Kousik Krishnan

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

Context Tachyarrhythmias are common after heart surgery and are associated with increased morbidity. Contribution This meta-analysis of 10 randomized, double-blind trials involving 1744 patients undergoing open-heart surgery found that, compared with placebo, amiodarone reduced atrial and ventricular arrhythmias, stroke, and length of hospital stay. Side effects included nausea and bradycardia that was not always deemed clinically important. Cautions Trial participants did not always receive prophylaxis with -blockers. Dosages and timing of amiodarone and length of follow-up varied across studies. Implications Amiodarone may benefit some patients undergoing heart surgery. We now need trials of prophylaxis with both -blockers and amiodarone. The Editors Atrial fibrillation and atrial flutter are common after cardiac surgery. Studies have estimated their incidence to be as high as 40% to 60% after coronary artery bypass grafting or cardiac valve surgery (1, 2). These arrhythmias most often develop between the second and fifth postoperative day (3), with a peak incidence in the first 2 to 3 days (4). Atrial fibrillation and atrial flutter increase the occurrence of postoperative stroke (4), perioperative myocardial infarction, heart failure, and readmission to the intensive care unit (and reintubation) (5); length of stay; and total cost of hospitalization (6, 7). Recent data suggest that atrial fibrillation and atrial flutter are independent risk factors for inpatient and long-term mortality after open-heart surgery (8). Amiodarone has complex pharmacokinetics and pharmacodynamics. Although it is categorized as a VaughnWilliams class III agent, amiodarone combines anti-adrenergic effects (9) with sodium-, calcium-, and potassium-channel blocking properties (10). Striking pharmacologic and therapeutic differences between short-term and long-term administration are not readily accounted for by plasma, tissue, or membrane levels of drug. The most rapid electrophysiologic effects of amiodarone are prolongation of AV nodal refractoriness and conduction time. These effects probably result from calcium-channel blockade and noncompetitive -receptor antagonism. Sinus bradycardia develops more gradually as a function of time while receiving a constant dose (11). Short-term amiodarone administration also blocks sodium channels (making the threshold voltage for activation more positive), thereby reducing automaticity (ectopic triggers) and prolonging conduction velocity (length of the tachycardia cycle) (12-14). Amiodarone may also reduce automaticity by decreasing the recruitment of voltage-dependent inward current (the pacemaker current) during spontaneous depolarization, reducing the slope of phase 4 of the action potential (14). Long-term therapy (weeks to months) results in prolongation of atrial and ventricular effective refractory periods because of potassium blockade (11, 15). Clinical trials of varying size and design have evaluated the efficacy of amiodarone in reducing the incidence of atrial fibrillation and atrial flutter after cardiac surgery (16-22). No prospective studies have intentionally been powered to detect decreases in major cardiovascular morbidity or mortality. Current American College of Cardiology/American Heart Association/European Society of Cardiology guidelines recommend -blocker therapy for all patients (without contraindications) before cardiac surgery and reserve therapy with amiodarone for patients at increased risk for postoperative atrial fibrillation and atrial flutter (those with a history of atrial fibrillation, left atrial enlargement, or valvular heart disease) (23). We performed a meta-analysis to compare the effect of treatment with amiodarone or placebo on the incidence of atrial fibrillation and atrial flutter, the incidence of major cardiovascular morbidity (ventricular tachycardia or fibrillation, stroke, or myocardial infarction), length of stay, and death. Subgroup analyses were done to compare patients who began amiodarone prophylaxis up to 13 days before surgery with those who received amiodarone intraoperatively or immediately postoperatively, and patients who received oral amiodarone with those who received intravenous amiodarone. Methods Literature Search We conducted this review in accordance with recommendations put forth by the QUOROM Group (24). We searched the English-language and nonEnglish-language literature by using MEDLINE, EMBASE, and CINAHL databases and the Cochrane Central Register of Controlled Trials from the earliest searchable dates through February 2005. Search terms were atrial fibrillation, amiodarone, and surgery. We also searched the bibliographies of published reviews but excluded unpublished data. Data Collection Inclusion criteria for the meta-analysis were established before the literature search. Studies had a randomized, controlled, double-blind design to compare amiodarone with placebo; included patients who underwent coronary artery bypass grafting or cardiac valve surgery (or both); measured the occurrence of atrial fibrillation, atrial flutter, or supraventricular tachycardia as a primary outcome; and clearly described drug administration, comorbid conditions, the risk profile of study cohorts, study design, and methods. One author screened titles and abstracts before manuscript retrieval. Three authors read all retrieved manuscripts and made the final decision on which studies met the inclusion criteria. All data were abstracted independently and in duplicate by 2 of the authors by using a standardized data collection form. Discrepancies in the data abstracted were resolved by consensus among all authors. We assessed reported randomization methods and completeness of follow-up but avoided use of a formal or aggregated score for quality assessment because such use can produce inconsistent results (25). Statistical Analysis Incidences of atrial fibrillation, atrial flutter, stroke, ventricular tachycardia or fibrillation, myocardial infarction, and death were treated as dichotomous variables. Summary effects for the dichotomous variables were calculated as relative risks. Length of stay was treated as a continuous variable. The summary effect for data on length of stay was calculated as the weighted mean difference. Data on length of stay were included in calculating the summary effect only if both the mean and standard deviation were specified. We pooled data by using the DerSimonianLaird random-effects model (26). Statistical heterogeneity for all variables was assessed by using the I2 measure because this measure is independent of the number of studies that are pooled and of the effect-size metric (27). To assess for possible publication bias, we used the test proposed by Egger and colleagues (28), which provides an assessment of funnel-plot asymmetry (expressed as a P value) by applying an inverse-variance weighted approach. For each variable, studies were assigned a MantelHaenszel weight that was directly proportional to the sample size and inversely proportional to the variance of each study. For subgroup analysis, studies were organized into 2 categories according to when amiodarone or placebo was initially administered. Studies were categorized as preoperative if administration of amiodarone or placebo began before surgery or perioperative if drug or placebo was administered during or immediately after surgery. To compare the efficacy of oral versus intravenous administration of amiodarone, we excluded trials in which both routes were used. Publication bias was assessed by using StatsDirect software, version 2.3.1 (StatsDirect Ltd., Sale, United Kingdom). All other statistical calculations were performed by using Review Manager (RevMan) statistical software, version 4.2.7 for Windows (The Cochrane Collaboration, Oxford, United Kingdom). Continuous data are expressed as the mean and standard deviation, unless otherwise specified. A 2-sided P value less than 0.05 was considered significant. Role of the Funding Source We received no intramural or extramural funding for this study. Results Figure 1 shows the trial selection process. Searches identified 1989 potentially relevant citations. Of these, we considered and retrieved 17 citations for possible inclusion in the meta-analysis (16-22, 29-38). We excluded 4 studies because they were not double-blind (16-18, 22), 1 because it compared amiodarone with propranolol rather than placebo (19), 1 because the characteristics of the participants and details of the study methods were not provided (20), and 1 because the amiodarone regimen (a single oral dose of 1.2 g) differed markedly from those used in other studies (21). Figure 1. Flow diagram of study selection. Table 1 provides information on the patients and design of the included studies. One thousand seven hundred forty-four patients were included. In 4 studies, amiodarone or placebo was administered before surgery. In 6 studies, therapy was given during or immediately after surgery. Five studies included patients who underwent coronary artery bypass grafting only, and 5 included patients who had coronary artery bypass grafting or valve surgery. All patients received at least 2 g of amiodarone by the second postoperative day. Amiodarone was administered orally in 5 studies, intravenously in 2 studies, and both orally and intravenously in 3 studies. Eight studies reported ventricular tachycardia and fibrillation, 8 reported stroke, and 4 reported myocardial infarction. Follow-up data were limited to inpatient stay for all studies except that by Giri and associates (34), which included information on death at 30 days. No study included in our analysis gave data on adequacy of patient follow-up (dropout rate). Table 1. Randomized, Controlled Trials Included in the Meta-Analysis Table 2 shows medical and surgical data for the included patients. The mean patient age was 64.4 years, and the mean left ventricular ejection fraction was 0.49

Detection of Atrial Fibrillation With Concurrent Holter Monitoring and Continuous Cardiac Telemetry Following Ischemic Stroke and Transient Ischemic Attack

Atrial fibrillation (AF) is a major risk factor for recurrent ischemic stroke. We aimed to compare the detection rate of AF using continuous cardiac telemetry (CCT) versus Holter monitoring in hospitalized patients with ischemic stroke or transient ischemic attack (TIA). Between June 2007 and December 2008, 133 patients were admitted to an academic institution for ischemic stroke or TIA and underwent concurrent inpatient CCT and Holter monitoring. Rates of AF detection by CCT and Holter monitoring were compared using the McNemar paired proportion test. Among the 133 patients, 8 (6.0%) were diagnosed with new-onset AF. On average, Holter monitoring was performed for 29.8 hours, and CCT was performed for 73.6 hours. The overall rate of AF detection was higher for Holter monitoring compared with CCT (6.0%; 95% confidence interval [CI], 2.9-11.6 vs 0; 95% CI, 0-3.4; P = .008). Holter detection of AF was even higher in specific subgroups (those with an embolic infarct pattern, those age >65 years, and those with coronary artery disease). Holter monitoring detected AF in 6% of hospitalized ischemic stroke and TIA patients, with higher proportions in high-risk subgroups. Compared with CCT, Holter monitoring is significantly more likely to detect arrhythmias.

Usefulness of Transesophageal Echocardiography to Confirm Clinical Utility of CHA2DS2-VASc and CHADS2 Scores in Atrial Flutter

The CHA(2)DS(2)-VASc and CHADS(2) risk stratification schemes are used to predict thromboembolism and ischemic stroke in patients with atrial fibrillation. However, limited data are available regarding the utility of these risk stratification schemes for stroke in patients with atrial flutter. A retrospective analysis of 455 transesophageal echocardiographic studies in patients with atrial flutter was performed to identify left atrial (LA) thrombi and/or spontaneous echocardiographic contrast (SEC). The CHA(2)DS(2)-VASc (Congestive heart failure, Hypertension, Age ≥75 years [doubled risk weight], Diabetes mellitus, previous Stroke/transient ischemic attack [doubled risk weight], Vascular disease, Age 65 to 74 years, Sex) and CHADS(2) (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke/transient ischemic attack [double risk weight]) scores were calculated to stratify the risk of stroke or transient cerebrovascular ischemic events. Transesophageal echocardiography revealed LA thrombi in 5.3% and SEC in 25.9% of patients. Using CHADS(2), LA thrombus was found in 2.2% of the low-intermediate-risk group and 8.3% of the high-risk group (p = 0.005). SEC was found in 19.8% of the low-intermediate-risk group and 32% of the high-risk group (p = 0.004). Using CHA(2)DS(2)-VASc, LA thrombus was found in 1.7% of the low-intermediate-risk group and 6.5% of the high-risk group (p = 0.053). SEC was found in 11.8% of the low-intermediate-risk group versus 30.9% of the high-risk group (p = 0.004). The sensitivity for LA thrombus/SEC with a high CHADS(2) and CHA(2)DS(2)-VASc score was 64.8% and 88.7%, respectively (p = 0.0001). The specificity for LA thrombus/SEC with high CHADS(2) and CHA(2)DS(2)-VASc scores was 52.6% and 28.9%, respectively (p = 0.0001). In conclusion, both CHA(2)DS(2)-VASc and CHADS(2) scores are useful for stroke risk stratification in patients with atrial flutter. CHA(2)DS(2)-VASc had greater sensitivity for LA thrombus and SEC detection at the cost of reduced specificity.

Reassessing Risk Factors for High Defibrillation Threshold: The EF-SAGA Risk Score and Implications for Device Testing.

To reevaluate risk factors for high defibrillation threshold (DFT) and propose a risk assessment tool.

Rescue permanent iliac vein pacing after epicardial lead failure: an unusual reversal of pacing fortune

Surgical lead placement is generally considered as a last resort for patients who require permanent pacing and who are unable to accommodate transvenous leads. The technique is limited by the need for direct epicardial access and reduced reliability of epicardial leads (compared with modern transvenous leads) [Belott and Reynolds. Permanent pacemaker and implantable cardioverter defibrillator implantation. In Ellenbogen KA, Kay GN, Lau CP, Wilkoff BL (eds). Clinical Cardiac Pacing, Defibrillation, and Resynchronization Therapy. Philadelphia: Saunders Elsevier, 2007; pp. 561-651]. We report a patient with limited venous access and a poorly functioning epicardial ventricular lead, who was successfully upgraded to a dual-chamber endocardial pacing system via the iliac vein. Pacemaker lead implantation from the iliac vein is an often overlooked option for patients with limited central venous access. In our patient, a pacing upgrade was achieved after the presumptive final option had been exhausted.

Cybersecurity for Cardiac Implantable Electronic Devices: What Should You Know?

Medical devices have been targets of hacking for over a decade, and this cybersecurity issue has affected many types of medical devices. Lately, the potential for hacking of cardiac devices (pacemakers and defibrillators) claimed the attention of the media, patients, and health care providers. This is a burgeoning problem that our newly electronically connected world faces. In this paper from the Electrophysiology Section Council, we briefly discuss various aspects of this relatively new threat in light of recent incidents involving the potential for hacking of cardiac devices. We explore the possible risks for the patients and the effect of device reconfiguration in an attempt to thwart cybersecurity threats. We provide an outline of what can be done to improve cybersecurity from the standpoint of the manufacturer, government, professional societies, physician, and patient.

Reversible cardiomyopathy in an adolescent with idiopathic aortic cusp ventricular tachycardia.

This report describes the case of an asymptomatic patient with a ventricular tachycardia-induced cardiomyopathy that resolved completely after successful radiofrequency ablation. This type of presentation and outcome has not been reported in the pediatric literature.

Intercostal muscle twitching from right ventricular apical pacing

A patient with a dilated cardiomyopathy underwent successful implantation of a cardiac resynchronization therapy defibrillator. The device system included an active fixation lead placed at the right ventricular (RV) apex. Pacing from the RV apex unexpectedly led to left‐sided intercostal muscle stimulation and twitching. This intercostal muscle twitching resolved completely with movement of the lead to the RV outflow tract. (PACE 2011;1–2)

His Bundle Pacing.

Traditional right ventricular (RV) pacing for the management of bradyarrhythmias has been pursued successfully for decades, although there remains debate regarding optimal pacing site with respect to both hemodynamic and clinical outcomes. The deleterious effects of long-term RV apical pacing have been well recognized. This has generated interest in approaches providing more physiological stimulation, namely, His bundle pacing (HBP). This paper reviews the anatomy of the His bundle, early clinical observations, and current approaches to permanent HBP. By stimulating the His-Purkinje network, HBP engages electrical activation of both ventricles and may avoid marked dyssynchrony. Recent studies have also demonstrated the potential of HBP in patients with underlying left bundle branch block and cardiomyopathy. HBP holds promise as an attractive mode to achieve physiological pacing. Widespread adaptation of this technique is dependent on enhancements in technology, as well as further validation of efficacy in large randomized clinical trials.

Novel Implantable Cardioverter-defibrillator Lead Placement in a Patient with a Prosthetic Tricuspid Valve

As the placement of transvenous leads across a prosthetic tricuspid valve is preferentially avoided, one must consider alternative solutions to provide necessary pacing and/or defibrillator therapy. Here, we present a case of novel placement of an implantable cardioverter-defibrillator (ICD) lead in the right atrium, in order to provide safe ICD therapy in a patient with a prosthetic tricuspid valve.