Surgical Results and Protocols in theSpectrum of Tetralogy of Fallot

JOHN W. KIRKLIN, M.D., EUGENE H. BLACKSTONE, M.D., JAMES K. KIRKLIN, M.D.,ALBERT D. PACIFICO, M.D., JOSE ARAMENDI, M.D.,* LIONEL M. BARGERON, JR., M.D.

Between 1967 and July 1982, 1103 operations were performedfor the tetralogy of Fallot of all types with 116 (10.5%) hospitaldeaths. Eighty-eight hospital deaths (10.5%) occurred in the836 patients undergoing repair. The incremental risk factorsfor hospital death after repair include pulmonary arterial prob-lems (p = 0.0002), major associated cardiac anomalies (p< 0.0001), small size (young age) (p < 0.0001), and more thanone previous operation (p = 0.0004). Absent pulmonary valveis a risk factor (p = 0.04). In patients with pulmonary stenosis,the hospital mortality has decreased with time (p = 0.08), butthe incremental risk of a high hematocrit (p = 0.0003) and oftransannular patching (p = 0.05) has persisted. In the currentera, the risk of repair in patients with pulmonary stenosis isestimated to be 1.6% (70% confidence limits [CL] 0.7% to 3.5%)at age 5 years, and at age 12 months to be 4.1% (CL 2.7% to6.3%) without a transannular patch and 7.7% (CL 5.3% to11%) with one. When pulmonary atresia is present, the prob-ability of hospital death after repair when a valved extracardiacconduit is used is estimated to be lowest (5%; CL 2% to 8%)between 5½/2 and 16 years of age. No deaths occurred among53 patients with pulmonary stenosis receiving a primary pal-liative Blalock-Taussig or Gore-Tex shunt, and six deaths(12%) occurred in 51 patients with pulmonary atresia. Seriousinterim complications (sudden death, brain abscess) after theseshunts occurred in two (1.9%; CL 0.6% to 4.5%) of the patientsoperated on. No iatrogenic pulmonary arterial problems havebeen recognized. Protocols based on these results are pre-sented. Many of these selective recommendations may becomeunnecessary if the damaging effects of cardiopulmonary bypassare overcome by future research.

r HE TETRALOGY OF FALLOT includes a wide spectrumof anomalies, some with pulmonary stenosis and

some with pulmonary atresia, some with associated con-genital or iatrogenic anomalies of the right and left pul-monary arteries, and some with major associated cardiacanomalies. Many patients have had one or more pre-

Presented at the Annual Meeting of the American Surgical Asso-ciation, May 12-14, 1983, Boca Raton, Florida.

* Current address: Avda. Montevideo 11, 30, Durango-Viscaya,Spain.

Reprint requests: John W. Kirklin, M.D., Department of Surgery,University of Alabama in Birmingham, University Station, Bir-mingham, Alabama 35294.

Submitted for publication: May 16, 1983.

From the Departments of Surgery and Pediatrics, Universityof Alabama in Birmingham School of Medicine and the

Medical Center, Birmingham, Alabama and the AlabamaCongenital Heart Disease Diagnosis and Treatment Center

vious operations, which often impose their own addi-tional problems. Many treatment protocols and surgicalmethods have been applied to the management of pa-tients with the tetralogy.A 15'/2-year experience, the continuation of a previ-

ously reported I 1 -year experience, 1,2 has been analyzed,with emphasis on determining current results and riskfactors. On the basis of this, as well as data concerninglate results,3'4 modifications of a previously recom-mended treatment protocol are suggested.

Material and Methods

Material

1103 operations were performed on 967 patients fortetralogy of Fallot between 1967 and July 1982. Theoperative notes, all clinical and laboratory records anddocuments, and the autopsy findings when available,were reviewed. The anatomic findings were recatego-rized into current terminology from descriptions in theoperative notes, angiocardiographic reports, and autopsyfindings.

Methods

For this study, tetralogy of Fallot is considered to bea congenital cardiac anomaly characterized by a largeventricular septal defect (VSD) that is subaortic in po-sition, pulmonary stenosis or atresia with anterior andleftward deviation of the infundibular septum and itsparietal extension and of sufficient severity that there isright ventricular hypertrophy and similar left and rightventricular systolic pressures (PLV and PRV), and a vari-able amount of dextroposition of the aorta. When theaortic dextroposition was so extreme that 90% or more

0003-4932/83/0900/0251 $01.55 © J. B. Lippincott Company

251

252TABLE 1. Hospital Mortality after All Operations Performed for

Tetralogy of Fallot (UAB, 1967-July 1982)

Hospital Deaths

Operation N No. % CL (SO)

Repair 836 88 10.5 9.4-11.7Pulmonary stenosis 713 64 9.0 7.9-10.2Pulmonary atresia 123 24 20 16-24

Palliative operations 186 22 12 9-15"Manifolding" operations 4 0 0 0-38Banding of large A-P collateral 2 0 0 0-61Miscellaneous other operations

before repair 16 2 12 4-27Late orthotopic pulmonary

valve insertion 14 0 0 0-13Replacement of valved

extracardiac conduit 9 1 11 1-33Other operations late after

repair 36 3 8 4-16Original repair at UAB 23 2 9 3-19Original repair elsewhere 13 1 8 1-24

Total 1103 116 10.5 9.6-11.6

CL = 70% confidence limits, A-P = Aorto-pulmonary.

of the aorta was over the right ventricle, the diagnosiswas considered to be double outlet right ventricle.5 TheVSD was sometimes beneath both the pulmonary andaortic valve.6 Usually, the VSD was perimembranous,but sometimes a bar of muscle separated it from thetricuspid annulus.

If there was even a tiny opening between the rightventricle and pulmonary artery, pulmonary stenosisrather than atresia was considered to be present. In somepatients, pulmonary atresia was present at the time ofrepair, but an earlier cineangiographic study just beforeshunting showed the right ventricular outflow tract tobe patent although severely narrowed. Such patients arecategorized as having pulmonary stenosis at the time ofthe shunt and pulmonary atresia later.The major morphologic variants encountered are

shown in Appendix -Table 1. The major associatedcardiac anomalies are in Appendix 1 -Table 2, the as-sociated iatrogenic problems in Appendix 1-Table 3,and demographic and surgical variables in Appendix1 -Table 4. The minor associated lesions are shown inAppendix 2. For the purpose of this study, cases of te-tralogy of Fallot were considered "uncomplicated" ifpulmonary arterial problems (Appendix 1), major as-sociated cardiac anomalies (Appendix 1), more than 1previous operation, and the absent pulmonary valve syn-drome were not present.The technique of intracardiac repair was similar

throughout the period,7 except that since about 1979,a right atrial approach has been used frequently.89 Stan-dard hypothermic cardiopulmonary bypass (CPB) wasthe support technique, except for 150 patients in the

KIRKLIN AND OTHERS

years 1971 to 1978, in whom the repair was done com-pletely or in part during profoundly hypothermic totalcirculatory arrest, and 214 patients in whom a very lowflow (0.5 L- min-' m-2) was used during part or all ofthe repair (Appendix 1, Table 5). Intermittent aorticcross-clamping was used until about 1973, one periodof aortic cross-clamping after profoundly cooling theheart was used from 1973 to 1977,10 and since January1977, the cold cardioplegic method was used."" 2Between September 1, 1971, and mid- 1978, a protocol

of routine primary repair was practiced for patients withpulmonary stenosis. Beginning in 1979, as a result of aprevious study,'3 a selective protocol was adopted usingan initial palliative anastomotic operation in very youngpatients with pulmonary stenosis and the probable needofa transannular patch and in all patients with pulmonaryatresia, and subsequent repair at about age 3 years.Throughout most of the period, the end-to-side Bla-

lock-Taussig (B-T) shunt on the side opposite that oftheaortic arch'4 was the preferred method of palliation.Since about 1978, a Gore-Tex interposition shunt be-tween the undivided subclavian and pulmonary arter-ies'5"16 (usually on the side of the aortic arch) has beenthe preferred method of palliation for infants less thanabout 2 months of age. For the purposes of this study,these two procedures are referred to as "classical"shunts. Before about 1978, the Waterston shunt,'7 theLaks-Castaneda modification of the B-T shunt,'8 or atransannular patch without closure of the VSD'9 weresometimes selected for palliation.

All hospital deaths were reviewed to determine themodes and causes of death.

Every patient who received a "classical" shunt as theinitial operation was successfully traced for subsequentevents, including subsequent operations and death. Thedate of inquiry was December 31, 1982.

Data Analyses

In contrast to most previous studies, the analyses weremade of the entire morphologic spectrum of tetralogyof Fallot, rather than separately of various subsets. Like-wise, the analyses included all types of surgical inter-ventions.

Standard analytic methods were used. P values greaterthan 0.20 were considered to indicate insignificant dif-ferences unlikely to be confirmed in a larger sample.When the p value was less than or equal to 0.2, variableswere retained in the analysis in an attempt to avoid typeII errors, and the p values were used evidentially as wellas for hypothesis testing.20 Relations are considerednearly certainly true ones (likely to be present in aninfinitely large sample) when the p value is equal to orless than 0.05, probably true when between 0.05 and0.1, and possibly true when between 0.1 and 0.2.

Ann. Surg. * September 1983

TETRALOGY OF FALLOT 253TABLE 2. Hospital Mortality after Repair of Tetralogy ofFallot (1967-July 1982; n = 836; 88 Hospital Deaths)

Uncomplicated Pulmonary Arterial Major Associated More than One PreviousCases Problems Cardiac Anomalies Operation

Hospital Deaths Hospital Deaths Hospital Deaths Hospital Deaths

Category n No. % CL(%)* n No. % CL(%) n No. % CL(%) n No. % CL(%)

Tetralogy of Fallot(pulmonary stenosis)

Simple repair 399 15 3.8 2.8-5.0 21 3 14 6-27 26 4 15 8-26 20 3 15 7-28Transannular patchf 126 10 8 5-11 63 13 21 15-27 17 11 65 49-78 11 4 36 19-56Valved extracardiac conduitt 4 0 0 0-38 4 1 25 3-63 5 1 20 3-53Orthotopic pulmonary valvet 2 0 0 0-61 6 1 17 2-46

Tetralogy of Fallot(pulmonary atresia)

Simple repair 6 0 0 0-27 4 0 0 0-38 2 0 0 0-61Transannular patcht 10 0 0 0-17 18 3 17 7-31 1 0 0 0-85 8 3 38 17-62Valved extracardiac conduitt 24 1 4 0.5-13 35 11 31 23-41 7 2 29 10-55 5 0 0 0-32Orthotopic pulmonary valvet 1 0 0 0-85 3 2 67 24-96 4 2 50 18-82

Note: Only "Uncomplicated Cases" (cases exclusive ofthe other threecategories and without absent pulmonary valve) is an exclusive category.

A multivariate logistic regression analysis2' was madeof risk factors for hospital death after repair of tetralogyofFallot in all its variations (see Appendix 1 for variablesused in the analysis). A patient in whom a repair was

made but at that same operation the patch was perfo-rated or removed because ofa very high post-repair ratiobetween right ventricular and left ventricular systolicpressure (PRV/LV) is included nonetheless as having hada repair and a post-repair PRV/LV of 1 was used in theanalyses. There were three such cases in patients withpulmonary stenosis and 13 in those with pulmonaryatresia.

Analyses were also made of risk factors for hospitaldeath after a primary "classical" shunt. The variablesexamined are in Appendix 3.

Evident differences in hospital mortality are consid-ered to be present when the 70% confidence limits (CL)are no longer overlapping. At the exact point where theyseparate, the p value is generally less than 0.15 in logisticanalysis and less than 0.1 in binomial comparisons.Others may wish to use other confidence limits in de-fining evident differences and, therefore, these have beencalculated for important comparisons (Appendix 4).The details ofthe methodology used in comparing the

hospital mortality of primary repair with that of two-stage repair is given in Appendix 4.

Results

Overall Hospital Mortality

Many different kinds of operations were required forthe spectrum of the tetralogy of Fallot in the entire pe-riod of 1967 to July 1982, and overall the hospital mor-tality rate of these was 10.5% (Table 1).

* CL = 70% Confidence limits.t As part of the total repair.

Hospital Mortality After Repair

Over the entire 151/2 year period, 88 (10,5%; 70% CL9.4% to 11.7%) of 836 patients died in the hospital afterrepair. The mortality varied under varying circum-stances (Table 2).

TABLE 3. Incremental Risk Factors for Hospital Death after Repairof Tetralogy ofFallot (UAB, 1967-July 1982; n = 836;

88 Hospital Deaths)

LogisticIncremental Risk Factors Coefficient ± SD p Value

Presence of pulmonary arterialproblems 1.0 ± 0.32 0.002

More than 1 previous palliativeoperation 1.6 ± 0.44 0.0004

Size of PatientIf pulmonary stenosis (ln BSA) -1.2 ± 0.54 0.02

(ln BSA)2 1.1 ± 0.52 0.04If pulmonary atresia (In BSA)2 5.3 ± 1.79 0.003

If Pulmonary Stenosis:High hematocrit (1/hematocrit) -1.6 ± 0.45 0.0003Use of transannular patch 0.7 ± 0.34 0.05Early date of operation (years

since Jan. 1, 1967) -0.08 ± 0.046 0.08Absent pulmonary valve 1.6 ± 0.81 0.04Presence of major associated

cardiac anomaly 2.0 ± 0.43 <0.0001If Pulmonary Atresia:Use of valved extracardiac

conduit or orthotopicpulmonary valve 2.3 ± 0.82 0.006

High post-repair (OR)PRV/LV(PRV/LV)2 2.4 ± 0.74 0.001

InterceptsPulmonary stenosis: -0.25Pulmonary atresia: -6.5.

right ventricular systolic pressurePRV/LV~left ventricular systolic pressure

SD-standard deviation, BSA-body surface area (m2), ln-loga-rithm, OR-operating room.

VOl. 198.- NO. 3

2541.0

0.9

0.8

0.7

0.6

0.o

0.4

0.3

0.2

Pul0thHclNo19f

0.2 0.4

Age 3 mos 12 r

KIRKLIN AND OTHERS

monary Stenosiserwise Uncomplicated Case- 0.45Transannular PatchB2

p(Major Associated Cardiac Anomaly) < 0.000 1p(Body Surface Area) < 0.000 1

MAJOR ASSOCIATED CARDIAC ANOMALY

UNCOMPLICATED CASE

. .1- - ~~~~WN 6.i.6 0.8

mos 36 mos 5 years

1.010 years

1.2 1.4 1.1

Ann. Surg. * September 1983

FIG. 1. Nomogram from themultivariate equation (Ta-ble 3) demonstrating theshape ofthe relation ofbodysurface area (and age) andthe presence or absence ofa major associated cardiacanomaly to the probabilityof hospital death after therepair of tetralogy of Fallotwith pulmonary stenosis.The conditions of the plotare noted in the upper leftcorner (See Material andMethods for definition of"uncomplicated" case). Thehorizontal axis is body sur-face area, and the medianage ofpatients (in this study)of a given body surface areais indicated. The dashed linesenclose the 70% confidence

6 limits.

Body Surface Area (m2)

Incremental Risk Factors for Hospital Death after Re-pair (Table 3)

In all forms of the tetralogy, pulmonary arterial prob-lems (congenital and/or iatrogenic) have increased (ap-proximately doubled) the probability of hospital death(Appendix 1, Table 6 and Appendix 1, Table 7).The presence of major associated cardiac anomalies

has increased the risk of operation in patients with pul-

monary stenosis (Fig. 1 and Appendix 1, Table 2). Thisis also apparent from the contingency tables of the ex-

perience in the current era (Tables 4 and 5).A high hematocrit has been associated with an in-

creased probability of hospital death in patients withpulmonary stenosis (Table 6).

In all forms of the tetralogy, more than one palliativeoperation before the repair has been a risk factor.

In patients with pulmonary stenosis, small size (young

TABLE 4. Hospital Mortality after Repair (Primary or after a Single Previous Shunt) of "Uncomplicated" Tetralogy ofFallot with PulmonaryStenosis (see Material and Methods for definition), and after Classical Shunting Operations, in the Current Era (1979-July 1982)

Age (Months)

<6 6 < 12 12 < 24 >24 Total

Hospital Hospital Hospital Hospital HospitalDeaths Deaths Deaths Deaths Deaths

n No. n No. n No. n No. n No. % CL(%)

RepairSimple 4 0 10 0 55 1 69 1 1.4 0.2-4.9Transannular patch 4 0 15 1 19 1 5 0.7-17Other 1 0 1 0 0 0-85

Classical shunts 11 0 4 0 6 0 2 0 23 0 0 0-8

Total 11 0 8 0 20 0 73 2 112 2* 1.8 0.6-4.2

* One was age 28 years, Down's syndrome, institutionalized, NYHAClass IV, died p.o. day 32 with chronic pulmonary insufficiency; one

was 3 years of age and died of acute pulmonary insufficiency.CL = 70% confidence limits.

co-CCu.

0

0

0._

Co0I

%.00

I-

0~

2o

TETRALOGY OF FALLOT

age) has increased the probability of hospital death (Fig.1 and Table 6). Increased hospital mortality becomesevident (see Material and Methods for definition) as theage is reduced from 5 years (Table 6), where the risk ofrepair without a transannular patch is 1.1% (CL 0:7%to 1.9%) to 17 months, where the risk is 3.1% (CL 1.9%to 4.8%). In pulmonary atresia, the relations have beendifferent (Table 3). When a valved extracardiac conduitis used and the post-repair PRV/LV is 0.67, the risk iscurrently lowest (estimated to be 5%, CL 2% to 8%)when the patient size is between a body surface areaof 0.65 m2 (4'/2 years) and one of 1.5 m2 (±16 years)(Fig. 2).

In patients with pulmonary stenosis, the use ofa trans-annular patch in the repair has increased the probabilityof hospital death (Tables 3 and 6). Although this is asignificant association, it is a weak one, as can be seenfrom the overlapping confidence limits at any given pa-tient size (age) (Table 6).

Earlier date of operation has been a risk factor inpatients with pulmonary stenosis. This trend of decreas-ing risk with time is reflected in the low hospital mor-tality in the current era of 1979 to July 1982 (Table 4).The absent pulmonary valve syndrome, as part of the

tetralogy of Fallot, has been a risk factor (Table 3 andAppendix 1, Table 1).The use of a valved extracardiac conduit (or ortho-

topic pulmonary valve) has been associated with an in-creased probability of hospital death in patients withpulmonary atresia. This increased probability is evidentat all ages (Fig. 2).

High post-repair (operating room) PRV/Lv has been anincremental risk factor for hospital death (Fig. 3). Theincreased risk becomes evident when PRV/Lv exceedsabout 1.0 after simple, non-conduit repairs, and whenit exceeds about 0.8 after conduit repair.

255TABLE 5. Hospital Mortality after Repairfor Tetralogy ofFallot withPulmonaty Stenosis in the Current Era, 1979-July 1982. Only the

"Uncomplicated" Category is a Mutually Exclusive One

Hospital Deaths

Category n No. % CL* (%)

Uncomplicated 89 2 2.2 0.7-5.3Pulmonary arterial problems 22 3t 14 6-26Absent pulmonary valve 6 2t 33 12-62Major associated cardiac

anomalies 16 5§ 31 18-47Multiple VSDsll 4 2 50 18-82Complete A-V¶ canal

defect 11 3 27 12-47Others 1 0 0 0-85

More than one previouspalliative operation 6 2** 33 12-62

* CL = 70% Confidence limits.t One was 10 months old and two were 30 months old.t Ages were 7 days and 15 days.§ Ages were 8, 17, 17, 26, 30 months.11 VSD = Ventricular septal defect.¶ A-V = Atrioventricular.** Ages 17 and 69 months.

Hospital Mortality after Primary Classical ShuntingOperationsOver the entire 1 5'/2-year experience, 6 hospital deaths

(6%; CL 3% to 9%) occurred among 104 patients re-ceiving primary "classical" shunting operations (Table7) done by the Blalock-Taussig end-to-side method orby Gore-Tex interposition between the ipsilateral sub-clavian and pulmonary arteries. No deaths occurred inthe 53 patients with pulmonary stenosis, and six deathsoccurred among the 51 with pulmonary atresia.By multivariate analysis (Table 8), tetralogy with pul-

monary atresia (rather than stenosis) has been a riskfactor, as has been very young age (Fig. 4). The risksalso were less in the more recent experience (early dateof operation has been a risk factor).

TABLE 6. Specific Estimates of the Probability ofHospital Death after the Repair in 1982 of "Uncomplicated" Tetralogy of Fallotand Pulmonary Stenosis, Obtainedfrom the Multivariate Logistic Equation (Table 3)

Estimated Probability of Hospital Death

3 Months* 12 Months* 24 Months* 36 Months* 60 Months*Transannular

Hematocrit Patch P (%) CL (%) P (%) CL (%) P (%) CL (%) P (%) CL (%) P (%) CL (%)

0.45 No 16 10-24 4.1 2.7-6.3 2.4 1.5-3.8 1.8 1.1-2.9 1.1 0.7-1.9Yes 26 18-37 7.7 5.3-11 4.5 3.0-6.7 3.5 2.3-5.3 2.2 1.4-3.5

0.55 No 26 17-38 7.6 4.9-12 4.5 2.8-7.0 3.4 2.1-5.5 2.2 1.3-3.6Yes 41 29-53 14 9.7-19 8.3 5.7-12 6.5 4.3-9.6 4.1 2.6-6.4

* Age at repair, corresponding to median body surface areas (m2)of 0.27, 0.41, 0.50, 0.56, and 0.70.

P-probability expressed as per cent, CL = 70% confidence limits.

VOl. 198.- NO. 3

KIRKLIN AND OTHERS

PSsnalY AtrheeUncomplicated Case

Post Repair P- a 0.67NV/t'V

p(Repalr) u 0.000p(Body Surface Area) * 0.003

LVED EXTRACARDIAC CONDUIT

FIG. 2. Nomogram as in fig-ure 1, demonstrating theshape of the relation ofbodysurface area and the use of avalved extracardiac conduit(or orthotopic valve) to theprobability of hospital deathin patients with pulmonaryatresia.

12 mo 36 0mo 60 mos 7 years 10 years

Body Surface Area (m)

Interim Results after "Classical" Shunting Procedures(Table 9)

From 1967 to July 1982, early (<30 days after op-eration) non-fatal shunt closure occurred in seven (7%)

1.0

0.9

* 0.8S

a; 0.7

go.0X 0.50>, 0.4

3 0.3a-O 0.2

0.1

Pulmonary AtrealaUncomplicated Case

Body Surface Areaa 0. int

VALVED EXTRACARDIAC CONDUIT

SIMPLE REPAI

of 104 patients receiving primary Blalock-Taussig orGore-Tex interposition shunts. In the current era, withthe use of the Gore-Tex interposition shunts in verysmall babies, early shunt closures have not occurred.Late shunt closure occurred in three patients (3%) and

p(Condult) a 0.000

P(PV/LV Ma 0°°0

FIG. 3. Nomogram as in fig-ure 1, demonstrating theshape ofthe relation ofpost-repair PRV/LV in the operat-ing room and the type ofrepair to the probability ofhospital death after repair oftetralogy of Fallot with pul-monary atresia.

0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8

Post Repair (OR) PRV/LV

2561.0

0.9

a

;0.7

a 0.60X0.5

0)0 0O.430.3*.wO 0.2....WL

0.1'

Age

0.0 -0.2

Ann. Surg. * September 1983

Vol. 198 . No. 3 TETRALOGY OF FALLOT 257TABLE 7. Hospital Deaths after Primary Shunts for Tetralogy ofFallot (1967-July 1982, n = 141)

Pulmonary Stenosis Pulmonary Atresia Totals

Hospital Deaths Hospital Deaths Hospital Deaths

N n % CL (%) N n % CL(%) N n % CL (%)

Classical Blalock-Taussig shunt 44 0 0 0-4 40 4* 10 5-17 84 4 5 2-9Gore-Tex subclavian-PA shunt 9 0 0 0-19 11 2t 18 6-38 20 2 10 3-22

Total 53 0 0 0-4 51 6 12 7-18 104 6 6 3-9

Waterston anastomosis 17 4 24 12-39 6 2 33 12-62 23 6 26 16-39Palliative RV-PA connection 9 3 33 15-56

Transannular patch 2 1 50 7-93 6 2 33 12-62 8 3 38 17-62Valved conduit - - 1 0 0 0-85 1 0 0 0-85

Miscellaneous non-standard shuntsor revisions 1 0 0 0-85 4 0 0 0-38 5 0 0 0-32

Total 73* 5 7 4-11 68* 10 15 10-21 141 15 11 8-14

* Ages: I day, 3 days, 1.7 months, 3 months.t Ages: 2 days, 3 days.t In addition, one patient with pulmonary stenosis survived both

inadvertent left subclavian artery anastomosis to left pulmonary vein

required premature complete repair. Later shunting pro-

cedures were performed electively in seven patients withpulmonary atresia, as part of a staged approach to a

complex problem and not for closure of the originalshunt.Sudden death, without explanation or autopsy, oc-

curred 4 months after operation in one patient. Non-fatal brain abscess occurred in one patient with pul-monary stenosis. Gangrene of the hand occurred im-mediately after a classical Blalock-Taussig shunt in one

patient, requiring digital amputation. No iatrogenic pul-monary arterial problems secondary to the shunt havebeen identified.

Overall Hospital Mortality in the Current Era

Two deaths (1.8%) occurred among 112 operationsfor uncomplicated tetralogy of Fallot in the current era

of 1979 to July 1982 (Table 4). The risk ofhospital deathin uncomplicated cases with pulmonary stenosis selectedfor repair was 2.2% (CL 0.7% to 5.3%) (Tables 4 and 5).One death in a patient with a previously performed rightBlalock-Taussig shunt may have been caused by humanerror. At operation, the tented-up right pulmonary ar-

tery was misidentified as the subclavian artery and li-gated. This was recognized 18 hours later and the liga-ture removed and placed on the subclavian artery, butthe patient died with pulmonary insufficiency on post-operative day 3. The other death is described in the tablefootnote. There were no deaths from shunting in pa-tients with pulmonary stenosis.

and later complete repair, one patient with pulmonary atresia had Gore-Tex interposition graft inadvertently to A-P collateral artery, and diedafter central shunt I day later. CL = Confidence limits, PA = Pulmonaryartery, and RV-PA = Right ventricle to pulmonary artery.

In the more complex cases, the risk ofrepair remainedrelatively high in the current era (Table 5).

Data for Design ofa Protocol

A comparison is made (Fig. 5) of the hospital mor-

tality of 1) one-stage primary repair in 1982 of uncom-plicated tetralogy of Fallot with pulmonary stenosis atvarious patient sizes (age) with 2) the combined risk(4.6%; CL 3.2% to 6.8%) of the two-stage repair (seeAppendix 4 for definition and methodology). The 70%confidence limits of the risk of the two approaches are

non-overlapping in patients smaller than 0.34 m2 (youn-ger than about 6 months of age) when a transannularpatch is not used; and smaller than 0.38 m2 (youngerthan about 8 months of age) when a transannular patchis used (Appendix 4, Table 1). The p value for the dif-

TABLE 8. Incremental Risk Factors for Hospital Death after PrimaryBlalock-Taussig or Gore-Tex Interposition Shunting Operations,

1967-July 1982, for Tetralogy ofFallot with Pulmonary Stenosis, n= 53 (0 Deaths); for Tetralogy of Fallot with Pulmonary Atresia, n= 51 (six Deaths); andfor Tricuspid Atresia, n = 23 (One Death).

(See Appendix 3 for variables analyzed)

Incremental Risk Factor Logistic Coefficient ± SD* p Value

TFt with pulmonaryatresia 2.1 ± 1.22 0.09

Young age (In age) -0.7 ± 0.25 0.024Earlier date of operation

(years since 1/1/67) -0.28 ± 0.151 0.06

Intercept: -1.0.* SD = Standard deviation.t TF = Tetralogy of Fallot.

KIRKLIN AND OTHERS

1982

p(Pulmonary Atresia)= 0.09

p(Age)- 0.004

PULMONARY ATRESIA

t - \ - PULMONARY STENOSIS-------

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

2 4 6 8 10

FIG. 4. Nomogram from themultivariate equation (Ta-ble 8), demonstrating theshape of the relation of ageat operation and the pres-ence of pulmonary atresiato the probability ofhospitaldeath after primary Blalock-Taussig and Gore-Tex in-terposition shunts, whendate of operation is 1982.

12

Age (months)at Operation

ference at these ages is 0.07. The degree of uncertainty,in terms ofconfidence limits and p values, in concludingthat two-stage repair is safer than primary repair insmaller patients at various body surface area (ages) isdisplayed in Appendix 4, Table 1.The data for protocol design for complicated cases

and for tetralogy with pulmonary atresia are those pro-vided from the multivariate analysis (Table 3), used toidentify the time of lowest risk using current methods.

Discussion

Comments on the Study Methods

The study and comparisons are non-concurrent andnon-randomized, and the results must be interpretedwith this in mind. However, treatment was carried outby a sequence of formal protocols. In one, from 1967to 1972, a shunting procedure was done for patients withpulmonary stenosis or atresia less than 4 to 5 years old,

TABLE 9. Events other than Hospital Death after Primary Blalock-Taussig and Gore-Tex Interposition Shuntsfor Tetralogy of Fallot (1967-July 1982, n = 104)

Pulmonary Stenosis Pulmonary Atresia Total(n= 53) (n= 51) (n= 104)

Events No. % CL (%) No. % CL (%) No. % CL (%)

Early (<30 days) shunt closure, withsuccessful reoperation 4 8 4-13 3 6 3-11 7* 7 4-10

Premature repair because of shunt closure 2 4 1-9 1 2.0 0.3-6.5 3 2.9 1.3-5.7Later shunting operations 0 0 0-4 7t 14 9-21 7 7 4-10Sudden death it 1.9 0.2-6.3 0 0 0-4 1 1.0 0.1-3.2Brain abscess 1§ 1.9 0.2-6.3 0 0 0-4 1 1 0.1-3.2Gangrene of the hand IT 1.9 0.2-6.3 0 0 0-4 1 1 0.1-3.2Planned repair

Elsewhere 4 8 4-13 1 2.0 0.3-6.5 5 5 3-8UAB 32 60 52-68 16 31 24-39 48 46 41-52

* None have occurred since 1979; none had initial Gore-Tex in-terposition shunts; three were less than 30 days old.

t None for shunt closure.t Four months after operation, cause entirely unknown; date of

operation 1980.

§ Non-fatal; age 28 months at shunt in 1971; occurred 15 monthsafter operation.

1971.CL = 70% confidence limits.

2581.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0. 1

m0)a

._n0CI-

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*-E.0~D

D

co

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Ann. Surg. * September 1983

TETRALOGY OF FALLOT

1.0

FIG. 5. Nomogram demon-strating the shape of the re-lation of body surface area(and age) and the probabil-ity of hospital death afterprimary and 2-stage repairwithout a transannular patchof uncomplicated tetralogyof Fallot with pulmonarystenosis. The straight linewith its dashed 70% confi-dence limits represents 2-stage repair, the risk ofwhichvaries trivially with patientsize (age) at the time of theinitial shunting operation.The curving line representsthe risk of primary repair.(Definitions and details ofthe calculation are given inAppendix 4.) The body sur-face area (age) below whichthe 70% confidence limitsseparate is indicated by thevertical line labeled 70%o CL.

*z 0.9

c] 0.80) 0.

C 0.7

O 0.60

I

0.50

> 0.4

.

0.3

.0

0L- 0.2

0. 1

I259

Pulmonary StenosisUncomplicated CaseHct - 0.50

NO Transannular Patch

1982

O.* ~ If -1 -L L 1-1 1

0.20 0.25A 0.30

AGE I mo 3 mos 6 n

* I *_ *I I I I I I I I I -ZIl_L I I*

35 0.4 0.45ya 2 0.60 0.65 0 70

ios 1 year 2 years 3 years yars

Body Surface Area (m2 )

based upon an earlier study of the Mayo Clinic expe-rience."2 In the second protocol, used between 1972 and1979, virtually routine primary repair was done at what-ever age the patient with pulmonary stenosis presentedfor treatment, based upon the excellent results presentedby Barratt-Boyes et al.22 Results in this era were ex-

amined in detail in a previous study.'3 A third protocolwas used from 1979 to the present; in it, primary repairwas done for most patients with pulmonary stenosis inwhom use ofa transannular patch was not anticipated,23but otherwise in infants an initial shunt was done andrepair deferred to about 3 years of age. In the presentstudy, emphasis is placed on results in this current era.

Relation of the Results to other Reports

Near-routine primary repair of the tetralogy of Fallotwith pulmonary stenosis has given good results even inyoung infants in a few centers.22'24'25 Generally, insufficientdetails are given in reports of these experiences to cate-gorize patients morphologically as has been done in thecurrent study. However, Castaneda and Norwood reporta higher hospital mortality rate (10%) in the very young

(<1 month of age), with a progressive decrease as age

increases, to a mortality rate of 4.9% in patients over 1

year ofage25; the differences are not statistically significant.Arciniegas et al.2627 and many other groups report ex-

cellent results from a protocol of near-routine shunting

when operation is required in infancy and subsequentrepair at age 3 to 5 years.26'27 A selective protocol, withinitial palliative operations in infants under some con-

ditions and primary repair under others, has given ex-

cellent results for Starr et al.,28 Ebert et al.,29 Bender,30and others.

Excellent 10- and 20-year results in nearly all hospitalsurvivors have been reported from several centers,3'4emphasizing that the primary determinant of the long-term result is hospital mortality. A single classical pal-liative operation has not been shown adversely to affectlate result when the repair is completed by 3 to 5 years

of age. The studies of Wessel et al.3' and of Ebert32 dosuggest that use of a transannular patch may compro-

mise late functional results.

Implications of the Study as Regards Treatment Pro-tocols

The present study supports the idea of an increasedrisk of repair in the very young patient with uncompli-cated tetralogy of Fallot and pulmonary stenosis. How-ever, the study indicates that a probable difference (non-overlapping 70% confidence limits) in hospital mortalityafter primary and two-stage repair without a transan-nular patch is present only in patients less than 6 monthsof age (Fig. 5 and Appendix 4, Table 1), and in the case

of repair with a transannular patch-only in those less

Vol. 198 - No. 3

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260 KIRKLIN AND OTHERS Ann. Surg. September 1983

than 8 months of age (Appendix 4, Table 1). This sug-gests that a two-stage repair is indicated only when pa-tients are in need of operation before these ages, pro-viding the surgical group is experienced in open oper-ations in small infants. Groups desiring to practiceprimary repair, unless it is nearly certain (non-overlap-ping 95% confidence limits) that two-stage repair is safer,will do primary repair, according to these data, unlessthe infant is less than 2 to 4 months old (Appendix 4,Table 1). Those wishing to use two-stage repair, if it iseven "possibly safer" (non-overlapping 50% confidencelimits), will do primary repair only over the age of 8 to12 months (Appendix 4, Table 1).This current study indicates that a relatively high hos-

pital mortality follows repair in infancy of tetralogy withassociated pulmonary arterial problems or with majorassociated cardiac anomalies, and that it is lower whererepair is done at an older age. Therefore, an initial clas-sical shunting operation is advised for most patients inthis category, followed by repair at 3 to 5 years of age.In the case of associated pulmonary arterial problems,the initial shunting procedure may also have the favor-able effect of enlarging the pulmonary arteries.

There is no indication that the high risk of repair withorthotopic pulmonary valve insertion in the criticallyill small infant with tetralogy and the absent pulmonaryvalve syndrome has declined in the current era. There-fore, a protocol of simultaneous Gore-Tex interpositionshunting and main pulmonary artery ligation (with laterrepair) is currently recommended.

Since the hospital mortality following repair of an un-complicated case of tetralogy of Fallot with pulmonaryatresia with a valved extracardiac conduit varies accordingto the size (age) of the patient (Table 3 and Fig. 2) therepair, when possible, should be done at about 5 to 10years of age. This age is also advantageous in that anadult-sized homograft valved conduit can be used. Whensymptoms, cyanosis, and polycythemia require operationin infancy or early childhood, an anastomotic operationis recommended, and repair is deferred until near theoptimal age.The situation is less stringent when the repair of te-

tralogy of Fallot with pulmonary atresia requires simplyan infundibular resection and/or the insertion ofa trans-annular patch (Table 3 and Fig. 3). When the case isotherwise uncomplicated, the protocol for tetralogy ofFallot with pulmonary stenosis is recommended.

Possible Mechanisms Underlying Some ofthe Risk Fac-tors

Pulmonary arterial problems not only tend to resultin high post-repair PRV/LV, but also to produce under-

perfusion of some parts of the lung and probably over-perfusion of other parts. These combined effects en-hance the probability ofimpaired function ofthe cardiacand pulmonary subsystems early after operation.The incremental risks of small size (young age) of the

patient are probably the result ofthe increased sensitivityof small patients to the damaging effects of cardiopul-monary bypass (CPB), demonstrated in a previousstudy.33 Neither in the previous study nor in this te-tralogy experience did the use of profoundly hypother-mic total circulatory arrest lessen the risk of hospitaldeath or morbidity, and thus presumably it did not re-duce the damaging effects of the CPB that was used forthe induction and reversal ofthe profound hypothermia.In some operations on acyanotic patients, the incre-mental risk of young age has been neutralized,34'35 andin time with better understanding of the phenomenainvolved, this should happen in tetralogy of Fallot aswell.The incremental risk of high hematocrit is probably

related to its correlation with and reflection of arterialhypoxia, and its widespread chronic effects. Deeply cy-anotic patients have a strong tendency to develop pul-monary hemorrhage and edema early after the construc-tion of a systemic-pulmonary artery shunt,36 and theyalso, more than acyanotic patients, tend to develop pleuraland peritoneal effusions immediately after CPB. Theircapillary permeability may be chronically greater thannormal, and they do have abnormalities of their clottingmechanisms. All this may increase the sensitivity ofdeeplycyanotic patients to the damaging effects of CPB andaccount for high hematocrit being an incremental risk.Surgical groups with a small experience managing patientswith tetralogy of Fallot, may elect at times to do a classicalshunting operation for even older children with the te-tralogy and severe polycythemia. Six to 12 months later,the hematocrit should be lower, and the risk of repairshould be less.

AcknowledgementsThe authors thank Mr. Rob Brown for his contributions to all as-

pects of the data collection and analysis, Mr. William Tracy and Ms.Sandy O'Brien for their work on the graphics, and Ms. Nancy Fergusonfor her work with the manuscript. Dr. Edwin Bradley, Department ofBiostatistics and Biomathematics, provided statistical advice and con-sultation.

References1. Kirklin JW, Payne WS, Theye RA, DuShane JW. Factors affecting

survival after open operation for tetralogy of Fallot. Ann Surg1960; 152:485-493.

2. Kirklin JW, Wallace RB, McGoon DC, DuShane JW. Early andlate results after intracardiac repair of tetralogy of Fallot. 5-year review of 337 patients. Ann Surg 1965; 162:578-589.

Vol. 198 - No. 3 TETRALOGY OF FALLOT 2613. Fuster V, McGoon DC, Kennedy MA, et al. Long-term evaluation

(12 to 22 years) of open heart surgery for tetralogy of Fallot.Am J Cardiol 1980; 46:635-642.

4. Katz NM, Blackstone EH, Kirklin JW, et al. Late survival andsymptoms after repair of tetralogy of Fallot. Circulation 1982;65:403-410.

5. Piccoli G, Pacifico AD, Kirklin JW, et al. Changing results andconcepts in the surgical treatment ofdouble outlet right ventricle.Am J Cardiol, September 1983.

6. Neirotti R, Galindez E, Kreutzer G, et al. Tetralogy of Fallot withsubpulmonary ventricular septal defect. Ann Thoracic Surg1978; 25:51-56.

7. Pacifico AD, Kirklin JW, Blackstone EH. Surgical managementof pulmonary stenosis in tetralogy of Fallot. J Thorac Car-diovasc Surg 1977; 74:382-395.

8. Edmunds LH Jr, Saxena NC, Friedman S, et al. Transatrial repairof tetralogy of Fallot. Surgery 1976; 80:681-688.

9. Hudspeth AS, Cordell AR, Johnston FR. Transatrial approach tototal correction of tetralogy of Fallot. Ciculation 1963; 27:796-800.

10. Sapsford RN, Blackstone EH, Kirklin JW, et al. Coronary per-fusion versus cold ischemic arrest during aortic valve surgery.A randomized study. Circulation 1974; 49:1190-1199.

11. Follette D, Fay K, Mulder D, et al. Prolonged safe aortic clampingby combining membrane stabilization, multidose cardioplegia,and appropriate pH reperfusion. J Thorac Cardiovasc Surg1977; 74:682-694.

12. Conti VR, Bertranou EG, Blackstone EH, et al. Cold cardioplegiaversus hypothermia for myocardial protection. J Thorac Car-diovasc Surg 1978; 76:577-589.

13. Kirklin JW, Blackstone EH, Pacifico AD, et al. Routine primaryrepair vs. two-stage repair of tetralogy of Fallot. Circulation1979; 60:373-386.

14. Blalock A, Taussig HB. The surgical treatment of malformationsofthe heart in which there is pulmonary stenosis or pulmonaryatresia. JAMA 1945; 128:189-202.

15. Klinner W, Pasini M, Schaudig A. Anastomose zwichen Systemund Lungenarterie mit hilfe von Kunststoffprothesen bei cy-anotischen Herzvitien. Thoraxchirurgie 1962; 10:68-75.

16. de Leval MR, McKay R, Jones M, et al. Modified Blalock-Taussigshunt. J Thorac Cardiovasc Surg 1981; 81:112-119.

17. Waterson DJ. Treatment of Fallot's tetralogy in children under1 year of age. Rozhl 1962; 41:181-187.

18. Laks H, Castaneda AR. Subclavian arterioplasty for the ipsilateralBlalock-Taussig shunt. Ann Thorac Surg 1975; 19:319-321.

19. Piehler JM, Danielson GK, McGoon DC, et al. Management ofpulmonary atresia with ventricular septal defect and hypo-plastic pulmonary arteries by right ventricular outflow con-struction. J Thorac Cardiovasc Surg 1980; 80:552-567.

20. Kempthorne 0. Of what use are tests of significance and tests ofhypothesis. Commun Statist 1976; 5:763-777.

21. Walker SH, Duncan DB. Estimation of the probability ofan eventas a function of several independent variables. Biometrika1967; 54:167-179.

22. Barratt-Boyes BG, Neutze JM. Primary repair oftetralogy ofFallotin infancy using profound hypothermia with circulatory arrestand limited cardiopulmonary bypass: a comparison with con-ventional two-stage management. Ann Surg 1973; 178:406-411.

23. Blackstone EH, Kirklin JW, Bertranou EG, et al. Preoperativeprediction from cineangiograms of postrepair right ventricularpressure in tetralogy of Fallot. J Thorac Cardiovasc Surg 1979;78:542-552.

24. Castaneda AR, Freed MD, Williams RG, Norwood WI. Repairoftetralogy ofFallot in infancy. Early and late results. J ThoracCardiovasc Surg 1977; 74:372-381.

25. Castaneda AR, Norwood WI. Fallot's tetralogy. In Stark J, deLeval M, eds. Surgery for Congenital Heart Defects. London:Grune & Stratton, 1983; 321-329.

26. Arciniegas E, Farooki ZQ, Hakimi M, Green EW. Results oftwo-stage surgical treatment of tetralogy of Fallot. J Thorac Car-diovasc Surg 1980; 79:876-883.

27. Arciniegas E, Farooki ZQ, Hakimi M, et al. Early and late resultsof total correction of tetralogy of Fallot. J Thorac CardiovascSurg 1980; 80:770-778.

28. Starr A, Bonchek LI, Sunderland CO. Total correction oftetralogyof Fallot in infancy. J Thorac Cardiovasc Surg 1973; 65:45-57.

29. Tucker WY, Turley K, Ullyot DJ, Ebert PA. Management ofsymptomatic tetralogy ofFallot in the first year of life. J ThoracCardiovasc Surg 1979; 78:494-501.

30. Bender HW Jr, Fisher RD, Conkle DM, et al. Selective operativetreatment for tetralogy of Fallot: rationale and results. AnnSurg 1976; 183:685-690.

31. Wessel HU, Cunningham WJ, Paul MH, et al. Exercise perfor-mance in tetralogy of Fallot after intracardiac repair. J ThoracCardiovasc Surg 1980; 80:582-593.

32. Ebert PA. Second operations for pulmonary stenosis or insuffi-ciency after repair of tetralogy of Fallot. Am J Cardiol 1982;50:637-640.

33. Kirklin JK, Westaby S, Blackstone EH, et al. Complement andthe damaging effects of cardiopulmonary bypass. J ThoracCardiovasc Surg, in press.

34. Rizzoli G, Blackstone EH, Kirklin JW, et al. Incremental riskfactors in hospital mortality rate after repair of ventricular sep-tal defect. J Thorac Cardiovasc Surg 1980; 80:494-505.

35. Stui*r M, Blackstone EH, Kirklin JW, et al. Determinants ofearly and late results of repair of atrioventricular septal (canal)defects. J Thorac Cardiovasc Surg 1982; 84:523-542.

36. Ferencz C. The pulmonary vascular bed in tetralogy of Fallot. II.Changes following a systemic-pulmonary arterial anastomosis.Bull Johns Hopkins Hosp 1960; 106:100-118.

Appendix 1

Factors examined in the multivariate analysis for incre-mental risk factors for hospital death after repair of tetralogyof Fallot were:

1) Morphologic variants examined are in Appendix 1, Ta-ble 1.

2) Major associated cardiac anomalies are in Appendix 1,Table 2. They were analyzed separately initially, but many ofthe subsets had the same coefficients, and others had 0% or

100% events, so that the final analysis contained only the term"major associated cardiac anomaly, yes-no."

3) Iatrogenic cardiac conditions examined are in Appendix1, Table 3.

4) Other continuous variables examined are in Appendix1, Table 4.

5) Surgical variables examined are in Appendix 1, Table 5.6) Congenital pulmonary arterial anomalies (Appendix 1,

Table 6) and iatrogenic pulmonary arterial problems were co-alesced into pulmonary arterial problems (Appendix 1, Table7) in the final analysis.

262

TABLE I (APPENDIX 1). Morphologic Variants in Patients Undergoing Repair of Tetralogy ofFallot (UAB 1967-July 1982)

Pulmonary Stenosis Pulmonary Atresia Total(n = 713) (n = 123) (n = 836)

Hospital Hospital HospitalDeaths Deaths Deaths

Variants n % of 713 No. % n % of 123 No. % n % of 836 No. %

Pulmonary stenosis:Low lying infundibular

stenosis 3 1 4.3 1 3 - - - - 3 1 3.7 1 3Others (infundibular

valvar, annular,supravalvar) 682 95.7 63 9.2 - - - - 682 81.6 63 9.2

Pulmonary Atresia*Infundibular 15 12 0 0 15 1.8 0 0Valvar - - 43 35 8 19 43 5.1 8 19Atresia of main pulmonary

artery - - 65 53 16 25 65 7.8 16 25Absent pulmonary valve* 22 3.1 5 23 - - 22 2.6 5 23Congenital pulmonary arterial

anomalies (see Appendix1, Table 6)

Large aorto-pulmonarycollateral arteries 11 1.5 2 18 59 48 13 22 70 8.4 15 21

* Mutually exclusive categories.

TABLE 2. (APPENDIX 1): Major Associated Cardiac Anomalies in Patients Undergoing Repair of Tetralogy ofFallot (UAB, 1967-July 1982)

Pulmonary Stenosis Pulmonary Atresia Total(n = 713) (n = 123) (n = 836)

Hospital Hospital HospitalDeaths Deaths Deaths

Major Associated CardiacAnomaly n % of 713 No. % n % of 123 No. % n % of 836 No. %

Multiple VSDs* 20 2.8 8 40 2 1.6 0 0 22 2.6 8 36Complete A-V canal defect* 20 2.8 7 35 0 0 - 20 2.4 7 35Patent ductus arteriosus 29 4.1 6 21 18 15 4 22 47 5.6 10 21Anomalous origin of LCAfromPA* 1 0.14 0 0 0 0 1 0.12 0 0

Aortico-pulmonary window* 2 0.28 0 0 0 0 - 2 0.24 0 0Coronary-pulmonary artery

fistula* 0 - 0 4 3.3 1 25 4 0.5 1 25Subaortic stenosis* 3 0.4 2 67 0 0 3 0.4 2 67Moderate or severe aortic

incompetence* 0 - 0 - 2 1.6 1 50 2 0.24 1 50Partial anomalous

pulmonary venousconnection 7 1.0 0 0 2 1.6 1 50 9 1.1 1 11

Total anomalous pulmonaryvenous connection* 1 0.14 1 100 0 0 - 1 0.12 1 100

Unroofed coronary sinus 2 0.28 1 50 0 - 0 2 0.24 1 50Straddling tricuspid valve 3 0.4 0 0 0 0 3 0.4 0 0Smal tricuspid valve ring 2 0.28 0 0 0 0 - 2 0.24 0 0Severe tricuspid

incompetence 2 0.28 1 50 2 1.6 0 0 4 0.5 1 25Mitral stenosis 1 0.14 0 0 0 0 - 1 0.12 0 0Dextrocardia* 6 0.8 2 33 0 0 - 6 0.7 2 33Situs ambiguus* 2 0.28 1 50 0 0 - 2 0.24 1 50Situs inversus totalis* 2 0.28 0 0 0 0 - 2 0.12 0 0Ebstein's malformation 1 0.14 0 0 0 0 - 1 0.12 0 0

* Included together in multivariate analysis as "major associated VSD-ventricular septal defect; A-V-atrioventricular; LCA-leftcardiac anomalies." coronary artery; PA-pulmonary artery.

KIRKLIN AND OTHERS Ann. Surg. - September 1983

vol. 1198 No.3 TETRALOGY OF FALLOT i

TABLE 3 (APPENDIX 1). Iatrogenic Cardiac Conditions in Patients Undergoing Repair of Tetralogy ofFallot (UAB, 1967-July 1982)263

Pulmonary Stenosis (n = 713) Pulmonary Atresia Total (n = 836)(n = 123)

Hospital Hospital HospitalDeaths* Deaths* Deaths*

Iatrogenic Cardiac Conditions Presentat Repair n %of 713 No. % n % of 123 No. % n % of 836 No. %

Classical shunt (single B-T or Gore-Tex Interposition shunt) 169 23.7 11 6.5 29 24 3 10 198 23.7 14 7.1

Single other palliative operation 85 11.9 10 12 32 26 7 22 117 14.0 17 15More than 1 previous palliative e

procedure 31 4.3 7 23 19 15 5 26 50 6.0 12 24latrogenic pulmonary arterial problems

(See Appendix 1, Table 6)

Total 285 40.0 28 9.8 80 65 15 19 365 43.7 43 11.8

* Deaths after repair. B-T-Blalock-Taussig.

TABLE 4 (APPENDIX 1). Continuous Variables in Patients Undergoing Repair of Tetralogy ofFallot (UAB, 1967-July 1982)

Pulmonary Stenosis (n = 713) Pulmonary Atresia (n = 123) Total (n = 836)

Variable Median Range Median Range Median Range

Age 69.7 months 7 days-55.5 years 103.6 months 12.5 months-51.4 years 74.5 months 7 days-55.5 yearsBSA (m2) 0.728 months 0.184 days-2.289 years 0.853 months 0.433 months-2.032 years 0.743 months 0.184 days-2.289 yearsHematocrit 0.48 months 0.27 days-0.84 years 0.52 months 0.34 months-0.81 years 0.49 months 0.27 days-0.84 yearsPost-repair (OR)

PRV/LV 0.488 months 0.164 days-1.286 years 0.652 months 0.192 months-1.857 years 0.500 months 0.164 days-1.857 years

BSA-body surface area (m2). p right ventricular systolic pressureOR-operating room. RV/LV left ventricular systolic pressure

TABLE 5 (APPENDIX 1). Surgical Variables in Patients Undergoing Repair of Tetralogy ofFallot (UAB, 1967-July 1982)

Pulmonary Stenosis Pulmonary Atresia Total(n = 713) (n = 123) (n = 836)

Hospital Hospital HospitalDeaths Deaths Deaths

Variable n %of713 No. % n %of123 No. % n %of836 No. %

Type of repairSimple 463 64.9 23 5.0 11 9 0 0 474 56.7 23 4.9Transannular patch 210 29.5 34 16 32 26 3 9 242 28.9 37 15Non-valved extracardiac conduit 2 0.28 1 50 1 0.8 1 100 3 0.4 2 67Valved extracardiac conduit 13 1.8 1 8 73 59 18 25 86 10.3 19 22Orthotopic pulmonary valve 25 3.5 5 20 6 4.9 2 33 31 3.7 7 23

Surgical approachRight ventriculotomy 678 95.1 61 9.0 121 98.4 24 20 799 95.6 85 10.6Right atriotomy 35 4.9 3 9 2 1.6 0 0 37 4.4 3 8

Support techniqueCPB 386 54.1 20 5.2 35 28 5 14 421 50.4 25 5.9Total circulatory arrest (TCA) 115 16.1 25 22 35 28 8 23 150 17.9 33 22Low flow (LF) (0.5 1. min-'.

m-2) 180 25.2 14 7.8 34 28 5 15 214 25.6 19 8.9Combined TCA and LF 32 4.5 5 16 19 15 6 32 51 6.1 11 22

Methods of myocardial protectionIschemic arrest 489 68.6 39 8.0 62 50 12 19 551 65.9 51 9.3Cold cardioplegia 224 31.4 25 11 60 49 12 20 284 34.0 37 13.0Coronary perfusion - 1 0.8 0 0 1 0.12 0 0

264 KIRKLIN AND OTHERS Ann. Surg * September 1983TABLE 6 (APPENDIX 1). Pulmonary Arterial Problems (Both Congenital and Iatrogenic) in Patients Undergoing Repair

of Tetralogy ofFallot (UAB, 1967-July 1982)

Pulmonary Stenosis Pulmonary Atresia Total(n = 713) (n = 123) (n = 836)

Hospital Hospital HospitalDeaths Deaths Deaths

PulmonaryArterialProblems* n %of713 No. % n %of123 No. % n %of836 No. %

Absenceofcentralportionofrightand/orleftPA 7 1.0 1 14 2 1.6 0 0 9 1.1 1 11Anomalous origin of right and/or left PA (centrally) 12 1.7 3 25 3 2.4 2 67 15 1.8 5 33Bifurcation PA stenosis 17 2.4 3 18 13 11 5 38 30 3.6 8 27Stenosis of origin of right and/or left PA 46 6.5 9 20 46 37 15 33 92 11.0 24 26Stenosis of central right and/or left PA 39 5.5 8 21 28 23 8 29 67 8.0 16 24Incomplete distribution of right and/or left PA 10 1.4 4 40 18 15 7 39 28 3.3 11 39Total patients 97 14 19 20 72 59 20 28 169 20 39 23

* Not mutually exclusive subgroups, with a number ofpatients hav- PA-pulmonary artery.ing more than one problem.

TABLE 7 (APPENDIX 1). Pulmonary Arterial Problems (Both Congenital and Iatrogenic) in Patients Undergoing Repairof Tetralogy ofFallot (UAB, 1967-July 1982)

Pulmonary Stenosis Pulmonary Atresia Total(n =713) (n = 123) (n = 836)

Hospital Deaths Hospital Deaths Hospital DeathsPulmonary Arterial

Problems n No. % CL (%) n No. % CL (%) n No. % CL (%)

No 616 45 7.4 6.2-8.6 51 4 8 4-14 667 49 7.3 6.3-8.5Yes 97 19 20 15-25 72 20 28 22-34 169 39 23 20-27

Total 713 64 9.0 7.9-10.2 123 24 20 16-24 836 88 10.5 9.4-11.7

CL = 70% confidence limits.

Appendix 2

MinorAssociated Cardiac Anomalies in Patients UndergoingRepair ofTetralogy ofFallot (UAB, 1967-July 1982)(Appendix 2, Table 1)

TABLE I (APPENDIX 2). Minor Associated Cardiac Anomalies in Patients Undergoing Repairofthe Tetralogy ofFallot (UAB, 1967-July, 1982)

Pulmonary Stenosis Pulmonary Atresia Total(n = 713) (n = 123) (n = 836)

Minor Associated Cardiac Anomalies

Anomalous origin of LAD from RCAPersistent left superior vena cavaAbsent right superior vena cavaAzygos extension of the inferior vena cavaJuxtaposition of atrial appendagesAtrial septal defectAberrant origin right subclavian arteryVascular ringCongenital heart block

LAD-left anterior descending coronary arte

Hospital Hospital HospitalDeaths Deaths Deaths

n % of 713 No. % n % of 123 No. % n % of 836 No. %

32 4.5 3 9 2 1.6 1 50 34 4.1 4 1261 8.6 9 15 6 4.9 3 50 67 8.0 12 18

--- - 1 0.8 0 0 1 0.12 0 01 0.14 1 100 - - - 1 0.12 1 1001 0.14 0 0 - - 1 0.12 0 0

67 9.4 14 21 8 7 3 38 75 9.0 17 231 0.14 0 0 1 0.8 0 0 2 0.24 0 01 0.14 0 0 - - 1 0.12 0 01 0.14 0 0 -- - 1 0.12 0 0

ry. RCA-right coronary artery.

VoL 198 . No. 3 TETRALOGY C

Appendix 3

Factors Examined in the Multivariate Analysis for In-cremental Risk Factorsfor Hospital Death after PrimaryBlalock-Taussig or Gore-Tex Interposition Shunts

Patients with tricuspid atresia undergoing these proceduresin the same time period (23 patients, one death in a patient28 days old) were added to increase the n.

1) DiagnosisTetralogy of Fallot (pulmonary stenosis)Tetralogy of Fallot (pulmonary atresia)Tricuspid Atresia

2) Type of shuntBlalock-TaussigGore-Tex Interposition Shunt

3) Age at operation4) Date of operation

Appendix 4

A) The estimate of the current probability of hospital orinterim death (within 3 years of the shunt and including hos-pital death after the repair) or morbidity (specifically brainabscess) for the two-stage repair of uncomplicated tetralogy ofFallot with pulmonary stenosis was estimated as follows:The probability of hospital death after shunting came from

the multivariate logistic equation in Table 8, solved for te-tralogy of Fallot with pulmonary stenosis, age 5 months (themedian age of shunted patients, 1979-July 1982), and year ofoperation 1982. This probability is 0.02%, CL 0.004% to0.09%. (Had the age of 1 month been used, the probabilitywould be 0.6%, CL 0.1% to 2.3%, a trivial difference).The probability of interim events after shunting was esti-

mated to be 1.9% CL 0.6% to 4.5%. This probability was basedon the experience of two such events (brain abscess in onecase, sudden death in a second) among 104 patients receivingclassical shunts (Table 9).The probability of hospital death after secondary repair

came from the multivariate equation in Table 3, solved for"uncomplicated" case (see Material and Methods for defini-tion) with pulmonary stenosis, size of patient 0.56 m2 (age 36months), hematocrit 0.50, date ofoperation 1982. It was solvedfor transannular patch-no for figure 5 and Appendix 4, Table1, and for transannular patch-yes for Appendix 4, Table 1.These 3 probabilities were combined to give the total prob-

ability for two-stage repair without a transannular patch of4.6%, CL 3.2% to 6.8%, aivd with a transannular patch of6.9%,CL 4.9% to 9.6%, as folldws:

Ptloag _= I -( I - Pshunt) * Psocondary mpi)The confidence limits were obtained by first obtaining the

variance as follows:

Var(P.,,) = (1 - Pwosa)2

[Var(Pshunt) + +Va(Pinterim) +Var(Ps,ondary)I-Pshunt 1 7---Pinterim 1-Pscondaj

Assuming that the variance ofPmsw is related to the vari-ance of a logistic Z (where Z = ln [(P..,,/(1-P )])the confidence limits were calculated by first solving the fol-lowing equation for Var(Z):

Var(P.WO..) = (1 - P')Ptwo - [Var(Zmoa)]

)F FALLOT 265TABLE 1 (APPENDIX 4). Degree of Uncertainty at Various BSA andAge that Two-stage Repair of Uncomplicated Tetralogy ofFallotwith Pulmonary Stenosis has in 1982 a Lower Combined Risk(Probability ofHospital Death, Interim Mortality or Important

Morbidity, and Death at Secondary Repair)than does Primary Repair

Without WithTransannular Transannular

Patch Patch

BSA Age p Confidence BSA Age(m2) (Months) Value* Limitst (m2) (Months)

0.38 9 0.20 45% 0.42 130.37 8 0.17 50% 0.41 120.35 7 0.10 64% 0.39 100.341 6.3 0.08 68%t 0.379 90.338 6 0.07 70% 0.376 80.33 5.5 0.05 76% 0.365 80.29 3 0.01 90% 0.33 60.26 2 0.003 95% 0.30 4BSA-body surface area.* Single-tailed p value supporting the null hypothesis that primary

repair is as safe as two-stage repair. Below this size (age) the p valueis still smaller.

t The specific confidence limits which separate at the stated BSA(age).,

t Exactly ±1 standard deviation of Z, the logistic transformationof the probability of hospital death or morbidity.

The confidence limits were then calculated as follows:

CL(Z) = Z ± kVVar(Z)For 70% confidence limits k = 1.04; for 95% confidence limitsk = 1.96; for 50%, k = 0.6745.

B) The probability of hospital death after primary repair,with the same stipulations as in A), were obtained from thelogistic regression equation in Table 3.

C) The p-value for the difference between the probabilityof hospital death after primary versus two-stage repair is ob-tained by solving for t as follows:

t = -v,stw Zpnmary repairYVar(Ztwow par) + Var(Zm,r, m,,)t is then converted to a single-tailed p value using the normaldistribution.D) The equivalent non-overlapping confidence limits for

a given p value for the difference between primary and two-stage repair was calculated using the relationships:

Ztwo-sug repw -Znmary repawrk Var(Z,"w |rq) + V 7ar(Zpm J)

which is related to t above by:

(YVar(Z.,. + YVar(Zp,.,y pw,)t = k -

rx

VVar(Z. ,,) + Var(Zpniary repair)

where k is converted to a two-tailed p value utilizing the nor-mal distribution, and the confidence coefficient calculated asone minus that p value (e.g., a k of 1.96, p = 0.05 convertsto 95% confidence limits).

E) The degree of uncertainty (expressed as non-overlappingconfidence limits and p values) in the conclusion that two-stage repair is safer than primary repair for infants with un-complicated tetralogy of Fallot, can now be calculated for anygiven patient size (age) (Appendix 4, Table 1).