Heart and Vessels / Prevalence of early repolarization syndrome and long-term clinical outcome in patients with the diagnosis of idiopathic ventricular fibrillation

Idiopathic ventricular fibrillation (IVF) is diagnosed in up to 14% of sudden cardiac death (SCD) survivors. Early repolarization syndrome (ERS) in patients with ventricular tachyarrhythmia is characterized by an elevated J-point in inferior and/or antero-lateral leads. Our objectives were to determine the prevalence of ERS in IVF patients, and to evaluate potential differences in clinical outcome. Out of 3,552 implantable cardioverter defibrillator (ICD) carriers, 758 SCD survivors were retrospectively identified from the databases of the Medical Universities of Vienna and Innsbruck within the last three decades. Early repolarization pattern (ERP) was classified either as "notching" or "slurring". Endpoints were defined as appropriate ICD therapies for ventricular tachyarrhythmia, either anti-tachycardia pacing or shock, and all-cause mortality. After exclusion of recognized reasons for SCD, 50 patients were assigned to the diagnosis of IVF (6.6%). An ERP was identified in 10 patients, most of them with notching (n=8). After a mean follow-up of 11.26.7 years (539.3 patient years), appropriate ICD therapies were found in 50% of ERS and 43% of IVF patients without ERP (p=0.732). In ERS patients, all ICD therapies were found in patients with notching pattern. Similarly, incidence of inappropriate ICD therapies, and all-cause mortality was comparable (30% vs. 23%, p=0.707; 10% vs. 5%, p=0.496, respectively). In 758 SCD survivors, we found a low prevalence of IVF and ERS. Similar event rates were reported concerning all-cause mortality and ICD therapies for ventricular tachyarrhythmia after long-term follow-up in this cohort.(VLID)364364

Journal of Clinical Medicine / New Cardiovascular Biomarkers in Ischemic Heart DiseaseGDF-15, A Probable Predictor for Ejection Fraction

Background: Various biomarkers have been associated with coronary artery disease (CAD) and ischemic heart failure. The aim of this study was to investigate the correlation of serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), and soluble suppression of tumorigenicity 2 (sST2) with left ventricular ejection fraction (EF) in CAD patients and controls. Methods and Results: CAD patients were divided into three groups according to their EF as measured by the biplane Simpson method (5384%, 3152%, 30%). Overall, 361 subjects were analyzed. In total, 155 CAD patients had an EF of 5384%, 71 patients had an EF of 3152%, and 23 patients had an EF of 30% as compared to 112 healthy controls (age 51.3 9.0 years, 44.6% female). Mean ages according to EF were 62.1 10.9, 65.2 10.1, and 66.6 8.2 years, respectively, with females representing 29.0, 29.6, and 13.0%. suPAR, GDF-15, H-FABP, and sST2 values were significantly higher in CAD patients and showed an exponential increase with decreasing EF. In a multiple logistic regression model, GDF-15 (p = 0.009), and NT-brain natriuretic peptide (p = 0.003) were independently associated with EF. Conclusion: Biomarkers such as suPAR, GDF-15, H-FABP, and sST2 are increased in CAD patients, especially in highly impaired EF. Besides NT-proBNP as a well-known marker for risk prediction, GDF-15 may be an additional tool for diagnosis and clinical follow-up.(VLID)491673

Heart and Vessels / Long-term physical activity leads to a significant increase in serum sRAGE levels : a sign of decreased AGE-mediated inflammation due to physical activity?

There is growing evidence that low levels of the circulating soluble receptor of advanced glycation end products (sRAGE) are a valuable predictor of cardiovascular disease (CVD). The aim of this prospective study was to investigate the influence of long-term physical activity on serum sRAGE levels. 109 subjects were recruited, and 98 completed the study. Participants were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. sRAGE was measured at baseline and after 2/6/8 months by ELISA. Backwards, multiple linear regression analysis was performed to investigate the association of co-variables age, sex, BMI, and performance at baseline, HbA1c, and lipoprotein a with baseline sRAGE levels. We identified BMI and lipoprotein a as significant predictors for baseline sRAGE levels. Compared to subjects with a performance gain 4.9% subjects with a gain > 5% showed a significant increase in sRAGE levels up to 22%. sRAGE serum levels correlate negatively with lipoprotein a levels and BMI and long-term physical activity leads to a significant increase in serum sRAGE levels (922%), whereby the sRAGE increase is most pronounced in subjects with initially low-performance levels, suggesting that in particular, these subject profit the most from increased physical activity. The sport-mediated increase of sRAGE might be a sign of decreased AGE-mediated inflammation and highlight the protective effect of sports on CVD and other disease which are at least partly mediated by an increased inflammation status. Clinical trials registration NCT02097199.(VLID)359103

PLOS ONE / Presence of isolated tricuspid regurgitation should prompt the suspicion of heart failure with preserved ejection fraction

Background Diastolic dysfunction of the left ventricle is common but frequently under-diagnosed. Particularly in advanced stages affected patients may present with significant functional tricuspid regurgitation (TR) as the most prominent sign on echocardiography. The underlying left ventricular pathology may eventually be missed and symptoms of heart failure are attributed to TR, with respective therapeutic consequences. The aim of the present study was to determine prevalence and mechanisms underlying TR evolution in heart failure with preserved ejection fraction (HFpEF). Methods and results Consecutive HFpEF patients were enrolled in this prospective, observational study. Confirmatory diagnostic tests including echocardiography and invasive hemodynamic assessments were performed. Of the 175 patients registered between 2010 and 2014, 51% had significant (moderate or severe) TR without structural abnormalities of the tricuspid valve. Significant hemodynamic differences between patients with and without relevant TR were encountered. These included elevated pulmonary vascular resistance (p = 0.038), reduced pulmonary arterial compliance (PAC, p = 0.005), and elevated left ventricular filling pressures (p = 0.039) in the TR group. Multivariable binary logistic regression analysis revealed diastolic pulmonary artery pressure (p = 0.029) and PAC (p = 0.048) as independent determinants of TR. Patients were followed for 18.114.1 months, during which 32% had a cardiac event. While TR was associated with outcome in the univariable analysis, it failed to predict event-free survival in the multivariable model. Conclusions The presence of isolated functional TR should prompt the suspicion of HFpEF. Our data show that significant TR is a marker of advanced HFpEF but neither an isolated entity nor independently associated with event-free survival.(VLID)486885

Patients with Heart Failure and Preserved Ejection Fraction Are at Risk of Gastrointestinal Bleeding

Aims. Two thirds of patients with heart failure and preserved ejection fraction (HFpEF) have an indication for oral anticoagulation (OAC) to prevent thromboembolic events. However, evidence regarding the safety of OAC in HFpEF is limited. Therefore, our aim was to describe bleeding events and to find predictors of bleeding in a large HFpEF cohort. Methods and Results. We recorded bleeding events in a prospective HFpEF cohort. Out of 328 patients (median age 71 years (interquartile range (IQR) 67–77)), 64.6% (n = 212) were treated with OAC. Of those, 65.1% (n = 138) received vitamin-K-antagonists (VKA) and 34.9% (n = 72) non-vitamin K oral anticoagulants (NOACs). During a median follow-up time of 42 (IQR 17–63) months, a total of 54 bleeding events occurred. Patients on OAC experienced more bleeding events (n = 49 (23.1%) versus n = 5 (4.3%), p < 0.001). Major drivers of events were gastrointestinal (GI) bleeding (n = 18 (36.7%)]. HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score (hazard ratios (HR) of 2.15 (95% confidence interval (CI) 1.65–2.79, p < 0.001)) was the strongest independent predictor for overall bleeding. In the subgroup of GI bleeding, mean right atrial pressure (mRAP: HR of 1.13 (95% CI 1.03–1.25, p = 0.013)) and HAS-BLED score (HR of 1.74 (95% CI 1.15–2.64, p = 0.009)] remained significantly associatiated with bleeding events after adjustment. mRAP provided additional prognostic value beyond the HAS-BLED score with an improvement from 0.63 to 0.71 (95% CI 0.58–0.84, p for comparison 0.032), by C-statistic. This additional prognostic value was confirmed by significant improvements in net reclassification index (61.3%, p = 0.019) and integrated discrimination improvement (3.4%, p = 0.015). Conclusion. OAC-treated HFpEF patients are at high risk of GI bleeding. High mRAP as an indicator of advanced stage of disease was predictive for GI bleeding events and provided additional risk stratification information beyond that obtained by HAS-BLED score