ventricular septal defect: clinical and hemodynamic changes in the first five years of life

Fundamentals of clinical cardiology

Ventricular septal defect: Clinical and

hemodynamic changes in the first five years of life

George Collins, M.B., Ch.B. F.R.C.P.(C.) LoLlise Culder, M.D. I’eru Rose, B.Sc., M.B., B.S., C.R.C.P. Lnngford Kidd, ill.D., F.R.C.P.(Ed.) John Keith, M.D., F.R.C.P.(C.)

Toronto, Ontario, Cunndu

T here has been considerable interest in the past decade in the natural history

of isolated ventricular septal defect. Spon- taneous closure,1-6 progressive pulmonary vascular obstruction,‘-‘” right ventricular outflow tract obstruction,16-l7 and aortic insufficiency18-“0 have been documented.

Such changes are obviously important in decisions for or against surgical intervention.

To assess the likelihood of such develop- ments, a group of children with ventricular septal defects, apparent since infancy, have lIeen followed now for 5 years. All children were catheterized at the time of presentation to the cardiologist, and 213 of 236 children considered to have adequate hemodynamic data were included in the study. Thirteen of these patients, on the basis of repeat catheterization and angiography have since been excluded, 6 because associated lesions were discovered (2 with atria1 septal defect, 2 kvith patent ductus arteriosus, one with coarctation, and one with peripheral pulmonary artery stenosis) and 7 lIecause of errors in diagnosis (3 with

A-V communis, 2 with common ventricle, one with double-outlet right ventricle, and 1 with Gerbode defect). This report sum- marizes the clinical and hemodynamic changes in the remaining 200 patients with isolated ventricular septal defects.

Material and methods

Clinical examinations, including chest x-rays and electrocardiograms (ECG’s) were performed at least once each year. The timing of repeat catheterization and possible surgical intervention was at the discretion of the attending physician. Sick infants not responding to medical manage- ment were recommended for pulmonary artery banding, and increasing pulmonary vascular resistance was considered an indi- cation for surgical closure of the defect.

Catheterization was performed under light sedation with chlorpromazine, meperi- dine, and promethazine.21 Pressures were recorded on an Electronics for Medicine DR-8 recorder, using a Stratham P23Db transducer located at one third the chest thickness below the sternum. Oxygen satu-

From the Department of Cardiology and The Research Institute, Hospital for Sick Children, Toronto, and the Depart- ment of Paediatrics, University of Toronto, Toronto, Ontario.

This work was supported by grants from the Ontario Heart Foundation and National Health Grants, Canada. Reprint requests to: V. Rose, M.B.. B.S., Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada.

696 Collins et al. Am. Hcavt 1. Xovembcr, 3372

Number

of patlents per month,

1 3 6 9 12

Age (months)

Fig. 1. Histogram shows age distribution and hemodynamic group at the time of first cardiac catheterization. There were no children catheterized in the first month of life. The number of patients studied per month is averaged over the two or three months age periods indicated. The horizontal divisions de- note hemodynamic groupings at the time of study.

rations and contents were assessed using a Wood oximeter and Van Slyke analysis. Oxygen consumption was calculated in all instances using a figure of 180 ml. per square meter per minute.22 The pulmonary artery was entered in all cases. Total pulmonary vascular resistance was calculated throughout. In 29 studies either the systemic oxygen saturation or the arterial pressure, or both, were not recorded by direct needle puncture. As none of these children had elevated pulmonary artery pressure, cuff pressures were used, and an arterial saturation of 95 per cent was as- sumed. Calculations and analyses were made using conventional Fick formulas.

For the sake of analysis, the patients were grouped according to hemodynamic findings at the first study in infancy. This grouping, which has been reported on pre- viously,12 is not age-dependent, as illustrated in Fig. 1. There were 36 patients in Group I, 68 in Group II, 46 in Group III, 39 in Group IV, and 11 in Group V.

GYOIL$ I: P/S flow ratio < 2:l; PA @es- mre < 50 $er cent systemic. Of the 36 patients in this group, 5 were lost to follow-up.

VENTRICULAR SEPTAL DEFECT

PROSPECTIVE STUDY GROUP I

PBF !,tres/MZ

12 -r-l

PVR dynes/M2

600 i-7

Follow up Years

Fig. 2. Group I. Hemodynamic changes in 8 patients who were restudied. (x = Group I defect P/S Flow Ratio <2:1, PAP <SOoI, systemic; c = spontaneous closure demonstrated angiographically.)

One child died at 11 months of age, on an Indian reservation, with pneumonia. The local pathologist described partial closure of the defect by fibrous tissue.

The remaining 30 patients were followed for 5 years. Six presented in heart failure and another 7 with cardiomegaly were digitalized. All but 4 were asymptomatic by 2 years of age, and digoxin was discontinued in all patients by 3 years of age. Pansystolic murmurs persisted in 19 patients but the intensity of the murmur diminished and 13 patients lost their palpable thrill. In 6 patients the murmur disappeared. There was a significant reduction in heart size in all patients with cardiomegaly and the ECG reverted from right or combined ventricular to left ventricular hypertroph) and then to normal. In 16 patients both chest x-ray and ECG became normal. A summary of the clinical findings in infancy and the subsequent changes is given in Table I.

With this satisfactory clinical progress only 8 patients in this group had repeat catheterization. The changes in pulmonary blood flow and vascular resistance are shown in Fig. 2. In all but two patients there was a reduction in size of the left-to- right shunt, with normal pulmonary artery pressures and P/S flow ratios of less than 1.2 : 1. One of these 2 patients was restudied at 26 months because of persistent cardiomegaly and combined ventricular hyper-

trophy on the ECG. While the pulmonary artery pressure was normal, there was an increase in the size of the left-to-right shunt and a change in the P/S ratio from 1.5 to 2.0 : 1. Subsequent clinical follow-up showed a diminished intensity of the murmur, with loss of the thrill, and reduction in heart size. The abnormal ECG persisted un- changed. T\vo patients in whom the murmur had disappeared were shown angiographically to have closed their defect spontaneously.

Group II: PjSJEow ratio >Z:l; S/P resistance ratio > 7:l. There were 68 patients in this group, hut 6 were lost to follow-up. Four children died in infancy and 6 others, \Iho did not respond to medical manage- ment, underwent palliative surgery. The 7 patients developing right ventricular outflow tract obstruction, and 2 with acquired aortic ins&icienry (with similar patients in Groups III and IV) are the subject of another communication and will not be discussed in this report.

Twenty-seven of the remaining 43 patients improved with supervision, becoming asymptomatic. Twenty-one were undersized, with weights below the tenth percentile for age (using the Boston Children’s Medical Center growth chart), and 9 had signs of heart failure. Nineteen were maintained on digoxin for the first year. Twenty- three patients with pansystolic murmurs and thrills had large hearts with electrical evidence of combined or right ventricular hypertrophy. Digoxin was stopped in 16

patients by 3 years of age. All showed accelerated growth after infancy, with only 4 remaining at weights below the twenty- fifth percentile by 5 years of age. While typical auscultatory findings persisted in most, there was a reduction in heart size in all patients with large hearts initially, and serial ECG’s progressed to left ventricular hypertrophy and normal. In 5 children the defects closed spontaneously. These clinical changes are summarized in Table II. Seventeen of these 27 children had repeat hemodynamic evaluations between 2 and 5 years of age. All children studied showed a fall in pulmonary blood

flow without alteration in vascular resistance (Fig. 3). In 3 spontaneous closure was confirmed angiographically.

Sixteen patients who failed to show this

Tabbe I. Ventriccdar septtrl defect. Present study-Group I

Auscultation PanSM 8: thrill PanSkI Ejection SM No murmur

x-my CT ratio 657Oc/,

60-65 7; 556Ov/, 50-55 ::, <soq-,

ECG IiVH CVH LVH Normal

‘4 4

11 8

0 6

6 17

2 0

17 6 2

0 0

12 14

4

0 2%

12 16

There were 30 patients in Group I in infancy. In the table are the number of patients with each finding when first examined in infancy, and subsequently at 5 years of age.

*Both children were recatheterized. Pan% = pansystolic murmur; SM = systolic murmur; CT =

cardiothoracic; RVH = right ventricular hypertrophy; CVH = combined ventricular hypertrophy; LVII = left ventricular hypertrophy.

clinical improvement underwent surgical correction between the ages of 2 and 5. Ten were digitalized in infancy for heart failure. All but 2 were below the third weight percentile for age at presentation. None of these patients thrived, and all but one remained below the tenth percentile (with 8 below the third percentile) at the time of surgery. The abnormal clinical, radiologic, and electrocardiographic findings of infancy persisted in these patients until surgical intervention (Table II).

Thirteen patients were restudied prior to surgery. Nine patients showed persistently high pulmonary blood flow without alteration in pulmonary vascular resistance, but 4 patients showed a reduction in pulmonary blood flow with rising pulmonary vascular resistance (Fig. 4). These hemodynamic changes preceded any definite clinical change and only one of the 4 patients showed pure right ventricular hypertrophy electrocardiographically.

Group III: P/S$ow ratio > 2 : 1; S/P resistance ratio 5 to 7: 1. There were 46 patients in this group, but 4 were lost to

60s Collins cl ill.

PBF litres/M2

PVR dynes/M2

Follow-up Years

7’chle I I. I ‘entricultrr septcll defect. Presmt study-Group II.

23 (13) 18 (13) 2 (0) 4 (0) 2 (3) 0 (3)

0 (0) 5 (0)

4 (6) (1 ($1 8 (5) 1 (5)

11 (5) 9 (5) 4 (0) 12 (2) 0 (0) 5 (‘I,

3 (4) 0 (r, 21 (11) 3 (II)

3 (0) 7 (1) 0 (1) 17 (I))

-~-

follow-up. Three children died in infancy and 3 others required palliative surgery. Three patients developed right ventricular outflo\v tract ohtruction and 2 acquired aortic insufficiency.

Eleven of the remaining 31 patients iln- proved clinically under supervision. be-

coming asymptomatic 1~4. 5 Jrears of age. All Imt one were undersized \vhen first, seen and 5 had signs of congestive heart failure. Se\:en patients m:ere maintained on digoxin for the first year. All had the classical auscultatory findings of a pansystolic murmur and thrill, with an apical middiastolic murmur, and 7 showed significantly enlarged hearts radiologically and electrical evidence of combined ventricular hypertrophy. Digoxin jvas stopped Iwt\veen the ages of 2 and 4 years in 6 patients and all hut 2 children had n-eights o\‘er the twenty.- fifth percentile 11~ 5 years of age. While 6 patients had persistent murmur and thrill, all l)ut 3 children had a reduction in heart size, and the ECG’s reverted to left \-entricular hypertrophy or registered normal. In 2 children the defects closed spontaneously (Table I 1 I).

Ten of these 11 children had repeated hemodynamic e\.aluation. In each patient the pulmonary blood flow fell, and although 2 patients still had flow ratios greater than 3/l, their pulmonary artery pressures I\-ere normal. Tile only children to increase pulmonary \zcular resistance I\-ere the I sllon-n to hax:e an intact septum at the

second study (Fig. 5, -4). Six patients developed progressive pul-

monary vascuhr ol)struction. ‘I’li ree prc- sented in failure in infancy, and 5 lvere undersized. ‘I‘hree had pansystolic slur- mm-s and thrills initially. The cardiotho-

racic ratios rmged from 57 to 6.5 per cent, and all had coml)ined \.entricular hypertrophy. ‘~I\-0 patients in \\.hom the pansystolic murmur and tllrill persisted she\\-ed a significant reduction in heart size and p~llmonar)- vascularity, and ECG progression to right ventricular hypertrophy. The? \\.ere operated on at 2 years, 4 months, and 3 years, 6 months, without prior catheterization. Studies in both, one year after surgical closure, showed the total pulmonary resistances to be X00 and 9.50 dynes per square meter, respectively. Another child, whose parents refused surgery, NY\S cyanosed by 5 years and had only a soft ejection murmur and palpable I’z. While the heart was smaller, and the vascularity reduced, the ECG still showed combined ventricular hypertrophy. The remaining 3 children \\-ere operated on at beta-een 15 and 27 months, on the basis of hemodynamic changes, Ivithout obvious change in clinical findings except a slight reduction in the heart size radiologically.

Fourteen patients had persistence of their large defects and because of symptoms 13 had surgical corrections between the ages of 15 months and 4 years. Seven patients presented in lleart failure and 9 had initial \\-eights below the third percentile. There \vas little or no change in the clinical, radiologic, or electrocardiographic findings up to the time of surgery, except that 4 children with short murmurs initially, developed the typical pansystolic murmur and thrill and one child showed an ECG change from combined to left ventricular hypertrophy (Table IIIj.

Thirteen of these patients were restudied before surgery. Five showed some reduction in pulmonary blood flow with a slight rise in vascular resistance. In the other patients the findings did not change (Fig. 5, B).

Group IT,-: P~S.@ow ratio > 2 : I; S/P re- sisfancc ratio <5 : 1. Of 39 children in this group, 2 lvere lost to follow-up, 4 died, and 5 required palliative surgery in infancy. Three children developed infundibular obstruction and one acquired aortic insufficiency.

Seven of the remaining 24 patients became asymptomatic in the first 5 years of life. Initially all had body weights below the tenth percentile for age, with 5 below the third percentile. Four children pre-

PBF l,tres/M*

PVR dynes/M2 800-r-l

YEARS

Fig. 1. Group II. Changes in pulmonary blood flow and vascular resistance in 13 of the patients who underwent surgical correction. (O = Group I I defect, P/S Flow Ratio >1:1, S/P Resistance Ratio > 7:l: n = Group IV defect, P/S Flow Ratio >2:1, S/P Resistance Ratio <5:1.)

l’nBle III. Irenfricular septnl defect. Present stzdy-Group III

iZuscultation PanSYI & thrill Pa11SYl Ejection SW1 No murmur

X-ray CT ratio 65-7076

60-6.5’;) %-SW/b so-SS(;;,

less than SO’, 0 ECG

RL’H CVH LVH Normal

11 (11) 6 (12)

0 (1) 2 (3) 0 (5) 1 (9 0 (0) 2 (0)

2 (6) 0 (0) 5 (9) 3 (9) 3 (4) J- (8) 1 (1) 3 (3) 0 (0) 1 (0)

1 (2) 0 (4) 7 (18) 0 (15) 3 (0) 6 (1) 0 (()) 5 (0)

There are 3i patients in Group III in infancy. 11 of whom were followed clinically for 5 years. Firrures in lmrentheses refer to those children operated on before the age of 5 years. The “follow-up” examination is tbat immediately ~*rior to surgery.

.\bbreviations as in Table I.

sented in heart failure and 2 others Lvere digitalized in the first year. The auscultatory findings in 6 were classical. Radiologi- cally, heart sizes were greater than 59 per cent of the transthoracic diameter in all patients and 6 had biventricular hypertrophy. By 5 years all showed accelerated growth. While the pansystolic murmur and

YEARS

Fig. 5, A and B. Group III. .A, The fall in p~~lmonary blood flow recorded in 10 patients who improved clinically while under supervision. (x = Group 1 defect; c = spontaneous closure.) B, Changes in pulmonary blood flow and vascular resistance in 12 patients prior to surgical correction. Permission for surgery had been refused in the one child with severe pulmonary vasclllar obstruction. l = Group II defect; n = Group IV defect.)

l’uble IV. ~~‘entriculnr septtrl defect. Present study-Group II’

Criteria Infancy F&w-up

Aztscultatiotl PanSiLl & thrill PanSRl Ejection SM No murmur

S-my CT ratio 65-709;,

60-65 7; .55-60$. SO-SS(,‘;,

EC’C; KVH CVH LVH Normal

6 (14) 4 (13) 0 (0) 0 (0) 1 (,3) 1 (3) 0 (0) 2 (1)

2 (3) 0 (3) 4 (10) 0 (8) 1 (4) 3 (5) 0 (()) 4 (1)

1 (3) 0 (7) 6 (14) 1 (10) 0 KY 2 (0) 0 (0) 4 (0)

There are 24 patients in Group IV in infancy. 7 of whom mere followed clinically for 5 years. Pigures in parenthrses refer to findings in children submitted for surgical correction before the age of 5 years. The followup findings are those recorded immediately before surgery.

Abbreviations as in Table I.

thrill persisted in 4 children, all showed a reduction in the heart size and ECG changes to either left ventricular Iiyper- trophy or normal (Table IV). In 2 children the defect closed spontaneously.

In 5 of these patients, repeat cardiac catheterization was performed. In 2 pa-

tients there was a significant reduction in total pulmonary vascular resistance associated with spontaneous closure (Fig. 6, A).

Six children developed progressive pul-

monary vascular obstruction. When first seen all had weights below the third percentile and 4 were in heart failure. Five had pansystolic murmurs and thrills. All had enlarged hearts with increased vascular markings radiologically. Three children had right ventricular hypertrophy on their initial ECG (Table IV). In one child, in whom surgery was refused, the shunt was reversed by 5 years of age. Clinically she was cyanosed and she had a palpable right ventricular heave and loud pulmonary com- ponent of the second heart sound without a murmur. Radiologically her heart was small, the right ventricle and main pulmonary artery \I-ere enlarged, and the pulmonary vessels showed peripheral “cut- off.” One child, in whom the murmur IX- came soft and short in association with a loud I’, and a reduction in heart size, had surgical closure at 2 years without further investigation. The postoperative reco\:ery was uneventful, but at a study 8 months later the total pulmonary vascular resistance was 1,140 dynes per square meter. She died 4 years later with severe pulmonary vascular disease. The other 4 children had surgical correction between 18 and 36

VSD in the first jive yeurs of life 701

PVR dynes/M2

PVR dynes/M2

1 2 3 4 5

Follow-up Years

Fig. 6, A and B. Group IV. A, Hemodynamic findings in 5 of 7 patients who improved clinically while under supervision. (x = Group I defect; c = spontaneous closure.) B, Hemodynamic findings in 12 patients, 11 of whom had surgical corrections attempted. (0 = Group II defect; q = Group IV defect.)

months, on the basis of hemodynamic changes, without obvious change in the clinical parameters (Fig. 6, B).

Eleven children had persistent large defects and because of symptoms 9 had surgical closure between the ages of 2 and 4 years. All but one child had weights below the third percentile at initial examination. Five presented in heart failure. All but two had pansystolic murmurs associated with a thrill. Cardiomegaly with pulmonary ple- thora was seen radiologically without excep- tion, as was combined ventricular hypertrophy. This clinical picture persisted un- changed until surgical intervention, although in 3 patients the ECG progressed from a combined pattern to right ventricular hypertrophy (Table IV).

Seven of these children had repeat hemodynamic evaluation. In one instance, there was a dramatic increase in flow associated with a fall in pulmonary vascular resistance. The other 6 children had a persistent high flow without change in resistance (Fig.

6, B). Group V: P/S.flow ratio <2:1; PA pres-

sure > 50 per cent systemic. Of the 11 patients in this group, one child died in heart failure at 2 months, and another died during surgical correction at 7 months. A third

child underwent surgical closure at 25 years.

Five of the remaining 8 children presented with heart failure and all received digoxin. All had a harsh pansystolic murmur associated with a thrill. The chest x-ray showed a cardiothoracic ratio greater than 60 per cent in 6 patients, and all had abnormal ECG’s (Table V).

Rlarked clinical improvement was noted in 4 patients on follow-up. They were asymptomatic after the first year, and stopped digoxin by the end of the second year. The heart size returned to normal as did the ECG. While 2 still have pansystolic murmurs and the associated thrill, the absence of a murmur in the other two sug- gests spontaneous closure-in one this has been proved by catheterization.

While the remaining 4 children are rela- tively asymptomatic, growth has been re- tarded (3 are in the tenth percentile), the murmurs persist, and the hearts are enlarged and hyperactive. Cardiac catheterization demonstrated in each an increase in the left-to-right shunt, with flow ratios ranging from 2.2 to 3.1 : 1. Pulmonary pressures have, however, fallen to normal levels, and there is a reduction in pulmonary xxs-

cular resistance (Fig. 7).

702 Collins et al.

Retrospective Study Prospective Study PBF hes/M2

PVR dynes/M2

YEARS

Fig. 7. Group V. Six of the 8 patients in this group followed for 5 years had repeat heart catheterization. I II 4 patients the fall in pulmonary vascular resistance (P VR) was associated with increased flow. I’HF = pulmonary blood fow.

Tuble 1:. I’entriculur sepal defect. Present study--Group 1’

il uscultation PanSYI & thrill PanSM No murmur

X-ray CT rrl tio 60-65 94

S-60’;,;, so-55(,‘b

E(‘G 1<\-I I CVH J,VH Normal

8 0 0

6 2 0

3 5 0 0

5

5 L

There are 8 patients in Group V in infancy. This table is a summary of findings when first examined in infancy and subwluently at 5 years of age.

.‘ibbreviations as in Table I.

Discussion

The children analyzed in this report n-et-e selected because of symptoms for cardiac assessment in the first year of life. Such selection precludes discussion of the natural history of this condition, Imt the results of such a study are of practical value to phy- simians \\.I10 treat children \vith cong:enital heart disease. C’omparison of the incidence of hemodynamic groups in 120 c~hildreu from this study (called “prospective study” in Fig. X), who survived infancy without surgery and who neither closed their defects

o-2 2-14 (years)

191 223 Patients 200 120

ITi<. 8. The hemodynamic group in 41-l children with isolated ventricular septal defects, catheterized between 1955 and 1961, compared with LOO infants in this prospective study. The 120 children in the 1 to 5 year age group are those children who survived infancy without surgery, excluding those with sl)ontaneolls closure or acquired infrlndibular stenosis.

spontaneously nor developed infundihlar stenosis, with 223 children over the age of 2 in a previous study’” (called “retrospective study” in Fig. 8) does suggest that the infants in this study reflect the clinical spec- trum normally seen in this condition. The louver incidence of (koup \’ patients can he explained hy the early surgery and younger age in this study.

The children in (koup I tend to ha\.e smaller hearts and a lower incidence of heart failure (20 per cent) than those in other groups, l)ut initial physical findings did not facilitate classification of indix-idual patients. There are changes, ho\\-ever, on

subsequent examinations which suggest ;I good prognosis. 111 particular, accelerated gro\\-th, a reduction in heart size, or an electrocardiographic evolution to left \-entricular hypertrophy correlate \vith a reduction in the size of the defect. Assessment of ultimate prognosis is facilitated by grouping the infants on the lwsis of pulmonary.- to-systemic flo\\- ratio. The patients 111 (;rollp I Ilxtl relati\-ely SIKIII defects rc- stric.ting tile size of tlJc> lrft-to-rigllt sllunt. ‘l’l~ere 1~;~s a furtller reduction in the sim of these defects and a LO per cwlt incidence of spontaneous c1osure iII the tirst 5 years of life. I;urtlier follo\v-up is necessary to deterlnine the ultinlate inciclcnce of closure,

but these children with persistent small defects have normal hearts functionally, radiologically, and electrocardiographically \vitll little increase in pulmonary blood flon-. The clinical course is that of a “maladie de Roger” defect.“”

There xvere 14 children with pulmonary vascular resistances greater than 400 dynes initially. This finding was not restricted to the l.ery young, as 6 of the children were o\w- 6 months of age at the time of study. The flow ratio nxs less than 2 to 1 in 11 patients, and while the remaining 3 were assigned to Group I\’ on the basis of flop- ratio, absolute values for pulmonary Mood flow iu each was less than 8 L. per minute per square meter. In these children the size of the defect was not reflected hy the pulmonary blood folv, as is illustrated by later findings in 12 patients. With a fall in resistance after infancy, 6 showed increased pulmonary blood flow, indicative of a large defect, while 6 had small defects, 3 of which closed. \Vhile the mechanism for the initially high pulmonary vascular resistance is not known, it could result from delayed resolution of the fetal vascular pattern in the lung. As none of the 6 patients with persistent large defects developed arteriolar damage, it is possible that delayed resolu- tiou of this fetal vascular pattern occasion- ally protects these patients from the Eisen- menger reaction. The smaller number of patients iu this group prevents a definite conclusion. Further olxer\ration is necessary to understand one patient whose defect closed spontaneously, yet at 5 years of age had a pulmonary xrascular resistance of 5X0 dynes per square meter.

Infants \vith a flow ratio greater than 2 to 1 lla\re a variable natural evolution. Some die in infancy, while others tend to close their defects; the majority, however, lla\-e persistence of their large defect and may de\-elop the Eisenmenger reaction’laZ5 of progressive pulmonary arteriolar obstruction. The actual mortality rate in these children uxs 7 per cent; I)ut as palliative surgery ~~1s undertaken only in au wucr- ,gc’llC\. _ , \\.llcu medical treatulent failed lo cwntrol heart failure, as marl>~ as 16 per c‘twt II~;I\ 1)~ at- risli of cl\,iug iu Llie tirsl >‘ear of life.

Approximately 75 per cent of the cliil- tlren sur\i\-ed infancy without surgery and

II Death in Infancy

PaIllative surgery

LARGE VSD

SMALL V 5 D

Fig. 9. The mortality rate and incidence of palliative surgery in infancy in those children who initially had flow ratios greater than 2 to 1. The shaded area represents those children who had a reduction in size of the defect. The interrupted lines indicate children with incomplete follow-up.

had regular assessments and repeat catheterization. The proportion of these children who reduced the size of their defect varied from 50 per cent in Group II to 2.5 per cent in Group IV (Fig. 9). Of the 45 children who underwent this change, 9 had com- pletely closed defects. This incidence of I’0 per cent spontaneous closure in those cliil- dren \\.I10 decrease the size of their defect is independent of hemodynamic grouping, and x-ery similar to the incidence of spontaneous closure in children who initially have a small or restrictive ventricular septal defect.

The large defect persisted in 70 patients, 60 per cent of those with a flow ratio greater than 2 to 1, n-110 sur\Gved infancy without surgery. This finding was proportionally more frequent in Group IV than in GrouD II (Fig. 9j. While half of these children llab no clinical or hemodynamic change up to the time of surgery, 22 per cent had an ele- vation in pulmonary vascular resistance indicative of the Eisenmenger reaction, and 19 per cent developed gradients at the right \,entricular le\-el, suggesting progressive 0l)struction to flow across the rig11 t ventricular outflow tract.

Comparison of those patients I\-ith persistent large defects \vllo do not damage their pulmonary arterioles \\-itli those \\‘I10 do rlla>. Ilelp elucidate the precipitating lacloi-s iI1 1lie llisemiienger reactiou. Cer- tainl~~ all cllildreu xv110 develop progressi\xs pulmonary arteriolar disease Ila\.e lo\v resistance and excessive pulmonary blood flow in infancy, but not all childreu xvitll

704 Cbllim ct al. Am. Hrart 3. h’ovember. 1972

these early findings develop this change. It was not possible to separate those with a reactive pulmonary vascular bed 011 the basis of clinical or hemodynamic finclings in infancy. Subsequent clinical ch:rnges tended to follow ratller than precede the early rise in vascular resistance, and it is felt that only repeat hemodynamic e\-aluation by 12 to 15 months of age will identify such children at a time when corrective surgery may prevent progression of‘ the x,ascular lesion. A more detailed comparison of these children will be presented later.

Summary

Two hundred consecutive infants with isolated ventricular septal defects were assessed clinically and l~emodynamically and then followed throughout the first 5 years of life. Those infants who had flow ratios less than 2 to 1 generally became asymptomatic because of diminution in size of the defect. Complete closure owurred spontaneously in 20 per cent.

The majority of infants had flow ratios greater than 2 :l and in these the n:ltural evolution varied. At least 15 per writ of these infants may die from their cardiac lesion in infancy. I Ioxvever, approximately 40 per cent of those ~+io survive will have closed defects, and 20 per cent of those who show this reduction in size will have spontaneously closed defects by 5 years of age. Those children in whom the large defect persists remain symptomatic and fail to thrive. There is little or no change in clinical, radiologic, or electrocardiographic findings up to the time of surgery, but hemodynamic reassessment indicates tllat at least 20 per cent of such children may develop progressive pulmonary arteriolar disease and that such changes, mllell they are going to occur, will be evident hemo- dynamically in the second year of life.

When all the children with flow ratios greater than 2 to 1 are considered, the mortality rate was 7 per cent; 9 pcxr cent required palliative surgery in infanq ; 6 per cent underwent spontaneous closure; and 10 per cent delreloped the Eisemnenger reaction.

The authors wish to express their appreciation to Drs. Fowler, Braudo, and Disenhouse, members of the department who allowed their patients to be included in this study. Many of the pediatricians on

the hospital staff referred patients for assessment. Residents and fellows, working in the department during the 7 year period of the study, assisted in clinical and hemodynamic evaluations. The com- parability of the hemodynamic data attests to the high standards maintained in the laboratory by nurses under supervision of Mrs. Janiss. The analysis was made easy by an efficient record room staff under the direction of Miss McLaughlin.

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REFERENCES

Evans, J. R., Rowe, K. D., and Keith, J. I).: Spontaneous closure of ventricular septal defect, Circulation 22:1044, 1960. Nadas, A. S.. Scott, L. I’., Hauck, A. J., and Rudolph, A. M.: Spontaneous functional closinc of veniricular sepia1 defects, N. Engl. J. Med: 264:309, 1961. Augustsson, YI. H., Arcilla, R. A., Bicoff, J. l’., Moncada, R., and Gasul, B. M.: Spontaneous functional closure of ventricular septal defects in fourteen children demonstrated by serial cardiac catheterisation and angiocardiography, Pediatrics 31:958, 1963. Hoffman, J. I. E., and Rudolph, A. M.: The natural history of ventricular septal defects in infancy, Am. J. Cardiol. 16:634, 1965. Mitchell, S. C., Berendes, II. R’., and Clark, I&‘. iLI.: The normal closure of the ventricular septum, AM. HEART J. 73:334, 1967. I*i, M. D., Collins, G., Disenhouse, R., and Keith, J. I>.: Spontaneous closure of ventricular septal defect, Can. Med. Assoc. J. 100:737, 1969. I,ucas, K. V., Adams, I’., r\nderson, R. C., Mavne. N. G.. Lillehei. C. \V.. and \‘arco. R. I..: The’na&tral history of isolatei ventricula; sept,ll defects, Circulation 24:1372, 1961. Stanton, ii. E., and Fyler, D. G.: The natur,ll history of pulnlonary hypertension in children with ventricular septal defects assessed by seri,ll right-heart catheterisation, Pediatrics 27:62.1, 1961. \Veidman, \V. H., Dushane, J. \V., and Kincaid, 0. R’.: Observation concerning progressive pulmonary vascular obstruction in children with ventricular septal defects, AhI. HEAKT J. 65:148, 1963. Auld, I’. A. >‘I., Johnson, A. L., Gibbons, J. E., and McGregor, M.: Changes in pulmonary vascular resistance in infants and children with left-to-right intracardiac shrlnts, Circulation 27:257, 1963. Kidd, L., Rose, V., Collins, G., and Keith, J. I>.: \‘entricular septal defect in infancy, Anr. HEAK,~ J. 69:1, 1965. Kidd, I,., Rose, \‘., Collins, G., and Keith, J. 11.: The hemodynamics in ventricular septal defect in childhood, Ax. HEART 1. 70:732, 1965. Ritter, D. G., Feldt, R. c., Weidman, 1%‘. H., and Dushane. 1. W.: Ventricular seutal defect, Suppl. III, &&lation 31 and 32:42’, 1965. Iverson, E., Linde, L. M., and Kegel, S.: The diagnosis of progressive pulmonary vascular disease in children with ventricular septal defects, J. Pediatr. 68:594, 1966.

15. Anderson, 12. A., Levy, 21. AI., Naeye, IZ. I,., and Tabakin, H. S.: Rapidly progressing pulmonary vascular obstructive disease: Association with ventricular septal defects during early childhood, Am. J. Cardiol. 19:854, 1967.

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19. I’lauth, \V. H., Braunwald, E., Rockoff, S. D., ?vIason, D. T., and Morrow, A. G.: \‘entricular septal defect and nortic regurgitation-Clinical, hemodynamic, and surgical considerations, .\m. J. Med. 39:582, 1965.

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ventricular septal defect: clinical and hemodynamic changes in the first five years of life

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