Inspiratory muscle training – an inspiration for more effective cardiac rehabilitation in heart failure patients?

Reduced physical performance and exercise-induced dyspnoea are key symptoms of heart failure with reduced left ventricular ejection fraction (HFrEF). The underlying causes discussed beside the cardiac dysfunction include reduced pulmonary capacity as well as peripheral maladaptation mechanisms,1–3 which are associated with marked functional deconditioning of skeletal muscle and reduced muscle mass.1–4 Sarcopenia and muscular dysfunction is prevalent in 30–50% of HFrEF patients5 and may play an important role for these symptoms. Interestingly, these symptoms and pathophysiological mechanisms do not affect only peripheral muscle structure and function, but also the respiratory muscles. Inspiratory muscle weakness is prevalent in 30–50% of outpatient clinic HFrEF patients.6,7 Maximal inspiratory pressure, PImax, as a measure for respiratory muscle strength, has been shown to be associated with New York Heart Association functional capacity as well as to correlate with the cardiac index8 and overall low quality of life.6 Moreover, PImax has been demonstrated to be a significant marker of adverse outcome (hazard ratio: 0.925; 95% confidence interval (CI): 0.879–0.975; χ2: 8.62) independent of heart failure aetiology.8 Consequently, PImax is an established surrogate marker and a therapeutic target for interventions in many trials.6,9 Exercise based cardiac rehabilitation in HFrEF patients improves exercise and functional capacity and reduces exercise induced dyspnoea and other relevant symptoms.10,11 Most of the evaluated programmes included aerobic endurance training alone or in combination with resistance training according to current guidelines.10,11 Based on current knowledge, guidelines10,12 recommend inspiratory muscle training (IMT) ‘on demand’ with focus on patients with respiratory muscle weakness. Recommendations for IMT in HFrEF patients are summarized in Table 1. Current recommendations for inspiratory muscle training in heart failure patients (according to Piepoli et al.10 and Cahalin et al.12). PImax: maximal inspiratory pressure Current recommendations for inspiratory muscle training in heart failure patients (according to Piepoli et al.10 and Cahalin et al.12). PImax: maximal inspiratory pressure The results of two small meta-analyses13–14 demonstrate that especially HFrEF patients with respiratory muscle weakness do benefit from IMT. The results revealed: Increase in PImax (weighted mean difference (WMD): 16.52, 95% CI: 13.87–19.17, p<0.0001);13 Improvement in VE/VCO2 slope (WMD: –5.78, 95% CI: 7.7–3.85, p<0.01);14 Improvement in VO2 peak (standardized mean difference (SMD): 3.02 ml/min per kg, 95% CI: 0.43–5.61 ml/min per kg, p = 0.02);13 Reduction of dyspnoea (SMD: –0.95, 95% CI: –1.5 to –0.39, p < 0.01);14 Extension of the six-minute walking distance (+ 69.00 m (95% CI: 7.21–130.79), p < 0.03).13 Against this background, Sadek et al.15 present an extended meta-analysis aiming to evaluate the effects of IMT on inspiratory muscle strength, functional capacity and dyspnoea in HFrEF patients, by summarizing the published research on the effects of IMT. Moreover, they intended to identify the best mode of IMT intervention in terms of load of PImax, the frequency of training sessions and the total duration of the intervention programme. They included seven eligible studies containing data of 203 patients, mean age ranging from 53 to 76 years with HFrEF (ejection fraction < 40%). PImax values ranged from 48 to 82 cmH2O, characterizing the investigated patients as being affected by respiratory muscle weakness. The sample size of all included studies was small with an average of 29 patients. Typical training protocols involved training sessions three, six or seven times per week with intensities ranging from 30% to 60% of PImax, as recommended by current guidelines. Duration of the intervention programmes ranged from six to 12 weeks. Their obtained findings confirm the results of earlier meta-analyses and show a significant improvement of PImax, walking distance and dyspnoea in all studies. An important finding of this meta-analysis is the ‘evidence’ that the programme design had a decisive influence on the effectiveness of inspiratory training. Studies applying a load of 60% PImax, which is the upper level of the current recommendations regarding respiratory training in HFrEF, achieved the best effects. In addition, training sessions six times per week showed better results than programmes with less frequent sessions, and a duration of the training programme of 12 weeks was superior to shorter programmes. These results demonstrate that the better outcome may be achieved when the intensity, frequency and duration of the inspiratory training are each performed at the upper limits of the current recommendations. In practical terms, this means that the intensity should be set as high as possible and should ideally reach 60% of the maximum value. The design of future programmes should entail daily exercise sessions with minimum programme duration of 12 weeks. With these findings, the authors of the meta-analysis have provided helpful hints for the designing of more effective inspiratory training programmes in the future. Nevertheless, there are still gaps in the knowledge regarding IMT and future studies have to prove these findings and answer the questions of how to identify patients mostly in need of IMT and the additional benefits from this training mode compared with or in combination with usual exercise training for this group of patients. Moreover, most of the studies have focused on the efficacy of IMT compared with non-exercising control groups as well as its efficacy only to improve PImax.13,14 In the future, we need answers about the effectiveness of IMT when provided in addition to conventional exercise-based rehabilitation programmes. In addition, evaluation should be made of what the comprehensive benefits are besides those on PImax, for instance on VO2 peak or quality of life as important outcome parameters in HFrEF patients. A systematic review and meta-analysis provided by Neto et al.16 aimed to investigate the effects of combined exercise and IMT as compared with conventional exercise on respiratory muscle strength, quality of life and exercise capacity. The results of only three studies (N = 89) that did meet the inclusion criteria demonstrate significant differences in PImax of 20.89 cm H2O (95% CI 14.0 to 27.78) and quality of life of 4.43 (95% CI 0.72 to 8.14) in the combined intervention group as compared with the conventional exercise group. No significant additional effects were seen with respect to VO2peak (0.89 ml/kg/ per min (95% CI – 1.24 to 2.86; ns) and exercise time (0.7 min (95% CI, 0.22 to 1.62; ns).16 Interestingly, one of the three studies17 showed the most significant improvement in VO2 peak in patients with low inspiratory strength, emphasizing the clinical value of IMT in these patients. However, further investigations are needed to improve the evidence for this hypothesis. More recently published studies have focused on the influence of high intensity interval training on clinically relevant respiratory parameters18 as well as central haemodynamics and skeletal muscle oxygenation during exercise.19 A randomized controlled study18 assessed exercise oscillatory ventilation (EOV) cardiorespiratory exercise testing in heart failure patients. The results showed high intensity aerobic interval training (HIT) (30 s at 100% peak VO2 separated by 60 s passive rest) alone or in combination with resistance exercises to improve EOV duration (79.0 ± 13.0% to 50.0 ± 25.0% of total exercise duration, p < 0.001; 29 ± 31%, effect size of 0.94). However, HIT did not mediate changes in the average EOV amplitude (5.2 ± 2.0 to 4.9 ± 1.6 l/min) and length (44.0 ± 10.9 to 41.0 ± 6.7 s) (p > 0.05). These findings are important since EOV is prevalent in 19–51% of heart failure patients20 and an independent risk factor for poor prognosis in heart failure patients irrespective of other gas exchange variables.21 The role of different exercise modality and characteristics, as well as the role of additional IMT on EOV, need further investigation. Findings of an explorative study19 demonstrate the well-known effects of HIT (4 × 4 min protocol) on submaximal exercise capacity to be mediated by improved microvascular oxygen delivery-to-utilization matching (time constant of oxygen uptake (t VO2) HIT 71 ± 19 to 59 ± 14 vs. control 68 ± 23 to 69 ± 24, p = 0.02; significant difference between groups). In contrast, the results show no changes in cardiac output kinetics, which is in contrast to earlier studies22 and adds important information to understanding how HIT influences the exercise capacity in HFrEF patients. Further studies have to identify the role of inspiratory muscle weakness in this context. In summary, IMT is proven to be an inexpensive and well-tolerated exercise option in patients affected with respiratory muscle weakness. Nevertheless, the current evidence does not allow the general recommendation of IMT as a fixed integral part of the cardiac rehabilitation in HFrEF patients. However, existing evidence shows promising clinical results and the meta-analysis by Sadek et al.15 adds important information to the current level of knowledge concerning the therapeutic value and application of IMT. The results demonstrate the best effects to be achieved when the intensity, frequency and duration of the inspiratory training are each at the upper limit of the current recommendations. Since high frequency and long-term programmes are of greater efficacy during rehabilitation patients should be provided with the necessary devices, knowledge and motivation that will enable them to continue IMT home based. Nevertheless, the value of this method as an additional training option must be understood in more detail in further studies. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) received no financial support for the research, authorship, and/or publication of this article.