Rationale and design of the randomized multicentre His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) trial:HOPE HF Trial rationale and design

Aims In patients with heart failure and a pathologically prolonged PR interval, left ventricular (LV) filling can be improved by shortening atrioventricular delay using His‐bundle pacing. His‐bundle pacing delivers physiological ventricular activation and has been shown to improve acute haemodynamic function in this group of patients. In the HOPE‐HF (His Optimized Pacing Evaluated for Heart Failure) trial, we are investigating whether these acute haemodynamic improvements translate into improvements in exercise capacity and heart failure symptoms. Methods and results This multicentre, double‐blind, randomized, crossover study aims to randomize 160 patients with PR prolongation (≥200 ms), LV impairment (EF ≤ 40%), and either narrow QRS (≤140 ms) or right bundle branch block. All patients receive a cardiac device with leads positioned in the right atrium and the His bundle. Eligible patients also receive a defibrillator lead. Those not eligible for implantable cardioverter defibrillator have a backup pacing lead positioned in an LV branch of the coronary sinus. Patients are allocated in random order to 6 months of (i) haemodynamically optimized dual chamber His‐bundle pacing and (ii) backup pacing only, using the non‐His ventricular lead. The primary endpoint is change in exercise capacity assessed by peak oxygen uptake. Secondary endpoints include change in ejection fraction, quality of life scores, B‐type natriuretic peptide, daily patient activity levels, and safety and feasibility assessments of His‐bundle pacing. Conclusions Hope‐HF aims to determine whether correcting PR prolongation in patients with heart failure and narrow QRS or right bundle branch block using haemodynamically optimized dual chamber His‐bundle pacing improves exercise capacity and symptoms. We aim to complete recruitment by the end of 2018 and report in 2020

On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of His-SYNC

Background The His-SYNC pilot trial was the first randomized comparison between His bundle pacing in lieu of a left ventricular lead for cardiac resynchronization therapy (His-CRT) and biventricular pacing (BiV-CRT), but was limited by high rates of crossover. Objective To evaluate the results of the His-SYNC pilot trial utilizing treatment-received (TR) and per-protocol (PP) analyses. Methods The His-SYNC pilot was a multicenter, prospective, single-blinded, randomized, controlled trial comparing His-CRT vs BiV-CRT in patients meeting standard indications for CRT (eg, NYHA II–IV patients with QRS >120 ms). Crossovers were required based on prespecified criteria. The primary endpoints analyzed included improvement in QRS duration, left ventricular ejection fraction (LVEF), and freedom from cardiovascular (CV) hospitalization and mortality. Results Among 41 patients enrolled (aged 64 ± 13 years, 38% female, LVEF 28%, QRS 168 ± 18 ms), 21 were randomized to His-CRT and 20 to BiV-CRT. Crossover occurred in 48% of His-CRT and 26% of BiV-CRT. The most common reason for crossover from His-CRT was inability to correct QRS owing to nonspecific intraventricular conduction delay (n = 5). Patients treated with His-CRT demonstrated greater QRS narrowing compared to BiV (125 ± 22 ms vs 164 ± 25 ms [TR], P < .001;124 ± 19 ms vs 162 ± 24 ms [PP], P < .001). A trend toward higher echocardiographic response was also observed (80 vs 57% [TR], P = .14; 91% vs 54% [PP], P = .078). No significant differences in CV hospitalization or mortality were observed. Conclusions Patients receiving His-CRT on-treatment demonstrated superior electrical resynchronization and a trend toward higher echocardiographic response than BiV-CRT. Larger prospective studies may be justifiable with refinements in patient selection and implantation techniques to minimize crossovers

Repeated infections of dengue (serotype DENV-2) in lung cells of BALB/c mice lead to severe histopathological consequences

To determine the effect of DENV (serotype 2) repeated infections on lung cells is the main goal of this study. From the result, lung histology of control BALB/c mice showed normal alveolar morphology, while vehicle control BALB/c mice highlighted a slight thickening of the alveolar septum. Lung histopathology of BALB/c mice infected twice by DENV-2 showed the presence of hemorrhage, plasma leakage and presence of hemosiderin-laden macrophages (HLMs). Notably, in the lung of BALB/c mice infected four times by DENV-2, we observed thickening and disruption of the alveolar septum, inflammatory cell infiltration, plasma leakage and increased cellularity. Megakaryocyte releasing platelets were also found into the lung alveolus. Overall, our findings showed severe histopathological damage in lungs repeatedly infected by DENV-2, allowing us to argue that they can be linked to pulmonary complication. Result also showed that the number of infections with similar total DENV-2 titer led to different histopathological changes

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049