Access to and clinical use of cardiac implantable electronic devices and interventional electrophysiological procedures in the European Society of Cardiology Countries: 2016 Report from the European Heart Rhythm Association.

AIMS: The aim of this analysis was to provide comprehensive information on the access to and use of cardiac implantable electronic device (CIED) and catheter ablation therapy in the European Society of Cardiology (ESC) area. METHODS AND RESULTS: The European Heart Rhythm Association (EHRA) has been collecting descriptive and quantitative data on invasive arrhythmia therapies since 2008. This year 50 of the 56 ESC member countries provided data for the EHRA White Book. Up-to-date information on procedure rates for the last 5 years together with information on demographics, economy, vital statistics, local healthcare systems, and training activities is presented for each country and the 5 geographical ESC regions. Our analysis indicated that considerable heterogeneity in the access to arrhythmia therapies still exists across the ESC area. In 2015, the CIED implantation rates per million population were highest in the Western followed by the Southern and Northern European countries. The catheter ablation activity was largest in the Western followed by the Northern and Southern areas. Overall, the procedure rates were 3-10 times higher in the European than in the non-European ESC countries. Economic resources were not the only driver for utilization of arrhythmia therapies as in some Eastern European countries with relative low gross domestic product the procedure rates exceeded the average values. CONCLUSION: These data will help the healthcare professionals and stakeholders to identify and to understand in more depth the trends, disparities, and gaps in cardiac arrhythmia care and thereby promote harmonization of cardiac arrhythmias therapies in the ESC area

The role of transforming growth factor-beta in Marfan syndrome

The starting point, in Marfan syndrome (MFS) appears to be the mutation of fi brillin-1 gene whose deconstructed protein product cannot bind transforming growth factor beta (TGF-b), leading to an increased TGF-b tissue level. The aim of this review is to review the already known features of the cellular signal transduction downstream to TGF-b and its impact onthe tissue homeostasis of microfibrils, and elastic fi bers. We also investigate current data onthe extracellular regulation of TGF-b level including mechanotransduction and the feedback cycles of integrin-dependent and independent activation of the latent TGF-b complex. Togetherthese factors, by the destruction of the connective tissue fi bers, may play an important role inthe development of the diverse cardiac and extracardiac manifestations of MFS and many of them could be a target of conservative treatment. We present currently investigated drugs for thetreatment of the syndrome, and explore possible avenues of research into pathogenesis of MFS in order to improve understanding of the disease

May Strenuous Endurance Sports Activity Damage the Cardiovascular System of Healthy Athletes? A Narrative Review

The positive effects of physical activity are countless, not only on the cardiovascular system but on health in general. However, some studies suggest a U-shape relationship between exercise volume and effects on the cardiovascular system. On the basis of this perspective, moderate-dose exercise would be beneficial compared to a sedentary lifestyle, while very high-dose physical activity would paradoxically be detrimental. We reviewed the available evidence on the potential adverse effects of very intense, prolonged exercise on the cardiovascular system, both acute and chronic, in healthy athletes without pre-existing cardiovascular conditions. We found that endurance sports activities may cause reversible electrocardiographic changes, ventricular dysfunction, and troponin elevation with complete recovery within a few days. The theory that repeated bouts of acute stress on the heart may lead to chronic myocardial damage remains to be demonstrated. However, male veteran athletes with a long sports career show an increased prevalence of cardiovascular abnormalities such as electrical conduction delay, atrial fibrillation, myocardial fibrosis, and coronary calcifications compared to non-athletes. It must be underlined that the cause–effect relationship between such abnormalities and the exercise and, most importantly, the prognostic relevance of such findings remains to be established

Transcriptional co-activators YAP1-TAZ of Hippo signalling in doxorubicin-induced cardiomyopathy

Aims Hippo signalling is an evolutionarily conserved pathway that controls organ size by regulating apoptosis, cell proliferation, and stem cell self-renewal. Recently, the pathway has been shown to exert powerful growth regulatory activity in cardiomyocytes. However, the functional role of this stress-related and cell death-related pathway in the human heart and cardiomyocytes is not known. In this study, we investigated the role of the transcriptional co-activators of Hippo signalling, YAP and TAZ, in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in response to cardiotoxic agents and investigated the effects of modulating the pathway on cardiomyocyte function and survival. Methods and results RNA-sequencing analysis of human heart samples with doxorubicin-induced end-stage heart failure and healthy controls showed that YAP and ERBB2 (HER2) as upstream regulators of differentially expressed genes correlated with doxorubicin treatment. Thus, we tested the effects of doxorubicin on hiPSC-CMs in vitro. Using an automated high-content screen of 96 clinically relevant antineoplastic and cardiotherapeutic drugs, we showed that doxorubicin induced the highest activation of YAP/TAZ nuclear translocation in both hiPSC-CMs and control MCF7 breast cancer cells. The overexpression of YAP rescued doxorubicin-induced cell loss in hiPSC-CMs by inhibiting apoptosis and inducing proliferation. In contrast, silencing of YAP and TAZ by siRNAs resulted in elevated mitochondrial membrane potential loss in response to doxorubicin. hiPSC-CM calcium transients did not change in response to YAP/TAZ silencing. Conclusions Our results suggest that Hippo signalling is involved in clinical anthracycline-induced cardiomyopathy. Modelling with hiPSC-CMs in vitro showed similar responses to doxorubicin as adult cardiomyocytes and revealed a potential cardioprotective effect of YAP in doxorubicin-induced cardiotoxicity