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Effect of beta-blocker in plasma norepinephrine levels in patients with heart failure
The 8th Annual Scientific Meeting
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HFSA
S51
122
124
Effect of Beta-Blocker in Plasma Norepinephrine Levels in Patients with Heart failure Jose A. Figueiredo neto,1 Cesar Grupi,2 Charles Mady2; 1Cardiology, University Federal of Maranha˜o, Sa˜o Luis, Maranha˜o, Brazil; 2Heart Institute (InCor) University of Sa˜o Paulo Medical School, University of Sa˜o Paulo Medical School, Sa˜o Paulo, Sa˜o Paulo, Brazil
Uric Acid and Immune Activation in Chronic Heart Failure Stepan von Haehling,1 Josef Niebauer,2 Darlington O. Okonko,1 Ewa A. Jankowska,1 Stefan D. Anker1; 1Clinical Cardiology, National Heart and Lung Institute, London, United Kingdom; 2Department of Medicine/Cardiology, Herzzentrum Leipzig, Leipzig, Germany
Background: Excessive activation in neurohumoral factors occur in patients with heart failure (HF) and have been associated with shortened life expectance. Concentration of plasma norepinephrine, wich are an index of sympathetic activation, are an independent predictor of mortality for patients with HF. Use of beta-blocker is a therapeutic alternative capable of atenuated neurohumoral activation. However, the reasons for these favorable effects, and especially roles played by neurohumoral factors in mediating them remain controversial. Objective: The aim of this study was evaluated the effect of beta-bloker treatment in plasma norepinephrine levels during short and longterm treatment in patients with HF. Methods: We studied forty patients with HF underwent beta-blocker therapy. Criteria for entry into the study included New York Heart Association (NYHA) functional class II toIV and left ventricular ejection fraction (LVEF) ⬍45% on raionunuclide ventriculography. Criteria for exclusion from the study included bradycardia (heart rate ⬍45 beats/min), hypotension (systolic blood pressure ⬍90mmHg), and general contraindications to beta-blocker. Baselines measurements included catecolamines, ventricular dimensions by two-dimensional Doppler echocardiography, and radionucleotide ventriculography to assess LVEF. At the end of one, three and six months baselines measurements were repeated. Results were expressed as mean ⫾ SEM. The changes in parameters after introduction of betablockers were assessed by analysis of variance for repeated measurements followed by paired t test. A p value ⬍0.05 was considered statistically significant. Results: After one month, norepinephrine levels decreased from 758 ⫾ 62 pg/ml to 410 ⫾ 31 pg/ml (p ⬍ 0.01). decreased in norepinephrine persisted during the 3-month period (408 ⫾ 36 pg/ml, p ⬍ 0.01), but returned to pretreatment levels after 6 months (730 ⫾ 38 pg/ml). The LVEF did not change at one month point, but increased at the end of three months (29.84 ⫾ 1.61% to 34.64 ⫾ 1.92 %; p ⬍ 0.001)and at the end of six months (29.84 ⫾ 1.61% to 38.56 ⫾ 1.95%; p ⬍ 0.001). End-diastolic dimension did not change in the one month period, but significantly decreased at the end of three months(67.7 ⫾ 1.31mm to 65.92 ⫾ 1.26 mm; p ⬍ 0.01) and at the end of six months(67.7 ⫾ 1.31 mm to 63.96 ⫾ 1.29 mm; p ⬍ 0.001). Conclusion: This study demonstrated that beta-blocker therapy decreased plasma norepinephrine levels during short term beta-blockade but not improve left ventricular contractile function, which improved only in the later phase of treatment.
Background: Chronic heart failure (CHF) is a state of chronic inflammation, and tumor necrosis factor-alpha has been recognised to play an important role in this setting. Accumulating evidence suggests that immunoregulatory CD4⫹CD25⫹ T cells are essential in regulating the immune response to self and foreign antigen. These cells appear to be key suppressor cells involved in the control of many pathophysiological diseases. Manipulation of these cells and control of their function may offer new perspectives for the treatment of inflammatory diseases. Methods: We analysed the correlation of serum uric acid levels with the proportion of CD4⫹CD25⫹ T cells. We recruited 14 cachectic and non-cachectic CHF patients and 13 healthy controls. Cachexia was defined as a weight loss of ⬎7.5% over a period of ⬎6 months. Fluorescences-activated cell sorting was performed using the antibody-flurochrome conjugates CD3-PC5, CD4-FITC, CD8-ECD, and CD25R-RD1. Patients were on standard treatment for CHF, and no patient was taking allopurinol. Results: Cachectic and non-cachectic CHF patients were not different for age (p ⫽ 0.19), global kidney function (p ⫽ 0.17), left ventricular ejection fraction (p ⫽ 0.82), and peak oxygen consumption (p ⫽ 0.08). Uric acid levels were significantly increased in patients with documented weight loss due to CHF (p ⫽ 0.0024). In CHF patients, uric acid (545 ⫾ 51 mmol/l) was strongly related to the proportion of CD4⫹CD25⫹ T cells (r ⫽ 0.83, p ⫽ 0.0002). In contrast, in healthy control subjects (uric acid 308 ⫾ 17 mmol/l, p ⫽ 0.0003 vs CHF patients) this relationship was not present (r ⫽ ⫺0.16, p ⫽ 0.59). Conclusions: Direct effects of uric acid may only be apparent in patients with chronic disease. If this abnormality is present in the long-term this may contribute to tissue immune activation, local tissue damage, and finally to wasting disease. Counteracting uric acid production by inhibiting xanthine oxidase activity may have favourable immunologic effects (less free radical formation, less secondary effects on apoptosis induction and tissue damage).
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The Role of Spironolactone upon Chagas’ Cardiomyopathy Felix J.A. Ramires,1 Vera C. Salemy,1 Barbara M. Ianni,1 Daniel G. Martins,1 Angelina Billate,1 Edecio C. Neto,1 Charles Mady1; 1Heart Institute (InCor), University of Sa˜o Paulo, Medical School, Sa˜o Paulo, SP, Brazil
The Clinical Value of Brain Natriuretic Peptide (BNP) Level Monitoring after Acute Exacerbation in Congestive Heart Failure Patients 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, Kwandwondo, Republic of Korea; 2RRC of MOST & KOSEF, Research Inst. of Med. Eng. & Rehab. (RIMIRE), Wonju, Kwangwondo, Republic of Korea; 3Emergency Medicine, Yonsei University, Wonju College of medicine, Wonju, Kwangwondo, Republic of Korea
Chagas’ disease is one of the most important causes of dilated cardiomyopathy in South and Central America. It is an inflammatory cause of cardiomyopathy. Whether it could have the same response of the aldosterone antagonism as demonstrated before in other dilated cardiomyopathies. Our objective was to evaluate the role of spironolactone upon myocardial remodeling in a Chagas’ cardiomyopathy model. We studied 60 Sirius Hamsters divided into: control (C) infected (Inf) and Inf plus spironolactone (Infsp, 40 mg/kg/day by gavage). The animals were kept for 11 months and the treatment started from the T. cruzi inoculation time. The 2-D echocardiogram with color doppler was performed and the left ventricular end diastolic diameter (LVEDD), fractional shortening (FS), isovolumetric relaxation time (IRT) and myocardial performance index (MPI) were evaluated. The interstitial collagen volume fraction (ICVF) was evaluated by videomorphometry using picrosirius red stained myocardial tissue. The animals were sacrificed under avertin anesthesia with potassium chloride infusion. The body weight (BW) was C:190g, Inf:167g*, Infsp:198g (*p ⬍ 0.05, compared to C and Infsp), the LVEDD/BW was C:0.31, Inf:0.35*, Infsp: 0.29 (*p ⬍ 0.05, compared to C and Infsp), FS was C:38, Inf: 35.5, Infsp: 38 (with no statistical difference), IRT was C: 23 msec, Inf: 26 msec*, Infsp: 22 msec (*p ⬍ 0.05, compared to C and Infsp) and MPI was C: 0.6, Inf:0.7, Infsp: 0.6 (with no statistical difference). The collagen is depicted in the table. Therefore, we observed that spironolactone prevented the myocardial remodeling also in Chagas’ cardiomyopathy and may prevent the diastolic impairment. Interstitial collagen volume fraction ICVF (%) Left ventricle Right ventricle
C
Inf
Infsp
p
0,34 ⫾ 0.04 1.76 ⫾ 0.24* 0.96 ⫾ 0.07† *具0.05 vs C/Infsp †具0.05 vs C 0.62 ⫾ 0.09 2.25 ⫾ 0.20* 1.47 ⫾ 0.16† *具0.05 vs C/Infsp †具0.05 vs C
Background: Because BNP level is closely related to left ventricular end diastolic pressure, reduced values may be indicative of improving status in congestive heart failure (CHF). The aim of this study was to evaluate the clinical value of serial plasma BNP level assessment after acute exacerbation in congestive heart failure patients. Methods: Between Oct 2002 and June 2003, 88 patients were included. The blood BNP (Triage, Biosite) level, functional status and prognostic parameter were analyzed on admission and at follow-up period (mean 4.5 month). We calculated BNP reduction ratio [100*(baseline BNP- follow-up BNP)/baseline BNP]. We excluded patients with AMI, chronic stable CHF, and chronic renal failure. Bad prognostic parameter was defined clinical deterioration or readmission and death. Result: 1. Mean age was 68.7 ⫾ 9.3 and male was 44.3% (n ⫽ 39). Most frequent etiology for CHF was dilated cardiomyopathy (n ⫽ 32, 36.4%). Other clinical etiologies were distributed in ischemic cardiomyopathy or previous MI history (n ⫽ 22, 25.0%), valvular heart disease (n ⫽ 21, 23.9%) and others (congenital heart disease, HCMP, etc., n ⫽ 13, 14.8%). 2. Mean ejection fraction of LV was 41.9 ⫾ 16.5% and left ventricle end-diastolic diameter was 6.0 ⫾ 1.0cm. Mean NYHA classification score was 3.03 ⫾ 0.66 3. Mean baseline BNP level on admission was 899.1 ⫾ 1062.7 pg/ml and follow-up level of BNP was 463.6 ⫾ 477.7 pg/ml. Mean BNP reduction ratio was 58.1 ⫾ 31.4% (⫺19.2% ∼95.0%). 4. Clinical deterioration or readmission and death (3 patients) were 11 patients (12.5%). 5. There were no significant differences for baseline BNP level, follow-up BNP level between the group with good prognosis and bad prognosis. And Age, left ventricular dimension and ejection fraction were no differences between the two groups. Only significant difference between the two groups was BNP reduction ratio (66.4 ⫾ 25.7 vs. 31.9 ⫾ 35.2%, p ⫽ 0.033). In a multivariable model, the BNP reduction ratio was the marker with the strongest relation of bad prognosis (p ⫽ 0.012). In conclusion, this study demonstrates that the monitoring of BNP level, especially BNP reduction ratio, may predict improving of acute exacerbated status in CHF patients but further study for the large population will be considered.
•
HFSA
S51
122
124
Effect of Beta-Blocker in Plasma Norepinephrine Levels in Patients with Heart failure Jose A. Figueiredo neto,1 Cesar Grupi,2 Charles Mady2; 1Cardiology, University Federal of Maranha˜o, Sa˜o Luis, Maranha˜o, Brazil; 2Heart Institute (InCor) University of Sa˜o Paulo Medical School, University of Sa˜o Paulo Medical School, Sa˜o Paulo, Sa˜o Paulo, Brazil
Uric Acid and Immune Activation in Chronic Heart Failure Stepan von Haehling,1 Josef Niebauer,2 Darlington O. Okonko,1 Ewa A. Jankowska,1 Stefan D. Anker1; 1Clinical Cardiology, National Heart and Lung Institute, London, United Kingdom; 2Department of Medicine/Cardiology, Herzzentrum Leipzig, Leipzig, Germany
Background: Excessive activation in neurohumoral factors occur in patients with heart failure (HF) and have been associated with shortened life expectance. Concentration of plasma norepinephrine, wich are an index of sympathetic activation, are an independent predictor of mortality for patients with HF. Use of beta-blocker is a therapeutic alternative capable of atenuated neurohumoral activation. However, the reasons for these favorable effects, and especially roles played by neurohumoral factors in mediating them remain controversial. Objective: The aim of this study was evaluated the effect of beta-bloker treatment in plasma norepinephrine levels during short and longterm treatment in patients with HF. Methods: We studied forty patients with HF underwent beta-blocker therapy. Criteria for entry into the study included New York Heart Association (NYHA) functional class II toIV and left ventricular ejection fraction (LVEF) ⬍45% on raionunuclide ventriculography. Criteria for exclusion from the study included bradycardia (heart rate ⬍45 beats/min), hypotension (systolic blood pressure ⬍90mmHg), and general contraindications to beta-blocker. Baselines measurements included catecolamines, ventricular dimensions by two-dimensional Doppler echocardiography, and radionucleotide ventriculography to assess LVEF. At the end of one, three and six months baselines measurements were repeated. Results were expressed as mean ⫾ SEM. The changes in parameters after introduction of betablockers were assessed by analysis of variance for repeated measurements followed by paired t test. A p value ⬍0.05 was considered statistically significant. Results: After one month, norepinephrine levels decreased from 758 ⫾ 62 pg/ml to 410 ⫾ 31 pg/ml (p ⬍ 0.01). decreased in norepinephrine persisted during the 3-month period (408 ⫾ 36 pg/ml, p ⬍ 0.01), but returned to pretreatment levels after 6 months (730 ⫾ 38 pg/ml). The LVEF did not change at one month point, but increased at the end of three months (29.84 ⫾ 1.61% to 34.64 ⫾ 1.92 %; p ⬍ 0.001)and at the end of six months (29.84 ⫾ 1.61% to 38.56 ⫾ 1.95%; p ⬍ 0.001). End-diastolic dimension did not change in the one month period, but significantly decreased at the end of three months(67.7 ⫾ 1.31mm to 65.92 ⫾ 1.26 mm; p ⬍ 0.01) and at the end of six months(67.7 ⫾ 1.31 mm to 63.96 ⫾ 1.29 mm; p ⬍ 0.001). Conclusion: This study demonstrated that beta-blocker therapy decreased plasma norepinephrine levels during short term beta-blockade but not improve left ventricular contractile function, which improved only in the later phase of treatment.
Background: Chronic heart failure (CHF) is a state of chronic inflammation, and tumor necrosis factor-alpha has been recognised to play an important role in this setting. Accumulating evidence suggests that immunoregulatory CD4⫹CD25⫹ T cells are essential in regulating the immune response to self and foreign antigen. These cells appear to be key suppressor cells involved in the control of many pathophysiological diseases. Manipulation of these cells and control of their function may offer new perspectives for the treatment of inflammatory diseases. Methods: We analysed the correlation of serum uric acid levels with the proportion of CD4⫹CD25⫹ T cells. We recruited 14 cachectic and non-cachectic CHF patients and 13 healthy controls. Cachexia was defined as a weight loss of ⬎7.5% over a period of ⬎6 months. Fluorescences-activated cell sorting was performed using the antibody-flurochrome conjugates CD3-PC5, CD4-FITC, CD8-ECD, and CD25R-RD1. Patients were on standard treatment for CHF, and no patient was taking allopurinol. Results: Cachectic and non-cachectic CHF patients were not different for age (p ⫽ 0.19), global kidney function (p ⫽ 0.17), left ventricular ejection fraction (p ⫽ 0.82), and peak oxygen consumption (p ⫽ 0.08). Uric acid levels were significantly increased in patients with documented weight loss due to CHF (p ⫽ 0.0024). In CHF patients, uric acid (545 ⫾ 51 mmol/l) was strongly related to the proportion of CD4⫹CD25⫹ T cells (r ⫽ 0.83, p ⫽ 0.0002). In contrast, in healthy control subjects (uric acid 308 ⫾ 17 mmol/l, p ⫽ 0.0003 vs CHF patients) this relationship was not present (r ⫽ ⫺0.16, p ⫽ 0.59). Conclusions: Direct effects of uric acid may only be apparent in patients with chronic disease. If this abnormality is present in the long-term this may contribute to tissue immune activation, local tissue damage, and finally to wasting disease. Counteracting uric acid production by inhibiting xanthine oxidase activity may have favourable immunologic effects (less free radical formation, less secondary effects on apoptosis induction and tissue damage).
123
125
The Role of Spironolactone upon Chagas’ Cardiomyopathy Felix J.A. Ramires,1 Vera C. Salemy,1 Barbara M. Ianni,1 Daniel G. Martins,1 Angelina Billate,1 Edecio C. Neto,1 Charles Mady1; 1Heart Institute (InCor), University of Sa˜o Paulo, Medical School, Sa˜o Paulo, SP, Brazil
The Clinical Value of Brain Natriuretic Peptide (BNP) Level Monitoring after Acute Exacerbation in Congestive Heart Failure Patients 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, Kwandwondo, Republic of Korea; 2RRC of MOST & KOSEF, Research Inst. of Med. Eng. & Rehab. (RIMIRE), Wonju, Kwangwondo, Republic of Korea; 3Emergency Medicine, Yonsei University, Wonju College of medicine, Wonju, Kwangwondo, Republic of Korea
Chagas’ disease is one of the most important causes of dilated cardiomyopathy in South and Central America. It is an inflammatory cause of cardiomyopathy. Whether it could have the same response of the aldosterone antagonism as demonstrated before in other dilated cardiomyopathies. Our objective was to evaluate the role of spironolactone upon myocardial remodeling in a Chagas’ cardiomyopathy model. We studied 60 Sirius Hamsters divided into: control (C) infected (Inf) and Inf plus spironolactone (Infsp, 40 mg/kg/day by gavage). The animals were kept for 11 months and the treatment started from the T. cruzi inoculation time. The 2-D echocardiogram with color doppler was performed and the left ventricular end diastolic diameter (LVEDD), fractional shortening (FS), isovolumetric relaxation time (IRT) and myocardial performance index (MPI) were evaluated. The interstitial collagen volume fraction (ICVF) was evaluated by videomorphometry using picrosirius red stained myocardial tissue. The animals were sacrificed under avertin anesthesia with potassium chloride infusion. The body weight (BW) was C:190g, Inf:167g*, Infsp:198g (*p ⬍ 0.05, compared to C and Infsp), the LVEDD/BW was C:0.31, Inf:0.35*, Infsp: 0.29 (*p ⬍ 0.05, compared to C and Infsp), FS was C:38, Inf: 35.5, Infsp: 38 (with no statistical difference), IRT was C: 23 msec, Inf: 26 msec*, Infsp: 22 msec (*p ⬍ 0.05, compared to C and Infsp) and MPI was C: 0.6, Inf:0.7, Infsp: 0.6 (with no statistical difference). The collagen is depicted in the table. Therefore, we observed that spironolactone prevented the myocardial remodeling also in Chagas’ cardiomyopathy and may prevent the diastolic impairment. Interstitial collagen volume fraction ICVF (%) Left ventricle Right ventricle
C
Inf
Infsp
p
0,34 ⫾ 0.04 1.76 ⫾ 0.24* 0.96 ⫾ 0.07† *具0.05 vs C/Infsp †具0.05 vs C 0.62 ⫾ 0.09 2.25 ⫾ 0.20* 1.47 ⫾ 0.16† *具0.05 vs C/Infsp †具0.05 vs C
Background: Because BNP level is closely related to left ventricular end diastolic pressure, reduced values may be indicative of improving status in congestive heart failure (CHF). The aim of this study was to evaluate the clinical value of serial plasma BNP level assessment after acute exacerbation in congestive heart failure patients. Methods: Between Oct 2002 and June 2003, 88 patients were included. The blood BNP (Triage, Biosite) level, functional status and prognostic parameter were analyzed on admission and at follow-up period (mean 4.5 month). We calculated BNP reduction ratio [100*(baseline BNP- follow-up BNP)/baseline BNP]. We excluded patients with AMI, chronic stable CHF, and chronic renal failure. Bad prognostic parameter was defined clinical deterioration or readmission and death. Result: 1. Mean age was 68.7 ⫾ 9.3 and male was 44.3% (n ⫽ 39). Most frequent etiology for CHF was dilated cardiomyopathy (n ⫽ 32, 36.4%). Other clinical etiologies were distributed in ischemic cardiomyopathy or previous MI history (n ⫽ 22, 25.0%), valvular heart disease (n ⫽ 21, 23.9%) and others (congenital heart disease, HCMP, etc., n ⫽ 13, 14.8%). 2. Mean ejection fraction of LV was 41.9 ⫾ 16.5% and left ventricle end-diastolic diameter was 6.0 ⫾ 1.0cm. Mean NYHA classification score was 3.03 ⫾ 0.66 3. Mean baseline BNP level on admission was 899.1 ⫾ 1062.7 pg/ml and follow-up level of BNP was 463.6 ⫾ 477.7 pg/ml. Mean BNP reduction ratio was 58.1 ⫾ 31.4% (⫺19.2% ∼95.0%). 4. Clinical deterioration or readmission and death (3 patients) were 11 patients (12.5%). 5. There were no significant differences for baseline BNP level, follow-up BNP level between the group with good prognosis and bad prognosis. And Age, left ventricular dimension and ejection fraction were no differences between the two groups. Only significant difference between the two groups was BNP reduction ratio (66.4 ⫾ 25.7 vs. 31.9 ⫾ 35.2%, p ⫽ 0.033). In a multivariable model, the BNP reduction ratio was the marker with the strongest relation of bad prognosis (p ⫽ 0.012). In conclusion, this study demonstrates that the monitoring of BNP level, especially BNP reduction ratio, may predict improving of acute exacerbated status in CHF patients but further study for the large population will be considered.