Protamine Sulfate-Induced Coronary Vasospasm Resulting in Takotsubo Cardiomyopathy

Takotsubo syndrome (TTS), also known as stress-induced cardiomyopathy, is characterized by new left ventricular (LV) dysfunction out of proportion to any known coronary artery disease that usually follows an emotional or physical stress. The disease process mimics acute coronary syndrome (ACS), with acute chest pain, moderate elevations in serum troponins, and electrocardiographic changes. While spontaneous return to normal left ventricular function is typical, the morbidity and mortality of TTS is significant, with increased risk for major adverse cardiac events and disease recurrence.1 The understanding of the pathogenesis of TTS is incomplete, although recent work has identified that several processes likely occur to produce the characteristic findings. During periods of acute stress, excessive catecholamine release can cause intense vasoconstriction of coronary microcirculation, impairing myocardial perfusion despite open epicardial coronary arteries. Microvascular dysfunction leads to regional myocardial ischemia and stunning, particularly in the apical segments of the heart.2 Additionally, coronary vasospasm can further reduce blood flow and contribute to myocardial injury, and its role in the development of TTS is an area of investigation.2-3 Protamine sulfate is a commonly used agent to reverse anticoagulation with heparin during and following cardiac surgery. While numerous adverse reactions to protamine exist in the literature, a systematic review examining drugs associated with TTS did not identify protamine sulfate as a possible trigger.4 However, one case report detailed a woman who developed TTS following a severe protamine sulfate reaction requiring extracorporeal membrane oxygenation (ECMO) therapy.5 To our knowledge, no case reports have definitively shown coronary vasospasm to be the driving mechanism for TTS cardiomyopathy secondary to protamine sulfate administration. We herein present the case of a 78-year-old female who developed stress-induced cardiomyopathy secondary to coronary vasospasm in the setting of an adverse reaction to protamine after completion of mitral valve replacement surgery. The characteristic findings of TTS were observed on intraoperative transesophageal echocardiography (TEE), and left heart catheterization (LHC) immediately post-op demonstrated active coronary vasospasm. The patient would require rescue with ECMO before eventually regaining full myocardial function.