Why Strength Training is Vital for Patients with Heart Failure

Introduction

Heart failure (HF) is a multi-faceted and life-threatening syndrome characterised by significant morbidity and mortality, poor functional capacity and quality of life (QoL), and high costs. Accordingly, reducing its social and economic burden has become a major global public health priority. The magnitude of the problem of HF cannot be assessed with precision since reliable, population-based estimates of its prevalence, incidence, and prognosis are lacking, particularly epidemiological data on HF in developing countries, where HF has different characteristics compared with the Western world, are needed. Nevertheless, there are an estimated 64 million people with HF worldwide. Although incidence has remained stable or has even slightly declined over time, prevalence is increasing due to the ageing of the population and the prolongation of the lives of cardiac patients by modern therapeutic innovations (1).

As highlighted, HF is characterised by functional limitations and consequent loss of QoL and has a significant impact on prognosis. A systematic review and meta-analysis of 44 observational longitudinal cohort studies with a total of 22,598 patients with HF showed that patients with poor physical functional performance in the Six Minute Walking Test (6MWT), the Short Physical Performance Battery (SPPB), and the Gait Speed Test had worse prognosis in terms of larger risk of hospitalisation or mortality than patients with good physical functional performance (2). Another systematic review and meta-analysis also showed a strong relationship between physical performance and prognosis among patients with HF. Six-minute walk distance (6MD) test cut-off values were significantly associated with mortality (hazard ratio [HR], 2.04; 95% CI, 1.48-2.83; p < 0.001) and cardiovascular disease (HR, 2.18; 95% CI, 1.68-2.83; p < 0.001) (3).

An old couple doing strength training for heart failure.

In my post, ‘Exercise: The Medicine Since Antiquity’, I have discussed the role exercise has played in preserving health and preventing and managing various diseases since almost 600 BC. A systematic review showed that exercise also improves functional capacity and QoL in patients with heart failure (4).

Though a multi-component exercise program (one that consists of strength, endurance, flexibility and balance training) is required to improve functional capacity, the discussion is limited to the role of strength training in improving functional capacity and QoL in patients with heart failure. Considering the significant role strength training plays in the preservation of health and prevention and management of various diseases, the role of strength training in the prevention and management of other cardiovascular diseases, diabetes mellitus, metabolic syndrome, obesity, healthy ageing and recovery from critical illnesses has been discussed in detail in my upcoming books on lifestyle medicine (Lifestyle Medicine: Management of Obesity, Volume One; Lifestyle Medicine: Lifestyle- and Age-Related Diseases and Healthy Ageing, Volume Two; Lifestyle Medicine: Lifestyle Interventions for Healthy Ageing, Volume Three).

What is Heart Failure?

Heart failure (HF) is a complex clinical syndrome characterised by impaired contractile performance of the myocardium, leading to the inability of the heart to supply adequate amounts of blood to meet the metabolic needs of peripheral tissues. The common causes of heart failure include increased preload and afterload, neurohormonal dysregulation, cardiac ischemia and intrinsic abnormalities of the myocardium. A detailed discussion on heart failure is beyond the scope of this text. However, salient patient characteristics in patients with heart failure, which warrant the use of resistance training in managing these patients, will be discussed here briefly. There are three types of heart failure, viz. left-sided, right-sided or biventricular heart failure. The left-sided heart failure is the most common and, based on the pumping ability, is further sub-divided into two types:

Heart failure with reduced ejection fraction

As a result of the weakened heart muscles, contractility of the left ventricle is impaired. Therefore, adequate blood is not pumped out into the circulation during systole. While a normal left ventricle ejects about 55% to 60% of the blood in it at the end of the diastolic phase, in heart failure with reduced ejection fraction (HFrEF), it pumps equal to less than 40% of the blood in it at the end of the diastolic phase. Heart failure with reduced pumping ability is sometimes referred to as “systolic” heart failure (5).

Heart failure with preserved ejection fraction

Originally, heart failure with preserved ejection fraction (HFpEF) was believed to be due solely to aberrant relaxation of the left ventricle (LV) and reduced LV compliance. However, our understanding of the pathophysiology of HFpEF has evolved over time, and it is now gaining recognition as a systemic, multi-organ disorder similar to other ageing-related disorders (geriatric syndromes) (6). Although the left ventricle pumps out greater than or equal to 50% of the blood in it, the cardiac output is reduced significantly due to inadequate filling during diastole. The heart failure with preserved pumping ability is also known as “diastolic” heart failure (5).

It is now well-accepted that despite similar clinical presentations for all patients with HF, HFrEF and HFpEF are mechanistically distinct diseases (7).

Origin of symptoms in heart failure

Exercise intolerance, i.e., low exercise capacity, accompanied by symptoms of dyspnea and fatigue, is a hallmark of patients with heart failure and is of clinical relevance because it is associated with poor function, quality of life, and prognosis (8, 9). Understanding the pathophysiology of exercise intolerance in patients with HF may enable the development of targeted therapeutic strategies to improve exercise and functional capacity and, thereby, quality of life. The pathophysiological mechanisms of exercise intolerance in patients with HF are multifactorial. Though the traditional view considers malfunction of the heart as a pump as the leading cause, research over the last few decades has shown that although the complex pathophysiology of HF begins with an abnormality of the heart as the prime mover, over time, it leads to adaptive changes in multiple body organs and systems, including the cardiovascular, musculoskeletal, renal, neuroendocrine, haemostatic, immune and inflammatory systems. These changes play a vital role in the pathogenesis of HF syndrome and its progression (10). As a result, the decrease in maximal exercise capacity is more severe than predicted by indices of left ventricular dysfunction (11).

Various studies suggest that the normalisation of central hemodynamic factors by pharmacological agents, which increase cardiac output and/or reduce pulmonary capillary wedge pressure(9, 12) or after cardiac transplantation (9), do not immediately improve exercise tolerance.

Factors contributing to exercise intolerance in heart failure

As highlighted, there is a poor correlation between central hemodynamic parameters (such as left ventricular ejection fraction, left ventricular end-diastolic dimension, cardiac index [cardiac output/body surface area], or pulmonary capillary wedge pressure) and exercise intolerance as well as the degree of functional limitation in patients with chronic heart failure (13, 14). Recently, the involvement of the so-called peripheral mechanisms (viz., disorders within organs and systems outside the circulatory system) in the pathogenesis of exercise intolerance and reduced functional capacity has been recognised. Although impairment in cardiac reserve is considered to be the primary underlying factor in HF, reduced exercise and functional capacity are also affected by key patient characteristics and multisystem dysfunction, including ageing, impaired pulmonary reserve vascular dysfunction, as well as peripheral and respiratory skeletal muscle dysfunction (15, 16).

Ageing is of greater relevance in patients with HFpEF, which is the most common form of heart failure among older individuals. As discussed, HFpEF is now recognised as a systemic multi-organ geriatric syndrome (6). Therefore, several age-related extra-cardiac mechanisms contribute to the symptoms of exercise intolerance in older patients with HFpEF (6). The ramifications of the concept of HFpEF as a systemic geriatrics syndrome are extensive and may explain why pharmacological trials to date have been neutral. Accordingly, a multidisciplinary approach focused on age-related drivers of exercise intolerance is needed to improve outcomes in these patients (6). Age-related diseases, including various geriatrics syndromes, and their management have been discussed in detail in my post ‘Healthy Ageing – Adding Years to Life and Life to Years.’ Discussion on impairment of cardiac and pulmonary reserve is beyond the scope of this text. However, peripheral and respiratory skeletal muscle dysfunction, important contributors to the manifestation of exercise intolerance in patients with HF, will be discussed in detail.

To begin with, it is essential to define and differentiate exercise intolerance, exercise capacity and functional capacity. Exercise intolerance is defined as an “impairment in the capacity to perform physical activities (PA) accompanied by symptoms of significant dyspnea and/or fatigue” (15). Exercise capacity may be defined as “the maximum amount of physical exertion that a subject can sustain”. In contrast, functional capacity may be defined as “the ability to perform activities of daily living that require sustained, submaximal aerobic metabolism” (15).

Role of skeletal muscle in exercise intolerance

Maximal oxygen uptake (VO2 max) is the gold standard measure of exercise capacity (17). The Fick equation states that VO2 equals cardiac output (CO) multiplied by the peripheral O2 extraction, defined as the difference in O2 content in the arterial blood and mixed venous blood (i.e., arteriovenous oxygen difference [a-v O2 diff ]).

VO2 = CO X ([O2]A – [O2]v)

where CO is the product of stroke volume (SV) and the heart rate (HR), [O2]A is the arterial oxygen content, and [O2]v is the mixed venous oxygen content.

Determinants of VO2 max

Oxygen is taken up from the atmosphere and delivered to the muscles by an interdependent system of transport components functioning as a “bucket brigade” consisting of the lungs, heart, blood and circulation, and the muscles themselves. However, the discussion here will be limited to the alterations in the muscles, which adversely impact the extraction and utilisation of oxygen in the skeletal muscle and, thereby, the exercise capacity. Broadly speaking, skeletal muscle mass (18, 19), skeletal muscle fibre types (20), and skeletal muscle mitochondrial oxidative capacity (21) are important determinants of VO2 max and, thus, exercise capacity. Several anatomical, biochemical, and functional alterations in skeletal muscles have been reported in patients with heart failure. These include skeletal muscle atrophy, a shift from slow-twitch type 1 (oxidative), fatigue-resistant to fast-twitch, type 2 (glycolytic) muscle fibres, mitochondrial abnormalities, and increased inducible nitric oxide synthase expression with a resulting increase of nitric oxide and causing a decrease in mitochondrial creatine kinase, a key enzyme necessary for the transfer of high-energy phosphates from mitochondria to cytosol (15, 22).

These aspects will be discussed in detail subsequently.

The muscle hypothesis of chronic heart failure

Recognising the role of skeletal muscle abnormalities in the pathophysiology and symptoms of heart failure, Coats et al. proposed a ‘muscle hypothesis’ of heart failure (23). They suggested that abnormal skeletal muscle in chronic heart failure is a key abnormality that can explain much of the pathophysiology and symptoms of heart failure. The muscle hypothesis proposes that structural and functional changes within skeletal muscles (i.e., Skeletal myopathy) initiate another cycle of deterioration similar to that of neuroendocrine activation that participates in the pathogenesis of chronic heart failure and is responsible for the occurrence of symptoms and progression of the disease (23). Impairment of the left ventricular function leads to several neurohormonal and metabolic adjustments and compensatory mechanisms, including sympathetic activation, vagal withdrawal, and peripheral vasoconstriction (24). The most important of these is peripheral vasoconstriction, which serves to maintain effective perfusion of vital organs (e.g., heart, brain) at the expense of skeletal muscle tissue and splanchnic organs (i.e., kidney, liver and gut) (24, 25).

In the short-term, these adaptations are helpful and life-saving; however, in the long-term, they lead to harmful consequences, including increased catabolic processes compared to anabolic processes, resulting in a loss of muscle mass with subsequent development of macroscopic and microscopic disorders within the structure, metabolism and functioning of skeletal muscles (23, 24), as discussed above. Enhanced catabolic activity may result in a transition from nonwasted heart failure to cardiac cachexia (26). The muscle hypothesis also suggests that abnormalities in the skeletal muscle lead to the excessive activation of ergoreflex in patients with CHF (23, 26).

Ergoreflex

During exercise, sympathetic outflow and ventilation increase proportionally to exercise intensity so as to meet the metabolic demands of exercising skeletal muscles. This response is mediated by three cardiorespiratory reflexes that are highly centrally integrated: baroreflex, chemoreflex, and ergoreflex (27). Ergoreflex is a peripheral reflex arising in skeletal muscle, triggered by mechanical and metabolic stimuli during muscle activity. It is overactive in patients with CHF and contributes significantly to impaired exercise tolerance (24, 26). Ergoreceptors are grossly differentiated into mechanoreceptors, which are activated early by muscle contraction and tendon stretch, and metaboreceptors, which respond to the accumulation of metabolites in the exercising muscle and through afferent fibres, inform the brain stem on the level of muscular activity (24, 26).

Mechanoreflex (reflex from mechanoreceptors) is activated at the start of exercise and is elicited by muscle contractions and tendon stretch. On the other hand, Metaboreflex (reflex from metaboreceptors) is activated during exercise after a latency period, after the metabolites accumulate to a certain level (27). Metaboreceptors are especially sensitive to lactic acid, but also prostaglandins, bradykinin and hydrogen and potassium ions (26, 27). Mechano- and metaboreflex together constitute the ergoreflex, a neural mechanism linking cardiovascular function and ventilation to exercise intensity (27). The main effect of mechanoreflex is inhibition of the vagal tone, while metaboreflex results in increased sympathetic outflow (148). Afferent stimuli from ergoreceptors reach the central nervous system, where they are integrated with afferents from chemo- and baroreceptors. The integration of the stimuli from ergoreflex, chemoreflex and baroreflex results in an integrated response of the cardiorespiratory system, leading to increased ventilation, increased heart rate, increased peripheral resistance (due to vasoconstriction in the non-exercising muscles) and cardiac output, resulting in increased systemic blood pressure. While increased blood pressure promotes greater perfusion of the exercising muscles, increased ventilation facilitates greater blood oxygenation (148). The combined effect of these changes is that more well-oxygenated blood is diverted to the working muscles.

Ergoreflex in heart failure

As discussed, patients with heart failure often develop various anatomical, biochemical and functional abnormalities in the skeletal muscles. According to the muscle hypothesis, skeletal muscle myopathy seen in patients with HF causes an increased ergoreflex sensitivity, leading to dyspnea on effort, fatigue and autonomic imbalance with sympathetic activation and vagal withdrawal (24, 27). Ergoreflex is particularly overactive in patients suffering from cardiac cachexia and generates the greatest loss of muscle mass in the course of heart failure, initiating a vicious cycle (24, 26). Long-term over-activation of the ergoreflex system may be harmful as it maintains an abnormal neurohormonal and vasoconstrictor environment that favours the progression of the disease. While chronic sympathetic overactivity leads to abnormalities of myocardial structure and function, peripheral vasoconstriction and the resultant increased peripheral resistance would increase left ventricular afterload as well as reduce the perfusion of the skeletal muscle, thus worsening muscle damage (27). A clear association has been observed between symptom severity, NYHA functional class, muscle wasting, and ergoreflex overactivity (26). Detection of ergoreflex overactivity in HF patients further corroborates the ‘muscle hypothesis’ of chronic heart failure. However, on the positive side, exercise training is a useful therapeutic tool for HF to blunt ergoreflex sensitivity, restore the sympathovagal balance, and increase tolerance to physical activity (27).

Role of vascular dysfunction in exercise intolerance

As demonstrated by the Fick equation, peak VO2 (exercise capacity) depends on cardiac output as well as peripheral oxygen extraction (consumption). During maximal exercise, skeletal muscle has the highest oxygen consumption (15). With ageing and chronic illnesses, impaired endothelial-dependent vasodilation reduces systemic O2 delivery. In a patient with heart failure, loss of endothelial vasodilator bioavailability due to increased systemic inflammation/oxidative stress, increase in vasoconstrictive substances (endothelin-1, angiotensin II), increased sympathetic stimulation due to overactive ergoreflex lead to a significant reduction in O2 supply to the working muscles, which is further aggravated as exercise intensity increases (15).

Furthermore, interstitial extracellular space increases as a result of the reduction in myocyte mass and/or numbers (due to muscle atrophy), an increase in interstitial fibrosis (especially with ageing) or adipose tissue (with obesity), and a reduction in capillary density. An increase in interstitial volume in the skeletal muscle space leads to considerable limitations in O2 diffusion and extraction as well as peak VO2 (15). Considering that O2 is the critical component in aerobic metabolism and, therefore, in sustaining exercise, every step in the O2 transport pathway offers a potential cause for exercise intolerance. Such a state of chronic under-perfusion of the muscles relative to the demands, especially during exercise, leads to a greater reliance on anaerobic metabolism and early metabolic acidosis due to the buildup of lactic acid in the working muscles (15). As highlighted, lactic acid is a potent stimulant for metaboreceptors. Together with enhanced sympathetic drive, byproducts from anaerobic metabolism stimulate ventilation, thus aggravating dyspnoea; besides, lactic acid buildup in muscles aggravates fatigue (15).

Underperfusion of skeletal muscle and other tissues in CHF not only impairs aerobic metabolism but also induces oxidative and inflammatory stress (28), which in turn are associated with muscle wasting (29, 30).

Role of respiratory muscles in exercise intolerance

The exaggerated ventilatory response in HF patients during exertion, discussed above, leads to respiratory muscle exhaustion. Respiratory muscle fatigue activates respiratory metaboreflex, resulting in sympathetic activation and peripheral vasoconstriction, which diverts more oxygenated blood to the fatiguing respiratory muscles, effectively reducing skeletal muscle blood flow and further compromising exercise capacity (15, 31, 32, 33). Current scientific evidence seems to confirm that exaggerated metaboreflex activity of respiratory muscles in HF is the primary cause of exercise intolerance and sympathetic–adrenal system hyperactivity (34).

Furthermore, several studies have demonstrated that patients with chronic heart failure may present with significant loss of respiratory muscle strength and endurance (15, 35, 36). These impairments are associated with various abnormalities in respiratory muscle structure and function, including a shift in muscle fibre type. However, these abnormalities are different from those in peripheral skeletal muscles. Paradoxically, in the respiratory muscles, there is a shift from type II, fast-twitch, glycolytic fibre to type I, slow-twitch, oxidative (fatigue resistant) fibres (9, 15). Besides, there is an increase in oxidative capacity and mitochondrial density, an increase in capillary density, and a reduction in glycolytic capacity (15). Apparently, these adaptations result from increased work and frequency of breathing associated with HF (9, 15). Respiratory muscle weakness significantly contributes to the reduced ventilatory capacity and thus increases perceived dyspnoea during physical activity (15, 36).

Notably, inspiratory muscle training (IMT) may improve exercise and functional capacity, independently of pulmonary function, in both HFpEF and HFrEF (15, 36). Some benefits from IMT result from the attenuation of the inspiratory muscle metaboreflex (36). Accordingly, IMT is being increasingly incorporated as an essential component of a rehabilitation program in patients with HF (15).

Skeletal muscle abnormalities in patients with heart failure

Skeletal muscle atrophy in heart failure

A large percentage of patients with chronic heart failure develop cachectic phenotype; loss of muscle mass directly contributes to exercise intolerance and impairs activities of daily living, which is a strong predictor of quality of life and mortality (9). Muscle loss is primarily driven by the ubiquitin-proteasome system (UPS, a major intracellular protein degradation system which plays an important role in muscle homeostasis and health), autophagy, and myostatin-mediated signalling (myostatin, a myokine, is a negative regulator of muscle mass) (9). In addition to the activation of catabolic factors, the downregulation of insulin-like growth factor 1 (IGF-1), one of the most potent anabolic factors in skeletal muscle, also leads to a loss of muscle mass (9). Besides reduction in muscle mass, secondary modification of contractile proteins (ubiquitinylation and carbonylation) also leads to an impairment in contractile force generation (9).

Several studies have examined the association of muscle mass with prognosis in patients with chronic heart failure. The presence of muscle wasting in patients with chronic heart failure provides prognostic information beyond conventional risk factors (37). Many studies have demonstrated that low muscle mass is independently associated with a higher risk of mortality in patients with chronic heart failure (37, 38, 39, 40, 41).

Some other studies have examined the association of body mass index (BMI) with mortality and found that underweight or low BMI was associated with increased mortality (42, 43). Notably, studies have also supported previous findings of an ‘obesity paradox’ for heart failure survival and reported a reduced risk of death in people with overweight and class I or II obesity. However, class III obesity was associated with an increased risk of all-cause mortality compared with overweight (43). Besides the increased risk of mortality, sarcopenia in patients with heart failure results in low muscle strength, quality of life and exercise capacity and predisposes to risk of frailty, thereby increasing the risk of falls, fractures, and hospitalisation (38). Sarcopenia and frailty have been discussed in detail in my post, ‘Healthy Ageing – Adding Years to Life and Life to Years.’

Skeletal muscle alterations in HFrEF and HFpEF

While skeletal muscle alterations in patients with HFrEF have been documented for about three decades, in patients with HFpEF, muscle alterations have been described only over the last decade. Largely, muscle alterations range from a shift in fibre type and capillarisation to initiation of atrophy and modulation of mitochondrial energy supply. By and large, molecular alterations in the muscle are more severe in patients with HFrEF than in patients with HFpEF (9).  

Muscle alterations in HFrEF

Muscle atrophy

It is well documented in the current literature that patients with HFrEF exhibit muscle atrophy (9). In a trial titled ‘Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) trial, the appendicular skeletal muscle mass of the arms and legs combined was assessed in 200 patients with chronic HF using dual-energy X-ray absorptiometry (DEXA). Muscle wasting was seen in 39 (19.5%) patients. Notably, left ventricular ejection fraction (LVEF) was correlated with muscle wasting; patients with lower LVEF had more muscle wasting and lower muscle strength. Accordingly, these patients presented with a reduced exercise capacity (lower peak VO2 and exercise time) (44). Another SICA-HF study produced similar results. Out of 196 patients who participated in this study, 38 patients (19.4%) were found to have muscle wasting using DEXA. Older patients were more likely to have muscle wasting compared with younger patients. In this study also, LVEF was correlated with muscle wasting; patients with lower LVEF tended to have greater muscle wasting and accordingly had poor performance in the 6-minute walk test (45).

Indeed, many patients with HFrEF develop a wasting syndrome, termed cardiac cachexia (46, 9). In general, cachexia has been defined as the loss of at least 5% oedema-free body weight in the previous 12 months (or a BMI < 20kg/m2) in patients with chronic diseases and at least three of the following clinical or laboratory criteria: decreased muscle strength, fatigue, anorexia, low fat-free mass index and abnormal biochemistry characterised by increased inflammatory markers (C-reactive protein, interleukin (IL)-6, anaemia (Hb < 12 g/dl), or low serum albumin (< 3.2 g/dl). The fat mass may reduce or remain stable (47). It frequently occurs in patients with chronic diseases, including cancer and other inflammatory conditions such as heart failure (HF), chronic obstructive pulmonary disease and chronic kidney disease. When it occurs due to congestive heart failure, it is known as cardiac cachexia, and a vicious cycle is established between the loss of skeletal muscle mass and cardiac mass (48). Its prevalence rate varies widely between 10% (49) to 8-42% (47), depending on the cachexia definition and the study population.

Skeletal muscle wasting is an essential component of cachexia; it often precedes cachexia development and predicts poor outcomes in heart failure (47, 49). Cardiac cachexia results in significantly reduced functional capacity (46) and increases the risk of morbidity and mortality independent of important clinical variables such as age, ventricular function or heart failure functional class (37, 47). Reportedly, the mortality rate of patients with cardiac cachexia increases by 50% within 18 months of diagnosis (50). In combination with low peak oxygen consumption, it identifies a subset of patients at extremely high risk of death (37). In patients with HFrEF, knee extensor muscle power has been found to independently predict rehospitalisation (51). Also, reduced functional capacity assessed by either Short Physical Performance Battery (SPPB) or the 6-minute walking test (6 MWT) was independently associated with increased 1-year post-discharge adverse outcomes in hospitalised elderly patients with acute heart failure (52).

Several diverse mechanisms are involved in muscle atrophy in HFrEF. These include reduced protein synthesis via reduced expression of insulin-like growth factor 1 (IGF 1) or increased protein degradation, including activation of the ubiquitin-proteosome system, autophagy, and apoptosis (53). Additional mechanisms include activation of the sympathetic nervous system (53), upregulation of the renin-angiotensin-aldosterone system (9, 49, 53), systemic inflammation (9, 49, 53), and upregulation of the myostatin signalling pathway (9, 53). In HF patients, the resulting imbalance between anabolic and catabolic pathways in favour of the catabolic cascade is responsible for muscle atrophy, reduced muscle mass, and function (53).

As discussed in my post, ‘Healthy Ageing – Adding Years to Life and Life to Years’, loss of muscle mass (sarcopenia) is associated with an increased risk of frailty. Frailty can change the prognosis and treatment approach of several chronic diseases, including heart failure. As discussed above, frailty is highly common in older patients with CVD. A systematic review and meta-analysis found that the pooled prevalence of pre-frailty in individuals with HF was 46% and 40% for frailty (54). In a recent multicenter randomised controlled trial, of the 349 older patients hospitalised for acute decompensated heart failure, 97% of the patients were frail or prefrail at baseline (55). Cardiac cachexia, sarcopenia and frailty, despite overlap in definitions, are distinct clinical entities that often coexist in patients with heart failure. All these conditions are serious complications in patients with heart failure and are associated with higher hospitalisation and mortality rates (56). Besides the loss of muscle mass, changes in muscle fibre type, capillarisation and atrophy/modulation of mitochondria have also been documented in both HFrEF and HFpEF and may contribute to exercise intolerance in these patients.

Changes in fibre type and capillarisation

As discussed above, type I and type II muscle fibres differ in energy metabolism, contractile speed and force generation, and fatigability. Therefore, changes in the fibre type composition of the respective muscle will have significant consequences on physical function. Various studies have demonstrated changes in the composition of skeletal muscle fibre type in patients with HF, which are associated with exercise intolerance (12). In patients with HFrEF, there is an unfavourable shift from type I oxidative fatigue-resistant fibres towards type II glycolytic fibres; accordingly, patients with chronic HF have a reduced proportion of type I slow-twitch fibres and a higher proportion of type II fast-twitch fibres (9, 12, 57). 

Notably, exercise capacity has been associated with the proportion of type I muscle fibres (9). Type I fibres have a greater oxidative capacity and mitochondrial density and are relatively fatigue resistant; besides, type I fibres have a high amount of myoglobin and a high capillary content. Thus, a reduction in type I fibres reduces the skeletal muscle’s oxidative capacity and limits exercise capacity. However, muscle fibre atrophy may not be seen in all heart failure patients, and muscle attributes other than fibre size may be contributing to exercise intolerance (57). Heart failure also leads to a reduction in myosin heavy-chain type I, an isoform that is more abundant in type-I slow-twitch fibres, leading to decreased tension in myosin heavy-chain I fibres. This represents a potential molecular mechanism contributing to skeletal muscle weakness and exercise intolerance in patients with heart failure (12, 58).

The shift in fibre-type composition, as discussed above, may be due to skeletal muscle mitochondrial abnormalities, which will be discussed subsequently, and the related reduction of ATP synthesis needed by type I slow-twitch oxidative fibres. Reduced availability of ATP leads to an adaptation of type-I fibres to utilise glycogen as an alternative energy source, thus shifting fibre-type composition from type-I towards type II phenotype (59). This may enable these patients to better cope with physical demands in case of insufficient ATP production by mitochondria. Another important issue is the quantification of skeletal muscle fibre capillarisation. Studies have shown that the number of capillaries per fibre is reduced in HFrEF (9, 57), which is predicted to impair oxygen diffusion from the capillaries into the myocytes (57).

Abnormalities in skeletal muscle mitochondria and oxidative capacity

Mitochondria is the main site of energy production. Under normal physiologic conditions, oxidative phosphorylation in the mitochondria produces enough ATP to meet the energy (ATP) demands of skeletal muscle at rest and during exercise (59). Therefore, a reduction in mitochondrial capacity to synthesise ATP to meet the energy demands of the skeletal muscle due to mitochondrial dysfunction can lead to impaired muscle performance (59, 60).   In patients with HF, high-energy phosphate (such as phosphocreatine [PCr] and ATP) stores are lower in skeletal muscle, even after cardiac transplantation, supporting the concept that skeletal muscle bioenergetics may be compromised in patients with HF (60). Mitochondrial energy production is reduced in both cardiac and skeletal muscle in patients with HF, lending weight to the concept of systemic mitochondrial cytopathy. HF is associated with reduced mitochondrial biogenesis (the process by which cells increase mitochondrial numbers) and function in both heart and skeletal muscle (60). The failing heart has been described as “energy-deprived”, and mitochondrial dysfunction is mainly responsible for this energy supply-demand mismatch (59). Various mitochondrial abnormalities include defects in oxidative metabolism (59), decreased mitochondrial volume density (59), impaired mitochondrial electron transport chain activity (61), increased formation of reactive oxygen species (61), shifted metabolic substrate utilisation (61), aberrant mitochondrial dynamics (61), altered ion homeostasis (61) and altered ATP transfer to the contractile apparatus via the creatine kinase shuttle (60). Besides, cardiac and skeletal muscle bioenergetics is impaired due to reduced oxygen availability (60). The intrinsic skeletal muscle metabolic abnormalities in patients with chronic HF have been clearly demonstrated using phosphorus P 31 nuclear magnetic resonance spectroscopy. These metabolic abnormalities possibly contribute to skeletal muscle contractile dysfunction and, thus, reduced exercise capacity in patients with HF (59).

Muscle alterations in HFpEF

Muscle atrophy

Dual-energy X-ray absorptiometry (DEXA) evaluation of 60 older HFpEF patients and 40 age-matched healthy controls revealed that the per cent total lean body mass and leg lean mass were significantly reduced in patients with HFpEF compared to the controls, suggesting the presence of skeletal muscle atrophy (9, 62). Remarkably, loss of muscle mass negatively correlated with reduced peak VO2 (exercise capacity) (9, 62). Notably, obesity is common in HFpEF (63). In my books’ Lifestyle Medicine: Management of Obesity, Volume One’ and ‘Lifestyle Medicine: Lifestyle- and Age-Related Diseases and Healthy Ageing, Volume Two’, I have discussed the association of ectopic fat in muscles in obesity and older people, respectively. Intramuscular fat adversely impacts muscle quality and, consequently, muscle function. Various studies have evaluated skeletal muscle composition in HFpEF patients. In a study by Haykowsky et al., MRI Scans in patients with HFpEF and age-matched healthy controls showed that despite similar total thigh area, thigh compartment area (TC), subcutaneous fat (SCF), or skeletal muscle (SM) in both groups, intermuscular fat (IMF) area, percent IMF/TC, and the ratio of IMF/SM were significantly increased, while percent SM/TC was significantly reduced. In multivariate analyses, IMF area and IMF/SM ratio were independent predictors of peak VO2, while SM area was not. These data suggest that abnormalities in skeletal muscle composition may contribute to the severely reduced exercise capacity in older HFpEF patients and thus may be potential targets for novel therapeutic strategies in this common, debilitating disorder of older people (64). Another study by Haykowski et al. also reported substantially higher total fat mass, total per cent fat, abdominal subcutaneous fat, intra-abdominal fat and thigh intermuscular fat in HFpEF patients compared to age-adjusted healthy controls (65). Notably, thigh intermuscular fat (62, 65) and intermuscular fat to skeletal muscle (IMF/SM) ratio (62) were inversely associated with peak VO2 (exercise capacity). These findings suggest that intermuscular fat could be a potential target for therapy in patients with HFpEF.

Changes in fibre type and capillarisation

As in HFrEF patients, skeletal muscle biopsies in patients with HFpEF showed a reduced percentage of type I, slow-twitch, oxidative fibres and an increased percentage of type II, fast-twitch, glycolytic fibres (9, 62). As discussed above, type I fibres have a greater oxidative capacity and mitochondrial density and are relatively fatigue-resistant. Thus, they contribute substantially to the ability to perform sustained aerobic exercise. As highlighted, the percentage of type I fibres is an independent predictor of peak VO2 (exercise capacity), and therefore, a reduction in type I fibres limits exercise capacity (9, 62). In addition to the shift in fibre type composition, as seen in HFrEF patients, the capillary to fibre ratio is reduced in HFpEF patients (9, 62), which apparently leads to reduced muscle blood flow and oxygen transport in skeletal muscle (62).

Abnormalities in skeletal muscle mitochondria and oxidative capacity

Based on muscle biopsies obtained from 20 HFpEF patients and 17 age-matched healthy controls, Molina et al. reported 46% lower mitochondrial content in HFpEF patients compared with controls (66). Besides, skeletal muscle mitochondrial function was considerably lower in patients with HFpEF compared with healthy controls, even after adjusting for age, sex and body mass index (62, 66, 67). Abnormalities in skeletal muscle mitochondrial content (66) and oxidative capacity (62, 66, 67) are associated with exercise intolerance and represent promising therapeutic targets.

Significance of muscle abnormalities in the alleviation of exercise intolerance

As highlighted, irrespective of the treatment used, generally, there is a delay between the hemodynamic effect and any objective change in exercise tolerance. Drug therapy and cardiac transplantation take weeks or months to improve exercise tolerance. The delay in improvement in symptoms and exercise tolerance after effective hemodynamic improvement with pharmacotherapy or even cardiac transplantation may be explained by the structural and metabolic changes in the skeletal muscle (23, 68). The peripheral skeletal muscle pathophysiology has become the weakest link in the chain of oxygen delivery and utilisation needed for physical activity and must be reversed for any objective improvement in exercise tolerance. These limiting changes are only reversed slowly by heart failure treatments, mainly by treatments that positively affect the peripheral abnormalities contributing to exercise intolerance, either directly or via the training adaptations in response to increased exercise training (68).

Resistance training in heart failure patients

As discussed, skeletal muscle alterations seen in patients with HF are considered an important determinant of exercise intolerance in CHF. Furthermore, as highlighted, the vast majority of patients with HF are frail or prefrail and low skeletal muscle mass and function predict outcomes. Resistance training (RT) is a primary exercise intervention to develop strength and stimulate muscle hypertrophy. Accordingly, for HF patients, resistance training may be an important strategy for preventing sarcopenia, maintaining and incrementing muscle mass, and enhancing exercise tolerance (69). However, despite well-described abnormalities of skeletal muscle structure and function in HF patients, traditionally, resistance training has been discouraged for fear of a further deterioration of left ventricular function and potential adverse LV remodelling due to the high afterload during lifting (69, 70). Nonetheless, resistance training has now made its way into current cardiac rehabilitation guidelines, including those directed towards patients with heart failure. Resistance training was first recommended in cardiac rehabilitation as a complement to aerobic exercise prescription, with due caution (71). The most recent guidelines published by the American Physical Therapy Association (APTA) on the management of heart failure patients strongly recommend the inclusion of resistance training for stable HFrEF (classes I-III) (72). The American College of Sports Medicine’s (ACSM) Guidelines for Exercise Testing and Prescription also advocate resistance training for heart failure patients (73).

Benefits of resistance training for HF patients

Numerous studies have analysed the beneficial effects and safety of resistance training in patients with HF. However, most of the data pertains to HFrEF and studies integrating RT into the exercise regime for HFpEF are limited. Therefore, discussion on the health benefits of RT relates mainly to patients with HFrEF unless specified otherwise. Various studies have demonstrated that RT results in improvements in exercise capacity (as measured by VO2 peak) (46, 69, 73), functional capacity (6-min walk distance) (70, 46, 69), and lower body and upper body muscular strength (70, 46, 69). Ten weeks of resistance training in older women resulted in a 43% increase in muscle strength compared to controls (70). Furthermore, there was a 299% increase in submaximal muscle endurance measured by the number of lifts at an intensity of 90% of the baseline 1-RM (70). Notably, muscle mass was unchanged, indicating that RT in HF improved skeletal muscle ultrastructural abnormalities and/or neuromuscular function rather than simply enhancing muscle mass (70).

As discussed in my book, Lifestyle Medicine: Lifestyle- and Age-Related Diseases and Healthy Ageing, Volume Two’, minimal levels of muscular strength, endurance and power are necessary to maintain functional independence throughout the lifespan. While lower body strength is vital for mobility and function, upper body strength is also essential for a range of Activities of Daily Living (ADLs), e.g., lifting objects, including lifting or pulling oneself up from the ground in the event of a fall, a common occurrence in individuals with chronic conditions and physical impairments. Falls in older people have been discussed in my book referred to above. As discussed, patients with HF have lower muscle mass and strength and thus, the performance of ADLs is lower in HF patients compared to age-matched non-HF controls and this decrease is related to both reduced aerobic capacity and muscle strength (69). Moreover, loss of muscle strength and power leads to reduced mobility and participation in recreational and social events and thus adversely impacts an individual’s health-related quality of life (HRQoL). Resistance training, through its effects on exercise and functional capacity, significantly improves HRQoL (46, 69, 73). Notably, some studies have reported that central hemodynamic response is comparable during resistance training and aerobic training (AT), and resistance training does not adversely affect left ventricular systolic function or remodelling (46). Furthermore, direct comparison does not reveal significant differences between RT and AT regarding exercise/functional capacity and cardiac structure and function (46, 69). Also, cardiorespiratory fitness (CRF) measured via VO2 peak did not statistically differ significantly between AT and RT; however, only four studies have directly compared AT to RT (69).

Furthermore, the findings related to VO2  peak in response to RT are not in accordance with the training principle of specificity, discussed under the principles of physical fitness training. The principle of specificity states that ‘training adaptations (both metabolic and mechanical) for an individual will occur specifically to the muscle groups trained, the intensity of the exercise, the metabolic demands of the exercise and/or specific movements and activities.’ As AT and RT differ significantly, including in terms of metabolic demands, it defies logic that RT and AT will produce ‘similar’ improvements in VO2. While RT substantially improves muscle strength and endurance, most studies have shown that RT does not markedly increase VO2 max (74). RT has been shown to evoke an improvement of VO2 max only when the subject’s initial VO2 max at the beginning of the training is lower than the average values of VO2 max for the corresponding age (74). There was a significant correlation between the initial VO2 max and RT-induced increase in VO2 max. RT may improve VO2 max when the initial relative VO2 max is lower than 25ml/kg/min for older subjects and lower than 40ml/kg/min for young subjects (74). The RT-induced increment in VO2 max may result from an enhancement in the muscle mass and the consequent increase in O2 consumption (74). Besides, increased muscle strength per se improves mobility. Therefore, RT can be expected to improve concurrently both muscular fitness and cardiorespiratory fitness (VO2 max) within a single mode of RT only when subjects have initial low fitness levels (74).

Therefore, after the initial improvement, for further improvement in VO2 max, aerobic exercise training will have to be incorporated into the exercise training program. This is supported by the findings that combined AT and RT results in greater improvements in exercise capacity (VO2 peak), muscle strength, HRQoL (46, 75, 76, 77), and mobility (6-min walk distance (46, 75, 77). Still, as RT does improve VO2 max initially in patients with low VO2 max, in patients with HFrEF who are unable or unwilling to participate in aerobic exercise training programs, RT alone helps achieve relevant benefits (46). A meta-analysis involving 240 patients aged 48-76 years with HFrEF examined the role of RT as a standalone therapy in patients with CHF. The study found that RT as a single intervention can increase muscle strength (1RM), aerobic capacity (VO2 peak) and quality of life (QoL) (78).

As highlighted, studies integrating RT into the exercise regime for HFpEF patients are rare. In a small RCT, a 3-month supervised combined endurance/resistance training in addition to the usual care resulted in significant improvements in exercise capacity (peak VO2), physical dimensions of quality of life (QoL), and diastolic function as assessed by echocardiography, when compared with controls (79). The study demonstrated that a short-term supervised combined exercise training program incorporating aerobic and resistance exercise programs is feasible, safe, and effective in patients with HFpEF. Nolte et al. examined the effects of combined endurance/resistance training over a longer period of 6 months in patients with diastolic dysfunction (DD) and overt HFpEF. The study concluded that a structured 6-month combined endurance and resistance exercise training program is feasible and adequately enhances exercise capacity and diastolic function in patients with DD and manifest HFpEF (80).

Another small RCT evaluated the effectiveness of super-circuit training (SCT, combined aerobic-resistance circuit training) versus continuous aerobic training (CAT) on cardiac mechanical function (using echocardiography) in post-MI patients with reduced left ventricular function (RLVF). Though both SCT and CAT produce beneficial effects, however, in comparison to aerobic training alone, SCT resulted in a greater improvement of the diastolic function, measured as E/e ratio, and an increase in the left ventricular ejection fraction (LVEF) compared with aerobic exercise training alone. Besides, improvement in the patient’s aerobic fitness and physical component of QoL was greater in the SCT group compared to the CAT group (81). However, given the small sample sizes of the above trials and the relatively younger age profile of the subjects, who were mostly free of complex disorders, these encouraging results need further investigation and confirmation by studies with large populations. A recent AHA/ACC scientific statement, based on a review of the currently available literature, demonstrated that supervised exercise training in patients with chronic HFpEF produced a similar or larger magnitude of improvement in exercise capacity compared to patients with HFrEF. In contrast, most pharmacological intervention trials for HFpEF so far have produced neutral primary outcomes. However, only studies integrating aerobic exercise training were included in the review and studies using other exercise forms, including resistance training, were excluded (82).

A recent AHA/ACC/HFSA Clinical Practice Guideline, based on a meta-analysis of RCTs, suggested that exercise training results in improvement in functional capacity, exercise duration, health-related QoL, and reduction in HF hospitalisation in patients with HFrEF as well as HFpEF. Besides, exercise training improved endothelial function, blunted catecholamine spillover, and increased peripheral oxygen extraction and peak oxygen consumption. In a disparate group of elderly patients hospitalised for acute decompensated HF, an early, individualised, progressive rehabilitation program integrating various physical-function domains (strength, balance, mobility and endurance) initiated during or early after hospitalisation for HF and continued after discharge led to greater improvement in physical function compared to usual care (83).

Prescription of resistance exercise

Resistance exercise prescription based on ‘FITT-VP’ factors has been discussed in my post ‘Weight Training Program Design for Optimum Health.’ However, when prescribing RT exercises in heart failure patients, there are slight variations in these FITT-VP factors, particularly intensity and type of resistance exercise. As discussed, under types of resistance training exercises, resistance training exercises can be classified according to many different criteria. In the context of heart failure patients, classification based on the type of muscle contractions is more relevant. Based on the type of muscle contraction, resistance exercises can be broadly divided into two types, viz. isometric or static and isotonic or dynamic resistance exercises. As discussed under cardiovascular responses to resistance training, isometric (static) resistance exercises result in a disproportionate increase in both systolic and diastolic blood pressure. This, associated with a modest increase in HR, results in a significant increase in rate pressure product (RPP), leading to a substantial increase in myocardial oxygen consumption. This is often a concern in clinical populations, especially patients with cardiovascular diseases. Therefore, dynamic resistance training exercises are the preferred exercise choice for patients with cardiovascular diseases. Hereafter, in the context of cardiac rehabilitation, the term resistance training will refer to dynamic resistance training unless specified otherwise.

Concerning RT, FITT-VP factors, exercise order, number of repetitions and sets performed, speed of movement, and the duration of rest periods between sets and exercises can be manipulated to optimise muscle adaptations. Of these, training intensity and volume are key components that directly affect muscular adaptations (84). In the context of resistance training, intensity (I~Intensity) refers to the amount of weight lifted during resistance training exercises. Exercise intensity, i.e., the magnitude of load or amount of weight lifted in a set, is widely considered one of the most important of these variables amongst the FITT-VP factors for exercise prescription for the rehabilitation of patients with cardiovascular disease as it affects both the effectiveness (drives adaptations) as well as medical safety of exercise training (85). Evidence suggests training load changes can affect the acute metabolic, hormonal, neural and cardiovascular responses to training (86).

However, what exercise intensity should be selected during resistance training in patients with various CVDs continues to be debated. As a result, recommendations for exercise intensity during dynamic resistance exercises in CVD patients vary markedly between countries/continents and/or institutions. A systematic review analysed 13 position stands (institutional guidelines) providing recommendations for resistance training in patients with cardiovascular disease. Consensus occurred only for the number of sets (one to three) and training frequency (two to three sessions per week). However, recommendations concerning other major training variables, including intensity, exercise order, rest interval between sets and exercises and the number and types of exercises, were quite divergent. Most glaring differences were evident in the exercise intensity, which ranged from 30% up to 80% of 1-RM (87).

Therefore, before discussing optimum exercise intensity for resistance training in HF patients, it will be helpful to consider the primary aim for including resistance training in cardiovascular rehabilitation programs. As highlighted, skeletal muscle abnormalities are common in HF patients. Furthermore, an increasing deconditioning of the skeletal muscle with a loss of muscle mass and function (sarcopenia) is commonly seen in elderly patients and patients with diabetes mellitus (88). As highlighted, HF, particularly HFpEF, is more commonly seen in older people. Similarly, diabetes and heart failure are closely related; while patients with diabetes are at an increased risk of developing heart failure, patients with heart failure are at a higher risk of developing diabetes (89). Proper resistance training can improve muscular strength even in old and very old people (88). Therefore, the main aim of including resistance training in patients with HF is, or at least should be, to optimise muscle mass and function (strength) (69, 90). Consequently, intensity prescriptions for resistance training must reflect the load necessary for these gains while maintaining a balance between optimum efficacy and medical safety.

As discussed under exercise prescription guidelines in my post ‘Weight Training Program Design for Optimum Health’, intensity is most often prescribed as a percentage of an individual’s one repetition maximum (1-RM) for a given exercise, but any RM or RM range may also be selected for prescribing intensity (e.g., 6-RM, 12-RM, 6-12-RM). The procedure for determination of 1-RM and RM range has been discussed under exercise prescription guidelines. However, it is necessary to note that the number of repetitions that can be completed at a given percentage of 1-RM varies extensively from person to person. Besides genetic factors, the number of repetitions completed also depends on factors such as mode of training (free weights vs. machines), area of the body trained (e.g., upper vs. lower), single vs. multi-joint exercises, and probably more (86). Furthermore, the recommended range for intensity and repetitions will vary widely depending on the component of muscular fitness (strength, hypertrophy, power, local muscular endurance) the individual wishes to pursue. Nevertheless, to improve general muscular fitness, a load in the range of 8-12 RM is effective (73).

Resistance exercise intensity (load/weight) for the development of various components of muscular fitness is typically prescribed based on what is known as the “repetition continuum”, which postulates that high-intensity training optimises increases in maximal strength, moderate-intensity training optimises increases in muscular hypertrophy, and low-intensity training optimises increases in local muscular endurance (86). However, newer research does not support some of the above assumptions. The training protocol for improvements in muscular strength will vary depending on the individual’s training status. For improving muscular strength, loads >60% of 1-RM are recommended. In untrained individuals, a wide spectrum of training intensities (40% to 85% of 1-RM) will improve strength, with maximal gains seen at a mean training intensity of 60% of 1-RM, or 8-12 RM range. However, as one progresses to advanced training, for improvement of maximal strength (1-RM), higher training intensity (80% to 100% of 1-RM) and wider RM range (1-12 RM) is necessitated, with maximal gains in strength occurring at a mean training intensity of 80% of 1-RM and RM range of 1-6 RM (73). Notably, research suggests a dose-response relationship between load and strength gains. Though heavy load training is clearly required for optimising 1RM, marked improvements in strength are routinely observed with low loads (> 20 repetitions per set). Even resistance-trained individuals demonstrate improvements in strength when training with very light loads, although to a lesser extent than heavy loads (86). Training in the “strength zone” as per the RM continuum (1 to 5 repetitions per set) maximises gains in strength as training in this zone enhances neuromuscular adaptations that facilitate force production (86). Compared to long-term low-intensity (at ~30% of 1-RM) resistance training, long-term high-intensity (at ~80% of 1-RM) resistance training leads to greater neural adaptations, as evidenced by higher increases in percentage voluntary activation and electromyographic amplitude during maximal force production. This may explain the different increases in muscle strength despite similar muscle hypertrophy following high-intensity versus low-intensity resistance training (90).

For enhancement of muscular hypertrophy (i.e., attempting to increase or preserve muscle mass), a much wider range of training intensities than those required for muscular strength is effective. In accordance with the previous research, loads > 60% of 1RM were needed to stimulate hypertrophy, with a load of 70%-80% of 1-RM or 8-12 RM range, commonly known as the ‘hypertrophy zone’ on the RM continuum, considered optimal (73). However, newer research into low-load training has demonstrated that lifting heavy loads is not the only driver of muscle hypertrophy (73, 86). Various studies have shown that training with low loads (30-60% of 1RM) produces similar muscle hypertrophy to training with moderate and high loads (> 60% of 1RM) when training is performed to volitional fatigue/failure (73, 84). In other words, irrespective of the training load, performing RT sets to volitional failure will result in hypertrophy, even with loads as little as 30% of 1-RM (73). Nevertheless, ~30% of 1-RM appears to be the minimum threshold for loading and below this, hypertrophic gains are compromised (86). Hence, muscle hypertrophy can be achieved across a wide range of light and heavy loads, with a repetition range of 6-20 RM as the most useful. However, for achieving muscle hypertrophy in low-load training, a high level of effort (training to volitional fatigue/failure) is necessary to stimulate the highest threshold motor units (type IIb motor units, which have high activation threshold, innervate the most muscle fibres, and generate the greatest force during contraction) (86). However, exercising to volitional fatigue at all times is not necessary to produce significant muscle hypertrophy, especially when training with high loads. Evidence suggests that considerable muscle hypertrophy occurs when the bulk of training sets, with moderate to high loads, are performed with ~3-4 repetitions in reserve (84). However, if RT is not performed to volitional fatigue, a minimum RT intensity threshold (> 60% of 1 RM) is necessary to optimise muscle hypertrophy (84). In older individuals as well, light load training seems to be at least as effective as heavier load training, if not more, for inducing muscle hypertrophy (86). Though it appears from the above discussion that the theory proposed in the repetition continuum does not necessarily hold true for muscle hypertrophy, training with low loads tends to produce more discomfort, displeasure, and a higher rating of perceived exertion compared to training with moderate-to-high loads. Thus, from a practical point of view, training with moderate loads is likely to be more pleasurable, thereby enhancing long-term adherence (86).

Another important training variable which influences muscle hypertrophy, with an established linear dose-response relationship, is RT volume (number of sets X number of repetitions) (84, 86). Greater RT volume (28-30 sets/muscle/week) results in greater muscle hypertrophy than lower volume (6-10 sets/muscle/week) in both trained and untrained individuals (84). However, it has been suggested that volume load (volume X load lifted [i.e., intensity]) is the main driver of exercise-induced muscle hypertrophy (84, 86). On a set-equated basis, lower-load sets would naturally result in higher volume loads than heavier-load sets due to the higher number of repetitions performed, thus influencing outcomes.

Resistance exercise training prescription for patients with heart failure

As discussed above, even very low-intensity resistance training can improve muscle mass, provided the exercise is performed to volitional muscle failure. Furthermore, though high-load training is requisite for maximising gains in strength, significant improvement in strength is seen even with low loads. However, as discussed, in the past, there was a reluctance to integrate RT in cardiac and HF populations, mainly due to the concern over the increased pressure-load and resultant altered hemodynamics associated with lifting, which was speculated would be greater with higher loads/intensities (69). Nevertheless, an assessment of the effect of resistance exercises performed at different intensities on blood pressure response, heart rate and cardiac output in patients with CVDs shows that the number of repetitions (volume of training) and the duration of the exercise are more important than the intensity (46, 88, 91). Various studies have demonstrated that low-intensity resistance training, with more repetitions (i.e., higher training volume), results in a more pronounced increase in blood pressure, cardiac output and heart rate (69, 88, 90). This is because, due to the lower number of repetitions that can be performed with high-intensity training, the time duration of a high-intensity session is shorter in comparison to a low-intensity session, thereby preventing a full cardiovascular response compared to a longer, lower-intensity RT session (69, 90). In other words, performing high-intensity resistance training with heavier loads but fewer repetitions results in lower cardiovascular stress than with lighter loads with more repetitions (92). Performing low-intensity resistance training with a higher number of repetitions seems to promote acute increases in sympathetic ANS activity, which may be related to cardiovascular stress. In contrast, high-intensity resistance training with fewer repetitions does not significantly impact autonomic modulation compared to a control session (92). Furthermore, the rest interval between exercise sets should be more than 1 minute to allow for greater recovery of the hemodynamic responses (91).

As a result of these varied physiological and neurological changes, which are promoted best during high-intensity, low repetition RT, dynamic resistance training performed at higher intensities (at >70% of 1-RM) should therefore be considered in cardiac rehabilitation (90). Regarding RM, sets of <10 repetitions of high intensity should be preferred to high repetitions with low intensity (91). Additionally, training to failure with low loads tends to produce high levels of lactic acid in the muscles, which tends to cause discomfort and a higher rating of perceived exertion than training with moderate-to-high loads with low repetitions. Thus, from a practical standpoint, training with moderate to heavy loads is likely to be more enjoyable, which may lead to long-term adherence (86). As highlighted, the majority of patients with heart failure are frail or pre-frail. Besides, most of the patients joining cardiac rehabilitation programs have little or no experience in resistance exercise training and/or the use of the equipment (88). Therefore, a familiarisation process at low intensity (< 30% of 1-RM) is essential as this provides the opportunity to learn and practice proper lifting techniques without compensatory movements and breath-holding. The significance of the Valsalva manoeuvre and proper breathing technique has been discussed under cardiovascular responses to resistance training.

As highlighted, the Valsalva manoeuvre accompanying straining muscular efforts, common during heavy resistance training exercises, is generally of a duration insufficient to lower BP and a consequent rebound increase in BP. Besides, as recommended, exhaling slowly during lifting movement (concentric phase) can reduce the BP response by as much as 40% to 50%. Various guidelines for resistance training recommend starting resistance exercise with 30-50% of 1-RM, and based on the concept of Progressive Resistance Exercise, discussed under resistance exercise prescription guidelines based on FITT-VP factors, intensity should be increased up to 60% of 1-RM and further up to 70-80% of 1RM in selected patients (46, 72, 73, 88). These Guidelines only provide corridors within which resistance exercise training is safe and effective, and it is up to the cardiac rehabilitation professional to decide the optimal training intensity for individual patients (46, 88). However, as a helpful, practical guideline for optimum load selection, the load should never exceed the extent that the patient can lift without compensatory movements and/or breath holding (46).

Although most guidelines recommend intensity based on a percentage of 1-RM, testing for 1-RM loads may not be clinically feasible in many patients (72, 93). The procedure for testing 1-RM and the drawbacks of this method for prescribing training intensity have been discussed in my post, ‘Weight Training Program Design for Optimum Health.’ Alternatively, resistance exercise training intensity can be prescribed based on the RM range, as discussed under exercise prescription guidelines in the above post.

Other variables of exercise prescription viz frequency, time, and type will be broadly similar to the resistance exercise prescription guidelines discussed in the above post.

Safety of resistance training in patients with CVD

As discussed under cardiovascular responses to dynamic resistance exercise, excessive BP elevations have been documented only with high-intensity resistance training in the range of 80% to 100% of 1-RM performed to exhaustion and such elevations are generally not seen with low- to moderate-intensity resistance training performed with correct breathing technique and avoidance of the Valsalva manoeuvre (70). Research has documented that intra-arterial blood pressure during resistance training at an intensity range of 40-60% of 1-RM in cardiac patients remains within a clinically tolerable range (94). As discussed under cardiovascular responses to resistance training, heart rate increases modestly during resistance exercise to volitional fatigue. As a result, RPP, an indirect measure of myocardial oxygen consumption, does not reach extremely high levels during resistance training, as recommended above (95). Notably, data suggests that trained bodybuilders had a lower RPP than novice lifters or sedentary controls (95).

Furthermore, as highlighted under cardiovascular responses to resistance training, low-intensity resistance exercise, performed to volitional failure, results in a higher volume of work and produces higher heart rates than a single repetition with a 1-RM load. Accordingly, RPP will be higher during low-intensity resistance training with more repetitions than high loads with fewer repetitions, leading to greater cardiovascular stress. Importantly, there is indirect evidence that, compared to aerobic exercise, resistance training produces a more favourable balance in myocardial oxygen supply and demand due to lower HR and higher myocardial (diastolic) perfusion pressure (70, 95). Notably, compared to aerobic exercise, resistance exercise elicits less strain on the cardiorespiratory system (72).

Featherstone et al. compared the physiological responses to maximal repetition, dynamic resistance training exercises performed at various intensities, with maximal aerobic exercise on a treadmill. Twelve stable, aerobically trained patients with coronary artery disease performed both a maximal aerobic exercise on a treadmill and maximal repetition (to fatigue) resistance exercise at intensities of 40%, 60%, 80% and 100% of maximal voluntary contraction (1-RM). Heart rates achieved during resistance training were significantly lower (74 to 92 beats/min) than those achieved during aerobic exercise (157 beats/min). Although systolic blood pressures were similar during both forms of exercise, diastolic blood pressures were higher during all lifts (range 93 to 117 mm Hg) than with aerobic exercise (79 mm Hg). Due to considerably higher heart rate during aerobic exercise and similar systolic blood pressure during both forms of exercise, the peak rate pressure product was greater with aerobic exercise than with all lifts, thereby suggesting lower myocardial oxygen demand during dynamic resistance training compared with aerobic exercise. Furthermore, higher diastolic blood pressures seen during resistance exercises suggest a possible benefit from increased myocardial perfusion pressure. Besides, the ratio of the diastolic pressure-time index to rate pressure product, an indirect estimate of the balance between myocardial oxygen supply and demand, was higher for all lifts than for aerobic exercise. Therefore, estimated myocardial oxygen supply-to-demand balance appears more favourable with maximal repetition resistance training than with maximal treadmill exercise. Most importantly, while 5 of 12 (41.6%) patients developed ST-segment depression (>1 mm) during maximal treadmill exercise, no symptoms or electrocardiographic evidence of ischemia occurred during maximal repetition resistance exercises (96).

The study suggested that there is a hemodynamic basis for including dynamic resistance exercise training in the rehabilitation of selected cardiac patients, even at high intensities and with maximal repetitions, as such resistance training may maintain an appropriate myocardial oxygen supply-to-demand ratio. Therefore, resistance exercise training, including maximal repetitions at high intensity, appears to be a safe activity if supervised correctly in a selected group of cardiac patients (96).

A recent systematic review and meta-analysis found that resistance training in HF patients is safe and effective. No serious events related to resistance exercise training were reported during RT exercise sessions in the HF population (69). Another recent review with particular emphasis on old age, frailty and physical limitations showed that RT is feasible, safe and effective in patients with CAD and HF. None of the available studies reported serious adverse effects related to RT in cardiac patients (46).

Contraindications to resistance training in patients with CVDs

Absolute contraindications

Unstable angina (70, 94), decompensated HF (70, 94), uncontrolled arrhythmias (70, 94), severe pulmonary hypertension (mean pulmonary arterial pressure >55 mm Hg), severe and symptomatic aortic stenosis, acute myocarditis, endocarditis or pericarditis, uncontrolled hypertension (>180/110 mm Hg), aortic dissection, Marfan syndrome (70), severe stenotic or regurgitant valvular disease, hypertrophic cardiomyopathy (94), high-intensity RT (80% to 100% of 1-RM) in patients with active proliferative retinopathy or moderate or worse nonproliferative diabetic retinopathy (70).

Relative Contraindications (clearance from physician required before participation)

Major risk factors for CHD, diabetes at any age (70), uncontrolled hypertension (>160/>100mm Hg) (70, 94), low functional capacity (<4 METs), musculoskeletal limitations, individuals who have implanted pacemakers or defibrillators (70).

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