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Background Transforming growth factor s (TGFs) signaling has been shown to promote myocardial fibrosis and remodeling with coronary artery disease (CAD), and previous studies show a major role for fibrosis in the initiation of malignant ventricular arrhythmias (VA) and sudden cardiac arrest (SCA). Common single nucleotide polymorphisms (SNPs) in TGFs pathway genes may be associated with SCA. Objective We examined the association of common SNPs among 12 candidate genes in the TGFs pathway with the risk of SCA. Methods SNPs (n = 617) were genotyped in a case-control study comparing 89 patients with CAD and SCA caused by VA to 520 healthy control subjects. Results Nineteen SNPs among 5 genes (TGFB2, TGFBR2, SMAD1, SMAD3, SMAD6) were associated with SCA after adjustment for age and sex. After permutation analysis to account for multiple testing, a single SNP in TGFBR2 (rs9838682) was associated with SCA (odds ratio: 1.66, 95% confidence interval: 1.08 to 2.54, P = .02). Conclusion We show an association between a common TGFBR2 polymorphism and risk of SCA caused by VA in the setting of CAD. If validated, these findings support the role of genetic variation in TGFs signaling in SCA susceptibility.

Background Atrial arrhythmias are associated with inflammation. The cause and effect of the association are unknown. Objective The purpose of this study was to test the hypothesis that atrial tachyarrhythmias contribute to inflammation. Methods We performed a prospective observational study wherein C-reactive protein (CRP) and interleukin-6 (IL-6) levels from the femoral vein and coronary sinus (CS) were compared before curative ablation for atrial flutter (AFL; n=59) and paroxysmal supraventricular tachycardia (SVT; n=110). Follow-up levels were obtained at 1 and 6 months. Results Peripheral levels of both biomarkers were significantly higher in the AFL group. After multivariate adjustment, only those in the AFL group who presented in AFL or atrial fibrillation (AF) had significantly elevated CRP levels (odds ratio 1.26; P = .033). Levels of each marker were similar in the CS and peripheral blood in the SVT group; in the AFL group, both CRP and IL-6 were significantly lower in the CS than in the periphery ( P = .0076 and P = .0021, respectively). CRP was significantly lower a median of 47 days after AFL ablation (from a median of 6.28 mg/L to a median of 2.92 mg/L; P = .028) and remained reduced at second follow-up. IL-6 decreased across three time points after AFL ablation ( P = .002). No reduction in inflammatory biomarkers was observed after SVT ablation. Conclusions CRP and IL-6 levels are elevated in patients presenting in AFL. Given the lower CS values in these patients, their origin appears to be systemic rather than cardiac. Because these levels significantly fall after ablation of AFL, the atrial tachyarrhythmia appears to be the cause (not the effect) of the inflammation.

Background Previous studies suggest that beta-adrenergic receptor (sAR) single nucleotide polymorphisms (SNPs) are associated with out-of-hospital sudden cardiac death (SCD) and overall mortality, but did not specifically examine risk of ventricular arrhythmias (VA). Objective This study examined the effects of functional SNPs of s1AR and s2AR on the risk of VA and SCD in patients with coronary artery disease (CAD). Methods s1AR (Ser49Gly, Arg389Gly) and s2AR (Gly16Arg, Gln27Glu) SNPs were genotyped in a case-control study comparing 107 patients with CAD and aborted SCD due to VA with 287 CAD control subjects and 101 healthy control subjects. These variants were also examined in the Heart and Estrogen Replacement Study (HERS) cohort of women with CAD followed for SCD (n = 66) and nonfatal VA (NFVA) (n = 33) over 6.8 years. Results In the case-control study, no statistically significant association was observed for the odds of SCD with any of the SNPs or haplotypes tested. Similarly, HERS revealed null effects for these SNPs and haplotypes in relation to risk of SCD, SCD + NFVA, and all-cause mortality. Point estimates and confidence intervals for risk of SCD associated with s2AR27 were similar in both populations (Glu27 carriers vs Gln27 homozygotes: adjusted odds ratio 1.23 [95% confidence interval 0.75 to 2.03, P = .41] in the case-control study, and adjusted relative risk (RR) 1.18 [95% confidence interval 0.69 to 2.00, P = .55] in HERS). These null findings trend in the opposite direction and differ from previous published estimates ( P = .01 and .07, respectively). Conclusion We did not find an increase in risk of SCD associated with any of these common sAR polymorphisms.