Strain imaging detects impaired systolic function despite preserved global LVEF in HFpEF that may contribute to the pathophysiology of the HFpEF syndrome. (LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction; NCT00887588).

BACKGROUND Approximately 4% of black Americans carry a valine-to-isoleucine substitution (V122I) in the transthyretin protein, which has been associated with late-onset restrictive amyloid cardiomyopathy and increased risks of death and heart failure. METHODS We determined genotype status for the transthyretin gene (TTR) in 3856 black participants in the Atherosclerosis Risk in Communities study and assessed clinical profiles, mortality, and the risk of incident heart failure in V122I TTR variant carriers (124 participants [3%]) versus noncarriers (3732 participants). Cardiac structure and function and features suggestive of cardiac amyloidosis were assessed in participants who underwent echocardiography during visit 5 (2011 to 2013), when they were older than 65 years of age. RESULTS After 21.5 years of follow-up, we did not detect a significant difference in mortality between carriers (41 deaths, 33%) and noncarriers (1382 deaths, 37%; age- and sex-stratified hazard ratio among carriers, 0.99; 95% confidence interval [CI], 0.73 to 1.36; P = 0.97). The TTR variant was associated with an increased risk of incident heart failure (age- and sex-stratified hazard ratio, 1.47; 95% CI, 1.03 to 2.10; P = 0.04). On echocardiography at visit 5, carriers (46 participants) had worse systolic and diastolic function, as well as a higher level of N-terminal pro–brain natriuretic peptide, than noncarriers (1194 participants), although carriers had a low prevalence (7%) of overt manifestations of amyloid cardiomyopathy. CONCLUSIONS We did not detect a significant difference in mortality between V122I TTR allele carriers and noncarriers, a finding that contrasts with prior observations; however, the risk of heart failure was increased among carriers. The prevalence of overt cardiac abnormalities among V122I TTR carriers was low. (Funded by the National Heart, Lung, and Blood Institute and others.)

Background Although HF disproportionately affects older adults, little data exist regarding the prevalence of American College of Cardiology/American Heart Association heart failure (HF) stages among older individuals in the community. Additionally, the role of contemporary measures of longitudinal strain (LS) and diastolic dysfunction in defining HF stages is unclear. Methods HF stages were classified in 6,118 participants in the Atherosclerosis Risk in Communities study (age 67 – 91 years) at the fifth study visit as follows: stage A (asymptomatic with HF risk factors but no cardiac structural or functional abnormalities), B (asymptomatic with structural abnormalities, defined as left ventricular hypertrophy, dilation or dysfunction, or significant valvular disease), C1 (clinical HF without prior hospitalization), and C2 (clinical HF with prior hospitalization). Results Using the traditional definitions of HF stages, only 5% of examined participants were free of HF risk factors or structural heart disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and 6% Stage C2. Worse HF stage was associated with a greater risk of incident HF hospitalization or death at a median follow-up of 608 days. LVEF was preserved in 77% and 65% in Stages C1 and C2 respectively. Incorporation of LS and diastolic dysfunction into the Stage B definition reclassified 14% of the sample from Stage A to B and improved the net reclassification index (p=0.028) and integrated discrimination index (p=0.016). Abnormal LV structure, systolic function (based on LVEF and LS), and diastolic function (based on e′, E/e′, and left atrial volume index) were each independently and additively associated with risk of incident HF hospitalization or death in Stage A and B participants. Conclusions The majority of older adults in the community are at risk for HF (Stages A or B), appreciably more compared to previous reports in younger community-based samples. LVEF is robustly preserved in at least two-thirds of older adults with prevalent HF (Stage C), highlighting the burden of HFpEF in the elderly. LV diastolic function and LS provide incremental prognostic value beyond conventional measures of LV structure and LVEF in identifying persons at risk for HF hospitalization or death.