Exercise training as therapy for chronic heart failure

Background

More than 14 million Europeans suffer from heart failure (HF). Despite significant improvements in the treatment of HF, morbidity and mortality remain unacceptably high [1]. In addition, the costs for HF care approach 2% of the healthcare expenditure in Western Europe. One of the hallmarks of HF is severe exercise intolerance with pronounced fatigue and dyspnoea, even at low workloads, resulting in a markedly decreased quality of life. However, the severity of exercise limitation in HF is not correlated to the extent of cardiac dysfunction alone. Peripheral disturbances such as impaired vasoreactivity, impaired skeletal muscle energy metabolism and functional iron deficiency are as important as cardiac function to determine exercise capacity [2].

Because exercise training tackles both central and peripheral disturbances, it is an attractive therapy from a pathophysiological point of view. Indeed, 25 years of research have demonstrated the numerous physiologic, musculoskeletal and psychosocial benefits of exercise training. These benefits are clinically translated into improved exercise capacity, improved quality of life and improved outcome in patients with HF. This article provides general information on the clinical evidence of exercise training in HF and includes practical advice on how to prescribe exercise to HF patients.

Benefits of exercise training

In contrast to the former belief, exercise training in HF patients has proven to be safe and has no adverse effect on left ventricular remodelling [3].

Exercise capacity and quality of life

With regard to benefit on exercise capacity, a meta-analysis of 29 randomised controlled trials (RCT) including 848 patients revealed a mean improvement of VO2peak of 2.16 ml/kg/min [4].  Although modest in absolute terms, this means an increase of 13% which translates into a considerably better quality of life [5]. VO2peak is a strong and independent prognosticator in HF, and even small changes in VO2peak are associated with significantly improved outcomes [6]. In addition to VO2peak, exercise training has positive effects on health-related quality of life. A meta-analysis of 13 RCT demonstrated that exercise training results in a clinically important improvement in the Minnesota Living with Heart Failure Questionnaire (MLWHFQ) (mean difference: -5.8 points) [3].  

Hospitalisations and mortality

The HF-ACTION trial randomised 2,331 patients (median age 59 yrs, 27-30% women) suffering from HF with reduced ejection fraction (HFrEF) either to three months of supervised aerobic exercise training at moderate intensity (three days/week, exercise capacity at 60-70% of heart rate reserve) or to usual care [7]. This study showed in an intention-to-treat analysis that exercise training was associated with an 11% lower adjusted risk for all-cause mortality or all-cause hospitalisation and a 15% lower adjusted risk for cardiovascular mortality or HF hospitalisation.

The most recent Cochrane review of exercise training included 33 trials with 4,740 patients with HF (mainly HFrEF) with the HF-ACTION trial contributing approximately 50% [3]. There was a trend towards a reduction in mortality with exercise in trials with >1 year of follow-up. Exercise training, when compared to usual care alone, reduced the rate of overall (25%) and HF-specific hospitalisation (39%).

Indications and contraindications

The 2016 European Society of Cardiology heart failure guidelines [8] firmly recommend that:

• Regular aerobic exercise is encouraged in patients with HF to improve functional capacity and symptoms (Class I indication, level of evidence A); and
• Regular aerobic exercise is encouraged in patients with HF to reduce the risk of HF hospitalisation (Class I indication, level of evidence A).

Contraindications for participation in an exercise training programme are listed in Table 1 [9].

Table 1. Contraindications for exercise training in HF.

Exercise prescription

• It is mandatory that (sub)maximal exercise capacity is measured with a symptom-limited cardiopulmonary exercise test (CPET). A CPET will give information on the degree of cardiac impairment and will objectively measure VO2peak and other prognostic factors (VE/VCO2slope, oscillatory ventilation). Based on the results of CPET, one can
  • Determine training intensity and perform training adjustments
  • Determine risk and prognosis
  • Re-test after exercise training programme to objectify improvement in exercise capacity
• A universal agreement on the best training modality in heart failure does not exist. Rather, an individualised approach is recommended, based on clinical evaluation and personal preferences. Training protocols vary in a number of ways: intensity (aerobic and anaerobic), type (endurance, resistance) and method (continuous and interval).
  • Continuous endurance training is the best described form of exercise training and, because of its well-demonstrated efficacy and safety, is highly recommended in the guidelines. It is characterised by a moderate-to-high exercise intensity at steady-state condition of aerobic energetic yield, allowing the patient to perform prolonged training sessions (45-60 min duration). The exercise is usually performed on a bicycle or treadmill.
  • Interval training is characterised by short bouts (10-30 sec) of moderate-to-high intensity (50-100% VO2peak), with a recovery phase performed at low or no workload. High intensity interval training (HIIT) was studied in the SMARTEX trial [10]. In this study, patients performed 4x4 min bouts of high-intensity exercise (90-95% VO2peak), interspersed with 4 min recovery periods at low intensity. The authors showed that HIIT was not superior to moderate continuous training in changing aerobic capacity or left ventricular remodelling. As such, HIIT is a valuable option in selected HFrEF patients.
  • Resistance/strength training has been proposed to prevent the wasting syndrome and to incorporate upper body exercise, which is important to complete daily life tasks. It is important to prescribe dynamic resistive exercise training of small muscle groups and to avoid Valsalva manoeuvres.
• Setting: it is recommended to initiate exercise training in a structured, supervised, centre-based programme. This can be either in-hospital or in a specialised private facility, as long as close supervision and direct monitoring of heart rate and blood pressure are available, especially when HF symptoms are severe. Most centre-based programmes offer an eight to 12-week training programme. Thereafter, a gradual transition to a home-based programme - with or without telemonitoring tools - is encouraged, stimulating the patient to remain active for a longer time period and to adhere to the exercise training.
• To increase long-term adherence to exercise training, the patient’s preferences should be taken into account [11].

The main characteristics of the most frequently applied training schemes in HF are shown in Table 2.

Table 2. Main characteristics of the most frequently applied training schemes in HF.

Patients with ICD and CRT devices

Special heart failure populations

The potential benefits of exercise training after ICD implantation include acquaintance with device settings, instruction about physical activity (including arm movements), psychological support and improvement of exercise capacity. One single-centre study showed that exercise training on top of CRT doubled the improvement in exercise capacity and further improved haemodynamic measures and quality of life [12].

ICD and CRT-D patients should start exercise training under medical supervision and monitoring of heart rate. Exercise level and ICD programming should be adapted to keep the maximal heart rate 20 beats below the ICD intervention zone. The following patient information should be readily available to reduce the risk of incidents: 1) underlying heart disease and indication of ICD implantation; 2) triggers for arrhythmia (e.g., ischaemia) and the arrhythmic substrate; 3) the ICD intervention heart rate; 4) the tachy-therapy that will be delivered.

Heart failure with preserved ejection fraction (HFpEF)

So far, only small single-centre trials have been performed in which exercise training has been evaluated as treatment for HFpEF. From a recent meta-analysis of eight intervention trials of exercise training in HFpEF [13], we learn that endurance training, either alone or in combination with strength training, has several benefits, including improvements in exercise capacity, as measured objectively by VO2peak [14], quality of life [15] and diastolic dysfunction [16].  

Women

It is worrying that women with HF are severely underrepresented in exercise intervention trials. Only four RCT (a total of 84 women), with the most recent study dating from 2005 [17], have specifically studied the efficacy of exercise training on health-related outcomes in women. Despite the low sample, and the single-centre design of these trials, the data indicate that aerobic exercise training and strength training significantly improve VO2peak, health-related quality of life and muscle strength, similarly to men. When it comes to hard endpoints, the sub-analysis of the HF-ACTION trial - stratified according to sex - is of particular interest [18]. Aerobic training was associated with a 26% reduction in the combined endpoint in women (n=290 in exercise group), whereas there was no decrease in men (n=682 in exercise group).

This subanalysis provides proof of concept that women, although they achieved lower VO2peak at baseline and their training adherence was lower compared to men, may benefit even more from exercise training than men with regard to outcome.

Future directions

A joint effort from clinicians and researchers should be made to achieve the following goals in the future:

• Aim to enhance long-term maintenance of exercise training for HF, e.g., by home-based cardiac rehabilitation and telemonitoring-assisted programmes.
• Aim to improve adherence to exercise training, e.g., by defining causes for non-adherence, development of motivational tools, design of personalised training programmes.
• Aim to “fit” the training programme to the patient’s phenotype, with patient variables including age, gender, comorbidities, type of HF. Ideally, a biomarker that would distinguish responders from non-responders to exercise training could guide in this personalised approach.
• Aim to increase dissemination of efficacy of exercise training in HF to cardiologists, physiotherapists, regulatory organisations and patients. According to the ExtraHF survey, non-implementation of an exercise training programme was, in 20% of the centres, due to scientific underestimation of the utility and safety of exercise training [19].

Conclusions

• Exercise training is an evidence-based adjunct treatment modality for patients with heart failure.
• The benefits of exercise training entail both central and peripheral adaptations and are clinically translated into anti-remodelling effects, increased exercise capacity and reduced morbidity and mortality.
• Cardiopulmonary exercise testing is mandatory to objectify exercise capacity objectively and to define training intensity.
• Ideally, a patient-tailored exercise training programme is prescribed instead of a “one size fits all” approach.
• Increasing long-term adherence and reaching the frailest patients are challenging goals for future initiatives in the field.