We read with great interest the state-of-the-art review from Valero-Muñoz et al. (1) in a recent issue of JACC: Basic to Translational Science. The authors described the more commonly used murine models of heart failure with preserved ejection fraction (HFpEF). They emphasize the importance of including the number of comorbidities typically seen in patients with HFpEF, in addition to the cardiac diastolic dysfunction, which, to date, represent a cardinal point of HFpEF diagnosis. In this comprehensive review, one model appears to be missing, which considering the high prevalence of obesity and metabolic abnormalities in patients with HFpEF, is of utmost importance.
Female and male mice fed with a diet rich in sugars and/or saturated fatty acids (i.e., Western diet) develop severe cardiac diastolic dysfunction, elevated filling pressures, exercise intolerance, as well as myocardial fibrosis, measured at both noninvasive and invasive assessments 2, 3, 4. Despite a mild reduction of systolic function reported in mice fed with the Western diet, left ventricular ejection fraction remains 50% or higher, as seen in patients with HFpEF.
The effects appear to be related to the specific nutrients in the diet: a diet rich in saturated fatty acids and/or sugars promotes HFpEF, and one rich in “healthy fats,” namely unsaturated fatty acids (UFAs), preserves cardiorespiratory fitness, body composition, and cardiac diastolic function in obese patients with HFpEF (5). Similarly, mice fed with a diet rich in UFA and low in saturated fatty acids and sugars showed a preserved cardiac diastolic dysfunction and did not gain excess body weight compared with mice fed with an isocaloric diet with similar content of total fat, proteins, and carbohydrates, but rich in sugars and saturated fatty acids.
Of note, a pilot study aimed at increasing UFA consumption in obese patients with HFpEF is currently ongoing (NCT03310099).
In conclusion, we congratulate the authors for their extremely comprehensive and well-written review, but suggest the addition of Western diet–induced obesity to the list of murine models of HFpEF, which presents not only with severe diastolic dysfunction, but also with the typical metabolic abnormalities reported in a large proportion of patients with HFpEF.
Footnotes
Please note: Dr. Carbone is supported by a Mentored Clinical & Population Research Award (16MCPRP31100003) from the American Heart Association, a Virginia Commonwealth University Department of Internal Medicine, and a VCU Pauley Heart Center Pilot Project Grant Program 2017. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Scienceauthor instructions page.
References
- 1.Valero-Muñoz M., Backman W., Sam F. Murine models of heart failure with preserved ejection fraction: a “fishing expedition.”. J Am Coll Cardiol Basic Trans Science. 2017;2:770–789. doi: 10.1016/j.jacbts.2017.07.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Bostick B., Habibi J., DeMarco V.G. Mineralocorticoid receptor blockade prevents Western diet-induced diastolic dysfunction in female mice. Am J Physiol Circ Physiol. 2015;308:H1126–H1135. doi: 10.1152/ajpheart.00898.2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Carbone S., Mauro A.G., Mezzaroma E. A high-sugar and high-fat diet impairs cardiac systolic and diastolic function in mice. Int J Cardiol. 2015;198:66–69. doi: 10.1016/j.ijcard.2015.06.136. [DOI] [PubMed] [Google Scholar]
- 4.Chiang S.-H., Harrington W.W., Luo G. Genetic ablation of CD38 protects against Western diet-induced exercise intolerance and metabolic inflexibility. PLoS One. 2015;10 doi: 10.1371/journal.pone.0134927. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Carbone S., Canada J.M., Buckley L.F. Dietary fat, sugar consumption and cardiorespiratory fitness in patients with heart failure with preserved ejection fraction. J Am Coll Cardiol Basic Trans Science. 2017;2:513–525. [Google Scholar]