Estimated transmitral E- and A-wave overlapping predicted prognosis in patient with heart failure with preserved ejection

Abstract Background The impact of heart rate (HR) variability on clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is not fully understood. Variations in HR may affect transmitral blood flow and consequently left ventricular filling and left atrial pressure. Changes in HR can cause the transmitral E-wave and A-wave to merge at higher HRs, while their interval lengthens at slower HRs (Figure: left). A recent study (Izumida. ESC Heart Fail. 2020;7:3231) demonstrated that the degree of overlap or interval between E- and A-waves can be estimated using resting HR and the deceleration time of the E-wave (DcT) on Doppler echocardiography. Purpose This study aims to investigate the relationship between the estimated overlap length between E- and A-waves and prognosis in patients with HFpEF. Methods Echocardiography was performed before hospital discharge in 398 patients (80±9 years, 59.0% female) hospitalized for decompensated HFpEF who were registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry. The overlap length between E- and A waves was estimated using the formula [6.2 × HR (bpm) + 0.81 × DcT (ms) -589 (ms)] as previously described (a negative value means distance between two waves). Patients were divided into four groups based on quartiles of overlap length (Q1 to Q4, with Q4 representing the highest overlap length) and followed for a median duration of 759 days (interquartile range: 370, 1107 days) to observe all-cause mortality. Results The estimated overlap length in the study patients was -167±85 ms, and 105 deaths occurred during follow-up. The overlap length was selected as an independent predictor for all-cause mortality by Cox proportional hazards regression analysis (p=0.04), whereas HR or DcT was not. Kaplan-Meier curves indicated the difference in all-cause mortality among 4 groups (Figure: Right, p=0.02 by log-rank test), and the Q4 group (335 to -123ms) showed significantly higher mortality than the Q2 (-124 to -173 ms, p=0.03). Conclusion The overlap length of E and A predicted mortality in HFpEF patients, and the presence of overlap or shorter interval were associated with higher mortality. Optimal HR based on overlap length may be a new target for HFpEF therapy.Figure 1