RT Journal Article
T1 Non-invasive assessment of HFpEF in mouse models: current gaps and future directions
A1 Villalba Orero, María
A1 Garcia-Pavia, Pablo
A1 Lara-Pezzi, Enrique
AB Background: Heart failure (HF) with preserved ejection fraction (HFpEF) prevalence is increasing, and large clinical trials have failed to reduce mortality. A major reason for this outcome is the failure to translate results from basic research to the clinics. Evaluation of HFpEF in mouse models requires assessing three major key features defining this complex syndrome: the presence of a preserved left ventricular ejection fraction (LVEF), diastolic dysfunction, and the development of HF. In addition, HFpEF is associated with multiple comorbidities such as systemic arterial hypertension, chronic obstructive pulmonary disease, sleep apnea, diabetes, and obesity; thus, non-cardiac disorders assessment is crucial for a complete phenotype characterization. Non-invasive procedures present unquestionable advantages to maintain animal welfare and enable longitudinal analyses. However, unequivocally determining the presence of HFpEF using these methods remains challenging. Main text: Transthoracic echocardiography (TTE) represents an invaluable tool in HFpEF diagnosis, allowing evaluation of LVEF, diastolic dysfunction, and lung congestion in mice. Since conventional parameters used to evaluate an abnormal diastole like E/A ratio, isovolumic relaxation time, and E/e′ may pose limitations in mice, including advanced TTE techniques to characterize cardiac motion, including an assessment under stress, will improve diagnosis. Patients with HFpEF also show electrical cardiac remodelling and therefore electrocardiography may add valuable information in mouse models to assess chronotropic incompetence and sinoatrial node dysfunction, which are major contributors to exercise intolerance. To complete the non-invasive diagnosis of HF, low aerobic exercise capacity and fatigue using exercise tests, impaired oxygen exchange using metabolic cages, and determination of blood biomarkers can be determined. Finally, since HFpEF patients commonly present non-cardiac pathological conditions, acquisition of systemic and pulmonary arterial pressures, blood glucose levels, and performing glucose tolerance and insulin resistance tests are required for a complete phenotyping. Conclusion: Identification of reliable models of HFpEF in mice by using proper diagnosis tools is necessary to translate basic research results to the clinics. Determining the presence of several HFpEF indicators and a higher number of abnormal parameters will lead to more reliable evidence of HFpEF.
PB BioMed Central
SN 1741-7015
YR 2022
FD 2022-10-14
LK https://hdl.handle.net/20.500.14352/95471
UL https://hdl.handle.net/20.500.14352/95471
LA eng
NO Villalba-Orero, M., Garcia-Pavia, P., & Lara-Pezzi, E. (2022). Non-invasive assessment of HFpEF in mouse models: current gaps and future directions. BMC medicine, 20(1), 349. https://doi.org/10.1186/s12916-022-02546-3
NO Plan Estatal de I+D+I
NO Pro CNIC Foundation
NO Spanish Ministerio de Ciencia e Innovacion
NO Instituto de Salud Carlos III Spain
NO Ministerio de Ciencia e Innovación Spain
NO European Regional Development Fund European Union
NO Agencia Estatal de Investigación Spain
DS Docta Complutense
RD 7 oct 2024