Inflammation and right ventricular structure and function in health and disease

Abstract

Right heart failure is common and serious. For the vast majority of patients with right heart failure there are few if any treatments beyond diuretics, salt, and fluid management. The lack of drug development in this area may be anchored in the erroneous belief that the right heart is a passive observer in physiology that fails whenever right heart afterload increases. Case reports and clinical heterogeneity have shown in recent years that right ventricular function is not stereotyped and that adaptation is possible. In this dissertation, I discuss one paradigmatic approach to looking for right heart targeted therapy and show an association between Histamine H2 receptor antagonist (H2RA) use and right ventricular structure and function in healthy men and women. Subsequent work described in this dissertation demonstrated that H2RA use is also associated with left ventricular morphology, the incidence of heart failure, and survival in individuals with pulmonary hypertension. I then describe other potential therapeutic targets in the form of inflammatory markers that are associated with right ventricular structure and function in healthy men and women and outcomes in individuals with pulmonary arterial hypertension. This work is the foundation of a five year randomized controlled trials of H2RAs in individuals with pulmonary arterial hypertension and it is hoped that with further validation will form the basis for additional therapeutic targets of inflammation in individuals with right heart failure.