Asymptomatic ventricular arrhythmias in patients with obstructive lung disease. Should they be treated?
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Anti-Arrhythmia Agents↗
Biomedical subjects
C M Pratt
Publications and source records attributed to C M Pratt.
Efficacy and safety of sustained-release diltiazem as replacement therapy for beta blockers and diuretics for stable angina pectoris and coexisting essential hypertension: a multicenter trial.
To determine if a sustained-release form of the calcium entry blocker diltiazem would be a satisfactory substitute for the combination of beta-adrenergic blocking agent and thiazide diuretic in the treatment of systemic hypertension and angina pectoris, 38 patients were studied in a 4-center trial. Blood pressure and heart rate were measured in the supine position, immediately after and 5 minutes after standing. Modified Bruce protocol treadmill tests were performed to determine the time to onset of 1 mm ST-segment depression, time to onset of chest pain and time to termination of exercise. Diltiazem monotherapy resulted in equivalent blood pressure control in 28 of 38 patients (74%). In the remaining patients, blood pressure control was achieved with resumption of the diuretic. Blood pressure with beta blocker plus diuretic compared with diltiazem were, in the supine position 137 +/- 22/82 +/- 7 (+/- 1 standard deviation) versus 139 +/- 22/82 +/- 8 mm Hg, immediately after standing 131 +/- 20/84 +/- 9 versus 133 +/- 21/82 +/- 10 mm Hg and after standing for 5 minutes 134 +/- 19/85 +/- 8 versus 137 +/- 18/85 +/- 9 mm Hg (difference not significant for each). The heart rate with diltiazem was higher supine (67 +/- 11 versus 60 +/- 11 beats/min), standing (73 +/- 13 versus 64 +/- 14 beats/min) and 5 minutes after standing (73 +/- 14 versus 63 +/- 14 beats/min, p less than 0.01 for each).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
Efficacy and tolerance of Ethmozine (moricizine HCl) in placebo-controlled trials.
To investigate the tolerance and efficacy of moricizine HCl, single-blind placebo-controlled trials were conducted. The early protocols involved patients hospitalized for 14 days, and daily Holter monitoring was used to document efficacy and the degree of spontaneous variability of ventricular premature complexes (VPCs). Moricizine HCl was given orally from 2.9 to 15.3 mg/kg 3 times daily. Patients with lethal ventricular arrhythmias were excluded. Additional outpatient trials were conducted to define long-term efficacy and safety. A dose-response relation between moricizine HCl and the percentage of reduction in frequency of benign or potentially lethal ventricular arrhythmias was documented. Eighty-five percent of patients achieved a reduction in VPCs greater than 75% with daily dosages ranging from 10.1 to 15 mg/kg. This corresponded to a 95% decrease in mean frequency of VPCs. Long-term studies demonstrated no evidence of compromise in left ventricular function, and the proarrhythmic rate was only 2%. Symptomatic side effects were mild and usually well tolerated. Nausea, the most common, occurred in 11% of patients and dizziness in 9%. These results indicate that moricizine HCl is an effective and well-tolerated antiarrhythmic agent.
Anti-Arrhythmia Agents↗
Antiarrhythmic efficacy of Ethmozine (moricizine HCl) compared with disopyramide and propranolol.
In the investigation of new antiarrhythmic drugs, comparative trials with clinically available antiarrhythmic agents provide a perspective from which to judge the new investigational agent. Two clinical investigations of moricizine HCl, each using a placebo-controlled, double-blind, crossover design, are summarized. In the first study, 18 patients with greater than or equal to 30 ventricular premature complexes (VPCs) per hour (mean 369 +/- 95) were given propranolol (120 mg daily) compared with moricizine HCl (816 +/- 103 mg daily). Propranolol suppressed 38% of VPCs in the study group, moricizine HCl, 81% of VPCs, and the combination of both drugs, 87%. Moricizine HCl was more effective than propranolol in suppressing VPCs at all individual levels greater than 70% (p less than 0.05, McNemar's test). The combination of moricizine HCl and propranolol was well tolerated. The second investigation used a placebo-controlled, double-blind, crossover design to compare the efficacy of disopyramide (600 mg daily) and moricizine HCl (800 mg daily) in 27 patients. Patients had greater than or equal to 40 VPCs/hr on a 24-hour ambulatory electrocardiogram. During moricizine HCl administration, the mean VPC frequency decreased from 524 to 151 VPCs/hr (71.2% reduction). In contrast, disopyramide reduced VPC frequency from 535 to 253 VPCs/hr (52.8% reduction) and demonstrated significantly greater side effects (p less than 0.05). Moricizine HCl was more effective than disopyramide in suppressing VPCs at all individual percent reduction levels greater than 70% (p less than 0.05, McNemar's test). Moricizine HCl was more effective in suppressing VPCs than either disopyramide or propranolol, with significantly fewer side effects.
Adult↗
Electrophysiology of Ethmozine (moricizine HCl) for ventricular tachycardia.
Moricizine HCl, an antiarrhythmic phenothiazine drug, was investigated for its efficacy against ventricular tachycardia (VT) in a group of 60 patients from 8 institutions using electrophysiologic testing before and after oral administration. Moricizine HCl significantly prolonged PR, QRS, AH and HV intervals and cycle length for atrioventricular nodal block, but had minimal or no effect on repolarization or cardiac refractory periods. Induction of sustained VT (in 33 patients) and nonsustained VT (in 14 patients) occurred at baseline. During moricizine HCl therapy, sustained VT was induced in 31 patients and nonsustained VT in 7 patients. In individual patients, suppression of VT induction was obtained in 18% of patients with sustained VT and in 27% of patients with nonsustained VT. Cycle length of induced VT was significantly prolonged by moricizine HCl therapy. During prospective follow-up of 37 patients, electrophysiologic study predicted recurrence of nonrecurrence of VT with a sensitivity value of 82% and specificity of 65%.
Adult↗
Effects of Ethmozine (moricizine HCl) on ventricular function using echocardiographic, hemodynamic and radionuclide assessments.
Ventricular arrhythmias combined with left ventricular (LV) dysfunction in patients portend a poor prognosis. Most antiarrhythmic agents have not been sufficiently investigated to adequately describe detrimental effects on LV function; we report the effects of moricizine HCl on ventricular function in 4 trials highlighting patients with LV dysfunction. Quantitative 2-dimensional echocardiography was used to evaluate 81 patients pre- and posttreatment. There was no change in mean global LV ejection fraction (EF) during placebo compared with moricizine HCl therapy (47 +/- 15% vs 46 +/- 14%, p greater than 0.05). In a separate trial, radionuclide LVEF at rest and exercise tolerance testing were performed in 24 patients with life-threatening ventricular arrhythmias who had a mean control LVEF of 40 +/- 19%. No significant change during moricizine HCl therapy (38 +/- 19%, p greater than 0.05) was detected and exercise parameters were unchanged. Rest and exercise LV function was measured during right-sided heart catheterization in a placebo-controlled study of 20 patients with ventricular tachycardia. Moricizine HCl was well tolerated without hemodynamic deterioration in all but 3 patients, who could be identified by their inability to increase stroke volume index during exercise. Finally, the relation between initial LV function and resultant antiarrhythmic efficacy indicates that moricizine HCl controls arrhythmias best in patients with LVEF greater than 30%.
Adult↗
Spontaneous variability of ventricular arrhythmias in patients at increased risk for sudden death after acute myocardial infarction: consecutive ambulatory electrocardiographic recordings of 88 patients.
The Cardiac Arrhythmia Pilot Study, sponsored by the National Heart, Lung, and Blood Institute, is a multicenter, prospective, randomized, double-blind trial designed to identify patients having 10 or more ventricular premature complexes (VPCs) per hour within 6 to 60 days of acute myocardial infarction. The present investigation selected patients after acute myocardial infarction who had ambulatory electrocardiographic qualifying arrhythmia for CAPS. An additional baseline electrocardiogram was recorded before enrollment in the study to assess baseline spontaneous variability of VPCs. A total of 88 patients (15 women, 73 men, aged 57 +/- 10 years) were studied. The 43 patients (49%) receiving beta-blocking drugs were included because the dose was not altered between the 2 consecutive electrocardiographic recordings. This investigation shows that a 95% reduction in VPCs is required to document a significant drug effect rather than variability alone if 1 day of control and 1 day of treatment electrocardiographic recording are compared. Similarly, based on 1 day of electrocardiographic recording before and after antiarrhythmic therapy, 1,780% increase in VPC frequency is required to establish "arrhythmia aggravation" from an antiarrhythmic drug rather than from variability alone based on a 95% confidence interval. Variability of ventricular arrhythmias is independent of left ventricular function, whereas patients taking beta-blocking therapy tend to have greater VPC variability (p = 0.052), even though VPC frequencies were lower (59 +/- 19 vs 138 +/- 31 VPCs/hour, p less than 0.006) than those not taking beta-blocking drugs.
Adrenergic beta-Antagonists↗
Asymptomatic telephone ECG transmissions as an outpatient surveillance system of ventricular arrhythmias: relationship to quantitative ambulatory ECG recordings.
Although ambulatory ECG recordings provide quantitative information in the follow-up of patients with ventricular arrhythmias, they are performed infrequently, potentially missing serious arrhythmias in the unmonitored periods. Telephone ECG systems offer "real-time" ECG information, theoretically functioning as an arrhythmia surveillance system. Thus we incorporated frequent telephone ECG transmissions in two antiarrhythmic drug protocols. The first investigation was designed to show the relationship of telephone and ambulatory ECGs in patients with frequent ventricular tachycardia (VT). The second protocol selected patients with "nonlife-threatening" frequent premature ventricular complexes (PVCs) in whom a second placebo period was instituted to simulate the clinical situation of asymptomatic arrhythmia increase. In both drug trials there was a strong linear relationship between the log-transformed PVC counts of telephone ECG and concomitant PVC, couplet, and VT frequencies on ambulatory ECG. In the VT population, greater than or equal to 1 PVC on telephone ECG reflected the presence of VT on ambulatory ECG (sensitivity 87%; specificity 77%). In the second study, telephone ECG transmissions with PVCs on three consecutive transmissions reflected the change from less than or equal to 10 PVCs/hour to greater than or equal to 40 PVCs/hour on ambulatory ECG within 48 hours. These data support the concept that daily surveillance by means of telephone ECG provides arrhythmia information of qualitative clinical relevance.
Ambulatory Care↗
Prinzmetal's angina during 5-fluorouracil chemotherapy.
Variant angina developed during intravenous 5-fluorouracil therapy in a patient without prior history of angina pectoris. Ambulatory electrocardiography demonstrated S-T segment elevation and ventricular ectopy during pain, whereas no symptoms or S-T segment changes occurred during placebo therapy. Prophylaxis with both nifedipine and diltiazem was successful in preventing recurrence. It is believed that 5-fluorouracil induced coronary vasospasm and that this was prevented by prophylactic calcium antagonist therapy. Drug-induced coronary artery spasm may be the cause of 5-fluorouracil-associated chest pain.
Angina Pectoris, Variant↗
Spontaneous arrhythmia detected on ambulatory electrocardiographic recording lacks precision in predicting inducibility of ventricular tachycardia during electrophysiologic study.
This study investigates the relation of spontaneous ventricular arrhythmia on ambulatory electrocardiographic (ECG) monitoring to the subsequent inducibility of ventricular tachycardia during programmed electrical stimulation. Eighty patients (65 men, 15 women), whose mean age was 58 years, presented with one of the following: sustained ventricular tachycardia (n = 54); sudden death requiring resuscitation (n = 4); ventricular fibrillation (n = 11); or syncope thought to be of cardiac origin (n = 11). All patients had 24 hour ambulatory electrocardiograms and programmed electrical stimulation while receiving no antiarrhythmic therapy. Programmed electrical stimulation resulted in inducible sustained ventricular tachycardia (defined as a rate of greater than or equal to 120 beats/min for greater than or equal to 1 minute or requiring intervention) in 53 of the 80 patients. There was no measure of frequency or complexity of spontaneous arrhythmia detected on ambulatory ECG that could identify the degree of subsequent ventricular tachycardia inducibility during programmed electrical stimulation. In fact, 25% of patients who had inducible sustained ventricular tachycardia had little or no spontaneous arrhythmia on ambulatory ECG. Furthermore, of the 53 patients with inducible sustained ventricular tachycardia, 28 and 55% had no couplets or nonsustained ventricular tachycardia, respectively, during ambulatory monitoring. The combination of a clinical presentation of sustained ventricular tachycardia, confirmed coronary artery disease and a left ventricular ejection fraction of less than 30% had a better positive predictive value than did any ambulatory ECG criterion in predicting the inducibility of sustained ventricular tachycardia.
Aged↗
Activation of the complement system by recombinant tissue plasminogen activator.
Recent trials have shown that recombinant tissue plasminogen activator (rt-PA) is an effective thrombolytic agent in patients with acute myocardial infarction. Because rt-PA converts plasminogen to plasmin, which is known to activate complement in vitro, we tested the hypothesis that rt-PA can induce in vivo activation of complement. Studies were performed in 12 patients with acute myocardial infarction. Six control patients had patent coronary arteries and did not receive rt-PA; these patients had normal values of the components of the complement system C4a (409 +/- 111 ng/ml) and C5a (8.8 +/- 1.8 ng/ml) with a slight elevation of C3a (204 +/- 6.6 ng/ml) in samples collected before coronary arteriography (253 +/- 25 minutes after onset of pain). After coronary arteriography, there was a slight decrease in the values of C4a (224 +/- 37 ng/ml), C5a (7.3 +/- 1.3 ng/ml) and C3a (164 +/- 35 ng/ml). The remaining six patients had complete coronary occlusion and received rt-PA (80 to 150 mg intravenously). In this treated group, before coronary arteriography the values of C4a (406 +/- 51.6 ng/ml) and C5a (8.1 +/- 1.9 ng/ml) were normal, and those of C3a were slightly elevated (250 +/- 76 ng/ml). All complement values obtained before rt-PA were similar to those in the untreated group. However, after administration of rt-PA (but before any angiographically detectable reperfusion), there was a striking increase in C4a (2,265 +/- 480 ng/ml; p less than 0.01), C3a (600 +/- 89 ng/ml; p less than 0.05) and C5a (30.0 +/- 4.5 ng/ml; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Antiarrhythmic efficacy and hemodynamic effects of cibenzoline in patients with nonsustained ventricular tachycardia and left ventricular dysfunction.
This was a prospective single-blind, placebo-controlled study of cibenzoline in 21 patients with five or more runs of nonsustained ventricular tachycardia (VT) and left ventricular dysfunction (mean left ventricular ejection fraction 36 +/- 24%). Ambulatory electrocardiographic monitoring revealed a baseline of 616 +/- 431 runs of VT/day on placebo. Of the 18 patients tolerating the drug, 14 (77%) patients initially had a 75% or greater reduction in VT (177 +/- 164 runs of VT/day, p less than .05). A repeat ambulatory electrocardiogram documented long-term suppression of VT in 13 of 14 patients at 1 month (2.1 +/- 1.3 runs VT/day, p less than .01), in 10 of 14 patients at 3 months (2.5 +/- 1.9 runs VT/day, p less than .01), and in nine of 14 patients at 6 months (1.5 +/- 0.8 runs VT/day, p less than .01). Aggravation of arrhythmia or drug failure was seen in four of 18 (22%) patients (new onset of sudden cardiac death, two patients; sustained VT, two patients). Hemodynamic measurements were obtained with the use of right heart catheterization in patients at rest and exercising during the placebo phase and after 60 hr of oral cibenzoline. Group hemodynamic variables, both measured and derived, showed no detrimental effect of cibenzoline. However, in three of 21 patients (mean ejection fraction 21%), cibenzoline was discontinued due to severe depression of left ventricular function. Caution is recommended in the use of cibenzoline in patients with left ventricular ejection fractions of less than 25%.
Aged↗
Creatine kinase isoform analysis in the detection and assessment of thrombolysis in man.
Recent demonstrations of the efficacy of intravenous thrombolytic therapy in acute myocardial infarction have emphasized the need for a noninvasive index of successful reperfusion. The tissue form of MM creatine kinase (MM3) is known to undergo posttranslational conversion to modified forms MM2 and MM1 after release into the plasma following acute infarction. Since this conversion is rapid, sustained elevation of plasma MM3 may be a marker of the prolonged creatine kinase release characteristic of nonreperfused infarction. Therefore, we investigated the rate of decline of plasma MM3 in a consecutive series of patients undergoing thrombolytic therapy of acute myocardial infarction, all of whom underwent acute angiography to assess treatment success, as well as in 30 conventionally treated patients. Among 55 patients with angiographically documented successful reperfusion (group IA), the rate of decline of MM3 was 4.18 +/- 1.25%/hr (mean +/- SD); in contrast, the rate of decline was 2.37 +/- 1.11%/hr in 39 patients with angiographically documented unsuccessful reperfusion (group IB) and 1.77 +/- 1.46%/hr among the 30 patients receiving conventional treatment (group II) (p less than .001 for groups IB and II vs group IA). A cutoff value of 3.1%/hr minimized the overlap between the groups; 48/55 (87%) patients with successful reperfusion had a rate of decline of MM3 of 3.1%/hr or more, while 29 of 39 (74%) patients in whom thrombolysis was unsuccessful and 27 of 30 (90%) patients receiving conventional treatment had a rate of decline less than 3.1%/hr (p less than .001 for groups IB and II vs group IA).(ABSTRACT TRUNCATED AT 250 WORDS)
Angioplasty, Balloon↗
The hemodynamic effects of sotalol and quinidine: analysis by use of rest and exercise gated radionuclide angiography.
This placebo-controlled, double-blind trial compared the hemodynamic effects of sotalol and quinidine with the use of rest and exercise gated radionuclide angiography. Patients had frequent ventricular premature depolarizations (greater than or equal to 30 VPDs/hour) and depressed cardiac function (mean ejection fraction 43 +/- 15%). Resting left ventricular ejection fraction and stroke volume index increased (p less than .002, p less than .001, respectively) during sotalol therapy, associated with a concomitant fall in heart rate (p less than .001). Quinidine also increased mean left ventricular ejection fraction, but less so than did sotalol (p less than .05). Quinidine significantly decreased left ventricular end-diastolic (p less than .05) and end-systolic (p less than .002) volumes, but had no effect on stroke volume index or heart rate. Neither drug affected cardiac index. Quinidine resulted in no symptomatic deterioration in left ventricular function or serious arrhythmia aggravation. In contrast, five patients on sotalol developed either decompensated congestive heart failure (two patients), arrhythmia aggravation (two patients), or hypotension associated with bradyarrhythmia (one patient). These patients had a unique hemodynamic profile that can be used to identify patients likely to have a poor outcome on sotalol. This profile reflected a lack of cardiac reserve, characterized by an inability to increase stroke volume and cardiac output with supine bicycle exercise.
Aged↗
Potentially deleterious effects of long-term vasodilator therapy in patients with heart failure.
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Angiotensin-Converting Enzyme Inhibitors↗
Design of a multicenter, double-blind study to assess the effects of prophylactic diltiazem on early reinfarction after non-Q-wave acute myocardial infarction: diltiazem reinfarction study.
This protocol describes the design of an international study to examine the potential prophylactic effect of 14 days of diltiazem therapy to prevent early reinfarction in patients initially presenting with non-Q-wave acute myocardial infarction. Reinfarction was defined by the detection of a secondary elevation of plasma MB-creatine kinase. The results of clinical trials, instrumental in this protocol design, that established the increased propensity for early reinfarction after initial non-Q-wave infarction are described and the implications of the present study are discussed.
Clinical Trials as Topic↗
Diltiazem and reinfarction in patients with non-Q-wave myocardial infarction. Results of a double-blind, randomized, multicenter trial.
We performed a multicenter, double-blind, randomized study to evaluate the effect of diltiazem on reinfarction after a non-Q-wave myocardial infarction. Nine centers enrolled 576 patients: 287 received diltiazem (90 mg every six hours) and 289 received placebo. Treatment was initiated 24 to 72 hours after the onset of infarction and continued for up to 14 days. The primary end point, reinfarction, was defined as an abnormal reelevation of MB creatine kinase in plasma within 14 days. Reinfarction occurred in 27 patients in the placebo group (9.3 percent) and in 15 in the diltiazem group (5.2 percent)--a 51.2 percent reduction in cumulative life-table incidence (P = 0.0297; 90 percent confidence interval, 7 to 67 percent). Diltiazem reduced the frequency of refractory postinfarction angina (a secondary end point) by 49.7 percent (P = 0.0345; 90 percent confidence interval, 6 to 73 percent). Mortality was similar in the two groups (3.1 and 3.8 percent, respectively, in the placebo and diltiazem groups), but adverse drug reactions (most of which were mild) were more common in the diltiazem group. Nevertheless, the drug was well tolerated, despite concurrent treatment with beta-blockers in 61 percent of the patients. We conclude that diltiazem was effective in preventing early reinfarction and severe angina after non-Q-wave infarction and that it was also safe and generally well tolerated.
Aged↗
Hemodynamic effects of moricizine at rest and during supine bicycle exercise: results in patients with ventricular tachycardia and left ventricular dysfunction.
To evaluate the hemodynamic effects of moricizine, 20 patients with frequent nonsustained ventricular tachycardia (VT) with a mean left ventricular ejection fraction (EF) of 39 +/- 14% were enrolled in a prospective single-blind, placebo-controlled study. Hemodynamic measurements were performed at rest and during supine bicycle exercise on placebo and moricizine therapy (10 mg/kg/day). Although 16 of 19 patients experienced no rest or exercise deterioration in hemodynamic parameters during drug dosing, three patients had acute deterioration of pulmonary capillary wedge pressure and cardiac index (CI) on moricizine. During follow-up of 6 +/- 3 months, two subgroups were identified: 10 of 19 patients had effective long-term reduction in VT, whereas 9 of 19 patients had poor control of ventricular arrhythmia or congestive heart failure and were discontinued from the trial. Baseline EF and hemodynamic parameters at rest were similar in both patient subgroups. However, protocol dropouts had a hemodynamic response to exercise on moricizine that was significantly depressed as compared to patients with a favorable antiarrhythmic outcome (p less than 0.02). The following hemodynamic profile characterizes patients unlikely to have an antiarrhythmic response to moricizine: an increase in CI of less than 1.0 L/min/m2 and no increase in left ventricular stroke work index during supine exercise.
Exercise Test↗