[Show abstract][Hide abstract] ABSTRACT: Recent studies have shown that several genetic variants near the PITX2 locus on chromosome 4q25 are associated with atrial fibrillation (AF). However, the mechanism that mediates this association remains unclear. Basic murine studies suggest that reduced PITX2 expression is associated with left atrial dilatation. We sought to examine the association between single nucleotide polymorphisms (SNPs) near PITX2 and left atrial size in patients with AF.
We prospectively enrolled 96 consecutive patients (mean age 60 ± 10 years, 72% male) with drug-resistant AF (57% paroxysmal, 38% persistent, and 5% long-standing persistent) who underwent catheter ablation. Following DNA extraction from blood obtained pre-operatively, SNPs rs10033464 and rs2200733 were genotyped using the Sequenom MassARRAY. Left atrial volume (LAV) was determined using three-dimensional imaging (CT or MRI prior to first ablation) and by investigators blinded to genotype results.
The minor allele frequencies at SNPs rs10033464 and rs2200733 were 0.14 and 0.25, respectively. Using multivariable linear regression, homozygosity for the minor allele at rs10033464 (recessive model) was independently associated with larger LAV (P = 0.002) after adjustment for age, gender, BMI, height, type, and duration of AF, left ventricular ejection fraction, history of hypertension, valve disease, and antiarrhythmic drug use. The strength of the association was reconfirmed in a bootstrap study with 1000 resamplings. In contrast, no association was found between rs2200733 variant alleles and LAV.
SNP rs10033464 near the PITX2 locus on 4q25 is associated with LAV. Left atrial dilatation may mediate the association of common variants at 4q25 with AF.
Clinical Medicine Insights: Cardiology 05/2015; 9:39-45. DOI:10.4137/CMC.S21712
[Show abstract][Hide abstract] ABSTRACT: Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with the common –1306C/T matrix metalloproteinase-2 single nucleotide polymorphism (MMP2 SNP), which reduces the synthesis of matrix metalloproteinase-2 enzyme. Understanding the factors that mediate this association may improve current preventive and therapeutic strategies for AF.Methods
To test the hypothesis that MMP2 SNP is associated with atrial fibrosis, the study was designed as a single center, observational, cross-sectional study. One hundred consecutive patients with symptomatic drug-resistant AF who underwent catheter ablation between September 2009 and February 2011 were enrolled. The endocardial bipolar electrogram voltage was measured point by point in the left atrium as panel data clustered by patient and compared with the result of genetic testing for MMP2 SNP.ResultsMMP2 SNP was present in at least 1 copy in 43% of patients, the minor allele frequency was 0.27, and genotype frequencies were in Hardy-Weinberg equilibrium (Χ2 = 2.34, P = .126). The overall mean atrial voltage for the 4878 measures in 87 patients was 0.89 ± 1.10 mV. MMP2 SNP was significantly associated with reduced bipolar voltage in codominant (–0.11 mV per T copy, P = .003) and dominant (–0.18 mV if CT or TT, P <.001) models clustered by patient and adjusted for age, ethnicity, gender, body mass index, coronary artery disease, hypertension, paroxysmal vs persistent AF, left atrial size, left ventricular ejection fraction, rhythm during voltage sampling, and previous ablations. The results were robust to exclusion of patients with nonsinus rhythm during voltage mapping (n = 13) and of those with prior ablation procedures (n = 5).Conclusions
We report a strong association between a common MMP2 promoter polymorphism and atrial scar fibrosis. Impaired tissue remodeling may mediate the previously reported association between the –1306C/T MMP2 polymorphism and AF.
[Show abstract][Hide abstract] ABSTRACT: The reported complication rate of catheter ablation of atrial fibrillation (AF) varies.
Our goal was to assess temporal trends and the effect of both institutional and individual operators' experience on the incidence of complications.
All patients undergoing AF ablation at Johns Hopkins Hospital between February 2001 and December 2010 were prospectively enrolled in a database. Major complications were defined as those that were life-threatening, resulted in permanent harm, required intervention, or significantly prolonged hospitalization.
Fifty-six major complications occurred in 1190 procedures (4.7%). The majority of complications were vascular (18; 1.5%), followed by pericardial tamponade (13; 1.1%) and cerebrovascular accident (12; 1.1%). No cases of death or atrioesophageal fistula occurred. The overall complication rate decreased from 11.1% in 2002 to 1.6% in 2010 (P <.05). On univariate analysis, demographic and clinical factors associated with the increased risk of complications were CHADS(2) score of ≥2 (hazard ratio [HR] = 2.5; 95% confidence interval [CI] = 1.4-4.4; P = .002), female gender (HR = 2.0; 95% CI = 1.2-3.5; P = .014), and age (HR = 1.03; 95% CI = 1.0-1.1; P = .042). Gender and CHADS(2) score of ≥2 remained independent predictors of complication on multivariable analysis.
The complication rate of catheter ablation of AF decreased with increased institutional experience. Female gender and CHADS(2) score of ≥2 are significant independent risk factors for complications and should be considered when referring patients for AF ablation.
Heart rhythm: the official journal of the Heart Rhythm Society 07/2011; 8(12):1869-74. DOI:10.1016/j.hrthm.2011.07.025 · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Catheter ablation is a widely accepted treatment for drug refractory atrial fibrillation (AF). The purpose of our study was to examine secular trends in the demographic profile of patients undergoing AF ablation.
Data for 792 patients who underwent catheter ablation for AF at Johns Hopkins Hospital between years 2001 and 2009 were systematically reviewed. There has been a steady increase in total number of procedures and repeat procedures. The majority of patients undergoing AF ablation at our institution are men (76.6%). Females accounted for 36.0% of patients in 2001 versus 19.6% in 2009. A total of 93.3% of patients undergoing AF ablation were Caucasian. The mean age of patients has increased over time (52 years in 2001 to 60 years in 2009, P = 0.015) and the number of antiarrhythmic drugs (AADs) used prior to first ablation has decreased (2.3 to 1.2, P = 0.009). In addition, the mean duration of AF prior to first referral has decreased (7.8 years in 2001 vs 4.2 years in 2009).
There is a significant gender and racial disparity in patients undergoing AF ablation favoring Caucasian men that warrants further investigation. We also observed a significant increase in age of patients, decrease in number of AADs, and increase in number of repeat procedures. These results are important when interpreting outcomes of AF ablation and designing future trials.