Gene expression underscores the impact of impaired mobility on peri-operative/interventional complications in older cardiac patients

Abstract Background/Introduction The frailty syndrome is highly prevalent in elderly patients with heart disease. Phenotypes of physical frailty such as deterioration of mobility, strength or gait speed are relevant in clinical practice. These phenotypes are associated with a worse prognosis. The specific physiological pathways are not yet clearly understood. Transcriptomic analysis in skeletal muscle can provide information about these processes, and finally can be used to develop novel treatment options. Purpose Determination of gene expression levels in physical frailty phenotypes predictive for perioperative/interventional complications in older patients undergoing cardiac surgery (e.g. coronary artery bypass graft) or transcatheter aortic valve implantation (TAVI). Methods From 06/2021 to 07/2022, patients ≥ 70 year of age referred for elective cardiac surgery or TAVI were included in the study. At hospital admission, physical frailty was assessed in terms of low gait speed (5-meter Walk Test; ≥ 6 sec), moderately/severe impaired mobility (Timed Up-and-Go (TUG); ≥ 10 sec), and reduced handgrip strength (dynamometer; ≤ 27 kg ♂; ≤ 16 kg ♀). Total RNA was isolated and sequenced from muscle specimens (M. quadriceps femoris) collected during surgery/intervention. Perioperative complications (mortality and major morbidity) were primary endpoints. Differential gene expression analysis was performed using DESeq2, adjusted for age, sex, estimated glomerular filtration rate (eGFR) and number of comorbidities. Results 63 patients (77.6 ± 4.3 years) referred to cardiac surgery (n= 34, 54%) or TAVI (n= 29, 46%) were enrolled (Table 1). Overall, 19 patients (30.6%) were characterized as frail by low gait speed, 43 (68.3%) by moderately/severe impaired mobility, and 19 (30.2%) by low handgrip strength. In total, 37 patients (59%) experienced ≥ 1 complication (e.g. need of transfusion, atrial fibrillation, delirium); one patient died. Frail patients showed altered gene expression levels (e.g. TAVI: 89 down- and 78 up-regulated genes). Interestingly, the expression of the genes MYLK4 (Fold Change - 1.8), KANSL1-AS1 (FC 2.0) and JMJD4 (FC 1.4) were significantly altered (Figure 1) in all three phenotypes of physical frailty, but only in TAVI patients. Conclusion Dysregulation of genetic determinants in the muscle was associated with reduced mobility. The detection of corresponding biomarkers (e.g. in plasma) could improve the accuracy of detection of physical frailty p