Insulin resistance is associated with subclinical myocardial dysfunction and reduced functional capacity in heart failure with preserved ejection fraction.

Background: Obesity and insulin resistance are prevalent in heart failure with preserved ejection fraction (HFpEF) and are associated with adverse cardiovascular outcomes. Measuring insulin resistance is difficult outside of research settings, and its correlation to parameters of myocardial dysfunction and functional status is unknown.
Methods: A total of 92 HFpEF patients with New York Heart Association class II to IV symptoms underwent clinical assessment, 2D echocardiography, and 6-min walk (6 MW) test. Insulin resistance was defined by estimated glucose disposal rate (eGDR) using the formula: eGDR = 19.02 - [0.22 × body mass index (BMI), kg/m ² ] - (3.26 × hypertension, presence) - (0.61 × glycated hemoglobin, %). Lower eGDR indicates increased insulin resistance (unfavorable). Myocardial structure and function were assessed by left ventricular (LV) mass, average E/e' ratio, right ventricular systolic pressure, left atrial volume, LV ejection fraction, LV longitudinal strain (LVLS), and tricuspid annular plane systolic excursion. Associations between eGDR and adverse myocardial function were evaluated in unadjusted and multivariable-adjusted analyses using analysis of variance testing and multivariable linear regression.
Results: Mean age (SD) was 65 (11) years, 64 % were women, and 95 % had hypertension. Mean (SD) BMI was 39 (9.6) kg/m ² , glycated hemoglobin 6.7 (1.6) %, and eGDR 3.3 (2.6) mg × kg ^-1  min ^-1 . Increased insulin resistance was associated with worse LVLS in a graded fashion [mean (SD) -13.8 % (4.9 %), -14.4 % (5.8 %), -17.5 % (4.4 %) for first, second, and third eGDR tertiles, respectively, p = 0.047]. This association persisted after multivariable adjustment, p = 0.040. There was also a significant association between worse insulin resistance and decreased 6 MW distance on univariate analysis, but not on multivariable adjusted analysis.
Conclusion: Our findings may inform treatment strategies focused on the use of tools to estimate insulin resistance and selection of insulin sensitizing drugs which may improve cardiac function and exercise capacity.
Competing Interests: Disclosures SJS has received research grants from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and has received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardiora, Coridea, CVRx, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Eisai, Imara, Impulse Dynamics, Intellia, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sanofi, Shifamed, Tenax, Tenaya, and United Therapeutics. KS is a consultant and advisory board member of AstraZeneca, Bayer, Boehringer-Ingelheim, Imbria, Janssen, Novartis, Novo Nordisk, and Rivus and receives honoraria. The other authors have no relevant disclosures.
(Copyright © 2023. Published by Elsevier Ltd.)