Renal Function and Exercise Training in AmbulatoryHeart Failure Patients With a Reduced Ejection Fraction

doi:10.1016/j.amjcard.2018.06.011

The American Journal of Cardiology

Volume 122, Issue 6, 15 September 2018, Pages 999-1007

https://doi.org/10.1016/j.amjcard.2018.06.011 Get rights and content

Patients with chronic kidney disease (CKD) and/or end-stage renal disease are less active and experience significant functional limitations. The impact of a structured aerobic exercise intervention on outcomes in ambulatory heart failure (HF) patients with comorbid CKD is unknown. HF-ACTION enrolled 2,331 outpatients with HF and a reduced ejection fraction (i.e., ≤35%) from April 2003 to February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to the presence of CKD, defined as an estimated glomerular filtration rate <60 ml/min/1.73 m². A total of 2,091 patients (90%) had serum creatinine measured and were included in the final analytical cohort. The prevalence of CKD was 41% at baseline. In patients with and without CKD, respectively, the incidence of all-cause death and hospitalization was 75% and 63% over a median follow-up of 30 months. After adjusting for potential confounders, CKD was associated with increased risk of the composite of all-cause mortality and hospitalization (hazard ratio 1.18, 95% confidence interval 1.04 to 1.33; p value ≤0.01). With the exception of a marginally greater improvement in exercise duration in response to aerobic exercise training (estimate ± standard error: 0.9 ± 0.2 minutes vs 1.4 ± 0.1 minutes; p value = 0.01), there was no interaction between treatment arm and CKD on functional status, health-related quality of life, or clinical outcomes (p value ≥0.05 for all interactions). In conclusion, the prevalence of CKD was high in ambulatory reduced ejection fraction patients and was associated with a poorer overall prognosis but not a differential response to aerobic exercise training.

Section snippets

Methods

The study design¹² and primary results13, 14 of the HF-ACTION trial (ClinicalTrials.gov Number: NCT00047437) have been previously reported. HF-ACTION was a multicenter, randomized, placebo-controlled trial designed to assess the long-term efficacy and safety of a structured exercise intervention in medically stable outpatients with long-term HFrEF. A total of 2,331 patients were recruited from 82 centers in the United States, Canada, and France from April 2003 to February 2007. Enrollment

Results

A total of 2,091 ambulatory HFrEF patients (90%) had sCr measured at baseline and were included in the final analytical cohort (Supplementary Table 1). At the time of enrollment, 41% of patients (n = 856) met the prespecified definition for CKD (i.e., eGFR <60 ml/min/m²; Figure1). In contrast, less than 5% of patients (n = 101) had an eGFR <30 ml/min/m² (i.e., Stage 4 and/or 5).

Patients with comorbid CKD tended to be significantly older, were more likely to self-identify as white, and had a

Discussion

The present analysis found the prevalence of comorbid CKD to be approximately 40% in outpatients with HFrEF. There are 3 commonly used GFR estimating equations for sCr, including the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and CKD-EPI, which were derived and validated in disparate study populations and as a result may provide different estimates of the prevalence of CKD and have variable accuracy and prognostic value. The purported advantage of the CKD-EPI equation is

Disclosure

APA is supported by a National Heart, Lung, and Blood Institute (NHLBI) T32 postdoctoral training grant (5T32HL069749). All other authors declare no relevant financial disclosures.