Myelofibrosis Is Associated with Poor Cardiovascular Outcomes after Heart Failure Hospitalization

Background: Myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are at high risk of cardiovascular (CV) disease including heart failure (HF). Prior studies have suggested patients with MPN are at increased risk of HF. Among patients with MPN, those with MF have the most aggressive disease with significantly shortened survival. However, data on CV outcomes among patients with MF are sparse. Therefore, we examined CV outcomes among patients with MPN hospitalized for HF.

Methods: This was a retrospective cohort analysis of the National Readmission Database (NRD) of adult patients with a primary diagnosis of HF from 2017 and 2018 with a history of MPN (N = 4632), which were identified using ICD-10 codes. The primary outcome was 90-day unplanned CV-related readmission (readmission for HF, arterial thrombotic event [ATE], or venous thromboembolism [VTE]). Secondary outcomes were index hospitalization death and 90-day any-cause unplanned readmission. Propensity scores (PS) for estimating probability of MF were calculated using non-parsimonious multivariable logistic regression that included all baseline patient characteristics examined. PS weighting (PSW) was utilized to adjust for potential confounders. Patients with MF were compared with patients with ET or PV and standardized mean difference (SMD) was calculated for variables before and after PSW. Imbalances between groups were significant if SMD for a given covariable was ≥ 0.10. Hazard ratios (HR) were estimated for 90-day readmission outcomes using Cox proportional hazards regression and odds ratio (OR) for estimating index hospitalization death were calculated using logistic regression.

Results: A total of 3748 patients with ET or PV (2639 ET, 1109 PV) and 884 with MF were included. Prior to PSW, patients with MF were older (mean age 77.7 vs 74.3 years), more likely to have anemia (53.8% vs 47.2%) and less likely to be female (44.9% vs 56.1%), have systolic HF (39.9% vs 46.1%), and cardiogenic shock (1.6% vs 3.4%) compared with ET/PV, Table. After PSW, baseline characteristics were well balanced between groups. After PSW, MF was associated with increased risk of 90-day CV readmission (HR 1.18, 95% CI 1.08 - 1.30), index hospitalization death (OR 1.67, 95% CI 1.38 - 2.01), and 90-day any-cause readmission (HR 1.26, 95% CI 1.17 - 1.35). Additionally, MF was associated with increased risk of 90-day HF readmission (HR 1.24, 95% CI 1.12 - 1.38) but not ATE (HR 0.62, 95% CI 0.47 - 0.81) or VTE-readmission (HR 0.72, 95% CI 0.43 - 1.19), Figure.

Conclusions: Patients with MPN admitted with HF have high rates of 90-day CV-related and any-cause readmissions. MF was associated with higher risk of 90-day CV-related, HF, and any-cause readmission compared with patients with ET or PV. Patients with MF had higher risk of index HF hospitalization mortality compared with ET or PV. More investigation is needed in order to identify risk factors for adverse CV outcomes in patients with MPNs with HF, particularly those with MF. Although preventing thrombotic complications and managing CV risk are part of routine care for ET and PV patients, this study highlights the importance of incorporating CV risk management in MF patients.