Hypercontractile Cardiac States Simulating Hypertrophic Cardiomyopathy PATRICIA C. COME, M.D., BERNADINE H. BULKLEY, M.D., ZACHARY D. GOODMAN, M.D., GROVER M. HUTCHINS, M.D., BERTRAM PITT, M.D., AND NICHOLAS J. FORTUIN, M.D. SUMMARY Hypertrophic cardiomyopathy (HCM) or idiopathic hypertrophic subaortic stenosis (IHSS) has been defined as an autosomal dominant myocardial disease characterized by specific physical findings, echocardiographic features, asymmetric septal hypertrophy and disordered myocardial architecture. Echocardiographic and scintiphotographic studies failed to reveal evidence of asymmetric septal hypertrophy in four patients with systolic anterior movement of the mitral valve and the typical auscultatory and
peripheral pulse abnormalities characteristic of HCM. Postmortem examination in one patient demonstrated mild concentric left ventricular hypertrophy and a normal arrangement of myocardial muscle fibers. These observations in four patients demonstrate that both systolic anterior movement of the mitral valve and the physical findings characteristic of HCM are not specific for the autosomal dominant myocardial disease characterized by asymmetric septal hypertrophy and abnormal septal histology.
HYPERTROPHIC CARDIOMYOPATHY (HCM) or idiopathic hypertrophic subaortic stenosis (IHSS) has been defined by certain physical findings," 2 and characteristic hemodynamic," 2 angiographicl'3 and pathologic abnormalities.1' 2, 4-7 Echocardiography provides a valuable noninvasive means of recognizing HCM and, in many institutions, has replaced catheterization as a means of confirming clinical diagnoses. Major echocardiographic features of HCM include abnormal thickness8" of the interventricular septum which is asymmetrically hypertrophied relative to the left ventricular free wall,9-1" systolic anterior movement of the mitral valve'2, '3 and reduction of systolic septal thickening and amplitude of systolic septal excursion.8 Myocardial imaging with a radioactive tracer, thallium 201,'4 has also demonstrated the presence of disproportionate septal thickness and appears to be an additional noninvasive means of diagnosing HCM, particularly when adequate echocardiographic definition of the interventricular septum is not feasible technically. A unified concept of hypertrophic cardiomyopathy as an autosomal dominant myocardial disease characterized by asymmetric septal hypertrophy and disordered myocardial architecture has been proposed.2'" This paper reports four patients with typical physical findings of HCM and echocardiographic documentation of systolic anterior movement of the mitral valve in whom a combination of echocardiographic and scintiphotographic studies and, in one instance, postmortem examination failed to demonstrate asymmetric septal hypertrophy. Systolic anterior movement of the mitral valve and the auscultatory and peripheral pulse abnormalities characteristic of HCM do not therefore appear to be specific for the autosomal dominant myocardial dis-
ease characterized by asymmetric septal hypertrophy and abnormal septal histology. Materials and Methods Echocardiographic Studies
The echocardiographic examinations were performed with a Smith-Kline Ekoline 20 A Ultrasonoscope using a 0.5 inch diameter, 2.25 MHz transducer focused at 7.5 cm. The echocardiograms were recorded on a Cambridge strip chart recorder or Honeywell direct writing recorder (patient 3). Standard techniques were employed to record tracings from the anterior and posterior mitral leaflets and from the septum and posterior wall just below the mitral leaflets. Systolic and end-diastolic cavity dimensions and septal and posterior wall thicknesses were measured at this level,"5 and the ratio of end-diastolic septal to posterior wall thickness calculated. In addition to end-diastolic measurements in the dimensional area, other measurements were obtained according to the methods employed by Henry et al.6 Wall thickness measurements were made simultaneously with the electrocardiographic P wave, prior to the left ventricular wall thinning observed with atrial systole. The septum was measured in the area of the left ventricle below the mitral leaflets and the left ventricular posterior wall was measured at the level of the posterior mitral valve leaflet. A ratio of septal to posterior wall thickness was calculated based on measurements in those areas. Systolic septal excursion and percent thickening were measured by methods described previously.8 Ejection fraction was determined from the echocardiographic systolic and end-diastolic dimensions. Phonocardiograms16 were performed using Leatham microphones (Cambridge Instrument Co.) and carotid pulse tracings were obtained with the use of a transducer with time constant greater than three seconds. None of the illustrative material was retouched.
From the Department of Medicine, Cardiovascular Division, The Johns Hopkins University and Johns Hopkins Hospital, Baltimore, Maryland. Supported by MIRU Contract PH 43 NHLI 167-1444 from the National Institutes of Health. Dr. Come is supported by a Research Fellowship of the American Heart Association, Maryland Affiiliate. Dr. Come's present address is Department of Medicine, Beth Israel Hospital, Boston,
Myocardial Imaging
In three patients thallium 201 myocardial perfusion imaging" and technetium 99m gated cardiac blood pool imaging'8 were performed. Following intravenous injection of 1.7 to 1.8 mCi of ionic thallium 201, myocardial images
Massachusetts.
Address for reprints: Nicholas J. Fortuin, M.D., Department of Medicine, Cardiovascular Division, The Johns Hopkins University School of Medicille, The Johns Hopkins Hospital, Baltimore, Maryland 21205. Received September 13, 1976; revision accepted January 27, 1977.
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were recorded in the 40° left anterior oblique projection. Maximal septal thickness and mid posterior free wall thickness were measured'4 and septal to left ventricular free wall thickness ratios determined. From the gated cardiac blood pool image performed in both the anterior and 40° left anterior oblique projections,'8 left ventricular ejection fraction was calculated.'9 Patient Studies
Case I An asymptomatic 32-year-old white male was referred for evaluation of a murmur detected on a routine physical examination. His father was known to have a murmur. Physical examination revealed normal blood pressure, clear lungs, and normal jugular pulse. The carotid upstroke was brisk. A hyperdynainic, thrusting left ventricular impulse was palpable in the fifth intercostal space in the midclavicular line. SI was loud, S2 physiologically split. A grade IlI/VI harsh early to mid systolic murmur was audible between the apex and the left sternal border. The intensity of the murmur decreased with isometric handgrip exercise and dramatically increased and became longer with both the Valsalva maneuver and inhalation of amyl nitrite. An S4 was noted following the latter maneuver. The electrocardiogram revealed deep Q waves in leads III and aV, suggestive of septal hypertrophy, but voltage criteria for left ventricular hypertrophy were not present. The chest X-ray was normal. The echocardiogram showed systolic anterior movement of the mitral valve (fig. I), an end-diastolic septal thickness of 1.2 cm, an end-diastolic posterior wall thickness of I.I cm, and a septal to posterior wall thickness ratio of l1 (fig. 2). A ratio of 1.1 was also obtained when the septum (1.4 cm) and left ventricular posterior wall (1.3 cm) were measured according to the method of Henry et al.6 Systolic septal excursion was 6 mm and percent systolic septal
RV
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thickening was 50%. The left ventricular cavity dimensions were 4.5 cm in end diastole and 2.5 cm in systole, with a calculated ejection fraction of 81%. Thallium 201 myocardial perfusion images (fig. 3D) demonstrated equal thicknesses of the septal and posterior left ventricular free walls and ejection fraction by gated blood pool imaging was 80%. Ca.e 2 A 60-year-old white male was referred for echocardiographic examination to evaluate an intermittent systolic murnmur of 21/2 years duration which had increased in intensity two months previously. He had had mild hypertension for 15 years. There was no history of angina pectoris or symptoms of congestive failure or syncope. The family history was negative for cardiac disease or sudden death. The physical examination revealed a blood pressure of 160/90. The carotid upstroke was brisk and bifid. A nonsustained left ventricular heave and systolic thrill were palpable 2 cm to the left of the midclavicular line in the fifth intercostal space. The first sound was of normal intensity. S2 was not audibly split and an S4 sound was noted at the apex. A harsh, grade IV/VI crescendo-decrescendo systolic murmur beginning shortly after the first sound and ending just prior to the second sound was audible maximally at the apex with radiation toward the base. The murmur was not audible over the carotid arteries. The intensity of the murmur decreased with leg elevation and handgrip and increased markedly with assumption of the sitting position, inhalation of amyI nitrite and performance of Valsalva maneuver (fig. 4). The electrocardiogram revealed first degree atriovenitricular biock (PR interval of 0.24 seconds) and increased QRS voltage in the left precordial leads. The echocardiogram (fig. 5) showed systolic anterior movement of the mitral valve, septum and posterior wall measurements of 1.1 cm in end diastole, and a septal to posterior wall thickness ratio of l.0.
icm[
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Mitral Valve
FIGURE 1. Echocardiogram from patient I demonstrates systolic anterior movement of the mitral valve (indicated by the small black arrows). A simultaneous electrocardiogram, recorded in lead II, can be faintly seen at the bottom of the echocardiographic recording. RV right ventricular cavity. A 1 cm calibration marker has been superimposed on the echocardiogram. =
400,,'
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HYPERCONTRRACTILE CARDIAC STATES/Come et al.
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A 56-year-old white female was referred for evaluation of chest pain, dyspnea, syncope, and a systolic murmur. The family history was positive for sudden death in a 42-year-old sister who was known to have a murmur. When first examined, the patient had a regular pulse of 92 and a cuff blood pressure of 80/60 mm Hg. The carotid pulse showed a brisk upstroke and bifid contour. There was no jugular venous distention and the lungs were clear. A brisk, tapping precordial impulse was palpable in the fifth intercostal space in the mid-clavicular line. There was an associated apical thrill. Apexcardiography demonstrated an enlarged "a" wave, equal to 22% of the height of the systolic wave, and a bifid systolic impulse. The first sound was prominent and a soft S4 was present. A grade IV/VI diamond-shaped long systolic murmur was audible maximally at the apex, with radiation to the axilla and to the left sternal border. The murmur dramatically increased in intensity with both performance of the Valsalva maneuver and inhalation of amyl nitrite. When seen on subsequent oc-
LV intermittent >Sj Z j k
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ClIRCULATION
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Fi' (RI} 8. Echocardiographic scan from the mitral valve area to the left ventricular dimensional area in patient 4. Systolic anterior movement of the mitral valve is demonstrated (small black arrows). The septum measures Ic.enC and the posterior wall 1.1 cm in thickness.
cardiogram except for continued prominence of the "a" wave. The electrocardiogram was normal and did not change during periods of chest discomfort. The radiographic cardiac silhouette was also normal. At the time of cardiac catheterization the murmur was not audible. Systolic and diastolic pressures in the right and left ventricular cavities were normal. There were no gradients across the right or left ventricular outflow tracts. Cine left ventriculography revealed a normal sized left ventricle with normal wall movement, an ejection fraction of 79% and no mitral regurgitation. In the region of the left ventricular outflow tract 1-2 cm below the level of the aortic valve, there was a small protrusion of the basal interventricular septum into the left ventricular outflow tract. The mitral valve did not move into the outflow tract during systole. The coronary arteries had no detectable narrowings and coronary spasm could not be demonstrated following intravenous injection of ergonovine. Echocardiographic examination, performed at a time when the systolic murmur was grade IV, revealed anterior movement of the mitral valve to abut the septum in systole (fig. 8). End-diastolic septal and posterior wall thicknesses were both 1.1 cm (fig. 8), resulting in a septal to posterior wall thickness ratio of 1.0. The ratio of septum (1.3 cm) to left ventricular posterobasal wall (1.1 cm) was 1.2. Systolic septal excursion was 1 cm and percent systolic septal thickening was 64%. Left ventricular cavity dimensions were 3.4 cm in diastole and 2.0 cm in systole, resulting in a calculated ejection fraction of 80%. The aortic valve echo showed a mid-systolic closing movement, followed by reopening of the valve leaflets, a pattern previously described in patients with hypertrophic cardiomyopathy." The patient had repeat echocardiography performed at a time when her murmur was grade I to 2 in intensity and her peripheral cuff blood pressure was 105/70 mm Hg. The left ventricular cavity dimensions were larger. 4.6 cm in diastole
and 2.6 cm in systole, but the calculated ejection fraction was still 81%. Systolic anterior movement of the mitral valve and mid systolic closure of the aortic valve were not demonstrated. Scintiphotographic studies were not obtained since the patient refused further medical assessment.
Discussion The physical findings,' 2 including their changes with provocative maneuvers, the systolic anterior movement of the mitral valve to approximate the interventricular septum,'2 13 and the increased ejection fractions'0 21 seen in our four patients are characteristic of the primary myocardial disease known as hypertrophic cardiomyopathy or idiopathic hypertrophic subaortic stenosis. The patients, however, are atypical in several respects. First, they lack asymmetric septal hypertrophy, the abnormality considered by some investigators to be the major diagnostic criterion for the disease,9,"," and the sign now used by some investigators as a genetic marker for HCM.1" 21 The absence of both asymmetric septal hypertrophy and abnormal thickness of the interventricular septum was documented by echocardiographic definition of the septum and posterior wall in three patients, by radionuclide imaging with thallium 201 in three patients and by postmortem examination of the heart in one patient. Second, the septum was not hypokinetic, as demonstrated by echocardiographic studies in the three patients in whom the septum was well defined. Percent systolic thickening of the interventricular septum was normal, in contrast to the decreased values of 0-22% previously described for some patients with HCM.8 The amplitudes of left septal excursion in the three patients with technically adequate echocardiograms were within the previously reported normal range of 5-10 mm.8 Third, a normal arrangement of muscle fibers was present in the ventricular septum of the autopsied patient, in contrast to the dis-
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ordered myocardial architecture which has been described for patients with hypertrophic cardiomyopathy.4' ' 7,11 In the autopsied patient, however, an area of endocardial fibrosis was present in the left ventricular outflow tract opposite the anterior leaflet of the mitral valve. Similar endocardial plaques have frequently been described in pathologic studies of patients with hypertrophic cardiomyopathy2' 5 22 and are thought to result from recurrent contact of the anterior mitral leaflet with the upper interventricular septum.2' 22
The patients demonstrated both increased ejection fractions and systolic anterior movement of the mitral valve. It is possible that hyperkinetic left ventricular wall movement, which leads to rapid ventricular ejection, may create a Venturi effect resulting in forward systolic movement of the mitral valve, as has previously been suggested.23 That increased contractility, particularly in the setting of a small left ventricular cavity, may result in systolic anterior movement of the mitral valve and a systolic murmur is suggested by a case recently reported from our institution.24 A 70-yearold woman with sepsis and acute gastrointestinal bleeding developed a new systolic murmur, associated with echocardiographic evidence of systolic anterior movement of the mitral valve, when given intravenous pressor therapy for hypotension. Postmortem examination revealed normal cardiac valves, normal thicknesses of the septal and left ventricular free walls and normal septal histology. It is likely that hypovolemia and changes in myocardial contractility induced by pressor therapy were of major importance in the generation of her abnormal mitral valve movement and the murmur. One of our patients (case 4) demonstrated, on repeated examinations, a remarkable variability in her physical signs and echocardiographic abnormalities, despite the absence of intervening changes in symptomatology, drug therapy, or apparent changes in fluid balance. It is of interest that the cardiac murmur and abnormal mitral valve movement were present when the left ventricular cavity was small but were not present when the cavity size was larger. We speculate that unrecognized endogenous physiologic mechanisms caused changes in intravascular volume and/or cardiac contractility which, in turn, were responsible for the changes in her physical signs and echocardiogram. The other three patients reported above, however, continued to have the typical murmurs and carotid pulse abnormalities on repeated follow-up examinations, suggesting the possibility of a continued hypercontractile state. The patients reported in this study demonstrate that a thickened, asymmetrically hypertrophied and hypokinetic septum is not a prerequisite for the presence of systolic anterior movement of the mitral valve or for the typical auscultatory and peripheral pulse abnormalities characteristic of hypertrophic cardiomyopathy. Our studies are supported by previous observations that the clinical syndrome of HCM can occur in the absence of asymmetric septal hypertrophy.5, 6, 22, 2527 We propose that certain clinical features of hypertrophic cardiomyopathy, including the characteristic physical findings and systolic anterior movement of the mitral valve, may result from a heterogeneous group of disorders in which hypercontractile cardiac action is the common finding and in which a wide spectrum of wall thicknesses from normal to grossly hypertrophic may be
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found. This group of disorders would include not only those patients with the primary myocardial disease hypertrophic cardiomyopathy, characterized by asymmetric septal hypertrophy and disordered myocardial architecture, but also those patients with hypercontractile hearts who lack both asymmetric septal hypertrophy and bizarre septal histology. It is possible that the latter group of patients may represent an early phase of hypertrophic disease and that they will later develop the more typical findings of hypertrophic cardiomyopathy. It is also possible that longstanding hypercontractility per se may stimulate the development of asymmetric hypertrophy and abnormalities of myocardial architecture. It is noteworthy that each of the four patients reported here had evidence of mild, symmetric left ventricular hypertrophy. In two of these antecedent hypertension may have been responsible, but there was no obvious cause in the other two. Whether ventricular hypertrophy is the cause of or result of hypercontractility in these patients is uncertain. The noninvasive techniques of phonocardiography, external pulse recording, echocardiography, and scintiphotography enable early recognition of this group of patients, many of whom may be asymptomatic and therefore not routinely subjected to more invasive investigative techniques. Periodic re-examination may clarify whether these patients will progress to typical hypertrophic cardiomyopathy or whether they will remain a separate subgroup, varying in their symptomatology, prognosis, and necessity for and response to therapeutic interventions.
Acknowledgment The authors wish to thank Ms. Lisa Grue for her secretarial assistance, Ms. Sandra Dorsey for assisting in the echocardiographic and phonocardiographic evaluations, Dr. Ian Bailey and Messrs. William Schafer and Henry Manspeaker for performing the scintiphotographic studies, and Drs. Myron L. Weisfeldt and Richard S. Ross for their helpful review of the manuscript.
References 1. Braunwald E, Lambrew CT, Rockoff D, Ross J, Morrow AG: Idiopathic hypertrophic subaortic stenosis: 1. A description of the disease based upon an analysis of 64 patients. Circulation 29 & 30: (suppl IV): IV-3, 1964 2. Epstein SE, Henry WL, Clark CE, Roberts WC, Maron BJ, Ferrans VJ, Redwood DR, Morrow AG: Asymmetric septal hypertrophy. Ann Intern Med 81: 650, 1974 3. Redwood DR, Scherer JL, Epstein SE: Biventricular cineangiography in the evaluation of patients with asymmetric septal hypertrophy. Circulation 49: 1116, 1974 4. Teare D: Asymmetrical hypertrophy of the heart in young adults. Br Heart J 20: 1, 1958 5. Roberts WC: Valvular, subvalvular and supravalvular aortic stenosis: Morphologic features. Cardiovasc Clin 5: 98, 1973 6. Henry WL, Clark CE, Roberts WC, Morrow AG, Epstein SE: Differences in distribution of myocardial abnormalities in patients with obstructive and nonobstructive asymmetric septal hypertrophy (ASH): Echocardiographic and gross anatomic findings. Circulation 50: 447, 1974 7. Maron BJ, Ferrans VJ, Henry WL, Clark CE, Redwood DR, Roberts WC, Morrow AG, Epstein SE: Differences in distribution of myocardial abnormalities in patients with obstructive and nonobstructive asymmetric septal hypertrophy (ASH): Light and electron microscopic findings. Circulation 50: 436, 1974 8. Rossen RM, Goodman DJ, Ingham RE, Popp RL: Ventricular systolic septal thickening and excursion in idiopathic hypertrophic subaortic stenosis. N Engl J Med 291: 1317, 1974 9. Henry WL, Clark CE, Epstein SE: Asymmetric septal hypertrophy. Echocardiographic identification of the pathognomonic anatomic abnormality of IHSS. Circulation 47: 225, 1973 10. Abbasi AS, Macalpin RN, Eber LM, Pearce ML: Echocardiographic diagnosis of idiopathic hypertrophic cardiomyopathy without outflow obstruction. Circulation 46: 897, 1972
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11. Henry WL, Clark CE, Epstein SE: Asymmetric septal hypertrophy (ASH): The unifying link in the IHSS disease spectrum: Observations regarding its pathogenesis, pathophysiology, and course. Circulation 47: 827, 1973 12. Shah PM, Gramiak R, Kramer DH: Ultrasound localization of left ventricular outflow obstruction in hypertrophic obstructive cardiomyopathy. Circulation 40: 3, 1969 13. Henry WL, Clark CE, Glancy DL, Epstein SE: Echocardiographic measurement of the left ventricular outflow gradient in idiopathic hypertrophic subaortic stenosis. N Engl J Med 288: 989, 1973 14. Bulkley BH, Rouleau JR, Strauss HW, Pitt B: Idiopathic hypertrophic subaortic stenosis: Detection by thallium 201 myocardial perfusion imaging. N Engl J Med 293: 1113, 1975 15. Feigenbaum H: Clinical applications of echocardiography. Prog Cardiovasc Dis 14: 531, 1972 16. Feigenbaum H: Echocardiography. Philadelphia, Lea and Febiger, 1972, p 113 17. Strauss HW, Harrison K, Langan JK, Lebowitz, Pitt B: Thallium-201 for myocardial imaging: Relation of thallium-201 to regional myocardial perfusion. Circulation 51: 641, 1975 18. Strauss HW, Pitt B: The gated cardiac blood pool scan: Use in patients
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with coronary heart disease. Am J Cardiol, in press 19. Dodge HT, Sandler H, Ballew DH, Lord JD: Use of biplane angiography for the measurement of left ventricular volume in man. Am Heart J 60: 762, 1960 20. Wilson WS, Criley JM, Ross RS: Dynamics of left ventricular emptying in hypertrophic subaortic stenosis: A cineangiographic and hemodynamic study. Am Heart J 73: 4, 1967 21. Clark CE, Henry WL, Epstein SE: Familial prevalence and genetic transmission of idiopathic hypertrophic subaortic stenosis. N Engl J Med 289: 709, 1973 22. Pomerance A, Davies MJ: Pathological features of hypertrophic obstructive cardiomyopathy (HOCM) in the elderly. Br Heart J 37: 305, 1975 23. Henry WL, Clark CE, Epstein SE: Mechanism of outflow obstruction in IHSS. Circulation 47 & 48 (suppl IV): IV-177, 1973 24. Bulkley BH, Fortuin NJ: Systolic anterior motion of the mitral valve without asymmetric septal hypertrophy. Chest 69: 694, 1976 26. Bercu BA, Diettert GA, Danforth WH, Pund EE, Ahlvin RC, Belliveau RR: Pseudoaortic stenosis produced by ventricular hypertrophy. Am J Med 25: 814, 1958 27. Brock R: Functional obstruction of the left ventricle (acquired aortic subvalvular stenosis). Guy's Hospital Reports 106: 221, 1957
Natural History of Ventricular Septal Defect A Study Involving 790 Cases PIERRE CORONE, M.D., FRANCOISE DOYON, STATISTICIAN, SERGE GAUDEAU, M.D., FRANCOIS GUERIN, M.D., PIERRE VERNANT, M.D., HENRI DUCAM, M.D., CLAUDE RUMEAU-ROUQUETTE, M.D., AND PATRICK GAUDEUL, M.D. SUMMARY The development of 790 untreated patients affected by ventricular septal defect (VSD) has been the object of a 25-year study. Of these patients, 72% had had at least one catheterization; 13% had several. The mean observation interval is six years, and the average age at the latest data is 19.5 years. This study covers 4717 patient-years. For the entire population, the incidence rate of aortic regurgitation is 6.3% (4.3 for 1000 patient-years) and that of bacterial endo-
carditis is 3.7% (2.4 for 1000 patient-years). Twenty-five patients died, 15 of them between the ages of one and 39. Of the 499 cases with several clinical examinations, 71% remained stable. In 21%, changes suggesting some level of closure developed; in 7%, infundibular stenosis began to evolve and in 1% pulmonary vascular disease began to appear or became accentuated. These different rates are studied and discussed in relation to patients' age, VSD type, and various follow-up characteristics.
THE EVOLUTION OF THE VENTRICULAR SEPTAL DEFECT (VSD) in the first years of life has been the focus of several studies. These have shown that large septal defects are particularly serious during the early years but that spontaneous closure occurs in about one third of all cases.'-5 The development of patients who are older than one year and affected by VSD has not been studied extensively.6' One is generally astonished by the frequency of VSDs noticed at birth (about two out of 1000 living children) and even at school age (one out of 1000 children) and the rare observation of this abnormality in adults.8-" Late mortality, the possibility of late closure, or transformation into cyanotic diseases (tetralogy of Fallot or the Eisenmenger complex) have been offered as explanations."2 13 In addi-
tion, a certain number of patients affected by VSD and free of all symptoms may not be recognized or may avoid seeing physicians, and thus escape medical statistics.3 This study endeavors to give further information about this late evolution. A relatively older population (469 subjects out of 790 were more than four years old when they entered the study) was followed by the same medical team for a long period.
From the University Hospital Centers (C.H.U.) Pitie-Salpetriere, Henri Mondor and Enfants y Malades, Departments of Pediatric Cardiology, Paris, France. With the help of the Groupe de Recherches Epidemiologiques sur la Mere et l'Enfant (I.N.S.E.R.M.). Supported in part by the Office Public d'Hygiene Sociale (O.P.H.S.). Address for reprints: Dr. P. Corone, C.H.U. Pitie-Salpetriere, 83, Boulevard de l'HMpital, 75634 Paris Cedex 13, France. Received July 19, 1976; revision accepted December 28, 1976.
Materials and Methods This study involves 790 cases of VSD, 272 of which were initially examined as outpatients at the Hopital des Enfants Malades, while 518 of them were examined at a cardiology service of a university hospital (Broussais, La Pitie and Henri Mondor in Paris). Patients with an associated stenosis of the pulmonary tract (excluding all those with cyanosis) or aortic regurgitation were included in this study, along with patients with isolated VSD. Patients with minor malformations that would not affect prognosis were also included (140 [18%], see table 1). Neither patients with complex cardiopathies
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Hypercontractile cardiac states simulating hypertrophic cardiomyopathy. P C Come, B H Bulkley, Z D Goodman, G M Hutchins, B Pitt and N J Fortuin Circulation. 1977;55:901-908 doi: 10.1161/01.CIR.55.6.901 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1977 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/55/6/901
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peripheral pulse abnormalities characteristic of HCM. Postmortem examination in one patient demonstrated mild concentric left ventricular hypertrophy and a normal arrangement of myocardial muscle fibers. These observations in four patients demonstrate that both systolic anterior movement of the mitral valve and the physical findings characteristic of HCM are not specific for the autosomal dominant myocardial disease characterized by asymmetric septal hypertrophy and abnormal septal histology.
HYPERTROPHIC CARDIOMYOPATHY (HCM) or idiopathic hypertrophic subaortic stenosis (IHSS) has been defined by certain physical findings," 2 and characteristic hemodynamic," 2 angiographicl'3 and pathologic abnormalities.1' 2, 4-7 Echocardiography provides a valuable noninvasive means of recognizing HCM and, in many institutions, has replaced catheterization as a means of confirming clinical diagnoses. Major echocardiographic features of HCM include abnormal thickness8" of the interventricular septum which is asymmetrically hypertrophied relative to the left ventricular free wall,9-1" systolic anterior movement of the mitral valve'2, '3 and reduction of systolic septal thickening and amplitude of systolic septal excursion.8 Myocardial imaging with a radioactive tracer, thallium 201,'4 has also demonstrated the presence of disproportionate septal thickness and appears to be an additional noninvasive means of diagnosing HCM, particularly when adequate echocardiographic definition of the interventricular septum is not feasible technically. A unified concept of hypertrophic cardiomyopathy as an autosomal dominant myocardial disease characterized by asymmetric septal hypertrophy and disordered myocardial architecture has been proposed.2'" This paper reports four patients with typical physical findings of HCM and echocardiographic documentation of systolic anterior movement of the mitral valve in whom a combination of echocardiographic and scintiphotographic studies and, in one instance, postmortem examination failed to demonstrate asymmetric septal hypertrophy. Systolic anterior movement of the mitral valve and the auscultatory and peripheral pulse abnormalities characteristic of HCM do not therefore appear to be specific for the autosomal dominant myocardial dis-
ease characterized by asymmetric septal hypertrophy and abnormal septal histology. Materials and Methods Echocardiographic Studies
The echocardiographic examinations were performed with a Smith-Kline Ekoline 20 A Ultrasonoscope using a 0.5 inch diameter, 2.25 MHz transducer focused at 7.5 cm. The echocardiograms were recorded on a Cambridge strip chart recorder or Honeywell direct writing recorder (patient 3). Standard techniques were employed to record tracings from the anterior and posterior mitral leaflets and from the septum and posterior wall just below the mitral leaflets. Systolic and end-diastolic cavity dimensions and septal and posterior wall thicknesses were measured at this level,"5 and the ratio of end-diastolic septal to posterior wall thickness calculated. In addition to end-diastolic measurements in the dimensional area, other measurements were obtained according to the methods employed by Henry et al.6 Wall thickness measurements were made simultaneously with the electrocardiographic P wave, prior to the left ventricular wall thinning observed with atrial systole. The septum was measured in the area of the left ventricle below the mitral leaflets and the left ventricular posterior wall was measured at the level of the posterior mitral valve leaflet. A ratio of septal to posterior wall thickness was calculated based on measurements in those areas. Systolic septal excursion and percent thickening were measured by methods described previously.8 Ejection fraction was determined from the echocardiographic systolic and end-diastolic dimensions. Phonocardiograms16 were performed using Leatham microphones (Cambridge Instrument Co.) and carotid pulse tracings were obtained with the use of a transducer with time constant greater than three seconds. None of the illustrative material was retouched.
From the Department of Medicine, Cardiovascular Division, The Johns Hopkins University and Johns Hopkins Hospital, Baltimore, Maryland. Supported by MIRU Contract PH 43 NHLI 167-1444 from the National Institutes of Health. Dr. Come is supported by a Research Fellowship of the American Heart Association, Maryland Affiiliate. Dr. Come's present address is Department of Medicine, Beth Israel Hospital, Boston,
Myocardial Imaging
In three patients thallium 201 myocardial perfusion imaging" and technetium 99m gated cardiac blood pool imaging'8 were performed. Following intravenous injection of 1.7 to 1.8 mCi of ionic thallium 201, myocardial images
Massachusetts.
Address for reprints: Nicholas J. Fortuin, M.D., Department of Medicine, Cardiovascular Division, The Johns Hopkins University School of Medicille, The Johns Hopkins Hospital, Baltimore, Maryland 21205. Received September 13, 1976; revision accepted January 27, 1977.
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were recorded in the 40° left anterior oblique projection. Maximal septal thickness and mid posterior free wall thickness were measured'4 and septal to left ventricular free wall thickness ratios determined. From the gated cardiac blood pool image performed in both the anterior and 40° left anterior oblique projections,'8 left ventricular ejection fraction was calculated.'9 Patient Studies
Case I An asymptomatic 32-year-old white male was referred for evaluation of a murmur detected on a routine physical examination. His father was known to have a murmur. Physical examination revealed normal blood pressure, clear lungs, and normal jugular pulse. The carotid upstroke was brisk. A hyperdynainic, thrusting left ventricular impulse was palpable in the fifth intercostal space in the midclavicular line. SI was loud, S2 physiologically split. A grade IlI/VI harsh early to mid systolic murmur was audible between the apex and the left sternal border. The intensity of the murmur decreased with isometric handgrip exercise and dramatically increased and became longer with both the Valsalva maneuver and inhalation of amyl nitrite. An S4 was noted following the latter maneuver. The electrocardiogram revealed deep Q waves in leads III and aV, suggestive of septal hypertrophy, but voltage criteria for left ventricular hypertrophy were not present. The chest X-ray was normal. The echocardiogram showed systolic anterior movement of the mitral valve (fig. I), an end-diastolic septal thickness of 1.2 cm, an end-diastolic posterior wall thickness of I.I cm, and a septal to posterior wall thickness ratio of l1 (fig. 2). A ratio of 1.1 was also obtained when the septum (1.4 cm) and left ventricular posterior wall (1.3 cm) were measured according to the method of Henry et al.6 Systolic septal excursion was 6 mm and percent systolic septal
RV
Voi[ 55, No 6, JtNf 1977
thickening was 50%. The left ventricular cavity dimensions were 4.5 cm in end diastole and 2.5 cm in systole, with a calculated ejection fraction of 81%. Thallium 201 myocardial perfusion images (fig. 3D) demonstrated equal thicknesses of the septal and posterior left ventricular free walls and ejection fraction by gated blood pool imaging was 80%. Ca.e 2 A 60-year-old white male was referred for echocardiographic examination to evaluate an intermittent systolic murnmur of 21/2 years duration which had increased in intensity two months previously. He had had mild hypertension for 15 years. There was no history of angina pectoris or symptoms of congestive failure or syncope. The family history was negative for cardiac disease or sudden death. The physical examination revealed a blood pressure of 160/90. The carotid upstroke was brisk and bifid. A nonsustained left ventricular heave and systolic thrill were palpable 2 cm to the left of the midclavicular line in the fifth intercostal space. The first sound was of normal intensity. S2 was not audibly split and an S4 sound was noted at the apex. A harsh, grade IV/VI crescendo-decrescendo systolic murmur beginning shortly after the first sound and ending just prior to the second sound was audible maximally at the apex with radiation toward the base. The murmur was not audible over the carotid arteries. The intensity of the murmur decreased with leg elevation and handgrip and increased markedly with assumption of the sitting position, inhalation of amyI nitrite and performance of Valsalva maneuver (fig. 4). The electrocardiogram revealed first degree atriovenitricular biock (PR interval of 0.24 seconds) and increased QRS voltage in the left precordial leads. The echocardiogram (fig. 5) showed systolic anterior movement of the mitral valve, septum and posterior wall measurements of 1.1 cm in end diastole, and a septal to posterior wall thickness ratio of l.0.
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FIGURE 1. Echocardiogram from patient I demonstrates systolic anterior movement of the mitral valve (indicated by the small black arrows). A simultaneous electrocardiogram, recorded in lead II, can be faintly seen at the bottom of the echocardiographic recording. RV right ventricular cavity. A 1 cm calibration marker has been superimposed on the echocardiogram. =
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A 56-year-old white female was referred for evaluation of chest pain, dyspnea, syncope, and a systolic murmur. The family history was positive for sudden death in a 42-year-old sister who was known to have a murmur. When first examined, the patient had a regular pulse of 92 and a cuff blood pressure of 80/60 mm Hg. The carotid pulse showed a brisk upstroke and bifid contour. There was no jugular venous distention and the lungs were clear. A brisk, tapping precordial impulse was palpable in the fifth intercostal space in the mid-clavicular line. There was an associated apical thrill. Apexcardiography demonstrated an enlarged "a" wave, equal to 22% of the height of the systolic wave, and a bifid systolic impulse. The first sound was prominent and a soft S4 was present. A grade IV/VI diamond-shaped long systolic murmur was audible maximally at the apex, with radiation to the axilla and to the left sternal border. The murmur dramatically increased in intensity with both performance of the Valsalva maneuver and inhalation of amyl nitrite. When seen on subsequent oc-
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906
VOIe 55, No 6, JTINF 1977
ClIRCULATION
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cardiogram except for continued prominence of the "a" wave. The electrocardiogram was normal and did not change during periods of chest discomfort. The radiographic cardiac silhouette was also normal. At the time of cardiac catheterization the murmur was not audible. Systolic and diastolic pressures in the right and left ventricular cavities were normal. There were no gradients across the right or left ventricular outflow tracts. Cine left ventriculography revealed a normal sized left ventricle with normal wall movement, an ejection fraction of 79% and no mitral regurgitation. In the region of the left ventricular outflow tract 1-2 cm below the level of the aortic valve, there was a small protrusion of the basal interventricular septum into the left ventricular outflow tract. The mitral valve did not move into the outflow tract during systole. The coronary arteries had no detectable narrowings and coronary spasm could not be demonstrated following intravenous injection of ergonovine. Echocardiographic examination, performed at a time when the systolic murmur was grade IV, revealed anterior movement of the mitral valve to abut the septum in systole (fig. 8). End-diastolic septal and posterior wall thicknesses were both 1.1 cm (fig. 8), resulting in a septal to posterior wall thickness ratio of 1.0. The ratio of septum (1.3 cm) to left ventricular posterobasal wall (1.1 cm) was 1.2. Systolic septal excursion was 1 cm and percent systolic septal thickening was 64%. Left ventricular cavity dimensions were 3.4 cm in diastole and 2.0 cm in systole, resulting in a calculated ejection fraction of 80%. The aortic valve echo showed a mid-systolic closing movement, followed by reopening of the valve leaflets, a pattern previously described in patients with hypertrophic cardiomyopathy." The patient had repeat echocardiography performed at a time when her murmur was grade I to 2 in intensity and her peripheral cuff blood pressure was 105/70 mm Hg. The left ventricular cavity dimensions were larger. 4.6 cm in diastole
and 2.6 cm in systole, but the calculated ejection fraction was still 81%. Systolic anterior movement of the mitral valve and mid systolic closure of the aortic valve were not demonstrated. Scintiphotographic studies were not obtained since the patient refused further medical assessment.
Discussion The physical findings,' 2 including their changes with provocative maneuvers, the systolic anterior movement of the mitral valve to approximate the interventricular septum,'2 13 and the increased ejection fractions'0 21 seen in our four patients are characteristic of the primary myocardial disease known as hypertrophic cardiomyopathy or idiopathic hypertrophic subaortic stenosis. The patients, however, are atypical in several respects. First, they lack asymmetric septal hypertrophy, the abnormality considered by some investigators to be the major diagnostic criterion for the disease,9,"," and the sign now used by some investigators as a genetic marker for HCM.1" 21 The absence of both asymmetric septal hypertrophy and abnormal thickness of the interventricular septum was documented by echocardiographic definition of the septum and posterior wall in three patients, by radionuclide imaging with thallium 201 in three patients and by postmortem examination of the heart in one patient. Second, the septum was not hypokinetic, as demonstrated by echocardiographic studies in the three patients in whom the septum was well defined. Percent systolic thickening of the interventricular septum was normal, in contrast to the decreased values of 0-22% previously described for some patients with HCM.8 The amplitudes of left septal excursion in the three patients with technically adequate echocardiograms were within the previously reported normal range of 5-10 mm.8 Third, a normal arrangement of muscle fibers was present in the ventricular septum of the autopsied patient, in contrast to the dis-
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HYPERCONTRACTILE CARDIAC STATES/Come et al.
ordered myocardial architecture which has been described for patients with hypertrophic cardiomyopathy.4' ' 7,11 In the autopsied patient, however, an area of endocardial fibrosis was present in the left ventricular outflow tract opposite the anterior leaflet of the mitral valve. Similar endocardial plaques have frequently been described in pathologic studies of patients with hypertrophic cardiomyopathy2' 5 22 and are thought to result from recurrent contact of the anterior mitral leaflet with the upper interventricular septum.2' 22
The patients demonstrated both increased ejection fractions and systolic anterior movement of the mitral valve. It is possible that hyperkinetic left ventricular wall movement, which leads to rapid ventricular ejection, may create a Venturi effect resulting in forward systolic movement of the mitral valve, as has previously been suggested.23 That increased contractility, particularly in the setting of a small left ventricular cavity, may result in systolic anterior movement of the mitral valve and a systolic murmur is suggested by a case recently reported from our institution.24 A 70-yearold woman with sepsis and acute gastrointestinal bleeding developed a new systolic murmur, associated with echocardiographic evidence of systolic anterior movement of the mitral valve, when given intravenous pressor therapy for hypotension. Postmortem examination revealed normal cardiac valves, normal thicknesses of the septal and left ventricular free walls and normal septal histology. It is likely that hypovolemia and changes in myocardial contractility induced by pressor therapy were of major importance in the generation of her abnormal mitral valve movement and the murmur. One of our patients (case 4) demonstrated, on repeated examinations, a remarkable variability in her physical signs and echocardiographic abnormalities, despite the absence of intervening changes in symptomatology, drug therapy, or apparent changes in fluid balance. It is of interest that the cardiac murmur and abnormal mitral valve movement were present when the left ventricular cavity was small but were not present when the cavity size was larger. We speculate that unrecognized endogenous physiologic mechanisms caused changes in intravascular volume and/or cardiac contractility which, in turn, were responsible for the changes in her physical signs and echocardiogram. The other three patients reported above, however, continued to have the typical murmurs and carotid pulse abnormalities on repeated follow-up examinations, suggesting the possibility of a continued hypercontractile state. The patients reported in this study demonstrate that a thickened, asymmetrically hypertrophied and hypokinetic septum is not a prerequisite for the presence of systolic anterior movement of the mitral valve or for the typical auscultatory and peripheral pulse abnormalities characteristic of hypertrophic cardiomyopathy. Our studies are supported by previous observations that the clinical syndrome of HCM can occur in the absence of asymmetric septal hypertrophy.5, 6, 22, 2527 We propose that certain clinical features of hypertrophic cardiomyopathy, including the characteristic physical findings and systolic anterior movement of the mitral valve, may result from a heterogeneous group of disorders in which hypercontractile cardiac action is the common finding and in which a wide spectrum of wall thicknesses from normal to grossly hypertrophic may be
907
found. This group of disorders would include not only those patients with the primary myocardial disease hypertrophic cardiomyopathy, characterized by asymmetric septal hypertrophy and disordered myocardial architecture, but also those patients with hypercontractile hearts who lack both asymmetric septal hypertrophy and bizarre septal histology. It is possible that the latter group of patients may represent an early phase of hypertrophic disease and that they will later develop the more typical findings of hypertrophic cardiomyopathy. It is also possible that longstanding hypercontractility per se may stimulate the development of asymmetric hypertrophy and abnormalities of myocardial architecture. It is noteworthy that each of the four patients reported here had evidence of mild, symmetric left ventricular hypertrophy. In two of these antecedent hypertension may have been responsible, but there was no obvious cause in the other two. Whether ventricular hypertrophy is the cause of or result of hypercontractility in these patients is uncertain. The noninvasive techniques of phonocardiography, external pulse recording, echocardiography, and scintiphotography enable early recognition of this group of patients, many of whom may be asymptomatic and therefore not routinely subjected to more invasive investigative techniques. Periodic re-examination may clarify whether these patients will progress to typical hypertrophic cardiomyopathy or whether they will remain a separate subgroup, varying in their symptomatology, prognosis, and necessity for and response to therapeutic interventions.
Acknowledgment The authors wish to thank Ms. Lisa Grue for her secretarial assistance, Ms. Sandra Dorsey for assisting in the echocardiographic and phonocardiographic evaluations, Dr. Ian Bailey and Messrs. William Schafer and Henry Manspeaker for performing the scintiphotographic studies, and Drs. Myron L. Weisfeldt and Richard S. Ross for their helpful review of the manuscript.
References 1. Braunwald E, Lambrew CT, Rockoff D, Ross J, Morrow AG: Idiopathic hypertrophic subaortic stenosis: 1. A description of the disease based upon an analysis of 64 patients. Circulation 29 & 30: (suppl IV): IV-3, 1964 2. Epstein SE, Henry WL, Clark CE, Roberts WC, Maron BJ, Ferrans VJ, Redwood DR, Morrow AG: Asymmetric septal hypertrophy. Ann Intern Med 81: 650, 1974 3. Redwood DR, Scherer JL, Epstein SE: Biventricular cineangiography in the evaluation of patients with asymmetric septal hypertrophy. Circulation 49: 1116, 1974 4. Teare D: Asymmetrical hypertrophy of the heart in young adults. Br Heart J 20: 1, 1958 5. Roberts WC: Valvular, subvalvular and supravalvular aortic stenosis: Morphologic features. Cardiovasc Clin 5: 98, 1973 6. Henry WL, Clark CE, Roberts WC, Morrow AG, Epstein SE: Differences in distribution of myocardial abnormalities in patients with obstructive and nonobstructive asymmetric septal hypertrophy (ASH): Echocardiographic and gross anatomic findings. Circulation 50: 447, 1974 7. Maron BJ, Ferrans VJ, Henry WL, Clark CE, Redwood DR, Roberts WC, Morrow AG, Epstein SE: Differences in distribution of myocardial abnormalities in patients with obstructive and nonobstructive asymmetric septal hypertrophy (ASH): Light and electron microscopic findings. Circulation 50: 436, 1974 8. Rossen RM, Goodman DJ, Ingham RE, Popp RL: Ventricular systolic septal thickening and excursion in idiopathic hypertrophic subaortic stenosis. N Engl J Med 291: 1317, 1974 9. Henry WL, Clark CE, Epstein SE: Asymmetric septal hypertrophy. Echocardiographic identification of the pathognomonic anatomic abnormality of IHSS. Circulation 47: 225, 1973 10. Abbasi AS, Macalpin RN, Eber LM, Pearce ML: Echocardiographic diagnosis of idiopathic hypertrophic cardiomyopathy without outflow obstruction. Circulation 46: 897, 1972
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11. Henry WL, Clark CE, Epstein SE: Asymmetric septal hypertrophy (ASH): The unifying link in the IHSS disease spectrum: Observations regarding its pathogenesis, pathophysiology, and course. Circulation 47: 827, 1973 12. Shah PM, Gramiak R, Kramer DH: Ultrasound localization of left ventricular outflow obstruction in hypertrophic obstructive cardiomyopathy. Circulation 40: 3, 1969 13. Henry WL, Clark CE, Glancy DL, Epstein SE: Echocardiographic measurement of the left ventricular outflow gradient in idiopathic hypertrophic subaortic stenosis. N Engl J Med 288: 989, 1973 14. Bulkley BH, Rouleau JR, Strauss HW, Pitt B: Idiopathic hypertrophic subaortic stenosis: Detection by thallium 201 myocardial perfusion imaging. N Engl J Med 293: 1113, 1975 15. Feigenbaum H: Clinical applications of echocardiography. Prog Cardiovasc Dis 14: 531, 1972 16. Feigenbaum H: Echocardiography. Philadelphia, Lea and Febiger, 1972, p 113 17. Strauss HW, Harrison K, Langan JK, Lebowitz, Pitt B: Thallium-201 for myocardial imaging: Relation of thallium-201 to regional myocardial perfusion. Circulation 51: 641, 1975 18. Strauss HW, Pitt B: The gated cardiac blood pool scan: Use in patients
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with coronary heart disease. Am J Cardiol, in press 19. Dodge HT, Sandler H, Ballew DH, Lord JD: Use of biplane angiography for the measurement of left ventricular volume in man. Am Heart J 60: 762, 1960 20. Wilson WS, Criley JM, Ross RS: Dynamics of left ventricular emptying in hypertrophic subaortic stenosis: A cineangiographic and hemodynamic study. Am Heart J 73: 4, 1967 21. Clark CE, Henry WL, Epstein SE: Familial prevalence and genetic transmission of idiopathic hypertrophic subaortic stenosis. N Engl J Med 289: 709, 1973 22. Pomerance A, Davies MJ: Pathological features of hypertrophic obstructive cardiomyopathy (HOCM) in the elderly. Br Heart J 37: 305, 1975 23. Henry WL, Clark CE, Epstein SE: Mechanism of outflow obstruction in IHSS. Circulation 47 & 48 (suppl IV): IV-177, 1973 24. Bulkley BH, Fortuin NJ: Systolic anterior motion of the mitral valve without asymmetric septal hypertrophy. Chest 69: 694, 1976 26. Bercu BA, Diettert GA, Danforth WH, Pund EE, Ahlvin RC, Belliveau RR: Pseudoaortic stenosis produced by ventricular hypertrophy. Am J Med 25: 814, 1958 27. Brock R: Functional obstruction of the left ventricle (acquired aortic subvalvular stenosis). Guy's Hospital Reports 106: 221, 1957
Natural History of Ventricular Septal Defect A Study Involving 790 Cases PIERRE CORONE, M.D., FRANCOISE DOYON, STATISTICIAN, SERGE GAUDEAU, M.D., FRANCOIS GUERIN, M.D., PIERRE VERNANT, M.D., HENRI DUCAM, M.D., CLAUDE RUMEAU-ROUQUETTE, M.D., AND PATRICK GAUDEUL, M.D. SUMMARY The development of 790 untreated patients affected by ventricular septal defect (VSD) has been the object of a 25-year study. Of these patients, 72% had had at least one catheterization; 13% had several. The mean observation interval is six years, and the average age at the latest data is 19.5 years. This study covers 4717 patient-years. For the entire population, the incidence rate of aortic regurgitation is 6.3% (4.3 for 1000 patient-years) and that of bacterial endo-
carditis is 3.7% (2.4 for 1000 patient-years). Twenty-five patients died, 15 of them between the ages of one and 39. Of the 499 cases with several clinical examinations, 71% remained stable. In 21%, changes suggesting some level of closure developed; in 7%, infundibular stenosis began to evolve and in 1% pulmonary vascular disease began to appear or became accentuated. These different rates are studied and discussed in relation to patients' age, VSD type, and various follow-up characteristics.
THE EVOLUTION OF THE VENTRICULAR SEPTAL DEFECT (VSD) in the first years of life has been the focus of several studies. These have shown that large septal defects are particularly serious during the early years but that spontaneous closure occurs in about one third of all cases.'-5 The development of patients who are older than one year and affected by VSD has not been studied extensively.6' One is generally astonished by the frequency of VSDs noticed at birth (about two out of 1000 living children) and even at school age (one out of 1000 children) and the rare observation of this abnormality in adults.8-" Late mortality, the possibility of late closure, or transformation into cyanotic diseases (tetralogy of Fallot or the Eisenmenger complex) have been offered as explanations."2 13 In addi-
tion, a certain number of patients affected by VSD and free of all symptoms may not be recognized or may avoid seeing physicians, and thus escape medical statistics.3 This study endeavors to give further information about this late evolution. A relatively older population (469 subjects out of 790 were more than four years old when they entered the study) was followed by the same medical team for a long period.
From the University Hospital Centers (C.H.U.) Pitie-Salpetriere, Henri Mondor and Enfants y Malades, Departments of Pediatric Cardiology, Paris, France. With the help of the Groupe de Recherches Epidemiologiques sur la Mere et l'Enfant (I.N.S.E.R.M.). Supported in part by the Office Public d'Hygiene Sociale (O.P.H.S.). Address for reprints: Dr. P. Corone, C.H.U. Pitie-Salpetriere, 83, Boulevard de l'HMpital, 75634 Paris Cedex 13, France. Received July 19, 1976; revision accepted December 28, 1976.
Materials and Methods This study involves 790 cases of VSD, 272 of which were initially examined as outpatients at the Hopital des Enfants Malades, while 518 of them were examined at a cardiology service of a university hospital (Broussais, La Pitie and Henri Mondor in Paris). Patients with an associated stenosis of the pulmonary tract (excluding all those with cyanosis) or aortic regurgitation were included in this study, along with patients with isolated VSD. Patients with minor malformations that would not affect prognosis were also included (140 [18%], see table 1). Neither patients with complex cardiopathies
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Hypercontractile cardiac states simulating hypertrophic cardiomyopathy. P C Come, B H Bulkley, Z D Goodman, G M Hutchins, B Pitt and N J Fortuin Circulation. 1977;55:901-908 doi: 10.1161/01.CIR.55.6.901 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1977 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/55/6/901
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