Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport.

To study the route by which plasma insulin enters cerebrospinal fluid (CSF), the kinetics of uptake from plasma into cisternal CSF of both insulin and [14C]inulin were analyzed during intravenous infusion in anesthetized dogs. Four different mathematical models were used: three based on a two-compartment system (transport directly across the blood-CSF barrier by nonsaturable, saturable, or a combination of both mechanisms) and a fourth based on three compartments (uptake via an intermediate compartment). The kinetics of CSF uptake of [14C]inulin infused according to an "impulse" protocol were accurately accounted for only by the nonsaturable two-compartment model (determination coefficient [R2] = 0.879 +/- 0.044; mean +/- SEM; n = 5), consistent with uptake via diffusion across the blood-CSF barrier. When the same infusion protocol and model were used to analyze the kinetics of insulin uptake, the data fit (R2 = 0.671 +/- 0.037; n = 10) was significantly worse than that obtained with [14C]inulin (P = 0.02). Addition of a saturable component of uptake to the two-compartment model improved this fit, but was clearly inadequate for a subset of insulin infusion studies. In contrast, the three-compartment model accurately accounted for CSF insulin uptake in each study, regardless of infusion protocol (impulse infusion R2 = 0.947 +/- 0.026; n = 10; P less than 0.0001 vs. each two-compartment model; sustained infusion R2 = 0.981 +/- 0.003; n = 5). Thus, a model in which insulin passes through an intermediate compartment en route from plasma to CSF, as a part of a specialized transport system for the delivery of insulin to the brain, best accounts for the dynamics of this uptake process. This intermediate compartment could reside within the blood-CSF barrier or it may represent brain interstitial fluid, if CNS insulin uptake occurs preferentially across the blood-brain barrier.

Prognostic value of angiographic indices of coronary artery disease from the Coronary Artery Surgery Study (CASS).

The Coronary Artery Surgery Study, CASS, enrolled 24,959 patients between August 1975 and June 1979 who were studied angiographically for suspected coronary artery disease. This paper compares the prognostic value for survival without early elective surgery of eight different indices of the extent of coronary artery disease: the number of diseased vessels, two indices using the number of proximal arterial segments diseased, two empirically generated indices from the CASS data, and the published indices of Friesinger, Gensini, and the National Heart and Chest Hospital, London. All had considerable prognostic information. Typically 80% of the prognostic information in one index was also contained in another. Our analysis shows that good prediction from angiographic data results from a combination of left ventricular function and arteriographic extent of disease. Prognosis may reasonably be obtained from three simple indices: the number of vessels diseased, the number of proximal arterial segments diseased, and a left ventricular wall motion score. These three indices account for an estimated 84% of the prognostic information available. 6-yr survival varies between 93 and 16% depending upon the values of these three indices.

Regimen-related toxicity in patients undergoing bone marrow transplantation.

Bone marrow transplantation is associated with significant morbidity and mortality, some of which is due to high-dose chemoradiotherapy. In order to quantitate toxicity that was felt to be due to the preparative regimen (termed regimen-related toxicity [RRT]), a system was developed in which toxicities were graded from 0 (none) to 4 (fatal). One hundred ninety-five patients who underwent marrow transplantation for leukemia were studied retrospectively to determine whether toxicities that were clinically felt to be due to the preparative regimen were influenced by other factors such as disease status, graft-versus-host disease (GVHD) prophylaxis, and allogenicity. All patients developed grade I toxicity in at least one organ, and 30 developed grades III-IV (life-threatening or fatal) RRT. RRT was more common in relapsed patients v remission patients (P = .04), in those receiving 15.75 Gy total body irradiation (TBI) v 12.0 Gy TBI (P = .028), and in those receiving allogeneic marrow v autologous marrow (P = .0029). Autologous marrow recipients did not develop grades III-IV toxicity in this study. A multivariate analysis controlling for autologous marrow grafting showed that the dose of TBI was the only statistically significant predictor of grades III-IV RRT. Those patients who developed grade III RRT were unlikely to survive 100 days from transplant, though not all deaths could be attributed to RRT. Patients who developed grade II toxicity in three or more organs were more likely to die within 100 days than those developing grade II toxicity in two or less organs (P = .0027). This system was generally able to distinguish RRT from other toxicities observed in marrow recipients.

Regimen-related toxicity and early posttransplant survival in patients undergoing marrow transplantation for lymphoma.

Ninety-five patients transplanted for malignant lymphoma were retrospectively evaluated for regimen-related toxicity (RRT) and early posttransplant survival. Nineteen patients developed life-threatening (grade 3) or fatal (grade 4) RRT in one or more organs. Grade 3 or 4 RRT was more common in patients with advanced disease versus those transplanted earlier in their course (P = .008), and was more common in patients with advanced disease conditioned with cytarabine (Ara-C)/total body irradiation (TBI) versus those prepared with cyclophosphamide (CY)/TBI (P = .033). There was no significant difference in the incidence of grade 3 or 4 toxicity in autologous, histocompatibility locus antigen (HLA)-identical, or HLA-mismatched marrow recipients. Grade 3 or 4 RRT tended to be more common and 100-day survival worse in patients with a Karnofsky performance status of less than 90 (P = .063 and .0002, respectively). Patients receiving 20 Gy or more of mediastinal irradiation before coming to transplant had more idiopathic or cytomegalovirus (CMV) interstitial pneumonitis than those who received less than 20 Gy (30% v 9%, P = .027). The probability of survival decreased with the number of organs in which toxicity was observed (P = .0001). Severe or fatal toxicities directly related to the preparative regimen are a significant problem in the treatment of patients with advanced malignant lymphoma and can be reduced by carrying out transplantation earlier in the course of the disease.

Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience.

PURPOSE: To analyze results of 127 patients undergoing myeloablative therapy followed by marrow transplantation for relapsed or refractory Hodgkin's disease. PATIENTS AND METHODS: Twenty-three patients had primary refractory disease, 34 were in early first relapse or second complete remission (CR), and 70 had refractory first relapse or disease beyond second CR. Preparative regimens included total-body irradiation (TBI) and chemotherapy (n = 61) or chemotherapy only (n = 66). Sixty-eight patients received autologous marrow, six syngeneic marrow, and 53 allogeneic marrow. RESULTS: The 5-year actuarial probabilities of survival, event-free survival (EFS), relapse, and nonrelapse mortality for the entire group were 21%, 18%, 65%, and 49%, respectively. HLA-identical allogeneic marrow recipients had a statistically lower relapse rate compared with recipients of autologous marrow, but survival, EFS, and nonrelapse mortality rates were not significantly different. In the multivariate analysis, higher performance status and absence of bulky disease predicted for improved EFS and lower relapse rates, while fewer prior treatment regimens predicted for improved EFS and lower nonrelapse mortality rates. Additionally, the univariate analysis showed that patients who underwent transplantation with disease refractory to chemotherapy or beyond second CR had a worse outcome compared with those who had less advanced disease. CONCLUSION: Outcome with transplantation for patients with Hodgkin's disease is improved if transplantation is performed early after relapse when disease burden is less, tumor chemosensitivity is greater, and the patient is likely to have a better performance status. The use of HLA-matched sibling marrow results in a lower relapse rate and, thus, for some individuals, may be preferable to the use of autologous marrow.

Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle.

Between October 1979 and January 1988, 101 patients with malignant lymphoma who failed initial induction treatment or relapsed received high-dose combination chemotherapy or chemoradiotherapy followed by infusion of autologous bone marrow. Twenty-eight of the 101 patients survive, 18 of whom are disease-free for a median of 26 (range, 12 to 66) months. The 5-year actuarial probabilities of survival, event-free survival (EFS), and relapse from transplantation were 20%, 11%, and 84%, respectively. Multivariate analysis showed that the likelihood of EFS was decreased among patients transplanted with a Karnofsky score of less than 80%. Recurrent lymphoma after transplant was the most important cause of treatment failure with 36 of 62 relapses occurring within 100 days from marrow infusion. Early, but not late relapse, was more frequent in patients transplanted for advanced lymphoma, and both early and late relapses were increased among patients with impaired pretransplant clinical performance or high-grade histology of lymphoma. Ten patients who relapsed post-transplant are alive, seven in remission. Further improvement of these results will require earlier transplantation, improved preparative regimens, or early posttransplant therapy.

Myocardial infarction in young adults: angiographic characterization, risk factors and prognosis (Coronary Artery Surgery Study Registry).

OBJECTIVES: This study examined the angiographic characteristics, coronary risk factors and prognosis in young men and women with a history of myocardial infarction compared with that in older patients. BACKGROUND: There are few data regarding myocardial infarction in young adults. It is undetermined whether the development of myocardial infarction at a young age represents a form of coronary heart disease with an adverse prognosis. METHODS: Of the 8,839 patients with a history of myocardial infarction in the Coronary Artery Surgery Study (CASS), there were 294 men < or = 35 years old and 210 women < or = 45 years old. Coronary anatomy, baseline characteristics and prognosis were compared in younger and older patients. RESULTS: Young men and women more often had angiographically normal coronary arteries, nonobstructive disease < 70% stenosis and single-vessel disease than older patients (p < 0.0001). Current smoking was more frequent in young patients (p < 0.0001). Hypertension and diabetes were more frequent in both older men and women, whereas a positive family history of premature coronary disease was significantly more prevalent only in young men. The survival rate at 7 years was improved for young men compared with that in older men (84% vs. 75%, p = 0.0094) and for young women compared with that in older women (90% vs. 77%, p = 0.0004). When multivariate analysis was applied to the data, the survival advantage for young patients remained after adjustment. CONCLUSIONS: Young patients with a myocardial infarction have a favorable prognosis compared with that in older patients.

Validation of exercise-enhanced risk assessment of coronary heart disease events: longitudinal changes in incidence in Seattle community practice.

Noninvasive criteria developed in a learning series for exercise-enhanced risk assessment for events due to coronary heart disease have been applied to a test series in a later population sample. Men in the same age and risk groups for each pretest clinical classification show similar gradients of risk. Thus, exercise-enhanced criteria for risk assessment are validated. Age-standardized event rates show a reduction longitudinally in healthy men and patients who have had coronary bypass surgery.

Bundle branch block in patients with chronic coronary artery disease: angiographic correlates and prognostic significance.

The onset of bundle branch block during acute myocardial infarction is indicative of ischemia in the distribution of the left anterior descending coronary artery. However, whether patients with chronic coronary artery disease and bundle branch block have a predominance of left anterior descending artery lesions is not known. Similarly, the prognostic implications of bundle branch block have been studied primarily in the setting of acute myocardial infarction, and the independent prognostic implications of bundle branch block in patients with chronic coronary artery disease are not known. The electrocardiograms (ECGs) of 15,609 patients with chronic coronary artery disease who underwent coronary and left ventricular angiography as part of the Coronary Artery Surgery Study (CASS) were reviewed, and 522 patients with bundle branch block were identified. Patients with bundle branch block had both more extensive coronary artery disease and worse left ventricular function than did patients without bundle branch block. However, no particular location of coronary artery stenosis or left ventricular wall motion abnormality predominated in patients with bundle branch block. During a follow-up period of 4.9 +/- 1.3 years, 2,386 patients died. Actuarial probability of mortality at 2 years in patients with left bundle branch block was more than five times that in patients without bundle branch block (p less than 0.0001), and in patients with right bundle branch block the mortality rate was approximately twice that in patients without bundle branch block (p less than 0.0001). Stepwise Cox regression analysis showed that left bundle branch block, but not right bundle branch block, was a strong predictor of mortality, independent of degree of heart failure, extent of coronary disease and other variables (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Research collaboration.

The complexity and cost of cardiovascular medical care dictate research to deliver high quality and cost-conscious cardiovascular care. This goal is aided by modeling medical decision making. To be useful, the modeling must be based on real data so that the results can serve as a guide to actual practice. It is suggested that a registry of randomized clinical trials and larger data bases in cardiovascular disease and health care delivery be established. The registry would be a resource for those desiring to model decision making. The registry would contain key words allowing retrieval by modelers accessing the registry and would contain contact information for consideration of possible collaborative work. The initiation of such a registry should contain plans for its evaluation to determine whether the registry itself is a cost-effective tool to encourage the needed research.

Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol.

OBJECTIVES: Do the benefits of intensive lipid-lowering therapy extend to patients with only borderline or moderately elevated levels of low density lipoprotein (LDL) cholesterol? BACKGROUND: The merits of the present LDL cholesterol treatment goal of < or = 100 mg/dl need to be clarified for patients without high levels of LDL cholesterol, particularly for those patients previously classified as having only borderline high (130 to 159 mg/dl) or desirable (101 to 130 mg/dl) levels. METHODS: Disease change and clinical events were examined in LDL cholesterol subgroups in the Familial Atherosclerosis Treatment Study (FATS) trial, a randomized, blinded, quantitative arteriographic comparison of one conventional and two intensive lipid-lowering strategies in men with coronary artery disease, a positive family history and apolipoprotein B > or = 125 mg/dl. The primary end point, disease change per patient, was measured as the mean change in severity of stenosis (delta %SProx) among nine standard proximal segments. RESULTS: Of the 120 patients completing the 30-month protocol, 60 had a baseline LDL cholesterol < 90th percentile (mean LDL cholesterol 152 mg/dl) and 60 > 90th percentile (mean LDL cholesterol 221 mg/dl). Thirty-one patients had levels < 160 mg/dl (mean LDL cholesterol 134 mg/dl) and 89 > 160 mg/dl (mean LDL cholesterol 205 mg/dl). Patients with LDL cholesterol < 90th percentile benefited angiographically from therapy (delta %SProx = -1.5% diameter stenosis [regression] during intensive therapy vs. +2.3% diameter stenosis [progression] during conventional therapy, p < 0.01), as did patients with LDL cholesterol < 160 mg/dl (delta %SProx = -4.2% vs. +3.3% diameter stenosis, p = 0.0001). By comparison, angiographic benefit was less pronounced among those entering with very high LDL cholesterol (delta %SProx = -0.2% vs. +1.9% diameter stenosis, p = 0.07) or with LDL cholesterol > or = 160 mg/dl (delta %SProx = +0.2% vs. +1.6% diameter stenosis, p = 0.13). Intensive therapy resulted in a statistically significant reduction in clinical events only in the subgroup with baseline LDL cholesterol < 90th percentile (2 of 42 vs. 8 of 29 patients initially enrolled, p = 0.01) and a trend toward fewer events in patients with LDL cholesterol < 160 mg/dl (2 of 20 vs. 6 of 15 patients, p = 0.05). No such difference was seen in the higher LDL cholesterol subgroups. CONCLUSIONS: Treatment benefit in the FATS trial was not confined to patients with very high levels of LDL cholesterol and was in fact particularly evident in those patients with levels < 160 mg/dl. Such patients should be considered more likely, not less, to benefit from intensive lipid-lowering therapy.

Prevalence and prognostic significance of silent and symptomatic ischemia after coronary bypass surgery: a report from the Coronary Artery Surgery Study (CASS) randomized population.

The prevalence and prognostic significance of postoperative myocardial ischemia, as detected by exercise testing, were prospectively assessed in 174 patients from the Coronary Artery Surgery Study (CASS) randomized surgical population who had exercise testing before and 6 months after coronary artery bypass graft surgery. Whereas the prevalence of symptomatic ischemia significantly decreased postoperatively (52% vs. 6%, p less than 0.001), the frequency of silent myocardial ischemia did not change (30% vs. 29%). Survival at 12 years after bypass surgery based on the 6-month postoperative exercise test results was significantly better for the 112 patients with no ischemia (80%) than for the 51 patients with silent ischemia (68%) or the 11 patients with symptomatic ischemia (45%). These data show that coronary artery bypass graft surgery diminishes the overall prevalence of symptomatic but not silent ischemia and that both silent and symptomatic ischemia adversely affect the postoperative prognosis of these patients.

Comparison of coronary artery bypass surgery and medical therapy in patients with exercised-induced silent myocardial ischemia: a report from the Coronary Artery Surgery Study (CASS) registry.

To determine whether coronary artery bypass surgery would prolong survival in patients with silent myocardial ischemia during exercise testing, the data on 692 such patients from the Coronary Artery Surgery Study (CASS) registry were analyzed. The patients were followed up for up to 7 years after medical (n = 424) or surgical (n = 268) therapy. Stratification of patients into subsets was based on the results of cardiac catheterization. Surgical benefit was greatest in the patients with three vessel coronary artery disease or abnormal left ventricular function. Among the 75 patients with three vessel coronary disease and left ventricular dysfunction, the 7 year survival rate was 37% for the medical group and 90% for the surgical group (p less than 0.0001). Thus, among patients with silent myocardial ischemia during exercise testing in this nonrandomized study, survival appeared to be enhanced by coronary artery bypass surgery in subsets of patients with severe coronary artery disease and abnormal left ventricular function.

Should airline pilots be eligible to resume active flight status after coronary bypass surgery?: a CASS registry study.

Medical certification to return to work after coronary bypass surgery in occupations that carry a risk to public safety is controversial, particularly for airline pilots. To address this issue, 10,312 patients from the CASS registry who underwent coronary bypass surgery were studied and 2,326 men with clinical and postoperative characteristics similar to those of the average airline pilot who might apply to renew his license after surgery were selected. The 5 year probability of remaining free of an acute cardiac event, defined as acute coronary insufficiency, myocardial infarction or sudden death, was 0.92 +/- 0.01 (mean +/- SE) for the 1,207 men without previous myocardial infarction and 0.98 +/- 0.01 for the 122 men who never smoked and did not have a history of hypertension. Among the 1,119 men with a previous myocardial infarction, the probability of remaining free of acute cardiac events was 0.91 +/- 0.02 and 0.92 +/- 0.02 when left ventricular contraction score was 5 to 9 and 10 or greater, respectively. In this patient subgroup, mortality rate was similar to that of the age-matched U.S. male population when the left ventricular contraction score was 5 to 9 (4.0% versus 4.3%; p = NS) but significantly worse when the left ventricular contraction score was 10 or greater (7% versus 4.2%; p = 0.05). The data from this CASS registry study are pertinent to the question of operationally unlimited first-class medical certification of carefully selected airline pilots after coronary bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of exercise testing in identifying patients with improved survival after coronary artery bypass surgery.

To determine whether exercise testing can identify patients whose survival might be prolonged by coronary artery bypass surgery, the results of bypass surgery were compared with those of medical therapy alone in 5,303 nonrandomized patients from the Coronary Artery Surgery Study registry who underwent exercise testing. Patients in the two treatment groups differed substantially with regard to important baseline variables. Analysis of 32 variables by Cox's regression model for survival revealed an independent beneficial effect of bypass surgery on survival (p less than 0.00001). Patients were then stratified into subsets according to the results of exercise testing. Surgical benefit was greatest in the 789 patients who exhibited at least 1 mm of ST segment depression and who could exercise only into stage 1 or less. Among the 398 patients with three vessel coronary disease showing these characteristics, 7 year survival was 58% for the medical group and 81% for the surgical group (p less than 0.001). There was no difference in survival between the surgical and medical groups among the 1,545 patients without ischemic ST segment depression who were able to exercise into stage 3 or greater. Thus, in patients who demonstrate ischemia on exercise testing and whose exercise capacity is limited, coronary bypass surgery appears to improve survival in comparison with medical therapy alone.

Five-year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). CASS Participating Investigators and Staff.

OBJECTIVES: The Coronary Artery Surgery Study (CASS) required participants to undergo follow-up angiography at 5 years to identify clinical and angiographic features associated with progression of coronary artery disease. BACKGROUND: The CASS randomized 780 patients at 11 participating clinical centers between an initial strategy of medical therapy versus bypass surgery. Five clinical sites accomplished follow-up angiography in > 50% of their randomized subjects within a 42- to 66-month period after the entry arteriogram (n = 314). METHODS: Qualified clinical site angiographers, using side by side film review, evaluated an average of 13 segments/patient on both arteriograms for initial stenosis severity, morphologic features, lesion location and occurrence of disease progression or occlusion. Progression was defined as further definite narrowing by > or = 15% and occlusion as lesion progression to > or = 98%. Lesions were subcategorized as to whether they were univariate and had or had not been treated with bypass surgery. Multivariate logistic regression analyses were performed. RESULTS: For nonbypassed segments, right coronary artery and left anterior descending artery proximal and midlocations were associated with disease progression. For stenosis-containing segments, the initial severity, a non-left anterior descending artery location and increased treadmill duration predicted progression. Segment occlusion was associated with initial lesion severity, right coronary artery location and subsequent interval myocardial infarction. There were few predictors of progression or occlusion in bypassed arteries, other than initial lesion severity. CONCLUSIONS: Univariate and multivariate associations with lesion progression and occlusion included diabetes, lesion location, elevated cholesterol level, interval infarction and lesion morphology. These angiographic results, collected in a prospective trial, are consistent with known risk factors.

Effects of smoking on survival and morbidity in patients randomized to medical or surgical therapy in the Coronary Artery Surgery Study (CASS): 10-year follow-up. CASS Investigators.

OBJECTIVES: The goal of this study was to ascertain how continued cigarette smoking or smoking cessation related to long-term survival and morbidity in patients with established coronary artery disease managed with medical therapy or coronary bypass surgery. BACKGROUND: Although the association of cigarette smoking with coronary artery disease is well established, the morbidity and mortality associated with smoking behavior in patients with such disease receiving medical or surgical therapy are less well established. METHODS: The 780 patients randomized to medical therapy or coronary bypass surgery in the Coronary Artery Surgery Study (CASS) were subgrouped according to smoking behavior during a mean 11.2-year follow-up interval. Comparisons between smokers and nonsmokers were accomplished by univariate and Cox time-dependent multivariate analyses. RESULTS: Survival at 10 years after entry into the study was 82% among 468 patients who reported no smoking during follow-up (nonsmokers) compared with 77% among the 312 smokers (p = 0.025). Survival was 80% among those who smoked at entry but stopped (quitters) versus 69% among those who continued smoking (p = 0.025). For patients who smoked at baseline and were randomized to bypass surgery, survival at 10 years was 84% among quitters and 68% among nonquitters (p = 0.018); the difference in survival between quitters (75%) and nonquitters (71%) was less among those randomized to medical therapy (p = NS). Among those who smoked at baseline, continued smoking increased the relative risk of death by 1.73. After 10 years, smokers, in comparison with nonsmokers, were less likely to be angina free and more likely to be unemployed and had more activity limitation and more hospital admissions (primarily for chest pain, heart attack, cardiac catheterization, peripheral vascular surgery and stroke). CONCLUSIONS: Thus, among patients with documented coronary artery disease, continued cigarette smoking may result in decreased survival--especially among those undergoing bypass surgery. Moreover, smokers have more angina, more unemployment, a greater limitation of physical activity and more hospital admissions.

Medical and surgical management of early Q wave myocardial infarction. I. Effects of surgical reperfusion on survival, recurrent myocardial infarction, sudden death and functional class at 10 or more years of follow-up.

To define the outcome of patients given medical or surgical therapy for Q wave myocardial infarction, 387 patients were followed up for 10 to 13 years (mean 11.4). On study entry the groups had similar distributions for variables such as mean age, gender, previous myocardial infarction, abnormal creatine kinase activity, area of infarction, number of vessels diseased and clinical classification. The hospital mortality rate of the medical versus surgical group was 11.5% (23 of 200) versus 5.8% (11 of 187) (p = 0.07). Early reperfusion (that is, less than or equal to 6 h) resulted in a lower mortality rate than did medical therapy--2% (2 of 100) versus 11.5% (23 of 200) (p less than 0.05)--whereas the hospital mortality rate with late reperfusion was 10.3% (9 of 87). The long-term mortality rate of the medical and surgical groups was 41% (82 of 200) versus 27% (51 of 187) (p = 0.0007) with use of an adjusted Cox proportional hazards model. In the survivors, the differences between medical and surgical groups in recurrent myocardial infarction, mortality associated with reinfarction and sudden death were prospectively followed and evaluated by the life table method. Recurrent myocardial infarction was not prevented by surgical reperfusion or medical therapy (23% in both groups), however, the mortality rate in patients with recurrent infarction was higher in the medical therapy group--36.6% (15 of 41) versus 17.5% (7 of 40) (p = 0.04). The mortality difference did not depend on early or late surgical reperfusion. In the in-hospital survivors, the incidence of sudden death was 17.5% in the medical (31 of 177) versus 7.4% (13 of 176) in the surgical group (p = 0.01). This difference was much more pronounced in the early reperfusion group. Functional class was significantly lower than that for medical therapy in the early reperfusion but not the late reperfusion group. Thus, in comparable groups given medical and surgical therapy for acute myocardial infarction and followed up for greater than or equal to 10 years, surgical reperfusion appears to offer improved longevity in selected cases (when implemented early) but does not prevent recurrent myocardial infarction. The associated mortality with recurrent myocardial infarction is less as is the incidence of sudden death. Finally, lower functional class occurs most often in patients given early reperfusion.

Medical and surgical management of early Q wave myocardial infarction. II. Effects on mortality and global and regional left ventricular function at 10 or more years of follow-up.

To determine the long-term effect of surgical reperfusion on survival and left ventricular function of patients with anterior and inferior Q wave myocardial infarction, 387 patients were followed up for greater than or equal to 10 years after early Q wave infarction. In the anterior infarction group, 102 received conventional therapy and 101 underwent surgical reperfusion. The overall hospital mortality rate in the medically and surgically treated patients was different (16.7% [17 of 102] versus 6.9% [7 of 101], p less than 0.05). The cumulative 13 year actuarial mortality rate widened between the anterior medical and surgical groups (54% versus 31%, p = 0.0003) by the adjusted Cox proportional hazards model. The hospital mortality rate with early reperfusion (that is, less than or equal to 6 h of symptom onset) was 2% (1 of 51), whereas the mortality rate with late reperfusion was 12% (6 of 50). The 13 year actuarial cumulative mortality rate was significantly lower in both the early and late reperfusion groups (30% and 33%, respectively) than in the conventional therapy group (54%, p = 0.0006). The mortality rate in patients receiving surgery after surviving initial medical therapy was 50% (15 of 30). In the survivors of anterior Q wave myocardial infarction, improved global ejection fraction was seen in the patients undergoing early (54 +/- 13%) and late (50 +/- 10%) surgery relative to those receiving conventional therapy (43 +/- 11%, p less than 0.05). Only the early reperfusion group had better regional function of the anterior wall than that of the conventional therapy group. Thus, ventricular function correlated with improved long-term survival. In the patients with inferior Q wave myocardial infarction, the overall hospital mortality rate in the medical and surgical groups was not different (6.1% [6 of 98] versus 4.6% [6 of 86], p = NS). Likewise, the 13 year actuarial cumulative mortality rate was not different between the medical and surgical groups overall (32% versus 30%, p = 0.29) by the adjusted Cox proportional hazards model. The hospital mortality rate in the early reperfusion group was lower than that in the late reperfusion group (2.0% [1 of 49] versus 8.1% [3 of 37], p = NS). The 13 year actuarial cumulative mortality rate was lower in the early surgical group compared with that in the medical group (19% versus 32%, p = 0.04). The late surgical group had a similar 13 year actuarial cumulative mortality rate to that of the medical group (47% versus 32%, respectively, p = 0.47).(ABSTRACT TRUNCATED AT 400 WORDS)

Prognostic importance of a clinical profile and exercise test in medically treated patients with coronary artery disease.

To identify predictors of mortality in medically treated patients with symptomatic coronary artery disease, 30 variables were analyzed in 4,083 patients. Regression analysis demonstrated that seven variables were independent predictors of survival. A high risk subgroup (annual mortality rate above 5%) was identified, consisting of patients with either a congestive heart failure score of 3 to 4 or 1 mm or greater ST segment depression and final exercise stage of 1 or less. When all 30 variables were analyzed conjointly, the left ventricular contraction pattern (p less than 0.0001) and the number of diseased coronary vessels (p less than 0.003) proved to be the most important predictors of survival. In a subgroup of 572 patients with three vessel coronary disease and preserved left ventricular function, the probability of survival at 4 years ranged from 53% for patients only able to achieve stage 1/2 of exercise to 100% for patients able to exercise into stage 5 (p less than 0.004). Thus, in patients with defined coronary pathoanatomy, clinical and exercise variables primarily relating to the functional state of the left ventricle are helpful in assessing prognosis.