- Email: [email protected]
Early Elevations in BNP up to Two Months before Actual Decompensation Predict Heart Failure Hospitalizations
S36 Journal of Cardiac Failure Vol. 15 No. 6S Suppl. 2009 a substantial amount of research has elucidated its usefulness in diagnosing heart failure, risk stratification, and monitoring, but only little is known about its value in predicting the length of hospital stay (LHS) in patients admitted with CHF exacerbation. Objectives: To identify the predictors of prolonged hospital stay in patients with systolic CHF exacerbation with special emphasis on the predictive value of NT-proBNP. Design and Setting: A prospective study in a tertiary heart care setting. Methods: After exclusion of other causes of elevated NT-proBNP, patients with systolic CHF are enrolled. The LHS for those patients is calculated once the patient is medically clear for discharge to exclude placement issues. Admission NT-proBNP, age, gender, New York Heart Association (NYHA) class, ejection fraction (EF), and presence of two or more organ systems affected are evaluated for each patient. A total of 1127 patients’ constitutes the study population. Results: While NT-ProBNP is correlated with the LHS (r 5 0.49, p 5 0.004), on multivariate analysis the most significant LHS predictor was patient’s age (p!0.001) followed by affection of two or more organ systems (p!0.01) and EF (p50.03). Gender, NYHA class and NT-proBNP do not appear to predict the LHS in our study. Conclusion: NT-proBNP does not appear to predict the LHS in patients admitted with CHF exacerbation.
decompensated HF (p!.0001). Patients without HF hospitalizations had stable BNP levels over 292 days. Patients who had a BNP measurement within 2 weeks of hospitalization (mean 5.5 days) had a significant increase in their BNP level detected as early as 148 days prior to decompensation. In the 5 days before decompensation, BNP levels were not significantly different from BNP at the time of hospital admission.
109 The Degree of Natriuretic Peptide System Activation in Stable and High Risk Chf Characterized by Increased Cystatin C Is Not Reflected in cGMP Activation John A. Schirger1, Horng H. Chen1, Josh Slusser2, David Hodge2, Denise Heublein1, Alessandro Cataliotti1, Sharon Sandberg1, John C. Burnett, Jr.1; 1Cardiovascular Diseases, Cardiorenal Research Laboratory, Mayo Clinic, Rochester, MN; 2 Department of Biostatistics, Mayo Clinic, Rochester, MN Background: Cardiorenal syndrome (CRS) is characterized by neurohumoral activation, sodium retention, ventricular dysfunction and congestion, and renal insufficiency (RI). The congestive heart failure (CHF) component evolves from asymptomatic, to stable symptomatic to overt symptomatic CHF. The natriuretic peptide system (NPS), including atrial (ANP) and brain (BNP) natriuretic peptides is progressively activated during progression of CHF. Less is known about the second messenger, cGMP, of the NPS across the spectrum of CHF. RI in CHF remains an important clinical challenge and Cystatin C is emerging as an important marker of RI. Further work is needed in characterizing Cystatin C across the spectrum of CHF and CRS. Methods: We prospectively looked at the NPS, including ANP, NT-proANP, BNP, and NT-proBNP, as well as plasma cGMP, NPS to cGMP ratios and Cystatin C in three groups of subjects: normal volunteers (n510), stable CHF patients (n519), and higher risk CHF patients (based on recent hospitalization for CHF, n520). The groups are reported in that order below. Statistical analysis was carried out by ANOVA with p!0.05 accepted as significant (*). Results: Each component of the NPS increased in the plasma across the three groups with highest levels in the high risk CHF. However, cGMP levels did not vary significantly across groups (626 6 303 vs 914 6 521 vs 959 6 509 pmol/mL, NS). The ratio NT-proANP/ cGMP increased across the 3 groups (0.60 6 0.55 vs 1.02 6 0.52 vs 1.46 6 1.08,*), but the ratios of ANP/cGMP, BNP/cGMP, and NT-proBNP/cGMP did not vary significantly across groups. Importantly, the mean Cystatin C levels increased with stable and high risk CHF groups (0.9 6 0.1 vs 1.4 6 0.3 vs 1.8 6 0.7,*). Conclusions: Despite the increase of each component of the NPS measured in the stable and high risk CHF, cGMP did not increase significantly across the same groups. Except for the ratio NT-proANP/cGMP, the ratios of the NPS to cGMP did not vary across groups either, suggesting the need to further refine our understanding of the coupling of the NPS with its second messenger, cGMP. Importantly, we report for the first time that Cystatin C varies across these phenotypes of CHF, suggesting that it may be an important marker of the development of CRS.
110 Early Elevations in BNP up to Two Months before Actual Decompensation Predict Heart Failure Hospitalizations Pam R. Taub1, Ellen Fitzpatrick1, Kimberly Tran1, Kevin Shah1, Kevin Jiang1, Paul Clopton1, Mitchell Saltzburg2, Robert Fitzgerald1, Alan Maisel1; 1Divison of Cardiology, Veterans Affairs San Diego Health Care System, University of California San Diego, San Diego, CA; 2Cardiology, Midwest Heart Specialists, Lombard, IL Background: B-type natriuretic peptide (BNP) has become mainstay in the diagnosis or exclusion of acute heart failure (HF). However, criteria for interpreting BNP changes in the outpatient setting and in detecting early subclinical congestion prior to clinical decompensation have not been established. Methods: 192 patients with HF and at least 5 BNP measurements over 6 month to 2 year period were recruited and over 2000 clinical visits with BNP levels were reviewed. Decompensation was defined as hospitalization for HF. Baseline BNP was determined to be the first BNP value upon study enrollment not corresponding to hospitalization. Results: 16 patients in the low baseline BNP group (BNP !200 pg/ml) and 59 patients in the high baseline BNP group (BNPO200 pg/ml) had hospital admissions. Patients in the low baseline BNP group had 564% increase (SEM 174.5) while those in the high baseline BNP group had a 60% increase (SEM 16) prior to hospitalization for
Conclusions: Patients with low baseline BNP had significantly larger changes in BNP levels before decompensation than those with higher baseline BNP levels. Patient without HF hospitalizations have stable BNP levels. In patients who had a BNP measurement within 2 weeks of hospitalization BNP concentrations showed a continuous rise before admission for decompensation. This represents an important window for diagnosis and therapeutic intervention. Understanding the clinical significance of changes in BNP levels prior to decompensation maybe useful in diagnosing subclinical congestion and preventing hospitalization.
111 Comparison of Cardiac and Inflammatory Biomarker Levels between Carriers and Non-Carriers of MYBPC3 Gene Mutation for Hypertrophic Cardiomyopathy W.H. Wilson Tang1, Baozhong Xin2, Leah Nye2, Sabe De1, Allen G. Borowski1, Stanley L. Hazen1, Heng Wang2; 1Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH; 2 Das Deutsch Center Clinic for Special Needs Children, Middlefield, OH Background: Several sarcomeric gene mutations have been identified in the pathogenesis of hypertrophic cardiomyopathy (HCM). We recently reported the lack of difference in natriuretic peptide levels between carriers and non-carriers for such mutations. Comparisons of other cardiac and inflammatory biomarker levels between carriers and non-carriers have not been examined in a prospective manner. Methods: From a large cohort of Amish families with a specific myosin binding protein C (MYBPC3) gene mutation (c.3330þ2TOG), we measured plasma cardiac troponin I (cTnI), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP) levels (Abbott Architect) and compared levels between homozygous probands, and their asymptomatic carrier and non-carrier relatives. Results: A total of 125 consecutive subjects were enrolled and genotyped, including 3 homozygous carriers (all phenotype-positive), 55 heterozygous carriers, and 67 non-carriers. Overall, homozygous carriers have significantly higher plasma MPO (1832 6 2149 vs 236 6 378 pg/ mL, p!0.01) but not hsCRP (2.1 6 2.9 vs 1.8 6 3.4 mg/L, p 5 0.44) than heterozygous carriers. However, the mean and median levels were similar between asymptomatic carriers and non-carriers on all three biomarkers (non-carrier MPO 243 6 509 pg/mL; hsCRP 1.82 6 2.7mg/L). All homozygous carriers have detectable cTnI (mean 0.09 6 0.15 ng/mL). Conclusion: Although plasma MPO and cTnI were significantly elevated in homozygous carriers of MYBPC3 mutation compared to their asymptomatic relatives who are heterozygous carriers, biomarker levels were similar between asymptomatic carriers versus non-carriers of MYBPC3 mutation.
112 Troponin Release in Patients Admitted with Acute Decompensated Heart Failure and Renal Dysfunction: Results from the Pilot Phase of the PROTECT Trial Marco Metra1, Howard C. Dittrich2, Gad Cotter3, Barry M. Massie4, Piotr Ponikowski5, Gang Jia6, Kenji P. Fujita6, Christopher M. O’Connor7; 1University of Brescia, Brescia, Italy; 2University of California, San Diego, San Diego, CA; 3 Momentum Research, Inc, Durham, NC; 4University of California, San Francisco,
decompensated HF (p!.0001). Patients without HF hospitalizations had stable BNP levels over 292 days. Patients who had a BNP measurement within 2 weeks of hospitalization (mean 5.5 days) had a significant increase in their BNP level detected as early as 148 days prior to decompensation. In the 5 days before decompensation, BNP levels were not significantly different from BNP at the time of hospital admission.
109 The Degree of Natriuretic Peptide System Activation in Stable and High Risk Chf Characterized by Increased Cystatin C Is Not Reflected in cGMP Activation John A. Schirger1, Horng H. Chen1, Josh Slusser2, David Hodge2, Denise Heublein1, Alessandro Cataliotti1, Sharon Sandberg1, John C. Burnett, Jr.1; 1Cardiovascular Diseases, Cardiorenal Research Laboratory, Mayo Clinic, Rochester, MN; 2 Department of Biostatistics, Mayo Clinic, Rochester, MN Background: Cardiorenal syndrome (CRS) is characterized by neurohumoral activation, sodium retention, ventricular dysfunction and congestion, and renal insufficiency (RI). The congestive heart failure (CHF) component evolves from asymptomatic, to stable symptomatic to overt symptomatic CHF. The natriuretic peptide system (NPS), including atrial (ANP) and brain (BNP) natriuretic peptides is progressively activated during progression of CHF. Less is known about the second messenger, cGMP, of the NPS across the spectrum of CHF. RI in CHF remains an important clinical challenge and Cystatin C is emerging as an important marker of RI. Further work is needed in characterizing Cystatin C across the spectrum of CHF and CRS. Methods: We prospectively looked at the NPS, including ANP, NT-proANP, BNP, and NT-proBNP, as well as plasma cGMP, NPS to cGMP ratios and Cystatin C in three groups of subjects: normal volunteers (n510), stable CHF patients (n519), and higher risk CHF patients (based on recent hospitalization for CHF, n520). The groups are reported in that order below. Statistical analysis was carried out by ANOVA with p!0.05 accepted as significant (*). Results: Each component of the NPS increased in the plasma across the three groups with highest levels in the high risk CHF. However, cGMP levels did not vary significantly across groups (626 6 303 vs 914 6 521 vs 959 6 509 pmol/mL, NS). The ratio NT-proANP/ cGMP increased across the 3 groups (0.60 6 0.55 vs 1.02 6 0.52 vs 1.46 6 1.08,*), but the ratios of ANP/cGMP, BNP/cGMP, and NT-proBNP/cGMP did not vary significantly across groups. Importantly, the mean Cystatin C levels increased with stable and high risk CHF groups (0.9 6 0.1 vs 1.4 6 0.3 vs 1.8 6 0.7,*). Conclusions: Despite the increase of each component of the NPS measured in the stable and high risk CHF, cGMP did not increase significantly across the same groups. Except for the ratio NT-proANP/cGMP, the ratios of the NPS to cGMP did not vary across groups either, suggesting the need to further refine our understanding of the coupling of the NPS with its second messenger, cGMP. Importantly, we report for the first time that Cystatin C varies across these phenotypes of CHF, suggesting that it may be an important marker of the development of CRS.
110 Early Elevations in BNP up to Two Months before Actual Decompensation Predict Heart Failure Hospitalizations Pam R. Taub1, Ellen Fitzpatrick1, Kimberly Tran1, Kevin Shah1, Kevin Jiang1, Paul Clopton1, Mitchell Saltzburg2, Robert Fitzgerald1, Alan Maisel1; 1Divison of Cardiology, Veterans Affairs San Diego Health Care System, University of California San Diego, San Diego, CA; 2Cardiology, Midwest Heart Specialists, Lombard, IL Background: B-type natriuretic peptide (BNP) has become mainstay in the diagnosis or exclusion of acute heart failure (HF). However, criteria for interpreting BNP changes in the outpatient setting and in detecting early subclinical congestion prior to clinical decompensation have not been established. Methods: 192 patients with HF and at least 5 BNP measurements over 6 month to 2 year period were recruited and over 2000 clinical visits with BNP levels were reviewed. Decompensation was defined as hospitalization for HF. Baseline BNP was determined to be the first BNP value upon study enrollment not corresponding to hospitalization. Results: 16 patients in the low baseline BNP group (BNP !200 pg/ml) and 59 patients in the high baseline BNP group (BNPO200 pg/ml) had hospital admissions. Patients in the low baseline BNP group had 564% increase (SEM 174.5) while those in the high baseline BNP group had a 60% increase (SEM 16) prior to hospitalization for
Conclusions: Patients with low baseline BNP had significantly larger changes in BNP levels before decompensation than those with higher baseline BNP levels. Patient without HF hospitalizations have stable BNP levels. In patients who had a BNP measurement within 2 weeks of hospitalization BNP concentrations showed a continuous rise before admission for decompensation. This represents an important window for diagnosis and therapeutic intervention. Understanding the clinical significance of changes in BNP levels prior to decompensation maybe useful in diagnosing subclinical congestion and preventing hospitalization.
111 Comparison of Cardiac and Inflammatory Biomarker Levels between Carriers and Non-Carriers of MYBPC3 Gene Mutation for Hypertrophic Cardiomyopathy W.H. Wilson Tang1, Baozhong Xin2, Leah Nye2, Sabe De1, Allen G. Borowski1, Stanley L. Hazen1, Heng Wang2; 1Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH; 2 Das Deutsch Center Clinic for Special Needs Children, Middlefield, OH Background: Several sarcomeric gene mutations have been identified in the pathogenesis of hypertrophic cardiomyopathy (HCM). We recently reported the lack of difference in natriuretic peptide levels between carriers and non-carriers for such mutations. Comparisons of other cardiac and inflammatory biomarker levels between carriers and non-carriers have not been examined in a prospective manner. Methods: From a large cohort of Amish families with a specific myosin binding protein C (MYBPC3) gene mutation (c.3330þ2TOG), we measured plasma cardiac troponin I (cTnI), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP) levels (Abbott Architect) and compared levels between homozygous probands, and their asymptomatic carrier and non-carrier relatives. Results: A total of 125 consecutive subjects were enrolled and genotyped, including 3 homozygous carriers (all phenotype-positive), 55 heterozygous carriers, and 67 non-carriers. Overall, homozygous carriers have significantly higher plasma MPO (1832 6 2149 vs 236 6 378 pg/ mL, p!0.01) but not hsCRP (2.1 6 2.9 vs 1.8 6 3.4 mg/L, p 5 0.44) than heterozygous carriers. However, the mean and median levels were similar between asymptomatic carriers and non-carriers on all three biomarkers (non-carrier MPO 243 6 509 pg/mL; hsCRP 1.82 6 2.7mg/L). All homozygous carriers have detectable cTnI (mean 0.09 6 0.15 ng/mL). Conclusion: Although plasma MPO and cTnI were significantly elevated in homozygous carriers of MYBPC3 mutation compared to their asymptomatic relatives who are heterozygous carriers, biomarker levels were similar between asymptomatic carriers versus non-carriers of MYBPC3 mutation.
112 Troponin Release in Patients Admitted with Acute Decompensated Heart Failure and Renal Dysfunction: Results from the Pilot Phase of the PROTECT Trial Marco Metra1, Howard C. Dittrich2, Gad Cotter3, Barry M. Massie4, Piotr Ponikowski5, Gang Jia6, Kenji P. Fujita6, Christopher M. O’Connor7; 1University of Brescia, Brescia, Italy; 2University of California, San Diego, San Diego, CA; 3 Momentum Research, Inc, Durham, NC; 4University of California, San Francisco,