Paul Dorian

A previously well 67-year-old woman presents to her family physician with new-onset palpitations and fatigue over the last 6 weeks. These symptoms have adversely affected her quality of life, and she reports difficulty in performing daily activities. She takes no medications. On physical examination

Background—: Although implantable cardioverter-defibrillators (ICDs) lower mortality in stable patients with low ejection fraction late after myocardial infarction, randomized trials of ICD versus control subjects implanted early after myocardial infarction do not show mortality benefit. Our objective was to investigate possible mechanisms underlying the lack of mortality benefit in the Defibrillation in Acute Myocardial Infarction Trial (DINAMIT). Methods and Results—: This is a secondary analysis of the prospective randomized clinical trial. Outpatients with recent (6 to 40 days) acute myocardial infarction, left ventricular dysfunction (ejection fraction P <0.001). The reduction in sudden death in ICD patients was completely offset by increased nonarrhythmic deaths, which were greatest in patients receiving ICD shock therapy (hazard ratio, 6.0; 95% confidence interval, 2.8 to 12.7). Conclusions—: In patients receiving ICDs early after myocardial infarction, those factors that are associated with arrhythmia requiring ICD therapy are also associated with a high risk of nonsudden death, negating the benefit of ICDs in this setting.

Atrial fibrillation causes a significant burden on patients and the health care system. The main goals of atrial fibrillation therapy are to improve symptoms and reduce morbidity. There have been significant recent developments in both stoke prophylaxis and rhythm/rate control. The results of the ACTIVE W study emphasize the importance of effective oral anticoagulant therapy in patients with moderate-to-high risk for stroke. The RE-LY study showed superiority of dabigatran, an oral direct thrombin inhibitor, over warfarin in the prevention of stroke, or systemic embolism. Dronedarone, a new antiarrhythmic drug with multiple class effects, has been recently approved by the US Food and Drug Administration for the treatment of atrial fibrillation. Dronedarone has moderate rhythm and rate control efficacy; however, dronedarone significantly reduced cardiovascular hospitalization, cardiovascular death, and stroke in the large ATHENA trial. There is also an important shift in the paradigm of the goals of atrial fibrillation therapy. Instead of focusing solely on the electrocardiographic outcomes of treatment and considering "rhythm versus rate control," one needs to consider "symptom control" as well as patient well-being. This review will suggest that patient based outcomes rather than ECG-based outcomes should be the primary goals of treatment. Original reports and reviews on specific topics were identified through Medline. Randomized controlled trials were selected as the primary source of information. Analysis included critical review of the evidence available to date.

Dronedarone, a recently approved antiarrhythmic agent, is a chemical analog of amiodarone. It has an approximately 15% bioavailability, with plasma concentrations markedly increasing after a high-fat meal; it is recommended to be taken with food. The primary metabolic clearance pathway for dronedarone is via the hepatic enzyme system (primarily cytochrome P450 3A4 [CYP3A4]); the half-life of dronedarone is 27 to 31 hours. Strong CYP3A4 inhibitors, such as ketoconazole, are associated with a marked increase in dronedarone maximum concentration and are thus contraindicated; inducers of CYP3A4 will conversely decrease dronedarone exposure. Dronedarone is a substrate for P-glycoprotein (P-gp) and will lead to an increase in concentration of P-gp substrates such as digoxin. Dronedarone will cause a small increase in creatinine concentrations, without a change in glomerular filtration rate (GFR). Gender, renal dysfunction, weight, and age have little effect on the pharmacokinetics of dronedarone, and dose adjustment for these variables is not required.

The transvenous implantable cardioverter defibrillator (ICD) has emerged as the primary therapy for patients at high risk of life-threatening ventricular arrhythmias. A high number of ICD recipients will require subsequent adjunctive treatment with antiarrhythmic drugs (AADs). This review provides an overview of potential reasons for AAD initiation, candidates for treatment, current medical options, and possible drug-device interactions.

Background: The effect of cardiac resynchronization therapy (CRT) on physical function and Quality of Life (QoL) in patients who require an implantable defibrillator but do not meet guideline criteria for CRT has not been studied in detail. Methods and Results: This was a randomized study of 72 patients with high risk of sudden cardiac death, ejection fraction (EF) ≤35%, mild‐to‐moderate heart failure symptoms, and QRS > 120 ms. Patients received a CRT defibrillator and were randomized to CRT turned ON or OFF. Objective and subjective measures were performed at baseline and after 6 months. There was no difference in change in left ventricular end‐systolic volume (ESV) by radionuclid angiogram scan, the primary endpoint, between the CRT ON group (ΔESV =−7 ± 52 mL), and CRT OFF group (ΔESV =−30 ± 47 mL). Similarly, echocardiogram measures of ESV and EF showed no difference between the two groups. In the CRT ON group, selected measures of QoL and subjective exercise tolerance but not heart failure symptoms improved significantly. Six‐minute walk distance prolonged in the CRT ON group (baseline 313.6 ± 114.4 m, 6‐month 365.0 ± 122.5 m, P = 0.01), but the difference in change in walk distance between the two groups was not significant. Conclusion: Further studies with larger sample size and longer follow‐up will be required to allow definite conclusions regarding the potential benefit of CRT in this patient population.