Work

Effect of JAK1/2 inhibition on High-Output Heart Failure Associated With Myeloproliferative Disease

Year: 2020

Type: article

Abstract: T here are reports of some patients with myeloproliferative disease (MPD) developing high-output heart failure (HOHF) (1).Another hematological disorder, multiple myeloma, is also known to be related to HOHF (2).According to the common pathological conditions in these 2 hematologic diseases, possible mechanisms for high-output states are increased oxygen demand secondary to splenomegaly and hepatomegaly caused by extramedullary hematopoiesis, and a reduction of systemic vascular resistance caused by elevated circulatory proinflammatory and angiogenic cytokines, such as interleukin (IL)-6, IL-8, tissue necrosis factor-alpha, and vascular endothelial growth factor (1,3,4).Ruxolitinib, a JAK1/2 inhibitor, has recently emerged as a new therapeutic agent for MPD and is reported to improve splenomegaly and its associated symptoms by reducing extramedullary hematopoiesis (5).This has raised the possibility of JAK1/2 inhibition for the amelioration of HOHF symptoms associated with MPD by reducing extramedullary hematopoiesis and circulatory cytokines.Herein, we present a case that supports this possibility. CASEA 75-year-old male patient with an 11-year history of MPD, which was initially diagnosed as polycythemia vera and later developed into myelofibrosis, was referred to our cardiovascular clinic for suspected heart failure.Except for hypertension, for which he was prescribed calcium-channel blockers, he had no prior history of cardiovascular disease.He was treated with hydroxyurea 6 years after the MPD diagnosis and developed shortness of breath during walking and peripheral edema 1 year later.Plasma brain natriuretic peptide (BNP) levels were 19.4 pg/ml at MPD diagnosis and increased to 143.9 pg/ml at the time of referral.Echocardiography identified dilatation of all 4 cardiac chambers (left ventricular end-diastolic diameter 61 mm; right ventricular end-diastolic diameter 48 mm; left atrial volume 74 ml; and right atrial volume 76 ml) along with hyperdynamic left ventricular function with mild mitral regurgitation and tricuspid regurgitation.The left ventricular end-diastolic diameter had increased from 52 mm at diagnosis to 61 mm at referral.HOHF associated with MPD was suspected, and right heart catheterization (RHC) was performed.The cardiac output was estimated using the Fick's method, and the LaFarge equation was used for estimating oxygen consumption (6).Systemic vascular resistance was calculated by dividing the difference between mean arterial pressure and mean right atrial pressure by cardiac output.The findings were consistent with a high-output state: an elevated cardiac output (9.03 l/min), slightly elevated pulmonary capillary wedge pressure (11 mm Hg) and right atrial pressure (10 mm Hg), elevated mixed venous oxygen saturation (80%), and a decreased systemic vascular resistance (753.0 dynesscm À5 ).A diagnosis of HOHF associated with MPD was made based on RHC results and marked splenomegaly, which provided evidence of extramedullary hematopoiesis.Other causes of high cardiac output state, namely, anemia, hyperthyroidism, vitamin insufficiency, systemic arteriovenous

Source: JACC CardioOncology

DOI: 10.1016/j.jaccao.2020.02.018