263 - A RARE CASE OF DILATED CARDIOMYOPATHY INDUCED BY A JAK INHIBITOR

Case background: The Janus Kinase (JAK) pathway is involved in the signalling of several inflammatory players implicated in the pathogenesis of axial spondyloarthritis (axSpA). Targeting JAK is thus an attractive and novel therapeutic intervention in this inflammatory rheumatic disease. Clinical trials of JAK inhibitors (JAKi) have yielded favorable results in key clinical domains of axSpA, with an acceptable safety profile. Cardiovascular disease is a frequent comorbidity in axSpA patients and patients with axSpA have a higher mortality because of CVD, which is the most frequent cause followed by malignant diseases. A 32-year-old female presented in July 2023 after being found on the floor of her apartment alone with bruising, urinary and fecal incontinence, and right-sided facial droop and weakness. A transthoracic echocardiogram (TTE) was done to rule out cardiac causes for the syncopal episode.

Surprisingly, TTE demonstrated apical wall motion abnormalities consistent with dilated cardiomyopathy, with a left ventricular ejection fraction (LVEF) of 48% and a large apical thrombus measuring 17 x 17 mm (Figure 1). CT coronary angiogram showed normal coronary arteries. Cardiac MRI showed delayed gadolinium enhancement at the apex. She was noted to have started taking a JAK2 inhibitor, tofacitinib 5mg daily, for ankylosing spondylitis two weeks before presenting, given the ineffectiveness of various monoclonal antibodies and biologics, including infliximab. The JAK2 inhibitor was discontinued due to concerns of cardiomyopathy, and warfarin therapy was initiated for her thrombus. Two months later, in September 2023, a TTE revealed complete resolution of LV function and absence of thrombus with contrast-enhanced imaging (Figure 1). Anticoagulation with warfarin was stopped in October 2023, after a three-month course. A repeat echocardiogram in January 2024 revealed normal cardiac structure and function with no thrombus.

Management Challenges: This clinical case presents a rare instance of JAKi cardiomyopathy, as suggested by the patient's history of starting JAKi for ankylosing spondylitis and the subsequent development of transient left ventricular dysfunction within two weeks. There is only one other case related to JAKi and dilated cardiomyopathy that we could find in the literature (3).

The presence of a large apical thrombus further complicated the patient's condition, necessitating anticoagulation therapy. However, the complete recovery of left ventricular function and resolution of the thrombus on follow-up imaging highlights the transient nature of this potentially drug-related dilated cardiomyopathy and the effectiveness of timely management strategies.

The decision to discontinue anticoagulation after a three-month course was appropriate, given the absence of thrombus recurrence on subsequent imaging. The normalization of LV function and structure on repeat TTE subsequently indicates a favourable outcome for the patient.

This is the only other known case of JAKi related transient dilated cardiomyopathy. This warrants further surveillance of adverse cardiac outcomes related to JAKi.