Abstract 994 MicroRNA-22 as a potential diagnostic tool in sarcopenic heart failure

Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5
MicroRNA-22 as a potential diagnostic tool in sarcopenic heart failure
M. Vatic¹, A. A. Derda², T. Garfias Macedo¹, G. Loncar³, S. D. Anker⁴, T. Thum⁵, S. von Haehling¹, für die Studiengruppe: SICA-HF
¹Herzzentrum, Klinik für Kardiologie und Pneumologie, Universitätsmedizin Göttingen, Göttingen; ²Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover; ³Dedinje Cardiovascular Institute, Faculty of Medicine, University of Belgrade, Belgrade, SRB; ⁴CC11: Med. Klinik m.S. Kardiologie, Charité - Universitätsmedizin Berlin, Berlin; ⁵Institut für Molekulare und Translationale Therapiestrategien, OE-8886, Medizinische Hochschule Hannover, Hannover;
Background: Progressive loss of skeletal muscle mass and strength (sarcopenia) is a natural consequence of aging and is common in chronic diseases, such as heart failure (HF). Muscle wasting leads to vulnerability and frailty and represents an independent predictor of survival in chronic HF patients. Circulating small non-coding RNAs (microRNAs) are emerging as promising non-invasive diagnostic biomarkers of sarcopenia. MicroRNA-22 (miR-22) was reported as a positive regulator of cardiac and skeletal muscle proliferation and differentiation. Furthermore, miR-22 was shown to be downregulated during fibro-adipogenic fatty infiltration and muscle degeneration. The study aimed to investigate the association of circulating miR-22 with sarcopenia and its potential for predicting sarcopenia in heart failure patients. Methods: We conducted a retrospective analysis of 176 ambulatory patients with HF enrolled in the multicentric, observational SICA-HF study (Studies Investigating Comorbidities Aggravating Heart Failure). The diagnosis of sarcopenia was extracted from medical records, based on a reduction in appendicular skeletal muscle mass. Body composition was assessed by DEXA-Scan. Exercise capacity was examined by cardiopulmonary exercise test. RNA was isolated from serum and miR-22 concentrations were measured by miR-specific TaqMan PCR analyses. Determinants of sarcopenia were analyzed using univariate and multivariate logistic regression analysis with sarcopenia serving as a dependent variable. Results: The overall prevalence of sarcopenia was 15.9%. Sarcopenic HF patients were older compared to non-sarcopenic HF patients (74.5 [68.7-80.2] vs. 68.4 [60.9-74.8]; p=0.001), had a lower BMI (25.1 [22.4-26.8] vs. 29.2 [26.0-32.9] kg/m²; p<0.001), lower total lean mass (49.7 ± 5.8 vs. 55.1 ± 11.6 kg; p=0.006), higher NTproBNP levels (3693.2 [1183.3-5000.0] vs. 1066.4 [521.3-2453.6] pg/ml; p<0.001), lower left ventricular ejection fraction (16.8 [15.0-20.0] vs. 35.0 [30.0-40.0] %; p=0.025), lower maximal handgrip strenght (31.1 ± 6.0 vs. 37.0 ± 13.0 kg; p=0.016), lower absolute peak VO₂(1181.3 ± 379.5 vs. 1593.0 ± 487.0 mL/min; p<0.001) and a lower 6-minute walk test distance (389.0 ± 135.5 vs. 466.3 ± 120.0 m; p=0.009). Serum level of miR-22 was significantly downregulated in sarcopenic HF patients (5.2 ± 0.8 vs. 5.7 ± 0.9; p=0.032). Concentration of miR-22 correlated with the presence of sarcopenia (r=-0.161, p=0.032) and cachexia (r=-0.153, p=0.042). In the multivariate regression model adjusted for age, diabetes mellitus, ejection fraction, NTproBNP levels and absolute peak VO_2,miR-22 levels (OR 0.410, 95%CI 0.193-0.868, p=0.020) and BMI (OR 0.784, 95%CI 0.642-0.959, p=0.018) remained associated with presence of sarcopenia in heart failure patients. Conclusion: Prevalence of sarcopenia in our cohort of ambulatory HF patients was with 15.9% high. Sarcopenia in HF patients was independently associated with miR-22 profile, proposing a potential novel epigenetic biomarker of alteration of skeletal muscle in HF patients.
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