Asymmetric septal hypertrophy (ASH) and its obstructive form, idiopathic hypertrophic subaortic stenosis (IHSS), in pediatrics

ALBERT K. HARVEY, DD. Oklahoma City, Oklahoma

IHSS. The father had no siblings, but two uncles had Although idiopathic hypertrophic died suddenly of disease at early ages. subaortic stenosis usually occurs in Case 1 adults, the possibility of its presence in children must not be overlooked. It An 18-year-old white girl said she had not experienced dyspnea, exercise intolerance, syncope, or chest pain. She has been reported even as early as was a senior in high school and had participated in dra- infancy and in stillborn fetuses. The matic and athletic activities. Physical examination condition appears to be genetically showed the pulse rate to be 74 and the blood pressure transmitted, with the natural history 110/64 mm. Hg. Pulses on the upper and lower ex- one of progressive disease. The tremities were strong and symmetric. The point of atypical location of an aortic stenosis maximum intensity (PMI) was not enlarged, and no type murmur is a clue to early thrill or precordial heave was perceptible. There was a diagnosis. is Grade 2/6 harsh systolic ejection murmur along the lower confirmative of a diagnosis. Four case left sternal border, which was transmitted well to the reports are presented. apex. No diastolic component was present. The phono- cardiogram showed an intermittent fourth heart sound. An x-ray film of the chest showed the heart size and vascularity of the lung field to be normal. An elec- trocardiogram (EKG) revealed left ventricular hyper- trophy with marked ST and T wave changes in the left precordial leads. The echocardiogram showed abnormal Idiopathic hypertrophic subaortic stenosis (IHSS) systolic anterior motion of the mitral leaflet, with partial is a subaortic obstruction of the left ventricular narrowing of the outflow tract, but septal thickness could outflow tract secondary to hypertrophy of the not be delineated well for measurement. Cardiac ventricular septum and systolic anterior motion of catheterization was performed, and a pressure gradient the mitral valve. The entity has been known also as of 10 mm. Hg between the left and the at hypertrophic obstructive cardiomyopathy, func- rest was slightly elevated. When isoproterenol was used tional aortic stenosis, and muscular subaortic as a provocative agent, the patients heart rate increased stenosis, but a more appropriate term for the from the resting state of 82 to 143 per minute, and the anatomic abnormalities of IHSS is asymmetric sep- gradient increased from 10 to 59 mm. Hg with little tal hypertrophy (ASH). The condition usually is change in systemic blood pressure. Provocation testing seen in adults, but has been reported in stillborn with amyl nitrite inhalation did not show a change in gradient. The resting end-diastolic pressure was in the fetuses, infants, children, and adolescents. The four high normal range at 16 mm. Hg. Biplane cineangiog- cases of IHSS in adolescence to be presented here rams showed a hypercontractile left ventricle, with oblit- illustrate the wide variability in clinical presenta- eration of the apical portion of the ventricular cavity. The tion. aortic and mitral valves appeared normal. The left ventricular wall was considerably thickened, and there Report of cases was a conic, or funnel-like, area beneath the aortic valve Cases 1 and 2 which decreased symmetrically in caliber to the level of Two adolescent girls, sisters aged 13 and 18, were re- the mitral area. These observations pointed to IHSS with ferred to the Michigan State University Pediatric car- mild obstruction during rest and a significant obstruc- diology clinic because of a family history of IHSS. Their tive gradient on isoproterenol stimulation. father had had for left ventricular out- flow tract obstruction at age 35 and had been able to Case 2 carry on his duties as a minister without serious symp- A 13-year-old white girl was the youngest of three chil- toms until his sudden death at age 49. Autopsy showed dren. She gave no history of chest pain, dyspnea, palpita-

Idiopathic hypertrophic subaortic stenosis 176/57 tions, or syncope. Physical examination showed her blood father, now aged 65, had been hospitalized at age 26 for pressure to be 110/58 mm. Hg, with equal pulses on both what he called an enlarged heart. However, he went on to the upper and lower extremities. The lungs were clear to play professional football after hospitalization with no auscultation. The PMI was full and in the fourth inter- adverse effects. At the time of his sons admission, the costal space. No thrill was palpable. Cardiac ausculta- father said he had had occasional dizzy spells, syncopal tion revealed a Grade 3/6 high-pitched blowing regurgit- episodes, dyspnea, and chest pain, but had not seen a ant systolic murmur, which was heard best at the left physician for these symptoms. His echocardiogram was lower sternal border and apex, with radiation to the consistent with nonobstructive ASH and calcific aortic axilla and upper left sternal border. There was no di- stenosis. astolic murmur. An x-ray film of the chest showed a mild Physical examination of the patient at admission to enlargement of the cardiothoracic diameter and normal Ingham Medical Center showed his pulse rate to be 80, pulmonary vascularity. The EKG showed left ventric- respiration rate 30, and the blood pressure 104/60 mm. ular hypertrophy, left atrial hypertrophy, and ST and Hg. The patient was semicomatose and unresponsive to T wave changes. was performed verbal stimulation, but responded appropriately to tac- and showed a gradient of 80 mm. Hg on pullback from tile and painful stimulation. His level of consciousness the left ventricle to the aorta. There was no gradient varied from severe CNS depression to agitation. His skin across the aortic valve. Moderate elevation of the left was pale and diaphoretic. The Grade 4/6 holosystolic ventricular end-diastolic pressure was present. No pro- murmur was still present. All peripheral pulses were vocative tests were performed. Cineangiography showed palpable, but weak and thready. There was no evidence moderate enlargement of the left ventricle, prominent of cyanosis, clubbing, or petechial hemorrhages of the papillary muscles, and reduction in the left ventricular nail beds. Deep tendon reflexes were equal and symmet- cavity during systole. A linear translucent area was ric. Babinskis signs were not present. There was no present along the left ventricular outflow tract below evidence of paralysis. The cranial nerves appeared to be the level of the aortic valve. Mild mitral regurgitation intact. The cardiac monitor showed markedly irregular was noted with dilatation of the left . These rhythm, consisting mainly of junctional ectopic beats observations were consistent with a diagnosis of IHSS and occasional premature ventricular contractions with obstruction of the left ventricular outflow tract at (PVCs). Because it was difficult to maintain the blood rest and mild to moderate mitral regurgitation. Pro- pressure, a Neo-synephrine intravenous drip was given pranolol therapy was initiated. until the systolic blood pressure reached 110 mm. Hg. In an attempt to decrease myocardial contractility and pos- Case 3 sibly reduce the outflow obstruction, the patient was A 12-year-old white boy had lost consciousness while given propranolol intravenously in a dose of 4 mg. every playing basketball and started having generalized con- 6 hours. The following morning his vital signs, cardiac vulsions. He was transferred unconscious to Hurley Med- rhythm, and mental status were markedly improved. ical Center in Flint, Michigan. A complete blood count Approximately 36 hours after admission, the patient and measurement of arterial blood gases gave results started having bradycardia with frequent PVCs. The within normal limits. The pulse was regular at 28, and rhythm improved when atropine was given intrave- the blood pressure was 130/80 mm. Hg. Physical exam- nously. On the same day cardiac catheterization was ination showed a Grade 4/6 holosystolic murmur with a performed and showed marked bilateral ventricular quadruple rhythm, which was loudest on auscultation at hypertrophy with large pressure gradients between the the left lower sternal border and at the apex. The chest ventricles and outflow tracts bilaterally in the range of was asymmetric with prominence of the left chest wall 100 mm. Hg. In an attempt to relieve the obstruction of and a palpable heave and thrill over the left precordium. the left ventricle, 6 mg. of propranolol was injected intra- A chest x-ray film showed massive enlargement of the venously during the procedure, but this therapeutic trial heart with normal pulmonary vasculature. The EKG did not seem to relieve the outflow tract obstruction. showed marked left ventricular hypertrophy and bilat- Intravenous administration of Neo-Synephrine was nec- eral atrial hypertrophy. Echocardiography showed a essary to maintain systemic pressure. massive ventricular septum and marked systolic an- On the third day emergency surgical intervention was terior motion of the mitral valve. Premature closure of performed. Extracorporeal circulation and copotassium the aortic valve provided further evidence of severe were used during the procedure. Left obstructive IHSS. The patient was transferred to the ventricular septal myectomy by the transaortic route pediatric cardiology service at Ingham Medical Center, was done in an attempt to relieve obstruction of the left Lansing, Michigan. ventricular outflow tract. Relief of obstruction of the The pertinent past history included periodic chest pain right ventricular outflow tract was accomplished by and dyspnea for 2 years prior to admission. However, at right ventricular septal myectomy and reconstruction of no time had these symptoms been severe enough to pre- the outflow tract with a dacron patch. An intra-aortic vent him from being active in sports. Because of these balloon pump was inserted before the patient left the symptoms, a cardiovascular examination had been per- operating room. The surgical procedure was well toler- formed by his pediatrician, who thought that the patient ated. had a murmur due to a "small hole in the heart." Postoperatively the blood pressure was maintained by The family history was significant in that the patients Neo-Synephrine drip. Ventilatory support and the

177/58 Nov. 1980/Journal of AOA/vol. 80/no. 3 intra-aortic balloon pump were continued for 2 days. normal myocardium of the right ventricle and the free Otherwise the patients postoperative course was unre- wall of the left ventricle. Pulmonary edema, passive markable, except for congestive heart failure, which was hepatic congestion, and cerebral edema with foci of mi- treated successfully by sodium restriction and diuretic croscopic hemorrhage were observed and were thought to medications. Propranolol 30 mg. four times a day was be secondary to cardiac arrest. The observations at au- continued postoperatively when repeat echocardiog- topsy were consistent with IHSS. raphy indicated some residual obstruction of left ventricular outflow. The patient was discharged in stable Physiology condition 14 days postoperatively. Pathologic examination of specimens of the left and In 1957, Brock drew attention to IHSS by report- right ventricular septa showed gross evidence of myocar- ing three cases of obstruction of the left ventricular dial hypertrophy with microscopic cellular hypertrophy outflow tract secondary to septal muscular hyper- and vacuolation of individual myocardial fibers. The en- trophy. He reported three additional cases 2 years docardium showed fibrosis and collagenization. The nuc- later.2 Since that time, IHSS has been studied ex- lei were markedly enlarged and varied in size and shape. tensively and has been found 3 to be a dynamic The morphologic picture was consistent with the clinical obstructive form of subaortic stenosis. diagnosis of IHSS with bilateral obstruction of the out- Symptoms are similar to those of valvular aortic flow tracts. stenosis, but physical examination shows a mur- Case 4 mur similar to that of aortic stenosis but in an atypical location along the left sternal border and A 12-year-old white girl collapsed while running in the gymnasium at school. She was given cardiopulmonary apex. Palpation of the neck shows the carotid pulse resuscitation at the school and again by ambulance at- upstroke to be rapid instead of delayed as in aortic tendants on the way to a nearby hospital. Cardiopulmo- stenosis. This sign is called the bisferious pulse, nary function was temporarily maintained at a small which has a "spike and dome configuration" due to outlying hospital, and the patient was transferred by the absence of obstruction in early systole but de- ambulance to the Ingham Medical Center, where she was veloping in middle and late systole secondary to found to be in a seizure on admission to the emergency dynamic narrowing of the left ventricular outflow room. After control of the seizure, the patient was coma- tract between the anterior mitral valve leaflet and tose and hypotensive, with a blood pressure of 76/48 mm. the abnormally thickened ventricular septum.5 Hg. Respirations were shallow and rapid at 60 per min- The mitral valve movement is recognized as ute. The pulse was weak at a rate of 150 per minute. The characteristic of IHSS, but in patients with ASH skin was cool and cyanotic. There were generalized rales and rhonchi on auscultation of both lung fields. Murmurs without obstruction, there is no abnormal systolic were not auscultated. Her eyes were deviated to the movement of the mitral valve. right, with reactive pupils. Deep tendon reflexes were During forward movement of the anterior mitral absent. valve leaflet, a large pressure difference is pro- A chest x-ray film showed pulmonary edema and an duced between the left ventricle and the aorta. Be- enlarged, globular heart. The EKG showed sinus tachy- cause of the dynamic nature of the entity, the cardia, left anterior hemiblock, anterior wall ischemia, pressure difference or gradient varies with the and occasional PVCs, with short paroxysms of ventric- amount of obstruction produced. The gradient and ular tachycardia. Echocardiography was technically murmur are reduced or abolished by interventions difficult to perform because of the patients unstable that decrease left ventricular ejection velocity and condition. Continuous cardiovascular resuscitative ef- increase left ventricular volume. Agents that may forts were needed because of cardiac arrhythmias, per- sistent hypotension, and hypoxia. All resuscitative ef- produce this physiologic change are phenylephrine forts to sustain effective cardiac action failed, and the and propranolol. Nitroglycerin, amyl nitrite, and patient died approximately 2 hours after admission. isoproterenol, on the other hand, increase myocar- Her parents reported that 5 days prior to admission, dial contractility and decrease ventricular volume she had complained of mild cephalalgia, which did not and thus increase the obstruction and the intensity keep her from attending school. The only other pertinent of the murmur.4 past history was of a syncopal episode when she was 10 Provocative testing with isoproterenol in Case 1 years of age. This had resulted in a scalp contusion and resulted in an increase in the pressure gradient laceration, for which the patient had been treated in the from ventricle to aorta, indicating a tendency emergency room and released. The family history was toward obstruction under conditions of increased noncontributory. sympathetic tone, as in exercise. Knowledge of Autopsy showed marked asymmetric septal hyper- such tendencies is important to physicians so they trophy. Microscopic examination of the affected area showed marked irregular hypertrophic myocardial fibers can determine the need for restrictions in activity with some areas arranged in crisscross pattern. Fibrous and propranolol therapy. thickening of the endocardium was present. There was Propranolol was tried without benefit in Case 3.

Idiopathic hypertrophic subaortic stenosis 178/59 This indicated that surgical intervention was when the condition appears to be sporadic it may be needed, since obstruction of left ventricular outflow inherited in a recessive pattern. In 1973, Henry was not relieved by medication alone. Partial re- and colleagues" discovered that every patient with sidual obstruction postoperatively necessitated the IHSS has echocardiographic evidence of asymmet- long-term use of propranolol. ric septal hypertrophy (ASH). Using ASH as a marker in the echocardiographic investigation of Gross and histologic observations in IHSS family members of patients with known IHSS, The principal gross pathologic observation in IHSS Clark and associates" provided evidence that most is marked thickening of the ventricular septum, so patients with this entity have a genetic defect that it is out of proportion to the free wall of the left is transmitted as an autosomal dominant trait with ventricle. At autopsy Menges and colleagues6 a high degree of penetrance. found that the ratio of the width of the septum to Because of this familial prevalence, the children the thickness of the free wall of the left ventricle of a patient with known IHSS were evaluated, and varied from 1.55 to 1.76 in three affected by two of three children (Cases 1 and 2) were found to IHSS, whereas the ratio in normal hearts averaged have IHSS. In Case 3 the father of the patient has 0.98. They suggested that a ratio of 1.3 or more be ASH. used as a criterion of IHSS. The endocardium at the left ventricular outflow tract usually is thickened Clinical evaluation by fibrous tissue, as is the anterior mitral leaflet. IHSS may be suspected on the basis of symptoms Atrial cavities generally are dilated, whereas and clinical signs, but a definitive diagnosis can be ventricular cavities seldom are dilated. made only by special studies. The most common Teare7 in 1958 first described the histopathologic symptom is exertional dyspnea. In one study," 63 pattern as a "bizarre and disorganized arrange- percent of patients with diagnosed hypertrophic ment of muscle bundles associated with hyper- obstructive cardiomyopathy had dyspnea or exces- trophy of individual muscle fibres and their nuc- sive fatigue on exertion. Angina pectoris is also lei." Electron microscopic studies by Ferrans and common with IHSS. Palpitations and light- associates8 also showed disorganization in the ar- headedness, or presyncope, also are frequent com- rangement of muscle cells, myofibrils, and myofil- plaints, but syncope is present in only about one aments. Muscle cells often were short and broad, fourth of the patients." These symptoms are simi- with increased cellular branching, extensive side- lar to those of valvular aortic stenosis. to-side intercellular junctions, and widened Z A complete cardiovascular examination is abso- bands. Alterations in the shape of the muscle cells lutely necessary for symptomatic children. In a and disorientation of myofibrillar structure were study by the National Heart and Lung Institute, unique to IHSS and differentiated this entity from Maron and associates 7 found that 33 of 35 children other types of cardiomyopathy. with symptomatic IHSS (94 percent) had systolic The disorganized cellular architecture in IHSS ejection murmurs, which were heard loudest at the resembles that of primitive and incompletely dif- lower left sternal border or at the apex. The mur- ferentiated muscle cells. It has been postulated by mur usually was of Grade 3/6 or louder. Such mur- Ferrans and associates 8 that this entity is congeni- murs are harsh and have a diamond-shaped con- tal, and the subsequent inefficient contractility of figuration on auscultation. The murmur may or disorganized myocardium leads to hypertrophy of may not be transmitted to the neck. The systolic affected (ASH) and, if this is severe, murmur may be suggestive of aortic stenosis, but to actual outflow tract obstruction (IHSS). The re- its atypical location suggests its true significance, port of muscular subaortic stenosis in a stillborn since it is faint or absent in the aortic listening fetus and in infante-1 supports this hypothesis. area. A precordial systolic thrill may be felt along The pathologic specimens in Cases 3 and 4 the left sternal border or in the suprasternal notch. showed the characteristic septal hypertrophy with Occasionally the murmur is high pitched, and mi- microscopic hypertrophy of the muscle cells, disor- tral insufficiency may be suspected. A diastolic ganization of cellular architecture, and fibrosis of component to the murmur is rare. the endocardium in the affected areas. In the aortic area, the second heart sound is usu- ally of normal intensity. Occasionally there is Familial incidence paradoxic splitting of the second heart sound. An Brent and colleagues" offered evidence that IHSS ejection click is not auscultated in the aortic area, may be familial. Emanuel and associates" studied but may be heard at the apex. There is a third heart the modes of inheritance of IHSS, but in some cases sound in about a third of the cases and a fourth did not find familial linkage. They suggested that heart sound in about half the cases, but these are

179/60 Nov. 1980/Journal of AOA/vol. 80/no. 3 best detected with a ." The fast Menges and colleagues. Latter and associates" rising carotid arterial pulse, or bisferious pulse, is reported that the ratio of 1.3 is not specific for ASH characteristic. A dominant "a" wave may be in infancy, since this ratio is found also in normal present in the jugular venous pulse. Signs of con- infants and infants with a variety of cardiac le- gestive heart failure are uncommon in adults, but sions. However, the ratio of 1.3 does not persist may be the first indication of IHSS in infants." after a child is 2 years of age unless the child has Atrial fibrillation and arterial hypertension are cardiomyopathy. Therefore, a ratio of 1.3 is unreli- common complications. able in patients less than age 2 but is highly reli- Roentgenograms of the chest may or may not able for detecting ASH in older children, adoles- show cardiac enlargement in ASH and IHSS. Per- cents, and adults. not and colleaguess stated that cardiomegaly was The echocardiogram is of use also for determin- present in all their cases of subaortic muscular ing the increase in ejection fraction in IHSS 19 and stenosis in infants and children. However, Maron for quantitative prediction of the left ventricular and colleagues" reported: "There was no relation outflow gradient by measurement of the distance between the degree of cardiac enlargement and the from the septum to the anterior mitral leaflet.5 age of the patient, severity of symptoms or mag- Premature closure of the aortic valve may be an nitude of outflow obstruction." Mild enlargement of additional observation on echocardiography. the left atrium may be present. The EKG generally will show left ventricular Natural history hypertrophy and sometimes biventricular or atrial The natural history of IHSS is that of progressive hypertrophy. The diagnosis may be made at cardiac obstruction in most cases." This was documented catheterization if a left ventricular outflow tract first by Tafur and colleagues22 in 1964. A case pressure gradient at rest exceeds 10 mm. Hg," but presentation by Williams and associates 23 in 1973 there is no gradient across the aortic valve. effectively documented the progression of outflow Provocation testing may demonstrate an elevated obstruction of the left ventricle in a 15-year-old girl gradient in patients with IHSS who have no in whom a gradient of 70 mm. Hg developed in obstruction at rest, but are at risk of obstruction 5 years. Though clinical deterioration is progress- during exercise (Case 1). Symptomatic patients in- ive, its rate is variable. The major observation by variably will have a systolic pressure gradient ex- Frank and Braunwald 24 was of "extreme var- ceeding 40 mm. Hg at rest. However, it is possible iability of the course in patients with IHSS." to have obstruction without symptoms, as in Case Maurice and associates 25 found that two thirds of 2. ASH patients less than 20 years old were asymp- Angiocardiography shows asymmetric hyper- tomatic. It appears, therefore, that the entity may trophy of the left ventricle with encroachment on be congenital and be present microscopically at the left ventricular outflow cavity by the anterior birth, but progress at a variable rate, with symp- leaflet of the mitral valve or the interventricular toms or obstruction appearing in most cases in the septum. In children, the appearance in the lateral third decade of life or later. view of an inverted cone formed by the hyper- Because of this natural history of progression of trophied septum anteriorly and the anterior mitral IHSS, arrangements have been made to follow leaflet posteriorly has been observed." Cases 1-3 regularly for evidence of continued clini- The most important noninvasive procedure in cal deterioration and progressive obstruction. the diagnosis of ASH and IHSS is echocardiog- raphy, which has confirmed the original angiog- Prognosis raphic observation that the anterior mitral leaflet Cardiac size has been found" to be of little prognos- moves forward abnormally during ventricular sys- tic significance. Swan and colleagues" found that tole. On echocardiographic investigation of pa- the end-diastolic pressure in the left ventricle tients with IHSS, Abbasi and colleagues" found shows close correlation with prognosis and the risk that the width of the interventricular septum was of sudden death. This is demonstrated not only on much greater than normal; the thickness of the cardiac catheterization but when the EKG shows posterior left ventricular wall was normal or left atrial hypertrophy, since the high end-diastolic slightly increased; and the ratio of the width of the pressure is thought to be due to dilatation of the left interventricular septum to that of the posterior atrium and inflow resistance to the left ventricle. wall was equal to or greater than 2.0. In 1973, Atrial fibrillation is poorly tolerated, with rapid Henry and associates" suggested a ratio of 1.3 ob- deterioration in most cases." Other common served echocardiographically because of its corre- complications of IHSS are infective endocarditis, lation with the ratio observed at necropsy by arterial hypertension, and embolism."

Idiopathic hypertrophic subaortic steno 181k61 The risk of sudden death is high in IHSS. In a ever, therapy is palliative and not corrective, since cooperative international study, 27 IHSS accounted hypertrophy of cardiac muscle may continue. for 9 percent of 254 sudden unexpected deaths of Therapy does not protect completely against sud- children. In the National Heart and Lung Institute den death, but will reduce symptoms in most cases. study, 17 60 percent of patients with symptomatic IHSS showed clinical deterioration or died. Thirty- Comment one percent of symptomatic patients died suddenly, The four cases of IHSS reported here cover a for a mortality rate of 4 percent per year. Some spectrum of presentations, from that of an asymp- patients were asymptomatic at the time of their tomatic adolescent with a familial history of IHSS demise, suggesting that a ventricular arrhyth- to that of a severely symptomatic adolescent who mia rather than outflow obstruction was the cause suffered unexpected death. The first patient was of death. The risk of sudden death is higher in seen because of a family history of IHSS and a patients with a strong family history of IHSS than cardiac murmur and the second because of mild in those with sporadic disease. The risk is small in symptoms, a cardiac murmur, and a family history ASH patients without obstruction. Administration of IHSS. The third patient had been known to have of propranolol and myectomy do not offer complete cardiovascular symptoms for about 2 years prior to protection against sudden death. admission, but the symptoms were not recognized by his physician as suggestive of IHSS. The fourth Treatment patient had a history of only one episode of syncope, Patients with nonobstructive asymptomatic ASH but its cause was recognized only after her sudden generally are identified by a murmur, an abnormal demise. EKG, or evaluation of the members of the family of Primary physicians should be aware that asym- a patient with known IHSS. Though it is rare for a metric septal hypertrophy and its obstructive form, patient with nonobstructive asymptomatic disease idiopathic hypertrophic subaortic stenosis, affect to die suddenly, such patients generally should be children as well as adults. There is a high familial followed closely for progression of obstruction. incidence, which makes echocardiographic studies They are restricted from competitive sports, and if mandatory for family members of a patient with an elevated gradient is discovered on provocative known IHSS. Symptoms are similar to those of testing, they are restricted in all athletic activities. valvular aortic stenosis. The clinical clue to IHSS is Patients with obstructive symptomatic ASH the atypical location of the murmur at the lower generally suffer from exertional dyspnea, angina, left sternal border and apex, instead of the usual presyncope, or syncope. Symptoms are caused by location at the base of the heart. If a patient has a ischemic cardiac muscle. Beta-adrenergic blocking cardiac murmur and unexplained syncope, an agents are the mainstay of therapy, propranolol echocardiogram is necessary to rule out IHSS. being the most widely used.5.28 Propranolol may be The risk of sudden death with IHSS is high. beneficial by reducing the oxygen demands of the Early diagnosis and therapy may be palliative, but hypertrophied cardiac muscle and by reducing they do not protect the patient completely from myocardial contractility through sympathetic sudden death. blockade. Most favorable changes occur when sym- pathetic tone is high, as in physical stress. Prop- The cases reviewed came from a clinical rotation served at ranolol has been used with success even for infants the Michigan State University Pediatric Cardiology when the dose is regulated to maintain plasma Clinic and Ingham Medical Center under the direction of Gita Mody, M.D., and David Matisoff, M.D., assistant levels between 40 and 90 ng./m1.29 Digitalis is con- professors of human development (cardiology), Michigan traindicated unless there is atrial fibrillation with State University, College of Human Medicine. a fast ventricular response. Subacute bacterial endocarditis occasionally oc- curs in symptomatic patients with severe obstruc- 1. Brock, R.C.: Functional obstruction of the left ventricle (acquired tion. It has been suggested 5 that antibiotic aortic subvalvular stenosis). Guys Hosp Rep 106:221-38, 1957 prophylaxis be employed when a patient with IHSS 2. Brock, R.: Functional obstruction of the left ventricle (acquired aortic undergoes a dental or surgical procedure. subvalvular stenosis). Guys Hosp Rep 108:126-43, 1959 3. Braunwald, E., et al.: Idiopathic hypertrophic subaortic stenosis. I. A Surgical intervention is advisable if there is no description of the disease based upon an analysis of 64 patients. Circula- response to medical management. The most widely tion (Suppl 4) 30:IV-1-119, Nov 64. American Heart Association Monograph 10. American Heart Association, New York, 1964 used procedure is transaortic septal myotomy/ 4. Epstein, S.E., et al.: Asymmetric septal hypertrophy. Ann Intern Med myectomy. 81:650-80, Nov 74 Tajik and colleagues3° expressed the opinion that 5. Henry, W.L., et al.: Echocardiographic measurement of the left ventricular outflow gradient in idiopathic hypertrophic subaortic all children with IHSS should be treated. How- stenosis. N Engl J Med 288:989-93, 10 May 73

181/62 Nov. 1980/Journal of AOA/vol. 80/no. 3 6. Menges, H., Jr., Brandenburg, R.O., and Brown, A.L., Jr.: The clinical, 23. Williams, R.G., Ellison, R.C., and Nadas, A.S.: Development of left hemodynamic, and pathologic diagnosis of muscular subvalvular aortic ventricular outflow obstruction in idiopathic hypertrophic subaortic stenosis. Circulation 24:1126-36, Nov 61 stenosis. Report of a case. N Engl J Med 288:868-71, 26 Apr 73 7. Teare, D.: Asymmetrical hypertrophy of the heart in young adults. Br 24. Frank, S., and Braunwald, E.: Idiopathic hypertrophic subaortic Heart J 20:1-8, 1958 stenosis. Clinical analysis of 126 patients with emphasis on the natural 8. Ferrans, V.J., Morrow, A.G., and Roberts, W.C.: Myocardial ultra- history. Circulation 37:759-88, May 68 structure in idiopathic hypertrophic subaortic stenosis. A study of opera- 25. Maurice, P., et al.: Les cardiomyopathies obstructives. I. Etude tively excised left ventricular outflow tract muscle in 14 patients. Circu- clinique et radiologique a propos de 50 cas. Arch Mal Coeur 59:375-90, lation 45:769-92, Apr 72 Mar 66 9. Neufeld, H.N., Ongley, PA., and Edwards, J.E.: Combined congenital 26. Swan, D.A., et al.: Analysis of symptomatic course and prognosis and subaortic stenosis and infundibular pulmonary stenosis. Br Heart J treatment of hypertrophic obstructive cardiomyopathy. Br Heart J 22:686-90, 1960 33:671-85, Sep 71 10. Barr, P.A., et al.: Idiopathic hypertrophic obstructive cardio- 27. Lambert, E.C., et al.: Sudden unexpected death from cardiovascular myopathy causing severe right ventricular outflow tract obstruction in disease in children. A cooperative international study. Am J Cardiol infancy. Br Heart J 35:1109-15, 1973 34:89-96, Jul 74 11.Maron, B.J., et al.: Asymmetric septal hypertrophy (ASH) in infancy. 28.Cohen, L.S., and Braunwald, E.: Amelioration of angina pectoris in Circulation 50:809-20, Oct 74 idiopathic hypertrophic subaortic stenosis with beta-adrenergic block- 12.Brent, LB., et al.: Familial muscular subaortic stenosis. An un- ade. Circulation 35:847-51, May 67 recognized form of "idiopathic heart disease" with clinical and autopsy 29.Shand, D.G., Sell, C.G., and Oates, J.A.: Hypertrophic obstructive observations. Circulation 21:167-80, Feb 60 cardiomyopathy in an infant. Propranolol therapy for three years. Med 13.Emanuel, R., Withers, R., and OBrien, K.: Dominant and recessive Intelligence 285:843, 1971 modes of inheritance in idiopathic cardiomyopathy. Lancet 2:1065-7, 13 30.Tajik, J.J., et al.: Idiopathic hypertrophic subaortic stenosis (IHSS) in Nov 71 children. Abstract. Circulation (Suppl 4) 48:IV-222, Oct 73 14.Henry, W.L., Clark, C.E., and Epstein, S.E.: Asymmetric septal Hurst, J.W., et al., Eds.: The heart, arteries and veins. Ed. 4. McGraw- hypertrophy. Echocardiographic identification of the pathognomonic anatomic abnormalities of IHSS. Circulation 47:225-33, Feb 73 Hill Book Co., New York, 1978 15.Clark, C.E., Henry, W.L., and Epstein, S.E.: Familial prevalence and genetic transmission of idiopathic hypertrophic subaortic stenosis. N Engl J Med 289:709-14, 4 Oct 73 Accepted for publication in September 1979. Updating, as nec- Hardarson, T., et al.: Prognosis and mortality of hypertrophic 16. essary, has been done by the author. obstructive cardiomyopathy. Lancet 2:1462-7, 29 Dec 73 Dr. Harvey was awarded first prize in the 1979 writing 17.Maron, B.J., et al.: Asymmetric septal hypertrophy in childhood. awards program sponsored by the American College of Os- Circulation 53:9-19, Jan 76 teopathic Pediatricians. The paper was presented at the annual 18. Pernot, C., et al.: Radiological patterns of obstructive car- meeting of the ACOP held in Orlando, Florida, April 1-4, 1979. diomyopathy of the left ventricle in childhood. Am Heart J 86:462-6, Oct 73 19.Abbasi, A.S., et al.: Echocardiographic diagnosis of idiopathic hyper- At the time this paper was written, Dr. Harvey was a senior trophic cardiomyopathy without outflow obstruction. Circulation pediatric resident at Lansing General Hospital, Osteopathic, 46:897-904, Nov 72 Lansing, Michigan, and a clinical instructor in pediatrics at 20. Larter, W.E., et al.: The asymmetrically hypertrophied septum. Michigan State University—College of Osteopathic Medicine. Further differentiation of its causes. Circulation 53:19-27, Jan 76 Max H. Robins, D.O., was the chairman of the Division of 21. Wood, R.S., et al.: Muscular subaortic stenosis in childhood. Report of Pediatric Medicine at that time. Dr. Harvey is now in the pri- occurrence in three siblings. Pediatrics 30:749-58, Nov 62 vate practice of pediatrics in Oklahoma City, Oklahoma. 22. Tafur, E., et al.: The development of outflow tract obstruction of the left ventricle in idiopathic myocardial hypertrophy. Circulation Dr. Harvey, 5514 Southwestern, Suite 16, Oklahoma City, 30:569-77, Oct 64 Oklahoma 73109.

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