Characterization of heart failure patients with reverse left ventricular remodelling post‐angiotensin receptor blockers/neprilysin inhibitors therapy

Abstract

AimsTo assess the effect of angiotensin receptor blockers/neprilysin inhibitors (ARNI) on left ventricular (LV) ejection fraction (LVEF) and LV dimensions in a real-life cohort of heart failure and reduced ejection fraction (HFrEF) patients, while analysing patient characteristics that may predict reverse LV remodelling. Methods and resultsThe ARNI-treated HFrEF patients followed at a single tertiary medical centre HF-outpatient clinic were included in the study. Clinical and echocardiographic parameters were evaluated prior to ARNI initiation, and while on ARNI therapy, assessing patient characteristics associated with reverse LV remodelling. The cohort included 91 patients (mean age 60.5 years, 90% male) and 47 (52%) patients exhibited ARNI responsiveness, defined as an increase in LVEF during therapy. Overall, LVEF increased by 19% post-ARNI (23.8 to 28.4%, P < 0.001). Subgroup analysis revealed several parameters associated with significant LVEF improvement, including baseline LVEF <30%, non-ischaemic HF aetiology, lack of cardiac resynchronization therapy (CRT), better initial functional class and ARNI initiation within 3 years from HF diagnosis (P ≤ 0.001 for all). Significant reduction in LV dimensions was noted in patients with lower initial LVEF, non-ischaemic HF and no CRT. Further combined subgrouping of the study population demonstrated that patients with both LVEF <30% and a non-ischaemic HF gained most benefit from ARNI with an average of 51% improvement in LVEF (19.9 to 30%, P < 0.001). Conclusions The ARNI treatment response is not uniform among HFrEF patient subgroups. More pronounce reverse LV remodelling is associated with early ARNI treatment initiation in the course of HFrEF, and in those with LVEF <30%, non-ischaemic HF and no CRT.

Add-on Sacubitril/Valsartan Therapy Induces Left Ventricular Remodeling in Non-responders to Cardiac Resynchronization Therapy to a Similar Extent as in Heart Failure Patients Without Resynchronization

“…Of note, CRT patients in our study were non-responders and therefore our results may not apply to all CRT patients. Indeed, the absence of CRT was a predictor of reverse LV remodeling after the initiation of SV in a registry study on patients with HFrEF including 43% with an implanted CRT device [ 18 ]. The authors’ proposed explanation for this finding was that the potential myocardial reserve was already realized by cardiac resynchronization, thereby leaving no room for further improvement with SV.…”

Clinical efficacy of angiotensin receptor-neprilysin inhibitor in de novo heart failure with reduced ejection fraction

“…One prospective study on patients with HFrEF demonstrated the effect of treatment with ARNI on both LV and LA reverse remodeling, despite the inclusion of patients with long-lasting disease [ 12 ]. In addition, Maizels et al [ 13 ] reported that the effect of ARNI therapy on CRR was greater in selective patients, especially in those receiving ARNI treatment within 3 years from HF diagnosis, thereby demonstrating that they had greater LVEF improvement than other patients. Similarly, our study showed that increase of LVEF in the de novo group was approximately 1.5 times higher than that in the prior HF group (12.0 vs. 7.4%, p = 0.010).…”

Long‐term impact of angiotensin receptor‐neprilysin inhibitor based on short‐term treatment response in heart failure

“…Angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), 3–6 beta‐blockers, 7–10 and mineralocorticoid receptor antagonists (MRAs) 11,12 have been recognized as the cornerstones in the pharmacologic treatment of HF. Recent studies have reported that compared with enalapril, angiotensin receptor–neprilysin inhibitors (ARNI) reduce morbidity and mortality by improving the ejection fraction (EF) and inducing left ventricular (LV) reverse remodelling in patients with HF with reduced ejection fraction (HFrEF) 13–19 . Currently, HF guidelines recommend ARNI as the frontline therapy for patients with HFrEF 20–22 .…”

“…Recent studies have reported that compared with enalapril, angiotensin receptor–neprilysin inhibitors (ARNI) reduce morbidity and mortality by improving the ejection fraction (EF) and inducing left ventricular (LV) reverse remodelling in patients with HF with reduced ejection fraction (HFrEF). 13 , 14 , 15 , 16 , 17 , 18 , 19 Currently, HF guidelines recommend ARNI as the frontline therapy for patients with HFrEF. 20 , 21 , 22 However, whether ARNI remain effective in patients who achieved an improvement in LV systolic function or significant LV reverse remodelling after a certain period of treatment as well as in patients without these improvements is unclear.…”