title: Novel Therapeutic Strategies for Reducing Right Heart Failure Associated Mortality in Fibrotic Lung Diseases.
abstract: Fibrotic lung diseases carry a significant mortality burden worldwide. A large proportion of these deaths are due to right heart failure and pulmonary hypertension. Underlying contributory factors which appear to play a role in the mechanism of progression of right heart dysfunction include chronic hypoxia, defective calcium handling, hyperaldosteronism, pulmonary vascular alterations, cyclic strain of pressure and volume changes, elevation of circulating TGF-β, and elevated systemic NO levels. Specific therapies targeting pulmonary hypertension include calcium channel blockers, endothelin (ET-1) receptor antagonists, prostacyclin analogs, phosphodiesterase type 5 (PDE5) inhibitors, and rho-kinase (ROCK) inhibitors. Newer antifibrotic and anti-inflammatory agents may exert beneficial effects on heart failure in idiopathic pulmonary fibrosis. Furthermore, right ventricle-targeted therapies, aimed at mitigating the effects of functional right ventricular failure, include β-adrenoceptor (β-AR) blockers, angiotensin-converting enzyme (ACE) inhibitors, antioxidants, modulators of metabolism, and 5-hydroxytryptamine-2B (5-HT2B) receptor antagonists. Newer nonpharmacologic modalities for right ventricular support are increasingly being implemented. Early, effective, and individualized therapy may prevent overt right heart failure in fibrotic lung disease leading to improved outcomes and quality of life.
authors.affiliation: Section of Pulmonary & Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Ayodeji
authors.initials: A
authors.lastname: Adegunsoye
authors.affiliation: Department of Cardiology, Deborah Heart and Lung Center, Browns Mills, NJ 08015, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Levy
authors.affiliation: Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Olusegun
authors.initials: O
authors.lastname: Oyenuga
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D005355:Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D054460:rho-Associated Kinases