Importance of (perimembranous) ventricular septal aneurysm in the natural history of isolated perimembranous ventricular septal defect

CONGENITAL HEART DISEASE

lmuortanceof (PerimembranouslVentricularSeutal ‘- Aneurysm6 the Natural Hisiory of Isolated’ Perimembranous VentricularSeptalDefect CLAUDIO RAMACIOTI-I,

MD, ANDRE KEREN, MD, and NORMAN H. SILVERMAN,

Records were reviewed of 247 patknts found to have fsofated perfmembranctus ventrkular septal defect (VSD) on cross-sectknal echocardkgraphy. Patients were separated into 2 groups: those in whom a perimembranous ventricular septal aneurysm (VSA) was associated with the VSD (group A, 77% of patients) and those In whom a VSA was not present (group B, 23 % ). The VSD was assessed by clinkal (125 in group A, 24 in group B) and hemodynamk criteria (65 in group A, 33 in group B). Ihe median follow-up perkd was 27 months (range 3 months to 25 years). In group A, the VSD closed spontaneously in 11% of the patients, improved clinically in 33% and required sur-

MD

gkal closure in 11%. In group B, the VSD cksed spontaneously in only 2 % , improved clinically in 16% and required surgical closure in 47%. When considering larger VSDs only, 28% required surgery in group A, whereas 84% required surgery in group B (p
T

he natural history of isolated ventricular septal defect (VSD) shows that many of these defects either close or diminish in size spontaneously.*-1* Tissue tags adjacent to perimembranous defects, probably originating from the tricuspid valve, are involved in the spontaneous closure or diminution in size of these defects.11,12,1g-22We have termed this tissue perimembranous ventricular septal aneurysm (VSA). The ac-

tual incidence of VSA associated with isolated perimembranous VSD has not been documented, and the extent to which VSAs modify the natural history of VSDs is unknown. VSA associated with VSD can be readily recognized by echocardiography,l4,15 even if no clinical signs are present or when it is not detected by angiography. We reviewed the records of 277 consecutive patients with an isolated perimembranous VSD to assess the frequency of VSA in association with an isolated perimembranous VSD by echocardiography, and how its presence influenced the natural history.

From the Department of Pediatrics and the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California. Dr. Ramaciotti is supported by a Fellowship in Pediatric Echocardiography, Rio de Janeiro, Brazil. Dr. Keren is supported by the Heiden Israeli Fellowship and the Fogarty International Fellowship, Bethesda, Maryland. Manuscript received April 8, 1985; revised manuscript received June 24.1985, accepted June 25.1985. Address for reprints: Norman H. Silverman, MD, University of California, San Francisco, M342A, San Francisco, California 94143.

Methods Four hundred forty patients had an isolated VSD diagnosed by cross-sectional echocardiography from January 1980 to September 1984. In 277 (63%), the VSD was considered to be in the perimembranous area and the patients’ clinical records were reviewed to assess their progress. The echocardiographic criteria for the 260

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diagnosis of the VSD have been reported.l*s19 In 210 patients an associated VSA could be defined by criteria described previously [Fig, 1).14.15The echocardiographic studies were performed using various types of ultrasound equipment, initially a Toshiba SSH 10A and subsequently Advanced Technology Laboratory Mark 500 and Mark 600 instruments with pulsed Doppler capabilities. From January 1982, the echocardiographic studies were combined with range-gated pulsed Doppler ultrasound. Based on the echocardiographic findings 2 groups were identified: those who had a VSA [group A] and those who did not (group B). For the purpose of analysis, a patient was considered to have a small VSD on the basis of absence of cardiac failure, a holosystolic murmur compatible with a VSD, a second heart sound that split normally with normal intensity of the pulmonic component, and, in some cases, a third sound or a short apical middiastolic murmur. The chest radiograph in these patients showed a normal or mildly increased cardiothoracic ratio and normal or mildly increased pulmonary vascular@. The electrocardiogram was normal, or showed, at most, evidence of mild left ventricular enlargement. None of these patients had ever

FIGURE 1. Methods used to define a pseudoaneurysm patlent In group IIA, with a moderate-sired shunt boffom feff, parasternal short-ax18 vlew; fop r&&f, the ventricular septal defect and adherence of the parrsternal short-ax18 plane with the beam passing atrium (RA). A = anterlor; A0 = aorta; I = lnferlor: or; R = right; S = superlor.

f, !986

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undergone cardiac catheterization by the clinicians caring for them. Eleven patients who had signs and symptoms compatible with congestive heart failure at some time received digitalis or diuretic drugs but did not undergo cardiac catheterization. These patients are considered the “symptomatic group.” Patients who underwent cardiac catheterization were arbitrarily grouped according to hemodynamic findings, Group I comprised 16 children in group A and 1 in group B, with a pulmonary to systemic flow ratio (Qp:Qs) smaller than 2:l and with pulmonary systolic arterial pressure less than 50% of systemic systolic arterial pressure. Group II comprised 27 children in group A and 9 in group B, with a Qp:Qs greater than 2:l but with a pulmonary systolic arterial pressure less than half systemic systolic arterial pressure. Group 111 comprised 20 children in group A and 22 in group B, with a Qp:Qs greater than 2:l and pulmonary systolic arterial pressure more than 50% of systemic systolic pressure. No patient had hemodynamic findings of Qp:Qs less than 2:l and pulmonary systolic arterial pressures higher than half systemic systolic arterial pressure.

(/aqe arrows) associated wlth perlmembranous ventricular septel defect from a and relatlvely normal pulmonary arterial presaure. Top /eff, parasternal long-axls vkw; aplcal4-chamber vlew In anatomlc orlentatlon. Smal arrow~aada Indicate the base of base of the pseudoaneurysm to It. Soffom r/gftf, M-mode recording generated from the through right ventricle (RV), pseudoaneurysm, trlcuspld valve leaftlet (TV), and right L = left; LA = left atrlum; LV = left ventricle; LVO = left ventricular outflow: P = posterl-

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TABLE Septal

HISTORY

I Comparison Defect

OF VENTRICULAR

of Flndlngs

in Patients

With VSA (n = 190) Findings

n

Spontaneous closure Became smaller Unchanged Eisenmenger SWMY Lost to follow-up First visit, no follow-up VSA = ventricular

21 63 56 1 21

(11%) (33%) (29.5%) (0.5%) (11%) (9.5%)

10

(5.5%)

18

septal

(%)

SEPTAL DEFECT

with

Ventricular

Without n

VSA (n = 57) W)

(2%)

1 9 8

(16%) (14%)

27 12

(47%) (21%)

aneurysm.

Serial cardiac catheterizationwas performed in 19 patientsto define changesin shunt size and in pulmonary artery pressure.In patients without these serial hemodynamics measurements,a decreasein size of the VSD was consideredto have occurredif symptoms diminished and if physical signs, electrocardiogram and chest radiograph improved. Echocardiographic signsincluded a decreasein the sizeof the VSD during serial cross-sectionalechocardiographicexamination and a decreasein the size of the previously enlarged left ventricle and atrium. Closureof the VSD wasdefined by sequentialclinical and ultrasonic studies. This included a normal physical examination, normal electrocardiogram,and a normal chest radiograph. Using echocardiography, closure was defined by our failure to image the VSD we had noted previously and by our inability to find pulsed Doppler evidence of a VSD. In 4 patientsultrasound confirmed closure of a VSD, whereas in 18 the closurewas defined only by clinical criteria. In no case wasa cardiaccatheterizationperformedto confirm the spontaneousclosure of the VSD. For the purposesof this study,the time of the examination when the defect was reported closed was assumed to be the time at which closure had occurred. The agesof the patientsat cardiaccatheterizationin groups IIA and IIIA were compared with those in groupsIIB and IIIB using an unpaired t test.All other statistical comparisonswere performed using the chisquare test.

Results Thirty patients (20 in group A and 10 in group B) were excluded from the study becauseno further clinical information was available: therefore,247 patients were analyzed.A VSA was identified in 190patients in groupA (77% of the total population),101 male and 89 female patients.The outcomeof our clinical studyis summarized in Table I. Among the 57 without a pseudoaneurysm(groupB, 23%), 32 were male and 25 were female patients. Only 1 patient, who had Down’s syndrome, showed clinical characteristics of the Eisenmenger’ssyndrome,severalyears subsequentto the family’s refusal of surgical treatment. The mean ageat the first cardiac catheterizationof patients in group IA was 49.1 f 47.9 months (k stan-

dard deviation). The patient in group IB underwent a first cardiac catheterization at the age of 13 months. Patients in groups IIB and IIIB underwent cardiac catheterizationat a mean age of 16.1 f 10.4 months. Patients in goups IIA and IIIA underwent cardiac catheterization significantly later than patients in groupsIIB and IIIB (meanageof 23.6 f 34.7 months)(p
19136

group IIIA. Eight in group A had Down’s syndrome;3 underwent operation before 1 year of age,2 before 2 years,and 3 after 2 years,1 of the latter with infundibular stenosis.Among the 13caseswithout Down’s syndrome, infundibular stenosisdeveloped in 2, both of whom underwent operation,at agesof 2.5and 6 years, Of the other 11patients,2 underwent operationbefore 6 months of age and 4 between 6 and 12 months, all becauseof congestiveheart failure. One patient underwent operation at 18 months of ageand 4 patients between 3 and 8 years of age,with Qp:Qs > 2:1 but normal pulmonary arterial pressuresand no cardiac failure. In group B, 27patients(47%)were referred for surgical closureof their VSD. The patient in group IB was operated on at age 4 years becausemoderate aortic insufficiency developed; 6 were from group IIB, 19 from group IIIB and 1 patient with infundibular stenosis and no measurementof pulmonary arterial pressure.Four underwent surgicalclosurebefore6 months of age,6 between6 and 12months,5 between12and 18 months, 1 between 18 and 24 months and 5 after 2 yearsof age.Five patientsunderwent surgerybetween ages 14 months and 10 years becauseof associated infundibular stenosis.The indication for surgical therapy in these patients did not differ from that for patients in group A. A VSA was found in 83% (115 of 138) of small VSDs, i.e., those followed clinically plus those in groupsI, and in 60.5%of patients(47of 78)in groupsII and III. The higher frequency of small defects with VSA was significant [p
Discussion Echocardiographyis the most sensitive method of identifying VSA. VSA was diagnosedby angiography in only one-third of our patients. Although auscultatory findings of an early systolic click associatedwith VSA has been reported,23v24 a definite early systolic click was found in less than 5% of our patients. Of the isolated perimembranousVSDs, 77% were associatedwith a VSA. The incidence was greaterin patients with small defects.The potential candidates for surgical closure of an isolated VSD, however, are usually those with higher pulmonary blood flow or high pulmonary arterial pressureat cardiac catheterization (groupsII and III]. Thus, it is in thesegroups that the echocardiographicfinding of a VSA is most important. Our data show that in patients with VSA surgical closure was required much less often. This finding has been suggested in previous stud-

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ies.13s:!” 22~25~2h: In contrast with our findings, a recent study7 did not show a more favorable natural history when the VSA was defined by angiography.However, the methods in this study may not have reflected the actual distribution of this entity within the spectrumof VSD. In contrastto the findings of the Joint Study of the Natural History of CongenitalHeart Defect,13in which VSA wasdiagnosedafter 2 yearsor life, we found VSA to be an early phenomenonin the natural history, occurring during the first 2yearsof life, and in about50% of casesin the first 6 months. The VSA was imaged on the first echocardiogramin 93% of cases.The 1.2VSAs not identified during the first study were examined during the first year of our study, when the resolution of our ultrasound equipment was inferior to that of equipment now in use.Five patientsdescribedasnow showing a VSA on the first examination were identified restrospectivelyashaving a VSA. The remaining 7 had small defects;5 were newborns, 1 was 2 months old and 1 was 2.5 years old. The VSAs were imaged during a subsequentexamination in the first year of life in all but 1 patient. In 9 premature infants, VSA was identified in the first month of life. In the subgroupof patientswith Down’s syndrome, VSA did not appearto confer the samefavorable prognosis.28,2g Fourteen of 15 patients had easily identifiable VSAs, but 9 required surgical closureof the VSD, and 1 patient in whom surgerywas refused had clinical findings compatible with Eisenmenger’s syndrome. This may relate to a slightly different position of the defects within the VSD in this condition. Our data suggestthat VSD associatedwith VSA has a higher incidence of closure and diminution in size than VSD without VSA, but we did not ascertainthe real incidence of closure or diminution in size in the group B becausea significant number of patientswere lost to follow-up. One difficulty in determining the natural history is that many of the smaller VSDs are managedby pediatriciansrather than referred to large centers for follow-up. We found spontaneousclosure of VSDs in 11% of patientswith a positive echocardiographic diagnosisof a VSA during a median period of follow-up of 30 months, which is a lower rate of closurethan that shown previously for isolatedVSD (14to 6370).l-~ The difference may, at least in part, be explained by somestudy characteristics.BecauseVSA is, we believe, a specific marker for defects in the perimembranousarea of the ventricular septum,we were not consideringsmall defectsin the muscular septum, which probably have a higher rate of spontaneousclosure.Also, many of the defectslost to follow-up might have closedspontaneously.Our study may have been biased toward patients with symptoms and possibly larger defects, because these are the patients more often referred for echocardiography.Furthermore,the relatively short median period of follow-up may account for the lack of complete documentationof spontaneousclosure in some cases. Left ventricular-right atria1shunt associatedwith perimembranous VSD is believed to be a result of anomaliesof the tricuspid valve.30This shunt has also beendescribedin patientswith a VSA associatedwith

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Alpert BS, Cook DH, Varghese PJ, Rowe RD. Spontaneous closure of smaI1 a VSD.11813 In a recent study using cineangiographyin 4.ventricuolr septal defects: ten year follow-up. Pediatrics 1979;63:204-206. perimembranous VSD with left ventricular to right 5. Hoffman JIE. Rudolph AM. The natural history of isolated ventricular atria1shunt, a VSA was demonstratedin all casese31 septol defects with special reference to selection of potients for surgery. In: Rudolph AM ed. Advances 1g70.;7-7g in Pediatrics. Chicago: Yearbook Medical PubSinceusing pulsedDoppler ultrasound,we have noted lisher. the presenceof a systolic jet entering the right atrium 6. Corone’ P, ’Doyon ’ F. Gaudeau S, Guerin F, Vernant P, Ducam H. RumeauC, Gaudeul P. Notural history of ventricular septal defect. A study in some patientswith a VSA. In our last 61patients,10 Rouquette involving 790 cases. CircuIotion 1977;55:906-915. (15%) had a systolic jet entering the right atrium. In 7. Bonham-Carter RE. Devenir de 144 enfants atteints d’une communication k&e et cotheteris6e avant I’age d’un on. Coeur Special none was there clinical suspicionof it. Cardiac cathe- inter-ventriculaire 1973;366-374. terization in our seriesalsoshowed10% of the patients Issue 6. Dickinson DF, Arnold R, Wilkinson JL. Ventricular septal defect in chilwith a left ventricular-right atria1shunt. Changesin dren born in Liverpool 1960 to 1969. Evaluation of natural course and surgical the anatomyof the tricuspid valve related to the devel- implications in an unselected population. Br Heart J 1981;46:47-54. WH, Blount SG, DuShane JW, Gersony WM. Hayes CJ, Nades opment of the VSA may facilitate the appearanceof a 9.AS.Weidman Clinical course in ventricular septal defect. Circulation 1977;55:suppI I:Ileft ventricular-right atria1shunt and tricuspid regur- 56-I-69. Collins G, Calder L, Rose V, Kidd L. Keith J. Ventricular septol defect: gitation. Prospective studies using pusled Doppler 10. clinical and hemodynamic changes in the first five years of life. Am Heart J techniquesare neededto delineatethe frequency and 1g72,64:6g5-705, 11. bhesler E, Korns ME, Edwards JE. Anomalies of the tricuspid valve, natural history of these associatedlesions. pouches, resembling aneurysms of the membranous ventricular Identification of VSA by echocardiographyis im- including septum. Am J Cardiol 1968;21:661-668. portant becausethe actualsize of the defect wasusual- 12. Anderson RH, Lenox CC, Zuberbuhler JR. Mechanisms of closure of ly small in most patients, and a VSA suggestsa more perimembranous ventricular septal defect. Am J Cardiol 1983;52:341-345. Freedom RM, White RD, Pierone DR. Varghese PJ. Krovetz LJ. Rowe RD. benign prognosis.Indeed, the size of the defect in the 13. The natural history of the so-called aneurysm of the membranous ventricular septumon the cross-sectionalimage may yield an erro- septum in childhood. Circulation 1974;49:375-383. Snider AR, Silverman NH, Schiller NE, Ports TA. Echocardiographic neous assessmentof its magnitude becausethe VSA 14. of ventricular septa1 aneurysms. Circulation 1979;59:920-926. may significantly reducethe areathroughwhich left to evaluation 15. Canale JM. Sahn DJ, Valdes-Cruz LM. Allen HD, Goldberg SJ, Ovitt TW. right ventricular shunting occurs. Identification of Accuracy of two-dimensional echocardiogrophy in the detection of aneuof the ventricular septum. Am Heart J 1981;101:255-259. VSA is also a hallmark of the location of the defect rysms 16. Nadas AS, Fyler DC. Pediatric Cardiology. Philadelphia: W.B. Saunders, within the perimembranous area. 1972:348. Our data confirm that perimembranousVSA is as- 17. Keith JD. Prevalence, incidence and epidemiology. In: Keith JD, Rowe sociatedwith a better prognosisin isolated perimem- RD, Vlad P, eds. Heart Disease in Infancy and Childhood. New York: Mac1978’3-13’ branousVSD than with a VSD with no VSA. We be- mi’lon’ 18. Sdverman NH, Snider AR. Two-dimensional echocardiography in conheart disease. Norwalk, CT: Appleton-Century-Crofts. 1982:70-85. lieve that VSA formation is an important mechanism genital 19. Sutherland GR, Goodman MJ, Smallhorn JF, Guiterras P, Anderson RH, in the closure of perimembranous VSD and may be Hunter S. Ventricular septal defects. Two-dimensional echocardiographic operativein diminishing the sizeof thoseVSDs that do ond morphological correlations. Br Heart j 1982;47:316. Nugent EW. Freedom RM, Rowe RD. Wagner HR, Rees JK. Aneurysm of not close completely [Table I). We have also shown 20. the membranous septum in ventricu1ar septol defect (abstr]. Circulation I:I-82. that the VSA is an early phenomenon in the natural 1977;56:sUppl history of ventricular defects.We suggestthat the tim- 21. Misra KP, Hildner FJ, Cohen LS, Narula OS, Samet P. Aneurysm of the ventricular septum. A method for spontaneous closure of vening of cardiac catheterization and surgery might be membranous tricuIar septal defect. N Engl 1 Med 1970;283:58-61. delayed when a perimembranousVSA can be shown 22. Varghese PJ, Izukawa T, Celermajer J. Simon A. Rowe RD. Aneurysm of membranous ventricular septum. A method of spontaneous closure of by echocardiography, even in patients with large the smaI1 ventricular septal defect. Am J Cardiol 1969;24:531-536. VSDs. 23. Pieroni DR, Bell BB, Krovetz LJ, Varghese PJ, Rowe RD. Auscultatory of aneurysm of the membranous ventricular septum associated Acknowledgment: We are indebted to Drs. Julien recognition with small ventricular septol defect. Circulation 1971;54:733-739. Hoffman and Abraham Rudolph for their help and 24. Pickering D, Keith JD. Systolic clicks with ventricular septal defects. A of aneurysm of ventricular septum? Br Heart J 1971;33:538-539. criticism of the manuscript, to Dr. William Lutin for sign 25. Varghese PJ, Rowe RD. Spontaneous closure of ventricular septa1 defects help with statistical analysis, to Drs. Saul Robinson, by aneurysm01 formation of the membranous septum. J Pediatr 1969; Paul Stanger, Harold Tarnoff, Marvin Auerback, 75:700-703. Vidne BA, Chiariello L, Wagner H, Subramanian S. Aneurysm of the Claude Rogeand Michael Cooper for referring their 26. membranous ventricular septum. Surgical consideration and experience in patientsfor echocardiographicexamination, to Heath- 29 cases. J Thorac Cardiovasc Surg 1976;71:402-409. Beerman LB, Park SC, Fischer DR. Fricker FJ, Mathews RA, Neches WH, er Silverman for editorial assistance,and to Martha 27. Lenox CC, Zuherhuhler JR. Ventricular septal defect associated with aneuPrince for preparation of the manuscript. rvsm of the membronous seotum. IACC 1985:5:118-123.

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2ll. Shaher RM, Farina MA, Porter iH, Bishop h. Clinical aspects of congenito1 heart disease in mongolism. Am J Cardiol 1972;29:497-503. 29. Greenwood RD, Nadas AS. The clinical course of cardiac disease in Down’s syndrome. Pediatrics 1976;58:893-897. 30. Perry EL, Burchell HB, Edwards JF. Congenital communications between the left ventricle and the right otrium: coexisting ventricular septal defect and double tricusnid orifice. Proc Staff Meet Mavo Clin 1949:24:198-206. 31. Burrows ‘PE, Fellows KE. Ke&e JF. Cineangiograph; of the perimembranous ventricular septal defect with left ventricular-right atria1 shunt. JACC 1983;1:1129-1134.