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Original Investigation
March 17, 2021

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

Author Affiliations
  • 1Department of Medicine, Cardiovascular Medicine Division, Brigham and Women’s Hospital, Boston, Massachusetts
  • 2Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
  • 3Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 4Cardiovascular Division, University of Minnesota, Minneapolis
  • 5Department of Medicine–Geriatrics/Gerontology, University of Mississippi Medical Center, Jackson
  • 6Sections on Cardiovascular Medicine and Geriatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina
JAMA Cardiol. 2021;6(5):509-520. doi:10.1001/jamacardio.2021.0131
Key Points

Question  Are subtle impairments in systolic function, based on left ventricular ejection fraction (LVEF) and strain, associated with heart failure (HF) risk in late life?

Findings  In this community-based cohort study, among 3552 older adult participants, 983 (27.7%) had 1 or more of the following: LVEF less than 60%, longitudinal strain less than 16.0%, and/or circumferential strain (less than 23.7%, although LVEF was less than 50% in only 50 (1.4%.) At a median of 5.5 years of follow-up, values of LVEF, longitudinal strain, and circumferential strain below these thresholds were each associated with incident HF and HF with reduced ejection fraction independent of clinical comorbidities, diastolic function, and each other.

Meaning  Current routine assessments of LV function may substantially underestimate the prevalence of prognostically important impairments in systolic function in late life.


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.

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