Prognostic biomarkers in pediatric pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease of the pulmonary vasculature. Despite the introduction of targeted therapies, prognosis remains poor. In pediatric PAH, reliable prognostic biomarkers are needed to inform clinicians on disease progression and risk of mortality, in order to be able to assess the need for escalation of medical therapy, consider surgical options such as Pott's shunt and listing for (heart)-lung transplantation. This review provides an overview of prognostic biomarkers that are considered to carry potential for the clinical management of pediatric PAH. These include conventional physiological biomarkers [resting heart rate, heart rate variability (HRV), a child's growth], biomarkers of functional status [World Health Organization functional class, 6-minute walk distance (6MWD), parameters derived from cardiopulmonary exercise testing (CPET), daily physical activity level], electrocardiographic biomarkers, circulating serum biomarkers (natriuretic peptides, uric acid, neurohormones, inflammatory markers, and novel circulating biomarkers), and multiple hemodynamic biomarkers and imaging biomarkers [echocardiography and cardiac magnetic resonance (CMR)]. In recent years, many potential prognostic biomarkers have become available for the management of PAH in children. As the available prognostic biomarkers reflect different aspects of the disease process and functional implications, a multi-marker approach appears the most useful for guiding therapy decisions and improve outcome in pediatric PAH.

Serum Matrix Metalloproteinase 2 (MMP-2) Levels in Children with Pulmonary Hypertension Associated with Congenital Heart Disease

“…Higher HR in our cases is explained by the increased RV afterload, which leads to an impaired RV stroke volume and sympathetic activation, resulting in a higher HR to maintain adequate oxygen delivery to the body, particularly during activity [24]. This is in agreement with another study on children conducted by Ploegstra and Berger who reported tachycardia in cases with PAH-CHD [25].…”

Value of Red Cell Distribution Width in Children with Congenital Heart Disease Associated- Pulmonary Arterial Hypertension

“…This mechanism ensures that the cardiac output remains sufficient to deliver an adequate supply of oxygen to the body, particularly during physical exertion [9]. This is in agreement with other studies conducted by Ploegstra and Berger [10], Hildenbrand et al [11] and Chemla et al [12] addressing tachycardia in patients having PAH-CHD.…”

Insights and perspectives into clinical biomarker discovery in pediatric heart failure and congenital heart disease—a narrative review

“…Several biomarkers for HF including the extensively investigated atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) have been identified and are applied clinically in the adult population to assess the diagnosis, severity and management of the HF condition before and after treatment (13)(14)(15)(16)(17). BNP as a clinical biomarker in the assessment of pediatric HF and CHD is straightforward and can be a significant factor in the diagnosis and treatment (7,12,18).…”