Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.

Background The prognostic significance of uric acid (UA) levels in acute stroke is unclear, so the objective of this study was to determine the association between levels of serum UA (SUA) and mortality in acute stroke. Methods and Results Consecutive patients (n=435) presenting with ischemic stroke and intracerebral hemorrhage were included in the study. The length of stay in hospital and the occurrence of death were recorded. On univariate analysis, the occurrence of death was associated with older age, smoking, presence of congestive heart failure or atrial fibrillation, absence of hyperlipidemia, and intracerebral hemorrhage as the index event. Furthermore, glucose, urea, creatinine and SUA at admission were significantly higher in patients who died, whereas total and high-density-lipoprotein cholesterol were significantly lower. On multiple logistic regression analysis, the independent relationship between higher SUA levels and death was confirmed (odds ratio (OR), 1.37; 95%confidence interval (CI), 1.13-1.67; p=0.001). The only other variables independently associated with the occurrence of death were urea concentration and presence of atrial fibrillation. If urate was >7.8 mg/dl (0.47 mmol/L), then there would be a high probability of early death (87%). Conclusions Elevated levels of SUA are independently associated with an increased risk of early death in acute stroke. (Circ J 2007; 71: 1120 - 1127)

Background: The prevalence, clinical characteristics and natural history of patients with hypertrophic cardiomyopathy (HCM) and midventricular obstruction (MVO) have not been adequately studied. Methods and Results: A single-center cohort consisting of 423 patients (mean age, 49.3±17.2 years; 66.2% male) was thoroughly followed up for a median of 84 months (7 years; range, 6–480 months). MVO, characterized by the echocardiographic appearance of midventricular muscular apposition with a simultaneous mid-cavitary gradient ≥30mmHg, was identified in 34 patients (8%). Patients with MVO tended to be more symptomatic during their initial evaluation (>90% presented with NYHA class ≥II) compared to the rest of the HCM cohort. Apical aneurysm formation was identified in more than one-fourth of patients with MVO (26.5%), being a characteristic of the group. On multivariate Cox regression hazard analysis, presence of MVO strongly predicted progression to end-stage (burnt out) HCM and related heart failure (HF) deaths (hazard ratio, [HR], 2.62; 95% confidence interval [CI]: 1.2–8.8; P=0.047), as well as sudden death and associated lethal arrhythmic events (HR, 3.3; 95% CI: 1.26–8.85; P=0.016). Conclusions: MVO is a distinct phenotype of HCM associated with unfavorable prognosis in terms of end-stage HCM, sudden death and lethal arrhythmic events. The high adverse outcome rate necessitates early recognition of MVO and appropriate therapeutic interventions. (Circ J 2013; 77: 2366–2374)

Introduction : The short-term effects of multifactorial intervention for cardiovascular disease (CVD) prevention on renal function and serum uric acid (SUA) levels in patients with stage 3 chronic kidney disease (CKD) and multiple CVD risk factors are unclear. The aim of the study was to...