Comparison of sustained-release quinidines given twice daily to patients with ventricular ectopy.

To compare the steady-state kinetic profiles and ectopy-suppression rates of two sustained-release forms of quinidine with those of a conventional quinidine preparation, 18 patients with ventricular ectopy were studied in randomized crossover fashion. The drugs were conventional quinidine sulfate 300 mg q6h, sustained-release quinidine sulfate 600 mg q12h, and sustained-release quinidine gluconate 648 mg q12h. Following baseline electrocardiographic ambulatory monitoring, each drug was given for three days, with repeat ambulatory monitoring and serial plasma drug level determinations performed on the third day. There were no washout periods between treatments. Plasma quinidine levels were assayed by both enzyme multiplied immunoassay technique (EMIT) and quinidine-specific high-performance liquid chromatography (HPLC) methods. Using actual steady-state HPLC values, there were no differences in the area under the plasma concentration-time curve (AUC) among the three treatments; the dose-corrected AUC was greater for quinidine gluconate than for the other two preparations. Using EMIT values, mean plasma quinidine levels from the conventional quinidine sulfate regimen were greater during the last five hours of the 12-hour study interval. A consistently strong inverse relationship between EMIT plasma quinidine levels and hourly ectopy rates was present in only one of eight (13%) responders. Diurnal variation of quinidine kinetics was observed after two days of each treatment; trough values at midnight were slightly lower than trough values at noon. Among patients demonstrating at least 70% suppression of premature ventricular contractions (PVCs), there were no differences in ectopy rates or ectopy-suppression rates among treatments. Dosing sustained-release quinidine sulfate 600 mg or quinidine gluconate 648 mg q12h was clinically acceptable in the small number of responders studied.

Sudden cardiac death in Air Force recruits. A 20-year review.

We reviewed the clinical and autopsy records of the 19 sudden cardiac deaths that occurred among the 1,606,167 US Air Force healthy, medically screened recruits (90% male; 17 to 28 years old) during a 42-day basic training period between 1965 and 1985. Sixteen (all male) died suddenly of underlying structural heart disease, whereas no anatomic cause of death was identified in the remaining three. Thirty-two nonsudden, noncardiac deaths occurred during the same period, and only two had structural heart disease. Strenuous physical exertion was associated with sudden death in 17 of 19 cases (0.017 deaths per 50,000 exercise-hours), and the most frequent underlying etiology was myocarditis. Sudden cardiac death, a rare event in healthy young adults, is usually associated with exertion.

A practical and effective protocol for the post angiographic management of patients with critical stenosis of the left main coronary artery.

The management of newly diagnosed left main obstruction varies throughout institutions. At some Centers, very aggressive measures including intra-aortic balloon counterpulsation and emergent revascularization are routine protocol. Twenty consecutive patients with greater than 50% luminal narrowing of the left main coronary artery were treated over a 1 year period. Routine post catheterization protocol for 19 patients included intensive care observation, continuation of nonparenteral anti-anginal agents, and coronary revascularization within 24 hours of diagnosis. One patient experienced severe hemodynamic embarrassment at the time of catheterization and underwent emergency coronary bypass. All patients were discharged uneventfully following successful surgery. Based on this experience, it is felt that with surgical support, patients with significant left main stenosis can be treated with standard anti-anginal therapy, and undergo elective revascularization without complications.

Quinidine assays: enzyme immunoassay versus high performance liquid chromatography.

Plasma quinidine results determined by enzyme multiplied immunoassay (EMIT) (Syva) were compared with results from a quinidine-specific high performance liquid chromatographic (HPLC) assay. During a clinical study, 16 patients with stable ventricular arrhythmias were treated with three oral quinidine preparations given during three consecutive 3-day periods. Seventeen plasma samples were drawn from each patient at steady-state during each period. Each specimen was divided into two portions, one for assay by EMIT and the other for assay by HPLC. EMIT assays were done on a Syva Autolab 6000 System using Syva quinidine kits and bilevel Ortho Diagnostics controls. The overall mean (+/- SD) quinidine concentrations by EMIT and HPLC were 2.16 +/- 0.58 and 1.81 +/- 0.60, respectively, n = 816, with a mean overall EMIT/HPLC ratio of 1.23 +/- 0.18. Mean ratios in individual patients ranged from 1.01 to 1.56; the average of mean individual ratios was 1.23 +/- 0.13. The EMIT assay, which also reports dihydroquinidine and small amounts of quinidine metabolites as quinidine, reported quinidine values that averaged 1.2-fold greater than results from a quinidine-specific HPLC method.

Ischemia-associated intraventricular conduction disturbances during exercise testing as a predictor of proximal left anterior descending coronary artery disease.

To determine the incidence and significance of transient intraventricular conduction abnormalities occurring in association with myocardial ischemia during exercise testing, the recordings of 2,200 consecutive exercise tests were reviewed. Ten patients (0.45%) were identified as having both ischemia and intraventricular conduction abnormalities that developed transiently during the exercise test. In all 10 patients both typical angina and electrocardiographic evidence of ischemia developed during exercise. Among the 10 patients, left anterior hemiblock developed in 4, left posterior hemiblock in 2, right bundle branch block (RBBB) in 2, RBBB with left axis deviation in 1, and left anterior hemiblock progressing to complete left bundle branch block (LBBB) in 1. All 10 patients had cardiac catheterization showing significant obstruction of the left anterior descending (LAD) coronary artery at or before the origin of the first septal branch. Eight patients were treated surgically and 2 medically, all with relief of ischemic symptoms. Nine of the 10 had repeat exercise stress testing without angina or electrocardiographic evidence of ischemia and without recurrence of the transient intraventricular conduction disturbance. It is concluded that the development of transient intraventricular conduction abnormalities associated with myocardial ischemia during exercise testing is an uncommon occurrence (0.45%). When such conduction disturbances do develop, the existence of significant disease in the proximal portion of the LAD coronary artery is strongly suggested. With control of myocardial ischemia, the transient conduction disturbances during exercise are ameliorated.