Randolph E. Patterson

Current concepts: evaluation of patients after acute myocardial infarction: indications for cardiac catheterization and surgical intervention.

AN important question facing physicians today is whether to recommend cardiac catheterization to the patient who has just had an acute myocardial infarction. Although it has long been recognized th...

Can noninvasive exercise test criteria identify patients with left main or 3-vessel coronary disease after a first myocardial infarction?*

This study attempts to determine whether exercise treadmill testing with clinical, electrocardiographic, and thallium-201 myocardial perfusion imaging data can identify which patients have left main or 3-vessel (anatomically high-risk) coronary artery disease (CAD) after their first transmural myocardial infarct (MI). Twelve exercise test criteria for high-risk disease were compared in 40 patients referred for cardiac catheterization; 34 had a history of chest pain and 17 had angiographically defined high-risk CAD. A thallium image defect outside the vascular distribution of the MI was the most reliable criterion to distinguish patients with high-risk CAD (p = 0.00052 for Fishers exact test of discrimination). Thallium imaging was somewhat more sensitive (92 versus 65%, p = 0.108) when patients with negative thallium imaging criteria who failed to achieve 85% of the age-predicted maximal heart rate were excluded. Failure to achieve 85% of predicted heart rate was by itself a useful criterion for detecting high-risk CAD (p = 0.017), especially in patients not taking propranolol (p = 0.004). Development of positive S-T segment depression at less than 70% predicted heart rate also discriminated left main or 3-vessel disease from less extensive CAD (p = 0.016). Other criteria failed to discriminate significantly between high-risk and less extensive CAD in patients after their first MI (p greater than 0.05). S-T segment depression (p = 0.199) or chest pain (p = 0.577) during exercise testing were particularly unreliable. Further, none of the criteria for high-risk CAD were influenced by irreversible left ventricular dysfunction. It is concluded that patients with thallium imaging defects outside the region of the infarct, decreasing blood pressure during exercise, failure to achieve 85% of predicted heart rate, or S-T depression at less than 70% of predicted heart rate have a high probability of having left main or 3-vessel disease. Patients without these criteria have a very low probability of having high-risk CAD and probably do not need coronary angiography for the purpose of excluding these high-risk coronary lesions after a first MI.

Bayesian comparison of cost-effectiveness of different clinical approaches to diagnose coronary artery disease

The objective of this study was to compare the cost-effectiveness of four clinical policies (policies I to IV) in the diagnosis of the presence or absence of coronary artery disease. A model based on Bayes theorem and published clinical data was constructed to make these comparisons. Effectiveness was defined as either the number of patients with coronary disease diagnosed or as the number of quality-adjusted life years extended by therapy after the diagnosis of coronary disease. The following conclusions arise strictly from analysis of the model and may not necessarily be applicable to all situations. As prevalence of coronary disease in the population increased, it caused a linear increase in cost per patient tested, but a hyperbolic decrease in cost per effect, that is, increased cost-effectiveness. Thus, cost-effectiveness of all policies (I to IV) was poor in populations with a prevalence of disease below 10%, for example, asymptomatic people with no risk factors. Analysis of the model also indicates that at prevalences less than 80%, exercise thallium scintigraphy alone as a first test (policy II) is a more cost-effective initial test than is exercise electrocardiography alone as a first test (policy I) or exercise electrocardiography first combined with thallium imaging as a second test (policy IV). Exercise electrocardiography before thallium imaging (policy IV) is more cost-effective than exercise electrocardiography alone (policy I) at prevalences less than 80%. 4) Noninvasive exercise testing before angiography (policies I, II and IV) is more cost-effective than using coronary angiography as the first and only test (policy III) at prevalences less than 80%. 5) Above a threshold value of prevalence of 80% (for example patients with typical angina), proceeding to angiography as the first test (policy III) was more cost-effective than initial noninvasive exercise tests (policies I, II and IV). One advantage of this quantitative model is that it estimates a threshold value of prevalence (80%) at which the rank order of policies changes. The model also allows substitution of different values for any variable as a way of accounting for the uncertainty inherent in the data. In conclusion, it is essential to consider the prevalence of disease when selecting the most cost-effective clinical approach to making a diagnosis.

Can exercise electrocardiography and thallium-201 myocardial imaging exclude the diagnosis of coronary artery disease? Bayesian analysis of the clinical limits of exclusion and indications for coronary angiography.

Abstract The objective of this study was to determine whether exercise electrocardiography can be combined with thallium-201 myocardial imaging and the clinical history to exclude the diagnosis of coronary artery disease. All 96 patients in this study were referred for coronary angiography because of chest pain but did not have prior myocardial infarction; 52 percent had coronary artery disease. Each patients chest pain was classified as either typical or not typical of angina pectoris. Negative tests with inadequate exercise stress (less than 85 percent of the age-predicted maximal heart rate) and combined tests with discordant results (either exercise electrocardiography or thallium imaging positive and the other test negative) were judged nondiagnostic. Nondiagnostic tests that contributed most to the uncertainty of results were classified separately: exercise electrocardiogram, 35 patients; thallium imaging, 9 patients; and combined exercise electrocardiogram and thallium imaging, 50 patients. The ability of each test to rule out coronary artery disease was defined by its predictive error (probability of coronary disease despite a negative test): history of chest pain not typical of angina, 26 percent (11 of 42); exercise electrocardiogram, 22 percent (5 of 23); thallium imaging, 27 percent (6 of 35); and negative findings on both exercise electrocardiogram and thallium imaging, 6 percent (1 of 17). Finally, when only the patients with atypical chest pain were considered, there was zero (0 of 15) predictive error if both tests were negative. Negative exercise electrocardiography and thallium imaging during adequate stress ruled out any coronary artery disease in these patients with considerable reliability (94 percent) and excluded multivessel disease with even greater reliability. These exclusion tests for coronary artery disease were most reliable in patients in whom the clinical diagnosis of coronary artery disease was least likely, as defined by Bayes theorem. It is concluded that there is no perfect noninvasive test to exclude coronary disease in all patient populations; however, coronary angiography is not necessary to rule out the diagnosis of coronary artery disease in patients whohave (1) no clinical indicators of a very high probability of coronary disease, such as typical angina, (2) adequate exercise stress, (3) negative exercise electrocardiogram and (4) negative exercise thallium images.

Relation between exercise-induced changes in ejection fraction and systolic loading conditions at rest in aortic regurgitation

To examine the role of systolic wall stress at rest in determining left ventricular performance during exercise in aortic regurgitation (AR), systolic wall stress (measured by M-mode echocardiography) was related to changes in left ventricular function during maximal exercise (evaluated by radionuclide ventriculography) in 30 patients with chronic aortic regurgitation. Of these 30 patients, 7 had a normal exercise response, defined as an absolute increase in ejection fraction of 5% or greater (Group I) and 23 had abnormal exercise response, defined as no change (less than 5% change) or a decline (less than or equal to 5%) in ejection fraction (Group II). Patients in Group I had a significantly lower radius/wall thickness ratio (2.5 +/- 0.2 versus 3.1 +/- 0.1, p less than 0.01) and lower peak systolic wall stress (123 +/- 11 versus 211 +/- 12 X 10(3) dynes/cm2, p less than 0.01) than patients in Group II. An increase in ejection fraction during exercise was seen in 6 of the 9 patients with normal systolic wall stress at rest (less than 150 X 10(3) dynes/cm2), but in only 1 of 21 patients with elevated systolic wall stress (p less than 0.001). Peak systolic wall stress at rest varied linearly, and inversely with changes in left ventricular ejection fraction during exercise (r = 0.60, p less than 0.001). Groups I and II did not differ in ejection fraction at rest, clinical symptoms or maximal work load achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantification of valve regurgitation by radionuclide angiography before and after valve replacement surgery

Radionuclide gated cardiac blood pool imaging was used to quantify the severity of valve regurgitation in 20 patients, by calculating the ratio of left ventricular to right ventricular stroke counts (end-diastolic minus end-systolic counts in right and left ventricular regions of interest). This ratio (the stroke index ratio) was substantially higher in patients with aortic and mitral regurgitation (3.91 +/- 1.45) than in a control group of 10 patients without regurgitation (1.32 +/- 0.15), p less than 0.001. The stroke index ratio correlated closely (r = 0.947) with measurements of regurgitant fraction derived from simultaneous determinations of total and forward stroke volumes during cardiac catheterization. After aortic and mitral valve replacement in 18 patients, the stroke index ratio decreased from 4.03 +/- 1.46 to 1.38 +/- 0.23 (p less than 0.001), a value not significantly different from that observed in patients without regurgitation. All three patients with residual postoperative regurgitation had a stroke index ratio greater than 2 standard deviations above the mean values for the control group (greater than 1.62), whereas the remaining 15 patients, who had no evidence of regurgitation, had values within the normal range. Therefore, radionuclide gated blood pool scanning provides a noninvasive method of quantifying valve regurgitation and assessing the results of medical or surgical interventions.

Practical diagnosis of coronary artery disease: A Bayes' theorem nomogram to correlate clinical data with noninvasive exercise tests☆

Recent technologic advances have presented the physician with many diagnostic tests for coronary artery disease (CAD).’ Bayes’ theorem can be used to correlate clinical and noninvasive test data to evaluate patients for CAD.2-4 This rather complex Bayesian analysis remains underused in clinical practice because of the continuing need for a practical format. Thus, our purpose was to develop a Bayesian nomogram to diagnose CAD by integrating clinical data with the results of 1 or more noninvasive tests. This report illustrates its clinical usefulness in deciding indications for any test to diagnose CAD in different patients.

Scintigraphic quantification of asynchronous myocardial motion during the left ventricular isovolumic relaxation period: A study in the dog during acute ischemia

Asynchronous motion of left ventricular myocardium during the period of left ventricular isovolumic relaxation has often been observed in patients with coronary artery disease. Detection and quantitation of this abnormality with noninvasive nuclear tracer methods, however, have not yet been reported. Thus, functional images of regional left ventricular time to minimum counts (or volume), computed from gated blood pool image sequences, were analyzed to detect and quantitate myocardial asynchrony during this interval. The method was tested by comparing regional with global time to minimum counts before and after coronary artery occlusion in the awake dog. After occlusion, minimum counts in the ischemic region occurred later in the cardiac cycle than did global minimum counts (average difference 69 +/- 37 ms, p less than 0.001). Before occlusion, however, minimum counts in the same region occurred at the same moment as global minimum counts (average difference 4 +/- 12 ms, NS). Thus, acute ischemia in dogs produces a pronounced asynchrony in myocardial motion during the earliest moments of diastole. The magnitude of this asynchrony (69 ms) probably corresponds to the length of the global isovolumic relaxation period in these animals after occlusion. This method might be useful in detecting and quantitating isovolumic asynchrony in ischemia and changes in this asynchrony with therapy (verapamil therapy, for example).

Spatial distribution of [14C]-lidocaine and blood flow in transmural and lateral border zones of ischemic canine myocardium

The purpose of this study was to determine the spatial distribution of lidocaine relative to blood flow in ischemic, normal and border zone canine myocardium. Ischemic zone tissue was distinguished from normal zone tissue by a special microsphere technique in adjacent sections 4 to 5 mm wide from the center to the lateral border of the ischemic region in 14 open chest dogs. Gamma-labeled microspheres were separated by a special technique from carbon-14 ([14C])-lidocaine in the same tissue sample. Blood flow (mean value +/- 1 standard deviation) was reduced to 46 +/- 25 percent of normal in the ischemic subepicardium and 17 +/- 18 percent of normal in the subendocardium. [14C]-lidocaine was 0.56 +/- 0.12 microgram/g in normal myocardium 10 minutes after bolus injection of [14C]-lidocaine; it was reduced to 91 +/- 15 percent of normal in ischemic subepicardium and 58 +/- 12 percent of normal in the subendocardium. Blood flow and lidocaine concentration were uniformly lowest in gross samples from the central and intermediate ischemic zones, and highest in the gross samples from the border normal zone (p less than 0.05). The values for flow and lidocaine in samples from the border ischemic zone were intermediate, that is, higher than values from central ischemic (p less than 0.05) and lower than values from border normal zone samples (p less than 0.05). However, the labeling technique for normal zone tissue revealed that the values of blood flow and lidocaine in the gross samples from the lateral border of the ischemic zone were intermediate between those of adjacent ischemic and normal samples because of the mixture of overlapping normal and ischemic tissues components--not because of a unique mildly ischemic region. Both blood flow and lidocaine concentration were lower in the subendocardial third than in the subepicardial third of the ischemic zone (p less than 0.05) even after the contribution of normal zone tissue was subtracted, suggesting a gradient of ischemia across the transmural border zone. In conclusion, lidocaine is distributed uniformly in ischemic components from the center to the lateral border of the ischemic zone, but there is an endocardial to epicardial gradient. Both lateral and transmural border zone distributions must be considered to understand the mechanisms of drug effects in myocardial ischemia.

Effect of verapamil on pH of ischemic canine myocardium

Verapamil has been shown to depress the contractility of ischemic myocardium. The present study was designed to determine whether that effect is due to an increase in ischemic injury caused by the drug or whether it might reflect a protective effect. A critical partial occlusion was effected on the left anterior descending coronary artery of 16 open chest foxhounds. A fiberoptic pH probe was implanted in the subendocardium of the ischemic zone, and coronary blood flow was reduced by 79% from a control value of 38 +/- 4 ml/min and held constant. Mean coronary perfusion pressure was decreased 48% from its control value of 90 +/- 6 mm Hg and remained constant. Eight animals were treated with intravenous verapamil, beginning 20 to 30 minutes after the onset of ischemia, in incremental doses (5, 10 and 20 micrograms/kg per min) and eight were treated with placebo. The pH of the ischemic zone increased after institution of treatment in the verapamil group (+ 0.04 +/- 0.05 pH unit) whereas it decreased in the placebo group (- 0.06 +/- 0.4 pH unit) during the first dose (p less than 0.05). Although the difference in pH between the two groups was marked at all doses (p less than 0.03) compared with control partial occlusion, verapamil caused no significant change in heart rate (+ 0.1 +/- 1 beat/min in the verapamil group versus + 0.6 +/- 4.5 beats/min in the placebo group), mean arterial pressure (- 7.5 +/- 4 versus - 4.3 +/- 3 mm Hg, respectively) or cardiac output (- 0.2 +/- 0.07 versus - 0.02 +/- 0.04 liters/min, respectively) comparing control with the first or the second dose of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)