Clinical Response to Personalized Exercise Therapy in Heart Failure Patients with Reduced Ejection Fraction is Accompanied by Skeletal Muscle Histological Alterations.

Tatiana Lelyavina,Alexey Sergushichev,Maria Sitnikova,Maria Bortsova,Oksana Ivanova,Renata Dmitrieva,Victoria Galenko,Elena Ignatieva,Galina Yukina,Anna Kostareva,Margarita Komarova,Natalia Khromova

doi:10.3390/ijms20215514

Abstract

Heart failure (HF) is associated with skeletal muscle wasting and exercise intolerance. This study aimed to evaluate the exercise-induced clinical response and histological alterations. One hundred and forty-four HF patients were enrolled. The individual training program was determined as a workload at or close to the lactate threshold (LT1); clinical data were collected before and after 12 weeks/6 months of training. The muscle biopsies from eight patients were taken before and after 12 weeks of training: histology analysis was used to evaluate muscle morphology. Most of the patients demonstrated a positive response after 12 weeks of the physical rehabilitation program in one or several parameters tested, and 30% of those showed improvement in all four of the following parameters: oxygen uptake (VO2) peak, left ventricular ejection fraction (LVEF), exercise tolerance (ET), and quality of life (QOL); the walking speed at LT1 after six months of training showed a significant rise. Along with clinical response, the histological analysis detected a small but significant decrease in both fiber and endomysium thickness after the exercise training course indicating the stabilization of muscle mechanotransduction system. Together, our data show that the beneficial effect of personalized exercise therapy in HF patients depends, at least in part, on the improvement in skeletal muscle physiological and biochemical performance.

Highlights

Heart failure (HF) is one of the most life-threatening conditions in cardiovascular patients in the world
We have previously shown that VO2 at lactate threshold and pH threshold might be used as a significant diagnostic and prognostic marker in HF patients [15], and that the prescription of individualized aerobic exercise program based on the definition of lactate threshold resulted in significantly better therapeutic outcome (VO2 peak, left ventricular ejection fraction, exercise tolerance) than in patients who undergo aerobic training prescribed based on the estimation of the VO2 peak [16,17]
The study included 144 heart failure patients New York Heart Association (NYHA) III class who underwent personalized aerobic exercise programs based on the estimation of the lactate threshold

Summary

Introduction

Heart failure (HF) is one of the most life-threatening conditions in cardiovascular patients in the world. Pathological skeletal muscle changes include a shift in fiber type, induction of atrophy, development of insulin resistance, dysregulation of lipid metabolism, and ectopic fat deposition All these factors lead to significant loss of skeletal muscle mass, a decrease in quality of life, and poor prognosis in CHF patients. We showed that the regeneration potential of bone marrow and skeletal muscle resident stem cells in CHF patients was not severely affected by disease, and under standardized in vitro conditions, these cells maintained proliferation activity [7] and differentiated actively into myotubes [8] This indicates that exercise-induced activation of the regeneration potential of skeletal muscle stem cells might contribute to muscle tissue restoration and better performance in CHF patients

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