Abstract
BACKGROUND: Left ventricular ejection fraction (LVEF) is an essential tool for heart failure (HF) assessment but is limited by load dependence. Additional tools are needed to risk-stratify normal LVEF populations. We aimed to assess the prognostic value of systolic blood pressure-indexed left ventricular end-systolic volume ratio, or cardiac contractility index (CCI). METHODS: In a prospective observational cohort study of people newly diagnosed with HF, we defined characteristics and outcomes associated with LVEF and CCI, including after stratification into HF with reduced ejection fraction or HF with preserved ejection fraction. We used UK Biobank to assess whether CCI is associated with subclinical myocardial dysfunction and incident HF. RESULTS: In people with HF, mortality increased over tertiles of declining CCI (P<0.001). Within the HF with preserved ejection fraction group, below-median CCI was associated with distinct clinical characteristics and an all-cause mortality risk approximately twice that of those with above median CCI (observed event rate 17.3/100 patient-years versus 8.8/100 patient-years; P<0.001), similar to those with HF with reduced ejection fraction. Modeled as continuous variables, there was a curvilinear relationship between mortality across the detected range of CCI, while there was no clear association with mortality risk across a wide range of LVEF (20%-55%). In UK Biobank for participants without HF and normal LVEF, below-median CCI was associated with ≈33% increased risk of incident HF (adjusted hazard ratio, 1.33 [1.01-1.75]; P=0.043). Decreasing CCI was also associated with lower myocardial contractility defined using global radial and circumferential strain. CONCLUSIONS: CCI is a simple, noninvasive, relatively afterload-independent method to stratify HF risk in populations with normal LVEF. Its simplicity means CCI could be applied to existing clinical trial data sets or used be as an inclusion criterion in future randomized controlled trials.