• Pulmonary vascular disease
• Secondary pulmonary hypertension
• Congenital heart disease
• Transposition of the great arteries
• Epidemiology

Pulmonary hypertension (PH) represents a severe problem affecting patients' wellbeing and is considered to occur in approximately 5.7% of patients with congenital heart disease (CHD) following corrective surgery.1 Particularly prone to the development of PH are patients with post-tricuspid shunt lesions, with an even higher incidence.

Because surgical strategy for transposition of the great arteries (TGA) has changed from atrial switch to anatomical correction, survival rates after arterial switch operation (ASO) have become excellent, with an early mortality of only 1% in the recent era2 and survival rates at 25 years of approximately 97%.3 However, morbidity and late sequelae remain a problem, leading to a freedom from reoperation of 82% at 23 years.2 Problems such as aortic root dilatation, aortic stenosis/recoarctation, outflow tract obstruction, pulmonary or supravalvular pulmonary stenosis and arrhythmia may occur, especially in longer term follow-up.2–4 Given the nature of the operation with reimplantation of the coronary arteries at neonatal age, particular attention is paid to the integrity of the coronary artery perfusion. Despite initial concerns, the incidence of relevant, symptomatic coronary artery disease is reported to be relatively low, although the reported prevalence varies between 2.1% and 11.3%.4 5

In this journal, Zijlstra et al 6, report on a less obvious problem in patients with TGA after anatomical correction. The authors report on a selected patient cohort with simple transposition from tertiary centres for PH in five countries, who presented with PH postoperatively, despite timely corrective surgery (within 6 weeks). Interestingly, the authors describe two phenotypic presentations, one with an early onset after surgery (within the first year after surgery) and the other with a late presentation (>1 year postoperatively). Unfortunately, both forms share a poor prognosis, despite the use of advanced therapies. Although rare, this subgroup of patients with TGA and PH after ASO requires particular clinical attention as it is associated with significant morbidity and especially increased mortality after ASO.6

Due to high incidence of patients in their group, who required early atrioseptostomy (84%) compared with patients with TGA without PH (40%),7 the authors hypothesise that antenatal factors, such as a restrictive physiology, prenatal hypoxic pulmonary blood flow and increased bronchial perfusion, may play a causative role altering the normal programming of pulmonary vascular development and may explain the early onset of pulmonary vascular disease (PVD).

The authors also point out that no genetic testing has been performed in this patient cohort and speculate that underlying gene mutations, which have been described to be associated with PH, may also play a causative role in this setting, potentially explaining a certain susceptibility to PVD. The associations of genetic mutations in the setting of PH in conjunction with CHD have been recognised previously by Li et al.8

Given the design of the study, based on a case collection from multiple tertiary centres, the authors were unable to provide accurate incidence estimates for PH in TGA/ASO patients. Although the nature and magnitude of the problem can be gauged based on the results provided by Zijlstra et al, acknowledging the risk of patients with TGA for developing PH is of interest to consciously screen for PH in the follow-up of this population.

To gain further insight into the incidence of disease, we searched the German National Register for Congenital Heart Defects database, which has shown to be representative of the spectrum of CHD.9 The registry currently includes 50 092 patients with CHD. Of these, 1737 patients had complete TGA as a diagnosis and 871 underwent primary ASO. Following careful electronic and manual search and by applying similar inclusion criteria as Zijlstra et al, we were only able to identify one patient with ASO for TGA with severe PH in the registry (see figure 1). As a consequence, based on this registry, the prevalence of disease is estimated at 0.11% (95% CI 0.29% to 0.64%).

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Figure 1

Data from the German National Registry of congenital heart disease. ASO, arterial switch operation; CHD, congenital heart disease; PH, pulmonary hypertension; TGA, transposition of the great arteries.

Hence the incidence in this mainly Caucasian cohort is overall comparable but slightly lower, compared with previously published reports of TGA case series where incidence has been estimated at 0.6%–1%.

The paper by Zijlstra et al is also interesting from a pathophysiological point of view. The described case series suggests that alternative mechanisms for the development of PH may exist in CHD, thus complementing the established pathogenic concept focusing entirely on long-standing increase in pulmonary blood flow leading to PVD and PH. This paper, therefore, highlights the need for an extension of the latest clinical classification of PH associated with CHD.10

The article by Zijlstra et al is a denotative example of multicentre collaboration, facilitating accurate characterisation and description of patients with a rare but important phenotypic presentation, which must not be missed. All in all, the case series illustrates a challenging patient cohort and emphasises the necessity to screen patients after ASO for possible PH. Patients should undergo a thorough and complete workup for PH, excluding other treatable causes or contributing factors of their PH. Those patients’ outpatient care should be linked to dedicated specialist PH clinics.

Further collaborative clinical research and consensus over uniform follow-up protocols are needed to facilitate clinical research and to compare these challenging patients followed at different centres with rare presentation of PH following ASO. This may also help to delineate best possible care strategies.11

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