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Biomedical subjects

T B Graboys

Publications and source records attributed to T B Graboys.

At least 19 recordsLinked to original sources

Results of a second-opinion trial among patients recommended for coronary angiography.

OBJECTIVE: To assess the feasibility of carrying out a second-opinion trial for patients urged to undergo coronary angiography and to assess the long-range outcome of such patients denied that procedure, and the criteria evolved for reaching such a conclusion. DESIGN: A case series of patients referred for a second opinion as to the need for coronary angiography. Patients were followed up by questionnaire, telephone call, and center visits. SETTING: Cardiovascular referral center and teaching hospital in Boston, Mass. PATIENTS: One hundred seventy-one patients with coronary artery disease (144 men, average age 60 years; range, 36 to 88 years). Three patients became unavailable for follow-up during a mean of 46.5 months. OUTCOME MEASURES: Concordant-discordant outcome as to the second opinion, cardiac events, invasive interventions, quality of life questionnaire, and level of symptoms. RESULTS: One hundred thirty-four (80%) of the 168 patients were judged not to require angiography; it was recommended in six. In 28 (16%) recommendation was deferred pending further studies. At a mean follow-up of 46.5 months among the 168 patients, there were seven cardiac deaths (annualized cardiac mortality of 1.1%); 19 patients experienced a new myocardial infarction (2.7% annualized rate), while 27 patients (4.3%) were judged to have developed unstable angina. Twenty-six patients (15.4%) ultimately underwent either coronary bypass or angioplasty. CONCLUSIONS: In a large fraction of medically stable patients with coronary disease who are urged to undergo coronary angiography, the procedure can be safely deferred. While there may be a limitation in terms of generalizing this experience to all patients with coronary disease, we reasonably conclude that an estimated 50% of coronary angiography currently being undertaken in the United States is unnecessary, or at least could be postponed.

Adult

The prevalence of proarrhythmic events during moricizine therapy and their relationship to ventricular function.

The prevalence of proarrhythmic events during moricizine therapy was studied in 144 patients who were treated for symptomatic ventricular tachycardia or ventricular fibrillation. The overall incidence of proarrhythmia was 15.3%. (Twenty-two patients exhibited 23 events.) Ventricular fibrillation occurred in six patients (which led to three deaths), incessant ventricular tachycardia occurred in seven, and new sustained ventricular tachycardia in four. Patients with proarrhythmia had significantly lower left ventricular ejection fraction (24% vs 39%; p less than 0.0001), higher prevalence of congestive heart failure (68% vs 36%; p less than 0.005), and higher incidence of previous proarrhythmia (45% vs 9%; p less than 0.0001). No significant difference between the two groups was found in respect to age, arrhythmia at presentation, underlying heart disease, moricizine dose, or concomitant drug therapy.

Drug Evaluation

Effect of the combination of low-dose mexiletine and metoprolol on ventricular arrhythmia.

Antiarrhythmic drug therapy is often ineffective or poorly tolerated. Combining antiarrhythmic agents with different electrophysiologic properties may have a synergistic antiarrhythmic effect when compared with each drug alone. If a lower dose of each drug can be used, combination therapy may also result in lower incidence of side effects. The goal of our study was to assess the complementary effect of low-dose mexiletine and metoprolol, when compared with either drug alone. Ten patients with frequent ventricular arrhythmias including 7 patients with nonsustained ventricular tachycardia were evaluated in an open-label sequential study. The response to drug therapy was evaluated by 24-h continuous EKG monitoring, exercise stress testing, and echocardiogram after each treatment. Combination therapy effectively reduced ventricular arrhythmias in 8 patients (80%) in contrast to only 1 patient (10%) on metoprolol alone and 4 patients (40%) on mexiletine alone. In 5 patients (71%) ventricular tachycardia was abolished. The number of couplets was reduced from 51 +/- 39 to 1.9 +/- 2.4 (p less than 0.01) and total premature ventricular beats from 7790 +/- 9047 to 597 +/- 515 (p = 0.06). Combination therapy was well tolerated without proarrhythmia or precipitation of congestive heart failure. It is concluded that low-dose mexiletine combined with metoprolol is effective in suppressing ventricular arrhythmias in selected patients, and enhances the antiarrhythmic effect of either drug alone without significant side effects.

Aged

Ethics in cardiovascular medicine. Task Force II: The relation of cardiovascular specialists to patients, other physicians and physician-owned organizations.

1. The American College of Cardiology acknowledges the continuum of changing societal, medical and economic perspectives affecting traditional medical ethics. Primacy of patient responsibility remains paramount to the cardiovascular specialist who at the same time should participate in the development of broader societal programs. 2. Medical decisions should be freely and jointly formulated by the patient and the cardiovascular specialist with appropriate sensitivity to such matters as mental competence, pertinent medical information and standards of care, sufficient time for contemplation, informed consent, patient right of refusal, physician right to refuse to provide inappropriate care and the right of patient, physician or third party payer to seek consultation or additional opinions. 3. The cardiovascular specialist should make a special effort to clarify and document patient preferences regarding end-of-life treatment through some form of advance directive. 4. The cardiovascular specialist bears a moral obligation to provide medical care to any patient who is HIV positive or has AIDS. 5. A conflict of interest occurs when a cardiovascular specialist places personal or financial interest ahead of the welfare and health of a patient. Professional accountability should be established through local or regional peer review. 6. The American College of Cardiology encourages and supports a renewed dedication to the principles of medical ethics, particularly in the field of cardiovascular disease. Cardiovascular specialists are encouraged to participate in the promulgation of medical ethics by teaching and by example, individually and with others.

Acquired Immunodeficiency Syndrome

Reproducibility of exercise-induced ventricular arrhythmia in patients undergoing evaluation for malignant ventricular arrhythmia.

In patients with malignant ventricular arrhythmia, the utility of exercise testing for exposing arrhythmias and guiding antiarrhythmic drug selection and dosage is not yet generally accepted. A major reservation relates to the issue of reproducibility of arrhythmia provocation. This prospective study comprised 28 patients referred for evaluation of ventricular arrhythmia. In half of these subjects the clinical arrhythmia was sustained ventricular tachycardia or ventricular fibrillation. Maximal exercise testing adhering to a Bruce protocol was performed on 2 separate days. No antiarrhythmic drugs were administered at the time of testing. Of the 28 patients, 27 had an increase in arrhythmia with exercise. The prevalence rates of arrhythmia were greater than 80% and did not significantly differ between test 1 and test 2. Excluding infrequent single ventricular premature complexes, the reproducibility of a test with positive outcome was 76%. Similarly, test-retest agreement, a bidirectional measure of reproducibility, was greater than 74%. Kappa coefficients ranged from 0.26 to 0.36 for all grades of arrhythmia, indicating that reproducibility was consistently greater than by chance alone. Linear regression analysis of arrhythmia frequency in the 2 tests yielded R values of 0.76 to 0.96 and slopes of 0.82 to 1.2. No patient had enough spontaneous variability in repetitive forms to suggest spurious efficacy or aggravation. For ventricular premature complexes there was an 8 to 14% incidence of spurious efficacy and a 4 to 7% incidence of spurious aggravation. These results suggest that exercise-induced ventricular arrhythmia is sufficiently reproducible to serve as an adjunct method in the evaluation and management of patients with potentially life-threatening ventricular arrhythmias.

Adult

The effect of caffeine on ventricular ectopic activity in patients with malignant ventricular arrhythmia.

We evaluated the effect of caffeine on ventricular ectopic activity in a group of 50 consecutive patients with malignant ventricular arrhythmia. The clinical arrhythmia in these patients (mean age, 61 years) was recurrent ventricular tachycardia in 21 (42%), ventricular fibrillation in three (6%), and symptomatic nonsustained ventricular tachycardia in 26 (52%). Forty-two (84%) had either ischemic heart disease or cardiomyopathy. Each patient underwent two short-term drug trials on successive days, receiving either decaffeinated coffee mixed with 200 mg of caffeine or the decaffeinated drink alone. Continuous electrocardiographic recordings were made during the 30-minute control period, the three-hour observation period, and the hourly bicycle exercise tests. Forty-five patients (90%) exhibited ventricular couplets and 29 patients (58%) had salvos of ventricular tachycardia during the testing. However, no differences between the caffeine and decaffeinated trials were observed in either individual or group data on total or repetitive ventricular arrhythmia. Serum catecholamine levels reflected the average increase in serum caffeine level but were not associated with enhanced arrhythmia. We found no evidence that a modest dose of caffeine is arrhythmogenic, even among patients with known life-threatening arrhythmia.

Caffeine

Combination antiarrhythmic therapy for management of malignant ventricular arrhythmia.

The efficacy of combination drug therapy in the suppression of ambient ventricular arrhythmia was retrospectively evaluated in a study of 49 patients discharged from the hospital taking 2 membrane-active antiarrhythmic agents. Thirty-one patients (63%) had ischemic heart disease, 15 had miscellaneous cardiac disorders and 3 were free of ostensible heart disease. Therapy in all patients had previously been unsuccessful with an average of 3.7 single membrane-active drugs. Antiarrhythmic agents were discontinued for at least 48 hours to determine baseline arrhythmia levels by Holter monitoring and maximal exercise treadmill testing. Ventricular premature beats were evaluated according to the grading system of Lown and Wolf. Data on ventricular ectopic activity were obtained during Holter monitoring and exercise testing for both a control ("drug-free") period and for a period of combination therapy. During the control period, ventricular tachycardia was recorded during 23% of monitored hours, and the level was nearly twofold greater during stress testing. After institution of combined therapy, the percent of monitored hours of arrhythmia were reduced during Holter monitoring, with a greater reduction in couplets and ventricular tachycardia than in single ventricular premature beats. Ventricular tachycardia was more difficult to provoke by exercise testing in patients taking combination therapy than in control subjects. These data indicate that combination therapy can significantly reduce the density of ventricular ectopic activity in patients refractory to monotherapy. During an average follow-up of 26 months, 23 patients (47%) were able to receive decreased drug dosages, affording diminished adverse effects and improved tolerance to long-term use.

Anti-Arrhythmia Agents

Determinants of survival in patients with malignant ventricular arrhythmia associated with coronary artery disease.

The long-term survival data in patients with coronary artery disease and a history of malignant ventricular arrhythmia, defined as noninfarction ventricular fibrillation (VF) or hemodynamically compromising ventricular tachycardia (VT) followed for up to 9 years, were analyzed. In this group of 161 patients there was a total of 57 deaths, of which 35 (63%) were sudden. Life-table analysis demonstrated a 10% sudden death rate for all patients in the first year and a 7% annual rate in the subsequent 4 years. In patients managed noninvasively, the overall mortality rate was 27% over 9 years, or 3% per year. Suppression of ventricular tachycardia on both ambulatory monitoring and exercise testing was associated with improved survival. In patients evaluated by electrophysiologic testing the sudden death rate was 1.4% per year over an average of 5 years. This survival rate was not different compared with the noninvasive group (p = 0.09). Measures of left ventricular dysfunction and the frequency of ventricular arrhythmia before and after drug therapy were associated with a risk of sudden cardiac death by univariate analysis. Multivariate regression analysis identified 4 variables as independent predictors of sudden cardiac death: rales (p = 0.009), the number of runs of VT during exercise testing while receiving antiarrhythmic drug therapy (p = 0.0003), a history of congestive heart failure (p = 0.0009) and the number of premature beats on Holter monitoring (p = 0.01). These findings support the concept that suppression of repetitive arrhythmia on Holter monitor and exercise testing is a marker for improved survival among patients with malignant ventricular arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis

Spontaneous variability and circadian distribution of ectopic activity in patients with malignant ventricular arrhythmia.

Day to day variability of ventricular ectopic activity was analyzed in 45 patients with a history of malignant ventricular tachyarrhythmias who underwent two successive 24 h periods of ambulatory electrocardiographic (ECG) monitoring in the absence of antiarrhythmic drugs; 26 were male and 19 female, with a mean age of 56 years (range 15 to 76). The total number of single ventricular premature beats, couplets and ventricular tachycardia beats and runs on days 1 and 2 demonstrated a consistent overall correlation (r = 0.76 to 0.84). Individual variability was evaluated by regression analysis with determination of 95% confidence limits. The minimal decrease in arrhythmia density necessary to distinguish true drug effect from spontaneous variability was 64% for single ventricular premature beats, 83% for couplets, 90% for ventricular tachycardia runs and 93% for ventricular tachycardia beats. To meet the criteria for arrhythmia aggravation, the arrhythmia density had to increase by 400, 877, 1,500 and 2,400%, respectively. Multivariate analysis disclosed an inverse relation between day to day arrhythmia variability and baseline arrhythmia density and age. Variability was more pronounced in patients with coronary artery disease but was not influenced by the type of presenting arrhythmia or left ventricular function. The diurnal distribution of arrhythmias and heart rate followed a distinct circadian pattern. These data indicate that, despite good group reproducibility, spontaneous arrhythmia variability in individuals is substantial, necessitating standards to define both drug effect and arrhythmia aggravation.

Adolescent