Intersecting Pathways: The Impact of Philadelphia-Negative Chronic Myeloproliferative Neoplasms on the Pathogenesis and Progression of Heart Failure with Preserved Ejection Fraction

<b>Background</b>: 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 <i>JAK2</i> mutations, may contribute to the development of HFpEF, especially by promoting inflammation and increasing thrombotic risk. <b>Methods</b>: 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. <b>Results</b>: Patients with MPNs had a significantly higher prevalence of HFpEF compared to controls (<i>p</i> = 0.008), higher H₂FPEF scores (median 5 vs. 3, <i>p</i> < 0.001), and significant echocardiographic abnormalities, including a higher left ventricular mass index (LVMI) (100.1 vs. 76.6 g/m², <i>p</i> < 0.001), E/e' (11.00 vs. 7.00, <i>p</i> < 0.001), and pulmonary artery systolic pressure (PASP) (26.0 vs. 7.42 mmHg, <i>p</i> < 0.001). Multivariable logistic regression models identified male sex (OR = 8.993, <i>p</i> = 0.001) and the presence of <i>JAK2</i> mutation (OR = 5.021, <i>p</i> = 0.002) as independent risk factors for HFpEF in this population. <b>Conclusions</b>: Patients with chronic MPNs, particularly males and those with <i>JAK2</i> mutations, are at an increased risk of HFpEF, highlighting the importance of routine cardiologic assessment to improve outcomes in this patient population.