The role of heart disease in American fiction has received less attention from scholars of literature, history, and medicine than have portrayals of tuberculosis, cancer, or HIV/AIDS, despite the fact that heart disease topped mortality charts for most of the 20th century. This article surveys manifestations of coronary artery disease in popular works of 20th-century American fiction to trace how authors and their protagonists grappled with the disease while knowledge of pathophysiology and therapeutics evolved. Countering Susan Sontag's mechanistic vision of patient encounters-where disease is absent of metaphor-we pair popular fiction with concurrent historical analysis to show that the proliferation of technological narratives of cardiac therapeutics could not displace the deeply symbolic nature of characters' encounters with heart disease. Because of the limited ability of the biomedical narrative to convey the meanings of disease and treatments, doctors and patients need to communicate through the rich possibilities of metaphor.