Mark D. Carlson

A new pacemaker algorithm for the treatment of atrial fibrillation: Results of the Atrial Dynamic Overdrive Pacing Trial (ADOPT)

OBJECTIVES The Atrial Dynamic Overdrive Pacing Trial (ADOPT) was a single blind, randomized, controlled study to evaluate the efficacy and safety of the atrial fibrillation (AF) Suppression Algorithm (St. Jude Medical Cardiac Rhythm Management Division, Sylmar, California) in patients with sick sinus syndrome and AF. BACKGROUND This algorithm increases the pacing rate when the native rhythm emerges and periodically reduces the rate to search for intrinsic atrial activity. METHODS Symptomatic AF burden (percentage of days during which symptomatic AF occurred) was the primary end point. Patients underwent pacemaker implantation, were randomized to DDDR with the algorithm on (treatment) or off (control), and were followed for six months. RESULTS Baseline characteristics and antiarrhythmic drugs used were similar in both groups. The percentage of atrial pacing was higher in the treatment group (92.9% vs. 67.9%, p < 0.0001). The AF Suppression Algorithm reduced symptomatic AF burden by 25% (2.50% control vs. 1.87% treatment). Atrial fibrillation burden decreased progressively in both groups but was lower in the treatment group at each follow-up visit (one, three, and six months) (p = 0.005). Quality of life scores improved in both groups. The mean number of AF episodes (4.3 +/- 11.5 control vs. 3.2 +/- 8.6 treatment); total hospitalizations (17 control vs. 15 treatment); and incidence of complications, adverse events, and deaths were not statistically different between groups. CONCLUSIONS The ADOPT demonstrated that overdrive atrial pacing with the AF Suppression Algorithm decreased symptomatic AF burden significantly in patients with sick sinus syndrome and AF. The decrease in relative AF burden was substantial (25%), although the absolute difference was small (2.50% control vs. 1.87% treatment).

Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial.

OBJECTIVES This study compared a biphasic waveform with a conventional monophasic waveform for cardioversion of atrial fibrillation (AF). BACKGROUND Biphasic shock waveforms have been demonstrated to be superior to monophasic shocks for termination of ventricular fibrillation, but data regarding biphasic shocks for conversion of AF are still emerging. METHODS In an international, multicenter, randomized, double-blind clinical trial, we compared the effectiveness of damped sine wave monophasic versus impedance-compensated truncated exponential biphasic shocks for the cardioversion of AF. Patients received up to five shocks, as necessary for conversion: 100 J, 150 J, 200 J, a fourth shock at maximum output for the initial waveform (200 J biphasic, 360 J monophasic) and a final cross-over shock at maximum output of the alternate waveform. RESULTS Analysis included 107 monophasic and 96 biphasic patients. The success rate was higher for biphasic than for monophasic shocks at each of the three shared energy levels (100 J: 60% vs. 22%, p < 0.0001; 150 J: 77% vs. 44%, p < 0.0001; 200 J: 90% vs. 53%, p < 0.0001). Through four shocks, at a maximum of 200 J, biphasic performance was similar to monophasic performance at 360 J (91% vs. 85%, p = 0.29). Biphasic patients required fewer shocks (1.7 +/- 1.0 vs. 2.8 +/- 1.2, p < 0.0001) and lower total energy delivered (217 +/- 176 J vs. 548 +/- 331 J, p < 0.0001). The biphasic shock waveform was also associated with a lower frequency of dermal injury (17% vs. 41%, p < 0.0001). CONCLUSIONS For the cardioversion of AF, a biphasic shock waveform has greater efficacy, requires fewer shocks and lower delivered energy, and results in less dermal injury than a monophasic shock waveform.

Impact of Implantable Cardioverter-Defibrillator, Amiodarone, and Placebo on the Mode of Death in Stable Patients With Heart Failure Analysis From the Sudden Cardiac Death in Heart Failure Trial

Background— The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction ≤35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown. Methods and Results— SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death. Conclusions— ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.

Right ventricular outflow tract ventriculartachycardia: Detection of previously unrecognized anatomic abnormalities using cine magnetic resonance imaging☆

Abstract Objectives. This study attempted to determine whether cine magnetic resonance imaging (MRI), because of its unique ability to image the right ventricle, detects abnormalities in patients with right ventricular outflow tract ventricular tachycardia. Background. Right ventricular outflow tract ventricular tachycardia occurs in the absence of apparent structural heart disease. Methods. We compared cine MRI scans in 22 patients with right ventricular outflow tract ventricular tachycardia, 16 subjects without structural heart disease and 44 patients with other cardiovascular diseases. Echocardiography was performed in 21 patients with ventricular tachycardia. Results. All 22 patients with ventricular tachycardia had normal left ventricular function and no evidence of coronary artery disease. Cine MRI revealed right ventricular structural and wall motion abnormalities more often in patients with ventricular tachycardia (21 [95%] of 22) than in normal subjects (2 [12.5%] of 16, p

Importance of Atrial Flutter Isthmus in Postoperative Intra-Atrial Reentrant Tachycardia

BackgroundIn survivors of congenital heart surgery, intra-atrial reentrant tachycardia (IART) often develops. Previous reports have emphasized the atriotomy scar as the central barrier around which a reentrant circuit may rotate but have not systematically evaluated the atrial flutter isthmus in such patients. We sought to determine the role of the atrial flutter isthmus in supporting IART in a group of postoperative patients with congenital heart disease. Methods and ResultsNineteen postoperative patients with IART underwent electrophysiological studies with entrainment mapping of the atrial flutter isthmus for determining postpacing intervals. Radiofrequency ablation was performed at the identified isthmus in an effort to create a complete line of block. Twenty-one IARTs were identified in 19 patients, with a mean tachycardia cycle length of 293±73 ms. The atrial flutter isthmus was part of the circuit in 15 of 21 (71.4%). In the remaining 6 of 21, the ablation target zone was at sites near atrial incisions or suture lines. Ablation was successful in 19 of 21 (90.4%) IARTs and in 14 of 15 (93.3%) cases at the atrial flutter isthmus. ConclusionsIn most of our postoperative patients, the atrial flutter isthmus was part of the reentrant circuit. The fact that the atrial flutter isthmus is vulnerable to ablation suggests that whenever IART occurs late after repair of a congenital heart defect, the atrial flutter isthmus should be evaluated. These data support the theory that some form of conduction block between the vena cava is essential for the establishment of a stable substrate for the atrial flutter reentrant circuit.

Selective stimulation of parasympathetic nerve fibers to the human sinoatrial node.

Background In animals, parasympathetic nerve fibers that innervate the sinoatrial node can be selectively stimulated to increase atrial cycle length. These nerve fibers course through an epicardial fat pad at the margin of the right superior pulmonary vein, the superior vena cava, and the right atrium. We hypothesized that similar nerves exist and can be selectively stimulated in humans. Methods and Results Microscopic examination of fat pads excised from the margin of the right superior pulmonary vein, the superior vena cava, and the right atrium during two human autopsies revealed the presence of nerve fibers and ganglia. We electrically stimulated this epicardial fat pad in 16 patients during cardiac surgery. The fat pads were stimulated with continuous-pulse trains for 15 seconds via a hand-held bipolar electrode using constant current (10–15 mA), constant pulse width (0.02–0.05 msec), and at 6.6, 10, 20, 25, and 30 Hz. The mean atrial cycle length ±1 SEM increased from 734±34 msec at baseline to a maximum of 823±61 msec at 6.6 Hz, 1,167±125 msec at 10 Hz, 1,734±281 msec at 20 Hz, 2,993±661 msec at 25 Hz, and 2,461±668 msec at 30 Hz during nerve stimulation. Linear regression analysis showed that the response of atrial cycle length to sinoatrial parasympathetic nerve stimulation was frequency dependent. The maximum response and complete decay of the response occurred within 4–8 seconds of initiation or termination of sinoatrial parasympathetic nerve stimulation. Atrioventricular conduction time and the PR interval did not change during sinoatrial parasympathetic nerve stimulation, even when the atria were paced at the baseline heart rate. Conclusions Electrical stimulation of parasympathetic nerve fibers in a fat pad near the sinoatrial node increased atrial cycle length without affecting atrioventricular nodal conduction. This is the first study in which such nerve fibers that innervate the sinoatrial node have been selectively stimulated in humans.

Definition of the best prediction criteria of the time domain signal-averaged electrocardiogram for serious arryhthmic events in the postinfarction period

Objective. The goal of this study was to establish guidelines for the prognostic use of the time domain signal-averaged electrocardiogram (ECG) after myocardial infarction. Background. Previous studies of the prognostic use of the signal-averaged ECG in postinfarction patients had one or more of the following limitations: a small study group, empiric definition of an abnormal recording and possible bias in the selection of high risk groups or classification of arrhythmic events, or both. To correct for these limitations, a substudy was conducted in conjunction with the Cardiac Arrhythmia Suppression Trial (CAST). Methods. Ten centers recruited 1,211 patients with acute myocardial infarction without application of the ejection fraction or Holter criteria restrictions of the main CAST protocol. Several clinical variables, ventricular arrhythmias on the Holter recording, ejection fraction and six signal-averaged ECG variables were analyzed. Patients with bundle branch block were exluded from the analysis, and the remaining 1,158 were followed for up to 1 year after infarction. The classification of arrhythmic events was reviewed independently by the CAST Events Committee. Results. During an average (±SD) follow-up of 10.3 ± 3.2 months, 45 patients had a serious arrhythmic event (nonfatal ventricular tachycardia or sudden cardiac arrhythmic death). A Cox regression analysis with only the six signal-averaged ECG variables indicated that the filtered QRS duration at 40 Hz ≥120 ms (QRSD-40 Hz) at a cutpoint ≥120 ms was the most predictive criterion of arrhythmic events. In a regression analysis that included all clinical, Holter and ejection fraction variables, a QRSD-40 Hz ≥120 ms was the most significant predictor (p Conclusions. The signal-averaged ECG predicts serious arrhythmic events in the first year after infarction better than do clinical, ejection fraction and ventricular arrhythmia variables, and QRSD-40 Hz ≥120 ms provides the best predictive criterion in this clinical setting.

Classification of death in antiarrhythmia trials

OBJECTIVES We sought to develop and apply a new scheme for the classification of death to be used in trials of antiarrhythmia treatments. BACKGROUND Because presently accepted classifications of death do not fully describe or tabulate all significant aspects of terminal events, nor do they consider unique aspects of arrhythmia investigations, a new classification scheme that addresses these issues is desirable. METHODS A classification scheme of deaths that occur in antiarrhythmia trials was developed using the following categories: 1) primary organ cause (cardiac [arrhythmic, nonarrhythmic or unknown], noncardiac or unknown); 2) temporal course (sudden, nonsudden or unknown); 3) documentation (witnessed, monitored [yes, no or unknown]); 4) operative relation (preoperative, perioperative or postoperative); and 5) system relation (procedure related, pulse generator related and lead related [yes, no or unknown]). RESULTS The classification scheme was used in a clinical trial of a new implantable cardioverter-defibrillator (1,250 patients, of whom 79 died) and used in an application for device market approval. Application of the classification to data reported using an older classification scheme is demonstrated. CONCLUSIONS We propose a descriptive classification scheme that 1) fully describes and tabulates all significant aspects of terminal events; 2) incorporates previously used categorizations of death and new categorizations that address unique aspects of arrhythmia investigations; and 3) tabulates sufficient data to allow comparison with other studies. Events in a clinical trial of implantable defibrillator therapy were classified using the new classification scheme.

Life-threatening ventricular arrhythmias due to transient or correctable causes: high risk for death in follow-up

OBJECTIVES This study evaluated the prognosis of patients resuscitated from ventricular tachycardia (VT) or ventricular fibrillation (VF) with a transient or correctable cause suspected as the cause of the VT/VF. BACKGROUND Patients resuscitated from VT/VF in whom a transient or correctable cause has been identified are thought to be at low risk for recurrence and often receive no primary treatment for their arrhythmias. METHODS In the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, patients with a potentially transient or correctable cause of VT/VF were not eligible for randomization. The mortality of these patients was compared with the mortality of patients with a known high risk of recurrence of VT/VF in the AVID registry. RESULTS Compared with patients having high risk VT/VF, those with a transient or correctable cause for their presenting VT/VF were younger and had a higher left ventricular ejection fraction. These patients were more often treated with revascularization as the primary therapy, more commonly received a beta-blocker, less often required therapy for congestive heart failure and less commonly received either an antiarrhythmic drug or an implantable cardioverter defibrillator. Nevertheless, subsequent mortality of patients with a transient or correctable cause of VT/VF was no different or perhaps even worse than that of the primary VT/VF population. CONCLUSIONS Patients identified with a transient or correctable cause for their VT/VF remain at high risk for death. Further research is needed to define truly reversible causes of VT/VF. Meanwhile, these patients may require more aggressive evaluation, treatment and follow-up than is currently practiced.

Role of Permanent Pacing to Prevent Atrial Fibrillation Science Advisory From the American Heart Association Council on Clinical Cardiology (Subcommittee on Electrocardiography and Arrhythmias) and the Quality of Care and Outcomes Research Interdisciplinary Working Group, in Collaboration With the Heart Rhythm Society

This advisory summarizes the current database on pacing modalities and algorithms used to prevent and terminate atrial fibrillation (AF). On the basis of the evidence indicating that ventricular pacing is associated with a higher incidence of AF in patients with sinus node dysfunction, a patient who has a history of AF and needs a pacemaker for bradycardia should receive a physiological pacemaker (dual chamber or atrial) rather than a single-chamber ventricular pacemaker. For patients who need a dual-chamber pacemaker, efforts should be made to program the device to minimize the amount of ventricular pacing when atrioventricular conduction is intact. Many pacemakers and implantable defibrillators have features designed to prevent AF and to terminate AF with rapid atrial pacing. The evidence to support their use is limited, although these algorithms appear to be safe and usually add little additional cost. For patients who have a bradycardia indication for pacing and also have AF, no consistent data from large randomized trials support the use of alternative single-site atrial pacing, multisite right atrial pacing, biatrial pacing, overdrive pacing, or antitachycardia atrial pacing. Even fewer data support the use of atrial pacing in the management of AF in patients without symptomatic bradycardia. At present, permanent pacing to prevent AF is not indicated; however, additional studies are ongoing, which will help to clarify the role of permanent pacing for AF.