Is ARIS (aerobic/resistance/inspiratory muscle training) the optimal exercise training programme for chronic heart failure patients?

This editorial refers to ‘Combined aerobic/resistance/inspiratory muscle training as the ‘optimum’ exercise program for patients with chronic heart failure: ARISTOS-HF randomized clinical trial’, by I. D Laoutaris et al. pp. 1626–1635.

Exercise-based cardiac rehabilitation (EBCR) in chronic heart failure (CHF) has received the highest class of recommendation and level of evidence (IA) since 2008. This was reconfirmed in the 2016 update and the recent expert consensus report on clinical practice update (2019).¹ Exercise training (ET) has been granted IA class of recommendation in the updated position paper from the Secondary Prevention and Rehabilitation section of the European Association of Preventive Cardiology.² Although there is an agreement on the ET modes that have an effect on the patients’ exercise tolerance, muscular and cardiovascular improvement, well-being and quality of life (QoL), an inter-clinician variance, and disagreement exists on which ET mode or combination is the best and should be broadly prescribed. Moderate continuous aerobic training (MCAT) is the most established but high-intensity interval training (HIIT) has been proposed although not superior to MCAT.³ Additionally, resistance training (RT) may increase muscle strength, and aerobic capacity⁴ while inspiratory muscle training (IMT) improves exercise capacity and QoL.⁵ Exercise training combinations have been also investigated. The idea of settling down all arguments, proposing an optimal way to exercise patients, was well addressed but not completely resolved by the use of a digital training and decision support system; the EXPERT tool (https://www.escardio.org/Education/Practice-Tools/CVD-prevention-toolbox/expert-tool).⁶

Laoutaris et al. try to provide an answer with regards to the ‘optimum’ ET programme investigating the idea of combining aerobic training (AT) with RT and IMT.⁷ The name of this unique ET programme is ARIS which resembles to the name of Ares (Mars) the powerful ancient Greek god. They contacted a multicenter randomized clinical trial under the name ARISTOS-HF. ‘Aristos’ means ‘optimal’ in Greek language and this is what the study investigates: whether ARIS is powerful enough to become optimal! The final answer as to whether this statement is true is the resultant of the answers given to the following scientific questions:

Do we really need this study? This is an obvious question since our experience so far with all forms of AT might seem adequate enough so as we are not in need of an additional ET mode. Unfortunately, this is not the case if we consider the HF-ACTION results with modest improvements in exercise capacity and the patients’ health status; not to mention the modest significant reduction in all hard endpoints.⁸ The subsequent effort to replace aerobic endurance training with HITT has also failed to show any significant differences with regards to left ventricular remodelling or aerobic capacity.³ Additionally, RT if combined with interval training increases VO_2peak and with endurance continuous training increases VO_2peak, muscle strength and HRQoL.^9,10 Finally, the combination of IMT and AT provided additional benefits in functional and serum biomarkers compared to AT alone.¹¹ This latter study (Vent-HeFT) was contacted by almost the same group of investigators and actually resulted in the formulation of the ‘aerobic/resistance/inspiratory (ARIS) muscle training hypothesis in heart failure’.¹²

Is the ARIS hypothesis worth of investigating? The ARIS hypothesis is a comprehensive extension of the ‘muscle hypothesis’ which seems nowadays rather inadequate to fully explain the modest responses to ET demonstrated in the modern randomized control trials (RCT). Aerobic/resistance/inspiratory hypothesis still includes the primary idea that exercise intolerance and prognosis in chronic HF is due to peripheral muscle pathology but extends it to also include the pathological respiratory muscle function which is often present in this population. Therefore, from the exercise physiology point of view, it seems extremely interesting to investigate the superiority of an ARIS programme over the already used modes of ET.¹³

Has this study been designed to deliver solid results thus being able to fully test this hypothesis? The RCT design of the study, the comparison of almost all already investigated ET modes or their combinations with the ARIS programme, the ET design according to current recommendations and the use of satisfactory total programme duration and ET frequency and duration (12 weeks, 3 sessions per week, and 60 min per session) makes this study quite adequate and rather demanding in terms of design. We can easily understand how difficult it is to contact an RCT with four different EBCR groups. Nevertheless, these groups were balanced in terms of HF aetiology and the recruited cohort was balanced with regards to New York Heart Association class; almost half of the patients had a moderate to severe physical activity limitation. On the other hand, we would prefer to see more women recruited (common disadvantage of the majority of EBCR clinical trials)¹⁴ and the number of patients meeting the target sample size. A withdrawal/lost in follow-up of 15% was low and shows good adherence to the programmes. Of major importance, the majority of the patients were under contemporary medication (high percentage of b-blockers usage and also aldosterone antagonists) and participated in an exercise based multi-disciplinary CR programme which included all core components (i.e. phycosocial support, nutrition counselling, or home visits) and not in an ET programme alone.² This allows us to assume that all differences found in aerobic and functional capacity, cardiac remodelling, and QoL could be attributed to the different ET modalities.

Are the results convincing that ARIS is powerful and the optimal mode for ET in CHF? A definite answer to this question is not easy but thanks to this trial a new scientific and fruitful discussion will certainly start. The ARIS programme obviously affected towards improvement the exercise capacity of the patients when compared with the other ET modes. VO_2peak was not statistically significant improved but there was a significant improvement in exercise time, also reflected in the 6-min walk test (6MWT). VO_2peak may have been generally considered as an important predictor of HF prognosis¹⁵ but a recent meta-analysis questions the validity of both VO_2peak and 6MWT after EBCR as mortality and hospitalization prognosticators.¹⁶ Although the non-significant trend towards increasing VO_2peak may be explained by the rather short duration of the ET programme,¹⁷ the different cardiopulmonary exercise testing (CPET) protocols used or the non-optimal number of the recruited patients, we still cannot ignore the 19% VO_2peak increase in the ARIS group which was the highest among all ET groups. Furthermore, we cannot ignore the higher circulatory power that ARIS achieved compared to the other ET modes. This index (the production of VO_2peak and SBP_peak) is extremely important; by incorporating cardiac output, blood pressure, and arteriovenous oxygen difference in peak exercise it actually represents the cardiac pumping response to exercise. It is also of greater prognostic value than VO_2peak in HF patients under b-blockers.¹⁸ The improvement of this index shows the high potentiality of ARIS as a powerful ET programme. We did not expect to see any differences in global left ventricular function considering the short duration of the study.¹⁹ However, the effect of ARIS on reducing left ventricular end-systolic dimension (LVESD) more that AT or AT/RT cannot be overseen since LVESD is a strong predictor of reverse remodelling.²⁰ Finally, the QoL improvement that ARIS demonstrated over AT and AT/RT could be attributed to the unquestionable enhancement of inspiratory and limb muscle function which consequently lead to the demonstrated dyspnoea reduction both in CPX and the 6MWT.

What has to be the next step for ARIS? ARISTOS-HF trial was a highly demanding and difficult to conduct RCT the results of which may seem preliminary but are extremely important. The ARIS muscle hypothesis has been thoroughly tested for the first time, the combination of three different ET modes is now proposed as a potent ET programme showing many benefits over the existing ones and IMT is introduced as an equal ET component. In the future, we expect to see the ARIS programme fighting for a leading position in the field of EBCR through a long-term (>6 months) RCT, recruiting a balanced population of men and women, powered enough to provide answers also on clinical endpoints (i.e. hospitalizations). As we tend nowadays to diverge from the ‘one size fits all’ CR approach towards tailor fit programmes along the lines of precision medicine, ARIS has also to prove whether it is feasible for any CHF patient or remains the basis of a more personalized protocol in which the three different ET components could be precisely adjusted with regards to patient assessment, ET frequency, intensity, time-duration, and type of exercise so as to achieve the optimal (‘aristos’) ET programme. A personalized expansion of ARIS in CHF patients with co-morbidities that could be benefited by the IMT component (i.e. cachectic/frail, chronic obstructive pulmonary disease, cardio-oncology) or its integration in a tele-rehabilitation setup could be extremely challenging. In any case, by improving exercise capacity and QoL while showing anti-remodelling properties, ARIS has already shown some of its strong powers (Figure 1).

Figure 1

ARIS programme effects and future challenges. ARIS, aerobic/resistance/inspiratory muscle training; CHF, chronic heart failure; CR, cardiovascular rehabilitation; LVESD, left ventricular end-systolic dimension; QoL, quality of life; 6MWT, 6-min walk test.

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Conflict of interest: none declared.

The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Preventive Cardiology or of the European Society of Cardiology.

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