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The c-Jun NH(2)-terminal kinase (JNK) pathway of the mitogen-activated protein kinase (MAPK) signaling cascade regulates cell function and survival after stress stimulation. Equally robust studies reported dichotomous results suggesting both protective and detrimental effects of JNK during myocardial ischemia-reperfusion (I/R). The lack of a highly specific JNK inhibitor contributed to this controversy. We recently developed a cell-penetrating, protease-resistant peptide inhibitor of JNK, d-JNKI-1. Here we report on the effects of d-JNKI-1 in myocardial I/R. d-JNKI-1 was tested in isolated-perfused adult rat hearts. Increased activation of JNK, p38-MAPK, and extracellular signal-regulated kinase-1/2 (ERK1/2), as assessed by kinase assays and Western blotting, occurred during I/R. d-JNKI-1 delivered before onset of ischemia prevented the increase in JNK activity while not affecting ERK1/2 and p38-MAPK activation. JNK inhibition reduced ischemic injury, as manifested by increased time to contracture (P < 0.05) and decreased left ventricular end-diastolic pressure during ischemia (P < 0.01), and enhanced posthypoxic recovery of systolic and diastolic function (P < 0.01). d-JNKI-1 reduced mitochondrial cytochrome-c release, caspase-3 activation, and the number of apoptotic cells determined by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (P < 0.05), indicating suppression of the mitochondrial machinery of apoptosis. d-JNKI-1 delivered at the time of reperfusion did not improve functional recovery but still prevented apoptosis. In vivo, d-JNKI-1 reduced infarct size after coronary artery occlusion and reperfusion by approximately 50% (P < 0.01). In conclusion, d-JNKI-1 is an important compound that can be used in preclinical models to investigate the role of JNK signaling in vivo. Inhibition of JNK during I/R is cardioprotective in anesthetized rats in vivo.

Little is known concerning the influence of remote prior coronary artery bypass grafting (CABG) on the outcome of patients with acute myocardial infarction (AMI). Therefore, this study evaluated 2,494 patients with AMI of whom 219 (8.8%) had a history of CABG a mean of 7.1 +/- 3.7 years before the index AMI. Compared with all other patients, those with a history of CABG had an increased prevalence of a history of prior AMI (153 [70%] vs 547 [24%]), congestive heart failure (48 [22%] vs 236 [10%]), and angina pectoris (165 [75%] vs 787 [35%]), all p < 0.001. There was no difference in age, but patients with prior CABG were more often men (192 [88%] vs 1,702 [75%], p < 0.001). During the hospitalization for AMI, patients with prior CABG had more recurrent ischemic pain (100 [46%] vs 732 [32%, p < 0.001]), and more frequently developed non-Q-wave AMI (72 [33%] vs 514 [23%], p < 0.01). In-hospital mortality did not differ among patients with or without prior CABG (15 [7%] vs 195 [9%]). At hospital discharge, more patients with prior CABG had complex ventricular ectopic activity on 24-hour ambulatory electrocardiographic monitoring (48 of 74 [65%] vs 327 of 797 [41%], p < 0.0001), and radionuclide ejection fraction < 0.45 (53 of 99 [54%] vs 430 of 1,024 [42%], p < 0.01). Among patients undergoing coronary angiography during the first 2 months, multivessel coronary artery disease was more prevalent among patients with prior CABG (78 of 107 [73%] vs 508 of 959 [53%], p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Most patients do not undergo acute reperfusion after myocardial infarction, and which of these patients should undergo coronary angiography is still debated., Methods and Results: We analyzed the 1-year clinical outcomes and rates of coronary angiography performed as late as 60 days after myocardial infarction in 3,804 patients admitted between 1979 and 1988 and followed in six different centers. Patients less than 75 years old were classified into low-, medium-, and high-risk groups using a multivariate analysis of historical and clinical variables gathered during the first 8 hospital days. Patients who underwent early reperfusion (17%, all after 1984) were analyzed separately. To analyze time trends, patients were compared before and after mid-1984. Mortalities from day 9 through 1 year were similar for the two time periods in the low- (3.3% versus 2.5%) and medium-risk (7.4% versus 5.6%) groups, but mortality was lower for the high-risk group after 1984 (31.6% versus 20.0%). The proportion of patients undergoing coronary angiography increased dramatically in each group after 1984 (low risk, 18% versus 48%; medium risk, 23% versus 49%; high risk, 10% versus 32%, before and after 1984, respectively). Furthermore, a large percentage of patients (more than 40%) in the low-risk group did not have at least one of the indications for coronary angiography recently recommended by a joint task force. Among patients undergoing coronary angiography, the proportion of patients with three-vessel coronary artery disease decreased after 1984, whereas the proportion undergoing mechanical revascularization in the year after infarction increased in all risk groups., Conclusions: Despite the recent development of noninvasive techniques with high sensitivity for detecting high-risk patients after myocardial infarction, coronary angiography is being performed increasingly in all patients, including those determined to be at low risk for complications based on clinical data. The economic consequences of such a trend could be considerable, and its impact requires careful analysis.

The impact of right bundle branch block on long-term prognosis after anterior wall myocardial infarction is unclear. In 932 patients with Q wave anterior infarction, the short- and long-term prognostic significance of the presence of right bundle branch block was analyzed. Compared with 754 patients without block, 178 patients with right bundle branch block after myocardial infarction showed an increased incidence of left ventricular failure (72% versus 52%, p less than 0.001) and increased in-hospital (32% versus 8%, p less than 0.001) and 1 year after hospital discharge (17% versus 7%, p less than 0.001) cardiac mortality rates. The presence of right bundle branch block was an independent predictor of increased in-hospital and 1-year mortality when entered in a multivariate analysis. However, the absence of left ventricular failure identified a subgroup of patients with right bundle branch block with low in-hospital (4%) and 1 year postdischarge (5%) cardiac mortality rates comparable with those of patients with neither failure nor right bundle branch block (1.7% and 4.8%, respectively). In the presence of left ventricular failure, patients with associated right bundle branch block had higher in-hospital (43% versus 14%, p less than 0.01) and 1 year postdischarge (24% versus 9%, p less than 0.01) cardiac mortality rates than those of patients with failure but no right bundle branch block. Thus, the presence of right bundle branch block after anterior myocardial infarction is an independent marker of poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

In a large population of patients (n = 3666) who were discharged from the hospital after acute myocardial infarction and followed up for 1 year, factors associated with recurrent nonfatal (n = 171) or fatal (n = 74) infarction were identified. Also, the effects of combining various end points (recurrent nonfatal or fatal infarction and other cardiac death) in multivariate analyses, a practice common in many small studies that evaluate the predictive-value of various treatments or special tests, was examined. In univariate analyses, patients with nonfatal recurrent infarction did not differ with respect to age or gender from infarct-free survivors, but they more often had a history of previous myocardial infarction, congestive heart failure, angina pectoris, and diabetes; more severe pulmonary congestion was present on chest x-ray during the admission, and a non-Q wave index infarction was more frequent. Patients with either a fatal or nonfatal recurrent infarction had more angina pectoris during follow-up (55% to 60%) compared with 27% in event-free survivors and 31% in patients who died of other cardiac causes in whom this factor could be assessed before death. In multivariate analyses, historical and clinical prognostic factors were ranked differently for fatal or nonfatal reinfarction and other cardiac causes of death; angina pectoris at follow-up was highly related to recurrent infarction (fatal or nonfatal), along with a history of diabetes, and a non-Q wave index infarction. These factors were not independently related to other causes of cardiac death.(ABSTRACT TRUNCATED AT 250 WORDS)

Little is known concerning late outcome and prognostic factors after acute myocardial infarction in the very elderly (greater than 75 years of age). Accordingly, this study compared the clinical course and mortality rate for up to 1 year in a large multicenter data base that included 702 patients greater than 75 years of age (mean +/- SD 81 +/- 4 years), with a less elderly subset of 1,321 patients between 65 and 75 years of age (mean 70 +/- 3 years). The postdischarge 1 year cardiac mortality rate was 17.6% for those greater than 75 years of age compared with 12.0% for patients between 65 and 75 years of age (p less than 0.01). There were differences in the prevalence of several factors, including female gender, history of angina pectoris, history of congestive heart failure, smoking habits and incidence of congestive heart failure during hospitalization. Multivariate analyses of predictors of cardiac death in hospital survivors selected different factors as important in the two age subgroups; age was selected in the 65 to 75 year age group but was not an independent predictor in the very elderly. The survival curves beginning at day 10 for patients 65 to 75 and in those greater than 75 years old were similar for up to 90 days but diverged later. In the very elderly, 63% of late cardiac deaths were sudden or due to new myocardial infarction, similar to the causes of 67% of deaths in the younger age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated heart rate (HR) during hospitalization and after discharge has been predictive of death in patients with acute myocardial infarction (AMI), but whether this association is primarily due to associated cardiac failure is unknown. The major purpose of this study was to characterize in 1,807 patients with AMI admitted into a multicenter study the relation of HR to in-hospital, after discharge and total mortality from day 2 to 1 year in patients with and without heart failure. HR was examined on admission at maximum level in the coronary care unit, and at hospital discharge. Both in-hospital and postdischarge mortality increased with increasing admission HR, and total mortality (day 2 to 1 year) was 15% for patients with an admission HR between 50 and 60 beats/min, 41% for HR greater than 90 beats/min and 48% for HR greater than or equal to 110 beats/min. Mortality from hospital discharge to 1 year was similarly related to maximal HR in the coronary care unit and to HR at discharge. In patients with severe heart failure (grade 3 or 4 pulmonary congestion on chest x-ray, or shock), cumulative mortality was high regardless of the level of admission HR (range 61 to 68%). However, in patients with pulmonary venous congestion of grade 2, cumulative mortality for patients with admission HR greater than or equal to 90 beats/min was over twice as high as that in patients with admission HR less than 90 beats/min (39 vs 18%, respectively); the same trend was evident in patients with absent to mild heart failure (mortality 18 vs 10%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The value of 0.1 mV or greater of S-T segment elevation in at least one right precordial lead (V4R to V6R) in defining right ventricular myocardial infarction was assessed prospectively in 43 subjects (33 consecutive patients with enzymatically confirmed infarction of varying type and location, 4 patients with unstable angina and 6 healthy volunteers). Patients with acute myocardial infarction were studied with radionuclide ventriculography and technetium-99m stannous pyrophosphate myocardial scintigraphy 18.2 +/- 14.3 (mean +/- standard deviation) and 85.1 +/- 18.0 hours after the onset of symptoms, respectively. Eleven patients (Group A: 9 patients with transmural inferior infarction, 1 with transmural inferolateral infarction and 1 with transmural anteroseptal infarction) demonstrated right precordial S-T segment elevation and 22 patients (Group B: 6 patients with transmural inferior infarction, 2 with transmural posterior infarction, 3 with transmural inferolateral infarction, 3 with transmural anteroseptal infarction, 3 with transmural extensive anterior infarction, 4 with subendocardial anterior infarction and 1 with unclassified infarction) did not. Right ventricular ejection fraction was significantly lower in Group A (0.47 +/- 0.11) than in Group B (0.60 +/- 0.12) (p less than 0.01). Right ventricular total wall motion score was 63.8 +/- 15.6 percent of normal in Group A versus 94.3 +/- 8.5 percent in Group B (p less than 0.001). Technetium-99m pyrophosphate uptake (2+ or greater) over the right ventricle occurred in nine patients (81.8 percent) in Group A and in one patient (4.5 percent) in Group B (p less than 0.001). No patient with unstable angina and no healthy volunteer had S-T segment elevation in a right precordial lead. S-T segment elevation of 0.1 mV or greater in one or more of leads V4R to V6R is both highly sensitive (90 percent) and specific (91 percent) in identifying acute right ventricular infarction.

To test the hypothesis that single-photon emission computed tomography (SPECT) of 99mTc-pyrophosphate (99mTc-PPi) with and without the overlay of tomographic blood pool scintigrams might detect small infarcts not identified by planar imaging, 52 patients were studied 3.2 +/- 2.0(SD) days after hospital admission for suspected acute myocardial infarction. Patients were chosen prospectively for tomographic study primarily, but not exclusively, because planar four-view imaging with 99mTc-PPi was either negative or equivocal. SPECT was performed with a commercial rotating detector system immediately after planar imaging on one occasion. Corresponding 99mTc-PPi and blood pool sections were mapped into opposite halves of a bichromic color table and displayed as an overlay. Planar images, SPECT and SPECT with blood pool overlay were interpreted separately and in random order without knowledge of clinical data. Seventeen patients had transmural infarcts (four anterior, 13 inferior), 19 had nontransmural infarcts, and 16 patients did not have acute myocardial infarction. The sensitivity of SPECT with blood pool overlay was significantly better than planar imaging for the entire group with myocardial infarction (97% vs 78%; p less than .025); this was primarily due to increased sensitivity in the detection of nontransmural myocardial infarction (95% vs 67%; p less than .05), although in one additional patient inferior transmural myocardial infarction was also detected by the SPECT overlay technique. The specificities of the SPECT overlay technique and planar imaging were not significantly different; however, receiver operating characteristic analysis showed enhanced observer confidence with the tomographic method. SPECT without overlay was intermediate in sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess various factors associated with anterior S-T segment depression during acute inferior myocardial infarction, 47 consecutive patients with electrocardiographic evidence of a first transmural inferior infarction were studied prospectively with radionuclide ventriculography an average of 7.3 hours (range 2.9 to 15.3) after the onset of symptoms. Thirty-nine patients (Group I) had anterior S-T depression in the initial electrocardiogram and 8 (Group II) did not have such "reciprocal" changes. There was no difference between the two groups in left ventricular end-diastolic or end-diastolic volume index or left ventricular ejection fraction. Stroke volume index was greater in Group I than in Group II. There were no group differences in left ventricular total or regional wall motion scores. A weak correlation existed between the quantities (mV) or inferior S-T segment elevation and reciprocal S-T depression. No relation between anterior S-T segment depression and the left ventricular end-diastolic volume index could be demonstrated; the extent of left ventricular apical and right ventricular wall motion abnormalities, both frequently associated with inferior infarction, did not correlate with the quantity of anterior S-T depression. These data show that anterior S-T segment depression occurs commonly during the early evolution of transmural inferior infarction, is not generally a marker of functionally significant anterior ischemia and cannot be used to predict left ventricular function in individual patients. Anterior S-T segment depression may be determined by reciprocal mechanisms.

Whether ventricular fibrillation occurring within 48 h after acute myocardial infarction is associated with particular clinical features and poor prognosis, especially in patients with anterior myocardial infarction, is still debated. Therefore, clinical variables and in-hospital and 1 year mortality rates were analyzed in 2,088 patients, aged 18 to 95 years (mean +/- SD 64 +/- 12), admitted to the hospital with acute myocardial infarction between 1979 and mid 1984. One hundred forty-seven patients (7%) had at least one episode of ventricular fibrillation occurring within 48 h of hospital admission. Of these, 25% died during their initial hospitalization compared with 13% of patients without early ventricular fibrillation (p less than 0.001). In greater than 50% of patients with early ventricular fibrillation, the immediate cause of death was left ventricular failure or cardiogenic shock. In contrast, the 1 year mortality rate after hospital discharge was not significantly greater in patients with than in those without early ventricular fibrillation (15 versus 11%, respectively), particularly in the subgroup of patients with anterior myocardial infarction in which the mortality rate tended to be lower in patients with early ventricular fibrillation (8 versus 14%, respectively). Similar mortality results were found when only primary (not associated with left ventricular failure) ventricular fibrillation was analyzed. The left ventricular ejection fraction and the incidence of complex ventricular arrhythmias from 24 h ambulatory electrocardiographic monitoring obtained at hospital discharge were not different in survivors with or without early ventricular fibrillation (0.45 +/- 0.13 versus 0.49 +/- 0.14 and 41 versus 41%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

"Persistently abnormal" technetium-99m stannous pyrophosphate myocardial scintigrams (PPi+) appear to be associated with a relatively poor prognosis after acute myocardial infarction (AMI). To assess the incidence and implications of PPi+, we performed a retrospective analysis in 29 patients with and 25 patients without diabetes mellitus who had abnormal myocardial scintigrams within 4 days of AMI and who had follow-up scintigrams at least 3 months after hospital discharge. There were no significant differences between patients with and without diabetes as regards age, incidence of transmural or nontransmural AMI, or degree of left ventricular dysfunction after AMI. Persistently abnormal PPi+ occurred more commonly in patients with diabetes than in nondiabetic patients (18 of 29, 62%, compared to 3 of 25, 12%; p less than 0.001). Patients with chronic PPi+ had more frequent cardiac complications following hospital discharge (p less than 0.005) including death, recurrent AMI, unstable angina, and intractable congestive heart failure. Postmortem analysis in two patients with diabetes and chronic PPi+ revealed marked myocytolysis. Thus, patients with diabetes mellitus have an increased incidence of post-AMI "persistently abnormal" technetium (PPi+) scintigrams and relatively poor prognosis following myocardial infarction.

The topographic relationship between the uptake of technetium-99m pyrophosphate (PPi) and myocardial infarction delineated by 2,3,5-triphenyl tetrazolium chloride (TTC) was studied in a canine model of permanent coronary occlusion (24-48 hr). Photographs of TTC staining and scintigraphic images of PPi uptake were planimetered for infarct area. In addition, narrow tissue samples (3 X 10 mm) were taken on both sides of the TTC border and counted for PPi uptake. A significant correlation (p less than 0.001) was found between area of PPi uptake and area of myocardium unstained by TTC (r = 0.84 in epicardium and r = 0.91 in endocardium). The slope relating PPi to TTC for all infarcts was 1.01 +/- 0.11, indicating that variations in infarct size were followed equally by the two techniques. Tissue counting showed the ratio of PPi activity just inside the infarct to activity just outside the infarct to be 9.2 +/- 0.6 (mean +/- s.e.m.). Thus, PPi is distributed topographically in a manner identical to the distribution of irreversibly injured myocardium as delineated by TTC.

Submaximal exercise testing with radionuclide ventriculography was performed in 117 patients prior to hospital discharge 16.7 +/- 6.7 days (SD) following acute myocardial infarction. The hypothesis tested in this study was that patients with different locations and types of infarction have different functional responses to submaximal exercise prior to discharge. The distribution of the myocardial infarctions were anterior transmural in 33, inferior transmural in 39, anterior nontransmural in 23, inferior nontransmural in 19, and indeterminant in three. Patients with transmural infarction generally had significantly larger resting left ventricular volumes at end-diastole and end-systole and lower ejection fractions and systolic blood pressure/end-systolic volume indexes than patients with nontransmural infarctions (p less than 0.05). During submaximal exercise, the change in end-systolic volume was significantly different in these two groups. When patients were separated further into anterior and inferior transmural subgroups, the patients with anterior transmural infarction had significantly lower left ventricular ejection fractions and higher right ventricular ejection fractions than the group with inferior transmural infarction (p less than 0.05). In response to exercise, the group with anterior transmural infarction had a significant decrease in left ventricular ejection fraction and a blunted systolic blood pressure/left ventricular end-systolic volume index, in comparison to patients with inferior myocardial infarction (p less than 0.05); this was the only group to have a significant increase in end-systolic volume. The group variance for the parameters studied was large, particularly during exercise when the individual responses were frequently directionally opposite from the group means. The group with anterior transmural infarction was the most homogeneous, with 26 of 33 having a directionally abnormal response to submaximal exercise. It was concluded that the group with anterior transmural infarction generally displayed the most abnormal left ventricular function. However, despite significant group differences in resting ventricular function with different infarcts, the intragroup variability at rest and in response to exercise was too great to permit an accurate prediction of the subject's resting ventricular performance or to permit a prediction of exercise response based solely on location of the infarct.

The contention that mortality after acute myocardial infarction (AMI) is increased in women compared with men has been controversial, with findings in a recent multicenter study suggesting that gender plays an important prognostic role. To assess whether or not early and late mortality after AMI is greater in women, 2,089 patients (1,551 men, 538 women) were followed for 1 year after AMI. In the hospital, women had an increased mortality compared to men (17.5 vs 12.3%, p less than 0.003) and were on average 7 years older, whereas after hospital discharge and up to 1 year no difference in mortality was observed. Multivariate analyses of historical, clinical and laboratory features demonstrated that gender had no independent predictive value when variables that included age, congestive heart failure in the hospital, history of congestive failure, prior AMI and diabetes mellitus were considered. Moreover, when age stratification was performed, the significant difference of in-hospital mortality between genders was no longer present. Causes of death in the hospital and during 1 year after hospital discharge were similar between men and women, whether or not age stratification was performed. Several baseline clinical characteristics were different between men and women; a history of systemic hypertension and congestive heart failure occurred more frequently in women and previous AMI and smoking occurred more commonly in men. Also, the value of several other important prognostic indicators after AMI, such as the ejection fraction, was found to differ between men and women.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial rupture following infarction usually is an acute and dramatic event. Rarely, it may take a subacute course, allowing surgical treatment. We report herein a case of subacute rupture of the heart in a 54 year old patient with acute myocardial infarction. The rupture was diagnosed by the appearance of a radiopaque halo around the heart during radionuclide ventriculography. The patient subsequently underwent surgical resection of a large anterolateral aneurysm and a 2 inch long rupture of the myocardium and survived. Clinical suspicion, prompt diagnosis, and surgical intervention are important in the management of this relatively unusual complication of infarction.

Since current data on vasopressin (AVP) secretion during the early phase of myocardial infarction is not extensive, plasma AVP was measured in 26 patients with acute myocardial infarction. Twelve had an increased AVP concentration (23.2 +/- 7.0 pg/ml; mean +/- SEM) whereas 14 had an AVP level less than 3 pg/ml (1.96 +/- 0.14 pg/ml). The patients with AVP greater than 3 pg/ml had higher heart rate and plasma osmolality than those with AVP less than 3 pg/ml. Blood pressure values were the same in both groups of patients. There was no difference in peak CPK and iso CPK activities between the two groups. Seven patients with AVP greater than 3 pg/ml died within the next few days, while only 1 patient with AVP less than pg/ml died. It thus appears that increased AVP concentration during acute myocardial infarction is associated with a poor prognosis. Whether it is a cause or a consequence of an unfavourable course of myocardial infarction remains to be determined.

Some studies have reported increased short-term mortality and higher incidence of multivessel coronary artery disease in patients with inferior myocardial infarction and complete heart block, but information is lacking on clinical outcome after hospital discharge. Therefore, data were obtained and analyzed in 749 patients who were admitted with inferior myocardial infarction to four different centers and followed up for 1 year. Six hundred fifty-four patients (Group 1) did not have complete heart block and 95 (Group 2) had complete heart block during their hospital stay (incidence rate 12.8%). Compared with Group 1, Group 2 patients were older (66 versus 61 years, p less than 0.01), more often had signs of left ventricular failure (p less than 0.001) and had higher peak creatine kinase values (1,840 versus 1,322 IU/liter, p less than 0.001). The in-hospital mortality rate was higher in Group 2 than in Group 1 (24.2 versus 6.3%, p less than 0.001). However, at discharge there was no difference between Group 1 and Group 2 in clinical characteristics, left ventricular ejection fraction (0.52 +/- 0.12 versus 0.52 +/- 0.11) or incidence of complex ventricular arrhythmias on ambulatory electrocardiographic monitoring. Furthermore, during the year after hospital discharge, patients in Groups 1 and 2 did not have significantly different mortality rates (6.4 versus 10.1%, p = NS). The incidence rate of reinfarction (4%) was the same in Groups 1 and 2. The incidence of coronary artery bypass surgery was slightly but not significantly higher in Group 1 compared with Group 2 (11 versus 4%).(ABSTRACT TRUNCATED AT 250 WORDS)

It is important to select patients in the convalescent phase of acute myocardial infarction in whom knowledge of coronary anatomy may identify those potentially suitable for intervention aimed at improving prognosis. However, differing guidelines have been proposed, and by applying some of these guidelines to our large database of patients after acute myocardial infarction, several problem areas were identified. These include lack of considering patients with resting ischemia beyond day 5 of hospitalization, management of patients with reduced ventricular function or patients not exercise tested, and the role of coronary angiography in the elderly. Based on this experience and further analysis in 1,848 patients surviving beyond day 5 of hospitalization, a modified decision scheme for coronary angiography was developed and then tested in a second population (n = 780). In the new scheme, patients over 75 years of age are considered individually. Those under 75 years of age with severe resting ischemia in the hospital at any time beyond the first 24 hours (18% mortality between day 6 and year 1), and hospital survivors with a history of previous myocardial infarction and clinical or radiographic signs of left ventricular failure in the hospital (25% 1-year mortality after discharge), are recommended for coronary angiography. Among the remaining patients, some will perform an exercise test, and those with an ischemic response or poor workload (11% 1-year mortality) are also assigned to coronary angiography. When an exercise test is not performed, a resting radionuclide left ventricular ejection fraction is recommended, and coronary angiography is considered if the value lies between 0.20 and 0.44 (12% 1-year mortality). This relatively simple scheme does not make general recommendations in the elderly, considers patients with in-hospital left ventricular failure or reduced left ventricular function or both, and approaches the problem of patients who do not perform an exercise test. This general approach would avoid early coronary angiography in patients with an average 1-year mortality risk after discharge of 3% and recommend coronary angiography in those at increased risk (average mortality rate, 16%) who make up about 55% of this population under 75 years of age.

In order to assess the relative impact on left and right ventricular function of nontransmural and transmural acute myocardial infarction (AMI), we performed radionuclide ventriculography in 86 patients (54 men and 32 women) within 16 hours after a first infarct. Nontransmural infarction was present in 19 patients (11 anterior and 8 inferior). Transmural infarction was found in 67 patients (30 anterior and 37 inferior). Left ventricular ejection fractions were higher (0.57 +/- .014 vs 0.46 +/- 0.14, p less than 0.005) and left ventricular end-systolic volume lower (29 +/- 11 vs 42 +/- 20 ml/m2, p = 0.013) in patients with nontransmural infarction compared to those with transmural infarction. Right ventricular ejection fraction also may have been different in the two groups (0.63 +/- 0.15 vs 0.55 +/- 0.13, p = 0.057). In patients with inferior infarction, left and right ventricular ejection fractions were similar in patients with nontransmural and transmural infarction (0.60 +/- 0.09 vs 0.55 +/- 0.10, p = 0.119 and 0.58 +/- 0.14 vs 0.51 +/- 12, p = 0.226). On the other hand, patients with anterior transmural infarction had lower left ventricular ejection fractions (0.36 +/- 0.12 vs 0.54 +/- 0.17, p = 0.003) but similar right ventricular ejection fractions (0.60 +/- 0.13 vs 0.66 +/- 0.14, p = 0.14) compared to those with nontransmural anterior infarction. In 29 additional patients with a history of previous infarction, no differences in any of the parameters studied were found between those with transmural and those with nontransmural infarcts.(ABSTRACT TRUNCATED AT 250 WORDS)

The "doughnut" pattern on Tc-99m pyrophosphate (PPi) myocardial scintigraphy is characterized by a border of tracer uptake surrounding a central zone of relatively decreased activity. This pattern is generally associated with large transmural anterior myocardial infarcts (MI) caused by occlusion or critical stenosis of the left anterior descending coronary artery. Such infarcts typically involve a significant portion of the anterior wall and are associated with a complicated clinical course and poor prognosis. In order to evaluate the relationship between the presence of the doughnut pattern and left ventricular (LV) function, radionuclide ventriculography was performed within 15 days after infarction in 58 patients with transmural anterior MI. In patients without previous MI, 15/38 (39.5%) had doughnut scintigrams. These patients demonstrated significant reductions in LV ejection fraction (EF) (28 +/- 10% versus 45 +/- 12%, P less than 0.001) and normalized LV wall motion scores (29 +/- 11% versus 61 +/- 10%, P less than 0.001) when compared with patients with "nondoughnut" scintigrams. Patients with doughnut scintigrams had a significantly greater incidence of severe septal hypokinesis (P less than 0.001) and apical dyskinesis (P less than 0.03). LV end-systolic volumes were also larger in the patients with doughnut scintigrams (73 +/- 32 ml versus 40 +/- 17 mI/M2, P less than 0.005). In contrast, there was no significant difference in LVEF, normalized LV wall motion score, or LV volumes between doughnut and nondoughnut groups in patients with previous MI.

This study examines patients with a first myocardial infarction (MI) (about 70% of the population, n = 2089), and identifies factors associated with 1-year cardiac mortality in patients discharged alive. With the use of multivarate analysis of variables observed at hospital discharge in patients with a first MI, age was the most important predictor, followed by left ventricular ejection fraction (LVEF) (determined in 56%) and other variables. Based on this finding, age subsets (less than or equal to 50, 51 to 70, greater than 70 years) were related to LVEF groups (less than or equal to 0.40, 0.41 to 0.50, greater than 0.50). Patients with a first MI who were less than 50 years of age with LVEF greater than 0.40 and patients between 51 and 70 years of age with LVEF greater than 0.50 had a very low risk for 1-year cardiac death, 1.2 +/- 1.1% (95% confidence interval). Such patients comprised 47% of individuals with a first MI having an LVEF determination. Mortality in the remaining patients less than 70 years was 7.4 +/- 3.5%. Mortality for patients greater than 70 years was high, 22.2 +/- 6.6%. Thus with LVEF as the only predischarge test, a sizable low risk group can be identified among patients with a first MI.

The left ventricular (LV) ejection fraction (EF) is known to be an independent predictor of late prognosis after acute myocardial infarction. Despite a previous report that early heart failure (evidenced only by advanced pulmonary rales in the hospital) can predict prognosis in the absence of severe depression of the LVEF at hospital discharge, the potentially strong influence of various measures of in-hospital heart failure on the predictive ability of LVEF has not been generally appreciated. Accordingly, in 972 patients with acute myocardial infarction the effect on late mortality of the presence or absence in-hospital of both clinical and radiographic signs of LV failure in subgroups of patients with normal, moderately or severely depressed LVEF was examined and measured close to hospital discharge. Patients were divided into 3 groups according to LVEF: group I LVEF less than or equal to 40, n = 265; group II LVEF 0.41 to 0.50, n = 241 and group III LVEF greater than or equal to 0.51, n = 466. When clinical signs of LV failure were present at any time during the coronary care unit period, the 1-year mortality rate after hospital discharge in groups I, II and III was 26, 19 and 8%, compared with 12% (p less than 0.01), 6% (p less than 0.01) and 3% (p less than 0.02), respectively, when signs of LV failure were absent.(ABSTRACT TRUNCATED AT 250 WORDS)

The location and extent of myocardial infarction (MI) are important predictors of patient course. The current study tests the hypothesis that MI size could be measured accurately using rotating gamma camera single-photon emission computed tomography ( SPECT ) and technetium-99m pyrophosphate (PPi) and that the accuracy of these measurements was independent of MI location and transmural or nontransmural distribution. SPECT was performed in 38 dogs 48 hours after ligation of the left anterior descending coronary artery (14 dogs) or left circumflex coronary artery (LC) (24 dogs) at the mid-level or below. Projection images were corrected for center-of-rotation and field nonuniformity and processed with a 1-dimensional low-pass filter to diminish rib activity. Sixteen 0.5-cm-thick transverse sections, including the entire left ventricle, were reconstructed by filtered backprojection , low-pass filtered, contrast enhanced and processed with a 3-dimensional boundary enhancement operator. The boundary of PPi uptake in each slice was marked automatically using an algorithm that combined a directional derivative and a threshold, and required continuity of the boundary in 3 dimensions. The total number of volume elements that showed abnormal tracer uptake were summed, corrected to absolute volume, and multiplied by the specific weight of cardiac muscle. Scintigraphic MI weight was compared with pathologic MI weight. There was an excellent correlation between scintigraphic and pathologic MI weight. The poorer correlation for nontransmural compared with transmural MIs is most likely a function of size alone, since MIs that weighed less than 10 g (n = 12, range 1.3 to 9.5 g), both transmural and nontransmural, showed a similar correlation: S = 1.07 X P + 0.56 (r = 0.81, standard error of the slope = 0.245).(ABSTRACT TRUNCATED AT 250 WORDS)

Submaximal exercise testing with radionuclide ventriculography (RVG) was performed in 117 patients before hospital discharge 17 +/- 7 days (+/- standard deviation) after an acute myocardial infarction (MI). The hypothesis tested in these studies was that submaximal exercise testing coupled to RVG allows the identification of patients at risk for future ischemic events in the subsequent 6 months, irrespective of MI location and type. The sites of MI were characterized as anterior transmural in 33, inferior transmural in 39, limited nontransmural in 18, extensive nontransmural in 24 and indeterminant in 3. During 6 months of follow-up, 9 patients died, 14 had recurrent MI, 18 had refractory angina pectoris, 16 had limiting angina and 17 had congestive heart failure. Discriminant function analysis ranked exercise changes in left ventricular (LV) ejection fraction and end-systolic volume the most important of all clinical, exercise and scintigraphic variables for predicting future cardiac events. The predictive accuracy of changes in LV ejection fraction and end-systolic volume were 93 and 91%, respectively, for the entire group, and were significantly more sensitive than any degree of ST-segment depression or elevation (p less than 0.001). These findings were generally independent of MI location and type. Thus, submaximal exercise RVG after MI is an accurate means of identifying patients at risk for major cardiac events in the 6 months after hospital discharge.

Circadian variation of the onset of acute myocardial infarction has been noted in many studies and may carry important pathophysiologic implications. However, only a few previous studies have attempted subgroup analyses. In 4,796 patients with documented acute myocardial infarction, the time of symptom onset was recorded. As in other studies, the peak of onset occurred in the morning from 6:01 AM to 12:00 noon, and 28% of the population (1.16 times the average percentage for the other time periods) experienced symptom onset in that period (p less than 0.001). There was a second, lower peak (25%) in the evening between 6:01 PM and 12:00 midnight, which was also observed in some previous studies. We sought to determine whether or not the presence of subgroups with specific clinical characteristics would exhibit different patterns and thereby contribute to these peaks in the overall population. In patients with a history of congestive heart failure (n = 606) or with non-Q wave infarction (n = 832), a pronounced peak (29%) occurred only in the evening. Two nearly equal peaks were observed in patients older than 70 years of age (n = 1,422), smokers (n = 2,057), diabetics (n = 767), women (n = 1,213), and patients taking beta-blocking drugs (n = 847). Finally, in patients with a previous myocardial infarction (n = 1,104), no peaks were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

In patients who survive the acute phase of myocardial infarction, those with multivessel coronary artery disease generally have a worse prognosis than those with single-vessel disease. However, some patients with significant multivessel stenoses have a good prognosis, whereas some with a significant single-vessel stenosis have a poor prognosis. Thus, although definition of coronary anatomy may be helpful, it is a not a fail-safe prognosticator. In this retrospective analysis, the association of abnormalities at rest and during submaximal exercise testing with radionuclide ventriculography after acute myocardial infarction with major cardiac complications (death, recurrent infarction, severe angina or congestive heart failure) in the ensuing 6 months was assessed in patients with single and multivessel disease. Coronary angiography and submaximal exercise testing with radionuclide ventriculography were performed within 3 months of each other in 42 patients. Eleven of the 16 patients with single-vessel coronary stenosis had major cardiac complications. The subsequent course of these 16 patients was correctly predicted by left ventricular ejection fraction (LVEF) less than or equal to 0.40 in 8 patients, by LVEF less than 0.55 in 7 patients, by failure of LVEF to increase by 0.05 units in 13 patients, and by an increase in left ventricular end-systolic volume index (LVESVI) during exercise greater than 5% above baseline in 11 patients. Of the 26 patients with multivessel coronary artery disease, 24 had major cardiac complications. The subsequent course of these 26 patients was correctly predicted in 13 by LVEF less than or equal to 0.40, in 20 by LVEF less than 0.55, in 25 by a failure of LVEF to increase by 0.05 units during exercise, and in 20 by an increase in LVESVI by greater than 5% during exercise. Thus, submaximal exercise testing with radionuclide ventriculography may provide valuable prognostic information concerning the occurrence of major cardiac events after myocardial infarction not only in patients with multivessel disease, but also in those with single-vessel disease. Exercise-induced abnormalities of left ventricular function may have greater prognostic importance than the delineation of coronary arterial anatomy or the assessment of residual left ventricular function at rest.

Prognosis for patients with non-Q wave myocardial infarction is controversial although a number of studies have shown a less favorable outlook after hospital discharge for patients with non-Q wave than for those with Q wave infarction. Therefore, the in-hospital and 1-year prognosis was investigated in a sufficiently large patient population (n = 2,024) to allow stratification by subgroups, in particular by age and previous myocardial infarction. Patients with non-Q wave infarction (n = 444; 22% of the total study population) were somewhat older (65 vs. 63 years, p less than 0.001) and had an increased incidence of previous myocardial infarction (46% vs. 24%, p less than 0.001) and congestive heart failure (21% vs. 8%, p less than 0.001) than patients with Q wave infarction. In-hospital mortality of patients with non-Q wave infarction was lower (8.1% vs. 11.5%; p less than 0.06), whereas their 1-year mortality after hospital discharge was significantly higher (13.7% vs. 9.2%, p less than 0.05) than for patients with Q wave infarction. However, total mortalities at 1 year were nearly equal. When patients were subgrouped by presence or absence of a previous myocardial infarction, patients in both subgroups exhibited mortality patterns typical of the entire population with Q wave or non-Q wave infarction. However, when stratified by age and previous infarction, in-hospital mortality for patients with non-Q wave infarction was significantly lower only in patients older than 70 years of age. Similarly, the higher mortality after hospital discharge in patients with non-Q wave infarction occurred only in patients older than 70 years of age without previous myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

The time between coronary artery occlusion and reperfusion remains the decisive factor for myocardial function in acute myocardial infarction. Of 110 patients admitted to hospital less than 3 hours after the onset of chest pain, 83 underwent intracoronary thrombolysis with streptokinase or urokinase. 27 patients underwent mechanical recanalization with the aid of a steerable guide wire (Schneider 0.014") followed by transluminal angioplasty of the residual stenosis. 70 of 83 patients (84%) were recanalized by intracoronary streptokinase perfusion within 45 +/- 10 minutes. By mechanical recanalization the occluded artery could be recanalized in 27 patients within 6 +/- 1 minutes. During the same session transluminal angioplasty was performed while the affected coronary artery was perfused for 20 minutes with 20,000-50,000 U streptokinase. 2 patients died after intracoronary thrombolysis (2.4%) and 1 patient died after mechanical recanalization (3.7%). 25 of 26 survivors of the mechanical recanalization group were discharged after bicycle stress testing, and 1 patient underwent a coronary bypass operation. In the intracoronary thrombolysis group, 4 patients presented with reobstruction of the affected vessel within 24 hours of the intervention (4.8%). Of the remaining 66 patients. 20 underwent transluminal coronary angioplasty (285), 16 coronary bypass (22%) and 30 received drug therapy (43%). Left ventricular injection fraction, measured 24 hours after treatment, was 63 +/- 10% in the mechanical recanalization group and 53 +/- 9% in the intracoronary thrombolysis group.

Studies using arginine–glycine–aspartate (RGD)-PET agents in cardiovascular diseases have been recently published. The aim of this systematic review was to perform an updated, evidence-based summary about the role of RGD-based PET agents in patients with cardiovascular diseases to better address future research in this setting. Original articles within the field of interest reporting the role of RGD-based PET agents in patients with cardiovascular diseases were eligible for inclusion in this systematic review. A systematic literature search of PubMed/MEDLINE and Cochrane library databases was performed until October 26, 2021. Literature shows an increasing role of RGD-based PET agents in patients with cardiovascular diseases. Overall, two main topics emerged: the infarcted myocardium and atherosclerosis. The existing studies support that αvβ3 integrin expression in the infarcted myocardium is well evident in RGD PET/CT scans. RGD-based PET radiotracers accumulate at the site of infarction as early as 3 days and seem to be peaking at 1–3 weeks post myocardial infarction before decreasing, but only 1 study assessed serial changes of myocardial RGD-based PET uptake after ischemic events. RGD-based PET uptake in large vessels showed correlation with CT plaque burden, and increased signal was found in patients with prior cardiovascular events. In human atherosclerotic carotid plaques, increased PET signal was observed in stenotic compared with non-stenotic areas based on MR or CT angiography data. Histopathological analysis found a co-localization between tracer accumulation and areas of αvβ3 expression. Promising applications using RGD-based PET agents are emerging, such as prediction of remodeling processes in the infarcted myocardium or detection of active atherosclerosis, with potentially significant clinical impact.