PULMONARY HYPERTENSION AND CONGENITAL HEART DISEASE: THE CLINIC BEYOND THE EVIDENCE

Eisenmenger syndrome (ES), first described by Victor Eisenmenger, was defined by Paul Wood in pathophysiologic terms as “pulmonary hypertension (PH) at systemic level, caused by a high pulmonary vascular resistance (PVR), with reversed or bidirectional shunt at aorto–pulmonary, ventricular, or atrial level.” It represents the most severe hemodynamic phenotype of pulmonary arterial hypertension (PAH) in association with congenital heart disease (CHD) and develops in the presence of large, unrepaired atrial or ventricular septal defects, arterial shunts, or complex forms of CHD. Although therapeutic management has rapidly advanced in recent years, these patients were not included in randomized controlled trials for specific pulmonary arterial hypertension drugs, except for bosentan. However, in clinical practice we apply treatment strategies combining drugs targeting multiple pathobiological pathways. The clinical case we describe is that of a 44–year–old patient, suffering from Down syndrome, with ES due to subaortic VSD and a a patency of Botallo duct, followed in our PH clinic of the "Ruggi D‘Aragona" University Hospital for about 9 years. The patient, on dual therapy with Macitentan 10 mg and Sildenafil 60 mg, was in the intermediate–high risk class, stationary. During the last two checks, there was a progressive worsening of the hemodynamic parameters, walking distance of only 100 meters, with SpO2 at baseline 90% and desaturation during the 6mwt. On cardiac color Doppler ultrasound evidence of TAPSE 18 mm, PAPS 100 mmHg, RAA 20 cm²; TAPSE/PAPS 0.18. The patient presented in WHO class 3. The only RCTs currently available concern the use of bosentan, but in clinical practice, initial monotherapy with an endothelin receptor antagonist or a phosphodiesterase type 5 inhibitor for symptomatic patients is proposed. Reassess and consider escalation to a double combination therapy in case of clinical worsening or inadequate clinical response. Consider uptitration with the addition of prostanoids when inadequate response and timely assess the eligibility for transplantation. For our patient therefore, in consideration of the impossibility of surgery, although there is little evidence on prospective observational studies based on cohorts of a few patients, we added selexipag 200 ug x 2/day to titrate therapy.This case opens the door to still unclear scenarios in which unfortunately the only weapon available remains the clinician‘s judgment and experience.