ENTRECTINIB–INDUCED ACUTE RIGHT HEART FAILURE IN A PATIENT WITH METASTATIC LUNG ADENOCARCINOMA

Abstract

Abstract We report a case report of a 45–year–old woman with a recent diagnosis of stage IV lung adenocarcinoma (PDL1 60%) with brain metastases, who started entrectinib 600 mg orally once daily. Four days after entrectinib initiation, the patient activated the emergency medical services for acute onset of marked fatigue and hypotension. The ECG performed by the emergency unit showed a marked ST–segment elevation in the infero–lateral leads. Therefore, emergent coronary angiography was performed and no evidence of coronary disease was reported. Subsequently, the patient was admitted to the Coronary Care Unit. Clinical evaluation revealed labile hemodynamics, as the patient presented mental confusion, persistent hypotension (BP 90/50 mmHg) and bradycardia (HR 30 bpm). Laboratory testing showed elevated NT–pro BNP, troponin I and transaminases, normal CRP. The electrocardiogram showed persistent diffuse ST–segment elevation. Transthoracic echocardiogram showed severe dilatation and hypokinesia of the right ventricular (GLS VDx –4.5%), with diastolic “D–shape”, normal left ventricular ejection fraction, no significant valvular disease, circumferential pericardial effusion. Clinical, laboratory and instrumental findings suggested a condition of acute right heart failure. We performed urgent computed tomography pulmonary angiography (CTPA) which resulted negative for acute pulmonary embolism. Hence, supportive therapy with dobutamine, norepinephrine and fluid resuscitation was started, with subsequent hemodynamic stabilization. Since no other etiology was demonstrated by the extensive testing, we attributed the acute right ventricular dysfunction to the recent introduction of entrectinib therapy. Therefore, the drug was discontinued. During the hospitalization we observed a rapid normalization of electrocardiogram and right ventricle function by transthoracic echocardiogram, accompanied by a progressive improvement of laboratory parameters. In order to better define right ventricle function and dimension, the patient underwent cardiac magnetic resonance imaging which showed a normal right ventricle ejection fraction (RV EF 52%), the absence of myocardial edema or late gadolinium enhancement and normal volume of the right ventricle. After six days of hospitalization the patient was discharged. Our case report adds to the limited available literature of cardiac toxicity of entrectinib.