Improvement in quality of life with sacubitril/ /valsartan in cardiac resynchronization non-responders: The RESINA (RESynchronization plus an Inhibitor of Neprilysin/Angiotensin) registry

Abstract

Background: Clinical management of cardiac resynchronization therapy (CRT) nonresponders is difficult, and their prognosis is poor. The aim of the present study was to evaluate whether treatment with sacubitril/valsartan can improve quality of life (QoL) parameters in these patients. Methods: 35 non-responders to CRT were included (75 ± 7 years, 28% females, mean left ventricular ejection fraction 28 ± 8%, 54% non-ischemic cardiomyopathy) with maximally optimized drug therapy and New York Heart Association class II-III. They were all on angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and were switched to sacubitril/valsartan. One week before and 6 months after initiation of the therapy they completed both the Minnesota Living with Heart Failure (MLWHF) and the 12-item Kansas City Cardiomyopathy Questionnaires (KCCQ-12). The primary 2 outcome was the effect of sacubitril/valsartan on the physical, clinical, social and emotional QoL parameters and number of hospitalizations. Results: The mean total scores of both questionnaires improved from baseline to the follow-up visit at 6-months (KCCQ 40 ± 10 to 47 ± 10; p < 0.001; MLWHF 40 ± 15 to 29 ± 15; p < 0.001). The best results were seen in the KCCQ total symptom domains (77% improvement), the MLWHF physical domain (81% improvement), and the MLWHF emotional domain (71% improvement). Two patients died during follow-up. The mean number of hospitalizations reduced significantly (1 ± 0.6 vs. 0.5 ± 0.8; p = 0.003) Conclusions: In CRT non-responders, sacubitril/valsartan significantly improved overall QoL, physical limitations and emotional domains and reduced the number of hospitalizations.

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure

“… 336 In patients considered to be doing poorly with CRT, small nonrandomized studies have suggested that substituting sacubitril-valsartan for an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker may be beneficial. 381 , 382 In addition, consideration should be given to addition of aldosterone antagonists and sodium-glucose cotrans-porter-2 inhibitors.…”

Add-on Therapy With Sacubitril/Valsartan and Clinical Outcomes in CRT-D Nonresponder Patients

“…Very limited data have been published thus far on an add-on strategy with S/V administrated in CRT patients. [7][8][9] A post hoc analysis showed that 38% of CRT nonresponder patients at 6 months were still eligible for add-on therapy with S/V therapy. 7 In the setting of nonresponders to CRT, the retrospective study by Chun et al 8 showed a better clinical outcome for patients who were treated with S/V; however, they did not report data on increased CRT responsiveness after initiation of S/V therapy, nor the echocardiographic changes after institution of S/V therapy.…”

“…5 S/V also has a remarkable impact on the left ventricular (LV) reverse remodeling, an improvement on mitral regurgitation (MR) and a decrease of ventricular arrhythmia (VA) events. 6 Given these benefits, it seems plausible that S/V as "add on" on top of CRT may provide additional benefits in patients with HFrEF; however, few studies have tested this approach [7][8][9] and none have investigated patients with CRT-D implanted because of associated VA. The aim of this analysis was to evaluate the clinical impact of the add-on S/V therapy among CRT-D nonresponder patients, in a prospective single-center observational cohort study.…”

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure

“…Even in patients who have normalized their EF with CRT, withdrawal of GDMT has been shown to lead to poor outcomes 336 . In patients considered to be doing poorly with CRT, small nonrandomized studies have suggested that substituting sacubitril‐valsartan for an angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker may be beneficial 381,382 . In addition, consideration should be given to addition of aldosterone antagonists and sodium‐glucose cotransporter‐2 inhibitors. LV lead position is an important determinant of CRT response such that patients with more septal lead positions respond less favorably compared to those with leads placed in lateral positions 383 .…”