Large overdoses of venlafaxine may induce acute heart failure with severe left ventricular dysfunction. We describe two fatal cases of venlafaxine poisoning documented by post-mortem myocardial ultrastructural examination and by the determination of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV) concentrations in cardiac tissue.

Case 1: a 38-year-old woman developed acute left ventricular failure after an overdose of a 4200mg extended-release VEN. Light microscopy examination of cardiac tissue revealed cardiac myocytes displaying focal acidophilic necrosis of the myofibrils, with a very mild inflammatory cellular infiltration. Focal disappearance of myofibrils and aggregates of mitochondria in cardiac myocytes were observed at electron microscopy. The following post-mortem concentrations were noted in the heart: VEN 18mg/kg, ODV 21mg/kg. Case 2: a 38-year-old woman also presented acute heart failure after the ingestion of an unknown amount of VEN and verapamil. Light and electron microscopy showed cardiac myocytic changes similar to those found in case 1. Myocardial tissue concentration was: VEN 50.6mg/kg, ODV 74.2mg/kg.

The exact mechanism behind acute heart failure following large VEN overdoses remains not fully understood. The interpretation of the microscopic changes in cardiac tissue remains difficult as most of the severely poisoned patients also experienced severe complications or received large doses of catecholamines. Myofibrillar necrosis, when present, is not associated with a significant inflammatory reaction. Finally, significant amounts of VEN and ODV can be found in myocardial tissue.