Transposition of the great arteries (TGA) is one of the most common congenital heart diseases (CHD) presenting at birth with cyanosis [1]. Unpalliated TGA has a 90% mortality rate within the first year of life [2]. Survival improved dramatically after the introduction of radical surgery in the form of atrial switch procedures by Drs Ake Senning in 1959 and William Mustard in 1964; this became standard practice in the 1970s [3,4]. The initial patients who underwent Mustard and Senning correction operations are now well into adulthood, making long-term follow-up possible. Prior studies reported that 60–80% of patients were alive 30 years after repair [5–7]. Complications encountered in adult life are well-characterized and include sinus node dysfunction, atrial arrhythmias, sudden death, systemic right ventricular (RV) dysfunction, tricuspid regurgitation, pulmonary hypertension (PH), and baffle obstructions and leaks [5–8].

PH has been documented in up to 7% of patients surviving to adulthood after the atrial switch procedure. After the development of PH, individuals have reduced exercise tolerance and quality of life [9]; additionally, PH has been associated with an adverse prognosis [9,10]. Although catheterization is required for the diagnosis of PH, there have been few studies that have investigated PH using catheterization in the long-term follow-up of these individuals [10]. We therefore conducted a retrospective cohort study of adults with TGA who underwent the atrial switch procedure to assess the prevalence, characteristics, and prognosis of PH using catheterization data.

This study was conducted in strict adherence with the principles of the Declaration of Helsinki and was approved by the Clinical Investigation Ethics Committee of Tokyo Women’s Medical University (5619). De-identified participant data will not be shared in public.

In the present study, PH was detected in 33% of patients with TGA after undergoing the atrial switch procedure. Additionally, patients in the PH group had increased cardiac death and heart failure. Finally, improvements in PH and the NYHA class were achieved by the initiation of accurate therapy in the three of the five patients who underwent a second catheterization during the follow-up period. These three patients had isolated postcapillary or precapillary PH.

PH is a serious complication of atrial switch procedures documented in up to 7% of patients surviving to adulthood [9]. The main reason for the discrepant rate observed in our study and prior studies might result from differing inclusion criteria. Prior studies included all patients who underwent atrial switch procedures and survived to adulthood. Conversely, the present study only included patients who underwent catheterization. Another study that included patients who underwent catheterization after the atrial switch procedure reported that PH was detected in 54.5% of patients referred for catheterization [10]. The indications for catheterization in the previous study and our study were heart failure or worsening functional capacity. PH rates may be higher in patients with symptoms such as shortness of breath.

In the current study, patients in the PH group had an adverse prognosis; they had a higher number of prior arrhythmia events, BNP, and systemic RV EDV/EDVI, and a lower systemic RV ejection fraction. Additionally, PH was postcapillary in all cases except for one case. These findings demonstrated that PH in adulthood after the atrial switch procedure might result from RV heart failure. Prognosis in the PH group might be poor due to advanced RV heart failure. After the atrial switch procedure, systemic RV dysfunction can develop at any stage. However, it is almost uniformly present in older patients, thereby indicating that the anatomic RV is unable to sustain the systemic circulation over long follow-up periods [6,13]. A previous study reported that pulmonary stenosis can be helpful in supporting the RV function of patients with TGA who underwent atrial switch procedures [14]. Although we did not analyze pulmonary stenosis in the present study, the presence of pulmonary stenosis might have affected systemic RV function. Although systemic RV function in the non-PH group was also low (42.5 ± 8.1%), PH was not detected in the non-PH group. One reason for this might be the low levels of RV end-diastolic pressures and PCWP of the non-PH group. Low levels of RV end-diastolic pressures and PCWP indicate low afterload of the pulmonary circulation; therefore, PH would not have been detected in the non-PH group.

The management of PH in patients with TGA requiring atrial switch procedures remains unknown. Previous studies demonstrated that pulmonary vasodilators were effective for patients with precapillary PH after they underwent atrial switch procedures [8,15]. Conversely, because postcapillary PH might result from RV dysfunction, standard heart failure treatment might be effective. As for the pharmacological therapy for RV dysfunction, renin-angiotensin-aldosterone system blockers did not seem to convey benefits for RV function or exercise capacity [16,17]. In contrast, β-blockers may have a beneficial role in systemic RV [18]. The effectiveness of CRT for systemic RV has not been established. According to the European working group on CHD, CRT should be considered for patients with a NYHA class ≥II, impaired systemic RV function, and right bundle-branch block, and for patients who are already receiving LV pacing with systemic RV dyssynchrony and dysfunction [19]. Thus, among 13 patients in the present study with PH, six (46%) received an ACE-I or ARB, and seven (54%) received a β-blocker. One patient had his/her pace maker upgraded to CRT. Among the five patients who underwent a second catheterization during the follow-up period, patient 3 was diagnosed with precapillary PH. Subsequently, patient 3 received higher doses of the pulmonary vasodilators and showed improved PH and exercise tolerance. Patients 1 and 5 were diagnosed with isolated postcapillary PH and had enough margin for standard heart failure therapy. These patients received enhanced medical therapy and showed improvements in their PH and exercise tolerance. Patients 2 and 4 received full medications for heart failure at the first catheterization. Although the two patients underwent advanced heart failure therapy including CRT, their PH and exercise tolerance did not improve. Early interventions by medication might assist in improving PH and exercise tolerance among those with postcapillary PH due to systemic RV dysfunction. Although none of the patients underwent mechanical circulatory support and heart transplantation, the American Heart Association suggests that patients with systemic RV and advanced heart failure who do not respond to or are unsuitable for CRT and failing medical therapy should be referred to mechanical support or heart transplantation before other organ failure and PH occur [20].

To our knowledge, the number of patients who underwent catheterization after the atrial switch procedure is larger than that reported in previous studies. In our study, there were five patients who underwent a second catheterization during the follow-up period. As mentioned above, early interventions for systemic RV dysfunction via medications might assist in improving PH and exercise tolerance. Catheterization at an appropriate time is necessary for the early diagnosis of PH. Because a previous report and our study showed PH onset 20 years after the atrial switch procedure [10], it might be better to perform a catheterization 10 years after the atrial switch procedure and then follow-up every 5 years.

The present study had several limitations that merit mentioning here. First, this was a retrospective study based on a medical chart review. Second, because the number of cases was too small, adjustment or multivariable analysis could not perform in the present study. Third, the eligible patients were limited to those who had catheterization performed between April 2007 and March 2020. Although we have been performing catheterization on all patients in the remote period after the atrial switch procedure based on our department policy, patients who died before this period or who had catheterization performed outside of this period were excluded from the present study. Fourth, in this study, because 36/40 (90%) patients in this study have undergone catheterization before 2018, we did not use the current definition of PH that was presented at the 6th World Symposium on PH. The results of the present study may be different if the new definition of PH was used. Fifth, because the treatment protocol was determined by the responsible physician, the medication prescribed differed from patient to patient. Finally, the follow-up period of the present study was short, thus the long-term prognosis of patients with PH was not investigated.

PH is very prevalent in adults with TGA who underwent the atrial switch procedure and is associated with an adverse prognosis. Early therapy for systemic RV might improve PH and exercise tolerance after the atrial switch procedures.

Data sharing: The data underlying this article will be shared on reasonable request to the corresponding author.