Correlation between sarcopenia and left ventricular myocardial mass in chronic heart failure patients

Abstract Sarcopenia is defined as a progressive age‐related syndrome of reduced whole‐body muscle mass, muscle strength, and muscle function. Patients with heart failure (HF) and sarcopenia are inclined to have decreased muscle strength. The current research suggests that skeletal muscle changes are the main manifestations of sarcopenia, but myocardium is not mentioned as skeletal muscle. The myocardium changes significantly with the progression of HF. Measuring myocardial quality has become an important and accessible way to assess HF by detecting changes in myocardial quality in patients with sarcopenia. Due to its economical, simple, and effective advantages in measuring myocardial quality, real‐time three‐dimensional echocardiography provides a convenient and reliable method for clinical diagnosis of HF and sarcopenia. This will be conducive to the screening of sarcopenia in people with chronic HF to better guide clinical treatments. This review describes the definition and diagnostic criteria of sarcopenia, the characteristics of HF with sarcopenia, and the related study of myocardial quality.

suggests that skeletal muscle changes are the main manifestations of sarcopenia, but myocardium is not mentioned as skeletal muscle. The myocardium changes significantly with the progression of HF. Measuring myocardial quality has become an important and accessible way to assess HF by detecting changes in myocardial quality in patients with sarcopenia. Due to its economical, simple, and effective advantages in measuring myocardial quality, real-time three-dimensional echocardiography provides a convenient and reliable method for clinical diagnosis of HF and sarcopenia.
This will be conducive to the screening of sarcopenia in people with chronic HF to better guide clinical treatments. This review describes the definition and diagnostic criteria of sarcopenia, the characteristics of HF with sarcopenia, and the related study of myocardial quality.

K E Y W O R D S
chronic heart failure, myocardial mass, sarcopenia

| SARCOPENIA-REL ATED HF AND REDUCED MYO C ARD IAL MA SS
It is well established that sarcopenia is closely related to chronic HF (CHF). The prevalence of sarcopenia in elderly patients with CHF is higher than that in patients without a condition of CHF. CHF may cause sarcopenia through common pathogenetic pathways, including inflammation, hormonal changes (such as insulin-like growth factor-1, angiotensin, sex hormone, myostatin), physical inactivity, low ventricular ejection fraction, malnutrition, and oxidative stress. 3 In contrast, sarcopenia, or a reduction of muscle strength and mass, may favor the development of CHF via different mechanisms. Recent studies confirm that CHF is characterized by the presence of several modifications, including those related to hormones (including insulin, growth hormone, prolactin, thyroid hormones, catecholamines, and corticosteroids), apoptosis, physical inactivity, low muscle blood flow, and endothelial dysfunction. 4 These HF-related factors may be activated by the development of sarcopenia. Moreover, patients with CHF are prone to displaying decreased exercise tolerance and exercise ability. Consequently, this accelerates the development of sarcopenia.
As is well known, changes in the myocardial cells and myocardial mass are important clinical changes of CHF. For instance, atrophy of myocardial cells and reduction of myocardial mass are essential stages of HF. Due to the strong correlation between sarcopenia and CHF, the effect of sarcopenia on myocardial mass is highly significant. Furthermore, both cardiac and skeletal muscle is striated muscle. 3 Consequently, sarcopenia, whose main manifestation is skeletal muscle, is also related to myocardial mass.

| IMPLI C ATI ON S OF HAVING BOTH SARCOPENIA AND REDUCED MYO C ARD IAL MA SS OR HF
Generally, a series of symptoms, such as dyspnea, low physical ability, frailty, and reduced ejection fraction, would appear in the early stage of CHF, with some maybe appearing latter. Now we can infer that the symptoms above are not only caused by decreases of cardiac function, but also sarcopenia. Sarcopenia can result in low muscle mass and decreased muscle function of whole-body muscle (for example limb muscle, respiratory muscle, and myocardial muscle), leading to those symptoms. Compared with healthy people or patients with a single disease, once complicated with sarcopenia and HF or reduced myocardial function, patients are more prone to disease progression and poorer prognosis.

| MECHANIS MS OF REDUCED MYO C ARD IAL MA SS IN SARCOPENIA
The relationship between sarcopenia and myocardial mass deserves our attention. Based on previous research and theory, this review puts forward the following opinions about mechanisms of reduced myocardial mass in sarcopenia, as shown in myocardium is gradually affected by hypoxia and necrosis. The fiber cells replacing the injured myocardium further contribute to decreased myocardial mass. 5 Furthermore, in CHF, impaired autophagy (which may lead to increased oxidative stress and reduced adenosine triphosphate production) ultimately contributes to age-related skeletal muscle loss. 4 Recent studies confirm that the endothelial function in CHF patients with sarcopenia is greatly reduced. 5 In the elderly, sarcopenia is closely associated with atherosclerosis. As a result, sarcopenia may contribute to the formation of CHF lesions. In fact, recent research has proposed the term "cardiac skeletal myopathy" to clarify the mechanism. 6 It is an important cause of decreased physical fitness and poor cardiopulmonary function in elderly CHF patients.
2. Like skeletal muscle, myocardial mass is one of the direct targets of sarcopenia. At first, similar to the skeletal muscle, the myocardium is also a striated muscle. 5 Therefore, the corresponding pathological mechanism may also be similar. Sarcopenia is characterized by atrophy of the type II muscle fibers and a progressive denervation and re-innervation process that results in the loss of a motor unit. 2 From a histopathological perspective, muscle dystrophy is majorly manifested as atrophy and apoptosis of skeletal muscle fibers and continuous reduction of organelles, such as mitochondria dysfunction. 7 In cardiomyocytes, angiotensin II may lead to apoptosis, ubiquitin-proteasome system activation, continuous sympathetic nerve activity, and excessive oxidative stress by modifying the insulin-like growth factor-1 signal. This may cause mitochondrial damage, muscle protein degradation, and decreased appetite, eventually leading to muscle atrophy. 8 These findings were confirmed in animal models. In addition, animal studies suggest that the advancement of age results in the oxidative damage of mitochondrial DNA and an increase in intercellular connective tissue within cardiomyocytes. 9 These cellular changes are linked to sarcopenia. Secondly, the infiltration of fat and connective tissue is another important element of reduced muscle mass. As adipose tissue is constantly deposited between muscle fibers, the number of muscle satellite cells continues to decrease, and muscle function declines further. 3 In addition, sarcopenia can also weaken left ventricular mass (LVM) through some common pathways, including muscle tissue remodeling, complications (eg, frailty and CHF), low nutritional intake, and lack of activity. 3,5 Finally, the activation of ubiquitin and increased protein degradation can lead to a reduction in muscle protein synthesis. 9 Therefore, we conclude that sarcopenia could lead to a decrease in LVM even without CHF.
3. Skeletal muscle may affect the myocardial mass directly.
In animal model experiments, it is observed that a class of substances, such as Akt protein kinase B, is secreted by the skeletal muscle. 10 These substances are known as cardiac protective factors and may reduce cardiac injury. 3 However, recent evidence suggests that pathological changes of skeletal muscle in patients with sarcopenia may reduce the protective effects of cardiac protective factors. 5 Research shows that LVM atrophy arises in conjunction with losses of skeletal muscle. 3,5 Sarcopenia may lead to a decrease in the peripheral skeletal muscle, a decrease in myocardial muscle mass, and accelerated myocardial hypertrophy, thereby worsening CHF. As a result, sarcopenia is closely related to myocardial mass.

| A SS E SS MENT OF LOW MYO C ARD IAL MA SS
It is important to examine the myocardium for the assessment and

| CON CLUS ION
In summary, this review summarizes the findings of sarcopenia, HF, and myocardial mass from epidemiology, pathology, clinical reports, and other research. In patients with HF, sarcopenia is not only manifested as skeletal muscle changes, but also as myocardial transformations. In addition, this review infers from previous research that myocardial quality is modified in patients with sarcopenia. In patients with CHF and sarcopenia, peripheral muscle decline is accompanied by a decrease in myocardial mass.
Using cardiac mass and myocardial quality as indices to evaluate sarcopenia may prove effective for the screening of sarcopenia in people with CHF. Additionally, it may guide clinical treatments.

ACK N OWLED G M ENTS
Health Commission of Shandong Province, Grant/Award Number: 2015BJYB21.