Histamine H 2 Receptor Antagonists, Left Ventricular Morphology, and Heart Failure Risk

Background Myocardial H2 receptor activation may promote cardiac fibrosis and apoptosis in preclinical models and histamine H2 receptor antagonist (H2RA) use may improve symptoms in participants with heart failure (HF); however, relationships between H2RA use, incident HF, and longitudinal change in left ventricular (LV) morphology are not known. Objectives We sought to determine whether H2RA use is associated with incident HF and change in LV morphology over time. Methods This study included 6,378 men and women from MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter prospective observational cohort of participants without cardiovascular disease at baseline. Cox proportional hazards were used to estimate the association between H2RA use and incident HF in adjusted models. In participants with cardiac magnetic resonance imaging (CMR), associations between H2RA use, baseline LV morphology (n = 4,691), and longitudinal change in the LV (n = 2,806) were estimated using linear regression. Results H2RAs were used by 313 participants but not by the other 6,065 individuals. During a median follow-up of 11.2 years, 236 participants developed HF. In adjusted models, baseline H2RA use relative to nonuse was associated with 62% lower risk for incident HF (p = 0.02). H2RA use was associated with preserved stroke volume, LV end-diastolic volume, and mass/volume ratio as measured by CMR over approximately 10 years (all p < 0.05). There were no associations between H2RA use and LV mass or ejection fraction. Conclusions H2RA use was associated with reduced risk for incident HF. Changes in left heart morphology over time suggest less age-related change in H2RA users. These associations suggest histamine signaling may be important in the pathogenesis of HF.