Incidence, Risk Factors, and Prognostic Implications of Heart Failure Hospitalizations Among Patients with Myeloproliferative Neoplasms

Introduction:

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are chronic leukemias associated with increased risk of cardiovascular disease (CVD), including heart failure (HF). Prior studies of patients hospitalized with HF have suggested that patients with MPN are at increased risk of readmission for HF and thrombosis, compared with patients without MPN. However, among patients with MPN without prior known HF, incidence, risk factors and prognostic implication of HF hospitalization have not been well-characterized.

Methods:
This was a multicenter retrospective cohort study of MPN patients with ≥ 1 transthoracic echocardiogram (TTE) after diagnosis of MPN at New York University Langone Health or Massachusetts General Hospital from 2010 to 2023. Patients with prior hospitalization for HF or reduced left ventricular ejection fraction (LVEF; < 50%) on first TTE were excluded. H2FPEF score, a scoring system that integrates risk factors for HF including clinical factors (age, body mass index [BMI], hypertension, and atrial fibrillation [AF]) and echocardiographic findings, was calculated for all patients.

To identify risk factors for HF hospitalization, variables that were different between patients with versus without HF hospitalization after first TTE (p < 0.10) were entered into a stepwise backward Fine-Gray competing-risk regression was performed with death as a competing risk. Variables that remained statistically significant (p < 0.05), as well as age, sex, MPN type and driver mutation, were kept in the model.

To explore the association between HF hospitalization and all-cause mortality, multivariable Cox proportional hazards regression was performed and adjusted for age, MPN type, MPN driver mutation, treatment for MPN, aspirin use, prior AF, prior atherosclerotic cardiovascular disease (ASCVD, including coronary artery disease, peripheral arterial disease, and prior stroke), prior venous thromboembolism (VTE), H2FPEF score, diabetes and spleen size.

Results:

Of the 490 patients included, 43.3% had PV, 41.6% ET, and 15.1% had MF at time of TTE, 52.7% were female and 86.1% were White race. 86 patients (17.6%) had HF hospitalization after first TTE with a median time of 34 months (IQR 15, 59) from TTE. Patients who had HF hospitalization were older (median 78 vs 71 years) and more likely to be White (94.2% vs 84.4%). The proportion of patients with PV (41.9% vs 43.6%), ET (46.5% vs 40.6%), and MF (11.6% vs 15.8%) were similar between patients with and without HF hospitalization. The proportion of patients with a JAK2 driver mutation (81.4% vs 77.2%) was similar between groups. After stepwise competing-risk regression, age (adjusted subhazard ratio [aSHR] 1.19, 95% CI 1.07 – 1.32), spleen size (aSHR 1.37, 95% CI 1.10 – 1.71), WBC (aSHR 1.03, 95% CI 1.01 – 1.04), at least moderate mitral regurgitation (aSHR 11.13, 95% CI 2.98 – 41.58), diabetes (aSHR 9.34, 95% CI 2.11 – 41.23), and H2FPEF Score ≥ 6 (aSHR 7.17, 95% CI 1.64 – 31.38) were associated with increased risk of HF hospitalization. Treatment with ruxolitinib at time of TTE (aSHR 0.10, 95% CI 0.01 – 0.98) was associated with decreased risk of HF hospitalization.

Patients who had HF hospitalization had higher rates of all-cause death (67.4% vs 24.5%, p < 0.001). After multivariable Cox proportional hazards regression, HF hospitalization was associated with an increased risk of all-cause mortality (aHR 1.55, 95% CI 1.04 – 2.33).

Conclusions:

Among patients with MPN with ≥1 TTE after diagnosis, hospitalization for HF was common. Our study suggests that HF hospitalization is associated with worse overall survival in MPN patients. Our results suggest that traditional risk factors for HF, including diabetes, mitral regurgitation, and H2FPEF score were associated with HF hospitalization in patients with MPN as well as potential MPN-specific risk factors including spleen size and WBC. Additionally, there was an association with ruxolitinib and reduced risk of HF hospitalization. It is well-known that inflammation may play a role in the development of HF, whether reduction in inflammatory signaling reduces HF hospitalization in patients with MPN merits further investigation. Clinicians should be aware of HF and monitor patients with MPN, especially those with cardiovascular risk factors, closely for the development of HF.