Introduction Non-responders to cardiac resynchronization therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcome of patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials with no data on the specific cohort of CRT-NRs. The aim of this study was to compare the echocardiographic and biomarker changes in CRT-NR patients treated with versus without SV, and in patients with HFrEF on SV therapy. Methods CRT-NR patients initiated on SV (group I), CRT-NR patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (group II), and patients with HFrEF (without CRT) initiated on SV (group III) were identified in our heart failure (HF) registry. CRT-NR was defined as < 10% improvement in left ventricular ejection fraction (LV EF) 6 months after the implantation. Echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at baseline and at the end of follow-up were compared. Results A total of 275 patients (group I, 70; group II, 70; and group III, 135) were included. After a follow-up of 7.54 ± 1.8 months (mean ± standard deviation [SD]), LV EF (%) increased in group I (25.2 ± 5.7 versus 29.4% ± 6.7; p < 0.001) and in group III (26.6 ± 6.4 versus 29.9 ± 6.7; p < 0.001). LV end-systolic diameters (mm) decreased in group I (56.6 ± 9.0 versus 54.3 ± 8.7; p = 0.004) and in group III (55.9 ± 9.9 versus 54.3 ± 11.2; p = 0.021). The levels of NT-proBNP (pg/mL) decreased in group I (2058.86 [1041.07–4502.51] versus 1121.55 [545–2541]; p < 0.001) and in group III (2223.35 [1233.03–4795.96] versus 1123.09 [500.38–2651.27]; p < 0.001). The extent of improvement was similar in groups I and III (p > 0.05). No significant changes were detected in group II. Conclusion SV therapy induced similar improvements in echocardiographic parameters and in NT-proBNP levels in CRT-NR patients and in patients with HFrEF without resynchronization.

Background/Objectives: Conduction system pacing (CSP) is a potential alternative to biventricular pacing (BVP) in heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB) or non-LBBB. Available data also suggest that unlike BVP, CSP may improve clinical outcome in patients with right bundle branch block (RBBB), although its effects on cardiac mechanics and energetics are ill-defined. Herein, we report on echocardiographic and clinical outcomes of CSP in this patient cohort. Methods: CSP either with His bundle pacing or LBB area pacing was attempted as a primary strategy in patients with RBBB, QRS duration ≥ 130 ms, LVEF < 35% and NYHA II-IV symptoms after optimized medical therapy for 6 months. Data on functional status, NT-proBNP and echocardiographic parameters were collected at baseline and 6 months after CSP. Results: CSP performed in 16 patients reduced QRS duration from 155.3 ± 12.8 ms to 130 ± 16.5 ms (p < 0.001), increased LVEF from 27 ± 7% to 33 ± 9% (p = 0.01), improved LV global longitudinal strain from −7 ± 3% to −10 ± 4% (p = 0.004) and improved LV peak strain dispersion from 126 ± 28 ms to 96 ± 23 ms (p = 0.004). Global myocardial work index increased from 582 ± 277 mmHg% to 840 ± 306 mmHg% (p = 0.003), as did global constructive work (900 ± 374 mmHg% to 1203 ± 393 mmHg%; p = 0.006) and global work efficiency (from 71 ± 7% to 77 ± 8%; p = 0.004). NYHA class (12.5% with NYHA II, 87.5% with NYHA III before vs. 25% with NYHA I, 50% with NYHA II and 25% with NYHA III at 6 months; p = 0.002) and 6 min walk distance (from 354 ± 88 m to 411 ± 95 m; p = 0.003) improved, while NT-proBNP decreased (from 4093 ± 7215 ng/L to 2087 ± 2872 ng/L, p = 0.003). Conclusions: CSP improved functional capacity and echocardiographic parameters related to cardiac functions and myocardial work in HFrEF patients with RBBB. Nevertheless, these results await further confirmation by large-scale, multi-center randomized trials.

Background: Sacubitril/valsartan (S/V) improves left ventricular (LV) function and clinical outcome in heart failure (HF) with reduced ejection fraction (HFrEF). Data on its clinical value in the specific cohort of HFrEF patients demonstrating no adequate response to cardiac resynchronization therapy (CRT nonresponders; CRT-NRs) are limited. Herein, we investigated the impact of S/V initiated as a replacement for ACEi/ARB therapy in CRT nonresponder (CRT-NR) patients. Methods: Our HF database was searched to identify CRT-NRs who received S/V treatment for at least 6 months as a replacement for ACEi/ARB (Group I; 70 patients) and CRT-NRs who remained on ACEi/ARB (Group II, 70). In addition, HFrEF patients without CRT indication who received S/V therapy for at least 6 months (Group III; 135) were also included in this analysis. The primary endpoint was the composite of all-cause mortality including heart transplantation (HTx) or left ventricular assist device implantation (LVAD) and HF hospitalization (HFH). Secondary endpoints were (i) all-cause mortality+HTx+LVAD and (ii) HFH analyzed separately. Results: Over a median follow-up of 22 months, the primary composite endpoint occurred in 27 out of 70 patients (38.57%) in Group I, 43 out of 70 patients (61.42%) in Group II, and 60 out of 135 patients (44.42%) in Group III. The differences were significant between Groups I and II (p: 0.005), as well as between Group II and III (p: 0.012), while the two groups on S/V (Group I and III) demonstrated similar outcomes (p = 0.465). HFH analyzed separately as a secondary endpoint occurred in 19 out of 70 patients (27.14%) in Group I, 38 out of 70 patients (54.28%) in Group II, and 36 out of 135 patients (26.66%) in Group III (Group I vs. II p: 0.001; Groups II vs. III p: 0.001, Group I vs. III, p: 0.896). All-cause mortality+HTx+LVAD analyzed separately as the other secondary endpoint demonstrated no significant differences among the three groups. Conclusions: S/V therapy improved HFH but not mortality in CRT-NR patients. Comparable improvement was demonstrated after SV in the CRT-NR and in the general HFrEF cohort with no CRT indication.