<p>Takotsubo (stress) cardiomyopathy (TTC) is an uncommon acute heart failure syndrome characterized by transient hypocontractility that usually affects a circumferential segment of the myocardium along the heart’s apicobasal axis and spans multiple coronary artery territories. Classically, TTC occurs after an intense physical or emotional insult and is thought to be caused by catecholamine toxicity. The most frequent anatomic variant presents with apical hypokinesis and basal hyperkinesis, but the hypocontractility may also localize to the mid-ventricle or base, also known as “reverse TTC.” Here, we describe a middle-aged woman who developed profound acute hypoxemic respiratory failure and mixed cardiogenic-distributive shock after an adverse reaction to alteplase treated with high-dose epinephrine. The patient was found to have a severely depressed left ventricular ejection fraction (10–15%) with apex-sparing hypokinesis and no evidence of obstructive coronary artery disease, consistent with reverse TTC. The patient’s ejection fraction recovered to the normal range within days with supportive measures. This case highlights the distinctive echocardiographic features of this rare, potentially life-threatening form of TTC.</p><p>Videos are available for this article.</p>