Intersecting Pathways: The Impact of Philadelphia-Negative Chronic Myeloproliferative Neoplasms on the Pathogenesis...

Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent worldwide due to ageing and comorbidities. Emerging evidence suggests that Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), particularly those with JAK2 mutations, may contribute to the development of HFpEF, especially by promoting inflammation and increasing thrombotic risk. Methods: This prospective case-control study assessed 58 patients with Philadelphia-negative MPNs and 41 controls, by clinical, paraclinical, and echocardiographic evaluation, to diagnose diastolic dysfunction and HFpEF according to the ESC guideline criteria. Results: Patients with MPNs had a significantly higher prevalence of HFpEF compared to controls (p = 0.008), higher H₂FPEF scores (median 5 vs. 3, p < 0.001), and significant echocardiographic abnormalities, including a higher left ventricular mass index (LVMI) (100.1 vs. 76.6 g/m², p < 0.001), E/e' (11.00 vs. 7.00, p < 0.001), and pulmonary artery systolic pressure (PASP) (26.0 vs. 7.42 mmHg, p < 0.001). Multivariable logistic regression models identified male sex (OR = 8.993, p = 0.001) and the presence of JAK2 mutation (OR = 5.021, p = 0.002) as independent risk factors for HFpEF in this population. Conclusions: Patients with chronic MPNs, particularly males and those with JAK2 mutations, are at an increased risk of HFpEF, highlighting the importance of routine cardiologic assessment to improve outcomes in this patient population.