Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia with a strong genetic component. Molecular pathways involving the homeodomain transcription factor Shox2 control the development and function of the cardiac conduction system in mouse and zebrafish. Here we report the analysis of human SHOX2 as a potential susceptibility gene for early-onset AF. To identify causal variants and define the underlying mechanisms, results from 378 patients with early-onset AF before the age of 60 years were analyzed and compared to 1870 controls or reference datasets. We identified two missense mutations (p.G81E, p.H283Q), that were predicted as damaging. Transactivation studies using SHOX2 targets and phenotypic rescue experiments in zebrafish demonstrated that the p.H283Q mutation severely affects SHOX2 pacemaker function. We also demonstrate an association between a 3′UTR variant c.*28T>C of SHOX2 and AF (p = 0.00515). Patients carrying this variant present significantly longer PR intervals. Mechanistically, this variant creates a functional binding site for hsa-miR-92b-5p. Circulating hsa-miR-92b-5p plasma levels were significantly altered in AF patients carrying the 3′UTR variant (p = 0.0095). Finally, we demonstrate significantly reduced SHOX2 expression levels in right atrial appendages of AF patients compared to patients with sinus rhythm. Together, these results suggest a genetic contribution of SHOX2 in early-onset AF.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-016-0557-2) contains supplementary material, which is available to authorized users.

(1) Since the thoracic cage has inherent weakness anteriorly near the sternum, attention is needed when the anterior approach is used. (2) Hernias with persistent pain and entrapped lung usually need reconstruction with a patch in order to avoid late complications such as recurrent pulmonary infections and hemoptysis due to strangulation.

PET provides functional data, confirms a CT diagnosis and may even increase diagnostic sensitivity in comparison with CT alone in selected cases. Specificity can be compromised by postoperative changes or chronic inflammatory reactions induced by the graft. CT and/or echocardiography should remain the first diagnostic step in case of a suspected infection because of their broad and fast availability. If confirmation is needed or diagnosis is not achievable using conventional methods, PET might be chosen as the next modality to gain additional information in experienced centres.

BackgroundThe number of patients presenting with acute myocardial infarction (AMI) and being untreatable by interventional cardiologists increased during the last years. Previous experience in emergency coronary artery bypass grafting (CABG) in these patients spurred us towards a more liberal acceptance for surgery. Following a prospective protocol, patients were operated on and further analysed.MethodsWithin a two year interval, 127 patients (38 female, age 68±12 years, EuroScore (ES) II 6.7±7.2%) presenting with AMI (86 non-ST-elevated myocardial infarction (NSTEMI), 41 STEMI) were immediately accepted for emergency CABG and operated on within six hours after cardiac catheterisation (77% three-vessel-disease, 47% left main stem stenosis, 11% cardiogenic shock, 21% preoperative intraaortic balloon pump (IABP), left ventricular ejection fraction 48±15%).Results30-day-mortality was 6% (8 patients, 2 NSTEMI (2%) 6 STEMI (15%), p=0.014). Complete revascularisation could be achieved in 80% of the patients using 2±1 grafts and 3±1 distal anastomoses. In total, 66% were supported by IABP, extracorporal life support (ECLS) systems were implanted in two patients. Logistic regression analysis revealed the ES II as an independent risk factor for mortality (p<0.001, HR 1.216, 95%-CI-Intervall 1.082-1.366).ConclusionsQuo ad vitam, results of emergency CABG for patients presenting with NSTEMI can be compared with those of elective revascularisation. Complete revascularisation obviously offers a clear benefit for the patients. Mortality in patients presenting with STEMI and cardiogenic shock is substantially high. For these patients, other concepts regarding timing of surgical revascularisation and bridging until surgery need to be taken into consideration.

AimsIn infective endocarditis (IE), a severe inflammatory disease of the endocardium with an unchanged incidence and mortality rate over the past decades, only 1% of the cases have been described as polymicrobial infections based on microbiological approaches. The aim of this study was to identify potential biodiversity of bacterial species from infected native and prosthetic valves. Furthermore, we compared the ultrastructural micro-environments to detect the localization and distribution patterns of pathogens in IE.Material and methodsUsing next-generation sequencing (NGS) of 16S rDNA, which allows analysis of the entire bacterial community within a single sample, we investigated the biodiversity of infectious bacterial species from resected native and prosthetic valves in a clinical cohort of 8 IE patients. Furthermore, we investigated the ultrastructural infected valve micro-environment by focused ion beam scanning electron microscopy (FIB-SEM).ResultsBiodiversity was detected in 7 of 8 resected heart valves. This comprised 13 bacterial genera and 16 species. In addition to 11 pathogens already described as being IE related, 5 bacterial species were identified as having a novel association. In contrast, valve and blood culture-based diagnosis revealed only 4 species from 3 bacterial genera and did not show any relevant antibiotic resistance. The antibiotics chosen on this basis for treatment, however, did not cover the bacterial spectra identified by our amplicon sequencing analysis in 4 of 8 cases. In addition to intramural distribution patterns of infective bacteria, intracellular localization with evidence of bacterial immune escape mechanisms was identified.ConclusionThe high frequency of polymicrobial infections, pathogen diversity, and intracellular persistence of common IE-causing bacteria may provide clues to help explain the persistent and devastating mortality rate observed for IE. Improved bacterial diagnosis by 16S rDNA NGS that increases the ability to tailor antibiotic therapy may result in improved outcomes.