relation of cystatin c to natriuretic peptide, creatinine clearance, and prognosis in patients with...

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109 Long-Term Clinical Variation of N-Terminal-Pro-Brain-Natriuretic-Peptide in Stable Chronic Heart Failure Patients Morten Schou 1 , Finn Gustafsson 2 , Andreas Kjaer 3 , Per R. Hildebrandt 1 ; 1 Cardiology and Endocrinology, Frederiksberg University Hospital, DK-Frederiksberg, Denmark; 2 Cardiology, Rigshospital University Hospital, DK-Copenhagen, Denmark; 3 Nuclear Medicine and Clinical Physiology, Rigshospitalet University Hospital, DK- Copenhagen, Denmark Introduction: The proposed use of N-terminal-pro-brain-natriuretic-peptide (NT- proBNP) for monitoring of chronic heart failure (CHF) patients will require accurate information about long-term clinical variation (CV) of the peptide. The aim of the present study was therefore to identify long-term CV of NT-proBNP in stable CHF patients. Methods: Medication, biochemical variables and NYHA-class were re- corded at one and two year follow up in patients treated in our heart failure clinic. Only patients without changes in medication and NYHA class, who were not hospi- talised or died in the period from first follow-up until 12 months after the second follow-up were included. A total of 78 out of 328 patients fulfilled the criteria. Per- cent-changes were calculated as (Level 2-year -Level 1-year )/Level 1-year * 100 %. Clinical variation was calculated as the year-to-year-variation-coefficient: SD/mean. Results: Demographic data (median and range): Age (yrs): 73 [51-82]; Height (cm): 182 [149- 192]; Sex (males/females): 50/28; NYHA class (I/II/III): 8/62/8; left ventricular ejec- tion fraction (fraction): 30 [13-45]; Year-to-year CVof NT-proBNP was calculated to 30 % (median) (range: 0-111 %) (%-changes range: -87%-397 %). Log-transforma- tion of NT-proBNP (skewed to the right) reduced the year-to-year CV to 4.7 % (range: 0-22 %) (%-changes range: -18 %-38 %). Conclusions: Long-term CV of plasma concentrations of NT-proBNP in stable CHF patients is approximately 30 % but the variation is substantial (range: 0-111 %). Therefore, high long-term CV of NT-proBNP does not necessarily carry prognostic significance within the subse- quent 12 months and changes have to be interpreted with caution in stable patients. Plasma concentrations of NT-proBNP exhibited lognormal distribution and the low CV of log(NT-proBNP) indicates that NT-proBNP levels are fairly constant during stable conditions. 110 Relation of Cystatin C to Natriuretic Peptide, Creatinine Clearance, and Prognosis in Patients with Chronic Systolic Heart Failure Wilson Tong 1 , Frederick Van Lente 2 , Richard W. Troughton 3 , Gary S. Francis 1 , Randall C. Starling 1 , Allan L. Klein 1 , W. H. Wilson Tang 1 ; 1 Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH; 2 Clinical Pathology, Cleveland Clinic, Cleveland, OH; 3 Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand Introduction: Cystatin C is a new marker that has been implicated as a more refined predictor of renal function and an independent prognostic marker in chronic heart failure (HF). We sought to better understand the relationship of cystatin C with dis- ease severity as measured by plasma N-terminal pro B-type natriuretic peptide (NT- proBNP) and estimated creatinine clearance (CrCl), and their relative prognostic values. Methods: We identified 138 consecutive subjects with chronic, stable, systolic heart failure (NYHA II-IV, LVEF 35%) and measured plasma levelsof cys- tatin C and NT-proBNP. CrCl was estimated by the Cockcroft-Gault equation. We prospectively examined long-term clinical outcomes (death, transplant, and HF hos- pitalizations) over 41 6 17 months. Results: Plasma cystatin C levels increased with worsening renal insufficiency (Spearman’s r 5 0.57, p!0.0001). Using multivariable logistic regression, only estimated CrCl and plasma NT-proBNP levels were found to have independent associations with plasma cystatin C levels. When considering the subgroup of patients with preserved renal function (CrCl $ 60 mL/min), plasma NT-proBNP is still associated with plasma cystatin C levels. Upon adjustment for CrCl, increasing plasma cystatin C quartiles remained a significant risk factor for ad- verse outcome (RR: 1.70, 95% CI: 1.26 - 2.33, p!0.001), and independent of plasma NT-proBNP levels (Figure). Conclusion: In our study cohort of patients with chronic systolic heart failure, plasma cystatin C correlates with plasma NT-proBNP levels even in the setting of preserved renal function. Cystatin C remains an independent prognostic marker in chronic systolic heart failure after adjusting for creatinine clearance and plasma NT-proBNP levels. 111 Economic Impact of Brain Natriuretic Peptide Measurement for Evaluation of Dyspneic Patients in the Emergency Department: A Randomized, Controlled Study Lyle J. Olson 1 , Raquel M. Schears 1 , Alfredo L. Clavell 1 , Keith R. Seid 1 , Paula J. Santrach 1 , Kent R. Bailey 1 , Kirsten Hall Long 1 ; 1 Cardiovascular Diseases, Mayo Clinic, Rochester, MN Measurement of brain natriuretic peptide (BNP) in dyspneic patients increases diag- nostic accuracy for congestive heart failure (CHF). Limited information is available regarding economic outcomes attributable to BNP assay. The aim of this study was to assess the economic impact of BNP assay in elderly dyspneic patients presenting to emergency department (ED). Methods. Dyspneic patients $ 65 years were enrolled in a randomized, controlled trial; hemodynamically unstable patients were excluded. BNP (Biosite assay) levels were measured prior to physician assessment with ran- domization in 1:1 ratio to either BNP 1) level reported or 2) level not reported. ED physicians made triage decisions guided by clinical judgment and nomogram for interpretation of BNP level. Primary economic outcome was mean total hospital cost per subject. Secondary outcomes included admission rate, service assignment, discharge diagnosis and length of stay. Differences between groups were compared by rank sum, chi-square, and nonparametric bootstrap methods, as appropriate. Costs reflect 2005 constant dollars. Results. 207 patients were randomized to 2 groups comprised of 103 and 104 subjects, respectively. There were no differences in subject characteristics including comorbid conditions, service assignment or BNP levels (ta- ble). 55 subjects in BNP level reported group and 66 in level not reported group had BNP level O 200 pg/ml. No differences in admission rates were observed (78% vs. 86%; p 5 0.21). Mean length of stay of admitted patients was similar at 4.2 days. To- tal direct medical costs, on average, were $3,066 less for subjects with BNP reported although this difference was not significant (p 5 0.23, 95% CI of mean cost differ- ence: $-10,091, $3,226). Conclusion. Although measurement of BNP may have di- agnostic utility, we did not observe a significant effect on overall admission rates or total cost. However, the large standard deviation of mean costs and skewed cost data limited statistical power. Additional research is warranted to determine whether trends observed in favor of BNP measurement are of economic importance. Total Group (N 5 207) BNP (N 5 103) No BNP (n 5 104) p-values Age (years) 78.5 80.1 0.11 Gender (M/F) 50M 54M 0.63 LVEF % (N 5 61, 65) 50.9 6 16.0 51.0 6 15.6 0.98 Serum creatinine (mg/dL) 1.6 6 1.3 1.5 6 0.8 0.21 BNP level (N 5 100, 95)(pg/ml) 530 6 752 591 6 627 0.54 S34 Journal of Cardiac Failure Vol. 12 No. 6 Suppl. 2006

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Page 1: Relation of Cystatin C to Natriuretic Peptide, Creatinine Clearance, and Prognosis in Patients with Chronic Systolic Heart Failure

109Long-Term Clinical Variation of N-Terminal-Pro-Brain-Natriuretic-Peptidein Stable Chronic Heart Failure PatientsMorten Schou1, Finn Gustafsson2, Andreas Kjaer3, Per R. Hildebrandt1; 1Cardiologyand Endocrinology, Frederiksberg University Hospital, DK-Frederiksberg, Denmark;2Cardiology, Rigshospital University Hospital, DK-Copenhagen, Denmark; 3NuclearMedicine and Clinical Physiology, Rigshospitalet University Hospital, DK-Copenhagen, Denmark

Introduction: The proposed use of N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) for monitoring of chronic heart failure (CHF) patients will require accurateinformation about long-term clinical variation (CV) of the peptide. The aim of thepresent study was therefore to identify long-term CV of NT-proBNP in stable CHFpatients. Methods: Medication, biochemical variables and NYHA-class were re-corded at one and two year follow up in patients treated in our heart failure clinic.Only patients without changes in medication and NYHA class, who were not hospi-talised or died in the period from first follow-up until 12 months after the secondfollow-up were included. A total of 78 out of 328 patients fulfilled the criteria. Per-cent-changes were calculated as (Level2-year-Level1-year)/Level1-year* 100 %. Clinicalvariation was calculated as the year-to-year-variation-coefficient: SD/mean. Results:Demographic data (median and range): Age (yrs): 73 [51-82]; Height (cm): 182 [149-192]; Sex (males/females): 50/28; NYHA class (I/II/III): 8/62/8; left ventricular ejec-tion fraction (fraction): 30 [13-45]; Year-to-year CV of NT-proBNP was calculated to30 % (median) (range: 0-111 %) (%-changes range: -87%-397 %). Log-transforma-tion of NT-proBNP (skewed to the right) reduced the year-to-year CV to 4.7 %(range: 0-22 %) (%-changes range: -18 %-38 %). Conclusions: Long-term CV ofplasma concentrations of NT-proBNP in stable CHF patients is approximately 30% but the variation is substantial (range: 0-111 %). Therefore, high long-term CVof NT-proBNP does not necessarily carry prognostic significance within the subse-quent 12 months and changes have to be interpreted with caution in stable patients.Plasma concentrations of NT-proBNP exhibited lognormal distribution and the lowCV of log(NT-proBNP) indicates that NT-proBNP levels are fairly constant duringstable conditions.

110Relation of Cystatin C to Natriuretic Peptide, Creatinine Clearance, andPrognosis in Patients with Chronic Systolic Heart FailureWilson Tong1, Frederick Van Lente2, Richard W. Troughton3, Gary S. Francis1,Randall C. Starling1, Allan L. Klein1, W. H. Wilson Tang1; 1CardiovascularMedicine, Cleveland Clinic, Cleveland, OH; 2Clinical Pathology, Cleveland Clinic,Cleveland, OH; 3Medicine, Christchurch School of Medicine and Health Sciences,Christchurch, New Zealand

Introduction: Cystatin C is a new marker that has been implicated as a more refinedpredictor of renal function and an independent prognostic marker in chronic heartfailure (HF). We sought to better understand the relationship of cystatin C with dis-ease severity as measured by plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) and estimated creatinine clearance (CrCl), and their relative prognosticvalues. Methods: We identified 138 consecutive subjects with chronic, stable,

systolic heart failure (NYHA II-IV, LVEF 35%) and measured plasma levels of cys-tatin C and NT-proBNP. CrCl was estimated by the Cockcroft-Gault equation. Weprospectively examined long-term clinical outcomes (death, transplant, and HF hos-pitalizations) over 41 6 17 months. Results: Plasma cystatin C levels increased withworsening renal insufficiency (Spearman’s r 5 0.57, p!0.0001). Using multivariablelogistic regression, only estimated CrCl and plasma NT-proBNP levels were found tohave independent associations with plasma cystatin C levels. When considering thesubgroup of patients with preserved renal function (CrCl $ 60 mL/min), plasmaNT-proBNP is still associated with plasma cystatin C levels. Upon adjustment forCrCl, increasing plasma cystatin C quartiles remained a significant risk factor for ad-verse outcome (RR: 1.70, 95% CI: 1.26 - 2.33, p!0.001), and independent of plasmaNT-proBNP levels (Figure). Conclusion: In our study cohort of patients with chronicsystolic heart failure, plasma cystatin C correlates with plasma NT-proBNP levelseven in the setting of preserved renal function. Cystatin C remains an independentprognostic marker in chronic systolic heart failure after adjusting for creatinineclearance and plasma NT-proBNP levels.

111Economic Impact of Brain Natriuretic Peptide Measurement for Evaluation ofDyspneic Patients in the Emergency Department: A Randomized, ControlledStudyLyle J. Olson1, Raquel M. Schears1, Alfredo L. Clavell1, Keith R. Seid1, Paula J.Santrach1, Kent R. Bailey1, Kirsten Hall Long1; 1Cardiovascular Diseases, MayoClinic, Rochester, MN

Measurement of brain natriuretic peptide (BNP) in dyspneic patients increases diag-nostic accuracy for congestive heart failure (CHF). Limited information is availableregarding economic outcomes attributable to BNP assay. The aim of this study was toassess the economic impact of BNP assay in elderly dyspneic patients presenting toemergency department (ED). Methods. Dyspneic patients $ 65 years were enrolledin a randomized, controlled trial; hemodynamically unstable patients were excluded.BNP (Biosite assay) levels were measured prior to physician assessment with ran-domization in 1:1 ratio to either BNP 1) level reported or 2) level not reported.ED physicians made triage decisions guided by clinical judgment and nomogramfor interpretation of BNP level. Primary economic outcome was mean total hospitalcost per subject. Secondary outcomes included admission rate, service assignment,discharge diagnosis and length of stay. Differences between groups were comparedby rank sum, chi-square, and nonparametric bootstrap methods, as appropriate. Costsreflect 2005 constant dollars. Results. 207 patients were randomized to 2 groupscomprised of 103 and 104 subjects, respectively. There were no differences in subjectcharacteristics including comorbid conditions, service assignment or BNP levels (ta-ble). 55 subjects in BNP level reported group and 66 in level not reported group hadBNP level O 200 pg/ml. No differences in admission rates were observed (78% vs.86%; p 5 0.21). Mean length of stay of admitted patients was similar at 4.2 days. To-tal direct medical costs, on average, were $3,066 less for subjects with BNP reportedalthough this difference was not significant (p 5 0.23, 95% CI of mean cost differ-ence: $-10,091, $3,226). Conclusion. Although measurement of BNP may have di-agnostic utility, we did not observe a significant effect on overall admission ratesor total cost. However, the large standard deviation of mean costs and skewed costdata limited statistical power. Additional research is warranted to determine whethertrends observed in favor of BNP measurement are of economic importance.

Total Group (N 5 207)BNP

(N 5 103)No BNP(n 5 104) p-values

Age (years) 78.5 80.1 0.11Gender (M/F) 50M 54M 0.63LVEF % (N 5 61, 65) 50.9 6 16.0 51.0 6 15.6 0.98Serum creatinine (mg/dL) 1.6 6 1.3 1.5 6 0.8 0.21BNP level (N 5 100, 95)(pg/ml) 530 6 752 591 6 627 0.54

S34 Journal of Cardiac Failure Vol. 12 No. 6 Suppl. 2006