Heather A. Wroblewski

A Randomized Trial Evaluating Amiodarone for Prevention of Atrial Fibrillation After Pulmonary Resection

BACKGROUND Atrial fibrillation (AF) occurs commonly after anatomic pulmonary resection. In this study, the efficacy of amiodarone for prevention of post-pulmonary resection AF was investigated. METHODS One hundred thirty patients undergoing lobectomy, bilobectomy, or pneumonectomy were randomly assigned prospectively to receive amiodarone (n = 65) or no prophylaxis (control group, n = 65). The amiodarone group received 1,050 mg by continuous intravenous infusion over 24 hours, initiated at the time of anesthesia induction, followed by 400 mg orally twice daily until hospital discharge or for a maximum of 6 days. The primary endpoint was AF requiring treatment during hospitalization. Secondary endpoints included postoperative length of hospital and intensive care unit stays. RESULTS There were no significant differences between the amiodarone and control groups in demographics, comorbid conditions, extent of pulmonary resection, or preoperative or postoperative use of beta-blockers or calcium-channel blockers. The incidence of AF was lower in the amiodarone group than in the control group (13.8% versus 32.3%, p = 0.02; relative risk reduction = 57%). There was no difference between the amiodarone and control groups in median length of hospital stay (7 versus 8 days, p = 0.79), but median length of intensive care unit stay was shorter in the amiodarone group (46 versus 84 hours, p = 0.03). There was no significant difference between the amiodarone and control groups in the incidence of pulmonary complications or other adverse effects. CONCLUSIONS Amiodarone prophylaxis significantly reduces the incidence of AF after anatomic pulmonary resection, and is associated with a significant reduction in length of intensive care unit stay.

A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy

OBJECTIVE Atrial fibrillation is common after esophagectomy. The objective of this study was to determine the efficacy and safety of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy. METHODS Eighty patients undergoing transthoracic esophagectomy were randomly, prospectively assigned to receive amiodarone (n = 40) or no prophylaxis (control group, n = 40). Amiodarone-treated patients received the drug by continuous infusion, initiated at the time of induction of anesthesia, at a rate of 0.73 mg/min (43.75 mg/h), and continued for 96 hours (total dose 4200 mg). The primary end point was atrial fibrillation requiring treatment. Secondary end points included any atrial fibrillation lasting longer than 30 seconds and postoperative hospital and intensive care unit stays. RESULTS There were no significant differences between the amiodarone and control groups in demographic characteristics, comorbid conditions, or preoperative or postoperative use of beta-blockers or calcium-channel blockers. The incidence of atrial fibrillation requiring treatment was lower in the amiodarone group than in the control group (15% vs 40%, P = .02, relative risk reduction 62.5%). There were no significant differences between the amiodarone and control groups in median hospital stay (11 days vs 12 days, P = .31) or median intensive care unit stay (68 hours vs 77 hours, p = .097). There were no significant difference between the groups in the incidences of adverse effects. CONCLUSIONS Amiodarone prophylaxis significantly reduced the incidence of atrial fibrillation after transthoracic esophagectomy.

Prophylaxis of Atrial Fibrillation After Noncardiac Thoracic Surgery

Atrial fibrillation (AF) occurs commonly after noncardiac thoracic surgery, including lobectomy, pneumonectomy and esophagectomy. While not as extensively investigated as AF following cardiac surgery, some strategies for prophylaxis of AF after noncardiac thoracic surgery have been studied. Evidence from prospective, randomized controlled studies supports the use of beta-blockers, diltiazem, amiodarone or magnesium for prevention of AF after pulmonary resection. Limited evidence supports the efficacy of intravenous amiodarone for prevention of AF after esophagectomy. Further study is necessary to determine the safest and most effective methods of prophylaxis of AF after noncardiac thoracic surgery, and to identify patients most likely to benefit from AF prophylaxis.

Enhanced Sensitivity to Drug-Induced QT Interval Lengthening in Patients With Heart Failure Due to Left Ventricular Systolic Dysfunction

Patients with heart failure (HF) are at increased risk for drug‐induced torsades de pointes (TdP) due to unknown mechanisms. Our objective was to determine if sensitivity to drug‐induced QT interval lengthening is enhanced in patients with HF. In this multicenter, prospective study, 15 patients with atrial fibrillation or flutter requiring conversion to sinus rhythm were enrolled: 6 patients with New York Heart Association class II to III HF (mean ejection fraction [EF], 30% ± 9%), and 9 controls (mean EF, 53% ± 6%). Patients received ibutilide 1 mg intravenously. Blood samples and 12‐lead electrocardiograms were obtained prior to and during 48 hours postinfusion. Serum ibutilide concentrations at 50% maximum effect on Fridericia‐corrected QT (QTF) intervals (EC50) were determined, and areas under the effect (QTF interval vs time) curves (AUECs) were calculated. Ibutilide concentration—QTF relationships were best described by a sigmoidal Emax model with a hypothetical effect compartment. Median [interquartile range] AUEC from 0 to 4 hours was larger in the HF group than in controls (1.86 [1.86–1.93] vs 1.82 [1.81–1.84] s·h; P = .04). Median EC50 was lower in the HF group (0.48 [0.46–0.49] vs 1.85 [1.10–3.23] μg/L; P = .008). Sensitivity to drug‐induced QT interval lengthening is enhanced in patients with systolic HF, which may contribute to the increased risk of drug‐induced TdP.

Pharmacokinetics of ibutilide in patients with heart failure due to left ventricular systolic dysfunction

Study Objective. To assess whether the increased risk of ibutilide‐induced torsade de pointes in patients with heart failure may be due to increased ibutilide exposure, we sought to determine if the pharmacokinetics of ibutilide are altered in patients with heart failure due to left ventricular systolic dysfunction.

High Risk of QT Interval Prolongation and Torsades de Pointes Associated with Intravenous Quinidine Used for Treatment of Resistant Malaria or Babesiosis

ABSTRACT Cardiac toxicity may be associated with drugs used for malaria. Torsades de pointes (TdP) is a well-known adverse effect of quinidine when used for atrial fibrillation. Intravenous quinidine doses for resistant malaria are 2 to 3 times higher than those used for arrhythmias. Among 6 patients receiving quinidine for malaria or babesiosis, 4 developed QT interval prolongation and 2 experienced TdP. Clinicians should be aware that recommended doses of quinidine for malaria carry a high TdP risk.

The Influence of Progesterone Alone and in Combination With Estradiol on Ventricular Action Potential Duration and Triangulation in Response to Potassium Channel Inhibition

Progesterone Effects on Ventricular Action Potential. Introduction: Females are at increased risk for torsades de pointes (TdP). Some evidence suggests that progesterone may protect against TdP, but few data exist regarding the effects of progesterone on cardiac repolarization. We determined the effects of progesterone alone and in combination with estradiol on ventricular action potential duration (APD) and triangulation in response to potassium channel inhibition.