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.     

Prognosis for the newborn with transposition of the great arteries

To determine the prognosis for the newborn with transposition of the great arteries, the clinical course of 112 consecutive neonates with dextro-transposition was reviewed. Patients were managed with balloon atrial septostomy at initial cardiac catheterization, palliative operation if needed in the 1st year of life and Mustard's intraatrial baffle repair.The 1st month of life was the period of greatest risk (8 percent mortality rate). Between balloon septostomy and baffle repair, 14 of 103 patients at risk (14 percent) either died or had a cerebrovascular accident. The mortality rate at baffle repair was 14 percent (10 deaths in 71 patients), and there were 3 late postoperative deaths. Actuarial analysis of the data indicates that with this plan of management, approximately 50 percent of newborns with transposition of the great arteries will survive 5 years with excellent function and an additional 15 to 20 percent will survive with one or more medical handicaps.     

Low Muscle Levels of Pyridoxine in McArdle's Syndrome

Pyridoxal phosphate is a covalently bound cofactor of glycogen phosphorylase. Phosphorylase is a major muscle protein and therefore represents a significant pool of pyridoxal phosphate. Muscle pyridoxine content was measured in three patients with myophosphorylase deficiency (McArdle's syndrome) in whom there was a marked diminution or absence of phosphorylase protein as determined by acrylamide gel electrophoresis. Total muscle pyridoxine in the patients with McArdle's syndrome (0.55 ± 0.08 μg/g wet weight, mean ± SD) was markedly reduced compared with 11 human control subjects who had normal levels of muscle phosphorylase (total muscle B₆ = 2.49 ± 0.47). Despite such drastically low levels of muscle pyridoxine, these patients had no evidence of pyridoxine “deficiency.” These results suggest that low muscle B₆ in McArdle's syndrome represents the specific loss of pyridoxal phosphate normally bound to phosphorylase apoenzyme and imply that phosphorylase pyridoxal phosphate accounts for 75 to 80 percent of the total pyridoxine in normal human muscle.     

Symptomatic, electrocardiographic, metabolic, and hemodynamic alterations during pacing-induced myocardial ischemia

Atrial pacing has been used to assess the physiologic impact of coronary artery disease (CAD). Several variables have served as markers of pacing-induced myocardial ischemia, but their specificities and sensitivities are unknown. Accordingly, in 28 patients, incremental atrial pacing was performed. Of the 28, 10 had no CAD. The left ventricular ejection fraction (LVEF) (by gated equilibrium blood pool scintigraphy) increased in this group (0.60 ± 0.11 [mean ± standard deviation] before pacing to 0.67 ± 0.13 at peak-pacing, p = 0.002). In no patient did left ventricular end-diastolic pressure increase by > 5 mm Hg. No patient had lactate production, and 2 (20%) had electrocardiographic S-T segment depression ≥0.1 mV. Four (40%) had chest pain with atrial pacing. In the remaining 18 patients with CAD, atrial pacing caused a decrease in LVEF ≥0.05 (0.46 ± 0.10 to 0.33 ± 0.09, p < 0.001) and new segmental wall motion abnormalities in all, indicating pacing-induced myocardial ischemia. Only 8 (44%) had an increase in left ventricular end-diastolic pressure of > 5 mm Hg, and only 9 (50%) had lactate production. Ten (56%) had ischemic electrocardiographic changes, and 12 (67%) had chest pain. Thus, the electrocardiographic, metabolic, and hemodynamic alterations that may accompany pacing-induced ischemia are specific but relatively insensitive markers of ischemia. In contrast, chest pain during atrial pacing is a nonspecific occurrence, appearing with similar frequency in normal subjects and patients with CAD and pacing-induced ischemia.     

Value of radionuclide ventriculography in the immediate characterization of patients with acute myocardial infarction

The ability of admission radionuclide ventriculography to discriminate among various clinical subsets was evaluated in patients with acute myocardial infarction. One hundred patients with acute myocardial infarction were evaluated within 8 ± 3.1 hours (mean ± standard deviation) after the onset of chest pain. Forty-one patients were in Killip functional class I, 52 in class II and 7 in class III. The mean radionuclide left ventricular ejection fraction was significantly lower in patients with higher Killip classification because of significant elevation of mean left ventricular end-systolic volume rather than significantly altered mean end-diastolic volume. Killip classification frequently failed to correlate with ejection fraction in individual cases. Admission chest X-ray findings were categorized according to the presence of findings suggestive of impaired left ventricular function. Mean left ventricular ejection fraction was significantly lower in patients with abnormal than in patients with normal chest X-ray findings because of significant elevations in both mean end-diastolic and end-systolic volumes. The chest X-ray findings frequently failed to correlate with ejection fraction in individual cases.Stepwise linear regression analysis was employed to analyze the ability of historical, physical, electrocardiographic and chest X-ray findings to predict radionuclide left ventricular ejection fraction. The most predictive variables in order of decreasing significance were anterior myocardial infarction, abnormal chest X-ray findings, rales to two thirds of the posterior thorax, previous myocardial infarction, transmural myocardial infarction and heart rate greater than 100 beats/min. However, even these six optimal predictive variables could explain only 42 percent of the observed variability in left ventricular ejection fraction. Thus, early radionuclide ventriculography adds significantly to the discriminant power of clinical and radiographic characterization of ventricular function in patients with acute myocardial infarction.     

Serial changes in markers of disease activity with corticosteroid treatment in sarcoidosis

Serial changes in various markers of disease activity with corticosteroid therapy were assessed in 12 patients with active sarcoidosis. After six weeks of treatment with 40 mg daily of prednisone, all but one patient demonstrated symptomatic and radiographic improvement. For the entire patient group, there were corresponding improvements in forced vital capacity, from 59.2 +/- 5.5 to 70.5 +/- 5.3 percent of the predicted value (p less than 0.001, Student paired t test), serum angiotensin-converting enzyme levels, from 66.0 +/- 12.1 to 28.2 +/- 4.0 U/ml (p = 0.003), 67gallium lung scanning scores, from 3.6 +/- 0.2 to 0.8 +/- 0.3 (p less than 0.001), serum gamma globulin levels, from 2.40 +/- 0.2 to 1.5 +/- 0.1 g/dl (p less than 0.001), and erythrocyte sedimentation rate, from 26.8 +/- 2.7 to 14.8 +/- 3.0 mm per hour (p less than 0.001). Changes in percent of bronchoalveolar lavage fluid lymphocytes were less impressive (from 28.7 +/- 4.9 to 21.2 +/- 5.1, p = 0.034), but the geometric mean number of bronchoalveolar lavage fluid-IgG-secreting cells decreased from 23,861 to 3,830 (p = 0.013). Serial evaluations in five patients treated with decreasing doses of alternate-day prednisone for an additional 10 1/2 months indicated that changes in 67gallium lung scanning scores corresponded most closely to the clinical course in five of five patients. Determination of serum angiotensin-converting enzyme levels also closely paralleled the clinical course in four of five patients, whereas the other parameters measured were more variable markers of clinical response. However, abnormalities of bronchoalveolar lavage fluid-IgG-secreting cells often persisted in the absence of clinically evident disease, and the percentages of bronchoalveolar lavage fluid lymphocytes were frequently normal in patients who responded subsequently to corticosteroids. Larger prospective studies are warranted to more extensively evaluate various measurements of disease activity, especially bronchoalveolar lavage fluid analysis, in sarcoidosis.     

Further insights into digoxin-quinidine interaction: Lack of correlation between serum digoxin concentration and inotropic state of the heart

The digoxin-quinidine interaction was studied in nine healthy human subjects aged 26 to 31 years. A single oral dose (400 mg) of quinidine sulfate administered to subjects taking digoxin resulted in a mean (± standard error of the mean) increase within 1 to 6 hours in the serum digoxin concentration of 0.12 ± 0.01 ng/ml (p <0.0001), an increase of 21 percent. Continued quinidine administration for 24 hours resulted in a 59 percent increase in the mean serum digoxin concentration from 0.68 ± 0.04 to 1.04 ± 0.06 ng/ml (alpha = 0.05). At the same time, however, systolic time intervals demonstrated a lengthening of the mean left ventricular ejection time index from 406 ± 4 to 419 ± 2 ms (alpha = 0.05) and the mean Q?S₂ Index from 524 ± 6 to 532 ± 7 ms (difference not significant [NS]). When compared with the shortening of these intervals predicted from the digoxin dose-response curve if digoxin were the only variable, the lengthening actually observed for both intervals was highly significant. The negative inotropic effect of quinidine administration alone was assessed with systolic time intervals in four subjects. The left ventricular ejection time index lengthened from 419 ± 3 to 425 ± 6 ms (NS) and the Q?S₂ index from 541 ± 6 to 550 ± 7 ms (NS). Therefore, the lengthening of these intervals in subjects taking digitalis after the addition of quinidine represents more than just the negative inotropic effect of quinidine, and occurs despite the increase in serum digoxin concentration.The results of this study support the view that quinidine displaces digoxin from tissue-binding sites as a major mechanism of the interaction. Furthermore, it appears that quinidine may specifically displace digoxin from cardiac-binding sites. These results raise important questions concerning the recommendation to reduce the maintenance digoxin dose when concomitant quinidine therapy is initiated.     

Exercise assessment of sinoatrial node function following the Mustard operation

To screen for sinoatrial node dysfunction following the Mustard procedure for transposition of the great arteries, we studied the chronotropic response to graded maximal treadmill exercise in 29 patients at mean 6.7 years after operation. Although 93% of patients had normal resting heart rate (HR), 83% demonstrated significant depression of maximum HR and/or recovery HR after termination of exercise. These findings were similarly present among a subset of 13 patients with normal exercise tolerance. Resting and exercise-induced HR in 10 patients receiving chronic digoxin therapy were no different than in the 19 patients without medication. Sixteen patients with abnormal chronotropic responses to exercise had intracardiac electrophysiologic evaluation which confirmed sinoatrial node dysfunction in nine. Abnormal HR responses did not correlate with clinical symptoms, cardiac arrhythmias, or postoperative hemodynamics. Maximal exercise testing may be a sensitive noninvasive method to identify sinoatrial node dysfunction in postoperative children.     

Carotenoids and vitamin A: the effect of hypocholesterolemic agents on serum levels

Serum total carotenoid (STC) and vitamin A levels were done as part of the biochemical screening in comparative studies of lipid lowering agents in type Ila hyperlipoproteinemic patients. STC levels were reduced following bile acid sequestering agent administration (colestipol 30 g/d) by 30% (P less than 0.01). Clofibrate and avicel placebo had inconsistent and nonsignificant effects on the STC levels. Serum vitamin A levels were not significantly altered by any of the test agents. The STC level changes were not correlated with concomitant changes in low-density lipoprotein-cholesterol (LDL-C) during any of the treatment regimens. It is suggested that STC level changes are related to alterations in the absorption of carotenoids during bile acid sequestrant administration.