Bruce A. Koplan

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.

Heart Failure Decompensation and All-Cause Mortality in Relation to Percent Biventricular Pacing in Patients With Heart Failure: Is a Goal of 100% Biventricular Pacing Necessary?

OBJECTIVES The goal of this analysis was to determine the appropriate biventricular pacing target in patients with heart failure (HF). BACKGROUND Cardiac resynchronization therapy (CRT) decreases the risk of death and HF hospitalization. However, the appropriate amount of biventricular pacing is ill-defined. METHODS Mortality and HF hospitalization data from patients undergoing CRT in 2 trials (CRT RENEWAL [Cardiac Resynchronization Therapy Registry Evaluating Patient Response with RENEWAL Family Devices] and REFLEx [ENDOTAK RELIANCE G Evaluation of Handling and Electrical Performance Study]; n = 1,812) were analyzed in a post-hoc fashion. Subjects were grouped based on percent biventricular pacing quartiles with the use of Kaplan-Meier survival analysis. RESULTS Subjects were age 72 +/- 11 years; 72% were men and 67% had coronary artery disease. Subjects paced 93% to 100% (quartiles 2 to 4) had a 44% reduction in hazard of an event compared with subjects paced 0% to 92% (quartile 1; hazard ratio [HR]: 0.56, p < 0.00001). Subjects paced 98% to 99% (quartile 3) had similar outcomes as subjects paced 93% to 97% (quartile 2; HR: 0.97, p = 0.82). Subjects paced 100% (quartile 4) had similar outcomes as subjects paced 98% to 99% (HR: 0.78, p = 0.17). There was a significant interaction between a history of atrial arrhythmia and percent pacing. Subjects with a history of atrial arrhythmia were more likely to be paced < or =92% (p < 0.001). CONCLUSIONS For CRT patients in this retrospective analysis, the greatest magnitude of benefit was observed with >92% biventricular pacing.

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.

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.

Glycopeptides Are No More Effective than β-Lactam Agents for Prevention of Surgical Site Infection after Cardiac Surgery: A Meta-analysis

A meta-analysis was performed to investigate whether a switch from beta-lactams to glycopeptides for cardiac surgery prophylaxis should be advised. Results of 7 randomized trials (5761 procedures) that compared surgical site infections (SSIs) in subjects receiving glycopeptide prophylaxis with SSIs in those who received beta -lactam prophylaxis were pooled. Neither agent proved to be superior for prevention of the primary outcome, occurrence of SSI at 30 days (risk ratio [RR], 1.14; 95% confidence interval [CI], 0.91-1.42). In subanalyses, beta-lactams were superior to glycopeptides for prevention of chest SSIs (RR, 1.47; 95% CI, 1.11-1.95) and approached superiority for prevention of deep-chest SSIs (RR, 1.33; 95% CI, 0.91-1.94) and SSIs caused by gram-positive bacteria (RR, 1.36; 95% CI, 0.98-1.91). Glycopeptides approached superiority to beta-lactams for prevention of leg SSIs (RR, 0.77; 95% CI, 0.58-1.01) and were superior for prevention of SSIs caused by methicillin-resistant gram-positive bacteria (RR, 0.54; 95% CI, 0.33-0.90). Standard prophylaxis for cardiac surgery should continue to be beta-lactams in most circumstances.

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.

Development and validation of a simple risk score to predict the need for permanent pacing after cardiac valve surgery

OBJECTIVES The study objective was to develop and validate a simple risk score to predict postoperative permanent pacing (PPM) after valve surgery. BACKGROUND Our ability to identify patients preoperatively that will require PPM is poor. A simple preoperative risk score to predict PPM after valve surgery could assist both clinical practice and research. METHODS All valve surgery patients at our institution from 1992 to 2002 were included (n = 4,694). Two-thirds of the patients were randomly selected to form a risk score prediction group (PG), and the score was then applied to the remaining patients (validation group [VG]). RESULTS Preoperative right bundle branch block (odds ratio [OR], 3.6; 95% confidence interval [CI], 2.3 to 5.7) and multivalve surgery that included the tricuspid valve (OR, 3.7; 95% CI, 2.3 to 6.1) were the strongest independent predictors of PPM, while multivalve surgery that did not include the tricuspid valve (OR, 2.1; 95% CI, 1.3 to 3.3), preoperative left bundle branch block (OR, 2.0; 95% CI, 1.3 to 2.9), preoperative PR interval >200 ms (OR, 1.9; 95% CI, 1.3 to 3.0), prior valve surgery (OR, 1.8, 95% CI, 1.2 to 2.7), and age >70 years (OR, 1.4; 95% CI, 1.04 to 2.0) also predicted PPM. A risk score from 0 to 6 identified patients in the VG with incidences of PPM of 1.9%, 5.2%, 8.7%, 11.5%, 21%, 36%, and 50%, respectively. CONCLUSIONS A simple risk score incorporating preoperative conduction, age, prior valve surgery, and surgery type predicts PPM after valve surgery. This score may be useful in the perioperative management of valve surgery patients.

Pharmacological Stress Thallium Scintigraphy With 2-Cyclohexylmethylidenehydrazinoadenosine (WRC-0470) A Novel, Short-Acting Adenosine A2A Receptor Agonist

BACKGROUND Pharmacological stress imaging with adenosine or dipyridamole is associated with a high incidence of side effects, including hypotension, chest pain, AV conduction abnormalities, and bronchospasm. Although the desired coronary vasodilatory response is mediated primarily by the adenosine A2A receptors, these side effects result from stimulation of the A1, A2B, or A3 adenosine receptors. We hypothesized that a selective adenosine A2A receptor agonist would induce coronary vasodilatation appropriate for pharmacological stress imaging, without evoking adenosine receptor-mediated side effects. METHODS AND RESULTS Infusions of a potent and selective A2A adenosine receptor agonist, WRC-0470 (0.1 to 3 micrograms kg-1. min-1 for 10 minutes), to five open-chest dogs produced dose-related left anterior descending (LAD) and left circumflex (LCx) coronary artery vasodilatation without altering mean arterial pressure, heart rate, left atrial pressure, or left ventricular dP/dt. In the same dogs, adenosine (300 micrograms . kg-1. min-1 for 4 minutes) produced coronary vasodilatation that was limited by significant hypotension. To determine the utility of WRC-0470 for pharmacological stress imaging, the hemodynamic responses to WRC-0470 (0.6 microgram.kg-1.min-1 for 10 minutes) and adenosine (250 micrograms.kg-1.min-1 for 4 minutes) were compared in dogs with critical LAD stenoses. 201T1 was injected at the peak WRC-0470 stress response. WRC-0470 increased LCx flow nearly fivefold but did not significantly lower mean arterial pressure. Anteroseptal defects were readily apparent in slice images from all dogs. The mean defect ratio (LAD/LCx) was 0.59 +/- 0.06. CONCLUSIONS The potent A2A-selective adenosine receptor agonist WRC-0470 is a short-acting coronary vasodilator with potential utility for pharmacological stress perfusion imaging.