Advanced Pulmonary Hypertension Shortens Survival in Polycythemia Vera

Rationale Pulmonary Hypertension (PH) is a known complication of myeloproliferative neoplasms, with prevalence estimated to be as high as 50%. PH is a progressive, morbid, and deadly condition characterized by elevated pulmonary artery pressures leading to right heart failure and death if untreated. Symptoms of PH, such as dyspnea, chest pain, presyncope, lower extremity edema, and profound fatigue, overlap with those of Polycythemia Vera (PV). Yet, the impact of PH on outcomes and survival in patients with PV is not known. To address this gap, we investigated the effect of PH on survival in a large cohort of patients with PV. Methods In this retrospective study, we identified all patients with PV who underwent echocardiography (echo) at the Silver MPN Center of Weill Cornell Medicine. Baseline data including age, sex, date of PV diagnosis, death status, date of progression (if applicable), comorbid medical conditions, laboratory values, pathology, medications, and echocardiography were collected from the WMC MPN research data repository and manually reviewed for accuracy. All patients with PV who underwent echo between February 2011 and July 2023 were included. Of 570 patients with PV, 133 had at least one echo. Overall survival (OS) did not differ between patients with echo data and a propensity score matched cohort of 266 PV patients without echo (no-ECHO cohort), indicating baseline health was not associated with echo. PH diagnosis was based on tricuspid regurgitation jet velocity determined by echo, with standard cutoffs of >2.8 m/s for PH and >3.4 m/s for advanced PH. Survival was modeled using Kaplan Meier estimates and Cox Proportional Hazard Models. Results The prevalence of PH and advanced PH in this PV cohort was 25% and 6.8% respectively. Median age at echo was 73 years, with no significant difference related to PH. The median duration of PV prior to echo was 6.9 years. Patients with PH were slightly older than those without PH (median age 75 vs 71 years, p=0.03) but had significantly longer duration of PV before echo (median duration 12 vs 5 years, p<0.001). No significant differences were observed between advanced PH, mild PH, and no PH groups regarding sex, history of thrombosis, and other medical factors. Kaplan-Meier analysis showed median survival for advanced PH was 0.72 years, significantly (p=0.003) shorter than for mild PH (5.0 years) and no PH (not reached). Ten-year survival rates were 55% for no PH, 29% for mild PH and 17% for advanced PH (p= 0.003). Cox Proportional Hazard Models adjusted for age at echo and thrombosis history, identified advanced PH as independently associated with death (HR= 3.1 CI: 1.4-7.1). Interestingly, progression-free survival (PFS) was also significantly shorter in PH patients compared to those without PH (71% vs. 92%, p= 0.008). Logistic regression identified age (odds ratio 3.9) and duration of PV (odds ratio 6.7) as significant risk factors for PH. Receiver operator characteristic (ROC) analysis identified Age > 70 and PV duration > 8 years as the optimal cutoffs for PH screening. Conclusions For patients with PV, advanced PH is independently associated with 3-fold shortened survival, representing a significant, prognosis-altering diagnosis. Based upon logistic regression and ROC optimization, we recommend echocardiographic screening for symptomatic patients, those older than 70 years, and those with PV for longer than 8 years. This study highlights the importance of understanding the natural history of PH in PV, generating an algorithm to identify PH, inclusive of right heart catheterization, and addressing best therapies for pre-capillary, post-capillary and combined pre/post-capillary PH in the at risk PV patients.