The effects of ageing and adrenergic challenge on electrocardiographic phenotypes in a murine model of long QT syndrome type 3.

Long QT Syndrome 3 (LQTS3) arises from gain-of-function Nav1.5 mutations, prolonging action potential repolarisation and electrocardiographic (ECG) QT interval, associated with increased age-dependent risk for major arrhythmic events, and paradoxical responses to β-adrenergic agents. We investigated for independent and interacting effects of age and Scn5a+/ΔKPQ genotype in anaesthetised mice modelling LQTS3 on ECG phenotypes before and following β-agonist challenge, and upon fibrotic change. Prolonged ventricular recovery was independently associated with Scn5a+/ΔKPQ and age. Ventricular activation was prolonged in old Scn5a+/ΔKPQ mice (p = 0.03). We associated Scn5a+/ΔKPQ with increased atrial and ventricular fibrosis (both: p < 0.001). Ventricles also showed increased fibrosis with age (p < 0.001). Age and Scn5a+/ΔKPQ interacted in increasing incidences of repolarisation alternans (p = 0.02). Dobutamine increased ventricular rate (p < 0.001) and reduced both atrioventricular conduction (PR segment-p = 0.02; PR interval-p = 0.02) and incidences of repolarisation alternans (p < 0.001) in all mice. However, in Scn5a+/ΔKPQ mice, dobutamine delayed the changes in ventricular repolarisation following corresponding increases in ventricular rate. The present findings implicate interactions between age and Scn5a+/ΔKPQ in prolonging ventricular activation, correlating them with fibrotic change for the first time, adding activation abnormalities to established recovery abnormalities in LQTS3. These findings, together with dynamic electrophysiological responses to β-adrenergic challenge, have therapeutic implications for ageing LQTS patients

Herd-level animal management factors associated with the occurrence of bovine neonatal pancytopenia in calves in a multicountry study

Since 2007, mortality associated with a previously unreported haemorrhagic disease has been observed in young calves in several European countries. The syndrome, which has been named ‘bovine neonatal pancytopenia’ (BNP), is characterised by thrombocytopenia, leukocytopenia and a panmyelophthisis. A herd-level case-control study was conducted in four BNP affected countries (Belgium, France, Germany and the Netherlands) to identify herd management risk factors for BNP occurrence. Data were collected using structured face-to-face and telephone interviews of farm managers and their local veterinarians. In total, 363 case farms and 887 control farms were included in a matched multivariable conditional logistic regression analysis. Case-control status was strongly associated with the odds of herd level use of the vaccine PregSure® BVD (PregSure, Pfizer Animal Health) (matched adjusted odds ratio (OR) 107.2; 95% CI: 41.0–280.1). This was also the case for the practices of feeding calves colostrum from the calf’s own dam (OR 2.0; 95% CI: 1.1–3.4) or feeding pooled colostrum (OR 4.1; 95% CI: 1.9–8.8). Given that the study had relatively high statistical power and represented a variety of cattle production and husbandry systems, it can be concluded with some confidence that no other herd level management factors are competent causes for a sufficient cause of BNP occurrence on herd level. It is suggested that genetic characteristics of the dams and BNP calves should be the focus of further investigations aimed at identifying the currently missing component causes that together with PregSure vaccination and colostrum feeding represent a sufficient cause for occurrence of BNP in calves

Mobile app-based symptom-rhythm correlation assessment in patients with persistent atrial fibrillation

Background: The assessment of symptom-rhythm correlation (SRC) in patients with persistent atrial fibrillation (AF) is challenging. Therefore, we performed a novel mobile app-based approach to assess SRC in persistent AF.Methods: Consecutive persistent AF patients planned for electrical cardioversion (ECV) used a mobile app to record a 60-s photoplethysmogram (PPG) and report symptoms once daily and in case of symptoms for four weeks prior and three weeks after ECV. Within each patient, SRC was quantified by the SRC-index defined as the sum of symptomatic AF recordings and asymptomatic non-AF recordings divided by the sum of all recordings.Results: Of 88 patients (33% women, age 68 +/- 9 years) included, 78% reported any symptoms during recordings. The overall SRC-index was 0.61 (0.44-0.79). The study population was divided into SRC-index tertiles: low (= 0.73). Patients within the low (vs high) SRC-index tertile had more often heart failure and diabetes mellitus (both 24.1% vs 6.9%). Extrasystoles occurred in 19% of all symptomatic non-AF PPG recordings. Within each patient, PPG recordings with the highest (vs lowest) tertile of pulse rates conferred an increased risk for symptomatic AF recordings (odds ratio [OR] 1.26, 95% coincidence interval [CI] 1.04-1.52) and symptomatic non-AF recordings (OR 2.93, 95% CI 2.16-3.97). Pulse variability was not associated with reported symptoms.Conclusions: In patients with persistent AF, SRC is relatively low. Pulse rate is the main determinant of reported symptoms. Further studies are required to verify whether integrating mobile app-based SRC assessment in current workflows can improve AF management

Isolated Subepicardial Right Ventricular Outflow Tract Scar in Athletes With Ventricular Tachycardia

BACKGROUND High-level endurance training has been associated with right ventricular pathological remodeling and ventricular tachycardia (VT). Although overlap with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been suggested, the arrhythmogenic substrate for VTs in athletes is unknown. OBJECTIVES The goal of this study was to evaluate whether electroanatomic scar patterns related to sustained VT can distinguish exercise-induced arrhythmogenic remodeling from ARVC and post-inflammatory cardiomyopathies. METHODS In 57 consecutive patients (mean age 48 +/- 16 years; 83% male) undergoing catheter ablation for scar-related right ventricular VT, 2 distinct scar distributions were identified: 1) scars involving the subtricuspid right ventricle in 46 patients (group A); and 2) scars restricted to the anterior subepicardial right ventricular outflow tract in 11 patients (group B). RESULTS Definite ARVC or post-inflammatory cardiomyopathy was diagnosed in 40 (87%) of 46 group A patients but was not diagnosed in any patients in group B. All group B patients underwent intensive endurance training for a median of 15 h/week (interquartile range [IQR]: 10 to 20 h/week) for a median of 13 years (IQR: 10 to 18 years). The cycle lengths of scar-related VTs were significantly faster in group B patients (257 +/- 34 ms vs. 328 +/- 72 ms in group A; p = 0.003). Catheter ablation resulted in complete procedural success in 10 (91%) of 11 group B patients compared with 26 (57%) of 46 group A patients (p = 0.034). During a median follow-up of 27 months (IQR: 6 to 62 months), 50% of group A patients but none of the group B patients had a VT recurrence. CONCLUSIONS This study describes a novel clinical entity of an isolated subepicardial right ventricular outflow tract scar serving as a substrate for fast VT in high-level endurance athletes that can be successfully treated by ablation. This scar pattern may allow distinguishing exercise-induced arrhythmogenic remodeling from ARVC and post-inflammatory cardiomyopathy. (C) 2017 by the American College of Cardiology Foundation

Mobile app-based symptom-rhythm correlation assessment in patients with persistent atrial fibrillation

BACKGROUND: The assessment of symptom-rhythm correlation (SRC) in patients with persistent atrial fibrillation (AF) is challenging. Therefore, we performed a novel mobile app-based approach to assess SRC in persistent AF. METHODS: Consecutive persistent AF patients planned for electrical cardioversion (ECV) used a mobile app to record a 60-s photoplethysmogram (PPG) and report symptoms once daily and in case of symptoms for four weeks prior and three weeks after ECV. Within each patient, SRC was quantified by the SRC-index defined as the sum of symptomatic AF recordings and asymptomatic non-AF recordings divided by the sum of all recordings. RESULTS: Of 88 patients (33% women, age 68 ± 9 years) included, 78% reported any symptoms during recordings. The overall SRC-index was 0.61 (0.44-0.79). The study population was divided into SRC-index tertiles: low (<0.47), medium (0.47-0.73) and high (≥0.73). Patients within the low (vs high) SRC-index tertile had more often heart failure and diabetes mellitus (both 24.1% vs 6.9%). Extrasystoles occurred in 19% of all symptomatic non-AF PPG recordings. Within each patient, PPG recordings with the highest (vs lowest) tertile of pulse rates conferred an increased risk for symptomatic AF recordings (odds ratio [OR] 1.26, 95% coincidence interval [CI] 1.04-1.52) and symptomatic non-AF recordings (OR 2.93, 95% CI 2.16-3.97). Pulse variability was not associated with reported symptoms. CONCLUSIONS: In patients with persistent AF, SRC is relatively low. Pulse rate is the main determinant of reported symptoms. Further studies are required to verify whether integrating mobile app-based SRC assessment in current workflows can improve AF management