Associazione Nazionale Medici Cardiologi Ospedalieri




Baratto Claudia Milano(Milano) – Ospedale San Luca IRCCS Istituto Auxologico Italiano | Gagliardi Maria Felicia Mialno(Milano) – Ospedale San Luca IRCCS Istituto Auxologico Italiano | Liberatore Michele Milano(Milano) – Ospedale San Luca IRCCS Istituto Auxologico Italiano

Background. Recreational methamphetamine is widely used worldwide (about 35 million people), mainly as 3,4-Methyl​enedioxy​methamphetamine (MDMA). A definite association has been established between methamphetamine and pulmonary arterial hypertension (PAH). This drug-associated form of PAH shares histological, clinical and hemodynamic characteristics, prognosis and treatment strategies with idiopathic PAH. However, the association between MDMA and a rarer and devasting form of PAH with concomitant venous involvement (pulmonary veno-occlusive disease, PVOD), has never been reported. Notably, initiation of PAH-specific treatment in PVOD may lead to catastrophic consequences.

Case description. A 32-year-old man was fast-track referred to our PH Centre in December 2023, due to high echocardiographic probability of pulmonary hypertension (PH). After interrogation, he admitted the regular use of MDMA. No other risk factor for PAH was found. Right heart catheterization showed a pre-capillary PH (mean pulmonary artery pressure 35 mmHg; wedge pressure 12 mmHg; pulmonary vascular resistance 5.9 WU) with low cardiac output (2.2 L/min/m2) and no acute response to vasoreactivity testing. Exercise capacity was severely reduced (oxygen consumption 19.6 mL/Kg/min, 50% of predicted) due to absent stroke volume reserve, accompanied by augmented exercise hyperventilation (VE/VCO2 slope 60) and exercise-induced desaturation (SaO2 94 à 77%), this latter not explained by a right-to-left shunt. Diffusion capacity of the lung was severely reduced (DLCO 28%). Chest CT and perfusion scan excluded both thromboembolic etiology and parenchymal lung disease. A diagnosis of PVOD was made, based on the presence of pre-capillary PH, oxygen desaturation, extreme exercise hyperventilation and very low DLCO, even in the absence of pathognomonic CT features. Counselling for stopping MDMA abuse was offered. Cautious monotherapy with macitentan was started and was well tolerated. A genetic testing for EIF2AK4 is ongoing. Contact with transplant center has been performed. A follow-up RHC has been planned before careful therapy up-titration.

Conclusions. This is the first case reported of the potential association between methamphetamines and PVOD. Due to the large worldwide use of MDMA, this link should be considered because of its prognostic and therapeutic implications. The diagnosis of PVOD is a clinical one, needing a high index of suspicion especially in the absence of chest CT findings.