Abstract
BACKGROUND: Decreased renal function has been consistently associated with increased mortality among patients with systolic heart failure. The relationship between estimated glomerular filtration rate (eGFR) and other high-risk features including reduced cardiorespiratory fitness has not been previously reported in this patient population. METHODS: The HF-ACTION trial was a prospective, randomized trial of exercise therapy versus usual care in patients with systolic heart failure. Patients with class 2-4 heart failure and a left ventricular ejection fraction of ≤ 35% were recruited. Serum creatinine was measured up to 1 year prior to entry. The 4-variable modified Modification of Diet in Renal Disease equation was used to calculate eGFR. Peak oxygen consumption (peak VO(2)) was directly measured using gas exchange analysis during progressive exercise testing to volitional fatigue or adverse signs/symptoms. RESULTS: Of 2,091 subjects (mean age 59 ± 13 years, with serum creatinine available at baseline), 72% were men, and 61, 33, and 5% were Caucasians, African Americans, and others, respectively. Older age, diabetes, and hypertension were all more frequent with declining eGFR. The Pearson correlation between eGFR and peak VO(2) was 0.22 (p < 0.0001). Age was negatively correlated with both eGFR (r = -0.44, p < 0.0001) and peak VO(2) (r = -0.27, p < 0.0001). The peak VO(2) tended to decline across decreasing levels of eGFR. Individuals with an eGFR <30 ml/min/1.73 m(2) had, on average, 2.1 high-risk features including peak VO(2) <14 ml/kg/min, age >75 years, diabetes, and functional class 3-4 symptoms. Conversely, those with an eGFR >90 ml/min/1.73 m(2) had relatively few (1.0) high-risk characteristics. CONCLUSIONS: Reduced renal filtration is associated with impaired cardiorespiratory fitness and a clustering of high-risk features in systolic heart failure patients which portend a more complicated course and higher all-cause mortality.