The Influence of Body Mass Index on Clinical Interpretation of Established and Novel Biomarkers in Acute Heart Failure.

BACKGROUND: Body mass index (BMI) is a known confounder for natriuretic peptides, but its influence on other biomarkers is less well described. We investigated whether BMI interacts with biomarkers' association with prognosis in patients with acute heart failure (AHF). METHODS AND RESULTS: B-type natriuretic peptide (BNP), high-sensitivity cardiac troponin I (hs-cTnI), galectin-3, serum neutrophil gelatinase-associated lipocalin (sNGAL), and urine NGAL were measured serially in patients with AHF during hospitalization in the AKINESIS (Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic Heart Failure) study. Cox regression analysis was used to determine the association of biomarkers and their interaction with BMI for 30-day, 90-day and 1-year composite outcomes of death or HF readmission. Among 866 patients, 21.2%, 29.7% and 46.8% had normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) or obese (≥ 30 kg/m2) BMIs on admission, respectively. Admission values of BNP and hs-cTnI were negatively associated with BMI, whereas galectin-3 and sNGAL were positively associated with BMI. Admission BNP and hs-cTnI levels were associated with the composite outcome within 30 days, 90 days and 1 year. Only BNP had a significant interaction with BMI. When BNP was analyzed by BMI category, its association with the composite outcome attenuated at higher BMIs and was no longer significant in obese individuals. Findings were similar when evaluated by the last-measured biomarkers and BMIs. CONCLUSIONS: In patients with AHF, only BNP had a significant interaction with BMI for the outcomes, with its association attenuating as BMI increased; hs-cTnI was prognostic, regardless of BMI.

Minimal Clinically Important Differences in 6-Minute Walk Test in Patients With HFrEF and Iron Deficiency.

BACKGROUND: The 6-minute walk test (6MWT) is widely used to measure exercise capacity; however, the magnitude of change that is clinically meaningful for individuals is not well established in heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: To calculate the minimal clinically important difference (MCID) for change in exercise capacity in the 6MWT in iron-deficient populations with HFrEF. METHODS: In this pooled secondary analysis of the FAIR-HF and CONFIRM-HF trials, mean changes in the 6MWT from baseline to weeks 12 and 24 were calculated and calibrated against the Patient Global Assessment (PGA) tool (clinical anchor) to derive MCIDs in improvement and deterioration. RESULTS: Of 760 patients included in the 2 trials, 6MWT and PGA data were available for 680 (89%) and 656 (86%) patients at weeks 12 and 24, respectively. The mean 6MWT distance at baseline was 281 ± 103 meters. There was a modest correlation between changes in 6MWT and PGA from baseline to week 12 (r = 0.31; P < 0.0001) and week 24 (r = 0.43; P < 0.0001). Respective estimates (95% confidence intervals) of MCID in 6MWT at weeks 12 and 24 were 14 meters (5;23) and 15 meters (3;27) for a "little improvement" (vs no change), 20 meters (10;30) and 24 meters (12;36) for moderate improvement vs a "little improvement,", -11 meters (-32;9.2) and -31 meters (-53;-8) for a "little deterioration" (vs no change), and -84 meters (-144;-24) and -69 meters (-118;-20) for "moderate deterioration" vs a "little deterioration". CONCLUSIONS: The MCID for improvement in exercise capacity in the 6MWT was 14 meters-15 meters in patients with HFrEF and iron deficiency. These MCIDs can aid clinical interpretation of study data.