Unstable angina pectoris: National cooperative study group to compare surgical and medical therapy: III. Results in patients with S-T segment elevation during pain

A prospective randomized study comparing intensive medical therapy with urgent coronary bypass surgery for the acute management of patients with unstable angina pectoris was carried out by nine cooperating medical centers under the auspices of the National Heart, Lung, and Blood Institute. Between 1972 and 1976, a total of 288 patients were entered into the study; 79 of these (27 percent of the total study group) with 70 percent or more fixed obstruction in one or more coronary arteries had episodes of pain at rest associated with transient S-T segment elevation. Forty-two were randomized to medical and 37 to surgical therapy. The hospital mortality rate was 4.8 percent for the medical and 5.4 percent for the surgical group (difference not significant). The rate Of in-hospital myocardial infarction was 12 percent in the medical and 14 percent in the surgical group (difference not significant).During the 1st and 2nd years of follow-up, 25 percent in the medical and 15 percent in the surgical group complained of New York Heart Association class III or IV angina (difference not significant). During an average follow-up period of 42 months 45 percent of the medically treated patients later underwent surgery to relieve unacceptable angina. In the medical group 65 percent were working full- or part-time at the end of 1 year and 61 percent at the end of 2 years of follow-up; comparable figures for the surgically treated group were 63 and 68 percent.The results indicate that patients with unstable angina pectoris with transient S-T segment elevation during pain at rest with fixed obstruction of 70 percent or more in one or more coronary arteries do not differ significantly from patients with pain at rest associated with transient S-T segment depression or T wave inversion. The condition of such patients can be stabilized, and they can be managed with a maximal medical program including propranolol and long-acting nitrates in pharmacologic doses with good control of pain in most and no increase in rate of early mortality or myocardial infarction. Later, elective surgery can be performed with a lower risk and good clinical results if the patient's angina fails to respond to intensive medical therapy.     

Time-related changes in the Q-T interval in acute myocardial infarction: possible relation to local hypocalcemia

In 63 patients with either acute transmural or nontransmural myocardial infarction, the Q-T interval was prolonged beyond normal limits on at least 1 of the 5 days after infarction in 27 patients (8 with transmural and 19 with nontransmural infarction). The time-related changes in the corrected Q-T (Q-Tc) interval were defined for the entire sample and showed significant expansion, maximal on day 2, from a preinfarction control value. By day 5, the Q-Tc interval was no longer significantly prolonged and was not expanded beyond normal limits in any patient. Various possible causes of Q-T prolongation in myocardial infarction are local hypothermia, local conduction delay, neurogenic effect and local hypocalcemia. Collateral evidence suggests that the letter may contribute significantly to prolongation.     

Acute aortic arch dissection: reevaluation of the indications for medical and surgical therapy.

Of 42 patients with dissection of the aorta, 4 had important arch involvement. Results were good in 2 patients treated medically. In two other patients wrapping the arch with a Dacron graft successfully prevented fatal hemorrhage. This technique avoids the need for arch replacement in selected cases. From this experience and a review of others a flow sheet was developed to guide decision-making in the surgical and medical management of patients with aortic dissection.     

Surgical correction of truncus arteriosus in infancy

An 8 week old infant with severe heart failure from type 1 truncus arteriosus underwent successful corrective surgery employing the Rastelli procedure with use of deep hypothermia and total circulatory arrest. Postoperative hemodynamic studies showed complete closure of the septal defect, disappearance of truncal stenosis, but presence of mild porcine valve stenosis. This procedure is possible even in very small subjects and is preferable to palliative pulmonary arterial banding.     

Renal vascular lesions after chemotherapy with vinblastine,bleomycin, and cisplatin

A 30 year old man with metastatic embryonal carcinoma became hypertensive during vinblastine, bleomycin, and cisplatin therapy. Three months after completion of therapy, accelerated hypertension occurred (blood pressure 210/140 mm Hg). Nitroprusside failed to control the hypertension, but captopril resulted in a prompt and sustained normalization of the blood pressure. The plasma renin activity was markedly elevated before therapy. Renal biopsy disclosed “onionskin” narrowing of the interlobular arteries and fibrin thrombosis of a majority of the afferent arterioles. A form of drug-induced renovascular hypertension is suggested.     

Comparative response of right and left ventricles to volume overload.

The cardiac volume data of 49 normal children were compared with those of 23 with secundum atrial septal defect and 24 with patent ductus arteriosus. Significantly smaller ventricular end-diastolic volumes were observed in the normal infants than in older children (right ventricle 53.9 versus 75.5 cm3/m2; left ventricle 46.7 versus 63.6 cm3/m2). "Distensibility" of the right ventricle (DRV), left ventricle (DLV) and left atrium increased normally with age. DRV and DLV were similar shortly after birth; thereafter, DRV increased more rapidly than DLV (mean DRV 12.7; mean DLV 7.8 cm3/m2 per mm Hg, P less than 0.001). In both atrial septal defect and patent ductus arteriosus, the ipsilateral (involved) ventricles had increased volume, increased output, normal ejection fraction and increased distensibility. The contralateral (left) ventricle in atrial septal defect was smaller than normal (39.6 versus 49.7 cm3, P less than 0.001), and had a smaller ejection fraction (0.63 versus 0.71, P less than 0.01) and output (3.70 versus 4.57 liters/min per m2, P less than 0.005). In contrast, the contralateral (right) ventricle in patent ductus arteriosus remained normal. Left atrial maximal volume was larger than normal in atrial septal defect (46.6 versus 35.9 cm3/m2, P less than 0.001). The left atrial and left ventricular volumes in patent ductus arteriosus were, respectively, 152 and 142 percent of normal, indicating comparable response to the volume load. The left head changes in atrial septal defect may be related both to a functionally restrictive defect and to the difference in distensibility of the ventricles.     

Atherosclerosis—Relationship to coronary blood flow

Human atherosclerotic plaques in coronary arteries consist of a variable mixture of lipids, cells and fiber proteins synthesized by the cells. The 2 major space-occupying components of the advanced lesions, which together obstruct the lumen, are the fibrous cap and the necrotic core from which the lesions derive their name. The smooth muscle cells, which make up most cells of the plaque, including the fibrous caps, are produced by migration from the media as well as by proliferation of these cells in the intima. The lipids, mostly supplied by circulating lipoproteins, are present not only in the atheromatous acellular core, but also in the cytoplasm of the cells of the lesion and extracellularly, often attached to 1 or more constituents of the fibrous matrix of the plaque (collagen, elastin and proteoglycans).In both human and rhesus monkey coronary arteries, the lumen becomes more stenotic as the plaque becomes larger and enlarges as the plaque becomes smaller in response to lipid-lowering therapy. Recent studies in other nonhuman primate models of advanced atherosclerosis have questioned the influence of the plaque lesion on coronary blood flow. For example, in the cynomolgus species of macaque (M. fascicularis), depending on how the plaques are induced, the artery lumens may dilate as the plaques become larger because the outside diameters of the arteries increase. Furthermore, some diseased arteries are found to stenose further when the animals with advanced coronary plaques are treated by measures that substantially reduce the lipids in the plaques.Questions now being studied in several animal models and in human arteries include the relative influence of the degree of medial involvement, of lesion cell types, and of lesion circumferential localization (concentric versus eccentric) on these paradoxical phenomena.     

Mid-ventricular obstruction: A variant of obstructive cardiomyopathy

In two patients with clinical and catheterization findings of hypertrophic obstructive cardiomyopathy, the level of intraventricular obstruction was found to be in the mid-ventricular area rather than at the junction of the inflow and outflow tracts. One patient died suddenly shortly after unsuccessful outflow tract myectomy. In vivo recognition of this probably rare variant form of obstructive cardiomyopathy rests mainly on the angiographic appearance of the left ventricle and on the recording of pressures in multiple sites of the left ventricular cavity. Surgical relief of the obstruction in these patients is not likely to be obtained by a transaortic left ventricular outflow myectomy but may require either papillary muscle resection by the transatrial or transventricular approach or mid-ventricular septectomy, or both.     

Sustained beneficial hemodynamic responses to large doses of transdermal nitroglycerin in congestive heart failure and comparison with intravenous nitroglycerin

The hemodynamic effects of a new transdermal preparation of nitroglycerin were evaluated in 9 patients with chronic congestive heart failure (CHF). A graded infusion of nitroglycerin was administered initially to establish the dose-response relation for nitroglycerin and estimate the dose of topical nitroglycerin to be applied. Significant hemodynamic improvement was observed 0.5 to 1.0 hour after the cutaneous application of the nitroglycerin-impregnated polymer. The peak effect occurred at 6 hours, with the left ventricular filling pressure decreasing from 24 ± 2 to 18 ± 1 mm Hg (mean ± standard error of the mean) (p < 0.01) and the cardiac index increasing from 2.0 ± 0.2 to 2.6 ± 0.2 liters/min/m² (p < 0.01). The systemic vascular resistance decreased from 1,860 ± 198 to 1,531 ± 162 dynes s cm^?5 (p < 0.01). Heart rate and mean arterial pressure were unchanged. Significant hemodynamic benefit was observed for 24 hours, and no rebound deterioration occurred upon withdrawal of the drug. The average dose of transdermal nitroglycerin applied was 51 ± 6 cm² (1.7 ± 0.2 mg/kg; 6 of the 9 patients received 64 cm²). Thus, topical application of a new nitroglycerin-impregnated polymer induces an improvement in cardiac performance that is sustained for 24 hours in patients with chronic CHF. However, substantial doses of the drug may be required to produce a satisfactory hemodynamic response in most patients with CHF.     

Action potential and contraction of heart muscle

Current concepts of the mechanisms responsible for the cardiac action potential are reviewed, as are the relations between the electrical activity and cardiac contraction. The development of techniques allowing direct control of the membrane voltage of cardiac cells has led to a rapid increase in our understanding of the cellular basis of cardiac electrophysiology. There appear to be 8 separately identifiable ionic channels that interact to produce the distinctive cardiac action potential. These “voltage clamp” methods also provide a new approach to the study of excitation-contraction coupling in heart muscle. The application of these methods has led to several new ideas about the relation between membrane voltage and contraction. In addition to triggering contraction, the cardiac action potential plays an important role in the control of contraction, and the nature of this electrical control is examined.     

Biventricular dynamics during quantitated anteroseptal infarction in the porcine heart.

The porcine heart has been shown to have close anatomic similarity to the human heart and was used as the experimental model in this study to gain further understanding of the early responses of both ventricles during acute anteroseptal myocardial infarction. High fidelity pressure and flow data were measured and multiple preejection and ejection variables were calculated for both ventricles. Infarct weight and distribution in both ventricles were quantitated. The standard infarction resulted from single stage ligation of the left anterior descending coronary artery just beyond its midpoint and second left ventricular branch. It comprised an average of 15.8 percent of total ventricular myocardium with an infarct/perfused ratio of 0.62 and a periinfarction transition zone of 7.5 mm, and involved significant portions of both ventricles and the interventricular septum. Performance characteristics of both ventricles were altered significantly by anteroseptal infarction and involved all phases of contraction--end-diastole, isovolumic systole and ventricular ejection. Although contractile alterations in the right ventricle were significant, they were somewhat delayed, yielding relatively low correlation coefficients with analogous left ventricular contractile indexes. These correlations became quite distinct during specific ventricular stresses. Comparison of anterolateral and anteroseptal infarction, matched in terms of infarct size, indicated that the right ventricular changes in the latter were related to direct involvement of the right ventricular free wall and septum rather than secondary to left ventricular alterations.     

Primary hyperparathyroidism masked by hypothyroidism

In a woman with myxedema and normal total and ionized plasma calcium levels, persistent hypercalcemia developed when she was treated with thyroxine. A parathyroid adenoma was subsequently removed, with return of plasma calcium levels to normal. Hypothyroidism may therefore be a further cause of "masked" primary hyperparathyroidism. The mechanism of masking is likely to have been mediated by hypomagnesemia.     

Nonalcoholic liver disease. Overlooked causes of liver injury in patients with heavy alcohol consumption.

Alcoholic subjects with abnormal liver chemistry studies are often assumed to have alcoholic liver disease, even though the diagnosis is not established by liver biopsy. To determine the magnitude of nonalcoholic liver disease in patients with heavy alcohol consumption, the data on 145 consecutive patients judged to consume at least 80 g of alcohol daily for prolonged periods, and who underwent liver biopsy at the University of Chicago, were reviewed. Nonalcoholic liver disease was suspected clinically and confirmed by liver biopsy in 40 (28 per cent), whereas alcoholic liver disease was suspected in 105 but confirmed in only 83 (80 per cent). The remaining 22 patients had liver disorders, including cholangitis or pericholangitis, acute hepatitis or some form of chronic hepatitis, for which they required appropriate therapy. Neither clinical features, hepatitis B surface antigen (HBsAg), anti-HBsAg nor serum glutamic oxaloacetic transaminase to serum glutamic pyruvic transaminase (SGOT:SGPT) ratios distinguished these 22 patients from those with alcoholic liver disease. Thus, liver biopsy is necessary for the identification of nonalcoholic liver disease in patients suspected of harboring alcoholic liver disease, since other clinical features do not allow identification of these patients.