BackgroundEnvironmental enrichment (EE) in laboratory animals improves neurological function and motor/cognitive performance, and is proposed as a strategy for treating neurodegenerative diseases. EE has been investigated in the R6/2 mouse model of Huntington's disease (HD), where increased social interaction, sensory stimulation, exploration, and physical activity improved survival. We have also shown previously that HD patients and R6/2 mice have disrupted circadian rhythms, treatment of which may improve cognition, general health, and survival.Methodology/Principal FindingsWe examined the effects of EE on the behavioral phenotype and circadian activity of R6/2 mice. Our mice are typically housed in an “enriched” environment, so the EE that the mice received was in addition to these enhanced housing conditions. Mice were either kept in their home cages or exposed daily to the EE (a large playground box containing running wheels and other toys). The “home cage” and “playground” groups were subdivided into “handling” (stimulated throughout the experimental period) and “no-handling” groups. All mice were assessed for survival, body weight, and cognitive performance in the Morris water maze (MWM). Mice in the playground groups were more active throughout the enrichment period than home cage mice. Furthermore, R6/2 mice in the EE/no-handling groups had better survival than those in the home cage/no-handling groups. Sex differences were seen in response to EE. Handling was detrimental to R6/2 female mice, but EE increased the body weight of male R6/2 and WT mice in the handling group. EE combined with handling significantly improved MWM performance in female, but not male, R6/2 mice.Conclusions/SignificanceWe show that even when mice are living in an enriched home cage, further EE had beneficial effects. However, the improvements in cognition and survival vary with sex and genotype. These results indicate that EE may improve the quality of life of HD patients, but we suggest that EE as a therapy should be tailored to individuals.

BACKGROUND: Maintenance of sinus rhythm is challenging in patients with longstanding persistent atrial fibrillation (PeAF). Minimally invasive surgical AF ablation may improve outcomes when combined with catheter ablation (the 'convergent' procedure). This study evaluates the safety and efficacy of the convergent procedure versus catheter ablation alone in longstanding PeAF. METHODS: 43 consecutive patients with longstanding PeAF underwent subxiphoid endoscopic ablation of the posterior left atrium followed by catheter ablation from 2013-2018. The primary outcome was AF-free survival at 12 months; secondary outcomes included change in EHRA class, echocardiographic data, procedural complications, freedom from anti-arrhythmic drugs (AADs), and long term arrhythmia-free survival. Outcomes were compared with a matched group of 43 patients who underwent catheter ablation alone. Both groups underwent multiple catheter ablations as required. Baseline characteristics were similar between groups. RESULTS: After 12 months, the convergent procedure was associated with increased AF-free survival on AADs (60.5 % versus 25.6%, p=0.002) and off AADs (37.2% versus 13.9%, p=0.025), versus catheter ablation. Allowing for multiple procedures, after 30.5±13.3 months' follow-up the convergent procedure was associated with increased arrhythmia-free survival on AADs (58.1% versus 30.2%, p=0.016) and off AADs (32.5% versus 11.6%, p=0.036) versus catheter ablation. There were more complications in the convergent procedure group (11.6% versus 2.3%, p=0.2). Multivariate analysis identified only the convergent procedure (OR 3.06 (1.23-7.6), p=0.017) as predictive of arrhythmiafree survival long term. CONCLUSIONS: In longstanding PeAF, the convergent procedure is associated with improved arrhythmia-free survival versus catheter ablation alone. Complication rates are significant but have been shown to depreciate with experience.

Background Recent reports have demonstrated high troponin levels in patients affected with COVID-19. In the present study, we aimed to determine the association between admission and peak troponin levels and COVID-19 outcomes. Methods This was an observational multi-ethnic multi-centre study in a UK cohort of 434 patients admitted and diagnosed COVID-19 positive, across six hospitals in London, UK during the second half of March 2020. Results Myocardial injury, defined as positive troponin during admission was observed in 288 (66.4%) patients. Age (OR: 1.68 [1.49–1.88], p < .001), hypertension (OR: 1.81 [1.10–2.99], p = .020) and moderate chronic kidney disease (OR: 9.12 [95% CI: 4.24–19.64], p < .001) independently predicted myocardial injury. After adjustment, patients with positive peak troponin were more likely to need non-invasive and mechanical ventilation (OR: 2.40 [95% CI: 1.27–4.56], p = .007, and OR: 6.81 [95% CI: 3.40–13.62], p < .001, respectively) and urgent renal replacement therapy (OR: 4.14 [95% CI: 1.34–12.78], p = .013). With regards to events, and after adjustment, positive peak troponin levels were independently associated with acute kidney injury (OR: 6.76 [95% CI: 3.40–13.47], p < .001), venous thromboembolism (OR: 11.99 [95% CI: 3.20–44.88], p < .001), development of atrial fibrillation (OR: 10.66 [95% CI: 1.33–85.32], p = .026) and death during admission (OR: 2.40 [95% CI: 1.34–4.29], p = .003). Similar associations were observed for admission troponin. In addition, median length of stay in days was shorter for patients with negative troponin levels: 8 (5–13) negative, 14 (7–23) low-positive levels and 16 (10–23) high-positive ( p < .001). Conclusions Admission and peak troponin appear to be predictors for cardiovascular and non-cardiovascular events and outcomes in COVID-19 patients, and their utilisation may have an impact on patient management.

No abstract

No abstract

Leadless left bundle branch area pacing (LBBAP) represents the merger of two rapidly progressing areas in the field of cardiac resynchronisation therapy (CRT). It combines the attractive concepts of pacing the native conduction system to allow more physiological activation of the myocardium than conventional biventricular pacing, with the potential added benefits of avoiding long-term complications associated with transvenous leads via leadless left ventricular endocardial pacing. This perspective article will first review the evidence for the efficacy of leadless pacing in CRT. We then summarise the procedural steps and pilot data for leadless LBBAP, followed by a discussion of the safety and efficacy of this novel technique. Finally, we will examine how further mechanistic evidence may shed light to which patients may benefit most from leadless LBBAP, and how improvements in current experience and technology could promote widespread uptake and expand current clinical indications.

Conduction System Pacing (CSP) delivered by His Bundle Pacing (HBP) or Left Bundle Pacing (LBP) are exciting novel interventions in the field of Cardiac Resynchronization Therapy (CRT). As the evidence base for CSP grows, the volume of implants worldwide is projected to rise significantly in the coming years. As such, physicians will be confronted with increasingly prevalent and vital issues arising in long-term follow up, including the management of infected, malfunctioning, or redundant CSP leads. Transvenous lead extraction (TLE) is the first-line option for removal of pacing leads when indicated in these circumstances. The evidence base for TLE in the context of CSP is still in its infancy. In this article, we first provide a brief overview of TLE. We then examine the data on the long-term performance of HBP leads. Next, we describe the features of the Medtronic Select Secure 3,830 lead, and how experience of TLE of this lead in the paediatric population has informed our practice. Finally, we review the current evidence for TLE in HBP and LBP, and discuss how future studies can address gaps in our current knowledge.

A significant number of right bundle branch block (RBBB) patients receive cardiac resynchronization therapy (CRT), despite lack of evidence for benefit in this patient group. His bundle (HBP) and left bundle pacing (LBP) are novel CRT delivery methods, but their effect on RBBB remains understudied. We aim to compare pacing-induced electrical synchrony during conventional CRT, HBP, and LBP in RBBB patients with different conduction disturbances, and to investigate whether alternative ways of delivering LBP improve response to pacing. We simulated ventricular activation on twenty-four four-chamber heart geometries each including a His-Purkinje system with proximal right bundle branch block (RBBB). We simulated RBBB combined with left anterior and posterior fascicular blocks (LAFB and LPFB). Additionally, RBBB was simulated in the presence of slow conduction velocity (CV) in the myocardium, left ventricular (LV) or right ventricular (RV) His-Purkinje system, and whole His-Purkinje system. Electrical synchrony was measured by the shortest interval to activate 90% of the ventricles (BIVAT-90). Compared to baseline, HBP significantly improved activation times for RBBB alone (BIVAT-90: 66.9 ± 5.5 ms vs. 42.6 ± 3.8 ms, p &lt; 0.01), with LAFB (69.5 ± 5.0 ms vs. 58.1 ± 6.2 ms, p &lt; 0.01), with LPFB (81.8 ± 6.6 ms vs. 62.9 ± 6.2 ms, p &lt; 0.01), with slow myocardial CV (119.4 ± 11.4 ms vs. 97.2 ± 10.0 ms, p &lt; 0.01) or slow CV in the whole His-Purkinje system (102.3 ± 7.0 ms vs. 75.5 ± 5.2 ms, p &lt; 0.01). LBP was only effective in RBBB cases if combined with anodal capture of the RV septum myocardium (BIVAT-90: 66.9 ± 5.5 ms vs. 48.2 ± 5.2 ms, p &lt; 0.01). CRT significantly reduced activation times in RBBB in the presence of severely slow RV His-Purkinje CV (95.1 ± 7.9 ms vs. 84.3 ± 9.3 ms, p &lt; 0.01) and LPFB (81.8 ± 6.6 ms vs. CRT: 72.9 ± 8.6 ms, p &lt; 0.01). Both CRT and HBP were ineffective with severely slow CV in the LV His-Purkinje system. HBP is effective in RBBB patients with otherwise healthy myocardium and Purkinje system, while CRT and LBP are ineffective. Response to LBP improves when LBP is combined with RV septum anodal capture. CRT is better than HBP only in patients with severely slow CV in the RV His-Purkinje system, while CV slowing of the whole His-Purkinje system and the myocardium favor HBP over CRT.