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Biomedical subjects

C M Pratt

Publications and source records attributed to C M Pratt.

At least 73 records · Page 4Linked to original sources
PubMed1990

The Cardiac Arrhythmia Suppression Trial: background, interim results and implications.

The Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular premature complexes (VPCs) in survivors of acute myocardial infarction would reduce arrhythmic death risk. Instead, a preliminary finding from the CAST was that the encainide and flecainide groups had a 3.6-fold increase in arrhythmic death compared with their placebo group. These unfortunate results were especially surprising in that the CAST population represented patients in whom the risk of arrhythmic death was only moderate and the risk of proarrhythmia was thought to be low. In contrast, the arrhythmic death rate of the CAST placebo group was unusually low, to the extent that it paralleled the arrhythmic death rate in previous clinical trials of patients surviving myocardial infarction with no ventricular arrhythmia. The excessive arrhythmic death rate in patients taking encainide and flecainide occurred over the duration of the CAST, implying a proarrhythmic effect that may be due to mechanisms that are unique in this population, and thus challenging traditional concepts of proarrhythmia. The existing knowledge regarding the proarrhythmic and negative inotropic effects of encainide and flecainide are reviewed. The previous pharmaceutical database experience with these 2 antiarrhythmic drugs exceeded 3,000 patients; however, there was no indication of this serious proarrhythmic effect. In contrast, the CAST population taking encainide and flecainide totaled only 725 patients who were followed for 10 months and had an extremely high proarrhythmic event rate. The reasons for this discrepancy are discussed. The results of the CAST emphasize the power of a randomized, placebo-controlled clinical trial to uncover previously unsuspected benefits or liabilities of traditional therapies.

Anilides↗
PubMed1990

Hemodynamic effects of intravenous and oral sotalol.

Beta-adrenergic blocking agents may have negative inotropic effects that are particularly worrisome in patients with depressed cardiac function. Their membrane-stabilizing properties may be a contributing factor. Sotalol is currently thought not to cause significant myocardial depression. Intravenous sotalol administration has minimal effects on resting stroke volume, although heart rate and consequently cardiac output are significantly decreased. Systolic blood pressure decreases, with a minimal change in diastolic or mean pressure. Hemodynamic effects are usually seen within 15 to 20 minutes of administration. Hemodynamic indexes are maintained even in patients with mildly depressed ejection fractions (mean ejection fraction of 43 +/- 15%) after oral sotalol administration. Although heart rate decreases, cardiac index is unchanged because of a significant increase in stroke volume index. The latter results from an increase in preload (secondary to bradycardia) and a decrease in afterload. Sotalol is well tolerated, although occasionally it may cause worsening heart failure. This is seen in patients with markedly depressed left ventricular function and inadequate cardiac reserve characterized by an inability to increase stroke volume and cardiac output with exercise. Long-term (1-year) patient follow-up reveals no significant hemodynamic deterioration from initial values obtained after oral administration.

Administration, Oral↗
PubMed1990

Efficacy and safety of moricizine in patients with congestive heart failure: a summary of the experience in the United States.

Patients with ventricular premature beats (VPBs) and congestive heart failure (CHF) have an increased risk of sudden death, yet suppression of arrhythmia in this population is frequently complicated by proarrhythmia and by the negative inotropic effects of antiarrhythmic drugs. The purpose of this study was to evaluate the safety and efficacy of moricizine in patients with clinical CHF. The New Drug Application data base submitted to the Food and Drug Administration was analyzed. A total of 908 patients were treated with moricizine for ventricular arrhythmias; CHF developed in 49 of them (5.4%). Of the 908 patients, 374 had a history of CHF, 326 of whom tolerated moricizine for a mean of 97 +/- 217 days. New-onset CHF occurred only once (1/546 = 0.2%). Recurrence or exacerbation of clinical CHF during treatment with moricizine occurred in 48 of 374 patients (12.8%), 28 of whom continued to take moricizine with alteration in CHF therapy. The mean left ventricular ejection fraction (LVEF) of those patients in whom CHF developed was 26%. It is important to note that patients with a history of CHF were as likely to have suppression of VPBs (defined as greater than or equal to 75% reduction) as those without a history of CHF. In fact, suppression of arrhythmia was achieved as often in patients with LVEF less than 30% as in those with more preserved LVEF. Of the 374 patients with a history of CHF, 15 (4%) had a proarrhythmic event within 14 days of therapy. The incidence of sudden cardiac death in this group was 0.8%. These proarrhythmia rates compare favorably with those of other antiarrhythmic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1990

Lack of diurnal variation in the onset of non-Q wave infarction.

Data concerning the time of onset of myocardial infarction were obtained for 540 of the 544 patients with creatinine kinase (CK)-MB-confirmed non-Q wave myocardial infarction enrolled in the multicenter Diltiazem Reinfarction Study. Data were also collected for 627 patients who were screened but excluded. Among the 1,167 patients, no diurnal pattern of onset could be found at either 2- or 6-hour intervals. Among the 540 patients enrolled in the trial, no pattern could be found at these intervals either, although at 8-hour intervals, 27% of infarctions occurred between midnight and 8:00 AM, compared with 37% between 8:00 AM and 4:00 PM and 36% between 4:00 PM and 12:00 AM (p = 0.02). In contrast to the patterns previously noted for Q wave myocardial infarction, there was no preponderance of non-Q wave infarction in the late morning. Circadian rhythm was also absent among patients not treated with beta-blockers as well as among patients presenting with ST segment elevation on their enrollment electrocardiograms. Diabetics, women, and patients with first infarction were more likely to present during the afternoon hours. We conclude that the late morning preponderance seen for Q-wave myocardial infarction is not discernable in patients with non-Q wave myocardial infarction. This observation suggests that the pathogenesis of these two infarct subtypes is different or that the process of thrombotic coronary occlusion in Q wave infarction (sustained) differs from that in non-Q wave infarction (nonsustained).

Adrenergic beta-Antagonists↗
PubMed1990

Altered myocardial perfusion in patients with angina pectoris or silent ischemia during exercise as assessed by quantitative thallium-201 single-photon emission computed tomography.

The extent of abnormally perfused myocardium was compared in patients with and without chest pain during treadmill exercise from a large, relatively low-risk consecutive patient population (n = 356) referred for quantitative thallium-201 single-photon emission computed tomography (SPECT). All patients had concurrent coronary angiography. Patients were excluded if they had prior coronary angioplasty or bypass surgery. Tomographic images were assessed visually and from computer-generated polar maps. Chest pain during exercise was as frequent in patients with normal coronary arteries (12%) as in those with significant (greater than 50% stenosis) coronary artery disease (CAD) (14%). In the 219 patients with significant CAD, silent ischemia was fivefold more common than symptomatic ischemia (83% versus 17%, p = 0.0001). However, there were no differences in the extent, severity, or distribution of coronary stenoses in patients with silent or symptomatic ischemia. Our major observation was that the extent of quantified SPECT perfusion defects was nearly identical in patients with (20.9 +/- 15.9%) and without (20.5 +/- 15.6%) exertional chest pain. The sensitivity for detecting the presence of CAD was significantly improved with quantitative SPECT compared with stress electrocardiography (87% versus 65%, p = 0.0001). Although scintigraphic and electrocardiographic evidence of exercise-induced ischemia were comparable in patients with chest pain (67% versus 73%, respectively; p = NS), SPECT was superior to stress electrocardiography for detecting silent myocardial ischemia (52% versus 35%, respectively; p = 0.01). The majority of patients in this study with CAD who developed ischemia during exercise testing were asymptomatic, although they exhibited an angiographic profile and extent of abnormally perfused myocardium similar to those of patients with symptomatic ischemia. The prognostic significance of quantified perfusion defects detected by SPECT remains to be assessed.

Adult↗
PubMed1990

Silent myocardial ischemia in patients with coronary artery disease. Possible links with diastolic left ventricular dysfunction.

Silent myocardial ischemia is now recognized as a common manifestation within the clinical spectrum of coronary artery disease and has important physiological, hemodynamic, and prognostic implications. Asymptomatic ST segment shifts during ambulatory 24-hour electrocardiographic monitoring and exercise treadmill testing are far more frequent than symptomatic ST shifts and are associated with abnormal myocardial perfusion as assessed by radionuclide scintigraphy. Seemingly healthy asymptomatic patients and patients with stable coronary artery disease, unstable angina, or recent myocardial infarction are all at higher risk of subsequent cardiovascular morbidity if there is evidence of silent ischemia. Hemodynamic studies have clearly documented the adverse effects of ischemia on left ventricular systolic function. Furthermore, diastolic relaxation and filling appear to be altered by both symptomatic and asymptomatic ischemia during atrial pacing and dynamic exercise independent of changes in systolic function. The majority of patients with coronary artery disease have abnormal diastolic parameters at rest, regardless of anginal symptoms, which are partially reversible after coronary revascularization procedures such as angioplasty and bypass surgery. Regional diastolic dysfunction from scar or ischemia can lead to asynchronous myocardial relaxation and thus affect global diastolic function, depending on the extent and severity of the regional abnormalities. Diastolic function seems more susceptible to ischemia than systolic function and can take longer to recover.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1989

Prevalence and characteristics of proarrhythmia from moricizine (Ethmozine).

Moricizine was studied in 908 patients with ventricular arrhythmia. Proarrhythmia occurred in 29 (3.2%). When the type of proarrhythmia and the type of ventricular arrhythmia were correlated, no proarrhythmic events occurred in patients with benign ventricular arrhythmia. Three of the 4 deaths due to proarrhythmia occurred in patients with lethal ventricular arrhythmia and 14 of the 15 serious proarrhythmic events occurred in patients with potentially lethal ventricular arrhythmia. The overall proarrhythmia incidence in lethal and potentially lethal ventricular arrhythmias was not different (3.2 vs 3.7%, respectively). Proarrhythmia occurred in patients with more significant structural heart disease or conduction defects at baseline, but was not related to the baseline frequency of ventricular premature complexes. There was no relation between dose of moricizine and incidence of proarrhythmia. All 29 proarrhythmic events occurred within 10 days and 26 of 29 (90%) took place within 7 days of therapy start. Thus, moricizine has a low proarrhythmic potential, especially in patients with lethal ventricular arrhythmias, and may have the best risk/benefit ratio among first-line drugs used in these patients.

Adult↗
PubMed1989

The inverse relationship between baseline left ventricular ejection fraction and outcome of antiarrhythmic therapy: a dangerous imbalance in the risk-benefit ratio.

Each year, millions of prescriptions are written for antiarrhythmic drug suppression of ventricular arrhythmias. A large portion of these prescriptions are written for patients with asymptomatic, complex ventricular arrhythmias and organic heart disease, termed "potentially malignant" or "potentially lethal." Since arrhythmia suppression in this population is of unproven benefit, we performed the following study: A total of 246 patients (42% with significant left ventricular dysfunction) had complex ventricular arrhythmias, and were treated with one of eight antiarrhythmic drugs (Vaughan Williams classes IA, IB, IC, II, and III). The extent of arrhythmia suppression and the development of serious complications resulting from therapy after 2 weeks was of primary interest. A total of 82 of 246 (33%) maintained adequate (protocol definition) suppression of both ventricular premature beats (VPBs) as well as nonsustained ventricular tachycardia (VT) for 2 weeks, mostly in patients with left ventricular ejection fraction (LVEF) greater than or equal to 40% (p = 0.04 versus LVEF less than 40%). Life-threatening complications of antiarrhythmic therapy occurred most frequently in the 61 patients with an LVEF less than 30% compared to the 185 patients with LVEF greater than or equal to 30% (15% versus 2.1%, p = 0.0005). Suppression of VT was achieved nearly twice as commonly in patients with an LVEF greater than or equal to 30% than in those with an LVEF less than 30% (67% versus 36%; p = 0.0008). Life-threatening complications occurred seven times as frequently in patients presenting with nonsustained VT and an LVEF less than 30% (18% versus 2.3%; p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1989

Exercise testing in women with chest pain. Are there additional exercise characteristics that predict true positive test results?

Women have a notoriously high rate of false positive exercise test results. Since the exercise ST segment response has low specificity in predicting CAD in women, we examined additional exercise parameters in 200 women with a history of chest pain compatible with angina and having ST segment depression greater than or equal to 1 mm recorded during a Bruce treadmill test. All subsequently had coronary arteriography. Two groups were compared: group A (n = 80) with CAD (greater than or equal to 70 percent stenosis of one or more coronary artery) and group B (n = 120) with angiographically confirmed normal coronary arteries (normal or minimal placquing). The exercise criteria analyzed included: (1) chest pain during exercise, (2) percent target heart rate, (3) extent of ST shift, (4) morphology of the ST segment slope, (5) time to normalization of the ST segment, and (6) total exercise duration. Multivariate analysis (using a stepwise logistic regression model) identified four independent exercise variables associated with the likelihood of CAD: (absence of MVP, p = .003; exercise duration less than 5 min, p = .02; ability to reach target heart rate, p = .027; time to ST normalization greater than or equal to 6 min, p less than .001). False positive exercise test results were more likely to occur when the following exercise test variables were present: ability to exercise to stage 3 of the Bruce protocol and a rapid (less than or equal to 4 minutes) normalization of ST shift after cessation of exercise. Attention to these additional exercise variables allows more careful selection of women requiring more definitive (and expensive) testing.

Angina Pectoris↗
PubMed1988

Relation of left ventricular dilation during acute myocardial infarction to systolic performance, diastolic dysfunction, infarct size and location.

The quantification of left ventricular (LV) volumes and assessment of their relation to systolic and diastolic dysfunction, infarct size and anatomic location were performed in 54 patients with a first acute myocardial infarction (AMI). Blood pool radionuclide angiography was used to assess LV end-diastolic, end-systolic, and stroke volume indexes, ejection fraction and peak diastolic filling rate. Infarct size was estimated from plasma MB creatine kinase activity. Substantial LV dilation occurred within the initial 24 hours of AMI. The peak diastolic filling rate was low, even in those patients with a normal ejection fraction. In comparison with inferior AMI (n = 25), patients with anterior AMI (n = 29) had a larger end-diastolic volume index (105 +/- 8 vs 81 +/- 4 ml/m2, p less than 0.01) and end-systolic volume index (64 +/- 7 vs 37 +/- 4 ml/m2, p less than 0.001), but similar stroke volume index (41 +/- 3 vs 43 +/- 2 ml/m2, difference not significant). No significant relation was noted between infarct size estimated by MB creatine kinase and any volumetric index. On repeat study (day 10 after AMI), end-diastolic and end-systolic volume indexes increased further (p less than 0.05 vs day 1) but ejection fraction and peak diastolic filling rate were unchanged. It was concluded that: (1) LV dilation occurs within hours of AMI in both inferior and anterior AMI, but is more marked in the latter; (2) significant LV diastolic dysfunction is the rule, even in patients with preserved LV systolic function; and (3) LV dilation is an early compensatory mechanism that maintains normal stroke volume, even in patients with severely reduced LV function.

Cardiac Volume↗
PubMed1988

The natural history of benign and potentially malignant ventricular arrhythmias with special reference to nonsustained ventricular tachycardia.

Ambulatory ECG recordings are routinely used to identify patients at increased risk of sudden cardiac death and to monitor changes in ventricular arrhythmias during antiarrhythmic drug therapy. The arrhythmia frequency established during the initial baseline has previously been reported to change during a second placebo monitoring period in patients with non-life-threatening ventricular arrhythmias, but the extent to which this applies to patients with nonsustained ventricular tachycardia has not been examined. To extend these observations to patients with potentially lethal ventricular arrhythmias, we studied 53 patients enrolled in one of two investigational antiarrhythmic drug trials that introduced a second single-blind placebo period (placebo-pulse) an average of 16 months after successful arrhythmia suppression. Thirty-eight of the 53 patients had runs of nonsustained ventricular tachycardia recorded during the initial baseline (placebo I) period, with 63% averaging greater than or equal to 10 runs per day. There was a marked reduction in the arrhythmia frequencies between the two placebo periods: 55% for ventricular premature beats, and 77% for pairs (p less than 0.001, respectively). Of the 38 patients with nonsustained ventricular tachycardia, there was a 72% reduction (892 +/- 531 vs 245 +/- 18 runs of VT/day, placebo I vs II; p = 0.0001), with 32% having total suppression of nonsustained ventricular tachycardia during the second placebo period. The results of this trial extend our previous observations of long-term spontaneous changes in arrhythmia frequency to patients with symptomatic, potentially lethal ventricular arrhythmia and support the recommendation for periodic reassessment of baseline arrhythmia frequency to determine the continued need for antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1988

Intravenous fenoldopam in heart failure: comparing the hemodynamic effects of dopamine1 receptor agonism with nitroprusside.

Dopamine1 receptors mediate hemodynamic effects that may be beneficial in patients with congestive heart failure. We infused the selective dopamine1 receptor agonist, fenoldopam mesylate (SKF 82526 J), to evaluate hemodynamic and neurohumoral changes during continuous intravenous infusion in patients with congestive heart failure and compared them with the effects of nitroprusside, a traditional vasodilator that works by a distinctly different mechanism. In 15 patients with a mean radionuclide ejection fraction of 17%, the agents were infused in a random-ordered, double-blinded, crossover, active drug-controlled protocol after optimal dosing was determined during a titration period. Hemodynamic changes were induced in minutes with both drugs during a mean (+/- standard deviation) infusion dose of 1.45 +/- 1.66 micrograms/kg/min for fenoldopam and 2.99 +/- 1.59 micrograms/kg/min for nitroprusside. At 1 hour, mean blood pressure decreased and cardiac index rose with both drugs, and the effect lasted throughout the 6-hour infusion period. Nitroprusside, but not fenoldopam, reduced right heart filling pressures (including mean pulmonary capillary wedge, mean right atrial, and mean pulmonary artery pressures) during the infusion period. Both drugs caused significant reduction in systemic vascular and pulmonary arteriolar resistances. No significant change occurred in plasma norepinephrine levels. Fenoldopam ameliorates some of the adverse hemodynamic changes that occur during heart failure but does not reduce right heart filling pressures as does nitroprusside. Because of fenoldopam's unique characteristics, it may benefit certain patients with heart failure.

Adult↗
PubMed1988

Quantification of infarct size by 201Tl single-photon emission computed tomography during acute myocardial infarction in humans. Comparison with enzymatic estimates.

We prospectively investigated whether 201Tl single-photon emission computed tomography (SPECT) could accurately diagnose the presence and quantify the extent of acute myocardial infarction when compared with infarct size assessed by plasma MB-creatine kinase activity. Thirty patients with enzymatic evidence of infarction were imaged within 12-36 hours of chest pain (mean, 23.4 hours). No patient had a previous infarction, and none underwent intervention seeking to restore coronary patency. Infarct size was quantified with computer-generated polar maps of the myocardial radioactivity and expressed as a percentage of the total left ventricular volume. To assess left and right ventricular performance, blood-pool gated radionuclide angiography was performed immediately after SPECT. All 30 patients had perfusion defects consistent with myocardial infarction. Scintigraphic and enzymatic estimates of infarct size correlated well for the group as a whole (r = 0.78, p less than 0.001, SEE = 9.1) but especially for those patients with anterior infarction (r = 0.91, p less than 0.001, SEE = 7.9). The poor correlation observed in patients with inferior infarction (r = 0.50, p less than 0.05, SEE = 10.0) was believed to be related to the frequent occurrence of right ventricular involvement because SPECT assessed only left ventricular damage, whereas the enzymatic method estimated the myocardial injury in both ventricles. A quantitative index of right ventricular infarct size, derived from the relation between the scintigraphic and enzymatic estimates, had a strong inverse correlation with right ventricular ejection fraction (r = -0.89, p less than 0.001, SEE = 3.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Creatine Kinase↗