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Only Large Changes (>80%) in BNP Modify Risk in Patients with Chronic Heart Failure
The 11th Annual Scientific Meeting
HFSA
S105
108 Only Large Changes (O80%) in BNP Modify Risk in Patients with Chronic Heart Failure Wayne L. Miller1, Karen A. Hartman1, Mary F. Burritt1, Diane E. Grill1, John C. Burnett1, Allan S. Jaffe1; 1Cardiovascular, Mayo Clinic, Rochester, MN Introduction: B-type natriuretic peptide (BNP) has been used to estimate prognosis in chronic heart failure (HF) patients. Large biologic variability, however, potentially limits the usefulness of serial measurements. The magnitude of change in BNP levels necessary to be clinically meaningful remains to be established. Accordingly, we assessed changes (increases and/or decreases) in BNP during two years of follow-up to attempt to answer this question. Methods: A cohort of 172 ambulatory Class III-IV HF patients with complete serial (enrollment to event or last follow up) BNP data were studied from June 2001 to January 2004. Primary endpoint was death/cardiac transplantation (tx) or hospitalizations for HF. The magnitude of BNP changes was categorized as: 1) No change: !20% increase or decrease from enrollment; 2) $ 20 to #80% increase or decrease; 3) O80% increase or decrease. Results: The majority of patients were male (76%), Class III (92%), with an ischemic etiology (55%). At enrollment the median BNP value was 305 (CI: 118-521) pg/mL. BNP was elevated (O95th percentile for age and gender normal population) in 122 (64.2%) patients. Changes in BNP levels are shown in the Table. Conclusion: BNP increases O80% were associated with increased risk and decreases O80% with reduced risk for mortality/tx and hospitalization. Lesser increases and decreases or no change in BNP levels were associated with no change in risk from that provided by an elevated BNP level at enrollment. During clinical follow-up in ambulatory HF patients only large changes in BNP levels (either increases or decreases) are predictive of death and the need for hospitalization. There is no pattern associated with low risk.
107 Combined Assays of Big ET-1 and Nt-proANP Improve the Predictive Value of Survival in Severe Congestive Heart Failure Jean-Marie Ketelslegers1, Sylvie A. Ahn2, Michel F. Rousseau2; 1Endocrine Laboratory, University of Louvain; 2Division of Cardiology, University of Louvain, Brussels, Belgium Background: Big ET-1 and Nt-proANP have prognostic significance in congestive heart failure (CHF) but their combined predictive value had never been assessed in comparison to their isolated predictive value in patients with severe CHF. Methods: We analyzed the combined predictive values of big ET-1 and Nt-proANP, determined by Elisa (Biomedica Gruppe, Wien, Austria), in 47 fully treated patients with severe CHF (NYHA III-IV, mean EF: 20 6 6%; mean age: 66 6 8 years; ischemic n 5 38, non-ischemic n 5 9). Thirthy healthy subjects served as controls. The mean followup was 81 6 15 months. Data were assessed by the Cox proportional hazards model and Kaplan-Meier survival analysis (JMP software; SAS Institute). Results: In CHF patients, big ET-1 and Nt-proANP (fmol/mL; geometric mean and range) were significantly higher than in controls (p ! 0.001): 3.8 (1.3-14.5) vs 1.0 (0.8e1.2) and 5528 (1129e18180) vs 1692 (1466e1952), respectively. Overall median survival was of 26 months. Big ET-1 above 4.0 fmol/mL (10 vs 31 months; log-rank; Kaplan-Meier: p ! 0.0002) or Nt-proANP above 6483 (10 vs 43 months; p ! 0.0012) are strong predictors of survival but the predictive power is much improved when both markers are combined (p ! 0.0001) (figure). Conclusion : Predictive survival in severe CHF is much better when big ET-1 and Nt-proANP are combined rather than if considered separately. This approach identifies a subgroup of patients with a very high mortality risk eligible for more aggressive therapies.
BNP Increases (N 5 69) $ 20%e#80% O80% No Change (N 5 27) BNP Decreases (N 5 76) $ 20%e#80% O80%
Mortality/Tx
Hospitalizations
8/27 (29.6%) 17/42 (40.5%) 10/27 (37%)
15/27 (55.6%) 22/42 (52.4%) 12/27 (44.4%)
12/48 (25.0%) 5/28 (17.8%)
18/48 (37.5%) 5/28 (17.8%)
109 Norepinephrine Density Is Decreased in Human Failing Myocardium Nezam Haider1, Pardise Moraghebi1, J. Zhang1, Arnold Jacobson1, Chandrashekhar1, Jagat Narula1; 1Cardiovascular Diseases, University California, Irvine Medical Center, Irvine, CA
Y. of
Background: Norepinephrine (NE) is released from its storage granules when the nerve is stimulated and enters the synaptic cleft to bind to alpha and beta-receptors on the effector cells. Chemical signaling is terminated by a rapid reuptake of neurotransmitter into presynaptic nerve terminals mainly via NE transport systems (NET). Previous studies in animal model of heart failure showed that both increased neuronal release of NE and decreased efficiency of NET contribute to decreased myocardial NE content which correlates directly with decreasing the left ventricular ejection fraction. Objective: For the first time we designed this study to analyze NET density in human failing myocardium as a possible cause of decreased NE reuptake. Methods and results: Eight explanted hearts were obtained from patients undergoing heart transplantation; 4 patients with idiopathic dilated cardiomyopathy (IDCM), and 4 patients with ischemic cardiomyopathy (ISCM). Eight normal myocardial tissues, obtained from victims of road accidents were used as control group. In addition, in 5 subjects with end-stage HF myocardial tissues were obtained at the time of Left Ventricular Assist Device (LVAD) placement and from explanted heart at the time of transplant. NET protein density was determined by immunoblot and compared by densitometric analysis. NET density was significantly lower in failing myocardium compared to control group with lowest density in IDCM group. NET density significantly increased after LVAD placement in 4 of 5 subjects with severe HF. In Conclusion: Present study shows that NET density is decreased in human subjects with HF, and may normalize following LVAD placement.
110 NT-proBNP Levels and Risk Factors for Congestive Heart Failure in Korean General Population Based on a Large Cohort Study B.S. Yoo1, K.H. Lee1, M.S. Ahn1, J.Y. Kim1, S.H. Lee1, J.H. Yoon1, K.H. Choe1; 1 Cardiology, Wonju College of Medicine, Yonsei University, Wonju, Kangwondo, Republic of Korea Median survival of the subgroup with both markers above cut-offs was of 5 months (C), while it was over 91 months when markers were below these limits (A). Patients with only one marker above the cut-off had a median survival of 22 months (B).
Background: BNP or NT-proBNP levels may serve as a useful marker of cardiovascular risk in a screening setting of the general population. We evaluated that reference value and clinical usefulness of NT-proBNP at high risk of CHF within the Korean
HFSA
S105
108 Only Large Changes (O80%) in BNP Modify Risk in Patients with Chronic Heart Failure Wayne L. Miller1, Karen A. Hartman1, Mary F. Burritt1, Diane E. Grill1, John C. Burnett1, Allan S. Jaffe1; 1Cardiovascular, Mayo Clinic, Rochester, MN Introduction: B-type natriuretic peptide (BNP) has been used to estimate prognosis in chronic heart failure (HF) patients. Large biologic variability, however, potentially limits the usefulness of serial measurements. The magnitude of change in BNP levels necessary to be clinically meaningful remains to be established. Accordingly, we assessed changes (increases and/or decreases) in BNP during two years of follow-up to attempt to answer this question. Methods: A cohort of 172 ambulatory Class III-IV HF patients with complete serial (enrollment to event or last follow up) BNP data were studied from June 2001 to January 2004. Primary endpoint was death/cardiac transplantation (tx) or hospitalizations for HF. The magnitude of BNP changes was categorized as: 1) No change: !20% increase or decrease from enrollment; 2) $ 20 to #80% increase or decrease; 3) O80% increase or decrease. Results: The majority of patients were male (76%), Class III (92%), with an ischemic etiology (55%). At enrollment the median BNP value was 305 (CI: 118-521) pg/mL. BNP was elevated (O95th percentile for age and gender normal population) in 122 (64.2%) patients. Changes in BNP levels are shown in the Table. Conclusion: BNP increases O80% were associated with increased risk and decreases O80% with reduced risk for mortality/tx and hospitalization. Lesser increases and decreases or no change in BNP levels were associated with no change in risk from that provided by an elevated BNP level at enrollment. During clinical follow-up in ambulatory HF patients only large changes in BNP levels (either increases or decreases) are predictive of death and the need for hospitalization. There is no pattern associated with low risk.
107 Combined Assays of Big ET-1 and Nt-proANP Improve the Predictive Value of Survival in Severe Congestive Heart Failure Jean-Marie Ketelslegers1, Sylvie A. Ahn2, Michel F. Rousseau2; 1Endocrine Laboratory, University of Louvain; 2Division of Cardiology, University of Louvain, Brussels, Belgium Background: Big ET-1 and Nt-proANP have prognostic significance in congestive heart failure (CHF) but their combined predictive value had never been assessed in comparison to their isolated predictive value in patients with severe CHF. Methods: We analyzed the combined predictive values of big ET-1 and Nt-proANP, determined by Elisa (Biomedica Gruppe, Wien, Austria), in 47 fully treated patients with severe CHF (NYHA III-IV, mean EF: 20 6 6%; mean age: 66 6 8 years; ischemic n 5 38, non-ischemic n 5 9). Thirthy healthy subjects served as controls. The mean followup was 81 6 15 months. Data were assessed by the Cox proportional hazards model and Kaplan-Meier survival analysis (JMP software; SAS Institute). Results: In CHF patients, big ET-1 and Nt-proANP (fmol/mL; geometric mean and range) were significantly higher than in controls (p ! 0.001): 3.8 (1.3-14.5) vs 1.0 (0.8e1.2) and 5528 (1129e18180) vs 1692 (1466e1952), respectively. Overall median survival was of 26 months. Big ET-1 above 4.0 fmol/mL (10 vs 31 months; log-rank; Kaplan-Meier: p ! 0.0002) or Nt-proANP above 6483 (10 vs 43 months; p ! 0.0012) are strong predictors of survival but the predictive power is much improved when both markers are combined (p ! 0.0001) (figure). Conclusion : Predictive survival in severe CHF is much better when big ET-1 and Nt-proANP are combined rather than if considered separately. This approach identifies a subgroup of patients with a very high mortality risk eligible for more aggressive therapies.
BNP Increases (N 5 69) $ 20%e#80% O80% No Change (N 5 27) BNP Decreases (N 5 76) $ 20%e#80% O80%
Mortality/Tx
Hospitalizations
8/27 (29.6%) 17/42 (40.5%) 10/27 (37%)
15/27 (55.6%) 22/42 (52.4%) 12/27 (44.4%)
12/48 (25.0%) 5/28 (17.8%)
18/48 (37.5%) 5/28 (17.8%)
109 Norepinephrine Density Is Decreased in Human Failing Myocardium Nezam Haider1, Pardise Moraghebi1, J. Zhang1, Arnold Jacobson1, Chandrashekhar1, Jagat Narula1; 1Cardiovascular Diseases, University California, Irvine Medical Center, Irvine, CA
Y. of
Background: Norepinephrine (NE) is released from its storage granules when the nerve is stimulated and enters the synaptic cleft to bind to alpha and beta-receptors on the effector cells. Chemical signaling is terminated by a rapid reuptake of neurotransmitter into presynaptic nerve terminals mainly via NE transport systems (NET). Previous studies in animal model of heart failure showed that both increased neuronal release of NE and decreased efficiency of NET contribute to decreased myocardial NE content which correlates directly with decreasing the left ventricular ejection fraction. Objective: For the first time we designed this study to analyze NET density in human failing myocardium as a possible cause of decreased NE reuptake. Methods and results: Eight explanted hearts were obtained from patients undergoing heart transplantation; 4 patients with idiopathic dilated cardiomyopathy (IDCM), and 4 patients with ischemic cardiomyopathy (ISCM). Eight normal myocardial tissues, obtained from victims of road accidents were used as control group. In addition, in 5 subjects with end-stage HF myocardial tissues were obtained at the time of Left Ventricular Assist Device (LVAD) placement and from explanted heart at the time of transplant. NET protein density was determined by immunoblot and compared by densitometric analysis. NET density was significantly lower in failing myocardium compared to control group with lowest density in IDCM group. NET density significantly increased after LVAD placement in 4 of 5 subjects with severe HF. In Conclusion: Present study shows that NET density is decreased in human subjects with HF, and may normalize following LVAD placement.
110 NT-proBNP Levels and Risk Factors for Congestive Heart Failure in Korean General Population Based on a Large Cohort Study B.S. Yoo1, K.H. Lee1, M.S. Ahn1, J.Y. Kim1, S.H. Lee1, J.H. Yoon1, K.H. Choe1; 1 Cardiology, Wonju College of Medicine, Yonsei University, Wonju, Kangwondo, Republic of Korea Median survival of the subgroup with both markers above cut-offs was of 5 months (C), while it was over 91 months when markers were below these limits (A). Patients with only one marker above the cut-off had a median survival of 22 months (B).
Background: BNP or NT-proBNP levels may serve as a useful marker of cardiovascular risk in a screening setting of the general population. We evaluated that reference value and clinical usefulness of NT-proBNP at high risk of CHF within the Korean