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Cardiac-related clinical practice guidelines have become an integral part of the practice of cardiology. Unfortunately, these guidelines are often long, complex, and difficult for practicing cardiologists to use. Guidelines should be condensed and their format upgraded, so that the key messages are easier to comprehend and can be applied more readily by those involved in patient care. After presenting the historical background and describing the guideline structure, we make several recommendations to make clinical practice guidelines more user-friendly for clinical cardiologists. Our most important recommendations are that the clinical cardiology guidelines should focus exclusively on (1) class I recommendations with established benefits that are supported by randomized clinical trials and (2) class III recommendations for diagnostic or therapeutic approaches in which quality studies show no benefit or possible harm. Class II recommendations are not evidence based but reflect expert opinions related to published clinical studies, with potential for personal bias by members of the guideline committee. Class II recommendations should be published separately as "Expert Consensus Statements" or "Task Force Committee Opinions," so that both majority and minority expert opinions can be presented in a less dogmatic form than the way these recommendations currently appear in clinical practice guidelines.

The association of a group of prespecified atherosclerotic risk genotypes with recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) was investigated in a cohort of 1,008 patients after infarction during an average follow-up of 28 months. We used a carrier-ship approach with time-dependent survivorship analysis to evaluate the average risk of each carried genotype. Contrary to expectation, the hazard ratio for recurrent coronary events per carried versus noncarried genotype was 0.89 (95% confidence interval 0.80 to 0.99, p = 0.03) after adjustment for relevant genetic, clinical, and environmental covariates. This hazard ratio, derived from the 7 prespecified genotypes, indicated an average 11% reduction in the risk of recurrent coronary events per carried versus noncarried genotype. At 1 year after hospital discharge, the cumulative probability of recurrent coronary events was 26% in those who carriedor =1, 20% for those with 2 to 4, and 13% for those withor =5 of these genotypes (p = 0.02). This unexpected risk reversal is a likely consequence of changes in the mix of risk factors in pre- and postinfarction populations. In conclusion, this under appreciated, population-based, risk-reversal phenomenon may explain the inconsistent associations of genetic risk factors with outcome events in previous reports involving coronary populations with different risk attributes.

In a large prospective study of myocardial ischemia, exercise thallium studies were performed in 896 patients 1 to 6 months after an acute coronary event (acute myocardial infarction, 70%; unstable angina, 30%). Thallium images were analyzed quantitatively and classified as normal or demonstrating either a reversible defect after 2 to 4 hours or having only a fixed defect. The effect of the thallium findings on the time to end point (cardiac death, nonfatal infarction, or unstable angina) were examined by Kaplan-Meier curves and compared using the log-rank statistic. Follow-up averaged 23 months. The likelihood of cardiac death, nonfatal infarction, and unstable angina was similar in patients who had a normal exercise thallium test result or showed only a fixed defect. Moreover, cardiac events were not related to the size of a fixed defect. In contrast, both cardiac death and nonfatal infarction were increased in patients with the largest areas of reversible defects, although the sensitivity for nonfatal myocardial infarction was suboptimal. The presence of a fixed defect on exercise thallium in patients who are stable an average of 2.6 months after an acute cardiac event is associated with a prognosis similar to that of a normal exercise thallium test.

This study was undertaken to examine whether clinical factors predict reinfarction within 1 year of a first acute myocardial infarction (AMI) and to quantify the subsequent influence of reinfarction on long-term mortality. Data from 3,695 patients with a first AMI included in the Secondary Prevention Reinfarction Israeli Nifedipine Trial Registry were analyzed. The 1 -year reinfarction incidence was 6.0% (220 of 3,695) and in-hospital mortality during reinfarction was 31%. Patients with reinfarction were older (63.0 vs 60.8 years) at entry. The independent clinical predictors for 1-year reinfarction were (adjusted relative odds): peripheral vascular disease (2.12), anterior location of the first AMI (1.62), angina before the first AMI (1.53), congestive heart failure on admission (1.34), diabetes (1.33), systemic hypertension (1.28) and age increment (1.13). One-year reinfarction rate increased from 4.0% in patients with 0 or 1 risk factor to 23.3% in patients with 5 to 6 risk factors (p

Patients admitted to the coronary care unit who received both intravenous nitroglycerin and heparin were studied to evaluate heparin dosage requirements. Physicians ordered all nitroglycerin and heparin doses as well as coagulation studies without knowledge of this study. Activated partial thromboplastin time (APTT) values obtained during steady-state heparin administration were considered therapeutic if the ratio of APTT/APTT-baseline wasor = 1.5. Sixty patients with myocardial infarction or unstable angina were included in the study. The initial therapeutic heparin dose of 1,014 +/- 151 units/hour produced an APTT ratio of 2.0 +/- 0.5. At the time of the initial therapeutic dose, the nitroglycerin dose was 110 +/- 108 micrograms/min. There was a significant correlation between the initial therapeutic dose and both total (r = 0.56; p = 0.0001) and lean (r = 0.26; p0.05) body weight. Comparison of patients with nitroglycerin dosesandor = 100 micrograms/min revealed a significant difference in the initial therapeutic dose (971 +/- 147 vs 1,077 +/- 136 U/hour, p0.01), but not the initial therapeutic dose standardized to total body weight (14.0 +/- 2.5 vs 13.5 +/- 2.7 U/kg/hour). Similarly, analysis of variance revealed a significant difference in the initial therapeutic dose (p0.05), but not the initial therapeutic dose standardized to weight among 5 different nitroglycerin dosage ranges (10 to 533 micrograms/min). Neither aspirin use, thrombolytic therapy nor decreasing or discontinuing the nitroglycerin dose significantly affected heparin requirements. Thus, contrary to prior reports, clinically significant heparin resistance induced by nitroglycerin was not found.

The incidence of secondary ventricular fibrillation (VF) complicating acute myocardial infarction (AMI) was 2.4% in a large cohort of unselected patients with AMI (142 of 5,839). Secondary VF was more frequent in patients with recurrent AMI (4%) than in those with a first AMI (1.9%) (p

Among 4,720 consecutive hospital survivors from acute myocardial infarction (AMI) treated in 13 coronary care units between July 1981 and August 1983, the estimated prevalence of electrocardiographic left ventricular (LV) hypertrophy was 6.1%. The prevalence of electrocardiographic LV hypertrophy increased with age and was higher in patients with previous myocardial infarction, angina and systemic hypertension. Mean age of patients with electrocardiographic LV hypertrophy was 67.2 vs 61.4 years in counterparts free of electrocardiographic LV hypertrophy. Patients with electrocardiographic LV hypertrophy had a higher rate of congestive heart failure on admission, or developing during their stay in coronary care units. The 1- and 5-year mortality rates were 19.7 and 46.6% among patients with electrocardiographic LV hypertrophy versus 8.7 and 26.2%, respectively (p less than 0.001) in patients without this finding. The covariate-adjusted odds ratio of 1-year mortality was 1.88 for the presence of electrocardiographic LV hypertrophy when age alone was adjusted for, and 1.51 (90% confidence interval, 1.09 to 2.10) when multiple covariate adjustment was undertaken. After multiple covariate adjustment for 5-year mortality after discharge, the relative risk associated with electrocardiographic LV hypertrophy was 1.51 (90% confidence interval, 1.26 to 1.80). The results of the present study showed that the presence of electrocardiographic LV hypertrophy on the discharge electrocardiogram of survivors from AMI is associated with a 1.5-fold increase of short- and long-term mortality. Patients with electrocardiographic LV hypertrophy, potentially at an increased post-discharge risk, may be candidates for early noninvasive testing and more intensive follow-up after recovering from AMI.

Paroxysmal atrial fibrillation (AF), a frequent complication of acute myocardial infarction (AMI), was found to be a weak independent predictor of the longterm mortality in surviving patients in 2 recent studies. 1,2 We are unaware of any studies on the prognostic impact of chronic AF on patients with AMI. The present study assesses the short- and long-term outcomes of patients with chronic AF having an AMI.

Studies in both humans and nonhuman animals show that the mitral anulus changes its size, shape and position during the cardiac cycle. 1–3 Left ventricular (LV) contraction results in shortening along both the short and long axis of the left ventricle. With each systole, the mitral anulus moves toward the apex in a cephalocaudal direction. 1–3 It has also been observed that the displacement of the mitral anulus during the systole is reduced with dilated cardiomyopathy. 4 We examined the relation between the amount of systolic excursion of the mitral anulus and LV systolic function as measured by radionuclide ventriculography and a variety of echocardiographic techniques.

A normal exercise thallium-201 scintigram has been shown to confer an excellent prognosis over a 1- to 4-year follow-up period. However, progression of coronary disease could result in cardiovascular mortality with increasing time. Therefore, the vital status of 309 patients with normal stress thallium myocardial imaging was determined after an average of 10.3 years. Deaths were classified as cardiac or noncardiac. Statistical analysis was performed using Kaplan-Meier survival curves. Standardized mortality ratios were calculated and compared with those of an age- and sex-matched general population. Followup was complete in 288 patients (93%). Of 18 deaths, only 3 were cardiac; the remaining 15 were mainly secondary to cancer. Thus, cardiac mortality was 1% and total mortality 6.3% at 10 years. In addition, both all-cause and cardiac mortality rates were significantly less than would be expected in an age- and sex-adjusted segment of the general population. Thus, normal exercise thallium scintigraphy retains its high negative predictive value for death ≤10 years after initial testing. This supports the use of stress thallium imaging to predict which patients with suspected coronary artery disease are at low risk for cardiac death and thus do not need invasive testing.

Controlled clinical trials have demonstrated the efficacy of reducing the blood levels of low-density lipoprotein cholesterol in reducing the incidence of coronary artery disease in hypercholesterolemic middle-aged men. However, a similar reversibility of the risk of coronary artery disease has not been demonstrated for high-density lipoprotein cholesterol elevation and triglyceride reduction. Therefore, the effect of administering 400 mg of bezafibrate retard daily versus placebo (double blind) to patients with myocardial infarction preceding randomization by 6 months to 5 years, or a clinically manifest anginal syndrome documented by objective evidence of dynamic myocardial ischemia, or both, is being investigated. Three thousand subjects (aged 45 to 74 years) are being enrolled from 19 cardiac departments in Israel, with total serum cholesterol between 180 and 250 mg/dl, high-density lipoprotein cholesterolor = 45 mg/dl and triglyceridesor = 300 mg/dl. In addition, low-density lipoprotein cholesterol concentrations are required to beor = 180 mg/dl (or = 160 mg/dl for patients aged50 years). Patients needing lipid-modifying therapy, exhibitingor = 1 prespecified exclusion criterion or not giving informed consent, or a combination, are not randomized. The primary end points for evaluating efficacy are the incidence of fatal and nonfatal myocardial infarction, and sudden death. The hypothesized effect of bezafibrate administration under the aforementioned protocol is to reduce an estimated cumulative end point event incidence ofor = 15% by 20 to 25% over an average follow-up period of 6.25 years, through early 1998, when the last patient recruited will have completed 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolysis is now generally accepted as the initial treatment for patients with acute myocardial infarction (AMI). The extent to which this therapy is implemented in daily practice and the reasons for exclusion from thrombolytic therapy among 413 consecutive patients with AMI hospitalized in 18 coronary care units in Israel during a 1-month survey were prospectively investigated. Thrombolytic therapy administered to 145 patients (35%) was given to 38% of men versus 29% of women (p = not significant), to 38% of patients less than 75 years old compared with 18% of the very elderly (p less than 0.005), and more often to patients with a first or anterior AMI (40 and 48%) than to counterparts with recurrent or inferior AMI (23 and 31%, respectively, p less than 0.005 for both). The 2 most frequent reasons for excluding patients from thrombolysis were late arrivals to coronary care units (33%) and lack of ST elevation on the admission electrocardiogram (28%). Hospital mortality was 6% in the thrombolytic group versus 20% in patients found ineligible for thrombolysis. The significance of this difference is not clear as treatment was not randomized.

Percutaneous cardiac catheterization for the diagnosis of cardiac disease has now become a routine and safe procedure with widespread application. Rarely, however, complications do occur that require emergency surgical intervention. The results of immediate surgical exploration are usually good; however, the long-term follow-up of these patients is unknown. This study reviews our experience with surgery for complications of cardiac catheterization and the long-term follow-up.

The clinical implications of ventricular premature complexes in patients with coronary heart disease have received increasing interest. It has been suggested that ventricular premature complexes of right ventricular origin have more benign implications than those that originate from the left ventricle. To define more precisely the relation between the site of origin of ventricular premature complexes and the presence and severity of coronary heart disease in patients with a chest pain syndrome, 39 patients with ventricular premature complexes of right or left ventricular contour who were undergoing cardiac catheterization and coronary arteriography for evaluation of chest discomfort were studied. Ninteen patients had left and 17 had right ventricular premature complexes and 3 had both. Of the 19 with left ventricular premature complexes, 15 had coronary artery disease (12 with two or three vessel obstruction and 3 with single vessel obstruction). Four had normal cardiac catheterization studies. Twelve patients had asynergy on ventriculography. The 17 patients with right ventricular premature complexes had similar angiographic findings. Eleven of the 17 had coronary artery disease (8 with triple vessel disease and 3 with isolated obstruction of the left anterior descending coronary artery). Six had normal arteries. Eight of the 11 with coronary artery disease and right ventricular premature complexes also had asynergy. All three patients with both left and right ventricular premature complexes had coronary obstructive disease. These findings indicate that in patients with a chest pain syndrome there is no relation between the site of origin of ventricular premature complexes and either the prevalence or severity of coronary artery disease.

The frequent association of new ST-T wave changes without Q waves in the surface electrocardiogram of patients with the intermediate coronary syndrome necessitates a better understanding of the pathophysiologic significance of this finding. A previous study in patients with stable coronary artery disease indicated that the surface electrocardiogram is insensitive in detecting epicardial Q waves. This relation was evaluated in 21 patients with the intermediate syndrome, characterized by recurrent chest pain at rest associated with significant new S-T or T wave abnormalities, or both, and no new Q waves in the surface electrocardiogram at the time of open heart coronary bypass surgery. Unipolar electrograms were recorded from the epicardial surface of the left ventricle before the bypass procedure. In 19 patients, epicardial electrograms revealed initial R waves over areas of the left ventricle in which the acute S-T and T wave abnormalities were evident in the surface electrocardiogram. Two patients had epicardial Q waves (one laterally and one inferiorly). In seven patients, a transmural biopsy specimen was also obtained from the ische.nic area. All showed histologically normal myocardium without evidence of early inflammatory or necrotic tissue. Of the 19 patients discharged, only one demonstrated new postoperative Q waves that had been detected by epicardial recordings before bypass. In summary, patients with the intermediate syndrome exhibiting S-T or T wave abnormalities, or both, without new Q waves in the surface electrocardiogram generally do not have Q waves either in the intraoperative epicardial or postoperative surface electrocardiogram. In addition, no histopathologic abnormalities are apparent in biopsy specimens taken from the ischemic area.

Because the right anterior oblique view is widely accepted as the best “single” projection for assessing wall motion, the utility of this view during first pass radionuclide angiography was studied in 44 patients who also underwent contrast ventriculography and coronary arteriography. Of the 44 patients, 8 had a normal heart and 14 had coronary artery disease with normal wall motion on contrast ventriculography. All also had normal contraction on radionuclide angiography. On contrast ventriculography, 22 patients had coronary artery disease and asynergy involving 34 left ventricular segments. Of 17 segments localized to the anterior and apical asynergic areas on contrast ventriculography, 16 were accurately localized with radionuclide angiography. Similarly, of 17 inferior asynergic areas, 13 were also shown to be inferior on radionuclide angiography. In addition, quantitative assessment of the severity of asynergy using the hemiaxis method demonstrated a good correlation between asynergic severity as defined with radionuclide angiography and contrast ventriculography. Of 11 anterior areas, 7 defined as hypokinetic with contrast ventriculography demonstrated chordal shortening of 20.1 ± 5.2 percent (mean ± standard error of the mean) ( P P After appropriate background subtraction, determination of ejection fraction using radionuclide angiography showed a correlation of 0.839 between the left anterior oblique and right anterior oblique projections independent of the sequence of injection. In addition, ejection fraction determined with radionuclide angiography in the left ( r = 0.824) and right ( r = 0.801) anterior oblique views correlated well with ejection fraction assessed from contrast ventriculography. Thus, first pass radionuclide angiography performed in the right anterior oblique view is a sensitive noninvasive means of assessing the location and severity of asynergy as well as global left ventricular performance in patients with coronary artery disease.

The utility of Bayes' theorem in the noninvasive diagnosis of coronary artery disease (CAD) was analyzed in 147 patients who underwent electrocardiographic stress testing, thallium-201 perfusion imaging and coronary angiography. Eighty-nine patients had typical anginal chest discomfort and 58 had atypical chest pain. Sensitivity and specificity of the tests and prevalence of CAD at each level of testing were tabulated and compared with the results generated from Bayes' theorem. The sensitivity of electrocardiographic stress was higher in patients with multivessel CAD than in patients with 1-vessel CAD. Sensitivity, but not specificity, of each test was dependent, in part, on the result of the other test. However, the probabilities calculated from Bayes' theorem when used for sequential testing are remarkably close to the tabulated data. Thus, Bayes' theorem is useful clinically despite some evidence of test dependence. Sequential test analysis by Bayes' theorem is most useful in establishing or ruling out a diagnosis when the pretest prevalence is approximately 50% and when the 2 tests are concordant.

The increasing use of changes in the S-T segment of local epicardial electrograms to quantitate myocardial infarct size has led to the need for a better understanding of this method. Accordingly, we studied the local electrographic, tension and biochemical changes that occurred after coronary occlusion and subsequent reperfusion in 44 dogs using epicardial electrograms from 10 to 12 sites, Walton-Brodie strain gauge arches and myocardial ratios of potassium ion to sodium ion (K+/Na+). After coronary occlusion for 1 hour, total S-T segment elevation increased from 10.2 +/- 2.4 to 78.3 +/- 13.7 mv (P less than 0.001) and tension development decreased to 63.6 +/- 7.0% of control value (P less than 0.001); occlusion for 3 hours resulted in a total S-T segment elevation increase from 5.8 +/- 3.4 to 56.7 +/- 8.7 mv (P less than 0.001) and a tension decrease to 61.4 +/- 5.3% (P less than 0.001) of control value. After reperfusion two types of response were observed. In nine experiments new local pathologic Q waves appeared in an average of 5.3 of 8.2 ischemic electrode sites within 5 to 10 minutes of reperfusion concomitant with a marked further decrease in total tension from 67.3 +/- 5.5% to 42.4 +/- 6.0% of control value (P less than 0.001). Simultaneously, total S-T elevation decreased from 66.1 +/- 8.2 to 25.3 +/- 3.4 mv (P less than 0.001). In seven experiments no Q waves appeared after reperfusion and there was no significant change in tension. Total S-T elevation again decreased from 58.3 +/- 12.7 to 27.1 +/- 5.7 mv (P less than 0.025). When normal saline solution was perfused distal to the coronary arterial occlusion total S-T elevation decreased from 68.0 +/- 3.6 to 36.3 +/- 5.2 mv (P less than 0.001). After 3 hours of coronary occlusion, myocardial K+ decreased and Na+ increased in the ischemic zone, resulting in a significant decrease in the K+/Na+ ratio (P less than 0.005). Reperfusion for 2 hours resulted in a further depletion of K+ and an increase in Na+ with a resultant complete reversal of the K+/Na+ ratio (P less than 0.001). In summary, after reperfusion the S-T segment abnormalities rapidly decreased in all experiments despite the appearance of new Q waves in more than half of these studies concomitant with either a decrease or no change in contractile ability and continuing myocardial K+ loss and Na+ accumulation. S-T segment mapping therefore appears to be of limited value in assessing the effect of reperfusion on infarct size. The decrease in S-T segments that occurred with perfusion of either blood or saline solution suggests a "washout" phenomenon.

The effects of digoxin (priming dose of 0.04 mg/kg body weight followed by infusion of 0.02 mg/kg per min) on local tension and length characteristics of the nonischemic, border and ischemic left ventricular zones were studied in 30 dogs using Walton-Brodie strain gauge arches and mercury-in-Silastic segment length gauges. Total tension in the nonischemic zone increased to 130.9 ± 5.3 percent (P < 0.001) of the control level in association with parallel changes in preejection and ejection tension and rate of rise of tension when infusion of digoxin was instituted 15 to 30 minutes after ligation. Consistent increases in tension variables were noticed when infusion of digitalis was initiated 45 to 60 minutes or 2 to 3 hours after ligation. Segment length remained unchanged. In the border zone, total tension decreased to 68.9 ± 5.9 percent (P < 0.01) 15 to 30 minutes after coronary occlusion and increased to 106.8 ± 9.7 percent (P < 0.01) after infusion of digitalis. When infusion of digitalis was instituted 45 to 60 minutes or 2 to 3 hours after occlusion, similar increases in total tension and other tension variables were seen. Segment length again showed no significant changes. There was an increase in total tension in 5 of the 12 ischemic zones studied when digitalis was infused 15 to 30 minutes after coronary arterial ligation, whereas a consistent (3 to 5 percent) decrease in tension was observed when infusion of digitalis was instituted 45 to 60 minutes and 2 to 3 hours after coronary occlusion. There was no increase in segment length. In summary, digitalis uniformly increased contraction of the nonischemic and border zones after coronary arterial ligation, but the effects on contraction and aneurysmal bulging in the ischemic zone were minimal.

Phentolamine and nitroprusside have recently been shown to improve myocardial performance in the presence of ischemia. The comparative effects of these agents on both local contraction and degree of ischemia in central ischemic, border and nonischemic zones were studied in 10 dogs using Walton-Brodie strain gauges and epicardial electrograms (8 to 12 sites). After coronary occlusion, total tension and rate of tension rise in the border zone decreased to 80.0 ± 8.5 and 76.0 ± 10.5 percent, respectively, whereas total S-T elevation increased from 7.1 ± 2.1 to 117.6 ± 12.1 mv. Tension in the nonischemic zone decreased slightly but not significantly (88.5 ± 9.1 percent). Phentolamine (0.25-2.0 mg/min) decreased systolic pressure by 21.4 ± 2.2 mm Hg and increased tension in the border zone from 80.0 ± 8.5 to 100.4 ± 10.8 percent ( P P P P P P P P P P Thus, both phentolamine and nitroprusside improve local myocardial contractile ability. However, phentolamine, in contrast to nitroprusside, increases the area of ischemic injury as measured by S-T segment elevation. In part, this effect of phentolamine is due to its positive chronotropic action. Thus, each vasodilator agent must be evaluated individually to assess its action in the setting of acute myocardial infarction.

Controversy has existed concerning the value of nitroglycerin therapy in acute myocardial infarction. With use of Walton-Brodie strain gauge arches and mercury-in-Silastic segment length gauges, the effects of nitroglycerin (30 mug/kg intravenously) were studied on local tension and length characteristics of the ischemic, border and nonischemic zones of the left ventricle in 10 open chest dogs. In the nonischemic zone total tension increased to 144.8 +/- 13.6 (mean +/- standard error of the mean) percent (P less than 0.005) of control levels, and segment length decreased to 79.4 +/- 4.4 percent (P less than 0.01) with infusion of nitroglycerin 15 to 30 minutes after coronary ligation. Changes were similar in the groups given nitroglycerin 45 to 60 minutes and 2 to 3 hours after ligation. The border zone exhibited an increase in total tension to 132.3 +/- 8.4 percent (P less than 0.005) of control level and a decrease in segment length to 79.0 +/- 2.4 percent (P less than 0.001) in the 15 to 30 minute group. In the 45 to 60 minute group, tension increased to 117.9 +/- 4.8 percent (P less than 0.005), whereas length decreased to 86.8 +/- 1.4 percent (P less than 0.001); and in the 2 to 3 hour group tension increased to 124.9 +/- 6.0 percent (P less than 0.005), and length decreased to 91.9 +/- 3.5 percent (P less than 0.001). The decrease in magnitude of responsiveness in the 45 to 60 minute and 2 to 3 hour postligation groups compared with the 15 to 30 minute postligation group was highly significant (P less than 0.005). The central ischemic zone showed no significant change in tension or length in any group. Maximal response to nitroglycerin administration in both tension and length parameters was observed within 30 to 60 seconds and was concomitant with a decrease in systolic pressure to 73.3 +/- 1.9 percent (P less than 0.001) and an increase in heart rate to 107.2 +/- 1.0 percent. Nitroglycerin improves the contractile performance of the nonischemic and border zones after coronary occlusion without affecting the central ischemic zone. However, the border zone exhibits a progressive decrease in contractile response as a function of time. These data suggest that nitroglycerin has the overall effect of functionally reducing the extent of the ischemic area and strongly supports its potential clinical usefulness in acute myocardial infarction.

Two hundred sixteen consecutive patients were evaluated to determine the value of pathologic Q waves in predicting the presence and severity of ventricular asynergy. Of 64 patients with pathologic Q waves, 95 percent demonstrated asynergy. Q waves in the anterior leads denoted asynergy in 30 of 30 patients, anterior asynergy in 29 of 30 and an anterior aneurysm in 25. Q waves in the inferior leads indicated asynergy in 30 of 33 patients, inferior asynergy in 25 of 30 and an associated aneurysm in 19. Conversely, of 52 patients with an aneurysm, 44 also had pathologic Q waves. If Q waves were present, 72 percent of asynergic zones exhibited akinesis or dyskinesis; however, in the absence of Q waves an aneurysm was present in only 22 percent (P less than 0.0001). Hemodynamically, anterior asynergy, whether defined by Q waves or by ventriculography, was associated with more left ventricular dysfunction than was inferior asynergy (P less than 0.01). Of 21 patients with a cardiomyopathy, none had pathologic Q waves. The data indicate that pathologic Q waves can aid significantly in predicting the presence and location of a severely asynergic zone. Although their absence does not exclude the possibility of asynergy, the latter is much less likely and, if present, amy be of milder form.

Electrophysiologic changes caused by partial coronary occlusion have not previously been examined. In nine dogs, refractory periods and conduction times were determined using the extrastimulus method after a 50 percent reduction in coronary blood flow. In another five dogs, ventricular automaticity was studied after the production of complete heart block. After 5 minutes of partial coronary occlusion the refractory period in the ischemic zone shortened from 164.6 ± 4.2 (mean ± standard error of the mean) to 149.6 ± 5.8 msec (P < 0.001); after 60 minutes it shortened further to 142.5 ± 5.6 msec, resulting in a dispersion of refractoriness. Intramyocardial conduction time from the ischemic to the non-ischemic zone was prolonged from 48.6 ± 1.6 to 60.0 ± 3.3 msec (P < 0.01), whereas conduction time from the nonischemic to the ischemic zone remained unchanged. No significant changes were observed in ventricular automaticity after partial coronary occlusion (idioventricular rate 56.0 ± 6.4 versus 51.2 ± 6.6 beats/min). Reperfusion 1 hour after partial occlusion resulted in a return of the refractory period and conduction time to preocclusion values, but there were no changes in idioventricular rate. Thus, after a 50 percent reduction in coronary blood flow, the decrease in local refractory period and prolongation of conduction time result in underlying electrical instability predisposing to reentrant arrhythmias whereas automaticity is unchanged. These abnormalities are fully abolished when reperfusion is instituted after 60 minutes of partial coronary occlusion.

The effects of intracoronary diatrizoate meglumine and diatrizoate sodium (Renografin-76) on regional contraction were examined in the normal coronary circulation and during partial (50 percent) coronary occlusion in 11 dogs using strain and length gauges. Intracoronary injections of Renografin-76 (1.5 cc) (1.690 mosM/liter; 0.19 mEq Na/ml), equiosmolar dextrose solution and 0.19 mEq Na+/ml saline solution were made randomly. Renografin-76 caused a decrease in preejection tension to 87.4 +/- 4.3 percent (p less than 0.025), total tension to 74.6 +/- 3.3 percent (p less than 0.01) and ejection tension to 11.9 +/- 12.6 percent (p less than 0.001) of control value. Segment length increased to 106.7 +/- 7.3 percent of control value. These changes lasted only 12 +/- 2 (range 5 to 20) seconds (mean +/- standard error of the mean). During partial coronary occlusion and after injection of Renografin-76, preejection tension decreased from 91.7 +/- 6.3 to 53.8 +/- 3.9 percent (p less than 0.01), total tension from 89.9 +/- 5.0 to 59.7 +/- 3.5 percent (p less than 0.01) and ejection tension from 22.8 +/- 8.1 to 17.8 +/- 10.9 percent, whereas segment length increased from 112.7 +/- 3.7 to 130.7 +/- 4.6 percent (p less than 0.01) of control value. In contrast to findings in the normal coronary circulation, tension and length changes lasted 54 +/- 16 (range 15 to 180) seconds (p less than 0.05). The hyperemic response during normal coronary circulation was completely abolished during partial coronary occlusion. Prior administration of nitroglycerin did not shorten the duration of the myocardial depressant effects of Renografin. Injections of equiosmolar dextrose or saline solution produced qualitatively similar but quantitatively less marked changes. Thus, intracoronary Renografin-76 has an accentuated and prolonged depressant effect on the ischemic as compared with the normally perfused myocardium; this effect is not solely due to its hyperosmolarity or sodium concentration.

An experimental model of a prolapsing left atrial tumor mass has been utilized In dogs to study the hemodynamic events of the cardiac cycle and the cineangiographic and echocardiographic manifestations of this condition. The characteristic ventricular notch has been correlated with the timing of the expulsion of the simulated tumor mass from the left ventricle to the left atrium. The early notch seen with small simulated tumors delays aortic ejection by 0.02 to 0.03 second and results in abbreviated aortic ejection time and minimal distortion of the E-F slope of anterior mitral leaflet motion in the echocardiogram. Larger masses lead to late ventricular notching, transiently interrupt aortic flow and may displace the anterior mitral leaflet until It impinges on the interventricular septum in mid-diastole and at the onset of systole. A transient systolic Increment of coronary flow is observed after expulsion of the tumor from the left ventricle into the left atrium. There is an echo-free interval immediately after opening of the mitral valve, indicating that tumor motion lags perceptibly behind the initial blood flow through the mitral orifice. The sudden expulsion of the mass from the ventricle to the atrium early in systole represents an in vivo example of the quick release phenomenon.

The comparative effects of dopamine and isoproterenol on local myocardial contraction and ischemic injury after coronary occlusion were evaluated in 10 dogs. Dopamine (2.5 to 5 mug/kg per min) and isoproterenol (0.125 to 0.25 mug/kg per min) were randomly infused for 20 minutes, and segmental tension (Walton-Brodie gauge) of central ischemic, border and nonischemic myocardial zones and epicardial electrograms (10 to 12 sites) were simultaneously recorded. After coronary occlusion, tension in border zones decreased to 73.5 +/- 6.4 percent (mean +/- standard error of the mean) and tension in central zones to 60.6 +/- 9.9 percent (P less than 0.001) of control level, whereas total S-T elevation (sigmaST) rose from 10.8 +/- 1.6 to 98.4 +/- 14.0 mv and average S-T elevation (ST) from 1.6 +/- 0.2 to 10.8 +/- 1.6 mv (P less than 0.001). Isoproterenol increased heart rate from 148.7 +/- 6.9 to 170.6 +/- 7.7 beats/min (P less than 0.010) and improved tension in the border zone to 110.5 +/- 8.5 percent (P less than 0.010) and improved tension in the border zone to 110.5 +/- 8.5 percent (P less than 0.005) and nonischemic zone to 128.4 +/- 6.7 percent (P less than 0.02). Tension in the central zone was unchanged. However, sigmaST increased from 98.4 +/- 14.0 to 126.9 +/- 14.7 mv (P less than 0.005) and ST from 10.8 +/- 1.6 to 14.2 +/- 1.6 mv (P less than 0.001). Dopamine did not change heart rate but increased tension in the border zone from 72.4 +/- 7.9 to 124.4 +/- 16.8 percent (P less than 0.001) and tension in the nonischemic zone from 86.0 +/- 10.0 to 133.3 +/- 10.0 percent (P less than 0.01). Tension in the central zone was unimproved. However, sigmaST and ST did not increase (sigmaST from 99.8 +/- 10.8 to 97.7 +/- 13.9 mv and ST from 11.1 +/- 1.3 to 10.8 +/- 1.5 mv). Atrial pacing was used to increase heart rate during infusion of dopamine to 180.0 +/- 7.6 beats/min but neither sigmaST nor ST increased. In summary, both dopamine and isoproterenol decrease contraction abnormalities in the border and nonischemic zones after after acute coronary occlusion. Although isoproterenol increases both heart rate and S-T segment elevation, dopamine does not adversely affect either variable.

The progressive transmural electrographic, biochemical and ultrastructural changes as a function of time after acute coronary occlusion were systematically assessed in eight dogs. Transmural plunge electrodes with poles 1 mm apart were placed in the ischemic and nonischemic zones, and coronary occlusion was maintained for 4 hours. Transmural full thickness biopsy specimens were obtained from each zone for electron microscopy before, and 1 and 4 hours after occlusion. Endocardial and epicardial layers were also obtained for assessment of myocardial potassium ion (K+) and sodium ion (Na+) concentrations. Before coronary occlusion, local Q waves were recorded an average depth of 1.0 +/- 0.34 mm from the endocardial surface. After 1 hour of occlusion, Q waves appeared at an average depth of 3.8 +/- 0.67 mm and progressed to a depth of 5.2 +/- 0.7 mm at 2 hours, 6.2 +/- 0.5 mm at 3 hours and 7.0 +/- 0.5 mm at 4 hours. After 1 hour, ultrastructural changes of early ischemia, including a decrease in glycogen and mild mitochondrial swelling, were seen in the endocardial layer; the epicardial layer showed normal morphologic features. After 4 hours, the endocardial layer showed well developed ischemic changes marked by the loss of mitochondrial cristae, vacuolization, the appearance of amorhopous mitochondrial cristae, vacuolization, the appearance of amorphous mitochondrial densities, an increase in interfibrillary space and the appearance of I bands. In contrast, the epicardial layer at this time showed only early ischemic changes. At the end of 4 hours, the endocardial layer showed a marked decrease in myocardial K+ concentration and an increase in Na+ concentration leading to complete reversal of K+/Na+ ratio (0.7 +/- 1.0; P less than 0.001). In the epicardial layer, a smaller decrease in K+ concentration and an increase in Na+ concentration occurred, resulting in a diminution but not a reversal of K+/Na+ ratio (1.4 +/- 0.2; P less than 0.005). Thus, the dynamic evolution of an acute myocardal infarction involves a sequential progression from endocardium to epicardium as a function of time, resulting in an epicardial "border zone" in the early stages after acute coronary occlusion.

To determine the quantitative relation between partial coronary obstruction and its resultant effects on local contraction, the left anterior descending coronary artery was partially obstructed (while the decrease in both distal pressure and flow were observed) and local tension and length weremeasured in 10 open chest dogs. A pressure gradient index ([AO-COR] /AO) across the obstruction was derived, where AO = mean aortic pressure and COR = mean distal coronary pressure, and was correlated with change in flow (controlflow = 95.3 ± 3.8 ml/100 g). Contractile function of ischemic and nonischemic zones was measured using both Walton-Brodie strain and mercury-in-Silastic segment length gauges. Small pressure gradients (index 0.27 ± 0.03 [mean ± standard error of the mean]) and decreases in distal flow (to 74.2 ± 1.6 ml/100 g) caused no change in tension or length. Further reduction in distal pressure (gradient index 0.52 ± 0.04) and flow (to 50.0 ± 0.8 ml/100 g) produced a decrease in tension to 87.3 ± 3.6 percent of control level (P < 0.005) and an increase in length to 129.1 ± 4.6 percent (P < 0.01). The upstroke of the tension curve during the ejection phase persisted despite the decrease in total tension. Additional reduction of pressure (gradient index 0.71 ± 0.03) and flow (27.7 ± 1.3 ml/100 g) caused a marked decrease in tension to 55.5 ± 11.9 percent of control level (P < 0.01) and an increase in length to 182.0 ± 14.1 percent (P < 0.001). The tension curve demonstrated loss of ejection tension with a negative slope inscribed during the ejection phase. Total occlusion resulted in no additional decrease in distal pressure and, although flow decreased to 5.0 ± 1.2 ml/100 g, no further change in tension (56.8 ± 9.3 percent) or length (183.3 ± 8.9 percent) occurred. Thus, an acute reduction in coronary pressure and flow of 50 percent or more results in regional contraction abnormalities that are further accentuated as the pressure and flow are reduced by 75 percent or more. Maximal abnormalities produced by total occlusion are similar to those produced by a reduction in flow of 75 percent or more.

1. 1. Racial differences of heart disease in Africa are discussed together with apparent differences in standards of normality of electrocardiograms and serum lipid patterns. 2. 2. The high incidence of ischemic heart disease in white South Africans and its virtual absence in the Bantu has been stressed. 3. 3. Heart diseases peculiar to Africa, such as idiopathic cardiac hypertrophy and endomyocardial fibrosis, are described. 4. 4. The difference in altitude found in two South African cities is shown to result in a different incidence of patent ductus arteriosus and in various differences in blood findings. The possibility of these blood differences causing different incidences of myocardial infarction is discussed. 5. 5. The general pattern of heart disease and its relationship to the pattern of other diseases in South Africa receives brief mention.

To study the effects of nitroprusside infusion on the regional contractile performance of the left ventricle after coronary occlusion, local tension and segment length of the ischemic, border and nonischemic zones were studied using Walton-Brodie strain gauge arches and mercury-in-Silastic tubing segment length gauges in open chest dogs. The effect of this intervention on the time period for functional reversibility of the affected areas after revascularization was also examined. Fifteen minutes after occlusion of the left anterior descending coronary artery, nitroprusside (4 to 11 mug/kg per min) was infused to keep systolic pressure 20 to 25% below control levels for 2 hours after occlusion and then 1 hour after reperfusion. The ischemic zone showed no change in either tension or length although there was a gradual continuing decrease in tension. However, in the border zone total tension which had decreased to 81.4 +/- 9.6 (standard error of the mean) percent of control level 15 minutes after coronary occlusion, increased to 87.5 +/- 11.3% immediately after nitroprusside infusion and continued at that level for 2 hours. Preejection tension rate of tension rise and ejection tension demonstrated parallel increases. Segment length, which had increased to 144.1 +/- 4.5% of control level after coronary occlusion, declined to 115 +/- 10.7% (P less than 0.02) immediately after the onset of infusion. The nonischemic zone showed a sustained increase in all tension variables (P less than 0.01) and a decrease in segment length during the period of nitroprusside infusion with a return to control value after discontinuation of the infusion. The immediate deterioration in tension in the ischemic zone caused by reperfusion after 2 hours of occlusion was prevented by nitroprusside. The border zone continued to maintain improved tension after reperfusion but exhibited an immediate decrease from 84.1 +/- 7.8% to 69.1 +/- 11.7% (P less than 0.05) after discontinuation of nitroprusside. In summary, nitroprusside infusion provides a sustained increase in tension and decrease in length of the border and the nonischemic zones after acute coronary occlusion whereas the ischemic zone remains unaffected. Although administration of nitroprusside fails to prolong the time period for functional reversibility of the affected zones with reperfusion, it appears to prevent further deterioration.

Use of propranolol in acute myocardial infarction is limited by its cardiodepressant effects. The effects of nitroglycerin (0.4 mg intravenously) on regional myocardial dysfunction produced by total or partial (50 percent) coronary occlusion and intravenous administration of propranolol (1.0 mg/kg) were evaluated using pairs of ultrasonic crystals implanted subendocardially in the nonischemic and ischemic zones in 14 open chest dogs. During partial coronary occlusion, systolic shortening (% delta L) in the ischemic zone decreased from 20.9 +/- 5.3 to 7.2 +/- 6.4 (p less than 0.001). Propranolol did not change it significantly. Nitroglycerin increased % delta L from 6.7 +/- 4.5 to 11.2 +/- 5.3 (p less than 0.01). The nonischemic zone was unaffected by partial coronary occlusion but showed a decrease in % delta L from 18.6 +/- 6.2 to 15.6 +/- 5.1 (p less than 0.01) with propranolol. Nitroglycerin increased % delta L from 15.6 +/- 5.1 to 17.3 +/- 5.9 (p less than 0.02). During total coronary occlusion, nitroglycerin administration after propranolol improved % delta L in the nonischemic but not in the ischemic zone. Nitroglycerin caused a significant decrease in left ventricular systolic and end-diastolic pressures. Heart rate remained unchanged. It is concluded that nitroglycerin reversed myocardial depressant effects of propranolol in both the partially ischemic and the nonischemic zones after acute coronary occlusion.

While exercise thallium imaging has improved sensitivity and specificity for detection of coronary artery disease (CAD), Its predictive value for morbid cardiac events is unclear. Of 532 consecutive patients who underwent exercise thallium Imaging, follow-up was complete in 515 (97%) after an average of 36 months (range 31 to 48). Two hundred six patients had an abnormal exercise thallium response and 309 had a normal response. Twenty morbid cardiac events occurred (13 deaths and 7 acute myocardial Infarctions [AMI]). Of the 13 patients who died, 12 had abnormal thallium results. Overall, 5.8% of the patients with abnormal thallium results died, in contrast to 0.3% of patients with normal results. Of the 7 patients who had a nonfatal AMI, 3 had abnormal exercise thallium results. Moreover, similar proportions of patients (1.4% and 1.3%) with normal and abnormal exercise thallium results had nonfatal AMI. Presence or absence of pathologic Q waves and inclusion of exercise electrocardiographic results did not significantly after the results. Thus, although a normal exercise thallium response significantly reduces the likelihood of cardiovascular death, its predictive value for nonfatal AMI is limited. Moreover, the relatively low event rate for patients with a positive exercise thallium response further limits Its prognostic value.