Background/Objectives: Heart transplantation (HTX) is the definitive treatment for advanced heart failure (AdHF). The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (S/V) has been shown to reduce heart failure (HF) hospitalizations and mortality when compared to conventionally administered HF medications (i.e. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs)). Nevertheless, limited data are available on the hemodynamic (HD) effects of ARNI in patients with AdHF. Therefore, the aim of the present study was to compare echocardiographic, laboratory, and HD parameters relevant to HF before and after switching to ARNI in patients with AdHF awaiting HTX. Methods: A retrospective analysis was conducted utilizing available data on HD parameters, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, data on kidney function, HF therapy, and comorbidities. The study cohort comprised 13 AdHF patients (3 women, 10 men; mean age 56.4 ± 9 years) of whom 53.8% presented with non-ischemic and 46.2% with ischemic etiology. All patients were awaiting heart transplantation (HTX) and were transitioned to ARNI therapy between 2018 and 2021. Results: After switching to ARNI, we observed significant improvements: in left ventricular ejection fraction (LVEF: 27.27 ± 1.04% vs. 23.65 ± 1.02%, p = 0.03; data are given as mean ± SEM after vs. before ARNI therapy, respectively), cardiac output (CO: 4.90 ± 0.35 L/min vs. 3.83 ± 0.24 L/min, p = 0.013), and stroke volume (SV: 70.9 ± 5.9 mL vs. 55.5 ± 4.12 mL, p = 0.013). Significant reductions in systemic vascular resistance (SVR: 1188 ± 79.8 vs. 1600 ± 100 DS/cm⁵, p = 0.004) and pulmonary vascular resistance (PVR: 232.5 ± 34.8 vs. 278.9 ± 31.7 DS/cm⁵, p = 0.04) were also noted. Central venous pressure (CVP), pulmonary arterial systolic and diastolic pressures (PAPs and PAPd), pulmonary capillary wedge pressure (PCWP), and NT-proBNP levels did not exhibit significant changes upon ARNI administration. Conclusions: Early transition to ARNI therapy offers significant benefits for invasively measured hemodynamic parameters in patients with AdHF, potentially aiding in the stabilization and improvement of this vulnerable patient population.

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.

Aims: Classifying patients as responders or non-responders to cardiac resynchronization therapy (CRT) has been recently challenged, suggesting that preventing heart failure (HF) progression may also provide survival benefits. We assessed a novel classification based on echocardiographic left ventricular (LV) reverse remodelling and the occurrence of acute HF hospitalization (HHF) or sustained ventricular arrhythmia (VA) within 1-year post-CRT. Methods and results: Patients implanted with a CRT defibrillator (CRT-D) at our department between 2010 and 2020 were classified based on the change in LV ejection fraction (LVEF) within 1 year as responders (increase ≥ 10%), non-progressors (increase <10%) or progressors (decline). Patients in each category were further divided based on the occurrence or absence of an HHF/VA event within 1-year post-implantation. Long-term survival free of heart transplantation or LV assist device implantation was calculated for all six subgroups. Cohorts demonstrating no significant between-group differences were grouped together and reclassified as improved, stabilized or worsened. One hundred nineteen responders, 79 non-progressors and 69 progressors were identified based on the echocardiographic response. Long-term event-free survival was higher for responders as compared with non-progressors (hazard ratio [HR] 0.51, P = 0.002) or progressors (HR 0.34, P < 0.0001). Furthermore, non-progressors had better outcome than progressors (HR 0.63, P = 0.03). Long-term prognosis in patients was superior with versus without an HHF/VA event within each group of responders (HR 0.47, P = 0.03), non-progressors (HR 0.31, P = 0.0001) or progressors (HR 0.38, P = 0.0004). No survival difference was found between responders and non-progressors with no event (HR 0.69, P = 0.09), who were recategorized as improved. Long-term prognosis was also similar in responders with any event and in progressors with no event (HR 0.98, P = 0.88; stabilized), as well as in non-progressors and progressors with any event (HR 0.87, P = 0.63; worsened). Median survival rates demonstrated significant differences between the improved, stabilized and worsened groups (102.3, 62.0 and 24.4 months; HR 0.53, P = 0.006 between improved and stabilized; HR 0.41, P < 0.0001 between stabilized and worsened; HR 0.21, P < 0.0001 between improved and worsened cohorts, respectively). Conclusions: Long-term survival can be predicted based on the change in LVEF and on the occurrence of an HHF/VA event within 1-year after CRT-D implantation. Stabilized patients have significantly better prognosis as compared with the worsened group. Patients with strikingly poor prognosis can be identified using this assessment method.

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.