Comparative study of myocardial ischemia during angina at rest and on exertion using thallium-201 scintigraphy

To compare the results of thallium-201 myocardial scintigraphy during angina at rest with those observed during effort angina, 81 patients were selected in whom the existence of acute myocardial ischemia was indicated both by typical transient S-T segment or T wave changes and by typical anginal pain. In these patients, scintigrams were obtained during 58 attacks of angina on effort (group 1) and during 40 attacks of angina at rest (group 2); 16 patients were studied during both types of angina. The attack at rest was spontaneous in 20 patients and induced by ergonovine maleate in 20 patients.In the presence of S-T segment elevation or transient normalization of inverted T waves, scintigrams were positive in all 24 studies at rest and in 19 of 20 studies during exercise. By contrast, in the presence of S-T segment depression scintigrams were positive in 14 (95 percent) of 15 studies during angina at rest, but in only 20 (53 percent) of 38 during angina on effort. Neither the degree of S-T segment changes nor their duration after injection of thallium was significantly different in resting studies relative to exercise studies, but the heart rate and double product were consistently higher during exercise.The marked difference in sensitivity in detecting ischemia in angina at rest with S-T segment depression compared with detection during exertional angina, even in the same patients, suggests that different pathogenetic mechanisms are responsible for the attack. Conversely, a similar mechanism operating in angina at rest and on exertion during S-T segment elevation and normalization of T waves is suggested by the similarity of thallium-201 scintigraphic findings in this situation. The findings are compatible with the hypothesis of a regional reduction in myocardial blood flow in angina at rest, independently of the direction of S-T segment change, and in exertional angina with S-T segment elevation or normalization of inverted T waves; they suggest an inadequate increase in myocardial blood flow in angina on effort with S-T segment depression.     

Relation between regional myocardial uptake of rubidium-82 and perfusion: Absolute reduction of cation uptake in ischemia

Experiments were undertaken using rubidium-82 and positron tomography to examine the relation between myocardial perfusion and cation uptake during acute ischemia. Rubidium-82 was repeatedly eluted from a strontium-82-rubidium-82 generator. In six dogs emission tomograms were used to measure the delivered arterial and myocardial concentrations at rest and after coronary stenosis, stress and ischemia. There was a poor overall relation between regional myocardial uptake and flow measured by microspheres and a large individual variability. Extraction of rubidium-82 was inversely related to flow. Significant regional reduction of cation uptake was detected in the tomograms when regional flow decreased by more than 35 percent. This reduction was significantly greater when ischemia was present. A small but significant decrease (33.0 ± 9.1 percent, mean ± standard deviation) in the myocardial uptake of rubidium-82 was detected only when flow was increased by more than 120 percent in relation to a control area after administration of dypiridamole.The technique using rubidum-82 and tomography was applied in five volunteers and five patients with angina pectoris and coronary artery disease. Myocardial tomograms recorded at rest and after exercise in the volunteers showed homogeneous uptake of cation in reproducible and repeatable scans. In contrast, the patients with coronary artery disease showed an absolute mean decrease of 36 ± 14 percent in regional myocardial uptake of rubidium-82 after exercise. These abnormalities persisted in serial tomograms for more than 20 minutes after the symptoms and electrocardiographic signs of ischemia.     

Variable susceptibility to dynamic coronary obstruction: An elusive link between coronary atherosclerosis and angina pectoris

Growing evidence suggests that dynamic coronary obstructions play an important but elusive role in the genesis of ischemic events. Dynamic coronary obstructions can develop during certain phases of coronary disease as a result of a variable combination of vasoconstriction, arterial wall lesions, and increased thrombotic tendency. In a certain phase of their disease some patients develop dynamic coronary obstruction, while others with a similar degree of fixed atherosclerotic obstruction do not.     

Precordial electrocardiographic mapping after exercise in the diagnosis of coronary artery disease.

A technique is described for recording the precordial electrocardiographic body surface map before and after exercise. The technique provides an extra dimension to the conventional exercise electrocardiogram because a measurement can be made of the area and severity of S-T segment changes that are projected onto the front of the chest. Sixteen lead isopotential surface maps were recorded before and after exercise in 109 patients with angina who subsequently underwent coronary arteriography. In addition, exercise electrocardiograms were obtained in 53 of these patients using three orthogonal leads and in all patients using a single chest unipolar chest lead. Precordial surface mapping after exercise was found to have a greater sensitivity (95 percent) than electrocardiography using either the orthogonal leads (68 percent) or a single chest lead (64 percent) (P less than 0.01). The specificity of the three techniques did not differ significantly (P greater than 0.05). The technique of precordial surface mapping after exercise improves the ability to diagnose coronary artery disease and can easily be applied to clinical practice.     

Krypton-81m in the physiologic assessment of coronary arterial stenosis in man.

Fifteen patients with frequent anginal chest pain underwent diagnostic cardiac catheterization. After coronary arteriography a specially designed cardiac catheter was seated in the aortic root, permitting the continuous infusion of krypton-81m into the right and left aortic sinuses. A gamma camera, areas of interest and a visual display unit were used to record images and the regional myocardial equilibrium of activity before, during and after a standarized atrial pacing test. The unique physical properties of krypton-81m allowed the continuous imaging and recording of moment to moment changes in regional myocardial perfusion. This investigation revealed that when the coronary arteriogram was normal or revealed lumonal stenosis of less than 50 percent, regional myocardial perfusion was uniform at rest and during stress. Two patients with a previous history of myocardial infarction had defects of regional perfusion at rest and during stress. Krypton scintigraphy demonstrated reversible regional defects in myocardial perfusion during stress in seven patients with greater than 70 percent stenosis of one or more coronary arteries. Alterations in regional myocardial perfusion occurred within 30 seconds of the start of atrial pacing in all the patients and preceded the onset of electrocardiographic signs of ischemia or chest pain.     

Wolff-Parkinson-White syndrome: long follow-up and an Anglo-American historical note

A patient who developed palpitation in 1917 was later found to have the Wolff-Parkinson-White syndrome and survived to the age of 86, when he died of emphysema. Shortly before he first presented, a report of another patient had been published that can now retrospectively be recognized as containing the first tracings from a case of the Wolff-Parkinson-White syndrome; its coauthors were a distinguished American cardiologist, Alfred E. Cohn, who had worked with Sir Thomas Lewis, and his British research fellow, Francis R. Fraser.     

Hydralazine in the management of left ventricular failure.

This study was designed to compare the short and long-term effects of hydralazine when used as a vasodilator in the treatment of left ventricular failure. The hemodynamic changes after the acute intravenous and long-term oral administration of hydralazine were compared in a group of 16 patients with left ventricular failure (14 patients with congestive cardiomyopathy and two with hypertensive heart failure). After 20 mg of hydralazine, administered intravenously there was a 56 percent increase in stroke volume (P < 0.001) and a 27 percent decrease in left ventricular filling pressure (P < 0.001) but no significant change in heart rate despite a 16 percent decrease in mean arterial pressure (P < 0.001).Seven of the patients then took hydralazine, 200 to 300 orally/day for 4 to 6 weeks. They were restudied during therapy with the drug and again 48 to 72 hours after stopping it. After the period of oral treatment there was a 71 percent increase in stroke volume (P < 0.001) and a 25 percent decrease in left ventricular filling pressure (P < 0.05). Forty-eight to 72 hours after discontinuation of drug administration, left ventricular filling pressure had returned to the control value (?3 percent, P < 0.05), but the stroke volume was still slightly elevated (14 percent, P < 0.05). The results show that oral administration of hydralazine can produce sustained benefit with changes similar to those induced by intravenous administration. The second control study after discontinuation of hydralazine therapy confirmed that these changes had been induced by and were dependent on the drug.     

Electrocardiographic mapping after exercise for evaluation of coronary bypass graft surgery

Electrocardiographic mapping after exercise adds an extra dimension to the routine exercise test because a measure can be made of the area and severity of electrocardiographic changes that occur after exercise. The value of this technique in assessing coronary bypass graft surgery was investigated in 50 patients who had postoperative coronary angiography after undergoing such surgery. The patients were classified into three groups: The 35 patients in Group 1 were free of pain at follow-up and had no new precordial Q waves. Among these, 24 patients had patent grafts and no precordial area of S-T segment change after exercise. The remaining 11 patients had areas of exercise-induced S-T segment change postoperatively; 10 of the 11 had at least one blocked graft and 1 had a patent although poorly functioning graft. The 10 patients in Group 2 continued to have chest pain after operation. Eight of the 10 had an area of S-T segment change that persisted after exercise and at least one blocked graft; the 2 patients without precordial S-T segment changes after exercise had patent grafts. The five patients in Group 3 were in poorer condition after operation; three had greater areas of S-T segment change after exercise, and the remaining two had new areas of Q waves. All patients had at least one occluded graft.

In 8 (16 percent) of the 50 patients studied before operation precordial areas of S-T segment change after exercise that were identified with electrocardiographic mapping were not identified using a modified 12 lead system. After operation, mapping revealed precordial areas of ischemia in 24 patients; In 4 (17 percent). These areas were not detected with the modified 12 lead electrocardiogram. Electrocardiographic mapping after exercise is a simple noninvasive test that objectively describes the effects of coronary bypass surgery on myocardial ischemia and aids in interpretation of a patient's report of a change in the frequency of angina. Because it provides more information than a modified 12 lead system it may reduce the need for postoperative angiocardiography.     

Inability of exercise-induced R wave changes to predict coronary artery disease

To determine the value of exercise-induced R wave changes in diagnosing coronary disease 200 patients undergoing coronary angiography were studied with 16 lead precordial exercise mapping. R wave amplitude was calculated before and immediately after exercise as the sum of R in all 16 leads, the sum of the R waves in the left plus the S waves in the right precordial leads, as well as the sum of the R waves only in those leads that manifested S-T segment depression. Coronary artery disease was found in 154 patients; S-T depression developed in 122 (sensitivity 79 percent); the sum of R increased or remained unchanged in 61 and decreased in 93 (sensitivity 40 percent). Forty-six patients did not have coronary artery disease; S-T depression developed in 5 (specificity 89 percent); the sum of R increased or was unchanged in 30 and decreased in 16 (specificity 35 percent). Similar results were obtained using the other criteria for calculating R wave amplitude. Exercise-induced S-T depression was identified in 5.1 ± 2.6 (mean ± standard deviation) of the 16 precordial leads and in 2.0 ± 1.1 of the chest leads of the standard electrocardiogram (p < 0.01). Thus, electrocardiographic alterations found in the standard chest leads represent only a small variable proportion of the total projection. When the whole precordial area was analyzed, R wave changes were so unpredictable that they could not be used in the diagnosis of coronary disease.     

Clinical value of calcium antagonists in treatment of cardiovascular disorders

All calcium antagonists have the ability to decrease the symptoms and signs in some patients with ischemic heart disease and help lower the blood pressure in hypertensive persons, but in clinical doses nifedipine does not exhibit antiarrhythmic properties, although these are an important part of the action of verapamil, diltiazem and some substances with a similar chemical structure. In certain disorders beta-adrenergic blocking drugs are useful adjuncts, and under some circumstances, particularly variant angina and supraventricular arrhythmias, specific calcium antagonists are the drugs of choice. More data are needed to define the role of calcium antagonists during cardiopulmonary bypass, in the protection of the ischemic myocardium, in the management of hypertrophic cardiomyopathy and in specific cases of primary pulmonary hypertension. When used with an appropriate sense of perspective and careful observation, calcium antagonists provide useful additional means of helping selected patients suffering from particular cardiovascular diseases.     

A new rationale for the clinical approach to the patient with angina pectoris

The interpretation of the ischemic or nonischemic nature of chest pain cannot be based on the anatomic information provided by coronary arteriography. Ischemia can occur in the absence of atherosclerotic lesions; conversely, stenoses themselves may not limit myocardial blood supply when adequately compensated by collaterals. Moreover, ischemia is often caused by functional coronary factors, such as spasm, which can occur in the presence of an extremely variable degree of coronary atherosclerotic lesions. Therefore, when the clinical diagnosis is uncertain, objective detection of ischemia must be based on a functional rather than an anatomic evaluation. A positive diagnosis can be made when typical transient changes in the electrocardiogram, myocardial perfusion scintigrams, ventricular function, or myocardial metabolism can be documented during an episode of chest pain. However, acute transient myocardial ischemia can sometimes occur without typical chest pain and, on other occasions, without typical electrocardiographic changes.The objective diagnosis of ischemia requires documentation during an episode which can occur spontaneously (ambulatory electrocardiographic monitoring and telephone transmission of the electrocardiogram during pain are useful for this purpose) or be induced by exercise testing (when the history indicates exertional pain) or by other provocative tests (when the history indicates pain not necessarily related to increased heart activity or when the results of the exercise stress test are negative). Once the diagnosis of acute ischemic episodes is made, the prevailing pathogenetic mechanisms responsible for the anginal attacks can usually be inferred with a reasonable degree of certainty from the history and the exercise stress test. The maximal level of exercise that a patient can tolerate without signs or symptoms of ischemia provides information on the residual coronary reserve. Attacks that occur clearly below this ceiling are most likely caused by an impaired myocardial blood supply rather than an excessive demand. Impairment of supply is likely to play a major role in angina at rest as well as in nocturnal, postprandial and cold-induced angina and for episodes occurring for levels of exertion usually well tolerated. So far, spasm is the only documented cause of impaired supply. Few patients have anginal attacks caused only by increased demands or only by reduced supply, the majority having attacks caused by both mechanisms. Calcium antagonists and nitrates are the treatment of choice in ischemic episodes caused by impaired coronary blood supply.     

Relation between the precordial projection of S-T segment changes after exercise and coronary angiographic findings.

The recent introduction of electrocardiographic mapping permits measurement of the precordial area and severity of exercise-induced S-T segment changes. This study was designed to compare this technique with a modified 12 lead electrocardiogram in defining the degree and site of coronary artery disease. One hundred patients, who later had diagnostic coronary arteriography, underwent an exercise test using both 16 point precordial mapping and a modified 12 lead electrocardiogram. The sensitivity of electrocardiographic mapping (96 percent) for the diagnosis of coronary artery disease was significantly greater than that of the modified 12 lead electrocardiogram (80 percent). However, the specificity of the two lead systems was similar. Typical precordial projections of S-T segment change were found when the left main stem or proximal left anterior descending coronary artery were narrowed or when there was isolated disease of the left anterior descending or right coronary artery. Widespread precordial changes were found in patients with three vessel disease. Although there was no significant difference in the sensitivity (66 percent) and specificity (100 percent) of electrocardiographic mapping and of the 12 lead system in identifying three vessel disease, there was a significant difference in sensitivity (electrocardiographic mapping 74 percent, 12 lead system 42 percent) in identifying isolated single vessel disease. In addition, information regarding the presence of left main stem or proximal left anterior descending coronary arterial narrowing was obtained only with electrocardiographic mapping. The superiority of electrocardiographic mapping over the modified 12 lead electrocardiogram has been shown, and clinical application of this technique should be useful in the management of patients presenting with chest pain.     

Assessment of coronary venous bypass graft function using krypton-81m.

Fifteen patients with intractable angina pectoris underwent coronary angiography and coronary arterial bypass graft surgery. After the operation, a continuous infusion of krypton-81m was delivered into each graft. A gamma camera and multichannel analyzer were used to record the regional myocardial distribution of perfusion provided by each graft. The disappearance of myocardial activity at the end of each infusion was used to calculate the flow per unit volume in the myocardial distribution provided by each vessel. Myocardial perfusion provided by the grafts to all the major coronary arteries were recorded individually as high spatial resolution images. Myocardial flow rates in the distribution of each graft were measured using the washout of krypton-81m. The rates were 0.5 to 2.0 ml/g per min in the 13 patients with no evidence of previous myocardial infarction. Krypton-81m was infused into grafts to the left anterior descending coronary artery in two patients with a history and electrocardiographic evidence of previous anterior myocardial infarction. The grafts provided poor perfusion to the anterior and apical portions of the ventricles. An experimental model of myocardial perfusion was used to demonstrate that the washout of krypton-81m can be used to measure flow per unit volume within or above the physiologic range.     

Evaluation of the effects of catheter sampling for the study of platelet behavior in the pulmonary and coronary circulation

To study the effects of sampling through cardiac catheters on indices of platelet function, we measured the levels of platelet factor 4 (PF₄), beta thromboglobulin (BTG), and platelet aggregate ratio (PAR) in 10 patients with atrioventricular accessory pathway (AVNAP), six patients with primary pulmonary hypertension (PPH), and six patients with critical narrowing of the left anterior descending artery (LAD). In AVNAP and LAD patients samples were drawn simultaneously from a peripheral vein, coronary sinus, and brachial artery; in AVNAP patients samples were also obtained from the axillary vein before the coronary sinus was entered. In PPH patients samples were drawn from pulmonary artery, aorta, and a peripheral vein; in these patients the effects of an intravenous infusion of prostacyclin (PGl₂) (2 to 8 ng/kg/min) on PF₄, BTG, and PAR were also studied at all sampling sites. In all patients arterial, coronary sinus, pulmonary arterial, and axillary venous levels of PF₄, BTG, and PAR significantly exceeded those measured in the peripheral vein. PGl₂ infusion resulted in a significant decrease of PF₄ at all sampling sites, while no consistent BTG changes were observed and PAR levels did not decrease in the peripheral vein. Although a considerable interpatient variability in PF₄ levels was observed, a significant (r = 0.91) correlation was found in patients with AVNAP between simultaneous coronary sinus and arterial PF₄ levels. The value of PF₄ coronary sinus-arterial difference in LAD patients was consistently higher than that calculated in AVNAP patients (54.5 ± 28.9 vs 4.2 ± 3.8 ng/ml). In conclusion: (1) a considerable and variable degree of platelet activation occurs with catheter sampling, preventing the measurement of absolute levels of platelet metabolites; (2) among the indices examined PF₄ appears the most sensitive for detecting changes in platelet activity; and (3) the measurement of coronary sinus-arterial PF₄ differences may provide information on directional changes in transcardiac platelet behavior.     

Myocardial infarction in the dog: Effects of intravenous propranolol

The effects of propranolol on myocardial perfusion and metabolism during acute myocardial infarction were studied in 18 mongrel dogs. A reversible snare was placed on the left anterior descending coronary artery; regional myocardial perfusion was continuously measured using the short-lived isotope krypton-81m, and myocardial metabolism was assessed using the epicardial electrocardiogram and measurement of release of creatine kinase activity from the affected segment of myocardium. Six dogs with no arterial occlusion acted as “sham operated” dogs; six others in which the snare was occluded acted as a control group and a third group of six were given propranolol, 0.5 mg/kg, 30 minutes after coronary occlusion. All variables were recorded before and for 5 hours after coronary occlusion. Dogs treated with propranolol showed a significant improvement in regional myocardial perfusion to the affected segment, decreased loss of electrically active myocardium at the end of each experiment for any given degree of early S-T segment elevation and a delay in the local release of creatine kinase activity compared with that in the control dogs. These results suggest that propranolol exerts a beneficial effect on the progress of ischemic myocardial damage when given shortly after the onset of infarction.     

Malabsorption and macroamylasemia. Response to gluten withdrawal

A 36 year old woman presented with malabsorption and macroamylasemia. The macroamylase was characterized and shown to be a complex of pancreatic amylase and immunoglobulin A(IgA). The patient had the clinical and histologic features of adult celiac disease, and responded to a gluten-free diet. The macroamylase complex disappeared from the serum after gluten withdrawal, a hitherto unreported finding in the syndrome of malabsorption and hyperamylasemia.