Table 3.

Noninvasive End Points With Potential Use as End Points in Clinical Trials in Children

End Point Modality	Potential Treatment Goals to be Considered	Strengths	Limitations
WHO‐FC	WHO‐FC improvement	Convenience Predictive of transplant‐free survival in pediatric PAH	Variability in classifications among clinicians Definitions of symptoms may differ and not be reliable in children
NT‐proBNP	NT‐proBNP lowering	Simple procedure (plasma) Likely predictive of transplant‐free survival in pediatric PAH prognosis	Not a specific indicator for PAH only Impacted by cause of PAH The normal value of NT‐proBNP in children can vary with age
Echocardiography	TAPSE improvement 3‐Dimensional right ventricular function Fractional area change	Widely used for monitoring in patient population 3‐Dimensional echocardiography offers new options with end points	High operator variability Likely larger sample size No consensus on which echocardiographic end point should be used as a primary outcome
Actigraphy	Physical activity count Heart rate variability	Children friendly Simple and can continuously record physical activity for days and weeks Correlates with 6MWD Test, mPAP, and PRVi Sensitive and, thus, potentially requires smaller sample size	Needs to be validated in an interventional trial Needs to optimize the cutoff values for different levels of physical activities across different devices Seasonal and school/holiday influences
PRO	Not studied	Direct measurement of how a patient feels, functions, and survives	Not being developed

6MWD indicates 6‐Minute Walking Distance; mPAP, mean pulmonary arterial pressure; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; PAH, pulmonary arterial hypertension; PRO, patient‐reported outcome; PVRi, pulmonary vascular resistance index; TAPSE, tricuspid annular plane systolic excursion; WHO‐FC, World Health Organization functional class.