ACC 2006 ANNUAL SESSION HIGHLIGHTS
Cardiac Arrhythmias
Steven M. Markowitz, MD, FACC*
Cornell University Medical Center-New York Presbyterian Hospital, Division of Cardiology, New York, New York.
* Reprint requests and correspondence: Dr. Steven M. Markowitz, Cornell University Medical Center-New York Presbyterian Hospital, Division of Cardiology, Starr-4, 525 East 68th Street, New York, New York 10021. (Email: smarkow{at}med.cornell.edu).
|
Abbreviations and Acronyms
| | AF = atrial fibrillation | | AFFIRM = Atrial Fibrillation Follow-Up Investigation of Rhythm Management trial | | APAF-3 = Ablation for Paroxysmal Atrial Fibrillation | | ARMYDA-3 = Atorvastatin for Reduction of Myocardial Dysrhythmias After Cardiac Surgery trial | | FDA = Food and Drug Administration | | HOPE = Heart Outcomes Prevention Evaluation trial | | ICD = implantable cardioverter-defibrillator | | LIFE = Losartan Intervention For Endpoint reduction in hypertension trial | | MADIT II = Multicenter Automatic Defibrillator Implantation Trial II | | PVI = pulmonary vein isolation |
|
In the general topic area of cardiac arrhythmias, 497 abstracts were submitted for consideration and 160 were accepted for presentation at the 2006 ACC meeting. In addition, late-breaking clinical trials were presented evaluating ablation of atrial fibrillation (AF), prevention of postoperative atrial fibrillation, and treatment of neurally mediated syncope.
 |
Treatment of AF
|
|---|
The Ablation for Paroxysmal Atrial Fibrillation (APAF) trial was a randomized, controlled study of circumferential pulmonary vein ablation versus antiarrhythmic drug therapy for paroxysmal atrial fibrillation (1). The trial enrolled 198 patients (age 57 ± 10 years, 66% male) with paroxysmal atrial fibrillation, who were then randomized to catheter ablation or antiarrhythmic therapy using flecainide, sotalol, or amiodarone. As of March 2006, nine-month follow-up was completed for 150 patients. The primary end point of the study was freedom from AF at 12 months, which was achieved in 87% of patients who underwent catheter ablation compared with 29% of patients treated with antiarrhythmic drugs. Repeat ablation was required in five patients because of recurrent AF or atrial tachycardia. In addition, evidence of left atrial reverse remodeling was present based on a decrease in left atrial dimensions in patients who had catheter ablation. A secondary analysis indicated that amiodarone and flecainide were superior to sotalol at the dosages used in this trial (freedom from atrial fibrillation 50% vs. 38% vs. 6%, respectively).
A retrospective, case-control study of pulmonary vein isolation (PVI), direct current cardioversion, and atrioventricular node ablation for atrial fibrillation was reported by Lakkireddy et al. (2). Cases were matched for baseline clinical characteristics, and the mean age of patients in each study arm was 70 years. The study involved a total of 138 patients in the PVI group, 139 in the cardioversion group, and 133 in the atrioventricular node ablation group; procedures were performed between 1996 and 2004. Long-term mortality rates were significantly lower in the PVI group compared with cardioversion and atrioventricular node ablation (1.4% vs. 15% vs. 31%). Also, there were fewer strokes and transient ischemic attacks in the PVI group (4% vs. 18% vs. 5%).
Results were reported of a phase III randomized, placebo-controlled, multicenter trial of a novel antiarrhythmic drug, RSD1235, in patients with AF or atrial flutter. Pratt et al. (3) randomized 276 patients to RSD1235 or placebo stratified by duration of arrhythmia. Fifty-two percent of patients treated with the active drug had a conversion to sinus rhythm versus 4% in the placebo group. Of note, there was no evidence of torsades de pointes in the treatment group. There was one death in a patient with critical aortic stenosis who received RSD1235.
|
Epidemiology and prevention of AF
|
|---|
The influence of race on susceptibility to AF was examined in a meta-analysis by Novaro et al. (4). Seven randomized clinical trials in acute myocardial infarction and acute coronary syndromes were included, resulting in a pooled population of 95,787 patients (2.9% African American, 97.1% Caucasian). Although African-American patients had higher prevalences of hypertension, diabetes, tobacco, and prior myocardial infarction, the incidence of atrial fibrillation was lower in African-American versus Caucasian patients (4.3% vs. 7.6%).
To examine the role of race with regard to ischemic stroke in AF, Shen et al. (5) conducted a review of the Kaiser Permanente database of hospitalized patients in Southern California. After identifying all patients hospitalized for nonrheumatic AF, African-American patients were found to have a higher risk of stroke regardless of whether they were taking warfarin during follow-up. The hazard ratio for ischemic stroke in AF for African Americans was 1.6 compared with Caucasians, after adjusting for the known stroke risk factors of age, gender, warfarin use, hypertension, diabetes, and heart failure (Table 1). The same group found a different race profile for the risk of hemorrhagic stroke in patients with AF treated with warfarin (6). There was a progressive increase in hemorrhagic risk from Caucasian, African-American, Hispanic, and Asian subgroups (adjusted hazard ratios 1, 1.97, 2.24, and 3.43, respectively). These studies implicate the role of genetic factors in the development of AF and stroke.
Gender differences in ischemic stroke risk were studied by Konety et al. (7) through an analysis of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial. Of the 4,060 patients enrolled in this trial, 39% were women. Prescription rates of warfarin were similar for men and women, but absolute stroke rates were higher for women (5.0%) compared with men (3.1%). The relative risk of stroke remained elevated in women despite adjustment for multiple known stroke risk factors, international normalized ratio, and randomization group. These findings highlight the importance of considering gender when assessing patients for warfarin therapy.
Brar et al. (8) studied the association of diabetes, insulin, and prevalence of AF and flutter in a large heart failure population. They used a managed care database of 28,009 patients with heart failure, of whom 48% had diabetes; of the diabetic patients, 38% were insulin users. Insulin users had less atrial fibrillation, with an odds ratio of 0.81 compared with nondiabetic patients, but diabetic non-insulin users did not differ significantly from nondiabetic patients with regard to the prevalence of AF. They concluded that insulin use may be protective against AF in patients with heart failure.
The role of left atrial dilatation in the pathogenesis of AF was addressed through an echocardiographic study by Wachtell et al. (9). They analyzed echocardiograms for 939 hypertensive patients with left ventricular hypertrophy randomized in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, a randomized study of atenolol or losartan for antihypertensive treatment, with patients followed up for a mean of 4.8 years. In 58 patients, AF developed during follow-up, and predictors of new-onset AF were baseline left atrial diameter (hazard ratio 1.93 per cm higher) and reduction of left atrial diameter with treatment (hazard ratio 0.19 per cm lower). They concluded that monitoring left atrial dimension may contribute to the prevention of AF during antihypertensive treatment by prompting further intervention to achieve a reduction in left atrial diameter.
Salehian et al. (10) studied the effects of ramipril and vitamin E on the incidence of AF in the Heart Outcomes Prevention Evaluation (HOPE) study. The study enrolled 8,334 patients in sinus rhythm at baseline, all of whom were at least 55 years of age with cardiovascular disease or diabetes plus one risk factor for cardiovascular disease. The patients were randomized in a 2 x 2 factorial design to ramipril, vitamin E, or the combination and followed up for an average of 4.5 years. There was no significant difference in the development of AF in the ramipril and placebo groups (2.0% vs. 2.25%). A different conclusion was reached in a study by Jibrini et al. (11), who performed a meta-analysis of seven randomized, controlled trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in different cardiovascular subsets. Treatment with these agents reduced the relative risk of AF in patients with hypertension by 23%, after myocardial infarction by 11%, after cardioversion by 51%, and in patients with heart failure by 32%.
A randomized trial of atorvastatin showed a reduction of postoperative AF after cardiac surgery in the Atorvastatin for Reduction of Myocardial Dysrhythmias After Cardiac Surgery (ARMYDA-3) trial (12). As presented by Dr. Di Sciascio, 200 patients undergoing elective cardiac surgery were randomized to receive atorvastatin (40 mg daily) or placebo starting seven days before surgery. Occurrence of in-hospital AF was significantly lower in the statin group (35%) versus the placebo group (57%), and treatment benefit was independent of possible confounding factors, with a 60% risk reduction evident by multivariate analysis. Peak postoperative levels of C-reactive protein were significantly lower in patients without AF, irrespective of the study assignment. The investigators concluded that atorvastatin significantly reduces postoperative AF and that the anti-inflammatory effects of statins may contribute to this clinical effect.
|
Sudden cardiac death and implantable cardioverter-defibrillators
|
|---|
Chow et al. (13) studied the predictive value of QRS duration and microvolt T-wave alternans testing in patients with ischemic cardiomyopathy. In a prospective database of 768 patients with ischemic heart disease and ejection fractions 
35%, univariate predictors of long-term mortality included a nonnegative T-wave alternans test and a QRS duration >120 ms. In a multivariate model, T-wave alternans but not QRS duration was predictive of all-cause and arrhythmic mortality, and there was no interaction between T-wave alternans and QRS duration. The adjusted hazard ratio of a nonnegative T-wave alternans was 2.24 for all-cause long-term mortality and 2.29 for arrhythmic mortality.
Aryana et al. (14) studied the circadian, daily, and seasonal distribution of ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators (ICDs). In this retrospective review of 154 ICD recipients, spontaneous episodes of ventricular tachycardia and fibrillation were more common in the winter (51% of episodes), and there was a significant correlation between average daily temperature and ventricular tachycardia and fibrillation. Ventricular arrhythmias were more common on Fridays (16.5% of episodes), and the circadian pattern showed a bimodal distribution with more episodes in the morning and evening.
Recalls and safety alerts for implantable defibrillators were addressed in two studies. Hauser et al. (15) conducted a six-year prospective multicenter study of defibrillator pulse generators that failed or required replacement because of manufacturer recalls. They found that average implant times of failed or recalled generators were shorter for devices with rate-responsive pacing and cardiac resynchronization. They concluded that devices with advanced pacing capabilities are more likely to show poor performance related to premature battery depletion, electronic or housing failure, and manufacturers’ recalls. Kendig et al. (16) retrospectively reviewed the long-term mortality of 1,644 patients who had defibrillators implanted between 1996 and 2004 in their institution. Forty-three percent of recipients had a device subject to a U.S. Food and Drug Administration (FDA) recall or safety alert. The long-term mortality of patients with devices not subject to a recall or alert was 30%, and there was no excess long-term mortality identified in patients with devices subject to recalls or alerts (31% with FDA class I recalls, 24% with FDA class II recalls, 38% with safety alerts) (Fig. 1).
View larger version (20K):
[in this window]
[in a new window]
|
Figure 1 Prevalence and impact on patient mortality of Food and Drug Administration (FDA) recalls and safety alerts relating to implantable cardioverter-defibrillators. Reprinted with permission (16). *p = 0.016.
|
|
Three abstracts identified a poor prognosis in patients with renal dysfunction who received an ICD. Goldenberg et al. (17) retrospectively analyzed the outcomes associated with renal dysfunction in patients enrolled in Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II). For each 10-unit reduction in estimated glomerular filtration rate, they found that the risk of mortality increased by 16%. No ICD benefit was documented in patients with the most severe renal dysfunction (<35 ml/1.73 m2). Cuculich et al. (18) reported that chronic kidney disease was a strong independent predictor of mortality in patients with ischemic or nonischemic cardiomyopathy who had ICD implantation for primary prevention of sudden death (hazard ratio 10.5). Dobesh et al. (19) showed 63% mortality at two years in hemodialysis patients who received ICDs after syncope or cardiac arrest.
|
Cardiac resynchronization
|
|---|
Several studies assessed the predictive value of noninvasive testing for response to cardiac resynchronization. In a study of 40 patients with coronary disease who met indications for cardiac resynchronization, Bleeker et al. (20) reported that a transmural posterolateral scar detected by contrast-enhanced magnetic resonance imaging predicted failure to have a response to biventricular pacing. In the absence of posterolateral scar and the presence of severe dyssynchrony, the response rate to resynchronization was 95%, as assessed by an improvement of 
1 New York Heart Association functional class and an improvement of 25% in 6-min walk distance. In patients with severe dyssynchrony but the presence of a posterolateral scar, the response rate remained low at 18%.
Further evidence supporting the importance of scar location in cardiac resynchronization was reported by Jansen et al. (21). In this study of 49 patients, contrast-enhanced magnetic resonance imaging identified posterolateral scar in 13, other scar in 10, and no scar in 16. Resynchronization resulted in less acute hemodynamic benefit (as assessed by change in acute left ventricular dP/dt) in patients with posterolateral scar compared with other scar or no scar. The patients with posterolateral scar also had less remodeling as assessed by change in left ventricular systolic volume.
Similarly, Sauer et al. (22) reported that left ventricular lead positioning over infarcted myocardium results in less improvement in ejection fraction in patients with ischemic cardiomyopathy. Of 108 patients, 21 had left ventricular leads positioned over an infarcted segment, as identified by either nuclear imaging or echocardiography before the procedure. Left ventricular ejection fraction increased less in the group with leads positioned over infarcted compared with noninfarcted territory (+1.4% vs. +3.9%).
The benefits of site-specific pacing to prevent adverse remodeling were studied by Tse et al. (23) in a randomized study of 29 patients with high-grade atrioventricular block and no structural heart disease. Patients were randomized to implantation of the ventricular lead at the right ventricular septum or the apex. In the group with septal implantation, there was no change in ejection fraction over 24 months of follow-up, but apical implantation resulted in a reduction in ejection fraction from 54% to 47%. Septal pacing was associated with more synchronous left ventricular contraction.
|
Neurally mediated syncope
|
|---|
In a randomized trial of 223 patients, van Dijk et al. (24) tested the effects of physical counterpressure maneuvers to prevent recurrent neurally mediated syncope. The median yearly syncope burden was significantly lower among patients trained in counterpressure maneuvers (median 0.0) compared with patients who had conventional treatment (median 0.6). During a mean follow-up of 14 months, 51% of patients with conventional treatment versus 32% of patients trained in these maneuvers experienced recurrent syncope.
|
Conclusions
|
|---|
In summary, the 2006 American College of Cardiology Annual Scientific Session highlighted one of the first randomized clinical trials showing the superiority of catheter ablation over antiarrhythmic drug therapy in selected patients with paroxysmal AF. Race was identified as a risk factor for AF and stroke, emphasizing the need for further study of genetic influences on these conditions. Strategies to prevent AF through antihypertensive management were evaluated, and a randomized trial for prophylaxis of postoperative AF with statin therapy was presented. Efforts to refine risk stratification for sudden death were reported, as were studies concerning the outcomes of patients who received implantable defibrillators. Prediction of response to resynchronization was a topic addressed by several interesting studies, particularly in patients with ischemic cardiomyopathy.
|
References
|
|---|
- Pappone C, Augello G, Sala S, et al. A controlled randomized trial of circumferential pulmonary vein ablation versus antiarrhythmic drug therapy for curing paroxysmal atrial fibrillation. the Ablation for Paroxysmal Atrial Fibrillation (APAF) trial. 2006Presented at: ACC 55th Annual Meeting; Atlanta, GA: March 11–14.
- Lakkireddy DR, Patel D, Ryschon K, et al. Is pulmonary vein isolation (PVI) a better therapeutic option than atrioventricular node ablation (AVNA) and direct current cardioversion (DCC)? Mortality differences in patients with atrial fibrillation(abstr) J Am Coll Cardiol 2006;47(Suppl A):17A.
- Pratt C, Roy D, Juul-Moller S, et al. ACT III Investigators Efficacy and tolerance of RSD1235 in the treatment of atrial fibrillation or atrial flutterresults of a phase III, randomized, placebo-controlled, multicenter trial. (abstr) J Am Coll Cardiol 2006;47(Suppl A):10A.
- Novaro GM, Asher CR, Pinski SL, et al. Blacks are less susceptible to atrial fibrillation despite an adverse risk profilea meta-analysis. (abstr) J Am Coll Cardiol 2006;47(Suppl A):33A.
- Shen AYJ, Yao JF, Chen W, et al. Risk of ischemic stroke and atrial fibrillationis there an ethnic difference in its incidence and in the efficacy of warfarin?. (abstr) J Am Coll Cardiol 2006;47(Suppl A):35A.
- Shen AYJ, Yao JF, Chen W, et al. Risk of hemorrhagic stroke in atrial fibrillationis there an ethnic difference in its incidence and in the effect of warfarin?. (abstr) J Am Coll Cardiol 2006;47(Suppl A):363A.
- Konety SH, Joslyn SA, Olshansky B. Are there gender differences in risk of ischemic stroke in patients with atrial fibrillation who are anticoagulated? Results from the AFFIRM trial(abstr). J Am Coll Cardiol 2006;47(Suppl A):10A.
- Brar SS, Liu ILA, Khan SS, et al. Diabetes, insulin, and the prevalence of atrial fibrillation and flutter in a large heart failure population(abstr) J Am Coll Cardiol 2006;47(Suppl A):10A.
- Wachtell K, Gerdts E, Aurigemma G, et al. Does reduction in left atrial diameter during antihypertensive treatment reduce new-onset atrial fibrillation in hypertensive patients with left ventricular hypertrophythe LIFE study. (abstr) J Am Coll Cardiol 2006;47(Suppl A):9A.
- Salehian O, Healey J, Almerri K, et al. Neither ramipril nor vitamin E reduced the incidence of atrial fibrillation. Results of the HOPE study(abstr). J Am Coll Cardiol 2006;47(Suppl A):8A.
- Jibrini MB, Molnar J, Arora R, et al. Prevention of atrial fibrillation via abrogation of the renin-angiotensin systema pooled meta-analysis of randomized controlled clinical trials. (abstr) J Am Coll Cardiol 2006;47(Suppl A):9A.
- Patti G, Chello M, Candura D, et al. A randomized trial of atorvastatin for reduction of post-operative atrial fibrillation in patients undergoing cardiac surgery. Results from the ARMYDA-3 (Atorvastatin for Reduction of Myocardial Dysrhythmias after Cardiac Surgery) study. 2006Presented at: ACC 55th Annual Meeting; Atlanta, GA: March 11–14.
- Chow T, Saghir S, Bartone C, et al. QRS duration and microvolt T-wave alternans testing in patients with ischemic cardiomyopathy(abstr) J Am Coll Cardiol 2006;47(Suppl A):5A.
- Aryana A, Mohiuddin SM, Pingili CS, et al. Circadian, daily, and seasonal distributions of ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillator(abstr) J Am Coll Cardiol 2006;47(Suppl A):4A.
- Hauser RG, Hayes DL, Epstein AE, et al. Multicenter experienced with 1,355 failed and recalled implantable cardioverter-defibrillators(abstr) J Am Coll Cardiol 2006;47(Suppl A):20A.
- Kendig AC, Khan M, Tchou PJ, et al. Implantable cardioverter-defibrillator FDA recalls and safety alertsprevalence and impact on patient mortality. (abstr) J Am Coll Cardiol 2006;47(Suppl A):20A.
- Goldenberg I, Moss AJ, McNitt S, et al. Relationship between renal function, risk of sudden cardiac death, and benefit of the implantable cardiac defibrillator in post myocardial infarction patients with left ventricular dysfunction(abstr) J Am Coll Cardiol 2006;47(Suppl A):19A.
- Cuculich P, Sanchez JM, Kerzner R. Is there a role for implantable cardioverter-defibrillator therapy for the primary prevention of sudden death in patients with chronic kidney disease(abstr) J Am Coll Cardiol 2006;47(Suppl A):19A.
- Dobesh DP, Stein K, Mittal S, et al. Natural history of hemodialysis patients receiving an implantable cardioverter-defibrillator for secondary prevention(abstr) J Am Coll Cardiol 2006;47(Suppl A):15A.
- Bleeker GB, Kaandorp TAM, Lamb HJ, et al. Effect of postero-lateral scar tissue on clinical and echocardiographic improvement following cardiac resynchronization therapy(abstr) J Am Coll Cardiol 2006;47(Suppl A):12A.
- Jansen AH, van Dantzig JM, Bracke F, et al. Influence of location of scar tissue in cardiac resynchronization therapy(abstr) J Am Coll Cardiol 2006;47(Suppl A):21A.
- Sauer WH, Hutchinson M, Mainigi SK, et al. Left ventricular positioning over infarcted myocardium results in less improvement in ejection fraction in patients with ischemic cardiomyopathy following cardiac resynchronization therapy(abstr) J Am Coll Cardiol 2006;47(Suppl A):12A.
- Tse HF, Lam YM, Tang MO, et al. Avoidance of left ventricular dyssynchrony detected by tissue Doppler echocardiography by permanent right ventricular septal pacing in patients with high-grade atrioventricular block(abstr) J Am Coll Cardiol 2006;47(Suppl A):23A.
- van Dijk N, Quartieri F, Blanc JJ, et al. The Physical Counterpressure Manoeuvre Trial (PC-Trial). study on the effectiveness of physical counterpressure manoeuvres in preventing vasovagal syncope. 2006Presented at: ACC 55th Annual Meeting; Atlanta, GA: March 11–14.
Top
Treatment of AF
Epidemiology and prevention of...