John H Cleator, Ehab S Kasasbeh, David X Zhao, Douglas B Sawyer
The goal for treatment of medical refractory Hypertrophic Obstructive Cardiomyopathy (HCM) is reduction of the hypertrophied left ventricular septum which obstructs blood flow. A surgical approach consists of an open-heart myomectomy, while the less invasive percutaneous approach involves creating a myocardial infarction by injecting 95 to 100% ethanol through a septal artery, a procedure termed alcohol septal ablation (ASA). Although less invasive than myomectomy, there are several limitations of alcohol septal ablation. The most important appears to be full thickness infarction that is often complicated by heart block and ventricular tachycardia/fibrillation. The ideal therapy for septal hypertrophy would be to find an agent that induces a less severe injury and/or atrophy of the hypertrophied septum. We review several alternative techniques for selective injury of the septum and describe the ideal characteristics of such an ideal agent. Our central hypothesis is that the anthracycline antibiotic such as doxorubicin may be the perfect agent. Anthracycline-based chemotherapies have been used in the treatment of solid and hematological tumors for many years. These agents have known cardiotoxic side effects that are related to cumulative dose which can lead to heart failure. Although the mechanism of action of doxorubicin cardiotoxicity is controversial, it is very clear that these agents cause atrophy of the myocardium, induce apoptosis and necrosis, as well as anti-angiogenic effects. We propose that selectively treating the hypertrophied septum of HCM patients with injection of the anthracycline doxorubicin will lead to superior outcomes compared to ASA.
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