Rehabilitation of Patients with Coexisting COPD and Heart Failure

ABSTRACT

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) frequently coexist, significantly reducing the patient's quality of life (QoL) and increasing morbidity, disability and mortality. For both diseases, a multidisciplinary disease-management approach offers the best outcomes and reduces hospital readmissions. In both conditions, muscle dysfunction may dramatically influence symptoms, exercise tolerance/performance, health status and healthcare costs. The present review describes muscular abnormalities and mechanisms underlying these alterations. This review also discusses studies on training programs for patients with COPD, CHF and, where available, combined COPD-CHF diagnosis. Dyspnea, peripheral muscles and activities of daily living (ADL) represent a potential starting point for improving patients’ functioning level and quality of life in COPD and CHF. A synergy of the combined diagnostic, pharmacological and rehabilitation treatment interventions is also essential. Integration between exercise training, drug therapy and nutritional care could be a valid, synergic and tailored approach for patients presenting with both diseases, and may have a positive impact on the exercise performance.

KEYWORDS:

• Chronic obstructive pulmonary disease
• chronic heart failure
• rehabilitation, exercise

Incidence, prevalence and time course

The incidence and prevalence of chronic diseases have increased steadily in recent decades and are continuing to rise. With the progressive ageing of the population, patients with chronic diseases such as chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are increasing in number (1). COPD and CHF frequently coexist due to common risk factors, causing a significant additional increase in morbidity, disability and mortality and a deterioration of quality of life (2–4). COPD is an independent predictor of mortality and hospitalizations in ambulatory CHF patients (2, 5) and represents a confounding factor for the diagnosis of CHF. On the other hand, the risk of unrecognized ventricular dysfunction in COPD is well known among both pulmonologists and cardiologists (6).

Schell et al. in a study involving 14,828 individuals conducted in the United States from 1999 to 2008 showed that 995 (6.7%) had COPD, and of these 12.1% also had CHF (6). The prevalence of COPD in CHF ranges from 12% to 32% (1–3) while CHF is prevalent in more than 20% of patients with COPD (4, 5) depending on the population studied (community, outpatient, inpatient, elderly stable patients or different COPD phenotypes), cohort of elderly stable patients and cohort of COPD severity. Diagnostic criteria applied based on objective measurements of respiratory function or simple clinical assessment as different criteria to define CHF have influenced different epidemiological rate. Although each disease is an independent predictor of morbidity, mortality, impaired functional status and health service use, the combination of the two diseases results in patients who are particularly frail and characterized by a high risk of rehospitalizations due to exacerbations with the related burden of costs (1).

It should be emphasized that both conditions are chronic progressive diseases with a similar fluctuating course marked by frequent exacerbations, and characterized by a vicious cycle of dyspnea, decreased activity, new exacerbations, depression and social isolation (7, 8). The combination of COPD and CHF presents many diagnostic challenges such as dyspnea, orthopnea, exercise intolerance, fatigue, muscle weakness, but none is unique to either single disease and clinical symptoms and signs require careful interpretation in conjunction with objective evidence of the presence of each condition (9).

Pathophysiological derangements

COPD

There are many pathophysiological central and peripheral causes of dyspnea and exercise intolerance in COPD. The main central factors are ventilatory abnormalities (10) with expiratory flow limitation, dynamic hyperinflation, and increased ventilatory demand and work of breathing (11) that can lead to gas exchange abnormalities (12). Other important central factors are hemodynamic limitations caused by large swings in intrathoracic pressure, consequential augmented sympathetic activity with the risk of left ventricular (LV) hypertrophy, endothelial dysfunction, increased arterial stiffness and cardiac autonomic dysfunction (13). Resting heart rate increases with the severity of COPD and is a predictor of mortality (14). Resting heart rate is a readily available clinical variable that improves risk prediction in patients with COPD over that of pulmonary function alone (14).

The negative relationship between the level of emphysema and impaired LV filling is well known. Reduced stroke volume and lower cardiac output without changes in the ejection fraction (15, 16) and reduced systolic output with competition for blood flow between peripheral and respiratory muscles determine a negative relationship between hyperinflation and O₂ pulse at peak exercise (17). Patients with pulmonary hypertension (PH) at rest present a lower cardiac index at 60% of maximum work rate (18). Exercise-induced PH is observed in the majority of COPD patients and might contribute to limiting exercise tolerance (18). During exercise, COPD patients show an increase in arterial pulmonary pressure and a limited stroke volume response to exercise resulting from the increased preload (19). Apart of the peripheral and systemic factors causing dyspnea and exercise intolerance, in patients with COPD there is evidence of skeletal muscle dysfunction and weakness, loss of oxidative fibers, fiber type shift towards glycolytic fiber dominance with early lactate release, decrease in muscle protein synthesis and increase in protein degradation (11).

The skeletal muscle dysfunction can be worsened by ageing, nutritional depletion, medications, smoking, oxidative stress (11), inflammation (11, 20), and physical inactivity (7).

In summary, the factors limiting exercise in patients affected by COPD are metabolic abnormalities and abnormal gas exchange (both increasing the ventilatory requirements), abnormal lung mechanics (dynamic hyperinflation), pulmonary arterial hypertension, peripheral artery disease, heart-lung interaction, and peripheral muscle dysfunction (10–20).

CHF

Also in subjects with CHF there are many pathophysiological causes of exercise intolerance with skeletal and respiratory myopathy, muscle fatigue and dyspnea.

In CHF patients, muscle mass loss and skeletal muscle wasting have serious therapeutic and clinical implications (21, 22). In the case of CHF, the ‘muscle hypothesis’ ascribes much of the functional limitation to skeletal myopathy (23). Exercise tolerance correlates poorly with measures of left ventricular (LV) performance such as LV ejection fraction (24). Skeletal muscle function and predominance can be remarkably preserved even in the face of severe LV impairment (25).

The proposed factors limiting exercise in patients affected by CHF have been related to LV dysfunction (26, 27), vasoconstriction (26, 28), increased afterload (28), sympathoexcitation and vagal withdrawal (28), increased ergoreceptor activity (28), increased tumor necrosis factor (TNF) production (28), insulin resistance (28), ventilatory abnormalities (11, 26, 28), inactivity (11, 28), catabolic state (11, 28), and peripheral vascular dysfunction (26, 28).

A common pathophysiological background?

Despite the large differences between their primary impairment, the two diseases share striking similarities concerning the functional, structural and metabolic skeletal muscle abnormalities, but there are also notable differences between the peripheral (limb) muscles and the respiratory ones (diaphragm) which could impose the need for different training modalities (29).

Low exercise tolerance and dyspnea have a large influence on health status in both COPD and CHF (30). The combined presence of COPD and heart failure (HF) due to systolic dysfunction is associated with an increased burden of comorbidities (as impaired perfusion of the diaphragm and respiratory failure are common precipitants of infection), arrhythmias (31), lower use of evidence-based HF medications, longer hospital stays, and increased in-hospital non-cardiovascular (CV) mortality (although the post-discharge mortality is similar) (32). This fact should not surprise because many aspects of the physiopathology are similar and the result of the combined presence of COPD and CHF is an add-on effect.

Recent information support the idea that patients with diastolic dysfunction failure constitute a new subgroup of the heterogeneous population of patients with heart failure with a preserved ejection fraction. (33). The common presence of diastolic dysfunction in CHF and COPD remains a future challenge in term of diagnosis, treatment and training response.

There are also impressive similarities between the two disorders in regard with the muscular alterations underlying either impairment: hypoxia, oxidative stress, medication, nutritional depletion, disuse atrophy, protein degradation and reduced protein synthesis are the common molecular bases of skeletal muscle atrophy in both diseases (26, 31). Muscle atrophy contributes to muscle fatigue during exercise, forcing patients to stop exercising even if they have not yet exhausted their heart and lung capacity (26, 30, 31). Muscle abnormalities are not limited to the lower limbs: histologic and metabolic data show that peripheral muscles undergo a shift from oxidative to glycolytic energy metabolism, whereas the opposite is observed in the diaphragm (26).

Indicators of primary organ failure (forced expiratory volume in 1 sec and ejection fraction) are poor determinants of exercise capacity in both diseases (26) while fat free mass is a strong predictor of peripheral muscle strength, to a lesser extent of VO₂ peak, and not at all of peripheral muscle endurance (26). In addition to primary organ dysfunction, impaired skeletal muscle performance is a strong predictor of low exercise capacity (31).

Rehabilitation strategy

COPD

Pulmonary rehabilitation leads to an improvement in exercise capacity, quality of life and emotional function, reduced hospitalization, reduced unscheduled health care visits and improved symptoms (34). In COPD, exercise training leads to an increase in peak work rate, peak oxygen uptake, oxygen uptake at ventilatory threshold, muscle fiber size, muscle fiber capillarization, oxidative characteristics of skeletal muscle, and cardiac autonomic function during exercise, while it reduces the ventilatory requirement and dyspnea (34). Furthermore, in patients with COPD, exercise training reduces the degree of dynamic lung hyperinflation leading to improved arterial oxygen content and central hemodynamic responses, thus increasing the systemic muscle oxygen availability (31). Pulmonary rehabilitation lowers chest wall volumes during exercise by decreasing the abdominal volumes, and the improvement in exercise capacity following rehabilitation is independent of the pattern of exercise-induced dynamic hyperinflation (29, 35).

Among endurance training (ET) protocols, interval training is a good alternative to continuous exercise especially in patients with severe lung disease (36). Interval training allows intense loads to be applied to peripheral muscles for sufficiently long periods to induce physiological training effects with lower symptoms of dyspnea and leg discomfort. These effects are associated with improved central hemodynamic responses and peripheral muscle fiber characteristics (37). Studies on interval vs. continuous training seem to show that the two modalities do not differ as regards their effect on measures of exercise capacity or health-related quality of life (36–38). Hence, interval training may be considered as an alternative to continuous training in patients with varying degrees of COPD severity (36–38). This is even more important because it has been shown that at the cessation of exercise, in subjects with COPD, is not associated with decreasing muscular force, instead it is rather preserved as has been shown by using isokinetic pedal-force measurements (39) allowing much higher than peak work rate to be performed intermittently as long as the ventilatory response amplitude does not exhaust the physiological reserve (39). In COPD subjects, a large gain in skeletal muscle adaptation are the main goal during exercises protocol. In this direction, sinusoidal exercise, with a cycle time of 60 s superimposed upon a mean work rate at critical power, resulted in minimal fluctuations in the exercise ventilation (40). Thus, high-intensity exercise, with excursions well above peak aerobic power was sustained for up to 20 min in COPD patients, and the end-exercise ventilation was less than peak (40).

In addition, resistance training (RT) is a useful additional intervention in pulmonary rehabilitation. A recent review found significantly increased leg muscle strength using a combination of RT and ET, compared to ET alone (41), thus favoring a combined use of the two interventions. Hence, RT should be incorporated in rehabilitation of COPD together with ET.

Further improvements in terms of early treatment of relapses, reduction in hospitalizations and in medications use have been highlighted when an action plan (42, 43) and an educational and counselling program were added. Previous studies in COPD have also demonstrated the safety, feasibility and efficacy of rehabilitation programs performed at home with or without monitoring at a distance (telehealth) (44, 45).

CHF

Cardiac rehabilitation programs in CHF lead to an improvement in exercise capacity, quality of life and psychological well-being, a reduction in CV mortality and morbidity, a reduction in unplanned hospital admissions due to improved symptoms (46, 47) and improvement in routine ADLs (48).

Exercise training has beneficial (both direct and reflex) sympatho-inhibitory effects and favorable benefits on normalization of neurohumoral excitation (31), on an increase in peak oxygen uptake, in peak cardiac output, in oxygen uptake at ventilatory threshold (being the lactate and anaerobic threshold increased), in endothelial function, in muscle fiber size & capillarization and in oxidative characteristics of skeletal muscle: all these conditions leads to a decrease in the ventilatory requirement and dyspnea (46, 47).

Recently, a systematic review has also reported that exercise training is able to improve diastolic function in patients with heart failure (49).

Also in CHF patients, interval or intermittent training has been proposed to be more effective than sessions of continuous exercise for improving exercise capacity (50, 51). The rationale for the use of interval training is that the recovery/low intensity intervals partially restore the phosphocreatine levels, allowing a reloading of myoglobin stores and more oxidative degradation of oxygen (52). Interval training is able to maintain cardiac output and minute ventilation at constant levels, to better improve muscle oxidative capacity, endothelium function, LV diastolic and systolic function as its remodeling (52) compared to the continuous training modality. Further described benefits of interval training are the increase in aortic dilatation capacity, LV diastolic function, arterial function and ventricular-aortic coupling (53).

In CHF patients, RT has been proposed in combination with ET as showing an additional improvement in left ventricular function, peak lactate levels, muscle strength, and muscle endurance (54).

Similarly to COPD, few studies have been performed on home-based tele-rehabilitation in CHF patients (55). Piotrowicz et al (55). found in 111 CHF patients that home-based tele-monitored Nordic walking was safe and effective in improving the 6-min walking distance (6MWT) and quality of life.

Table 1 summarizes the similar benefits of exercise training in COPD and CHF patients.

Table 1. Common benefits of exercise training in COPD and CHF.

Improves functional status and increases exercise capacity

Decreases symptoms (dyspnea and muscle fatigue)

Improves autonomic activation

Increases musculoskeletal blood flow and endothelial function

Increases oxidative and metabolic muscle capacity

Attenuates and/or reverses skeletal muscle atrophy

Improves quality of life

Prolongs exercise duration

Decreases cardiovascular demand and ventilatory requirement

A common protocol and setting?

The two branches of rehabilitation are similar in many aspects. Regarding organization and goals: both cardiac and pulmonary rehabilitation services are comprehensive, long-term programs involving medical assessment, prescribed exercise training, cardiac and respiratory risk factor modification, education and behavioral counseling followed by tailored therapies to improve the physical and psychological condition of the patient and promote long-term adherence to health enhancing behaviors (34, 46–48).

The main goals of cardiopulmonary rehabilitation exercise training programs are focused on improving the skeletal muscles, which are regarded to be dysfunctional in both CHF and COPD. Accordingly, following completion of a cardiopulmonary rehabilitative exercise training there are important peripheral muscular adaptations in both disease conditions: namely increased capillary density, blood flow, mitochondrial volume density, fiber size, distribution of slow twitch fibers, and decreased lactic acidosis and vascular resistance (11). In both diseases, the decreased lactic acidosis at a given level of submaximal exercise not only offsets the occurrence of peripheral muscle fatigue and, consequently, muscle task failure and muscle discomfort, but also concurrently attenuates the additional burden on the respiratory muscles caused by the increased respiratory drive, thereby reducing dyspnea sensations (11).

In each disease, aerobic exercise training has multiple effects on both the heart and lung, e.g. it favors hemodynamic regulation (reduction in muscle metaboreflex and mechanoreflex overactivation, reduction in sympathetic drive and vasoconstriction, and increase in neural control of the cardiovascular system), it strengthens the respiratory and locomotor muscles (increase in muscle oxidative capacity, local muscle blood flow and oxygen capability, reduction in muscle acidosis and in respiratory and peripheral muscle fatigue, reduction in locomotor and respiratory muscle discomfort) and it promotes ventilatory regulation (decrease in the burden of breathing, dynamic hyperinflation, dyspnea) (46–48).

However, there are some documented differences between the two settings: patients admitted to cardiac rehabilitation are on the average younger, smoke less, weigh more, have a markedly better functional status, and are more likely to be employed in an occupation than their counterparts in pulmonary rehabilitation (56). In addition, cardiac rehabilitation patients have fewer comorbidities and use fewer medications than the pulmonary group. The number of hospitalizations and days spent in hospital in the year preceding rehabilitation, however, are greater in cardiac patients than in pulmonary patients (56).

In the literature, there are some examples of delivery of combined pulmonary and cardiac rehabilitation in the same setting: Evans et al. recruited 27 CHF and 44 COPD patients and demonstrated that similar training programs for COPD and CHF were effective and feasible, suggesting that service provision could be targeted around common disability rather than around the primary organ disease (57). Patients with CHF who underwent endurance training showed a similar improvement to COPD patients in their exercise performance and health status (57). In addition, some maintenance community cardiorespiratory programs have been proposed in the same settings for COPD and CHF patients with good results (58). Striking similarities in the muscular derangements of these patients should encourage a collaboration between clinicians and researchers in both fields to come up with further solutions for these disabling conditions (59).

When compared to CHF alone, the presence of coexisting COPD and CHF was associated with older age, more comorbidities, reduced exercise capacity, increased CV mortality and increased hospitalization for HF, but it did not show a differential response to exercise training (60). However, despite the increasing incidence of chronic diseases in general and, among them, the high prevalence of coexistent CHF and COPD, there are still no studies in the literature examining an integrated approach to the two diseases, even though their coexistence implies a far greater functional deficit and impact on quality of life (QoL).

An increased ventilatory response to exertional metabolic demand is a common finding in patients with coexistent COPD and CHF; exercise is a model of integrative physiology and provides a great opportunity for studying the combined cardiopulmonary insufficiency. High V'_E-V'_CO2 slope (poor ventilatory efficiency) has been found to be a key physiological abnormality in symptomatic COPD patients, in particular during exercise, while cardiocirculatory comorbidities such as CHF and pulmonary hypertension (PH) have been found to increase V'_E-V'_CO2 (61). It is reasonable to hypothesize that COPD-CHF patients characterized by greater ventilatory inefficiency would present with a deleterious combination of higher VD/VT and lower PaCO2 compared to their counterparts with lower V'_E-V'_CO2 (62).

Breathlessness and poor exercise tolerance in overlapping COPD–CHF are strongly influenced by inter-patient variability in the extent of the stimulation of the respiratory centers through peripheral chemoreceptors as excessive exercise ventilation hastens dynamic abnormalities in pulmonary mechanics (62). COPD–CHF patients who present hypocapnia during exercise, however, had worse mechanical inspiratory constraints and higher dyspnea scores for a given work rate, leading to poorer exercise tolerance. Decreasing the neural drive without disturbing pulmonary gas exchange (e.g., through exercise training) might prove useful to enhance exercise tolerance in these patients (62).

Unfortunately, to our knowledge, only one recent paper (63) has demonstrated the feasibility and utility of a multidisciplinary nurse- and therapist-oriented program carried out after the in-hospital rehabilitation period in patients with coexisting COPD-CHF. Bernocchi et al. (63) randomized 112 patients with combined CHF and COPD to an integrated tele-rehabilitation home-based program vs. no intervention, and demonstrated the effectiveness of the 4-month program: only in the intervention group did the patients significantly improve the exercise tolerance and QoL, reducing dyspnea and fatigue, maintaining a better physical activity profile, decreasing impairment/disability and increasing the days free from hospitalizations. The range of adherence to physical activity varied from a minimum of 41% to a maximum of 251% when patients, spontaneously performed more activity then expected by the protocol. The satisfaction with the assistance provided was very high. This study, unique in its field, was based on an innovative platform of tele-management, tele-monitoring and tele-rehabilitation (63).

Table 2 summarizes the interventions that have been performed in a similar way in both cardiac and pulmonary rehabilitation, and which should be therefore used in patients with coexisting COPD and CHF.

Table 2. Similar interventions performed in both cardiac and pulmonary rehabilitation.

Aerobic training

Resistance training

Optimization of medications

Education on correct lifestyle

Breathing techniques

Respiratory muscle training

Psychological support

Diet and nutritional counselling

Future research

Future studies should be carried out in order to: (1) better understand the determinants of exercise limitation resulting from a complex interaction between CHF and COPD with the negative mechanical consequences of increased exercise ventilation; (2) better understand the relative contribution of leg effort to exercise limitation, muscle dysfunction and poor muscle O2 delivery (impaired muscle blood flow), and the breathlessness related to exertional ventilation; (3) gain new insights into the behavior of this patient group; (4) identify subgroups of COPD–CHF patients in whom lessening the ventilatory response to exertion is more likely to positively impact on exertional dyspnea, in order to develop further therapeutic and rehabilitative interventions; (5) compare different rehabilitation programs aimed at increasing mechanical-ventilatory reserves and/or decreasing the ventilatory drive, e.g., rehabilitative strategies associated with low to-minimal ventilatory stress, such as small muscle mass training, neuromuscular electrical stimulation, interval training and one-legged training, should be accurately studied and tested; (6) compare the effectiveness of rehabilitation across the large heterogeneity of COPD and CHF forms (e.g., more extensive emphysema, advanced cachexia, or resting hypoxemia).

Conclusions

Based on recent studies, COPD and CHF would seem to coexist more often than expected from their separate prevalence. At least in patients with excessive symptoms despite optimal treatment, additional investigations should be carried out to check for a possible coexistence of the two diseases (64). There are numerous and increasingly emerging contact points between the two diseases as regards the ethiopathogenesis and the expression of symptoms. These frail patients need, on the one hand, to be continually encouraged to carry on performing physical activity to maintain an adequate level of independence in activities of daily living (ADLs) and, on the other, to be educated and followed to learn how to recognize early signs and symptoms of a possible worsening. In this context, a case manager (nurse–tutor and physiotherapist–tutor) would be able to resolve the majority of patients’ clinical and physical needs, either alone or with the help of specialists. A synergy in the combined diagnostic, pharmacological and rehabilitation interventions is also mandatory. Integration between exercise training, medications and nutritional care could offer a valid, synergic and tailored approach for patients affected by both diseases, which could positively impact on their exercise performance.

Declaration of interest statement

The authors report no conflicts of interest.The authors alone are responsible for the content and writing of the paper.

Acknowledgments

The Authors thank Rosemary Allpress for English revision and Laura Comini for technical assistance.