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Aims: Efficient use of preventive cardiac therapies is often limited by inefficient risk prediction, calling for new prediction tools. Ventricular premature complexes (VPCs) elicit electrocardiographic changes in the repolarization of the first post-extrasystolic normal beat. The aim of this study was to assess whether this post-extrasystolic ST segment and T wave variation (PEST) conveys prognostic information regarding the mortality risk of cardiac patients. Methods: PEST was calculated from 30-min ECGs obtained from 941 survivors of acute myocardial infarction (AMI) as mean difference between the sum of squared voltages from three orthogonal leads (XYZ) of the first (post-extrasystolic) and second (reference) beat after each VPC, in a time window between the limits ϕ1 and ϕ2. Optimal limits yielding a maximum area under the receiver-operating characteristics (ROC) curve were determined by systematic testing, covering the time window from the J point to the end of the T wave. A strong association was found with ϕ1/ϕ2 encompassing 40–230 ms after the J point, which was used to calculate PEST in the analysis. Kaplan-Meier curves and univariable/multivariable Cox proportional hazards models were used to study mortality prediction by PEST. The findings were validated in an independent cohort of 1.788 general population subjects aged 60 years or older. Results: The area under the ROC curve for PEST was 0.72, with an optimum cutoff at ≤ −6.69 mV2. The 88 patients with PEST values below this cutoff had a considerably higher mortality than the remainder of the patients (25% vs. 5.8%, p < 0.0001; univariable hazard ratio 4.7, 95% CI 2.4–12.0, p < 0.001). In a multivariable Cox regression analysis considering left-ventricular ejection fraction, presence of diabetes mellitus, and Global Registry of Acute Coronary Events (GRACE) score, PEST remained significantly associated with mortality (hazard ratio 3.6, 95% CI 1.9–6.9, p < 0.0001). In the validation cohort, abnormal PEST was also associated with significantly increased 4-year mortality (11.9% vs. 4.3%, p = 0.00095). Conclusion: PEST is a strong independent predictor of all-cause mortality in AMI survivors and elderly subjects from the general population. While the pathophysiology of this association remains to be investigated, PEST may complement current risk prediction tools in various clinical settings. [ABSTRACT FROM AUTHOR] more...

To facilitate understanding of human cardiomyocyte (CM) subtype specification, and the study of ventricular CM biology in particular, we developed a broadly applicable strategy for enrichment of ventricular cardiomyocytes (VCMs) derived from human embryonic stem cells (hESCs). A bacterial artificial chromosome transgenic H9 hESC line in which GFP expression was driven by the human ventricular-specific myosin light chain 2 (MYL2) promoter was generated, and screened to identify cell-surface markers specific for MYL2-GFP-expressing VCMs. A CD77+/CD200- cell-surface signature facilitated isolation of >97% cardiac troponin I-positive cells from H9 hESC differentiation cultures, with 65% expressing MYL2-GFP. This study provides a tool for VCM enrichment when using some, but not all, human pluripotent stem cell lines. Tools generated in this study can be utilized toward understanding CM subtype specification, and enriching for VCMs for therapeutic applications. more...

Introduction Coordinated expression of transcription factors in adult heart regulates gene expression programs responsible for cardiomyocyte function. As many of these factors are also essential for cardiac development, it is [...], Human mutations in or variants of TBX20 are associated with congenital heart disease, cardiomyopathy, and arrhythmias. To investigate whether cardiac disease in patients with these conditions results from an embryonic or ongoing requirement for Tbx20 in myocardium, we ablated Tbx20 specifically in adult cardiomyocytes in mice. This ablation resulted in the onset of severe cardiomyopathy accompanied by arrhythmias, with death ensuing within 1 to 2 weeks of Tbx20 ablation. Accounting for this dramatic phenotype, we identified molecular signatures that posit Tbx20 as a central integrator of a genetic program that maintains cardiomyocyte function in the adult heart. Expression of a number of genes encoding critical transcription factors, ion channels, and cytoskeletal/myofibrillar proteins was downregulated consequent to loss of Tbx20. Genome-wide ChIP analysis of Tbx20-binding regions in the adult heart revealed that many of these genes were direct downstream targets of Tbx20 and uncovered a previously undescribed DNA-binding site for Tbx20. Bioinformatics and in vivo functional analyses revealed a cohort of transcription factors that, working with Tbx20, integrated multiple environmental signals to maintain ion channel gene expression in the adult heart. Our data provide insight into the mechanisms by which mutations in TBX20 cause adult heart disease in humans. more...

Disturbed wound healing (DWH) following elective foot and ankle surgery is associated with a number of known risk factors. The purpose of this study was to determine if peripheral artery disease (PAD) is a potential risk factor that contributes to an increase in postoperative DWH. In a case–control study, we analyzed all patients undergoing elective foot and ankle surgery between January 1, 2014 and December 31, 2017 at two institutions and identified 51 patients with postoperative DWH. After matching with 51 control patients without DWH, all 102 patients were evaluated for PAD. The prevalence of PAD was significantly higher in the DWH group compared to the control group (41.2% vs 19.6%, p < 0.01). This difference was even more distinctive for patients with any abnormal ankle–brachial index (ABI) (51.0% vs 19.6%, p < 0.001). After adjustment for diabetes, hypertension, hypercholesterolemia, and smoking, any abnormal ABI or a history of PAD remained an independent risk factor for DWH (odds ratio 3.28; 95% CI 1.24–8.71). In this dual-center study, postoperative DWH was associated with significantly higher rates of PAD. These findings suggest that preoperative evaluation for PAD could be a helpful tool to identify patients at high risk for postoperative wound complications undergoing foot and ankle surgery. This trial is registered with drks.de, number DRKS00012580. [ABSTRACT FROM AUTHOR] more...

Objectives Studies addressing optimal postprocedural pharmacological management after endovascular stenting of iliofemoral post-thrombotic venous obstruction are lacking. We report our early clinical experience with a combination of rivaroxaban and clopidogrel in patients after iliofemoral post-thrombotic venous obstruction stenting. Methods Demographic, procedural, and follow-up data of nine patients (seven women; mean age of 32 ± 11 years) undergoing 10 procedures for iliofemoral post-thrombotic venous obstruction performed between August 2012 and January 2014 were retrospectively reviewed. After endovascular intervention, all patients were administered 20 mg rivaroxaban once daily (s.i.d.) and 75 mg clopidogrel s.i.d. or every second day depending on the individual drug responsiveness for at least six months. The adenosine diphosphate-induced platelet aggregation (platelet aggregation, in aggregation units × min) was assessed on a Multiplate analyzer. Patency was verified venographically at procedure end and was evaluated with duplex ultrasound in regular follow-ups. Results Iliofemoral venous flow was successfully re-established by percutaneous endovascular angioplasty and stent implantation in nine left-sided and one bilateral iliofemoral post-thrombotic venous obstruction. Under dual treatment strategy of rivaroxaban and clopidogrel with platelet aggregation control (median (range): 285 aggregation units × min (192; 402)), none of the patients experienced restenosis or stent thrombosis, respectively. After a median follow-up of 14 months (range: 6–26 months), the primary patency rate was 100% and no in-stent restenosis, stent occlusion or relevant minor or major bleeding occurred. Conclusion Combined factor Xa inhibition and tailored antiplatelet therapy after stenting of iliofemoral post-thrombotic venous obstruction were safe and performed favorably in terms of vessel patency. [ABSTRACT FROM AUTHOR] more...

Background--The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by 18F-fluorodeoxyglucose (18perscript>F-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI 18F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of 18F-FDG positron emission tomography/ magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. Methods and Results--We prospectively enrolled 49 patients with ST-segment-elevation myocardial infarction and performed 18F-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, 99mTcsestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of 18F-FDG-uptake and late gadolinium enhancement showed substantial overlap (κ=0.66), whereas quantitative analysis demonstrated that 18F-FDG extent exceeded late gadolinium enhancement extent (33.2±16.2% left ventricular myocardium versus 20.4±10.6% left ventricular myocardium, P<0.0001) and corresponded to the area at risk (r=0.87, P<0.0001). The peripheral blood count of CD14high/CD16+ monocytes correlated with the infarction size and 18F-FDG signal extent (r=0.53, P<0.002 and r=0.42, P<0.02, respectively). 18F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar, and the standardized uptake valuemean was associated with left ventricular functional outcome independent of infarct size (Δ ejection fraction: P<0.04, Δ end-diastolic volume: P<0.02, Δ end-systolic volume: P<0.005). Conclusions--In this study, the intensity of 18F-FDG uptake in the myocardium after acute myocardial infarction correlated inversely with functional outcome at 6 months. Thus, 18F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury. [ABSTRACT FROM AUTHOR] more...