Association of elevated pulmonary artery systolic pressure with hematologic progression in myeloproliferative neoplasms.

6575 Background: Pulmonary hypertension (PH) is associated with myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Prior studies have suggested that patients with MPN and cardiovascular disease (CVD) with PH are at increased risk of progression of MPN to secondary MF or acute leukemia. Further characterization of risk of hematologic progression among all-comers with MPN is lacking. Methods: In this single-center, retrospective cohort study, patients with MPN and ≥ 1 transthoracic echocardiogram (TTE) after diagnosis were identified. PH was defined as an estimated pulmonary artery systolic pressure (PASP) ≥ 40 mmHg on first TTE after MPN diagnosis. Primary outcome was hematologic end-point, composite of progression of MPN to secondary MF, acute leukemia, death related to MPN, or bone marrow transplantation (BMT). Secondary endpoint was major adverse cardiovascular events (MACE), composite of arterial thrombosis, venous thromboembolism, heart failure (HF) and CV death. Multivariable Fine-Gray competing-risk regression (with non-hematologic death and non-CV death as competing-risks for hematologic endpoint and MACE, respectively) were used to estimate risk of outcomes. Results: Of 272 patients with MPN identified, 69 (25.4%) had PH on first TTE. Patients with PH were older at MPN diagnosis, had more MF (27.5% vs 11.8%, p = 0.004), and prior HF (18.8% vs 6.4%, p = 0.004). Patients with PH had higher rates of secondary mutations (24.6% vs 13.3%, p = 0.024), particularly in ASXL1 (8.7% vs 2.5%, p = 0.034) and RUNX1(4.3% vs 0, p = 0.016). After a median follow-up of 46.2 months (IQR 29.3, 69.1), hematologic endpoint (30.4% vs 8.4%, p < 0.001 and MACE (53.6% vs 23.6%, p < 0.001) were higher in PH group. Rates of secondary MF (13.0% vs 4.9%, p = 0.030), acute leukemia (13.0% vs 0.5%, p < 0.001), and death related to MPN (8.7% vs 1.5%, p = 0.01) but not BMT (2.9% vs 3.4%, p = 1.00) were higher in PH. After adjusting for age, sex, MPN type, mutation, and time from MPN to first TTE, PH was associated with higher risk of hematologic endpoint (aSHR 3.70, 95% CI 1.55 – 8.82). After adjusting for the same variables as well as LVEF, left atrial size, prior CVD, PH was associated with increased risk of MACE (aSHR 2.38, 95% CI 1.42 – 3.97). Conclusions: Among patients with MPN, PH on TTE was associated with increased risk of hematologic progression and MACE. Prospective studies are needed to confirm our findings. Further investigation into the underlying mechanisms of PH in MPN should be conducted. Table: see text