group in the DECAAF II trial, according to Dr. Marrouche.

“If the fibrosis is advanced, do PVI only,” he said.

However, if fibrosis remains at an early stage, defined by these data as stage II or lower, the data from DECAAF indicated that there is a benefit, according to Dr. Marrouche.

“DECAAF tells you to target early disease,” he said. Asked if he would now apply these data to treatment of patients with early fibrosis, he replied, “Yes, that’s what I am concluding.”

Several aspects of the design of DECAAF II, such as the use of a follow-up MRI to assess ablation at 3 months, were praised by Paul J. Wang, MD, director, Stanford Cardiac Arrhythmia Service, Stanford (Calif.) University, but he did not agree with Dr. Marrouche’s interpretation. This included the contention that scar formation was easier to achieve in patients with less atrial fibrosis.
 

DECAAF II is not a positive trial

Based on his reading of the correlation coefficients, expressed as an r value, which were 0.237 and 0.493 for the low- and high-fibrosis groups, respectively, “the difference in lesion formation in low- and high-fibrosis groups seems difficult to prove,” Dr. Wang pointed out.

In addition, “the authors suggest that the failure to achieve a good ablation lesion may account for the AFib recurrence,” said Dr. Wang, editor-in-chief of the American Heart Association’s Circulation: Arrhythmia and Electrophysiology. However, due to the many other potential variables influencing this risk, “this is difficult to show.”

Ultimately, despite a benefit observed among patients with a low level of fibrosis that was identified in an as-treated subgroup, “DECAAF II joins the numerous studies [evaluating the addition of an intervention relative to PVI alone] that have not achieved the primary endpoint,” Dr. Wang concluded.

An ESC-invited discussant, Christophe Leclercq, MD, chief of cardiology at Centre Hospitalier Universitaire, Rennes, France, made the same point. He said several previous studies have made the concept of achieving greater ablation to reduce AF recurrence “attractive,” but this “was not confirmed in DECAAF II.”

He also would not endorse MRI-guided ablation in resistant AFib among patients with early disease.

“There was a positive result observed in those with a low stage of fibrosis, but there were also more complications in those undergoing MRI-guided ablation,” he said.

Dr. Marrouche reports financial relationships with Abbott, which provided funding for this study. Dr. Wang had no disclosures. Dr. Leclercq reported financial relationships with Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical.

The addition of image-guided atrial fibrosis ablation did not significantly reduce the risk of recurrence relative to pulmonary vein isolation (PVI) alone in patients with treatment-resistant atrial fibrillation (AFib), according to results of an intention-to-treat analysis of the randomized DECAAF II trial.

Mitchel L. Zoler/MDedge News

However, there was a significant advantage for the addition of image-guided ablation in the subgroup of patients with stage I or II fibrosis, and this is a clinically meaningful finding, Nassir F. Marrouche, MD, reported at the annual congress of the European Society of Cardiology.

“Patients at early stages [of fibrosis] appear to do well if you do a good job covering the myopathy [with scar formation], and that is an important message,” said Dr. Marrouche, the principal investigator.

The underlying hypothesis of the DECAAF trial was that ablation guided with MRI imaging would prove superior to PVI alone in the treatment of resistant AF. There were 843 participants randomized at 44 centers. At baseline, all underwent a late gadolinium-enhancement MRI, a technique that allows detection of fibrotic tissue.

After randomization, those in the control group underwent standard of care PVI alone. Those in the intervention group underwent ablation of areas of the atrium revealed to be fibrotic on the MRI scan in addition to PVI.
 

Five percent risk reduction not significant

After a median follow-up of 12 months, recurrence of AFib, which was the primary endpoint, was observed in 43% in the intervention group and 46.1% in the control group. The relative 5% reduction for treatment was not statistically significant (hazard ratio, 0.95; 95% confidence interval, 0.778-1.17; P = .63).

As part of the study protocol, MRI was repeated 3 months after treatment in all patients. This permitted the investigators to evaluate the degree of scar formation in relation to the fibrosis covered in the intervention group. Independent reviewers rated this coverage on levels from 1 to 5, with 5 representing complete coverage.

In this analysis, it was found that ablation resulted in higher levels of lesion formation in those with early stages of disease, defined as stage I or II fibrosis, but lower levels in advanced stages.

“The more myopathy, the more disease, the less likelihood of lesion formation,” reported Dr. Marrouche, professor of medicine in the section of cardiology at Tulane University, New Orleans.

Attributed to the greater levels of fibrosis coverage, the risk of AF recurrence over the course of follow-up was significantly reduced in the intervention relative to the control group on as-treated analysis in patients who had stage I or II fibrosis at baseline. (HR 0.841, 95% CI, 0.732-0.968; P < .05).

Subgroup data called clinically meaningful

“This has huge implications going forward,” Dr. Marrouche maintained. In the context of a series of previous trials, including DECAAF I, which associated advanced fibrosis with higher risk of failing ablation, DECAAF II provides the groundwork for “where and how to ablate.”

Taken together, the DECAAF data suggest that there is no value in ablating advanced fibrosis. Due to the poor scar formation needed to reduce risk of AF recurrence, there are no benefits to outweigh the slightly greater risk of strokes and other adverse events observed among the intervention group in the DECAAF II trial, according to Dr. Marrouche.

“If the fibrosis is advanced, do PVI only,” he said.

However, if fibrosis remains at an early stage, defined by these data as stage II or lower, the data from DECAAF indicated that there is a benefit, according to Dr. Marrouche.

“DECAAF tells you to target early disease,” he said. Asked if he would now apply these data to treatment of patients with early fibrosis, he replied, “Yes, that’s what I am concluding.”

Several aspects of the design of DECAAF II, such as the use of a follow-up MRI to assess ablation at 3 months, were praised by Paul J. Wang, MD, director, Stanford Cardiac Arrhythmia Service, Stanford (Calif.) University, but he did not agree with Dr. Marrouche’s interpretation. This included the contention that scar formation was easier to achieve in patients with less atrial fibrosis.
 

DECAAF II is not a positive trial

Based on his reading of the correlation coefficients, expressed as an r value, which were 0.237 and 0.493 for the low- and high-fibrosis groups, respectively, “the difference in lesion formation in low- and high-fibrosis groups seems difficult to prove,” Dr. Wang pointed out.

In addition, “the authors suggest that the failure to achieve a good ablation lesion may account for the AFib recurrence,” said Dr. Wang, editor-in-chief of the American Heart Association’s Circulation: Arrhythmia and Electrophysiology. However, due to the many other potential variables influencing this risk, “this is difficult to show.”

Ultimately, despite a benefit observed among patients with a low level of fibrosis that was identified in an as-treated subgroup, “DECAAF II joins the numerous studies [evaluating the addition of an intervention relative to PVI alone] that have not achieved the primary endpoint,” Dr. Wang concluded.

An ESC-invited discussant, Christophe Leclercq, MD, chief of cardiology at Centre Hospitalier Universitaire, Rennes, France, made the same point. He said several previous studies have made the concept of achieving greater ablation to reduce AF recurrence “attractive,” but this “was not confirmed in DECAAF II.”

He also would not endorse MRI-guided ablation in resistant AFib among patients with early disease.

“There was a positive result observed in those with a low stage of fibrosis, but there were also more complications in those undergoing MRI-guided ablation,” he said.

Dr. Marrouche reports financial relationships with Abbott, which provided funding for this study. Dr. Wang had no disclosures. Dr. Leclercq reported financial relationships with Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical.

The addition of image-guided atrial fibrosis ablation did not significantly reduce the risk of recurrence relative to pulmonary vein isolation (PVI) alone in patients with treatment-resistant atrial fibrillation (AFib), according to results of an intention-to-treat analysis of the randomized DECAAF II trial.

Mitchel L. Zoler/MDedge News

However, there was a significant advantage for the addition of image-guided ablation in the subgroup of patients with stage I or II fibrosis, and this is a clinically meaningful finding, Nassir F. Marrouche, MD, reported at the annual congress of the European Society of Cardiology.

“Patients at early stages [of fibrosis] appear to do well if you do a good job covering the myopathy [with scar formation], and that is an important message,” said Dr. Marrouche, the principal investigator.

The underlying hypothesis of the DECAAF trial was that ablation guided with MRI imaging would prove superior to PVI alone in the treatment of resistant AF. There were 843 participants randomized at 44 centers. At baseline, all underwent a late gadolinium-enhancement MRI, a technique that allows detection of fibrotic tissue.

After randomization, those in the control group underwent standard of care PVI alone. Those in the intervention group underwent ablation of areas of the atrium revealed to be fibrotic on the MRI scan in addition to PVI.
 

Five percent risk reduction not significant

After a median follow-up of 12 months, recurrence of AFib, which was the primary endpoint, was observed in 43% in the intervention group and 46.1% in the control group. The relative 5% reduction for treatment was not statistically significant (hazard ratio, 0.95; 95% confidence interval, 0.778-1.17; P = .63).

As part of the study protocol, MRI was repeated 3 months after treatment in all patients. This permitted the investigators to evaluate the degree of scar formation in relation to the fibrosis covered in the intervention group. Independent reviewers rated this coverage on levels from 1 to 5, with 5 representing complete coverage.

In this analysis, it was found that ablation resulted in higher levels of lesion formation in those with early stages of disease, defined as stage I or II fibrosis, but lower levels in advanced stages.

“The more myopathy, the more disease, the less likelihood of lesion formation,” reported Dr. Marrouche, professor of medicine in the section of cardiology at Tulane University, New Orleans.

Attributed to the greater levels of fibrosis coverage, the risk of AF recurrence over the course of follow-up was significantly reduced in the intervention relative to the control group on as-treated analysis in patients who had stage I or II fibrosis at baseline. (HR 0.841, 95% CI, 0.732-0.968; P < .05).

Subgroup data called clinically meaningful

“This has huge implications going forward,” Dr. Marrouche maintained. In the context of a series of previous trials, including DECAAF I, which associated advanced fibrosis with higher risk of failing ablation, DECAAF II provides the groundwork for “where and how to ablate.”

Taken together, the DECAAF data suggest that there is no value in ablating advanced fibrosis. Due to the poor scar formation needed to reduce risk of AF recurrence, there are no benefits to outweigh the slightly greater risk of strokes and other adverse events observed among the intervention group in the DECAAF II trial, according to Dr. Marrouche.

“If the fibrosis is advanced, do PVI only,” he said.

However, if fibrosis remains at an early stage, defined by these data as stage II or lower, the data from DECAAF indicated that there is a benefit, according to Dr. Marrouche.

“DECAAF tells you to target early disease,” he said. Asked if he would now apply these data to treatment of patients with early fibrosis, he replied, “Yes, that’s what I am concluding.”

Several aspects of the design of DECAAF II, such as the use of a follow-up MRI to assess ablation at 3 months, were praised by Paul J. Wang, MD, director, Stanford Cardiac Arrhythmia Service, Stanford (Calif.) University, but he did not agree with Dr. Marrouche’s interpretation. This included the contention that scar formation was easier to achieve in patients with less atrial fibrosis.
 

DECAAF II is not a positive trial

Based on his reading of the correlation coefficients, expressed as an r value, which were 0.237 and 0.493 for the low- and high-fibrosis groups, respectively, “the difference in lesion formation in low- and high-fibrosis groups seems difficult to prove,” Dr. Wang pointed out.

In addition, “the authors suggest that the failure to achieve a good ablation lesion may account for the AFib recurrence,” said Dr. Wang, editor-in-chief of the American Heart Association’s Circulation: Arrhythmia and Electrophysiology. However, due to the many other potential variables influencing this risk, “this is difficult to show.”

Ultimately, despite a benefit observed among patients with a low level of fibrosis that was identified in an as-treated subgroup, “DECAAF II joins the numerous studies [evaluating the addition of an intervention relative to PVI alone] that have not achieved the primary endpoint,” Dr. Wang concluded.

An ESC-invited discussant, Christophe Leclercq, MD, chief of cardiology at Centre Hospitalier Universitaire, Rennes, France, made the same point. He said several previous studies have made the concept of achieving greater ablation to reduce AF recurrence “attractive,” but this “was not confirmed in DECAAF II.”

He also would not endorse MRI-guided ablation in resistant AFib among patients with early disease.

“There was a positive result observed in those with a low stage of fibrosis, but there were also more complications in those undergoing MRI-guided ablation,” he said.

Dr. Marrouche reports financial relationships with Abbott, which provided funding for this study. Dr. Wang had no disclosures. Dr. Leclercq reported financial relationships with Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical.

Dapagliflozin might reduce the risk for ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF), a post hoc analysis of the DAPA-HF trial suggests.

The addition of dapagliflozin to standard therapy reduced the relative risk for the primary composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%, compared with placebo (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99). The absolute risk reduction was 1.5% (5.9% vs. 7.4%).

The benefit was consistent in a competing-risks analysis that included all-cause mortality (HR, 0.80; P = .043) and across the individual components of the composite outcome, James Curtain, MD, Cardiovascular Research Centre of Glasgow, said at the annual congress of the European Society of Cardiology.

As previously reported from the main trial, treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor cut the primary endpoint of cardiovascular death or worsening heart failure by 26% among 4,744 patients with HFrEF and in New York Heart Association functional class 2-4.

Cochair of the late-breaking science session, Lars Lund, MD, Karolinska Institute, Stockholm, pointed out that dapagliflozin reduced sudden cardiac deaths and related events to an extent similar to that observed for cardiovascular deaths, total mortality, and the main trial’s primary endpoint.

“So does that mean it has any particular effect on arrhythmic events or does it mean, such as a beta-blocker, for example, [it] reduces calcium transience and improves handling of calcium, or does it have an effect simply by improving heart failure?” he asked.

Dr. Curtain replied they are still trying to understand the effects of this new class of drug but that studies have shown dapagliflozin and other SGLT2 inhibitors have favorable effects on adverse cardiac remodeling, which contributes to sudden death and ventricular arrhythmia. They’ve also been shown to reduce cardiac chamber size, left ventricular hypertrophy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over time, consistent with a reduction in myocardial wall stress. “So it could indeed be one of several mechanisms by which they may exert a beneficial cardiac effect.”

Speaking with this news organization, Dr. Curtain pointed out that the Kaplan-Meier curves for the composite outcome began to separate early on, but that the clearest separation was after 9 months, suggestive of a positive action on adverse cardiac remodeling over time.

“This would improve the patients’ heart failure situation, but also thick ventricles are a key risk factor for the occurrence of sudden death and ventricular arrhythmias,” he said. “The effects on adverse cardiac remodeling, given its plausibility in terms of our Kaplan-Meier curves, are one [mechanism] that I’d look to in the first instance, but I’m sure there are more than one actions at play.”

According to the new analysis, the primary outcome occurred in 315 (6.6%) patients; there were 203 adjudicated sudden deaths (64%), 104 investigator-reported ventricular arrhythmias (33%), and 8 resuscitated cardiac arrests (3%). Independent predictors of the primary outcome were higher NT-proBNP levels (odds ratio, 1.54), previous ventricular arrhythmia (OR, 1.93), previous myocardial infarction (OR, 1.42), male sex (OR, 1.53), and higher body mass index (OR, 1.03).

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

Dapagliflozin might reduce the risk for ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF), a post hoc analysis of the DAPA-HF trial suggests.

The addition of dapagliflozin to standard therapy reduced the relative risk for the primary composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%, compared with placebo (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99). The absolute risk reduction was 1.5% (5.9% vs. 7.4%).

The benefit was consistent in a competing-risks analysis that included all-cause mortality (HR, 0.80; P = .043) and across the individual components of the composite outcome, James Curtain, MD, Cardiovascular Research Centre of Glasgow, said at the annual congress of the European Society of Cardiology.

As previously reported from the main trial, treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor cut the primary endpoint of cardiovascular death or worsening heart failure by 26% among 4,744 patients with HFrEF and in New York Heart Association functional class 2-4.

Cochair of the late-breaking science session, Lars Lund, MD, Karolinska Institute, Stockholm, pointed out that dapagliflozin reduced sudden cardiac deaths and related events to an extent similar to that observed for cardiovascular deaths, total mortality, and the main trial’s primary endpoint.

“So does that mean it has any particular effect on arrhythmic events or does it mean, such as a beta-blocker, for example, [it] reduces calcium transience and improves handling of calcium, or does it have an effect simply by improving heart failure?” he asked.

Dr. Curtain replied they are still trying to understand the effects of this new class of drug but that studies have shown dapagliflozin and other SGLT2 inhibitors have favorable effects on adverse cardiac remodeling, which contributes to sudden death and ventricular arrhythmia. They’ve also been shown to reduce cardiac chamber size, left ventricular hypertrophy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over time, consistent with a reduction in myocardial wall stress. “So it could indeed be one of several mechanisms by which they may exert a beneficial cardiac effect.”

Speaking with this news organization, Dr. Curtain pointed out that the Kaplan-Meier curves for the composite outcome began to separate early on, but that the clearest separation was after 9 months, suggestive of a positive action on adverse cardiac remodeling over time.

“This would improve the patients’ heart failure situation, but also thick ventricles are a key risk factor for the occurrence of sudden death and ventricular arrhythmias,” he said. “The effects on adverse cardiac remodeling, given its plausibility in terms of our Kaplan-Meier curves, are one [mechanism] that I’d look to in the first instance, but I’m sure there are more than one actions at play.”

According to the new analysis, the primary outcome occurred in 315 (6.6%) patients; there were 203 adjudicated sudden deaths (64%), 104 investigator-reported ventricular arrhythmias (33%), and 8 resuscitated cardiac arrests (3%). Independent predictors of the primary outcome were higher NT-proBNP levels (odds ratio, 1.54), previous ventricular arrhythmia (OR, 1.93), previous myocardial infarction (OR, 1.42), male sex (OR, 1.53), and higher body mass index (OR, 1.03).

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

Dapagliflozin might reduce the risk for ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF), a post hoc analysis of the DAPA-HF trial suggests.

The addition of dapagliflozin to standard therapy reduced the relative risk for the primary composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%, compared with placebo (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99). The absolute risk reduction was 1.5% (5.9% vs. 7.4%).

The benefit was consistent in a competing-risks analysis that included all-cause mortality (HR, 0.80; P = .043) and across the individual components of the composite outcome, James Curtain, MD, Cardiovascular Research Centre of Glasgow, said at the annual congress of the European Society of Cardiology.

As previously reported from the main trial, treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor cut the primary endpoint of cardiovascular death or worsening heart failure by 26% among 4,744 patients with HFrEF and in New York Heart Association functional class 2-4.

Cochair of the late-breaking science session, Lars Lund, MD, Karolinska Institute, Stockholm, pointed out that dapagliflozin reduced sudden cardiac deaths and related events to an extent similar to that observed for cardiovascular deaths, total mortality, and the main trial’s primary endpoint.

“So does that mean it has any particular effect on arrhythmic events or does it mean, such as a beta-blocker, for example, [it] reduces calcium transience and improves handling of calcium, or does it have an effect simply by improving heart failure?” he asked.

Dr. Curtain replied they are still trying to understand the effects of this new class of drug but that studies have shown dapagliflozin and other SGLT2 inhibitors have favorable effects on adverse cardiac remodeling, which contributes to sudden death and ventricular arrhythmia. They’ve also been shown to reduce cardiac chamber size, left ventricular hypertrophy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over time, consistent with a reduction in myocardial wall stress. “So it could indeed be one of several mechanisms by which they may exert a beneficial cardiac effect.”

Speaking with this news organization, Dr. Curtain pointed out that the Kaplan-Meier curves for the composite outcome began to separate early on, but that the clearest separation was after 9 months, suggestive of a positive action on adverse cardiac remodeling over time.

“This would improve the patients’ heart failure situation, but also thick ventricles are a key risk factor for the occurrence of sudden death and ventricular arrhythmias,” he said. “The effects on adverse cardiac remodeling, given its plausibility in terms of our Kaplan-Meier curves, are one [mechanism] that I’d look to in the first instance, but I’m sure there are more than one actions at play.”

According to the new analysis, the primary outcome occurred in 315 (6.6%) patients; there were 203 adjudicated sudden deaths (64%), 104 investigator-reported ventricular arrhythmias (33%), and 8 resuscitated cardiac arrests (3%). Independent predictors of the primary outcome were higher NT-proBNP levels (odds ratio, 1.54), previous ventricular arrhythmia (OR, 1.93), previous myocardial infarction (OR, 1.42), male sex (OR, 1.53), and higher body mass index (OR, 1.03).

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

After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.

wildpixel/iStock/Getty Images

When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.

The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).

“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”

The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.

Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.

The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
 

ECG used to define autonomic dysfunction

In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.

The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.

After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.

The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).

Arrhythmias warn of impending complications

“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”

Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.

“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”

Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.

“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
 

Data provide insight on unaddressed risk group

SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.

An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.

“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.

Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.

After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.

wildpixel/iStock/Getty Images

When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.

The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).

“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”

The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.

Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.

The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
 

ECG used to define autonomic dysfunction

In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.

The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.

After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.

The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).

Arrhythmias warn of impending complications

“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”

Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.

“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”

Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.

“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
 

Data provide insight on unaddressed risk group

SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.

An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.

“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.

Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.

After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.

wildpixel/iStock/Getty Images

When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.

The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).

“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”

The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.

Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.

The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
 

ECG used to define autonomic dysfunction

In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.

The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.

After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.

The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).

Arrhythmias warn of impending complications

“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”

Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.

“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”

Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.

“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
 

Data provide insight on unaddressed risk group

SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.

An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.

“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.

Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.

Medical therapy for heart failure guided by an implanted pulmonary artery pressure (PAP) sensor didn’t improve survival or risk for HF events like hospitalization over a year in a major randomized trial that entered a broad range of patients with mild to moderate disease.

But medical therapy adjustments based on PAP readings from the miniature CardioMEMS (Abbott) implant might well have surpassed conventional HF management for outcomes had the world not been turned upside down by SARS-CoV-2 and the pandemic lockdowns, assert researchers from the GUIDE-HF trial.

Something about the crisis, they concluded – although not without some pushback – led to better outcomes in the standard-care control group, apparently muddling any potential differences from those on PAP-guided management.

Working with regulators, the team conducted a “pre–COVID-19 impact analysis” that compared outcomes before the March 2020 national COVID-19 emergency declaration that forced much of the United States with shelter in place.

By that time, all of the trial’s patients had been followed for at least 3 months, and about three-fourths of its endpoints had already been counted, JoAnn Lindenfeld, MD, Vanderbilt University Medical Center, Nashville, Tenn., said at a media briefing prior to unveiling GUIDE-HF at the all-virtual European Society of Cardiology Congress 2021.

The pre–COVID-19 analysis, approved several months before the end of the trial – while the data were still blinded – had been “suggested by both regulatory agencies and professional societies in Europe and in the United States,” Dr. Lindenfeld said.

It pointed to a possible benefit for the CardioMEMS-guided strategy, a barely significant 19% drop in risk (P = .049) for the primary endpoint of death, HF hospitalization, or urgent HF hospital visit. The effect was driven by a 24% decline in HF events (P = .014), with no significant contribution from mortality.

“The benefits of hemodynamic monitoring and management in reducing heart failure hospitalizations extended to patients with less severe heart failure”; that is, those in New York Heart Association class 2 and any in NYHA class 3 with “elevated natriuretic peptides but no previous hospitalization,” said Dr. Lindenfeld, who is also lead author on the GUIDE-HF report published in the Lancet.

Such benefits would suggest that CardioMEMS-guided management can improve outcomes in an HF population much broader than the device’s current indication.

But as it happens, the trial’s prospectively defined 12-month primary outcomes were less impressive. A 12% decline in risk for the composite endpoint among patients managed by CardioMEMS failed to reach significance compared with standard management (P = .16).

“Several factors could explain the considerable loss of benefit of hemodynamic-guided management during the COVID-19 pandemic,” the Lancet report explained. They include “improved patient compliance with medical and dietary regimens, reduced respiratory infections, altered health-care provider behavior, changes in disease progression due to COVID-19, or other as yet unknown effects of a major pandemic.”
 

Expanded population

Importantly, GUIDE-HF had entered 1,000 patients in NYHA class 2-4 and either an HF hospitalization in the previous year or elevated natriuretic peptide levels. About 44% of the entrants in NYHA class 3 did not have a 1-year history of HF hospitalization.

That’s a more heterogeneous and potentially lower-risk cohort than patients in the randomized CHAMPION study of 11 years ago, which led to the implant’s approval on both sides of the Atlantic.

In that trial, CardioMEMS-guided management was followed by 30% drop in risk for HF hospitalization over 6 months (P < .001). But CHAMPION was limited to patients in NYHA class 3 with a history of HF hospitalization, the device’s current indication in both the United States and Europe.

The GUIDE-HF findings “reinforce that patients with class 3 heart failure and prior heart failure hospitalization are those in whom there is the clearest benefit, based on the prior CHAMPION trial. These are the patients where this monitoring strategy may be best targeted,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, said in an interview.

Although GUIDE-HF didn’t show a significant benefit for NYHA class 2 patients with elevated biomarkers, who aren’t covered by the device’s current labeling, that group showed “some suggestions of potential benefit,” noted Dr. Fonarow, who isn’t a coauthor on the Lancet report. So, “there may be select patients with class 2 heart failure where monitoring could be considered on a case-by-case basis.”

In an interview, Larry A. Allen, MD, MHS, said that, “while the technology is pretty amazing, the real question is whether it tells us something that we didn’t already know that leads to improved care. Unfortunately, as tested here, it doesn’t, or at least not enough to make a big difference.”

The pre–COVID-19 impact analysis “should be interpreted with caution, and not as the primary finding,” Dr. Allen, from the University of Colorado at Denver, Aurora, who is not a GUIDE-HF coauthor, said in an interview.

One might hypothesize, he said, “that, in the setting of limited in-person visits with loss of physical examination, perhaps CardioMEMS would be more – not less – helpful during the pandemic. And yet the opposite was seen.”

The pandemic has “markedly altered all kinds of aspects of patient care and trial conduct, but that doesn’t make the data derived during that period uninformative,” Dr. Allen said. “And as we are increasingly reminded, the future will be a new normal, not a prepandemic normal.”

A third group

The GUIDE-HF trial includes, in addition to the 1,000 randomized patients, a single-group observational cohort of 2,600 patients, whose outcomes will be reported at another time, noted the published report.

But in the randomized comparison, conducted at 118 centers in North America, all patients were implanted with the CardioMEMS device and blinded as to their assigned strategy. Enrollment took place between March 2018 and Dec. 20, 2019.

Of the 1,000 successfully implanted patients, 497 were assigned to the pressure-guided strategy, in which “titration of diuretics was recommended if pulmonary artery pressure provided evidence of excess intravascular volume, and titration of vasodilators was recommended if elevated vascular resistance was evident,” the report stated.

The remaining 503 patients assigned to standard care served as control subjects, for whom “investigators were aware of treatment assignment but did not have access to PAP data.”

The hazard ratio for the primary endpoint in the pressure-guided group, compared with the control group, was 0.88 (95% confidence interval, 0.74-1.05; P = .16) over a median follow-up of 11.7 months.

But in the sensitivity analysis comparing outcomes before and after the COVID-19 lockdowns, using established methodology, the report stated, the primary-endpoint HR was 0.81 (95% CI, 0.66-1.00; P = .049).

The difference is owed to improved outcomes in the control group under pandemic conditions, the researchers concluded. Patients assigned to conventional management –whatever that meant during shelter-in-place – experienced 21% fewer primary-endpoint events than their own rate before the pandemic. After the COVID-19 emergency was declared, there was no significant difference in event rates between the two randomization groups.

In the primary 12-month analysis, the HR for HF events in the guided-therapy was not significant reduced, at 0.85 (95% CI, 0.70-1.03; P = .096). But in the pre-COVID-19 analysis, that risk fell significantly with CardioMEMS-guided management, for an HR of 0.76 (95% CI, 0.61-0.95; P = .014).

An editorial accompanying the GUIDE-HF publication (Lancet. 2021 Aug 27. doi: 10.1016/S0140-6736[21]01914-0) asserts that the trial “did not enroll an ideal group of patients for showing the efficacy of pulmonary artery pressure monitoring, since many had baseline pressures in the target range with little possibility of short-term gain.”

Also, wrote John G. F. Cleland, MD, PhD, University of Glasgow, and Pierpaolo Pellicori, MD, Imperial College London, “follow-up was too short, and interventions did not substantially change pulmonary artery pressure.”

They continue: “Monitoring alone cannot improve outcome, but consequent actions might. The GUIDE-HF results are encouraging but inconclusive, and should inform further research, possibly a large, simple, open-label trial to investigate a system of care rather than a single technology.”

GUIDE-HF was funded by Abbott. Dr. Lindenfeld disclosed receiving research grants from AstraZeneca, Sensible Medical, and Volumetrix; and consulting for Abbott, Alleviant Medical, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave. Dr. Fonarow reported consulting for Abbott and that his institution has participated in the GUIDE-HF trial; he has elsewhere disclosed consulting for Amgen, AstraZeneca, CHF Solutions Lifesciences, Janssen, Medtronic, and Novartis. Dr. Allen had elsewhere reported consulting for Abbott, Amgen, Boston Scientific, and Novartis. Dr. Cleland disclosed receiving personal fees from Abbott for serving on an advisory board for the MitraClip device, unrelated to the CardioMEMS device. Dr. Pellicori reported no relevant conflicts.

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

Medical therapy for heart failure guided by an implanted pulmonary artery pressure (PAP) sensor didn’t improve survival or risk for HF events like hospitalization over a year in a major randomized trial that entered a broad range of patients with mild to moderate disease.

But medical therapy adjustments based on PAP readings from the miniature CardioMEMS (Abbott) implant might well have surpassed conventional HF management for outcomes had the world not been turned upside down by SARS-CoV-2 and the pandemic lockdowns, assert researchers from the GUIDE-HF trial.

Something about the crisis, they concluded – although not without some pushback – led to better outcomes in the standard-care control group, apparently muddling any potential differences from those on PAP-guided management.

Working with regulators, the team conducted a “pre–COVID-19 impact analysis” that compared outcomes before the March 2020 national COVID-19 emergency declaration that forced much of the United States with shelter in place.

By that time, all of the trial’s patients had been followed for at least 3 months, and about three-fourths of its endpoints had already been counted, JoAnn Lindenfeld, MD, Vanderbilt University Medical Center, Nashville, Tenn., said at a media briefing prior to unveiling GUIDE-HF at the all-virtual European Society of Cardiology Congress 2021.

The pre–COVID-19 analysis, approved several months before the end of the trial – while the data were still blinded – had been “suggested by both regulatory agencies and professional societies in Europe and in the United States,” Dr. Lindenfeld said.

It pointed to a possible benefit for the CardioMEMS-guided strategy, a barely significant 19% drop in risk (P = .049) for the primary endpoint of death, HF hospitalization, or urgent HF hospital visit. The effect was driven by a 24% decline in HF events (P = .014), with no significant contribution from mortality.

“The benefits of hemodynamic monitoring and management in reducing heart failure hospitalizations extended to patients with less severe heart failure”; that is, those in New York Heart Association class 2 and any in NYHA class 3 with “elevated natriuretic peptides but no previous hospitalization,” said Dr. Lindenfeld, who is also lead author on the GUIDE-HF report published in the Lancet.

Such benefits would suggest that CardioMEMS-guided management can improve outcomes in an HF population much broader than the device’s current indication.

But as it happens, the trial’s prospectively defined 12-month primary outcomes were less impressive. A 12% decline in risk for the composite endpoint among patients managed by CardioMEMS failed to reach significance compared with standard management (P = .16).

“Several factors could explain the considerable loss of benefit of hemodynamic-guided management during the COVID-19 pandemic,” the Lancet report explained. They include “improved patient compliance with medical and dietary regimens, reduced respiratory infections, altered health-care provider behavior, changes in disease progression due to COVID-19, or other as yet unknown effects of a major pandemic.”
 

Expanded population

Importantly, GUIDE-HF had entered 1,000 patients in NYHA class 2-4 and either an HF hospitalization in the previous year or elevated natriuretic peptide levels. About 44% of the entrants in NYHA class 3 did not have a 1-year history of HF hospitalization.

That’s a more heterogeneous and potentially lower-risk cohort than patients in the randomized CHAMPION study of 11 years ago, which led to the implant’s approval on both sides of the Atlantic.

In that trial, CardioMEMS-guided management was followed by 30% drop in risk for HF hospitalization over 6 months (P < .001). But CHAMPION was limited to patients in NYHA class 3 with a history of HF hospitalization, the device’s current indication in both the United States and Europe.

The GUIDE-HF findings “reinforce that patients with class 3 heart failure and prior heart failure hospitalization are those in whom there is the clearest benefit, based on the prior CHAMPION trial. These are the patients where this monitoring strategy may be best targeted,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, said in an interview.

Although GUIDE-HF didn’t show a significant benefit for NYHA class 2 patients with elevated biomarkers, who aren’t covered by the device’s current labeling, that group showed “some suggestions of potential benefit,” noted Dr. Fonarow, who isn’t a coauthor on the Lancet report. So, “there may be select patients with class 2 heart failure where monitoring could be considered on a case-by-case basis.”

In an interview, Larry A. Allen, MD, MHS, said that, “while the technology is pretty amazing, the real question is whether it tells us something that we didn’t already know that leads to improved care. Unfortunately, as tested here, it doesn’t, or at least not enough to make a big difference.”

The pre–COVID-19 impact analysis “should be interpreted with caution, and not as the primary finding,” Dr. Allen, from the University of Colorado at Denver, Aurora, who is not a GUIDE-HF coauthor, said in an interview.

One might hypothesize, he said, “that, in the setting of limited in-person visits with loss of physical examination, perhaps CardioMEMS would be more – not less – helpful during the pandemic. And yet the opposite was seen.”

The pandemic has “markedly altered all kinds of aspects of patient care and trial conduct, but that doesn’t make the data derived during that period uninformative,” Dr. Allen said. “And as we are increasingly reminded, the future will be a new normal, not a prepandemic normal.”

A third group

The GUIDE-HF trial includes, in addition to the 1,000 randomized patients, a single-group observational cohort of 2,600 patients, whose outcomes will be reported at another time, noted the published report.

But in the randomized comparison, conducted at 118 centers in North America, all patients were implanted with the CardioMEMS device and blinded as to their assigned strategy. Enrollment took place between March 2018 and Dec. 20, 2019.

Of the 1,000 successfully implanted patients, 497 were assigned to the pressure-guided strategy, in which “titration of diuretics was recommended if pulmonary artery pressure provided evidence of excess intravascular volume, and titration of vasodilators was recommended if elevated vascular resistance was evident,” the report stated.

The remaining 503 patients assigned to standard care served as control subjects, for whom “investigators were aware of treatment assignment but did not have access to PAP data.”

The hazard ratio for the primary endpoint in the pressure-guided group, compared with the control group, was 0.88 (95% confidence interval, 0.74-1.05; P = .16) over a median follow-up of 11.7 months.

But in the sensitivity analysis comparing outcomes before and after the COVID-19 lockdowns, using established methodology, the report stated, the primary-endpoint HR was 0.81 (95% CI, 0.66-1.00; P = .049).

The difference is owed to improved outcomes in the control group under pandemic conditions, the researchers concluded. Patients assigned to conventional management –whatever that meant during shelter-in-place – experienced 21% fewer primary-endpoint events than their own rate before the pandemic. After the COVID-19 emergency was declared, there was no significant difference in event rates between the two randomization groups.

In the primary 12-month analysis, the HR for HF events in the guided-therapy was not significant reduced, at 0.85 (95% CI, 0.70-1.03; P = .096). But in the pre-COVID-19 analysis, that risk fell significantly with CardioMEMS-guided management, for an HR of 0.76 (95% CI, 0.61-0.95; P = .014).

An editorial accompanying the GUIDE-HF publication (Lancet. 2021 Aug 27. doi: 10.1016/S0140-6736[21]01914-0) asserts that the trial “did not enroll an ideal group of patients for showing the efficacy of pulmonary artery pressure monitoring, since many had baseline pressures in the target range with little possibility of short-term gain.”

Also, wrote John G. F. Cleland, MD, PhD, University of Glasgow, and Pierpaolo Pellicori, MD, Imperial College London, “follow-up was too short, and interventions did not substantially change pulmonary artery pressure.”

They continue: “Monitoring alone cannot improve outcome, but consequent actions might. The GUIDE-HF results are encouraging but inconclusive, and should inform further research, possibly a large, simple, open-label trial to investigate a system of care rather than a single technology.”

GUIDE-HF was funded by Abbott. Dr. Lindenfeld disclosed receiving research grants from AstraZeneca, Sensible Medical, and Volumetrix; and consulting for Abbott, Alleviant Medical, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave. Dr. Fonarow reported consulting for Abbott and that his institution has participated in the GUIDE-HF trial; he has elsewhere disclosed consulting for Amgen, AstraZeneca, CHF Solutions Lifesciences, Janssen, Medtronic, and Novartis. Dr. Allen had elsewhere reported consulting for Abbott, Amgen, Boston Scientific, and Novartis. Dr. Cleland disclosed receiving personal fees from Abbott for serving on an advisory board for the MitraClip device, unrelated to the CardioMEMS device. Dr. Pellicori reported no relevant conflicts.

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

Medical therapy for heart failure guided by an implanted pulmonary artery pressure (PAP) sensor didn’t improve survival or risk for HF events like hospitalization over a year in a major randomized trial that entered a broad range of patients with mild to moderate disease.

But medical therapy adjustments based on PAP readings from the miniature CardioMEMS (Abbott) implant might well have surpassed conventional HF management for outcomes had the world not been turned upside down by SARS-CoV-2 and the pandemic lockdowns, assert researchers from the GUIDE-HF trial.

Something about the crisis, they concluded – although not without some pushback – led to better outcomes in the standard-care control group, apparently muddling any potential differences from those on PAP-guided management.

Working with regulators, the team conducted a “pre–COVID-19 impact analysis” that compared outcomes before the March 2020 national COVID-19 emergency declaration that forced much of the United States with shelter in place.

By that time, all of the trial’s patients had been followed for at least 3 months, and about three-fourths of its endpoints had already been counted, JoAnn Lindenfeld, MD, Vanderbilt University Medical Center, Nashville, Tenn., said at a media briefing prior to unveiling GUIDE-HF at the all-virtual European Society of Cardiology Congress 2021.

The pre–COVID-19 analysis, approved several months before the end of the trial – while the data were still blinded – had been “suggested by both regulatory agencies and professional societies in Europe and in the United States,” Dr. Lindenfeld said.

It pointed to a possible benefit for the CardioMEMS-guided strategy, a barely significant 19% drop in risk (P = .049) for the primary endpoint of death, HF hospitalization, or urgent HF hospital visit. The effect was driven by a 24% decline in HF events (P = .014), with no significant contribution from mortality.

“The benefits of hemodynamic monitoring and management in reducing heart failure hospitalizations extended to patients with less severe heart failure”; that is, those in New York Heart Association class 2 and any in NYHA class 3 with “elevated natriuretic peptides but no previous hospitalization,” said Dr. Lindenfeld, who is also lead author on the GUIDE-HF report published in the Lancet.

Such benefits would suggest that CardioMEMS-guided management can improve outcomes in an HF population much broader than the device’s current indication.

But as it happens, the trial’s prospectively defined 12-month primary outcomes were less impressive. A 12% decline in risk for the composite endpoint among patients managed by CardioMEMS failed to reach significance compared with standard management (P = .16).

“Several factors could explain the considerable loss of benefit of hemodynamic-guided management during the COVID-19 pandemic,” the Lancet report explained. They include “improved patient compliance with medical and dietary regimens, reduced respiratory infections, altered health-care provider behavior, changes in disease progression due to COVID-19, or other as yet unknown effects of a major pandemic.”
 

Expanded population

Importantly, GUIDE-HF had entered 1,000 patients in NYHA class 2-4 and either an HF hospitalization in the previous year or elevated natriuretic peptide levels. About 44% of the entrants in NYHA class 3 did not have a 1-year history of HF hospitalization.

That’s a more heterogeneous and potentially lower-risk cohort than patients in the randomized CHAMPION study of 11 years ago, which led to the implant’s approval on both sides of the Atlantic.

In that trial, CardioMEMS-guided management was followed by 30% drop in risk for HF hospitalization over 6 months (P < .001). But CHAMPION was limited to patients in NYHA class 3 with a history of HF hospitalization, the device’s current indication in both the United States and Europe.

The GUIDE-HF findings “reinforce that patients with class 3 heart failure and prior heart failure hospitalization are those in whom there is the clearest benefit, based on the prior CHAMPION trial. These are the patients where this monitoring strategy may be best targeted,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, said in an interview.

Although GUIDE-HF didn’t show a significant benefit for NYHA class 2 patients with elevated biomarkers, who aren’t covered by the device’s current labeling, that group showed “some suggestions of potential benefit,” noted Dr. Fonarow, who isn’t a coauthor on the Lancet report. So, “there may be select patients with class 2 heart failure where monitoring could be considered on a case-by-case basis.”

In an interview, Larry A. Allen, MD, MHS, said that, “while the technology is pretty amazing, the real question is whether it tells us something that we didn’t already know that leads to improved care. Unfortunately, as tested here, it doesn’t, or at least not enough to make a big difference.”

The pre–COVID-19 impact analysis “should be interpreted with caution, and not as the primary finding,” Dr. Allen, from the University of Colorado at Denver, Aurora, who is not a GUIDE-HF coauthor, said in an interview.

One might hypothesize, he said, “that, in the setting of limited in-person visits with loss of physical examination, perhaps CardioMEMS would be more – not less – helpful during the pandemic. And yet the opposite was seen.”

The pandemic has “markedly altered all kinds of aspects of patient care and trial conduct, but that doesn’t make the data derived during that period uninformative,” Dr. Allen said. “And as we are increasingly reminded, the future will be a new normal, not a prepandemic normal.”

A third group

The GUIDE-HF trial includes, in addition to the 1,000 randomized patients, a single-group observational cohort of 2,600 patients, whose outcomes will be reported at another time, noted the published report.

But in the randomized comparison, conducted at 118 centers in North America, all patients were implanted with the CardioMEMS device and blinded as to their assigned strategy. Enrollment took place between March 2018 and Dec. 20, 2019.

Of the 1,000 successfully implanted patients, 497 were assigned to the pressure-guided strategy, in which “titration of diuretics was recommended if pulmonary artery pressure provided evidence of excess intravascular volume, and titration of vasodilators was recommended if elevated vascular resistance was evident,” the report stated.

The remaining 503 patients assigned to standard care served as control subjects, for whom “investigators were aware of treatment assignment but did not have access to PAP data.”

The hazard ratio for the primary endpoint in the pressure-guided group, compared with the control group, was 0.88 (95% confidence interval, 0.74-1.05; P = .16) over a median follow-up of 11.7 months.

But in the sensitivity analysis comparing outcomes before and after the COVID-19 lockdowns, using established methodology, the report stated, the primary-endpoint HR was 0.81 (95% CI, 0.66-1.00; P = .049).

The difference is owed to improved outcomes in the control group under pandemic conditions, the researchers concluded. Patients assigned to conventional management –whatever that meant during shelter-in-place – experienced 21% fewer primary-endpoint events than their own rate before the pandemic. After the COVID-19 emergency was declared, there was no significant difference in event rates between the two randomization groups.

In the primary 12-month analysis, the HR for HF events in the guided-therapy was not significant reduced, at 0.85 (95% CI, 0.70-1.03; P = .096). But in the pre-COVID-19 analysis, that risk fell significantly with CardioMEMS-guided management, for an HR of 0.76 (95% CI, 0.61-0.95; P = .014).

An editorial accompanying the GUIDE-HF publication (Lancet. 2021 Aug 27. doi: 10.1016/S0140-6736[21]01914-0) asserts that the trial “did not enroll an ideal group of patients for showing the efficacy of pulmonary artery pressure monitoring, since many had baseline pressures in the target range with little possibility of short-term gain.”

Also, wrote John G. F. Cleland, MD, PhD, University of Glasgow, and Pierpaolo Pellicori, MD, Imperial College London, “follow-up was too short, and interventions did not substantially change pulmonary artery pressure.”

They continue: “Monitoring alone cannot improve outcome, but consequent actions might. The GUIDE-HF results are encouraging but inconclusive, and should inform further research, possibly a large, simple, open-label trial to investigate a system of care rather than a single technology.”

GUIDE-HF was funded by Abbott. Dr. Lindenfeld disclosed receiving research grants from AstraZeneca, Sensible Medical, and Volumetrix; and consulting for Abbott, Alleviant Medical, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave. Dr. Fonarow reported consulting for Abbott and that his institution has participated in the GUIDE-HF trial; he has elsewhere disclosed consulting for Amgen, AstraZeneca, CHF Solutions Lifesciences, Janssen, Medtronic, and Novartis. Dr. Allen had elsewhere reported consulting for Abbott, Amgen, Boston Scientific, and Novartis. Dr. Cleland disclosed receiving personal fees from Abbott for serving on an advisory board for the MitraClip device, unrelated to the CardioMEMS device. Dr. Pellicori reported no relevant conflicts.

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

Patients with atrial fibrillation (AFib) gained significant benefits from a 6-month program of supervised and unsupervised moderate exercise versus usual care, new randomized trial results show.  

Among 120 AFib patients in the ACTIVE-AF trial, those randomized to the exercise arm had significantly less frequent AFib recurrence and less severe symptoms over a 1-year period, said Adrian Elliott, PhD, who will present this late-breaking research at the European Society of Cardiology (ESC) Congress 2021.

The trial “demonstrates that some patients can control their arrhythmia through physical activity, without the need for complex interventions such as ablation or medications to keep their heart in normal rhythm,” Dr. Elliott, from the University of Adelaide, Australia, said in a statement from the ESC.

This is “the largest randomized controlled trial investigating the value of an exercise prescription in patients with symptomatic paroxysmal or persistent [AFib],” he told this news organization in an email.

The findings “really provide the evidence needed that recommending aerobic exercise in patients with symptomatic AFib can lower the severity of symptoms and prevent the recurrence of AFib for many patients,” he said. Aerobic exercise should be incorporated into patient treatment, he added, “alongside the use of medications, as guided by a cardiologist, and management of obesity, hypertension, and sleep apnea.”

Mina K. Chung, MD, lead author of a Scientific Statement from the American Heart Association on Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation, as previously reported, agrees.

The “findings support the AHA Scientific Statement that we should encourage our patients with AFib to include regular moderate exercise to help prevent AFib, reduce AFib burden, and improve AFib-related symptoms and quality of life,” Dr. Chung, a cardiologist at the Cleveland Clinic, summarized in an email.

“Our recommendation is to encourage AFib patients to aim for at least the AHA physical activity guidelines for the general population, which advise 150 minutes each week of moderate-intensity exercise,” Dr. Chung said.

This is a “reasonable” goal, but “some might argue that a slightly higher target of physical activity duration may be considered,” Dr. Elliott commented.

ACTIVE-AF, he noted, suggests that “as a general guide, patients [with AFib] should strive to build up to 3.5 hours per week of aerobic exercise and incorporate some higher intensity activities to improve cardiorespiratory fitness.”
 

Aim for 3.5 hours a week

A previous observational study showed that patients who improved their cardiorespiratory fitness over a 5-year period were significantly less likely to have AFib recurrences.

And in a randomized trial of 51 patients, 12 weeks of aerobic interval training reduced the time spent in AFib compared to usual care, during a 4-week follow-up.

ACTIVE-AF aimed to investigate the value of exercise in AFib in a larger, longer, randomized trial.

The researchers enrolled 120 patients with an average age of 65 years, of whom 43% were women.

Patients in the treatment group received individualized guided exercise from an exercise physiologist in the cardiology clinic once a week for 3 months, then every second week for the following 3 months along with a physical activity plan to follow at home for the other days – aiming to build up to 3.5 hours of physical activity a week.

The supervised sessions, Dr. Elliott explained, were typically higher intensity to raise cardiorespiratory fitness, while the home-based exercise was a moderate intensity aerobic activity of the patient’s choice, such as walking, indoor cycling, or swimming.

“We certainly cautioned against far exceeding this level,” he added.

Patients in the usual care group received exercise advice but no active intervention.

All patients received usual medical care from their cardiologist, who was blinded to the study group allocation.

The co-primary outcomes were AFib symptom severity score and the percentage of patients with recurrent AFib at 12 months, defined as having an AFib episode that lasted longer than 30 seconds or undergoing ablation or requiring ongoing anti-arrhythmic drug therapy.

At 12 months, the percentage of patients with AFib recurrence was significantly lower in the exercise group than in the control group (60% vs. 80%; hazard ratio, 0.50; 95% confidence interval, 0.33-0.78; P = .002).

This means that more patients in the exercise group had a normal heart rhythm without needing an invasive intervention (ablation) or continued use of drugs, Dr. Elliott stressed.

Patients in the exercise group also had significantly less severe symptoms – palpitations, shortness of breath, and fatigue – than patients in the control group.

“On average, patients were achieving close to 180 minutes [of physical activity] per week by 6 months of the intervention and attended 18 supervised sessions in the clinic,” Dr. Elliott said.

Cost was not a barrier since the sessions with an exercise physiologist were free.

Lack of time was the most common reason for missing the physical activity targets, especially for patients with work and family commitments.

Most patients liked the variety of physical activity options.

The researchers plan to determine any gender differences in ACTIVE-AF.

Further research is needed, Dr. Elliott added, to determine which type of exercise is best, whether exercise plus weight loss is synergistic, and whether exercise leads to better long-term freedom from arrhythmia, reduced hospitalization, and improved survival.

The study was partially supported by the National Heart Foundation of Australia through a postdoctoral fellowship to Dr. Elliott. The researchers and Dr. Chung have disclosed no relevant financial relationships.  

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

Patients with atrial fibrillation (AFib) gained significant benefits from a 6-month program of supervised and unsupervised moderate exercise versus usual care, new randomized trial results show.  

Among 120 AFib patients in the ACTIVE-AF trial, those randomized to the exercise arm had significantly less frequent AFib recurrence and less severe symptoms over a 1-year period, said Adrian Elliott, PhD, who will present this late-breaking research at the European Society of Cardiology (ESC) Congress 2021.

The trial “demonstrates that some patients can control their arrhythmia through physical activity, without the need for complex interventions such as ablation or medications to keep their heart in normal rhythm,” Dr. Elliott, from the University of Adelaide, Australia, said in a statement from the ESC.

This is “the largest randomized controlled trial investigating the value of an exercise prescription in patients with symptomatic paroxysmal or persistent [AFib],” he told this news organization in an email.

The findings “really provide the evidence needed that recommending aerobic exercise in patients with symptomatic AFib can lower the severity of symptoms and prevent the recurrence of AFib for many patients,” he said. Aerobic exercise should be incorporated into patient treatment, he added, “alongside the use of medications, as guided by a cardiologist, and management of obesity, hypertension, and sleep apnea.”

Mina K. Chung, MD, lead author of a Scientific Statement from the American Heart Association on Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation, as previously reported, agrees.

The “findings support the AHA Scientific Statement that we should encourage our patients with AFib to include regular moderate exercise to help prevent AFib, reduce AFib burden, and improve AFib-related symptoms and quality of life,” Dr. Chung, a cardiologist at the Cleveland Clinic, summarized in an email.

“Our recommendation is to encourage AFib patients to aim for at least the AHA physical activity guidelines for the general population, which advise 150 minutes each week of moderate-intensity exercise,” Dr. Chung said.

This is a “reasonable” goal, but “some might argue that a slightly higher target of physical activity duration may be considered,” Dr. Elliott commented.

ACTIVE-AF, he noted, suggests that “as a general guide, patients [with AFib] should strive to build up to 3.5 hours per week of aerobic exercise and incorporate some higher intensity activities to improve cardiorespiratory fitness.”
 

Aim for 3.5 hours a week

A previous observational study showed that patients who improved their cardiorespiratory fitness over a 5-year period were significantly less likely to have AFib recurrences.

And in a randomized trial of 51 patients, 12 weeks of aerobic interval training reduced the time spent in AFib compared to usual care, during a 4-week follow-up.

ACTIVE-AF aimed to investigate the value of exercise in AFib in a larger, longer, randomized trial.

The researchers enrolled 120 patients with an average age of 65 years, of whom 43% were women.

Patients in the treatment group received individualized guided exercise from an exercise physiologist in the cardiology clinic once a week for 3 months, then every second week for the following 3 months along with a physical activity plan to follow at home for the other days – aiming to build up to 3.5 hours of physical activity a week.

The supervised sessions, Dr. Elliott explained, were typically higher intensity to raise cardiorespiratory fitness, while the home-based exercise was a moderate intensity aerobic activity of the patient’s choice, such as walking, indoor cycling, or swimming.

“We certainly cautioned against far exceeding this level,” he added.

Patients in the usual care group received exercise advice but no active intervention.

All patients received usual medical care from their cardiologist, who was blinded to the study group allocation.

The co-primary outcomes were AFib symptom severity score and the percentage of patients with recurrent AFib at 12 months, defined as having an AFib episode that lasted longer than 30 seconds or undergoing ablation or requiring ongoing anti-arrhythmic drug therapy.

At 12 months, the percentage of patients with AFib recurrence was significantly lower in the exercise group than in the control group (60% vs. 80%; hazard ratio, 0.50; 95% confidence interval, 0.33-0.78; P = .002).

This means that more patients in the exercise group had a normal heart rhythm without needing an invasive intervention (ablation) or continued use of drugs, Dr. Elliott stressed.

Patients in the exercise group also had significantly less severe symptoms – palpitations, shortness of breath, and fatigue – than patients in the control group.

“On average, patients were achieving close to 180 minutes [of physical activity] per week by 6 months of the intervention and attended 18 supervised sessions in the clinic,” Dr. Elliott said.

Cost was not a barrier since the sessions with an exercise physiologist were free.

Lack of time was the most common reason for missing the physical activity targets, especially for patients with work and family commitments.

Most patients liked the variety of physical activity options.

The researchers plan to determine any gender differences in ACTIVE-AF.

Further research is needed, Dr. Elliott added, to determine which type of exercise is best, whether exercise plus weight loss is synergistic, and whether exercise leads to better long-term freedom from arrhythmia, reduced hospitalization, and improved survival.

The study was partially supported by the National Heart Foundation of Australia through a postdoctoral fellowship to Dr. Elliott. The researchers and Dr. Chung have disclosed no relevant financial relationships.  

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

Patients with atrial fibrillation (AFib) gained significant benefits from a 6-month program of supervised and unsupervised moderate exercise versus usual care, new randomized trial results show.  

Among 120 AFib patients in the ACTIVE-AF trial, those randomized to the exercise arm had significantly less frequent AFib recurrence and less severe symptoms over a 1-year period, said Adrian Elliott, PhD, who will present this late-breaking research at the European Society of Cardiology (ESC) Congress 2021.

The trial “demonstrates that some patients can control their arrhythmia through physical activity, without the need for complex interventions such as ablation or medications to keep their heart in normal rhythm,” Dr. Elliott, from the University of Adelaide, Australia, said in a statement from the ESC.

This is “the largest randomized controlled trial investigating the value of an exercise prescription in patients with symptomatic paroxysmal or persistent [AFib],” he told this news organization in an email.

The findings “really provide the evidence needed that recommending aerobic exercise in patients with symptomatic AFib can lower the severity of symptoms and prevent the recurrence of AFib for many patients,” he said. Aerobic exercise should be incorporated into patient treatment, he added, “alongside the use of medications, as guided by a cardiologist, and management of obesity, hypertension, and sleep apnea.”

Mina K. Chung, MD, lead author of a Scientific Statement from the American Heart Association on Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation, as previously reported, agrees.

The “findings support the AHA Scientific Statement that we should encourage our patients with AFib to include regular moderate exercise to help prevent AFib, reduce AFib burden, and improve AFib-related symptoms and quality of life,” Dr. Chung, a cardiologist at the Cleveland Clinic, summarized in an email.

“Our recommendation is to encourage AFib patients to aim for at least the AHA physical activity guidelines for the general population, which advise 150 minutes each week of moderate-intensity exercise,” Dr. Chung said.

This is a “reasonable” goal, but “some might argue that a slightly higher target of physical activity duration may be considered,” Dr. Elliott commented.

ACTIVE-AF, he noted, suggests that “as a general guide, patients [with AFib] should strive to build up to 3.5 hours per week of aerobic exercise and incorporate some higher intensity activities to improve cardiorespiratory fitness.”
 

Aim for 3.5 hours a week

A previous observational study showed that patients who improved their cardiorespiratory fitness over a 5-year period were significantly less likely to have AFib recurrences.

And in a randomized trial of 51 patients, 12 weeks of aerobic interval training reduced the time spent in AFib compared to usual care, during a 4-week follow-up.

ACTIVE-AF aimed to investigate the value of exercise in AFib in a larger, longer, randomized trial.

The researchers enrolled 120 patients with an average age of 65 years, of whom 43% were women.

Patients in the treatment group received individualized guided exercise from an exercise physiologist in the cardiology clinic once a week for 3 months, then every second week for the following 3 months along with a physical activity plan to follow at home for the other days – aiming to build up to 3.5 hours of physical activity a week.

The supervised sessions, Dr. Elliott explained, were typically higher intensity to raise cardiorespiratory fitness, while the home-based exercise was a moderate intensity aerobic activity of the patient’s choice, such as walking, indoor cycling, or swimming.

“We certainly cautioned against far exceeding this level,” he added.

Patients in the usual care group received exercise advice but no active intervention.

All patients received usual medical care from their cardiologist, who was blinded to the study group allocation.

The co-primary outcomes were AFib symptom severity score and the percentage of patients with recurrent AFib at 12 months, defined as having an AFib episode that lasted longer than 30 seconds or undergoing ablation or requiring ongoing anti-arrhythmic drug therapy.

At 12 months, the percentage of patients with AFib recurrence was significantly lower in the exercise group than in the control group (60% vs. 80%; hazard ratio, 0.50; 95% confidence interval, 0.33-0.78; P = .002).

This means that more patients in the exercise group had a normal heart rhythm without needing an invasive intervention (ablation) or continued use of drugs, Dr. Elliott stressed.

Patients in the exercise group also had significantly less severe symptoms – palpitations, shortness of breath, and fatigue – than patients in the control group.

“On average, patients were achieving close to 180 minutes [of physical activity] per week by 6 months of the intervention and attended 18 supervised sessions in the clinic,” Dr. Elliott said.

Cost was not a barrier since the sessions with an exercise physiologist were free.

Lack of time was the most common reason for missing the physical activity targets, especially for patients with work and family commitments.

Most patients liked the variety of physical activity options.

The researchers plan to determine any gender differences in ACTIVE-AF.

Further research is needed, Dr. Elliott added, to determine which type of exercise is best, whether exercise plus weight loss is synergistic, and whether exercise leads to better long-term freedom from arrhythmia, reduced hospitalization, and improved survival.

The study was partially supported by the National Heart Foundation of Australia through a postdoctoral fellowship to Dr. Elliott. The researchers and Dr. Chung have disclosed no relevant financial relationships.  

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

As politicians battle over masks and mandates, heated rhetoric has been used to describe the fourth heartbreaking surge in COVID as a “pandemic of the unvaccinated.”

While it may serve to further divide red and blue states, I disagree with the assertion that the current surge in cases is driven simply by the unvaccinated. Why? First, the premise would assume complete efficacy with our vaccinated population, which is statistically incorrect (at least 15 million of the U.S. population never completed a second round of injections), which means they were not considered “fully vaccinated.”

Alternately, we need to examine what has occurred in nations with significantly higher vaccination rates than ours (the United Kingdom and Israel) to realize that variants have overrun the dramatic success achieved in those countries as well. Israel, once considered to be the most vaccinated country in the world, is facing a brutal fourth wave of COVID that has sent the country spiraling into another heartbreaking lockdown.

The unvaccinated could hardly be blamed for what is happening in either of these highly vaccinated countries.
 

The concept of blame

So why use blame? It defeats the purpose of encouraging those who are hesitant or possibly misinformed or disenfranchised to move forward. It lacks compassion. It does not encompass the art and science of nursing (for example, the University of Southern Indiana), such as those that hospitals have used to frame optimal nursing care. I abhor the idea of labeling because it denies the prospect of future comprehension.

Labeling reminds me of one of the saddest cases in my career.
 

An unfortunate case

I was the nurse caring for a man from a motor vehicular accident where an entire family was brutally killed. My patient was alleged to be the cause, with a blood alcohol level of 0.40%+ post hydration, intubated and ventilated, with a flailed chest and multiple orthopedic injuries as well as blunt head trauma. He was secured to the bed with handcuffs, although that was unnecessary. Multiple times I was asked how I could possibly care for such an individual, by the police and even a few colleagues. But it was not my place to judge the man.

He was in pain, and he was dying. I comforted him for the 2 weeks it took his battered body to pass into the next realm. No one visited him except the police, eagerly waiting for the man to wake up to explain the tragic events that occurred. It was my job to ease what pain I could and protect him from labels. Did he deserve the labels? Who knew? I did not care. I cared about his writhing and his physical anguish.
 

The comparison

Blame did not help the situation then, nor does it help us move forward now. As nurses, we seek to work within a framework of understanding. As we tire of caring for thousands of COVID patients, we do not stop to ask if they “deserve” care or if they have taken precautions and lived reasonably prior to seeking assistance for disease. We would not be nurses if we did this.

Think about Gov. Greg Abbott, who has asked that Texans not be allowed to mandate masks for children returning to school. He has recently been diagnosed with COVID, despite assuring the public he is fully vaccinated. Politically, his diagnosis could be visualized as a fiasco for a purple state where he has been adamant in denying the efficacy of masks for children.

Yet, his diagnosis should not be fodder for the press. The first concern should be his health and well-being, similar for any man of his age and potential comorbidity.
 

Conclusion

We should be people first, human beings that remain interconnected by our need for care and survival, not conservatives, independents, or liberals, not “vaccinated or unvaccinated,” not seen as “breakthrough” infections, or the immunosuppressed possibly unable to mount a robust response to COVID.

Labels do not define the ability to effectively defeat coronavirus or variants, as highly vaccinated countries have demonstrated in recent months. We are in the midst of a global pandemic, and the battle is raging onward.

In fact, the longer this pandemic continues, the more likely it is we will need to live with this as an endemic disease, so we should stop blaming those who become ill and need support.

It could be any of us.

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

As politicians battle over masks and mandates, heated rhetoric has been used to describe the fourth heartbreaking surge in COVID as a “pandemic of the unvaccinated.”

While it may serve to further divide red and blue states, I disagree with the assertion that the current surge in cases is driven simply by the unvaccinated. Why? First, the premise would assume complete efficacy with our vaccinated population, which is statistically incorrect (at least 15 million of the U.S. population never completed a second round of injections), which means they were not considered “fully vaccinated.”

Alternately, we need to examine what has occurred in nations with significantly higher vaccination rates than ours (the United Kingdom and Israel) to realize that variants have overrun the dramatic success achieved in those countries as well. Israel, once considered to be the most vaccinated country in the world, is facing a brutal fourth wave of COVID that has sent the country spiraling into another heartbreaking lockdown.

The unvaccinated could hardly be blamed for what is happening in either of these highly vaccinated countries.
 

The concept of blame

So why use blame? It defeats the purpose of encouraging those who are hesitant or possibly misinformed or disenfranchised to move forward. It lacks compassion. It does not encompass the art and science of nursing (for example, the University of Southern Indiana), such as those that hospitals have used to frame optimal nursing care. I abhor the idea of labeling because it denies the prospect of future comprehension.

Labeling reminds me of one of the saddest cases in my career.
 

An unfortunate case

I was the nurse caring for a man from a motor vehicular accident where an entire family was brutally killed. My patient was alleged to be the cause, with a blood alcohol level of 0.40%+ post hydration, intubated and ventilated, with a flailed chest and multiple orthopedic injuries as well as blunt head trauma. He was secured to the bed with handcuffs, although that was unnecessary. Multiple times I was asked how I could possibly care for such an individual, by the police and even a few colleagues. But it was not my place to judge the man.

He was in pain, and he was dying. I comforted him for the 2 weeks it took his battered body to pass into the next realm. No one visited him except the police, eagerly waiting for the man to wake up to explain the tragic events that occurred. It was my job to ease what pain I could and protect him from labels. Did he deserve the labels? Who knew? I did not care. I cared about his writhing and his physical anguish.
 

The comparison

Blame did not help the situation then, nor does it help us move forward now. As nurses, we seek to work within a framework of understanding. As we tire of caring for thousands of COVID patients, we do not stop to ask if they “deserve” care or if they have taken precautions and lived reasonably prior to seeking assistance for disease. We would not be nurses if we did this.

Think about Gov. Greg Abbott, who has asked that Texans not be allowed to mandate masks for children returning to school. He has recently been diagnosed with COVID, despite assuring the public he is fully vaccinated. Politically, his diagnosis could be visualized as a fiasco for a purple state where he has been adamant in denying the efficacy of masks for children.

Yet, his diagnosis should not be fodder for the press. The first concern should be his health and well-being, similar for any man of his age and potential comorbidity.
 

Conclusion

We should be people first, human beings that remain interconnected by our need for care and survival, not conservatives, independents, or liberals, not “vaccinated or unvaccinated,” not seen as “breakthrough” infections, or the immunosuppressed possibly unable to mount a robust response to COVID.

Labels do not define the ability to effectively defeat coronavirus or variants, as highly vaccinated countries have demonstrated in recent months. We are in the midst of a global pandemic, and the battle is raging onward.

In fact, the longer this pandemic continues, the more likely it is we will need to live with this as an endemic disease, so we should stop blaming those who become ill and need support.

It could be any of us.

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

As politicians battle over masks and mandates, heated rhetoric has been used to describe the fourth heartbreaking surge in COVID as a “pandemic of the unvaccinated.”

While it may serve to further divide red and blue states, I disagree with the assertion that the current surge in cases is driven simply by the unvaccinated. Why? First, the premise would assume complete efficacy with our vaccinated population, which is statistically incorrect (at least 15 million of the U.S. population never completed a second round of injections), which means they were not considered “fully vaccinated.”

Alternately, we need to examine what has occurred in nations with significantly higher vaccination rates than ours (the United Kingdom and Israel) to realize that variants have overrun the dramatic success achieved in those countries as well. Israel, once considered to be the most vaccinated country in the world, is facing a brutal fourth wave of COVID that has sent the country spiraling into another heartbreaking lockdown.

The unvaccinated could hardly be blamed for what is happening in either of these highly vaccinated countries.
 

The concept of blame

So why use blame? It defeats the purpose of encouraging those who are hesitant or possibly misinformed or disenfranchised to move forward. It lacks compassion. It does not encompass the art and science of nursing (for example, the University of Southern Indiana), such as those that hospitals have used to frame optimal nursing care. I abhor the idea of labeling because it denies the prospect of future comprehension.

Labeling reminds me of one of the saddest cases in my career.
 

An unfortunate case

I was the nurse caring for a man from a motor vehicular accident where an entire family was brutally killed. My patient was alleged to be the cause, with a blood alcohol level of 0.40%+ post hydration, intubated and ventilated, with a flailed chest and multiple orthopedic injuries as well as blunt head trauma. He was secured to the bed with handcuffs, although that was unnecessary. Multiple times I was asked how I could possibly care for such an individual, by the police and even a few colleagues. But it was not my place to judge the man.

He was in pain, and he was dying. I comforted him for the 2 weeks it took his battered body to pass into the next realm. No one visited him except the police, eagerly waiting for the man to wake up to explain the tragic events that occurred. It was my job to ease what pain I could and protect him from labels. Did he deserve the labels? Who knew? I did not care. I cared about his writhing and his physical anguish.
 

The comparison

Blame did not help the situation then, nor does it help us move forward now. As nurses, we seek to work within a framework of understanding. As we tire of caring for thousands of COVID patients, we do not stop to ask if they “deserve” care or if they have taken precautions and lived reasonably prior to seeking assistance for disease. We would not be nurses if we did this.

Think about Gov. Greg Abbott, who has asked that Texans not be allowed to mandate masks for children returning to school. He has recently been diagnosed with COVID, despite assuring the public he is fully vaccinated. Politically, his diagnosis could be visualized as a fiasco for a purple state where he has been adamant in denying the efficacy of masks for children.

Yet, his diagnosis should not be fodder for the press. The first concern should be his health and well-being, similar for any man of his age and potential comorbidity.
 

Conclusion

We should be people first, human beings that remain interconnected by our need for care and survival, not conservatives, independents, or liberals, not “vaccinated or unvaccinated,” not seen as “breakthrough” infections, or the immunosuppressed possibly unable to mount a robust response to COVID.

Labels do not define the ability to effectively defeat coronavirus or variants, as highly vaccinated countries have demonstrated in recent months. We are in the midst of a global pandemic, and the battle is raging onward.

In fact, the longer this pandemic continues, the more likely it is we will need to live with this as an endemic disease, so we should stop blaming those who become ill and need support.

It could be any of us.

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

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

[email protected]

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

[email protected]

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

[email protected]

A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.

SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.

“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.

“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.

Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
 

Case details

The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.

When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.

The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.

In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report. 

With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.

The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.

Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.

The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.

A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.

The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.

There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.

Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.

Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.

Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.

However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.

This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.

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

A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.

SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.

“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.

“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.

Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
 

Case details

The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.

When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.

The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.

In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report. 

With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.

The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.

Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.

The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.

A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.

The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.

There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.

Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.

Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.

Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.

However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.

This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.

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

A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.

SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.

“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.

“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.

Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
 

Case details

The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.

When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.

The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.

In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report. 

With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.

The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.

Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.

The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.

A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.

The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.

There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.

Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.

Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.

Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.

However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.

This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.

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

The Food and Drug Administration has approved difelikefalin for treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis, the first agent approved from a novel class of kappa opioid receptor agonists.

Olivier Le Moal/Getty Images

Some nephrologists welcomed the Aug. 23 approval of this new option for treating pruritus, a relatively common and often hard-to-resolve complication of dialysis in patients with chronic kidney disease (CKD) that can substantially impinge on quality of life for some patients, but also voiced uncertainty about the role of a new agent with a modest trial track record that may be expensive and face insurance-coverage hurdles.

“Uptake of difelikefalin will depend on awareness of itch among patients dependent on hemodialysis, and on payment policies,” predicted Daniel E. Weiner, MD, a nephrologist at Tufts Medical Center in Boston. “Pruritus is underdiagnosed among people with kidney failure, and in some patients ongoing pruritus can be highly impactful on sleep and quality of life. The clinical trial results were very encouraging that difelikefalin is effective and safe,” which makes recognition of pruritus as a significant issue for patients a key factor in uptake of the new drug, Dr. Weiner, an investigator in a difelikefalin clinical study, said in an interview.

Other nephrologists acknowledged the substantial problem that itch can pose for many patients with CKD on dialysis but questioned the weight of evidence behind difelikefalin’s approval.
 

Two pivotal trials with fewer than 900 total randomized patients

The data considered by the FDA primarily featured results from two pivotal trials, KALM-1 and KALM-2. KALM-1 randomized 378 patients with CKD and on hemodialysis and with moderate to severe pruritus to intravenous treatment with difelikefalin or placebo three times a week for 12 weeks with a primary endpoint of an improvement (decrease) of at least 3 points from baseline in their Worst Itching Intensity Numerical Rating Scale (WI-NRS) score, which averaged just over 7 points at baseline. After 12 weeks on treatment, 52% of patients who received difelikefalin had at least a 3-point drop, compared with 31% of patients who received placebo, a significant difference. The results appeared in a 2020 report in the New England Journal of Medicine.

Confirmatory results came in the second pivotal trial, KALM-2, a similarly designed, 12-week study that randomized 473 patients, with 54% of those in the active arm achieving at least a 3-point cut in their baseline WI-NRS score, compared with 42% of patients who received placebo, a significant difference. A report at the Kidney Week meeting sponsored by the National Kidney Foundation in October 2020 presented the KALM-2 results, but the findings have not yet appeared in a published article.

In sum, the data suggest that treatment with difelikefalin will, on average, produce a clinically meaningful effect on itch compared with placebo in about 20% of patients, with nearly half the patients who receive the active drug having a less robust response and many patients who receive no active treatment also show a meaningful cut in their pruritus severity in a trial setting, noted Paul Palevsky, MD, professor of medicine at the University of Pittsburgh and chief of the renal section at the Veterans Affairs Pittsburgh Healthcare System.

The upshot is that questions linger over which patients are the best candidates for this drug and how it might perform in real-world practice given difelikefalin’s limited track record, Dr. Palevsky said in an interview.

In addition, the labeling specifies the indication is for patients with moderate to severe pruritus, but itching severity is not routinely quantified in these patients in current practice, added Dr. Palevsky, who is also president of the National Kidney Foundation.

Dr. Weiner noted that another unknown is the appropriate duration of treatment in real-world use.
 

What will it cost, and will it be covered?

The drug’s price and insurance coverage will likely be a major factor in uptake of the new drug, agreed both Dr. Weiner and Dr. Palevsky, especially the coverage decision for Medicare patients by the Centers for Medicare & Medicaid Services. A corollary is whether or not coverage for difelikefalin, which patients receive as an intravenous infusion during each of their usual three-times-a-week dialysis sessions, will lie outside of the bundled dialysis reimbursement payment. If is no mechanism exists to pay for difelikefalin separately beyond the current bundled dialysis rate, “I suspect it will not get used very much unless it is very inexpensive,” predicted Dr. Weiner.

Another issue is where difelikefalin fits within the lineup of standard treatment options. “A lot of people receiving hemodialysis suffer from pruritus and have not been successfully treated. For these individuals difelikefalin could be a game changer,” Dr. Weiner said.

Other nephrologists have a more positive take on the existing treatment options.

“Start systemic therapy for patients with itch that is significantly affecting quality of life; stepping up from topical therapy just delays effective treatment,” advised Hugh C. Rayner, MD, a nephrologist affiliated with Birmingham (England) Heartland’s Hospital who was lead author on a review of pruritus treatments for patients with CKD on hemodialysis.

“Standard systemic therapy is gabapentin or pregabalin,” an approach “supported by robust evidence confirmed in a Cochrane review,” he said in an interview. The impact of difelikefalin “will be limited as its effectiveness in reducing itch is modest at best and far inferior to gabapentin and pregabalin,” Dr. Rayner added. Difelikefalin’s “main downsides will be its cost, compared with gabapentin, and its gastrointestinal side effects.”
 

Adverse-event profiles

In KALM-1, the most frequent adverse effects from difelikefalin treatment was diarrhea, in 10% of patients, compared with a 4% rate among patients who received placebo. Vomiting occurred at a 5% incidence on difelikefalin and in 3% of patients on placebo. All serious adverse events occurred in 26% of patients on difelikefalin and in 22% of those who received placebo. Discontinuations because of an adverse event occurred in 8% of patients on difelikefalin and in 5% of the placebo patients.

An editorial that accompanied the published KALM-1 report in 2020 said “the findings are compelling, although diarrhea, dizziness, and vomiting were frequent side effects.”

Both Dr. Weiner and Dr. Palevsky were more reserved than Dr. Rayner in their appraisal of gabapentin and pregabalin, although Dr. Palevsky admitted that he has prescribed one or the other of these two drugs to “lots of patients,” especially gabapentin. “But they are not completely benign drugs,” he cautioned, a concern echoed by Dr. Weiner.

“Antihistamines, gabapentin, and pregabalin have a high side-effect burden in patients on hemodialysis and limited efficacy, and are poor options for chronic pruritus management,” explained Dr. Weiner. “I would favor difelikefalin to chronic prescription of these other agents” because difelikefalin “appears effective and has a very low side effect burden. Very few effective treatments for pruritus do not have side effects.”

Difelikefalin is a peripherally restricted, selective kappa opioid receptor agonist that exerts antipruritic effects by activating kappa opioid receptors on peripheral neurons and immune cells. The drug’s hydrophilic, small-peptide structure restricts passive diffusion across membranes, which limits the drug’s access to kappa opioid receptors in the central nervous system and hence reduces potential adverse effects.

The FDA made this approval decision without consulting an advisory committee. The companies that will market difelikefalin (Korsuva), Cara Therapeutics and Vifor Pharma, announced that their U.S. promotional launch of the drug starts early in 2022.

The KALM-1 and KALM-2 studies were sponsored by Cara Therapeutics and Vifor Pharma, the two companies that have been jointly developing difelikefalin. Dr. Pavelsky and Dr. Rayner had no relevant disclosures. Dr. Weiner was previously an adviser to Cara and Vifor and participated as an investigator in a difelikefalin clinical study, but more recently has had no relationships with the companies.

[email protected]

The Food and Drug Administration has approved difelikefalin for treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis, the first agent approved from a novel class of kappa opioid receptor agonists.

Olivier Le Moal/Getty Images

Some nephrologists welcomed the Aug. 23 approval of this new option for treating pruritus, a relatively common and often hard-to-resolve complication of dialysis in patients with chronic kidney disease (CKD) that can substantially impinge on quality of life for some patients, but also voiced uncertainty about the role of a new agent with a modest trial track record that may be expensive and face insurance-coverage hurdles.

“Uptake of difelikefalin will depend on awareness of itch among patients dependent on hemodialysis, and on payment policies,” predicted Daniel E. Weiner, MD, a nephrologist at Tufts Medical Center in Boston. “Pruritus is underdiagnosed among people with kidney failure, and in some patients ongoing pruritus can be highly impactful on sleep and quality of life. The clinical trial results were very encouraging that difelikefalin is effective and safe,” which makes recognition of pruritus as a significant issue for patients a key factor in uptake of the new drug, Dr. Weiner, an investigator in a difelikefalin clinical study, said in an interview.

Other nephrologists acknowledged the substantial problem that itch can pose for many patients with CKD on dialysis but questioned the weight of evidence behind difelikefalin’s approval.
 

Two pivotal trials with fewer than 900 total randomized patients

The data considered by the FDA primarily featured results from two pivotal trials, KALM-1 and KALM-2. KALM-1 randomized 378 patients with CKD and on hemodialysis and with moderate to severe pruritus to intravenous treatment with difelikefalin or placebo three times a week for 12 weeks with a primary endpoint of an improvement (decrease) of at least 3 points from baseline in their Worst Itching Intensity Numerical Rating Scale (WI-NRS) score, which averaged just over 7 points at baseline. After 12 weeks on treatment, 52% of patients who received difelikefalin had at least a 3-point drop, compared with 31% of patients who received placebo, a significant difference. The results appeared in a 2020 report in the New England Journal of Medicine.

Confirmatory results came in the second pivotal trial, KALM-2, a similarly designed, 12-week study that randomized 473 patients, with 54% of those in the active arm achieving at least a 3-point cut in their baseline WI-NRS score, compared with 42% of patients who received placebo, a significant difference. A report at the Kidney Week meeting sponsored by the National Kidney Foundation in October 2020 presented the KALM-2 results, but the findings have not yet appeared in a published article.

In sum, the data suggest that treatment with difelikefalin will, on average, produce a clinically meaningful effect on itch compared with placebo in about 20% of patients, with nearly half the patients who receive the active drug having a less robust response and many patients who receive no active treatment also show a meaningful cut in their pruritus severity in a trial setting, noted Paul Palevsky, MD, professor of medicine at the University of Pittsburgh and chief of the renal section at the Veterans Affairs Pittsburgh Healthcare System.

The upshot is that questions linger over which patients are the best candidates for this drug and how it might perform in real-world practice given difelikefalin’s limited track record, Dr. Palevsky said in an interview.

In addition, the labeling specifies the indication is for patients with moderate to severe pruritus, but itching severity is not routinely quantified in these patients in current practice, added Dr. Palevsky, who is also president of the National Kidney Foundation.

Dr. Weiner noted that another unknown is the appropriate duration of treatment in real-world use.
 

What will it cost, and will it be covered?

The drug’s price and insurance coverage will likely be a major factor in uptake of the new drug, agreed both Dr. Weiner and Dr. Palevsky, especially the coverage decision for Medicare patients by the Centers for Medicare & Medicaid Services. A corollary is whether or not coverage for difelikefalin, which patients receive as an intravenous infusion during each of their usual three-times-a-week dialysis sessions, will lie outside of the bundled dialysis reimbursement payment. If is no mechanism exists to pay for difelikefalin separately beyond the current bundled dialysis rate, “I suspect it will not get used very much unless it is very inexpensive,” predicted Dr. Weiner.

Another issue is where difelikefalin fits within the lineup of standard treatment options. “A lot of people receiving hemodialysis suffer from pruritus and have not been successfully treated. For these individuals difelikefalin could be a game changer,” Dr. Weiner said.

Other nephrologists have a more positive take on the existing treatment options.

“Start systemic therapy for patients with itch that is significantly affecting quality of life; stepping up from topical therapy just delays effective treatment,” advised Hugh C. Rayner, MD, a nephrologist affiliated with Birmingham (England) Heartland’s Hospital who was lead author on a review of pruritus treatments for patients with CKD on hemodialysis.

“Standard systemic therapy is gabapentin or pregabalin,” an approach “supported by robust evidence confirmed in a Cochrane review,” he said in an interview. The impact of difelikefalin “will be limited as its effectiveness in reducing itch is modest at best and far inferior to gabapentin and pregabalin,” Dr. Rayner added. Difelikefalin’s “main downsides will be its cost, compared with gabapentin, and its gastrointestinal side effects.”
 

Adverse-event profiles

In KALM-1, the most frequent adverse effects from difelikefalin treatment was diarrhea, in 10% of patients, compared with a 4% rate among patients who received placebo. Vomiting occurred at a 5% incidence on difelikefalin and in 3% of patients on placebo. All serious adverse events occurred in 26% of patients on difelikefalin and in 22% of those who received placebo. Discontinuations because of an adverse event occurred in 8% of patients on difelikefalin and in 5% of the placebo patients.

An editorial that accompanied the published KALM-1 report in 2020 said “the findings are compelling, although diarrhea, dizziness, and vomiting were frequent side effects.”

Both Dr. Weiner and Dr. Palevsky were more reserved than Dr. Rayner in their appraisal of gabapentin and pregabalin, although Dr. Palevsky admitted that he has prescribed one or the other of these two drugs to “lots of patients,” especially gabapentin. “But they are not completely benign drugs,” he cautioned, a concern echoed by Dr. Weiner.

“Antihistamines, gabapentin, and pregabalin have a high side-effect burden in patients on hemodialysis and limited efficacy, and are poor options for chronic pruritus management,” explained Dr. Weiner. “I would favor difelikefalin to chronic prescription of these other agents” because difelikefalin “appears effective and has a very low side effect burden. Very few effective treatments for pruritus do not have side effects.”

Difelikefalin is a peripherally restricted, selective kappa opioid receptor agonist that exerts antipruritic effects by activating kappa opioid receptors on peripheral neurons and immune cells. The drug’s hydrophilic, small-peptide structure restricts passive diffusion across membranes, which limits the drug’s access to kappa opioid receptors in the central nervous system and hence reduces potential adverse effects.

The FDA made this approval decision without consulting an advisory committee. The companies that will market difelikefalin (Korsuva), Cara Therapeutics and Vifor Pharma, announced that their U.S. promotional launch of the drug starts early in 2022.

The KALM-1 and KALM-2 studies were sponsored by Cara Therapeutics and Vifor Pharma, the two companies that have been jointly developing difelikefalin. Dr. Pavelsky and Dr. Rayner had no relevant disclosures. Dr. Weiner was previously an adviser to Cara and Vifor and participated as an investigator in a difelikefalin clinical study, but more recently has had no relationships with the companies.

[email protected]

The Food and Drug Administration has approved difelikefalin for treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis, the first agent approved from a novel class of kappa opioid receptor agonists.

Olivier Le Moal/Getty Images

Some nephrologists welcomed the Aug. 23 approval of this new option for treating pruritus, a relatively common and often hard-to-resolve complication of dialysis in patients with chronic kidney disease (CKD) that can substantially impinge on quality of life for some patients, but also voiced uncertainty about the role of a new agent with a modest trial track record that may be expensive and face insurance-coverage hurdles.

“Uptake of difelikefalin will depend on awareness of itch among patients dependent on hemodialysis, and on payment policies,” predicted Daniel E. Weiner, MD, a nephrologist at Tufts Medical Center in Boston. “Pruritus is underdiagnosed among people with kidney failure, and in some patients ongoing pruritus can be highly impactful on sleep and quality of life. The clinical trial results were very encouraging that difelikefalin is effective and safe,” which makes recognition of pruritus as a significant issue for patients a key factor in uptake of the new drug, Dr. Weiner, an investigator in a difelikefalin clinical study, said in an interview.

Other nephrologists acknowledged the substantial problem that itch can pose for many patients with CKD on dialysis but questioned the weight of evidence behind difelikefalin’s approval.
 

Two pivotal trials with fewer than 900 total randomized patients

The data considered by the FDA primarily featured results from two pivotal trials, KALM-1 and KALM-2. KALM-1 randomized 378 patients with CKD and on hemodialysis and with moderate to severe pruritus to intravenous treatment with difelikefalin or placebo three times a week for 12 weeks with a primary endpoint of an improvement (decrease) of at least 3 points from baseline in their Worst Itching Intensity Numerical Rating Scale (WI-NRS) score, which averaged just over 7 points at baseline. After 12 weeks on treatment, 52% of patients who received difelikefalin had at least a 3-point drop, compared with 31% of patients who received placebo, a significant difference. The results appeared in a 2020 report in the New England Journal of Medicine.

Confirmatory results came in the second pivotal trial, KALM-2, a similarly designed, 12-week study that randomized 473 patients, with 54% of those in the active arm achieving at least a 3-point cut in their baseline WI-NRS score, compared with 42% of patients who received placebo, a significant difference. A report at the Kidney Week meeting sponsored by the National Kidney Foundation in October 2020 presented the KALM-2 results, but the findings have not yet appeared in a published article.

In sum, the data suggest that treatment with difelikefalin will, on average, produce a clinically meaningful effect on itch compared with placebo in about 20% of patients, with nearly half the patients who receive the active drug having a less robust response and many patients who receive no active treatment also show a meaningful cut in their pruritus severity in a trial setting, noted Paul Palevsky, MD, professor of medicine at the University of Pittsburgh and chief of the renal section at the Veterans Affairs Pittsburgh Healthcare System.

The upshot is that questions linger over which patients are the best candidates for this drug and how it might perform in real-world practice given difelikefalin’s limited track record, Dr. Palevsky said in an interview.

In addition, the labeling specifies the indication is for patients with moderate to severe pruritus, but itching severity is not routinely quantified in these patients in current practice, added Dr. Palevsky, who is also president of the National Kidney Foundation.

Dr. Weiner noted that another unknown is the appropriate duration of treatment in real-world use.
 

What will it cost, and will it be covered?

The drug’s price and insurance coverage will likely be a major factor in uptake of the new drug, agreed both Dr. Weiner and Dr. Palevsky, especially the coverage decision for Medicare patients by the Centers for Medicare & Medicaid Services. A corollary is whether or not coverage for difelikefalin, which patients receive as an intravenous infusion during each of their usual three-times-a-week dialysis sessions, will lie outside of the bundled dialysis reimbursement payment. If is no mechanism exists to pay for difelikefalin separately beyond the current bundled dialysis rate, “I suspect it will not get used very much unless it is very inexpensive,” predicted Dr. Weiner.

Another issue is where difelikefalin fits within the lineup of standard treatment options. “A lot of people receiving hemodialysis suffer from pruritus and have not been successfully treated. For these individuals difelikefalin could be a game changer,” Dr. Weiner said.

Other nephrologists have a more positive take on the existing treatment options.

“Start systemic therapy for patients with itch that is significantly affecting quality of life; stepping up from topical therapy just delays effective treatment,” advised Hugh C. Rayner, MD, a nephrologist affiliated with Birmingham (England) Heartland’s Hospital who was lead author on a review of pruritus treatments for patients with CKD on hemodialysis.

“Standard systemic therapy is gabapentin or pregabalin,” an approach “supported by robust evidence confirmed in a Cochrane review,” he said in an interview. The impact of difelikefalin “will be limited as its effectiveness in reducing itch is modest at best and far inferior to gabapentin and pregabalin,” Dr. Rayner added. Difelikefalin’s “main downsides will be its cost, compared with gabapentin, and its gastrointestinal side effects.”
 

Adverse-event profiles

In KALM-1, the most frequent adverse effects from difelikefalin treatment was diarrhea, in 10% of patients, compared with a 4% rate among patients who received placebo. Vomiting occurred at a 5% incidence on difelikefalin and in 3% of patients on placebo. All serious adverse events occurred in 26% of patients on difelikefalin and in 22% of those who received placebo. Discontinuations because of an adverse event occurred in 8% of patients on difelikefalin and in 5% of the placebo patients.

An editorial that accompanied the published KALM-1 report in 2020 said “the findings are compelling, although diarrhea, dizziness, and vomiting were frequent side effects.”

Both Dr. Weiner and Dr. Palevsky were more reserved than Dr. Rayner in their appraisal of gabapentin and pregabalin, although Dr. Palevsky admitted that he has prescribed one or the other of these two drugs to “lots of patients,” especially gabapentin. “But they are not completely benign drugs,” he cautioned, a concern echoed by Dr. Weiner.

“Antihistamines, gabapentin, and pregabalin have a high side-effect burden in patients on hemodialysis and limited efficacy, and are poor options for chronic pruritus management,” explained Dr. Weiner. “I would favor difelikefalin to chronic prescription of these other agents” because difelikefalin “appears effective and has a very low side effect burden. Very few effective treatments for pruritus do not have side effects.”

Difelikefalin is a peripherally restricted, selective kappa opioid receptor agonist that exerts antipruritic effects by activating kappa opioid receptors on peripheral neurons and immune cells. The drug’s hydrophilic, small-peptide structure restricts passive diffusion across membranes, which limits the drug’s access to kappa opioid receptors in the central nervous system and hence reduces potential adverse effects.

The FDA made this approval decision without consulting an advisory committee. The companies that will market difelikefalin (Korsuva), Cara Therapeutics and Vifor Pharma, announced that their U.S. promotional launch of the drug starts early in 2022.

The KALM-1 and KALM-2 studies were sponsored by Cara Therapeutics and Vifor Pharma, the two companies that have been jointly developing difelikefalin. Dr. Pavelsky and Dr. Rayner had no relevant disclosures. Dr. Weiner was previously an adviser to Cara and Vifor and participated as an investigator in a difelikefalin clinical study, but more recently has had no relationships with the companies.

[email protected]

The death ‘dog’

Imagine you’re out in your backyard managing the grill for a big family barbecue. You’ve got a dazzling assortment of meat assorted on your fancy new propane grill, all charring nicely. Naturally, the hot dogs finish first, and as you pull them off, you figure you’ll help yourself to one now. After all, you are the chef, you deserve a reward. But, as you bite into your smoking hot sandwich, a cold, bony finger taps you on the shoulder. You turn and come face to face with the Grim Reaper. “YOU JUST LOST 36 MINUTES,” Death says. “ALSO, MAY I HAVE ONE OF THOSE? THEY LOOK DELICIOUS.”

PxHere

Nonplussed and moving automatically, you scoop up another hot dog and place it in a bun. “WITH KETCHUP PLEASE,” Death says. “I NEVER CARED FOR MUSTARD.”

“I don’t understand,” you say. “Surely I won’t die at a family barbecue.”

“DO NOT CALL ME SHIRLEY,” Death says. “AND YOU WILL NOT. IT’S PART OF MY NEW CONTRACT.”

A new study, published in Nature Food, found that a person may lose up to 36 minutes for every hot dog consumed. Researchers from the University of Michigan analyzed nearly 6,000 different foods using a new nutritional index to quantify their health effects in minutes of healthy life lost or gained. Eating a serving of nuts adds an extra 26 minutes of life. The researchers determined that replacing just 10% of daily caloric intake from beef and processed foods with fruits, vegetables, and nuts can add 48 minutes per day. It would also reduce the daily carbon footprint by 33%.

“So you go around to everyone eating bad food and tell them how much life they’ve lost?” you ask when the Grim Reaper finishes his story. “Sounds like a drag.”

“IT IS. WE’VE HAD TO HIRE NEW BLOOD.” Death chuckles at its own bad pun. “NOW IF YOU’LL EXCUSE ME, I MUST CHASTISE A MAN IN FLORIDA FOR EATING A WELL-DONE STEAK.”
 

More stress, less sex

As the world becomes a more stressful place, the human population could face a 50% drop by the end of the century.

John Hain/Pixabay

Think of stress as a one-two punch to the libido and human fertility. The more people are stressed out, the less likely they are to have quality interactions with others. Many of us would rather be alone with our wine and cheese to watch our favorite show.

Researchers have found that high stress levels have been known to drop sperm count, ovulation, and sexual activity. Guess what? There has been a 50% decrease in sperm counts over the last 50 years. That’s the second punch. But let’s not forget, the times are changing.

“Changes in reproductive behavior that contribute to the population drop include more young couples choosing to be ‘child-free,’ people having fewer children, and couples waiting longer to start families,” said Alexander Suvorov, PhD, of the University of Massachusetts, the paper’s author.

Let’s summarize: The more stress we’re dealing with, the less people want to deal with each other.

Who would have thought the future would be less fun?
 

‘You are not a horse. You are not a cow. Seriously, y’all. Stop it.’

WARNING: The following descriptions of COVID-19–related insanity may be offensive to some readers.

Greetings, ladies and gentlemen! Welcome to the first round of Pandemic Pandemonium. Let’s get right to the action.

South_agency/Getty Images

This week’s preshow match-off involves face mask woes. The first comes to us from Alabama, where a woman wore a space helmet to a school board meeting to protest mask mandates. The second comes from Australia, in the form of mischievous magpies. We will explain.

It is not uncommon for magpies to attack those who come too close to their nests in the spring, or “swooping season,” as it’s affectionately called. The magpies are smart enough to recognize the faces of people they see regularly and not attack; however, it’s feared that mask wearing will change this.

While you’re chewing on that exciting appetizer, let’s take a look at our main course, which has a distinct governmental flavor. Jeff Landry is the attorney general of Louisiana, and, like our space-helmet wearer, he’s not a fan of mask mandates. According to Business Insider, Mr. Landry “drafted and distributed sample letters intended to help parents evade mask-wearing ordinances and COVID-19 vaccination requirements for their children in schools.”

Up against him is the Food and Drug Administration’s Twitter account. In an unrelated matter, the agency tweeted, “You are not a horse. You are not a cow. Seriously, y’all. Stop it.” This was in response to people using the nonhuman forms of ivermectin to treat very human COVID-19.

Well, there you have it. Who will win tonight’s exciting edition of Pandemic Pandemonium? The first reader to contact us gets to decide the fate of these worthy contestants.
 

From venomous poison to heart drug

It’s not likely that anyone who sees a giant, venomous spider is thinking, “Hey! That thing could save my life!” It’s usually quite the opposite. Honestly, we would run away from just about any spider. But what if one of the deadliest spiders in the world could also save you from dying of a heart attack?

PxHere

You probably don’t believe us, right? That’s fair, but the deadly Fraser Island (K’gari) funnel web spider, might also be the most helpful. Investigators from the University of Queensland in Australia have found a way to extract a molecule from the spider’s venom that might help stop damage from heart attacks and may even preserve hearts being used for transplants. “The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival,” Nathan Palpant, PhD, of the university, noted in a written statement.

No one has ever developed a drug to stop the “death signal,” so maybe it’s time to befriend spiders instead of running away from them in horror. Just leave the venom extraction to the professionals.

The death ‘dog’

Imagine you’re out in your backyard managing the grill for a big family barbecue. You’ve got a dazzling assortment of meat assorted on your fancy new propane grill, all charring nicely. Naturally, the hot dogs finish first, and as you pull them off, you figure you’ll help yourself to one now. After all, you are the chef, you deserve a reward. But, as you bite into your smoking hot sandwich, a cold, bony finger taps you on the shoulder. You turn and come face to face with the Grim Reaper. “YOU JUST LOST 36 MINUTES,” Death says. “ALSO, MAY I HAVE ONE OF THOSE? THEY LOOK DELICIOUS.”

PxHere

Nonplussed and moving automatically, you scoop up another hot dog and place it in a bun. “WITH KETCHUP PLEASE,” Death says. “I NEVER CARED FOR MUSTARD.”

“I don’t understand,” you say. “Surely I won’t die at a family barbecue.”

“DO NOT CALL ME SHIRLEY,” Death says. “AND YOU WILL NOT. IT’S PART OF MY NEW CONTRACT.”

A new study, published in Nature Food, found that a person may lose up to 36 minutes for every hot dog consumed. Researchers from the University of Michigan analyzed nearly 6,000 different foods using a new nutritional index to quantify their health effects in minutes of healthy life lost or gained. Eating a serving of nuts adds an extra 26 minutes of life. The researchers determined that replacing just 10% of daily caloric intake from beef and processed foods with fruits, vegetables, and nuts can add 48 minutes per day. It would also reduce the daily carbon footprint by 33%.

“So you go around to everyone eating bad food and tell them how much life they’ve lost?” you ask when the Grim Reaper finishes his story. “Sounds like a drag.”

“IT IS. WE’VE HAD TO HIRE NEW BLOOD.” Death chuckles at its own bad pun. “NOW IF YOU’LL EXCUSE ME, I MUST CHASTISE A MAN IN FLORIDA FOR EATING A WELL-DONE STEAK.”
 

More stress, less sex

As the world becomes a more stressful place, the human population could face a 50% drop by the end of the century.

John Hain/Pixabay

Think of stress as a one-two punch to the libido and human fertility. The more people are stressed out, the less likely they are to have quality interactions with others. Many of us would rather be alone with our wine and cheese to watch our favorite show.

Researchers have found that high stress levels have been known to drop sperm count, ovulation, and sexual activity. Guess what? There has been a 50% decrease in sperm counts over the last 50 years. That’s the second punch. But let’s not forget, the times are changing.

“Changes in reproductive behavior that contribute to the population drop include more young couples choosing to be ‘child-free,’ people having fewer children, and couples waiting longer to start families,” said Alexander Suvorov, PhD, of the University of Massachusetts, the paper’s author.

Let’s summarize: The more stress we’re dealing with, the less people want to deal with each other.

Who would have thought the future would be less fun?
 

‘You are not a horse. You are not a cow. Seriously, y’all. Stop it.’

WARNING: The following descriptions of COVID-19–related insanity may be offensive to some readers.

Greetings, ladies and gentlemen! Welcome to the first round of Pandemic Pandemonium. Let’s get right to the action.

South_agency/Getty Images

This week’s preshow match-off involves face mask woes. The first comes to us from Alabama, where a woman wore a space helmet to a school board meeting to protest mask mandates. The second comes from Australia, in the form of mischievous magpies. We will explain.

It is not uncommon for magpies to attack those who come too close to their nests in the spring, or “swooping season,” as it’s affectionately called. The magpies are smart enough to recognize the faces of people they see regularly and not attack; however, it’s feared that mask wearing will change this.

While you’re chewing on that exciting appetizer, let’s take a look at our main course, which has a distinct governmental flavor. Jeff Landry is the attorney general of Louisiana, and, like our space-helmet wearer, he’s not a fan of mask mandates. According to Business Insider, Mr. Landry “drafted and distributed sample letters intended to help parents evade mask-wearing ordinances and COVID-19 vaccination requirements for their children in schools.”

Up against him is the Food and Drug Administration’s Twitter account. In an unrelated matter, the agency tweeted, “You are not a horse. You are not a cow. Seriously, y’all. Stop it.” This was in response to people using the nonhuman forms of ivermectin to treat very human COVID-19.

Well, there you have it. Who will win tonight’s exciting edition of Pandemic Pandemonium? The first reader to contact us gets to decide the fate of these worthy contestants.
 

From venomous poison to heart drug

It’s not likely that anyone who sees a giant, venomous spider is thinking, “Hey! That thing could save my life!” It’s usually quite the opposite. Honestly, we would run away from just about any spider. But what if one of the deadliest spiders in the world could also save you from dying of a heart attack?

PxHere

You probably don’t believe us, right? That’s fair, but the deadly Fraser Island (K’gari) funnel web spider, might also be the most helpful. Investigators from the University of Queensland in Australia have found a way to extract a molecule from the spider’s venom that might help stop damage from heart attacks and may even preserve hearts being used for transplants. “The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival,” Nathan Palpant, PhD, of the university, noted in a written statement.

No one has ever developed a drug to stop the “death signal,” so maybe it’s time to befriend spiders instead of running away from them in horror. Just leave the venom extraction to the professionals.

The death ‘dog’

Imagine you’re out in your backyard managing the grill for a big family barbecue. You’ve got a dazzling assortment of meat assorted on your fancy new propane grill, all charring nicely. Naturally, the hot dogs finish first, and as you pull them off, you figure you’ll help yourself to one now. After all, you are the chef, you deserve a reward. But, as you bite into your smoking hot sandwich, a cold, bony finger taps you on the shoulder. You turn and come face to face with the Grim Reaper. “YOU JUST LOST 36 MINUTES,” Death says. “ALSO, MAY I HAVE ONE OF THOSE? THEY LOOK DELICIOUS.”

PxHere

Nonplussed and moving automatically, you scoop up another hot dog and place it in a bun. “WITH KETCHUP PLEASE,” Death says. “I NEVER CARED FOR MUSTARD.”

“I don’t understand,” you say. “Surely I won’t die at a family barbecue.”

“DO NOT CALL ME SHIRLEY,” Death says. “AND YOU WILL NOT. IT’S PART OF MY NEW CONTRACT.”

A new study, published in Nature Food, found that a person may lose up to 36 minutes for every hot dog consumed. Researchers from the University of Michigan analyzed nearly 6,000 different foods using a new nutritional index to quantify their health effects in minutes of healthy life lost or gained. Eating a serving of nuts adds an extra 26 minutes of life. The researchers determined that replacing just 10% of daily caloric intake from beef and processed foods with fruits, vegetables, and nuts can add 48 minutes per day. It would also reduce the daily carbon footprint by 33%.

“So you go around to everyone eating bad food and tell them how much life they’ve lost?” you ask when the Grim Reaper finishes his story. “Sounds like a drag.”

“IT IS. WE’VE HAD TO HIRE NEW BLOOD.” Death chuckles at its own bad pun. “NOW IF YOU’LL EXCUSE ME, I MUST CHASTISE A MAN IN FLORIDA FOR EATING A WELL-DONE STEAK.”
 

More stress, less sex

As the world becomes a more stressful place, the human population could face a 50% drop by the end of the century.

John Hain/Pixabay

Think of stress as a one-two punch to the libido and human fertility. The more people are stressed out, the less likely they are to have quality interactions with others. Many of us would rather be alone with our wine and cheese to watch our favorite show.

Researchers have found that high stress levels have been known to drop sperm count, ovulation, and sexual activity. Guess what? There has been a 50% decrease in sperm counts over the last 50 years. That’s the second punch. But let’s not forget, the times are changing.

“Changes in reproductive behavior that contribute to the population drop include more young couples choosing to be ‘child-free,’ people having fewer children, and couples waiting longer to start families,” said Alexander Suvorov, PhD, of the University of Massachusetts, the paper’s author.

Let’s summarize: The more stress we’re dealing with, the less people want to deal with each other.

Who would have thought the future would be less fun?
 

‘You are not a horse. You are not a cow. Seriously, y’all. Stop it.’

WARNING: The following descriptions of COVID-19–related insanity may be offensive to some readers.

Greetings, ladies and gentlemen! Welcome to the first round of Pandemic Pandemonium. Let’s get right to the action.

South_agency/Getty Images

This week’s preshow match-off involves face mask woes. The first comes to us from Alabama, where a woman wore a space helmet to a school board meeting to protest mask mandates. The second comes from Australia, in the form of mischievous magpies. We will explain.

It is not uncommon for magpies to attack those who come too close to their nests in the spring, or “swooping season,” as it’s affectionately called. The magpies are smart enough to recognize the faces of people they see regularly and not attack; however, it’s feared that mask wearing will change this.

While you’re chewing on that exciting appetizer, let’s take a look at our main course, which has a distinct governmental flavor. Jeff Landry is the attorney general of Louisiana, and, like our space-helmet wearer, he’s not a fan of mask mandates. According to Business Insider, Mr. Landry “drafted and distributed sample letters intended to help parents evade mask-wearing ordinances and COVID-19 vaccination requirements for their children in schools.”

Up against him is the Food and Drug Administration’s Twitter account. In an unrelated matter, the agency tweeted, “You are not a horse. You are not a cow. Seriously, y’all. Stop it.” This was in response to people using the nonhuman forms of ivermectin to treat very human COVID-19.

Well, there you have it. Who will win tonight’s exciting edition of Pandemic Pandemonium? The first reader to contact us gets to decide the fate of these worthy contestants.
 

From venomous poison to heart drug

It’s not likely that anyone who sees a giant, venomous spider is thinking, “Hey! That thing could save my life!” It’s usually quite the opposite. Honestly, we would run away from just about any spider. But what if one of the deadliest spiders in the world could also save you from dying of a heart attack?

PxHere

You probably don’t believe us, right? That’s fair, but the deadly Fraser Island (K’gari) funnel web spider, might also be the most helpful. Investigators from the University of Queensland in Australia have found a way to extract a molecule from the spider’s venom that might help stop damage from heart attacks and may even preserve hearts being used for transplants. “The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival,” Nathan Palpant, PhD, of the university, noted in a written statement.

No one has ever developed a drug to stop the “death signal,” so maybe it’s time to befriend spiders instead of running away from them in horror. Just leave the venom extraction to the professionals.