Switching from ramipril to sacubitril/valsartan favorably alters electrocardiographic indices of ventricular repolarization in heart failure with reduced ejection fraction

Abstract

Background: Angiotensin receptor neprilysin inhibitor (ARNI, sacubitril/valsartan) reduces sudden death in heart failure with reduced ejection fraction (HFrEF). Corrected QT (QTc), T-wave peak to T-wave end interval (Tp-e) and Tp-e/QTc are electrocardiographic indices of ventricular repolarization heterogeneity. We aimed to assess the effects of switching from ramipril to ARNI on electrocardiographic indices of ventricular repolarization.

Methods: A total of 48 patients with HFrEF (mean age: 63.3 ± 11.7 years; 36 males, 77.1% ischaemic etiology) were enrolled. All patients had New York Heart Association functional class II–III, left ventricular ejection fraction ≤35% and previously switched from ramipril to ARNI treatment. The standard 12-lead electrocardiograms on ramipril treatment and 1 month after ARNI treatment were analysed; heart rate, QTc, Tp-e and Tp-e/QTc were calculated. Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores and N-terminal pro-BNP (NT-proBNP) values were recorded.

Results: QTc (415.2 ± 19.7 ms vs. 408.5 ± 20.8 ms, p = 0.022), Tp-e (100.7 ± 13.8 ms vs. 92.9 ± 12.1 ms, p < 0.001), Tp-e/QTc (0.242 ± 0.028 vs. 0.227 ± 0.029, p = 0.003) and heart rate (73.2 ± 4.7 bpm vs. 71.1 ± 4.9 bpm, p = 0.027) were reduced after ARNI. ARNI switch associated with improvement in MLWHFQ scores (32.4 ± 7.1 ms vs. 22.6 ± 7.0 ms, p < 0.001) and reduction of NT-proBNP (2457 ± 1879 pg/ml to 1377 ± 874 pg/ml, p < 0.001). Pearson’s correlation analysis revealed moderate correlations of MLWHFQ score with Tp-e (r = 0.543, p = 0.001) and Tp-e/QTc (r = 0.556, p = 0.001).

Conclusions: Switching from ramipril to ARNI favourably alters QTc, Tp-e and Tp-e/QTc in HFREF. ARNI reduces symptoms of HFREF assessed by MLWHFQ and lowers NT-proBNP levels. Reduction in Tp-e and Tp-e/QTc correlate with clinical improvement in patients with HFrEF.

Keywords:

• Angiotensin receptor neprilysin inhibitor
• ARNI
• sacubitril
• QTc
• Tp-e interval
• Tp-e/QTc ratio
• valsartan

Disclosure statement

AO has Medtronic proctorship fee and speaker honoraria from Daiichi Sankyo, Menarini, Bayer and Pfizer/BMS. Other authors have no competing interests and nothing to declare.