Heterotaxy syndromes or cardiac isomerisms, depending on the morphological school of thought employed, encompass a highly heterogeneous group of cardiac and extracardiac anomalies. These conditions represent some of the most complex profiles encountered in congenital heart disease units. Long-term data on treatment and prognosis for these patients are scarce. Identifying cases amenable to biventricular repair is essential, as univentricular pathways are associated with poorer short- and long-term outcomes within this patient population.
This study is a historical review analyzing five decades (1973–2021) of heterotaxy syndrome management. Its objective was to compare long-term outcomes of univentricular versus biventricular strategies. Patients were categorized by asplenia and polysplenia (Van Praagh’s school) instead of defining atrial appendage morphology, which provides insights into isomerism type and laterality (Anderson’s school). The primary endpoint was survival after birth.
A total of 230 patients were identified: 107 (47%) with polysplenia and 123 (53%) with asplenia. The majority (87%) followed a single-ventricle pathway, with 90% reaching the Fontan stage. Most patients exhibited a dominant right-ventricular morphology. One-third had total anomalous pulmonary venous drainage, and another third showed inferior vena cava interruption. The mean age for Fontan completion was 7.5 years, with an overall hospital mortality of 17%, decreasing to below 10% since 1995. Only one death occurred in the biventricular group.
With a median follow-up of 20 years, 43% of the cohort had died within 15 years. At 30 years, survival was markedly lower in the single-ventricle cohort compared to the biventricular group (53% vs. 93%; p = .001). Among single-ventricle patients, those achieving Fontan showed slightly higher survival rates at 20 years compared to those who did not (68% vs. 63%). Overall, asplenia patients had worse survival compared to those with polysplenia (63% vs. 80%; p < .001). Stratified analysis within Fontan patients showed worsening outcomes for asplenia compared to polysplenia (39% vs. 56%; p < .001).
Approximately 23% of the cohort required permanent pacemaker implantation. Multivariable analysis revealed independent mortality risk factors: univentricular physiology (OR = 7.2), absence of prior Glenn (OR = 3.6), asplenia (OR = 2.7), and the need for a permanent pacemaker (OR = 2.3).
The authors concluded that asplenia subtype presents worse survival, and univentricular pathways are associated with inferior outcomes compared to biventricular repair.
COMMENTARY
Discussing heterotaxy syndromes necessitates explaining the two schools of thought to avoid misunderstandings. Terminological inconsistencies in the literature complicate comparisons between studies.
On one side, Richard Van Praagh’s American school identifies three types of heterotaxy syndromes: asplenia, polysplenia, and a normal right spleen (mirror image of normal situs). Asplenia is associated with an intact inferior vena cava and higher prevalence of atrioventricular canal defects, often resulting in interatrial defects. Conversely, polysplenia frequently exhibits inferior vena cava interruption between the subhepatic and suprarenal segments, with venous blood reaching the superior vena cava through the azygos/hemiazygos system.
Robert H. Anderson’s European school, on the other hand, categorizes patients based on isomerism rather than abdominal organ arrangement. Differentiation relies on atrial appendage morphology, considered the most constant atrial structure. Anderson’s descriptions include atrial morphology, ventricular mass, and arterial trunks, along with atrioventricular and ventriculo-arterial connections.
Like any published study, it is crucial to highlight limitations. This is a retrospective, single-center study spanning five decades. Its applicability to smaller centers is limited due to the quaternary nature of the hospital. However, such patients should ideally be treated in highly specialized centers. The lengthy study period explains the predominance of single-ventricle pathways and delayed Fontan surgeries.
In conclusion, the findings of Graham et al. confirm and quantify pre-existing notions. Publishing such extensive experiences is a milestone, offering valuable guidance for managing this heterogeneous group of patients.
REFERENCE:
Graham G, Dearani JA, Niaz T, Crow S, Cetta F, Stephens EH. Outcomes of Biventricular and Single Ventricle Heterotaxy Patients: A Single Center Five-Decade Experience. Ann Thorac Surg. 2023 May;115(5):1206-1211. doi: 10.1016/j.athoracsur.2022.05.045.
