Left ventricular late diastolic strain rate predicts cardiovascular mortality in patients with heart failure with reduced ejection fraction

Abstract Background Left ventricular (LV) strain rate measures provide detailed information regarding LV contraction and filling pressures. These include global systolic strain rate (GSRs), early and late diastolic strain rates (GSRe and GSRa), and ratio of transmitral early filling velocity to GSRe (E/GSRe). Purpose To investigate the prognostic value of strain rate measures with regard to cardiovascular mortality in patients with heart failure with reduced ejection fraction (HFrEF). Methods The study population was retrospectively included from a HF clinic and consisted of patients with LV ejection fraction (LVEF) ≤45%. Echocardiography was obtained within 1 year of referral. The study endpoint was cardiovascular mortality, which was analysed using univariable and adjusted Cox proportional hazards models. Incremental prognostic information was assessed using Harrell’s C-index and continuous net reclassification improvement (NRI). Cubic spline analysis was used to dichotomise variables at a hazard ratio (HR) of 1 for better interpretability. Results The final study population consisted of 1160 patients with HFrEF (mean age 68±11.8 years, 72.7% male, LV ejection fraction (LVEF) 28.6±9.9%). During follow-up (median 10.1 years, IQR: 4.7-13.0), 333 (28.7%) met the outcome. Subjects who met the outcome generally had higher age and prevalence of male sex, a higher burden of comorbidities, and more severely impaired conventional echocardiographic parameters. All four strain rate measures were significantly associated with cardiovascular mortality (GSRs: HR 16.88 95% CI [8.42, 33.84] per 1 s-1 increase, GSRe: HR 0.29 [0.18, 0.47] per 1 s-1 increase, E/GSRe ratio: HR 1.31 [1.22, 1.41] per 1 unit increase, GSRa: HR 0.15 95% CI [0.23, 0.65] per 1 s-1 increase, p<0.0001 for all). However, only GSRa remained an independent predictor in multivariable Cox regression after adjustment for clinical risk factors including sex, age, mean arterial pressure, heart rate, body mass index, cigarette pack years, diabetes mellitus, total cholesterol, ischemic heart disease, and echocardiographic factors including LVEF, global longitudinal strain, tricuspid annular plane systolic excursion, LV mass index, LV internal diameter index, E/e’ ratio and left atrial volume index (HR 0.39 [0.23,0.65], p=0.0003). Furthermore, GSRa provided incremental prognostic information to a model containing all aforementioned parameters (Harrell’s C-index 0.789 vs. 0.792 and continuous NRI 0.158). GSRa was dichotomised at 0.5 s-1, and a Kaplan-Meier curve stratified according to this was plotted (log rank p<0.0001)(Figure 2). Conclusion GSRa is an independent predictor of cardiovascular mortality in patients with HFrEF after multivariable adjustment. GSRa provides incremental prognostic value over conventional echocardiographic measures in risk stratification of HFrEF patients. Our results suggest an increased risk of cardiovascular mortality associated with a GSRa below 0.5 s-1.Figure 1:Spline of HR according to GSRaFigure 2:Kaplan-Meier curve