Expression of myostatin and folistatin as a response to high-load strength training to counteract the loss of muscle mass in heart failure with preserved ejection fraction
Authors: Lara Vargas J , Pereira-Rodriguez J E , Penaranda-Florez D G , Ceballos-Portila L F , Pereira-Rodriguez P , Pineda-Salmeron G M , Hernandez-Sanchez A 
Published: October 2024

Abstract

Background and Purpose
Muscle loss is a common complication in patients with heart failure (HF) associated with a significant increase in morbidity and mortality. Myokines (muscle proteins) play a crucial role in the pathophysiology of the disease; in particular, an imbalance in myostatin and follistatin has been reported. Although strength training (ST) within a cardiac rehabilitation (CR) program can modulate the expression of these myokines, its effect in patients with HF with preserved ejection fraction (HFpEF) is unknown. We hypothesize that in this population, ST with high load and low repetitions can mitigate muscle cachexia with better myiokine overexpression in this population. Our objective is to evaluate the impact of a CR program with emphasis on high-load, low-repetition ST on the regulation of these muscle proteins, muscle gain and cardiorespiratory fitness (CRFit) in patients with HFpEF.

Methods
Quasi-experimental study of a CR program (24 sessions of 90 minutes, 3 times a week, for 8 weeks), with the following structure: warm-up (10 minutes), 30-minute ST of high loads (&gt;85% maximum repetition, 1MR) with low repetitions (3-5) and rest times between sets of 2 minutes; then 30 minutes of aerobic resistance training at moderate intensity (60-80% of maximum heart rate) and finally breathing exercises and cool-down (10 minutes). Myokines were determined by immunoassays. Muscular strength was determined by 1MR in biceps, triceps, lateral deltoid, quadriceps, hamstrings, gastrocnemius and soleus. For CRFit, maximum oxygen consumption (VO2) was measured and six-minute walk test protocol was also performed. Pre and post-intervention comparison was made using paired t test, Pearson's correlation was used in data analysis and a value of p&lt;0.05 was considered significant.

Results
59 patients were admitted, of which 8 of them left due to decompensation. Of the remaining 51 (62.7% male), the mean age was 66±8 years, all of them with HFpEF (M:55±2.4% vs W:54±2.1%; p=0.743). The other diagnoses in the study population were myocardial revascularization (52.94%), angioplasty (29.41%), valve replacement (11.6%), arterial hypertension (60%) and obesity (35%). After CR program it was observerd an improvement in VO2 (from 9.95±2.6 to 13.32±1.7; p=0.022) and meters traveled (243±41 to 349±14; p=0.002), and a decrease in myostatin levels (3337.1±69.2 to 2448.0±70.6; p=0.001) and elevation of follistatin (2167.4±96.9 to 3231.6±67.7; p=0.001). We found a strong positive correlation between follistatin levels and muscle percentage (r=0.8947 Pearson, graph1) and a strong negative correlation with myostatin and muscle percentage (r= -0.8034 Pearson, graph2).

Conclusion
A phase II CR program with a ST component based on high loads and low repetitions improved muscle strength and mass, FitCR and distance traveled in patients with HFpEF, without modify hemodynamic function. Follistatin levels increased by 49.09% and myostatin levels decreased by 26.65%.