Table 3

Potential Phase II Clinical Trial Targets

Parameters
Left ventricle
 Systolic function
 Ejection fractionSystolic time intervals
 Regional myocardial velocities, strain, systolic strain rateIsovolumic contraction time
 dP/dtNoninvasive single-beat end-systolic elastance
 End-systolic pressure/volume ratioEnd-systolic stress–velocity of circumferential fiber shortening relation
 Stroke workPre-load recruitable stroke work
 Diastolic function
 E wave velocity E/A ratio
 E wave deceleration time Pulmonary venous flow
 Color M-mode velocity of propagation E’
 E/e’ ratio Noninvasive single-beat end-systolic elastance
 End-diastolic pressure/end-diastolic volume End-diastolic pressure/stroke volume
 Early diastolic strain rate
 Structure
 Left ventricular end-systolic volume indexLeft ventricular end-diastolic volume index
 Left ventricular mass indexExtracellular volume fraction
 Relative wall thicknessLV mass/volume ratio
 Left atrium
 Left atrial volume/index (LAVI) Left atrial strain
 A velocity a’ velocity
 Left atrial function/index (LAFI)
Hemodynamics
 Right heart catheterization
 Pulmonary capillary wedge pressure Pulmonary artery pressure
 Pulmonary vascular resistance Transpulmonary gradient (mPAP-PCWP)
 Pulmonary vascular gradient (PADP-PCWP)
 Echocardiogram-derived
 Pulmonary capillary wedge pressure approximation by E/e’ Mean pulmonary artery pressure by end-diastolic pulmonary regurgitation gradient
 Systolic pulmonary artery pressure by tricuspid regurgitation gradient Pulmonary vascular resistance approximation by TR velocity/TVIRVOT ratio or RVSP-E/e’/RVOT VTI
Vascular and endothelial function
 Central pulse pressure Pulse wave velocity
 Flow mediated dilation Reactive hyperemia index
 Augmentation index
Exercise capacity
 Walking tests
 6-min walk test Shuttle walking test
 Cardiopulmonary exercise test
 VO2max VO2 at anaerobic threshold
 VE/VCO2Exercise oscillatory breathing (EOB)
Biomarkers
 Cardiac load and wall stress
 Natriuretic peptides
 Cardiac fibrosis and collagen turnover
 Procollagen type I N-terminal pro-peptides Procollagen type III N-terminal pro-peptides
 Matrix metalloproteinases Tissue inhibitors of matrix metalloproteinases
 β-galactoside-binding protein Galectin-3
 Inflammation
 Growth differentiation factor-15High-sensitivity C-reactive protein
 Interleukins
 Myocardial injury
 High-sensitivity troponin T

LV = left ventricular; mPAP = mean pulmonary artery pressure; PADP = pulmonary artery diastolic pressure; PCWP = pulmonary capillary wedge pressure; RVOT = right ventricular outflow tract; RVSP = right ventricular systolic pressure; TR = tricuspid regurgitation; TVIRVOT = right ventricular outflow tract time-velocity integral; VE/VCO2 = ventilatory equivalent ratio for carbon dioxide; VO2 = oxygen consumption; VO2max = maximum oxygen consumption.