Barbosa, M

Bicho, M

Falcão, LM

Matos, A

English

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CAN CLASSIC BIOMARKERS BE PROGNOSTICATORS IN HEART FAILURE? - DATA FROM THE REFERENCE STUDYMário Barbosa1, Andreia Matos2,3, Manuel Bicho2,3, Luiz Menezes Falcão3,41 Department of Internal Medicine, Hospital Lusíadas Lisboa, Lisbon, Portugal; 2 Genetics Laboratory and Environmental Health Institute-ISAMB, Faculty of Medicine, University ofLisbon, Portugal; 3 Instituto de Investigação Científica Bento da Rocha Cabral; 4 Faculty of Medicine, University of Lisbon; 5 Department of Internal Medicine, Santa Maria Hospital,Lisbon, Portugal.OBJECTIVE: We explored the relationship of aminoterminal b-type natriuretic peptide (NT-proBNP) and highly sensitive troponin t (hsTNT) with short-termprognosis (defined as the period of 90 days post-discharge), namely readmission due to HF and overall death, and long-term overall death.BACKGROUND: Although the role of natriuretic peptides and troponins as risk stratification markers is gaining importance, the current state of scientific knowledge does notallow to affirm that they are definitely established for the prognostic evaluation of heart failure (HF).PARTNERSHIPS            N=65 HF patientsMean age: 79.2 (SD 10.8)Median follow-up: 13.7 months[Q1: 6.7 to Q3: 18.9]RESULTS Characteristics Patients (n=65)Age, mean (SD) 79.2 ± 10.8Female Gender, n (%) 37 (56.9)Hypertension, n (%) 58 (89.2)Type 2 Diabetes, n (%) 25 (38.5)Dyslipidemia, n (%) 41 (63.1)Obesity, n (%) 17 (26.2)Atrial Fibrillation, n (%) 28 (43.1)Family History of CVD, n (%) 31 (47.7)Tabagism, n (%) 21 (32.3)Chronic Kidney Disease, n (%) 34 (52.3)GFR (Baseline), median 57.8 (43.8 - 82.2)GFR (Admission), median 47.9 (33.2 - 68.1)Previous Acute Myocardial Infarction, n (%) 27 (41.5)Hypertensive Cardiomyopathy, n (%) 44 (67.7)Ischemic Cardiomyopathy, n (%) 22 (33.8)Valvular Cardiomyopathy, n (%) 56 (86.2)LVEF, mean (SD) 50.38 ± 19.07NYHA class III, n (%) 43 (66.2)ACE Inhibitor, n (%) 43 (66.2)Beta Blocker, n (%) 38 (58.5)Mineralocorticoid Receptor Antagonists, n (%) 19 (29.2)Angiotensin II Receptor Blocker, n (%) 11 (16.9)Loop Diuretic, n (%) 54 (83.1)Digoxin, n (%) 8 (12.3)hsTnT, median 51.0 (31 - 117)Values are median (IQR), n (%), or mean±SD. IQR: interquartile range and minimum/maximum, SD: standard deviation, CVD: cardiovascular disease, GFR: glomerular filtration rate, ACE: Angiotensin-Converting-Enzyme.• Spearman's correlation showed an inversely proportional relation between NT-proBNP and LVEF (Coefficient: r = -0.365, P-value = 0.004).• The same statistical method evidenced an inverse correlation between NT-proBNP and baseline and admission GFR (Coefficient: r = -0.418, P-value<0.001 for baseline GFR and Coefficient: r = -0.438, P-value <0.001 for admissionGFR).METHODS: NT-proBNP and hsTnT were assessed in patients hospitalized with acute decompensated heart failure in class III or IV of New York Heart Association (NYHA).Comparison between patients with and without each of the events was performed for all variables using t-test or Wilcoxon Rank test as applicable. Categorical variables weresummarized by relative and absolute frequencies, and compared using chi-squared test or Fisher’s Exact test as applicable. Univariate Cox proportional hazard model was used toevaluate the relationship between variables and outcomes. The optimal cut-off value for each biomarker to predict the events was defined using the Youden Index. TheSpearman’s correlation coefficient was used to determine the relationship between variables.CONCLUSION: Elevated NT-proBNP and hsTNT determinations correlated with short and long-term outcomes. Moreover, the combined evaluation of the myonecrosis marker and of themyocardial stretch peptide provided complementary prognostic data, since we could not achieve a link with risk of early readmission when each biomarker was assessed isolatedly. Themortality hazard associated to elevated admission NT-proBNP was greater in the early post-discharge period weaning along with follow-up, which fundaments the theory that the first90 days post-discharge are critical. We highlight that elevated discharge values of NT-proBNP posed a greater long-term mortality risk than admission concentrations, which supportsthe utility of serial determinations and that, probably, aiming a lowest NT-proBNP as possible during hospitalization could be advantageous.#409Youden IndexCut-off NPV PPVNT-proBNP 21336 ng/L 0.91 0.64NT-proBNP admission: 100 ng/L[HR: 1.005, 95% CI: 1.002-1.009, P-value=0.002]Hazard of short-term mortalityNT-proBNP admission Cut-off: 21336 ng/L[HR: 10.524, 95% CI: 3.013-36.757, P-value<0.001]NT-proBNP admission: 100 ng/L[HR: 1.003, 95% CI: 1.001-1.006, P-value=0.013]NT-proBNP admission Cut-off: 21336 ng/L[HR: 4.791, 95% CI: 1.885-12.178, P-value<0.001]Hazard of long-term mortalityFigure 3: Long-term mortality - Kaplan Meier: Admission NT-proBNP ≥21336 ng/LNT-proBNP at admission to hospitalizationFigure 2: Short-term mortality - Kaplan Meier: Admission NT-proBNP ≥21336 ng/LFigure 1: Admission and discharge NT-proBNP levels and its association with obesity.Figure 4: Baseline comparison of subjects by long-term mortality status: Discharge NT-proBNP. Figure 5: Long-term mortality - Kaplan Meier: hsTnT ≥52 ng/L.NT-proBNP discharge: 100 ng/L[HR: 1.006, 95% CI: 1.001-1.011, P=0.028]Long-term mortality riskhsTNT at admission to hospitalization• As for long-term mortality, values of hsTnT ≥52 ng/L aggravated the hazard close to 5 times (HR: 4.942, 95% CI: 1.044-23.388, P value=0.044), which heightened to almost 6times if NT-proBNP at admission ≥21336 ng/L was considered (HR: 5.827, 95% CI: 1.168-29.075, P value=0.032).Youden IndexCut-off NPV PPVhsTNT 52 ng/L 0.85 0.62hsTNT admission: 10 ng/L[HR: 1.077, 95% CI: 1.007-1.151, P-value=0.030]Long-term mortality riskNT-proBNP≥21336 ng/LhsTnT≥52 ng/L[HR: 8.607, 95% CI: 1.413-52.427, P-value=0.02]8.6%Risk of early readmission 

Can Classic Biomarkers be Prognosticators in Heart Failure? - Data from the REFERENCE study

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Can Classic Biomarkers be Prognosticators in Heart Failure? - Data from the REFERENCE study

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