De novo implanted cardiac resynchronization therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain. In this multicentre, randomized, controlled trial, 360 symptomatic (New York Heart Association Classes II–IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥ 20%, and a wide paced QRS complex duration ≥ 150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalization, or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalization. Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm (odds ratio 0.11; 95% confidence interval 0.06–0.19; P < .001). All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% confidence interval 0.16–0.47; P < .001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)]. In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared with ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalization, or absence of reverse remodelling. Main inclusion criteria and randomization by arms showing the result of 360 patients (215 CRT-D vs. 145 ICD) analysed by intention to treat. Primary and secondary outcomes showing a substantial treatment effect of CRT-D compared with ICD alone. Among patients with HF and reduced LVEF with intermittent or permanent RV pacing, CRT-D upgrade resulted in a lower incidence of the composite of all-cause mortality, HF hospitalization, or <15% decrease in LVESV as the primary outcome. Secondary outcome of all-cause mortality and HF hospitalization also proved a substantially lower incidence in CRT-D patients compared with ICD. CI, confidence interval; CRT-D, cardiac resynchronization therapy with defibrillator; HF, heart failure; HR, hazard ratio; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; OR, odds ratio; RV, right ventricular.

Background. The present study aims to examine the oxidative stress‐related activation of poly(ADP‐ribose) polymerase (PARP), a cause of parthanatos in circulating mononuclear leukocytes of patients with chronic heart failure (CHF), that was rarely investigated in the human setting yet. Methods. Patients with CHF (n = 20) and age‐ and body mass index‐matched volunteers (n = 15) with a normal heart function were enrolled. C‐reactive protein, N‐terminal probrain‐type natriuretic peptide (pro‐BNP), plasma total peroxide level (PRX), plasma total antioxidant capacity (TAC), oxidative stress index (OSI), leukocyte lipid peroxidation (4‐hydroxynonenal; HNE), protein tyrosine nitration (NT), poly(ADP‐ribosyl)ation (PARylation), and apoptosis‐inducing factor (AIF) translocation were measured in blood samples of fasting subjects. Results. Plasma PRX, leukocyte HNE, NT, PARylation, and AIF translocation were significantly higher in the heart failure group. Pro‐BNP levels in all study subjects showed a significant positive correlation to PRX, OSI, leukocyte HNE, NT, PARylation, and AIF translocation. Ejection fraction negatively correlated with the same parameters. Among HF patients, a positive correlation of pro‐BNP with PRX, OSI, and PARylation was still present. Conclusions. Markers of oxidative‐nitrative stress, PARP activation, and AIF translocation in blood components showed correlation to reduced cardiac function and the clinical appearance of CHF. These results may reinforce the consideration of PARP inhibition as a potential therapeutic target in CHF.

This study aimed to investigate the impact of cardiac resynchronization therapy with a defibrillator (CRT-D) on mortality, comparing it with CRT with a pacemaker (CRT-P). Additionally, the study sought to identify subgroups, evaluate the time trend in treatment effects, and analyze patient characteristics, considering the changing indications over the past decades. PubMed, CENTRAL, and Embase up to October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on mortality. Altogether 26 observational studies were selected comprising 128 030 CRT patients, including 55 469 with CRT-P and 72 561 with CRT-D device. Cardiac resynchronization therapy with defibrillator was able to reduce all-cause mortality by almost 20% over CRT-P [adjusted hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.76–0.94; P < 0.01] even in propensity-matched studies (HR: 0.83; 95% CI: 0.80–0.87; P < 0.001) but not in those with non-ischaemic aetiology (HR: 0.95; 95% CI: 0.79–1.15; P = 0.19) or over 75 years (HR: 1.08; 95% CI 0.96–1.21; P = 0.17). When treatment effect on mortality was investigated by the median year of inclusion, there was a difference between studies released before 2015 and those thereafter. Time-trend effects could be also observed in patients’ characteristics: CRT-P candidates were getting older and the prevalence of ischaemic aetiology was increasing over time. The results of this systematic review of observational studies, mostly retrospective with meta-analysis, suggest that patients with CRT-D had a lower risk of mortality compared with CRT-P. However, subgroups could be identified, where CRT-D was not superior such as non-ischaemic and older patients. An improved treatment effect of CRT-D on mortality could be observed between the early and late studies partly related to the changed characteristics of CRT candidates.

Heart failure (HF) is a leading cause of mortality and hospitalization in the elderly. However, data are scarce about their response to device treatment such as cardiac resynchronization therapy (CRT). We aimed to evaluate the age-related differences in the effectiveness of CRT, procedure-related complications, and long-term outcome. Between 2000 and 2020, 2656 patients undergoing CRT implantation were registered and analyzed retrospectively. Patients were divided into 3 groups according to their age: group I, < 65; group II, 65–75; and group III, > 75 years. The primary endpoint was the echocardiographic response defined as a relative increase > 15% in left ventricular ejection fraction (LVEF) within 6 months, and the secondary endpoint was the composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Procedure-related complications were also assessed. After implantation, LVEF showed significant improvement both in the total cohort [28% (IQR 24/33) vs. 35% (IQR 28/40); p < 0.01)] and in each subgroup (27% vs. 34%; p < 0.01, 29% vs. 35%; p < 0.01, 30% vs. 35%; p < 0.01). Response rate was similar in the 3 groups (64% vs. 62% vs. 56%; p = 0.41). During the follow-up, 1574 (59%) patients died. Kaplan–Meier curves revealed a significantly lower survival rate in the older groups (log-rank p < 0.001). The cumulative complication rates were similar among the three age groups (27% vs. 28% vs. 24%; p = 0.15). Our results demonstrate that CRT is as effective and safe therapy in the elderly as for young ones. The present data suggest that patients with appropriate indications benefit from CRT in the long term, regardless of age.

Background and Aims. Resynchronization therapy (CRT) improves mortality and induces reverse remodeling in heart failure (HF) patients with reduced ejection fraction and wide QRS. Nonetheless, some patients do not improve despite the optimal medical therapy and right indications for device implantation. Therefore, finding biomarkers suitable for identification of those patients is crucial. Vitamin D plays a classic hormonal role in the regulation of bone metabolism and also has physiological functions in wide range of nonskeletal tissues. Based on recent studies, low levels of vitamin D seem to directly contribute to pathogenesis and worsening of HF. We planned to assess the role of vitamin D levels on clinical outcomes of HF patients undergoing CRT. Methods and Results. We enrolled 136 HF patients undergoing CRT. Total plasma vitamin D levels were measured at baseline and 6 months later. Primary endpoint was 5-year all-cause mortality; secondary endpoint was lack of good clinical response, defined as less than 15% increase of left ventricular ejection fraction after six months. During follow-up, 58 patients reached the primary, and 45 patients reached the secondary endpoint. Vitamin D levels less than 24.13 ng/mL predicted 5-year mortality (p=0.045) and poor clinical response (p=0.03) after adjusting to all significant baseline predictors. Conclusion. Our study showed that vitamin D deficiency has a significant impact in heart failure patients; it is an independent predictor of lack of midterm clinical response and long-term mortality in patients undergoing CRT. Therefore, monitoring vitamin D status of heart failure patients could be of clinical significance.