Who dies from what? Determining cause of death in South Africa's rural northleast

Summary Information on cause of death is essential for rational public health planning, yet mortality data in South Africa is limited

Steady-State Interaction Between Amiodarone and Phenytoin in Normal Subjects

Amiodarone has been reported to increase phenytoin levels. This study was designed to evaluate the pharmacokinetic basis of this interaction at steady-state. Pharmacokinetic parameters for phenytoin were determined after 14 days of oral phenytoin, 2 to 4 mg/kg/day, before and after oral amiodarone, 200 mg dairy for 6 weeks in 7 healthy male subjects. During amiodarone therapy, area under the serum concentration time curve for phenytoin was increased from 208 ± 82.8 (mean ± standard deviation) to 292 ± 108 mg · hr/liter (p = 0.015). Both the maximum and 24-hour phenytoin concentrations were increased from 10.75 ± 3.75 and 6.67 ± 3.51 μg/ml to 14.26 ± 3.97 (p = 0.016) and 10.27 ± 4.67 μg/ml (p = 0.012), respectively, during concomitant amiodarone treatment. Amiodarone caused a decrease in the oral clearance of phenytoin from 1.29 ± 0.30 to 0.93 ± 0.25 liters/ hr (p = 0.002). These results were due to a reduction in phenytoin metabolism by amiodarone as evidenced by a decrease in the urinary excretion of the principal metabolite of phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, 149 ± 39.7 to 99.3 ± 40.0 mg (p = 0.041) and no change in the unbound fraction of the total phenytoin concentration expressed as a percentage, 10.3 ± 2.7 versus 10.7 ± 2.1% (p = 0.28) during coadministration of amiodarone. The alterations in phenytoin pharmacokinetics suggest that steady-state doses of phenytoin of 2 to 4 mg/kg/day should be reduced at least 25% when amiodarone is concurrently administered. All dosage reductions should be guided by clinical and therapeutic drug monitoring

Usefulness of precordial T-wave inversion to distinguish arrhythmogenic right ventricular cardiomyopathy from idiopathic ventricular tachycardia arising from the right ventricular outflow tract

The 2 predominant causes of ventricular tachycardia (VT) arising from the right ventricle are arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic VT arising from the right ventricular outflow tract (RVOT). These arrhythmias can be adrenergically mediated and may be difficult to distinguish clinically. A minor criterion for the diagnosis of ARVC is T-wave inversion (TWI) in the right precordial leads during sinus rhythm. However, there have been reports of precordial TWI identified in patients with RVOT tachycardia. The purpose of this study was to determine whether patterns of precordial TWI could differentiate between the 2 groups. A multicenter registry of 229 patients with VT of right ventricular origin was evaluated. After appropriate exclusions (n = 29), 79 patients (58% men, mean age 40 ± 14 years) had ARVC, and 121 patients (41% men, mean age 48 ± 14 years) had RVOT tachycardia. During sinus rhythm, 37 patients (47%) with ARVC and 5 patients (4%) with RVOT tachycardia had TWI in leads V to V. For the diagnosis of ARVC, TWI in leads V to V had sensitivity of 47% and specificity of 96%. In conclusion, in patients with VT of right ventricular origin, the presence of TWI in electrocardiographic leads V to V supports the diagnosis of ARVC

Risk Stratification in Arrhythmic Right Ventricular Cardiomyopathy Without Implantable Cardioverter-Defibrillators

OBJECTIVES: The primary objective of this study is risk stratification of patients with arrhythmic right ventricular cardiomyopathy (ARVC). BACKGROUND: There is a need to identify those who need an automatic implantable defibrillator (ICD) to prevent sudden death. METHODS: This is an analysis of 88 patients with ARVC from three centers who were not treated with an ICD. RESULTS: Risk factors for subsequent arrhythmic deaths were pre-enrollment sustained or nonsustained ventricular tachycardia (VT) and decreased left ventricular function. CONCLUSION: These factors serve as proposed guidelines for implantation of an ICD in patients with ARVC to prevent sudden death

Psychological stress preceding idiopathic ventricular fibrillation

Emotional stress is well established as a trigger of sudden death in the context of coronary heart disease (CHD), but its role in patients experiencing cardiac arrest with apparently normal hearts is unknown. This study sought to determine the role of psychosocial stress as a precipitant of cardiac arrest in patients with apparently normal hearts, so-called idiopathic ventricular fibrillation (IVF). Methods: We interviewed 25 IVF survivors (12 men, 13 women) and 25 matched comparison patients regarding life events during the 6 months and 24 hours preceding the cardiac event. The comparison group consisted of patients with an acute myocardial infarction or angina pectoris requiring angioplasty but without cardiac arrest. Judges independently rated written summaries of these interviews for psychosocial stress at each time point on a three-point scale (low, moderate, severe). Results: During the 6 months before the cardiac event, 20 patients sustaining IVF had severe/moderate stress and five had low stress, whereas 10 comparison patients had severe/moderate stress and 15 had low stress (Fisher exact p .008). During the preceding 24 hours, nine patients with IVF had severe/moderate stress and 16 had low stress, whereas two comparison patients had severe/moderate stress and 22 had low stress (Fisher exact p .04) (one silent myocardial infarction could not be precisely dated). Conclusion: These data suggest that psychosocial stress is playing a role in otherwise unexplained cardiac arrest. Key words: idiopathic ventricular fibrillation, sudden cardiac death, psychologic stress, coronary heart disease