A Review of Treatments for HFrEF and Expert Q&A

Dr Fonarow, in a 2018 study, you and your colleagues found significant gaps in guideline-directed medical therapy for HFrEF.2 What are these gaps?

Dr Fonarow: There remain substantial gaps in the use and dosing of guideline-directed medical therapy for HFrEF. There are gaps in clinician knowledge regarding the evidence and guidelines, misperceptions on optimal strategies for sequencing and titration of guideline-directed medical therapy, and slow and variable uptake of newer therapies. Clinical inertia is also a driver – clinicians misperceive the patient as being stable despite the patient remaining at risk for underlying disease progression. There is a misaligned “one day” concept – as in, “We will get around to that therapy or uptitrating that dose one day,” but visit after visit, it does not occur. Additional factors are lack of clinical decision support and multidisciplinary care teams in most settings.

What are recommendations to clinicians on how to assess the benefits of drug therapies vs device therapies in some patients?

Dr Fonarow: The ACC/AHA/HFSA Heart Failure guidelines provide valuable guidance regarding the assessment of risk and benefits of medical therapies and device therapies in HFrEF.9 In most circumstances, it is not a consideration of drug therapy vs device therapy, but optimal drug therapy, and then assessment of whether additional device therapy is indicated to be added to optimal HFrEF drug therapy. With optimal medical management, many patients improve to the point that device therapy is not necessary.

Dr Hasan: Treatment decisions should be based on the clinical status of patients – assessing their symptoms (energy level, exercise tolerance, what makes them short of breath), objective measures such as heart rate and blood pressure (if improving), echocardiographic findings such as ejection fraction, and biomarkers such as brain natriuretic peptide. We also look at hospitalizations and emergency room visits for HF symptoms or intravenous diuretics. Another objective measure is the cardiopulmonary exercise test to measure a patient’s exercise tolerance and compare it to previous tests.

What further improvements or developments are needed in this area?

Dr Fonarow: The greatest need is identification and application of strategies for optimal implementation of existing evidence-based therapies for HFrEF. There is an urgent need to discover therapies that can improve outcomes in HFpEF, where currently not a single therapy has been shown to improve survival despite the fact that half of patients with HF have HFpEF and are at substantial risk.

Dr Hasan: We should continue to study medical therapy (such as expanding SGLT2 inhibitor indications to heart failure only, not just patients with HF and diabetes), continue to optimize device therapy such as biventricular pacing and lead placement to help patients respond to such therapy, and optimize treatment of comorbidities such as diabetes, chronic kidney disease, sleep apnea, hypertension, and obesity. Other novel therapeutic agents are being studied and are currently in early phases. We are continuing to make strides in the diagnosis of HF and our understanding of its etiology, including transthyretin amyloid cardiomyopathy (which we now know has been underdiagnosed), with now a treatment approved by the Food and Drug Administration.10


1.         Murphy SP, Ibrahim NE, Januzzi JL Jr. Heart failure with reduced ejection fraction: a review. JAMA. 2020;324(5):488-504. doi: 10.1001/jama.2020.10262

2.         Greene SJ, Butler J, Albert NM, et al. Medical therapy for heart failure with reduced ejection fraction: The CHAMP-HF registry. J Am Coll Cardiol. 2018;72(4):351-366. doi:10.1016/j.jacc.2018.04.070

3.         McMurray JJV, Packer M, Desai AS, et al; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi: 10.1056/NEJMoa1409077

4.         Velazquez EJ, Morrow DA, DeVore AD, et al; PIONEER-HF Investigators. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380(6):539-548. doi: 10.1056/NEJMoa1812851

5.         Kotecha D, Holmes J, Krum H, et al. Beta-Blockers in Heart Failure Collaborative Group. Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. Lancet. 2014;384(9961):2235-2243. doi: 10.1016/S0140-6736(14)61373-8

6.         Morales DR, Lipworth BJ, Donnan PT, Jackson C, Guthrie B. Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study. BMC Med. 2017;15(1):18. doi: 10.1186/s12916-017-0781-0

7.         Bassi NS, Ziaeian B, Yancy CW, Fonarow GC. Association of optimal implementation of sodium-glucose cotransporter 2 inhibitor therapy with outcome for patients with heart failure. JAMA Cardiol. 2020;5(8):1–5. doi: 10.1001/jamacardio.2020.0898

8.         Vaduganathan M, Claggett BL, Jhund PS, et al. Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials. Lancet. 2020;396(10244):121-128. doi: 10.1016/S0140-6736(20)30748-0

9.         Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e161. doi: 10.1161/CIR.0000000000000509

10.       Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73(22):2872-2891. doi: 10.1016/j.jacc.2019.04.003

This article originally appeared on The Cardiology Advisor