Factors impacting complication rates for catheter ablation of atrial fibrillation from 2003 to 2015.

Aims: Complications from catheter ablation for atrial fibrillation (AF) are well described. Changing aspects of AF ablation including patient populations referred, institutional experience, and emerging catheter and pharmacological options may impact complication rates. We assessed procedural complication trends in AF ablation patients from 2003­2015 to identify what factors affect adverse event rates. Methods and Results: We evaluated consecutively enrolled patients undergoing initial AF ablation from 2003 through 2015. Statistical analyses were performed to identify predictors of increased risk for major complications, which were defined as death, stroke, atrio-oesophageal fistula, phrenic nerve injury, cardiovascular events requiring blood transfusions or procedural interventions, or non-cardiovascular events requiring intervention. A total of 1475 patients (mean age 59.5 ± 10.5, 82% male) were evaluated. Major complications occurred in 3.9% (n = 58) of cases, including vascular access-site haematoma (1.3%), cardiac tamponade (1.1%), and cerebrovascular accident (CVA) (0.9%). Univariate analysis revealed increased risk of complications associated with hypertension (P = 0.048), CHA2DS2VASc score ≥1 (P = 0.015), and early institutional experience (P = 0.003). Populations with higher CHA2DS2VASc scores underwent AF ablation more frequently over time (P < 0.001). Novel catheters and anticoagulants did not appreciably affect complication rates. Multivariate analysis adjusting for hypertension, CHA2DS2VASc score, and institutional experience showed that higher CHA2DS2VASc score and early institutional experience were independent predictors of adverse events. Conclusion: Patient characteristics reflected in CHA2DS2VASc scoring and early institutional experience predict increased complication rates following AF ablation. Despite more patients with higher CHA2DS2VASc scores undergoing AF ablation, complication rates fell over time as institutional experience increased.

Single nucleotide polymorphisms in proximity to K-channel genes are associated with decreased longitudinal QTc variance.

BACKGROUND: Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Despite significant progress in identification of predisposing factors, the pathophysiology of AF remains to be elucidated. Previous studies have reported that single nucleotide polymorphisms (SNPs) in potassium-channel genes associate with AF and the instantaneous corrected QT interval (QTc). The purpose of this study was to examine the association between SNPs in proximity to KCNQ1, KCNH2, KCNE2, and KCNJ2 and longitudinal QTc variations in patients with AF. METHODS AND RESULTS: We conducted a retrospective cohort study of 800 electrocardiograms from 93 patients with AF. All patients were Caucasian, with an average age of 61.2 years, and 72% were male. Of all patients, 37% had persistent AF, and 63% had paroxysmal AF. Following DNA extraction from blood, SNPs at the AF-associated loci KCNQ1, KCNH2, KCNE2, and KCNJ2 were genotyped using the Sequenom MassARRAY. Using a linear regression model and adapting a resampling inference, a decrease in longitudinal QTc variance was found to associate with SNPs near KCNH2 (rs10240738) and KCNJ2 (rs8079702) when adjusted for patient age, gender, AF type, and average QTc. On average, patients with these SNPs had a shorter QTc interval. In addition, we fitted a multilevel mixed effects regression model accounting for subject level heterogeneity and found no longitudinal association between presence of SNPs near K-channel genes and changes in QTc. CONCLUSION: Polymorphisms near specific potassium-channel genes in AF patients are associated with decreased longitudinal QTc variance and a shorter average QTc. These results support the hypothesis that effects on myocardial repolarization may mediate the association of these SNPs and AF.

Diflunisal treatment is associated with improved survival for patients with early stage wild-type transthyretin (ATTR) amyloid cardiomyopathy: the Boston University Amyloidosis Center experience.

BACKGROUND: Diflunisal is a non-steroidal anti-inflammatory drug that stabilises transthyretin (TTR) and reduces neurologic deterioration in patients with polyneuropathy caused by hereditary transthyretin amyloidosis (ATTRv). METHODS: We conducted a retrospective cohort study of patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) treated with diflunisal for at least one year between 2009 and 2016 at the Boston University Amyloidosis Centre. Baseline and one year follow up characteristics were measured, including plasma chemistries and echocardiography. Cox proportional hazards analysis assessed the primary outcome of all-cause mortality. RESULTS: A total of 104 ATTRwt-CM patients were evaluated with 35 patients receiving diflunisal. Patients in the diflunisal group were younger (73.8 vs 76.8 years, p = 0.034), with lower B-type natriuretic peptide (BNP, 335 +/- 67 vs. 520 +/- 296 pg/mL, p = 0.006), similar troponin I (0.1 +/- 0.1 vs 0.2 +/- 0.3 ng/mL, p = 0.09), and better renal function (eGFR 67 +/- 17 vs 53 +/- 18 mL/min/1.73m2, p = 0.0002) at baseline. Over a median follow-up of 3.2 years, 52 deaths occurred. Diflunisal administration was associated with improved survival in unadjusted analysis (HR 0.13, 95% CI 0.05 - 0.36, p < 0.001) that persisted after adjustment for age, baseline BNP, eGFR, troponin I, interventricular septal thickness, and left ventricular ejection fraction (HR 0.18, 95% CI 0.06 - 0.51, p = 0.0006). Over the observation period, no significant changes in BNP, troponin I, interventricular septal thickness or left ventricular ejection fraction were observed with diflunisal treatment. A total of 14 patients (40%) discontinued diflunisal in this study, but only 3 within the first year. Mean eGFR in treated patients was 59 ml/min/1.73m2 at 1 year (change from baseline p = 0.03). CONCLUSION: Diflunisal administration in ATTRwt-CM was associated with improved survival and overall stability in clinical and echocardiographic markers of disease with decrement renal function.

Features of atrial fibrillation in wild-type transthyretin cardiac amyloidosis: a systematic review and clinical experience.

AIMS: Wild-type transthyretin (ATTRwt) cardiac amyloidosis has emerged as an important cause of heart failure in the elderly. Atrial fibrillation (AF) commonly affects older adults with heart failure and is associated with reduced survival, but its role in ATTRwt is unclear. We sought to explore the clinical impact of AF in ATTRwt. METHODS AND RESULTS: Patients with biopsy-proven ATTRwt cardiac amyloidosis (n = 146) were retrospectively identified, and clinical, echocardiographic, and biochemical data were collected. Patients were classified as AF or non-AF and followed for survival for a median of 41.4 ± 27.1 months. Means testing, univariable, and multivariable regression models were employed. A systematic review was performed. AF was observed in 70% (n = 102). Mean age was similar (AF, 75 ± 6 vs. non-AF, 74 ± 5 years, P = 0.22). Anticoagulant treatment of patients with AF was as follows: 78% warfarin, 17% novel anticoagulant, and 6% no anticoagulation. Amiodarone was prescribed to 24%. There were no differences in left ventricular ejection fraction (P = 0.09) or left atrial volume (P = 0.87); however, mean diastolic dysfunction grade was higher in AF (mean 2.7 ± 0.5 vs. 2.4 ± 0.5, P = 0.01). While creatinine (P = 0.52) and B-type natriuretic peptide (P = 0.48) were similar, patients with AF had lower serum transthyretin concentrations (221 ± 51 vs. 250 ± 52 µg/mL, P < 0.01). Survival between groups was similar (P = 0.46). CONCLUSIONS: These data provide an evidence basis for clinical management and demonstrate that AF in ATTRwt does not negatively impact survival. Further analysis of the relationship between transthyretin concentration and AF development is warranted.

Association of common variations on chromosome 4q25 and left atrial volume in patients with atrial fibrillation.

AIMS: 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. METHODS: 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. 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. CONCLUSION: 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.