Immune Checkpoint Inhibitor Therapy and Catastrophic Biventricular Takotsubo Syndrome

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, with cardiovascular immune-related adverse events reported in approximately 1% of patients. Among these, ICI-associated myocarditis has a reported incidence of 0.3%–1.0%, while Takotsubo cardiomyopathy remains extremely rare and likely underrecognized. We present a case of cardiogenic shock in a patient receiving durvalumab, initially presumed to have immune-mediated myocarditis, but ultimately diagnosed with stress-induced cardiomyopathy.


Description: A 68-year-old female with stage IIIC non-small cell lung cancer treated with durvalumab presented with left upper quadrant pain, elevated troponin (peak 7.05 ng/mL) and sustained monomorphic ventricular tachycardia (VT). Amiodarone and multiple cardioversion attempts failed to restore sinus rhythm. Patient underwent left heart catheterization, which showed no coronary obstruction. Left ventriculography revealed an ejection fraction of 30% with mid-ventricular hypokinesis, consistent with stress-induced (Takotsubo) cardiomyopathy. Hemodynamic data confirmed cardiogenic shock with biventricular failure (cardiac index 1.1, wedge pressure 22 mmHg). An Impella CP device and temporary pacemaker were placed. Corticosteroids were administered for presumed myocarditis; however, given the ventriculogram findings, clinical course, normal ESR and a lack of diffuse ST changes favored a diagnosis of Takotsubo cardiomyopathy. Her condition continued to decline, and she ultimately died on hospital day four from refractory cardiogenic shock and multiorgan failure.


Discussion: Within the growing spectrum of ICI-related cardiotoxicity, fewer than 20 cases of Takotsubo cardiomyopathy have been reported, suggesting it is rare and underrecognized. Differentiating it from ICI-related myocarditis, which carries up to 50% mortality, remains challenging. Recognition is crucial in steroid-unresponsive cases. Proposed mechanisms for ICI-induced Takotsubo include autonomic dysregulation, cytokine-driven catecholamine surges, and endothelial dysfunction, leading to myocardial stunning without coronary obstruction. As ICI use expands, greater recognition and reporting will be key to improving diagnosis and management.