A Modular Communicative Leadless Pacing-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown. METHODS: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%). RESULTS: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure. CONCLUSIONS: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.).

Impact of Age on Subcutaneous Implantable Cardioverter-Defibrillator in a Large Patient Cohort: Mid-Term Follow-Up.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an accepted alternative to transvenous (TV) ICD to provide defibrillation therapy to treat life-threatening ventricular tachyarrhythmias in high-risk patients. S-ICD outcomes by age group have not been reported. OBJECTIVES: In this study, the authors sought to report S-ICD outcomes in different age groups in a multicenter S-ICD post-approval study (PAS) involving the largest cohort of patients ever reported. METHODS: Patients were prospectively enrolled in the S-ICD PAS and stratified based on age: young, aged 15-34 years; adult, aged 35-69 years; and elderly, aged ≥70 years. Patient characteristics and clinical outcomes through 3 years of follow up after implantation were compared. RESULTS: The S-ICD PAS enrolled 1,637 patients. Elderly patients were more likely to receive an S-ICD as a replacement of a TV-ICD (15.1% elderly vs 12.3% adult vs 7.4% young). Secondary prevention indication decreased with age (32.7% young vs 22.2% adult vs 20.5% elderly). Mortality rate was significantly higher in the elderly group (24.0% elderly vs 13.0% adult vs 7.4% young; P < 0.0001), whereas the complication rate did not differ significantly (12.3% young vs 11.3% adult vs 8.1% elderly). Rates of appropriate shock (12.7% young vs 13.0% adult vs 13.8% elderly) and inappropriate shock (7.8% young vs 9.1% adult vs 8.8% elderly) rates did not differ between groups (P = 0.96 and P = 0.98, respectively). CONCLUSIONS: Implant complications and appropriate and inappropriate shock rates were similar among age groups. S-ICD for secondary prevention was more common in the young group. Replacing a TV-ICD for an S-ICD increases with age. (S-ICD System Post-Approval Study; NCT01736618).

Initial Experience With Intercostal Insertion of an Extravascular ICD Lead Compatible With Existing Pulse Generators.

BACKGROUND: This study assessed safety and feasibility of a novel extravascular implantable cardioverter defibrillator (ICD) lead when inserted anteriorly through a rib space and connected to various commercially available ICD pulse generators (PGs) placed in either a left mid-axillary or left pectoral pocket. Currently available or investigational, extravascular-ICDs include a subcutaneous or subxiphoid lead connected to customized extravascular-ICD PGs. METHODS: This novel extravascular-ICD (AtaCor Medical Inc, San Clemente, CA) employs a unique intercostal implant technique and is designed to function with commercial DF-4 ICD PGs. In this nonrandomized, single-center, acute study, 36 de novo or replacement ICD (transvenous ICD) patients enrolled to receive a concomitant extravascular-ICD lead inserted through an intercostal space along the left parasternal margin. extravascular-ICD leads were connected to DF-4 compatible ICD PGs positioned in either a left mid-axillary or pectoral pocket for acute sensing and defibrillation testing. Defibrillation testing started at 30 Joules (J) and stepped up or down in 5 to 10 joule increments depending on the success and limitations of the generator used. RESULTS: Successful acute defibrillation using ≤35 J was noted in 100% of left mid-axillary PG subjects (n=27, mean 16.3±8.6 J) and 83% of left pectoral PG subjects (n=6, mean 21.0±8.4 J). Furthermore, 24 of 27 (89%) of patients tested with a left, mid-axillary intermuscular PG had successful VF conversion with defibrillation energies at least 10 J below the maximum delivered output of the device. All evaluable episodes (n=93) were automatically sensed, detected, and shocked. No serious device-related intraoperative adverse events were observed. CONCLUSIONS: This first-in-human study documented the safe and reliable placement of a novel extravascular ICD lead with effective sensing and defibrillation of induced ventricular fibrillation using commercial DF-4 ICD PGs.

Postapproval Study of a Subcutaneous Implantable Cardioverter-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to avoid complications related to transvenous implantable cardioverter-defibrillator (TV-ICD) leads. Device safety and efficacy were demonstrated previously with atypical clinical patients or limited follow-up. OBJECTIVES: The S-ICD PAS (Subcutaneous Implantable Cardioverter-Defibrillator System Post Approval Study) is a real-world, multicenter, registry of U.S. centers that was designed to assess long-term S-ICD safety and efficacy in a diverse group of patients and implantation centers. METHODS: Patients were enrolled in 86 U.S. centers with standard S-ICD indications and were observed for up to 5 years. Efficacy endpoints were first and final shock efficacy. Safety endpoints were complications directly related to the S-ICD system or implantation procedure. Endpoints were assessed using prespecified performance goals. RESULTS: A total of 1,643 patients were prospectively enrolled, with a median follow-up of 4.2 years. All prespecified safety and efficacy endpoint goals were met. Shock efficacy rates for discrete episodes of ventricular tachycardia or ventricular fibrillation were 98.4%, and they did not differ significantly across follow-up years (P = 0.68). S-ICD-related and electrode-related complication-free rates were 93.4% and 99.3%, respectively. Only 1.6% of patients had their devices replaced by a TV-ICD for a pacing need. Cumulative all-cause mortality was 21.7%. CONCLUSIONS: In the largest prospective study of the S-ICD to date, all study endpoints were met, despite a cohort with more comorbidities than in most previous trials. Complication rates were low and shock efficacy was high. These results demonstrate the 5-year S-ICD safety and efficacy for a large, diverse cohort of S-ICD recipients. (Subcutaneous Implantable Cardioverter-Defibrillator [S-ICD] System Post Approval Study [PAS]; NCT01736618).

Infection in patients with subcutaneous implantable cardioverter-defibrillator: Results of the S-ICD Post Approval Study.

BACKGROUND: Early subcutaneous implantable cardioverter-defibrillator (S-ICD) studies included atypical cohorts of patients who were younger with fewer comorbidities. Recent S-ICD studies included patient populations with more comorbidities. OBJECTIVES: The goals of this study were to determine the incidence and predictors of S-ICD-related infection over a 3-year follow-up period and to use these results to develop an infection risk score. METHODS: The S-ICD Post Approval Study is a US prospective registry of 1637 patients. Baseline demographic characteristics and outcomes with 3-year postimplantation follow-up were compared between patients with and without device-related infection. A risk score was derived from multivariable proportional hazards analysis of 22 variables. RESULTS: Infection was observed in 55 patients (3.3%), with 69% of infections occurring within 90 days and a vast majority (92.7%) within 1 year of implantation. Late infections more likely involved device erosion; no infections occurred after year 2. The annual mortality rate postinfection was 0.6%/y. No lead extraction complications or bacteremia related to infection were observed. An infection risk score was created with diabetes, age, prior transvenous ICD implant, and ejection fraction as predictors. Patients with a risk score of ≥3 had an 8.8 hazard ratio (95% confidence interval 2.8-16.3) of infection compared with a 0 risk score. CONCLUSION: Infection rates in the S-ICD Post Approval Study were similar to other S-ICD populations and not associated with systemic blood-borne infections. Late infection (>1 year) is uncommon and associated with system erosion. A high-risk infection cohort can be identified that may facilitate preventive measures.

Outcomes of two versus three incision techniques: Results from the subcutaneous ICD post-approval study.

BACKGROUND: Traditionally, implantation of the subcutaneous implantable cardioverter defibrillator (S-ICD) requires incisions near the lateral chest wall, the xyphoid, and the superior sternal region (three-incision technique [3IT]). A two-incision technique (2IT) avoids the superior incision and has been shown to be a viable alternative in small studies with limited follow-up. OBJECTIVES: To report on the long-term safety and efficacy of the 2IT compared to the 3IT procedure in a large patient cohort. METHODS: Patients enrolled in the S-ICD post approval study (PAS) were stratified by procedural technique (2IT vs. 3IT). Baseline demographics, comorbidities and procedural outcomes were collected. Complications and S-ICD effectiveness in treating ventricular arrhythmias through an average 3-year follow-up period were compared. RESULTS: Of 1637 patients enrolled in the S-ICD PAS, 854 pts (52.2%) were implanted using the 2IT and 782 were implanted using the 3IT (47.8%). The 2IT became more prevalent over time, increasing from 40% to 69% of implants (Q1-Q4). Mean procedure time was shorter with 2IT (69.0 vs. 86.3 min, p < .0001). No other differences in outcomes were observed between the two groups, including rates of infection, electrode migration, inappropriate shocks and first shock efficacy for treating ventricular arrhythmias. CONCLUSION: In this large cohort of patients implanted with an S-ICD and followed for 3 years the 2IT was as safe and effective as the 3IT while significantly reducing procedure time.

Primary Results From the Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction (UNTOUCHED) Trial.

BACKGROUND: The subcutaneous (S) implantable cardioverter-defibrillator (ICD) is safe and effective for sudden cardiac death prevention. However, patients in previous S-ICD studies had fewer comorbidities, had less left ventricular dysfunction, and received more inappropriate shocks (IAS) than in typical transvenous ICD trials. The UNTOUCHED trial (Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction) was designed to evaluate the IAS rate in a more typical, contemporary ICD patient population implanted with the S-ICD using standardized programming and enhanced discrimination algorithms. METHODS: Primary prevention patients with left ventricular ejection fraction ≤35% and no pacing indications were included. Generation 2 or 3 S-ICD devices were implanted and programmed with rate-based therapy delivery for rates ≥250 beats per minute and morphology discrimination for rates ≥200 and <250 beats per minute. Patients were followed for 18 months. The primary end point was the IAS-free rate compared with a 91.6% performance goal, derived from the results for the ICD-only patients in the MADIT-RIT study (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy). Kaplan-Meier analyses were performed to evaluate event-free rates for IAS, all-cause shock, and complications. Multivariable proportional hazard analysis was performed to determine predictors of end points. RESULTS: S-ICD implant was attempted in 1116 patients, and 1111 patients were included in postimplant follow-up analysis. The cohort had a mean age of 55.8±12.4 years, 25.6% were women, 23.4% were Black, 53.5% had ischemic heart disease, 87.7% had symptomatic heart failure, and the mean left ventricular ejection fraction was 26.4±5.8%. Eighteen-month freedom from IAS was 95.9% (lower confidence limit, 94.8%). Predictors of reduced incidence of IAS were implanting the most recent generation of device, using the 3-incision technique, no history of atrial fibrillation, and ischemic cause. The 18-month all-cause shock-free rate was 90.6% (lower confidence limit, 89.0%), meeting the prespecified performance goal of 85.8%. Conversion success rate for appropriate, discrete episodes was 98.4%. Complication-free rate at 18 months was 92.7%. CONCLUSIONS: This study demonstrates high efficacy and safety with contemporary S-ICD devices and programming despite the relatively high incidence of comorbidities in comparison with earlier S-ICD trials. The inappropriate shock rate (3.1% at 1 year) is the lowest reported for the S-ICD and lower than many transvenous ICD studies using contemporary programming to reduce IAS. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02433379.

1-Year Prospective Evaluation of Clinical Outcomes and Shocks: The Subcutaneous ICD Post Approval Study.

OBJECTIVES: This study evaluated spontaneous arrhythmias and clinical outcomes in the S-ICD System PAS (Subcutaneous Implantable Cardioverter-Defibrillator Post Approval Study) cohort. BACKGROUND: The U.S. S-ICD PAS trial patient population more closely resembles transvenous ICD cohorts than earlier studies, which included many patients with little structural heart disease and few comorbidities. Early outcomes and low peri-operative complication rates were demonstrated in the S-ICD PAS cohort, but there are no data detailing spontaneous arrhythmias and clinical outcomes. METHODS: The S-ICD PAS prospective registry included 1,637 de novo patients from 86 U.S. centers. Descriptive statistics, Kaplan-Meier time to event, and multivariate logistic regression were performed using data out to 365 days. RESULTS: Patients (68.5% men; mean ejection fraction of 32.0%; 42.9% ischemic; 13.4% on dialysis) underwent implantation for primary (76.6%) or secondary prevention indication. The complication-free rate was 92.5%. The appropriate shock (AS) rate was 5.3%. A total of 395 ventricular tachycardia (VT) or fibrillation (VF) episodes were appropriately sensed, with 131 (33.2%) self-terminating. First and final shock efficacy (up to 5 shocks) for the 127 discrete AS episodes were 91.3% and 100.0%, respectively. Discrete AS episodes included 67 monomorphic VT (MVT) and 60 polymorphic VT (PVT)/VF, with first shock efficacy of 95.2% and 86.7%, respectively. There were 19 storm events in 18 subjects, with 84.2% conversion success. Storm episodes were more likely PVT/VF (98 of 137). CONCLUSIONS: In the first year after implantation, a predominantly primary prevention population with low ejection fraction demonstrated a high complication-free rate and spontaneous event shock efficacy for MVT and PVT/VF arrhythmias at rapid ventricular rates. (Subcutaneous Implantable Cardioverter-Defibrillator System Post Approval Study [S-ICD PAS; NCT01736618).

Understanding Outcomes with the EMBLEM S-ICD in Primary Prevention Patients with Low EF Study (UNTOUCHED): Clinical characteristics and perioperative results.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has shown favorable outcomes in large registries with broad inclusion criteria. The cohorts reported had less heart disease and fewer comorbidities than standard ICD populations. OBJECTIVE: The purpose of this study is to characterize acute performance for primary prevention patients with a left ventricular ejection fraction (LVEF) ≤35% (primary prevention ≤35%). METHODS: Primary prevention ≤35% patients with no prior documented sustained ventricular tachycardia (VT), pacing indication, end-stage heart failure, or advanced renal failure were prospectively enrolled. Analyses included descriptive statistics, Kaplan-Meier time to event, and multivariable linear and logistic regression. RESULTS: In 1112 of 1116 patients, an S-ICD was successfully implanted (99.6%). Predictors for longer procedure time included 3-incision technique, higher body mass index (BMI), performing defibrillation testing (DFT), imaging, younger age, black race, and European vs North American centers. Patients undergoing DFT (82%) were successfully converted (99.2%; 93.5% converting at ≤65 J). Higher BMI was predictive of failing DFT at ≤65 J. The rate of 30-day freedom from complications was 95.8%. Most complications involved postoperative healing (45%) or interventions after DFT or impedance check (19%). CONCLUSION: The procedural outcome data of UNTOUCHED reinforce that S-ICD therapy has low perioperative complication rates and high conversion efficacy of induced ventricular fibrillation, even in a higher-risk cohort with low LVEF and more comorbidities than previous S-ICD studies. Higher BMI warrants more careful attention to implant technique.

Anesthesia for subcutaneous implantable cardioverter-defibrillator implantation: Perspectives from the clinical experience of a U.S. panel of physicians.

BACKGROUND AND OBJECTIVE: Worldwide adoption of the subcutaneous implantable cardioverter-defibrillator (S-ICD) for preventing sudden cardiac death continues to increase, as longer-term evidence demonstrating the safety and efficacy of the S-ICD expands. As a relatively new technology, comprehensive anesthesia guidance for the management of patients undergoing S-ICD placement is lacking. This article presents advantages and disadvantages of different periprocedural sedation and anesthesia options for S-ICD implants including general anesthesia, monitored anesthesia care, regional anesthesia, and nonanesthesia personnel administered sedation and analgesia. METHODS: Guidance, for approaches to anesthesia care during S-ICD implantation, is presented based upon literature review and consensus of a panel of high-volume S-ICD implanters, a regional anesthesiologist, and a cardiothoracic anesthesiologist with significant S-ICD experience. The panel developed suggested actions for perioperative sedation, anesthesia, surgical practices, and a decision algorithm for S-ICD implantation. CONCLUSIONS: While S-ICD implantation currently requires higher sedation than transvenous ICD systems, the panel consensus is that general anesthesia is not required or is obligatory for the majority of patients for the experienced S-ICD implanter. The focus of the implanting physician and the anesthesia services should be to maximize patient comfort and take into consideration patient-specific comorbidities, with a low threshold to consult the anesthesiology team.

Subcutaneous implantable cardioverter-defibrillator Post-Approval Study: Clinical characteristics and perioperative results.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to reduce short- and long-term complications associated with transvenous ICD leads. Early multicenter studies included younger patients with less left ventricular systolic dysfunction and fewer comorbidities than cohorts with traditional ICD. OBJECTIVE: The purpose of this study was to characterize patient selection and the acute performance of the S-ICD in a contemporary real-world setting. METHODS: The S-ICD Post-Approval Study is a prospective registry involving 86 US centers. Patients were enrolled if they met criteria for S-ICD implantation, passed an electrocardiogram screening test, and had a life expectancy of >1 year. Analyses of descriptive statistics, Kaplan-Meier time to event, and multivariate logistic regression were performed. RESULTS: The study includes 1637 patients who underwent S-ICD implantation. The cohort included 68.6% (1123/1637) male patients, and 13.4% (220/1636) were receiving dialysis for end-stage renal disease. The mean age was 52 ± 15 years, with a mean left ventricular ejection fraction of 32.0% ± 14.6%. Electrocardiogram screening was successful for at least 1, 2, or 3 vectors in 100%, 93.8%, and 51.4% of patients, respectively. Medical imaging (65.1%, 1065/1636) and general anesthesia (64.1%, 1048/16) were used in a majority of patients, and 52.2% (855/1637) were implanted with the 2-incision technique. Induced ventricular tachycardia/ventricular tachycardia was successfully converted in 98.7% (1394/1412) of patients. The 30-day complication-free rate was 96.2%. Predictors of complications included diabetes, younger age, and higher body mass index. CONCLUSION: Contemporary US patients with S-ICD have more comorbidities than do previous cohorts with S-ICD, but they are younger with more end-stage renal disease than do patients with transvenous ICD. Implantation success is high, and short-term complication rates are acceptable.

Mortality Effect of ICD in Primary Prevention of Nonischemic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Implantation of an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) is controversial in view of the recent DANISH trial which suggested no benefit with ICD for primary prevention in patients with non-ischemic cardiomyopathy (NICMP). METHODS: We conducted a meta-analysis of randomized control trials studying the role of ICD in primary prevention of SCD in patients with NICMP. Only six studies were identified after the application of inclusion/exclusion criteria. RESULTS: Pooling of these randomized trials showed a statistically significant benefit of using ICDs in patients with NICMP [OR 0.76 (0.64 - 0.91), I2 = 0%]. Sensitivity analysis did not show a statistically significant mortality benefit of ICD in NICMP in trials which had adequate beta blocker, ACE/ARB and aldosterone receptor blocker (ALD-RB) use [OR 0.70 (0.41, 1.19), I2 = 70%]. CONCLUSION: The DANISH trial's failure to show mortality benefit may be due to the significant number of patients who had CRT. Our meta-analysis studied the independent effect of ICDs and showed them to be associated with net mortality benefits in patients who are not on optimal guideline directed medical therapy; especially the patients not on ALD-RB.

The Design of the Understanding Outcomes with the S-ICD in Primary Prevention Patients with Low EF Study (UNTOUCHED).

BACKGROUND: The UNTOUCHED study will assess the safety and efficacy of the subcutaneous implantable cardioverter defibrillator (S-ICD) in the most common cohort of patients receiving ICDs. The primary goal is to evaluate the inappropriate shock (IAS)-free rate in primary prevention patients with a reduced ejection fraction (EF) and compare with a historical control of transvenous ICD patients with similar programming. METHODS AND RESULTS: The UNTOUCHED study is a global, multicenter, prospective, nonrandomized study of patients undergoing de novo S-ICD implantation for primary prevention of sudden cardiac death with a left ventricular EF ≤35%. The primary end point of this trial is freedom from IAS at 18 months. The lower 95% confidence bound of the observed incidence will be compared to a performance goal of 91.6%, which was derived from the IAS rate in MADIT-RIT. The secondary end points are all-cause shock-free rate at 18 months, and system- and procedure-related complication-free rate at 1 month and 6 months. Enrollment of a minimum of 1,100 subjects from up to 200 centers worldwide is planned based on power calculations of the primary and principal secondary end points. CONCLUSIONS: This trial will provide important data regarding the rates of inappropriate and appropriate shock therapy in real-world use of the S-ICD in the most common group of patients receiving ICDs.

Inadvertent electrical isolation of the left atrial appendage during catheter ablation of persistent atrial fibrillation.

BACKGROUND: Left atrial appendage (LAA) isolation is rare and may be associated with impaired transport function and thromboembolism. OBJECTIVE: The purpose of this study was to determine the mechanisms of inadvertent isolation of the LAA during atrial fibrillation (AF) ablation. METHODS: This study consisted of 11 patients (ejection fraction 0.43 +/- 0.18, left atrial diameter 51 +/- 8 mm) with persistent AF who had LAA conduction block during a procedure for AF (n = 8) or atrial tachycardia (AT) (n = 3). RESULTS: LAA conduction block occurred during ablation at the Bachmann bundle region in 6 patients, mitral isthmus in 3, LAA base in 2, and coronary sinus in 1. The mean distance from the ablation site to the LAA base was 5.0 +/- 1.9 cm. LAA isolation was transient in all 6 patients in whom LAA conduction was monitored and was permanent in the 4 patients in whom conduction was not monitored during energy delivery. The remaining patient was noted to have LAA isolation during a redo procedure before any ablation. Nine of (82%) the 11 patients have remained arrhythmia-free without antiarrhythmic drugs at mean follow-up of 6 +/- 7 months, and all have continued taking warfarin. CONCLUSION: Electrical isolation of the LAA may occur during ablation of persistent AF and AT even when the ablation site is remote from the LAA. This likely is due to disruption of the Bachmann bundle and its leftward extension, which courses along the anterior left atrium and bifurcates to surround the LAA. Monitoring of LAA conduction during ablation of persistent AF or AT is important in avoiding permanent LAA isolation.

Amiodarone prophylaxis reduces major cardiovascular morbidity and length of stay after cardiac surgery: a meta-analysis.

BACKGROUND: Although evidence supports the prophylactic use of beta-blockade in cardiac surgery, postoperative atrial fibrillation or flutter occurs in 40% to 60% of patients. Trials that assessed whether amiodarone prophylaxis decreases the incidence of postoperative atrial tachyarrhythmias have had mixed results and were not specifically powered to detect changes in cardiovascular morbidity, length of stay, or mortality. PURPOSE: To see whether prophylactic administration of amiodarone decreases the incidence of major cardiovascular events, length of stay, and mortality after cardiac surgery. DATA SOURCES: English-language and non-English-language publications listed in the MEDLINE, EMBASE, and CINAHL databases and the Cochrane Central Register of Controlled Trials, and bibliographies of published reviews. Sources were searched from the earliest possible dates through February 2005. STUDY SELECTION: Double-blind, randomized studies comparing amiodarone with placebo that reported the incidence of supraventricular arrhythmia, atrial fibrillation, or atrial flutter as the primary end point. DATA EXTRACTION: Two investigators independently collected all data. Discrepancies were resolved by consensus. DATA SYNTHESIS: After DerSimonian-Laird random-effects models were used to combine data from 10 trials involving 1744 patients, amiodarone therapy was found to decrease the incidence of atrial fibrillation or flutter (relative risk, 0.64 [95% CI, 0.55 to 0.75]), ventricular tachycardia and fibrillation (relative risk, 0.42 [CI, 0.28 to 0.63]), stroke (relative risk, 0.39 [CI, 0.21 to 0.76]), and length of stay (weighted mean difference, -0.63 day [CI, -1.03 to -0.23 days]). All studies reported adverse events, but none indicated how these events were assessed. Three studies found significantly more adverse events with amiodarone therapy, including nausea permitting continuation of therapy, bradycardia of unclear clinical significance, and increased intensive care monitoring and support. LIMITATIONS: Not all studies used beta-blockade, and regimens were not uniform among trials. Few trials met the stringent inclusion criteria, some did not report each type of cardiovascular event, and none reported completeness of follow-up. CONCLUSIONS: Amiodarone prophylaxis decreases the occurrence of atrial fibrillation, ventricular tachyarrhythmias, and stroke and length of stay after cardiac surgery. To further evaluate the potential benefits of concomitant prophylaxis with beta-blockers and amiodarone, a multicenter, randomized, double-blind trial with cardiovascular outcomes that compares amiodarone with placebo in patients already receiving beta-blocker prophylaxis is needed.