Current Understanding of Circulating Biomarkers in Pulmonary Hypertension Due to Left Heart Disease

Abstract

Pulmonary hypertension due to left heart disease (PH-LHD; Group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most frequent cause of PH. Despite its prevalence, no effective therapies for PH-LHD are available at present. This is largely due to the lack of a concise definition for hemodynamic phenotyping, existence of significant gaps in the understanding of the underlying pathology and the impact of associated comorbidities, as well as the absence of specific biomarkers that can aid in the early diagnosis and management of this challenging syndrome. Currently, B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are guideline-recommended biomarkers for the diagnosis and prognosis of heart failure (HF) and PH. Endothelin-1 (ET-1), vascular endothelial growth factor-D (VEGF-D), and microRNA-206 have also been recently identified as new potential circulating biomarkers for patients with PH-LHD. In this review, we aim to present the current state of knowledge of circulating biomarkers that can be used to guide future research toward diagnosis, refine specific patient phenotype, and develop therapeutic approaches for PH-LHD, with a particular focus on PH-HFpEF. Potential circulating biomarkers identified in pre-clinical models of PH-LHD are also summarized here.

Prevalence of aortic stenosis and TAVR outcomes in patients with systemic sclerosis‐associated pulmonary hypertension

“…Investigating novel PAH biomarkers like endothelin-1, vascular endothelial growth factor, and microRNA-206 may help identify SSc patients at risk of accelerated valvular heart disease. 12 The AS patients also presented with a trend toward higher mean pulmonary artery pressure, lower 6-min walk distance, higher proportion of NYHA class 3 or 4, and a higher proportion of patients requiring parenteral pulmonary vasodilator therapy, relative to the cohort of patients without AS. This is despite only one patient having more than mild AS at PH diagnosis and six patients not showing evidence of AS at PH diagnosis.…”

“…Further studies are needed to understand the pathogenesis of AS in SSC‐PAH/PH patients. Investigating novel PAH biomarkers like endothelin‐1, vascular endothelial growth factor, and microRNA‐206 may help identify SSc patients at risk of accelerated valvular heart disease 12 …”

Protein biomarkers of cardiac remodeling and inflammation associated with HFpEF and incident events

“…VEGFD, a secreted regulator of angiogenesis, was associated with HFpEF and incident HF in the present analyses. VEGFD stimulates cardiac fibrosis and has a growing body of support in HF and pulmonary hypertension 38 . Incorporation of extracellular matrix degradation pathway and matrix biomarker profiling into HF and HFpEF prognostication has been proposed previously and the results of the present study support these efforts 39 .…”

Severe Aortic Valve Stenosis and Pulmonary Hypertension: A Systematic Review of Non-Invasive Ways of Risk Stratification, Especially in Patients Undergoing Transcatheter Aortic Valve Replacement

“…Especially in clinically asymptomatic patients, the determination of cardiovascular biomarkers, in addition to the gold standard of echocardiography, provides an additional diagnostic tool to assess severity and prognostic relevance. In addition to BNP and NT-proBNP, other molecular markers such as endothelin-1, vascular endothelial growth factor-D, and microRNAs play an important role in PH in the context of left heart disease (post-capillary PH) and thus also in patients with severe AS [10,11].…”