PLASMA LEVEL OF ANTIMONY CORRELATES WITH PULMONARY HYPERTENSION SEVERITY

Abstract

TOPIC: Pulmonary Vascular Disease TYPE: Original Investigations PURPOSE: Heavy metals are linked to cardiovascular disease, but the relationship between heavy metals and pulmonary arterial hypertension (PAH) is not clear. We hypothesized that there may be a correlation between heavy metal levels and the severity of pulmonary hypertension METHODS: A prospective, single center pilot study recruited patients from our pulmonary hypertension center over a period of 3 months. Patients with PAH who were ≥ 18 years old were eligible to participate. We obtained IRB approval and all the participated patients signed an informed consent. Blood and urine samples were collected to measure essential and non-essential metal levels in blood, plasma, and urine using an X Series II quadrupole inductively coupled plasma mass spectrometry (ICP-MS, Thermo Fisher Scientific). Also, we collected demographics, hemodynamics, last 6 minute walk distance (6MWD), last available BNP level, and REVEAL Lite 2 risk score. Statistical analysis was performed using statistical software R and p value<0.05 was considered significant. RESULTS: A total of 20 patients with PAH were included in the study. The mean age was 57.6±11.8 years, 80% were female and 6 patients had idiopathic PAH. All the patients were receiving PAH combination therapies including a prostanoid agent (13 on parenteral treprostinil, 1 on epoprostenol, 5 on inhaled treprostinil, and 1 on selexipag) with a mean parenteral treprostinil dose of 67.8±28.9 ng/kg/min. Mean last 6MWD was 312.7m±96.2 and mean last BNP level was 118.3±129.6 pg/ml. RVEAL Lite 2 risk score was low in 9 patients, intermediate in 6, and high in 4 patients. Mean hemodynamic values were mRAP 5.9±4.4 mmHg, mPAP 45.6±13.9 mmHg, PAWP 8±3.5 mmHg, CO 5.1±1.4L/min, CI 2.86±1.1 L/min/m2, and PVR 8.32±4.4 WU. There was significant correlation between plasma level of 121Sb (Antimony) and mRAP (r=0.47, p=0.036), CO (r=-0.50, p=0.026), CI (r=-0.54, p=0.014), PVR (r=0.52, p=0.019), and PA saturation (r=-0.54, p=0.016). CONCLUSIONS: We found significant correlations between plasma level of 121Sb and prognostic hemodynamic markers of disease severity in PAH patients without known prior history of occupational heavy metal exposure. CLINICAL IMPLICATIONS: Antimonial compounds are still used in treatment of Leishmaniasis with cardiac toxicity being one of the known potential side effects. Ventricular myocytes of guinea-pigs treated with trivalent antimony showed impaired contraction responses to changes in stimulus frequency, reduced calcium current, and elongated action potential. However, significant correlation between serum 121Sb levels with the prognostic hemodynamic markers of disease severity in PAH patients has not been reported. This finding may suggest that environmental 121Sb can have a potential role in pulmonary hypertension and right ventricular dysfunction. More studies are needed to further elucidate this role and its mechanism. DISCLOSURES: No relevant relationships by Ozan Akca, source=Web Response No relevant relationships by Lu Cai, source=Web Response No relevant relationships by Oscar Chen, source=Web Response Speaker/Speaker's Bureau relationship with United therapeutics Please note: $5001 - $20000 by Karim El-Kersh, source=Web Response, value=Honoraria Removed 04/21/2021 by Karim El-Kersh, source=Web Response Advisory Committee Member relationship with United therapeutics Please note: $1001 - $5000 by Karim El-Kersh, source=Web Response, value=Consulting fee Removed 04/21/2021 by Karim El-Kersh, source=Web Response Advisory Committee Member relationship with Actelion Please note: $5001 - $20000 by Karim El-Kersh, source=Web Response, value=Consulting fee Removed 04/21/2021 by Karim El-Kersh, source=Web Response Advisory Committee Member relationship with United Therapeutics Please note: Current Added 04/23/2021 by Karim El-Kersh, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Actelion Please note: 2019 and 2020 Added 04/23/2021 by Karim El-Kersh, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with United Therapeutics Please note: Current Added 04/29/2021 by Karim El-Kersh, source=Web Response, value=Honoraria Advisory Committee Member relationship with United Therapeutics Please note: Current Added 04/29/2021 by Karim El-Kersh, source=Web Response, value=Honoraria Advisory Committee Member relationship with Actelion Please note: 2019 and 2020 Added 04/29/2021 by Karim El-Kersh, source=Web Response, value=Honoraria Consultant relationship with Acceleron Pharma Please note: Current Added 04/29/2021 by Karim El-Kersh, source=Web Response, value=Consulting fee No relevant relationships by C. Danielle Hopkins, source=Web Response Consultant relationship with GE Healthcare Please note: 2019-Present Added 04/27/2021 by Jiapeng Huang, source=Web Response, value=Consulting fee Research grant relationship with Gilead Sciences Please note: 2020-2022 Added 04/27/2021 by Jiapeng Huang, source=Web Response, value=Grant/Research Support Consultant relationship with GE Healthcare Please note: 2019 to Present Added 04/27/2021 by Jiapeng Huang, source=Web Response, value=Consulting fee Research Funding relationship with Gilead Sciences Please note: 2020-2022 Added 04/27/2021 by Jiapeng Huang, source=Web Response, value=Grant/Research Support No relevant relationships by Caitlin Wessel, source=Web Response