Role of chronic exsposure to cigarette smoke on endoglin/CD105 expression in airway epithelium.

Dysregulation of airway epithelial cell function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD and is associated to tissue damage and disease severity. CD105 is a component of the receptor complex of TGF-β, a pleiotropic cytokine involved in cellular proliferation, differentiation and migration. CD105 regulates the expression of different components of the extracellular matrix suggesting a role of CD105 in cellular transmigration and remodeling processes. The aim of the present study was to investigate the expression of endoglin/CD105 in airway epithelium of COPD patients and its involvement in tissue remodeling and progression of COPD. We evaluated the immunoreactivity for CD105 expression in bronchial biopsies isolated from COPD patients and healthy controls (HC). The analysis of metaplastic epithelium was performed in bronchial biopsies by Image Analysis software (Leica Quantimet system). Finally, we investigated the expression of CD105 protein receptor in human bronchial epithelial cells (16HBE cells) exposed to 5% Cigarette Smoke Extract (CSE) for 12 days by western blot. We found that the CD105 immunoreactivity was significantly higher in bronchial epithelium of COPD than HC. Morphometric analysis of bioptic samples of COPD showed an increase of the immunoreactivity for CD105 in the area of metaplastic than in not metaplastic epithelium. Long term exposure to CSE significantly up-regulated CD105 expression in 16HBE. Chronic inflammation due to cigarette smoke might play a critic role on the alteration of CD105 protein expression in COPD, promoting tissue remodeling, angiogenesis and dysregulation of physiological reparative mechanisms, leading to squamous metaplasia

Electrocardiographic findings in patients with arrhythmogenic cardiomyopathy and right bundle branch block ventricular tachycardia.

AIMS: Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. METHODS AND RESULTS: From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. CONCLUSIONS: In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants

Continuous electrical monitoring in patients with arrhythmic myocarditis: Insights from a referral center

Background. The incidence and burden of arrhythmias in myocarditis are under‐reported. Objective. We aimed to assess the diagnostic yield and clinical impact of continuous arrhythmia monitoring (CAM) in patients with arrhythmic myocarditis. Methods. We enrolled consecutive adult patients (n = 104; 71% males, age 47 ± 11 y, mean LVEF 50 ± 13%) with biopsy‐proven active myocarditis and de novo ventricular arrhythmias (VAs). All patients underwent prospective monitoring by both sequential 24‐h Holter ECGs and CAM, including either ICD (n = 62; 60%) or loop recorder (n = 42; 40%). Results. By 3.7 ± 1.6 y follow up, 45 patients (43%) had VT, 67 (64%) NSVT and 102 (98%) premature ventricular complexes (PVC). As compared to the Holter ECG (average 9.5 exams per patient), CAM identified more patients with VA (VT: 45 vs. 4; NSVT: 64 vs. 45; both p < 0.001), more VA episodes (VT: 100 vs. 4%; NSVT: 91 vs. 12%) and earlier NSVT timing (median 6 vs. 24 months, p < 0.001). The extensive ICD implantation strategy was proven beneficial in 80% of the population. Histological signs of chronically active myocarditis (n = 73, 70%) and anteroseptal late gadolinium enhancement (n = 26, 25%) were significantly associated with the occurrence of VTs during follow up, even in the primary prevention subgroup. Conclusion. In patients with arrhythmic myocarditis, CAM allowed accurate arrhythmia detection and showed a considerable clinical impact