Uncommon cause of paradoxical low-flow low-gradient severe aortic stenosis due to pulmonary arterial hypertension

A 74-year-old female presented with dyspnea [New York Heart Association (NYHA) class IV and 94 % percutaneous oxygen saturation at room air]. She was diagnosed with pre-capillary pulmonary arterial hypertension (PAH) due to connective tissue disease [mean pulmonary arterial wedge pressure (mPAWP): 6 mmHg; pulmonary arterial pressure (PAP): 93/36 [59] mmHg; pulmonary vascular resistance (PVR): 12.2 Wood units; cardiac index (CI): 2.95 L/min/m²] and paradoxical low-flow low-gradient severe aortic stenosis (AS) [mean gradient: 16.7 mmHg; max jet velocity: 2.87 m/s; aortic valve area: 0.70 cm²; left ventricular ejection fraction (LVEF): 65 %; stroke volume index (SVi): 31.1 mL/m²]. The patient was treated for PAH, which was considered to be the underlying cause of the paradoxical low-flow low-gradient severe AS. After 10-month titration of riociguat (7.5 mg/day) and selexipag (1.6 mg/day), PAH [mPAWP: 9 mmHg; PAP: 55/23 (36) mmHg; PVR: 5.9 Wood units; CI: 3.10 L/min/m²] improved and normal-flow high-gradient severe AS became evident (mean gradient: 41.9 mmHg; max jet velocity: 4.04 m/s; aortic valve area: 0.70 cm²; LVEF: 65 %; SVi: 41.7 mL/m²). Although symptoms improved to NYHA class II, exertional dyspnea persisted. Accordingly, medication dosages were further increased, and transcatheter aortic valve replacement was successfully performed 12 months after treatment initiation.

We aimed to understand how group 1 pulmonary arterial hypertension (PAH) can lead to paradoxical low-flow low-gradient severe aortic stenosis (AS), recognize its key clinical and hemodynamic features, and differentiate it from group 2 pulmonary hypertension (PH) associated with left heart disease, including isolated post-capillary PH and combined post- and pre-capillary PH. We also explored hemodynamic changes after PAH therapy, including transition to normal-flow high-gradient severe AS.