Detection of myoglobin by radioimmmunoassay in human sera: its usefulness and limitations as an emergency room screening test for acute myocardial infarction

The results indicate that serum myoglobin determinations may be obtained by radioimmunoassay utilizing time periods for the testing which allow more useful clinical evaluation of patients. The data also demonstrate, however, that there are important temporal considerations in using serum myoglobin levels for the detection of acute myocardial infarcts and, if this test is used to determine in the Emergency Room whether patients have had acute myocardial infarcts, these limitations will have to be kept in mind. In addition, three other patient subgroups that might be expected to have elevated serum myoglobin levels by radioimmunoassay have been determined. These include patients with shock (irrespective of etiology), patients with severe renal insufficiency, i.e., those with serum creatinine levels equal to or greater than 8 mg. per cent, and possibly patients who have been on alcohol binges immediately prior to being seen in the Emergency Room.     

Continuous electrocardiographic monitoring in patients with unstable angina pectoris: Identification of high-risk subgroup with severe coronary disease,variant angina,and/or impaired early prognosis

We assessed the value of two-channel Holter monitoring during the initial hours of hospitalization in patients with unstable angina pectoris (UAP) to identify those with severe coronary artery disease (CAD), variant angina, and/or poor prognosis over the next 3 months. Accordingly, 116 UAP patients had Holter monitoring for 27 ± 7 (mean ± SD) (range 12 to 50) hours following hospitalization. Of these, 24 evolved myocardial infarction (MI) during monitoring and 92 did not. Transient ST segment alterations occurred in 21 of the 92. Of these 21, 4 had variant angina, were treated with calcium antagonists, and did well. Each of the remaining 17 had severe fixed CAD (left main or three-vessel) (n = 12) and/or poor prognosis over the 3 months after discharge as manifested by death (n = 1), MI (n = 3), and/or severe angina (n = 3). In contrast, 71 patients did not demonstrate transient ST segment alterations: none had variant angina (p < 0.001), nine had left main or three-vessel CAD (p < 0.001), and 50 were alive and well 3 months after discharge (p < 0.001). Ventricular tachycardia (VT) was demonstrated by Holter monitor in 5 of the 92 patients: four had three-vessel CAD and the other had severe persistent angina. Thus in patients hospitalized with unstable angina, transient ST segment alterations and/or VT on Holter monitor are specific predictors of “high-risk” subgroup UAP patients with left main or three-vessel CAD, variant angina, and/or impaired 3-month prognosis.     

Unstable angina pectoris: A randomized study of patients treated medically and surgically

Fifty patients with the clinical syndrome of unstable angina pectoris were evaluated. Twenty-seven were randomized into medical or surgical treatment groups and subsequently followed up. The results of the study reveal that: (1) there is approximately a 16 percent incidence rate of significant left main coronary artery disease in patients with this entity at our institution; (2) 10 percent of patients do not have angiographically significant coronary artery disease; (3) pain relief is better in the surgically treated patients, but the 1 1/2 year survival rate is not significantly different between the groups; (4) 50 percent of the medically treated patients again had the syndrome of unstable angina pectoris in the initial few months of the follow-up period; (5) the operative and late postoperative mortality rate in patients presenting with unstable angina pectoris and left main coronary artery disease in this small group of patients was 43 percent; and (6) four of six patients with this syndrome whose condition was deemed inoperable and who were not randomized died within the subsequent few months.     

Influence of dobutamine on hemodynamics and coronary blood flow in patients with and without coronary artery disease

The influence of dobutamine on hemodynamics and coronary blood flow was studied in patients after routine cardiac catheterization. The data demonstrated that dobutamine is a powerful inotropic agent at a dose that has a relatively small influence on heart rate. In patients without coronary artery disease dobutamine greatly increased coronary arterial perfusion. In patients with severe coronary artery disease dobutamine resulted in a much smaller increase in coronary perfusion, and the pattern of perfusion became more Inhomogeneous. The results suggest that dobutamine has a potential inotropic value but raise concern about its influence on regional myocardial perfusion in patients with serious coronary artery disease.     

Variant angina pectoris: a clinical and coronary arteriographic spectrum

The clinical course and coronary arteriographic findings in eight patients with Prinzmetal's variant angina pectoris are reviewed and contrasted to previously reported cases. In six patients with S-T-elevation inferiorly, three had normal coronary arteriograms, one had complete right coronary artery occlusion, one had diffuse triple-vessel disease, and one did not undergo coronary arteriography. In two patients with S-T-elevation anteriorly, severe stenosis of the anterior descending coronary artery was present. Medical treatment in four patients and surgical revascularization of the anterior descending coronary artery in two patients were both accompanied by marked symptomatic improvement. Spontaneous loss of angina occurred in two patients. During 17 months' mean follow-up, seven patients have remained free of angina and one died suddenly. Variant angina pectoris may be accompanied by a variety of coronary arteriographic findings and the prognosis appears more favorable than previously reported.     

Comparison of the influence of acute transmural and nontransmural myocardial infarction on ventricular function

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)     

Increased incidence and clinical correlation of persistently abnormal technetium pyrophosphate myocardial scintigrams following acute myocardial infarction in patients with diabetes mellitus

"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.     

Concomitant calcium antagonist plus isosorbide dinitrate therapy for markedly active variant angina

The present study was performed to assess the efficacy of concomitant calcium antagonist/isosorbide dinitrate therapy in patients with frequent episodes of variant angina and to compare such combination therapy with isosorbide dinitrate alone. We enrolled nine such patients (six men and three women, aged 47 ± 9 [mean ± standard deviation] years) in a long-term comparison of (1) oral isosorbide dinitrate (117 ± 63 mg per day) alone, (2) verapamil (453 ± 75 mg per day) + isosorbide dinitrate (given in the same dose as stated above), and (3) nifedipine (71 ± 14 mg per day) + isosorbide dinitrate (also given in the same dose as stated), each administered for 2 months. During isosorbide dinitrate therapy, these nine patients averaged 23.7 ± 37.3 chest pains per week, consumed 24.4 ± 47.4 sublingual nitroglycerin tablets per week, and demonstrated 46.5 ± 43.2 episodes per week of transient ST segment deviations on calibrated two-channel Holter monitoring. During therapy with verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate, the frequency of angina and ST segment deviations was dramatically reduced (verapamil/isosorbide dinitrate, 3.9 ± 3.6 chest pains per week and 3.5 ± 2.6 ST segment deviations per week, p < 0.05; nifedipine/isosorbide dinitrate, 3.1 ± 4.0 chest pains per week and 5.5 ± 6.6 ST segment deviations per week, p < 0.05). In all respects, verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate were similar to one another. Thus, in patients with very frequent episodes of variant angina, a calcium antagonist/isosorbide dinitrate combination is much more effective than isosorbide dinitrate alone in reducing the frequency of angina and ischemic ECG alterations.     

Evaluation of postextrasystolic T wave alterations in identification of patients with coronary artery disease or left ventricular dysfunction

This study was performed (1) to assess the value of postextrasystolic T wave alterations in identification of patients with cardiac disease and (2) to determine if their frequency depends on length of compensatory pause. In 52 patients a pacing catheter was placed in the right ventricular (RV) apex, and premature beats were programmed to occur 30 msec beyond RV refractory period. Postextrasystolic T wave alterations occurred in 32 patients, 13 with an 19 without coronary artery disease (CAD) (NS). Such alterations were also not related to presence of abnormal left ventricular (LV) ejection fraction (less than 0.55) or end-diastolic pressure (greater than 12 mm Hg). In 33 patients, premature beats were also introduced 330 msec beyond the RV refractory period to compare effects of long and short compensatory pauses on frequency of postextrasystolic T wave alterations. When the pause was near maximal, 18 patients had alterations in 60 ECG leads; when it was shorter, seven patients had alterations in 10 leads (p less than 0.001). Thus, judging from provoked postextrasystolic T wave alterations, such spontaneous changes appear neither sensitive nor specific in the identification of patients with cardiac disease. The frequency of postextrasystolic T wave changes depends on the length of the compensatory pause.     

ST isopotential precordial surface maps in patients with acute myocardial infarction.

ST amplitude distributions were studied in 41 patients with acute myocardial infarction by deriving isopotential maps from a 5 x 7 electrode precordial matrix. Independent data on infarct size and localization were obtained utilizing the technetium 99m stannous pyrophosphate scintigraphic method. The locus of maximal ST elevation was stable for at least two days in 86% of 27 patients with anterior infarction. A single maximum or maximum-minimum was found in 88% but 22% of the patients had multiple maxima and/or minima in at least two maps. Areas of significant ST elevation were often excluded from the precordial matrix. The site of maximal ST elevation correlated with scintigraphic infarct site but was displaced medially in lateral infarction. The relation between infarct size and sigmaST elevation was significant and curvilinear. sigmaST underestimated size in large anterior infarction. The correlation of the size and the number of sites with ST elevation greater than or equal to 1.5 mm was weak (r = 0.56). The degree of ST abnormality in 14 patients with inferior infarction decreased significantly during the initial 24 hours. The isopotential maps were similar to those obtained in anterior infarction but the polarity was reversed. The results provide limited support for the continued exploration of ST analysis as a clinical method but suggest that sizing methods should be based on total body surface mapping, taking into account the geometry and electrical properties of the torso.     

Submaximal exercise testing after acute myocardial infarction: myocardial scintigraphic and electrocardiographic observations.

The relation between global and regional left ventricular function and electrocardiographic signs of ischemia at rest and during submaximal supine exercise was studied in 27 patients 2 to 3 weeks after acute myocardial infarction. Dynamic myocardial scintigraphy was performed at rest and during submaximal exercise utilizing an in vivo method of labeling red blood cells with technetium-99m pertechnetate. Gated radionuclide blood pool scintigrams were obtained in a modified left anterior oblique, and in some patients also in the right anterior oblique projection, to measure left ventricular ejection fraction and segmental wall motion. Electrocardiographic monitoring of heart rate and rhythm was provided during the exercise. The submaximal exercise test was terminated when the patient's heart rate reached 125 beats/min or if angina, malignant ventricular ectopy or electrocardiographic evidence of myocardial ischemia developed before this rate was reached. The data demonstrate that patients with a recent anterior myocardial infarct, in contrast to patients with a recent inferior or nontransmural infarct, manifest a significant reduction in left ventricular ejection fraction with submaximal exercise. Of the eight patients with an anterior infarct, seven had segmental wall motion abnormalities at rest. Four of these eight manifested more severe abnormalities with submaximal exercise; three had abnormalities at rest that did not change with exercise. Four of the eight had a positive electrocardiographic response during exercise (two were taking digoxin). Of these four, only two had more marked wall motion abnormalities with effort. Of the 13 patients with an inferior infarct, 11 had apparently normal wall motion in the modified left anterior oblique projection at rest, including 2 who manifested segmental wall motion abnormalities with submaximal exercise; the 2 remaining patients had wall motion abnormalities at rest that, on exercise, became more marked in one and were unchanged in one. Four of the 13 had a positive electrocardiographic response with exercise (one was taking digoxin); only one of these had a detectably more severe wall motion abnormality with exercise. Of the six patients with a nontransmural infarct, four had no identifiable wall motion abnormalities at rest; in one of these, an abnormality developed with exercise. The remaining two patients had wall motion abnormalities at rest; in one, a positive electrocardiographic ischemic response developed with exercise. Patients with an anterior infarct appear to have a different functional ventricular response to submaximal exercise at the time of hospital discharge than patients with an inferior or nontransmural infarct. To identify ischemic responses with submaximal exercise in these patients one should ideally use both electrocardiographic monitoring and dynamic myocardial scintigraphy.     

Permanent pacing in patients with transient trifascicular block during acute myocardial infarction

Patients with acute myocardial infarction and transient complete atrioventricular (A-V) block in association with right bundle branch block and left anterior hemiblock have a high incidence rate of late sudden death presumably due to recurrent A-V block. Over a 5 year period, 18 patients demonstrated right bundle branch block and left anterior hemiblock and had transient complete block during an acute myocardial infarction and survived to hospital discharge. Of six patients who did not have permanent pacing, five died suddenly (one was lost to follow-up) with a mean survival time of 2.4 months after hospital discharge. Twelve subsequent patients received permanent demand pacemakers and had a significantly improved prognosis with a mean survival time of 18 months (P < 0.001). Six patients were still alive at an average follow-up time of 20 months. Prophylactic permanent pacing significantly improves the prognosis after acute myocardial infarction in this select subgroup of patients.     

Thallium-201 myocardial perfusion studies in patients with the mitral valve prolapse syndrome

To determine whether regional myocardial ischemia plays a role in patients with the mitral valve prolapse syndrome, we examined myocardial perfusion with exercise stress testing and thallium-201 myocardial scintigraphy. Twelve patients were studied, 11 women and one man aged 18 to 56 years, mean age 30 years. In all patients, mitral valve prolapse was documented by echocardiography or phonocardiography. Patients over 35 years of age underwent cardiac catheterization. Electrocardograms disclosed abnormalities during maximal exercise in eight of the 12 patients. In two patients, angina developed during exercise. Thallium-201 (²⁰¹TI) scintigrams were normal in the 11 patients with presumed or documented normal coronary arteries. One patient, in whom an apical defect was demonstrated on scintigraphy, had significant disease of the left main and left anterior descending coronary artery. Repeat testing after successful aortocoronary bypass grafting revealed improved exercise capacity and a normal ²⁰¹TI myocardial scintigram. The data indicate that patients with mitral valve prolapse alone do not have regional myocardial ischemia and that the presence of a defect on ²⁰¹TI myocardial scintigraphy following maximal stress testing would suggest the existence of concomitant coronary artery disease.     

Hemodynamic effects of intravenous prostacyclin in stable angina pectoris

Prostacyclin (PGI2) is a naturally occurring vasodilator and inhibitor of platelet aggregation that produces vasodilatation of the systemic, pulmonary and coronary vascular beds in animal models. Because the endogenous production of PGI2 is reduced in those with coronary arterial disease (CAD), it may have a therapeutic role in patients with ischemic heart disease. To assess its safety and efficacy in this clinical setting, 17 patients with stable angina and CAD received an incremental intravenous infusion of either PGI2 (n = 10) to a maximum dose of 10 ng/kg/min (average 9.8 +/- 0.8 [mean +/- standard deviation]), or diluent buffer solution (placebo) (n = 7). All patients who received PGI2 became flushed, but experienced no other adverse effects PGI2 caused an increase in heart rate (66 +/- 11 to 80 +/- 11 beats/min, p less than 0.001) and cardiac index (2.88 +/- 0.65 to 3.97 +/- 1.17 liters/min/m2, p less than 0.001) and a decrease in mean femoral arterial pressure (96 +/- 18 to 86 +/- 11 mm Hg, p less than 0.001), but no change in mean pulmonary arterial or capillary wedge pressure. Total systemic and pulmonary vascular resistance decreased significantly (p less than 0.001). In response to PGI2, mean coronary sinus blood flow did not change significantly (100 +/- 40 to 121 +/- 52 ml/min), but coronary vascular resistance decreased (1.07 +/- 0.40 to 0.83 +/- 0.36 U, p less than 0.001). No variable was altered by placebo infusion. PGI2 caused a marked increase in 6-keto PGF1 alpha (the stable metabolite of PGI2) concentrations in both arterial (42 +/- 29 to 567 +/- 216 pg/ml, p less than 0.001) and venous (46 +/- 31 to 604 +/- 229 pg/ml, p less than 0.001) blood but no demonstrable change in plasma renin activity. Thus, intravenous PGI2 to a dosage of 10 ng/kg/min is a safe and effective systemic, pulmonary and coronary arterial vasodilator in patients with CAD and stable angina pectoris.     

Radioimmunoassay of serum creatine kinase B isoenzyme in the diagnosis of acute myocardial infarction. Correlation with technetium-99m stannous pyrophosphate myocardial scintigraphy

In 80 patients admitted to a coronary care unit within 24 hours of chest pain thought to be due to acute myocardial infarction, routine diagnostic tests (electrocardiograms, total serum creatine kinase) as well as ^99mtechnetium stannous pyrophosphate, TcPYP myocardial scintigraphy and serial serum radioimmunoassay determinations of the B subunit of creatine kinase (CK-B), were performed. None of these patients had clinical evidence of acute cerebral injury. A definite decision regarding the presence of acute myocardial infarction could be made in 77 patients on the basis of the results of routine diagnostic tests. The calculated sensitivity, specificity and predictive value of an elevated serum CK-B level in the recognition of acute myocardial infarction were each 100 per cent. Serial TcPYP scintigraphy was 97 per cent sensitive and 70 per cent specific, and had a predictive value of 96 per cent for the recognition of acute myocardial infarction. Both serum CK-B analysis and TcPYP myocardial scintigraphy were helpful in the recognition of infarct extension, and serial studies with both techniques suggested the presence of asymptomatic extension of infarction in several patients.The predictive value of each of these techniques for the recognition of a myocardial infarct suggests that both may be of diagnostic assistance to the physician in clinical settings in which the history, electrocardiogram or total serum creatine kinase are for some reason not interpretable. These techniques may also prove complementary in furthering the ability to assess the extent of acute myocardial damage and the course of its progression.     

Efficacy of slow infusion of diazoxide in the treatment of severe hypertension without organ hypoperfusion

Diazoxide as usually given in a single bolus, may cause precipitous falls in blood pressure (BP) with resultant tissue hypoperfusion. To examine the efficacy and safety of slow infusion, we treated 18 patients with mean initial BP of $\text{220}\text{143}\text{mm Hg}$ by two regimens: group A (nine patients) received 15 mg/minute; group B (nine patients) received 30 mg/minute. The goal of therapy, diastolic BP of 100 to 105 mm Hg, was reached in 16 of the 18 with no immediate drug-related side effects. Infusion time was 38.1 minutes in group A and 20.7 minutes in group B. Slow intravenous infusion of diazoxide appears to be safe and effective treatment for severe hypertension and should replace the rapid bolus technique.     

Effect of hypertonic mannitol and intraaortic counterpulsation on regional myocardial blood flow and ventricular performance in dogs during myocardial ischemia.

Studies were performed to determine if intervention with hypertonic mannitol and intraaortic balloon counterpulsation increases regional myocardial blood flow during acute myocardial ischemia. Anesthetized dogs on right heart bypass were studied. Heart rate was kept constant by atrial pacing. Myocardial ischemia was provided by ligating the proximal left anterior descending coronary artery for 12 minute periods. Infusion of hypertonic mannitol begun immediately after ligation increased coronary blood flow to the ischemic area by 36 +/- 9.0% (standard error) (P less than 0.01) and to the nonischemic left ventricle by 21 +/- 8.8% (P less than 0.05) as compared with flow in the same regions during the control coronary ligation. Intraaortic balloon counterpulsation begun immediately after ligation increased regional coronary flow to the ischemic region by 20 +/- 8.4% (P less than 0.05) but did not significantly alter flow to the nonischemic left ventricle as compared with levels during the control ligation. Combined intraaortic counterpulsation and hypertonic mannitol increased coronary flow to the ischemic region by 46 +/- 13% (P less than 0.02) and to the nonischemic left ventricle by 59 +/- 22% (P less than 0.05) as compared with flow during occlusion of the left anterior descending artery with mannitol alone. The data demonstrate that both hypertonic mannitol and intraaortic counterpulsation increase left ventricular ischemic regional flow and that combined hypertonic mannitol and intraaortic balloon counterpulsation provide a greater increase in regional coronary blood flow to both the ischemic and nonischemic regions of the left ventricle than mannitol alone.