Echocardiographic findings of ventricular septal rupture in acute myocardial infarction.

Echocardiograms were recorded both before and after the clinical appearance of an autopsy-confirmed interventricular septal rupture in a patient with an acute myocardial infarction. The major findings were related to the upper portion of the interventricular septum. Before rupture, this portion of the septum was relatively akinetic with a slight anterior motion during systole, whereas after rupture there was a marked increase in the amplitude of septal motion with abrupt posterior motion occurring with the onset of ventricular diastole.     

Echocardiographic assessment of the effect of an antihypertensive regimen on left ventricular performance.

A regimen consisting of chlorthalidone, hydralazine and propranolol would be useful in some hypertensive patients with coronary artery disease or aortic dissection if it could be shown that reflex cardiac stimulation induced by hydralazine is completely neutralized by propranolol. Nine hypertensive patients were treated with chlorthalidone during week 1, chlorthalidone and hydralazine during week 2 and a combination of chlorthalidone, hydralazine and propranolol during week 3. Blood pressure, heart rate, mean velocity of circumferential fiber shortening (VCF) measured echocardiographically and plasma renin activity were measured weekly. This potent three drug regimen reduced mean blood pressure from 142 to 102 mm Hg, and with the third drug, propranolol, heart rate, VCF and plasma renin activity returned to control levels from the greater elevated levels produced by the diuretic drug and hydralazine. In six additional patients VCF (an index of left ventricular contractility) was found to be proportionate to the rate of rise of aortic pressure (dP/dt) or aortic shearing force. This regimen appears safe for use in patients with ischemic heart disease and aortic dissection.     

Noninvasive assessment of pulmonary hypertension from right ventricular isovolumic contraction time

In order to assess a noninvasive method of predicting pulmonary arterial pressure in adults, right ventricular systolic time intervals were determined with echocardiography simultaneously with pulmonary arterial end-diastolic pressure measurements. Right ventricular isovolumic contraction time was measured from echographic recordings of the tricuspid and pulmonary valves. Although this interval was found to increase as pulmonary arterial pressure increased, the method cannot be used to predict quantitatively the level of pulmonary arterial pressure in adults. However, an echocardiographically determined right ventricular contraction time of less than 25 ms suggests a normal pulmonary arterial pressure. In patients with pulmonary parenchymal diseases, echograms of the tricuspid and pulmonary valves are only rarely of such quality as to permit accurate delineation of the valvular events required for these measurements.     

Combined hemodynamic-ultrasonic method for studying left ventricular wall stress: comparison with angiography.

Calculation of left ventricular wall stress in man has traditionally required angiographic and left ventricular pressure measurement, making study of interventions difficult. We have developed a combined hemodynamic-ultrasonic technique for measuring left ventricular meridional wass stress (sigma m) throughout the cardiac cycle. Simultaneous measurements of left ventricular pressure, ultrasonically determined wall thickness (h[echo]), and minor axis (D[echol]) were made during cardiac catheterization in nine subjects, three with chronic left ventricular pressure overload, four with left ventricular volume overload and two with normal left ventricular function. Within 30 minutes, left ventricular cineangiography was performed in each subject and angiographic wall thickness (h[angio]) and minor axis (D[angio]) were measured. Comparison of values for each subject throughout the cardiac cycle (average 18 data points/cycle) yielded close correlation: For D(echo) versus D(angio), r values ranged from 0.82 to 0.98 whereas for h(echo) versus h(angio), r values ranged from 0.56 to 0.98 for the nine subjects. Meridional wall stress was calculated after the method of Sandler and Dodge as PRi2/h(2Ri + h), where Ri equals the inner wall radius, calculated as D/2 for both ultrasonic and angiographic methods. Agreement between ultrasonic and angiographic methods was excellent in each subject, with close superimposition of the stress-time plots constructed by the different techniques. In summary, a new method for measurement of left ventricular wall stress has been developed and validated by comparison with an angiographic reference standard. This method has potential advantages, including the ability to study meridional wall stress continuously and to assess its response to serial interventions.     

Sequential studies of left ventricular function and wall motion after coronary arterial bypass surgery

Left ventricular performance and segmental wall motion were studied sequentially in 12 patients during the 1st postoperative year after coronary arterial bypass graft surgery with use of computer-aided fluoroscopic analysis of radiopaque tantalum markers implanted into the left ventricular wall at operation. Measurements were made 1 week, 2 months and 1 year after operation. Ejection fraction decreased significantly early postoperatively (to 42 ± 3 percent [mean ± standard error of the mean]) but recovered to near preoperative values (55 ± 3 percent) at 2 months (49 ± 2 percent) and 1 year (51 ± 3 percent). Stroke volume increased from 51 ± 4 ml 1 week after operation to 70 ± 6 ml at 1 year; heart rate decreased from 91 ± 2 to 69 ± 4 beats/min during this interval. Both circumferential fiber shortening velocity and cardiac output were constant over the year. Total peripheral resistance was reduced in the early postoperative period. The data in the early postoperative period were consistent with those observed with an increase in heart rate alone, with only a small chronotropic augmentation of the myocardial contractile state. Total wall motion increased from 1 week to 2 months after operation primarily because of an increase in the extent of contraction of inferior wall segments, particularly in zones of previous infarction. Five of seven patients who had a preoperative myocardial infarction with hypokinesia of the infarcted region showed increased shortening in the region in the first 2 postoperative months. Four of six patients whose ejection fraction was less than 40 percent 1 week after operation had recurring angina; the six patients with a larger ejection fraction at this time had no recurrence.Because resting left ventricular performance varies significantly during the 1st postoperative year, it is concluded that (1) results of evaluations made at widely differing times after operation should not be pooled in determining operative results; (2) studies made 2 or more months postoperatively are not subject to the rapidly changing values associated with the early postoperative period; (3) frequent sequential studies of left ventricular performance are required to evaluate operative outcome in an individual patient; and (4) wall motion in regions of previous infarction can be improved by coronary bypass graft surgery.     

The apex impulse in mitral stenosis: graphic explanation of the palpable movements at the cardiac apex

Simultaneously recorded phonocardiograms and apexcardiograms of 39 patients with mitral stenosis (MS) were retrospectively analyzed. A notch on the upstroke of the apexcardiogram coincidental with the first heart sound (S1) occurred in 18 (47%) of the patients. The notch ratio or vertical distance from the onset of the apical impulse to the notch ratio or vertical distance from the onset of the apical impulse to the notch as a percentage of the total upstroke was measured and compared with the mean mitral diastolic gradient obtained at cardiac catheterization. Statistical analysis showed a significant relation (r = 0.61; p less than 0.01) between notch ratio and the mean mitral diastolic gradient. This study reaffirms that the complex palpable movements at the cardiac apex, consisting of a "tap" representing S1 occurring perceptibly after the onset of the apex impulse itself, are a useful diagnostic sign of MS. Furthermore, a graphic measurement of the extent of delay of S1 with respect to the onset of the apical thrust can provide a rough measure of the severity of the valvular obstruction.     

Early aortic valve closure in combined idiopathic hypertrophic subaortic stenosis and discrete subaortic stenosis

A patient with idiopathic hypertrophic subaortic stenosis (90 mm Hg resting intraventricular gradient) and discrete subaortic stenosis was found to have two separate systolic closing movements of the aortic valve on M mode echocardiography, each movement being associated with a separate systolic ejection murmur. The first closing movement occurred early in systole and was attributed to alterations in flow across the discrete stenosis. The second closing movement coincided with a later systolic murmur and systolic anterior motion of the mitral valve. This case supports the concept that timing of early closing movements of the aortic valve is useful in the diagnosis of subvalvular obstruction.     

Echocardiographic studies of the mitral valve in patients with congestive cardiomyopathy and mitral regurgitation

This echocardiographic study has demonstrated that the finding of systolic separation of the mitral leaflets is not specific for those patients with the late systolic clicklate systolic murmur syndrome but is also seen with ruptured chordae tendineae and in cardiomyopathy patients with mitral regurgitation. From these observations and with the help of observations of others, we have reasoned that the mitral regurgitation associated with cardiomyopathy is not due to mitral annulus dilatation but to papillary muscle dysfunction.     

Multiformity of induced unifocal ventricular premature beats in human subjects: Electrocardiographic and angiographic correlations.

Single ventricular premature responses induced by strength-interval pacing were elicited at multiple sites in 30 patients undergoing cardiac catheterlzation to determine if and under what circumstances unequivocally unifocal stimulated ventricular premature beats could manifest multiformity of the QRS configuration. Multiformity was defined as unifocal responses whose mean frontal axes differed by greater than 15 ° with or without associated morphologic differences in the horizontal leads. Multiformity occurred in 12 (40 percent) of 30 patients. A statistically significant association was found between multiformity and the presence of a quantitatively defined left ventricular wall motion abnormality (p < 0.01), prior myocardial infarction (p < 0.01) and a left ventricular ejection fraction of less than 0.60 (p < 0.05). Twelve (67 percent) of the 18 patients without multiformity had coronary artery disease, but only 4 of those 12 had a left ventricular wall motion abnormality or prior myocardial infarction, or both. Multiformity was also dependent on the site of stimulation and on the degree of prematurity. The results of this study indicate that the QRS configuration of early premature beats cannot be relied on as a predictor of their site of origin and multiformity is not necesarily synonymous with multifocality.     

Changes in left ventricular wall dimensions during regional myocardial ischemia

The relation between changes in left ventricular wall systolic thickening and other measures of left ventricular function were studied during regional ischemia in 14 open chest pigs. A fixed decrease in coronary peak blood flow from 46 ± 5 (standard error) to 13 ± 2 ml/min was produced using a screw clamp and flow probe placed around the left anterior descending coronary artery. Myocardial wall thickness was measured with a calibrated harpoon mercury strain gauge placed through the apical portion of the left ventricle and recorded continuously with left ventricular systolic pressure, the first derivative of left ventricular pressure rise ($\text{dP}\text{dt}$) and pressure-derived peak velocity of contraction. During systole, the left ventricle thickened by 10.7 ± 2.1 percent of its total average thickness of 12.7 ± 0.7 mm. Within 6 seconds of the onset of ischemia total myocardial wall thickness decreased from 1.356 ± 0.135 to 0.592 ± 0.081 mm (P < 0.001) or to 45.2 ± 5.1 percent of the control value. During ischemia, changes were noted in both the isovolumic and the ejection phases of systole in addition to left ventricular wall thinning of 0.282 ± 0.02 mm at enddiastole. There was no significant change in left ventricular pressure or its derived values. In two experiments isolated wall thickness alternans was observed. These studies indicate that myocardial wall thickness is more sensitive than ventricular pressure as a measure of local changes in myocardial function during regional myocardial ischemia.     

Perspectives and future trends in cellular electrophysiology: implications for the clinician

As a result of single fiber electrophysiologic studies, the clinical approach to the electrical behavior of the heart has improved. Three areas are examined: 1) the electrocardiographic waveform, 2) normal and abnormal cardiac rhythms, and 3) the mechanism of action of antiarrhythmic drugs. In each area, the results of single fiber studies have provided a conceptual framework for diagnostic and therapeutic decisions. These studies have also enabled investigators to test hypotheses formulated from clinical observations. It may be only a slight exaggeration to attribute many of our recent advances in each of the three areas to the development and use of the microelectrode.     

Atrial excitability and conduction in patients with interatrial conduction defects

Prolongation of P-wave duration is an accepted indicator of an interatrial conduction disturbance and may predispose patients to atrial arrhythmias. This study was performed to monitor electrophysiologic characteristics of the atria in patients with a prolonged P-wave duration. Atrial excitability and conduction times were compared in 7 patients with a P-wave duration < 115 ms (Group I) and 13 patients with a duration ≥ 115 ms (Group II). In contrast to the Group I patients, most of the 13 patients in Group II had atrial arrhythmias, including sinus nodal dysfunction (3 patients) and a history of atrial fibrillation or ectopic atrial tachycardia (6 patients). Electrophysiologic differences between the 2 groups included a higher late diastolic threshold in Group II (0.8 ± 0.2 mA versus 1.3 ± 0.2 mA; p < 0.005), and a greater increase in intraatrial conduction time (5 ± 10 ms versus 30 ± 20 ms; p < 0.005) and interatrial conduction time (5 ± 15 ms versus 30 ± 15 ms; p < 0.05) of early premature responses. There were no differences between the 2 groups in refractory periods, shape of the strength interval curve, or conduction times of premature responses occurring late in diastole.

These abnormalities in conduction time and excitability found in patients with a prolonged P-wave duration may predispose to the initiation of certain atrial tachyarrhythmias.     

Reproducibility and treatment of exercise-induced ventricular tachycardia

Fourteen patients with exercise-induced ventricular tachycardia (VT) underwent serial treadmill testing, and those with reproducible arrhythmia were treated with a β-adrenergic blocking agent. In 11 patients (79%), VT of similar rate, morphologic characteristics and duration was reproduced on 2 consecutive treadmill tests performed 1 to 14 days apart. Beta blockade prevented recurrent VT during acute testing in 10 of 11 patients and during chronic therapy in 9. Eight patients had a consistent relation between a critical sinus rate and the onset of VT. In these patients, successful therapy correlated with preventing achievement of the critical sinus rate during maximal exercise. Thus, serial exercise testing is an appropriate means of assessing efficacy of therapy in patients with exercise-induced VT, provided that reproducibility is established on 2 control tests before beginning treatment. Therapy with β-blocking agents is effective, especially when guided by the presence of a critical sinus rate-VT relation.     

Cholesterol and cardiovascular disease. An overview of Lipid Research Clinics (LRC) epidemiologic studies as background for the LRC Coronary Primary Prevention Trial

The Lipid Research Clinics (LRC) Program has implemented an integrated series of observational epidemiologic, community-based studies that provide a frame of reference for the results of the LRC Coronary Primary Prevention Trial (CPPT). The observational studies were performed in 16 populations sampled in the United States, Canada, the Soviet Union and Israel. Findings based on data from more than 80,000 study participants indicate that atherogenic profiles of plasma total, low-density lipoprotein and high-density lipoprotein cholesterol levels are highly prevalent in middle-aged adults. The lipoprotein cholesterol fraction components are related to a wide range of demographic, behavioral, anthropometric, medical status, drug utilization and hormonal factors, in addition to the well known major dietary and genetic determinants. The results of the LRC CPPT are directly applicable to high-risk, high total cholesterol, and high low-density lipoprotein cholesterol levels in middle-aged men. Considered jointly with the observational finding that the major burden of ischemic heart disease is associated with moderately elevated lipid levels, the LRC studies suggest that 2 concurrent approaches are necessary to achieve community control: approaches for high-risk person through individualized medical intervention and hygienic, population-oriented approaches toward achieving less atherogenic distributions of lipids and lipoproteins. With this combined approach, the current epidemic of ischemic heart disease can be controlled.     

Chronic mucocutaneous candidiasis. Immunologic studies of three generations of a single family.

A family consisting of eight members in three generations (age 10 months to 53 years) affected with chronic mucocutaneous candidiasis was studied along with three unaffected relatives. Dermatophytosis, loss of teeth and recurrent viral infections were present in some members. Results of tests for endocrinologic, muscle or liver disease, thymoma, iron deficiency, antitissue antibodies and malabsorption were normal in all patients. Antibody function and levels, B cell counts, serum complement, leukocyte enzymes, chemotaxis, phagocytosis and adherence were normal in all members. Plasma inhibitors to lymphocyte transformation and leukocyte inhibitory factor were not found. No unique HLA haplotype or antigen segregated in this family. Evaluation of cell-mediated immunity revealed total cutaneous anergy in three of eight whereas four of the other five had negative lymphocyte transformation and skin tests to Candida but responded normally to other antigens. Leukocyte inhibitory factor was not produced to Candida antigen in all four patients tested. T cell counts were within normal limits in all. Extensive evaluation of all limbs of the immune system in this family revealed a defect in cell-mediated immunity to Candida that appeared to be inherited as a dominant characteristic.     

Resting peripheral blood lactate elevation in survivors of prehospital cardiac arrest: Correlation with hemodynamic, electrophysiologic and oxyhemoglobin dissociation indexes

Thirteen patients who were survivors of sudden unexpected cardiac arrest in the community were followed up for up to 3 years. All showed an anomalous relation between erythrocyte levels of oxygen dissociation (P₅₀) and 2,3-diphosphoglyceric acid (2,3-DPG). This could not be explained by hemoglobinopathy, carbon monoxide or methemoglobinemias. Because lactate accumulation in red blood cells may alter oxygen dissociation, whole blood and red blood cell lactate levels were measured. An average of 4.4 measurements per patient were obtained over a mean time of 5.6 months of the post-hospital phase of the follow-up period, which had a total mean duration of 22 months. The patients did not have overt congestive heart failure and were not acidotic (mean venous pH = 7.35). Lactate levels were elevated (mean = 15.1 mg/100 ml ± 0.8 mg/100 [standard error of the mean], compared with normal values of 7.6 mg/100 ml ± 1.4 mg/100 ml; P < 0.01). When lactate was plotted against red blood cell 2,3-diphosphoglycerate, a positive curvilinear relation was found (r² = 0.12, P < 0.05). The production of lactate in chronic ischemia may increase red blood cell 2,3-diphosphoglycerate through glycolysis. The expected effect on oxygen dissociation of this increase in 2,3-diphosphoglycerate is offset by a counterbalancing leftward shift of the oxyhemoglobin dissociation curve by an increase in red blood cell lactic acid. When lactate was compared with left ventricular ejection fraction, there was a significant negative correlation (r = 0.86, P < 0.01). Serial 24 hour ambulatory electrocardiograms (mean 4 per patient) were analyzed for changes in quantity and severity of ventricular arrhythmia at the time of lactate determinations. Six patients had lactate level variation of more than 30 percent, and five of these six patients had an increase in quantity and severity of ventricular ectopic activity when their lactate levels were in the higher range. We conclude that elevated resting lactate levels correlate with impaired ventricular function, and fluctuations in a given patient may identify changes in clinical and electrophysiologic status.