The calcium channel blockers are useful in treating many cardiovascular disorders. Due to their anti-ischemic and spasmolytic properties, the cardioprotective effects of these agents have been studied in the setting of acute myocardial infarction. This paper will review this application with respect to limitation of infarct size, reduction of mortality, and incident morbidity rates. Of the agents currently available for clinical use, nifedipine has been studied most extensively. This agent shows no beneficial effects and its use can, in fact, be harmful in this setting. Of the few trials that have been conducted with verapamil, none have shown a preventive effect on death, reinfarction, or postinfarction angina. Both verapamil and diltiazem might limit infarct size although further confirmation is required. At the present time, diltiazem is the only agent shown to have short- and long-term benefits on clinical outcome in patients with acute myocardial infarction. The success of prophylactic diltiazem is, however, critically dependent on proper patient selection. In particular, those patients with non-Q wave infarction, normal left ventricular function, or both can be expected to derive the greatest benefit in terms of reduced mortality and incident morbidity.

Left ventricular hypertrophy (LVH) is a structural adaptation of the heart and is a response to increased hemodynamic and metabolic demands, which are most commonly caused by systemic hypertension. LVH induced by hypertension is associated with reduced myocardial compliance, structural alterations, and changes in coronary perfusion. Calcium entry blockers have caused LVH regression both in experimental studies and in clinical trials. Although their efficacy as antihypertensive agents is primarily due to their vasodilating properties, the mechanisms by which calcium entry blockers accomplish LVH regression are complex and include various hemodynamic and neurohumoral factors. Calcium entry blockade has decreased LVH with no apparent deterioration of left ventricular function. Because LVH is a major risk factor for sudden cardiac death and other cardiac morbidities, it is possible that the regression of LVH can improve the prognosis in hypertensive patients.

Paroxysmal atrial fibrillation (PAF) is a problematic clinical arrhythmia that is usually symptomatic. Unfortunately, few adequate trials and trial methods are available for assessment of the value of therapy, and traditional treatment has often been ineffective or associated with unacceptable side effects. Transtelephonic monitoring is a new method that allows evaluation of paroxysmal arrhythmias and arrhythmia-related symptoms in outpatients. We used a patient-initiated transtelephonic monitor system to evaluate the potential of flecainide, a class 1C antiarrhythmic, in prevention of symptomatic recurrences of PAF. Sixty-four patients qualified for the study (two or more PAF attacks documented within a 4-week baseline period) and entered a dose-finding phase to determine drug tolerance. Dose was incremented at weekly intervals from 200-300 and finally to 400 mg/day. The largest dose that was well tolerated was selected for the 4-month, double-blind, randomized, crossover comparison with placebo. Fifty-five patients entered and 53 received both treatments in the double-blind phase; 48 of these patients without protocol violations were evaluable for efficacy comparisons. Evaluable patients had undergone an average of 3.8 previous drug trials (range, 1-8); 30 were men, 18 had hypertension, and 14 had ischemic heart disease. The study demonstrated a highly significant correlation (p less than 0.0001) between perceived symptoms and documented PAF by transtelephonic monitoring. The rate of symptoms and PAF attacks was also significantly reduced by therapy (median dose, 300 mg/day). The first PAF attack occurred after a median of 3 days on placebo versus 14.5 days on flecainide (p less than 0.001) therapy. Similarly, the time interval between attacks was lengthened, from a median of 6.2 days on placebo to 27.0 days on flecainide (p less than 0.001) therapy. PAF was prevented in 15 patients (31%) during flecainide and four (9%) during placebo therapy (p = 0.013). However, during the study, 13 patients dropped out, seven because of adverse effects (five cardiac), five for other reasons, and one because of cardiac arrest/death. Adverse cardiac events occurred in a total of seven patients (11%) during flecainide therapy. Thus, transtelephonic monitoring is a useful method for documentation of the occurrence of paroxysmal arrhythmias such as PAF and its related symptoms during daily living and for assessment of new therapies in an outpatient setting.

For treatment of biopsy-proven rejections after cardiac transplantation, pulsed steroids of 1,000 mg methylprednisolone/day for 3 days have been conventionally used. This regimen results in severe side effects, both metabolically and with respect to the risk of infection. In a prospective and a more comprehensive retrospective clinical study, we investigated the effect of a 50% reduction in that dosage. A total of 512 positive biopsies were analyzed in 128 patients. Of these, 64 patients (120 biopsies) in group 1 received 500 mg/day for 3 days while the remaining 107 patients (392 biopsies) in group 2 were treated with 1,000 mg/day for 3 days (43 patients belonged to both groups 1 and 2). Response to treatment was assessed by control biopsies in a standardized time period until the next biopsy-proven rejection (maximum of 10 biopsies). The results in short and longer follow-up periods, considering the incidence and a newer empirical numerical grading scale, have demonstrated clearly comparable effects of myocardial histology. Reduced dosage of steroids is feasible and safe, and a decrease in steroid-related side effects can be achieved without jeopardizing the graft.

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.

The purpose of this study was to identify preoperative and intraoperative variables predictive of left ventricular dysfunction 6 months after aortic valve replacement. Patients were considered to have postoperative left ventricular dysfunction if the end-diastolic-volume index was greater than or equal to 101 ml/m2 or if the ejection fraction was less than or equal to 0.50. Data from 180 patients entered into the Veterans Administration Cooperative Study on Valvular Heart Disease who had technically satisfactory cardiac catheterizations 6 months postoperatively were analyzed by a series of univariate and multivariate analyses. For the 88 patients with preoperative aortic stenosis, the most powerful predictor of postoperative left ventricular dysfunction in the final multivariate model was preoperative left ventricular ejection fraction (p = 0.0001), followed by preoperative myocardial infarction (p = 0.012), aortic valve gradient (p = 0.020), and incomplete coronary revascularization (p = 0.059). Abnormal preoperative left ventricular ejection fraction had a sensitivity of 72% and a specificity of 82% in identifying patients with postoperative left ventricular dysfunction. Preoperative left ventricular systolic-volume index greater than or equal to 40 ml/m2 had a similar sensitivity and specificity (79% and 84%, respectively). For the 36 patients with aortic regurgitation, preoperative left ventricular ejection fraction was again the most powerful predictor of postoperative left ventricular dysfunction (p = 0.013), followed by left ventricular systolic pressure (p = 0.038) and arteriovenous oxygen difference (p = 0.054). For the 56 patients with mixed aortic stenosis and regurgitation, left ventricular systolic pressure (p = 0.007) and preoperative myocardial infarction (p = 0.022) were the variables predictive of postoperative left ventricular dysfunction. Although many patients with preoperative left ventricular dysfunction experience improved left ventricular performance after aortic valve replacement, performance does not always return to normal. For patients with either aortic stenosis or regurgitation, the strongest predictor of postoperative left ventricular dysfunction is preoperative dysfunction. These data support the concept that patients with moderate or severe aortic stenosis or regurgitation should be operated on before the onset of significant left ventricular dysfunction.

Nifedipine augments baroreflex mechanisms in in vivo animal models. Previous studies in our laboratory demonstrate that nifedipine potentiates baroreflex control of heart rate and vascular resistance in normal human subjects. To further define the neuroeffector mechanism of the autonomic effects of nifedipine, we directly measured postganglionic sympathetic nerve activity to muscle (MSNA, microneurography), before and after drug administration, during selective unloading of cardiopulmonary baroreceptors with lower body negative pressure (-10 mm Hg, LBNP-10), and during the cold pressor test. Twenty-three normal subjects (age, 23 +/- 1 years; mean +/- SEM) were studied in the control state and 20 minutes after administration of either nifedipine (10 mg s.l., 10 subjects), during nitroprusside infusion (0.37 +/- 0.03 microgram/kg/min i.v., eight subjects), or 20 minutes after sublingual administration of placebo (five subjects). We measured systemic arterial pressure, central venous pressure, heart rate, and MSNA. Nifedipine and nitroprusside produced similar increases in resting heart rate and MSNA and similar decreases in central venous pressure, whereas placebo had no effect on resting hemodynamics. During LBNP-10, hemodynamic changes were not significantly different among the three treatment groups. However, the percentage increase in MSNA during LBNP-10 was significantly augmented from a 24 +/- 9% increase before nifedipine to a 56 +/- 7% increase after nifedipine (p less than 0.05). Decreases in central venous pressure with LBNP-10 were nearly identical before compared with after nifedipine. Thus, nifedipine increased the cardiopulmonary baroreflex sympathetic sensitivity (change in total MSNA per mm Hg decrease in central venous pressure during LBNP-10) from 26.5 +/- 10.7 units/mm Hg to 74.9 +/- 19.0 units/mm Hg (p less than 0.01). In contrast, administration of hemodynamically similar doses of nitroprusside resulted in an attenuation of MSNA responses to LBNP-10. During LBNP-10, MSNA increased 57 +/- 12% before nitroprusside but only 14 +/- 4% during nitroprusside (p less than 0.01). The cardiopulmonary baroreflex sympathetic sensitivity was not significantly altered by nitroprusside (45.1 +/- 12.4 units/mm Hg before compared with 33.1 +/- 20.8 units/mm Hg during nitroprusside, p = NS). Placebo had no effect on the responses to LBNP-10. Nifedipine did not augment MSNA responses to the cold pressor test. To evaluate the linearity of sympathetic responses to cardiopulmonary baroreceptor unloading, graded LBNP (0, -5, -10, and -15 mm Hg) was applied in three additional subjects before and after nifedipine (10 mg s.l.).(ABSTRACT TRUNCATED AT 400 WORDS)

Of 22 randomized trials of rehabilitation with exercise after myocardial infarction (MI), one trial had results that achieved conventional statistical significance. To determine whether or not these studies, in the aggregate, show a significant benefit of rehabilitation after myocardial infarction, we performed an overview of all randomized trials, involving 4,554 patients; we evaluated total and cardiovascular mortality, sudden death, and fatal and nonfatal reinfarction. For each endpoint, we calculated an odds ratio (OR) and 95% confidence interval (95% CI) for the trials combined. After an average of 3 years of follow-up, the ORs were significantly lower in the rehabilitation than in the comparison group: specifically, total mortality (OR = 0.80 [0.66, 0.96]), cardiovascular mortality (OR = 0.78 [0.63, 0.96]), and fatal reinfarction (OR = 0.75 [0.59, 0.95]). The OR for sudden death was significantly lower in the rehabilitation than in the comparison group at 1 year (OR = 0.63 [0.41, 0.97]). The data were compatible with a benefit at 2 (OR = 0.76 [0.54, 1.06]) and 3 years (OR = 0.92 [0.69, 1.23]), but these findings were not statistically significant. For nonfatal reinfarction, there were no significant differences between the two groups after 1 (OR = 1.09 [0.76, 1.57]), 2 (OR = 1.10 [0.82, 1.47]), or 3 years (OR = 1.09 [0.88, 1.34]) of follow-up. The observed 20% reduction in overall mortality reflects a decreased risk of cardiovascular mortality and fatal reinfarction throughout at least 3 years and a reduction in sudden death during the 1st year after infarction and possibly for 2-3 years. With respect to the independent effects of the physical exercise component of cardiac rehabilitation, the relatively small number of "exercise only" trials, combined with the possibility that they may have had a formal or informal nonexercise component precludes the possibility of reaching any definitive conclusion. To do so would require a randomized trial of sufficient size to distinguish between no effect and the most plausible effect based on the results of this overview.

Although impairment of left ventricular function in acute myocardial infarction is closely related to extent of necrosis, function in the noninfarct zone also contributes to global performance and thus may be of prognostic importance. We evaluated left ventricular regional wall motion by the centerline chord method in 332 patients treated with intravenous tissue-type plasminogen activator (t-PA) in the multicenter Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial. All patients had acute contrast ventriculograms of suitable quality for analysis, and 266 patients had paired acute and day 7 ventriculograms. Enhanced function of the noninfarct zone was present during acute catheterization (+0.3 SD/chord) and was associated with preservation of the acute ejection fraction (p = 0.0001). Multiple linear regression analysis revealed the most powerful clinical factor associated with enhanced function of the noninfarct zone was the absence of multivessel disease (p = 0.0001). Clinical factors that were related weakly to noninfarct zone function included female gender (p = 0.08) and higher flow in the infarct artery (p = 0.03). Neither the degree of infarct zone dysfunction nor infarct location was associated with hyperkinesis of the noninfarct zone. In hospital, mortality was closely related to function in the noninfarct zone (p = 0.006), ejection fraction (p = 0.025), and the number of diseased vessels (p = 0.009) but was not related to infarct zone function (p = 0.128).(ABSTRACT TRUNCATED AT 250 WORDS)

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.