Antimyosin imaging in acute transmural myocardial infarctions: results of a multicenter clinical trial.

Murine monoclonal antimyosin antibody has been shown experimentally to bind selectively to irreversibly damaged myocytes. To evaluate the safety and efficacy of monoclonal antimyosin for identifying acute transmural infarction, 50 patients with acute Q wave myocardial infarction were entered into a phase I/II multicenter trial involving three clinical sites. Indium-111 antimyosin was prepared from an instant kit formulation containing 0.5 mg of diethylene triamine pentaacetic acid (DTPA)-coupled Fab fragment (R11D10) and 1.2 to 2.4 mCi of indium-111. Average labeling efficiency was 92%. Antimyosin was injected 27 +/- 16 h after the onset of chest pain. Planar or tomographic imaging was performed 27 +/- 9 h after injection in all patients, and repeat imaging was done 24 h later in 39 patients. Of the 50 patients entered, 46 showed myocardial uptake of antimyosin (sensitivity 92%). Thirty-one of 39 planar scans performed at 24 h were diagnostic; 8 showed persistent blood pool activity that cleared by 48 h. Focal myocardial uptake of antimyosin corresponded to electrocardiographic infarct localization. No patient had an adverse reaction to antimyosin. In addition, 125 serum samples, including 21 collected greater than 42 days after injection, were tested for human antimouse antibodies, and all samples were assessed as having undetectable titers. Intensity of antimyosin uptake was correlated with infarct location and the presence or absence of collateral vessels. There was a significant correlation between faint uptake and inferoposterior infarct location. In 21 patients who had coronary angiography close to the time of antimyosin injection, there was a significant correlation between faint tracer uptake and closed infarct-related vessel with absent collateral flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous transluminal coronary angioplasty in women compared with men.

OBJECTIVES: This study compares in-hospital and long-term outcome after angioplasty in women and men. BACKGROUND: The recognition that coronary artery disease is the most common cause of death in women has increased interest in outcome studies of coronary artery disease in women. METHODS: Patients who had previous coronary revascularization and those who underwent angioplasty in the setting of acute myocardial infarction were excluded. Angioplasty was performed with standard methods. Clinical data were retrieved from a clinical data base and analyzed with standard statistical methods. RESULTS: There were 2,845 women and 7,940 men. The women were older (62 +/- 11 vs. 57 +/- 10 years) and had more hypertension (54.5% vs. 40.1%), diabetes (19.3% vs. 11.7%), grade III to IV angina (71.5% vs. 58.4%) and congestive failure (4.3% vs. 2.1%) than men (all p < 0.0001). More men had a previous myocardial infarction (35.4% vs. 31.0%) and were taller and weighed more (all p < 0.0001). The men had lower ejection fractions and more multivessel disease (31.0% vs. 25.2%) (both p < 0.0001). In women there was a trend toward more Q wave myocardial infarctions (1.1% vs. 0.75%, p = 0.10), and hospital mortality was higher (0.7% vs. 0.1%, p < 0.0001). Angina at follow-up was more common in women 40.2% vs. 26.7%, p < 0.0001). The multivariate correlates of in-hospital death were short stature, reduced ejection fraction and multivessel disease, with trends for older age and female gender. Five-year survival was 95% in men and 92% in women (p = 0.0002). However, female gender was not a multivariate correlate of long-term survival and was accounted for by other characteristics, primarily age. The multivariate correlates of long-term survival were older age, congestive failure, reduced ejection fraction, multivessel disease, diabetes, hypertension and a trend for severe angina. No difference between women and men was noted in long-term freedom from myocardial infarction. There were more additional procedures in men than in women. CONCLUSIONS: Despite higher in-hospital mortality, long-term mortality and clinical outcome were similar in both genders when age and body habitus were accounted for.

A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue-type plasminogen activator (activase) in acute myocardial infarction.

A new, predominantly single chain preparation of recombinant tissue-type plasminogen activator was evaluated to determine coronary thrombolytic efficacy in 100 patients with acute myocardial infarction. At 3.6 +/- 1.2 hours (mean +/- SD) from symptom onset, patients received either intravenous tissue plasminogen activator (1.25 mg/kg body weight over 3 hours) or placebo on a 3:1 randomized, double-blind basis. Coronary angiography, performed 68 +/- 13 minutes after initiation of the study drug infusion, demonstrated patency of the infarct-related artery in 40 (57%) of 70 patients in the tissue plasminogen activator group compared with 3 (13%) of 23 patients in the placebo group (p less than 0.001). Patients in the placebo group were then eligible to receive intracoronary streptokinase. At 90 minutes the patency was observed in 49 (69%) of 71 tissue plasminogen activator patients compared with 5 (24%) of 21 placebo patients (p less than 0.001). At 120 minutes patency was observed in 59 (79%) of 75 patients of the tissue plasminogen activator group and in 10 (40%) of 25 in the intracoronary streptokinase/placebo group. A nadir value of less than 100 mg/dl fibrinogen occurred in 8 (11%) of 73 patients receiving tissue plasminogen activator versus 8 (40%) of 20 patients treated with intracoronary streptokinase (p = 0.002). Moderate or severe bleeding episodes occurred in 39% of patients treated with tissue plasminogen activator compared with 32% of patients who received placebo/intracoronary streptokinase (p = NS). Thus, this tissue plasminogen activator preparation achieves a high rate of recanalization and, at the doses employed, exhibits increased fibrinogen sparing compared with intracoronary streptokinase.

Use of cross-correlation function to detect patient motion during SPECT imaging.

We have developed a procedure to detect patient motion during a tomographic acquisition. The method uses frame-to-frame cross-correlation functions of the summed profiles in the vertical and horizontal directions of the planar images. The quantitative output derived from examination of the variation of the change in the pixel value, corresponding to the maximum of the cross-correlation function at each view, provides an effective and nonsubjective means of performing quality control on the presence and amount of movement during a single photon emission computed tomographic scan. In contrast to cine mode and sinogram display, easy to interpret hard copy can be generated through this procedure.

Effect of restenosis at one previously dilated coronary site on the probability of restenosis at another previously dilated coronary site.

The purpose of this study was to determine whether in patients with 2 sites dilated by percutaneous transluminal coronary angioplasty (PTCA), the sites undergo restenosis independently. Although restenosis remains a critical limitation after PTCA, there is little information separating site- and patient-dependent determinants of restenosis. In particular, if patients with 2 sites dilated have restenosis at 0 or 2 sites more frequently and at 1 site less frequently than expected by random chance, then patient-related factors may be important in the restenosis process. The source of data was the clinical data base at Emory University. Patients who had previously coronary surgery or PTCA, and those who underwent PTCA in the setting of acute myocardial infarction were excluded. In all, 515 patients with 2 sites dilated undergoing angiographic restudy at 4 months to 1 year after PTCA formed the study population. Site 1 was the first site dilated. At site 1, 224 of 515 sites (45%) were restenotic, and at site 2, 193 (33%) were restenotic. Multiple clinical and angiographic variables were analyzed as possible correlates of restenosis. The most powerful univariate and multivariate correlate of restenosis at either site 1 or 2 was the behavior of the other site. If site 2 was patent, then site 1 was restenotic 28% of the time compared with 69% if site 2 was restenotic. If site 1 was patent, site 2 was restenotic 20% of the time compared with 60% if site 1 was restenotic. This relation was stronger if the 2 sites were in the same coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of time required for reperfusion (thrombolysis or angioplasty, or both) and location of acute myocardial infarction on left ventricular functional reserve capacity several months later.

The purpose of this study was to determine whether reperfusion of acute myocardial infarction (AMI) by recombinant tissue-type plasminogen activator (rt-PA) or percutaneous transluminal coronary angioplasty, or both, would improve left ventricular (LV) function when it is measured several months later at rest or maximal bicycle exercise, or both. Radionuclide angiography was performed in 44 patients 5 months (range 6 weeks to 9 months) after AMI to assess function, and tomographic myocardial thallium-201 imaging was performed at maximal exercise and delayed rest to determine whether there was any evidence of myocardial ischemia. As expected, no patient had chest pain or redistribution of a thallium defect during the exercise test, because patients had undergone angioplasty (n = 28) or coronary bypass graft surgery (n = 5) where clinically indicated for revascularization. The LV ejection fraction was plotted as a function of the time elapsed between the onset of chest pain and the time when coronary angiography confirmed patency of the infarct-related artery (achieved in 91% of 44 patients by rt-PA [n = 31] or percutaneous transluminal coronary angioplasty [n = 9] ). Functional responses differed markedly between patients with anterior (n = 20) versus inferior (n = 24) wall AMI. LV ejection fraction during exercise correlated with time to reperfusion in patients with an anterior wall AMI (r = -0.58; standard error of the estimate = 11.9%; p less than 0.02) but not in patients with an inferior AMI (r = 0.10; standard error of the estimate = 13.1%; difference not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary surgery and coronary angioplasty in patients with two-vessel coronary artery disease.

There is uncertainty regarding the selection between coronary artery surgery and angioplasty in many patients with coronary artery disease, especially in those with 2-vessel disease. Whereas randomized trials will provide the best possible and most detailed data comparing therapy in these patients, clinical data bases may be used to provide a current perspective. The purpose of this study was to compare the long-term outcome of patients with 2-vessel coronary artery disease undergoing coronary surgery or angioplasty at Emory University hospitals in the years 1984 and 1985. Data on all patients with 2-vessel disease diagnosed at Emory University who underwent elective angioplasty or coronary surgery in the years 1984 and 1985 were compared. Categoric variables were analyzed by chi-square and continuous variables by unpaired t test. Survival was determined by the Kaplan-Meier method and differences in survival by the Mantel-Cox method. Determinants of survival were determined by Cox model analysis. There were 415 angioplasty patients and 454 surgical patients. Surgical patients were older and had more frequent systemic hypertension, diabetes mellitus, prior myocardial infarction, severe angina and congestive failure, and more significant narrowing in the left anterior descending coronary artery, totally occluded vessels and left ventricular dysfunction than did angioplasty patients. Complete revascularization was achieved more often in surgical patients. There was no difference in Q-wave myocardial infarction in the hospital. No angioplasty patient died compared with 1.1% of surgical patients (p = 0.03). Whereas 5-year survival was 93% in angioplasty patients and 89% in surgical patients (p = 0.11), there was no difference in risk-adjusted survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty or surgery for multivessel coronary artery disease: comparison of eligible registry and randomized patients in the EAST trial and influence of treatment selection on outcomes. Emory Angioplasty versus Surgery Trial Investigators.

The Emory Angioplasty versus Surgery Trial (EAST) showed that multivessel patients eligible for both percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass surgery (CABG) had equivalent 3-year outcomes regarding survival, myocardial infarction, and major myocardial ischemia. Patients eligible for the trial who were not randomized because of physician or patient refusal were followed in a registry. This study compares the outcomes of the randomized and registry patients. Of the 842 eligible patients, 450 did not enter the trial. Their baseline features closely resembled those of the randomized patients and follow up was performed using the same methods. In the registry there was a bias toward selecting CABG in patients with 3-vessel disease (84%) and PTCA in patients with 2-vessel disease (54%). Three-year survival for the registry patients was 96.4%, which was better than the randomized patients, 93.4% (p = 0.044). Angina relief in the registry was equal for CABG and PTCA patients and was better for the PTCA registry (12.4%) than PTCA randomized patients (19.6%) (p = 0.079). Thus, the registry confirms that EAST is representative of all eligible patients and does not represent a low-risk subgroup. Since baseline differences were small, improved survival in the registry may be due to treatment selection. Physician judgment, even in patients judged appropriate for clinical trials, remains a potentially important predictor of outcomes.

The role of digitalis in acute myocardial infarction.

Digitalis is useful in the control of atrial tachyarrhythmias complicating acute myocardial infarction, whether or not congestive heart failure is present. The drug can also be helpful in patients in the subacute and chronic phases of myocardial infarction if congestive heart failure is present. Digitalis is not, however, the drug of choice in the treatment of patients with left ventricular dysfunction complicating acute myocardial infarction.

Early noninvasive detection of successful reperfusion in patients with acute myocardial infarction.

Myoglobin (Mb) is a protein that enters rapidly and is rapidly cleared from plasma after coronary reperfusion. We sought to determine the accuracy with which a rapid rise in plasma [Mb] could predict successful coronary artery reopening in patients undergoing coronary arteriography in conjunction with attempted reperfusion in acute myocardial infarction. In 42 patients, plasma Mb levels were measured before and for at least 4 hours after attempted reperfusion. Thirty-five patients were successfully reperfused. In each, the plasma Mb level rose rapidly with peak [Mb] occurring at 111 +/- 8.1 (+/- SEM) minutes after application of therapy. In contrast, Mb levels rose more slowly in the seven patients who were not reperfused, with peak [Mb] occurring 360 +/- 61.4 minutes after attempted reperfusion. T25-100 (the time required for [Mb] to rise from 25% to 100% of peak value) was shorter in patients successfully reperfused (71 +/- 7.9 minutes) and longer (341 +/- 35.3 minutes) in patients in whom therapy was unsuccessful. A rapid rise in [Mb] after successful reperfusion was also evident by a more than 4.6-fold rise in [Mb] over the first 2 hours after reperfusion in all but five patients; in contrast, [Mb] rose by less than 4.6-fold over this same interval in every patient not successfully reperfused (sensitivity, 85%; specificity, 100%; predictive accuracy, 88%). We conclude that a rapid rise in plasma Mb level over the initial 2 hours after attempted reperfusion in acute myocardial infarction provides a useful index of successful reperfusion.

Emergency coronary bypass for cardiogenic shock.

Emergency coronary bypass for cardiogenic shock has been associated with a high operative mortality. From January 1983 through March 1986, 69 patients at Crawford W. Long Hospital underwent emergency coronary artery bypass. Seventeen of 69 were in shock, 15 with hypotension requiring treatment (intra-aortic balloon pump in 10; catecholamines in six). The other two patients had a low cardiac index and a pulmonary capillary wedge pressure greater than 25 mm Hg. Of these patients, nine presented with acute infarction, four with failed angioplasty, and four with uncontrollable angina. Four patients required cardiopulmonary resuscitation. After operation, 94% of the patients required catecholamine support and 71% were treated with an intra-aortic balloon pump. There were two hospital deaths (12%). The median postoperative stay for survivors was 9 days. Major complications occurred in 47%. Follow-up (100%, mean 20.5 months) revealed no late deaths, a 3 year survival of 88 +/- 8%, and a functional class of I in six patients, II in seven patients, and III in two patients. The nine patients who were working before operation all returned to work. Of the 52 emergency coronary bypass patients without shock, one patient died in the hospital (2%), 52% required catecholamines (p less than .05 vs shock group by chi-square analysis), and 12% required an intra-aortic balloon pump after operation (p less than .05 vs shock group by chi-square analysis). Median stay was 8 days. Complications occurred in 13% (p less than .05 vs shock group by chi-square analysis). Three year survival was 91 +/- 4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute myocardial infarction temporally related to cocaine use. Clinical, angiographic, and pathophysiologic observations.

Ischemic chest pain syndromes and myocardial infarction occurred within minutes to hours of cocaine use in nine persons ages 23 to 39 years. Five developed symptoms after taking cocaine intranasally; three, after intravenous use; and one, after smoking cocaine. Four were habitual users and five were recreational users; eight also smoked cigarettes heavily. Ischemic syndromes recurred in five who continued to use cocaine. Coronary arteriography showed an abnormal infarct-related vessel (more than 50% stenosis, total occlusion, or intraluminal thrombus) in seven patients. The noninfarct-related vessels were normal in eight patients. The left anterior descending coronary artery and the anteroapical left-ventricular wall were involved in all patients. After three patients had successful thrombolysis of the obstructed infarct-related vessel, angiography showed a normal underlying vessel.

Long-term clinical follow-up in patients with angiographic restudy after successful angioplasty.

BACKGROUND: Restenosis remains a critical limitation after coronary angioplasty. There is little information comparing long-term prognosis in patients who suffer from restenosis and others who do not. The purpose of this paper is to determine the clinical events in patients with restenosis or continued patency documented by restudy coronary arteriography. METHODS AND RESULTS: The source of data was the clinical data base at Emory University. Patients who had previous coronary surgery and patients who underwent angioplasty in the setting of acute myocardial infarction were excluded. A total of 3,363 patients undergoing angiographic restudy 4 months to 1 year after angioplasty were compared with 3,858 not undergoing restudy. In the restudy population, 1,570 had restenosis and 1,793 had patent arteries at all sites dilated. The restenosis patients were older and had more hypertension, more diabetes, more severe angina, more multivessel coronary artery disease, more severe stenoses, and less satisfactory original results. At restudy, in patients without restenosis, 38.7% had angina versus 70.7% in patients with restenosis (p < 0.0001). There were few deaths in the first 6 months. At 6 years, the survival rate was 0.95 without restenosis and 0.93 with restenosis (p = 0.16). At 6 months and 6 years, freedom from myocardial infarction was 0.97 and 0.88 without restenosis and 0.93 and 0.85 with restenosis (p = 0.0001). On multivariate analysis, restenosis was an independent correlate of myocardial infarction but not mortality. At 6 months and 6 years, freedom from coronary bypass surgery was 0.99 and 0.94 without restenosis and 0.91 and 0.78 with restenosis (p < 0.0001). At 6 months and 6 years, freedom from repeat angioplasty was 0.96 and 0.76 without restenosis and 0.44 and 0.20 with restenosis (p = 0.0001). The highest event rates were noted in the patients with restenosis with recurrent chest pain. Patients not undergoing restudy differed somewhat from the study group, and there were far fewer repeat revascularization procedures in the group not undergoing restudy. CONCLUSIONS: Patients with restenosis are more likely to have recurrent angina pectoris. Although there is no or little difference in survival, there is a difference in myocardial infarction rate in the patients with and without restenosis. The low myocardial infarction and death rates in the group suffering restenosis may be related to repeat revascularization in these patients; the principal events in the restenosis population are frequent repeat revascularization procedures.

Failed elective percutaneous transluminal coronary angioplasty requiring coronary artery bypass surgery. In-hospital and late clinical outcome at 5 years.

This study was performed to define the in-hospital and late clinical outcome at 5 years in 430 patients who had a failed elective percutaneous transluminal coronary angioplasty (PTCA) and underwent coronary artery bypass graft (CABG) surgery during their hospitalization. This group comprised 5.9% of 7,246 patients undergoing elective PTCA. CABG surgery was performed in 346 patients with ongoing myocardial ischemia (80.5%) and in 84 patients without ischemia (19.5%). Their mean age was 56 +/- 9 years, and 76.3% were male. One-vessel disease was present in 72.3%, and the mean left ventricular ejection fraction was 59 +/- 11%. Overall, 1.9 +/- 0.9 bypass grafts were placed. There was increased use of the internal thoracic artery in the nonischemic group. A new nonfatal postprocedural Q wave myocardial infarction occurred in 21.2% and occurred more frequently in the ischemic (25.4%) than in the nonischemic (3.6%) group (p less than 0.0001). There were six in-hospital deaths (1.4%), an incidence that did not differ between the two groups. Follow-up was 99.8% complete. There were 25 deaths (93.2 +/- 1.5%, 5-year survival), including 16 of cardiac cause (95.3 +/- 1.3%, 5-year cardiac survival). Q wave myocardial infarction occurred in 111 patients (91 in-hospital), and freedom from cardiac death or nonfatal myocardial infarction at 5 years was 71 +/- 3%. In the group going to CABG surgery with ongoing ischemia, the 5-year cardiac survival was 94.9 +/- 1.6%, and in the group without ischemia, the corresponding survival was 96.2 +/- 2.2%. By multivariate analysis, the presence of preoperative myocardial ischemia, pre-PTCA diameter stenosis less than 90%, and the presence of multiple-vessel disease correlated with the occurrence of cardiac death or nonfatal myocardial infarction at 5 years. At this large-volume center with extensive PTCA operator and surgical experience, the excellent survival and low event rates over 5 years support the concept that despite the failed elective PTCA procedure, there was little effect on long-term survival provided the patient underwent prompt successful surgical revascularization.

Influence of diabetes mellitus on early and late outcome after percutaneous transluminal coronary angioplasty.

BACKGROUND: Although patients with diabetes mellitus constitute an important segment of the population undergoing coronary angioplasty, the outcome of these patients has not been well characterized. METHODS AND RESULTS: Data for 1133 diabetic and 9300 nondiabetic patients undergoing elective angioplasty from 1980 to 1990 were analyzed. Diabetics were older and had more cardiovascular comorbidity. Insulin-requiring (IR) diabetics had diabetes for a longer duration and worse renal and ventricular functions compared with non-IR subjects. Angiographic and clinical successes after angioplasty were high and similar in diabetics and nondiabetics. In-hospital major complications were infrequent (3%), with a trend toward higher death or myocardial infarction in IR diabetics. Five-year survival (89% versus 93%) and freedom from infarction (81% versus 89%) were lower, and bypass surgery and additional angioplasty were required more often in diabetics. In diabetics, only 36% survived free of infarction or additional revascularization compared with 53% of nondiabetics, with a marked attrition in the first year after angioplasty, when restenosis is most common. Multivariate correlates of decreased 5-year survival were older age, reduced ejection fraction, history of heart failure, multivessel disease, and diabetes. IR diabetics had worse long-term survival and infarction-free survival than non-IR diabetics. CONCLUSIONS: Coronary angioplasty in diabetics is associated with high success and low complication rates. Although long-term survival is acceptable, diabetics have a higher rate of infarction and a greater need for additional revascularization procedures, probably because of early restenosis and late progression of coronary disease. The most appropriate treatment for these patients remains to be determined.