Twenty obese women were randomly assigned to consume (for 16 wk) either a 420-kcal/d liquid diet (n = 12) or a 1200-kcal/d balanced diet (n = 8). Thereafter, patients in both conditions were prescribed a 1200-kcal/d diet for the remainder of treatment (week 45). Six obese nondieters served as control subjects. Ambulatory electrocardiographic (Holter) monitor readings were obtained on all patients at baseline and weeks 3, 9, 13, 17, 19, and 45 of the study and were analyzed for ventricular premature depolarizations (VPDs) per hour, paired forms, and runs of ventricular tachycardia. There were no statistically significant changes in VPDs in any condition during treatment. Similarly, there were no significant changes in the PR, QRS, and corrected QT intervals. The results indicate that under appropriate medical supervision, very-low-calorie diets can be used safely for up to 16 wk by significantly obese patients free of pre-existing cardiac disease.

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after bone marrow transplantation. Well-documented manifestations of GVHD include dermatologic, gastrointestinal, hepatic, pulmonary, musculoskeletal, and hematologic manifestations and sicca syndrome. To date, the heart has only rarely been reported to be a target of GVHD. We report a series of patients who developed bradycardia, coronary artery disease, or cardiomyolysis in association with acute or chronic GVHD. The severity of these manifestations ranged from asymptomatic to fatal. The bradycardias were responsive to increased immunosuppression. Although they are uncommon, it is important to recognize these cardiac manifestations, because they may reflect GVHD activity and may be reversible by increasing immunosuppression.

In 11 of 25 patients (44%) with sustained ventricular tachycardia (VT) who received intravenous verapamil (5 to 10 mg), acute severe hypotension or loss of consciousness developed, necessitating immediate cardioversion. Comparison of these 11 patients with the 14 who did not have adverse effects after verapamil revealed no significant difference in age, heart disease, ejection fraction, blood pressure before verapamil administration, other oral or intravenous drugs use, verapamil dose or VT characteristics (rate and morphologic pattern). Although most patients with severe adverse effects after verapamil had prior myocardial infarction, deterioration also occurred in patients without coronary disease and in patients with a normal left ventricular ejection fraction. VT terminated after verapamil infusion in 6 patients. No single electrocardiographic morphologic pattern characterized these patients. A control group of 25 patients presenting with hemodynamically stable VT who received other antiarrhythmic agents was examined. Hypotension developed in only 1 patient during acute therapy and did not require emergency cardioversion. Thus, although verapamil may terminate VT, severe adverse effects occur much more often. Use of verapamil to differentiate supraventricular tachycardia with aberrant conduction from ventricular tachycardia is hazardous.

We have evaluated the influence of several factors on the binding of disopyramide to protein in human serum using a new ultrafiltration system and the enzyme multiplied immunoassay technique (EMIT) for disopyramide immunoassay. From these studies and those of other investigators, we conclude that the most significant in vivo factors influencing disopyramide binding in human serum are total disopyramide concentration, the concentration of alpha 1-acid glycoprotein, and the concentration of mono-N-dealkyldisopyramide. Significant variation in binding occurs in patients whose total disopyramide concentration is within the therapeutic range. The proportion of free disopyramide ranged from 16% to 54% in the sera of 50 cardiac patients whose total disopyramide concentration ranged from 0.5 to 5.8 mcg/ml. Since there is so much variation in the proportion of disopyramide that is free, and since it is the unbound form of the drug that is pharmacologically active, it is likely in patients whose arrhythmia responds to disopyramide therapy that unbound drug concentration will be a better indicator of drug efficacy and toxicity than will be total drug concentration. To test this hypothesis, we are investigating the relationship between steady state total and unbound disopyramide plasma levels in patients with supraventricular or ventricular arrhythmias, and pharmacologic response as determined by standard intracardiac electrophysiologic studies.

Sixty-two consecutive patients with chronic coronary artery disease referred for evaluation of nonsustained ventricular tachycardia (VT) underwent electrophysiologic studies. Sustained VT was induced by one to three ventricular extrastimuli in 28 patients (45%). Therapy was guided by the results of electrophysiologic testing in 44 patients: 19 patients without inducible sustained VT received no antiarrhythmic therapy, and 25 patients with inducible sustained or symptomatic nonsustained VT received therapy guided by the results of electrophysiologic studies. The results of electrophysiologic studies were ignored by physicians for a second group of 18 patients: four had inducible sustained VT but received no antiarrhythmic therapy, and 14 had inducible sustained or nonsustained VT and received antiarrhythmic therapy not guided by results of electrophysiologic testing. After a mean follow-up period of 28 months, 11 patients had died suddenly. Seven of the 11 patients who died suddenly had inducible sustained VT. Three of 44 patients in the group receiving therapy guided by electrophysiologic studies died suddenly versus eight of 18 in the group receiving therapy not guided by electrophysiologic studies (p = .001). Only one of 19 patients without inducible sustained VT who were not treated experienced sudden death. Two of four patients with inducible sustained VT who did not receive antiarrhythmic therapy died suddenly. Multivariate analysis of the relationship of induced arrhythmias, left ventricular ejection fraction, site of myocardial infarction, history of syncope, or type of antiarrhythmic therapy to outcome revealed a greater than twofold increased risk for sudden cardiac death in patients whose therapy was not guided by results of electrophysiologic study.(ABSTRACT TRUNCATED AT 250 WORDS)

Programmed stimulation and signal-averaged electrocardiography were performed in 43 consecutive patients with nonsustained ventricular tachycardia (VT) after healing of inferior (29 patients) or anterior wall (14 patients) acute myocardial infarction. Twenty-two patients had inducible sustained VT. Patients with inferior infarction and inducible sustained VT had significantly longer filtered QRS durations (125 +/- 19 vs 112 +/- 15 ms, p less than 0.01) and significantly lower voltage in the last 40 ms of the filtered QRS complex (19 +/- 5 vs 30 +/- 14 microV, p less than 0.05) than those without inducible sustained VT. In contrast, the signal-averaged electrocardiographic measurements in patients with anterior infarction and inducible sustained VT did not differ significantly from those without inducible sustained VT. The results of these studies were compared with those of 2 control groups: 45 patients without ventricular arrhythmias after myocardial infarction and 95 patients with spontaneous and inducible sustained VT after myocardial infarction. The signal-averaged electrocardiographic measurements in patients with spontaneous nonsustained VT after inferior infarction were intermediate between the control group without arrhythmias and the control group with sustained VT. The signal-averaged electrocardiograms in patients with nonsustained VT after anterior infarction were not significantly different from those in patients without ventricular arrhythmias. The study shows that the site of infarction influences the signal-averaged electrocardiogram in patients with VT after myocardial infarction. The signal-averaged electrocardiogram may be useful in identifying patients with nonsustained VT after a remote inferior myocardial infarction who have inducible sustained VT.

Ventricular tachycardia (VT) has been shown to arise from ischemically damaged left ventricular myocardium, which possesses heterogeneity of refractoriness and activation. Catheter techniques were used to study left ventricular refractoriness using the strength-interval relation and activation by local electrographic characteristics in 8 patients with and 6 patients without previous myocardial infarction (MI). Noninfarcted myocardium in patients with and without previous MI was similar overall with respect to refractoriness and excitability, whereas local electrographic duration in MI patients was longer (66 ± 2 vs 52 ± 3 ms, p < 0.005) and amplitude lower (3.9 ± 2.1 vs 6.1 ± 2.0 mV, p < 0.05). Comparisons of infarcted and noninfarcted regions in MI patients revealed an increased threshold of excitability at infarct sites (e.g., 1.9 ± 1.0 vs 0.7 ± 0.4 mA, p < 0.05) and prolongation of refractory periods (375 ± 118 vs 275 ± 13 ms, p < 0.05) at the lowest level of stimulating current. Shortening of refractory period as a result of change in pacing cycle length was not affected by infarction. The local electrographic duration (95 ± 17 ms) was significantly longer in infarcted regions than at noninfarcted sites (p < 0.005), but the electrographic amplitude (3.4 ± 3.0 mV) differed significantly only in noninfarct patients. It is concluded that considerable electrophysiologic disparity exists between infarcted and noninfarcted myocardium. Whether or not arrhythmogenic tissue possesses unique alterations in electrophysiologic characteristics remains to be established.

Twenty-six patients with refractory ventricular arrhythmias received the automatic implantable cardioverter-defibrillator. A patch lead only was placed during arrhythmia surgery in 7 other patients. During 13 +/- 6 (SD) months, the device discharged in 10 patients because of a sustained ventricular arrhythmia. No sudden deaths occurred. There were 31 complications in 17 patients, including postoperative refractory heart failure, coronary artery erosion, subclavian vein thrombosis, postoperative stroke after conversion of atrial fibrillation, atelectasis with pneumonia, symptomatic pleural effusions, and infection at the generator site. The cardioverter-defibrillator discharged in 9 asymptomatic patients, failed to terminate ventricular fibrillation during postoperative testing in 3 patients, and had premature battery failure in 4 patients. Tachycardia slowing during chronic amiodarone therapy and unipolar ventricular pacing during ventricular fibrillation precluded or delayed arrhythmia sensing. Thus, the cardioverter-defibrillator can be life saving, but its potential complications and interactions with antiarrhythmic drugs and pacemakers must be considered at patient selection.

One hundred nineteen patients with unexplained syncope (82%) or presyncope (18%) underwent complete electrophysiologic study (EPS). Symptoms were recurrent in 72% of the patients. Fifty-two percent of the patients had structural heart disease. Forty-one patients had normal EPS results and 78 had electrophysiologic abnormalities (ventricular tachycardia in 31, induced atrial flutter/fibrillation in 17, vasovagal syncope in 8, hypersensitive carotid sinus syndrome in 7, supraventricular tachycardia in 6, heart block in 5 and sick sinus syndrome in 4). The presence of structural heart disease (p = 0.0033) and previous myocardial infarction (p = 0.05) were the only clinical or electrocardiographic predictors of a positive EPS response. Therapy was guided by EPS and patients were followed for 27 +/- 20 months (mean +/- standard deviation). In the patients with negative EPS results, 76 +/- 11% (mean +/- standard error) were symptom-free at follow-up, compared to 68 +/- 10% in the group with positive EPS responses. No clinical variables helped to predict remission in the absence of therapy. One patient in the negative EPS response group and 2 patients in the EPS positive group died suddenly (cumulative survival 94 +/- 4%). Total cardiovascular mortality was 13% in the positive EPS response group, and 4% in the negative EPS response group. Thus, certain clinical characteristics are helpful in selecting patients for study. Electrophysiologically guided therapy is associated with a recurrence and sudden death rate similar to an untreated control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Seventy-four patients with sustained ventricular tachyarrhythmias had 22 ± 3 hours of Holter monitoring before and after 11 ± 6 days of amiodarone treatment. On control Holter recordings, 55 patients (group I) had frequent (more than 10 extrasystoles per hour) and/or complex (at least couplets) ventricular ectopic activity (VEA), and 19 patients (group II) had infrequent and simple VEA. A positive Holter monitor response to amiodarone was defined as a decrease in VEA by more than 85% and abolition of all complex VEA. In group I, 34 patients (62%) had a positive Holter monitor response. In group II, 16 patients (84%) had persistent, infrequent and simple VEA and 3 had frequent and/or complex VEA. During a mean follow-up of 13 ± 12 months, 22 patients (30%) had ventricular tachycardia (VT) or sudden death. In group I, VT or sudden death occurred in 6 of 34 (18%) patients with a positive Holter monitor response and 11 of 21 (52%) with a negative Holter monitor response (p < 0.01), and in group II, VT or sudden death occurred in 5 of 16 patients (31%) with persistent, infrequent and simple VEA. All episodes of VT or sudden death occurred after at least 2 weeks of amiodarone therapy (mean 5 ± 6 months). The predictive accuracy of a positive Holter monitor response as an indicator for subsequent prevention of sustained ventricular tachyarrhythmias and sudden cardiac death was 82% and for a negative Holter monitor response as an indicator of tachyarrhythmia or sudden death recurrence on therapy it was 52%. Thus, in patients with sustained ventricular tachyarrhythmias, (1) VEA on the Holter recording too infrequent to index a response to amiodarone will be present in 25% of patients; (2) amiodarone is usually effective in suppressing frequent and complex VEA; (3) abolition of complex and frequent ectopic activity during amiodarone therapy predicts control of sustained ventricular arrhythmias; and (4) failure to control VEA does not preclude control of sustained ventricular arrhythmias with amiodarone therapy in 50% of patients.

Alterations in ventricular excitability and vulnerability were assessed in nine isolated perfused rabbit hearts in and out of static external magnetic fields (4.7 tesla) associated with radiofrequency pulsing (5 gauss). Ventricular refractoriness was assessed with the strength interval relationship in and out of the NMR magnet. Strength interval curves were measured at threshold, at the midpoint of the strength interval relationship, and at 10 mA. The refractory period measured at threshold was 193 +/- 24 mS outside the magnet and 195 +/- 24 mS inside the magnet (P = ns). Ventricular refractoriness measured at the midpoint of the strength interval curve was 169 +/- 16 mS outside and 167 +/- 17 mS in the magnet (P = ns). At 10 mA the refractory period outside of the magnet was 162 +/- 16 mS and 161 +/- 17 mS in the magnet (P = ns). To assess ventricular vulnerability the repetitive response threshold and the ventricular fibrillation threshold were also determined in and out of the NMR magnet. The repetitive response threshold was 61 +/- 16 mA out of the magnet and 75 +/- 24 mA inside the magnet. This was significant at the P = 0.04 level. The ventricular fibrillation threshold was 71 +/- 14 mA out of the magnet and 81 +/- 20 mA in the magnet (P = ns). In summary, static magnetic fields associated with radiofrequency pulsing have no measureable effect on the strength interval relationship. There is no increase in ventricular vulnerability as assessed by the repetitive response threshold and the ventricular fibrillation threshold.

The role of the sympathetic nervous system in the systemic hemodynamic and regional blood flow responses to hypoxia was studied in awake dogs by pre-exposing the animals to phentolamine alone (alpha block) or to phentolamine plus propranolol (alpha + beta block). Hypoxia was produced by switching from room air to either an 8% or 5% oxygen-nitrogen mixture. During 8% oxygen breathing, cardiac output, heart rate, left ventricular dP/dt, dP/dt/P, myocardial oxygen consumption, and myocardial blood flow increased, and both total peripheral and coronary vascular resistance fell. These changes were similar in all groups with and without adrenergic blockade. However, during 5% oxygen breathing, the rises in cardiac output, heart rate, left ventricular dP/dt, myocardial oxygen consumption, and myocardial blood flow and the decrease in coronary vascular resistance were less marked in the group given alpha + beta block than the intact animals or group given alpha block. Coronary blood flow correlated with myocardial metabolic demands. Adrenal and skeletal muscle blood flows increased during hypoxia. Breathing 5% oxygen also increased flow to the brain, but renal and splanchnic flows showed only minor changes. These changes in organ vascular resistance were unaffected by the adrenergic blockade. Our results indicate that although the sympathetic nervous system plays an important role in the systemic hemodynamic responses to hypoxia, the dominant local metabolic factors probably are primarily responsible for hypoxic vasodilation in the awake dog.