Introduction
Cardiovascular disease (CVD) is the leading cause of morbidity and
mortality worldwide, of which
heart failure (HF) is among the top causes of cardiovascular mortality,
accounting for approximately 80000 deaths annually in the United States
alone (Virani et al., 2020).
HF is defined as a complex progressive disease that is secondary to
abnormal structure and function of the heart, which causes dysfunction
of ventricular systolic and/or diastolic function, thus impairing the
blood flow capacity of the heart under normal pressure or the ejection
capacity meeting the needs of metabolic organs. The four main triggers
of HF include ischemic heart disease, hypertensive heart
disease, idiopathic dilated
cardiomyopathy, and valvular heart
disease (Dokainish et al., 2017). Besides, pathogenesis and pathological
processes of HF it also involves comorbidities like obesity, type II
diabetes, and chronic kidney disease. Despite such complexity of HF
pathological mechanism, it is
believed that myocardial remodeling, caused by chronic activation of the
renin-angiotensin-aldosterone axis and the sympathetic nervous system
(SNS) is the key factor in the occurrence and development of HF
(Triposkiadis et al., 2009). Myocardial remodeling can initially
partially compensate for cardiac function, but with the aggravation of
myocardial remodeling, cardiac function gradually changes from
compensatory to decompensated, with obvious symptoms and signs
characterized by loss of myocytes, hypertrophy and fibrosis.
Indeed, HF therapies developed in the past decades are based on
evidence-based approaches to treat HF risk factors and the
implementation of treatment with angiotensin-converting enzyme (ACE)
inhibitors, β-blockers, coronary vascularization, implantable
cardioverter-defibrillators, and cardiac resynchronization therapies. As
indicated by data from Kaiser Permanente, the 1-year cardiovascular
hospitalization, mortality, and cardiovascular mortality has been
improved from 1998 to 2008 but remained high at 29.6%(Virani et al.,
2020), although, current diagnosis and treatment strategies are still
ineffective in many patients, and drug treatment is associated with many
complications and adverse reactions. Therefore, it is necessary to
improve the current symptomatic treatment methods by innovating
therapies to ideally target the specific pathological mechanism of HF.
The exploration of the pathogenesis of HF and the research of HF
therapeutic drugs are very dependent on basic and preclinical studies.
In these studies, the research on the transformation process from the
test bench to the clinical needs highly relevant experimental models to
carry out accurate relationship research. In view of the complex causes
of heart failure, current animal models used for HF research covers much
of the models commonly used for CVDs research. Therefore, this paper
firstly starts with a comprehensive overview of different models in
various species currently used in HF research and discuss their general
applicability. After that,we summarized the preclinical research review
of approved drugs for HF, which
would provide theoretical and practical guidance for researchers
considering preclinical studies for the treatment of HF.