Medical Management of Heart Failure with Preserved Ejection Fraction

Educational Objectives

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

1. Optimize management of common comorbidities associated with heart failure with preserved ejection fraction.
2. Appraise current evidence-based guidelines for the medical management of heart failure with preserved ejection fraction.

Summary

Heart failure (HF) with preserved ejection fraction (HFpEF): affects ≈50% of patients with HF; its increasing prevalence is attributed to an aging population and increasing prevalence of comorbidities (eg, obesity and diabetes) that are strongly associated with HFpEF; HFpEF affects men and women equally; HFpEF encompasses diverse patient populations with varying prognoses

Subcategorization: Shah et al (2015) evaluated patients with HFpEF categorized into 3 distinct groups, which included younger patients with moderate diastolic dysfunction and normal B type natriuretic peptide; obese patients with diabetes, sleep apnea, and impaired left ventricular relaxation; and older patients with chronic kidney disease, myocardial remodeling, pulmonary hypertension, and right ventricular dysfunction; the third group had 1.7-fold greater risk for mortality compared to the first group at 40-mo follow-up; Kao et al (2016) identified 6 subgroups of HFpEF; older women with low body mass index (BMI), renal dysfunction, and anemia, and patients with high prevalence of comorbidities including obesity, coronary artery disease, and renal dysfunction, had the worse prognoses compared with the other 4 subgroups

Definitions: Borlaug et al (2023) defined HFpEF as clinical heart failure with structural cardiac abnormality, and evidence of congestion (pulmonary or systemic) at rest or with exercise; distinguishing cardiac related shortness of breath from other causes (obesity, sedentary lifestyle, lung disease) is difficult; scoring systems, eg, H2FPEF and HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology), are helpful

Pathophysiology of HFpEF: is complex and heterogeneous, likely driven by comorbidities causing systemic inflammation, leading to coronary inflammation, hypertrophy, and fibrosis; in patients with HFpEF, cardiorespiratory impairment stems partly from HF but also significantly from other factors; this is important for managing patient expectations; elevated wedge pressure is a diagnostic criterion; exercise intolerance in HFpEF is not solely a cardiac issue; Sarma et al (2023) showed that altering wedge pressure did not significantly change peak oxygen uptake

Management: the 2022 guidelines by Heidenreich et al gave a 2A recommendation for the use of sodium glucose co-transporter 2 (SGLT2) inhibitors and 2B recommendation for mineralocorticoid receptor antagonists (MRA) in HFpEF; the use of angiotensin receptor neprilysin inhibitors (ARNI) is controversial; SGLT2 inhibitors should be avoided in patients with type 1 diabetes and those with estimated glomerular filtration rate <20 mL/min per 1.73 m² ; yeast infections are a concern with SGLT2 inhibitors; after starting an SGLT2 inhibitor, the clinician must assess for volume overload and consider an MRA (rather than a loop diuretic) for decongestion; one must consider comorbidities; empagliflozin (Anker et al [2021]) and dapagliflozin (Williams et al [2020]) have shown benefits in reducing mortality and hospitalizations and providing nephroprotective effects; dapagliflozin also shows promise in improving symptoms and 6 min walk distance

Hypertension management in HFpEF: recommendations for targeting blood pressure (BP) are provided; no specific agent is recommended because of negative trials with angiotensin receptor blockers and angiotensin converting enzyme inhibitors

Angiotensin receptor neprilysin inhibitors: are recommended in patients with EF <55%, multiple hospitalizations, congestion, or hypertension; the benefit of ARNIs is greater in patients with low EF and in women (Solomon et al [2017])

Obesity: the STEP-HFpEF trial by Kosiborod et al (2023) showed that semaglutide improved Kansas City Cardiomyopathy Questionnaire clinical summary scores and significantly reduced weight in patients with HFpEF and without diabetes; glucagon-like peptide 1 agonists, eg, semaglutide, are associated with reductions in N-terminal prohormone of brain natriuretic peptide and C-reactive protein (CRP), suggesting an effect on oxidative stress and inflammation; lifestyle changes, ie, exercise training and calorie restriction, improve oxygen uptake and quality of life

Iron deficiency: patients with HFpEF have a higher prevalence of iron deficiency than those with heart failure with reduced ejection fraction; the benefit of intravenous iron is not well established

Atrial fibrillation: the clinician must consider rhythm control because β blockers may have adverse outcomes due to chronotropic incompetence in HFpEF; evidence suggests that β blockers may increase HF hospitalizations in patients with left ventricular EF >70%; if possible, the clinician may reduce or stop β blockers in patients with HFpEF who do not require them for other conditions; phosphodiesterase 5 inhibitors and nitrates are not beneficial and may reduce exercise capacity in this population

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; Borlaug BA, Sharma K, Shah SJ, et al. Heart failure with preserved ejection fraction: JACC scientific statement. J Am Coll Cardiol. 2023;81(18):1810-1834. doi:10.1016/j.jacc.2023.01.049; Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2022 May 3;145(18):e1033. doi: 10.1161/CIR.0000000000001073.] [published correction appears in Circulation. 2022 Sep 27;146(13):e185. doi: 10.1161/CIR.0000000000001097.] [published correction appears in Circulation. 2023 Apr 4;147(14):e674. doi: 10.1161/CIR.0000000000001142.]. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063; Kao DP, Lewsey JD, Anand IS, et al. Characterization of subgroups of heart failure patients with preserved ejection fraction with possible implications for prognosis and treatment response. Eur J Heart Fail. 2015;17(9):925-935. doi:10.1002/ejhf.327; Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069-1084. doi:10.1056/NEJMoa2306963; Sarma S, MacNamara JP, Balmain BN, et al. Challenging the hemodynamic hypothesis in heart failure with preserved ejection fraction: Is exercise capacity limited by elevated pulmonary capillary wedge pressure? [published correction appears in Circulation. 2023 Aug 15;148(7):e7. doi: 10.1161/CIR.0000000000001176.]. Circulation. 2023;147(5):378-387. doi:10.1161/CIRCULATIONAHA.122.061828; Shah SJ, Katz DH, Selvaraj S, et al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015;131(3):269-279. doi:10.1161/CIRCULATIONAHA.114.010637; 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.

Disclosures

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

Acknowledgements

Dr. Prasad was recorded at Hearts in Sonoma: UCSF Update on Heart Failure Therapies, held September 19-21, 2024, in Sonoma, CA, and presented by University of California, San Francisco, School of Medicine. For information on upcoming CME activities from this presenter, please visit meded.ucsf.edu/continuing-education. Audio Digest thanks the speakers and the 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 0.50 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 0.50 CE contact hours.

Lecture ID:

FP731702

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.

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