H2 receptor antagonists and right ventricular morphology: the MESA right ventricle study

Abstract

Rationale: H2 receptor antagonist (H2RA) use is common and may act directly on the heart through myocardial H2 receptors or indirectly through changes in pulmonary vascular resistance.

Objectives: To determine the relationship between histamine H2RA use and right ventricular (RV) morphology.

Methods: We studied 4,122 participants in the Multi-Ethnic Study of Atherosclerosis without clinical cardiovascular disease who had magnetic resonance imaging assessment of RV morphology and ascertainment of medication use. Multivariable linear regression estimated cross-sectional associations between H2RA use and RV morphology after adjusting for demographics, anthropometrics, smoking status, diabetes mellitus, and hypertension. Further adjustments for co-medication use, left ventricular parameters, lung structure and function, renal function, or inflammatory markers were considered in separate models. Analyses in a subcohort restricted to H2RA or proton pump inhibitor users accounted for confounding by the indication of gastroesophageal reflux disease.

Measurements and main results: H2RA use was associated with lower RV mass (-0.7 g; 95% confidence interval, -1.2 to -0.2 g; P = 0.004) and smaller RV end-diastolic volume (-4.2 ml; 95% confidence interval, -7.2 to -1.2 ml; P = 0.006). This relationship was unchanged with adjustment for co-medication use, lung structure and function, renal function, and inflammation. The relationship with RV mass was independent of left ventricular mass. Results were similar in the smaller cohort restricted to proton pump inhibitor and H2RA users.

Conclusions: H2RA use was associated with lower RV mass and smaller RV end-diastolic volume. Additional study of histamine and H2 receptors in cardiopulmonary diseases affecting the RV may have direct clinical relevance.

Keywords: heart ventricles; histamine; histamine H2 receptors; pulmonary hypertension.

Figure 1.

Study sample. H2RA = histamine H₂ receptor antagonist; MESA = Multi-Ethnic Study of Atherosclerosis Study; MRI = magnetic resonance imaging; PPI = proton pump inhibitor; RV = right ventricular.

Figure 2.

Relationship of histamine receptor antagonist use with (A) right ventricular (RV) mass, (B) RV end-diastolic volume (RVEDV), and (C) RV ejection fraction (RVEF) after accounting for potential confounding arising from differences in lung structure and function (n = 2,700), renal function (n = 4,122), and inflammation (n = 4,012).