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Prognostic role of brain natriuretic peptide (BNP) levels in patients with type 2 diabetes mellitus
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Journal of Cardiac Failure Vol. 10 No. 4 Suppl. 2004
110
112
Effect of Endogenous Noradenaline Release on Peak Exercise Heart Rate in Subjects with Chronic Heart Failure Receiving Carvedilol Versus Metoprolol Timothy J. Vittorio,1 Duygu Onat,2 Paolo C. Colombo,2 John Stathopoulos,2 Cselaj Sulejman,2 Rose Andrew,2 Gillian Miller,2 Joshua Trufant,2 Rochelle Goldsmith,2 Ulrich P. Jorde1; 1Medicine, Heart Failure Program, New York University School of Medicine, New York, NY; 2Medicine, Columbia University College of P&S, New York, NY
Plasma B-type Natriuretic Peptide Levels in Infants and Children with Chronic Compensated and Acute Decompensated Heart Failure Jack F. Price,1,2 Kim Little,1 Brady S. Moffett,2 Jeffrey A. Towbin,1,2 Susan W. Denfield,1,2 John L. Jeffries,1,2 Sarah K. Clunie,1,2 William J. Dreyer1,2; 1Pediatrics (Cardiology), Baylor College of Medicine, Houston, TX; 2Pediatric Cardiology, Texas Children’s Hospital, Houston, TX
Background: Dose equivalency of metoprolol (Met) and carvedilol (Carv) for beta-1 blockade remains subject of ongoing debate. The degree of beta-1 blockade is best assessed in vivo by blunting of the exercise induced heart rate. Accorddingly, we examined baseline and peak exercise heart rate in subjects with chronic heart failure (CHF) treated with Carv or Met. To correct for possible differences in norepinephrine (NE) release due to beta-2 blockade, we also measured NE levels at baseline and peak exercise. Methods: Thirty-three subjects treated chronically with Carv (34.5 ⫾ 3.4 mg; n ⫽ 23) or Met XL (77.5 ⫾ 17.3 mg; n ⫽ 10) referred for cardiopulmonary exercise testing were studied prospectively. All subjects were in NSR, achieved RER ⱖ 0.95, and received the long acting form of Met, Met XL, which has 75% bioavailability of the short acting Met IR. Carv versus Met XL subjects did not differ (p ⬍ 0.05) with respect to age (52 vs 56 yrs), LVEF (25 vs 29 %), LVEDD (6.2 vs 6.3 mm), MAP (83.5 vs. 88.3 mmHg), baseline HR (73.6 ⫾ 2.4 vs 71.5 ⫾ 4.7 bpm), peak Vo2 (16.7 vs 15.7 ml/kg/min), exercise time (9.3 vs 9.1 min), and baseline (3.49 vs 4.01 nmol/l) plasma norepinephrine (NE) levels. However, and despite similar peak NE levels(17.1 ⫹ 1.8 vs 18.6 ⫹ 4.9 nmol/l), heart rate at peak exercise was higher in subjects receiving Carv (131.7 ⫾ 4.6 bpm) compared to those receiving Met.(112.6 ± 6.0 bpm), p ⫽ 0.029. Conclusion: Similar NE release and more complete beta-1 blockade as assessed by peak heart rate is observed in otherwise well matched subjects with CHF treated with a mean daily dose of 77.5 mg Met XL as compared to 35.5 mg Carv. Assuming a 75% bioavailability of Met XL, 35 mg Carv should provide less beta-1 blockade than 58 mg Met IR.
Background: Plasma B-type natriuretic peptide (BNP) is a sensitive marker of heart failure (HF) in adults. During episodes of acute decompensation, BNP levels rise above baseline levels of the compensated state. To date, no data exist examining BNP levels in children with chronic compensated (Co) and acute decompensated (De) HF. Methods: We reviewed the medical records of all infants and children admitted to our institution with acute DeHF from 10/03 to 4/04, and the records of all pts seen in the outpatient heart failure clinic with chronic CoHF from 2/04 to 4/04. Inclusion criteria for all pts: ejection fraction (EF%) ⬍ 45% or myocardial performance index ⬎0.5. Patients with chronic CoHF must have been followed as outpatients for at least 3 months. Exclusion criteria included age ⬎21 years and chronic or acute renal failure. Decompensated HF was defined as new onset or worsening HF symptoms requiring hospital admission for treatment with intravenous diuretics and/or inotropes. Results: 26 pts met inclusion criteria (DeHF n ⫽ 15, CoHF n ⫽ 11); mean age ⫽ 8.7 ⫾ 7.0 years. Diagnoses included dilated cardiomyopathy (n ⫽ 15), congenital heart disease (n ⫽ 5), myocardial ischemia (n ⫽ 3), acute graft rejection (n ⫽ 2) and hypertrophic cardiomyopathy (n ⫽ 1). Mean BNP levels were higher in children with DeHF compared to children with CoHF (2891 ⫾ 1422 pg/mL vs. 382 ⫾ 417 pg/mL, p ⬍ 0.0001). Plasma BNP levels correlated negatively with ejection fraction (r ⫽ ⫺0.6) and positively with left ventricular end-diastolic dimension (r ⫽ 0.5). BNP levels in 5 children with acute DeHF decreased after their clinical condition improved (2266 ⫾ 1244 pg/mL vs. 201 ⫾ 167 pg/mL, p ⬍ 0.02). Conclusion: Plasma B-type natriuretic peptide levels are higher in infants and children with acute DeHF compared to infants and children with chronic CoHF. Ventricular ejection fraction and left ventricular end-diastolic dimension correlate with BNP levels. After an episode of acute DeHF resolves, plasma BNP values decrease to levels similar to the compensated state.
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111 Prognostic Role of Brain Natriuretic Peptide (BNP) Levels in Patients with Type 2 Diabetes Mellitus Meenakshi A. Bhalla,1 Audrey Chiang,2 Victoria A. Epshteyn,2 Radmila Kazanegra,3 Vikas Bhalla,2 Paul Clopton,2 Padma Krishnaswamy,2 L. K. Morrison,2 Albert Chiu,3 Nancy Gardetto,3 Sunder Mudaliar,3 Steven V. Edelman,3 Robert R. Henry,3 Alan S. Maisel3; 1Medicine, University of Buffalo (Mercy Hospital), San Diego, CA; 2 University of California, San Diego, CA; 3Veterans Affairs Medical Center, San Diego, CA We hypothesized that BNP levels can predict cardiac mortality in diabetic patients. Design: 482 diabetic patients (majority males with NIDDM) from VAMC San Diego, were divided into two groups: a) patients referred by the physician for echocardiogram on the basis of clinical suspicion of cardiac dysfunction (Referred (R), n ⫽ 180) b) patients randomly selected from the diabetic clinic in which there was no suspicion of cardiac dysfunction, (Not-Referred (N-R), n ⫽ 302). These groups were followed, and all documented cardiac events and all-cause mortality in relation to initial BNP levels were examined. Results: There were 71 (14.7%) deaths during the follow-up period: 52/180 (29%) in Referred and 19/302 (6%) in Not-Referred group. In Referred group 30/52 (58%) died of cardiac cause, 10/52 (19%) non-cardiac, 2/52 (4%) renal and 10/52 (19%) due to unknown cause. Similarly 6/19 (32%) died of cardiac causes in the Not-Referred group. Median BNP level of the patients in both Referred and Not-referred groups, who died of: 1) cardiac causes were 537 and 87 pg/ml, 2) Noncardiac causes were 80 and 53 pg/ml, 3) unknown cause of death were 343 and 38 pg/ml respectively. ROC values for mortality in Referred and Non-Referred groups in relation to BNP, revealed the AUC to be 0.720 and 0.691 respectively (p ⬍ 0.01 in both). Among HDL, LDL, triglycerides, HgA1c, only the ROC for triglycerides significantly predicted mortality in diabetic patients. The specificity and negativepredictive values were higher in the Not-Referred versus Referred group across the range of BNP cut-points. The most accurate cut-point was a BNP of 120 pg/ ml in both the Not-Referred (87%) and Referred group (61%). Cox Regression (multivariable) showed BNP as the most significant predictor of the all cause mortality in Referred group. The Kaplan-Meier’s Survival curves showed the marked decrease in survival in patient group with BNP ⬎ 120pg/ml. Conclusion: BNP appears to be a reliable predictor of future cardiac and all cause mortality in diabetic patients.
The ‘Gray Zone’ of Diagnosis Using a Plasma BNP Levels for Congestive Heart Failure Byung-Su Yoo,1,2 Hyun-Suk Jung,1 Jang-Young Kim,1 Seung-Hwan Lee,1 Sung-Oh Hwang,3 Junghan Yoon,1 Kyung-Hoon CHoe1; 1Cardiology, Yonsei University, Wonju College of Medicine, Wonju, Kangwondo; 2RRC of MOST & KOSEF, Research Institute of Med. eng. & Rehab.(RIMIRE), Wonju, Kangwondo, Republic of Korea; 3Emergency Medicine, Yonsei University, Wonju College of Medicine, Wonju, Kangwondo, Republic of Korea Background: Brain natriuretic Peptide (BNP) is been used as a standard diagnostic tool to define heart failure. However, the significance of inappropriate levels of plasma BNP in the presence or absence of heart failure remains unclear. We evaluated the prevalence and clinical characteristics of patients with inappropriate BNP level. Methods: Of 3830 patients who measured BNP levels from Aug 2002 to Jun 2003 (mean age: 62.8 ⫾ 13.8, male 49%), 1048 patients were analyzed (control 661, systolic heart failure 387 patients). We defined systolic heart failure was EF ⬍ 50% and Left ventricular end-diastolic heart failure (LVEDD) ⬎ 5.5 with typical symptoms. BNP (Triage, Biosite) and routine chemicals were analyzed in blood samples obtained on admission or at first visit. Assessment was by clinical examination, resting 12 lead ECG, chest x-ray, blood and urine analysis and echocardiography. We defined that false positive test was elevated BNP (ⱖ100 pg/ml) with no other non-cardiac causes of elevated BNP and false negative test was not elevated BNP (⬍100 pg/ml) with definite LV systolic dysfunction. Patients with isolated left ventricular diastolic dysfunction or diastolic heart failure were excluded. And we excluded the patients with renal failure (Cr ⱖ 2.0mg/dl), endocrine disease and cor pumonale. Results: At 100 pg/ml, BNP had a sensitivity of 92.5% and specificity of 86.1%. 166 patients had inappropriate levels of BNP in the presence or absence of systolic heart failure. Of 166 patients (average age 73.8 ⫾ 9.3 years, 57% female), 72% had false positive test and 28% had false negative test. Patients with false negative test had a dilated cardiomyopathy (52.1%), stable CHF status (NYHA I, 26.2%) and previous MI history (12%). Patients with false positive test had a history of stable CHF (27.9%), hypertension (21.0%), diabetes mellitus (19.7%), valvular heart disease (15.3%), atrial fibrillation (11.23%). These patients were significantly older (average age 73.8 ⫾ 8.7 vs. 65.8 ⫾ 8.8 years, p ⫽ 0.001) than control group (BNP ⱖ 100pg/ml with decreased EF), with all other demographic and clinical criteria being similar. Conclusions: In BNP test for congestive heart failure, there was a gray zone as diagnostic tools in congestive heart failure. But, these patients will need a follow up for the relation to the clinical outcomes.
Journal of Cardiac Failure Vol. 10 No. 4 Suppl. 2004
110
112
Effect of Endogenous Noradenaline Release on Peak Exercise Heart Rate in Subjects with Chronic Heart Failure Receiving Carvedilol Versus Metoprolol Timothy J. Vittorio,1 Duygu Onat,2 Paolo C. Colombo,2 John Stathopoulos,2 Cselaj Sulejman,2 Rose Andrew,2 Gillian Miller,2 Joshua Trufant,2 Rochelle Goldsmith,2 Ulrich P. Jorde1; 1Medicine, Heart Failure Program, New York University School of Medicine, New York, NY; 2Medicine, Columbia University College of P&S, New York, NY
Plasma B-type Natriuretic Peptide Levels in Infants and Children with Chronic Compensated and Acute Decompensated Heart Failure Jack F. Price,1,2 Kim Little,1 Brady S. Moffett,2 Jeffrey A. Towbin,1,2 Susan W. Denfield,1,2 John L. Jeffries,1,2 Sarah K. Clunie,1,2 William J. Dreyer1,2; 1Pediatrics (Cardiology), Baylor College of Medicine, Houston, TX; 2Pediatric Cardiology, Texas Children’s Hospital, Houston, TX
Background: Dose equivalency of metoprolol (Met) and carvedilol (Carv) for beta-1 blockade remains subject of ongoing debate. The degree of beta-1 blockade is best assessed in vivo by blunting of the exercise induced heart rate. Accorddingly, we examined baseline and peak exercise heart rate in subjects with chronic heart failure (CHF) treated with Carv or Met. To correct for possible differences in norepinephrine (NE) release due to beta-2 blockade, we also measured NE levels at baseline and peak exercise. Methods: Thirty-three subjects treated chronically with Carv (34.5 ⫾ 3.4 mg; n ⫽ 23) or Met XL (77.5 ⫾ 17.3 mg; n ⫽ 10) referred for cardiopulmonary exercise testing were studied prospectively. All subjects were in NSR, achieved RER ⱖ 0.95, and received the long acting form of Met, Met XL, which has 75% bioavailability of the short acting Met IR. Carv versus Met XL subjects did not differ (p ⬍ 0.05) with respect to age (52 vs 56 yrs), LVEF (25 vs 29 %), LVEDD (6.2 vs 6.3 mm), MAP (83.5 vs. 88.3 mmHg), baseline HR (73.6 ⫾ 2.4 vs 71.5 ⫾ 4.7 bpm), peak Vo2 (16.7 vs 15.7 ml/kg/min), exercise time (9.3 vs 9.1 min), and baseline (3.49 vs 4.01 nmol/l) plasma norepinephrine (NE) levels. However, and despite similar peak NE levels(17.1 ⫹ 1.8 vs 18.6 ⫹ 4.9 nmol/l), heart rate at peak exercise was higher in subjects receiving Carv (131.7 ⫾ 4.6 bpm) compared to those receiving Met.(112.6 ± 6.0 bpm), p ⫽ 0.029. Conclusion: Similar NE release and more complete beta-1 blockade as assessed by peak heart rate is observed in otherwise well matched subjects with CHF treated with a mean daily dose of 77.5 mg Met XL as compared to 35.5 mg Carv. Assuming a 75% bioavailability of Met XL, 35 mg Carv should provide less beta-1 blockade than 58 mg Met IR.
Background: Plasma B-type natriuretic peptide (BNP) is a sensitive marker of heart failure (HF) in adults. During episodes of acute decompensation, BNP levels rise above baseline levels of the compensated state. To date, no data exist examining BNP levels in children with chronic compensated (Co) and acute decompensated (De) HF. Methods: We reviewed the medical records of all infants and children admitted to our institution with acute DeHF from 10/03 to 4/04, and the records of all pts seen in the outpatient heart failure clinic with chronic CoHF from 2/04 to 4/04. Inclusion criteria for all pts: ejection fraction (EF%) ⬍ 45% or myocardial performance index ⬎0.5. Patients with chronic CoHF must have been followed as outpatients for at least 3 months. Exclusion criteria included age ⬎21 years and chronic or acute renal failure. Decompensated HF was defined as new onset or worsening HF symptoms requiring hospital admission for treatment with intravenous diuretics and/or inotropes. Results: 26 pts met inclusion criteria (DeHF n ⫽ 15, CoHF n ⫽ 11); mean age ⫽ 8.7 ⫾ 7.0 years. Diagnoses included dilated cardiomyopathy (n ⫽ 15), congenital heart disease (n ⫽ 5), myocardial ischemia (n ⫽ 3), acute graft rejection (n ⫽ 2) and hypertrophic cardiomyopathy (n ⫽ 1). Mean BNP levels were higher in children with DeHF compared to children with CoHF (2891 ⫾ 1422 pg/mL vs. 382 ⫾ 417 pg/mL, p ⬍ 0.0001). Plasma BNP levels correlated negatively with ejection fraction (r ⫽ ⫺0.6) and positively with left ventricular end-diastolic dimension (r ⫽ 0.5). BNP levels in 5 children with acute DeHF decreased after their clinical condition improved (2266 ⫾ 1244 pg/mL vs. 201 ⫾ 167 pg/mL, p ⬍ 0.02). Conclusion: Plasma B-type natriuretic peptide levels are higher in infants and children with acute DeHF compared to infants and children with chronic CoHF. Ventricular ejection fraction and left ventricular end-diastolic dimension correlate with BNP levels. After an episode of acute DeHF resolves, plasma BNP values decrease to levels similar to the compensated state.
113
111 Prognostic Role of Brain Natriuretic Peptide (BNP) Levels in Patients with Type 2 Diabetes Mellitus Meenakshi A. Bhalla,1 Audrey Chiang,2 Victoria A. Epshteyn,2 Radmila Kazanegra,3 Vikas Bhalla,2 Paul Clopton,2 Padma Krishnaswamy,2 L. K. Morrison,2 Albert Chiu,3 Nancy Gardetto,3 Sunder Mudaliar,3 Steven V. Edelman,3 Robert R. Henry,3 Alan S. Maisel3; 1Medicine, University of Buffalo (Mercy Hospital), San Diego, CA; 2 University of California, San Diego, CA; 3Veterans Affairs Medical Center, San Diego, CA We hypothesized that BNP levels can predict cardiac mortality in diabetic patients. Design: 482 diabetic patients (majority males with NIDDM) from VAMC San Diego, were divided into two groups: a) patients referred by the physician for echocardiogram on the basis of clinical suspicion of cardiac dysfunction (Referred (R), n ⫽ 180) b) patients randomly selected from the diabetic clinic in which there was no suspicion of cardiac dysfunction, (Not-Referred (N-R), n ⫽ 302). These groups were followed, and all documented cardiac events and all-cause mortality in relation to initial BNP levels were examined. Results: There were 71 (14.7%) deaths during the follow-up period: 52/180 (29%) in Referred and 19/302 (6%) in Not-Referred group. In Referred group 30/52 (58%) died of cardiac cause, 10/52 (19%) non-cardiac, 2/52 (4%) renal and 10/52 (19%) due to unknown cause. Similarly 6/19 (32%) died of cardiac causes in the Not-Referred group. Median BNP level of the patients in both Referred and Not-referred groups, who died of: 1) cardiac causes were 537 and 87 pg/ml, 2) Noncardiac causes were 80 and 53 pg/ml, 3) unknown cause of death were 343 and 38 pg/ml respectively. ROC values for mortality in Referred and Non-Referred groups in relation to BNP, revealed the AUC to be 0.720 and 0.691 respectively (p ⬍ 0.01 in both). Among HDL, LDL, triglycerides, HgA1c, only the ROC for triglycerides significantly predicted mortality in diabetic patients. The specificity and negativepredictive values were higher in the Not-Referred versus Referred group across the range of BNP cut-points. The most accurate cut-point was a BNP of 120 pg/ ml in both the Not-Referred (87%) and Referred group (61%). Cox Regression (multivariable) showed BNP as the most significant predictor of the all cause mortality in Referred group. The Kaplan-Meier’s Survival curves showed the marked decrease in survival in patient group with BNP ⬎ 120pg/ml. Conclusion: BNP appears to be a reliable predictor of future cardiac and all cause mortality in diabetic patients.
The ‘Gray Zone’ of Diagnosis Using a Plasma BNP Levels for Congestive Heart Failure Byung-Su Yoo,1,2 Hyun-Suk Jung,1 Jang-Young Kim,1 Seung-Hwan Lee,1 Sung-Oh Hwang,3 Junghan Yoon,1 Kyung-Hoon CHoe1; 1Cardiology, Yonsei University, Wonju College of Medicine, Wonju, Kangwondo; 2RRC of MOST & KOSEF, Research Institute of Med. eng. & Rehab.(RIMIRE), Wonju, Kangwondo, Republic of Korea; 3Emergency Medicine, Yonsei University, Wonju College of Medicine, Wonju, Kangwondo, Republic of Korea Background: Brain natriuretic Peptide (BNP) is been used as a standard diagnostic tool to define heart failure. However, the significance of inappropriate levels of plasma BNP in the presence or absence of heart failure remains unclear. We evaluated the prevalence and clinical characteristics of patients with inappropriate BNP level. Methods: Of 3830 patients who measured BNP levels from Aug 2002 to Jun 2003 (mean age: 62.8 ⫾ 13.8, male 49%), 1048 patients were analyzed (control 661, systolic heart failure 387 patients). We defined systolic heart failure was EF ⬍ 50% and Left ventricular end-diastolic heart failure (LVEDD) ⬎ 5.5 with typical symptoms. BNP (Triage, Biosite) and routine chemicals were analyzed in blood samples obtained on admission or at first visit. Assessment was by clinical examination, resting 12 lead ECG, chest x-ray, blood and urine analysis and echocardiography. We defined that false positive test was elevated BNP (ⱖ100 pg/ml) with no other non-cardiac causes of elevated BNP and false negative test was not elevated BNP (⬍100 pg/ml) with definite LV systolic dysfunction. Patients with isolated left ventricular diastolic dysfunction or diastolic heart failure were excluded. And we excluded the patients with renal failure (Cr ⱖ 2.0mg/dl), endocrine disease and cor pumonale. Results: At 100 pg/ml, BNP had a sensitivity of 92.5% and specificity of 86.1%. 166 patients had inappropriate levels of BNP in the presence or absence of systolic heart failure. Of 166 patients (average age 73.8 ⫾ 9.3 years, 57% female), 72% had false positive test and 28% had false negative test. Patients with false negative test had a dilated cardiomyopathy (52.1%), stable CHF status (NYHA I, 26.2%) and previous MI history (12%). Patients with false positive test had a history of stable CHF (27.9%), hypertension (21.0%), diabetes mellitus (19.7%), valvular heart disease (15.3%), atrial fibrillation (11.23%). These patients were significantly older (average age 73.8 ⫾ 8.7 vs. 65.8 ⫾ 8.8 years, p ⫽ 0.001) than control group (BNP ⱖ 100pg/ml with decreased EF), with all other demographic and clinical criteria being similar. Conclusions: In BNP test for congestive heart failure, there was a gray zone as diagnostic tools in congestive heart failure. But, these patients will need a follow up for the relation to the clinical outcomes.