Painless Aortic Dissection Associated with Tyrosine Kinase Inhibitor Therapy

History of presentation

A 69-year-old male presented to the ED with a thoraco-abdominal aortic dissection (AD) (DeBakey type IIIB/Stanford classification B) and an intramural thoracic wall hematoma, detected during CT imaging. He arrived with hypertension (BP 160/92, heart rate 81) but was asymptomatic. Physical examination revealed palpable pulses.

Past medical history

Stage IV anorectal mucosal melanoma treated with ipilimumab/nivolumab, nivolumab+axitinib, radiation, currently on nivolumab+relatlimab. Prior superior mesenteric and right external artery dissection, right common iliac artery aneurysm, central adrenal insufficiency, hypothyroidism and recent hypertension-related syncopal episodes, leading to discontinuation of Losartan.

Investigations

Lab work was normal, EKG showed normal sinus rhythm. Echocardiogram was normal with ejection fraction 60-65%.

Management

The patient received IV labetalol and esmolol, following which BP improved. CT indicated chronicity with proximal thrombosis, and surgical intervention was not recommended. Cardiology started coreg 3.125 mg twice daily and a low-dose statin. He was discharged with oral anti-hypertensive meds for outpatient follow-up.

Causes

Hypertension, aging, atherosclerosis, connective tissue diseases like Marfan and Ehlers-Danlos syndromes, hereditary factors like Turner syndrome and bicuspid aortic valve, coarctation of the aorta, previous cardiac surgery, smoking, cocaine use, and iatrogenic factors such as VEGFR and TK inhibitors.

Mechanism of action

AD results from arterial wall tearing, causing a false lumen due to blood leakage through aortic media [2]. Stress or degeneration factors contribute [2]. Axatinib, a tyrosine kinase inhibitor blocking the TK activities of VEGFR, can lead to hypertension and cardiac dysfunction linked to AD [3]. It's unclear if AD-related hypertension is due to axatinib, suggesting tyrosine kinase inhibitors may directly contribute to AD.