Article Impact Level: HIGH Data Quality: STRONG Summary of Circulation, 151(25), 1814–1817. https://doi.org/10.1161/CIRCULATIONAHA.124.073058 Dr. Juan Qin et al.
Points
- Acute fulminant myocarditis is a severe form of heart inflammation where hyperactive Janus kinase enzymes can exacerbate the condition by creating communication nodes between overactive immune cells.
- Researchers at UCSF treated a 20-year-old woman with critical AFM whose heart was failing and required mechanical life support after corticosteroids proved ineffective for her condition.
- The medical team administered ruxolitinib, a JAK inhibitor, resulting in a rapid decrease in heart damage markers and a significant improvement in overall cardiac function.
- The patient’s heart recovered sufficiently to be weaned off mechanical support, and she was successfully discharged from the hospital just one week after starting the new therapy.
- While these early results in this and other patients are highly encouraging, the team stresses that formal clinical trials are necessary to validate this novel treatment approach.
Summary
A case study reports on a 20-year-old woman with acute fulminant myocarditis (AFM) and cardiogenic shock, presenting with a left ventricular ejection fraction (LVEF) of 10% and requiring venoarterial extracorporeal membrane oxygenation. After failing to improve on methylprednisolone, the patient was treated with oral ruxolitinib (10 mg twice daily). This intervention was associated with rapid clinical improvement, with LVEF returning to normal by day 9, permitting weaning from mechanical support and hospital discharge on day 19. Extensive infectious and genetic evaluations were unremarkable.
The therapeutic rationale was based on molecular evidence of immune hyperactivation. RNA sequencing of the patient’s peripheral blood mononuclear cells (PBMCs) before ruxolitinib administration revealed significant upregulation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway compared to 17 healthy controls and two cardiac pathology controls. Endomyocardial biopsy confirmed myocarditis with infiltrates of CD3+ lymphocytes and CD68+ histiocytes, alongside extensive expression of the interferon-γ–inducible marker HLA class II DR, indicating JAK/STAT activation within the heart tissue.
Single-cell analysis of 40,556 PBMCs across four time points demonstrated that ruxolitinib treatment modulated pathological immune activity. The therapy correlated with a significant reduction in pathogenic natural killer cells, intermediate monocytes, and activated T cells, with a false discovery rate <0.05 and a log2 fold change >1. Downstream STAT1/STAT3 signaling was significantly reduced, and populations of interferon-stimulated gene-positive monocytes nearly disappeared. A corresponding decrease in hyperexpanded T-cell clones was observed, suggesting that ruxolitinib may promote clinical recovery in AFM by reprogramming pathological immune signaling pathways; however, larger studies are required to confirm its efficacy.
Link to the article: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.073058
References Qin, J., Aras, M. A., Song, E. J., Connolly, A. J., Zhou, L., O’Brien, C., Salem, J.-E., Padmanabhan, A., & Moslehi, J. J. (2025). Insights into recovery from acute fulminant myocarditis following successful treatment with ruxolitinib by comprehensive single-cell profiling. Circulation, 151(25), 1814–1817. https://doi.org/10.1161/CIRCULATIONAHA.124.073058
