To determine whether antiplatelet therapies improve saphenous vein graft patency after coronary artery bypass grafting, we compared 1) aspirin (325 mg once daily), 2) aspirin (325 mg three times daily), 3) aspirin and dipyridamole (325 mg and 75 mg, respectively, three times daily), 4) sulfinpyrazone (267 mg three times daily), and 5) placebo (three times daily). Therapy with dipyridamole and sulfinpyrazone was started 48 hours before bypass graft surgery, and aspirin treatment was begun 12 hours before surgery as a single 325-mg dose. Postoperative treatment was started 6 hours after surgery and continued for 1 year. Graft patency data were obtained early (median, 9 days) and late (median, 367 days) after surgery. The early graft occlusion rate was decreased with all aspirin treatment regimens compared with that of the placebo regimen. At 1 year, in 406 patients with 1,315 grafts, the graft occlusion rate in all of the aspirin groups combined was 15.8% compared with 22.6% for the placebo group (p = 0.029). The patients taking aspirin once daily had a lower occlusion rate (13.2%) compared with the patients receiving placebo (p = 0.050). At 1 year, in the vein grafts placed to vessels less than or equal to 2.0 mm in diameter (804 distal sites), the graft occlusion rate in all of the aspirin groups was 20.1% compared with 32.3% for the placebo group (p = 0.008). In the vein grafts placed to vessels greater than 2.0 mm in diameter (511 distal sites), there was no difference in the occlusion rates between aspirin and the placebo group at 1 year (8.7% vs. 9.0%, p = 0.918).(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated medical in comparison to surgical plus medical (surgical) treatment of unstable angina using a prospective randomized protocol that stratified patients by clinical presentation and by invasive evaluation of left ventricular (LV) function. Clinical presentations were as follows--type 1: progressive or new onset angina relieved by medication; type 2: prolonged bouts of angina poorly or incompletely relieved by medication. Abnormal LV function was arbitrarily defined as ejection fraction less than 0.50 or LV end-diastolic pressure 16 mm Hg or more. Of 468 patients, 237 were assigned to medical and 231 to surgical therapy. There were 374 type 1 and 94 type 2 patients. LV function was normal in 334 and abnormal in 134 patients. Compared with results at 24 months, this 60-month follow-up study showed important differences in survival for patients with three-vessel disease: 75% for medical and 89% for surgical patients (p less than 0.02). The cumulative 5-year rate of repeat hospitalizations for cardiac reasons was less with surgical patients for either clinical presentation. For type 1, medical patients had a 56% rate, and surgical patients had a 42% rate (p = 0.004). For type 2, medical patients had a 62% rate, and surgical patients had a 43% rate (p = 0.05). Overall mortality did not differ between the two treatments, and this remained true in type 1 versus type 2 patients and in those with normal versus abnormal LV function. However, regression analysis of medical and surgical groups with ejection fraction as a continuous variable showed that mortality of medical patients depended on ejection fraction (p = 0.004), whereas the mortality of surgical patients did not (p = 0.76), and survival in the surgical group was higher in the lowest ejection fraction tercile-73% for medical and 86% for surgical patients, p = 0.03. We conclude that surgery improves survival in patients with three-vessel disease and leads to fewer subsequent hospitalizations for cardiac reasons. An impaired ejection fraction had an adverse impact on survival of medical patients but not on surgical patients, and mortality in surgical patients was improved compared with medical patients in the lowest ejection fraction tercile.

In the Second Mt. Sinai-New York University Reperfusion Trial, in which change of ejection fraction was the primary end point, the following secondary end points were prospectively assessed by serial coronary angiography: patency of the infarct artery both before intervention and 10-14 days later, acute and delayed recanalization rates, presence or absence of collateral flow, and complication rates of acute interventional catheterization. We assigned 393 patients randomly to groups receiving acute cardiac catheterization and a double-blind intracoronary infusion of streptokinase (SK arm), both streptokinase and nitroglycerin (SK-NTG arm), nitroglycerin alone (NTG arm), or conventional therapy without acute catheterization (control arm). Prospective stratification was based on duration of infarct pain before randomization: group A, less than 2 hours; Group B, 2-12 hours. Baseline patency rates were comparable in patients studied within 6 hours (30%, 40 of 135) and those studied later (24%, 32 of 133). This finding refutes the hypothesis that spontaneous recanalization occurs frequently after 6 hours. The acute recanalization rates of the SK arm (60%, 40 of 67) and the SK-NTG arm (63%, 29 of 62) did not differ. During streptokinase infusion, more vessels recanalized in group A (81%, 22 of 27) than in group B (56%, 57 of 102) (p less than 0.01); this was due to a significant reduction of recanalization rates from 75% (48 of 64) to 45% (26 of 62) with treatment after 6 hours (p less than 0.01). Delayed recanalization, that is, patency at end point but not postintervention, was seen in 17% (17 of 100) of total occlusions treated with streptokinase. In group A, all total occlusions treated with streptokinase recanalized either acutely (20 of 22) or delayed (two of 22), whereas in group B, 23% (18 of 78) remained obstructed. The reocclusion rate in the SK arms was 17% (11 of 65). In the NTG arm, recanalization occurred during intervention in 4% (two of 47) and delayed in 45% (21 of 47). At end-point angiography, the patency rates of the NTG arm (62%, 41 of 66) and the control arm (58%, 36 of 62) were comparable; those of the SK arms were higher (75%, 105 of 140) (p less than 0.01). Total occlusion was associated with collateral flow in 33% (66 of 199) at baseline; the prevalence of collaterals did not increase with time to angiography, which indicates that they had developed before the index event.(ABSTRACT TRUNCATED AT 400 WORDS)

We performed a prospective, randomized, double-blind trial in 194 unselected patients to determine the safety and efficacy of low molecular weight heparin (Fragmin) compared with standard heparin as the initial treatment of acute venous thromboembolism. Ninety-eight patients received continuous intravenous heparin, and 96 patients received Fragmin for 5-10 days. Doses were adjusted to maintain anti-Xa levels between 0.3 and 0.6 unit/ml for patients with a high risk for a bleeding complication and between 0.4 and 0.9 unit/ml for patients with a low risk for bleeding. Treatment was stopped when a therapeutic level of anticoagulation (International Normalized Ratio greater than 3.5) was reached with coumarins. Thirteen patients in the heparin group and 10 patients in the Fragmin group had a major bleeding complication. The incidence of major and minor bleeding complications combined decreased from 48.9% to 38.5% (95% confidence interval for the difference, -3.5% to +24.2%), corresponding with a relative bleeding risk reduction of 21.2%. There were no significant differences in efficacy as defined by new high-probability defects on repeat ventilation-perfusion scintigraphy of the lung in 80 patients: six of 46 patients in the heparin group and 3 of 34 patients in the Fragmin group had new defects (95% confidence interval for the difference, -9.4% to +17.8%). We conclude that low molecular weight heparin (Fragmin) given in adjusted, continuous, and intravenous doses is safe and effective as initial treatment of acute venous thromboembolism compared with heparin. There is a trend in risk reduction for bleeding in favor of low molecular weight heparin, a trend, however, that is smaller than expected compared with animal studies.

Intra-arterial blood pressure, cardiac output, heart rate, right heart indexes, urinary electrolytes, and urinary volume were monitored in eight patients with untreated (WHO Class I) essential hypertension. The patients were given synthetic atrial natriuretic factor (ANF) (99-126 alpha-hANP) at 1 and 2 pmol/kg/min in series (phases 1 and 2, 2 hours each dose) or vehicle (hemaccel) in random order on two separate occasions while on their usual diet. Arterial plasma ANF levels increased significantly from basal and time-matched placebo values from 25 +/- 2 and 28 +/- 3 pmol/l to 50 +/- 4 and 83 +/- 9 pmol/l at the end of phases 1 and 2, respectively (p less than 0.001). After 30 minutes during phase 2, systolic blood pressure decreased significantly by 20 +/- 4 mm Hg (p less than 0.001) from basal and time-matched placebo values and remained significantly reduced (-17 +/- 4 mm Hg, p less than 0.001) by the end of the recovery period (2 hours after infusions were completed). Pulmonary systolic blood pressure decreased by 5 +/- 1 mm Hg (phase 2, p less than 0.05). Cardiac output decreased by 0.5 +/- 0.1 l/min below baseline at the end of phase 2 of ANF infusion, whereas it increased significantly (p less than 0.02) by 0.6 +/- 0.1 l/min during vehicle infusion. Systemic diastolic, pulmonary diastolic, right atrial, and wedge pressures were not significantly changed during ANF or vehicle infusions, nor were pulmonary vascular resistance or heart rate altered. Systemic vascular resistance did not change significantly during both infusions, whereas during recovery, systemic vascular resistance decreased significantly after ANF infusion was discontinued (p less than 0.05). Microhematocrit levels increased dose dependently during ANF. The maximum increase was observed at the end of phase 2 (+4.7 +/- 1.7%), whereas the microhematocrit level decreased to -2.4 +/- 0.6% with vehicle (p less than 0.001) at the end of phase 2. Urinary sodium excretion increased significantly (p less than 0.02) by the end of phase 2 under ANF infusion (+38 +/- 15%), whereas it decreased (-10 +/- 6%) under placebo infusion by the end of phase 2. Urinary magnesium excretion was significantly increased during ANF infusion from phase 1 (p less than 0.02), whereas urinary potassium levels, calcium levels, creatinine levels, volume, and glomerular filtration rate did not differ significantly between the two infusions. Plasma renin, angiotensin II, aldosterone, and catecholamine concentrations did not change significantly during ANF or vehicle infusions.(ABSTRACT TRUNCATED AT 400 WORDS)

To compare St. Jude Medical and Medtronic Hall mechanical prosthetic heart valves, we prospectively randomized 90 consecutive patients requiring mechanical valve replacement and studied their rest and exercise hemodynamics by Doppler echocardiography. Fifty-six aortic and 42 mitral valves were implanted. All patients were examined preoperatively and postoperatively, and follow-up studies were obtained at rest and immediately after upright, treadmill exercise at 6 months (n = 68). Clinical parameters (mortality, morbidity, and congestive heart failure classification), as well as rest and exercise hemodynamics (valvular area, gradients, and left ventricular ejection fraction), were examined, and their relation to exercise duration was defined. Mortality (perioperative, 8.8% and late, 2.4%) was similar between patients in the two valve groups (five in each group). There was one late thromboembolic episode with each valve. Improvement in New York Heart Association congestive heart failure class was seen in 85% of patients at 6 months. There were no significant differences in calculated aortic valve areas (2.2 vs. 2.0 cm2), resting (24 vs. 21 mm Hg) and exercise (41 vs. 35 mm Hg) peak aortic gradients, and exercise duration between patients with the St. Jude Medical and Medtronic Hall aortic prostheses. In patients with aortic prostheses, valvular size was correlated with exercise duration (r = 0.41, p less than 0.05). In patients with mitral prostheses, we observed no significant differences between St. Jude Medical and Medtronic Hall prostheses in calculated mitral valve areas (3.4 cm2 vs. 3.4 cm2) and rest (2.5 vs. 3.0 mm Hg) and exercise (5.1 vs. 7.0 mm Hg) mean gradients.(ABSTRACT TRUNCATED AT 250 WORDS)

Refractory pump failure after cardiopulmonary bypass carries a high mortality. To assess the effectiveness of metabolic support for the heart in patients with refractory heart failure after hypothermic ischemic arrest for aortocoronary bypass surgery, we randomly assigned 22 patients to receive either intravenous glucose (50%), insulin (80 units/I), and potassium (100 meq/l) (GIK) infused at a rate of 1 ml/kg/hr for up to 48 hours or glucose (5%) and NaCl (0.225%) infused at the same rate (control). All patients required inotropic drug support, received intra-aortic balloon pump assistance, and had an initial mean cardiac index (CI) of 2.5 l/min/m2. At 12 and 24 hours, CI had risen significantly in the GIK but not in the control group (3.6 and 3.4 l/min/m2 vs. 2.5 and 2.7 l/min/m2, p less than 0.005). Time on the intra-aortic balloon pump (39 vs. 61 hours) and requirements for inotropic drug support were also significantly less in the GIK compared with the control group. Although the number of patients was relatively small, the GIK group also showed a trend for improved long-term survival: at 60 days after surgery, there were 10 of 11 survivors in the GIK-treated group compared with seven of 11 survivors in the control group. Although the exact mechanism for the beneficial effects of GIK on myocardial contractility remains to be elucidated, we conclude that GIK is safe and effective in the treatment of refractory left ventricular failure after aortocoronary bypass surgery.

In 78 consecutive patients with unstable angina, we performed coronary angiography randomized to either the first day of presentation or later during the hospital admission to assess the frequency of intracoronary thrombus and complex coronary morphology relative to the time of symptomatic presentation and the impact of these angiographic features on outcome. Early angiography (17 +/- 6 hours) was performed in 42 patients and late angiography in 36 patients (5.7 +/- 2.1 days). Twelve patients randomized to late angiography required urgent cardiac catheterization 3.9 +/- 2.2 days after admission. Coronary thrombi were present in 43% (18 of 42) of early angiography patients and in 38% (14 of 36) of late angiography patients (p = NS). Only 21% (five of 24) late elective angiography patients had coronary thrombi, but 75% (nine of 12) of late urgent angiography patients had thrombi (p less than 0.05 vs. both early and late elective angiography patients). There was no difference in the frequency of complex coronary morphology among patients randomized to early angiography (42%, or 15 of 36), late urgent angiography (42%, or five of 12), and late elective angiography (38%, or nine of 24). Cardiac events (death, myocardial infarction, and urgent revascularization) were more frequent in the patients with coronary thrombus (73%, or 23 of 32), complex coronary morphology (55%, or 16 of 29), and multiple-vessel disease (58%, or 29 of 50) than in the patients without these angiographic features (17%, or eight of 46; 31%, or 15 of 49; and 7%, or two of 28, respectively; all p less than 0.05). Multiple regression analysis demonstrated that coronary thrombus was the best angiographic predictor of cardiac events. Thus, angiographic detection of intracoronary thrombi varies according to the temporal relation between angiography and chest pain at rest.

The effect of retrograde cardioplegia delivered through the right atrium on right ventricular performance has not been critically examined in humans. We randomized 20 patients with right coronary artery lesions to receive cold blood cardioplegia solution either retrograde through the right atrium (group 1, n = 10) or antegradely (group 2, n = 10). The patients were similar in age, sex, severity of coronary artery disease, cross-clamp time, and completeness of revascularization. Before operation, right ventricular function was assessed by radionuclide ventriculography, and 18-24 hours after operation, right ventricular volumes and performance were assessed at a constant-paced heart rate by simultaneous hemodynamic-radionuclide measurements, before and after a fluid challenge. Intraoperative right ventricular temperatures were not different between the groups. Right ventricular volumes and ejection fractions were not different at baseline. After operation, at similar heart rates and loading conditions, there was a trend for the antegrade group to increase right ventricular end-systolic volume (p less than 0.1) whereas the retrograde group had no change in this parameter from the preoperative state. Postoperative ventricular function curves (p = NS, retrograde versus antegrade) suggest equivalent systolic performance in both groups. Right ventricular diastolic performance showed no significant differences between the two groups, suggesting no detriment to compliance due to right ventricular distension during operation. This suggests that retrograde cardioplegia adequately protects the right ventricular myocardium during bypass surgery and may be used as an alternative procedure in situations where ventricular cooling is inadequate with antegrade delivery due to severe coronary artery disease or aortic valvular disease.

To investigate the effect of Kawasaki syndrome on myocardial function, as well as the influence of high-dose intravenous gamma-globulin therapy on resolution of functional abnormalities, we studied 98 patients with Kawasaki syndrome during five time intervals from onset of illness: 1) 10 days or less, 2) 11-31 days, 3) 1-3 months, 4) 3-12 months, and 5) 1-3 years. Normal controls included 48 children under age 8 years, without known cardiovascular disease. Using two-dimensional directed M-mode echocardiograms, we obtained chamber dimensions, fractional shortening, rate-corrected velocity of shortening (Vcfc) adjusted for end-systolic wall stress, and early diastolic function parameters that included adjusted peak rates of left ventricular dimension change, wall thinning, and their respective timing. Left ventricular systolic and diastolic dimensions were larger (both p less than 0.01) in patients than in normal subjects in period 1. Stress-adjusted Vcfc was much lower in patients in the 3 months after disease onset; by period 5, contractility was comparable in patients and normal subjects. Adjusted indexes of early diastolic function did not differ significantly between patients and normal subjects. To investigate the effect of gamma-globulin, we analyzed data on 47 patients prospectively randomized to therapy with aspirin alone (n = 19, 40%) or to aspirin plus gamma-globulin, 400 mg/kg/day for 4 consecutive days (n = 28, 60%). In period 1, before treatment, the two groups had mean fractional shortening and stress-adjusted Vcfc comparable to each other but much lower than those of normal subjects (p less than or equal to 0.001). Patients treated with aspirin alone continued to have diminished fractional shortening and Vcfc compared with normal subjects in periods 2, 3, and 4 (all p less than or equal to 0.05). In contrast, fractional shortening and Vcfc in gamma-globulin-treated patients in these periods were comparable to those of normal subjects. By period 5, no difference was detected in systolic function or contractility between either treatment group and normal subjects. We conclude that early abnormalities of left ventricular contractility and myocardial function, as assessed by echocardiography, generally resolve by 1-3 years after disease onset and that recovery is accelerated by administration of IVGG in the acute phase.

ESVEM (Electrophysiologic Study Versus Electrocardiographic Monitoring) is an ongoing multicenter trial supported by the National Heart, Lung, and Blood Institute that began enrollment of patients on October 1, 1985. We describe here the methodology of the trial and data regarding enrollment of patients in the trial. The purpose of the trial is to determine whether electrophysiologic study or electrocardiographic Holter monitoring more accurately predicts antiarrhythmic drug efficacy in patients with aborted sudden death or sustained ventricular tachyarrhythmias. Consenting patients with inducible, sustained ventricular tachyarrhythmias and at least 480 premature ventricular contractions during 48 hours are randomized to undergo antiarrhythmic drug selection either by electrophysiologic study or by Holter monitoring. Up to six drugs (mexiletine, pirmenol, procainamide, propafenone, quinidine, and sotalol) are assessed in random order until one is predicted effective. An efficacy prediction is achieved in the electrophysiology limb if ventricular tachyarrhythmias are no longer inducible and in the Holter limb if ventricular ectopy is largely suppressed. Patients in whom a drug is predicted effective are followed while they are taking that drug to detect one of the three primary endpoints: arrhythmia recurrence, sudden death, or unmonitored syncope. In the first 37 months, 967 patients satisfied inclusion and exclusion criteria to undergo baseline studies. Two hundred eighty-six were eligible for and consented to randomization. In total, approximately 500 patients will be randomized and 285 subjects will be followed while receiving drugs that are predicted effective in this trial. Approximately 70 patients are expected to attain a primary end-point during a mean follow-up ot 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of cold on the threshold for myocardial ischemia and the efficacy of antianginal drugs in a cold environment were assessed in 24 patients with stable angina and exercise-induced ST depression. Treadmill exercise tests were done according to a randomized double-blind protocol 90 minutes after administration of placebo, 80 mg propranolol, or 120 mg diltiazem, each at both -8 degrees and 20 degrees C. Eight of the patients were classified by history as cold-sensitive before the study. For the entire group, none of the exercise end points differed significantly between cold and normal temperatures with placebo. However, cold-sensitive patients developed 1 mm ST depression 30% sooner (169 +/- 41 versus 244 +/- 38 seconds, p less than 0.01) at -8 degrees C compared with 20 degrees C. At the onset of ischemia, rate-pressure product was lower in the cold (19.8 +/- 1.0 versus 22.0 +/- 1.6 x 10(-3), p less than 0.05). Both propranolol and diltiazem prolonged time to onset of 1 mm ST depression at both temperatures. The magnitude of improvement at -8 degrees C was equal to that at 20 degrees C, and differences between the two drugs were not statistically significant. Only diltiazem prolonged total exercise duration. Thus, as assessed by exercise testing, cold does not worsen ischemic threshold in most stable angina patients. However, in a subgroup identifiable by history, ischemic threshold is lower in the cold. Propranolol and diltiazem are as effective for exercise-induced ischemia in a cold environment as at normal temperatures.

To determine the effect of metoprolol on silent ischemia and platelet aggregability, 10 patients with coronary artery disease were studied with a randomized, double-blind, placebo-controlled, crossover trial. Patients were treated with metoprolol (200 mg b.i.d.) or placebo for 1 week and then received the alternate therapy. Two days before the end of each treatment period, platelet aggregability was studied for 24 hours, and a 48-hour ambulatory electrocardiogram was obtained. Compared with placebo, metoprolol significantly decreased the total number (from 26 to 4, p less than 0.1) and duration (from 735 to 84 minutes, p less than 0.01) of silent ischemic episodes. This decrease was accompanied by a decrease in the mean blood pressure (from 127/81 to 118/71 mm Hg, p less than 0.01) and the mean heart rate (from 70 to 54 beats/min, p less than 0.01). The incidence of silent ischemic episodes in the morning was significantly higher in untreated patients than in treated patients. The few episodes observed during metoprolol treatment occurred at the same time as the peak incidence observed during placebo treatment. During placebo treatment, platelet aggregability increased from 6:00 to 9:00 AM as reflected by a decrease in the threshold concentrations of ADP and epinephrine required to induce biphasic platelet aggregation (from 4.8 +/- 0.8 to 2.6 +/- 0.4 microM, p less than 0.02; and from 7.3 +/- 2.3 to 1.8 +/- 0.9 microM, respectively, p less than 0.02). Metoprolol did not alter the basal level nor blunt the morning increase of platelet aggregability.(ABSTRACT TRUNCATED AT 250 WORDS)

To discover the underlying mechanisms involved in the beneficial long-term effects of angiotensin converting enzyme (ACE) inhibitors, we investigated the systemic and peripheral effects of short- and long-term ACE inhibition in patients with chronic heart failure. After assessing the short-term effects and dose titration with cilazapril, a new long-acting ACE inhibitor, 21 patients were randomized to receive either placebo or the ACE inhibitor. Seventeen patients completed the 3-month treatment. Central hemodynamic output, femoral blood flow (measured by thermodilution), oxygen saturation, and lactate and norepinephrine levels were determined simultaneously in the femoral vein and radial artery during treatment and after a 3-month rest and during symptom-limited bicycle exercise. Short-term ACE inhibition improved rest and exercise hemodynamic output, but it did not alter peak femoral blood flow, calculated leg oxygen consumption, or systemic oxygen uptake during exercise, despite significant reduction in femoral norepinephrine extraction and arterial angiotensin levels during exercise. In contrast, long-term ACE inhibition further improved exercise cardiac output and increased leg blood flow (from 2.3 to 2.9 l/min, p less than 0.05), leg oxygen consumption (from 277 to 403 ml/min, p less than 0.05), and systemic oxygen uptake (from 1,133 to 1,453 ml/min, p less than 0.05), whereas these variables remained unchanged with placebo treatment (p less than 0.02 between groups). Moreover, a moderate but significant increase in femoral oxygen extraction occurred after long-term therapy (ACE inhibitor: from 76% to 83%, p less than 0.05; placebo: from 75% to 74%, NS; p less than 0.01 between groups). We conclude that long-term ACE inhibition is clinically beneficial in that it improves blood flow to skeletal muscle during exercise over time. The long-term effects of ACE inhibition are, in part, probably related to peripheral (vascular) mechanisms, for example, by reversing the inability of peripheral vessels to dilate and by improving oxygen utilization.

In the Cardiac Arrhythmia Pilot Study (CAPS), patients early (6-60 days) after acute myocardial infarction (MI) with ventricular premature complexes (VPCs) of over 10 per hour were randomized to receive, unaware, therapy with one of four antiarrhythmic drugs (n = 402) or placebo (n = 100). Treatment success was defined as 70% or more decrease in VPC rate and 90% or more decrease in VPC runs. If the first active drug was ineffective, a second drug was given. If placebo was ineffective, a second placebo was given. To determine whether or not baseline clinical characteristics predict the response to antiarrhythmic therapy, 10 baseline variables were selected for investigation: age, prior MI, time from CAPS MI to randomization, ejection fraction, baseline VPC frequency, presence of runs (greater than or equal to 3 consecutive VPCs, greater than or equal to 100 beats/min), beta-blocker therapy, digitalis therapy, MI transmurality, and MI location. At the end of the first drug treatment, apparent treatment success in patients receiving placebo was associated on univariate analysis with absence of prior MI, with trends for younger age and Q wave MI, whereas in patients receiving active therapies, higher ejection fraction and younger age were associated with better suppression. In the encainide and flecainide treatments, where the greatest response was observed, absence of prior MI, higher ejection fraction, and younger age were associated with more successful treatment. In a multivariate analysis with these variables, ejection fraction and age remained significant for all active therapies, absence of prior MI and ejection fraction remained significant in the encainide and flecainide treatments, and absence of prior MI in the placebo treatment. Few variables except ejection fraction were associated with VPC suppression during the 1-year follow-up, and only lower ejection fraction and older age related to loss of long-term suppression. Thus, there are only a few independent baseline clinical variables (notably, ejection fraction) that substantially affect antiarrhythmic drug efficacy in suppressing VPCs in patients early after MI. Some variables, however, may be associated with spontaneous arrhythmia variability, leading to an apparent (placebo) response. These findings will be helpful in designing and interpreting treatment studies in patients after MI.

To evaluate the coronary thrombolytic efficacy of tissue plasminogen activator (t-PA) and early intravenous heparin, 134 patients with acute myocardial infarction were randomly assigned to combination therapy or t-PA only. At a median of 2.78 hours from symptom onset, 64 patients received both t-PA (1.5 mg/kg/4 hr) and a bolus of 10,000 units heparin, whereas 70 patients received t-PA alone at the same dose. All patients underwent coronary angiography 90 minutes after initiation of therapy to determine infarct vessel patency status, after which time the control group patients were eligible to receive heparin. Baseline demographic and angiographic characteristics were similar for the groups. Infarct vessel patency was 50 of 63 (79%) for combination t-PA and heparin and 54 of 68 (79%) for t-PA alone. Bleeding complications, as reflected by need for transfusion, were similar in the two groups: 13% in the patients treated with t-PA and heparin compared with 18% in patients treated with t-PA only (p = 0.53). The only intracranial hemorrhage in the trial occurred in a patient initially treated without heparin. Fibrinogen at 50 minutes after therapy was 32% decreased from baseline for the t-PA and heparin-treated patients compared with a 39% decrease in the control group. Predischarge left ventricular ejection fraction was similar for the two groups: 49.0 +/- 10.1% versus 50.2 +/- 11.9% for combined versus t-PA only therapy, respectively. We conclude that early intravenous heparin does not facilitate the fibrinolytic effect of t-PA at the doses tested.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the cardiopulmonary effects of maximum bicycle ergometer exercise in seven patients with implanted Intermedics Nova MR pacemakers for three types of pacing in a randomized sequence: VVI or AAI at 70 beats/min (SSI 70), rate-adaptive temperature-controlled pacing with the implanted Nova MR, and rate-adaptive activity-controlled pacing with a Medtronic Activitrax pacemaker taped to the chest wall, which triggered the implanted Nova MR in the VVT or AAT mode by skin electrodes. The maximum exercise tolerance was 67 W with SSI 70, 71 W with Activitrax pacing, and 91 W with Nova MR pacing; the maximum oxygen uptake as 17.6, 19.5, and 21.5 ml/min/kg, respectively. The highest heart rate achieved was 81 beats/min with SSI 70, 98 beats/min with the Activitrax, and 118 beats/min with the Nova MR on average; the mean rate increase from rest to maximum exercise was 11, 29, and 47 beats/min, respectively. With both rate-adaptive types of pacing (Nova MR and Activitrax), an increase in exercise tolerance and maximum heart rate could be achieved, but this increase was significantly more obvious with the temperature-controlled Nova MR than with the activity-controlled Activitrax. However, with a different form of exercise, for example, treadmill ergometry, the rate response of the Activitrax would presumably have been somewhat clearer.

Augmented right heart cooling (RHC) with bicaval cannulation, pulmonary artery venting, and intracavitary cooling has been advocated for prevention of right ventricular failure and supraventricular tachyarrhythmias after open heart surgery. To evaluate RHC, 78 patients undergoing coronary bypass surgery were prospectively randomized to receive added RHC (n = 38) or standard protection with single atrial cannulation (SC) (n = 40). RHC and SC patients were similar regarding right coronary artery occlusion (n = 10 and 12, respectively), number of grafts performed (3.7 +/- 1.0 and 3.4 +/- 0.9), and cross-clamp time per graft (10.2 +/- 1.8 and 9.8 +/- 2.3 minutes). RHC led to significantly lower right atrial (11.6 degrees +/- 1.0 degree vs. 19.5 degrees +/- 3.3 degrees C) and right ventricular (7.2 degrees +/- 1.9 degrees vs. 12.2 degrees +/- 1.9 degrees C) temperatures. There was no detectable deterioration in right heart function or left heart function in either group after cardiopulmonary bypass. Bypass time was longer in RHC patients (86.7 +/- 17.9 vs. 76.0 +/- 18.2 minutes, p less than 0.05). Technical problems related to multiple cannulation occurred in four RHC patients. After cross-clamp removal, creatine kinase-MB levels were significantly higher with RHC at 2 hours (14.2 +/- 7.6 vs. 6.4 +/- 4.6 IU/l, p less than 0.001), 12 hours (19.1 +/- 19.5 vs. 8.6 +/- 10.3 IU/l, p less than 0.005), and 24 hours (14.1 +/- 19.6 vs. 7.1 +/- 9.2 IU/l, p less than 0.05). Mortality and morbidity were similar in the two groups. In particular, supraventricular tachyarrythmias occurred in 11 (28.9%) RHC and 10 (25%) SC patients.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine 1) whether the effect of intravenous nitroglycerin (NG) therapy during acute myocardial infarction on creatine kinase infarct size is influenced by infarct location (anterior vs. inferior), timing (therapy less than 4 hours vs. greater than or equal to 4 hours after onset of pain), and dose response (mean blood pressure greater than or equal to 80 mm Hg vs. less than 80 mm Hg during the first 12 hours) and 2) whether NG therapy modifies infarct expansion, 310 patients were randomly allocated to NG (n = 154) and control (n = 156) groups. NG infusion was titrated to lower mean blood pressure by 10% in normotensive and 30% in hypertensive patients, but not below 80 mm Hg, and was maintained for 39 hours. Measurements included clinical variables, creatine kinase infarct size (geq) as well as left ventricular (LV) asynergy, LV ejection fraction, expansion index, and thinning ratio on serial two-dimensional echocardiography. Compared with controls, creatine kinase infarct size was less in the NG group (41 vs. 55 geq, p less than 0.001), in anterior (44 vs. 58 geq, p less than 0.05), and inferior (39 vs. 53 geq, p less than 0.025) NG subgroups, and in early than late NG subgroups (43% vs. 22% decrease). Other indexes of infarct size also improved (p less than or equal to 0.05) with NG compared with controls. Thus, by 10 days, LV asynergy was 40% less, LV ejection fraction was 22% more, and Killip class score was 41% less. A negative effect of mean blood pressure less than 80 mm Hg with NG was reflected in these indexes. In addition, expansion index increased (p less than 0.001) by 31% and thinning ratio decreased (p less than 0.001) by 17% in controls by 10 days but remained unchanged with NG. Infarct-related major complications were less frequent in the NG than the control groups: infarct expansion syndrome (2% vs. 15%, p less than 0.0005), LV thrombus (5% vs. 22%, p less than 0.0005), cardiogenic shock (5% vs. 15%, p less than 0.005), and infarct extension (11% vs. 22%, p less than 0.025). Mortality was less in NG than in control groups in-hospital (14% vs. 26%, p less than 0.01), at 3 months (16% vs. 28%, p less than 0.025) and 12 months (21% vs. 31%, p less than 0.05), but this advantage was only found in the anterior subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary recanalization rates and changes in the coagulation and fibrinolysis system were evaluated in a randomized fashion in patients with acute myocardial infarction after intracoronary administration of single-chain urokinase-type plasminogen activator (pro-urokinase: GE-0943) or urokinase. Three groups of patients were studied: group H (n = 50), 6,000 units pro-urokinase i.c.; group L (n = 44), 3,000 units pro-urokinase i.c.; and group U (n = 54), 960,000 IU urokinase i.c. Coronary recanalization rates determined angiographically after 45 minutes of intracoronary infusion averaged 90% in group H, 59% in group L, and 61% in group U. The differences were statistically significant between group H and the latter two groups. Pro-urokinase affected plasma proteins of the fibrinolytic system to a lesser degree than urokinase. Bleeding complications were present in one patient in group L, in none in group H, and in five in group U. Thus, intracoronary administration of 6,000 units pro-urokinase is more effective in coronary thrombolysis and causes less systemic fibrinogenolysis than intracoronary administration of urokinase.