Editorials
Exercise Capacity – Just a Powerful Prognostic Predictor, or a Potential Therapeutic Target in Patients With Chronic Heart Failure? –
2015 Volume 79 Issue 12 Pages 2547-2548
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2015 Volume 79 Issue 12 Pages 2547-2548
HF is the main cause of morbidity and mortality in cardiac patients, and therefore, predicting the prognosis of patients with HF is critically important for physicians when they stratify or counsel a patient to make therapeutic decisions. To date, many prognostic prediction models have been proposed and validated in patients with chronic HF.1–5
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Exercise capacity, though measured by different methods and expressed in various variables, has been shown in many studies to be an independent and powerful prognostic predictor in patients with chronic HF,1,3–7 but only a few prognostic models for HF have incorporated a measure of exercise capacity as a component.1,3–5 Specifically, the model by Frankenstein et al3 incorporated the 6-min walk distance (6MWD), the “HF and A Controlled Trial Investigating Outcomes of Exercise TraiNing” (HF-ACTION) model used duration in an exercise test,4 and the HF Survival Score (HFSS)1 and the Metabolic Exercise Cardiac and Kidney Index (MECKI) score5 incorporated peak oxygen uptake (V̇O2).
Of these, the MECKI score is unique because it incorporates variables in the cardiopulmonary exercise test (CPX), such as peak V̇O2 (% of the predicted value) and the slope of the relation between minute ventilation and carbon dioxide production (V̇E/V̇CO2 slope), in addition to cardiac function (left ventricular ejection fraction [LVEF]), renal function (estimated glomerular filtration rate), and metabolic parameters (hemoglobin and serum Na+). Originally, the MECKI score was built from multivariate analysis of the prognostic data of 2,716 patients in the MECKI HF registry in 13 Italian HF centers, which registered HF patients in NYHA classes I–III, with LVEF <40%, and able to perform a CPX.5
Validity of MECKI Score in Elderly HF PatientsIn this issue of the Journal, Carubelli et al8 demonstrate that the MECKI score has an equivalent prognostic predictive power in young (age <70) and elderly patients (age ≥70) with chronic HF. This finding is clinically relevant and important because, despite the fact that HF patients are mainly elderly, most of the previous prognostic models incorporating exercise variables have been validated in relatively young patient populations. In fact, the average or median age of the original study population was 50 years in the HFSS,1 59 years in the HF-ACTION model,4 and 60 years in the original MECKI score,5 all of which are much younger than the age of real-world HF patients.
The strength of the current study8 is the recruitment of a relatively large number of elderly HF patients (age ≥70years, 990 patients, 26% of the total cohort) from the multicenter HF registry. Therefore, the patient characteristics would be closer to those in the real-world compared with previous studies that recruited patients from randomized trials.4 In addition, Carubelli et al used “percentage of predicted peak V̇O2” normalized for age, sex, and body weight rather than peak V̇O2 in ml/kg/min, because peak V̇O2 is known to be age- and sex-dependent.9 Furthermore, the study included patients with peak respiratory exchange ratio (RER) <1.0 on CPX,5 which had often been treated as submaximal and unreliable, but has been recently considered acceptable, because both peak V̇O2 and V̇E/V̇CO2 slope have been shown to reliably predict prognosis even in patients with peak RER <1.0.10
Conversely, a limitation of the Carubelli study is the exclusion of patients who were unable to perform a CPX, an inevitable limitation of HF studies using CPX, which may have resulted in a selection bias toward a healthier HF patient cohort. An alternative way to avoid this limitation may be to use the 6-min walk test instead of a CPX, because a comparable prognostic utility has been shown for the 6MWD and peak V̇O2 in ambulatory systolic HF patients.11 However, there remains a concern whether the 6MWD can be totally substituted for peak V̇O2, because the 6MWD has been reported as less sensitive to changes in peak V̇O2 in the range >500 m.12
Is Exercise Capacity Just a Powerful Prognostic Predictor or a Potential Therapeutic Target in HF?On the basis of the finding that exercise capacity is a powerful predictor of the prognosis in chronic HF patients, we may anticipate that a therapy aiming to improve exercise capacity would improve the prognosis in these patients (Figure). Although there is no direct evidence demonstrating that improving exercise capacity per se leads to an improvement in HF prognosis, several mechanisms through which exercise training may improve HF prognosis have been postulated.13,14
Predictors of prognosis and/or potential therapeutic targets in patients with chronic heart failure (HF). Yellow boxes indicate previously reported predictors of HF prognosis, and blue boxes with dotted blue arrows indicate therapeutic interventions toward therapeutic targets. Exercise capacity is a powerful predictor of HF prognosis, yet to be shown as an important therapeutic target. BNP, B-type natriuretic peptide; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; Ex, exercise; HT, hypertension; NYHA, New York Heart Association classes; RAA, renin-angiotensin-aldosterone; V̇O2, oxygen uptake.
In fact, an observational study showed that an improvement in peak V̇O2 after exercise training was an independent predictor of better prognosis in HF patients,15 and a post-hoc analysis of HF-ACTION suggested a dose-response relation between exercise volume and an improvement in prognosis.16 In this context, whether recently proposed newer training modalities (such as high-intensity interval training or electrical muscle stimulation) improve HF prognosis may deserve attention.
In conclusion, Carubelli et al have successfully demonstrated the validity of the MECKI prognostic score incorporating CPX variables in elderly HF patients.8 Further studies are necessary to address whether exercise capacity is not only a powerful prognostic predictor but also an important therapeutic target in patients with HF.
