Less Ventricular Arrhythmias and ICD Shocks After Introduction of Sacubitril/Valsartan

Attempt to Explain the Paradigm

The first drug from the ARNI group (angiotensin and neprilysin receptor inhibitor) sacubitril/valsartan demonstrated its beneficial effect on the survival of patients with heart failure with reduced ejection fraction (HFrEF) in the PARADIGM-HF study. The lower total and cardiovascular mortality was given, among other things, by a lower incidence of sudden cardiac death. However, it was not clear what exactly caused this decrease—ventricular arrhythmias are naturally a candidate mechanism, but assessing their contribution to the etiology of sudden cardiac events is usually not reliably possible. It can only be assessed with certainty in patients whose heart rhythm is continuously recorded—i.e., if they have an implanted cardioverter-defibrillator (ICD) or a cardiac resynchronization therapy (CRT) device, ideally with telemonitoring. This is exactly what the study by Belgian arrhythmologists focused on.

Methodology and Course of the Study

The observed group consisted of patients with a left ventricular ejection fraction (LVEF) < 35% and with an ICD/CRT implanted for at least 6 months, who had previously been on optimal doses of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) and were then indicated for treatment with sacubitril/valsartan. Telemonitoring data was retrospectively analyzed for the same periods before and after they were switched from ACEi/ARB to sacubitril/valsartan; thus, the patients served as their own controls.

Over both periods, the number of arrhythmic events recorded by the device was determined: especially sustained ventricular tachycardias/fibrillations (VT/VF), the number of appropriate defibrillator shocks, non-sustained ventricular tachycardias (defined as ≥ 4 beats and lasting < 30 seconds), and the average number of ventricular extrasystoles (VES) per hour. Echocardiography was performed on patients at the beginning and end of the study. For the study purposes, reverse remodeling of the left ventricle in response to sacubitril/valsartan treatment was defined as an LVEF improvement of ≥ 5%.

Findings

Reduction in Ventricular Fibrillation and Tachycardia

A total of 151 patients were included, with a median follow-up period of 364 days before and after replacing ACEi/ARB with the corresponding dose of sacubitril/valsartan. After modifying the treatment, the VT/VF burden significantly decreased, both in terms of the number of affected patients (19 before the treatment change and 10 after) and the absolute number of episodes (51 episodes before the change vs. 14 after the change; both p < 0.001). Consequently, the number of appropriate shocks also decreased (16 vs. 6; p < 0.001). The average occurrence of non-sustained VT per patient also declined (7.7 ± 11.8 vs. 3.7 ± 5.4; p < 0.001).

Extrasystoles and Ventricular Remodeling

The average number of VES per hour significantly decreased, which was associated with an increase in the percentage of biventricular pacing among patients with CRT, whose biventricular pacing was < 90% at the study's start. More pronounced reverse left ventricular remodeling was associated with a lower burden of non-sustained VT and VES (both p < 0.05).

Discussion and Conclusion

This study only included patients with ICD/CRT, so the results cannot be reliably extrapolated to the entire population of patients with HFrEF. However, the study's conclusions suggest that a significant reduction in ventricular arrhythmias, including malignant ones, might be one of the reasons for decreased cardiovascular mortality following the introduction of sacubitril/valsartan. It also indicated that the positive effect in terms of the incidence of ventricular arrhythmias might be due to reverse left ventricular remodeling.

(luko)

Source: Martens P., Nuyens D., Rivero-Ayerza M. et al. Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction. Clin Res Cardiol 2019 Oct; 108 (10): 1074–1082, doi: 10.1007/s00392-019-01440-y.