Roger D. Blevins

Platelet hyperaggregability in patients with chest pain and angiographically normal coronary arteries

Forty-one patients with chest pain and angiographically normal coronary arteries were studied for platelet abnormalities. Patients with conditions known or suspected to be associated with chest pain or platelet dysfunction were excluded. After coronary angiography and 2-week withdrawal from all medications, platelet aggregometry was performed using peripheral venous plasma samples and 3 concentrations of adenosine diphosphate, 2.34, 1.17 and 0.58 microM, and epinephrine, 11, 1.1 and 0.55 microM, as stimuli. Platelet morphology in response to surface contact (adhesion) was evaluated by transmission electron microscopy to determine the percentage of platelets in the round/abortive (inactive), dendritic (intermediate) and spread (activated) forms. Plasma specimens obtained from healthy volunteers of similar age and sex were analyzed in parallel and served as control subjects. Compared with control subjects, patients had increased aggregation at all concentrations of both adenosine diphosphate and epinephrine (p less than 0.001). Patients also had fewer platelets in the dendritic form and more in the round/abortive and spread forms. Thus, patients with chest pain and normal coronary arteries have platelet hyperaggregability in vitro, although the clinical relevance of this finding is unclear.

The prognostic value of functional capacity in patients with mild to moderate heart failure.

Thirty patients with ischemic (n = 14) or idiopathic dilated (n = 16) cardiomyopathy were followed long-term to determine the prognostic value of measuring entry exercise capacity. At the time of referral for management of symptomatic heart failure, studies included radionuclide angiography, M-mode echocardiography, 24-hour Holter and graded exercise testing with measured oxygen peak consumption (peak VO2). Inclusion criteria were NYHA class II (n = 16) or III (n = 14) despite at least 3 months of treatment with digitalis and diuretics, left ventricular ejection fraction less than 50%, left ventricular end-diastolic diameter (LVEDD) greater than 50 mm, and exercise capacity limited by dyspnea or fatigue. Patients were treated with diuretics (100%), digitalis (83%), and vasodilators (60%) and were followed for at least 6 months (mean 15). The 1-, 2- and 3-year cumulative survival rates were 75.4%, 70.2%, and 70.2%, respectively. Univariate predictors of survival included measured peak VO2 (p = 0.0026), as well as age, estimated peak VO2 (based on exercise time), presence of left bundle branch block, LVEDD, and frequency of ventricular arrhythmias. Multivariate analysis revealed that measured peak VO2 was the single best independent predictor of survival (p less than 0.001). We conclude that assessment of functional capacity provides useful independent prognostic information in patients with mild to moderate heart failure.

Intravenous and oral loading versus oral loading alone with amiodarone for chronic refractory ventricular arrhythmias

To determine whether combined intravenous (i.v.) and oral loading with amiodarone can shorten its onset of action, a comparative study was conducted. Twenty patients with refractory ventricular arrhythmias were treated with amiodarone. All patients had frequent (greater than or equal to 30/hour) and complex (repetitive) ventricular premature beats on a 48-hour baseline Holter recording. Ten patients (group A) received oral loading alone: 800 mg/day for 7 days, 600 mg/day for 3 days, then a maintenance dose 200 to 400 mg/day. Ten patients (group B) received i.v. and oral loading: 5 mg/kg i.v., and then the same regimen as for group A. Follow-up 24-hour Holter recordings were obtained daily for 7 days, weekly for 1 month, and then monthly. Arrhythmia control was defined as at least a 70% reduction in ventricular premature beats, a 90% or greater reduction in couplets and abolition of ventricular tachycardia. The time to optimal ventricular arrhythmia control was shorter for group B (20 +/- 18 vs 105 +/- 83 days, p less than 0.05) and the cumulative amiodarone dose at the time of control was smaller for group B (10 +/- 8 vs 48 +/- 39 g, p less than 0.05). No complications were encountered with i.v. amiodarone. Thus, initial loading with i.v. amiodarone can shorten the time to optimal ventricular arrhythmia control and lower the cumulative dose required.

Relation of serum reverse T3 to amiodarone antiarrhythmic efficacy and toxicity

The relation of serum reverse T3 (rT3) to amiodarone efficacy and toxicity was studied in 31 patients with frequent and complex ventricular arrhythmias. Baseline studies included 48-hour Holter recordings and rT3 levels (normal 33 ng/dl or less). Amiodarone therapy was initiated with a 5 mg/kg infusion followed by 600 to 800 mg/day for 7 to 10 days, then 200 to 400 mg/day. Holters and rT3 levels were repeated every 1 to 3 months and amiodarone was titrated to achieve at least a 70% reduction in total ventricular premature complexes, at least a 90% reduction in couplets and abolition of ventricular tachycardia. The baseline rT3 level was 18 +/- 7 ng/dl (range 10 to 30) and patients were followed 12 +/- 9 months. Arrhythmia control was achieved in 25 patients (81%), including 21 patients with elevated rT3 levels (36 to 105 ng/dl) and 4 patients with normal rT3 (15 to 33 ng/dl). Six patients were uncontrolled with rT3 (27 to 90 ng/dl) and 14 patients had minor side effects with rT3 (27 to 123 ng/dl). Three of 4 patients in whom rT3 levels exceeded 130 ng/dl died suddenly (137 to 174 ng/dl before the event). Thus, amiodarone efficacy and minor toxicity occurs at rT3 levels less than 105 ng/dl and sudden death may be associated with levels greater than 130 ng/dl.

Arrhythmia control and other factors related to sudden death in coronary disease patients at intermediate risk

Thirty-three patients with coronary artery disease and frequent, complex ventricular arrhythmias (VA) were followed long-term to evaluate factors related to sudden death (SD). Patients with malignant VA (sustained ventricular tachycardia (VT), resuscitated SD, or acute myocardial infarction) were excluded. Baseline data included angiographic ejection fraction (EF), segmental wall motion, and Holter evidence of frequent (greater than 30/hr) and complex (repetitive) ventricular premature beats (VPBs). Control of VA was attempted with conventional or experimental agents and was defined as greater than or equal to 70% reduction in VPBs, greater than or equal to 90% reduction in couplets, and abolition of nonsustained VT on two consecutive Holter tapes. After 24 +/- 15 months of follow-up on the single most effective agent, 18 patients survived while 15 patients died suddenly. There was no difference between these groups with respect to age, sex, or baseline VA. Survivors had a higher EF (51% vs 34%, p less than 0.001), fewer dyskinetic segments (0.05 vs 1.0, p less than 0.01), and better VA control (83% vs 40%, p less than 0.01) than nonsurvivors. By analysis of variance, VA control was not independent of EF (F = 6.98, p less than 0.01). The 1-, 2-, and 3-year survival rates were 90%, 90%, and 82% for patients with EF greater than or equal to 40% and 22%, 11%, and 11%, for those with EF less than 40% and uncontrolled VA.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous lorcainide versus lidocaine in the treatment of frequent and complex ventricular arrhythmias

Abstract Thirty patients with frequent (≥30/hr) and repetitive ventricular premature beats (VPBs) unassociated with acute infarction were randomized to intravenous lorcainide (LOR) or lidocaine (LID). Following at least 2 hours of baseline Holter monitoring, patients received LOR, 2 mg/kg then 200 mg/24hr, or LID, 1 mg/kg then 2 mg/min, with rebolus if needed. Nonresponders detected by bedside telemetry were crossed over. Clinical response was 6 of 25 (24%) including two of nine crossovers with LOR and 8 of 26 (31%) including 3 of 12 crossovers with LID ( p = NS). By computer analysis of 24-hour Holter monitors and asymptotic regression of success rates at hourly intervals, it was projected that ≥80% reduction in VPBs occurred in 28% of LOR and in 25% of LID ( p = NS), and complete suppression of repetitive VPBs occurred in 102% of LOR and in 92% of LID ( p = NS). The mean drug levels were 405 ng/ml (range 371 to 463) with LOR and 3.4 μg/ml (range 2.1 to 3.6) with LID. Side effects were similar, occurring in 8 of 25 LOR trials and in 11 of 26 LID trials ( p = NS). Thus, LOR and LID effectively suppress repetitive VPBs and to a lesser extent VPB frequency. However, neither drug is superior and each may be an effective alternative when resistance to the other is encountered.