4301Diastolic dysfunction is an independent predictor of adverse events in patients with systolic dysfunction. Insights from the MADIT-CRT trial

Abstract

Abstract Background Diastolic dysfunction (DD) is common in patients with heart failure with reduced ejection fraction (HFrEF). However, its prognostic relevance in HFrEF, on top of conventional risk factors including natriuretic peptides, is unknown Purpose To show the prognostic contribution of DD in HFrEF Methods We analyzed 1155 baseline echocardiograms (63% of all available exams) in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study, comprising HFrEF patients with LVEF≤30%, QRS duration ≥130 ms, and NYHA class I/II. We classified DD according to ASE 2016 classification, based on transmitral Doppler velocities, mitral annular Tissue Doppler velocities, pulmonary venous flow velocities, and left atrial volumes. Using Cox regression and C-statistics we assessed the independent prognostic value of DD for nonfatal HF or death. We also evaluated CART (Classification And Regression Tree) analysis Results Patients were 64±11 years-old, 24% females, and mean LVEF was 24±5%. While 45% had impaired relaxation, 33% had pseudo-normal filling, 12% restrictive patter, 6% had indeterminate diastolic function, and 4% were not classifiable due to missing data. During a mean follow-up of 2.1±1.0 years, there were 233 adverse events. After multiple adjustment, compared to patients with impaired relaxation, those with pseudo-normal and restrictive filling had greater risk of HF/death (respectively HR 1.76, 95% CI 1.16–2.66, p=0.007; HR 2.70, 95% CI 1.58–4.60, p<0.001), independently of assigned treatment (p-interaction 0.34). Adding DD to conventional markers of risk improved prediction (C-statistic 0.733, 95% CI 0.689–0.776 versus 0.708, 95% CI 0.663–0.753, p=0.024). Finally, at CART analysis DD was the first parameter to be considered to risk stratify patients (Figure) Risk stratification tree Conclusions DD is a strong independent predictor of death or heart failure in HFrEF patients with mild symptoms and should be considered in assessment of risk in this population