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)

Prognostic implications of angiographically normal and insignificantly narrowed coronary arteries.

The clinical presentation and prognosis of 1,977 consecutive patients with normal coronary arteries or "insignificant" coronary artery disease (CAD) (no major epicardial artery with 75% or more luminal diameter narrowing) were examined. Compared with patients with significant CAD, these patients had a lower frequency of traditional cardiac risk factors and abnormalities on the rest and exercise electrocardiogram. Cardiac survival was 99% at 5 years of follow-up and 98% at 10 years for patients with normal or insignificantly narrowed coronary arteries. Patients with normal coronary arteries differed from those with insignificant CAD in their myocardial infarction free survival rate: 99% at 5 years and 98% at 10 years for patients with normal coronary arteries, compared with 97% at 5 years and 90% at 10 years for patients with insignificant CAD. A strong relation occurred between the amount of insignificant CAD and follow-up cardiac events (chi 2 = 21.5, p less than 0.0001). Cardiac risk factors were statistically related to the risk of follow-up cardiovascular events when considered alone (chi 2 = 4.93, p = 0.026), but this relation lost significance after adjusting for the effect of coronary anatomy. Patients in both groups continued to have cardiac symptoms that resulted in frequent hospitalizations, medication use and job disability. Almost 50% in any given year of follow-up could not perform activities of high metabolic equivalent requirement and 70% had continuing symptoms of chest discomfort. Although these patients are at low risk of death, many remain functionally impaired for years.

Predicting outcome in coronary disease. Statistical models versus expert clinicians.

To study the accuracy with which long-term prognosis can be predicted in patients with coronary artery disease, prognostic predictions from a data-based multivariable statistical model were compared with predictions from senior clinical cardiologists. Test samples of 100 patients each were selected from a large series of medically treated patients with significant coronary disease. Using detailed case summaries, five senior cardiologists each predicted one- and three-year survival and infarct-free survival probabilities for 100 patients. Fifty patients appeared in multiple samples for assessing interphysician variability. Cox regression models, developed using patients not in the test samples, predicted corresponding outcome probabilities for each test patient. Overall, model predictions correlated better with actual patient outcomes than did the doctors' predictions. For three-year survival, rank correlations were 0.61 (model) and 0.49 (doctors). For three-year infarct-free survival predictions, correlations with outcome were 0.48 (model) and 0.29 (doctors). Comparisons by individual doctor revealed Cox model three-year survival predictions were better than those of four of five doctors (model predictions added significant [p less than 0.05] prognostic information to the doctor's predictions, whereas the converse was not true). For infarct-free survival, the Cox model was superior to all five doctors. Where predictions were made by multiple doctors, the interphysician variability was substantial. 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.

Psychosocial and physical predictors of anginal pain relief with medical management.

This study was undertaken to identify psychosocial and physical characteristics that independently predict anginal pain relief. The original study group comprised over 570 patients in whom the characteristics were identified at the time of coronary arteriography and who were followed up after 6 months of standard medical therapy. In the subset of 382 of these patients who were assessed as having NYHA Class III or IV angina at the time of angiography, a multivariable analysis of 101 baseline descriptors showed that higher scores on the MMPI hypochondriasis scale, unemployment, and more severe right coronary occlusion were significant independent predictors of failure to achieve two-class improvement at follow-up. These three characteristics also predicted continuing severe angina in a subsequent, independent sample of 91 new patients. These findings could help physicians select appropriate treatment by prospectively identifying patients who are unlikely to respond to standard medical treatment of angina.

Randomized trials of coronary artery bypass surgery: impact on clinical practice at Duke University Medical Center.

Trends in practice patterns at Duke University Medical Center were assessed in patient groups comparable to those enrolled in the three major randomized trials of coronary artery bypass grafting (CABG). In addition, changes in practice patterns that appeared unrelated to the randomized trials were examined. Most patients with 75% or greater left main stenosis have been treated surgically after publication of the Veterans Administration Cooperative Study, but little change was noted in the proportion of patients with 50% left main stenosis who have been treated surgically. A trend towards selection of surgical therapy for patients with three-vessel disease and normal left ventricular function was evident before the publication of the European Coronary Surgery Study, although one-third of patients in this category continue to be treated nonsurgically after publication of the results of the trial. For the past decade, most patients who would have been eligible for the Coronary Artery Surgery Study have been treated nonsurgically. We have also documented trends in practice patterns that are independent of the results of randomized trials. The advent of percutaneous transluminal angioplasty has provided another therapeutic alternative that has been used increasingly. In addition, growing numbers of patients with advanced age, unstable angina, or markedly depressed left ventricular ejection fraction are being evaluated with cardiac catheterization despite the lack of supporting randomized trials. Randomized trials have placed our understanding of the effects of CABG on a sound foundation, but it is evident that clinicians continue to consider many other factors when therapeutic decisions are made.

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 significance of precordial ST-segment depression during inferior acute myocardial infarction.

To study the mechanism and prognostic importance of precordial ST-segment depression during inferior acute myocardial infarction, 162 patients admitted during 1969 through 1982 were identified. Patients with ST depression in leads V1, V2 and V3 had significantly larger infarctions as assessed by a QRS scoring system. Hospital mortality was 4% (3 of 75) among patients without ST depression, and 13% (11 of 87) in patients with ST depression. The relation between the amount of ST depression and hospital mortality was significant (p less than 0.001 by logistic regression), and remained significant (p less than 0.003) after adjusting for other potentially prognostic factors. Among patients discharged from the hospital, the 5-year survival was 92% in those without precordial ST depression and 80% in those with precordial ST depression (p = 0.058 by the Cox model). Precordial ST-segment depression on the admission electrocardiogram during an inferior acute myocardial infarction indicates a larger infarction, predicts a higher hospital mortality and suggests a worse long-term prognosis after discharge.

Factors affecting sensitivity and specificity of exercise electrocardiography. Multivariable analysis.

Unlike the predictive value of a diagnostic test, which depends on the prevalence of disease in the population tested, its sensitivity and specificity have been assumed to be constants. This assumption was examined in patients who had both exercise electrocardiography and cardiac catheterization. The effects on sensitivity of factors from clinical history, catheterization, and exercise performance were defined by multivariable logistic regression analysis in 1,401 patients with coronary disease; effects on specificity were defined by a similar analysis in 868 patients without coronary disease. Five factors had significant, independent effects on exercise electrocardiographic sensitivity: maximal exercise heart rate, number of diseased coronary arteries, type of angina, and the patient's age and sex. Only maximal exercise heart rate had a significant, independent effect on exercise electrocardiographic specificity. Thus, the sensitivity and specificity of exercise electrocardiography vary with clinical history, extent of disease, and treadmill performance; the sensitivity and specificity of other diagnostic tests may also vary.

"Left main equivalent" coronary artery disease: its clinical presentation and prognostic significance with nonsurgical therapy.

The clinical characteristics and nonsurgical prognosis of 55 patients with "left main (LM) equivalent" coronary artery disease (CAD) were evaluated and defined as: (1) greater than or equal to 75% diameter reduction of the left anterior descending coronary artery (LAD) before the takeoff of any large septal perforator or anterolateral (diagonal) branches; (2) greater than or equal to 75% diameter reduction of the left circumflex artery (LC) before the takeoff of any large marginal branch; and (3) absence of greater than or equal to 50% stenosis of the LM coronary artery. Compared with nonsurgically treated patients with greater than or equal to 75% stenosis of the LM artery, patients with LM equivalent CAD had a shorter duration of symptoms (median of 51 months vs 66 months) and more often had a Q wave on the electrocardiogram (60 vs 39%). Survival in patients with LM equivalent CAD (78% at 1 year and 55% at 5 years) was better than that in patients with LM disease with nonsurgical therapy (65% at 1 year and 40% at 5 years) (p = 0.02), although the rate of freedom from cardiovascular events was not significantly different. Compared with other nonsurgically treated patients with 2- or 3-vessel CAD involving the LAD and LC (28 and 42%, respectively, with progressive angina), patients with LM equivalent CAD had more severe anginal symptoms (55% with progressive angina) and a longer duration of symptoms (medians of 20 months in 2-vessel CAD, 36 months in 3-vessel CAD and 51 months in LM equivalent CAD).(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of ischemic heart disease in patients with TIA.

A prospective study was made of the morbidity and mortality from ischemic heart disease in 390 patients with focal TIA caused by atherosclerotic vascular disease. The 5-year cumulative rate of myocardial infarction or sudden death in these patients was 21.0%, a rate only slightly less than that of fatal or nonfatal cerebral infarction (22.7%). Risk factors including diabetes, angina, and ECG abnormalities were associated with an increase in morbidity and mortality from ischemic heart disease. A major factor associated with these cardiac events was the presence of atherosclerotic obstructive or ulcerative lesions in the carotid arteries. These observations indicate that focal TIA caused by carotid atherosclerosis is a predictor not only of cerebral infarction, but also of serious cardiac disease and death.

Clinical characteristics and long-term survival of patients with variant angina.

We studied 109 consecutive patients with variant angina who underwent cardiac catheterization over an 11 year period. All patients were followed for at least 6 months or until death, and 46 patients (22 treated medically and 24 treated surgically) were followed for 5 years or more. Of the 62 patients initially treated medically, 14 had nonfatal myocardial infarctions (12 within 1 month of catheterization) and 12 died (six within 6 months). Survival probabilities at 1, 3, and 5 years were 0.88, 0.84, and 0.77, respectively. Of the 48 surgically treated patients (including four patients initially treated medically and one initially treated with coronary angioplasty), four had nonfatal infarctions (three in the perioperative period) and three died (all in the perioperative period). The survival probability in these patients at 1 year was 0.94 and remained unchanged at 3 and 5 years. Only one nonfatal infarction and no deaths have occurred in the group of surgically treated patients subsequent to hospital discharge. Three additional patients were treated with coronary angioplasty. The single most important prognostic factor in medically treated patients was the presence or absence of fixed obstructive coronary artery disease. Infarction-free survival probabilities at 1 and 3 years in the 23 patients without significant coronary artery disease were 1.0 and 0.89, compared with 0.51 and 0.46 in the 39 patients with significant coronary disease. Analysis by the Cox model showed that variant angina patients had a higher probability of death and nonfatal infarction than did those with nonvariant angina coronary disease if other important prognostic variables were held constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Regression modelling strategies for improved prognostic prediction.

Regression models such as the Cox proportional hazards model have had increasing use in modelling and estimating the prognosis of patients with a variety of diseases. Many applications involve a large number of variables to be modelled using a relatively small patient sample. Problems of overfitting and of identifying important covariates are exacerbated in analysing prognosis because the accuracy of a model is more a function of the number of events than of the sample size. We used a general index of predictive discrimination to measure the ability of a model developed on training samples of varying sizes to predict survival in an independent test sample of patients suspected of having coronary artery disease. We compared three methods of model fitting: (1) standard 'step-up' variable selection, (2) incomplete principal components regression, and (3) Cox model regression after developing clinical indices from variable clusters. We found regression using principal components to offer superior predictions in the test sample, whereas regression using indices offers easily interpretable models nearly as good as the principal components models. Standard variable selection has a number of deficiencies.

Prognostic indicators from radionuclide angiography in medically treated patients with coronary artery disease.

The purpose of this investigation was to determine which variables obtained when performing radionuclide angiography predict subsequent survival or total events (cardiovascular death or nonfatal myocardial infarction) in stable patients with symptomatic coronary artery disease (CAD). Univariable and multivariable analyses of 6 variables, including ejection fraction (EF) at rest and exercise, change in EF with exercise, development of ischemic chest pain or electrocardiographic changes, left ventricular (LV) wall motion abnormalities and exercise time were examined in 386 patients followed up to 4.5 years. Univariate analyses revealed that the exercise EF was the variable most closely associated with future events (p less than 0.01), followed by EF at rest, wall motion abnormalities and exercise time. Multivariable analyses revealed that once the exercise EF was known, no other radionuclide variables contributed independent information about the likelihood of future events. Multivariable analyses also revealed that the exercise EF describes much of the prognostic information of coronary anatomy. Our findings suggest that the radionuclide angiogram is useful in predicting future events in patients with stable CAD, although examination in conjunction with other clinical descriptors will be necessary to further quantify this contribution.

The effect of crossovers on estimates of survival in medically treated patients with coronary artery disease.

Among 1661 consecutive patients with significant coronary artery disease treated medically at the Duke University Medical Center, 239 have undergone aortocoronary bypass surgery after at least 6 months of medical management. The purpose of this investigation was twofold: (1) to identify the distinguishing characteristics of these treatment crossovers; and (2) to illustrate a method of estimating the effect that withdrawing the crossovers from the analysis would have on the survival of the medically managed patients. Of 81 baseline characteristics compared, 25 were significantly (p less than 0.05) different between crossovers and noncrossovers. These included five characteristics that had previously been determined to be independent predictors favoring improved survival in medically treated coronary artery disease. A Cox regression analysis identified six variables independently associated with the time until crossover surgery. Crossover patients were younger and had superior ventricular function. A hazard score, which summarized in a single variable the overall risk of mortality, was developed from the prognostic baseline characteristics. Crossover patients had significantly (p = 0.003) lower hazard scores and hence would have been expected to have a superior survival compared with noncrossover patients. In our series, survival in the medically treated patients would likely have been higher had the crossovers remained in the medical group.

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.

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.

The prognosis for patients with new-onset angina who have undergone cardiac catheterization.

We investigated the prognostic significance of new-onset angina in patients in whom coronary anatomic characteristics were known. New onset angina was defined as angina of less than 3 months duration. Consecutive patients (n = 1727) with significant coronary artery disease (diagnosed at cardiac catheterization) and who had not had a prior myocardial infarction or congestive heart failure were studied. In patients with new-onset angina (n = 329) there was a higher incidence of single-vessel disease (43% vs 27%) and a lower incidence of triple-vessel (23% vs 35%) and left main artery (5% vs 10%) disease compared with patients with chronic angina (n = 1398). Patients were classified by the presence or absence of preinfarction angina (severe and prolonged angina at rest requiring hospitalization to rule out myocardial infarction). In patients treated without surgery and who did not have preinfarction angina, survival at 1 year was 97% for patients with new-onset angina and 98% for those with chronic angina (p = .27). Among patients not treated surgically who did not have preinfarction angina, at 1 year 16% with new-onset angina and 7% with chronic angina had suffered a cardiac event (nonfatal myocardial infarction or death, p = .006). In patients treated surgically who did not have preinfarction angina, survival at 1 year was 96% both for those with new-onset angina and those with chronic angina (p = .99). The risk of an event in patients treated surgically at 1 year was not statistically different in patients with new-onset angina and those with chronic angina (12% vs 11%, p = .27). Survival and event-free rates were lower in patients with preinfarction angina than in patients who did not have it.(ABSTRACT TRUNCATED AT 250 WORDS)