Incremental risk factors in hospital mortality rate after repair of ventricular septal defect

J THoRAc CARDIOVASC SURG 80:494-505, 1980

Incremental risk factors in hospital mortality rate after repair of ventricular septal defect A total (!l312 patients with single or multiple ventricular septal defects (VSD) with or without major associated lesions underwent surgical repair between 1967 and 1979. In the overall experience in patients without major associated defects. six hospital deaths (3.6%) occurred among 166 patients undergoing primary repair of single large VSDs. hut in the last 5 years. 0111' death (1.1 %) occurred among 94 patients. Among the 29 patients with multiple VSDs. nine deaths (31%) occurred. but only one (7%) among the 14 operated upon in the last 5 years. In both groups. young age was an incremental risk factorjor hospital death overall, but not in the last 5 years. Neither the location ofthe VSD nor the surgical approach were risk factors, Among 58 patients with major associated lesions and either single or multiple VSDs. 14 (24%) died after operation. In this subset. risk of hospital death did not decline during the 12 year period. and young age remained a significant incremental riskfactor throughout. Of 261 patients with a single VSD and without a straddling tricuspid valve, one (0.4%) developed complete heart block, as did two (4%) (!l47 patients with multiple VSDs. The decrease in hospital mortality rate with Time and the neutralization of young age and multiplicity of VSDs as important incremental risk factors resulted from improvements such as more precise preoperative diagnosis oflocation and number of VSDs and improved intraoperative and postoperative care. The incremental risk of major associated lesions. especially in the I'ery young and in Those with multiple VSDs. should be neutralized in the future by further research and development. However. in the meantime. management ill most subsets should be individualized.

Giulio Rizzoli, M.D.,* Eugene H. Blackstone, M.D., John W. Kirklin, M.D., Albert D. Pacifico, M.D., and Lionel M. Bargeron, Jr., M.D., Birmingham, Ala.

Although the risk of hospital death after repair of simple types of ventricular septal defect (VSD) in children and young adults became very low within 10 years of the start of open intracardiac surgery, I. 2 it remained higher in infants than in older children. In the 1970s the risk of repair of VSD in infants was reduced and today in a number of centers is low. :1-9 The factors responsible for the earlier higher risks in infants and for the recent improvements in results have not been fully determined. Complicated cases with major associated lesions or multiple VSDs still present important problems in treatment. Therefore, we undertook a study of our total experience with simple and complex cases of From the Departments of Surgery and Pediatrics, University of Alabama School of Medicine and Medical Center. Birmingham. Ala. Received for publication Jan. 18. 1980. Accepted for publication April 3. 1980. Address for reprints: John W. Kirklin, M.D., Department of Surgery, University Station, Birmingham, Ala. 35294. *Presently Assistant in Surgery, Instituto di Clinica Chirurgica Generale e Terapia Chirurgica, Padova , Italy.

494

VSD at the University of Alabama in Birmingham since Jan. 1, 1967. The purposes of the study were to identify the reasons for the improved results in recent years so that, by being cognizant of them, we could continue to obtain good results, and to determine the residual interacting variables or incremental risk factors which still increase the early risks of operation in some categories of patients. Their neutralization then can be made the subject of further research and study. Material and methods Patients. The case histories of all patients with surgically repaired VSDs and atrioventricular and ventriculo-arterial concordant connections, operated upon between January, 1967, and January, 1979, were reviewed, except those in whom the VSD was part of the tetralogy of Fallot or atrioventricular canal defect (Table I). For this study, only the 312 patients with "primary" VSD (that is, exclusive of the other subsets in Table I) are included. The 312 patients were divided into three groups, according to whether the VSD was small, large, or mul-

0022·5223/80/100494+12$01.2010 © 1980 The C. V. Mosby Co.

Volume 80 Number 4 October, 1980

Table I. Repair of VSDs * at VAB from 1967 to 1979 (n = 388)

Table III. Repair of "primary" VSD at VAB from 1967 to 1979 (n = 312)

Hospital deaths

Category "Primary" YSD YSD + Alt LLIPS + small or moderatesized YSD (without AI) Severe PS, infundibular and! or valvular + YSD (not TF)

No.

No.

312 42 27

30 0

7

I

9.6 0 4

I 3

I

%

43

70%CL

7.9%-11.7% 0%-5% 0.5%-12% 20%-68%

Legend: VSD, Ventricular septal defect. UAB, University of Alabama in

Birmingham.CL, Confidence limits. AI, Aortic insufficiency (prolapsed cusp without Al not included). LLIPS. Low-lying infundibular pulmonary stenosis. PS, Pulmonary stenosis. TF, Tetralogy of Fallot. *In hearts with concordant atrioventricular and ventriculo-arterial connections, without tetralogy of Fallot or atrioventricular canal. tThree of these had low-lying infundibular pulmonary stenosis.

Table II. Repair of "primary" VSDs at VAB (1967 to 1979) with and without major associated lesions or previous pulmonary artery banding (n = 312) Size or rype ofVSD

49 5

Incremental risks in VSD repair

Hospital deaths No.

No.

Small single YSD Large single YSD Multiple YSDs

46 219 47

3* 12 15

Totals

312

30

I

% 7 5.5 32 9.6

I

70%CL 3%-13% 3.9%-7.6% 24%-40% 7.9%-11.7%

For legend see Table I. *All had major associated defects.

Major associated lesions Subaortic stenosis Isolated PDA PAPYC Simultaneously repaired coarctation or interrupted arch Simultaneous repaired coarctation and PDA Simultaneous repaired coarctation and PDA; and congenital aortic stenosis Unrepaired coarctation Previously repaired coarctation or interrupted aortic arch Previously repaired coarctation with unrepaired recoarctati on Important mitral valve disease Straddling mitral valve; incompetent mitral valve with cleft Important mitral valve disease; PDA Tricuspid Incompetence, moderate or severe Hypoplastic RY; small tricuspid anulus Straddling tricuspid valve Unroofed coronary sinus Origin of RPA from ascending aorta Stenosis of upper trunk of RPA Stenosis at origin of RPA; stenosis at origin of upper trunk of RPA Long area of stenosis on LPA Absent LPA; PDA Mesoposition of the heart Situs inversus totalis Situs inversus totalis; PDA Dextrocardia; unrepaired coarctation Totals

tiple as defined previously!" (Table II). The single and multiple VSDs were categorized according to location. A number of associated cardiac lesions were present, and in 58 of the patients these either necessitated an important concomitant, preliminary, or subsequent surgical procedure or else they considerably complicated the repair of the VSD. These were termed major associated lesions, and in each individual case this designation was made without knowledge of the fate of the patient (Table III). Surgical methods. The operations were done by a variety of techniques, since the study covers a 12 year period. In general, cardiopulmonary bypass with moderate hypothermia was used prior to about 1971. Thereafter, surface cooling and cardiopulmonary bypass (since about 1976 surface cooling has been omitted) were used to induce profound hypothermia, and the operations were done under total circulatory arrest!' or during low-flow perfusion. Prior to about 1971, in-

No. ofpts.

No. of hospital deaths

I

0 4 0

2

1

2 5

o

2 18

2

o 4 I

3

1

o I

I 4 1 I

o o o o o

I I

o

2

I

o o o o I

I

58 14 (26%, CL 19%-34%)

Legend: PDA, Patent ductus arteriosus. PAPVC, Partial anomalous pul-

monary venous connection. RV, Right ventricle. RPA, Right pulmonary artery. LPA, Left pulmonary artery.

termittent aortic cross-clamping was used. Then we began to use more profound myocardial cooling and a single period of aortic cross-clamping. Since early 1977, cold cardioplegic myocardial preservation has been used." Postoperative care has evolved continuously since 1967, at which time intracardiac surgery in the infant was new to our institution. The protocols for care have been relatively stable since about 1975. Study methods. The hospital charts including the operative and postoperative notes were examined in detail for the patients operated upon since January, 1976, and all possibly important information including demographic data was extracted. The data extracted previously for use in our earlier publication 10 were used

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Table IV. Repair of "primary" VSD at UAR (1967 to 1979): Single large VSD, primary repair, without major associated lesions (n = 166) /974 to /979

Total

Hospital deaths

Hospital deaths Age (mo)

No.

< 3

14 12 23 21 27 69

~3<6 ~

~ ~ ~

6 < 12 12 < 24 24 < 48 48 Totals

% 8.4 7.2 13.9 12.7 16.3 41.6

No.

I

70% CL

3.6 6.9

No.

5%-31% 0%-15% 6%-25% 1%-15% 0%-7% 0%-3%

II 10 14 II 15 33

2.1%-5.8% 3.9%-11.5%)

94

14 0 13 5 0 0

2 0 3 I 0 0 6 5

166 (72

I

%

I

No.

%

%

1* 0 0 0 0 0

11.7 10.6 14.9 11.7 16.0 35.1

I

70%CL 1%-28% 0%-17% 0%-13% 0%-16% 0%-12% 0%-6%

9 0 0 0 0 0

0.1%-3.6%

1.1

Legend: The parentheses indicate the interval 1967 to 1974. The p value for the table (n = 166) = 0.01.

"A 1.2-month-oldbaby with preoperative seizures was admitted, sent to operation, intubated, and ventilated. The baby died on postoperativeday 3 with acute cardiac failure.

Table V. Repair of "primary" VSD at UAR (1967 to 1979): Single large VSD, primary repair, without major associated lesions (n = 166) Total

/974-/979

Hospital deaths Type

No.

No.

Perimembranous *

140 (62 10 7 7 2

6 5 0 0 0 0

166 (72

6 5

Subpulmonary A Y canal types Muscular Confluent Totals

I

I

Hospital deaths 70%CL

No.

4.3 8.1 0 0 0 0

2.5%-6.9% 4.5%-13.3%) 0%-17% 0%-24% 0%-24% 0%-61%

78

3.6 6.9

2.1%-5.8% 3.9%-11.5%)

94

%

9 4 I 2

No.

I

%

1.3 0 0 0 0

0 0 0 0 1.1

I

70%CL 0.2%-4.3% 0%-19% 0%-38% 0%-85% 0%-61% 0.1%-3.6%

Legend: The parentheses indicate the interval 1967 to 1974. AV, Atrioventricular.

"The p value for perimembranous versus all other VSDs = 0.40.

for patients operated upon before that date. The details of the events leading up to death and the preoperative and operative notes and autopsy findings (the last available in 20 of the 30 patients who died) were studied in the case of each nonsurvivor to determine the mode of death. Statistical analysis. We examined the relation of hospital death to a number of factors: demographic variables (age in months, body surface area in square meters, weight in kilograms, hematocrit value in percent, and date of operation expressed as number of months since Jan. 1, 1967); the anatomic situation at operation (small versus large VSD, multiplicity of VSDs, whether multiple, nontrabecular, or multiple trabecular [muscular], previous banding of the pulmo-

nary artery, and associated major lesions); and operative variables (surgical approach to the VSD, total ischemic time, and elapsed time on cardiopulmonary bypass). Preliminary data analysis included contingency table analysis of qualitative variables (the chi square statistic was used unless there were fewer than two events, in which case Fisher's exact test was used) and comparison of quantitative variables by means of the unpaired t test with respect to the event hospital death. Simple parametric and nonparametric rank correlation analyses were done with respect to hospital death. These indicated that separate, single, and multivariate logistic regression analyses!" be made in four groups of patients, those with and those without major associated lesions and, within these two groups, those

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Incremental risks in VSD repair

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Table VI. Repair of "primary" VSD at UAR (/967 to 1979): Single large VSD, primary repair, without major associated lesions (n = 166) 1974 to 1979

Total Hospital deaths Surgical approach

No.

No.

RA RA ....... RV RV

105 4 57

2 0 4

Totals

166

6

I

I

Hospital deaths 70% CL

No.

No.

1.9 0 7

0.6%-4.5% 0%-38% 4%-12%

65 2 27

1 0 0

3.6

2.1%-5.8%

94

%

1

1

%

Legend: RA, Right atrium. RV, Right ventricle. RA -+ RV, RA approach aborted to RV approach. The p value for the table (n

70% CL

1.5 0 0

0.2%-5.1% 0%-61% 0%-7%

1.1

0.1%-3.6%

=

166) = 0.23.

Table VII. Repair of "primary" VSD at UAR (1967 to 1979): Multiple VSDs, primary repair, without major associated defect (n = 29) 1974 to 1979

Total

Hospital deaths

Hospital deaths Age (rna) <3 2:3<6 2: 6 < 12 2: 12 < 24 2: 24 < 48 2: 48 Totals

I

I

70% CL

No.

No.

No.

I 4 5 7 5 7

0 2 1 3 3 0

0 50 20 43 60 0

0%-85% 18%-82% 3%-53% 20%-68% 29%-86% 0%-24%

1 2 3 4 I 3

29 (15

9

31 53

21%-42% 37%-69%)

14

8

%

Legend: The parentheses indicate the interval 1967to 1974. The p value for the table (n

with single and multiple YSDs. The information from these separate group analyses was used to make a final overall analysis. The logistic equation is In[P/(1 - P)] = Z Z = B; + !3,X t

+ ... + !3kXk

where In is the natural logarithm, P is the probability of hospital death, and Z has the form of a regression equation whereby the coefficients ({3i) translate the risk factor variables (Xi) to logit units; the more positive the the total logit units, the higher the degree of risk, and the more negative, the lesser the degree of risk. We estimated the coefficients by using a nonlinear logistic regression program. * Both stepwise forward and backward elimination algorithms were employed to *Available for the Statistical Analysis System from Frank Harrell, Ph.D., at Duke University, Durham, N. C.

=

29)

=

No. 0 0 0 I 0 0

I

%

I

70% CL

0 0 0 25 0 0

0%-85% 0%-61% 0%-47% 3%-63% 0%-85% 0%-47%

7

1%-22%

0.22.

identify risk factors, with a p value of 0.2 or less used as a criterion for inclusion. Confidence limits for the probability point were estimated by use of Z, the calculated variance of Z, and the 70% confidence limits of Z. These symmetrical logistic confidence limits were then transformed by the logistic equation to the asymmetrical confidence limits for the probabilities. 14 The statistical computations for these analyses were made by means of the Statistical Analysis System. * The logistic analysis was chosen in part because the probability of an event (here hospital death) is expressed as the additive effect of a number of variables with their appropriate coefficients and interaction terms. The resulting sigmoidal curve is consistent with our general clinical experience. IS These variables have been termed incremental risk factors (factors present *SAS User's Guide, SAS Institute Incorporated, Raleigh, N. C., 1979.

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Table VIII. Repair of "primary" VSD at UAR (1967 to 1979): multiple VSDs, primary repair, without major associated lesions (n = 29) 1974 to 1979

Total Hospital deaths Type

0 5

6 8

Nontrabecular* Nontrabecular + trabecular (I or 2)

I

No.

No.

%

I

0 62

Hospital deaths

70%CL

No.

0%-27% 83 38%0

%)9/23

No.

I

I

%

70%CL

2 3

0 I

0 33

0%-61% 4%-76%

0

0

0%-19%

7

1%-22%

39% CL27%-52%

Multiple (203) Trabecular (Swiss

15

4

27

14%-43%

9

29 (15

9 8

31 53

21%-42% 37%-69%)

14

cheesejt Totals

Legend: The parentheses indicate the interval 1967 to 1974. The p value for the table (n = 29) = 0.04. The p value for the table (n = 14) = 0.14.

"Two (rarely three) large single VSDs (e.g.• one perimembranous + one subpulmonary), none of which is trabecular.

t With or without a large nontrabecular VSD.

Table IX. Repair of "primary" VSD at UAR (1967 to 1979): Multiple VSDs, primary repair, without major associated lesions (n = 29) 1974 to 1979

Total Hospital deaths Surgical approach

No.

No.

RA RA -> RV RV LV

18 3 5 3

6 2

Totals

29

I

Hospital deaths

I

70% CL

No.

21%-48% 24%-96% 3%-53% 0%-47%

9 1

0

33 67 20 0

9

31

21%-42%

14

I

%

I

3

No.

I

%

I

70%CL

I

II

0 0 0

0 0 0

1%-33% 0%-85% 0%-85% 0%-47%

7

1%-22%

Legend: RA. Right atrium. RV. Right ventricle. LV. Left ventricle. RA ~ RA approach aborted to RV approach. The p value for the table (n = 29) = 0.33.

within the patient or associated with treatment which can be shown in risk-containing situations to increase the risk). No causative relations are implied. Rather, incremental risk factors increase the sensitivity to ever-present human errors and lack of scientific progress, the general causes for surgical failures. The logistic coefficients are presented ± I standard deviation. Proportions have been presented as percentage accompanied by asymmetrical 70% confidence limits, equivalent to ± I standard deviation.!" We t 7 previously have presented our reasons for selecting 70% confidence limits (rather than 90% or 50% ones) for proportional data which may be used in medical decision-making.

Results Overall hospital mortality rate. A total of 166 patients underwent primary repair of a single large VSD,

without major associated lesions, in the period 1967 to 1979, and hospital death occurred in six patients (3.6%). One hospital death (1.1%) occurred in the 94 patients of this group operated upon in the last 5 years (Table IV). Young age was associated with higher mortality rate in the overall group, but no such relation can be demonstrated in the 94 patients operated upon in the last 5 years. In the group of 166 patients, all deaths were in patients wtih perimembranous VSD, but the differences in mortality rate according to location of the defect were not significant (Table V). The surgical approach to the VSD was not related to hospital mortality rate (Table VI). Nine hospital deaths (31 %) occurred among the 29 patients undergoing primary repair of multiple VSDs without major associated lesions. One death (7%) occurred among the 14 operated upon in the last 5 year period (Table VII). The risk of operation was not sig-

Volume 80

Incremental risks in VSD repair

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October, 1980

Table XII. Repair of "primary" VSD at UAB from 1967 to 1979 (n = 312)

Table X. Repair of' 'primary" VSD at UAB from 1967 to 1979 (n = 312)* Hospital deaths Subgroup

No.

No·1

%

Single or multiple VSD without major associated lesion Single or multiple VSD with major associated lesion

254

16

6.3

58

14

Totals

312

30

I

70%CL

Mode of death

(n = 254)

4.7%-8.3%

Acute cardiac failure Severe pulmonary dysfunction Sudden death Neurologic death Transfusion reaction Bleeding

12,·2.3,4

18%-31%

24

9.6

7.9%-11.7%

"The p value for the table <0.0001.

Table XI. Repair of "primary" VSD at UAB from 1967 to 1979 (n = 312) Hospital deaths

I

I

Major associated lesion

No.

No.

Isolated PDA Simultaneous coarctation (or interrupted arch) repair Important mitral valve abnormality Others

18 4

4 3

22 75

12%-37% 37%-97%

8

2

25

9%-50%

34

8

24

16%-33%

Total patients

58

14

24

18%-31%

%

Without major associated lesions

70% CL

Legend: PDA, Patent ductus aneriosus.

nificantly affected by age. The location of the multiple VSDs was related to hospital mortality rate, with the presence of trabecular (muscular) VSDs increasing the risk (Table VIII). The surgical approach was not significantly related to hospital mortality rate (Table IX). The presence of major associated lesions significantly increased the risk of operation, 14 (24%) of 58 patients with these lesions dying in the hospital (Tables III and X). The highest mortality rate occurred when VSD repair was combined with simultaneous repair of coarctation or interrupted arch repair (Table XI). Among the 18 patients with associated patent ductus arteriosus, one (who lived) had multiple VSDs. The median age of the other 17 was 6 months, and the range was 1.2 to 471 months. The ages of the four who died were 1.3, 2.5, 3.3, and 6.0 months. Mode of hospital death. Among the 312 patients in the study group, 21 (70%) of the 30 hospital deaths were associated with acute cardiac failure (Table XII). Of the 30 deaths, 15 are now believed to be primarily the result of 19 management errors, 16 of which occurred in patients operated upon prior to 1974. Fifteen deaths are considered to be primarily the result of imcomplete scientific progress at the time the patient was

With major associated lesions (n = 58) 97

Total (n = 312)

21

4

I 2

Legend: Management errors (numbers of patients in parentheses) included: IExtubation without reintubation within a few hours of operation in seriously ill infants, 1968 (one), 1970 (one) 1972 (two). 2Undiagnosed and overlooked additional VSD, 1967 (two), 1968 (one), 1971 (one), 1972 (two), 1975 (one), 1978 (one). 3Severe pulmonary vascular disease, 1971 (one), 1972 (two). 'Despite heart block, no permanent pacing electrodes inserted at operation; patient died after rethoracotomy on postoperative day 12 for insertion of permanent pacing electrodes, 1971 (one). 'Clots in oxygenator and heat exchanger, clots in circle of Willis, 1971 (one). 'Patient given packed red blood cells of the wrong type, 1973 (one). "Self-extubauon without reintubation in the face of low cardiac output, 1975 (one). Other deaths are attributed to incomplete scientific progress. Special situations included: 'Death after prolonged ventilatory support 1972 (on postoperative day 25), 1977 (postoperative day 27). ·Hemorrhagic pulmonary edema with low left atrial pressure, 1978 (one). IOExsanguination when intracardiac monitoring devices pulled, 1978 (one).

cared for, and in some areas this incompleteness persists today. Multivariate analysis for incremental risk factors. Multivariate analysis showed no independent effect on hospital mortality rate (p > 0.20) of previous pulmonary artery banding, size of VSD if single, surgical approach to single or multiple VSDs, or elapsed time between start and end of cardiopulmonary bypass. Multivariate analysis with the logistic equation indicates that young age, multiple VSDs, and operative date early in the 12 year experience were incremental risk factors (Table XIII). Also, the significant interaction factor between date of operation and age (date of operation X In(age]) in the absence of major associated lesions indicates that, in operations done in the latter part of the experience, the incremental risk of young age becomes progressively less and is finally neutralized. Thus in operations done in the last few years of the experience, young age was no longer an incremental risk in patients with single or multiple VSDs without major associated lesions (Figs. I and 2). In the last few years, multiple VSD itself was only a weak

The Journal of

500

Rizzoli et al.

Thoracic and Cardiovascular Surgery

1.0 :I:

0.9

~

«

w 0.8

0

...J

0.7

a::

0.6

« ~

(f)

0

:I: I.L

0

>~

0.5 O.lf

:::i 0.3

m « m 0

0.2

0::

o,

0.1 0.0

0

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18

2lf

30

lf2

36

Slf

lf8

60

AGE (MONTHS) AT OPERATION Fig. 1. Nomogram of the logistic equation whose intercept and logit units are in Table XIII, where multiple ventricular septal defect is no (and its coefficient not used) and no major associated lesions were present. A. The date of operation is represented by contour lines.

O.lfO :I:

0.35

~

«

w

0

0.30

...J

« ~

a::

0.25

(f)

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END

>- 0.15

OF 1973 \

~

-,

:::i

m « m

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8:

0.05

-,

0

ENDOF'1978-

0.00

0

3

- __- __-_ -:_

6

9

12

=-_ =- _-::: _-= _-=- _-:. 15

18

- __-_

=-_ =-_=- __

21

24

AGE (MONTHS) AT OPERATION Fig. 1. Cont'd, B. Two dates of operation are shown, with the dashed lines representing the 70% confidence limits around the point estimate.

Volume 80

Incremental risks in VSD repair

Number 4

50 1

October, 1980

1.0 ::I:

0.9

...... « w 0.8

0

..J

«

......

a::

(J)

0.7 0.6

0

::I: lL.

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~

......

0.5 0.'1

:J 0.3 In

«

In 0

If

0.2

-

0.1

END OF 197e

AGE (MONTHS) AT OPERATION Fig. 2A. Nomogram of the logistic equation as in Fig. 1, but for patients with multiple ventricular septal defects.

1.0 ::I:

0.9

~

w 0.8

\

0

..J

~

a::

(J)

0

::I: lL.

\

0.7

""-

,

0.5

, END OF 1973 '

"-

0.'1

"-

...... :J 0.3 CD

« In 0

0:::

CL

,

0.6

0 ~

,

0.2 0.1 0.0

END OF 1978

a

----

------------

-----

3

6

9

-----

12

----- - - - - - - - - - - - 2'1 21 15 18

AGE (MONTHS) AT OPERATION Fig. 2B. For legend see Fig. 2A.

incremental risk factor (as is shown by the overlapping confidence limits for the late 1978 curves in Figs. IB and 2B; the p value for the mildly increased probability of hospital death with multiple VSDs is 0.19 at 3 months of age, 0.10 at 12 months, and 0.14 at 24 months). When major associated lesions accompanied

either single or multiple VSDs, the hospital mortality rate was not lower later in the experience, and young age and multiple VSDs continued to be important and significant incremental risk factors throughout the time course of the experience (Fig. 3). When the types of multiple VSDs and some of the

5 02

The Journal of Thoracic and Cardiovascular Surgery

Rizzoli et al.

1.0 I l-

-..

0.9

e::{

w 0.8

0

...J

0.7

a:

0.6

;:! (f)

.... .... -,

0

I

LL

0 ~

0.5

/

:J 0.3 CD

....

m 0.2 0

, ,SINGLE VSD -..

e::{

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MULTIPt.E

,

0.4

I-

....

....

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-,

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a... 0.1 0.0

---------=-"":--:_0

6

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18

21.1

30

36

1.12

48

60

AGE (MONTHS) AT OPERATION Fig. 3. Nomogram of the logistic equation as in Fig. I, but for patients with major associated lesions. VSD. Ventricular septal defect.

major associated lesions were identified separately in a more detailed multivariate analysis, no significant effect of type of multiple VSD was found (Table XIV). Isolated patent ductus arteriosus and simultaneously repaired coarctation were incremental risk factors, but of lesser magnitude than any other major associated lesion. Congenital mitral valve disease was the most important (coefficient = 3.7 logit units) incremental risk factor among the major associated lesions. Other interrelations. Twenty-five of the 312 patients had previously undergone pulmonary artery banding, sometimes associated with another procedure such as repair of coarctation. Among the 19 with no major associated lesion, one hospital death occurred, in a patient with multiple VSDs (5%, CL* 7% to 17%). Two hospital deaths (33%, CL 12% to 62%) occurred among the six patients with major associated lesions, and both had multiple VSDs. Patients with multiple VSDs were about the same age at the time of operation as were those with a single large VSD (median age 22 months versus 35 months, p = 0.23), but they were smaller in weight and body surface area (p = 0.10). Patients with major associated lesions were younger at operation than those without them (median age 18 months versus 42 months, *CL is confidence limits.

p = 0.003). The proportion of patients (58) with major associated lesions among the entire group (n = 312) was 18.6% (CL 16.3% to 21.1%), and this proportion was not significantly different among those with single small, single large, or multiple VSDs. Complete heart block was present at death or dismissal in three (1.1%, CL 0.5% to 2.3%) of 265 patients with single VSD with or without a major associated lesion, two of whom had straddling tricuspid valves. Two (50%, CL 18% to 82%) of four patients with straddling atrioventricular valves had heart block after repair. Thus, of 261 without straddling tricuspid valves, one (0.4%, CL 0.05% to 1.3%) had complete heart block. Two (4%, CL 1% to 10%) of 47 patients undergoing repair of multiple VSDs had complete heart block.

Discussion Some potential incremental risk factors were not evaluated in this study. Preoperative pulmonary vascular resistance was not considered, because in our previous study'" we had not seen a relation between it and hospital mortality rate. In part, this is because the levels of pulmonary vascular resistance which make surgical repair of VSD inadvisable are quite widely recognized, and few patients with this risk factor are operated upon. Elevation of pulmonary vascular resistance, particu-

Volume 80 Number 4 October. 1980

larly in older children, is clearly deleterious as regards long-term results. 10 Ratio of peak pressure in the right and left ventricles immediately after repair likewise was not studied, although a high postrepair ratio probably is related to mortality rate. In the current study, this seemed to us particularly to occur in patients with multiple VSDs and may reflect overlooked VSDs and residual shunting as much as residual pulmonary vascular disease. Long cardiac ischemic time. from aortic cross-clamping is probably an incremental risk factor, but it was not incorporated into the final analysis because interpretation of any relations would be difficult in view of the changing methods of myocardial preservation throughout the study period. When the VSD is single, no particular location is shown to be an incremental risk factor as regards hospital death. When a VSD in the inlet septum is associated with straddling tricuspid valve, repair is possible." but the risk of producing complete heart block by the operation has been high. No doubt this is due to the unusual position of the conduction system in such patients;" Now that this is known, avoidance of heart block may be possible more frequently. Multiple VSDs were an important incremental risk factor in the early part of the experience, but in simple analysis (Table VII) they cannot be shown to be so since 1974. The multivariate analysis (Figs. IBand 2B) suggests that, currently, multiple VSD is only a weak incremental risk factor. Our experience, as well as that recently reported by J. K. Kirklin and colleagues, 20 suggests that this improvement in results in large part is related to a higher proportion of repairs that are complete or nearly so and thus a higher proportion of patients with no or only small residual shunts. This can be attributed primarily to improved preoperative identification of multiplicity of VSDs by special cineangiographic techniques," but also to improving surgical methods and prompt reoperation for important residual shunts. We have not demonstrated that any given route of surgical approach is an incremental risk in repairing single VSDs. This is compatible with the reported excellent results obtained by others with either the right atrial or right ventricular approach. The right atrial approach is associated with a lower incidence postoperatively of right bundle branch block than is the right ventricular approach" Use of a left ventricular approach to some multiple VSDs did not seem to increase risk of hospital death and probably contributed to more complete repairs in this group of patients. 20. 23 Young age was an important incremental risk factor in the early part of our experience, but in both single and multiple VSDs without major associated lesions it

Incremental risks in VSD repair

50 3

Table XIII. Repair of "primary" VSD at VAB from 1967 to 1979 (n = 312, 30 deaths) Variable

Logistic coefficient ± SD *

Ln (age) -1.6 ± Multiple VSDs 2.4 ± If no major associated lesions: Date of operation -0.063 ± Date of operation x Ln (age) 0.010 ±

p

Value

0.36 0.55

p < 0.0001 P < 0.0001

0.0169 0.0050

p = 0.0002 p = 0.05

Legend: Intercept 3.9 ± 1.33 (p = 0.(03); if major associated lesions. subtract from intercept -2.1 ± 0.94 (p = 0.03). SD = standard deviation. *A table of the variance-covariance matrix is available upon request. which makes possible calculations of all predicted probabilities and their confidence limits.

Table XIV. Repair of "primary" VSD at VAB from 1967 to 1979 (n = 312, 30 deaths) Variable

Logistic coefficient ± SD *

Ln (age) -2.2 ± 0.47 Multiple VSDs (only non2.9 ± 1.20t trabecular) Multiple VSDs (all others) 2.2 ± O.60t If no major associated lesions: -0.08 ± 0.020 Date of operation Date of operation x Ln (age) 0.015 ± 0.0058 If major associated lesions: 3.7 ± 1.61 Mitral lesion 1.8 ± 1.12 Major associated lesions other than PDA or simultaneously repaired coarctation

p

Value p < 0.0001 = 0.02

P

p = 0.0003

p P

= =

0.0001 0.008

p = 0.02 P = 0.10

Legend: Intercept = 5.9 ± 1.68 (p = 0.0004); if major lesion, the intercept is adjusted by -4.1 ± 1.44 (p = 0.004). SD = standard deviation. *A table of the variance-covariance matrix is available upon request, which makes possible calculations of all predicted probabilities and their confidence limits.

t Not significantly different one from the other (p = 0.6).

was neutralized during the latter part of our experience (Tables IV and VII and in the late 1978 lines in Figs. IB and 2B). This information supports a continuing policy of primary repair, and not pulmonary artery banding, of large VSDs even in very young infants when signs or symptoms indicate the need for surgical intervention, and a policy of elective repair before 24 months of age. That the confidence limits around the point estimate of hospital mortality rate are broader in the first 3 months of life (Fig. 2B) indicates the wisdom still of deferring surgical treatment until 3 months of age or more unless operation is urgently indicated. The decrease in hospital mortality rate with time (that is, the negative correlation between date of operation and probability of hospital death, Tables XIII and XIV) is evident in patients with all types of VSDs

The Journal of

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Rizzoli et al.

Thoracic and Cardiovascular Surgery

without major associated anomalies. Open intracardiac surgery in the infant was essentially new to our institution in 1967, as it was to many institutions at that time. During the period covered by this study, preoperative, intraoperative, and early postoperative management protocols continuously changed and experience increased. The demonstrated decrease in fatal human errors (Table XII) is probably attributable to these factors. Another factor, scientific progress, has brought improved preoperative diagnostic accuracy and surgical techniques, particularly in multiple VSD; improved support techniques, such as profound hypothermia and total circulatory arrest 10; and improved methods of myocardial preservation." Despite the sensitivity of the very young infant and patients with multiple VSDs to any imperfections in treatment, these factors appear to have neutralized young age and multiplicity of VSDs as incremental risks. Major associated lesions continue in our experience to be important incremental risk factors (Table XIV). Thus they are sufficiently powerful as risk factors that they have not been suppressed by the factors just described. In this more sensitive group, young age and multiplicity of VSDs continue to be important and significant incremental risks (Fig. 3). The technical surgical methods are now available successfully to correct most of these associated lesions, but we believe that further improvement in intraoperative support techniques and myocardial preservation are required to improve the results in very young patients with these complex malformations. Until this scientific progress is made, we recommend modifications in the general plan of early primary repair for some of these infants. When coarctation is associated with large VSD, only the coarctation should be repaired. If the infant continues to have important heart failure postoperatively, to do poorly, then the VSD should be repaired. Usually, however, the infants do well after repair of the coarctation (or interrupted arch) alone.>' and either the VSD narrows spontaneously with the passage of time or else repair can be done later on an elective basis. We are aware of the favorable results of primary one-stage repair of both defects in four infants reported by Tiraboschi and colleagues. ": 26 However, only one patient was less than 3 months of age (2.5 months at repair), and two of the four were older than 6 months of age at the time of the one-stage repair. All had single VSD. We do not believe this experience is yet large enough to prove with reasonable certainty that the one-stage repair is advisable in the sick and very young infant in whom we have encountered the problem (three were less than 6 weeks of age and one was 4 months of age).

We are not sure why our experience indicated that an associated patent ductus arteriosus has been an incremental risk factor, because we did not have technical problems with its closure at the time of VSD repair by a technique we 27 have used for many years. We believe that the combination of patent ductus arteriosus and large VSD should be treated by primary one-stage repair in most infants because of the simplicity of the one-stage repair and because others have shown that good results can be obtained in this combination. 3 In most of the sick small infants with major associated defects, and especially in those in whom the VSD is multiple, management must be individualized. Until the incremental risk effect of young age in this particularly sensitive (high risk) group is neutralized by further research and development, our goal in these complex situations is the delaying of the intracardiac repair to 6 months of age or older when possible. Important contributions were made to this study by Dr. Edwin Bradley, Associate Professor of Biostatistics, University of Alabama in Birmingham, and we are indebted to him for these. We are also indebted to Ms. Sandy O'Brien for the graphics and editorial work. We appreciate being able to include in this study patients operated upon by our colleagues, Drs. R. B. Karp and N. T. Kouchoukos.

2

3

4

5

6

7

REFERENCES Lillehei CW, Cohen M, Warden HE, Ziegler NR, Varco RL: The results of direct vision closure of ventricular septal defects in eight patients by means of controlled cross circulation. Surg Gynecol Obstet 101:446-466, 1955 Cartmill TB, DuShane JW, McGoon DC, Kirklin JW: Results of repair of ventricular septal defects. J THORAC CARDIOVASC SURG 52:486-489, 1966 Barratt-Boyes BG, Neutze JM, Clarkson PM, Shardey GC, Brandt PWT: Repair of ventricular septal defect in the first two years of life using profound hypothermiacirculatory arrest techniques. Ann Surg 184:376-390, 1976 McNicholas K, de Leval M, Stark J, Taylor JFN, Macartney FJ: Surgical treatment of ventricular septal defect in infancy. Primary repair versus banding of pulmonary artery and later repair. Br Heart J 41: 133-138, 1979 Rein JG, Freed MD, Norwood WI, Castaneda AR: Early and late results of closure of ventricular septal defect in infancy. Ann Thorac Surg 24:19-26, 1977 Yacoub MH, Radley-Smith R, deGasperis C: Primary repair of large ventricular septal defects in the first year of life. G Ital Cardiol 8:827-831, 1978 Lincoln C, Jamieson S, Joseph M, Shinebourne E, Anderson RH: Transatrial repair of ventricular septal defects with reference to their anatomic classification. J THORAC CARDIOVASC SURG 74: 183-190, 1977

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8 Sigmann JM, Perry BL, Behrendt OM, Stern AM, Kirsh MM, Sloan HE: Ventricular septal defect. Results after repair in infancy. Am J Cardiol 39:66-71, 1977 9 McNicholas KW, Bowman FO Jr, Hayes CJ, Edie RN, Maim JR: Surgical management of ventricular septal defects in infants. J THORAC CARDlOVASC SURG 75:346353, 1978 10 Blackstone EH, Kirklin JW, Bradley EL, DuShane JW, Appelbaum A: Optimal age and results in repair of large ventricular septal defects. J THORAC CARDlOVASC SURG 72:661-679, 1976 II Barratt-Boyes BG, Simpson M, Neutze JM: Intra-cardiac surgery in neonates and infants using deep hypothermia with surface cooling and limited cardiopulmonary bypass. Circulation 43, 44:Suppl 1:25-30, 1971 12 Conti VR, Bertranou EG, Blackstone EH, Kirklin JW, Digerness SB: Cold cardioplegia versus hypothermia for myocardial protection. Randomized clinical study. J THORAC CARDlOVASC SURG 76:577-589, 1978 13 Walker SH, Duncan DB: Estimation of the probability of an event as a function of several independent variables. Biometrika 54:167-179, 1967 14 Ku HH: Notes on the use of the propagation of error formulas. J Res Nat Bureau Stand 70C:263-273, 1966 15 Kirklin JW: A letter to Helen. J THORAC CARDlOVASC SURG 78:643-654, 1979 16 Wallis WA, Roberts HV: Statistics. A New Approach, Brooklyn, N. Y., 1956, Free Press, pp 467-468 17 Blackstone EH, Kirklin JW, Pluth JR, Turner ME, Parr GVS: The performance of the Braunwald-Cutter aortic prosthetic valve. Ann Thorac Surg 23:302-318, 1977 18 Pacifico AD, Soto B, Bargeron LM Jr: Surgical treatment of straddling tricuspid valves. Circulation 60:655-664, 1979

19 Milo S, Ho SY, Macartney FJ, Wilkinson JL, Becker AE, Wenink ACG, de Groot ACG, Anderson RH: Straddling and overriding atrioventricular valves. Morphology and classification. Am J Cardiol 44: 1122-1134, 1979 20 Kirklin JK, Castaneda AR, Keane JF, Fellows KE, Norwood WI: Surgical management of multiple ventricular septal defects. J THORAC CARDlOVASC SURG 80:485-493, 1980 21 Bargeron LM Jr, Elliott LP, Soto B, Beam PR, Curry GC: Axial cineangiography in congenital heart disease. Section I. Circulation 56: 1075-1083, 1977 22 Hobbins SM, Izukawa T, Radford OJ, Williams WG, Trusler GA: Conduction disturbances after surgical correction of ventricular septal defect by the atrial approach. Br Heart J 41:289-292, 1979 23 Singh AK, de Leval MR, Stark J: Left ventriculotomy for closure of muscular ventricular septal defects. Ann Surg 186:577-580, 1977 24 Strafford MA, Hayes CG, Gritths SP, Hordof AJ, Edie RN, Bowman FO Jr, MaIm JR, Gersony WM: Management of the infant with coarctation of the aorta and ventricular septal defect (abst). Am J Cardiol 43:450, 1980 25 Tiraboschi R, Villani M, Bianchi T, Locatelli G, Vanini V, Crupi G, Parenzan L: Trattamento chirurgico del difetto interventricolare associato a coartazione aortica. G Ital Cardiol 8:811-820, 1978 26 Tiraboschi R, Alfieri 0, Carpentier A, Parenzan L: One stage correction of coarctation of the aorta associated with intracardiac defects in infancy. J Cardiovasc Surg 19: 1116, 1978 27 Kirklin JW, Silver AW: Technic of exposing the ductus arteriosus prior to establishing extracorporeal circulation. Mayo Clin Proc 33:423-425, 1958