William Likoff

Devolutionary pattern of coronary atherosclerosis in patients with angina pectoris: Coronary arteriographic studies

Abstract The devolutionary pattern of coronary atherosclerosis in patients with angina pectoris was studied in 47 persons cinearteriographically. Two subsets of patients were identified at the initial examination. The first comprised 12 patients who did not have coronary atherosclerosis. In these 12, the cinearteriographic findings remained normal on repeated study 15 to 73 months later. The second subset included 35 patients with severe obstructive coronary atherosclerosis. When coronary visualization was repeated 15 months later, arterial disease remained stable in 11 patients (31.4 percent). Significant progression of the arterial disease was observed in the remaining 24 patients (68.5 percent). The frequency of hyperlipidemia, clinical diabetes, systolic and diastolic hypertension and a positive family history of coronary heart disease was not significantly different in those with stable and progressive disease. Furthermore, the distribution of the initial disease did not distinguish one group from the other. Since collateral channels were more prolific in patients who ultimately were classified as having stable arterial disease, it is possible that the initial severity of disease in this group was greater than in those with progressive disease. None in the latter group noted a reduction in the frequency or severity of angina pectoris. One third of those with stable disease did record such a reduction. However, paradoxically, two patients with stable coronary disease had a new myocardial infarction in the interval between examinations. Our findings suggest that the devolutionary pattern of coronary atherosclerosis in patients with angina pectoris as observed cinearteriographicaliy is unpredictable and apparently unrelated to commonly cited risk factors. They indicate that the severity of angina pectoris is the most precise guide to progressive coronary artery disease even though progressive disease can occur without affecting angina. The occurrence of myocardial infarction in patients with stable disease underscores the fact that many determinants influencing myocardial perfusion are not identified by cinearteriography.

Electrophysiologic antagonism and synergism of potassium and antiarrhythmic agents

Abstract Interactions of potassium and antiarrhythmic agents on ventricular myocardial electrophysiology were studied in 25 isolated, perfused rabbit hearts by utilizing an intracellular microelectrode technic. Perfusion of quinidine (0.01 mg./ml.) in a normal concentration of potassium (5.6 mEq./L.) caused a significant decrease in the maximal rate of depolarization (−69.1%), heart rate (−40.4%) and the action potential duration per unit of time (−13.8%). Reduction in the height of action and resting potentials was insignificant. Lowering potassium to 0.8 mEq./L., in the presence of the same concentration of quinidine, significantly increased the maximal rate of depolarization (+82.5%), the height of action potential (+8.5%) and resting potential (+9.9%). The action potential duration per unit of time also showed a significant increase (+15.2%) to control value, although the heart rate was further decreased. Initial perfusion of a low potassium solution caused a significant increase in the height of action potential (+3.3%) and resting potential (+7.0%) as well as a significant decrease in the action potential duration per unit of time (−19.2%). The maximal rate of depolarization and the heart rate showed no significant changes. Addition of quinidine to this low potassium perfusate did not produce any appreciable changes in the maximal rate of depolarization, or in the height of action and resting potentials. The action potential duration per unit of time again returned to its control level. Hence, the electrophysiologic action of quinidine was nullified by a low potassium concentration in both groups of experiments. Quite a similar antagonism was demonstrated between low potassium concentration and other antiarrhythmic agents (antazoline and SU-11636), while high potassium concentration (12 mEq./L.) enhanced the depressive effects of these three drugs. The electrophysiologic mechanism of antiarrhythmic agents was discussed, and the clinical importance of controlling serum potassium concentration during the administration of these agents was suggested.

LATE SYSTOLIC MURMUR OF MITRAL REGURGITATION.

Abstract The late systolic murmur is a useful sign of mitral regurgitation. The murmur begins in mid-systole, increases in intensity during late systole, and ends with or envelopes aortic-valve clusure. This murmur is demonstrated by intracardiac phonocardiography in the inflow tract of the left ventricle in the path of the regurgitant jet. Left ventriculograms recorded by cineradiography demonstrate bulging of the septal leaflet of the mitral valve during early systole, and Grade II regurgitation confined to late systole. The 8 patients with the late systolic murmur and mitral regurgitation showed only minor pathophysiologic changes, which were confirmed by cardiac catheterization.

Myocardial infarction in patients with normal patent coronary arteries as visualized by cinearteriography

Myocardial infarction with normal coronary arteriographic findings is rare. Three patients are presented who had typical clinical and laboratory findings of acute myocardial infarction and normal coronary arteriograms. Two patients were male, 16 and 24 years old, respectively, and 1 was female, aged 36 years. None had major predisposing factors to precocious coronary atherosclerosis. Thrombocytosis was considered to be the etiologic factor in 1 male patient; no etiologic factor could be traced in the other male patient; estrogen therapy may be considered as the cause of the myocardial infarction in the female patient.

Bacterial endocarditis following cardiac surgery.

Intracardiac surgery for rheumatic and congenital heart disease entails direct trauma to both normal and abnormal endocardium. This communication inquires into the incidence and nature of the endocardial infections that develop subsequent to this injury. On the basis of an examination of 2,263 patients operated upon for acquired and congenital heart disease during a 5-year period terminating in November 1955, bacterial endocarditis appears to be an infrequent complication of surgery, is caused by organisms not so commonly encountered in unoperated patients, and is characterized by a clinical pattern quite different from that ordinarily associated with bacterial endocarditis. The rate of attrition in this group of patients is high, and unquestionably is related to the antibiotic resistance of the unusual organisms and the severity of the basic heart disease.

CLINICAL CORRELATION OF CORONARY ARTERIOGRAPHY.

Abstract Selective coronary arteriography is a satisfactory technic in the study of the distribution and severity of atherosclerosis in patients with coronary heart disease. This investigation analyzes the placement and gradation of pathology in patients with angina pectoris whose resting electrocardiograms varied from normal patterns to tracings indicative of past transmural myocardial infarctions. Atherosclerosis was visualized as a diffuse process involving two or three main arteries even in those individuals who had the earliest clinical form of coronary heart disease, namely, angina pectoris and a normal resting electrocardiogram. The severity of the atherosclerotic process in terms of its stenosing effect on the vascular vessels increased materially as the electrocardiographic tracing deteriorated from normal to a pattern indicative of a past transmural myocardial infarction. Channels of anastomosis did not develop when atherosclerosis was diffuse but not occlusive. Particular attention is drawn to patients with angina pectoris and normal resting electrocardiograms who had in the past RS-T or T wave abnormalities or both. The occlusive disease in these patients was considerable and hardly compatible with the term “mild coronary.”

Evaluation of “coronary vasodilators” by coronary arteriography

Abstract The primary purpose of a coronary vasodilator is to increase the caliber of the coronary vascular bed. Selective coronary arteriography currently is the most direct and effective means of evaluating changes in the size of the coronary arteries in the intact organism. Utilizing this method of examination, it is apparent that glyceryl trinitrate and erythrityl tetranitrate have coronary vasodilating actions even in those patients with overt and serious coronary atherosclerosis. The demonstration of this action, however, does not imply that coronary blood flow is consequently improved.

Malabsorption as a complication of congestive heart failure

Abstract Fat absorption by using radioactive neutral fat and fatty acid technics, has been measured in 25 patients with chronic congestive heart failure. In 56 per cent of the group definite mal-absorption was present with evidence of both a digestive as well as a primary absorptive defect. Treatment with diuretics or pancreatic supplements resulted in improved absorption. Histologic examination of the pancreas and small intestine in several of these patients demonstrated the presence of mucosal and interstitial congestion and edema which may help explain the results obtained.

Echocardiography in congenital heart disease: Preliminary observations∗

Abstract The rationale of using ultrasound in the diagnosis of congenital heart lesions is discussed, and our experience with 28 patients is presented. It is suggested that the echocardiogram is a safe and reliable bedside procedure that may be a useful adjunct in the diagnosis and follow-up of patients with congenital cardiac abnormalities. In the presence of intra- or extracardiac shunts, the resultant state of high flow across either the mitral or tricuspid valves is reflected by a rapid velocity of valve motion on the echocardiogram. This is demonstrated in patients with patent ductus arteriosus, ventricular septal defect and atrial septal defect. The velocity of mitral valve motion is also increased in patients with congenital mitral regurgitation. The identification of a congenital subaortic membranous diaphragm by using ultrasound is described. The echocardiographic criteria for making this diagnosis are listed. The importance of distinguishing this lesion from idiopathic subaortic hypertrophic stenosis is emphasized. Several interesting case reports illustrating the diagnostic value of this technic are presented. It is emphasized that these are preliminary observations. The possibilities for the future are discussed.

Myocardial infarction in subjects with normal coronary arteriograms

The pathophysiologic basis for myocardial infarction is an unfavorable balance between coronary blood flow and the metabolic needs of the myocardium. In most instances, this is caused by seriously obstructive coronary atherosclerosis. Other disorders, such as syphilitic occlusion of the coronary ostia, coronary embolism, dissecting aortic aneurysm, periarteritis nodosa and thromboangiitis obliterans may block or reduce the internal caliber of the coronary arteries and bring about an infarction. Determinants other than mechanical obstruction also may adversely influence coronary flow and, alone or in combination with factors that increase myocardial oxygen need, may be responsible for myocardial infarction. In severe aortic stenosis, marked elevation of the level of intraventricular pressure increases peripheral coronary resistance and reduces systolic coronary flow at a time when the metabolic needs of the heart muscle rise because of the thick ventricular wall, increased intraventricular pressure and prolonged ejection interval. Identical mechanisms bear the blame for the exceptional incidence of infarction in patients with idiopathic hypertrophic subaortic stenosis. The imbalance between coronary flow and the nutritional needs of the myocardium in isolated severe aortic regurgitation is caused by the abnormally depressed aortic diastolic pressure, which markedly reduces diastolic coronary perfusion, and the size and configuration of the left ventricle, thus increasing the metabolic demands of the myocardium. Explanations are less certain in restrictive and congestive cardiomyopathies. The basic pathophysiologic default may be a metabolic error that impedes normal cellular oxygen utilization. Indeed the term infarction may not apply in these types of cardiac disorders since the muscle necrosis is not caused by a perfusion deficit.