Beyond Thrombosis: Pulmonary Hypertension and Heart Failure in Patients With Myeloproliferative Neoplasms: JACC: CardioOncology State-of-the-Art Review

Abstract

Patients with myeloproliferative neoplasms (MPNs) are at increased risk for cardiovascular disease. Although thrombosis is a well-recognized complication, emerging evidence indicates that nonthrombotic conditions, including heart failure (HF) and pulmonary hypertension (PH), are also prevalent and associated with adverse cardiovascular and hematologic outcomes. Clinical and preclinical data suggest a shared pathophysiology linking MPNs to the development and progression of cardiomyopathy, HF, and both precapillary and postcapillary PH. Recent studies further support a bidirectional relationship, in which HF and PH are associated with hematologic progression and vice versa. Elucidating the mechanisms underlying these interactions may uncover novel therapeutic targets and inform clinical management. Here, the authors review the pathophysiology and impact of HF and PH in patients with MPNs.

Keywords: bidirectional cardio-oncology; cardiomyopathy; heart failure; leukemia; myelofibrosis; myeloproliferative neoplasms; pulmonary hypertension.

Graphical abstract

Figure 1

Pathophysiology of Precapillary Pulmonary Hypertension in MPNs Precapillary pulmonary hypertension (PH) in myeloproliferative neoplasms (MPNs) is multifactorial. Patients with MPNs are at increased risk for venous thromboembolism and chronic thromboembolic PH. Additionally, contributors may include bone marrow–derived endothelial progenitor cells (EPCs), activation of the JAK (Janus-associated kinase)/STAT (signal transducer and activator of transcription) signaling pathway, increased lysyl oxidase (LOX) expression by megakaryocytes and platelets, and extramedullary hematopoiesis. Additional details regarding the pathophysiology can be found in the corresponding text. SMC = smooth muscle cell.

Figure 2

Proposed Screening Algorithm for PH in Patients With MPNs Patients with MPNs and high clinical suspicion of PH should undergo screening with transthoracic echocardiography (TTE). Findings suggestive of PH should prompt RHC for definitive diagnosis of PH and hemodynamic assessment. PH management should follow established guidelines, with consideration of MPN-specific therapies when appropriate. The role of prospective screening for PH in MPNs warrants further investigation. Additional details regarding the pathophysiology can be found in the corresponding text. AT = acceleration time; CTEPH = chronic thromboembolic pulmonary hypertension; ERA = endothelin receptor antagonist; IVC = inferior vena cava; LV = left ventricle/ventricular; mPAP = mean pulmonary artery pressure; NT-proBNP = N-terminal pro–B-type natriuretic peptide; PA = pulmonary artery; PCWP = pulmonary capillary wedge pressure; PDE5i = phosphodiesterase 5 inhibitor; PRV = pulmonic regurgitation velocity; PVR = pulmonary vascular resistance; RA = right atrial/atrium; RHC = right heart catheterization; RV = right ventricle/ventricular; RVOT = right ventricular outflow tract; RVSP = right ventricular systolic pressure; TAPSE = tricuspid annular plane systolic excursion; TRV = tricuspid regurgitant velocity; WU = Wood units; other abbreviations as in Figure 1.

Central Illustration

The Association Between MPNs and Pulmonary Hypertension and Heart Failure Patients with myeloproliferative neoplasms (MPNs) are at increased risk for both thrombotic and nonthrombotic cardiovascular disease. Nonthrombotic cardiovascular diseases, particularly pulmonary hypertension and heart failure, are increasingly recognized and may carry a poor prognosis. Shared pathophysiologic mechanisms, including activation of the JAK (Janus-associated kinase)/STAT (signal transducer and activator of transcription) signaling pathway, may underlie these associations. Further research into the interplay among bone marrow, pulmonary vasculature, and cardiac function may lead to novel therapeutic strategies for both MPNs and cardiovascular disease. Additional details regarding the pathophysiology can be found in the corresponding text. CV = cardiovascular.