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Novel Therapies Affecting Care of Patients With Heart Failure From AHA 2021

Lee R. Goldberg, MD, MPH, FACC

Professor of Medicine
Division of Cardiovascular Medicine
Department of Medicine
Section Chief, Advanced Heart Failure and Cardiac Transplant
University of Pennsylvania
Philadelphia, Pennsylvania


Lee R. Goldberg, MD, MPH, FACC, has disclosed that he has received funds for research support from Respircardia and consulting fees from Abbott, Respircardia, and Viscardia.


View ClinicalThoughts from this Author

Released: December 9, 2021

Exciting studies assessing novel therapies for heart failure (HF), including a myosin inhibitor, statins, and electrical cardioversion for atrial fibrillation, were presented at the 2021 American Heart Association Virtual Scientific Sessions (AHA 2021). In this commentary, I briefly highlight 3 of these studies.

MAVERICK-LTE Cohort of the MAVA-LTE Study: Interim Results on Long-term Efficacy and Safety of Mavacamten in Patients With Nonobstructive Hypertrophic Cardiomyopathy
We have never had an effective drug for the treatment of hypertrophic cardiomyopathy, a common genetic myopathy. So, I am excited about the latest data on a novel therapy, the cardiac myosin inhibitor mavacamten. In this interim analysis of the MAVERICK-LTE cohort of the MAVA-LTE study, 43 patients with nonobstructive hypertrophic cardiomyopathy who had completed the phase II MAVERICK-HCM trial were further evaluated for long-term efficacy and safety of mavacamten. Patients were randomized 1:1 to receive either 200 ng/mL or 500 ng/mL of mavacamten. Owens and colleagues found that by Week 24, the median N-terminal pro B-type natriuretic peptide (NT-proBNP) decreased by 58% and decreased further to 67% at Week 48. The tissue Doppler E/e′ was decreased at Weeks 24 and 48 and the left atrial volume index was decreased at Week 48. A 5.4% decrease in left ventricular ejection fraction at Week 48 without significant changes in left ventricular stroke volume (Week 48 mean ± change: 0 ± 8.5 mL) was also noted. These are not the final results of the trial, but I think that they are exciting to see and validate the primary study results in a group of patients with a slightly different pathophysiology, although the core disease is the same. Although my colleagues and I are really excited to have a new class of drugs available to us, the FDA delayed the decision on mavacamten until April 28, 2022, so that the longer-term data can be reviewed. They did not ask for any new studies.

Decreased Risk of New-Onset Dementia in Patients With HF Associated With Statin Therapy
Many of my patients express concern about the stories of a connection between memory loss, dementia, and statin use. We often say, “Well, these patients had lots of risk. The reason they were on a statin is because they had vascular disease, which puts them at higher risk of having dementia.”

In this very interesting study of >200,00 patients with HF identified from a clinical information registry, the risk of incident dementia associated with statin use was estimated. The mean age of patients receiving statins (n = 59,290) was 73.4 ± 12.3 years, and 53% were male. that older patients are at higher risk of developing dementia because they have small embolic events and low perfusion to their brain, and many of them have vascular disease. Univariate and multivariate logistic regression on dementia incidence showed that statins had a significant effect (P <.001). Using propensity score matching and competing risk regression with Cox proportional–hazard model statin use was protective with an 18% lower risk of dementia incidence (multivariable-adjusted subdistribution HR: 0.82; P <.01) and a 14% lower risk of vascular dementia (subdistribution HR: 0.86; P <.01). Ren and colleagues suggest that statin use prevents small vessel disease in the brain, which we think is a mechanism of vascular dementia. There are probably the argument could be made that statins are actually protective in that setting.

Another difficult conversation to have with patients concerns the age they should stop the statin. I try to follow the guidelines, and I take great pride in my ability to say, “I’m going to do the right thing.” However, I have not been stopping the statin in my robust 79- or 80-year-old patients. This very interesting study supports my clinical decision-making process. Even though older patients may not see much benefit in terms of myocardial infarction, statins are quite safe and we are not seeing a lot of adverse events and so a reduction in the risk of developing dementia seems like a fair trade-off.

The results of this study makes us question and rethink what we’ve been taught, that starting patients on an anticoagulant and making sure they are on an adequate β-blocker or calcium channel blocker and to control their rate is sufficient.

Electrical Cardioversion for AF in Patients With HFpEF
Traditionally, we think that patients with HF and preserved ejection fraction (HFpEF) are at high risk of into atrial fibrillation (AF), and the RACE and AFFIRM trials showed that the combination of rate control and anticoagulation was an acceptable strategy for patients with AF who were otherwise well. In 2002, when these studies were published, rhythm control with antiarrhythmic drugs was less beneficial.

This new study by Tsuda and colleagues showed us that the health of patients with HFpEF and AF treated with rhythm control by electrical cardioversion (EC) may improve vs patients not receiving EC. Again, we already knew that it is probably better to be in sinus rhythm than not, but this study confirmed it by evaluating 162 patients admitted to the hospital with acute decompensated HF and left ventricular ejection fraction ≥50%. The 24 patients who had a successful and sustained restoration of sinus rhythm after EC, had reduced levels of BNP and a reduced incidence of major adverse cardiac events (HR: 0.19; 95% CI: 0.06-0.60), P <.01).

I think most of my patients who have HFpEF and a restored sinus rhythm feel better. Tsuda and colleagues had 14.8% success with EC, which was higher than what I expected. This result encourages me to be a little more aggressive with EC than what I’ve been doing. If EC works and the patient feels better but then goes back into AF, perhaps then ablation or antiarrhythmics therapy is needed.

Your Thoughts?
Which of these studies presented at AHA 2021 are you most interesting in learning more about? Answer the polling question and join the conversation by posting a comment. For more detailed data from these and other studies, download and reuse the Capsule Summary slides in your own noncommercial presentations.

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