Volume 17: Issue 3

Harrison (Hap) Farber,

Professor of Medicine, Director, Pulmonary Hypertension Center, Boston University/Boston Medical Center, Boston, MA

Editor's Memo

For this issue of Advances, we are examining the relationship between societal metabolic abnormalities and the development of pulmonary arterial hypertension (PAH)/pulmonary hypertension (PH) in the United States—and throughout the developed world. These abnormalities, frequently referred to as the metabolic syndrome—central obesity, insulin resistance, dyslipidemia, and systemic hypertension—are common, really epidemic, in the United States and now are even increasing in developing nations. As POGO (created by the cartoonist Walt Kelly) famously observed: “We have met the enemy and

Pulmonary hypertension (PH) encompasses a group of progressive and incurable cardiopulmonary disorders characterized by pulmonary vascular remodeling and increased mean pulmonary artery pressure leading to right heart failure. Emerging data suggest a common etiology for the reported diverse molecular and physiological abnormalities observed in the pulmonary vasculature: the metabolic theory of PH. This theory proposes that aberrations in metabolism and mitochondrial function are a major underlying cause for the cellular and organ level PH phenotype. Additionally, the metabolic theory of PH provides a rationale for the observed metabolic defects in other organs and systems outside of the pulmonary vasculature, including the right ventricle (RV), immune system, and skeletal muscle. However, whether these metabolic changes are driving disease and the timing and extent of these aberrations are still unknown. This review highlights: 1) key examples of metabolic alterations in the pulmonary vasculature, RV, inflammatory cells, and skeletal muscle; 2) examples of promising therapeutic interventions directly modifying metabolism; and 3) key remaining questions about the role of metabolic remodeling in PH.

Metabolic derangement is a pathologic feature of pulmonary arterial hypertension (PAH).1 Metabolic abnormalities such as aerobic glycolysis and impaired fatty acid oxidation are consistently observed across different animal models of PAH. Importantly, altered metabolism in human PAH and experimental models is not restricted to the pulmonary vasculature, raising the possibility that PAH is a systemic metabolic disease.2 For example, lipid accumulation is present in the myocardium and skeletal muscle of humans with PAH and the right ventricle exhibits increased glucose uptake compared with matched controls. As a result of these observations, targeting metabolic dysfunction has emerged as an important therapeutic approach for patients with PAH.3 This article will review key aspects of metabolism in PAH, existing metabolic data in humans, and will describe completed and ongoing clinical trials targeting metabolic dysfunction in patients with PAH.

On June 20, 2018, Guest Editor Anna Ryan Hemnes, MD, gathered a group of pulmonary hypertension specialists by telephone to talk about the role of metabolic disease in PH. Among the participants in the animated discussion was Roham Zamanian, MD, Director of the Adult Pulmonary Hypertension Program at Stanford University Medical Center. He directs the Vera Moulton Wall Center clinical database and biobank and focuses his research on clinical characterization and impact of novel risk factors such as methamphetamine use, and biomarkers such as insulin resistance in pulmonary arterial hypertension. Readers will recall his participation in the previous issue's roundtable on drug-induced PH. Joining Dr Zamanian were Ioana Preston, MD, Pulmonary Function Lab Director; Director, Pulmonary Hypertension Center; and Associate Professor, Tufts University School of Medicine; and Advances in Pulmonary Hypertension editor-in-chief Harrison W. Farber, MD.

Presentation: A woman aged 54 years with multiple sclerosis (MS), chronic obstructive pulmonary disease (COPD), and hypertension presented with progressive exertional dyspnea and fatigue noted over 8 months. Multiple sclerosis was diagnosed 15 years earlier and treated with subcutaneous interferon-β for 10 years with subjective and clinical benefits. She described gradual fatigue and breathlessness with walking, climbing stairs, and performing activities of daily living but denied exertional chest pain, syncope, or lower extremity edema. She attributed her symptoms to worsening MS, however, her treating neurologist did not identify clinical or magnetic resonance imaging (MRI) indicative of worsening progressive MS.

Memos

Editor's Memo

The Basic Science of Metabolism in Pulmonary Arterial Hypertension

Metabolomic Insights in Pulmonary Arterial Hypertension

Clinical Trials Targeting Metabolism in Pulmonary Arterial Hypertension

Pulmonary Hypertension Roundtable: Metabolic Disease and PH

Ask the Expert: What Is the Association Between Thyroid Disease and Pulmonary Hypertension: Do Pulmonary Arterial Hypertension Patients Need a Closer Look?

PH Grand Rounds: Interferon-Associated Pulmonary Arterial Hypertension

PH Professional Network: The Burden of Prior Authorization for Pulmonary Hypertension Medications: A Practical Guide for Managing the Process

Conference Abstracts

Guest Editor’s Memo

A Roundtable Discussion Addressing Patient-Centered Care and Quality of Life in Patients With Pulmonary Arterial Hypertension

Editor’s Memo

Pulmonary Hypertension Associated With Parenchymal Lung Disease