P4733Growth factors and atrophy-related genes are highly expressed in patients with HFpEF and are associated with elevated BNP and reduced exercise capacity and quality of life

Abstract

Purpose: Patients with heart failure (HF) showed changes in skeletal muscle function structure and metabolism. We aimed to elucidate the differences in expression of growth factors and atrophy-related genes in skeletal muscle between clinically stable outpatients with HF with preserved (HFpEF) and reduced ejection fraction (HFrEF) and age-matched healthy controls (HC). Methods: 55 participants were recruited prospectively at our University Hospital: 19 HFpEF, 18 HFrEF, 18 HC (age: 71±6 vs. 68±9 vs. 66±7 years; sex (m/f): 8/11 vs. 15/3 vs. 7/11 and BMI: 28.5±4.6 vs. 27.9±5.3 vs. 26.1±4.3 kg/m2, respectively). All participants underwent standardized tests including echocardiography, cardiopulmonary exercise test (CPET), 6-minute walk test (6MWT), muscle function tests, blood tests, QoL assessment as well as muscle biopsies from the vastus lateralis muscle. Total RNA was prepared (12 HFpEF, 13 HFrEF and 9 HC) and expression levels of genes for transforming growth factor beta (TGFβ), myostatin, atrogin 1, ubiquitin B (UBB), FBOX 32, insulin-like growth factor 1 (IGF-1) and FoxO1 were measured by RT-PCR. Results: Atrophy-related genes were expressed stronger in patients with HFpEF compared to HFrEF [(FBOX32: 10.3±3.1 vs. 7.1±2.8 AU, p=0.008); (Myostatin: 0.13±0.04 vs. 0.1±0.04 AU, p=0.03)]. All atrophy-related genes and growth factors were expressed stronger in both HFpEF and HFrEF compared to HC (p<0.04). Atogin-1 was associated inversely with increased daily activities using METs in one questionnaire (r=-0.4, p=0.03). The growth factor TGFβ1 was associated with reduced peak VO2 on the CPET (r= -0.4, p=0.03) and with increased BNP (r=0.5, p=0.002). Myostatin was associated with increased LV-Mass index (r=0.5, p=0.01) and inversely with reduced QoL (VAS-Score) (r=-0.5, p=0.009). Conclusion: Patients with HFpEF show increased gene expression of both atrophy-related genes and growth factors compared to those with HFrEF and HC. Atrophy-related genes and growth factors were associated with impaired exercise capacity, increased thickness of heart muscle, elevated BNP and reduced quality of life which all occurred independently of daily activity level. Thus, patients with HFpEF show distinct abnormalities in skeletal muscle gene expression that are more pronounced compared to patients with HFrEF.