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Clinical and pathologic observations were made in four infants who died with asymmetric septal hypertrophy in the first five months of life. One of these infants was stillborn and the other three were aged 1½ months, 4½ months, and 5 months at the time of their deaths. The three live-born infants demonstrated severe congestive heart failure and cardiac enlargement. The clinical features present in these three infants during life suggested a variety of other congenital cardiac malformations, including congenital mitral regurgitation, pulmonary stenosis, and endocardial fibroelastosis. In each of the four infants the ventricular septum was markedly hypertrophied and was thicker than the postero-basal left ventricular wall; septal to postero-basal free wall thickness ratios ranged from 1.8 to 2.6. Moreover, the septum of each infant contained a disordered arrangement of hypertrophied cardiac muscle cells. In three of the infants the myocardial cellular abnormalities were less marked in the left ventricular free walls than in the ventricular septum. In the fourth infant disorganized cardiac muscle cells were distributed widely in both the ventricular septum and left ventricular free wall; the clinical findings suggested the absence of left ventricular outflow obstruction in this infant. Asymmetric septal hypertrophy was documented in one first degree relative of each infant. It is concluded that asymmetric septal hypertrophy is a genetically transmitted disease that may present clinically in infancy and lead to infant death. Furthermore, the characteristic pathologic feature of asymmetric septal hypertrophy in adults, a disproportionately thickened ventricular septum containing numerous hypertrophied and disorganized cardiac muscle cells, can be present at birth.

Idiopathic left ventricular hypertrophy is diagnosed when hypertrophy without dilatation appears to be present without apparent cause. Since asymmetric septal hypertrophy occurs commonly, and since it may present nonspecifically as left ventricular hypertrophy, we hypothesized that many patients with idiopathic left ventricular hypertrophy might in fact have asymmetric septal hypertrophy. We therefore evaluated echocardiographically 39 patients with idiopathic left ventricular hypertrophy diagnosed by physical findings or electrocardiographic criteria or both. All family members of patients with known asymmetric septal hypertrophy were excluded. Of the 39, 33 had asymmetric septal hypertrophy, six were normal, and none had evidence of idiopathic left ventricular hypertrophy. All six of those with normal echocardiograms had left ventricular hypertrophy solely by electrocardiographic criteria and were without cardiac symptoms, suggesting a false-positive diagnosis. If idiopathic left ventricular hy...

Patients with typical idiopathic hypertrophic subaortic stenosis (IHSS) represent only one subgroup of a cardiac disease in which the characteristic anatomic abnormality is asymmetric septal hypertrophy (ASH). In most patients with ASH, left ventricular outflow obstruction is absent and cardiac dysfunction presumably is due to widespread involvement of the left ventricle by an underlying myocardial abnormality. In other patients with ASH, left ventricular outflow obstruction is present (typical IHSS) and constitutes a major feature of the hemodynamic and physical findings. To determine whether patients with outflow obstruction also have the underlying myocardial abnormality diffusely involving the left ventricle, the gross morphology of hearts from patients with and without outflow obstruction were studied both by necropsy and by echocardiography. Echocardiographic studies revealed that the ventricular septum was thicker in obstructive ASH, a finding confirmed by the postmortem studies. The necropsy studies also indicated that although the left ventricular free wall was thickened in both obstructive and nonobstructive ASH, the configuration of the left ventricular free wall was distinctly different in the two groups. In obstructive ASH, the free wall was hypertrophied and identical in appearance to that seen in valvular aortic stenosis. Moreover, echocardiographic studies indicated that the thickening of the free wall behind posterior mitral leaflet appeared to regress after operative relief of the outflow obstruction. In contrast, the left ventricular free wall of severely symptomatic patients without outflow obstruction had a markedly different and unique appearance; the free wall of left ventricle directly behind the posterior mitral leaflet was of normal or less than normal thickness, whereas the remaining free wall was nonuniformly thickened. On the basis of these findings and the microscopic data presented in the companion paper, we conclude that the myocardial abnormality in obstructive ASH (typical IHSS) is localized largely to the ventricular septum, with left ventricular free wall thickening occurring as a consequence of outflow obstruction. In symptomatic patients with nonobstructive ASH, however, the data suggest that the left ventricle, including free wall, is extensively involved with a primary myocardial abnormality.

Echocardiography is being used increasingly in cardiac diagnosis because it permits rapidly moving cardiac structures to be visualized with ease and safety. Echocardiographic studies previously have been limited to qualitative observations because detailed quantitative measurements of cardiac structural motion have required time-consuming manual information processing. A video scanner-analog computer system has been developed that greatly simplifies the analysis of routine echocardiograms. Up to eight nonoverlapping cardiac structures are first traced manually on transparent paper from selected portions of echocardiographic records, and then Converted by a television camera into a picture consisting of 525 video lines. These lines are processed sequentially by eight signal detectors, each generating a digital value proportional to the distance of the traced signals from the beginning of the video line. The data are converted to analog form by analog computer techniques and recorded on a strip chart. Evaluation of the system has demonstrated that signals of up to 12 Hz can be accurately processed without attenuation. In addition, a comparison of the scanner-derived instantaneous left ventricular transverse dimension with that measured directly from the original echocardiograms revealed excellent correlation ( r = 0.98). The use of this system to analyze cardiac structures may have wide applicability in cardiac research and diagnosis because it allows complex quantitative data to be obtained easily from routine echocardiograms.

During the past several years one-dimensional pulse-echo ultrasound techniques have proven extremely useful in cardiac diagnosis. A one-dimensional system, however, only visualizes structures lying along a single straight line. The spatial relationships of the various cardiac structures are therefore not so easily defined as with two-dimensional systems which display the heart by constructing a plane image composed of many straight lines. We have developed a sector scanning system for obtaining two-dimensional echocardiograms in real time using ultrasonic pulse-echo techniques. Images are produced by angling rapidly a single transducer through a 30-degree sector from a fixed spot (between ribs) on the patient's chest. Thirty complete sectors (or frames) are produced per second. The use of a large diameter transducer ensures that signal strength is good and cardiac structures, including endocardium, can be visualized. Other advantages include high transducer sensitivity, real time imaging and easy visualization of various regions of the heart. Experience with more than 100 patients indicates that diagnostic quality two-dimensional echocardiograms can be readily obtained in essentially the same patients from whom one-dimensional echocardiograms are recorded and can usually be performed in less time.

Beta-adrenergic blockade with propranolol caused mild impairment in cardiovascular adaptation to volume (blood infusion) and pressure (angiotensin infusion) challenges in the dog. The impairment was manifested by smaller increases in stroke volume and cardiac output. The altered response to angiotensin infusion was completely attributable to β-adrenergic blockade. The possible role of a non-specific effect of propranolol on cardiovascular adjustment to volume stress was also discussed.

The use of a digital computer to calculate cardiac catheterization data has been studied. The equipment and programming logic used by our laboratory are described. Specific features of on-line data transmission, cardiologist-computer interaction utilizing a series of on-off signals to prompt the computer and the ease with which this system can be utilized by regular laboratory personnel without special training are stressed.

The use of reflection oximetry when combined with fiber optics allows for accurate determination and long-term in vivo monitoring of oxygen saturation in peripheral vessels and in the heart. The oxygen saturations determined by fiber optics oximetry show excellent agreement with those obtained by routine spectrophotometry. Studies on the effects of variation in flow and hematocrit on the oxygen saturation determined by these methods are discussed.

A reliable long-term canine model for the echocardiographic evaluation of myocardial dimensions has not been previously described. Because of the configuration of the dog's chest wall, surface echocardiography is difficult to perform. Therefore, a small ultrasound transducer was designed for both short- and long-term experimental studies. In six dogs, a 1.7 by 0.5 cm, 2.25 megahertz lead titanate-zirconate echo transducer was sutured to the anterior epicardial surface of the right ventricle. The transducer was positioned to measure septal thickness, left ventricular posterior wall thickness and left ventricular transverse diameter in a manner similar to that used in clinical echocardiography. The animals were studied 2 weeks to 3 months postoperatively in the closed chest unanesthetized state. Echocardiographic determinations of septal and left ventricular wall thickness were in close agreement with results obtained at necropsy.

Measurement of acute serial changes in left ventricular volume is often desirable. Although left ventricular volumes estimated echocardiographically correlate well with results of angiographic methods, the sensitivity with which echocardiography can detect acute alterations in volume is unknown. Accordingly, the effect on transverse left ventricular dimension of interventions known to alter left ventricular volume (tilting and administration of nitroglycerin and phenylephrine) was studied in six normal subjects. Tilting significantly reduced end-diastolic dimension (from 48 ± 1.7 to 41.8 ± 1.5 mm, P < .01) and end-systolic dimension (from 32.2 ± 0.6 to 27.5 ± 0.8 mm, P < .001). Nitroglycerin also reduced end-diastolic dimension (from 44.8 ± 2.3 to 39.8 ± 2.1 mm, P < .02) and end-systolic dimension (from 30.2 ± 1.3 to 26.5 ± 1.2, P < .005). In contrast, phenylephrine increased end-diastolic dimension (from 42.3 ± 2.6 to 45.6 ± 2.6 mm, P < .025) but did not significantly alter end-systolic dimension (from 28.9 ± 2.0 to 31.8 ± 2.9 mm). Mean rate of circumferential fiber shortening (mean Vcf) was not altered significantly by tilting or by phenylephrine, but was increased by nitroglycerin (from 1.3 ± 0.1 to 1.7 ± 0.1 circ/sec, P < .005). In addition, a study of eight patients with chronic rheumatic mitral valve disease showed that there was a positive correlation between the percentage change in R-R intervals and the percentage change in transverse diastolic dimension ( y = .22 x - 10, r = 0.68). These results indicate that the anticipated changes in left ventricular volume are readily detected by echocardiography. Thus, this noninvasive technique may be uniquely valuable in situations in which it is desired to make serial measurements of left ventricular volume.

Previous studies have shown that abnormal cellular morphology is present in the ventricular septum of patients with asymmetric septal hypertrophy (ASH). The present study was undertaken to determine whether these morphologic abnormalities are limited to the ventricular septum of patients with ASH or are more diffusely distributed throughout the heart, and whether different patterns of distribution of the cellular abnormalities exist in patients with and patients without left ventricular outflow obstruction. Myocardium was obtained at operation or necropsy from 22 patients, including 14 with obstructive and eight with non-obstructive ASH, and studied by both light and electron microscopy. Many hypertrophied, bizarrely shaped, and abnormally arranged cardiac muscle cells, presumably a morphologic manifestation of the genetically transmitted myocardial defect in ASH, were present in the ventricular septum of all patients. In patients with obstructive ASH, these abnormalities were either absent or rarely found in muscle from the left and right ventricular free walls. This observation suggests that functional limitation in these patients is due largely to left ventricular outflow obstruction. In contrast, numerous disorganized cells were extensively distributed in the left and right ventricular feee walls from seven of eight symptomatic patients with non-obstructive ASH, suggesting that these abnormalities probably contribute importantly to functional impairment in such patients.

The recent introduction of time-sharing computer systems allows several different investigator to use simultaneously the same computer for analysis of real time data. This paper reports on a computer program written for such a system to perform on-line analysis of data from a cardiac catheterization laboratory. Physiologic analog signals from the patient were transmitted to an analog-to-digital conversion unit, which was attached to an IBM 1800 Process Control Computer. After conversion, the data were transferred by the 1800 into an IBM 360/50 digital computer, which was programmed to analyze atrial pressure, ventricular pressure, peripheral pressure (aortic or pulmonary artery), wedge pressure, brachial artery pressure and cardiac output signals obtained during both right and left heart catheterizations. After pertinent data were obtained from the basic signals, the computer was programmed to calculate various derived values, such as systolic and diastolic time intervals, valve gradients, valve areas, stroke work, stroke power and vascular resistances. Important technics were the use of on-off switches to communicate directly with the computer, interaction between the computer and the cardiologist, and safeguards to assure the cardiologist that accurate data were presented for analysis. Preliminary results indicate that such a program and hardware system can be used without specially trained personnel to analyze rapidly and accurately data obtained during cardiac catheterization.

The characteristic hemodynamic abnormality in idiopathic hypertrophic subaortic stenosis is a highly variable subaortic obstruction to left ventricular ejection. Previous studies have shown that during systole, the left ventricular outflow tract is narrowed by motion of the anterior mitral leaflet toward the ventricular septum. If this were responsible for the obstruction, we believed it would be possible to predict quantitatively the gradient in the disease from echocardiograms. We computed an obstruction index by dividing the duration of outflow narrowing by the mean septal-anterior mitral-leaflet distance and compared the result with the simultaneously measured peak left ventricular outflow pressure gradient in 56 beats from 11 patients with this form of subaortic stenosis. The correlation between the obstruction index and gradient was highly significant (gradient = 1.8 obstruction index - 35; r = 0.95). Echocardiography thus confirms that the pressure gradient in the disorder is caused by nar...

The pattern of inheritance of asymmetric septal hypertrophy, the characteristic anatomic abnormality in idiopathic hypertrophic subaortic stenosis, was studied by echocardiography in 30 fa...

Idiopathic hypertrophic subaortic stenosis (IHSS) is characterized by subaortic obstruction to left ventricular (LV) outflow. However, the obstruction is variable and many patients have no resting gradient and no clinical evidence of IHSS. Although a characteristic systolic movement of the anterior mitral valve leaflet can be demonstrated echocardiographically in many patients with IHSS, this may be absent in patients without obstruction under baseline conditions. Several necropsy studies of patients with IHSS have demonstrated that the ventricular septum characteristically is asymmetrically hypertrophied in relation to the posterior left ventricular wall. Since echocardiography can measure the thickness of the ventricular septum and the posterior LV free wall during life, we have evaluated the sensitivity and specificity of asymmetric septal hypertrophy (ASH) in diagnosing IHSS. The ventricular septum and posterior LV free wall were measured in 15 patients with IHSS documented by catheterization, 11 patients with other forms of fixed LV outflow obstruction, 52 patients with miscellaneous forms of heart disease, and 16 normal subjects. The mean septal-free wall ratio in normal subjects was 1.03, in fixed LV outflow obstruction 1.03, in miscellaneous heart disease 1.03, while in IHSS it was 1.68. The ratio exceeded 1.3 in all 15 patients with IHSS (including seven patients without a gradient under baseline conditions), and it was less than 1.3 in 78 of 79 patients without IHSS. Thus ASH (1) can be diagnosed noninvasively, (2) appears specific for IHSS, and (3) is independent of the degree of obstruction. Moreover, since our findings indicate that the detection of ASH identifies the pathognomonic anatomic abnormality in IHSS and includes a wider spectrum of patients (i.e. those without obstruction as well as clinically normal family members of patients with IHSS), we suggest that a more appropriate term for this disease entity is asymmetric septal hypertrophy or ASH.

The accuracy of real-time, two-dimensional echocardiography in diagnosing malformations of the great vessels was assessed in 11 infants (aged 5 to 29 months) with angiographically documented transposition of the great arteries (TGA), tetralogy of Fallot (TF) or pulmonary atresia. Adequate studies were obtained in 10 of the 11 infants. A great artery cross-sectioned by the echo beam (i.e., scanning the heart perpendicular to its long axis, at the origin of the great arteries) appears as a circle; when sectioned longitudinally it is sausage-shaped. TF was characterized by normally related great arteries; a posteriorly positioned circle (aorta) and an anterior, sausage-shaped structure (RV outflow tract). In pulmonary atresia, a large posterior circle (aorta) and an anterior sausage-shaped structure, ending proximal to the pulmonary valve (atretic outflow tract) were seen. In TGA, a posterior circle (pulmonary artery) was associated with another circle (aorta) which was located anteriorly and to its right (D-transposition). Thus, this technique provides a painless, rapid and accurate means of diagnosing congenital malformations of the great arteries in infants. It therefore may obviate the need for complete angiographlc studies in some seriously ill infants with cyanotic congenital heart disease.

Studies by echocardiography and necropsy show that, with rare exception, all patients with idiopathic hypertrophic subaortic stenosis (or hypertrophic cardiomyopathy) have a ventricular se...