Abstract-Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension. Key Words: AHA Scientific Statements ◼ bronchopulmonary dysplasia ◼ congenital diaphragmatic hernia ◼ congenital heart disease ◼ genetics ◼ persistent pulmonary hypertension of the newborn ◼ sickle cell disease © 2015 by the American Heart Association, Inc., and the American Thoracic Society.Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIR.0000000000000329 †Deceased. The American Heart Association and the American Thoracic Society make every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This document was approved by the American Heart Association Science Advisory and Coordinating Committee on May 12, 2015, the American Heart Association Executive Committee on July 22, 2015, and the American Thoracic Society on July 24, 2015.The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIR.0000000000000329/-/DC1. The American Heart Association requests that this document be cited as follows: Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, Hanna BD, Rosenzweig EB, Raj JU, Cornfield D, Stenmark KR, Steinhorn R, Thébaud B, Fineman JR, Kuehne T, Feinstein JA, Friedberg MK, Earing M, Barst RJ, Keller RL, Kinsella JP, Mullen M, Deterding R, Kulik T, Mallory G, Humpl T, Wessel DL; on behalf of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Clinical Cardiology, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Surgery and Anesthesia, and the American Thoracic Society. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation. 2015;132:2037-2099 Copies: This document is available on the World Wide Web site of the American Heart Associat...

Inhaled nitric oxide improves systemic oxygenation in infants with persistent pulmonary hypertension and may reduce the need for more invasive treatments.

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Summary Pulmonary hypertension (PH) is a deadly vascular disease with enigmatic molecular origins. We found that vascular extracellular matrix (ECM) remodeling and stiffening are early and pervasive processes that promote PH. In multiple pulmonary vascular cell types, such ECM stiffening induced the microRNA-130/301 family via activation of co-transcription factors YAP/TAZ. MicroRNA-130/301 controlled a PPARγ-APOE-LRP8 axis, promoting collagen deposition and LOX-dependent remodeling and further up-regulating YAP/TAZ via a mechanoactive feedback loop. In turn, ECM remodeling controlled pulmonary vascular cell crosstalk via such mechanotransduction, modulation of secreted vasoactive effectors, and regulation of associated microRNA pathways. In vivo, pharmacologic inhibition of microRNA-130/301, APOE, or LOX activity ameliorated ECM remodeling and PH. Thus, ECM remodeling, as controlled by the YAP/TAZ-miR-130/301 feedback circuit, is an early PH trigger and offers combinatorial therapeutic targets for this devastating disease.

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