ABSTRACT
BACKGROUND: Several non-sarcomeric genes have been postulated to act as modifiers in the phenotypic manifestations of hypertrophic cardiomyopathy (HCM). The development of atrial fibrillation (AF) in HCM has adverse prognostic implications with increased thromboembolism and functional class impairment. AIM: We tested the hypothesis that 2 non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] are associated with the development of AF. DESIGN: Prospective study. METHODS: Two polymorphisms in non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] were analysed in 159 HCM patients (49.3 ± 14.9 years, 70.6% male) and 136 controls. All subjects were clinically stable and in sinus rhythm at entry in the study, without ischemic heart disease or other significant co-morbidities that could mask the effect of the analysed polymorphisms (i.e. previous AF). Thirty-nine patients (24.4%) developed AF during a median follow-up of 49.5 months. RESULTS: Patients with the -344T>C polymorphism in CYP11B2 gene had a higher risk for AF development [HR: 3.31 (95% CI 1.29-8.50); P = 0.008]. In a multivariate analysis, the presence of the C allele in CYP11B2 gene [HR: 3.02 (1.01-8.99); P = 0.047], previous AF [HR: 2.81 (1.09-7.23); P = 0.033] and a left atrial diameter of ≥42 mm [HR: 2.69 (1.01-7.18); P = 0.048] were independent predictors of AF development. The presence of the polymorphic allele was associated with higher aldosterone serum levels. CONCLUSION: We have shown for the first time that the CYP11B2 polymorphism is an independent predictor for AF development in HCM patients. This highlights the importance of non-sarcomeric genes in the phenotypic heterogeneity of HCM. The association with higher aldosterone serum levels could relate to greater fibrosis and cardiac remodelling.
Subject(s)
Atrial Fibrillation/genetics , Cardiomyopathy, Hypertrophic/genetics , Cytochrome P-450 CYP11B2/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Aldosterone/blood , Atrial Fibrillation/blood , Atrial Fibrillation/etiology , Cardiomyopathy, Hypertrophic/blood , Cardiomyopathy, Hypertrophic/complications , Case-Control Studies , Collagen Type I/genetics , Collagen Type I, alpha 1 Chain , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Prospective StudiesABSTRACT
OBJECTIVES: To determine whether serial measures of the interleukin receptor family member soluble ST2 (sST2) provide additional prognostic information to baseline measures for long-term risk stratification of acutely decompensated heart failure (ADHF) patients. METHODS: We prospectively enrolled 72 ADHF patients. Blood samples were collected to measure sST2 concentrations at presentation and on day 4 of hospitalization. All patients were clinically followed, and vital status was registered. RESULTS: Between presentation and day 4, sST2 concentrations decreased from 62 ng/ml (interquartile range 38-105) to 44 ng/ml (interquartile range 26-72; p < 0.001). Both sST2 concentrations at presentation [hazard ratio (HR) 1.011, 95% confidence interval (CI) 1.005-1.016; p < 0.001] and on day 4 (HR 1.015, 95% CI 1.005-1.024; p = 0.003) were independent predictors of mortality. Patients with sST2 ≤ 76 ng/ml at presentation and ≤ 46 ng/ml on day 4 had the lowest mortality rates (3%), whereas those with both sST2 values above these cutoff points had the highest mortality (50%). C index and reclassification analyses demonstrated that the use of serial sST2 measures resulted in an improvement in the accuracy of mortality prediction. CONCLUSIONS: Among ADHF patients, sST2 concentrations tend to decrease following initiation of treatment and are prognostic both at presentation and during hospitalization. Serial sampling of sST2 adds prognostic information and may provide a basis for enhanced clinical decision making.
