Outcome of cardiac surgery in low birth weight and premature infantsq

Guido Oppidoa,*, Carlo Pace Napoleonea, Roberto Formigarib, Davide Gabbieria,Davide Pacinia, Guido Frascarolic, Gaetano Gargiuloa

aDepartment of Pediatric Cardiac Surgery, S. Orsola-Malpighi Hospital, University of Bologna Medical School, Via Massarenti, No. 9, Bologna, ItalybDepartment of Cardiology, S. Orsola-Malpighi Hospital, University of Bologna Medical School, Bologna, Italy

cDepartment of Anesthesiology, S. Orsola-Malpighi Hospital, University of Bologna Medical School, Bologna, Italy

Received 31 August 2003; received in revised form 10 March 2004; accepted 6 April 2004; Available online 18 May 2004

Abstract

Objective: Low birth weight or premature infants may require early surgical treatment of congenital cardiac lesions because of their poor

clinical status. Even thought early repair or palliation is carried out with incremental risk factor for morbidity and mortality, it has been

demonstrated to be preferable to medical management and delayed surgery. This retrospective study was undertaken to evaluate early and

mid-term results in infants, weighing less than 2500 g, who underwent surgery other than patent ductus arteriosus closure. Methods: Since

January 1993 to August 2002, 60 consecutive patients underwent early surgical treatment of congenital heart malformations at our institution.

27 patients were premature (born before 37 weeks of gestation). Ninety percent were severely symptomatic. Mean age at operation was 15.5

days (range 4–68 days). Mean weight was 2120 g (range 900–2500 g). Indications for surgery were: coarctation complex 11, transposition

of great arteries 9, interrupted or severely hypoplastic aortic arch 9, hypoplastic left heart syndrome 7, truncus arteriosus 5, other 19. Thirty-

five patients were operated on CPB, Deep Hypothermia with Circulatory Arrest was used in 9. Complete repair was achieved in 32 patients.

Aortic arch reconstruction was required in 32 cases. Results: There were nine early deaths (15%): heart failure (5), multiorgan failure (3),

sepsis (1). Age, weight, prematurity, type of surgery and use of cardio pulmonary by-pass did not influence early mortality. Mean intensive

care unit stay and duration of mechanical ventilation were 5.8 days and 75.5 h, respectively. Postoperative neurological complications did not

occur in any patient. At follow-up (mean 48 months) there were nine late deaths. Kaplan–Meier survival at 60 months was 70%.

Conclusions: Surgery for congenital heart disease can be performed in low weight critically ill infants with reduced, but still acceptable early

and mid-term survival.

q 2004 Elsevier B.V. All rights reserved.

Keywords: Congenital heart disease; Low birth weight; Cardio pulmonary by-pass; Cerebral protection

1. Introduction

The incidence of low birth weight, defined as a body

weight at birth less than 2500 g, in newborns affected by

congenital heart disease, has been reported by many authors

to be significantly higher when compared with normal

newborns population. Incidence of low birth weight in

congenital heart disease patients ranges between 8 and 18%

compared with 6% of the normal population, whereas no

significant differences have been found between the two

populations in terms of prematurity [1–5].

Continuous improvements in the management of pre-

mature or small for gestational age newborns, in the

neonatology intensive care units, have considerably reduced

the postnatal mortality of those babies; consequently, the

request for surgical treatment of congenital heart lesions

early in life in low weight babies, is expected to increase in

the up-coming future.

However, although the outcome of neonatal cardiac

surgery, has dramatically enhanced in the last two decades,

low body weight itself still constitutes an important risk

factor for morbidity and mortality [6–9].

Intensive medical therapy and continuous prostaglandin

infusion for prolonged time, in those neonates who benefit

ductus patency, may guarantee clinical stability with

European Journal of Cardio-thoracic Surgery 26 (2004) 44–53

www.elsevier.com/locate/ejcts

1010-7940/$ - see front matter q 2004 Elsevier B.V. All rights reserved.

doi:10.1016/j.ejcts.2004.04.004

q Presented at the joint 17th Annual Meeting of the European Association

for Cardio-thoracic Thoracic Surgeons, Vienna, Austria, October 12–15,

2003.* Corresponding author. Tel.: þ390-051-636-3361; fax: þ39-051-345-

990.

E-mail address: guidooppido@yahoo.com (G. Oppido).

the rationale of delaying surgery letting babies gain weight.

Nevertheless, this strategy seems not to be associated with

a better outcome and furthermore it is not always practicable

because of failure to thrive or permanent unstable

hemodynamic conditions. Chang and colleagues [10]

reported on a series of low birth weight and premature

infants who were managed according to three different

protocols: hospital survival rate was 82% in the complete

repair group, 78% in the palliated group and 77% in the

delayed surgery group, with an additional 10% mortality

rate at the time of surgery for the latter.

Aim of the present study was to report on the outcome of

the entire population of neonates and infants weighing less

than 2500 g who underwent surgery other than ductus

arteriosus closure at our institution in the last decade, with

the intent of giving our contribution to the determination of

the ideal treatment strategy in this challenging subgroup

of babies.

2. Material and methods

Preoperative and operative data were retrospectively

collected by reviewing the hospital records and the

computerised database of the Department of Pediatric

Cardiac Surgery of the S. Orsola-Malpighi Hospital,

Bologna, Italy.

Follow-up data were obtained from our institution

outpatient records and from our Catheterization Laboratory

database. Each patient underwent clinical examination,

chest X-ray and echocardiogram at 6–12 month regular

intervals.

Study period was 10 years: from January 1993 to August

2002. Inclusion criterion was: body weight less then 2500 g

at the time of surgery. Patients who underwent ductus

arteriosus closure alone, as well as low birth weight or

premature babies, who reached a body weight of more than

2500 g at the time of surgery, were not included in the study.

End-point was in-hospital mortality (within 30 days after

the operation).

2.1. Statistical analysis

Data are presented as mean ^ SD and range, unless

otherwise specified.

Statistical significance in the research of risk factors for

mortality, was determined with X2 test or Fisher’s Exact

analysis in the comparison of categorical variables and

Student’s t-test in the comparison of continuous variables.

All variables that achieved P , 0:2 in the univariate

analysis were included in a multivariate model and

examined by stepwise logistic regression. Significance

was defined as P , 0:05: Survival curves were obtained

by Kaplan–Meier product limit method and compared with

log rank test. Software used for statistical analysis was SPSS

(Chicago, IL, USA) for Windows version 8.0.

2.2. Patient population

A total of 60 consecutive patients (33 females and 27

males), either neonates or infants, met the inclusion criteria

in the study time period (Table 1). Twenty-seven (45%)

were born prematurely: 1 before the 28th week of gestation,

7 between the 29th and 32nd, 19 between the 33rd and 36th.

Thirty-three (55%) were full term low birth weight

newborns (less than 2500 g at birth). Mean weight at birth

was 2190 ^ 310 g.

2.3. Preoperative clinical conditions

All patients were preoperatively hospitalized either in the

neonatal intensive care unit or in our cardiac intensive care

unit: 54 (90%) were severely symptomatic because of their

underlying hemodynamic disorder: low output in left heart

obstructive lesions was the more recurrent clinical presen-

tation, severe cyanosis for right to left shunt or transposition

and congestive heart failure for unrestricted left to right

shunt were observed in the remaining.

Prenatal cardiac diagnosis was available in 21 patients.

Thirty-seven patients were ductus dependent and were

receiving prostaglandins, 10 were receiving high dose

catecholamines infusion, five were permanently ventilated,

three exhibited pulmonary complications in relation to

prematurity, three developed metabolic acidosis requiring

bicarbonates. None of the patients had intraventricular

hemorrhage, necrotizing enterocolitis or sepsis.

Mean age at operation was 15.5 ^ 13.4 days (range

4–68 days) and mean weight was 2120 ^ 370 g (range

900–2500 g).

2.4. Diagnoses

Cardiac diagnoses included: coarctation complex

(11 pts), transposition of great arteries (9 pts), interrupted

or severely hypoplastic aortic arch 9, hypoplastic left heart

Table 1

Patient demographics

No. (%)

Patients 60

Gender

Male 33 (55)

Female 27 (45)

Gestational age

# 28 weeks 1 (1.7)

29–32 weeks 7 (11.7)

33–36 weeks 19 (31.7)

$ 37 weeks 33 (55)

Mean ^ SD Range

Weight at operation 2120 ^ 370 g 900–2500 g

Weight at birth 2190 ^ 310 g 800–2500 g

Age at operation 15.5 ^ 13.4 days 4–68 days

G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) 44–53 45

syndrome 7, truncus arteriosus 5, double outlet right

ventricle 4, tetralogy of Fallot 3, pulmonary atresia

intact ventricular septum 4, double inlet left ventricle 3,

ventricular septal defect 1, tricuspid atresia 1, multiple

ventricular septal defects 1, complete atrio-ventricular

septal defect 1, anomalous origin of the right pulmonary

artery 1 (Table 2).

Associated non-cardiac malformations or syndromes

were present in 19 patients (32%) and are summarized in

Table 2.

2.5. Surgery

Anesthetic protocols did not differ from those used

in neonates with a body weight exceeding 2500 g

and entailed: Fentanil 1 – 2 mg/kg/dose, Vecuronium

0.1–0.2 mg/kg/dose, Midazolam 50–100 mg/kg/dose and

Sevofluorane.

Extracorporeal neonatal circuits sized 3/16–1/4 and were

primed with irradiated and deleucocytised red blood cells

and fresh frozen plasma, bicarbonates and heparin, achiev-

ing a hematocrit value of 30%. Aortic cannulation was

performed with ‘number 20’ Teflon straight cannula

(Sofracob s.a., Reventin Vaugris, France) which corre-

sponds to a 1.5 mm internal diameter tip. Bicaval venous

cannulation was performed entering the right atrium with

two 12 F curve cannulas (Baxter International, Inc. San

Diego, CA, USA); a single 20 F atrial venous cannula

(Baxter International, Inc. San Diego, CA, USA) was

preferred in all Norwood stage I operations. Oxygenators

utilized from 1993 to 2000 were hollow fibers Masterflow D

701 (Dideco Modena, Italy) and from 2000 to date hollow

fibers Lilliput D 901 (Dideco Modena, Italy). Intermittent

blood cold cardioplegia was administered antegradely into

the aortic root or coronary ostia. During cardio-pulmonary

bypass, blood gas analysis was achieved using alpha-stat

Table 2

Cardiac diagnoses and associated malformations or syndromes

Cardiac anomaly No. Syndromes No.

Coarctation complex 11 Charge 1

Coarctation 10 Down s. 1

Coarctation, VSD 1 DiGeorge s. 1

IAA/aortic arch hypoplasia 9 Eterotaxia s. 2

IAA 5 Rubistain-taybi s. 1

IAA, A-P window 1

Arch hypoplasia, VSD 2 Malformations No.

Arch hypoplasia, VSDs 1 Gastro-enteric 3

Transposition of great arteries 9 Oesophageal atresia 2

TGA/IVS 6 Anal atresia 1

TGA/VSD 1 Genito-urinary 4

TGA/VSD arch hypoplasia 1 Cryptorchism 1

TGA/VSDs arch hypoplasia 1 Multicystic kidney 1

Hypoplasic left heart syndrome 7 Vescico-ureteral reflux 1

Truncus arteriosus 5 Unilateral renal agenesis 1

Truncus type I A II A 3 Sensory organs 1

Truncus type IV A (with IAA) 2 Atresia auris 1

Double outlet right ventricle 4 Muscle-skeletal 2

DORV 3 Craniosynostosis 1

DORV, asplenia s. 1 Duchenne muscular dystrophy 1

Tetralogy of fallot 3 Central nervous system 3

ToF/PS 2 Corpus callosum agenesis 1

ToF/PA 1 Hydrocephalus 2

Pulmonary atresia intact V. septum 4

Double inlet left ventricle 3

DILV 1

DILV aortic arch hypoplasia 1

DILV, asplenia 1

VSD 2

VSD 1

VSDs 1

Tricuspid atresia, pulmonary atresia 1

Complete atrio-ven septal defect 1

Anomalous origin right pulmonary artery 1

VSD, ventricular septal defect; VSDs, multiple ventricular septal defects; IAA, interrupted aortic arch; A-P window, aortico-pulmonary window;

TGA/IVS, transposition of the great arteries with intact ventricular septum; TGA/VSD, transposition of the great arteries with intact ventricular septum;

DORV, double outlet right ventricle; ToF/PS, tetralogy of fallot; ToF/PA, tetralogy of fallot with pulmonary atresia; DILV, double inlet left ventricle.

G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) 44–5346

strategy. Pump flow was adjusted to maintain a blood

pressure not above 40 mmHg and a mixed venous blood

oxygen saturation, monitored continuously, never below

60–65%. Continuos ultrafiltration was carried out during

cardio-pulmonary by-pass in each patient.

Forty-six patients underwent median sternotomy and 14

underwent left postero-lateral thoracotomy in the third or

fourth intercostals space. Thirty-five (58%) patients were

operated on cardio-pulmonary by-pass and 25 (42%) under-

went off-pump procedures. Cardio-pulmonary by-pass and

X-clamp mean times were 178 ^ 87 min and 74 ^ 53 min,

respectively. Deep hypothermia (,18 8C) with circulatory

arrest was avoided in all patients but 9, all of them operated

on before 1996. In the anterior aortic arch surgery, cerebral

selective perfusion technique, at a body temperature of

22–24 8C, was always preferred during the last 6 years.

Aortic arch surgery alone or as part of more complex

procedures, was required in 32 cases (53%): anterior or

entire arch reconstruction in 21, isthmus and posterior arch

in 11. Anterior or entire arch reconstruction was part of

more complex procedures in 13 cases: Norwood stage I

operation 7, arterial switch operation 3, truncus arteriosus

repair 2, aortico-pulmonary window 1. In eight cases

anterior arch reconstruction was associated to: ventricular

septal defect closure 4, left ventricular outflow tract

obstruction release 2 pulmonary artery banding 2.

Each one of the 11 coarctation complex patients received

repair of the coarctation and contemporarily enlargement of

the posterior arch.

3. Results

Single stage complete repair was achieved in 32 patients;

staged univentricular palliation (18), or palliation in patients

with anatomy amenable to biventricular repair (10), were

undertaken in the remaining 28 (Table 3).

Postoperative mechanical ventilation mean time was

75.4 ^ 106 h (range 1–410 h) and postoperative intensive

care unit stay was 5.8 ^ 6.6 days (range 0.5–27 days).

3.1. Early Mortality

Nine patients died in the early postoperative period,

accounting for a hospital mortality of 15%. Causes of death

included: heart failure in five patients, multiorgan failure in

three, sepsis in one. At the univariate analysis (Table 4),

weight at surgery ðP ¼ 0:368Þ; age ðP ¼ 0:626Þ; gestational

age ðP ¼ 0:144Þ; type of surgery (correction or palliation)

ðP ¼ 1Þ; use of cardiopulmonary by-pass ðP ¼ 0:281Þ;

cerebral selective perfusion ðP ¼ 0:38Þ; associated non-

cardiac malformations or syndromes ðP ¼ 0:096Þ did not

result to be risk factors for early mortality.

The more frequent cardiac pathologies: coarctation

complex ðP ¼ 0:189Þ; transposition of great arteries

ðP ¼ 0:1Þ; interrupted or severely hypoplastic aortic arch

ðP ¼ 0:125Þ; hypoplastic left heart syndrome ðP ¼ 0:281Þ

and truncus arteriosus ðP ¼ 0:57Þ; were included in the

analysis and did not reach statistical significance as well.

Among all the variables investigated as risk factors for early

mortality, use of deep hypothermia with circulatory

arrest ðP ¼ 0:007Þ and longer cardiopulmonary bypass

ðP ¼ 0:002Þ and cross-clamping ðP ¼ 0:006Þ times, were

the only variables which reached statistical significance.

Among patients amenable for complete biventricular repair,

there was no difference between those who underwent

single-stage correction vs. those who underwent palliation

(15.6 vs. 20.0%, P ¼ 0:66).

Multivariate analysis by stepwise logistic regression

(Table 4) indicated, as the only significant independent risk

factor for early mortality, the use of deep hypothermia with

circulatory arrest (P ¼ 0:002; CI 0.05–0.34; odds ratio

½OR� ¼ 9:4), while a body weight less than 1500 g (when

analyzed as a dichotomic variable) reached P value ¼ 0:06

(CI 0.13–1.7), with an odds ratio ½OR� ¼ 3:5:

Table 3

Surgical procedures

Procedure No. CPB Type of surgery

Coarctation repair 11

End to end extended 9 Off Correction

End to end extended PAB 1 Off Palliation

Patch aortoplasty 1 Off Correction

Arch reconstruction 9

Arch reconstruction VSD closure 4 On Correction

Arch reconstruction PAB 2 On Palliation

Arch reconstruction LVOTO

release

2 On Correction

Arch reconstruction APW repair 1 On Correction

Truncus repair 5

Truncus repair 3 On Correction

Truncus repair aortic arch rec 2 On Correction

Arterial switch operation 10

ASO 6 On Correction

ASO VSD closure 1 On Correction

ASO VSD closure arch rec 1 On Correction

ASO PAB arch rec 1 On Palliation

Palliative* ASO arch rec 1 On Staged

Norwood I stage 7 On Staged

BT Shunt 12

BT Shunt 11 Off

(10)/on (1)

Pall(3)/stag(8)

BT Shunt pulm valvuloplasty 1 On Staged

Pulmonary artery banding 4 Off Pall(3)/stag(1)

VSD closure 1 On Correction

Pulmonary artery reimplantation 1 On Correction

Stag. or Staged, univentricular staged repair; Pall., palliated; CPB,

cardio pulmonary bypass; (on: operation performed on cardiopulmonary

bypass; off: operation performed without cardiopulmonary bypass); PAB,

pulmonary artery banding; VSD, ventricular septal defect; APW, aortico-

pulmonary window; LVOTO, left ventricular outflow tract obstruction;

Arch Rec, arch reconstruction; ASO, arterial switch operation; BT shunt,

Blalok Taussig shunt; Pulm valvuloplasty, Pulmonary valvuloplasty; (*)

Palliative arterial switch operation performed in a patient with {SDD}

double inlet left ventricle with transposition of the great artery, aortic arch

hypoplasia and subaortic stenosis.

G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) 44–53 47

3.2. Complications

Among 46 interventions carried out via median sternot-

omy, sternum was left open in 15 patients; mostly just to

prevent hemodynamic problems during the early post-

operative period for the more complex surgical

reconstructions.

The following complications occurred in 18 of the 51 early

survivors: two patients were successfully resuscitated from

cardiac arrest occurred in the day of surgery, nine developed

low cardiac output requiring prolonged high dose inotropic

support (dopamine and/or dobutamine . 10 mg/kg/min,

and/or adrenaline .0.1 mg/kg/min) and two of them needed

a systemic-to-pulmonary shunt resizing few hours after the

operation, six developed acute renal insufficiency, two had

pulmonary hypertensive crisis requiring inhaled nitric oxide

therapy and two had severe systemic postcoarctectomy

hypertension, four acquired sepsis and were found positive

Table 4

Univariate and multivariate analysis for early mortality

Dicotomic variables Patients Death Univariate Multivariate

No. % No. % P value Odds ratio 95% Confidence interval P value

Associated malformations or syndromes 0.096

Yes 19 31.7 0 0

No 41 68.3 9 21.9

Type of surgery 1.00

Correction 32 53.3 5 15.6

Palliation (mono- and biventricular) 28 46.7 4 14

Complete biventricular repair 0.66

One-stage 32 76.2 5 15.6

Palliation (biventricular) 10 23.8 2 20

Use of cardio pulmonary by-pass 0.281

Yes 35 58.3 7 20

No 25 41.7 2 8

Cerebral selective perfusion 0.38

Yes 12 40 1 7.1

No 23 60 6 26

Deep hypothermia with circulatory arrest 0.0064 9.4 0.05–0.34 0.002

Yes 9 26 5 55.5

No 26 74 2 7.6

Very low body weight (,1500 g) 0.218 3.5 0.13–1.7 0.06

Yes 6 10 2 33

No 54 90 7 13

Coarctation 0.189

Yes 11 18.3 0 0

No 49 81.7 9 18.3

Hypoplastic left heart syndrome 0.281

Yes 7 11.7 2 28.6

No 53 88.3 7 13.2

Interrupted or hypoplastic aortic arch 0.125

Yes 9 15 2 22.2

No 51 85 7 13.7

Truncus arteriosus 0.57

Yes 5 8.3 1 20

No 55 91.7 8 14.5

Transposition of the great arteries 1.00

Yes 9 15 1 11.1

No 51 85 8 15.7

Continuous variables Alive Death P value

No. Mean No. Mean

Weight at surgery 51 2.13 9 2.01 0.368

Age at surgery 51 15.86 9 13.44 0.626

Gestational age 51 36.94 9 35.33 0.144

Cardio pulmonary by-pass time 28 72.17 7 142.5 0.06

X-clamp time 25 156.4 4 266.8 0.02

G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) 44–5348

to blood colture and successfully treated with selective

antibiotic therapy, three patients required reintubation and

prolonged mechanical ventilation for non-cardiac-related

reasons: one had transitory phrenic nerve palsy, one disclosed

tracheomalacia and one developed bilateral atelettasia.

All the patients were pre- and postoperatively routinely

screened with cerebral echography by an experienced

neonatologist in order to exclude the occurrence of brain

damage at any time. Postoperative neurological compli-

cations were not observed in any patient.

3.3. Late mortality

Follow-up mean time was 48 ^ 33 months (range 2–123

months) and was 100% complete. Of the 51 early survivors

nine patients died during the follow-up (late mortality

17.5%), three of them within six months from the operation.

The following causes of death could be detected in all nine

patients: one heart failure and one shunt thrombosis (both

occurred within the sixth month after the operation, in

patients waiting for Norwood stage II procedure), two

severe pulmonary hypertension (one in a patient who

received valve replacement for mitral valve stenosis and one

in a patient who underwent pulmonary artery banding with a

reabsorbable band), one pneumonia, one ab ingestis, one

Duchenne muscular dystrophy, one patient died during

cardiac reoperation in another hospital and one during

esophageal reoperation.

Kaplan–Meier overall actuarial survival rate at 60

months was 70.0% (Fig. 1). There was no significant

difference ðP ¼ 0:88Þ in survival between term and preterm

patients (Fig. 2) (65.4 vs. 74.0%, respectively) or between

babies who underwent repair in respect to those who had

palliative procedures (Fig. 3) (74.7 vs. 64.6%, P ¼ 0:7).

3.4. Reinterventions

After a mean follow-up time of 48 ^ 33 months (range

2 –123 months), 29 out of 51 survivors needed 47

procedures (Table 5), either as catheter intervention

(20 procedures in 16 patients), or as surgical procedure

(27 operations in 21 patients).

The major interventions in the catheterization laboratory

were balloon angioplasty for recurrent coarctation in five

cases (after interrupted aortic arch repair in two and

coarctation repair in three), balloon pulmonary angioplasty

for peripheral pulmonary stenosis in five (two in one patient

after aortico-pulmonary window and interrupted aortic arch

repair, one after truncus and interrupted aortic arch repair,

one after BT-shunt and one after Norwood stage II

procedure) and balloon angioplasty/ valvuloplasty of a

narrowed homograft/heterograft in three.

Four patients (8%) needed six reoperations for residual

defects: subaortic stenosis resection two (both after inter-

rupted aortic arch repair), mitral valve replacement two,

mitral valve plasty one and residual ventricular septal defect

closure one.

Two patients had homograft/heterograft replacement due

to somatic overgrowth. The remaining 19 operations were

part of staged univentricular repair (13) or delayed

correction after palliation (6) and are reported in Table 5.

Fig. 1. Overall actuarial survival (Kaplan–Meier). Survival rate at 60 months was 70.0%. Patients at risk at any time are indicated in parentheses.

G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) 44–53 49

4. Discussion

Low birth weight and prematurity are well acknowledged

risk factors for mortality in infants with congenital heart

disease [11]. Early repair of congenital heart disease

offers the theoretical benefits of avoiding the negative

hemodynamic effects of congenital heart disease physiology

on the heart itself and other organs, which in low weight

babies might be less tolerated, thus avoiding progressively

more severe and sometime irreversible secondary organ

damages.

However, if compared with normal weight newborns

undergoing cardiac surgery, low weight babies show an

increased mortality [9,12]. On the other hand, deferring

Fig. 2. Term vs. premature patients actuarial survival. Comparison of premature patients (solid line) vs. term patients (dashed line) actuarial survival curves.

Survival rates at 60 months were 74.0 and 65.4%, respectively. Statistically significant difference was not found between the two curves (Log Rank test:

P ¼ 0:88). Patients at risk at any time are indicated in parentheses.

Fig. 3. Corrected vs. palliated patients actuarial survival. Comparison of corrected patients (solid line) vs. palliated patients (dashed line) actuarial survival

curves. Survival rates at 60 months were 74.7 and 64.6%, respectively. Statistically significant difference was not found between the two curves (Log rank test:

P ¼ 0:7). Patients at risk at any time are indicated in parentheses.

G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) 44–5350

surgical treatment in order to achieve an increase in body

size does not necessarily warrant an increase in

survival [10]. Indeed, non-cardiac factors may be

associated with low birth weight, and may jeopardize

the outcome of surgery, thus requiring careful evaluation

[9,12,13,14].

Our study population is composed by patients for whom,

due to severely symptomatic cardiac lesions, a conservative

approach by intensive medical treatment only, has been

judge to be at higher risk in respect to a prompt surgical

resolution. The overall 15% in-hospital mortality, compris-

ing palliative and corrective procedures as well as complex

cardiac malformations, shows that: an early surgical

strategy may be highly rewarding in the treatment of this

difficult group of patients. However, in our opinion this does

not necessarily mean that every low-weight neonate should

be aggressively treated by early surgery, unless intensive

medical treatment is required because of severely sympto-

matic cardiac lesions.

Cardio-pulmonary bypass time, aortic cross-clamp time

and the use of deep hypothermia with circulatory arrest were

the only risk factors found at univariate analysis; whereas

only the latter resulted as an independent variable associated

with early mortality.

Prolonged by-pass and aortic cross-clamp time may not

constitute risk factors themselves but could simply reflect

the more complex type of surgical procedure.

Probably, a type II error should be taken into account for

what concerns potentially important variables like: type of

cardiac malformation, type of surgery (palliation vs. repair),

use of cerebral selective perfusion, off-pump vs. on-pump

procedures, prematurity or presence of associated non-

cardiac malformations. Indeed, the 28% mortality of

Norwood stage I procedures in our group was fairly higher

in respect to the 0% of the patients who underwent repair of

aortic coarctation. For the same reason, we have no

statistical evidence of complete repair surgery to be at

higher risk in respect to palliation, due to the limited number

of patients and the relatively high heterogeneity of our study

group, which entails palliative operations both as part of a

staged monoventricular procedure as well as a bridge before

complete biventricular repair.

Age at surgery has been reported by Reddy and

coworkers (8) to be an important morbidity factor in low-

weight infants. We did not find any correlation between age

at surgery and surgical mortality ðP ¼ 0:63Þ:

Nineteen patients (32%) had associated non-cardiac

malformations, the literature reporting a prevalence

between 27 and 45% (2,4,6,10 and 15) with an ominous

surgical outcome (14). The reduced significance of this

variable in our analysis may be due to the low impact on the

early postoperative period exerted by the low degree of

malignancy of the types of extra cardiac malformations or

syndromes found in our study group. Indeed, three patients

died late after surgery (one patient with respiratory failure

due to Duchenne muscular dystrophy and two other during

non-cardiac surgery). Interestingly, bronco-pulmonary dys-

plasia and tracheo-bronchomalacia were a rare occurrence

in our patients, with only one neonate requiring post-

operative reintubation and prolonged mechanical venti-

lation. Similarly, necrotizing enterocolitis and

intraventricular hemorrhage [15–17] were not detected in

our patient population. Respiratory prematurity-related

issues, such as jaline membrane disease, were present in

three patients and required preoperative mechanical

ventilation.

Routine preoperative and postoperative cerebral echo-

graphic evaluation allowed us to rule out major neurological

complications, particularly intracranial bleeding.

Selective cerebral perfusion is our technique of choice

for brain protection since 1996, and is currently used in

all patients undergoing surgery of the anterior aortic arch.

While no definitive statement may be drawn from a

limited experience in such a heterogeneous group of high

risk patients, our study shows that primary complete

repair may be achieved with an acceptable mortality

(15.6% in our group), with no difference in respect to

palliation in patients with anatomy potentially amenable

Table 5

Re-interventions

No.

Catheter Intervention (number of patients) 16

Balloon aortic isthmus angioplasty 5

Balloon aortic valvuloplasty 1

Balloon pulmonary valvuloplasty 2

Balloon pulmonary angioplasty 5

Balloon HG/EG dilatation 3

Balloon ascending aorta angioplasty 1

Balloon common carotid artery angioplasty 1

Hemiazigos coil embolization 1

MAPCA coil embolization 1

Surgery (number of patients) 21

BCPA 6

BCPA pulmonary arteries plasty 3

BCPA RV outflow patch 1

Fontan 3

HG/EG replacement 2

Subaortic stenosis resection 2

Residual VSD closure 1

Mitral valve replacement 2

Mitral valve plasty 1

De-banding PA plasty VSDs closure 1

De-banding PA plasty VSD closure 1

De-banding PA plasty CAVC repair 1

De-banding PA plasty DORV repair 1

Take down BT shunt ToF repair 2

Cath, catheterization; HG, homograft; EG, heterograft; MAPCA, main

aortico-pulmonary collateral; BPCA, bidirectional cavo-pulmonary anasto-

mosis; VSD, ventricular septal defect; VSDs, multiple ventricular septal

defects; PA, pulmonary artery; CAVC, complete atrio-ventricular canal;

DORV, double outlet right ventricle; BT Shunt, Blalok Taussig shunt; ToF,

tetralogy of fallot.

G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) 44–53 51

to biventricular repair (20.0% in our group). Similarly, the

11.1% mortality of surgery in single ventricle-physiology

shows that a definitive monoventricular palliation may be

undertaken even in the setting of high risk low-weight

neonates.

In conclusion, even thought the management of low

birth weight and premature infants still represents a

major challenge for all who take care of such patients,

surgical treatment of their congenital malformations

should be undertaken as soon as satisfactory hemody-

namic stability and major organs recovery is achieved,

with enhanced, but still acceptable early and mid-term

morbidity and mortality.

4.1. Limits of our study

Limits of our study are certainly represented by the

relatively small number of patients, and the nature of any

retrospective study. In order to achieve a fair number of

patients to be included into univariate and multivariate

analysis, a decision was made to unify patients who

underwent surgery with and without cardiopulmonary

bypass, thus leading to a difficult interpretation of the

statistical results and potential underestimation of potentially

important variables. However, our study group represents a

difficult and relatively rare type of patient with congenital

heart disease, which deserves a multicentric study collecting

a large number of cases.

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Appendix A. Conference discussion

Dr T. Ebels (Groningen, The Netherlands): This paper is on 60 patients.

Are these all patients in the period from 1993 to 2002, or were there other

patients not included in the study, that had deferred treatment of any sort?

Dr Oppido: These are 60 consecutive surgical patients. We did not

collect all the babies who died before the operation or who were not

referred for surgery because of major non-cardiac clinical issues. Moreover,

we excluded all the premature and low birth weight babies for whom urgent

surgery was not indicated, or who reached a body weight superior to 2500

grams at the time of surgery.

Therefore, our population is composed by 60 consecutive patients who

needed urgent surgical treatment because of heart failure or some kind of

ductus dependent congenital cardiac malformation.

Dr M. Pozzi (Liverpool, UK): Would you be able to point out a cutoff

point in terms of weight with regards to seeing a difference in postoperative

complication, and in particular, neurological complication?

Dr Oppido: All of our patients were routinely screened with brain

ultrasound to rule out the presence of either preoperative or postoperative

neurological complications, which were excluded in all cases.

Dr T. Bottio (Padova, Italy): Did you support any one of these patients

with ECMO?

Dr Oppido: No, we did not.

Dr B. Maruszewski (Warsaw, Poland): Maybe I haven’t noticed, but

was one of your variables the date of the operation? Did the date of the

operation influence the outcome that you studied?

Were patients operated earlier, for example, in your time span? Did they

do better or worse? Was there any change depending on the date of the

operation?

Dr Oppido: We know from the literature that the earlier those patients

are operated the less complications seem to occur in the postoperative

period. We did not observe this in our patient population. We rather believe

that a major effort in order to stabilize the patient before surgery is

warranted, regardless the time needed.

G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) 44–5352

Dr Ebels: I don’t think this is an answer to the question. The question is

whether you performed better earlier in your experience or worse? Was

there a learning curve?

Dr Oppido: Yes, there was a learning curve in our experience.

Dr Maruszewski: But was it one of the variables?

Dr Oppido: No it was not.

Dr R. Bartkowski (Poznan, Poland): Have you had any experience

with hemofiltration or dialysis in this group of patients, renal failure or

any problems?

Dr Oppido: Acute renal failure occurred in 6 patients, but none of

them underwent any sort of hemofiltration or dialysis.

Dr F. Lacour-Gayet (Denver, CO, USA): I noticed in your analysis that

deep circulatory arrest was a risk factor. My question to you is, do you

avoid circulatory arrest and go to palliation or do you use full flow?

Dr Oppido: Deep hypothermia with circulatory arrest has been only

adopted before 1996 and for the treatment of hypoplastic left heart syndrome

or interrupted aortic arch, as it was for the 9 reported patients. Whereas,

cerebral selective perfusion is the current technique of choice since 1996.

G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) 44–53 53