All-Trans Retinoic Acid Syndrome Mimicking ST Segment Elevation Myocardial Infarction.
Authors: Kamal Arif H. , Henkel Danielle M. , Tefferi Ayalew , Wright Richard S. 
Published: April 2020

All-trans retinoic acid (ATRA) syndrome is a complex constellation of symptoms that arise in about 15% of patients who receive retinoic acid as therapy for acute promyelocytic leukemia (PML). This syndrome typically consists of fever, dyspnea, weight gain, pulmonary infiltrates, pleural or pericardial effusions, episodic hypotension, renal dysfunction, and leukocytosis. Rarely does this entity present as typical chest pain suggestive of an acute myocardial infarction.

A 39-year-old man diagnosed with acute PML treated with idarubicin and ATRA was admitted for febrile neutropenia, nausea, vomiting, cough, and epigastric pain despite being on ciprofloxacin and metronidazole at home. He continued to have low-grade fevers despite being on antibiotics and antifungals. On hospital day three, he was transferred to the CCU for worsening non-radiating left substernal chest pain associated with nausea and vomiting, new inferior lead 2 mm ST segment elevation, lateral lead T wave inversion, troponin and CKMB elevation, and hypotension not responding to frequent fluid boluses. A Swan-Ganz catheter was placed and pressors were started. The patient was found to have a dramatic neutrophil-predominant leukocytosis only hours after a CBC showed neutropenia. He also developed anuric acute renal failure. A cardiac catheterization was considered but could not be performed because of thrombocytopenia and the patient’s renal status. Subsequent EKG’s revealed more impressive changes. New 3 mm ST segment elevations and T wave inversions were noted in the lateral leads, the inferior lead ST segment elevations persisted and new inferior lead T wave inversions were present. An emergent echocardiogram was obtained which showed a significantly decreased LVEF at 36% and global LV hypokinesis without pericardial effusion. The constellation of symptoms was more suggestive of ATRA syndrome versus acute coronary syndrome and intravenous dexamethasone was started. The patient’s chest pain resolved spontaneously over the next three hours, the dramatic EKG findings and elevated cardiac enzymes resolved over the next few days, and the patient was transferred back to the admitting hematology service. A follow-up echocardiogram before discharge revealed a normal LVEF at 74% and no residual wall motion abnormalities. He eventually required hemodialysis for continued renal failure, which was continued as an outpatient after discharge. Of note, the patient’s fever resolved after beginning dexamethasone and multiple blood, urine, stool, and sputum cultures obtained remained negative throughout the hospital stay.

This clinical situation presents a very distinct dilemma in how to proceed with clinical care. The presenting symptoms, signs, diagnostics, and imaging alone were all suggestive of a worsening ischemic cardiac process. But in considering the clinical presentation as a whole, especially the concomitant renal failure, fever in the setting of broad-spectrum coverage, and dramatic leukocytosis, we were more convinced of a systemic reaction to recent ATRA use. We maintained a low threshold for beginning an acute coronary syndrome protocol involving antiplatelet agents but were supported in our diagnosis by the patient’s remarkable recovery shortly after beginning intravenous steroids.