Data for cardiovascular modeling.

Data are required for a meaningful approach to quality and cost-conscious cardiovascular care. How to identify the types of data available and their sources, advantages and limitations to their use, issues involved in combining data from different sources for decision modeling and some possible solutions are discussed in this summary of the Working Group on Data for Cardiovascular Modeling.

Estimated contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality: the Minnesota Heart Survey.

OBJECTIVES: This study assessed the possible contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality in the Minneapolis-St. Paul metropolitan area population between 1970 and 1984. BACKGROUND: Coronary artery bypass graft surgery is a major contemporary therapeutic approach for coronary heart disease. Its use has increased over the past two decades because it provides relief of symptoms and, in certain circumstances, prolongs life. During the period that age-adjusted coronary heart disease mortality has decreased, the use of coronary artery bypass graft surgery has increased dramatically, suggesting a relation. METHODS: All 30- to 74-year old Minneapolis-St. Paul area residents undergoing coronary artery bypass graft surgery between 1970 and 1984 (9,548 patients) were registered; their medical records were abstracted; and their survival was ascertained. These data were used in a medical survival probability model using a multivariate analytical approach developed from registries of patients treated medically. The model assumed that coronary artery bypass graft surgery was not available. Two annual mortality rates were compared: the observed Minneapolis-St. Paul annual coronary heart disease mortality rate and the modeled annual coronary heart disease mortality rate. The difference between these rates was the estimated contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality rates. RESULTS: Between 1970 and 1984, the estimated surgical contribution increased from 0.2% (increased mortality) to +6.6% of the annual decrease in Minneapolis-St. Paul coronary heart disease mortality. CONCLUSIONS: Between 1970 and 1984, the contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality, although small, gradually increased. This change appeared to be related to an increased frequency of coronary artery bypass graft surgery, improved operative mortality and changes in the clinical mix of surgical patients.

Clinical judgment and therapeutic decision making.

Clinical decision making is under increased scrutiny due to concerns about the cost and quality of medical care. Variability in physician decision making is common, in part because of deficiencies in the knowledge base, but also due to the difference in physicians' approaches to clinical problem solving. Evaluation of patient prognosis is a critical factor in the selection of therapy, and careful attention to methodology is essential to provide reliable information. Randomized controlled clinical trials provide the most solid basis for the establishment of broad therapeutic principles. Because randomized studies cannot be performed to address every question, observational studies will continue to play a complementary role in the evaluation of therapy. Randomized studies in progress, meta analyses of existing data, and increased use of administrative and collaborative clinical data bases will improve the knowledge base for decision making in the future.

Comparison of predictions based on observational data with the results of randomized controlled clinical trials of coronary artery bypass surgery.

Clinical decisions are most secure when based on findings from several large randomized clinical trials, but relevant randomized trial data are often unavailable. Analyses using clinical data bases might provide useful information if statistical methods can adequately correct for the lack of randomization. To test this approach, the findings of the three major randomized trials of coronary bypass surgery were compared with predictions of multivariable statistical models derived from observations in the Duke Cardiovascular Disease Databank. Clinical characteristics of patients at Duke University Medical Center who met eligibility requirements for each major randomized trial were used in the models to predict 5 year survival rates expected for medical and surgical therapy in each randomized trial. Model predictions agreed well with randomized trial results and were within the 95% confidence limits of the observed survival rates in 24 (92%) of 26 clinical subgroups. The overall correlation between predicted and observed survival rates was good (Spearman coefficient 0.73, p less than 0.0001). These results suggest that carefully performed analyses of observational data can complement the results of randomized trials.

Importance of clinical measures of ischemia in the prognosis of patients with documented coronary artery disease.

To examine the value of clinical measures of ischemia for stratifying prognosis, 5,886 consecutive patients who had symptomatic significant (greater than or equal to 75% stenosis) coronary artery disease were studied. Using the Cox regression model in a randomly selected half of the patients, the prognostically independent clinical variables were weighted and arranged into a simple angina score: angina score = angina course X (1 + daily angina frequency) + ST-T changes, where angina course was equal to 3 if unstable or variant angina was present, 2 if the patient's angina was progressive with nocturnal episodes, 1 if it was progressive without nocturnal symptoms and 0 if it was stable; 6 points were added for the presence of "ischemic" ST-T changes. This angina score was then validated in an independent patient sample. The score was a more powerful predictor of prognosis than was any individual anginal descriptor. Furthermore, the angina score added significant independent prognostic information to the patient's age, sex, coronary anatomy and left ventricular function. Patients with three vessel disease and a normal ventricle (n = 1,233) had a 2 year infarction-free survival rate of 90% with an angina score of 0 and a 68% survival rate with an angina score greater than or equal to 9. With an ejection fraction less than 50% and three vessel disease (n = 1,116), the corresponding infarction-free survival figures were 76 and 56%.(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility and cost-saving potential of outpatient cardiac catheterization.

To determine the feasibility and cost-saving potential of substituting outpatient for inpatient cardiac catheterization, 986 consecutive procedures were studied at a large referral hospital. Patients were classified prospectively as to their eligibility for outpatient cardiac catheterization according to published guidelines. Resource consumption was recorded, and cost savings were then calculated by analyzing the specific supply and personnel costs that could change as a result of inpatient versus outpatient status. Of the total of 986 patients who underwent diagnostic catheterization, 240 (24%) were outpatients, 279 (28%) were inpatients but had no exclusion criteria for outpatient catheterization and 467 (47%) were inpatients who had one or more exclusions for outpatient catheterization. The most common reasons for exclusion from outpatient catheterization were congestive heart failure (22%), unstable angina (15%), noncoronary heart disease (14%), recent myocardial infarction (11%) and severe noncardiac disease (9%). Inpatients with no exclusions for the outpatient procedure tended to be sicker than outpatients because they were older (p = 0.002), had a lower ejection fraction (p = 0.009) and had more triple vessel coronary artery disease (p less than 0.0001). The cost of the catheterization procedure itself was not different between inpatients and outpatients. Laboratory testing was more frequent among inpatients, however, and "room and board" costs were significantly higher. Although the difference in hospital charges for inpatients and outpatients was $580, a rigorous analysis indicated that the potential cost savings was only 38% of this amount, or $218 per eligible patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration of thrombolytic therapy in the community hospital: established principles and unresolved issues.

In patients with acute myocardial infarction presenting to community hospitals, thrombolytic therapy should be initiated as rapidly as possible under the supervision of a physician. Paramedic or nurse-initiated pre-hospital therapy is currently investigational. Each hospital must have a detailed evaluation and treatment protocol for acute myocardial infarction that specifies the timetable for patient evaluation, who should or should not receive thrombolytic therapy and the proper dose and mode of administration of the agent or agents to be used. Monitoring after the administration of thrombolytic therapy should focus on arrhythmias, hemodynamic problems, recurrent ischemia and bleeding. The role of early cardiac catheterization to detect patients who have unsuccessful thrombolysis or who require mechanical revascularization procedures is under active investigation. The design of the Thrombolysis and Angioplasty in Acute Myocardial Infarction (TAMI) 5 study, which addresses the role of acute interventional catheterization in the treatment of patients with acute myocardial infarction, is described.

Cardiac rupture, mortality and the timing of thrombolytic therapy: a meta-analysis.

This study examined the relation between the risk of cardiac rupture and the timing of thrombolytic therapy for acute myocardial infarction. To test the hypothesis that cardiac rupture is prevented by early thrombolytic therapy but is promoted by late treatment, randomized controlled trials of thrombolytic agents for myocardial infarction were pooled. A logistic regression model including 58 cases of cardiac rupture among 1,638 patients from four trials showed that the odds ratio (treated/control) of cardiac rupture was directly correlated with time to treatment (p = 0.01); at 7 h, the odds ratio was 0.4 (95% confidence limits 0.17 to 0.93); at 11 h, it was 0.93 (0.53 to 1.60) and at 17 h, it was 3.21 (1.10 to 10.1). Analysis of data from the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) trial independently confirmed the relation between time to thrombolytic therapy and risk of cardiac rupture (p = 0.03). Analysis of 4,692 deaths in 44,346 patients demonstrated that the odds ratio of death was also directly correlated with time to treatment (p = 0.006); at 3 h, the odds ratio for death was 0.72 (0.67 to 0.77); at 14 h, it was 0.88 (0.77 to 1.00) and at 21 h, it was 1 (0.82 to 1.37). Thrombolytic therapy early after acute myocardial infarction improves survival and decreases the risk of cardiac rupture. Late administration of thrombolytic therapy also appears to improve survival but may increase the risk of cardiac rupture.

Comparison of survival of amiodarone-treated patients with coronary artery disease and malignant ventricular arrhythmias with that of a control group with coronary artery disease.

Although amiodarone is effective in the treatment of ventricular arrhythmias, it is associated with serious toxic effects. In addition, the prognosis of patients with malignant ventricular arrhythmias and coronary artery disease treated with amiodarone remains poor. The survival of 54 consecutive patients with angiographically documented coronary artery disease and symptomatic ventricular tachycardia or ventricular fibrillation treated with amiodarone was compared with that of 5,125 medically treated patients with coronary artery disease. The amiodarone group was older, with worse left ventricular function and more peripheral and cerebrovascular disease. The 1 year survival probability was 0.73 for the amiodarone group and 0.94 for the control coronary artery disease group. At 2 years of follow-up, the survival probabilities were 0.60 and 0.90 for the amiodarone and the control group, respectively. When the survival curves were adjusted for group differences in baseline prognostic characteristics (integrated as a previously published hazard score), there was no difference in the prognosis of the two groups. These findings suggest that treatment with amiodarone of malignant ventricular arrhythmias associated with coronary artery disease maintains patients on an underlying survival curve determined by the degree of myocardial dysfunction, clinical characteristics and coronary anatomy, and that amiodarone does not have a deleterious effect on survival.

Prognosis in cardiogenic shock after acute myocardial infarction in the interventional era.

OBJECTIVES: The purpose of this study is to describe the outcome in cardiogenic shock treated with aggressive reperfusion therapy and to identify factors predictive of in-hospital and long-term mortality. BACKGROUND: Cardiogenic shock is the most common cause of death in patients admitted to the coronary care unit. Although studies have reported lower mortality rates in shock treated with angioplasty, few studies have described a cohort of patients with shock who were not selected because they were most likely to benefit from reperfusion therapy. METHODS: A consecutive series of 200 patients admitted with acute myocardial infarction complicated by cardiogenic shock were studied. RESULTS: The in-hospital mortality rate was 53%. Variables with significant univariable association with in-hospital death included patency of the infarct-related artery, patient age, lowest cardiac index, highest arteriovenous oxygen difference and left main coronary artery disease. The most important independent predictors of in-hospital death were patency of the infarct-related artery, cardiac index and peak creatine kinase, MB fraction. The mortality rate in patients with patent infarct-related arteries was 33% versus 75% in those with closed arteries and 84% in those in whom arterial patency was unknown. Patients who survived to hospital discharge were followed up for a median of 2 years, with a mortality rate of 18% after 1 year. The best descriptors of the relation between these variables and postdischarge mortality included age, peak creatine kinase, ejection fraction and patency of the infarct-related artery. CONCLUSIONS: In a large consecutive series of patients with cardiogenic shock with complete follow-up, patency of the infarct-related artery was most strongly associated with in-hospital and long-term mortality. This finding supports an aggressive interventional strategy in patients with cardiogenic shock.

Ergonovine maleate testing during cardiac catheterization: a 10-year perspective in 3,447 patients without significant coronary artery disease or Prinzmetal's variant angina.

The utility of ergonovine testing for coronary artery spasm was assessed in 3,447 patients with angiographically insignificant (less than 50% diameter stenosis) or no coronary artery disease. No patients clinically had Prinzmetal's variant angina. Overall, 4% had a positive ergonovine test result, defined by spasm causing greater than or equal to 75% focal stenosis. Complications related to ergonovine use occurred in 11 patients (0.03%). In a training sample of 1,136 patients (studied between 1980 and 1984), two independent predictors of spasm were found by using multivariate analysis: the amount of visible coronary artery disease on the coronary angiogram (p less than 0.0001) and a smoking history (p = 0.001). A model to predict spasm based on these variables was validated in a test group of 2,311 patients who received ergonovine from 1985 to 1989. This model allowed the identification of a subset of 400 patients in the validation sample who had a 10% positive test rate compared with a 2% positive test rate in the remaining patients. These results should permit clinicians who use provocative testing in the catheterization laboratory to reserve testing for the subset of this group of patients most likely to have abnormal findings.

Painless exercise ST deviation on the treadmill: long-term prognosis.

To evaluate the clinical correlates and long-term prognostic significance of silent ischemia during exercise, 1,698 consecutive symptomatic patients with coronary artery disease who had both treadmill testing and cardiac catheterization were studied. These patients were classified into three groups: Group 1 = patients with no exercise ST deviation (n = 856), Group 2 = patients with painless exercise ST deviation (n = 242) and Group 3 = patients with both angina and ST segment deviation during exercise (n = 600). Patients with exercise angina had a history of a longer and more aggressive anginal course (with a greater frequency of angina, with nocturnal episodes and/or progressive symptom pattern) and more severe coronary artery disease (almost two-thirds had three vessel disease). The 5 year survival rate among the patients with painless ST deviation was similar to that of patients without ST deviation (86% and 88%, respectively) and was significantly better than that of patients with both symptoms and ST deviation (5 year survival rate 73% in patients with exercise-limiting angina). Similar trends were obtained in subgroups defined by the amount of coronary artery disease present. In the total study group of 1,698 patients, silent ischemia on the treadmill was not a benign finding (average annual mortality rate 2.8%) but, compared with symptomatic ischemia, did indicate a subgroup of patients with coronary artery disease who had a less aggressive anginal course, less coronary artery disease and a better prognosis. Thus, silent ischemia during exercise testing in patients with symptomatic coronary artery disease represents an intermediate risk response in the spectrum of exercise-induced ischemia.

Identification of preoperative variables needed for risk adjustment of short-term mortality after coronary artery bypass graft surgery. The Working Group Panel on the Cooperative CABG Database Project.

OBJECTIVES: The purpose of this consensus effort was to define and prioritize the importance of a set of clinical variables useful for monitoring and improving the short-term mortality of patients undergoing coronary artery bypass graft surgery (CABG). BACKGROUND: Despite widespread use of data bases to monitor the outcome of patients undergoing CABG, no consistent set of clinical variables has been defined for risk adjustment of observed outcomes for baseline differences in disease severity among patients. METHODS: Experts with a background in epidemiology, biostatistics and clinical care with an interest in assessing outcomes of CABG derived from previous work with professional societies, government or academic institutions volunteered to participate in this unsponsored consensus process. Two meetings of this ad hoc working group were required to define and prioritize clinical variables into core, level 1 or level 2 groupings to reflect their importance for relating to short-term mortality after CABG. Definitions of these 44 variables were simple and specific to enhance objectivity of the 7 core, 13 level 1 and 24 level 2 variables. Core and level 1 variables were evaluated using data from five existing data bases, and core variables only were examined in an additional two data bases to confirm the consensus opinion of the relative prognostic power of each variable. RESULTS: Multivariable logistic regression models of the seven core variables showed all to be predictive of bypass surgery mortality in some of the seven existing data sets. Variables relating to acuteness, age and previous operation proved to be the most important in all data sets tested. Variables describing coronary anatomy appeared to be least significant. Models including both the 7 core and 13 level 1 variables in five of the seven data sets showed the core variables to reflect 45% to 83% of the predictive information. However, some level 1 variables were stronger than some core variables in some data sets. CONCLUSIONS: A relatively small number of clinical variables provide a large amount of prognostic information in patients undergoing CABG.

Survival and cardiac event rates in the first year after emergency coronary angioplasty for acute myocardial infarction.

One year survival and event-free survival rates were analyzed in 342 patients with acute myocardial infarction who were consecutively enrolled in a treatment protocol of early intravenous thrombolytic therapy followed by emergency coronary angioplasty. Ninety-four percent of the patients achieved successful reperfusion, including 4% with failed angioplasty whose perfusion was maintained by means of a reperfusion catheter before emergency bypass surgery. The procedural mortality rate was 1.2% and the total in-hospital mortality rate was 11%. Ninety-two percent of surviving nonsurgical patients who underwent repeat cardiac catheterization were discharged from the hospital with an open infarct-related artery. The related cumulative 1 year survival rate for all patients managed with this treatment strategy was 87%, and the cardiac event-free survival rate was 84%. The 1 year survival for hospital survivors was 98% and the infarct-free survival rate was 94%. Multivariable analysis identified the following factors as independent predictors of subsequent cardiovascular death: cardiogenic shock, greater age, lower ejection fraction, female gender and a closed infarct-related vessel on the initial coronary angiogram. Among patients with cardiogenic shock, despite a 42% in-hospital mortality rate, only 4% died during the first year after hospital discharge. Similarly, the in-hospital and 1 year postdischarge mortality rates were 19 and 4%, respectively, for patients with an initial ejection fraction less than 40, and 25 and 3%, respectively, for patients greater than 65 years. An aggressive treatment strategy including early thrombolytic therapy, emergency cardiac catheterization, coronary angioplasty and, when necessary, bypass surgery resulted in a high rate of infarct vessel patency.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of a coronary artery jeopardy score.

The prognostic value of a coronary artery jeopardy score was evaluated in 462 consecutive nonsurgically treated patients with significant coronary artery disease, but without significant left main coronary stenosis. The jeopardy score is a simple method for estimating the amount of myocardium at risk on the basis of the particular location of coronary artery stenoses. In patients with a previous myocardial infarction, higher jeopardy scores were associated with a lower left ventricular ejection fraction. When the jeopardy score and the number of diseased vessels were considered individually, each descriptor effectively stratified prognosis. Five year survival was 97% in patients with a jeopardy score of 2 and 95, 85, 78, 75 and 56%, respectively, for patients with a jeopardy score of 4, 6, 8, 10 and 12. In multivariable analysis when only jeopardy score and number of diseased vessels were considered, the jeopardy score contained all of the prognostic information. Thus, the number of diseased vessels added no prognostic information to the jeopardy score. The left ventricular ejection fraction was more closely related to prognosis than was the jeopardy score. When other anatomic factors were examined, the degree of stenosis of each vessel, particularly the left anterior descending coronary artery, was found to add prognostic information to the jeopardy score. Thus, the jeopardy score is a simple method for describing the coronary anatomy. It provides more prognostic information than the number of diseased coronary arteries, but it can be improved by including the degree of stenosis of each vessel and giving additional weight to disease of the left anterior descending coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of ventricular arrhythmias associated with treadmill exercise testing in patients studied with cardiac catheterization for suspected ischemic heart disease.

The prognostic information provided by ventricular arrhythmias associated with treadmill exercise testing was evaluated in 1,293 consecutive nonsurgically treated patients undergoing an exercise test within 6 weeks of cardiac catheterization. The 236 patients with simple ventricular arrhythmias (at least one premature ventricular complex, but without paired complexes or ventricular tachycardia) had a higher prevalence of significant coronary artery disease (57 versus 44%), three vessel disease (31 versus 17%) and abnormal left ventricular function (43 versus 24%) than did patients without ventricular arrhythmias. Patients with paired complexes or ventricular tachycardia had an even higher prevalence of significant coronary artery disease (75%), three vessel disease (39%) and abnormal left ventricular function (54%). In the 620 patients with significant coronary artery disease, patients with paired complexes or ventricular tachycardia had a lower 3 year survival rate (75%) than did patients with simple ventricular arrhythmias (83%) and patients with no ventricular arrhythmias (90%). Ventricular arrhythmias were found to add independent prognostic information to the noninvasive evaluation, including history, physical examination, chest roentgenogram, electrocardiogram and other exercise test variables (p = 0.03). Ventricular arrhythmias made no independent contribution once the cardiac catheterization data were known. In patients without significant coronary artery disease, no relation between ventricular arrhythmias and survival was found.

Clinical experience and predicting survival in coronary disease.

To study the accuracy with which long-term prognosis can be predicted in patients with coronary artery disease, prognostic predictions obtained from a large, diverse sample of practicing cardiologists were compared with predictions from a multivariable statistical model. Test samples of 10 patients each were selected from a large series of medically treated patients with significant coronary disease. Using detailed clinical summaries, 49 cardiologists each predicted the probability of 3-year survival and infarction-free survival for 10 patients. Cox regression models, developed using patients who were not in the test samples, were also used to predict corresponding outcome probabilities for each test patient. Overall, the model estimates of prognosis were significantly better than the doctors' predictions. The rank correlation of model predictions with 3-year survival was 0.60, compared with 0.52 for the physicians. Model predictions added significant prognostic information to the doctors' predictions, whereas the converse was not true. Where predictions were made by multiple doctors, the inter-physician variability was substantial. Neither practice characteristics nor extent of clinical experience significantly affected the physicians' predictive accuracy. In coronary artery disease, statistical models developed from carefully collected data can provide prognostic predictions that are more accurate than predictions of experienced clinicians made from detailed case summaries.

Natural history of cerebral complications of coronary artery bypass graft surgery.

We reviewed 1,669 patients who survived coronary artery bypass graft surgery between 1969 and 1981. A total of 75 cerebral complications were identified, including (1) altered mental state, (2) stroke, and (3) seizure in 64 patients (3.8%). Altered mental state (delirium, hypoxic-metabolic encephalopathy) occurred in 57 (3.4%). Postoperative arrhythmias were associated with an increased risk of altered mental state. Cerebral infarction occurred in 13 (0.8%). Patients who suffered stroke had a higher occurrence of carotid bruits and history of peripheral vascular disease. Seizures occurred in five patients (0.3%). Mortality in patients with a neurologic complication was 29%.

Estimating the likelihood of significant coronary artery disease.

Among 23 clinical characteristics examined in 3,627 consecutive, symptomatic patients referred for cardiac catheterization between 1969 and 1979, nine were found to be important for estimating the likelihood a patient had significant coronary artery disease. A model using these characteristics accurately estimated the likelihood of disease when applied prospectively to 1,811 patients referred since 1979 and when used to estimate the prevalence of disease in subgroups reported in the literature. Since accurate estimates of the likelihood of significant disease that are based on clinical characteristics are reproducible, they should be used in interpreting the results of additional noninvasive tests and in quantitating the added diagnostic value.

Estimating the likelihood of severe coronary artery disease.

PURPOSE: To determine which clinical characteristics obtained by a physician during an initial clinical examination are important for estimating the likelihood of severe coronary artery disease, and to determine whether estimates based on these characteristics remain valid when applied prospectively and in different patient groups. PATIENTS AND METHODS: We examined clinical characteristics predictive of severe disease in 6,435 consecutive symptomatic patients referred for suspected coronary artery disease between 1969 and 1983. RESULTS: Eleven of 23 characteristics were important for estimating the likelihood of severe coronary artery disease. A model using these characteristics accurately estimated the likelihood of severe disease in an independent sample of 2,342 patients referred since 1983. The model also accurately estimated the prevalence of severe disease in large series of patients reported in the literature. CONCLUSIONS: These findings suggest that the clinician's initial evaluation can identify patients at high or low risk of anatomically severe coronary artery disease. Cost-conscious quality care is encouraged by identifying patients at higher risk for severe coronary artery disease who are most likely to benefit from further evaluation.