Acute cardiotoxicity after initiation of the novel tyrosine kinase inhibitor gilteritinib for acute myeloid leukemia.

BACKGROUND: Gilteritinib is a novel FMS-like tyrosine kinase 3 inhibitor recently approved by the United States Food and Drug Administration in 2018 for relapsed or refractory acute myeloid leukemia. However, gilteritinib may be associated with underrecognized cardiotoxicities. CASE PRESENTATION: This case describes a patient with a history significant for hyperlipidemia who was diagnosed with relapsed acute myeloid leukemia. After four doses of gilteritinib monotherapy, she abruptly developed acute systolic heart failure with global hypokinesis and septal wall motion abnormalities. Two days after discontinuation, cardiac magnetic resonance imaging showed partial recovery of her left ventricular ejection fraction as well as myocardial edema and non-ischemic fibrosis suggestive of inflammatory cardiomyopathy. She underwent intravenous diuresis and eventually started guideline-directed heart failure therapy. Follow-up cardiac magnetic resonance imaging five months later showed improved ejection fraction with mild non-ischemic fibrosis and resolution of myocardial edema and inflammation. She later received an allogeneic stem cell transplant from a matched unrelated donor. CONCLUSIONS: Gilteritinib may be associated with early cardiotoxicities, including non-ischemic cardiomyopathy and myocarditis. Cardiac magnetic resonance imaging can be an important modality to help differentiate or diagnose early cardiotoxicities associated with novel targeted therapies.

Contemporary insights and novel treatment approaches to central sleep apnea syndrome in heart failure.

OPINION STATEMENT: Central sleep apnea (CSA) is a common and under-diagnosed condition commonly associated with Cheyne-Stokes respiration. It is particularly prevalent in the heart failure population affecting up to 40 % of all patients with heart failure. The pathophysiology associated with CSA is based on the underlying effects of hypoventilation and hyperventilation, with neurologic dysregulation of respiratory control as the primary defect. However, therapeutic options are limited because of the prevailing perception that CSA is a consequence, rather than cause of morbidity and mortality. At present, the main focus remains treating the underlying problem (ie, intensifying heart failure therapeutics, decongestion), whereas additional suggestions of using acetazolamide, progesterone, nocturnal oxygen, and theophylline have not been validated with contemporary clinical trials. Positive pressure ventilation is currently the primary recommendation for all patients with sleep-disordered breathing (CSA included), and in some patients may effectively reduce the apnea-hypopnea index. However, significant research is ongoing to determine how to treat this complex patient population.