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Biomedical subjects

C M Pratt

Publications and source records attributed to C M Pratt.

At least 55 records · Page 3Linked to original sources

Exploring the minimal dose of amiodarone with antiarrhythmic and hemodynamic activity.

Amiodarone in doses of 200 to 400 mg/day has shown promise in secondary prevention trials for reducing mortality in patients surviving myocardial infarction who have complex ventricular ectopy or nonsustained ventricular tachycardia, or both. In an attempt to explore the lowest dose of amiodarone with antiarrhythmic and hemodynamic activity, we studied 48 patients (mean age 53 +/- 11 years, ejection fraction 23 +/- 9%, clinical heart failure in 85%) with nonsustained ventricular tachycardia. This was a 3-month, randomized, parallel, double-blind pilot study comparing placebo (n = 16) with amiodarone 50 mg/day (n = 15) and 100 mg/day (n = 17). Patients randomized to amiodarone received a mean loading dose of 422 mg/day for the first study week. At the end of the 12 weeks, amiodarone (100 mg) significantly reduced ventricular premature complexes (177 +/- 64 to 98 +/- 38/hour), couplets (8 +/- 3 to 4 +/- 2/hour), and runs of nonsustained ventricular tachycardia (13 +/- 7 to 3 +/- 2/day), all p < 0.01 versus baseline. In addition, 10 of 14 patients taking 100 mg/day had total suppression of nonsustained ventricular tachycardia compared with 4 of 15 taking placebo, p = 0.021. Left ventricular ejection fraction improved by > or = 7% (absolute) in 11 of 29 patients taking amiodarone as compared with only 1 of 15 placebo patients (p = 0.02). In these 11 patients with the greatest measurable hemodynamic improvement, amiodarone significantly increased ejection fraction (21 +/- 7% to 33 +/- 11%, p < 0.01), stroke volume index (28 +/- 9 to 40 +/- 7 ml/m2, p < 0.01) and decreased end-systolic volume index (116 +/- 48 to 92 +/- 44 ml/m2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Risk of developing life-threatening ventricular arrhythmia associated with tefenadine in comparison with over-the-counter antihistamines, ibuprofen and clemastine.

An observational, historical cohort evaluation was performed to examine the hypothesis that terfenadine (Seldane) exposure increases the risk of developing life-threatening ventricular arrhythmias. The study population consisted of Medicaid recipients from 4 states that were included in the Computerized On-Line Medical Pharmaceutical Analysis and Surveillance System (COMPASS). The drug exposure period was defined prospectively as 30 days in all treatment cohorts. The primary end point was the development of life-threatening ventricular arrhythmias (ventricular tachycardia, fibrillation and flutter, and cardiac arrest and sudden death). The comparison cohorts included terfenadine (n = 181,672), over-the-counter antihistamines (n = 150,689), ibuprofen (n = 181,672) and clemastine (Tavist; n = 83,156). Over the exposure period, a total of 317 life-threatening ventricular arrhythmic events occurred, 244 of which were cardiac arrests. The incidence of total life-threatening ventricular arrhythmic events and cardiac arrests were more frequent in patients receiving over-the-counter antihistamines (relative risk 0.36) than in those receiving terfenadine, a finding that was consistent across all subgroups. There was no increased risk of life-threatening ventricular arrhythmias in the terfenadine cohort as compared with the ibuprofen cohort (relative risk 0.62), and in some analyses, the ibuprofen cohort had a significantly higher arrhythmic event rate. In all comparisons with the clemastine cohort, the terfenadine cohort had a statistically indistinguishable relative risk (1.08). Age, race, sex and cardiovascular risk were all considered in the adjusted relative-risk analyses. No baseline historical characteristic or imbalance of baseline medications explained the differences between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Transdermal nitroglycerin patch therapy reduces the extent of exercise-induced myocardial ischemia: results of a double-blind, placebo-controlled trial using quantitative thallium-201 tomography.

OBJECTIVES: This study prospectively evaluated whether transdermal nitroglycerin patches could limit the extent of exercise-induced left ventricular ischemia as assessed by quantitative thallium-201 tomography. BACKGROUND: Although antianginal medications are effective at reducing chest pain symptoms in patients with coronary artery disease, there is limited evidence that these agents can also reduce myocardial ischemia. METHODS: This was a randomized, double-blind, parallel, placebo-controlled trial evaluating nitroglycerin patch therapy in patients in stable condition with angiographic coronary artery disease and no previous myocardial infarction. All patients were weaned from antianginal agents and had a baseline symptom-limited treadmill test followed by thallium-201 tomography. Forty patients with perfusion defects involving > or = 5% of the left ventricle were randomized to receive either intermittent (12 h on/off) active nitroglycerin patch therapy (0.4 mg/h) or placebo. Exercise tomography was repeated a mean (+/- SD) of 6.1 +/- 1.8 days after randomization. RESULTS: Patients randomized to receive active patch therapy had a significant reduction in their total perfusion defect size (-8.9 +/- 11.1%) compared with placebo-treated patients (-1.8 +/- 6.1%, p = 0.04), which was most apparent in those with the largest (> or = 20%) baseline perfusion defects (-11.4 +/- 13.4% vs. 1.0 +/- 3.6%, respectively, p < 0.02). Furthermore, 7 (33%) of 21 patients receiving active therapy had a > or = 10% decrease in their perfusion defects compared with only 1 (5%) of 19 patients randomized to receive placebo (p = 0.002). Nitrate therapy did not significantly reduce heart rate, blood pressure or double product, indicating benefit through enhancement of coronary blood flow. CONCLUSIONS: Short-term, intermittent nitroglycerin patch therapy significantly reduces myocardial ischemia, particularly in patients with large ischemic perfusion defects. Thallium-201 tomography can be used to assess sequential changes in the extent of exercise-induced left ventricular ischemia.

Administration, Cutaneous↗

Effects of low dose transdermal scopolamine on heart rate variability in acute myocardial infarction.

OBJECTIVES: We hypothesized that by enhancing parasympathetic activity, low dose transdermal scopolamine would increase heart rate variability after myocardial infarction. BACKGROUND: Low heart rate variability is associated with increased mortality after acute myocardial infarction. METHODS: Conventional time domain heart rate variability was measured from 24-h Holter recordings of 61 consecutive male patients (mean age 58 +/- 10 years, left ventricular ejection fraction 44.7 +/- 15.5%) 6 days (median) after acute myocardial infarction. Patients were then randomly assigned to wear one patch of transdermal scopolamine or a matching placebo patch for 24 h, during which their 24-h heart rate variability was remeasured. RESULTS: Compared with placebo, transdermal scopolamine caused a significant increase in time domain measures of 24-h heart rate variability by 26% to 35% above baseline. Transdermal scopolamine was well tolerated. CONCLUSIONS: Low dose transdermal scopolamine safely increases cardiac parasympathetic activity and short-term heart rate variability after acute myocardial infarction. Whether the effect of transdermal scopolamine on heart rate variability is a reasonable surrogate for improvement of long-term morbidity and mortality requires an appropriate designed investigation.

Administration, Cutaneous↗

A reduction in the correlation dimension of heartbeat intervals precedes imminent ventricular fibrillation in human subjects.

Reduced reflexive control of heartbeat intervals occurs with advanced heart disease and is an independent risk factor for mortality. Based on a previous study of experimental myocardial infarction in pigs, we hypothesized that a deterministic measure of heartbeat dynamics, the correlation dimension of R-R intervals (D2), may be a better predictor of risk than a stochastic measure, such as the standard deviation (SD). We determined the point estimates of the heartbeat D2 (i.e., PD2s) in Holter electrocardiographic recordings from 11 high-risk patients who manifested ventricular fibrillation (VF) during the recording and in high-risk controls having only nonsustained ventricular tachycardia (14 patients) or premature ventricular complexes (13 patients). We found that PD2 reduction (i.e., PD2s < 1.2) precedes lethal arrhythmias by hours, but is not reduced in high-risk controls (p < 0.001; sensitivity, 91%; specificity, 85%). Heartbeat SD did not discriminate among the patients. Thus PD2 of heartbeat intervals may provide an important diagnostic test and early warning sign of VF.

Algorithms↗

Conventional heart rate variability analysis of ambulatory electrocardiographic recordings fails to predict imminent ventricular fibrillation.

OBJECTIVES: The purpose of this report was to study heart rate variability in Holter recordings of patients who experienced ventricular fibrillation during the recording. BACKGROUND: Decreased heart rate variability is recognized as a long-term predictor of overall and arrhythmic death after myocardial infarction. It was therefore postulated that heart rate variability would be lowest when measured immediately before ventricular fibrillation. METHODS: Conventional indexes of heart rate variability were calculated from Holter recordings of 24 patients with structural heart disease who had ventricular fibrillation during monitoring. The control group consisted of 19 patients with coronary artery disease, of comparable age and left ventricular ejection fraction, who had nonsustained ventricular tachycardia but no ventricular fibrillation. RESULTS: Heart rate variability did not differ between the two groups, and no consistent trends in heart rate variability were observed before ventricular fibrillation occurred. CONCLUSIONS: Although conventional heart rate variability is an independent long-term predictor of adverse outcome after myocardial infarction, its clinical utility as a short-term predictor of life-threatening arrhythmias remains to be elucidated.

Adult↗

Quantitative adenosine 201Tl single-photon emission computed tomography for the early assessment of patients surviving acute myocardial infarction.

BACKGROUND: We prospectively investigated whether adenosine 201Tl tomography (SPECT) could determine the extent of coronary artery disease, the presence of jeopardized myocardium, and the risk for in-hospital cardiac events in 120 clinically stable patients early (5 +/- 3 days) after myocardial infarction. METHODS AND RESULTS: All patients had coronary angiography and SPECT in close proximity. Adenosine SPECT identified 99% of infarct-related arteries and 82% of severely stenosed (> or = 70%) noninfarct arteries. Multivessel disease was accurately predicted in 69% of patients. Sixty-five percent of stenosed noninfarct arteries had matching thallium perfusion defects, and 92% of these were reversible. The specificity of adenosine SPECT was > 90%. Thallium redistribution occurred often within infarct (59%) and noninfarct (92%) zones. The patency status of the arteries, however, did not predict the presence or extent of jeopardized myocardium. The perfusion defect size was larger (p = 0.0001) in patients with (45 +/- 18%) than in those without (22 +/- 15%) in-hospital cardiac events. Furthermore, 90% of patients with events had a > or = 20% perfusion defect compared with only 38% of those without events (p = 0.0001). The positive-predictive accuracy for developing a cardiac event was 70% when the perfusion defect size was > 30%. The ischemic defect also was larger in patients with (19 +/- 14%) than in those without (10 +/- 10%) events (p = 0.001). The positive- and negative-predictive values for developing early postinfarction angina were 43% and 91%, respectively, when the ischemic defect was > 12%. CONCLUSIONS: In selected low-risk survivors of myocardial infarction, early quantitative adenosine SPECT is safe and accurate in detecting and localizing coronary stenoses, assessing the extent of jeopardized myocardium, and determining subsequent risk for in-hospital cardiac events.

Adenosine↗

Prognostic significance of ventricular premature depolarizations measured 1 year after myocardial infarction in patients with early postinfarction asymptomatic ventricular arrhythmia.

OBJECTIVES: The objective of this study was to examine the relation between death and the frequency of premature ventricular depolarizations measured approximately 1 year after myocardial infarction. BACKGROUND: The reported association between premature ventricular depolarizations and death in the weeks after myocardial infarction is in part the basis for the use of antiarrhythmic drugs. Such an association has not been reported on for observations obtained at a much greater interval after myocardial infarction. METHODS: We examined the association between mortality and premature ventricular depolarization rates measured 1 year after myocardial infarction in patients with asymptomatic ventricular arrhythmia early (between 6 and 90 days, median 28) after infarction, as measured by 24-h ambulatory electrocardiographic recording. The study group consisted of 502 patients enrolled in the Cardiac Arrhythmia Pilot Study during 1983 to 1985. They were followed up during the course of the study and subsequently by a National Death Index search (average follow-up interval 1,080 days). RESULTS: Death was recorded for 87 patients through 1987. Because patients were admitted to the Cardiac Arrhythmia Pilot Study only if they had greater than or equal to 10 ventricular premature depolarizations/h, the arrhythmia rate measured at baseline (that is, early after infarction) was not expected to, and did not, predict mortality. In 360 patients ventricular premature depolarization rates were measured approximately 1 year from their index myocardial infarction while they were not receiving antiarrhythmic therapy. In these patients, who had survived 1 year after the index infarction, the rate of ventricular premature depolarizations/h measured 1 year after infarction was highly predictive of subsequent death (p less than 0.001). Recent heart failure and a history of diabetes mellitus were also strongly predictive of death. CONCLUSION: The prognostic value of ventricular premature depolarizations observed 1 year after a myocardial infarction may be significant even in a sample selected for frequent ventricular premature depolarizations observed early after the event.

Arrhythmias, Cardiac↗

Heterotopic heart transplantation and native heart ventricular arrhythmias.

Heterotopic heart transplantation has been said to be contraindicated in patients with serious native heart arrhythmias that produce hemodynamic instability. Placement of heterotopic allografts, however, can theoretically act as a biological biventricular assist device to provide hemodynamic support during these unstable rhythms. Further, this operation might beneficially alter the hemodynamic milieu of heart failure such that the arrhythmias are ameliorated. Described is our experience with 4 patients with heart failure receiving heterotopic cardiac allografts, documenting changes in native heart arrhythmia that occurred. These cases demonstrate that heterotopic grafts can adequately sustain hemodynamics during malignant native heart dysrhythmia. We believe native heart ventricular arrhythmias are not a contraindication to heterotopic heart transplantation.

Arrhythmias, Cardiac↗

Avoiding interpretive pitfalls when assessing arrhythmia suppression after myocardial infarction: insights from the long-term observations of the placebo-treated patients in the Cardiac Arrhythmia Pilot Study (CAPS)

The Cardiac Arrhythmia Pilot Study (CAPS) was a 1 year trial that analyzed the safety and effectiveness of arrhythmia suppression in 502 patients surviving acute myocardial infarction who had greater than or equal to 10 ventricular premature depolarizations/h or greater than or equal to 5 runs of ventricular tachycardia on a Holter recording obtained 6 to 60 days after the acute infarction. Because 100 of these patients received placebo in a double-blind fashion for 1 year, a comprehensive objective analysis was performed of spontaneous arrhythmia changes based on real data rather than statistical estimates. In the CAPS placebo group, 19% developed some serious clinical event in 1 year (death, heart failure, proarrhythmia) that could likely be attributable to antiarrhythmic drug toxicity. A significant reduction in the frequency of ventricular premature depolarizations (p = 0.004) occurred in the first few weeks of "therapy" with a further significant (p less than 0.04) decrease between 3 to 12 months. After initiation of placebo antiarrhythmic therapy, 27% had "apparent ventricular premature depolarization suppression" (greater than or equal to 70% reduction) after one Holter recording evaluation and nearly half (48%) after six Holter recordings to assess suppression were performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

Bleeding complications following initiation of thrombolytic therapy for acute myocardial infarction: a comparison of helicopter-transported and nontransported patients.

STUDY OBJECTIVE: To evaluate the effect of helicopter transport of acute myocardial infarction (AMI) patients after initiation of thrombolysis on bleeding complications through hospital discharge. DESIGN: Prospectively identified incidence (cohort) study. SETTING: Air medical service of tertiary-care teaching hospital. TYPES OF PARTICIPANTS: Ninety-five consecutive AMI patients transported within 12 hours of the initiation of thrombolysis with recombinant tissue-type plasminogen activator were compared with 119 nontransported AMI patients treated in a similar manner. RESULTS: The transported and nontransported populations were similar with regard to age, sex, and infarct location. Transport was well tolerated with no episodes of cardiac arrest or cardioversion occurring during transport. Hypotension requiring fluids or increased pressors occurred in 18 patients. Bleeding complications of all types occurred in 43.2% of the transported and 49.6% of the nontransported patients, respectively (relative risk, 0.87; 95% confidence interval, 0.65 to 1.17). CONCLUSION: Helicopter transport of AMI patients after initiation of thrombolysis appears to be safe acutely and without a clinically significant increase in risk of bleeding complications through hospital discharge when accomplished by a highly skilled team.

Aircraft↗

The variable extent of jeopardized myocardium in patients with single vessel coronary artery disease: quantification by thallium-201 single photon emission computed tomography.

To assess the extent of jeopardized myocardium in patients with single vessel coronary artery disease of variable severity and location, quantitative exercise thallium-201 single photon emission computed tomography was performed in 158 consecutive patients with angiographically proved single vessel coronary artery disease. The extent of abnormal left ventricular perfusion was quantified from computer-generated polar maps of three-dimensional myocardial radioactivity. Patients with only a moderate (51% to 69%) stenosis tended to have a small perfusion defect irrespective of the coronary artery involved. Whereas a perfusion defect measuring greater than or equal to 10% of the left ventricle was found in 78% of patients with no prior infarction and severe (greater than or equal to 70%) stenosis, this was observed in only 24% of patients with moderate stenosis. Perfusion defect size increased with increasing severity of stenosis for the entire group without infarction and for those with left anterior descending, right and circumflex coronary artery stenosis. However, the correlation between stenosis severity and perfusion defect size was at best only modest (r = 0.38, p = 0.0001). The left anterior descending artery was shown to be the most important of the three coronary arteries for providing left ventricular perfusion. Proximal stenosis of this artery produced a perfusion defect approximately twice as large as that found in patients with a proximal right or circumflex artery stenosis. However, marked heterogeneity in perfusion defect size existed among all three vessels despite comparable stenosis severity. This was most apparent for the left anterior descending coronary artery, where mid vessel stenosis commonly produced a perfusion defect similar in size to that found in proximally stenosed vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Criteria for the accurate interpretation of changes in left ventricular ejection fraction and cardiac volumes as assessed by rest and exercise gated radionuclide angiography.

Although serial left ventricular ejection fraction and volumetric measurements using gated radionuclide angiography are commonly used to evaluate clinical changes and therapeutic outcomes in individual patients, criteria are not available for accurately interpreting whether a change in any of these hemodynamic measurements is clinically meaningful. Accordingly, the magnitude of inherent variability among sequential measurements of hemodynamic variables assessed by gated radionuclide angiography was investigated in a double-blind placebo-controlled fashion in 39 patients during two placebo periods separated by 6 weeks. All patients analyzed had remained clinically stable during the study period. Although the mean values for all hemodynamic variables between the two placebo periods were minimally changed, the differences in individual patients were striking. Criteria were developed to allow meaningful interpretation of changes in hemodynamic variables by estimating the likelihood that an observed change is due to variability alone. On the basis of this analysis of placebo radionuclide angiographic data, variation due to chance alone is unlikely to account for all variability if a change observed between the two rest gated studies in a patient is greater than or equal to 7% units for left ventricular ejection fraction, greater than or equal to 45 ml/m2 for end-diastolic volume index, greater than or equal to 35 ml/m2 for end-systolic volume index, greater than or equal to 20 ml/m2 for stroke volume index and greater than or equal to 1.25 liters/min per m2 for cardiac index. An observed 4% unit change in left ventricular ejection fraction (increase or decrease) after a medical intervention in an individual patient occurs by random variation greater than 25% of the time.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Volume↗

Antiarrhythmic and hemodynamic evaluation of indecainide and procainamide in nonsustained ventricular tachycardia.

The present trial was a placebo-controlled, randomized, parallel study comparing indecainide to procainamide. A 24-hour intravenous phase measured and compared invasive hemodynamics, followed by oral administration for assessment of arrhythmia suppression. Thirty-two patients (mean age 61 years) with asymptomatic or mildly symptomatic nonsustained ventricular tachycardia (VT) were evaluated, 15 while receiving indecainide and 17 while receiving procainamide. A total of 8 patients had serious toxicity during the intravenous phase; 6 receiving indecainide experienced increased left ventricular dysfunction or worsening arrhythmia (sustained VT, arrhythmic death) while 2 receiving procainamide developed serious hypotension. Proarrhythmia developed in 3 of 15 (20%) of the indecainide patients, but in no procainamide patient. In those tolerating indecainide, long-term suppression of ventricular premature complexes (VPCs) and of runs of VT was more consistent than with procainamide. While indecainide was a potent suppressor of spontaneous VPCs and VT, patients with significant left ventricular dysfunction could not tolerate it. The indecainide patients developing serious toxicity had a common hemodynamic profile: ejection fraction less than 25%, elevated left ventricular filling pressures, low cardiac and stroke volume index and minimal cardiac reserve. Indecainide has a poor risk-benefit ratio in patients similar to the current population, who have potentially lethal ventricular arrhythmias and severe left ventricular dysfunction.

Administration, Oral↗

Proarrhythmic potential of moricizine: strengths and limitations of a data base analysis.

Moricizine was studied in 908 patients with ventricular arrhythmias. A proarrhythmia occurred in 29 (3.2%). When the severity of the proarrhythmia and the type of presenting ventricular arrhythmia were correlated, no proarrhythmic events occurred in patients who presented with benign ventricular arrhythmias. Four deaths were attributed to the proarrhythmic effects of moricizine. Of these, 3 occurred in patients presenting with lethal ventricular arrhythmias. A total of 15 serious proarrhythmic events occurred, all of which resolved without lethal consequence. The overall proarrhythmia incidence in the lethal and potentially lethal ventricular arrhythmia categories was not different (3.2 vs 3.7%, respectively). Thus, a proarrhythmia occurred in patients with more advanced structural heart disease, and occurred almost exclusively in patients who presented with potentially lethal or lethal ventricular arrhythmia. There was no relation between the dose of moricizine and the incidence of proarrhythmic events. Of the 29 proarrhythmic events, 26 occurred within 7 days (90%) of the initiation of moricizine therapy. Thus, moricizine appears to have a low proarrhythmic potential in the populations tested, including patients presenting with lethal ventricular arrhythmias. The implications of the Cardiac Arrhythmia Suppression Trial on such a data base analysis are discussed.

Anilides↗