Table 1.

Summary of key preclinical studies of elamipretide in heart failure

Reference	Model	Results
Sabbah et al. [9]	Canine model of microembolization-induced advanced HF	Elamipretide (3 months) improved LVEF and indices of LV diastolic function, normalized plasma biomarkers (nt-proBNP, TNF-a, and CRP), SERCA2a activity, COX1 and ND1 DAMPs, and reversed mitochondrial abnormalities (respiration, ∆φm, maximum ATP synthesis rate, and ATP/ADP ratio) in LV myocardium compared to placebo
Eirin et al. [8]	Porcine model of renovascular hypertension manifesting HFpEF	Elamipretide (3 months) normalized mitochondrial respiration, mitochondrial calcium tolerance and permeability pore opening, mitochondrial membrane potential, SERCA2a activity, maximum of ATP synthesis rate, and mitochondrial complex I and IV activities, reduced ROS formation and cytochrome c release into the cytosolic compartment. Left ventricular relaxation was improved and cardiomyocyte hypertrophy reduced
Chiao et al. [64]	Old mice	Elamipretide (8 weeks) normalized diastolic functional deficit, increased Ea/Aa, and improved exercise tolerance with regression of cardiac hypertrophy accompanied by normalization of mitochondrial proton leak and ROS

ADP adenosine diphosphate, CRP C-reactive protein, DAMP DNA damage-associated molecular patterns, Ea/Aa early-to-late diastolic mitral annulus velocities, HF heart failure, HFpEF heart failure with preserved ejection fraction, LV left ventricle, LVEF left ventricular ejection fraction, nt-pro-BNP n-terminal pro-brain natriuretic peptide, ROS reactive oxygen species, SERCA2a sarco-/endoplasmic reticulum Ca²⁺ ATPase, TNF-a tumor necrosis factor-a, ∆φm membrane potential