Biological variation of high sensitive Troponin T in stable heart failure patients with ischemic or dilated cardiomyopathy.

INTRODUCTION: High sensitive Troponin (hsTn) assays enable detection of minimal marker elevation in heart failure patients previously deemed Troponin negative. Biovariability, reference change values (RCV), and index of individuality (II) have not been previously described for hsTnT although serial testing is important in interpreting low concentrations. For these values, a difference between ischemic heart disease (IHD) and dilated cardiomyopathy (dCMP) appears conceivable. METHODS: Change in hsTnT was determined alongside with clinical variables in 41 patients with stable chronic systolic dysfunction at 2-week-, 1-month-, 2-month-, and 3-month-intervals (IHD n = 17; dCMP n = 24). RESULTS: HsTnT was detectable in all patients. Individual hsTnT-variations at 2-week, 1-month, 2-month, and 3-month follow-up were 7.2, 22.6, 28.9, and 15.7%, respectively, corresponding to RCVs of 20.1, 62.5, 80.0, and 43.3%, respectively, for crude values. For log-normalised values, individual variations were 3.2, 2.8, 2.7, and 3.5%, respectively, corresponding to RCVs of 8.8, 7.9, 7.6, and 9.7%, respectively. The II was 0.03 to 0.33 according to interval. Aetiology of heart failure was not a consistent determinant of variation (p = 0.28; p = 0.07; p = 0.98; p = 0.03 for 2-week, 1-month, 2-month, and 3-month follow-up, respectively). CONCLUSION: While short-term biological variation of hsTnT is low, it becomes relatively more important for intermediate follow-up. It is not related to aetiology of heart failure. The corresponding indices of individuality indicate high individuality of values.

Reference change values and determinants of variability of NT-proANP and GDF15 in stable chronic heart failure.

Biovariability, reference change values (RCV), and index of individuality (IOI) have not been previously described for NT-proANP or GDF15. Also, the relation of changes of these markers to other clinical variables or biomarkers is unknown. In 41 patients with stable chronic systolic dysfunction, NT-proANP and GDF15 were measured alongside with clinical variables/markers comprising NT-proBNP, hsTnT, and hsCRP at four sampling intervals (2 weeks, 1-, 2-, 3-month intervals). At 2 weeks, 1-, 2-, and 3-month-follow-up, individual NT-proANP variations were 27.1, 22.5, 28.9, 15.6%, respectively, corresponding to RCVs of 53.2, 62.4, 80.2, and 43.2%, respectively. For GDF15, the respective individual variations were 6.8, 4.1, 5.5, 6.8%, corresponding to RCVs of 18.8, 11.5, 15.3 and 18.8%. Neither changes of NT-proANP or GDF15 correlated with changes in any of the clinical variables or biomarkers examined except for GDF15 with renal function. Baseline hormonal levels and clinical variables did not consistently influence the extent of change. The IOI was 0.19-0.35 according to interval for NT-proANP and 0.06-0.09 for GDF 15. In patients with CHF preselected for clinical stability changes of NT-proANP at intermediate follow-up do not correlate with changes in other variables; changes of GDF15 inversely correlate with renal function. The extent of change in both markers is not related to baseline hormonal levels or other baseline variables. RCVs are high for NT-proANP and low for GDF15, while inter-individual variation is high in GDF15 and intermediate in NT-proANP.

Variability of N-terminal probrain natriuretic peptide in stable chronic heart failure and its relation to changes in clinical variables.

BACKGROUND: We investigated the variability of N-terminal probrain natriuretic peptide (NT-proBNP) and its relation to known confounding variables in patients with stable chronic heart failure who were on a stable optimized medication regimen. METHODS: At 4 sampling intervals (14-day, 1-month, 2-month, and 3-month) the results for NT-proBNP measurements and several clinical variables were measured in samples from 41 patients with chronic systolic dysfunction who met 21 prespecified criteria for stability. RESULTS: Mean within-person NT-proBNP variabilities expressed as percentage CV were 17.6%, 18.9%, 15.5%, and 16.2% at 14-day, 1-month, 2-month, and 3-month follow-up, respectively, and the corresponding reference change values were 34.6%, 52.5%, 43.1%, and 45.0%, respectively. Within-person variability of NT-proBNP was not found to be associated with renal function, weight, or waist circumference. Likewise, age, sex, baseline NT-proBNP, New York Heart Association functional class, and ejection fraction did not influence variability of NT-proBNP. The index of individuality ranged from 0.07-0.15 depending on the time interval between test results. CONCLUSIONS: Although other reported studies have revealed variations in the range of 80%, in this prespecified stable heart-failure population variation of NT-proBNP at 14-day, 1-month, 2-month, and 3-month follow-up was lower and was not related to renal function or weight. In view of the low index of individuality we observed, within-person variation is quite low compared to between-person variation. Consideration of these facts is important for the interpretation of clinical trials and the use of NT-proBNP in monitoring patients with heart failure.