Clinical Outcomes in Patients with Ischemic versus Non-Ischemic Cardiomyopathy after Angiotensin-Neprilysin Inhibition Therapy

Abstract

Background: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. Methods and results: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). Conclusions: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.

Effects of sacubitril/valsartan on life quality in chronic heart failure: A systematic review and meta-analysis of randomized controlled trials

“…Third, we found significant heterogeneity among studies on some outcomes, which might result from the large differences in respect to control drugs, average dose, number of patients at different dose levels, and NYHA functional class among studies. Finally, although some studies reported that different population characteristics could have impacts on the treatment outcome with sacubitril/valsartan, such as the age and etiology differences, we did not conduct subgroup analysis ( 39 , 40 ). Because there was lack of data concerning sacubitril/valsartan therapy with respect to different ages, etiologies of HF, NYHA functional classes, control drugs, duration of follow-up, etc.…”

Effect of sacubitril/valsartan on the occurrence of cardiac arrhythmias and the risk of sudden cardiac death in heart failure: A meta-analysis of randomized controlled trials

“…Third, cardiac arrhythmias were not described in terms of sustained or non-sustained, fast or slow. Forth, data have shown a possible different effects of sacubitril/valsartan according to the HF etiology and age ( 42 , 43 ). Due to lack of data, the effects of sacubitril/valsartan on the risk of cardiac arrhythmias and SCD according to HF etiology and age remain unclear.…”

Exploration of Mechanisms of Sacubitril/Valsartan in the Treatment of Cardiac Arrhythmias Using a Network Pharmacology Approach

“…Any molecular mechanisms, where SV promotes arrhythmia, were not found in the current study. Clinical reports have indicated that SV can increase the incidence of ventricular arrhythmias in patients with HF ( 8 , 14 ), but with short follow-up times and small sample sizes. Etiology, gender differences, and inclusion of high-risk patients may also affect the results ( 4 ).…”

“…Drugs that inhibit myocardial remodeling ( 12 ), such as ARNI, may play antiarrhythmic roles by reducing the formation of ectopic impulses and reentry from the upstream mechanism ( 13 ). However, the controversy around SV remains: it increases the incidence of ventricular arrhythmias, especially in patients with ischemic heart disease ( 14 , 15 ), although after adjusting the outcomes, the cardiovascular death caused by etiologies of HF such as ischemic, non-ischemic, and hypertensive cardiomyopathies are similar ( 16 , 17 ). But, in men with ejection fraction of <35%, patients who recently took SV may be more prone to ventricular arrhythmias ( 18 ).…”