Pulmonary hypertension (PH) has been reported to be associated with myeloproliferative neoplasms (MPN) in 5% to 48% of MPN patients. Now, authors of the largest PH study in patients with Philadelphia chromosome-negative MPN have concluded that the prevalence of PH is lower than has been previously reported.
Pulmonary hypertension (PH) has been reported to be associated with myeloproliferative neoplasms (MPN) in 5% to 48% of MPN patients—a large variability likely related to the small cohorts of patients previously studied. Based on these earlier studies, both the European Society of Cardiology (ESC) and the European Respiratory Society recognized MPN as a specific cause of PH of unclear and/or multifactorial mechanisms. Now, authors of the largest PH study in patients with Philadelphia chromosome-negative MPN (Ph-MPN) have concluded that the prevalence of PH is lower (3.8%) than has been previously reported.
Several risk factors have been identified for developing PH among patients with Ph-MPN: obstruction of pulmonary vessels by circulating megakaryocytes, smooth muscle hyperplasia due to platelet-derived growth factor, and altered angiogenic status. There is an increased risk for thromboembolic events, and thus a high risk of pulmonary embolism leading to PH. Extramedullary hematopoiesis, a well-known complication of progressive massive fibrosis that involves the presence of circulating marrow progenitors in the lung parenchyma, may also cause PH.
The current prospective, observational cohort study, from March 2015 through June 2016, followed 158 patients with Ph-MPN (median age, 65 years; 50.6% were female; all were white; and the median duration of Ph-MPN at inclusion was 4 years). About half the subjects had polycythemia vera (PV), 34% had essential thrombocytosis (ET), 11% had primary myelofibrosis, 3% had post-ET myelofibrosis, and 2% had post-PV myelofibrosis. Transthoracic echocardiography (TTE) was performed on all 158 patients included in the study. When TTE results were abnormal, further investigations were performed according to current ESC guidelines. The primary study endpoint was the frequency of PH; the secondary endpoint was cause of PH. Once the etiology behind PH was established, no further tests were performed as part of the study.
Only 6 patients (3.8%) were found to have a high probability of PH. All 6 were examined with right heart catheterization, and all met the invasive criteria for PH (mean pulmonary pressure above 25 mmHg). In all 6 patients, causes other than MPN for PH were identified, although some contribution from the MPN could not be ruled out in 3 patients. Of the 6 patients with PH, 1 had ET, 2 had PV, and 3 had PMF.
By a median follow-up of 20 months from study inclusion, 5.1% (8 patients) of study patients had died but only 1 of these patients had PH. Four died from thromboembolic disease, thus the cause of death could be related to Ph-MPN. The patients with PH and confirmed Ph-MPN died from infection.
The findings, which were published online in the European Journal of Haematology, have led the authors to conclude that screening for PH in unselected patients with MPN is not justified.
Brabrand M, Hansen KN, Laursen CB, Larsen TS, Vestergaard H, Abildgaard N. Frequency and etiology of pulmonary hypertension in patients with myeloproliferative neoplasms [published online November 19, 2018]. Eur J Haemotol. doi: 10.1111/ejh.13197.