Incidence, Outcomes and Risk Factors for Atrial Fibrillation in Patients With JAK2V617F-Positive Myeloproliferative Neoplasms

Abstract

Background: The incidence, outcomes and risk factors for AF in the JAK2^V617F-positive MPN patients are still unknown.

Methods: The clinical profiles of patients with JAK2^V617F-positive MPN were retrospectively analyzed. Multivariable Cox regression analysis was performed to identify risk factors of AF, thereby developing a risk prediction model.

Results: A total of 439 patients were included (age 57 [12-87] years; 51.3% male). AF was associated with higher risks of stroke (p = 0.036, HR = 1.987, 95% CI 1.047-3.772) and mortality (p < 0.001, HR = 3.857, 95% CI 1.836-8.103). Multivariable Cox regression showed that TET2 mutation (p = 0.042, HR = 4.361, 95% CI 1.053-18.056) and increased IL-1β (p = 0.012, HR = 5.476, 95% CI 1.547-28.123) were significant risk factors for AF in patients with JAK2^V617F-positive MPN. Nomograms were constructed, allowing patients to be categorized into high- and low-risk groups. The 10-year AF-free survival rate was significantly lower in the high-risk group (62% vs. 91.7%; log-rank test: p = 0.002). The validation cohort confirmed that the survival without AF in the high-risk group was significantly worse than that in the low-risk group. The use of either interferon-α or ruxolitinib, was associated with longer AF-free survival in the high-risk group (p < 0.05).

Conclusion: AF was significantly associated with higher risks of stroke and mortality. TET2 mutation and increased IL-1β were independent risk factors of AF in patients with JAK2^V617F-positive MPN.

Keywords: JAK2 V617F; atrial fibrillation; cytokines; gene mutation; myeloproliferative neoplasms.