Heart Failure with Preserved Ejection Fraction in 2022

Educational Objectives

The goal of this program is to improve management of heart failure with preserved ejection fraction. After hearing and assimilating this program, the clinician will be better able to:

1. Choose evidence-based therapies for patients who have heart failure with preserved ejection fraction.
2. Counsel patients who have heart failure with preserved ejection fraction about the potential benefits of cardiac rehabilitation.

Summary

Data on heart failure with preserved ejection fraction (HFpEF): CHARM-Preserved Trial (Yusuf et al [2003]) — showed a reduction in hospitalizations for heart failure (HHF) among patients given candesartan; TOPCAT trial (Pitt et al [2014]) — demonstrated a reduction in risk for hospitalization with spironolactone; CHAMPION trial (Adamson et al [2014]) — showed an association between use of an implantable hemodynamic monitor and reduced risk for hospitalization in patients with HFpEF; SECRET trial (Kitzman et al [2016]) — showed that a dietary and/or exercise intervention can improve exertional tolerance in a select group of patients; risk for HHF and mortality were not affected; PARAGON-HF trial (Solomon et al [2019]) — compared sacubitril-valsartan (Entresto) vs valsartan in patients with HFpEF; failed to reach its primary end point or show a statistically significant reduction in risk for HHF or CV death; however, subgroup analyses suggest that women, patients in Western Europe, and those with lower EF, resistant hypertension, or who are taking spironolactone or eplerenone may derive benefit from sacubitril-valsartan; the drug received approval from the US Food and Drug Administration for use in HF independent of EF

Sodium-Glucose Cotransporter 2 Inhibitors

Background: initially developed for diabetes; all diabetes therapies must be proven safe from a cardiovascular (CV) standpoint

EMPEROR-Preserved Trial (Anker et al [2021]): showed a statistically significant reduction in the composite end point of HHF and CV death with empagliflozin in patients with HFpEF, largely driven by reduction in HHF; a reduction in the rate of decline of the estimated glomerular filtration rate was noted, as well as a statistically significant, albeit modest, increase in quality-of-life (QoL) scores; greater benefit was seen in patients not on spironolactone; a 17% reduction in the primary end point was seen among patients with EF >50%, along with improvement in QoL scores; at week 12, although considerable benefit was seen in the placebo and empagliflozin groups, benefit was greater with empagliflozin

PRESERVED-HF Trial (Nassif et al [2021]): studied dapagliflozin in HFpEF; primarily focused on QoL measures and functional status; a more clinically meaningful and rapid rise in QoL scores was seen, compared with the EMPEROR-Preserved Trial; the secondary outcomes measures revealed significantly greater reduction in weight among patients receiving dapagliflozin, compared with placebo

DELIVER Trial (Solomon et al [2022]): preliminary results suggest that dapagliflozin reached its primary end point (ie, reduction in composite risk for CV death and worsening HF among patients having HF with reduced EF (HFrEF) or HFpEF

Interatrial Shunt Devices

REDUCE-LAP II trial (Shah et al [2022]): a follow-up to the REDUCE-LAP trial, which suggested a hemodynamic benefit for the atrial shunt device; this trial focused on clinical outcomes; despite a strong physiological basis and careful inclusion criteria with regard to exercise hemodynamics, the placement of an atrial shunt device did not reduce the overall rate of HF events or improve health status in patients with HF; however, some of the prespecified secondary end points showed a potential benefit, particularly in patients without latent pulmonary vascular disease, which was defined as having pulmonary vascular resistance (PVR) >1.78 WU; a follow-up trial is planned

RELIEVE-HF trial (ongoing): approaching the target enrollment of ≈500 patients; includes all patients with HF and appropriate hemodynamics, rather than only those with mid-range or preserved EF; early data indicate that the V-Wave Ventura Interatrial Shunt System can be implanted safely and is associated with improved QoL in the first 100 patients; additionally, a decrease in the incidence of worsening symptoms and an increase in the incidence of improved symptoms has been reported; recent data also suggest that this device improves right and left ventricular structure and function, with the most notable benefit seen in the right ventricle (RV); despite concerns about the potential for RV failure due to diversion of blood from the left to the right side of the heart, it appears that reducing left atrial pressures may have a positive impact on the RV by reducing afterload

Other Recent Data

Cardiac rehabilitation in HFpEF: Mentz et al (2021) assessed the impact of cardiac rehabilitation on patients with HFrEF or HFpEF who had been admitted for an acute HF exacerbation and had adequate functional status; the rehabilitation program was led by an exercise physiologist and physical therapist, and targeted 4 specific domains (strength, balance, mobility, and endurance); the results show a statistically significant improvement in physical performance at 3 mo; the benefits extended to QoL, with statistically and clinically significant improvements in all components; patients with preserved EF appeared to derive the greatest benefit, despite being more severely ill and disabled at the start of the program; reduction in frailty and improvement in 6-min walk test distance and gait speed were also reported; although no difference in all-cause rehospitalization or mortality rates was noted, benefits were seen in HFpEF and HFrEF patients, with the former group deriving the greatest benefit

β-blocker withdrawal in patients with HFpEF: β-blockers are widely used in populations of patients with HFpEF, in clinical trials as well as in real-world data, despite the fact that they have been relegated to a class 3 recommendation for the treatment of hypertension; in a study by Palau et al (2021), β-blockers were withdrawn from patients with HFpEF; a reliable improvement in peak oxygen uptake and QoL scores was observed; these findings highlight the need for careful consideration when prescribing a β-blocker for patients with HFpEF who do not have a compelling indication for this class of drugs

New Approaches

Device therapy: splanchnic nerve ablation — aims to reduce preload, improve symptoms, and decrease risk for HHF; elevated pacing rates — under investigation in an ongoing trial despite previous negative studies; transcatheter interatrial shunt device — aims to achieve interatrial shunting through a different mechanism, with less potential for complications

Pharmacologic therapy: includes targeted treatments for HFpEF and pulmonary hypertension; mavacamten — a myosin inhibitor; being studied for its potential in treating HFpEF with a hyperdynamic phenotype; tirzepatide — a repurposed diabetes medication; reduces body weight in individuals with excess adiposity; being studied for its benefits in patients with HFpEF; finerenone — a mineralocorticoid receptor antagonist; under investigation in the FINEARTS-HF trial; promising preliminary data have been reported

Readings

Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-1461. doi:10.1056/NEJMoa2107038; Kitzman DW, Brubaker P, Morgan T, et al. Effect of caloric restriction or aerobic exercise training on peak oxygen consumption and quality of life in obese older patients with heart failure with preserved ejection fraction: A randomized clinical trial. JAMA. 2016;315(1):36-46. doi:10.1001/jama.2015.17346; Mentz RJ, Whellan DJ, Reeves GR, et al. Rehabilitation intervention in older patients with acute heart failure with preserved versus reduced ejection fraction. JACC Heart Fail. 2021;9(10):747-757. doi:10.1016/j.jchf.2021.05.007; Nassif ME, Windsor SL, Borlaug BA, et al. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med. 2021;27(11):1954-1960. doi:10.1038/s41591-021-01536-x; Palau P, Seller J, Domínguez E, et al. Effect of β-blocker withdrawal on functional capacity in heart failure and preserved ejection fraction [published correction appears in J Am Coll Cardiol. 2022 Mar 1;79(8):848]. J Am Coll Cardiol. 2021;78(21):2042-2056. doi:10.1016/j.jacc.2021.08.073; Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383-1392. doi:10.1056/NEJMoa1313731; Shah SJ, Borlaug BA, Chung ES, et al. Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial. Lancet. 2022;399(10330):1130-1140. doi:10.1016/S0140-6736(22)00016-2; Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-Neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381(17):1609-1620. doi:10.1056/NEJMoa1908655; Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362(9386):777-781. doi:10.1016/S0140-6736(03)14285-7.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Silverman was recorded at the 44th Cardiology Update, held June 2-4, 2022, in Charleston, SC, and presented by the Medical University of South Carolina. For information on upcoming CME activities from this presenter, please visit https:// medicine.musc.edu/education/cme. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

IM701502

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.