Usha B. Tedrow

Meta-analysis identifies six new susceptibility loci for atrial fibrillation

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10−8). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.

The long- and short-term impact of elevated body mass index on the risk of new atrial fibrillation the WHS (women's health study).

OBJECTIVES The purpose of this study was to characterize the relationship between changes in body mass index (BMI) and incident atrial fibrillation (AF) in a large cohort of women. BACKGROUND Obesity and AF are increasing public health problems. The importance of dynamic obesity-associated AF risk is uncertain, and mediators are not well characterized. METHODS Cases of AF were confirmed by medical record review in 34,309 participants in the Womens Health Study. Baseline and updated measures of BMI were obtained from periodic questionnaires. RESULTS During 12.9 +/- 1.9 years of follow-up, 834 AF events were confirmed. BMI was linearly associated with AF risk, with a 4.7% (95% confidence interval [CI]: 3.4 to 6.1, p < 0.0001) increase in risk with each kilogram per square meter. Adjustment for inflammatory markers minimally attenuated this risk. When updated measures of BMI were used to estimate dynamic risk, overweight (hazard ratio [HR]: 1.22; 95% CI: 1.02 to 1.45, p = 0.03), and obesity (HR: 1.65; 95% CI: 1.36 to 2.00; p < 0.0001) were associated with adjusted short-term increases in AF risk. Participants becoming obese during the first 60 months had a 41% adjusted increase in risk of the development of AF (p = 0.02) compared with those maintaining BMI <30 kg/m(2). The prevalence of overweight and obesity increased over time. The adjusted proportion of incident AF attributable to short-term elevations in BMI was substantial (18.3%). CONCLUSIONS In this population of apparently healthy women, BMI was associated with short- and long-term increases in AF risk, accounting for a large proportion of incident AF independent of traditional risk factors. A strategy of weight control may reduce the increasing incidence of AF. (Womens Health Study [WHS]: A Randomized Trial of Low-Dose Aspirin and Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer; NCT00000479).

Catheter ablation of ventricular tachycardia after repair of congenital heart disease : Electroanatomic identification of the critical right ventricular isthmus

Background— Catheter ablation of ventricular tachycardia (VT) after repair of congenital heart disease can be difficult because of nonmappable VTs and complex anatomy. Insights into the relation between anatomic isthmuses identified by delineating unexcitable tissue using substrate mapping techniques and critical reentry circuit isthmuses might facilitate ablation. Methods and Results— Sinus rhythm voltage mapping of the right ventricle was performed in 11 patients with sustained VT after repair of congenital heart disease. Unexcitable tissue from patch material, valve annulus, or dense fibrosis, identified from bipolar voltage (<0.5 mV) and pacing threshold (>10 mA), was defined as an anatomic isthmus boundary bordering 4 isthmuses between (1) the tricuspid annulus and scar/patch in the anterior right ventricular outflow, (2) the pulmonary annulus and right ventricular free wall scar/patch, (3) the pulmonary annulus and septal scar/patch, and (4) the septal scar/patch and tricuspid annulus. The reentry circuit isthmuses of all induced 15 VTs (mean cycle length, 276±78 ms; 73% poorly tolerated), identified by activation, entrainment, and/or pace mapping, were located in an anatomic isthmus (11 of 15 VTs in anatomic isthmus 1). Transecting the anatomic isthmuses by ablation lesions abolished all VTs. During 30.4±29.3 months of follow-up, 91% of patients remained free of VT. Conclusions— Reentry circuit isthmuses in VT late after repair of congenital heart disease are located within anatomically defined isthmuses bordered by unexcitable tissue. The boundaries can be identified with 3-dimensional substrate mapping and connected by ablation lines during sinus rhythm. These findings should facilitate catheter and surgical ablation of stable and unstable VTs.

Risk of death and cardiovascular events in initially healthy women with new-onset atrial fibrillation

CONTEXT The risks associated with new-onset atrial fibrillation (AF) among middle-aged women and populations with a low comorbidity burden are poorly defined. OBJECTIVES To examine the association between incident AF and mortality in initially healthy women and to evaluate the influence of associated cardiovascular comorbidities on risk. DESIGN, SETTING, AND PARTICIPANTS Between 1993 and March 16, 2010, 34,722 women participating in the Womens Health Study underwent prospective follow-up. Participants were 95% white, older than 45 years (median, 53 [interquartile range {IQR}, 49-59] years), and free of AF and cardiovascular disease at baseline. Cox proportional hazards models with time-varying covariates were used to determine the risk of events among women with incident AF. Secondary analyses were performed among women with paroxysmal AF. MAIN OUTCOME MEASURES Primary outcomes included all-cause, cardiovascular, and noncardiovascular mortality. Secondary outcomes included stroke, congestive heart failure, and myocardial infarction. RESULTS During a median follow-up of 15.4 (IQR, 14.7-15.8) years, 1011 women developed AF. Incidence rates per 1000 person-years among women with and without AF were 10.8 (95% confidence interval [CI], 8.1-13.5) and 3.1 (95% CI, 2.9-3.2) for all-cause mortality, 4.3 (95% CI, 2.6-6.0) and 0.57 (95% CI, 0.5-0.6) for cardiovascular mortality, and 6.5 (95% CI, 4.4-8.6) and 2.5 (95% CI, 2.4-2.6) for noncardiovascular mortality, respectively. In multivariable models, hazard ratios (HRs) of new-onset AF for all-cause, cardiovascular, and noncardiovascular mortality were 2.14 (95% CI, 1.64-2.77), 4.18 (95% CI, 2.69-6.51), and 1.66 (95% CI, 1.19-2.30), respectively. Adjustment for nonfatal cardiovascular events potentially on the causal pathway to death attenuated these risks, but incident AF remained associated with all mortality components (all-cause: HR, 1.70 [95% CI, 1.30-2.22]; cardiovascular: HR, 2.57 [95% CI, 1.63-4.07]; and noncardiovascular: HR, 1.42 [95% CI, 1.02-1.98]). Among women with paroxysmal AF (n = 656), the increase in mortality risk was limited to cardiovascular causes (HR, 2.94; 95% CI, 1.55-5.59). CONCLUSION Among a group of healthy women, new-onset AF was independently associated with all-cause, cardiovascular, and noncardiovascular mortality, with some of the risk potentially explained by nonfatal cardiovascular events.

Influence of Systolic and Diastolic Blood Pressure on the Risk of Incident Atrial Fibrillation in Women

Background— The influence of systolic and diastolic blood pressure (BP) on incident atrial fibrillation (AF) is not well studied among initially healthy, middle-aged women. Methods and Results— A total of 34 221 women participating in the Womens Health Study were prospectively followed up for incident AF. The risk of AF across categories of systolic and diastolic BP was compared by use of Cox proportional-hazards models. During 12.4 years of follow-up, 644 incident AF events occurred. Using BP measurements at baseline, we discovered that the long-term risk of AF was significantly increased across categories of systolic and diastolic BP. Multivariable-adjusted hazard ratios for systolic BP categories (<120, 120 to 129, 130 to 139, 140 to 159, and ≥160 mm Hg) were 1.0, 1.00 (95% CI, 0.78 to 1.28), 1.28 (95% CI, 1.00 to 1.63), 1.56 (95% CI, 1.22 to 2.01), and 2.74 (95% CI, 1.77 to 4.22) (P for trend <0.0001). Adjusted hazard ratios across baseline diastolic BP categories (<65, 65 to 74, 75 to 84, 85 to 89, 90 to 94, and ≥95 mm Hg) were 1.0, 1.17 (95% CI, 0.81 to 1.69), 1.18 (95% CI, 0.84 to 1.65), 1.53 (95% CI, 1.05 to 2.23), 1.35 (95% CI, 0.82 to 2.22), and 2.15 (95% CI, 1.21 to 3.84) (P for trend=0.004). When BP changes over time were accounted for in updated models, multivariable-adjusted hazard ratios were 1.0, 1.14 (95% CI, 0.89 to 1.46), 1.37 (95% CI, 1.07 to 1.76), 1.71 (95% CI, 1.33 to 2.21), and 2.21 (95% CI, 1.45 to 3.36) (P for trend <0.0001) for systolic BP categories and 1.0, 1.12 (95% CI, 0.82 to 1.52), 1.13 (95% CI, 0.83 to 1.52), 1.30 (95% CI, 0.89 to 1.88), 1.50 (95% CI, 1.01 to 1.88), and 1.54 (95% CI, 0.75 to 3.14) (P for trend=0.026) for diastolic BP categories. Conclusions— In this large cohort of initially healthy women, BP was strongly associated with incident AF, and systolic BP was a better predictor than diastolic BP. Systolic BP levels within the nonhypertensive range were independently associated with incident AF even after BP changes over time were taken into account.

Alcohol Consumption and Risk of Incident Atrial Fibrillation in Women

CONTEXT Previous studies suggest that consuming moderate to high amounts of alcohol on a regular basis might increase the risk of developing atrial fibrillation in men but not in women. However, these studies were not powered to investigate the association of alcohol consumption and atrial fibrillation among women. OBJECTIVE To prospectively assess the association between regular alcohol consumption and incident atrial fibrillation among women. DESIGN, SETTING, AND PARTICIPANTS Participants were 34 715 initially healthy women participating in the Womens Health Study, a completed randomized controlled trial conducted in the United States. Participants were older than 45 years and free of atrial fibrillation at baseline and underwent prospective follow-up from 1993 to October 31, 2006. Alcohol consumption was assessed via questionnaires at baseline and at 48 months of follow-up and was grouped into 4 categories (0, > 0 and < 1, > or = 1 and < 2, and > or = 2 drinks per day). Atrial fibrillation was self-reported on the yearly questionnaires and subsequently confirmed by electrocardiogram and medical record review. MAIN OUTCOME MEASURE Time to first episode of atrial fibrillation. RESULTS Over a median follow-up of 12.4 years, 653 cases of incident atrial fibrillation were confirmed. Age-adjusted incidences among women consuming 0 (n = 15,370), more than 0 and less than 1 (n = 15,758), 1 or more and less than 2 (n = 2228), and 2 or more (n = 1359) drinks per day were 1.59, 1.55, 1.27, and 2.25 events/1000 person-years of follow-up. Thus, compared with nondrinking women, women consuming 2 or more drinks per day had an absolute risk increase of 0.66 events/1000 person-years. The corresponding multivariate-adjusted hazard ratios (HRs) for incident atrial fibrillation were 1, 1.05 (95% CI, 0.88-1.25), 0.84 (95% CI, 0.58-1.22), and 1.60 (95% CI, 1.13-2.25), respectively. The increased hazard in the small group of women consuming 2 or more drinks per day persisted when alcohol intake was updated at 48 months (HR, 1.49; 95% CI, 1.05-2.11) or when women were censored at their first cardiovascular event (HR, 1.68; 95% CI, 1.18-2.39). CONCLUSIONS Among healthy middle-aged women, consumption of up to 2 alcoholic beverages per day was not associated with an increased risk of incident atrial fibrillation. Heavier consumption of 2 or more drinks per day, however, was associated with a small but statistically significant increased risk of atrial fibrillation.

Ventricular arrhythmias and sudden cardiac death

Management strategies for ventricular arrhythmias are guided by the risk of sudden death and severity of symptoms. Patients with a substantial risk of sudden death usually need an implantable cardioverter defibrillator (ICD). Although ICDs effectively end most episodes of ventricular tachycardia or ventricular fibrillation and decrease mortality in specific populations of patients, they have inherent risks and limitations. Generally, antiarrhythmic drugs do not provide sufficient protection from sudden death, but do have a role in reducing arrhythmias that cause symptoms. Catheter ablation is likewise important for reducing the frequency of spontaneous arrhythmias and is curative for some patients, usually those with idiopathic arrhythmias and no heart disease. Arrhythmia surgery is now infrequent, offered by only a few specialised centres for refractory arrhythmias. Advances in understanding of genetic arrhythmia syndromes and in technology for mapping and ablation of ventricular arrhythmias, and enhanced algorithms in implantable devices for rhythm management, have contributed to improved outcomes.

Incidence and predictors of major complications from contemporary catheter ablation to treat cardiac arrhythmias

BACKGROUND Updated understanding of the risks of catheter ablation is important because techniques have evolved for procedures treating non-life-threatening as well as potentially lethal arrhythmias. OBJECTIVE This prospective study sought to assess the incidence and predictors of major complications from contemporary catheter ablation procedures at a high-volume center. METHODS Over a 2-year period, 1,676 consecutive ablation procedures were prospectively evaluated for major complications throughout 30 days postprocedure. Predictors of major complications were determined in a multivariate analysis adjusted for demographics, clinical variables, ablation type, and procedural factors. RESULTS Rates of major complications differed between procedure types, ranging from 0.8% for supraventricular tachycardia, 3.4% for idiopathic ventricular tachycardia (VT), 5.2% for atrial fibrillation (AF), and 6.0% for VT associated with structural heart disease (SHD). Ablation type (ablation for AF [odds ratio (OR) 5.53, 95% confidence interval (CI) 1.81 to 16.83], for VT with SHD [OR 8.61, 95% CI 2.37 to 31.31], or for idiopathic VT [OR 5.93, 95% CI 1.40 to 25.05] all referenced to supraventricular tachycardia ablation), and serum creatinine level >1.5 mg/dl (OR 2.48, 95% CI 1.07 to 5.76) were associated with increased adjusted risk of major complications, whereas age, gender, body mass index, international normalized ratio level, hypertension, coronary artery disease, diabetes, and prior cerebrovascular accident were not associated with increased risk. CONCLUSION In a large cohort of contemporary catheter ablation, major complication rates ranged between 0.8% and 6.0% depending on the ablation procedure performed. Aside from ablation type, renal insufficiency was the only independent predictor of a major complication.

Ventricular tachycardia ablation: evolution of patients and procedures over 8 years.

Background— Evolving management of coronary artery disease, heart failure, and the use of implantable cardioverter-defibrillators impacts the characteristics of patients with recurrent ventricular tachycardia (VT). We investigated the substrate, procedure, and outcome evolution of all patients referred for VT ablation during the past 8 years. Methods and Results— From 1999 to 2006, 493 consecutive patients (358 male, 57±16 years) underwent 623 VT ablations: 131 had no structural heart disease (SHD), 213 had ischemic cardiomyopathies (ICMP), and 149 had nonischemic cardiomyopathies (NICMP). Although the main substrate is ICMP, the proportion of NICMP has increased from 27% to 35% (P=0.06) from 1999–2002 to the 2003–2006. The procedure abolished or modified inducible VTs in ≥75% of patients in all groups, but abolition of all monomorphic VTs was achieved in 125 (83%) patients without SHD, 180 (65%) with ICMP, and 99 (51%) with NICMP (P<0.0001). During a mean follow-up of 3.3±2.4 years, no deaths occurred in patients without SHD, but 75 patients (35%) with ICMP and 26 patients (17%) with NICMP died after a median of 13 months. Multivariate Cox regression analysis found that age, ejection fraction, and need for preprocedural mechanical hemodynamic support predicted mortality. Conclusions— The substrate causing VT in patients requiring ablation is evolving and determines the long-term outcome. In the setting of a normal heart, VT ablation is associated with a low risk of subsequent mortality, with no deaths occurring during a mean follow-up of >3 years. In contrast, in patients with SHD and recurrent VT, VT ablation can be helpful to suppress drug refractory VT, but long-term mortality remains significant.Background— Evolving management of coronary artery disease, heart failure, and the use of implantable cardioverter-defibrillators impacts the characteristics of patients with recurrent ventricular tachycardia (VT). We investigated the substrate, procedure, and outcome evolution of all patients referred for VT ablation during the past 8 years. Methods and Results— From 1999 to 2006, 493 consecutive patients (358 male, 57±16 years) underwent 623 VT ablations: 131 had no structural heart disease (SHD), 213 had ischemic cardiomyopathies (ICMP), and 149 had nonischemic cardiomyopathies (NICMP). Although the main substrate is ICMP, the proportion of NICMP has increased from 27% to 35% ( P =0.06) from 1999–2002 to the 2003–2006. The procedure abolished or modified inducible VTs in ≥75% of patients in all groups, but abolition of all monomorphic VTs was achieved in 125 (83%) patients without SHD, 180 (65%) with ICMP, and 99 (51%) with NICMP ( P <0.0001). During a mean follow-up of 3.3±2.4 years, no deaths occurred in patients without SHD, but 75 patients (35%) with ICMP and 26 patients (17%) with NICMP died after a median of 13 months. Multivariate Cox regression analysis found that age, ejection fraction, and need for preprocedural mechanical hemodynamic support predicted mortality. Conclusions— The substrate causing VT in patients requiring ablation is evolving and determines the long-term outcome. In the setting of a normal heart, VT ablation is associated with a low risk of subsequent mortality, with no deaths occurring during a mean follow-up of >3 years. In contrast, in patients with SHD and recurrent VT, VT ablation can be helpful to suppress drug refractory VT, but long-term mortality remains significant. Received January 28, 2008; accepted May 1, 2008.

FREEDOM FROM RECURRENT VENTRICULAR TACHYCARDIA AFTER CATHETER ABLATION IS ASSOCIATED WITH IMPROVED SURVIVAL IN PATIENTS WITH STRUCTURAL HEART DISEASE: AN INTERNATIONAL VT ABLATION CENTER COLLABORATIVE GROUP STUDY

BACKGROUND The impact of catheter ablation of ventricular tachycardia (VT) on all-cause mortality remains unknown. OBJECTIVE The purpose of this study was to examine the association between VT recurrence after ablation and survival in patients with scar-related VT. METHODS Analysis of 2061 patients with structural heart disease referred for catheter ablation of scar-related VT from 12 international centers was performed. Data on clinical and procedural variables, VT recurrence, and mortality were analyzed. Kaplan-Meier analysis was used to estimate freedom from recurrent VT, transplant, and death. Cox proportional hazards frailty models were used to analyze the effect of risk factors on VT recurrence and mortality. RESULTS One-year freedom from VT recurrence was 70% (72% in ischemic and 68% in nonischemic cardiomyopathy). Fifty-seven patients (3%) underwent cardiac transplantation, and 216 (10%) died during follow-up. At 1 year, the estimated rate of transplant and/or mortality was 15% (same for ischemic and nonischemic cardiomyopathy). Transplant-free survival was significantly higher in patients without VT recurrence than in those with recurrence (90% vs 71%, P<.001). In multivariable analysis, recurrence of VT after ablation showed the highest risk for transplant and/or mortality [hazard ratio 6.9 (95% CI 5.3-9.0), P<.001]. In patients with ejection fraction <30% and across all New York Heart Association functional classes, improved transplant-free survival was seen in those without VT recurrence. CONCLUSION Catheter ablation of VT in patients with structural heart disease results in 70% freedom from VT recurrence, with an overall transplant and/or mortality rate of 15% at 1 year. Freedom from VT recurrence is associated with improved transplant-free survival, independent of heart failure severity.