Multiple factors play into calculus of HF

In the world of heart failure, numbers count, especially the number used to track the efficiency of the heart, e.g., left ventricular ejection fraction, more commonly known as LVEF or EF. This is the benchmark used to characterize heart failure as reduced ejection fraction (HFrEF; below 45%), preserved ejection fraction (HFpEF; 55% and above), or — and this is the most recent addition — mid-range ejection fraction (HFmrEF; roughly 57%).

But what if that number misses the mark? What if the calculus of heart failure is not linear?

Longterm follow-up of data collected in the National Heart Lung and Blood Institute-sponsored Atherosclerosis Risk in Communities (ARIC) study suggests that longitudinal strain or circumferential stain on the heart, as well as subtle decrements in LVEF, are all independently associated with incident heart failure in those 75 or older.

Thus, the current routine practice of assessing ejection function “may substantially underestimate the prevalence of prognostically important impairments in systolic function in late life,” wrote Amil Shah, MD, of Brigham and Women’s Hospital, Boston, and colleagues in a paper publishing online by JAMA Cardiology.

“Contemporary echocardiographic data from this large, biracial, longitudinal cohort study of older adults suggest that lower values of LVEF, LS and CS are associated with incidence heart failure independent of clinical risk factors and with incidence HFrEF in particular,” the researchers wrote.

Moreover, although current guidelines define normal EF as more than 52% in men and more than 54% in women, the ARIC data suggest that heart failure risk starts to climb at EF <60%.

“The implications of this work are profound: LVEF remains relevant but no longer as a stand-alone measure, measures of strain matter both separately and in conjunction with LVEF, LVEF is a continuous function rather than a cut point, and the definition of normal LVEF is once again uncertain,” wrote JAMA Cardiology editors Clyde W. Yancy, MD, MSc, and Gregg C. Fonarow, MD, in a commentary published along with the study. “Any calculus that addresses prevention must now incorporate important clinical variables, especially age, hypertension, obesity, and ischemic heart disease; biomarkers; and comprehensive measures of ventricular function that include strain. Even the definition of American College of Cardiology/American Heart Association stage A HF is worth reconsideration.”

The ARIC cohort follow-up study included close to 5,000 study participants without heart failure with a mean age of 75 years who underwent protocol echocardiography at their fifth study visit, between 2011 through 2013. Data analysis was conducted from mid-2018 to early 2020.

Primary study outcomes included incident adjudicated heart failure and heart failure 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 without cardiovascular disease or risk factors.

Among the 4,960 ARIC participants included in the analysis (mean [SD] age, 75 [5] years; 2,933 [59.0%] female; 965 [19%] Black), LVEF was less than 50% in only 76 (1.5%).

In the 3,552 participants with complete assessment of LVEF, LS, and CS, 983 (27.7%) had LVEF less than 60%, LS less than 16% or CS less than 23.7%.

All three measures were independently associated with heart failure and reduced ejection fraction, and any combination of two was predictive of increased risk.

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).

The adjusted hazard ratio for LS and dichotomized LS were 1.37 (95% CI, 1.22-1.53) and 1.93 (95% CI, 1.46-2.55), respectively.

For continuous CS and dichotomized CS, the adjusted hazard ratios were 1.39 (95% CI, 1.22-1.57) and 2.30 (95% CI, 1.64-3.22), respectively.

“Although the magnitude of risk for incident heart failure 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%),” Shah and colleagues wrote.

The population-attributable risk associated with LVEF less than 60% was 11% compared with 5% using guideline-based limits.

The study findings were replicated in a separate cohort of participants in the Copenhagen City Heart Study (CCHS).

Shah and colleagues wrote that it is not clear why relatively subtle impairments in systolic function increase heart failure risk.

“Declines in LV diastolic function with age despite preserved LVEF are well recognized,” they wrote. “Alterations in LS and CS at rest have been associated with impairments in LV diastolic reserve with exercise. Of importance, impairments in LVEF, LS, and CS were most robustly associated with risk of incident HFrEF, supporting the hypothesis that these modest impairments in LV systolic function may reflect early contractile dysfunction and herald worsening dysfunction and frank reductions in LVEF.”

Yancy and Fonorow included a stern caution: “The stalwart assessment of ventricular systolic function, LVEF, is no longer sufficient, especially to gauge risk; adjunctive assessment of strain may add to the detection of an arc toward LV dysfunction and prompt earlier interventions to prevent clinical heart failure.”

  1. Left ventricular ejection fraction (LVEF), longitudinal strain, and circumferential stain were all independent predictors of incident heart failure and heart failure with reduced LVEF among elderly participants in the NHLBI-sponsored Atherosclerosis Risk in Communities study.

  2. The findings suggest that the current routine practice of assessing left ventricular function underestimates the prevalence of prognostically important impairments in systolic function in older people.

Salynn Boyles, Contributing Writer, BreakingMED™

Funding for this research was provided by the National Heart, Lung and Blood Institute, U.S. Health and Human Services.

Principal reserarcher Amil Shah reported receiving research support through Novartis and Philips Ultrasound through Brigham and Women’s Hospital and personal fees from Philips Ultrasound Advisory Board outside the submitted work. Reseracher Scott 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.

Commentary writer Clyde Yancy reported spousal employment with Abbott Labs Inc. and Gregg Fonarow reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards, Jansen, Medtronic, Merck and Novartis outside the submitted work.

Cat ID: 3

Topic ID: 74,3,282,402,494,730,3,255,925