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The effect of nesiritide on serum levels of B-natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in patients admitted for decompensated congestive heart failure
S52
Journal of Cardiac Failure Vol. 10 No. 4 Suppl. 2004
126
128
The Relation between Plasma Brain Natriuretic Peptide Concentration and Length of Hospital Stay in Patients with Congestive Heart Failure Yasser M. Farra, Philip F. Binkley; Davis Heart and Lung Institute and the Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH
Does the Underlying Etiology Influence Plasma B-Type Natriuretic Peptide levels of Patients With Isolated Chronic Aortic Regurgiation and Preserved Left Ventricular Function? Roopinder Sandhu,1 W.H. Wilson Tang,2 Roger M. Mills,2 Gary S. Francis2; 1 Department of Medicine, MetroHealth Medical Center, Cleveland, OH; 2Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH
Objective: This study was designed to test the hypothesis that the degree of increase of plasma brain natriuretic peptide (BNP) is associated with length of hospital stay and readmission rate for patients with congestive heart failure (CHF). Background: Increases in plasma BNP levels have been associated with morbidity, mortality, response to therapy, and need for hospitalization in patients with congestive heart failure. Given that the severity of CHF symptoms may be related to the length of hospital stay, it is plausible that plasma BNP levels are related to the probability of hospital discharge. Methods: Clinical variables and plasma BNP measures were retrospectively obtained from 116 patients admitted with a primary diagnosis of congestive heart failure. Patients were stratified into two groups with Group I defined as those having BNP concentrations below the group median and Group II those with levels above the median. Survival functions and cumulative hazard functions were generated based on the stratified patient groups. Cox regression modeling was performed to assess the influence of other clinical variables on the association of BNP strata on length of hospital stay. Results: Survival analysis demonstrated that mean time to discharge for Group II patients was virtually twice that of Group I patients (10 ⫾ 7.7 vs 5.7 ⫾ 4.4 days, respectively). Cox regression modeling with forward selection of variables demonstrated a significant time dependent decrease in the likelihood of hospital discharge for patients in Group II as compared to patients in Group I despite the addition of other clinical variables. Other variables significantly associated with a decreased likelihood of hospital discharge which entered the Cox model were male gender, history of coronary artery disease, history of hypertension, and a history of diabetes. All showed a time dependent progressive decrease in probability of discharge. Patients in Group II were significantly more likely to be readmitted to the hospital (p ⫽ .003) than Group I patients and tended to be admitted at an earlier time following discharge (33 ⫾ 35 days vs 51 ⫾ 50 days; p ⫽ 0.15). These results were obtained regardless of whether CHF was due to systolic dysfunction or isolated diastolic dysfunction. Conclusions: Plasma BNP levels measured during hospital admission are associated with length of hospital stay and rate of readmission. These measures may identify patients who will benefit from more aggressive therapeutic interventions early in the hospital admission and may aid in hospital resource allocation.
Background: In patients with isolated, severe, chronic aortic regurgitation (AR) and preserved left ventricular (LV) function, the relationship between plasma BNP levels, LV dimensions, and underlying etiology has not been well defined. Methods: We reviewed 63 consecutive patients with isolated, severe, chronic aortic regurgitation (3-4+) and preserved left ventricular function (EF ⬎50%) by echo seen at the Cleveland Clinic between 10/02 – 9/03 with plasma BNP levels (Biosite) drawn at the time of their evaluation. We excluded patients with other concomitant valvular diseases (including aortic stenosis), prosthetic heart disease, or radiation-induced valvular diseases. Results: In our cohort (mean age 48 ⫾ 16 years, 76% male, 70% symptomatic, mean LVIDd 55 ⫾ 10 mm, mean LVIDs 35 ⫾ 8 mm), mean plasma BNP was 99 ⫾ 117 pg/mL (range 5-540 pg/mL). A trend towards higher plasma BNP levels in symptomatic compared to asymptomatic patients was observed (110 ⫾ 123 vs 74 ⫾ 101 pg/ml respectively, p ⫽ 0.13). Despite similar LV dimensions, plasma BNP levels were significantly lower among patients with AR caused by bicuspid value disease (n ⫽ 33) versus dilated aorta (n ⫽ 22) or endocarditis (n ⫽ 8) (ANOVA p ⬍ 0.05, Figure). Conclusion: Stable patients with chronic isolated AR and preserved LV function present with a wide range of plasma BNP levels that may vary according to their underlying etiologies. Overall, patients with chronic AR caused by bicuspid valve disease had significantly lower plasma levels of BNP when compared to other etiologies. Interpretation of plasma BNP values in patients with chronic isolated AR should take into account the underlying etiology of chronic AR.
127 Osteopontin Plasma Levels Are Elevated in Severe Congestive Heart Failure: Effects of Spironolactone Therapy Michel F. Rousseau,1 Sylvie A. Ahn,1 Ronald Van Beneden,2 Virginie de Coninck,2 Annie A. Robert,3 Jean-Marie Ketelslegers,2 Hubert G. Pouleur1; 1Division of Cardiology, University of Louvain, Brussels, Belgium; 2Diabetes and Nutrition Unit, University of Louvain, Brussels, Belgium; 3School of Public Health, University of Louvain, Brussels, Belgium Background: Congestive heart failure induces an upregulation of pro-inflammatory cytokines, possibly resulting in further vascular and myocardial damage. Little is known however on the activation of osteopontin (OPN), a cytokine produced by cardiomyocytes and endothelial cells. Methods: To clarify the potential involvement of OPN in severe congestive heart failure and the effect of an aldosterone receptor antagonist on this inflammatory marker, we measured plasma concentrations of OPN (normal value : 124–394 ng/mL) and evaluated the effects of spironolactone (Spiro, 25 mg daily), in a subgroup of 96 patients enrolled in RALES (NYHA III-IV, mean EF : 25%) at entry (T0) into study, at 3 months (T3) and at 6 months (T6) and compared the changes to Placebo group. 50 patients were included in the Spiro group and 46 in the Placebo group. Results: Data were expressed in geometric mean [95% CI] and compared using a Student t-test on a logtransformed scale (see table). At baseline, OPN levels were elevated with no significant differences between groups. At T3, significant OPN reductions from baseline were observed in Placebo and Spiro groups (-10%*, p ⬍ 0.05 and -16%**, p ⬍ 0.01). At T6, significant OPN reduction was observed only in the Spiro group (-8% NS and -20%**, p ⬍ 0.01). However, none of the between groups comparisons reached statistical significance. Conclusions: Our data indicate that OPN levels are elevated in severe congestive heart failure and that sustained decrease of OPN with Spiro could reflect a better control of inflammatory process. However, considering the absence of significant difference between groups, this reduced inflammatory response probably play a minor role among the mechanisms underlying the survival benefit of Spiro in congestive heart failure. OPN Placebo T0 T3 T6 T3/T0 T6/T0
987 890 898 0.90* 0.92
[886-1099] [805-985] [767-1051] [0.83-0.98] [0.79-1.07]
OPN Spiro 1012 877 840 0.84** 0.80**
[902-1135] [791-971] [761-928] [0.77-0.93] [0.71-0.89]
Placebo vs Spiro 0.77 0.69 0.52 0.38 0.06
129 The Effect of Nesiritide on Serum Levels of B-Natriuretic Peptide (BNP) and N-Terminal ProBNP (NT-proBNP) in Patients Admitted for Decompensated Congestive Heart Failure Robert L. Fitzgerald,1 Rosemary Cremo,2 Albert Chiu,2 Paul Clopton,2 Vikas Bhalla,3 Alan S. Maisel2,3; 1Department of Pathology, VA San Diego Healthcare System, San Diego,; 2VA San Diego Healthcare System, San Diego, CA; 3University of California, San Diego, CA Objective: The objective was to determine the effect of nesiritide (hBNP) in combination with standard therapy on the concentrations of BNP and NT-proBNP. Background: BNP is synthesized in cardiac ventricles as a prohormone (108 amino acids) and when released into peripheral circulation is cleaved into the active hormone BNP (AA 77-108) and an inactive amino terminal fragment NT-proBNP (AA 1-76). Methods: Three groups of acutely decompensated congestive heart failure (CHF) patients received nesiritide for 24, 36 or 48 hours (N ⫽ 10, 9 and 8 respectively). Serial blood samples were collected. BNP and NT-proBNP were measured. Results: One hour following a bolus dose of nesiritide, the median concentrations of BNP increased about three fold (⬍0.001). The median baseline, 1 hr infusion, 24 hr infusion, 12 hr post infusion, and 24 hr post infusion concentrations of BNP were 1000, 3000, 2000, 660 and 780 pg/ml respectively (N ⫽ 27). The 4 and 6 hour post infusion mean percent change in BNP were significantly lower (⬍0.05) than baseline. As hypothesized, NTproBNP decreased with nesiritide administration. The median baseline, 1hr infusion, 24 hr infusion, 12 hr post infusion, and 24 hr post infusion concentrations of NTproBNP were 6500, 6600, 4700, 5600 and 5600 pg/mL respectively (N ⫽ 27). From the time point 12 hrs after initiation of therapy through 6 hours post infusion, the mean percent change in NT-proBNP were significantly (⬍0.05) lower than baseline. Conclusion: Nesiritide, in combination with standard therapy, significantly lowered the endogenous concentrations of natriuretic peptides during infusion and after dosing was completed.
Journal of Cardiac Failure Vol. 10 No. 4 Suppl. 2004
126
128
The Relation between Plasma Brain Natriuretic Peptide Concentration and Length of Hospital Stay in Patients with Congestive Heart Failure Yasser M. Farra, Philip F. Binkley; Davis Heart and Lung Institute and the Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH
Does the Underlying Etiology Influence Plasma B-Type Natriuretic Peptide levels of Patients With Isolated Chronic Aortic Regurgiation and Preserved Left Ventricular Function? Roopinder Sandhu,1 W.H. Wilson Tang,2 Roger M. Mills,2 Gary S. Francis2; 1 Department of Medicine, MetroHealth Medical Center, Cleveland, OH; 2Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH
Objective: This study was designed to test the hypothesis that the degree of increase of plasma brain natriuretic peptide (BNP) is associated with length of hospital stay and readmission rate for patients with congestive heart failure (CHF). Background: Increases in plasma BNP levels have been associated with morbidity, mortality, response to therapy, and need for hospitalization in patients with congestive heart failure. Given that the severity of CHF symptoms may be related to the length of hospital stay, it is plausible that plasma BNP levels are related to the probability of hospital discharge. Methods: Clinical variables and plasma BNP measures were retrospectively obtained from 116 patients admitted with a primary diagnosis of congestive heart failure. Patients were stratified into two groups with Group I defined as those having BNP concentrations below the group median and Group II those with levels above the median. Survival functions and cumulative hazard functions were generated based on the stratified patient groups. Cox regression modeling was performed to assess the influence of other clinical variables on the association of BNP strata on length of hospital stay. Results: Survival analysis demonstrated that mean time to discharge for Group II patients was virtually twice that of Group I patients (10 ⫾ 7.7 vs 5.7 ⫾ 4.4 days, respectively). Cox regression modeling with forward selection of variables demonstrated a significant time dependent decrease in the likelihood of hospital discharge for patients in Group II as compared to patients in Group I despite the addition of other clinical variables. Other variables significantly associated with a decreased likelihood of hospital discharge which entered the Cox model were male gender, history of coronary artery disease, history of hypertension, and a history of diabetes. All showed a time dependent progressive decrease in probability of discharge. Patients in Group II were significantly more likely to be readmitted to the hospital (p ⫽ .003) than Group I patients and tended to be admitted at an earlier time following discharge (33 ⫾ 35 days vs 51 ⫾ 50 days; p ⫽ 0.15). These results were obtained regardless of whether CHF was due to systolic dysfunction or isolated diastolic dysfunction. Conclusions: Plasma BNP levels measured during hospital admission are associated with length of hospital stay and rate of readmission. These measures may identify patients who will benefit from more aggressive therapeutic interventions early in the hospital admission and may aid in hospital resource allocation.
Background: In patients with isolated, severe, chronic aortic regurgitation (AR) and preserved left ventricular (LV) function, the relationship between plasma BNP levels, LV dimensions, and underlying etiology has not been well defined. Methods: We reviewed 63 consecutive patients with isolated, severe, chronic aortic regurgitation (3-4+) and preserved left ventricular function (EF ⬎50%) by echo seen at the Cleveland Clinic between 10/02 – 9/03 with plasma BNP levels (Biosite) drawn at the time of their evaluation. We excluded patients with other concomitant valvular diseases (including aortic stenosis), prosthetic heart disease, or radiation-induced valvular diseases. Results: In our cohort (mean age 48 ⫾ 16 years, 76% male, 70% symptomatic, mean LVIDd 55 ⫾ 10 mm, mean LVIDs 35 ⫾ 8 mm), mean plasma BNP was 99 ⫾ 117 pg/mL (range 5-540 pg/mL). A trend towards higher plasma BNP levels in symptomatic compared to asymptomatic patients was observed (110 ⫾ 123 vs 74 ⫾ 101 pg/ml respectively, p ⫽ 0.13). Despite similar LV dimensions, plasma BNP levels were significantly lower among patients with AR caused by bicuspid value disease (n ⫽ 33) versus dilated aorta (n ⫽ 22) or endocarditis (n ⫽ 8) (ANOVA p ⬍ 0.05, Figure). Conclusion: Stable patients with chronic isolated AR and preserved LV function present with a wide range of plasma BNP levels that may vary according to their underlying etiologies. Overall, patients with chronic AR caused by bicuspid valve disease had significantly lower plasma levels of BNP when compared to other etiologies. Interpretation of plasma BNP values in patients with chronic isolated AR should take into account the underlying etiology of chronic AR.
127 Osteopontin Plasma Levels Are Elevated in Severe Congestive Heart Failure: Effects of Spironolactone Therapy Michel F. Rousseau,1 Sylvie A. Ahn,1 Ronald Van Beneden,2 Virginie de Coninck,2 Annie A. Robert,3 Jean-Marie Ketelslegers,2 Hubert G. Pouleur1; 1Division of Cardiology, University of Louvain, Brussels, Belgium; 2Diabetes and Nutrition Unit, University of Louvain, Brussels, Belgium; 3School of Public Health, University of Louvain, Brussels, Belgium Background: Congestive heart failure induces an upregulation of pro-inflammatory cytokines, possibly resulting in further vascular and myocardial damage. Little is known however on the activation of osteopontin (OPN), a cytokine produced by cardiomyocytes and endothelial cells. Methods: To clarify the potential involvement of OPN in severe congestive heart failure and the effect of an aldosterone receptor antagonist on this inflammatory marker, we measured plasma concentrations of OPN (normal value : 124–394 ng/mL) and evaluated the effects of spironolactone (Spiro, 25 mg daily), in a subgroup of 96 patients enrolled in RALES (NYHA III-IV, mean EF : 25%) at entry (T0) into study, at 3 months (T3) and at 6 months (T6) and compared the changes to Placebo group. 50 patients were included in the Spiro group and 46 in the Placebo group. Results: Data were expressed in geometric mean [95% CI] and compared using a Student t-test on a logtransformed scale (see table). At baseline, OPN levels were elevated with no significant differences between groups. At T3, significant OPN reductions from baseline were observed in Placebo and Spiro groups (-10%*, p ⬍ 0.05 and -16%**, p ⬍ 0.01). At T6, significant OPN reduction was observed only in the Spiro group (-8% NS and -20%**, p ⬍ 0.01). However, none of the between groups comparisons reached statistical significance. Conclusions: Our data indicate that OPN levels are elevated in severe congestive heart failure and that sustained decrease of OPN with Spiro could reflect a better control of inflammatory process. However, considering the absence of significant difference between groups, this reduced inflammatory response probably play a minor role among the mechanisms underlying the survival benefit of Spiro in congestive heart failure. OPN Placebo T0 T3 T6 T3/T0 T6/T0
987 890 898 0.90* 0.92
[886-1099] [805-985] [767-1051] [0.83-0.98] [0.79-1.07]
OPN Spiro 1012 877 840 0.84** 0.80**
[902-1135] [791-971] [761-928] [0.77-0.93] [0.71-0.89]
Placebo vs Spiro 0.77 0.69 0.52 0.38 0.06
129 The Effect of Nesiritide on Serum Levels of B-Natriuretic Peptide (BNP) and N-Terminal ProBNP (NT-proBNP) in Patients Admitted for Decompensated Congestive Heart Failure Robert L. Fitzgerald,1 Rosemary Cremo,2 Albert Chiu,2 Paul Clopton,2 Vikas Bhalla,3 Alan S. Maisel2,3; 1Department of Pathology, VA San Diego Healthcare System, San Diego,; 2VA San Diego Healthcare System, San Diego, CA; 3University of California, San Diego, CA Objective: The objective was to determine the effect of nesiritide (hBNP) in combination with standard therapy on the concentrations of BNP and NT-proBNP. Background: BNP is synthesized in cardiac ventricles as a prohormone (108 amino acids) and when released into peripheral circulation is cleaved into the active hormone BNP (AA 77-108) and an inactive amino terminal fragment NT-proBNP (AA 1-76). Methods: Three groups of acutely decompensated congestive heart failure (CHF) patients received nesiritide for 24, 36 or 48 hours (N ⫽ 10, 9 and 8 respectively). Serial blood samples were collected. BNP and NT-proBNP were measured. Results: One hour following a bolus dose of nesiritide, the median concentrations of BNP increased about three fold (⬍0.001). The median baseline, 1 hr infusion, 24 hr infusion, 12 hr post infusion, and 24 hr post infusion concentrations of BNP were 1000, 3000, 2000, 660 and 780 pg/ml respectively (N ⫽ 27). The 4 and 6 hour post infusion mean percent change in BNP were significantly lower (⬍0.05) than baseline. As hypothesized, NTproBNP decreased with nesiritide administration. The median baseline, 1hr infusion, 24 hr infusion, 12 hr post infusion, and 24 hr post infusion concentrations of NTproBNP were 6500, 6600, 4700, 5600 and 5600 pg/mL respectively (N ⫽ 27). From the time point 12 hrs after initiation of therapy through 6 hours post infusion, the mean percent change in NT-proBNP were significantly (⬍0.05) lower than baseline. Conclusion: Nesiritide, in combination with standard therapy, significantly lowered the endogenous concentrations of natriuretic peptides during infusion and after dosing was completed.