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

Abstract

:No data on the add-on sacubitril/valsartan (S/V) therapy among cardiac resynchronization therapy with a defibrillator (CRT-D) nonresponder patients are currently available in literature. We conducted a prospective observational study including 190 CRT-D nonresponder patients with symptomatic heart failure with reduced ejection fraction despite the optimal medical therapy from at least 1 year. The primary endpoint was the rate of additional responders (left ventricular end-systolic volume reduction >15%) at 12 months from the introduction of S/V therapy. At the end of the 12 months follow-up, 37 patients (19.5%) were deemed as “additional responders” to the combination use of CRT + S/V therapy. The only clinical predictor of additional response was a lower left ventricular ejection fraction [OR 0.881 (0.815–0.953), P = 0.002] at baseline. At 12 months follow-up, there were significant improvements in heart failure (HF) symptoms and functional status [New York Heart Association 2 (2–3) vs. 1 (1–2), P < 0.001; physical activity duration/day: 10 (8–12) vs. 13 (10–18) hours, P < 0.001]. Compared with the 12 months preceding S/V introduction, there were significant reductions in the rate of HF rehospitalization (35.5% vs. 19.5%, P < 0.001), in atrial tachycardia/atrial fibrillation burden [6.0 (5.0–8.0) % vs. 0 (0–2.0) %, P < 0.001] and in the proportions of patients experiencing ventricular arrhythmias (21.6% vs. 6.3%; P < 0.001). Our results indicate that S/V add-on therapy in CRT-D nonresponder patients is associated with 19.5% of additional responders, a reduction in HF symptoms and rehospitalizations, AF burden, and ventricular arrhythmias.

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

“…The results of a few observational studies on the effects of SV therapy in CRT-NRs also support these expectations [ 14 – 16 ]. In a retrospective analysis, lower cardiac mortality was proven after 6-month follow-up in 22 CRT-NR patients who were started on SV treatment as compared to those 28 who remained on ACEi/ARB medication [ 14 ]. Improvement in quality-of-life indicators and a reduction in hospitalization rates were demonstrated after 6-month treatment with SV in the RESINA (Resynchronization plus an Inhibitor of Neprilysin/Angiotensin) registry [ 15 ].…”

“…Whether hospitalization and mortality endpoints in CRT-NRs on SV treatment will also be similar to what was demonstrated by the large-scale randomized PARADIGM trial in patients with HFrEF [11] should be answered by further investigations. The results of a few observational studies on the effects of SV therapy in CRT-NRs also support these expectations [14][15][16]. In a retrospective analysis, lower cardiac mortality was proven after 6-month follow-up in 22 CRT-NR patients who were started on SV treatment as compared to those 28 who remained on ACEi/ ARB medication [14].…”

“…However, the efficacy of SV in the specific subgroup of patients with HFrEF and previous CRT implantation-and specifically in those who did not respond to CRT-remains ill defined. In a few observational studies which enrolled a limited number of CRT-NR patients and had relatively short follow-up durations, the echocardiographic signs of cardiac remodeling, along with the improvement in functional status, quality of life, as well as reduced rates of hospitalization and mortality have been demonstrated after the initiation of SV [14][15][16].…”

What Can We Do in Patients Non-Responsive to Cardiac Resynchronisation Threapy?

“…Russo ve ark. 'nın 43 yaptığı, 190 hastanın dâhil edildiği ileriye dönük gözlemsel çalışma sonucunda, KRT'ye yanıt vermeyen (altıncı ayda değerlendirilen sol ventrikül sistol sonu hacimde < %15 azalma saptanan) hastalarda sakubitril/valsartan tedavisi ile hastaların %19,5'inde ek yanıt elde edildiği ve ek yanıtın tek belirleyicisinin daha düşük bazal sol ventrikül ejeksiyon fraksiyonu (SVEF) değerlerinin olduğu belirlendi. Bu veriler ışığında KRT'ye yanıt vermeyen hastalarda ACEI'ların yerine sakubitril/valsartan tedavisi düşünülebilir.…”

The Role of Sacubitril/Valsartan and Gliflozins in Heart Failure with Reduced Ejection Fraction after Cardiac Resynchronization Therapy

“…In a recent study, Russo et al analyzed the impact of ARNi in190 CRTD non-responder patients, with a median follow-up of 20 months from device implant; about 20 % of their population improved cardiac function and were classified as additional responders 39 .…”