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We investigated whether a combination of clopidogrel and glycoprotein (GP) IIb/IIIa inhibitors safely decreases hospital mortality, reinfarction, and major bleeding beyond either therapy alone in patients with non-ST-elevation myocardial infarction (NSTEMI). GP IIb/IIIa inhibitors and clopidogrel, separately, have been shown to decrease adverse outcomes in patients with non-ST-elevation acute coronary syndromes, but the need for combination therapy is uncertain. Multivariate and propensity analyses compared the frequency of death, reinfarction, and major bleeding during hospitalization in 38,691 patients with NSTEMI who were enrolled in the National Registry of Myocardial Infarction 4 from July 2000 to December 2003. Of these, 65% received GP IIb/IIIa inhibitors only, 16.1% clopidogrel only, and 18.8% combination therapy. Among patients who did not undergo percutaneous coronary intervention (PCI), the composite end point of death, reinfarction, and major bleeding was significantly lower with combination therapy than with GP IIb/IIIa inhibitors alone (odds ratio 0.77, 95% confidence interval 0.67 to 0.88). In contrast, this composite end point was significantly higher when combination therapy was employed rather than clopidogrel alone (odds ratio 1.55, 95% confidence interval 1.33 to 1.81). However, among patients who underwent PCI, the composite end point was similar between combination therapy and GP IIb/IIIa inhibitor-only groups (odds ratio 1.01, 95% confidence interval 0.89 to 1.14). Further, there was a strong trend toward a higher composite end point among patients who received combination therapy rather than clopidogrel alone (odds ratio 1.31, 95% confidence interval 0.99 to 1.72). In conclusion, commonly employed strategies using a GP IIb/IIIa inhibitor alone or with the combination of clopidogrel plus GP IIb/IIIa inhibitor in NSTEMI may not be justified in comparison with a simpler strategy of clopidogrel used alone, especially in patients who have not undergone PCI.

This study examines the safety and efficacy of low molecular weight heparin (LMWH) in combination with platelet glycoprotein (GP) IIb/IIIa inhibitors in patients with acute myocardial infarction (AMI). LMWH has been shown to be as effective as unfractionated heparin (UFH) in the treatment of acute coronary syndrome (ACS), but there are limited data regarding the safety and efficacy of LMWH in combination with GP IIb/IIIa inhibitors. We studied 37,320 patients in the National Registry of Myocardial Infarction 3 who were treated with GP IIb/IIIa receptor antagonists from April 1998 to September 2000. Using univariate analysis, clinical events were compared between 2,482 patients who received LMWH and 34,838 patients who were treated with UFH. To adjust for confounding covariates, a multivariate regression analysis was also performed. Major bleeding rates were 4.0% in patients on LMWH versus 4.2% in patients who were treated with UFH (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.80 to 1.23, p = 0.92). Similarly, there was no significant difference in the occurrence of recurrent myocardial ischemia (OR 0.93, 95% CI 0.82 to 1.06, p = 0.26), and in-hospital death (OR 0.86, 95% CI 0.71 to 1.05, p = 0.14) between groups. There was a trend toward a decreased risk of recurrent AMI in patients who received LMWH compared with those on UFH (1.5% vs 1.9%, OR 0.74, 95% CI 0.53 to 1.05, p = 0.09). LMWH appears to be a safe and effective alternative to UFH in patients with AMI who receive IIb/IIIa inhibitors.

The unstable angina pectoris (UAP) classification proposed by Braunwald in 1989, although often used, has never been validated in a large, prospective multicenter study in which all subgroups of patients were included. Patients with UAP or non-ST-elevation myocardial infarction (NSTEMI) were enrolled in the Thrombolysis In Myocardial Ischemia III Registry and classified according to the Braunwald classification for UAP. Clinical end points were compared at 6 weeks and 1 year. Of 3,318 patients, those with primary UAP had lower rates of recurrent myocardial infarction (MI) or death when compared with patients with secondary UAP and post-MI UAP at 6 weeks (4.1% vs 6.4% vs 13.4%, respectively; p

We sought to assess the impact of coronary angiography results on use of lipid-lowering agents among women enrolled in the Women’s Ischemia Syndrome Evaluation [WISE] study. WISE is a multicenter study designed to evaluate new diagnostic modalities among women undergoing angiography for suspected coronary artery disease (CAD). History of atherosclerosis, risk factors for CAD, and low-density lipoprotein (LDL) cholesterol are determined at baseline. The percentage of women at LDL cholesterol goal, use of lipid-lowering agents, and eligibility for lipid-lowering therapy were determined based on National Cholesterol Education Program II guidelines at baseline and 6-week follow-up. Among the 212 women for whom angiographic data were available, 84 had known atherosclerosis, 80 had no history of atherosclerosis but ≥2 risk factors (high risk), and 48 had no history of atherosclerosis and

Outcomes research using analysis of preexisting data is a relatively new field with the potential to improve the quality and effectiveness of medical care, and may provide a useful complement to randomized studies. Motivated by the growth of this research in the cardiovascular literature, this review offers a framework to identify the core concepts of outcomes research from database analyses by comparing and contrasting it with the randomized clinical trial.

Among 57,398 thrombolytic recipients in the National Registry of Myocardial Infarction 2, consultation with another physician was sought in 64% before initiating lytic therapy, although presenting features were typical, rather than atypical, in most patients. Consultation significantly delayed the administration of lytic therapy and was associated with increased hospital mortality.

Data from a national registry of myocardial infarction patients from June 1994 to April 1996 were analyzed to compare the presenting characteristics, acute reperfusion strategies, treatment patterns, and clinical outcomes among black and white patients. Blacks presented much later to the hospital after the onset of symptoms (median 145 vs 122 minutes, p

Data from a national registry (cohort) of myocardial infarction, which has enrolled 275,046 patients from June 1994 to April 1996, were analyzed to compare the baseline demographic and clinical characteristics, treatment patterns, and clinical outcomes among Hispanics, Asian-Pacific islanders, and native Americans with those of white Americans presenting to the hospital with acute myocardial infarction. Non-black minorities were younger, had a higher proportion of men, used the emergency medical services less frequently, and presented later to the hospital after the onset of symptoms (135 vs 122 minutes, p0.001) than whites. Also, non-black minorities were less likely to receive beta-blocker therapy at discharge (crude odds ratio 0.86, confidence interval 0.82 to 0.90) than whites, but they were generally as likely to receive intravenous thrombolytic therapy (with the exception of Asian-Pacific islanders) and undergo both coronary arteriography and revascularization procedures as their white counterparts. There were no significant differences in hospital mortality for non-black minorities compared with whites.

Very early administration of thrombolytic therapy for acute myocardial infarction (AMI) has significantly reduced mortality in eligible patients. The purpose of this study was to evaluate factors which influenced the time from symptom onset to hospital presentation and the time from hospital presentation to the onset of thrombolytic treatment in a large population of patients with AMI. This study included 212,990 patients from 904 hospitals that participated in the National Registry of Myocardial Infarction. The median time from symptom onset to hospital presentation for those treated was 1.5 hours versus 2.7 hours for those not receiving thrombolytic treatment. Older patients and women had increased delay times, as did those who arrived at the hospital during daytime hours. Of the 59,802 (28%) patients who received thrombolytic treatment, 23% were treated < 30 minutes from admission; 63%, < 60 minutes; and 83%, < 90 minutes. Time to treatment increased with age and was longer for women and for patients arriving between midnight and early morning. The most important factor associated with shorter time to treatment was the initiation of thrombolytic treatment in the emergency department rather than in the coronary care unit (47 vs 73 minutes, p < 0.0001). Hospital treatment times are much too long, given that quick identification and treatment of eligible patients are of primary importance in reducing mortality from AMI. To shorten these times, thrombolytic treatment should be initiated in the emergency department, and the effectiveness of hospital programs aimed at reducing time to treatment should be subject to continuing quality improvement surveillance.

This report presents baseline clinical and angiographic data from the Bypass Angioplasty Revascularization Investigation (BARI), a multicenter international trial assessing the relative efficacy of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass graft surgery (CABG) in selected patients with multivessel coronary artery disease. PTCA is commonly performed in patients with multivessel coronary artery disease, yet its long-term efficacy in comparison to CABG is unknown. From August 1988 through August 1991, 1,829 qualifying patients with multivessel disease suitable for either procedure were randomized to PTCA or CABG; sample size estimates were based on anticipated 5-year mortality. Two registry populations were also defined for follow-up: (1) 2,013 patients eligible for randomization but not randomized; and (2) 422 patients considered by angiography as unsuitable for randomization. Patients randomized in BARI were at relatively high risk for subsequent cardiac events: 39% were > or = 65 years old, 55% had prior myocardial infarction, 69% presented with unstable angina or non-Q wave myocardial infarction, and 43% had 3-vessel coronary artery disease. Patients randomized to PTCA and CABG were equally matched in all the important baseline variables. The randomized and the eligible but not randomized groups were similar in most respects. However, the nonrandomized group had a higher proportion with college education; fewer with a history of myocardial infarction, heart failure, diabetes, and smoking; and a somewhat better average ejection fraction. At the 3-month follow-up, PTCA had been performed more commonly in the nonrandomized eligible patients, especially those with 2-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the relative merits of primary percutaneous transluminal coronary angioplasty (PICA) and intravenous thrombolytic therapy for acute myocardial infarction, 12 tertiary care hospitals entered patients who had ≥30 minutes of chest pain and were admitted to a cardiac intensive care unit within 12 hours of symptom onset into a prospective registry. Of 1,170 such patients, 118 (10%) underwent primary PTCA and 230 (19%) received intravenous thrombolytic therapy within 6 hours of registry hospital admission (144 at the registry hospital and 86 prior to arrival at the registry hospital). Baseline demographic characteristics of PTCA and thrombolytic subgroups were remarkably similar. The interval from initial evaluation at the registry hospital to treatment was shorter with intravenous thrombolytic therapy than with primary PTCA (64 vs 104 minutes, p < 0.001), as was the interval from pain onset to treatment (184 vs 252 minutes, p < 0.001). Among the 230 thrombolytic patients, coronary arteriography and PTCA were performed within the first 24 hours in 44% and 18%, respectively, and during the entire hospitalization in 90% and 49%, respectively. During hospitalization, blood was transfused in 16% of the 230 thrombolytic patients versus 5.9% of the 118 PTCA patients (p < 0.001). Otherwise, adverse events during the initial hospitalization were similar in PTCA and thrombolytic groups. Survival at 1-year follow-up was 88% in the PTCA group and 91% in the thrombolytic group (p = NS), and survival free of reinfarction was 85% and 88%, respectively (p = NS). Multivariable analysis, adjusting for baseline characteristics, found no evidence that use of PTCA rather than thrombolytic therapy significantly impacted survival or survival free of reinfarction at 1 year. These observational registry data suggest that patients undergoing primary PTCA for acute myocardial infarction have similar demographic characteristics and similar outcome as patients receiving intravenous thrombolytic therapy.

To ascertain whether the outcome of patients with suspected myocardial infarction differs when chest pain is still present at initiation of thrombolytic therapy, participants in the Thrombolysis in Myocardial Infarction Phase II study, all of whom presented within 4 hours of symptoms onset, were retrospectively divided into 2 groups: (1) those with chest pain present at onset of intravenous thrombolysis, n = 3,000; and (2) those who were free of chest pain on beginning intravenous thrombolytic therapy, n = 337. Patients free of chest pain were older (58 vs 57 years, p = 0.01), more often women (23 vs 17%, p = 0.01), had fewer electrocardiographic leads with ST elevation (3.8 vs 4.1, p 0.55 (35 vs 31%, p = 0.001) and fewer developed congestive heart failure (12 vs 20%). At 1-year follow-up, fewer pain-free patients developed congestive heart failure (15 vs 21%, p = 0.009), but no differences existed between the 2 groups in frequency of death, reinfarction, coronary angioplasty, bypass surgery or anginal class. Thus, there are several observations in patients who were free of chest pain at onset of lytic therapy. (1) The majority developed enzymatic or electrocardiographic evidence of acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the long-term effect of thrombolytic therapy on left ventricular (LV) systolic function, 222 patients with acute myocardial infarction treated with intravenous tissue plasminogen activator within 4 hours of symptom onset underwent assessment of LV ejection fraction (EF) by radionuclide equilibrium angiography at hospital discharge and 1 year later. Mean EF at hospital discharge (46 ± 12) was similar to that at 1 year (45 ± 13). Stepwise multivariate linear regression analysis identified EF at discharge and patency of the infarct-related artery before discharge as independent predictors of EF change at 1 year (p = 0.0002 and 0.003, respectively). Random assignments to invasive versus conservative treatment strategies or to early versus delayed β-blocker therapy did not affect EF change during follow-up. No significant deterioration of EF was observed in patients with larger infarcts. However, EF decreased from 45 ± 10 at hospital discharge to 39 ± 12 (p = 0.005) at 1-year follow-up in a subgroup of patients with history of prior infarction. Thus, patients with acute myocardial infarction, treated with intravenous tissue plasminogen activator early after onset of symptoms, appear to have stable LV function between hospital discharge and 1 year follow-up. The change in EF between hospital discharge and 1 year can be predicted from the EF value at discharge, patency of the infarct-related artery before discharge and history of previous myocardial infarction.

Anticoagulant therapy is frequently used after thrombolytic agents in the treatment of acute myocardial infarction (AMI) although it is unclear that such therapy will prevent subsequent infarct vessel reocclusion. The role of duration of heparin therapy in maintaining infarct artery patency was studied retrospectively in 53 consecutive AMI patients who received streptokinase therapy and underwent coronary angiography acutely and at 14 +/- 1 days. Of the 39 patients with initial infarct vessel patency, patency at follow-up angiography was observed in 100% (22 of 22) of those who received greater than or equal to 4 days of intravenous heparin but in only 59% (10 of 17) of those patients who received less than 4 days of heparin (p less than 0.05). Of the 14 patients not initially recanalized after streptokinase, patent infarct-related arteries at follow-up angiography were found in 3 of 8 (38%) treated with greater than or equal to 4 days of heparin therapy but in none of the 6 patients treated for less than 4 days (difference not significant). No significant difference in hemorrhagic complications was noted between the short- and long-term heparin treatment groups. Thus, greater than or equal to 4 days of intravenous heparin therapy after successful streptokinase therapy in AMI is more effective in maintaining short-term infarct vessel patency than a shorter duration of therapy and it may maintain the short-term patency of the infarct vessel in those patients who later spontaneously recanalize.

The American College of Cardiology/American Heart Association guidelines for exercise testing do not take a position regarding the utility of routine stress testing after coronary artery bypass grafting (CABG). Our purposes were (1) to document the patterns of use of stress testing after CABG and (2) to establish whether the choice of stress testing strategy is associated with clinical characteristics of patients. The Routine versus Selective Exercise Treadmill Testing after Coronary Artery Bypass Graft Surgery (ROSETTA-CABG) Registry is a prospective multicenter study that examined the use of stress testing after CABG among 395 patients at 16 clinical centers in 6 countries. During the 12 months after CABG, 37% of patients underwent stress testing (range across centers 0% to 100%). Among patients who underwent stress testing, 24% had a clinical indication and 76% had it as a routine follow-up. A total of 65% of stress tests involved exercise treadmill testing alone, 17% involved stress nuclear perfusion imaging, 13% involved stress echocardiographic imaging, and 5% involved other types of stress tests, such as positron emission tomographic scans. The first stress test was performed at a median of 13 weeks after CABG, with 20% of patients having second tests at a median of 28 weeks and 6% having additional tests at a median of 34 weeks. Univariate and multivariate analyses demonstrated that the chief determinant of using routine stress testing was the clinical center. In conclusion, these results suggest that there is little consensus on the appropriate use of stress testing soon after CABG. Practice patterns vary widely; poorly diagnostic tests are used routinely; and the clinical center at which the procedure is performed, rather than the clinical characteristics of the patient, determines the use of stress testing after CABG.

The purpose of this study is to provide a contemporary qualitative and quantitative analysis of coronary angiograms from a large series of women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study who had suspected ischemic chest pain. Previous studies have suggested that women with chest pain have a lower prevalence of significant coronary artery disease (CAD) compared with men. Detailed analyses of angiographic findings relative to risk factors and outcomes are not available. All coronary angiograms were reviewed in a central core laboratory. Quantitative measurement of percent stenosis was used to assess the presence and severity of disease. Of the 323 women enrolled in the pilot phase, 34% had no detectable, 23% had measurable but minimal, and 43% had significant (50% diameter stenosis) CAD. Of those with significant CAD, most had multivessel disease. Features suggesting complex plaque were identified in10%. Age, hypertension, diabetes mellitus, prior myocardial infarction (MI), current hormone replacement therapy, and unstable angina were all significant, independent predictors of presence of significant disease (p0.05). Subsequent hospitalization for a cardiac cause occurred more frequently in those women with minimal and significant disease compared with no disease (p = 0.001). The common findings of no and extensive CAD among symptomatic women at coronary angiography highlight the need for better clinical noninvasive evaluations for ischemia. Women with minimal CAD have intermediate rates of rehospitalization and cardiovascular events, and thus should not be considered low risk.

Cardiac procedures are performed less frequently in Canada than in the United States (US), yet rates of cardiac death and myocardial infarction are similar. We therefore sought to compare long-term symptoms and quality of life in Canadian and American patients undergoing initial coronary revascularization. The 161 patients enrolled in the Bypass Angioplasty Revascularization Investigation at the Montreal Heart Institute were compared with 934 patients enrolled at 7 US sites. Patients’ outcomes were documented for 5 years after random assignment to percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Functional status was assessed using the Duke Activity Status Index. Canadian patients were significantly younger and had more angina at study entry. Death and nonfatal myocardial infarction were not significantly different between Canadian and US patients after adjustment for baseline risk. Canadian patients had significantly greater improvements in functional status at 1-year follow-up (Duke Activity Status Index score + 13.5 vs + 6.0, p = 0.002), but this difference progressively narrowed over 5 years. Angina was equally prevalent in Canadian and US patients at 1 year (16% vs 19%), but significantly more prevalent in Canadian patients at 5 years (36% vs 16%, p = 0.001). Repeat revascularization procedures were performed less often over 5 years among Canadian patients (26% vs 34%, p = 0.08), especially coronary artery bypass graft surgery after initial percutaneous transluminal coronary angioplasty (18% vs 32%, p = 0.03). These results suggest more anginal symptoms are required in Canada before coronary revascularization, but as a result Canadians receive greater improvements in quality of life after the procedure.

We sought to assess the impact of coronary angiography results on use of lipid-lowering agents among women enrolled in the Women's Ischemia Syndrome Evaluation [WISE] study. WISE is a multicenter study designed to evaluate new diagnostic modalities among women undergoing angiography for suspected coronary artery disease (CAD). History of atherosclerosis, risk factors for CAD, and low-density lipoprotein (LDL) cholesterol are determined at baseline. The percentage of women at LDL cholesterol goal, use of lipid-lowering agents, and eligibility for lipid-lowering therapy were determined based on National Cholesterol Education Program II guidelines at baseline and 6-week follow-up. Among the 212 women for whom angiographic data were available, 84 had known atherosclerosis, 80 had no history of atherosclerosis butor =2 risk factors (high risk), and 48 had no history of atherosclerosis and2 risk factors (low risk). At baseline, LDL cholesterol goals were met in 24% women with atherosclerosis, in 56% high-risk women, and in 88% low-risk women. Angiography revealed previously undiagnosed CAD in 70% of the high-risk and in 42% of the low-risk women. After angiography results were available, 6 women started lipid-lowering therapy and 2 stopped. Based on National Cholesterol Education Program II guidelines, 63 additional women would have been eligible for pharmacologic lipid-lowering therapy. Intensification of lipid-lowering therapy was not apparent 6 weeks after coronary angiography in women with newly diagnosed CAD or among women whose diagnosis was confirmed.

We reviewed data from the National Registry of Myocardial Infarction-2 to determine the differences in characteristics and outcomes in patients with acute myocardial infarction (AMI) who have undergone previous coronary artery bypass grafting (CABG), and those who have not, and between post-CABG patients who were treated with alteplase (recombinant tissue-type plasminogen activator [rt-PA]) and those who were treated with primary percutaneous transluminal coronary angioplasty (PTCA).Demographic, therapeutic, and outcome data from patients with AMI were collected at >1,000 hospitals in the United States in collaboration with National Registry of Myocardial Infarction-2. Of the 45,925 patients receiving reperfusion therapy, 2,544 of the 39,574 treated with rt-PA (6.4%) had a history of CABG, and 375 of the 6,351 treated with primary PTCA (5.9%) had a history of CABG. Patients with a history of CABG were older, more likely to be men, and had more comorbidities, but prior CABG was still an independent predictor of mortality after multivariate regression analysis (odds ratio 1.23; 95% confidence interval 1.05 to 1.44). Among the post-CABG patients who received rT-PA or underwent PTCA, there was no significant difference in in-hospital mortality rate or the combined end point of death and nonfatal stroke. Thus, (1) prior CABG is an independent predictor of mortality, and (2) for post-CABG patients with AMI who are not in shock and who are lytic-eligible, reperfusion therapy with rt-PA and PTCA result in similar outcomes with regard to in-hospital mortality and the combined end point of death and nonfatal stroke.

Among 57,398 thrombolytic recipients in the National Registry of Myocardial Infarction 2, consultation with another physician was sought in 64% before initiating lytic therapy, although presenting features were typical, rather than atypical, in most patients. Consultation significantly delayed the administration of lytic therapy and was associated with increased hospital mortality.

Data from a national registry of myocardial infarction patients from June 1994 to April 1996 were analyzed to compare the presenting characteristics, acute reperfusion strategies, treatment patterns, and clinical outcomes among black and white patients. Blacks presented much later to the hospital after the onset of symptoms (median 145 vs 122 minutes, p0.001), were more likely to have atypical cardiac symptoms (28% vs 24%, p0.001), and nondiagnostic electrocardiograms during the initial evaluation period compared with whites (37% vs 31%, p0.001). Also, blacks were less likely to receive intravenous thrombolytic therapy (adjusted odds ratio [OR] 0.76, 95% confidence intervals [CI] 0.71 to 0.80), coronary arteriography (adjusted OR 0.85, 95% CI 0.77 to 0.95), other elective catheter-based procedures (adjusted OR 0.87, 95% CI 0.78 to 0.96), and coronary artery bypass surgery (adjusted OR 0.66, 95% CI 0.58 to 0.75) than their white counterparts. Despite these differences in treatment, there were no significant differences in hospital mortality between blacks and whites.

This study examines the association between time to treatment with thrombolytic therapy and hospital outcomes in patients with acute myocardial infarction (AMI) enrolled in a national registry. A total of 71,253 patients hospitalized with AMI from June 1994 to July 1996 who received tissue plasminogen activator (t-PA) therapy in 1,474 United States hospitals were studied. In this study sample, approximately 39% of patients presented to participating hospitals within 2 hours of acute symptom onset and received t-PA; 36% were treated within 2.1 to 4 hours, 12% between 4.1 to 6 hours, and the remaining 13% thereafter. After controlling for potentially confounding factors, in-hospital death rates increased progressively with increasing delays in time of administration of t-PA. The lowest risk for dying during acute hospitalization was seen for those treated with t-PA within 2 hours of acute symptoms. No significant association was seen between time of administration of t-PA and in-hospital risk of recurrent AMI, myocardial ischemia, cardiogenic shock, major bleeding episodes, or stroke and/or intracranial bleeding. The incidence of sustained ventricular arrhythmias declined with progressively longer time to administration of t-PA. The results of this multihospital observational study suggest that patients with AMI treated earlier with t-PA are significantly more likely to survive the acute hospitalization than patients treated later. These data reinforce the benefits to be gained by treatment with t-PA as soon as possible following the onset of acute ischemic symptoms, and for community-wide efforts to reduce the duration of prehospital delay in patients with acute coronary disease.

Analysis of the changes in myocardial deformation produced by adrenergic stress has been limited by the imaging techniques used. We used rapid magnetic resonance imaging (MRI) myocardial tagging to map the dose-dependent response to incremental dobutamine in the normal human left ventricle. Thirteen volunteers underwent breath-hold tagged cine MRI during dobutamine infusion. Images were acquired throughout systole to a peak dose of 20 microg/kg/min. End-systolic percent circumferential shortening (%S) was measured at 3 transmural locations and 4 circumferential locations at 3 long-axis positions. Mean circumferential shortening velocity (CSV) was also calculated at each location and dose. Mean %S reached a maximum of 26 +/- 3% at 10 microg/kg/min compared with 21 +/- 4% at baseline (p

In patients, early after acute myocardial infarction (AMI), rapid magnetic resonance imaging (MRI) techniques have been used to assess left ventricular (LV) structure, global and regional function, infarct artery patency, or contrast uptake individually. We hypothesized that MRI could be used as a comprehensive evaluation of the post-AMI patient, studying all of these parameters in1 hour. Twenty-seven patients were studied after first AMI. Complete examinations were performed in 23 patients, 16 with anterior and 7 with inferior wall myocardial infarction, on day 5 +/- 2 after the event. For measurement of LV structure and regional function, a breath-hold segmented k-space gradient echo tagging sequence was used. A fat-suppressed segmented k-space breath-hold sequence was used for coronary artery imaging. MRI contrast-enhanced images during bolus gadoteridol transit through the myocardium were obtained to assess first-pass contrast uptake. No adverse events were noted during the MRI scanning, which was completed in 46 +/- 5 minutes. The LV mass index, end-diastolic and end-systolic volume indexes, and ejection fraction were (mean +/- SD) 107 +/- 13 g/m2, 87 +/- 23 ml/m2, 54 +/- 20 ml/m2, and 39 +/- 12%, respectively. Intramyocardial percent circumferential shortening was 11 +/- 6% at the apex, 14 +/- 4% in the midventricle, and 15 +/- 4% at the base. Flow within all infarct arteries was visualized. Seventeen of 23 patients had regions of reduced contrast uptake on first-pass imaging with mean signal intensity of 47 +/- 24% that of remote regions. In patients with recent AMI, comprehensive assessment of LV structure and function, infarct artery patency, and regional myocardial contrast uptake was safe and feasible with MRI of1 hour.

Cardiac ischemia during daily life activities, detected by ambulatory electrocardiographic (AECG) monitoring has been associated with increased risk for adverse outcomes. Because daily life ischemia is usually asymptomatic, prevalence and descriptive data of patients with asymptomatic cardiac ischemia (ACI) are not well defined. Accordingly, patients screened for the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial by 48-hour AECG monitoring were investigated to identify factors associated with ACI. A total of 1,820 patients with ischemia on a screening stress test and/or known or suspected coronary artery disease underwent AECG monitoring. Their mean age was 61 years, range 33 to 89; 83% were men and 81% were white. On AECG monitoring, ACI occurred in 897 patients (49%). There was a modest trend (p = 0.04) between increasing age and ACI prevalence. Increased risk for ACI was observed in patients reporting angina 6 weeks before screening (odds ratio 1.38, 99% confidence interval 1.08 to 1.77, p = 0.0008). There was a positive association between increases in heart rate during daily life and ACI prevalence (p < 0.0001). No daily, monthly, or seasonal variation in ACI prevalence was found, although ACI was more prevalent in northern than southern sites. In this group of clinically stable patients, selected on the basis of high risk for coronary artery disease, the prevalence of ACI was higher than expected from previous reports. Several readily available clinical characteristics (i.e., advanced age, recent angina, increased heart rate change with daily activity) were associated with significantly increased probability of ACI.

The aim of this study was to characterize patients with and without prior coronary artery bypass grafting (CABG) among a prospectively identified cohort of patients presenting with unstable angina or non-Q-wave myocardial infarction. Patients in the Thrombolysis in Myocardial Infarction phase III Registry Prospective Study presented within 96 hours of an episode of unstable angina or non-Q-wave acute myocardial infarction. Of 2,048 patients, 336 (16.4%) had prior CABG. Compared with those without prior CABG, patients were the same age, but were more likely to be men, white, diabetic, have a history of angina or myocardial infarction, to have received anti-ischemic medications in the prior week, and to receive intravenous heparin or nitroglycerin, or both, during hospitalization. They were equally likely to undergo coronary angioplasty or CABG. Death or nonfatal myocardial infarction occurred by day 10 in 4.5% of patients with prior CABG and 2.8% of patients without prior CABG (p = 0.11); and by day 42 in 7.7% and 5.1%, respectively (p = 0.03). The composite of death, myocardial infarction, or recurrent ischemia at 1 year was more common among patients with prior CABG (39.3% vs 30.2%, p = 0.002). By multiple logistic regression, prior CABG was not independently associated with the occurrence of death or myocardial infarction, or the composite of death, myocardial infarction, or recurrent ischemia either at 6 weeks or at 1 year. The likelihood of recurrent ischemic events is greater among patients with than without prior CABG, but is not likely explained by differences in baseline or treatment characteristics which reflect the degree of underlying cardiac disease.

Very early administration of thrombolytic therapy for acute myocardial infarction (AMI) has significantly reduced mortality in eligible patients. The purpose of this study was to evaluate factors which influenced the time from symptom onset to hospital presentation and the time from hospital presentation to the onset of thrombolytic treatment in a large population of patients with AMI. This study included 212,990 patients from 904 hospitals that participated in the National Registry of Myocardial Infarction. The median time from symptom onset to hospital presentation for those treated was 1.5 hours versus 2.7 hours for those not receiving thrombolytic treatment. Older patients and women had increased delay times, as did those who arrived at the hospital during daytime hours. Of the 59,802 (28%) patients who received thrombolytic treatment, 23% were treated30 minutes from admission; 63%,60 minutes; and 83%,90 minutes. Time to treatment increased with age and was longer for women and for patients arriving between midnight and early morning. The most important factor associated with shorter time to treatment was the initiation of thrombolytic treatment in the emergency department rather than in the coronary care unit (47 vs 73 minutes, p0.0001). Hospital treatment times are much too long, given that quick identification and treatment of eligible patients are of primary importance in reducing mortality from AMI. To shorten these times, thrombolytic treatment should be initiated in the emergency department, and the effectiveness of hospital programs aimed at reducing time to treatment should be subject to continuing quality improvement surveillance.

This report presents baseline clinical and angiographic data from the Bypass Angioplasty Revascularization Investigation (BARI), a multicenter international trial assessing the relative efficacy of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass graft surgery (CABG) in selected patients with multivessel coronary artery disease. PTCA is commonly performed in patients with multivessel coronary artery disease, yet its long-term efficacy in comparison to CABG is unknown. From August 1988 through August 1991, 1,829 qualifying patients with multivessel disease suitable for either procedure were randomized to PTCA or CABG; sample size estimates were based on anticipated 5-year mortality. Two registry populations were also defined for follow-up: (1) 2,013 patients eligible for randomization but not randomized; and (2) 422 patients considered by angiography as unsuitable for randomization. Patients randomized in BARI were at relatively high risk for subsequent cardiac events: 39% wereor = 65 years old, 55% had prior myocardial infarction, 69% presented with unstable angina or non-Q wave myocardial infarction, and 43% had 3-vessel coronary artery disease. Patients randomized to PTCA and CABG were equally matched in all the important baseline variables. The randomized and the eligible but not randomized groups were similar in most respects. However, the nonrandomized group had a higher proportion with college education; fewer with a history of myocardial infarction, heart failure, diabetes, and smoking; and a somewhat better average ejection fraction. At the 3-month follow-up, PTCA had been performed more commonly in the nonrandomized eligible patients, especially those with 2-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the relative merits of primary percutaneous transluminal coronary angioplasty (PTCA) and intravenous thrombolytic therapy for acute myocardial infarction, 12 tertiary care hospitals entered patients who hador = 30 minutes of chest pain and were admitted to a cardiac intensive care unit within 12 hours of symptom onset into a prospective registry. Of 1,170 such patients, 118 (10%) underwent primary PTCA and 230 (19%) received intravenous thrombolytic therapy within 6 hours of registry hospital admission (144 at the registry hospital and 86 prior to arrival at the registry hospital). Baseline demographic characteristics of PTCA and thrombolytic subgroups were remarkably similar. The interval from initial evaluation at the registry hospital to treatment was shorter with intravenous thrombolytic therapy than with primary PTCA (64 vs 104 minutes, p0.001), as was the interval from pain onset to treatment (184 vs 252 minutes, p0.001). Among the 230 thrombolytic patients, coronary arteriography and PTCA were performed within the first 24 hours in 44% and 18%, respectively, and during the entire hospitalization in 90% and 49%, respectively. During hospitalization, blood was transfused in 16% of the 230 thrombolytic patients versus 5.9% of the 118 PTCA patients (p0.001). Otherwise, adverse events during the initial hospitalization were similar in PTCA and thrombolytic groups. Survival at 1-year follow-up was 88% in the PTCA group and 91% in the thrombolytic group (p = NS), and survival free of reinfarction was 85% and 88%, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

To ascertain whether the outcome of patients with suspected myocardial infarction differs when chest pain is still present at initiation of thrombolytic therapy, participants in the Thrombolysis in Myocardial Infarction Phase II study, all of whom presented within 4 hours of symptoms onset, were retrospectively divided into 2 groups: (1) those with chest pain present at onset of intravenous thrombolysis, n = 3,000; and (2) those who were free of chest pain on beginning intravenous thrombolytic therapy, n = 337. Patients free of chest pain were older (58 vs 57 years, p = 0.01), more often women (23 vs 17%, p = 0.01), had fewer electrocardiographic leads with ST elevation (3.8 vs 4.1, p0.001), and the presenting event was confirmed less often as myocardial infarction than as chest pain without infarction (88 vs 96%, p0.001). There were no significant differences between the 2 groups for in-hospital death, reinfarction, recurrent ischemic events, stroke, overall hemorrhagic complications, coronary angioplasty or bypass surgery. At 6-weeks follow-up, more pain-free patients had resting ejection fraction0.55 (35 vs 31%, p = 0.001) and fewer developed congestive heart failure (12 vs 20%). At 1-year follow-up, fewer pain-free patients developed congestive heart failure (15 vs 21%, p = 0.009), but no differences existed between the 2 groups in frequency of death, reinfarction, coronary angioplasty, bypass surgery or anginal class. Thus, there are several observations in patients who were free of chest pain at onset of lytic therapy. (1) The majority developed enzymatic or electrocardiographic evidence of acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

The ability of radionuclide angiocardiography to quantitatively assess regional left ventricular function was studied in 33 patients undergoing biplane left ventricular cineangiography (45 ° right anterior oblique projection, and 60 ° left anterior oblique projection with 25 ° caudocranial angulation), and first pass (30 ° right anterior oblique projection) and multiple gated equilibrium (35 ° to 45 ° left anterior oblique projection with 20 ° to 25 ° caudocranial angulation) left ventricular scintigraphy within 48 hours. End-diastolic and end-systolic silhouettes of contrast angiograms were superimposed, and five segments were defined in each plane by radial lines originating from the end-diastolic center of mass. Segmental angiographic ejection fraction (end-diastolic area — end-systolic area/ end-diastolic area) was calculated for each segment by computerized planimetry. Similar segments were defined in the end-diastolic and end-systolic regions of interest of the first pass and gated left ventricular scintigrams, and the segmental scintigraphic ejection fraction (back-ground-corrected end-diastolic counts — background-corrected end-systolic counts/background-corrected end-diastolic counts) was obtained for each. A good correlation was observed between segmentai angiographic and scintigraphic ejection fraction in the segments corresponding to the anterobasal (r = 0.74), anterolateral (r = 0.70), apical (r = 0.77), diaphragmatic (r = 0.71), distal septal (r = 0.66), posterolateral (r = 0.71) and inferolateral (r = 0.60) left ventricular regions. The poor correlation in the posterobasal (r = 0.39), basal septal (r = −0.02) and superolateral (r = 0.05) segments was probably related to difficulty in defining the aortic valve, overlap of the left atrium and the left ventricle, and inability to visualize the high septum with these scintigraphic techniques. The reproducibility of scintigraphic segmental ejection fraction was studied in 13 patients in whom a second gated scintigram was performed 2 hours after the initial one. Excellent agreement (r = 0.93) was observed for scintigraphic segmental ejection fraction in the distal septal, posterolateral and inferolateral segments. Segmental scintigraphic ejection fraction enables accurate quantitative evaluation of the function of the anterobasal, anterolateral, apical, diaphragmatic, distal septal, posterolateral and inferolateral left ventricular regions with high reproducibility.

The effect of optimal medical therapy on coronary arterial anatomy was evaluated in 25 patients with unstable angina pectoris. Coronary arterial diameter and the extent of stenosis were exactly quantified in two successive coronary angiograms performed in each patient at approximately a 1 year interval (range 4 to 31 months, average 12.4 months). The measuring device was a vernier caliper with an accuracy of 0.05 mm. After 1 year of medical treatment 69 stenoses of the three major coronary branches showed no significant change: The average degree of area obstruction of 27 stenoses of the right coronary artery was 79 and 84 percent in the initial and second studies, respectively; that of 26 stenoses of the left anterior descending artery 78 and 77 percent, respectively, and that of 16 stenoses of the left circumflex artery 73 and 83 percent, respectively. In 11 patients, 14 stenoses showed a distinct progression of more than 20 percent area obstruction. All six stenoses showing more than 90 percent obstruction in the first angiogram progressed to complete obstruction within 1 year. In five other patients area obstruction in five stenoses regressed by more than 20 percent. The anatomy of vessel segments distal to obstructions remained unchanged within 1 year. It is concluded from these quantitative measurements that the distribution and severity of coronary lesions are similar in patients with stable and unstable angina pectoris. Coronary anatomy showed no significant change after 1 year of medical treatment. The rate of progression was substantially lower than previously reported in patients with stable angina pectoris.

This nonrandomized study compared the results of early coronary artery bypass grafting to those of initial medical therapy in a group of 2,023 patients with severe angina pectoris and 2 major epicardial coronary arteries having greater than or equal to 70% diameter luminal narrowing. Medical therapy was selected for 706 patients, and 1,317 patients were treated by coronary artery bypass grafting. The 6-year survival rate was 76% for patients treated medically and 89% for patients treated surgically (p less than 0.0001). Cox multivariate analysis showed that surgical treatment was a beneficial independent predictor of survival (p less than 0.001). For patients with 2-vessel coronary artery disease who had Canadian Heart Association class III and IV angina at presentation, surgical therapy provided a survival advantage for patients with impaired left ventricular function and proximal narrowing of 1 or more coronary arteries.

To assess the metabolic effects of myocardial substrate alteration In patients with coronary artery disease, glucose-insulin-potassium solution was administered intravenously for 30 minutes to 14 men with stable angiographically documented coronary artery disease. The glucose-insulin-potassium solution (300 g of glucose, 50 units of regular insulin and 80 mEq of potassium chloride per liter of water) was infused at a constant rate in each patient, but individual infusion rates ranged from 0.013 to 0.032 ml/kg per min (4 to 10 mg glucose/kg per min) in the 14 patients. Simultaneous arterial and coronary sinus samples were obtained at 15 minute intervals during a stable 30 minute control period and again at 15 minute intervals during the infusion; samples were assayed for glucose, lactate, free fatty acid and oxygen content. In all 14 patients, during the glucose-insulin-potassium infusion, arterial glucose and lactate increased and arterial free fatty acid levels fell; the magnitude of the changes in arterial lactate and free fatty acids as related to the rate of infusion. Arterial-coronary sinus differences (A-C s ) for glucose, lactate and free fatty acid levels correlated with the arterial concentrations of these substrates ( r = 0.66, 0.87 and 0.79, respectively). Regression analyses demonstrated myocardial thresholds for the uptake of these substrates as follows: glucose 79 mg/100 ml; lactate 300 μmole/liter; and free fatty acids 100 to 200 μEq/liter. Finally and most importantly, the reduction in A-C s oxygen values after glucose-insulin-potassium infusion correlated with the reduction in A-C s free fatty acid levels ( r = 0.64, P Myocardial substrate availability may be an important determinant of myocardial oxygen demand in patients with coronary artery disease. Infusion of glucose-insulin-potassium solution has the potential to alter myocardial substrate availability, thus improving the balance between myocardial oxygen demand and supply.

Employment and income status of 96 patients randomized into the Alabama portion of the National Cooperative Unstable Angina Study were evaluated before the patients' admission to the study and in 1977. All patients had at least 12 months of follow-up study (mean 38 months). The ratio of patients fully employed at the time of follow-up to those fully employed at entry into the study (baseline) was 0.68 for medically treated patients, 0.53 for surgically treated patients and 0.53 for patients in whom medical therapy failed and who later underwent operation. The changes in annual family income were +$1,111 for medical patients, −$2,447 for surgical and +$875 for those later undergoing surgery. Regression analysis revealed that nonwork income, initial work status, initial income, severity of angina while the patient was in the unstable angina study and the procedural variable (that is, persistent medical, early surgical or late surgical treatment) were associated with return to full-time employment. Changes in family income were related to change in work status, the procedural variable, the patient's education, initial work status, the spouse's income, occurrence of a myocardial infarction after entry into the unstable angina study, duration of angina before entry into the unstable angina study, marital status and sex. Patients who underwent initial surgery had the largest reduction in family income, related to the change in nonworking status at the time of follow-up interview.

To assess the change in angiographically visualized collaterals in evolving acute myocardial infarction (AMI), coronary arteriograms from 53 patients obtained 6.2 +/- 0.2 hours after onset of AMI symptoms were compared with follow-up angiograms obtained 14 +/- 1 days later. Collaterals were graded according to intensity score and percent of distal infarct-related artery visualized. Collateral intensity score and the percent of distal infarct vessel visualized by collaterals at baseline were low, and there was a significant increase in both values at follow-up angiography. The group of 20 patients with occluded infarct vessels at follow-up study accounted for these increases. In 33 patients with patent infarct vessels at repeat angiography, collateral intensity score and percent of segment visualized were unchanged. Among the patients with occluded infarct vessels at baseline and subsequent improvement in left ventricular (LV) ejection fraction (EF), baseline collateral score and percent of segment visualized were significantly greater than in patients in whom LVEF did not improve. Thus, in patients with evolving AMI, (1) angiographically visible collaterals are not extensive within the early hours of AMI, (2) the extent of collaterals on follow-up angiography may not be representative of that on the day of AMI, (3) collaterals are considerably more common 2 weeks after AMI, especially in patients with occluded infarct arteries during follow-up, and (4) collaterals present at the time of AMI are associated with improved LVEF at 2 weeks.

The incidence of pulmonary perfusion defects after routine cardiac Catheterization was assessed in 57 patients by comparing ventilationperfusion lung scans obtained before and 1 day after Catheterization. Patients were prospectively randomized to two groups, one in which right heart Catheterization was performed using an antecubital venous cutdown procedure and one in which the percutaneous femoral vein approach was used. Seven patients (12 percent) had new postcatheterization perfusion defects consistent with pulmonary emboli. These patients did not differ significantly from patients without new defects in clinical characteristics, duration of Catheterization, hemodynamic variables or route of right heart Catheterization. The data suggest that pulmonary embolism may be a more common complication of routine cardiac Catheterization than previously appreciated.

Twenty-eight patients admitted to the hospital with suspected acute myocardial infarction underwent baseline studies within 12 hours of onset of symptoms. Patients were then randomized to receive control infusion (0.45 percent sodium chloride at 20 ml/hour) (15 patients) or glucoseinsulin-potassium infusion (300 g glucose, 50 units regular insulin, 80 mEq KCl/liter water at 1.5 ml/kg per hour) (13 patients) for 48 hours. All patients received 0.45 percent sodium chloride for 2 more days. Coronary arteriograms and left ventriculograms were obtained in 26 (93 percent) of 28 patients 2 to 3 weeks after infarction. Radionuclide ejection fraction improved during glucose-insulin-potassium infusion (49 ± 4 to 55 ± 5 percent, p During experimental infusion pulmonary arterial end-diastolic pressure decreased in the glucose-insulin-potassium group (17 ± 2 to 12 ± 2 mm Hg, p These data suggest that glucose-insulin-potassium infusion after acute myocardial infarction in human beings (1) increases global ejection fraction, (2) Increases ejection fraction in the “infarcted zone” without changing ejection fraction in the “noninfarcted zone”, and (3) decreases pulmonary arterial end-diastolic pressure and end-diastolic and end-systolic volumes.

This study correlated the location and size of posterolateral myocardial infarcts (Mls) measured anatomically with that estimated by quantitative criteria derived from the standard 12-lead ECG. Twenty patients were studied who had autopsy-proved, single, posterolateral Mls and no confounding factors of ventricular hypertrophy or bundle branch block in their ECG. Left ventricular anatomic Ml size ranged from 1 to 46%. No patient had a ≥ 0.04-second Q wave in any electrocardiographic lead and only 55% had a 0.03-second Q wave. A 29-point, simplified QRS scoring system consisting of 37 weighted criteria was applied to the ECG. Points were scored by the ECG in 85% of the patients (range 1 to 8 points). Ml was indicated by a wide variety of QRS criteria; 19 of the 37 criteria from 8 different electrocardiographic leads were met. The correlation coefficient between MI size measured anatomically and that estimated by the QRS score was 0.72. Each point represented approximately 4% Ml of the left ventricular wall.

The aggregation of platelets to arachidonic acid was studied serially in patients admitted to the hospital with suspected acute myocardial infarction (MI) and no history of platelet-altering drug ingestion. Of 17 patients studied within the first 48 hours after MI, 16 had a marked decrease in aggregation, to 0.5 mM arachidonic acid (15 +/- 12% compared with 64 +/- 15% for control subjects, p less than 0.01). The exception was a patient with documented coronary artery spasm who was receiving nifedipine at the time of MI. He had a delayed but normal final percent aggregation. The aggregation response returned to normal at 2 to 4 days and was slightly above normal at 6 to 10 days (change not statistically significant). Thromboxane B2 formation correlated with the response of patients' platelets to arachidonic acid (38 +/- 15 ng in the low responders versus 161 +/- 30 ng/3 X 10(8) platelets/4 min in the normal responders, p less than 0.05). Low responding platelets after washing had normal adenosine diphosphate and adenosine triphosphate contents and aggregated and formed thromboxane B2 normally with arachidonic acid. The plasma of patients with MI was found to inhibit platelet aggregation and thromboxane B2 formation to arachidonic acid.

This study correlated the location and size of posterolateral myocardial infarcts (Mls) measured anatomically with that estimated by quantitative criteria derived from the standard 12-lead ECG. Twenty patients were studied who had autopsy-proved, single, posterolateral Mls and no confounding factors of ventricular hypertrophy or bundle branch block in their ECG. Left ventricular anatomic Ml size ranged from 1 to 46%. No patient had a ≥ 0.04-second Q wave in any electrocardiographic lead and only 55% had a 0.03-second Q wave. A 29-point, simplified QRS scoring system consisting of 37 weighted criteria was applied to the ECG. Points were scored by the ECG in 85% of the patients (range 1 to 8 points). Ml was indicated by a wide variety of QRS criteria; 19 of the 37 criteria from 8 different electrocardiographic leads were met. The correlation coefficient between MI size measured anatomically and that estimated by the QRS score was 0.72. Each point represented approximately 4% Ml of the left ventricular wall.

A preliminary report is presented of a prospective randomized trial conducted by eight cooperative institutions under the auspices of the National Heart and Lung Institute to compare the effectiveness of medical and surgical therapy in the management of the acute stages of unstable angina pectoris. To date 150 patients have been included in the randomized trial, 80 assigned to medical and 70 to surgical therapy; the clinical presentation, coronary arterial anatomy and left ventricular function in the two groups are similar. Some physicians have been reluctant to prescribe medical or surgical therapy by a random process, and the ethical basis of the trial has been questioned. Since there are no hard data regarding the natural history and outcome of therapy for unstable angina pectoris, randomization appears to provide a rational way of selecting therapy. Furthermore, subsets of patients at high risk may emerge during the process of randomization. The design of this randomized trial is compared with that of another reported trial. Thus far, the study has shown that it is possible to conduct a randomized trial in patients with unstable angina pectoris, and that the medical and surgical groups have been similar in relation to the variables examined. The group as a whole presented with severe angina pectoris, either as a crescendo pattern or as new onset of angina at rest, and 84 percent had recurrence of pain while in the coronary care unit and receiving vigorous medical therapy. It is anticipated that sufficient patients will have been entered into the trial within the next 12 months to determine whether medical or surgical therapy is superior in the acute stages of unstable angina pectoris.

To evaluate the effectiveness of the graded exercise test in predicting the extent of coronary artery disease and the degree of left ventricular dysfunction in patients with prior myocardial infarction, 100 consecutive patients underwent both graded exercise testing and coronary and left ventricular angiography at a median of 4 months after infarction. The studies caused no complications. An equal number of patients had anterior and inferior infarction. Coronary artery disease, defined as 70 percent or greater stenosis of luminal diameter, was present in three vessels in 31 patients, in two vessels in 35 patients, in one vessel in 33 patients and in no vessel in one patient. With “diagnostic” electrocardiographic criteria of 1 mm or greater J point depression plus a flat or downsloping S-T segment, 31 patients had an electrocardiographically positive exercise test; 27 of these (87 percent) had two or three vessel coronary artery disease. Of the 21 patients with a negative exercise test, 62 percent had coronary artery disease in no more than one vessel, 33 percent in two vessels and 5 percent in three vessels. Fourteen patients had S-T segment elevation during exercise; these patients had a lower ejection fraction and larger angiographic scar size than the remaining 86 patients. Patients terminating exercise because of symptoms of left ventricular dysfunction (fatigue or dyspnea) showed correlation between duration of exercise and ejection fraction ( r = 0.65) and between duration of exercise and angiographic scar size ( r = −0.62). Thus, several months after infarction, the graded exercise test can be performed safely and can be utilized to predict the extent of coronary artery disease and left ventricular dysfunction in selected groups of patients.

To determine whether acute elevation of plasma free fatty acids influences myocardial oxygen consumption in man, 17 patients underwent a metabolic study consisting of serial measurements of coronary sinus blood flow, heart rate and aortic blood pressure and arterial and coronary sinus determinations of oxygen, carbon dioxide, glycerol and free fatty acids both before and for 30 minutes after the intravenous administration of a bolus dose of 5,000 units of heparin. Of the 17 patients, 9 (group A) were fasting, and 8 (group B) ingested 100 g of fat 3 hours before the study in order to enhance post-heparin lipolysis. Marked elevation of arterial free fatty acid levels was seen in each group 30 minutes after administration of heparin (group A 713 ± 21 [mean ± standard error of the mean] to 1,757 ± 139 μmoles/liter, P < 0.001; group B 721 ± 57 to 2,668 ± 332 μmoles/liter, P < 0.001); significant increase in arterial-coronary sinus free fatty acid difference was also noted (group A 139 ± 11 to 298 ± 19 μmoles/liter, P < 0.001; group B 147 ± 11 to 334 ± 35 μmoles/liter, P < 0.001). Hemodynamic variables, including mean aortic pressure, heart rate, coronary sinus blood flow and coronary vascular resistance, were unchanged. Despite the marked increase in free fatty acids, myocardial oxygen consumption was unchanged 30 minutes after administration of heparin in both groups A and B. Myocardial triglyceride formation after heparin in both groups was suggested by (1) lack of change in cardiac respiratory quotient, (2) net myocardial glycerol uptake after heparin but not in the control state, and (3) oxygen extraction ratios totaling considerably in excess of 100 percent after heparin. The data suggest that acute elevation of plasma free fatty acids to pathophysiologic levels after heparin-induced lipolysis has no measurable effect on myocardial oxygen consumption in patients in stable condition, probably because the excess free fatty acids are stored as triglycerides rather than oxidized.

Biplane axial left cineventriculography represents the most accurate diagnostic technique for evaluating acquired and congenital heart disease. However, data have accumulated to indicate that without angled views of the left ventricle, the diagnosis will be incomplete and inaccurate in a significant number of patients. Left ventriculography is the acknowledged standard for left ventricular performance. However, comparison of the conventional or nonangled left anterior oblique left ventriculogram with the angled views of the left ventricle obtained with either two dimensional ultrasound or radionuclide left ventriculography may in many cases be invalid because dissimilar views are compared. The cranial-left anterior oblique view allows more accurate assessment of the precise degree and extent of asynergy, left ventricular aneurysms and ventricular septal defects. Left ventricular outflow tract abnormalities such as discrete subaortic stenosis and the obstructive form of hypertrophic cardiomyopathy can easily be distinguished. Lesions involving the mitral valve, especially mitral valve prolapse, are readily evaluated. Lastly, comparison with noninvasive tests of left ventricular performance can be more accurately performed.

The 3 year cumulative survival rate of 1,492 patients with left main coronary artery disease (50 percent or greater stenosis of luminal diameter) enrolled in the Collaborative Study in Coronary Artery Surgery (CASS) was 91 percent for the surgical group and 69 percent for patients treated medically (p less than 0.0001). Mortality was significantly greater in patients with impaired left ventricular function. The difference between medical and surgical therapy was significant for patients who had normal, moderately abnormal and severely impaired left ventricular function and for patients with stenosis of the left main coronary artery of 50 to 59, 60 to 69, 70 to 79 and 80 percent or greater. Aortocoronary bypass surgery did not significantly improve survival in patient subgroups who had (1) a nonstenotic dominant right or balanced coronary circulation, (2) a stenotic dominant right coronary artery and normal left ventricular function, and (3) left main coronary stenosis of 50 to 59 percent and normal or mildly abnormal left ventricular function. The Cox proportional hazards model was used to select baseline variables that were independent predictors of long-time mortality. The model selected left ventricular score, age, congestive heart failure score, hypertension, percent left main coronary arterial stenosis and coronary arterial dominance as the baseline variables most predictive of long-term survival. A clinical and angiographic prognostic risk index developed from these six baseline variables showed significantly improved survival for the surgical cohort in each of four risk categories. In the best and worst risk category, the 3 year survival rate was 97 and 82 percent, respectively, for the surgical group and 85 and 34 percent, respectively, for the medical group (p less than or equal to 0.0002). The data from this observational study show that coronary bypass surgery prolongs life in most patients with left main coronary artery disease, particularly those who have severe narrowing of the left main coronary artery or impaired left ventricular function. The results permit a better understanding of the natural history of left main coronary artery disease and permit a more accurate estimate of long-term survival for individual patients through the use of a clinical-angiographic risk index.

To determine whether myocardial oxygen consumption (MVO2) might be reduced when myocardial substrate uptake is changed from predominantly lipid to predominantly carbohydrate, measurements of arterialcoronary sinus glucose, lactate, free fatty acids, oxygen, carbon dioxide and coronary sinus blood flow (by thermodilution) were obtained in 13 fasting patients. Measurements were initially made in a basal control state and then repeated at 10, 20 and 30 minutes during an infusion of glucose-insulin-potassium. After 30 minutes of infusion, there was a three-fold increase in myocardial glucose uptake (44 ± 10 to 145 ± 19 +μmoles/min [mean ± standard error of the mean], P < 0.01), a two-fold increase in myocardial lactate uptake (35 ± 4 to 77 ± 10 μmoles/min, P < 0.001) and a 75 percent decrease in myocardial free fatty acid uptake (34 ± 5 to 9 ± 3 μmoles/min, P < 0.01). Cardiac respiratory quotient rose from 0.70 ± 0.05 to 0.93 ± 0.08 (P < 0.001). Sum of oxygen extraction ratios for glucose and lactate rose from 51 ± 7 percent at control to 155 ± 22 percent at 30 minutes of infusion (P < 0.001) and suggested that much of the enhanced myocardial carbohydrate uptake met a nonoxidative fate, such as glycogen formation. During glucose-insulin-potassium infusion, arterial-coronary sinus oxygen decreased by 13 percent, coronary sinus blood flow increased by 12 percent and MVO2 was unchanged. The increase in coronary sinus blood flow was associated with a 13 percent decrease in coronary vascular resistance and a small, but significant, increase in serum osmolarity (289 ± 3 to 299 ± 3 mOsm/liter, P < 0.001). It is concluded that glucose-insulin-potassium infusion, while causing prompt alteration in myocardial substrate utilization from lipid to carbohydrate, produces no significant measurable change in myocardial oxygen consumption. However, such infusion is accompanied by a measurable increase in coronary sinus blood flow and a decrease in coronary vascular resistance.

To assess the metabolic effects of myocardial substrate alteration in patients with coronary artery disease, glucose-insulin-potassium solution was administered intravenously for 30 minutes to 14 men with stable angiographically documented coronary artery disease. The glucose-insulin-potassium solution (300 g of glucose, 50 units of regular insulin and 80 mEq of potassium chloride per liter of water) was infused at a constant rate in each patient, but individual infusion rates ranged from 0.013 to 0.032 ml/kg per min (4 to 10 mg glucose/kg per min) in the 14 patients. Simultaneous arterial and coronary sinus samples were obtained at 15 minute intervals during a stable 30 minute control period and again at 15 minute intervals during the infusion; samples were assayed for glucose, lactate, free fatty acid and oxygen content. In all 14 patients, during the glucose-insulin-potassium infusion, arterial glucose and lactate increased and arterial free fatty acid levels fell; the magnitude of the changes in arterial lactate and free fatty acids was related to the rate of infusion. Arterial-coronary sinus differences (A-Cs) for glucose, lactate and free fatty acid levels correlated with the arterial concentrations of these substrates (r = 0.66, 0.87 and 0.79, respectively). Regression analyses demonstrated myocardial thresholds for the uptake of these substrates as follows: glucose 79 mg/100 ml; lactate 300 mu mole/liter; and free fatty acids 100 to 200 mu Eq/liter. Finally and most importantly, the reduction in A-Cs oxygen values after glucose-insulin-potassium infusion correlated with the reduction in A-Cs free fatty acid levels (r = 0.64, P less than 0.0001). This observation suggests that, in patients with coronary artery disease, glucose-insulin-potassium infusion may significantly diminish myocardial oxygen requirements by reduction of myocardial free fatty acid utilization and simultaneous enhancement of myocardial carbohydrate utilization. Myocardial substrate availability may be an important determinant of myocardial oxygen demand in patients with coronary artery disease. Infusion of glucose-insulin-potassium solution has the potential to alter myocardial substrate availability, thus improving the balance between myocardial oxygen demand and supply.

Total occlusion of the left main coronary artery was confirmed on review of the coronary angiograms in 12 (0.06 percent) of the 20,197 patients entered into the Coronary Artery Surgery Study (CASS) before coronary arterial surgery. Clinical features alone could not distinguish the patients with total occlusion of the left main coronary artery from those enrolled in the CASS with subtotal stenosis of this vessel. The right coronary artery had a stenosis greater than or equal to 70 percent of luminal diameter in 7 of the 12 patients. Collateral flow to the left coronary artery was defined as “substantial” or “limited” based on the presence or absence of clear visualization of the main channel of either the left anterior descending or left circumflex coronary artery during coronary angiography. Of the eight patients with “substantial” collateral flow, one (13 percent) had an aneurysmal or dyskinetic left ventricular wall segment, whereas all (100 percent) of the three patients with “limited” collateral flow had dyskinesia or an aneurysm (p This study indicates that patients with total occlusion of the left main coronary artery are uncommon and cannot be distinguished by presenting features alone from patients having subtotal stenosis of the left main coronary artery. “Substantial” coronary collateral blood flow is associated with better left ventricular wall motion than is “limited” collateral flow. Prolonged survival and lessening of symptoms may occur after coronary bypass grafting although long-term survival is possible without it.