Association of Left Ventricular Systolic Function with Incident Heart Failure in Late Life

Anne Marie Reimer Jensen, Rani Zierath, Brian Claggett, Hicham Skali, Scott D. Solomon, Kunihiro Matsushita, Suma Konety, Kenneth Butler, Dalane W. Kitzman, Tor Biering-Sørensen, Amil M. Shah

Research output: Contribution to journalArticlepeer-review

Abstract

Importance: Limited data exist regarding the association of subtle subclinical systolic dysfunction and incident heart failure (HF) in late life.

Objective: To assess the independent associations of subclinical impairments in systolic performance with incident HF in late life.

Design, Setting, and Participants: This study was a time-to-event analysis of participants without heart failure in the Atherosclerosis Risk in Communities (ARIC) study, a prospective, community-based cohort study, who underwent protocol echocardiography at the fifth study visit (January 1, 2011, to December 31, 2013). Findings were validated independently in participants in the Copenhagen City Heart Study (CCHS). Data analysis was performed from June 1, 2018, to February 28, 2020.

Exposures: Left ventricular ejection fraction (LVEF), longitudinal strain (LS), and circumferential strain (CS) measured by 2-dimensional and strain echocardiography.

Main Outcomes and Measures: Main outcomes were incident adjudicated HF and HF with preserved and reduced LVEF at a median follow-up of 5.5 years (interquartile range, 5.0-5.8 years). Cox proportional hazards regression models adjusted for demographics, hypertension, diabetes, obesity, smoking, coronary disease, estimated glomerular filtration rate, LV mass index, e', E/e', and left atrial volume index. Lower 10th percentile limits were determined in 374 participants free of cardiovascular disease or risk factors.

Results: Among 4960 ARIC participants (mean [SD] age, 75 [5] years; 2933 [59.0%] female; 965 [19%] Black), LVEF was less than 50% in only 76 (1.5%). In the 3552 participants with complete assessment of LVEF, LS, and CS, 983 (27.7%) had 1 or more of the following findings: LVEF less than 60%, LS less than 16.0%, or CS less than 23.7%. Modeled continuously or dichotomized, worse LVEF, LS, and CS were each independently associated with incident HF. The adjusted hazard ratio (HR) per SD decrease in LVEF was 1.41 (95% CI, 1.29-1.55); the HR for LVEF less than 60% was 2.59 (95% CI, 1.99-3.37). Similar findings were observed for continuous LS (HR, 1.37; 95% CI, 1.22-1.53) and dichotomized LS (HR, 1.93; 95% CI, 1.46-2.55) and for continuous CS (HR, 1.39; 95% CI, 1.22-1.57) and dichotomized CS (HR, 2.30; 95% CI, 1.64-3.22). Although the magnitude of risk for incident HF or death associated with impaired LVEF was greater using guideline (HR, 2.99; 95% CI, 2.19-4.09) compared with ARIC-based limits (HR, 1.88; 95% CI, 1.58-2.25), the number of participants classified as impaired was less (104 [2.1%] based on guideline thresholds compared with 692 [13.9%] based on LVEF <60%). The population-attributable risk associated with LVEF less than 60% was 11% compared with 5% using guideline-based limits, a finding replicated in 908 participants in the CCHS.

Conclusions and Relevance: These findings suggest that relatively subtle impairments of systolic function (detected based on LVEF or strain) are independently associated with incident HF and HF with reduced LVEF in late life. Current recommended assessments of LV function may substantially underestimate the prevalence of prognostically important impairments in systolic function in this population.

Original languageEnglish (US)
Pages (from-to)509-520
Number of pages12
JournalJAMA cardiology
Volume6
Issue number5
DOIs
StatePublished - May 1 2021

Bibliographical note

Funding Information:
Communities study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute; National Institutes of Health; US Department of Health and Human Services under contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I. This work was also supported by National Institutes of Health/National Heart, Lung, and Blood Institute grants R01HL135008 (Dr Shah), R01HL143224 (Dr Shah), R01HL150342 (Dr Shah), R01HL148218 (Dr Shah), and K24HL152008 (Dr Shah).

Funding Information:
receiving salary support from Agency for Healthcare Research and Quality through ABT Associates outside the submitted work. Dr Solomon reported receiving grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Lilly, Mesoblast, MyoKardia, Neurotronik, NIH/NHLBI, Novartis, Respicardia, Sanofi Pasteur, and Theracos and personal fees for consulting from Abbott, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Lilly, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Sanofi-Pasteur, Tenaya, Dinaqor, Tremeau, CellProThera, and Moderna outside the submitted work. Dr Matsushita reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Butler reported receiving grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Kitzman reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Biering-Sørensen reported receiving personal fees from Amgen Steering Committee for serving as a member of the Amgen-financed GALACTIC-HF (Registrational Study With Omecamtiv Mecarbil/ AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction) trial, personal fees from Amgen Advisory Board, grants from Sanofi Pasteur Research grant, personal fees from Sanofi Pasteur Advisory Board, speaker honorarium from Sanofi Pasteur, speaker honorarium from Novartis Speaker, and grants from GE Healthcare Research outside the submitted work. Dr Shah reported receiving research support from Novartis through Brigham and Women’s Hospital, research support from Philips Ultrasound through Brigham and Women’s Hospital, and personal fees from Philips Ultrasound Advisory Board outside the submitted work. No other disclosures were reported.

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© 2021 American Medical Association. All rights reserved.

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