Classification and pathophysiology of pulmonary hypertension

Abstract

Pulmonary hypertension is a fatal disease of multiple etiologies that is estimated to affect over 100 million people worldwide. The disease is defined hemodynamically as a mean pulmonary artery pressure ≥ 25 mmHg at rest. Despite important advances in our understanding of the pathobiology of this disease and improvements in patient management, outcomes are still poor and no curative treatments are currently available. The complex nature of this disease requires detailed clinical evaluation for accurate diagnosis and treatment. Recent advances in clinical recognition, classification, and understanding of the underlying pathological processes in pulmonary hypertension have led to improved diagnostic testing and therapeutic options for patients. A hallmark of pulmonary hypertension is an increased pulmonary vascular resistance which leads to progressive elevations in pulmonary artery pressure, resulting in compensatory right ventricular hypertrophy and, ultimately, heart failure. Clinically, these pulmonary vascular changes initially present as nonspecific symptoms, including unexplained dyspnea on exertion, fatigue, chest pain, and syncope. Signs of right ventricular dysfunction are also frequently present. Common pathogenic features of pulmonary hypertension include sustained pulmonary vasoconstriction, vascular remodeling of the small pulmonary arteries, in situ thrombosis, and increased vascular wall stiffness, resulting in increased pulmonary arterial pressure due to increased pulmonary vascular resistance. Despite improvements in clinical classification and understanding of the underlying pathogenic mechanisms of pulmonary hypertension, current therapies are limited to supportive care and targeting pulmonary vasoconstriction. There remains a need to identify novel therapeutic targets in this disease. This review provides a succinct overview of the clinical classification and pathophysiology of PH that can be used as a reference by physicians and physician-scientists.

Level of the SARS-CoV-2 receptor ACE2 is highly elevated in old-aged patients with aortic stenosis: implications for ACE2 as a biomarker for the severity of COVID-19

“…Severe AS often result in a pulmonary congestion, due to retrograde transmission of elevated lling pressures in the left heart, leading directly to an increase in pulmonary artery blood pressure (Sysol and Machado 2018). Almost all patients in our severe AS population had an elevated (>25 mmHg) right ventricular pressure, de ning these patients as group 2 pulmonary hypertensives (Sysol and Machado 2018). We identi ed an association between serum ACE2 activity and the calculated right ventricular systolic blood pressure (based on echocardiography).…”

“…We assumed that patients with severe aortic stenosis (AS) may represent a prime population of patients to study ACE2 levels in relation to COVID-19 mortality. AS is characterized by a chronic in ammatory process (Cho et al 2018;Cote et al 2013), leading to narrowing of the aortic root, elevated left ventricular pressure levels, and a passive backward transmission of lling pressures that increases pulmonary (and right ventricular) blood pressure (Sysol and Machado 2018), all of these being implicated in COVID-19 mortality (Zheng et al 2020). It has also been proposed that cardiovascular medication, in particular, inhibitors of the Renin-Angiotensin-Aldosterone system (RAASi) elevate serum ACE2 levels and potentially contribute to the mortality of COVID-19 (Vaduganathan et al 2020;Walls et al 2020;Zheng et al 2020).…”

<p>Updated Perspectives on Pulmonary Hypertension in COPD</p>

“…14 Smoking induces remodeling of pulmonary arteries, which could be further enhanced by chronic hypoxia. 19 Hypoxia induces endothelial cell damage, causing the release of molecules such as endothelin that leads to neighboring smooth muscle cell vasospasm and proliferation. 19 Although initial stages of vascular remodeling due to cigarette smoke exposure or early hypoxia exposure could still be a reversible process, persistent inflammation and chronic hypoxia seem to be largely irreversible.…”

“…19 Hypoxia induces endothelial cell damage, causing the release of molecules such as endothelin that leads to neighboring smooth muscle cell vasospasm and proliferation. 19 Although initial stages of vascular remodeling due to cigarette smoke exposure or early hypoxia exposure could still be a reversible process, persistent inflammation and chronic hypoxia seem to be largely irreversible. 19 Once the pulmonary artery wall has been remodeled, the intima layer thickens and the neointima shaped, remodeling reversion of the pulmonary vascular vessels is not possible.…”

“…Small reductions in the diameter of remodeled small pulmonary arteries can lead to significant increases in PVR. 19…”