Abstract
BackgroundPatients with Down’s syndrome and shunt lesions are at high risk of developing pulmonary arterial hypertension (PAH) earlier than patients without Down’s syndrome. However, data on the efficacy of PAH-specific therapy in patients with Down’s syndrome are limited. The aim of this retrospective analysis was to determine the long-term efficacy of the dual endothelin receptor antagonist, bosentan, in Eisenmenger's syndrome (ES) patients with Down’s syndrome.MethodsIn this observational study adults with Down’s syndrome with a confirmed diagnosis of ES (World Health Organization functional class III) and receiving bosentan therapy and were followed up long term. Clinical evaluation at baseline and follow-up visits included resting transcutaneous arterial oxygen saturation and laboratory assessments. Exercise capacity was evaluated using a 6-minute walk test where transcutaneous arterial oxygen saturation at peak exercise (SpO2), 6-minute walk distance (6MWD) and Borg dyspnoea index were assessed. A full echocardiographic assessment was conducted at baseline and follow-up visits.ResultsOverall, seven adults (mean age 29.6 ± 11.2 years; 57% male) received bosentan at a starting dose of 62.5 mg twice daily. This was increased to the target dose of 125 mg twice daily 4 weeks later. All patients remained on bosentan until the end of the study. After a mean (± standard deviation) duration of 52.2 ± 3.9 months (range: 46.0–55.5 months), 6MWD had increased from 199.6 ± 69.1 metres to 303.7 ± 99.9 metres (P < 0.05) and SpO2 at the end of the 6-minute walk test had increased from 61.6 ± 7.6% to 74.7 ± 6.2% (P < 0.05). Echocardiography demonstrated a significant change in acceleration time from 62.9 ± 11.6 m/s to 83.0 ± 9.6 m/s (P = 0.0156), and acceleration time/ejection time ratio from the pulmonary flow from 0.24 ± 0.04 at baseline to 0.30 ± 0.02 (P = 0.0156) at final follow-up.ConclusionsLong-term treatment with bosentan significantly improved exercise capacity and oxygen saturation following exercise in adult ES patients with Down’s syndrome. These data confirm that the presence of Down’s syndrome does not affect the response to oral bosentan therapy.
Highlights
Patients with Down’s syndrome and shunt lesions are at high risk of developing pulmonary arterial hypertension (PAH) earlier than patients without Down’s syndrome
Patients with congenital heart disease (CHD) with significant untreated left-to-right shunt lesions are at risk of developing pulmonary arterial hypertension (PAH)
The prevalence of CHD in patients with Down’s syndrome is 40–60% [10,11] and the types of malformation that are most commonly associated with trisomy 21 are the atrioventricular and ventricular septal defects (AVSD and Ventricular septal defect (VSD)), which together account for 76% of all CHD seen in patients with Down’s syndrome [12]
Summary
Patients with Down’s syndrome and shunt lesions are at high risk of developing pulmonary arterial hypertension (PAH) earlier than patients without Down’s syndrome. The Euro Heart Survey on adult CHD (a retrospective cohort study with a 5year follow-up) reported PAH in 531 (28%) patients [2], while a Dutch registry showed a PAH prevalence of 4.2% in 5970 adult patients with CHD [3]. In the latter registry, 58% of patients with a septal defect who developed PAH had ES. Patients with Down’s syndrome represent an important subgroup in the ES population as they are considered to be at risk of PAH earlier than patients without Down’s syndrome and have worse functional capacity [4]. AVSD is frequently reported as the most common cardiac defect, there is some evidence that this varies according to sex and ethnicity [8,10,11,12,13,14,15]
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