Effective Pharmacotherapy in Hereditary Pulmonary Arterial Hypertension: A Case of BMPR2 Mutation

Abstract Introduction BMPR2 gene mutations are a primary genetic cause of hereditary pulmonary arterial hypertension (PAH), leading to disrupted vascular repair, arterial narrowing, and elevated pulmonary pressures. This mutation typically results in a more severe PAH presentation, requiring combination therapy to manage symptoms effectively and slow disease progression. Description A 47-year-old morbidly obese female smoker with a history of hypertension and irritable bowel syndrome presented with acute hypoxic respiratory failure, raising concerns about new-onset heart failure. She had an elevated white blood cell count and tested positive for rhinovirus. Computed tomographic angiography ruled out pulmonary embolism, and Doppler of the lower extremities was negative for thrombosis. ProBNP was elevated at 6000 ng/L, and autoimmune testing, including lupus screening, was negative. Echocardiography showed a normal ejection fraction of 50-55% and normal diastolic function. Right ventricular systolic function was reduced, with a severe increase in cavity size at a pressure of 66 mmHg, moderate tricuspid regurgitation, and severe right atrial dilation. Right heart catheterization confirmed severe PAH, with elevated pulmonary artery pressures of 92/45 mmHg and a pulmonary vascular resistance (PVR) of 13 Woods units. An initial vasodilator challenge with Flolan improved cardiac output and reduced PVR, but pulmonary pressures remained high, necessitating a comprehensive treatment plan.The patient was started on tadalafil, a phosphodiesterase-5 inhibitor, known for reducing pulmonary pressures and enhancing exercise capacity in PAH. However, initial trials with the endothelin receptor antagonist macitentan were unsuccessful due to side effects, including significant facial and lower extremity swelling. Consequently, ambrisentan, another endothelin receptor antagonist, was considered as a potential alternative for better tolerance. She tested positive for the BMPR2 gene mutation. Given this mutation, the patient was later started on selexipag (Uptravi), a selective prostacyclin receptor agonist targeting the prostacyclin pathway, often disrupted in PAH due to BMPR2 mutations. Selexipag showed promising results, with the patient reporting significant symptom improvement, achieving NYHA Class II functional status, with enhanced tolerance for daily activities and recreational activities like kayaking, without dyspnea. Additionally, the patient's treatment included Bumex diuretics to manage fluid overload and losartan for blood pressure control. Discussion In this patient with PAH, initially dual-agent therapy was initiated. The addition of selexipag significantly improved her quality of life. This case highlights the critical role of pharmacotherapy in managing PAH associated with BMPR2 mutation.