Andrew G. Morrow

Idiopathic Hypertrophic Subaortic Stenosis: I. A Description of the Disease Based Upon an Analysis of 64 Patients

Idiopathic hypertrophic subaortic stenosis (IHSS) is a disease characterized by marked hypertrophy of the left ventricle, involving in particular the interventricular septum and the left ventricular outflow tract. During systole, the hypertrophied muscle in the outflow tract often narrows this region sufficiently to produce obstruction to left ventricular ejection. Although the reports of Schmincke and of Bernheim early in this century indicate that IHSS has been recognized for many years, particular attention has been directed to the disease only during the last 7 years.In most instances left ventricular hypertrophy is asymmetric, but occasionally it is diffuse and the lumen of the outflow tract is reduced by the concentrically hypertrophied muscle. Marked enlargement of the papillary muscles and of the trabeculae carneae, deformation of the mitral valve by the thickened ventricular septum, and thickening of the anterior mitral leaflet are commonly noted. In many hearts the hypertrophied septum bulges into the right ventricular outflow tract as well as into the left.On microscopic examination, the muscle bundles in the left ventricle are often arranged in a bizarre fashion and are separated by clefts. Individual muscle fibers obtained from the left ventricle are often greatly thickened, but tend to be shorter than normal. There is an increase in the size and numberof nerve fibrils and in the quantity of fluorescent material, presumably norepinephrine, in the affected muscle.Of the 64 patients with IHSS on which the present report is based, 67% were males and 33% were females. The patients with the familial form of the disease were distributed approximately equally between the 2 sexes. On the other hand, in the patients without a family history, 78% were males and only 22% were females. The average age was 25.7 years; the female patients were significantly older than the males. The discovery of a heart murmur was usually the first clinical manifestation of the disease. From a consideration of our patients, as well as those reported in the literature, it is evident that clinical findings may or may not be present at birth or in early childhood. The finding of a murmur before the age of 1 year in 9 of the 64 patients, and the reports of IHSS in a stillborn baby and in several infants, as well as the association of IHSS with congenital cardiac malformations, all support the concept that the disease may, at least in some instances, be congenital. On the other hand, in 20 of the 64 patients at least 1 detailed examination revealed no evidence of a heart murmur prior to the eventual discovery of the murmur, and in them it appears likely that many of the manifestations of the disease were acquired.Forty-eight of the 64 patients with IHSS were symptomatic, the most common symptoms being dyspnea, angina, dizziness and syncope. Although others have commented upon the absence of the clinical findings of congestive heart failure, clear evidence of cardiac decompensation was present in 14 of our patients.On physical examination the heart was usually enlarged, with a left ventricular lift. A double apical impulse was often palpable. Apex cardiograms usually showed an abnormally tall presystolic expansion wave (a wave). A systolic thrill was palpable in approximately one-half of the patients and tended to be present more frequently in patients with severe than in those with mild obstruction. Paradoxical splitting of the second heart sound during the respiratory cycle was present in 22 patients, and in them the systolic pressure gradients were significantly higher than in those without this finding. A fourth heart sound was audible in almost all of the patients in sinus rhythm while a third heart sound was heard less frequently. Seven of the 64 patients had early systolic ejection sounds. An ejection type systolic heart murmur was heard in all patients, and was most prominent along the left sternal border or at the apex. The systolic pressure gradients were significantly lower in the patients in whom the murmurs were relatively soft than in those with louder murmurs.Although the electrical axis in the frontal plane was usually normal, left axis deviation was noted in 14 patients. Normal sinus rhythm was present in all but 2 patients, who had atrial fibrillation. The patients with normal P waves were generally asymptomatic, but patients with electrocardiographic findings of left atrial or combined atrial enlargement were usually markedly disabled by their disease. The classical WPW pattern was present in 2 patients, and in a number of others an incomplete form was seen with a shortened P-R interval and/or a delta wave and a normal QRS duration. The obstruction to left ventricular outflow tended to be significantly more severe in the 27 patients with delta waves than in the 37 patients without this finding. Sixteen patients exhibited abnormally deep and broad Q waves. This finding occurred significantly more often in patients with the familial form of IHSS than in those with the nonfamilial form. It is likely that these abnormal Q waves are related to gross septal hypertrophy rather than myocardial infarction. Although the voltage criteria for left ventricular hypertrophy in the precordial leads were usually satisfied, there was no correlation between the height of RV5 or the sum of RV5 and SV1 and the magnitude of the systolic pressure gradient.On the conventional chest roentgenograms an abnormally large cardiothoracic ratio was noted in approximately one-half of the patients, and the left ventricle was consideredto be enlarged in almost all of the patients, but the magnitude of the cardiothoracic ratio and the extent of the left ventricular enlargement did not correlate with the systolic pressure gradient or the functional classification of the patient. Aortic dilatation is an uncommon finding in IHSS and the presence of marked dilatation in a patient with obstruction to left ventricular outflow suggests that valvular or discrete subvalvular stenosis rather than IHSS is present. Intracardiac calcification was never noted.The thickness of the free wall of the left ventricle and the width of the left ventricular cavity were measured on angiographic films exposed in the frontal projection at the end of diastole. No patient with IHSS exhibited an abnormally wide left ventricular cavity, and in a significant number of patients the width of the left ventricular cavity was less than that observed in patients with normal left ventricles or in those with valvular or discrete subvalvular aortic stenosis. The free wall of the left ventricle was thicker than normal in almost every patient with IHSS, and in some the left ventricular wall was found to be thicker than in any patient with discrete obstruction. However, there was no correlation between the thickness of the left ventricular myocardium during diastole and the peak systolic pressure gradient. The shape of the left ventricular cavity was abnormal in the majority of patients; an inward concavity at the midportion of the right inferior margin being the most common finding. It is presumed that this results from the bulging of the greatly hypertrophied interventricular septum into the left ventricular cavity. A long subvalvular area of narrowing commonly appeared to be responsible for the obstruction. Mitral regurgitation was present in nearly one-half of the patients, who were significantly older, and tended to have more clinical disability and a higher left ventricular end-diastolic pressure than those without this finding.In patients with IHSS the arterial pulse rises sharply, the upstroke times in the indirect carotid arterial pulses averaging 0.062 sec. in IHSS, compared to a normal average value of 0.088 sec. A carotid pulse with two peaks in systole was recorded in 35 of the 47 patients with IHSS, and in the other 12 patients in whom there was only a single peak there tended to be little if any obstruction to left ventricular outflow. The first derivative of the arterial pressure pulse tended to be greater than normal in IHSS, and was always higher in patients with IHSS than in those with valvular aortic stenosis.The systemic arterial pressure was normal in the majority of patients. The pulmonary artery systolic pressure exceeded 30 mm. Hg in 16 patients. A systolic pressure gradient within the right ventricular outflow tract was recorded in 10 patients and the right ventricular end-diastolic pressure was abnormally elevated in 21 patients. The a wave was the most prominent wave in the right and left atrial pressure pulses in almost every patient. The resting cardiac index varied widely. The mean left atrial pressure was abnormally elevated in 18 of the 42 patients in whom it was measured, while the left ventricular enddiastolic pressure exceeded the upper limit of normal in 47 of the 64 patients. The peak systolic left ventricular outflow pressure gradient, measured in the basal state, exceeded 100 mm. Hg in 14 patients, ranged between 50 and 100 mm. Hg in 21 patients and between 10 and 50 mm. Hg in 15 patients. The other 14 patients did not exhibit significant obstruction to left ventricular outflow in the basal state. No correlation was found between the most common symptoms in IHSS and the severity of obstruction. A distinct notch on the ascending limb of the left ventricular pressure pulse was usually recorded and its level was approximately equal to the peak pressure distal to the obstruction. In addition to obstruction to ventricular outflow, IHSS is characterized by an abnormally low ventricular compliance, an important consequence of which is impedance of ventricular filling. Atrial hypertrophy results and atrial systole assumes a particularly important role in ventricular filling.One of the most important features of IHSSis the variability of the hemodynamic findings. In 28 patients in whom measurements of the systolic pressure gradient were carried out at intervals

Catecholamine excretion and cardiac stores of norepinephrine in congestive heart failure

Abstract The role of the sympathetic nervous system in congestive heart failure was studied by determining the urinary excretion of norepinephrine and its concentration in cardiac tissue. Norepinephrine excretion averaged 22.5 μg. per day in normal subjects and 22.4 μg. per day in class I or II cardiac patients. It was increased in patients with heart failure, averaging 46.4 μg. per day in class III patients and 58.1 μg. per day in class IV patients. No significant increase in urinary excretion of epinephrine or vanilmandelic acid was observed in the patients with heart failure. The norepinephrine excretion was substantially increased in all patients by the stress of a corrective cardiac operation. The concentration of norepinephrine in atrial tissue was found to be reduced in patients with heart failure, averaging 0.49 μg. per gm. compared to 1.77 μg. per gm. in cardiac patients without failure. A reduction of norepinephrine was also observed in the left ventricle, and the concentrations in the ventricle were found to be lowest in the patients with the lowest atrial norepinephrine concentrations. Increased urinary excretion of norepinephrine was observed in patients with markedly depressed cardiac concentrations of the neurotransmitter substance. It is concluded that heart failure is associated with augmented activity of the sympathetic nervous system, reflected in increased norepinephrine excretion and often associated with a deficit of cardiac norepinephrine. It is suggested that in patients in whom depletion of neurotransmitter in the heart is most pronounced, there may be a relative deficiency of sympathetic function which in turn adversely affects the contractile state of the myocardium.

Idiopathic hypertrophic subaortic stenosis: Clinical, hemodynamic and angiographic manifestations

Abstract The diagnosis of idiopathic hypertrophic subaortic stenosis, i.e., left ventricular hypertrophy producing severe obstruction to left ventricular outflow, has been established in fourteen patients. All had systolic murmurs, most prominent either at the mitral or tricuspid areas. Left ventricular systole was prolonged, resulting in paradoxical splitting of the second heart sound. Electrocardiograms showed either left ventricular hypertrophy or anomalous atrioventricular excitation, and roentgenograms demonstrated left atrial and ventricular enlargement without aortic dilatation. Left heart catheterization revealed systolic pressure gradients within the ventricle ranging from 40 to 185 mm. Hg, and localized the site of obstruction to the left ventricular outflow tract in every patient. The left ventricular pressure pulses exhibited a characteristic notch in early ventricular systole, and a striking rise during atrial contraction. Both the palpable and recorded peripheral arterial pressure pulses rose rapidly during early systole, unlike those in valvular aortic stenosis [6]. Left ventricular angiocardiograms demonstrated a markedly thickened ventricular wall obstructing the outflow tract of the left ventricle only during a portion of the cardiac cycle. At open operation in five patients the angiocardiographic interpretations were confirmed; in two patients the hypertrophied muscular ring was incised longitudinally to relieve the obstruction and the early clinical and hemodynamic results of this operation are encouraging. With the delineation of its clinical, hemodynamic, angiocardiographic and anatomic features, idiopathic hypertrophic subaortic stenosis emerges as a specific entity which can be distinguished preoperatively from discrete valvular and subvalvular aortic stenosis. Its recognition is important in selecting for operation patients with all forms of obstruction to left ventricular outflow and in planning the surgical procedure.

Observations on the optimum time for operative intervention for aortic regurgitation. I. Evaluation of the results of aortic valve replacement in symptomatic patients.

A recent echocardiographic study of symptomatic patients who had aortic valve replacement for isolated aortic regurgitation indicated that patients in whom preoperative left ventricular end–systolic dimension (LVD[SYS]) exceeded 55 mm or fractional shortening (%FS) was less than 25% were at high risk of developing congestive heart failure and dying after an otherwise successful operation. Because indices of left ventricular systolic function might identify asymptomatic patients with aortic regurgitation who might benefit from earlier operation, 37 such patients were evaluated with serial echocardiograms (mean follow–up 34 months). Fourteen patients (38%) subsequently developed symptoms and were recommended for operation (SUBSQ OP). Twenty–three patients (62%) remain asymptomatic during follow–up (NON OP). LVD(SYS) and %FS were the most sensitive measurements for distinguishing on initial examination the patients who subsequently required operation from those who have not (LVD[SYS] 53.0 mm SUBSQ OP vs 44.3 mm NON OP, p = 0.001; %FS 28.8% SUBSQ OP vs 33.9% NON OP,p = 0.002). During serial studies, the maximum rate of change in end–systolic dimension exceeded 7 mm per year in only one patient. Four of five patients (80%) with end–systolic dimension greater than 55 mm developed symptoms and came to operation during a mean follow–up of 39 months. Of the 20 patients whose initial end–systolic dimension was 50 mm or less, only four patients (20%) developed symptoms and required operation, and none died during follow–up. Thus, an asymptomatic patient with aortic regurgitation whose end–systolic dimension is less than 50 mm appears to be at low risk and can be safely followed with echocardiograms at yearly intervals. Asymptomatic patients with end–systolic dimension of 50–54 mm are being followed with serial echocardiograms every 4–6 months. Operation is now being recommended to patients with end–systolic dimensions of 55 mm or greater, even in the absence of symptom.

Operative treatment in hypertrophic subaortic stenosis. Techniques, and the results of pre and postoperative assessments in 83 patients.

The results of operative treatment in 83 patients with idiopathic hypertrophic subaortic stenosis (IHSS) are described. Most patients with the disease are asymptomatic, or derive satisfactory symptomatic improvement from nonoperative therapy: administration of propranolol, exercise limitation, control of arrhythmia, etc. Operation is required, however, in 10-15% of patients, those who remain severely symptomatic after nonoperative treatment or who become refractory to it. Operation relieves symptoms in IHSS by relieving obstruction to left ventricular outflow, and for a patient to be considered an operative candidate severe obstruction must be documented at left heart catheterization either under resting conditions or after provocative interventions. All 83 patients were severely incapacitated — 58 in Class III and 24 in Class IV. Seventy had obstruction at rest (average gradient 96 mm Hg), and 13 had only provocable obstruction. At operation the hypertrophic interventricular septum was exposed via an aortotomy, and a vertical bar of muscle was resected between parallel myotomy incisions. There were six operative deaths (7%); no patient has died since 1970. Seven patients have died late after operation, five of them from causes unrelated to their heart disease or the operation. All surviving patients describe symptomatic improvement. Fifty-two patients with obstruction at rest preoperatively (average gradient 95 mm Hg) have been studied postoperatively: no resting gradient was evident in 47, while in the remaining five the gradient was less than 25 mm Hg. Recurrence of obstruction has never been observed at late catheterization (21 pts) or late echocardiographic examination (37 pts). Obstruction could not be provoked postoperatively in ten of the 11 patients who had large gradients only with the Valsalva maneuver or isoproterenol administration preoperatively. Obstructed and provocable obstructed patients had similar symptomatic improvement after operation. A variety of rhythm and conduction abnormalities were observed both pre and postoperatively, and these are described in detail. The results of operation in these 83 patients with IHSS demonstrate that gratifying symptomatic and hemodynamic improvement uniformly follows left ventriculomyotomy and myectomy. Relief of obstruction and amelioration of symptoms have proved to be long-lasting during postoperative observation periods extending to 14 years. Continued application of the operative procedure in properly selected patients appears to be indicated.

Posttransfusion Hepatitis After Exclusion of Commercial and Hepatitis-B Antigen-Positive Donors

Abstract In a prospective study the exclusion of commercial blood donors and donors positive for hepatitis-B antigen (HBAg) resulted in a hepatitis frequency of only 3.7 cases/1000 units transfused...

Conservative Management of Tricuspid Regurgitation in Patients Undergoing Mitral Valve Replacement

Among 100 consecutive patients undergoing mitral valve replacement, 28 had clinically and hemodynamically significant tricuspid regurgitation without tricuspid stenosis. In 21 patients the mitral valve was regurgitant, and in eight it was stenotic. The characteristic murmur of tricuspid regurgitation was present in 27 patients; 25 had abnormal venous distention, 14 peripheral edema, and seven ascites; and in 27 the liver was enlarged more than 4 cm below the costal margin. The mean right atrial pressure was abnormally high in every patient (average 11 mm Hg), and 25 had severe pulmonary hypertension (average systolic pressure 75 mm Hg). At the time of mitral replacement, 25 patients had no operative procedure on the tricuspid valve, and three had a tricuspid annuloplasty. Four patients died, a mortality rate (14%) not different from that in the patients without tricuspid regurgitation.Twenty-four patients were reassessed at postoperative intervals of one to four years (average 30 months). All evidenced symptomatic improvement; 16 observed no dietary restriction of sodium, six ate regular diets without added salt, and only two limited sodium intake more stringently. Postoperatively, mean right atrial pressures averaged 5 mm Hg and systolic pulmonary arterial pressures 39 mm Hg.In many patients with advanced mitral valve disease, associated tricuspid regurgitation is of a functional nature and secondary to right ventricular hypertension and dilatation of the tricuspid annulus. The present results indicate that in such patients tricuspid regurgitation will improve or disappear after mitral replacement and that tricuspid valve replacement is seldom necessary.

Myocardial Ultrastructure in Idiopathic Hypertrophic Subaortic Stenosis: A Study of Operatively Excised Left Ventricular Outflow Tract Muscle in 14 Patients

Electron microscopic studies revealed distinctive abnormalities in operatively resected myocardium from the left ventricular outflow tract in 14 patients with idiopathic hypertrophic subaortic stenosis. Bundles of muscle cells were severely disorganized, with cells running in different directions instead of in parallel. Muscle cells were wider and shorter than in hypertrophy due to other causes and showed increased cellular branching, extensive side-to-side intercellular junctions, widened Z bands, and evidence of formation of new sarcomeres. Some myofibrils were oriented obliquely or perpendicular to the longitudinal axes of the cells and some myofilaments that originated from a single Z band inserted into Z bands of other myofibrils. Examination of left ventricular apical myocardium in two patients revealed hypertrophied but normally arranged muscle cells. It is concluded that abnormal architecture of muscle cells is the basic morphologic feature of idiopathic hypertrophic subaortic stenosis.

Measurement of mitral orifice area in patients with mitral valve disease by real-time, two-dimensional echocardiography.

A quantitative assessment of mitral valve orifice area can be achieved in patients with pure mitral stenosis by cardiac catheterization. In the presence of mitral regurgitation, however, accurate measurement often is impossible because total diastolic flow through the mitral valve frequently is unknow. Using a recently developed real-time, two-dimensional echocardiography system, we are able to obtain cross-sectional images of the mitral valve by scanning the heart perpendicular to its long axis at the level of the tip of the mitral leaflets. Twenty consecutive patients undergoing operation for mitral valve disease were studied during the week prior to operation. In 18 of 20 (90%) the mitral orifice was imaged successfully in early diastole by two-dimensional echocardiography so that mitral valve orifice area could be measured directly in square centimeters. In 14 patients (ten with associated mitral regurgitation), mitral orifice area was measured both by echocardiography and directly at time of operation. In 12 of 14 (86%) patients, mitral orifice area by two-dimensional echocardiography was within 0.3 square centimeters of that measured at operation (correlation coefficient for all 14 patients equals 0.92). We conclude that two-dimensional echocardiography is extremely useful in the evaluation of patients with mitral valve disease because it provides a noninvasive method for directly measuring the mitral valve orifice area that is accurate even in the presence of mitral regurgitation.

Etiology of clinically isolated, severe, chronic, pure mitral regurgitation: Analysis of 97 patients over 30 years of age having mitral valve replacement

Abstract For many years rheumatic heart disease was considered the major cause of mitral regurgitation (MR) severe enough to necessitate mitral valve replacement (MVR). In most past studies of patients with mitral valvular disease, patients were subdivided on the basis of predominant mitral stenosis (MS) or predominant MR. This type of subdivision, however, does not provide as much information about etiology as can be obtained by dividing patients with mitral valve dysfunction into two groups based on the presence or absence of mitral valve obstruction. MS of any degree is recognized as usually having a rheumatic etiology. Likewise, most patients who have combined dysfunction of both mitral and aortic valves usually have a rheumatic etiology of their valvular lesions. The present study examines the etiology of the valvular disease in 97 patients over the age of 30 years in whom MVR was carried out for severe, chronic, pure MR unassociated with MS or aortic valve dysfunction.