Serotonin Receptor Blockers in Ischemic Mitral Regurgitation

Overview

This study is intended to investigate the effect of cyproheptadine (a 5HT2B receptor blocker) on mitral regurgitation severity.

Ischemic mitral regurgitation (MR) is a common and morbid complication of myocardial infarction (MI), doubling heart failure and mortality with currently limited therapies. Its mechanisms have been previously linked to left ventricle (LV) remodeling with secondary deformation of otherwise normal mitral leaflets. Recent studies are introducing new mechanistic elements, allowing possibilities for potential pharmacotherapeutic approaches. Normal mitral leaflets have the capacity to enlarge and adapt to even the largest LV dilatation to prevent MR. However, this compensatory mechanism is insufficient after MI, and the leaflets are abnormally thick with fibrotic changes. Those fibrotic changes could be related to a variation in blood serotonin (5-HT) levels after MI, which has been previously reported. Serotonin is a known cause of valve fibrosis through its 5HT type 2B receptor. In sheep models, the investigators have tested the hypothesis that a 5HT type 2B receptor blocker (cyproheptadine) can prevent adverse remodeling in the valve after MI. Cyproheptadine treatment was associated with increased valve leaflet surface, attenuated leaflet thickening and collagen deposition. Importantly, treated animals had less MR compared to non-treated animals. Thus the present study is a double-blind randomized trial to assess the effect of cyproheptadine on MR severity, mitral valve surface variation, and left ventricular size following MI. Serial imaging (3D echo and MRI) will assess valve adaptation, LV remodeling and MR.

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Central Contacts