Nonthrombotic Cardiovascular Conditions Also a Concern in MPNs

It is well known that patients with myeloproliferative neoplasms (MPNs) are at a heightened risk of thrombosis, but new evidence suggests nonthrombotic conditions like heart failure and pulmonary hypertension are also common among patients with MPNs.1

In a new article in JACC: CardioOncology, corresponding author Gabriela Hobbs, MD, of the Harvard Medical School, and colleagues argue that a better understanding of the interactions between MPNs and various types of heart disease may help improve patient care and lead to the development of better therapeutic options.

Two years ago, Hobbs and colleagues published research showing that patients with MPNs who experience pulmonary hypertension are at an increased risk of all-cause death, death from cardiovascular disease, and hematologic progression of MPN.2 Later that same year, they published data showing that patients with MPNs who were hospitalized for heart failure were at an increased risk of in-hospital death and 90-day cardiovascular-related readmissions.3

Still, even as the body of evidence tying pulmonary hypertension and heart failure to MPNs has increased, the underlying pathophysiology connecting the two cardiovascular diseases with MPNs has been under-explored, the authors said.1

In their paper, Hobbs and colleagues reviewed the current scientific literature and offered suggestions for future research.

Further research into the interplay between bone marrow, pulmonary vasculature, and cardiac function could help develop novel therapeutic strategies that could benefit both MPNs and cardiovascular disease. | Image credit: Tima - stock.adobe.com

Turning first to pulmonary hypertension, the investigators said a range of studies have estimated significantly different prevalences of the disease within the MPN population. Prevalence estimates have ranged from 4-58%, they noted, though a large meta-analysis suggested the prevalence was approximately one-third.4 Yet, Hobbs and colleagues said the prevalence of pulmonary hypertension appears to vary based on MPN phenotype. Myelofibrosis is associated with the highest prevalence of pulmonary hypertension, they noted, while polycythemia vera has the lowest rate.1 They said the data suggests there is a roughly equal distribution of precapillary, postcapillary, and combined pulmonary hypertension phenotypes among the MPN patient population.

How best to treat patients with MPN-associated pulmonary hypertension largely remains an open question. Hobbs and colleagues said patients with myelofibrosis, long-standing MPNs, signs of disease progression, or splenomegaly should be screened for pulmonary fibrosis. They said inhibition of Janus kinase 2 (JAK2) may improve patient outcomes, though more research is needed.

Data regarding the prevalence of heart failure in patients with MPNs is more limited, but Hobbs and colleagues said one study found that 17.6% of patients with MPNs who had no history of heart failure were later hospitalized for the conditions. It is not known whether its prevalence varies by MPN subtype, they said.5 As with pulmonary hypertension, the investigators said there is evidence suggesting that JAK2 inhibition might reduce the risk of heart failure, though they said the research into treatment options remains limited.

The investigators said there is a significant gap in the research related to non-thrombotic complications and MPNs, and thus prospective studies are necessary to better understand the true incidence of pulmonary hypertension and heart failure in people with MPNs.1 Such studies could also help elucidate the risk factors and pathophysiological mechanisms underlying the complications, they said.

Hobbs and colleagues concluded that the emerging evidence suggesting that both pulmonary hypertension and heart failure may be associated with an increased risk of hematologic progression in MPNs demonstrates the potential shared pathophysiology between the conditions. They said that shared pathophysiology could be connected with chronic inflammation and activation of the JAK/signal transducer and activator of transcription (STAT) pathway.

Hobbs and colleagues said further research into the interplay between bone marrow, pulmonary vasculature, and cardiac function could help develop novel therapeutic strategies that could benefit both MPNs and cardiovascular disease.

References

1. Leiva O, Liu O, Kanelidis A, et al. Beyond thrombosis: pulmonary hypertension and heart failure in patients with myeloproliferative neoplasms: JACC: CardioOncology state-of-the-art review. JACC CardioOncol. Published online July 3, 2025. doi:10.1016/j.jaccao.2025.05.010

2. Leiva O, Ren S, Neuberg D, et al. Pulmonary hypertension is associated with poor cardiovascular and hematologic outcomes in patients with myeloproliferative neoplasms and cardiovascular disease. Int J Hematol. 2023;117(1):90-99. doi:10.1007/s12185-022-03454-1

3. Leiva O, Alvarez-Cardona J, How J, Brunner A, Hobbs G. In-hospital and readmission outcomes of patients with myeloproliferative neoplasms and heart failure: Insights from the National Readmissions Database. Int J Cardiol Heart Vasc. 2023;49:101304. doi:10.1016/j.ijcha.2023.101304

4. Ferrari A, Scandura J, Masciulli A, Krichevsky S, Gavazzi A, Barbui T. Prevalence and risk factors for pulmonary hypertension associated with chronic myeloproliferative neoplasms. Eur J Haematol. 2021;106(2):250-259. doi:10.1111/ejh.13543

5. Leiva O, Soo S, Smilowitz N, et al. Myeloproliferative syndromes: clinical and epidemiological incidence, risk factors, and prognostic implications of heart failure hospitalizations among patients with myeloproliferative neoplasms. Blood. 2024;144(suppl 1):3188. doi:10.1182/blood-2024-207586