Slow and Steady Does Not Always Win the Race: Re-Evaluating Rate Control in Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction

Abstract

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are highly intertwined in their connection with hypertensive heart disease and continue to present a management dilemma for clinicians managing these patients. Beta-blockers (BBs) and non-dihydropyridine calcium channel blockers (non-DHP CCBs) have been used as the cornerstone of rate control therapy for patients with AF for decades, yet their role in HFpEF is controversial. BBs are still frequently prescribed in patients with HFpEF, typically those with conditions such as AF, coronary artery disease, or hypertension. Yet, a secondary analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) study has suggested that β blockage may be associated with a higher risk of hospitalization in patients with HFpEF. 1 Silverman DN Plante TB Infeld M Callas PW Juraschek SP Dougherty GB Meyer M. Association of β-blocker use with heart failure hospitalizations and cardiovascular disease mortality among patients with heart failure with a preserved ejection fraction: a secondary analysis of the TOPCAT trial. JAMA Netw Open. 2019; 2e1916598 Crossref Scopus (61) Google Scholar CCB, in contrast, is often avoided in patients with HF because of negative inotropy concerns, but an analysis of the OPTMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) showed no association between CCB prescription and mortality or HF hospitalization. 2 Wang X Ju J Chen Z Lin Q Zhang Z Li Q Zhang J Xu H Chen K. Associations between calcium channel blocker therapy and mortality in heart failure with preserved ejection fraction. Eur J Prev Cardiol. 2022; 29: 1343-1351 Crossref Scopus (1) Google Scholar Furthermore, a more recent post hoc analysis of TOPCAT reported a lower adjusted hazard of all-cause mortality in patients receiving CCB, primarily for an indication of hypertension. 2 Wang X Ju J Chen Z Lin Q Zhang Z Li Q Zhang J Xu H Chen K. Associations between calcium channel blocker therapy and mortality in heart failure with preserved ejection fraction. Eur J Prev Cardiol. 2022; 29: 1343-1351 Crossref Scopus (1) Google Scholar Beyond the question of BB or CCB, these investigations come during a period where rate suppression in patients with HFpEF is being challenged overall. BB discontinuation in patients with HFpEF was associated with improvement in functional capacity by cardiopulmonary exercise testing in a randomized trial, 3 Palau P Seller J Domínguez E Sastre C Ramón JM de La Espriella R Santas E Miñana G Bodí V Sanchis J Valle A Chorro FJ Llácer P Bayés-Genís A Núñez J. Effect of β-blocker withdrawal on functional capacity in heart failure and preserved ejection fraction. J Am Coll Cardiol. 2021; 78: 2042-2056 Crossref PubMed Scopus (43) Google Scholar and another study of personalized accelerated pacing in patients with HFpEF and implanted permanent pacemakers showed improved HF symptoms and biomarkers and improved AF burden. 4 Infeld M Wahlberg K Cicero J Plante TB Meagher S Novelli A Habel N Krishnan AM Silverman DN LeWinter MM Lustgarten DL Meyer M. Effect of personalized accelerated pacing on quality of life, physical activity, and atrial fibrillation in patients with preclinical and overt heart failure with preserved ejection fraction: the myPACE randomized clinical trial. JAMA Cardiol. 2023; 8: 213-221 Crossref PubMed Scopus (3) Google Scholar Reflecting on these and other concerns, the use of BB in the treatment of HFpEF has been removed in the most recent American College of Cardiology/American Heart Association HF treatment guidelines. 5 Heidenreich PA Bozkurt B Aguilar D Allen LA Byun JJ Colvin MM Deswal A Drazner MH Dunlay SM Evers LR Fang JC Fedson SE Fonarow GC Hayek SS Hernandez AF Khazanie P Kittleson MM Lee CS Link MS Milano CA Nnacheta LC Sandhu AT Stevenson LW Vardeny O Vest AR Yancy CW. 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. Circulation. 2022; 145: e895-e1032 PubMed Google Scholar For patients with AF and HFpEF, achieving the balance of adequate rate control and maximizing functional capacity can be tremendously challenging, and whether BB or CCB is the superior agent remains unknown.