45 Cardiac rehabilitation and chronic heart failure

All patients with established chronic heart failure (CHF), with or without an implantable cardioverter defibrillator (ICD) and with or without cardiac resynchronization therapy (CRT), require a multifactorial cardiac rehabilitation (CR) approach. The role of the multidisciplinary approach is considered elsewhere (see Chapter 54).

The traditional model of care delivery is thought to contribute to frequent hospitalizations. During these brief episodic encounters, little attention is paid to the numerous barriers to effective CHF treatment and the possible treatment of the common modifiable factors that are the cause of disease progression and thus hospital readmissions. To face these limitations, a CHF disease multidimensional management programme is necessary to curb the rising cost of management and to improve morbidity and mortality for individual patients.¹

CR is the ideal comprehensive structured disease intervention since it best addresses the complex interplay of medical, psychological, and behavioural factors facing CHF patients. It is a co-ordinated multidimensional intervention designed to stabilize or slow disease progression, alleviate symptoms, improve exercise tolerance, and enhance quality of life, thereby reducing morbidity and mortality.² In CHF populations, such a programme has been proven to improve functional capacity, recovery and emotional well-being and to reduce hospital admissions in CHF patients.

Exercise training as a key component in a CR programme may improve survival and reduce hospitalization in stable heart failure (HF) patients. It is recommended for all stable CHF patients. There is no evidence that it should be limited to any particular HF patient subgroup based on aetiology, NYHA class, left ventricular function, or medication (class of recommendation I, level of evidence A).³

Despite the virtues of CR, only a small percentage of eligible HF patients ever get referred, due to barriers such as lack of physician and patient-family awareness of its benefits, and logistical or financial constraints. Patients with CHF are a patient population that challenges CR with the need to employ active strategies to disseminate and implement appropriate standards of care.

Box 45.1 lists the core components of cardiac rehabilitation.

Careful history, physical examination, cardiac imaging, and biochemical assays are essential to describe fluid status and functional capacity accurately. Defining the severity of HF is vital before an appropriate rehabilitation programme can be started.^4,5 In particular, the following must be considered:

The assessment should lead to the formulation of a tailored, patient-specific, treatment plan and document short-term goals within the core components of care that guide intervention strategies.

Coexisting conditions are responsible for 40% of preventable hospital readmission. Causative factors (which include hypertension, coronary artery disease, arrhythmias), and precipitating factors (such as noncompliance with drug treatment; abuse of non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors; and nasal decongestants; infection; pulmonary emboli; dietary indiscretion; inactivity; hyperthyroidism) must be clearly identified. As the disease progresses and the patient ages, medication and remedies directed at the underlying pathology may be less relevant and the need for treatment of coexisting symptoms may outweigh the possible adverse consequences of some therapies for HF care.

According to clinical assessment, medical therapy should be oriented to achieve normal jugular venous pressure, resolution of orthopnea and oedema, systolic blood pressure of at least 80 mmHg, stable renal function, and the ability to walk the hospital ward without dizziness or dyspnoea.

Attendance at supervised exercise training sessions makes it possible to ensure that the patient is taking appropriate medical therapy. Treatment must be tailored according to the individual characteristics with the goal of prescribing according to international guidelines with adequate doses. A careful upward dosage titration is required in the introduction of both angiotensin converting enzyme (ACE) inhibitors and β-blockers up to the highest tolerated dosages. The up-titration schedule usually extends into the convalescent period after the patient has been discharged from the hospital.

The simultaneous presence of competing comorbidities further complicates pharmacological management. The ever-increasing complexity of polypharmacotherapy is intimidating, meaning that some therapies may not to be used, especially by practitioners who lack the time and expertise to pursue the kind of ‘micromanagement’ required with complex regimens. Although little evidence is available to guide polypharmacotherapy, collaborative disease management programmes (such as those provided in the CR setting) that include a careful review of medications can be very helpful for patients with chronic HF and multiple comorbidities.⁶

Educating patients about their condition and motivating their adherence to a course of therapy are steps towards success. A clear and comprehensible explanation of the basic purpose and action of each drug is required. Patients’ understanding and adherence of drug regiment should be periodically refreshed.

As the CHF syndrome starts and develops, the natural tendency for patients is to do whatever seems reasonable to avoid symptoms. Hence the recognition that effort induces undue breathlessness leads to progressive inactivity, contributing to skeletal muscle detraining and general unfitness that contribute to further progression of the HF syndrome. A sedentary lifestyle, with little or no physical activity during leisure time or at work, is a risk factor for the development and progress of cardiovascular disease.^7,8

For many years, standard medical advice was that exercise should be avoided for patients with CHF, with standard textbooks containing such advice as, ‘Reduced physical activity is critical in the care of patients with HF throughout their entire course’.⁹ There are some small studies suggesting that rest as a specific intervention may have some modest beneficial effects in terms of reducing heart size,^{10–  12} but these studies were carried out at a time when modern medical therapy was in its infancy and CHF had an exceptionally high mortality rate. A common problem with long-term rest has been thromboembolic complications and sudden death. Rest as an intervention has not been trialled in the modern therapeutic era.

Part of the concern about exercise comes from the possibility that it might be dangerous, particularly in patients with underlying ischaemic heart disease. The increased wall stress imposed by exercise might be expected to result in further cardiac enlargement. An influential paper reported on the effects of training in patients who had had a moderate-sized anterior myocardial infarct.¹³ There appeared to be some echocardiographic evidence of worsening cardiac function despite an improvement in exercise capacity. Further work in animal models¹⁴ suggested that training may worsen left ventricular function.

These observations were alarming: no treatment that worsens left ventricular function is likely to confer long-term benefit. However, the Judgutt study was relatively small, uncontrolled, and used a strenuous training programme. A key study was the EAMI trial in which 95 patients were randomized following an anterior myocardial infarction to a training regime or usual therapy. Although patients with a lower left ventricular ejection fraction (LVEF) at study entry showed ventricular enlargement after 6 months, there was no difference between the control and training groups.¹⁵ Similar findings have been reported elsewhere,¹⁶ and data from the longer term ELVD-CHF study suggested that training actually reduced left ventricular volumes and increased LVEF.¹⁷

Training might, of course, have some other dangerous effects, such as potentially increasing the risk of ventricular arrhythmias. Most of the early studies in the field used carefully supervised training regimes in carefully selected patients. Incremental exercise testing in patients with CHF is safe,^18,19 and now that large studies of relatively unselected and unsupervised patients have been conducted, the safety of training is established.²⁰

The benefits of exercise training for patients with ischaemic heart disease,²¹ and following myocardial infarction,^22,23 have been known for many years. Training can actually improve left ventricular systolic function in ‘normal’ older men,²⁴ and rehabilitation is helpful after cardiac events in older people,^25,26 the population most likely to suffer from CHF. Training apparently improves endurance exercise more than peak exercise capacity,²⁷ the very improvement likely to have the greatest symptomatic benefit for older patients who rarely if ever need to undertake maximal exercise. Given the effects of ageing on muscle strength and bulk, it is not surprising that training might be more generally helpful in older subjects.²⁸

The nature of these studies means that they must have included many patients with significant left ventricular impairment, and the lack of cardiac complication in the studies is further evidence that training is safe.

Although the pathophysiology of CHF is commonly discussed principally in terms of changes to central haemodynamic function, much research over the last 20 years or so has emphasized the fact that CHF is a multisystem disorder with abnormalities affecting many body systems from the central nervous system to bowel wall function to immunological function. The greatest contributor to exercise limitation appears to be changes to skeletal (rather than cardiac) muscle function (see discussions in Chapter 2 and Chapter 33).

A striking feature of the peripheral changes seen is how closely they resemble the effects of detraining in normal subjects. Activation of the renin–angiotensin²⁹ and sympathetic³⁰ systems, loss of skeletal muscle bulk, and depletion of oxidative enzymes^31,32 are all seen in both conditions (see Table 45.1). Given the apparent safety of training regimes, the similarity of CHF to detraining, and the beneficial effects of training in very similar patient groups, training as a specific intervention for CHF patients was an inevitable progression.

Early uncontrolled work including patients with severe left ventricular dysfunction showed promising results.^33,34 Sullivan and colleagues^35,36 were amongst the first to assess training systematically, and found that a training regimen improved exercise capacity by around 20% (as assessed by peak oxygen consumption). An important observation was that central haemodynamics at matched workloads was unchanged after training, and the changes responsible were presumably peripheral as reflected in a fall in arterial and venous lactate during exertion.

In a crossover trial, Coats and coworkers^37,38 demonstrated that exercise training improved exercise capacity by a similar proportion and helped improve symptoms.

Since these pioneering studies, the beneficial effects of training on peak exercise capacity have been repeatedly confirmed, and, indeed, the effects are greater than (and additive to) the effects of ACE inhibitors.³⁹

Training programmes produce a variety of improvements in HF patients, not simply an improvement in peak exercise capacity. There is improvement in endurance exercise capacity and an increase in both anaerobic and ventilatory thresholds.^36,40 In addition, the increased ventilatory response to exercise (as reflected in the increase in the relation between ventilation and carbon dioxide production) is improved by training,⁴¹ an effect not seen in normal subjects.⁴² Ventilation at matched submaximal workloads is reduced by training.^36,43 Peak exercise ventilation is increased, reflecting the increased overall exercise capacity following training.⁴⁴

As well as increasing maximal exercise capacity, training regimes also improve submaximal exercise capacity. This is perhaps a more important observation, as patients rarely encounter peak exertion in daily life. Training induces an increase both in the duration of exercise at a fixed workload,³⁶ and an increase in the distance covered in a six-minute walk test.^40,45

Quality of life measures are consistently improved by training, which is not something necessarily seen with all treatments that improve prognosis. The effect on quality of life may be more important than effects on abstract measures that do not really reflect day-to-day life. Patients self assessment scores during exercise tests are improved,^37,40 and there are improvements in anxiety and depression following training.⁴⁶

The best evidence for the effects of training on quality of life comes from the HF-ACTION study. Using the Kansas City Cardiomyopathy Questionnaire, the investigators found a marked benefit on quality of life persisting through the 3 years of the study (see Fig. 45.1).⁴⁷ The effect was the same regardless of the aetiology of the HF.

The abnormal sympathovagal balance of CHF is improved by training as shown by an increase in heart rate variability and reduction in noradrenaline spillover.³⁷ There is an improvement in circadian variability of heart rate in some studies,⁴⁸ although others have reported that only daytime heart rate variability is increased.⁴³

Training has a beneficial effect on the neurohormonal activation of CHF causing reductions in angiotensin, aldosterone, and arginine vasopressin.⁴⁹ It can also reduce sympathetic activation and natriuretic peptide levels.⁵⁰

As a consequence of increasing exercise performance, training has been found in many studies to increase maximal cardiac output and heart rate. The effects on submaximal cardiac output is not completely clear: most investigators suggest that at matched workload, cardiac output is unchanged by training,^35,43 but some have reported modest increases.³⁷ It is unlikely that changes to cardiac output mediate any benefit, however, as most patients have normal cardiac output responses to submaximal exercise before training.^51,52

There is some evidence to suggest that training might improve diastolic cardiac function with improved early diastolic filling and increases in peak filling rates at matched heart rates during exercise.^53,54 Other changes include a reduction in both cardiac volume and systemic vascular resistance together with increased endothelium-dependent vasodilation.^55,56 That arm vasodilation is improved after leg training⁵⁷ suggests that there are some structural effects of training on the vasculature.⁵⁸

Studies examining skeletal muscle histology have shown that mitochondrial density is increased by training, along with a shift back towards type I muscle fibres and an increase in the ratio of capillaries to myocytes.^59,–61 Many of these changes correlate with the improvement in exercise capacity seen, suggesting that the mechanism for improvement lies with changes to skeletal muscle rather than in any haemodynamic changes. Additional effects include a decrease in myocyte phosphocreatine depletion during exercise, and a shortening in the recovery time of phosphocreatine following exercise.⁶² Selective training of ventilatory muscle can also be beneficial.⁶³

Other effects in skeletal muscle include an increase in insulin-like growth factor,⁶⁴ suggesting that the insulin resistance of HF may be partially reversible by training. In addition, training also has a general antioxidant effect in skeletal muscle with an increase in skeletal muscle antioxidant enzymes.⁶⁵ A potential link to the improvement in exercise capacity and reduction in ventilatory response induced by training is via the abnormal activation of the ergoreflexes⁶⁶ closely associated with the abnormal exercise physiology of patients with CHF: the ergoreflex is reduced by training.⁶⁷

Formal studies of training have generally used quite strenuous training stimuli. Different studies have used different techniques ranging from home cycle training to supervised rowing (Table 45.2).

The effects of isometric exercise seem to be broadly unfavourable in CHF, with adverse haemodynamic consequences.^68,69 However, a resistive component of a training regime does seem to produce

benefits above what is gained from endurance training alone.⁷⁰ It may even be possible to achieve some benefits with very localized training,⁷¹ including of respiratory muscle alone.⁶³

The strenuous endurance approach is reasonably easy to follow for supervised patients in short-term clinical trials, but is not be broadly applicable for most patients with CHF. There is some evidence that rather more gentle regimes can have a beneficial effect. Belardinelli et al.⁷² found beneficial effects in patients with mild CHF with low-intensity training at only 40% of peak oxygen consumption, a finding confirmed in patients with more severe HF who trained at low workloads (〈50% of maximal) using supine cycle exercise in a deliberate attempt to minimize ventricular wall stress.⁴⁵

A further consideration is that most patients with CHF are elderly, and many have comorbidities that will greatly limit their capacity to take part in formal training programmes. One possible alternative approach is that of electrical muscle stimulation. It is possible to induce painless muscle contraction using large electrode plates, and devices can be programmed to deliver stimulation to several large muscle groups in the legs (quadriceps, gluteals, and hamstrings).⁷³ In normal subjects, such a device can have a training effect,⁷⁴ and we have shown that electrical muscle stimulation can have a beneficial training effect in patients with CHF (Fig. 45.2).⁷⁵ Whether programmed electrical muscle stimulation leads to prolonged benefits is not yet known.

An important observation is that the improvement in exercise capacity is proportional to compliance with the training regime.³⁸ That the benefits are not just short-term gains was confirmed by Kavanagh⁷⁶ who demonstrated that the effects lasted for at least a year, reaching a plateau at around 16 weeks–6 months. The HF-ACTION study demonstrates that the benefits of training persist for longer—up to 3 years.⁴⁷

A key question has been whether the apparently beneficial changes seen in the multitude of relatively small-scale studies translate into improvements in outcome. The ExtraMatch collaborative⁷⁷ included 801 patients who had been randomized into trials of exercise training. Follow-up was limited to just over 700 days, but there was a strong suggestion that patients randomized to training were not only less likely to be admitted to hospital, but had a better prognosis (Fig. 45.3).

Mounting a sufficiently large study to answer the question definitively has been very difficult, in part because of the problem of sponsorship, and in part because of the difficulty of running the trial. Blinding the intervention is, of course, impossible, and many patients randomized to usual care are likely to take up exercise once included in any study. There are also likely to be problems with drop-outs: compliance with the training regime is difficult to monitor, and it is easier for individual patients to resile from training than, say, from a drug trial—where the randomization and blinding makes it far less likely that crossovers will be a problem.

The HF-ACTION study²⁰ randomized 2331 patients to receive a training programme or usual care. The training programme consisted of 36 supervised 30-min sessions three times per week followed by home exercise five times per week at moderate intensity for 40 min. The control group was simply encouraged to take exercise. The primary endpoint was all-cause death and hospitalization.

Although the training group had a marked improvement in exercise capacity over the course of the trial, there was no effect on the primary endpoint. However, when adjustment was made for other prognostic indicators, there was a modest benefit in favour of training. The effect appears to be modest, but should be set in the context that at 3 years, only 30% of patients in the intervention limb were adhering to the recommended 120 min/week, and the median exercise duration per week was only around 50 min. The additional benefit of striking improvement in long-term quality of life⁴⁷ means that a structured exercise programme should now be part of the routine management of patients with CHF.

Improving adherence to a physical activity and exercise training programme is vital: without compliance, the programme is worthless. A step-by-step approach is helpful.

Assess current physical activity level and determine domestic, occupational, and recreational needs. Evaluate activities relevant to age, sex, and daily life. Assess readiness to change behaviour, self-confidence, barriers to increased physical activity, and social support in making positive changes.

The expected outcomes from exercise training programmes are highlighted in Box 45.2.

There is some obvious difficulty in determining heart rate targets in patients taking β-blockers. Patients on β-blockers benefit to the same extent as those not taking them,^79,80 and in HF-ACTION, nearly 95% of patients were taking a β-blocker at baseline. The heart rate at maximum exertion at baseline allows an appropriate target heart rate for training to be determined.

The key here is to make sure that there is adequate control of ventricular rate during exercise. Almost always, a β-blocker will be needed to control heart rate rather than simply digoxin alone. In HF-ACTION, just over one-fifth of the patients had AF at baseline, and there is no reason to exclude patients with AF from a training regime.

There are only limited data available, but there appear to be no adverse consequences for patients with ICDs undergoing a training programme.^81,82 There is a risk of device discharge from a rapidly accelerating heart rate,⁸² and certainly to start with, supervision by qualified staff is important, particularly to monitor the heart rate response to exercise. Training intensity should be determined by the heart rate response and established at a level to increase the heart rate to between 20 and 30 beats below the ICD detection rate.

The role of the multidisciplinary team in delivering counselling and education is considered elsewhere. In relation to the exercise component, however, some factors are particularly important.

Obesity has numerous adverse effects on haemodynamics and cardiac structure and function. On the other hand, obese chronic HF patients have a better prognosis than underweight patients.^83,84 Obesity should not be seen as a contraindication to exercise training, and training may help weight control.

Smoking should be strongly discouraged in CHF patients. In addition to the well-established adverse effects on coronary artery disease, which is the underlying cause in a substantial proportion of patients, smoking has adverse haemodynamic effects in patients with CHF, including increase heart rate and systemic blood pressure, mild increase in pulmonary artery pressure, ventricular filling pressure, and total systemic and pulmonary vascular resistance. Increased peripheral vasoconstriction may contribute to a mild reduction of stroke volume. Finally, in CHF patients, enhanced broncopathic susceptibility and breathing problems precipitate or aggravate HF.

Depression is extremely common in the HF population,⁴⁰ with a wide range of quoted prevalence rates across studies due to the use of different diagnostic instruments and the inclusion of different patient populations. Treatment of depression is an important clinical strategy as it is associated with more frequent hospital admissions, decline in activities of daily living, worse NYHA functional classification, and increased medical costs. However, depression commonly goes undiagnosed.

The depressed patient is far less likely to comply with a training regimen, and its recognition at an early stage is important. Patients may be unwilling to disclose emotional distress to their physicians for fear of being stigmatized with the label of mental illness. On the other hand, physicians may not address depression because they have not been adequately trained to recognize both typical and atypical depressive symptoms, because of time constraints in high-volume settings, or because they do not know how best to treat the condition. Recognition and management of depression may be enhanced through the use of multidisciplinary team or disease management programmes.^85,86

A good cardiac rehabilitation programme is characterized by a continuum of services that spans inpatient and outpatient rehabilitation.

Inpatient rehabilitation should begin as soon as possible after hospital admission and should be part of routine daily care for every HF inpatient. The main elements are appropriate strategies for optimal therapy; education with full participation of patient/caregiver; reassurance and support; mobilization when possible; and group education, according to clinical assessment and risk stratification. Progression of mobilization should be developed according to the patient’s clinical condition, functional capacity, age, and comorbidity under careful medical review and supervision.

As the length of stay for acute HF and procedures continues to decrease, patient and family attendance in outpatient cardiac rehabilitation assumes even greater importance. Structured outpatient cardiac rehabilitation is a crucial point for the development of a lifelong approach to prevention. Attendance should start soon after discharge from the hospital. Outpatient cardiac rehabilitation may be provided in a range of settings, such as HF clinics, non-clinic settings (community health centres and general medical practices), or a combination of these. It may also be provided on an individual basis at home, including a combination of home visits, telephone support, telemedicine, and specially developed self-education materials.

The main elements of outpatient cardiac rehabilitation include assessment, review and follow-up, therapy optimization, low or moderate intensity physical activity and exercise training, education, discussion and counselling.

Evaluation of ongoing cardiac rehabilitation programme objectives on a regular basis is a key to success.