400 Refractory pulmonary hypertension in a young woman

Aims Clinical case—Twenty-four years old Moroccan woman. Family history: parents and three siblings in good health. Methods and results Past medical history—In 2016, when she was 19 years old, she developed worsening exercise-induced dyspnoea. A right heart catheterization (RHC) was performed with evidence of increased median pulmonary artery pressure (mPAP 60 mmHg, wedge pressure 8 mmHg), cardiac index 2.27 l/min/m2. She was diagnosed with idiopathic pulmonary hypertension and combination therapy with sildenafil and macitentan was started with partial improvement. In August 2019, she became pregnant and vasodilatory therapy was suspended. The pregnancy was complicated by premature labor with foetal death. Specific therapy with sildenafil and macitentan was then restarted. Due to further clinical and haemodynamic impairment, triple combination therapy with selexipag was initiated. However, symptomatic deterioration progressed, and she was referred to a Pulmonary Hypertension Referral Center where HRTC of the chest showed centrilobular ground-glass opacities and interlobular septal thickening. Based on the imaging that was highly suspicious pulmonary veno-occlusive disease (PVOD), and the severe haemodynamic impairment (with pulmonary vascular resistance at RHC > 20 WU), assessment for lung transplantation was started. Recent medical history—she was transferred to our Center with Transplant Unit for lung transplant assessment. Pulmonary function testing demonstrated a restrictive disorder with severe reduction of DLCO (14%). At 6-min walking test, she could walk 100 m with desaturation up to 90% on O2 therapy. Evaluated by our multidisciplinary team, indications for lung transplantation were confirmed and she entered the transplant waiting list. At the end of February 2021: further clinical and haemodynamic deterioration with respiratory distress, reduction in urinary output and signs and symptoms of right-side heart failure; she was hospitalized in intensive care unit and required extra-corporeal membrane oxygenation (ECMO) circulatory support. Selexipag was suspended. On echocardiography: severe right ventricle hypertrophy and dilatation, tricuspid regurgitation velocity >4 m/s. Few days later, she underwent bilateral lung transplantation; anatomo-pathological evaluation of explanted organs confirmed PVOD. However, during post-operative monitoring, she suffered from two episodes of cardiac arrest on VT/VF which required multiple DC-shocks. Since no triggering causes were identified, an ICD was implanted for secondary prevention. Conclusions PVOD is a rare disease with clinical presentation and haemodynamic profile often similar to pulmonary arterial hypertension (and, therefore, the diagnosis is challenging) but the clinical course is more severe. The diagnosis requires clinical history and physical examination, together with multimodality imaging and functional testing. Bronchoalveolar lavage might be necessary. Patients do not usually respond satisfactorily to vasodilatory therapy but rather they are at high risk of drug-induced pulmonary oedema. Some case reports and case series have reported a slight benefit and/or clinical stabilization with vasodilatory therapy in selected patients; therefore, specific therapy can be used but cautiously and in experienced referral centres. Definitive therapy is lung transplantation (or heart-lung transplantation) and a multidisciplinary team is necessary for the appropriate management of these complicated patients. Ventricular arrhythmias are rare in patients with Group 1 pulmonary hypertension. In our specific clinical case, we suspect that ventricular arrhythmias might be related to the severely hypertrophic, and potentially fibrotic, right ventricle.