Chronic heart failure (CHF) affects 26 million people worldwide and it increases with aging and acute cardiovascular events. Current therapies for the reduced ejection fraction (HFrEF) are inadequate and almost no effect to preserve ejection fraction (HFpEF). Rodent models of heart failure have been widely used for drug discovery and significantly advanced the understanding of the mechanisms. Cynomolgus monkeys with metabolic dysfunctions are ideal models to verify these findings prior to the trial in humans because the monkey species are much closer to patients and can spontaneously progress to CHF (Fig 1).
KBI has screened over 1000 monkeys fed HFD for two years or longer with severe metabolic syndrome by echocardiography. About 38% of these monkeys were found to have different extents of systolic or diastolic dysfunction (Fig 2, 3, 4).
N-terminal pro-brain natriuretic peptide (NT-proBNP) is a specific biomarker used for the assessment of CHF progression and treatment responses in patients. As shown in Fig 5, NT-proBNP is significantly elevated in the CHF monkeys and it allows us to assess efficacy and toxicity of test drugs.
MRI T1 mapping for determination of extracellular matrix volume (ECV) as a surrogate for the interstitial cardiac fibrosis is a diagnostic tool for HF patients, especially those with HFpEF. KBI has validated this non-invasive technique in the HFpEF monkeys (Fig 6).
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