The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.OBJECTIVE To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTSAnalysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.INTERVENTION Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURESThe primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.CONCLUSIONS AND RELEVANCE Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.

Abstract:Background: Since the late 1990s, a growing number of clinical studies have indicated that long-term permanent right ventricular (RV) apical pacing will induce severe complications such as development of heart failure, increased burden of atrial fi brillation leading to decreased quality of life. Aim of the study: To investigate whether cardiac resynchronization therapy (CRT) using biventricular (BiV) pacing can prevent the development of left ventricular (LV) dysfunction, LV remodelling, worsening of the clinical status and quality of life in chronically RV paced patients with normal LV ejection fraction (EF). Methods and results:A total of 127 patients with Class I indication for permanent cardiac pacing and without established indication for CRT were subjected to 6 months of RV and BiV pacing in a patient-blinded, randomized crossover trial. Treatment effects of BiV pacing were evaluated for LV function, LV remodelling and clinical status. Conclusion: BiV pacing, compared to RV pacing, did not change LV function and quality of life in patients with the absence of LV dysfunction or remodelling, standard bradycardia pacing indications in a pilot phase (12-month follow-up) of the TUGENDHAT trial. The fi nal report will be published after 60-month follow-up termination (Tab. 5, Fig. 3, Ref. 30). Full Text in PDF www.elis.sk. Key words: BiV and RV pacing, LV remodelling, heart failure, atrial fi brillation, quality of life. Results of several trials have supported the fact that right ventricular (RV) apical pacing might lead to adverse clinical outcomes in patients with standard pacing indications. Nevertheless, RV apical pacing continues to be practiced by many physicians because of its easy accessibility and relative stability over time (1, 2). The optimal mode and site of pacing remain undefi ned.The detrimental effect of RV pacing is probably most important in patients with pre-existing left ventricular (LV) dysfunction and may lead to worsening of heart failure (3, 4). In RV pacing, the sequence of electrical activation resembles the activation pattern in left bundle branch block (LBBB). This asynchronous electrical pattern is accompanied by abnormal dyssynchronous mechanical interactions within the LV (5). Experimental data suggested that biventricular (BiV) pacing might preserve myocardial performance better than RV apical pacing in patients with atrioventricular (AV) block and normal systolic function (6). The underlying mechanism may be a signifi cant reduction in LV systolic dyssynchrony, as shown by Cojoc et al (7). In the majority of patients with severe LV dysfunction and severe clinical heart failure associated with either LBBB-or RV pacing-induced dyssynchrony, BiV pacing improves clinical status, reduces mortality and morbidity, reduces heart failure (HF) hospitalizations, reverses LV remodelling and improves LV function (8, 9). Therefore, BiV pacing is nowadays recommended in patients with ventricular dyssynchrony (QRS > 120 ms), severe LV dysfunction [LV ejection fraction (LVEF) < 0.35] ...

Background: Ceruloplasmin is an acute phase protein with plasma copper binding properties, and is a potent extracellular antioxidative enzyme. Inflammation and oxidative stress might explain the role of ceruloplasmin in the pathophysiology of heart failure. Study objective: The objective is to assess the correlation of ceruloplasmin levels with biomarkers of cardiac remodelling and myofibrosis in patients with acute decompensated heart failure. Patients and methods: Blood samples were taken and serum levels of soluble ST2, galectin-3, NT-proBNP and ceruloplasmin were analysed in 31 consecutive patients with systolic HF referred to tertiary care nurse lead heart failure clinic with acute decompensated CHF requiring i.v. diuretics. The mean patients' age was 68 years, mean left ventricular ejection fraction (LV EF) was 29%, 66% patients had ischemic aetilogy of CHF and 33% had atrial fibrillation. Results: The mean ceruloplasmin level was 0.243 g/l, mean galectin-3 level was 1.26 ng/ml, mean sST2 level was 38.15 ng/ml, and mean NT-proBNP was 1927 pg/ml. The ceruloplasmin level correlated with NT-proBNP (r = 0.58, p < 0.05) and with sST2 (r = 0.77, p < 0.001), sST2 levels correlated significantly with NT-proBNP (r = 0.66, p < 0.01). The ceruloplasmin level did not correlate with galectin-3 concentration. Conclusion: The ceruloplasmin level correlates with the biomarkers of cardiac remodelling (NT-proBNP, sST2), but not with the biomarker of myofibrosis (galectin-3). This finding supports the hypothesis of inflammatory re-* Corresponding author. F. Málek et al. 972 sponse in acute decompensated heart failure.