Improved current era outcomes in patients with heterotaxy syndromes§
Petros V. Anagnostopoulosa,*, Jeffrey M. Pearla, Courtney Octavea, Mitchell Cohena,
Angelika Gruessnerb, Erika Winteringa, Michael F. Teodoria
aPediatric Heart Center, The Phoenix Children’s Hospital, Phoenix, AZ, USA
bArizona Cancer Center, The University of Arizona, Tucson, AZ, USA
Received 31 August 2008; received in revised form 28 November 2008; accepted 3 December 2008; Available online 23 February 2009
Objective: Patients with heterotaxy syndrome have a myriad of visceral and cardiac malformations historically resulting in significant
morbidity and mortality. We sought to assess whether current era management strategies have improved outcomes in patients with visceral
heterotaxy. Methods: A retrospective review (1994—2008) of our database identified 45 consecutive heterotaxy patients who underwent surgical
present in 32 patients. Pulmonary outflow obstruction was present in 29 of the patients. Twenty patients had total anomalous pulmonary venous
return (TAPVR), of which 9 were obstructed. An initial neonatal surgical approach was performed in 27 patients. Thirty patients had systemic to
pulmonary artery shunt. Mean follow-up was 43.6 ? 47 months in RAI and 41.0 ? 40.8 months in LAI patients (p = 0.4). Results:There were three
hospital deaths, all after the first operation, and four interstage deaths (six RAI; one LAI). There were no deaths after cavopulmonary shunt,
Kawashima or Fontan operation. A multivariate Cox regression identified greater than moderate atrioventricular valve regurgitation (Hazard
Ratio (HR) 17.5, p = 0.017) and obstructed TAPVR (HR 17.5, p = 0.007) as factors associated with increased RAI mortality. Due to the absence of
late mortality in both groups, patient survival at 3 years were 79% in RAI and 94% in LAI patients and remained stable after that (p = 0.22). All
survivors but one are in NYHA class I or II, without significant cardiovascular related symptoms. LAI patients have a higher incidence of sinus node
dysfunction than RAI patients (47% vs 12.5%, p = 0.009). Conclusions: Surgical outcomes in heterotaxy patients are improving in the current era.
regurgitation and obstructed TAPVR remain risk factors for RAI mortality. Survivors are doing well with no activity restrictions, although LAI
patients maintain a higher proclivity of sinus node dysfunction.
# 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Keywords: Heterotaxy; Surgical outcomes; Atrial isomerism
Visceral heterotaxy syndromes are characterized by
abnormal development of left or right sided structures.
Although in heterotaxy there are distinct anatomic abnorm-
alities in the lungs and various intra-abdominal organs,
cardiac anomalies dictate for the most part of the long-term
outcome . The hallmark lesion of cardiac heterotaxy is the
similarity between the two atrial appendages [2,3]. Histori-
cally visceral heterotaxy has been associated with significant
morbidity and mortality [2,4—7]. Right atrial isomerism has
been described by some as one of the worst forms of
contemporary heart disease  with overall 5-year survival
ranging from 30% to 74% [9,10]. The results are better in left
atrial isomerism with 5-year survival rates ranging between
65% and 84%, which is still considerably lower than survival
for most other forms of congenital heart disease [2,10]. The
combination of structural abnormalities of systemic and
pulmonary venous connections, increased incidence of single
ventricle physiology, the presence of obstruction to the
pulmonary and aortic outflows, the increased incidence of
significant arrhythmias, and sepsis associated with splenic
dysfunction have all been implicated in the poor surgical
whether current era management strategies have improved
outcomes in patients with visceral heterotaxy we reviewed
Between June of 1994 and June of 2008 45 consecutive
patients who underwent surgical treatment for visceral
European Journal of Cardio-thoracic Surgery 35 (2009) 871—878
§Presented at the 22nd Annual Meeting of the European Association for
Cardio-thoracic Surgery, Lisbon, Portugal, September 14—17, 2008.
* Corresponding author. Address: The Phoenix Children’s Heart Center, 1920
E Cambridge Avenue, Ste 304, Phoenix, AZ 85006, USA. Tel.: +1 602 5460200;
fax: +1 602 5462697.
1010-7940/$ — see front matter # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
In your paper you state long-term outcome. I was very happy that you said
in your conclusion that this needs further follow-up because this is not a long-
term observation and I think that 4 years it’s at best a mid-term and not a long-
And since in the paper you also used the term quality of life instead of
functional classes, I think if you use quality of life I think you should tell us the
parameters you have used for your quality of life evaluations.
Dr Anagnostopoulos: We are a pretty young center, so we don’t have
historical data. We’re creating our history so that we can compare our data in
regurgitation. I suspect that if you excluded all those patients, the outcome of
right atrial isomerism and left atrial isomerism would be the same, although
we did not do that analysis.
In terms of how we do the arch reconstruction, we excise the ductal tissue
during the Norwood procedure, re-anastomose the aorta posteriorly and
performan anterior patch augmentation with ahomograft material. And in the
repairwithout anterior augmentation withapatch, kindofliketheTexasHeart
paper and series.
In terms of your comment on our follow-up period, I agree. We went back
and looked at our manuscript critically just before we came here and we
decided, as you correctly pointed out, that those were not long-term
outcomes. Those at best are mid-term outcomes. But we are going to
continue to follow-up on these patients and try to update our series in the
In terms of quality of life, yes, this is New York Heart Association
of life aspect of it. It’s just that this was a retrospective study and we got our
follow-up from the cardiology notes. And their recurrent theme is that these
patientswere doing excellent, whatever thatmeans. But no,wehave notdone
specific quality of life questionnaires.
P.V. Anagnostopoulos et al./European Journal of Cardio-thoracic Surgery 35 (2009) 871—878