Although an early repair of congenital heart diseases (CHD) can prevent the occurrence of pulmonary arterial hypertension (PAH), still, in some cases, PAH either persists or comes down after surgery only to reappear again. The European Society of Cardiology Guidelines classify these cases under Group D of PAH-CHD as per Galiè et al. [Table 1]. We are reporting a case of secundum atrial septal defect (ASD), left to right shunt with severe PAH who has undergone successful robotic assisted closure surgery and found to have persistence of PAH post operatively. These patients respond to pulmonary vasodilators (PVDs) such as phosphodiesterase inhibitors (PDEIs) and endothelin receptor antagonists (ERAs) to improve symptoms and exercise tolerance. Not much data are available in adults belonging to Group D regarding the dosage, response, and duration of therapy, particularly the impact of sudden stoppage of PVDs.
The present report involves an adult who continued to have a severe PAH even after a successful repair. With a combination of PDEIs and ERAs, she showed improvement in her symptoms and 6-min walk distance (6 MWD). On cessation of therapy due to pregnancy, worsening of symptoms and 6MWD were noted, and reintroduction showed an improvement documenting the need to continue PVDs to maintain a persistent benefit.
A 27-year-old female was diagnosed to have large secundum ASD with a severe PAH, without systemic arterial desaturation even after exercise. She is nondiabetic and normotensive and negative for human immunodeficiency virus antibodies. She was on thyroid replacement therapy. She had an uneventful delivery 2 years before presentation and was in the World Health Organization functional class III at the presentation. The diagnosis was confirmed by echocardiography and hemodynamic studies [Tables 2 and 3]. Three months after robotic surgical repair, she remained symptomatic, and 6MWD was 390 M. Blood investigations were normal. Echocardiogram revealed the persistence of severe PAH with right ventricular dysfunction without any residual shunt. She was started on tadalafil 20 mg once daily. She was on a periodic follow-up with clinical, biochemical, and echocardiographic assessment and are shown in Table 3. During follow-up, the dose of tadalafil was increased to 20 mg twice daily, and later, ambrisentan 5 mg once a day was added and was maintained on this combination.
Three and a half years after surgery, she presented with 6 weeks of pregnancy when PVDs were stopped as they were contraindicated. She has undergone a medical termination of pregnancy without our knowledge and not restarted PVDs and lost to follow-up. Nine months later, she reported with worsening dyspnea and 6MWD when echocardiographic and hemodynamic assessment revealed deterioration in right-sided pressures and increase in pulmonary vascular resistance. She was restarted on PVDs and at 6 months follow-up showed improvement in symptoms, 6 MWD, and regression of PA pressures assessed by echocardiogram.
Our case is an example of Group D of CHD-PAH, who responded to a combination of PVDs. There was worsening of symptoms and exercise tolerance with temporary cessation of PVDs, and reintroduction restored the lost gain. This report highlighted the need for the combination of PVDs and continuation without interruption.
PVDs are recommended in cases of CHD-PAH, and newer guidelines recommend combining different classes of PVDs for optimal benefit with lesser side effects.[2,3] PDEIs were first to be introduced in our case and dose uptitrated at a periodic intervals. Tadalafil, a long-acting PDEI, has an advantage of once- or twice-a-day dosing thereby improving patient’s compliance, and it was chosen as a first-line therapy in our case and ambrisentan was added as it effects transaminases to a lesser extent compared to bosentan. The addition of ambrisentan has been shown to maximize the effects of improving symptoms and exercise capacity without elevating transaminases. In optimal study, tadalafil and macitentan combination showed improvement in symptoms, 6 MWD, and reduction of pulmonary vascular resistance. Real-life data showed that 17%–32% of patients with PAH-CHD received combination therapy,[7,8] but no mention was made about the subgroups.
As PVDs were contraindicated in pregnancy, they were stopped in our case as she was insistent on continuing pregnancy, but not restarted for 9 months when she was lost to follow-up. With worsening of symptoms and fall in 6MWD, restarting the PVDs proved to be beneficial with improvement in exercise capacity. Long-term usage of PVDs beyond 3 years has been shown to progressively worsen exercise capacity in one study; however, in our case, there was a rapid deterioration of exercise capacity after withdrawal of PVDs, as confirmed by the reduction in 6MWD which showed a steady improvement after reintroduction.
6MWD is the best matric to assess exercise capacity and it is safe and can be repeated when in doubt. Although PA pressures remain high in some cases, improvement in symptoms and exercise capacity may be noticeable. In our case, although patient remained in functional class II, she showed improvement in exercise tolerance.
Our case is a rare case of PAH-CHD, in whom temporary cessation of PVDs resulted in worsening of symptoms and effort tolerance which was reversed with reintroduction of PVDs. This highlighted the importance of continuing lifelong therapy with PVDs to obtain a sustained response. Although this was an accidental observation in our case, and the message was clear that PVDs should not be discontinued unless there is a strong contraindication.
In the present case, NT-proBNP was not measured.
In the management of PAH-CHD, early detection and timely repair are vital. Persistence of PAH after surgery is a condition similar to PAH of unknown etiology and they should be on a combination of PVDs, preferably PDEIs and ERAs. A periodic uptitration of dosage to the maximum tolerable doses with close monitoring of transaminases is essential. The best objective parameter to assess effort tolerance is 6MWD. Our report focuses the need for combination of PVDs and long-term uninterrupted therapy.
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