Article title: Pulmonary hypertension with adult respiratory distress syndrome: prevalence, clinical impact, and association with central venous pressure Running head: Pulmonary Hypertension with ARDS

Background: Pulmonary hypertension (PH) occurs in patients with acute respiratory distress syndrome (ARDS); the most severe form comprises acute cor pulmonale (ACP). Here, we investigated the prevalence of PH in patients with ARDS to evaluate its correlation with ACP risk, ARDS severity and central venous pressure (CVP). Methods: We conducted a secondary analysis using data from the MIMIC-III open-source clinical database. The prevalence of PH associated with new-onset ARDS during the first 72 hours after intensive care unit (ICU) admission was investigated; moreover, the association between ACP risk score and PH was validated. We also evaluated the association between elevated CVP (mean CVP >10 mmHg) and PH and other clinical outcomes. Results: Among 2,434 patients who met the ARDS Berlin criteria and underwent echocardiography or pulmonary artery catheterization evaluation, a total of 583 (24.0%) patients were diagnosed with moderate or severe PH, of which 418 had low and 165 had high ACP risk. After adjustment for disease/ARDS severity, ACP risk score, and other demographic variables, elevated CVP was independently associated with the occurrence of PH [odds ratio, 2.239 (1.674, 2.993), p<0.005]. Among patients with PH, higher mean CVP was associated with prolonged hospital stay (13.4 vs. 15.2 days, p=0.041) and duration of ventilation (116.5 vs. 150.5 hours, p=0.023). Conclusions: Incidence of PH was 24.0% in patients with new-onset ARDS in this retrospective study. Elevated CVP is relevant with higher incidence of PH and worse clinical outcome; these highlighted the importance of hemodynamic monitoring in the management of ARDS. DOI: 10.1177/2045894020933087 Acute respiratory distress syndrome (ARDS) is frequently associated with pulmonary hypertension (PH), which is related to increased pulmonary vascular resistance and subsequent right ventricular dysfunction (1). Previous echocardiography (ECHO) (2) or pulmonary artery catheter (PAC) (3,4,5) studies have shown that mild to moderate elevation in mean pulmonary artery pressure (mPAP) occurs in most patients with ARDS. In particular, acute cor pulmonale (ACP), which is the most severe presentation of PH, is associated with a poor clinical outcome; this illustrates the importance of pulmonary hemodynamic assessment by intensivists (6). Recently, Dessap et al. proposed an ACP risk score that was validated in a prospective cohort of patients with ARDS, that study showed a 22% prevalence of ACP in 752 patients with moderate-severe ARDS (7). Although the importance of ACP identification and prevention is widely accepted in the management of ARDS (6,8), the prevalence, progression, and prognosis of PH associated with ARDS, has not been fully investigated(9). Additionally, scoring criteria have been limited to the field of mechanical ventilation (pneumonia as a cause of ARDS and driving pressure) and gas exchange (PaCO2 and PaO2/FiO2) and have not involved any hemodynamic monitoring parameters; notably, CVP has been associated with prognosis in critically ill patients (10, 11, 12) and should be included during the evaluation and identification of PH. Considering these limitations, we aimed to investigate the prevalence of PH in patients with new-onset ARDS, as well as in subgroups with varying levels of ACP DOI: 10.1177/2045894020933087 risk and ARDS severity; moreover, we aimed to evaluate the association between PH and a basic hemodynamic parameter: central venous pressure (CVP). We hypothesized that elevated CVP (mean CVP >10 mmHg) would be independently associated with the risk, severity, and clinical outcome of PH in patients with ARDS.