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REVIEW ARTICLE
Ahead of print publication  

The therapeutic role of exercise training in heart failure patients: A narrative review


1 First Department of Cardiology, Hippokrateion General Hospital, National and Kapodistrian University of Athens, Athens, Greece
2 State Department of Cardiology, “Hippokration” Hospital, Athens, Greece
3 Pilates Studio, Athens, Greece
4 First Department of Cardiology, Hippokrateion General Hospital, National and Kapodistrian University of Athens; Pilates Studio, Athens, Greece

Date of Submission06-Aug-2022
Date of Acceptance25-Oct-2022
Date of Web Publication24-Nov-2022

Correspondence Address:
Konstantinos Athanasios Gatzoulis,
First Department of Cardiology, Hippokrateion General Hospital, National and Kapodistrian University of Athens, Athens
Greece
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/hm.hm_23_22

  Abstract 

Cardiac rehabilitation (CR) is a complex intervention that improves functional capacity and quality of life in patients with heart failure (HF). Besides exercise training (ET), CR includes aggressive risk factor management, education about medication adherence, stress management, and psychological support. Current guidelines strongly recommend CR as an integral part of chronic and stable HF patient care. However, CR programs are underused for multiple reasons, namely, low physician referral and patient adherence, high cost, and lack of awareness. In this review, we present existing evidence of the beneficial effects of ET and CR in HF with reduced and preserved ejection fraction, the underlying pathophysiologic mechanisms by which exercise might alleviate symptoms, and the different types of exercise that can be used in HF. Current guidelines supporting the use of CR, reasons for its underutilization, and home-based CR as an alternative or adjunct to traditional center-based programs are also described.

Keywords: Cardiac rehabilitation, exercise training, heart failure



How to cite this URL:
Laina A, Soulaidopoulos S, Doundoulakis I, Arsenos P, Kordalis A, Xydis P, Xintarakou A, Kalantzis C, Chrysohoou C, Dilaveris P, Archontakis S, Sotiropoulos H, Sideris S, Gatzouli LS, Tsioufis K, Gatzoulis KA. The therapeutic role of exercise training in heart failure patients: A narrative review. Heart Mind [Epub ahead of print] [cited 2023 Jan 31]. Available from: http://www.heartmindjournal.org/preprintarticle.asp?id=361949


  Introduction Top


Heart failure (HF) is a major global epidemic affecting more than 64 million people worldwide.[1] Prevalence is increasing with age and HF has become one of the leading causes of hospitalization in the Western world.[1],[2] Despite significant therapeutic advances, morbidity and mortality remain unacceptably high along with hospitalization rates, rendering HF a substantial burden for the health-care system.[3] One of the hallmarks of chronic HF is exercise intolerance associated with decreased quality of life (QoL) and increased mortality.[4] Accumulating evidence support a beneficial role of exercise training (ET) in HF, improving functional capacity and QoL when reducing HF hospitalization.[5],[6],[7] However, cardiac rehabilitation (CR) programs are underused for multiple reasons, among which are low physician referral and patient adherence, high cost, and lack of awareness. This review focuses on existing evidence of the beneficial role of CR on HF and underlying pathophysiologic mechanisms. We also present different types of exercise in HF and current guidelines supporting the use of CR and reasons for its underutilization.


  Recommendations of Cardiac Rehabilitation in Current Heart Failure Guidelines Top


CR has been now recognized as an integral part of chronic and stable HF patient care and thus has been given Class I recommendation from the European Society of Cardiology,[2] the American Heart Association,[8] and the American College of Cardiology.[8] Patients with more severe diseases, comorbidities, and frailty should be offered a supervised exercise-based CR program (Class IIa). Patients with HF, stable angina, myocardial infarction, revascularization, and symptomatic peripheral arterial disease are CR candidates. Furthermore, moderate-intensity CR is recommended among patients with atrial fibrillation.[9] However, exercise should only be initiated in a clinically stable patient after optimizing medical treatment, including device implantation when required. CR is feasible in the absence of acute decompensated HF, complex ventricular arrhythmia, severely reduced muscle mass or function, pulmonary disease, and overloaded volume status. CR indications and contraindications are presented in [Table 1].[10],[11]
Table 1: Indications and contraindications for cardiac rehabilitation program participation

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  Definition and Components of Cardiac Rehabilitation Top


CR is a complex intervention comprising several components. In addition to physical activity, it includes patient baseline evaluation, aggressive risk factor management (i.e., lipids, diabetes, hypertension, smoking cessation, and weight loss), education about medication adherence, stress management, and psychological support.[12],[13] Typically, a complete course of CR is considered attending ≥36 supervised sessions for around 12 weeks. Although exercise remains the cornerstone element, the purpose of a CR program is to provide a multifaceted approach aiming to holistically improve patients' well-being and QoL by optimizing physical, mental, and social functioning [Figure 1]. CR programs do not provide solely ET but have evolved from a simple patient monitoring system to a multidisciplinary, comprehensive, and long-term intervention.[14] A CR team necessitates the collaboration of many specialties, including a primary care physician, cardiologists, cardiac surgeons, nurses, physical therapists, dietitians, pharmacists and psychologists, or social workers who communicate with referring physicians, patients, and families.[12],[13]
Figure 1: Core components of cardiac rehabilitation program

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  Pathophysiological Effect of Exercise in Heart Failure Top


Physical inactivity is considered a major cardiovascular (CV) risk factor. ET is a critical component of HF therapy as it helps relieve symptoms, improve QoL, reduce disability, and increase patients' ability to perform daily activities independently. Furthermore, exercise improves left ventricular ejection fraction (LVEF), end-diastolic and systolic volumes, maximal heart rate, systolic blood pressure, and cardiac output.[15],[16] Skeletal muscle dysfunction has an important role in exercise intolerance in HF.[17],[18] Physical training acts beneficially on skeletal muscle abnormalities and oxidative metabolism, improving oxygen consumption and lactate threshold, thus delaying the onset of anaerobic metabolism in skeletal muscle of HF patients.[18] Moreover, ET has been shown to counteract the deleterious effects of persistent sympathetic hyperactivation that characterizes HF patients.[19] Evidence suggests that ET is associated with reduced sympathetic activity, increased parasympathetic tone as demonstrated by increased heart rate variability (HRV), and reduced levels of circulating neurohormones.[20],[21],[22],[23],[24] In specific, HRV, which is markedly reduced in HF and a predictor of poor prognosis, is improved through ET both in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).[25],[26] Exercise restores endothelial dysfunction, which is implicated in the pathogenesis of HF, promoting nitric oxide (NO) release, improving impaired endothelium-dependent vasodilation, increasing endothelial nitric-oxide synthase expression, reducing reactive oxygen species, and inducing antioxidant enzymes, thus preventing NO scavenging.[27],[28],[29] Data also suggest reduced inflammatory cytokine concentration and platelet-related inflammatory mediators associated with ET.[30],[31],[32]


  The Benefit of Exercise Training in Heart Failure with Reduced Ejection Fraction Top


HF-ACTION trial is to date the largest controlled clinical trial aimed to test the efficacy and safety of ET among HF patients. Overall, 2,331 patients with HFrEF were enrolled and randomized either to usual care plus supervised sessions of aerobic ET or usual care alone and followed for 30 months. Regular aerobic ET was very well tolerated, safe, and improved QoL; however, no significant reductions were observed regarding the primary endpoint of the study, which was a composite of all-cause mortality and hospitalization.[6] Only after adjustment for high prognostic risk factors, the overall mortality or readmission decreased by 11% and the peak oxygen uptake (VO2) increased by an average of 4% in the exercise group compared with controls. Subsequent meta-analyses confirmed the beneficial role of ET in HFrEF.[16],[33],[34] A meta-analysis of randomized controlled trials (RCTs) of ET in patients with chronic HF reported small but significant improvements in LVEF and left ventricular end-diastolic and end-systolic volumes along with improved peak VO2 following aerobic moderate-intensity continuous training (MICT).[16] Wisløff et al. extended these findings by demonstrating greater antiremodeling benefits with high-intensity interval training (HIIT) compared to MICT in postmyocardial infarction HFrEF patients.[35] ET was associated with increased LVEF in a meta-analysis of clinically stable HFrEF patients, with the greatest benefit derived after long-term training (>6 months). HIIT performed for 2–3 months was also associated with increased LVEF, but resistance training (RT) performed alone or combined with aerobic training (MICT and HIIT) did not significantly affect LVEF.[34] A 2019 Cochrane review of CR in HF of 44 RCTs and 5,783 patients showed that participation in CR was associated with reduced rates of all-cause and HF-specific hospitalization, improving health-related QoL, compared to no exercise controls.[33] However, no significant impact of CR on all-cause mortality was identified in a 12-month follow-up period.[33]


  The Benefit of Exercise Training in Heart Failure with Preserved Ejection Fraction Top


Although most studies carried out to investigate the role of exercise in HF predominantly included HFrEF patients, increasing evidence suggests that ET in patients with HFpEF also improves exercise performance and QoL, reducing hospital admission.[36] A recent study comparing ET in patients with HFrEF and HFpEF showed that a significantly higher peak VO2 level was achieved in patients with HFpEF.[37] Results, though, are not uniform; while some studies showed atrial reverse remodeling and improved LV diastolic function,[38] other studies failed to show differences in left ventricular function and in arterial stiffness among patients with HFpEF.[39],[40],[41]


  Acute Heart Failure Top


ET after an episode of acute HF is rather difficult, given the severely impaired exercise tolerance. However, a number of studies have evaluated the role of prompt ET initiation following acute decompensated HF, showing improved functional capacity and reduced hospitalization rates.[42],[43],[44],[45] A randomized study of 72 HFrEF patients showed that ET within 2 weeks after acute cardiogenic pulmonary edema improved exercise duration, peak VO2, and ventilatory threshold.[42] A retrospective analysis of patients hospitalized with acute HF across an 8-year period showed that acute-phase CR initiation is associated with lower in-hospital mortality, shorter hospital stay length, and a lower 30-day readmission rate.[45] Physical Rehabilitation for Older Patients Hospitalized for HF (REHAB-HF) trial sought to assess the efficacy of a tailored CR intervention program among older frail patients hospitalized for acute decompensated HF. Despite functional improvement, no benefit in readmission and mortality was detected compared with usual practice.[43] Further studies are needed to establish the most appropriate management with respect to CR in this population.


  Advanced Heart Failure Top


Limited data exist about the role of ET in patients with advanced HF. Erbs et al. randomly assigned patients with chronic HF at New York Heart Association (NYHA) IIIb to ET or sedentary lifestyle and followed for 12 weeks.[46] Peak Vo2 and LVEF improved, along with endothelial function as assessed by flow-mediated dilation (FMD) in the ET group. Exercise has also been proposed in HF patients with mechanical circulatory support. A position paper by the HF Association of the European Society of Cardiology provides guidance for the implementation of exercise in clinical practice based on limited but promising data about the safety and efficacy of early mobilization and ET in ventricular assist device (VAD) recipients.[47] Evidence from observational studies suggests functional capacity, pulmonary function, and QoL improvement in patients with either left VAD (LVAD) or biventricular assist device participating in ET programs.[48],[49],[50] The REHAB-VAD trial randomized patients with newly implanted LVADs in CR or usual care, demonstrating that moderate-intensity aerobic training was safe and improved functional capacity, treadmill time, and leg strength in patients with continuous-flow LVAD.[51] Results are awaited from the Exercise training in patients with left ventricular assist device (Ex-VAD) clinical trial, aiming to investigate the effect of a 12-week supervised ET program on peak VO2 and QoL in LVAD patients.[52] Favorable outcomes in long-term survival and rehospitalization have also been reported in observational studies from heart transplant recipients participating in exercise-based CR programs.[53],[54],[55]


  Implantable Cardiac Devices Top


Patients with implantable cardiac devices, either implantable cardiac defibrillator (ICD) or cardiac resynchronization therapy (CRT) devices (CRT defibrillators [CRT-D] or CRT pacemakers [CRT-P]), are a challenging population for exercise-based CR, mainly due to the risk of appropriate or inappropriate ICD shocks, following moderate-to-high-intensity exercise. There is evidence of improved cardiorespiratory fitness and a lower likelihood of ICD shocks among HF patients with ICD who participate in supervised CR programs.[56] Lower ventricular arrhythmia burden, reduced sympathetic activity, and improved cardiorespiratory fitness may account for the protective effect of ET against ICD shocks. Exercise-based CR has also been proven both safe and effective in patients after CRT implantation, improving exercise capacity and QoL regardless of the response to CRT.[57],[58],[59] Exercise tolerance as assessed by a 6-min walk test and depression improved significantly in patients following ET program after ICD or CRT implantation, in contrast to the nonactive group which experienced more hospital admissions in a follow-up period of 10.5 months.[60]

Important considerations should be taken into account when prescribing ET in HF patients with devices.[61] First, moderate-to-high-intensity exercise should be discouraged in case of lamin A/C mutations or arrhythmogenic cardiomyopathy due to risk of disease progression.[62],[63],[64] Second, the psychological impact of ICD shocks might be a reason for sports discontinuation. In a multinational ICD Sports Safety Registry, 30%–40% of those who experienced ICD shocks stopped sports participation.[65] A way to reduce shock occurrence is to program detection zones high enough to prevent inappropriate shocks due to supraventricular arrhythmia or sinus tachycardia. Third, ET should be avoided when loss of consciousness may cause harm either to the athlete or another.[61] Regarding CRT recipients, appropriate device programing should be made to avoid loss of biventricular pacing during exercise. Evidence suggests rate-adaptive atrioventricular delay or interventricular optimization during exercise yield additional hemodynamic benefit to that provided by resting optimization.[66],[67] However, most CRT studies have been conducted in resting conditions and data concerning optimal programing in exercise is limited. Finally, activities carrying the risk of lead dislodgement and fracture, i.e. by repetitive arm movements, should be avoided in the first week following device implantation, and sports activities associated with a risk of chest trauma should be avoided indefinitely.[61]


  Types of Training in Heart Failure Top


Currently, there are no clearly designed practical guidelines for exercise prescription in the setting of HF. Three different ET modalities have been proposed in different combinations: (a) aerobic or endurance ET (continuous and interval); (b) strength/RT; and (c) inspiratory muscle training (IMT).

Aerobic or endurance training

Aerobic exercise or endurance training (i.e., cycling, walking, jogging, swimming, and dancing) is recommended for stable HF patients (NYHA I-III).[14] A meta-analysis has shown a beneficial effect of aerobic ET on left ventricular remodeling, improving end-diastolic and systolic volumes and LVEF in clinically stable HF patients.[16] Furthermore, aerobic ET improves functional capacity, VO2 and modifies CV risk factors.[16] Moderate continuous exercise (MCE) is the most commonly evaluated exercise modality, as it is efficient, safe, and well tolerated. Of note, in NYHA III patients with significantly reduced pretraining peak VO2 and/or high exercise-related risks, exercise intensity should be maintained as low as 40% of peak VO2 during the first 2 weeks, followed by a gradual increase in 50%–70% peak VO2, and if tolerated, up to 85% VO2peak.[61],[68],[69]

Aerobic interval training was compared to moderate continuous training (MCT) in a population of postmyocardial infarction HFrEF patients, resulting in increased peak VO2 and LVEF, reduced circulating levels of natriuretic peptides, and improved endothelial function as assessed by FMD.[35]

Recently, HIIT has emerged as an alternative exercise mode for HF patients. A meta-analysis demonstrated that HIIT resulted in peak VO2 improvement compared to MCE in HFrEF patients, without any differences observed in the minute ventilation − carbon dioxide production (VE/VCO2) slope and QoL.[70] HIIT in Patients with HFrEF study (SMARTEX) randomly assigned 261 HFrEF patients to HIIT or MCT and followed for 52 weeks.[71] HIIT was not superior to MCT in terms of exercise capacity and left ventricular remodeling and interestingly 51% of HIIT patients exercised below prescribed heart rate, and 80% of MCT exercised above their target.[71]

Resistance training

Until recently, RT was not recommended for HF patients under the notion of increasing afterload and accelerating adverse ventricular remodeling. At present, accumulated evidence suggests favorable outcomes of RT on CV health, reducing CV mortality, preventing obesity, improving insulin resistance, and reducing blood pressure.[72],[73],[74],[75],[76] Standard ET protocols usually involve a combination of aerobic and RT, that significantly improves exercise capacity, muscle strength, pulmonary function, and QoL in HF patients.[77],[78],[79] There are limited data to suggest RT as a standalone therapy in HF. A large meta-analysis showed no benefit of combined endurance/RT in left ventricular remodeling.[16] However, a more recent meta-analysis including 240 participants with HFrEF unable to participate in aerobic training evaluated RT as a single intervention, showing increased muscle strength, aerobic capacity, and QoL.[80] Resistance ET may complement, but not substitute aerobic ET, and could serve as an alternative approach for those unable to participate in aerobic training, in advanced HF or patients with very low exercise tolerance. Certain individuals such as older adults and women who are more likely to suffer from sarcopenia, thus needing muscle and bone mass increase, may benefit from RT as well.[81],[82]

Inspiratory muscle training

Patients with advanced HF suffer from muscle weakness and may benefit from IMT. This is a promising intervention that attenuates inspiratory muscle weakness and has been considered an adjunctive treatment to exercise and pharmacologic interventions in HF. However, IMT is underused in daily clinical practice, as there are limited data about its benefit. The addition of IMT to aerobic training or combined aerobic/resistance/inspiratory training has been studied in small HF population, showing improvement in inspiratory muscle performance, VO2peak, and functional status.[83],[84] A meta-analysis of 9 RCTs comparing IMT with sham or control subjects showed improvements in 6-min walk distance, peak VO2, and minute ventilation in HF patients.[85]


  Pilates Training in Heart Failure Top


Scarce data exist regarding the role of Pilates training in HF. This form of mind-body exercise has become a popular trend in rehabilitation and fitness programs aiming to improve flexibility, core strength, posture, and coordination of breathing with movement.[86],[87] Patients with NYHA I and II HF were randomized to a conventional exercise program or Pilates training.[88] A cardiopulmonary exercise test (CPET) performed 2 days after training revealed improved functional capacity in the Pilates group as assessed by improved peak VO2, tolerance during the CPET, and reduced diastolic blood pressure.[88] The role of other mind-body interventions (Tai Chi, yoga, and meditation) has been studied in HF, yielding encouraging results.[89],[90],[91],[92] A systematic review of RCTs (n = 1,314 participants) reported small-to-moderate improvements in QoL, exercise capacity, stress management, blood pressure, heart rate, HRV, and B-type natriuretic peptide levels.[93]


  Effect of Exercise Training on Mental Health Top


Depression and anxiety are most commonly reported among HF patients, 2–3 times higher than in the general population, increasing the risk of poor cardiac outcomes.[94],[95] Psychological issues are not adequately addressed though when it comes to the therapeutic management of HF. Participants from the ENHANCED trial underwent specific psychometric tests 12 months following participation in a CR program. Interestingly, greater physical activity levels were associated with less depressive and anxious symptoms.[96] Along this line, HF-ACTION indicated that exercise resulted in a modest reduction in depressive symptoms.[6] The demonstrable benefit of ET on alleviating depression symptoms in clinically stable HF patients was shown in a meta-analysis including over 3,000 participants.[97] Depression and anxiety have been associated with increased sympathetic activity, autonomic dysfunction with reduced HRV, inflammation, and endothelial dysfunction, each of which is linked with adverse prognosis in HF, and is significantly improved through exercise-based CR.[98],[99] Pharmacotherapy, on the other hand, is a key factor in depression and anxiety management; however, HF patients should be carefully monitored for adverse drug reactions. Cases of electrolyte abnormalities, reduced cardiac conduction and output, arrhythmias, and sudden cardiac death (SCD) have been reported with coadministration of antidepressants and HF medications.[100] In particular, the increased SCD risk among HF patients with concurrent psychiatric conditions could be effectively addressed with other modern nonpharmacological invasive cardiac electrophysiology diagnostic and therapeutic procedures.[101]


  Cardiac Rehabilitation Underutilization Top


Despite the clear benefits of CR and current guideline recommendations, participation rates remain low.[102],[103] Low patient referral, lack of accessibility to program sites, lack of insurance coverage, and low patient adherence are some major factors accounting for low CR enrollment rates. Interestingly, only around 20% of eligible patients participate in CR and among participants, completion rates remain suboptimal.[104] Of note, women, older adults, those living outside of urban areas, minorities, lower socioeconomic status individuals, and the uninsured are less likely to participate in CR compared to white male patients.[105],[106] For example, women are 36% less likely to be referred to participate in a CR program and less likely to complete the program compared to men.[107] Along this line, Black, Hispanic, and Asian patients were 20%, 36%, and 50% less likely, respectively, to receive CR referrals compared to white patients.[108] There are also differences in referral rates among countries, probably attributed to distinct healthcare policies and delivery systems.[109] Patients in low- and middle-income countries are even less likely to access CR than those in high-income countries.[110]

Effective strategies to mitigate CR underuse and increase participation are needed. Home-based CR (HBCR) programs have been increasingly introduced to widen access in CR.[111] Especially in the current COVID-19 pandemic era, HBCR is an alternative solution, where virtual meetings and digital education become more frequent in order to avoid crowding and travel limitations. HBCR relies on remote coaching with indirect exercise supervision and can be carried out at home or in other nonclinical settings such as community centers, health clubs, and parks. This alternative could help improve the delivery of CR services by overcoming barriers that hinder patients' participation in center-based CR (CBCR), including transportation costs, competing time demands, and the lack of a center near a patient's home.[112] Evidence suggests that short-term improvements in functional capacity, QoL, and CV risk factor control are similar in HBCR and CBCR.[111],[113] Moreover, recent evidence suggests that the combination of HBCR with CBCR might be superior in participant adherence.[112] Hybrid models of a combination of CBCR and HBCR could prove more attractive and effective.[114] However, data on the impact of HBCR on clinical events are lacking, as safety data for high-risk patients. The majority of HBCR studies included a low-to-moderate CV risk population. Notably, the cost of HBCR is not covered, while CBCR services are reimbursed by third-party payers, at least in the USA. There is evidence supporting the cost-effective benefit of CR, especially with exercise as a component.[115],[116] However, variability among CR programs and service delivery along with heterogeneity concerning exercise dose, session frequency, and type of exercise limit study comparability and therefore future research is further needed to determine the most cost-effective design of CR.[115],[116]


  Gaps in Evidence Top


Limited data exist regarding the efficacy and optimal implementation of exercise-based CR in the following specific populations: in older and frail HF patients, in patients with implantable devices, in acute HF, in HFpEF or patients with multiple comorbidities, and in patients who have undergone heart transplantation or valve replacement surgery. Moreover, data on the long-term effect of HBCR programs or combined CBCR with HBCR on clinical events are lacking; thus, large RCTs are needed. As previously mentioned, both referral and participation rates in CR programs remain poor, raising medical awareness through campaigns and medical conferences presenting alternative and cost-effective CR models may help increase participation rates in general and specifically among women, older adults, minorities, and low-and middle-income countries.


  Conclusion Top


In patients with stable HF, ET can relieve symptoms, improve exercise capacity and QoL, and reduce disability, hospitalization, and mortality. CR is beneficial in HF and is recommended as a Class IA indication in current guidelines. Aerobic ET is recommended for stable HF patients and MCE is the most commonly evaluated exercise modality, as it is efficient, safe, and well tolerated. However, despite strong and consistent recommendations, CR is underused. Motivation for participation in CR programs should be provided to every HF patient before discharge. HBCR and telemonitoring-assisted programs are an alternative to CBCR. Health-care givers should pay attention in incorporating ET as an integral part of HF therapeutic approach. Drug administration is of paramount importance in HF but not enough. Regular physical activity, smoking cessation, weight control, healthy diet, hypertension, diabetes, and hyperlipidemia management are important aspects to be considered and could be achieved through exercise-based CR programs.

Ethical statement

Ethical statement is not applicable for this article.

Financial support and sponsorship

Nil.

Conflicts of interest

Prof. Konstantinos Athanasios Gatzoulis is an Editorial Board Member of Heart and Mind. The article was subject to the journal's standard procedures, with peer review handled independently of Prof. Konstantinos Athanasios Gatzoulis and their research groups. There are no conflicts of interest.



 
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