Since the first report of the application of Doppler echocardiography in the evaluation of prosthetic heart valves 10 years ago, dozens of studies have reaffirmed the usefulness of this technique in the noninvasive assessment of transvalvular hemodynamics. Most of these studies have established "normal values" for Doppler-determined pressure gradients and valve areas of prosthetic mitral and aortic valves. Although these studies have established the "normal range," they have all emphasized the individual variability in clinically normal functioning valves. Most of these studies have confirmed the extraordinary sensitivity and specificity of Doppler in detecting prosthetic valve dysfunction. The study by Burstow et al further emphasizes the excellent correlation obtained with simultaneous Doppler and catheter transvalvular pressure gradient measurements. The addition of both color flow Doppler techniques and transesophageal echocardiography can only serve to enhance the clinical diagnostic accuracy of this technique. At the present time, Doppler echocardiography is clearly the procedure of choice for the evaluation of the patient with suspected prosthetic heart valve dysfunction.

To evaluate the variability in the reported diagnostic accuracy of the exercise electrocardiogram, we applied meta-analysis to 147 consecutively published reports comparing exercise-induced ST depression with coronary angiography. These reports involved 24,074 patients who underwent both tests. Population characteristics and technical and methodologic factors, including publication year, number of electrocardiographic leads, exercise protocol, use of hyperventilation, definition of an abnormal ST response, exclusion of certain subgroups, and blinding of test interpretation were analyzed. Wide variability in sensitivity and specificity was found (mean sensitivity, 68%; range, 23-100%; SD, 16%; and mean specificity, 77%; range, 17-100%; SD, 17%). The four study characteristics found to be significantly and independently related to sensitivity were the treatment of equivocal test results, comparison with a "better" test such as thallium scintigraphy, exclusion of patients on digitalis, and publication year. The four variables found to be significantly and independently related to specificity were the treatment of upsloping ST depressions, the exclusion of subjects with prior infarction or left bundle branch block, and the use of preexercise hyperventilation. Stepwise linear regression explained less than 35% of the variance in sensitivities and specificities reported in the 147 publications. There is wide variability in the reported accuracy of the exercise electrocardiogram. This variability is not explained by information reported in the medical literature.

The prevention of cardiovascular disease antedates our current preoccupation with risk factors for coronary heart disease and hypertension. Indeed, earlier preventive efforts have in part been so successful that many people have forgotten that they existed. The almost forgotten entity, beriberi heart disease, was first prevented in 1883 by Takaki of Japan. With diphtheria, it was the identification of the causative bacillus by Klebs in 1883, leading finally to the development of diphtheria toxoid by Ramon in 1923, which resulted in the disappearance of diphtheritic heart disease. Success in the attack on syphilitic heart and vascular disease began with Bordet and Gengou in 1901 with the discovery of the phenomenon of complement fixation, and with the formulation of Salvarsan by Ehrlich in 1907. The story of the prevention of rheumatic fever has a large cast of characters, but special recognition must be given to Coburn for his observations confirming the role of the hemolytic streptococcus published in 1931 and showing the prophylactic value of sulfanilamide published in 1939. The important association of maternal rubella with congenital heart malformations was revealed by Gregg in 1941. Alcoholic heart disease was identified particularly by Brigden and Evans in 1957 and 1959, respectively. In relation to coronary and hypertensive heart disease, the names of Anitschkow (1933), Leary (1935), and Keys (1948) in relation to diet, of Freis (1967) in the field of hypertension treatment, of White (1927) in relation to physical exercise, and of English, Willius, and Berkson (1940) and Hammond and Horn (1954) in the role of cigarette smoking, deserve special recognition.

We have speculated previously that the abrupt conversion from chronic stable to unstable angina and the continuum to acute myocardial infarction may result from myocardial ischemia caused by progressive platelet aggregation and dynamic vasoconstriction themselves caused by local increases in thromboxane and serotonin at sites of coronary artery stenosis and endothelial injury. Platelet aggregation and dynamic coronary artery vasoconstriction probably result from the local accumulation of thromboxane and serotonin and also relative decreases in the local concentrations of endothelially derived vasodilators and inhibitors of platelet aggregation, such as endothelium-derived relaxing factor (EDRF) and prostacyclin. With severe reductions in coronary blood flow caused by these mechanisms, platelet aggregates may increase, and an occlusive thrombus composed of platelets and white and red blood cells in a fibrin mesh may develop. When coronary arteries are occluded or narrowed for a sufficient period of time by these mechanisms, myocardial necrosis, electrical instability, or sudden death may occur. We believe that unstable angina and acute myocardial infarction are a continuum in relation to the process of coronary artery thrombosis and vasoconstriction. When the period of platelet aggregation or dynamic vasoconstriction at sites of endothelial injury and coronary artery stenosis is brief, unstable angina or non-Q wave infarction may occur. However, when the coronary artery obstruction by these mechanisms is prolonged for several hours, Q wave myocardial infarction results. Chronic endothelial injury and coronary artery stenosis are probably associated with the accumulation of platelets, white and red blood cells, and a fibrin mesh at the site of stenosis and endothelial injury.

The endothelium releases the powerful vasodilator and antiaggregatory substance, EDRF, both under basal conditions and upon stimulation by a wide variety of agents. Endothelial injury or dysfunction may play an important role in the spasmogenicity of the coronary artery, although other possible alterations related to atherosclerosis should also be considered. Among the possible stimuli, aggregating platelets are important as a source of vasoconstrictor substances. The endothelium may also produce the vasoactive substances EDHF and EDCF(s). Their pathophysiologic significance remains to be determined.

Three to four percent of patients who have myocardial revascularization without additional procedures have moderately severe or severe heart failure. Analysis of reported experience and data from two centers indicate that the severity of heart failure correlates poorly with left ventricular ejection fraction and other indexes of left ventricular function. Operative mortality ranges from 2.2% to 14.9% and roughly correlates with the severity of heart failure. By logistic regression, age, ejection fraction, presence of mitral regurgitation, and presence of left main coronary artery disease are identified as incremental risk factors for operative death. Long-term survival is affected by age, ejection fraction, sex, presence of left main coronary artery disease, severity of angina, and presence of mitral insufficiency.

The early and long-term results of myocardial revascularization are reviewed for four unidentified community hospitals, for Katholieke Universiteit (Leuven, Belgium), and for the University of Alabama at Birmingham at two different times. After operation, approximately 77% of patients are free from all ischemic events at 5 years and nearly 50% are free at 10 years. Over 90% of patients survive 5 years, and approximately 80% survive 10 years. Some of the incremental risk factors for early death after operation include older age; degree of left ventricular dysfunction; hemodynamic instability at the time of operation; recent myocardial infarction; number of diseased coronary vessels; associated mitral incompetence, ventricular aneurysm, or ventricular tachycardia; longer aortic cross-clamp time; and non-use of the internal mammary artery for revascularization. The number of diseased coronary arteries and the aggressiveness of the atherosclerotic process, degree of left ventricular dysfunction, older age, and non-use of the internal mammary artery are risk factors for reduced long-term survival.

We reviewed 14 reports from 1978 to 1988 of 6,136 patients with unstable angina pectoris treated by coronary artery bypass grafting (CABG). The mean age was 56.8 years, and 23% were female. Mean operative mortality in the 14 reports was 3.7% (1.2-8.5%). The mean incidence of perioperative myocardial infarction was 9.9% (3.8-17%). The mean incidence of postoperative low cardiac output was 16% (8-35%). No risk factors for morbidity or mortality different from those observed in patients with chronic stable angina were identified. Clinical subgroups of the heterogeneous group of patients with unstable angina pectoris are associated with different prognoses and treatment results. Variable pathological changes are associated with these subgroups. Reductions in morbidity and mortality of those patients undergoing CABG may require better preoperative management of the underlying pathological process and improved myocardial preservation at the time of CABG. Angina relief, improved survival, and reduction in late nonfatal myocardial infarction is similar to that observed in patients with chronic stable angina after CABG.

Over the last 20 years, operative mortality has decreased and late survival has improved for patients with chronic stable angina who have coronary artery bypass surgery. However, this favorable trend may not continue because the operation is now extended to elderly and high-risk patients. The most powerful predictors of operative mortality include indexes of left ventricular function, age, and the number of associated medical conditions. Female gender, severity of angina, and extent of coronary artery disease appear to be predictors of operative mortality in some series but not in all. Indexes of left ventricular dysfunction remain the most powerful predictors of late death, but the extent of coronary disease, older age, and presence of associated diseases (including noncardiac vascular disease) remain important determinants. Analyses of the randomized trials and registry studies reveal a consistent trend: in patients at high risk on the basis of clinical, functional, and anatomic characteristics, coronary artery bypass surgery prolongs survival in comparison with medical therapy alone. In patients determined to be at low risk, medical therapy is initially recommended with the realization that revascularization may be necessary subsequently if symptoms worsen or the severity of ischemia increases.