Douglas L. Packer

Worldwide Survey on the Methods, Efficacy, and Safety of Catheter Ablation for Human Atrial Fibrillation

Background—The purpose of this study was to conduct a worldwide survey investigating the methods, efficacy, and safety of catheter ablation (CA) of atrial fibrillation (AF). Methods and Results—A detailed questionnaire was sent to 777 centers worldwide. Data relevant to the study purpose were collected from 181 centers, of which 100 had ongoing programs on CA of AF between 1995 and 2002. The number of patients undergoing this procedure increased from 18 in 1995 to 5050 in 2002. The median number of procedures per center was 37.5 (range, 1 to 600). Paroxysmal AF, persistent AF, and permanent AF were the indicated arrhythmias in 100.0%, 53.0%, and 20.0% of responding centers, respectively. The most commonly used techniques were right atrial compartmentalization between 1995 and 1997, ablation of the triggering focus in 1998 and 1999, and electrical disconnection of multiple pulmonary veins between 2000 and 2002. Of 8745 patients completing the CA protocol in 90 centers, of whom 2389 (27.3%) required >1 procedure, 4550 (52.0%; range among centers, 14.5% to 76.5%) became asymptomatic without drugs and another 2094 (23.9%; range among centers, 8.8% to 50.3%) became asymptomatic in the presence of formerly ineffective antiarrhythmic drugs over an 11.6±7.7-month follow-up period. At least 1 major complication was reported in 524 patients (6.0%). Conclusions—The findings of this survey provide a picture of the variable and evolving methods, efficacy, and safety of CA for AF as practiced in a large number of centers worldwide and may serve as a guide to clinicians considering therapeutic options in patients suffering from this arrhythmia.

Updated Worldwide Survey on the Methods, Efficacy, and Safety of Catheter Ablation for Human Atrial Fibrillation

Background—The purpose of this study was to provide an updated worldwide report on the methods, efficacy, and safety of catheter ablation of atrial fibrillation (AF). Methods and Results—A questionnaire with 46 questions was sent to 521 centers from 24 countries in 4 continents. Complete interviews were collected from 182 centers, of which 85 reported to have performed 20 825 catheter ablation procedures on 16 309 patients with AF between 2003 and 2006. The median number of procedures per center was 245 (range, 2 to 2715). All centers included paroxysmal AF, 85.9% also included persistent and 47.1% also included long-lasting AF. Carto-guided left atrial circumferential ablation (48.2% of patients) and Lasso-guided ostial electric disconnection (27.4%) were the most commonly used techniques. Efficacy data were analyzed with centers representing the unit of analysis. Of 16 309 patients with full disclosure of outcome data, 10 488 (median, 70.0%; interquartile range, 57.7% to 75.4%) became asymptomatic without antiarrhythmic drugs and another 2047 (10.0%; 0.5% to 17.1%) became asymptomatic in the presence of previously ineffective antiarrhythmic drugs over 18 (range, 3 to 24) months of follow-up. Success rates free of antiarrhythmic drugs and overall success rates were significantly larger in 9590 patients with paroxysmal AF (74.9% and 83.2%) than in 2800 patients with persistent AF (64.8% and 75.0%) and 1108 patients with long-lasting AF (63.1% and 72.3%) (P<0.0001). Major complications were reported in 741 patients (4.5%). Conclusions—When analyzed in a large number of electrophysiology laboratories worldwide, catheter ablation of AF shows to be effective in ≈80% of patients after 1.3 procedures per patient, with ≈70% of them not requiring further antiarrhythmic drugs during intermediate follow-up.

Prognostic importance of defibrillator shocks in patients with heart failure.

BACKGROUND Patients with heart failure who receive an implantable cardioverter-defibrillator (ICD) for primary prevention (i.e., prevention of a first life-threatening arrhythmic event) may later receive therapeutic shocks from the ICD. Information about long-term prognosis after ICD therapy in such patients is limited. METHODS Of 829 patients with heart failure who were randomly assigned to ICD therapy, we implanted the ICD in 811. ICD shocks that followed the onset of ventricular tachycardia or ventricular fibrillation were considered to be appropriate. All other ICD shocks were considered to be inappropriate. RESULTS Over a median follow-up period of 45.5 months, 269 patients (33.2%) received at least one ICD shock, with 128 patients receiving only appropriate shocks, 87 receiving only inappropriate shocks, and 54 receiving both types of shock. In a Cox proportional-hazards model adjusted for baseline prognostic factors, an appropriate ICD shock, as compared with no appropriate shock, was associated with a significant increase in the subsequent risk of death from all causes (hazard ratio, 5.68; 95% confidence interval [CI], 3.97 to 8.12; P<0.001). An inappropriate ICD shock, as compared with no inappropriate shock, was also associated with a significant increase in the risk of death (hazard ratio, 1.98; 95% CI, 1.29 to 3.05; P=0.002). For patients who survived longer than 24 hours after an appropriate ICD shock, the risk of death remained elevated (hazard ratio, 2.99; 95% CI, 2.04 to 4.37; P<0.001). The most common cause of death among patients who received any ICD shock was progressive heart failure. CONCLUSIONS Among patients with heart failure in whom an ICD is implanted for primary prevention, those who receive shocks for any arrhythmia have a substantially higher risk of death than similar patients who do not receive such shocks.

Tachycardia-induced cardiomyopathy: A reversible form of left ventricular dysfunction

Eight patients, aged 5 to 57 years, with uncontrolled symptomatic tachycardia for 2.5 to 41 years (mean 15) and significant left ventricular (LV) dysfunction in the absence of any other apparent underlying cardiac disease underwent evaluation. Incessant tachycardia was present for 0.5 to 6.0 years (mean 2.1) in 7 patients. One patient had an ectopic atrial tachycardia and 7 patients had an accessory atrioventricular pathway that participated in reciprocating tachycardia. Six patients underwent surgery; the ectopic focus was ablated in 1 patient and an accessory pathway was divided in 5 patients. One patient underwent open ablation of the His bundle and 1 patient underwent closed-chest ablation of the atrioventricular conduction system. Myocardial biopsy specimens were obtained from 5 patients, none of which yielded a specific diagnosis. Pretreatment radionuclide angiography demonstrated a mean ejection fraction (EF) of 19 +/- 9% (range 10 to 35%). Following tachycardia control a marked improvement in LV function was noted in 6 of 8 patients at rest and in 1 additional patient during exercise. The EF increased to 33 +/- 17% (range 16 to 56%) an average of 8 days after treatment and to 45 +/- 15% (range 22 to 67%) at late follow-up 3.5 +/- 40 months (mean 17) later (p less than 0.005). Seven patients remain asymptomatic 11 to 40 months (mean 22) after the corrective procedure and have resumed normal activities. These findings suggest that chronic uncontrolled tachycardia may result in significant LV dysfunction, which is reversible in some cases after control of the arrhythmia.

Cryoballoon Ablation of Pulmonary Veins for Paroxysmal Atrial Fibrillation: First Results of the North American Arctic Front (STOP AF) Pivotal Trial

OBJECTIVES This study sought to assess the safety and effectiveness of a novel cryoballoon ablation technology designed to achieve single-delivery pulmonary vein (PV) isolation. BACKGROUND Standard radiofrequency ablation is effective in eliminating atrial fibrillation (AF) but requires multiple lesion delivery at the risk of significant complications. METHODS Patients with documented symptomatic paroxysmal AF and previously failed therapy with ≥ 1 membrane active antiarrhythmic drug underwent 2:1 randomization to either cryoballoon ablation (n = 163) or drug therapy (n = 82). A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and reablation if necessary. Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months. RESULTS Patients had highly symptomatic AF (78% paroxysmal, 22% early persistent) and experienced failure of at least one antiarrhythmic drug. Cryoablation produced acute isolation of three or more PVs in 98.2% and all four PVs in 97.6% of patients. PVs isolation was achieved with the balloon catheter alone in 83%. At 12 months, treatment success was 69.9% (114 of 163) of cryoblation patients compared with 7.3% of antiarrhythmic drug patients (absolute difference, 62.6% [p < 0.001]). Sixty-five (79%) drug-treated patients crossed over to cryoablation during 12 months of study follow-up due to recurrent, symptomatic AF, constituting drug treatment failure. There were 7 of the resulting 228 cryoablated patients (3.1%) with a >75% reduction in PV area during 12 months of follow-up. Twenty-nine of 259 procedures (11.2%) were associated with phrenic nerve palsy as determined by radiographic screening; 25 of these had resolved by 12 months. Cryoablation patients had significantly improved symptoms at 12 months. CONCLUSIONS The STOP AF trial demonstrated that cryoballoon ablation is a safe and effective alternative to antiarrhythmic medication for the treatment of patients with symptomatic paroxysmal AF, for whom at least one antiarrhythmic drug has failed, with risks within accepted standards for ablation therapy. (A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [Stop AF]; NCT00523978).

Prevalence and Causes of Fatal Outcome in Catheter Ablation of Atrial Fibrillation

OBJECTIVES The purpose of this study was to provide a systematic multicenter survey on the incidence and causes of death occurring in the setting of or as a consequence of catheter ablation (CA) of atrial fibrillation (AF). BACKGROUND CA of AF is considered to be generally safe. However, serious complications, including death, have been reported. METHODS Using a retrospective case series, data relevant to the incidence and cause of intra- and post-procedural death occurring in patients undergoing CA of AF between 1995 and 2006 were collected from 162 of 546 identified centers worldwide. RESULTS Thirty-two deaths (0.98 per 1,000 patients) were reported during 45,115 procedures in 32,569 patients. Causes of deaths included tamponade in 8 patients (1 later than 30 days), stroke in 5 patients (2 later than 30 days), atrioesophageal fistula in 5 patients, and massive pneumonia in 2 patients. Myocardial infarction, intractable torsades de pointes, septicemia, sudden respiratory arrest, extrapericardial pulmonary vein (PV) perforation, occlusion of both lateral PVs, hemothorax, and anaphylaxis were reported to be responsible for 1 death each, while asphyxia from tracheal compression secondary to subclavian hematoma, intracranial bleeding, acute respiratory distress syndrome, and esophageal perforation from an intraoperative transesophageal echocardiographic probe were causes of 1 late death each. CONCLUSIONS Death is a complication of CA of AF, occurring in 1 of 1,000 patients. Knowledge of possible precipitating causes is key to operators and needs to be considered during decision making with patients.

A population study of the natural history of Wolff-Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989.

BackgroundVirtually all natural history studies of Wolff-Parkinson-White (WPW) syndrome have been case series and, as such, have been constrained by referral biases, skewed age and sex distributions, or brief follow-up periods. The purpose of our study was to examine the natural history, the development of arrhythmias, and the incidence of sudden death in an entire cohort of pediatric and adult WPW patients from a community-based local population. Methods and ResultsWe identified 113 residents of Olmsted County, Minnesota, during the period 1953-1989 using the centralized records-linkage system provided by the Mayo Clinic and the Rochester Epidemiology Program Project. Medical records and ECGs were reviewed to confirm the diagnosis and to establish pathway location by ECG criteria. Follow-up, via record review and telephone interview, was complete in 95% of subjects through 1990. The incidence of newly diagnosed cases was approximately four per 100,000 per year. Preexcitation was not present on the initial ECG of22% of the cohort. Approximately 50%o of the population was asymptomatic at diagnosis, with 30%, o subsequently having symptoms related to arrhythmia at follow-up. Two sudden cardiac deaths (SCD) occurred over 1,338 patient-years of follow-up, yielding an overall SCD rate of 0.0015 (95% confidence interval, 0.0002-0.0054) per patient-year. No SCD occurred in patients asymptomatic at diagnosis. ConclusionsThe incidence of sudden death in a local community-based population is low and suggests that electrophysiological testing should not be performed routinely in asymptomatic patients with WPW syndrome. Nevertheless, young, asymptomatic patients, particularly those <40 years old, should return for medical follow-up should symptoms develop.

Prevention of atrial fibrillation: report from a national heart, lung, and blood institute workshop.

The National Heart, Lung, and Blood Institute convened an expert panel April 28 to 29, 2008, to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiological, and clinical literature about AF and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: (1) enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; (2) improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; (3) improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural, and electrical remodeling markers; (4) develop additional animal models reflective of the pathophysiology of human AF; (5) conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and (6) conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.The National Heart, Lung, and Blood Institute convened an expert panel April 28-29, 2008 to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiologic and clinical literature about AF, and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: 1) Enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; 2) Improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; 3) Improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural and electrical remodeling markers; 4) Develop additional animal models reflective of the pathophysiology of human AF; 5) Conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and 6) Conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.

Long-Term Progression and Outcomes With Aging in Patients With Lone Atrial Fibrillation: A 30-Year Follow-Up Study

Background— The long-term natural history of lone atrial fibrillation is unknown. Our objective was to determine the rate and predictors of progression from paroxysmal to permanent atrial fibrillation over 30 years and the long-term risk of heart failure, thromboembolism, and death compared with a control population. Methods and Results— A previously characterized Olmsted County, Minnesota, population with first episode of documented atrial fibrillation between 1950 and 1980 and no concomitant heart disease or hypertension was followed up long term. Of this unique cohort, 76 patients with paroxysmal (n=34), persistent (n=37), or permanent (n=5) lone atrial fibrillation at initial diagnosis met inclusion criteria (mean age at diagnosis, 44.2±11.7 years; male, 78%). Mean duration of follow-up was 25.2±9.5 years. Of 71 patients with paroxysmal or persistent atrial fibrillation, 22 had progression to permanent atrial fibrillation. Overall survival of the 76 patients with lone atrial fibrillation was 92% and 68% at 15 and 30 years, respectively, similar to 86% and 57% survival for the age- and sex-matched Minnesota population. Observed survival free of heart failure was slightly worse than expected (P=0.051). Risk for stroke or transient ischemic attack was similar to the expected population risk during the initial 25 years of follow-up but increased thereafter (P=0.004), although CIs were wide. All patients who had a cerebrovascular event had developed ≥1 risk factor for thromboembolism. Conclusions— Comorbidities significantly modulate progression and complications of atrial fibrillation. Age or development of hypertension increases thromboembolic risk.

Clinical Presentation, Investigation, and Management of Pulmonary Vein Stenosis Complicating Ablation for Atrial Fibrillation

Background—Although segmental or circumferential ablation is effective in eliminating pulmonary vein (PV)–mediated atrial fibrillation (AF), this procedure may be complicated by the occurrence of PV stenosis. Methods and Results—To establish the clinical presentation, diagnostic manifestations, and interventional management of PV stenosis, 23 patients with stenosis of 34 veins complicating ablation of AF were evaluated. Each patient became symptomatic 103±100 days after undergoing ablation. In 8 veins, the ablation producing the PV stenosis was a repeated procedure for continued AF. Nineteen patients presented with dyspnea on exertion, 7 with dyspnea at rest, 9 with cough, and 6 with chest pain. On multirow spiral computed tomography examination, the narrowest lumen of the affected PVs measured 3±2 mm compared with 13±3 mm at baseline (P≤0.001). The relative perfusion of affected lung segments on isotope scans was reduced to 4±3% of total perfusion compared with 22±10% in unaffected segments. At percutaneous intervention, these veins showed 80±13% stenosis, with a mean gradient of 12±5 mm Hg. This was significantly reduced to a residual stenosis of 9±8% (P≤0.001) and a residual gradient of 3±4 mm Hg (P≤0.001). Twenty veins were treated with balloon dilatation alone, whereas 14 veins were stented with standard 10-mm-diameter bare-metal stents. Although the symptomatic response was nearly immediate and impressive, 14 patients developed in-stent or in-segment restenosis, requiring repeated interventions in 13. Conclusions—Percutaneous intervention produces rapid and dramatic symptom relief in patients with highly symptomatic PV stenosis after radiofrequency ablation for AF. Nevertheless, alternative treatment methods will be required to decrease recurrent in-stent or in-segment restenosis.