Combining diastolic dysfunction and natriuretic peptides to risk stratify patients with heart failure with reduced ejection fraction

Background: Diastolic dysfunction (DD) might help to risk stratify patients with heart failure (HF) with reduced ejection fraction (HFrEF). Nonetheless, HF guidelines/risk scores don't consider DD. We aimed to show the independent prognostic value of DD for nonfatal HF/death in patients with HFrEF on top of natriuretic peptides (NP). Methods: We analyzed 1155 baseline echocardiograms of the MADIT-CRT study (LVEF≤30%, QRS ≥ 130 ms, NYHA class I/II), classifying DD according to 2016 ASE/EACVI classification. Results: Patients were 64 ± 11 years-old, 24% females, LVEF was 24 ± 5%, 58% had abnormal BNP (≥100 pg/ml). While 45% had impaired relaxation, 33% had pseudonormal filling, 12% restrictive pattern, 6% indeterminate diastolic function, 4% were not classifiable due to missing data. During a follow-up of 2.1 ± 1.0 years, there were 233 HF/death. Compared to patients without pseudonormal/restrictive filling and with normal NP (23%), patients with pseudonormal/restrictive filling, alone (15%) or combined to elevated NP (30%), were at higher risk of events (respectively padj = 0.025 and padj < 0.001), as opposed to those with abnormal NP alone (22%; padj = 0.55). Adding DD to conventional markers of risk and NP improved prediction (C-statistic 0.733 versus 0.708, p = 0.024). DD was the first parameter to be considered to risk stratify MADIT-CRT population, according to Classification-And-Regression-Tree analysis. Conclusions: Among HFrEF patients with mild symptoms, pseudonormal/restrictive filling, either alone or combined with elevated NP, was associated with high risk of events, as opposed to isolated elevation of NP. DD provided incremental risk prediction for death/HF beyond commonly used markers. These data might suggest to integrate DD into HF guidelines/risk scores.