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128: Decreased Expression of Thrombospondin-1 in Failing Hearts Could Favour Ventricular Remodelling
S110
Abstracts
The Journal of Heart and Lung Transplantation February 2009
Resting & Exercise Hemodynamics Group #
Normal(1) Exercise PH(2) DD(3)
# Patients 9 8 Resting (mean) mPAP(mmHg) 14.8(4.67) 18.5(3.58) CO(L/min) 5.5(1.59) 4.5(0.5) PCWP(mmHg) 8.1(4.45) 10.2(3.32) PVR(dyn*s*cm僒5 10.4.4(52.3) 145.9(54.1) TPG 6.7(3.52) 8.2(3) Exercise (mean) mPAP 24.1(3.01) 36.7(5.06) CO 10.8(2.98) 7.56(1.64) PCWP 10.6(5.38) 12.2(4.1) PVR 112.4(64.4) 246.8(76) TPG 13.4(6.28) 24.5(5.1)
8
DD ⴙ PcPH(4) 7
28.3(7.63) 24.7(3.63) 6.05(1.39) 4.76(1.01) 18(3.60) 15(3.91) 131.7(69.6) 180.8(70.4) 7.65(5.01) 9.7(3.3) 41(8.66) 11.8(3.9) 24.3(6.02) 124.1(56.1) 25.4(6.52)
46.8(6.8) 7.78(1.25) 21.4(1.39) 292(90.5) 25.4(6.5)
p⫽0.02) compared to iPAH cohort. Baseline NYHA functional class, 6MWD, and hemodynamics were similar between the two groups. Both cohorts received similar medical therapies which included single agent and combination therapy with prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase inhibitors. Despite similar baseline functional, hemodynamic, and disease characteristics, D⫹T APAH patients had a significantly poorer 5-year event-free survival (33.9 % vs 60.4%, p⫽0.05). Conclusions: D⫹T APAH maybe a distinct entity with potentially poorer outcomes as compared with iPAH. We speculate that this finding may be related to the injurous stimulus itself in combination with a potential genetic susceptibility. Our results need to be validated in larger prospective and epidemiologic studies.
TPG: transpulmonary gradient
128 Decreased Expression of Thrombospondin-1 in Failing Hearts Could Favour Ventricular Remodelling M. Batlle, F. Perez-Villa, A. Lazaro, E. Garcia-Pras, I. Vallejos, A. Arias, A. Sionis, A. Castel, E. Roig Thorax Institute - IDIBAPS Hospital Clı´nic, Barcelona, Spain; Thorax Institute - IDIBAPS Hospital Clı´nic, Barcelona, Spain; Thorax Institute - IDIBAPS Hospital Clı´nic, Barcelona, Spain; Thorax Institute - IDIBAPS Hospital Clı´nic, Barcelona, Spain; Hospital Clı´nic, Barcelona, Spain; Hospital Clı´nic, Barcelona, Spain; Hospital Clı´nic, Barcelona, Spain; Hospital Clı´nic, Barcelona, Spain; Hospital Clı´nic, Barcelona, Spain
127 Characterization of Patients with Drugs and Toxins Associated Pulmonary Arterial Hypertension: A Clinical and Outcomes Perspective S. Snook1, K. Kudelko1, E. Spiekerkoetter1, E. Fuh2, F. Haddad3, R.T. Zamanian1 1Division of Pulmonary & Critical Care Medicine, Stanford, CA; 2Internal Medicine, Stanford, CA; 3 Cardiovascular Medicine, Stanford, CA Purpose: Pulmonary arterial hypertension (PAH) is a life-threatening disease with a poor prognosis.While idiopathic (iPAH) and most associated PAH (APAH) cohorts are well studied, patients with drugs and toxins associated (D⫹T APAH), especially those with methamphetamine use, are not as well characterized.Recent studies have shown an association between iPAH and methamphetamine exposure.Based on our clinical experience, we hypothesized that D⫹T APAH is a distinct entity with a more progressive course than iPAH. In this study, we sought to characterize baseline and clinical outcomes in D⫹T APAH as compared to iPAH. Methods and Materials: Demographic, clinical, and outcomes data were gathered from the Vera Moulton Wall Center Pulmonary Vascular Disease Database and analyzed. Results: We compared 34 iPAH to 45 D⫹T APAH patients. Reported exposures included cocaine (21%), methamphetamines (40%), and diet-pills (30.6%). Combined exposure to stimulants and diet-pills accounted for 22.2% of our cohort. Surprisingly, we found an 8.5 years reported mean exposure time to stimulants and 1.7 years to anorexigens. Patients with D⫹T APAH were older (42.8⫾7.7 vs 38⫾7.6 yrs, p⫽0.007) and more obese (31.9⫾6.2 vs 28.4⫾7.6 kg/m2,
Purpose: Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis and an activator of tissue transforming growth factor 1 (TGF-1). Analysis with genetically modified mice suggested that TSP-1 had a protective role to the infiltration and tissue remodelling responses after infarction. The expression levels of TSP-1 and its putative role in ventricular remodelling have not been determined in human heart failure. Methods and Materials: We analysed the expression of TSP-1, TGF-1 and eNOS mRNA in myocardial biopsies from 34 patients (pts) with end-stage HF undergoing heart transplantation and 13 controls (donors without cardiopathy). Total RNA was extracted from the left ventricle and 1g was retrotranscribed. mRNA expression levels were quantified by Real-time PCR and are given as ng-equivalents of cDNA. Results: Pts mean age was 54⫾2 years and was similar to controls (51⫾72 years). Mean ejection fraction was 21⫾5%, end-diastolic diameter and end-systolic diameter were 73⫾10 and 61⫾11 mm, respectively. HF ethiology was ischemic in 18 pts and non ischemic in the remaining 16. TSP-1 mRNA expression in ventricular tissue from heart failure patients was lower (159.04⫾14.55 ng-equivalents(ngequi) of cDNA), than in control ventricles (234⫾30.66 ng-equi, p⬍0.05). Failing hearts also had lower levels of TGF-1 (68.42⫾4.36 vs 80.58⫾5.26 ng-equi, p⬍0.05) and eNOS (16.9⫾1.11 vs 24.14⫾1.92 ng-equi, p⬍0.002) mRNA expression than in control tissues. TSP-1 mRNA levels correlated with TGF-1 (p⫽0.001, R2⫽ 0.2). Conclusions: 1/ Decreased TSP-1 mRNA levels in failing hearts is in agreement with published results of lower circulating TSP-1 in such patients. 2/ The ventricular dilatation found in these patients could be due to lower expression of TSP-1. 3/ Surprisingly, TGF-1 mRNA levels were lower in failing hearts, which indicates that fibrogenesis takes place in earlier phases of heart failure. 129 Treatment of Endothelial Cells with ATG Prevents Transendothelial Migration of Leukocytes A. Beiras-Fernandez, I. Hartmann, I. Kaczmarek, G. Eissner, B. Reichart LM-University, Munich, Germany
Abstracts
The Journal of Heart and Lung Transplantation February 2009
Resting & Exercise Hemodynamics Group #
Normal(1) Exercise PH(2) DD(3)
# Patients 9 8 Resting (mean) mPAP(mmHg) 14.8(4.67) 18.5(3.58) CO(L/min) 5.5(1.59) 4.5(0.5) PCWP(mmHg) 8.1(4.45) 10.2(3.32) PVR(dyn*s*cm僒5 10.4.4(52.3) 145.9(54.1) TPG 6.7(3.52) 8.2(3) Exercise (mean) mPAP 24.1(3.01) 36.7(5.06) CO 10.8(2.98) 7.56(1.64) PCWP 10.6(5.38) 12.2(4.1) PVR 112.4(64.4) 246.8(76) TPG 13.4(6.28) 24.5(5.1)
8
DD ⴙ PcPH(4) 7
28.3(7.63) 24.7(3.63) 6.05(1.39) 4.76(1.01) 18(3.60) 15(3.91) 131.7(69.6) 180.8(70.4) 7.65(5.01) 9.7(3.3) 41(8.66) 11.8(3.9) 24.3(6.02) 124.1(56.1) 25.4(6.52)
46.8(6.8) 7.78(1.25) 21.4(1.39) 292(90.5) 25.4(6.5)
p⫽0.02) compared to iPAH cohort. Baseline NYHA functional class, 6MWD, and hemodynamics were similar between the two groups. Both cohorts received similar medical therapies which included single agent and combination therapy with prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase inhibitors. Despite similar baseline functional, hemodynamic, and disease characteristics, D⫹T APAH patients had a significantly poorer 5-year event-free survival (33.9 % vs 60.4%, p⫽0.05). Conclusions: D⫹T APAH maybe a distinct entity with potentially poorer outcomes as compared with iPAH. We speculate that this finding may be related to the injurous stimulus itself in combination with a potential genetic susceptibility. Our results need to be validated in larger prospective and epidemiologic studies.
TPG: transpulmonary gradient
128 Decreased Expression of Thrombospondin-1 in Failing Hearts Could Favour Ventricular Remodelling M. Batlle, F. Perez-Villa, A. Lazaro, E. Garcia-Pras, I. Vallejos, A. Arias, A. Sionis, A. Castel, E. Roig Thorax Institute - IDIBAPS Hospital Clı´nic, Barcelona, Spain; Thorax Institute - IDIBAPS Hospital Clı´nic, Barcelona, Spain; Thorax Institute - IDIBAPS Hospital Clı´nic, Barcelona, Spain; Thorax Institute - IDIBAPS Hospital Clı´nic, Barcelona, Spain; Hospital Clı´nic, Barcelona, Spain; Hospital Clı´nic, Barcelona, Spain; Hospital Clı´nic, Barcelona, Spain; Hospital Clı´nic, Barcelona, Spain; Hospital Clı´nic, Barcelona, Spain
127 Characterization of Patients with Drugs and Toxins Associated Pulmonary Arterial Hypertension: A Clinical and Outcomes Perspective S. Snook1, K. Kudelko1, E. Spiekerkoetter1, E. Fuh2, F. Haddad3, R.T. Zamanian1 1Division of Pulmonary & Critical Care Medicine, Stanford, CA; 2Internal Medicine, Stanford, CA; 3 Cardiovascular Medicine, Stanford, CA Purpose: Pulmonary arterial hypertension (PAH) is a life-threatening disease with a poor prognosis.While idiopathic (iPAH) and most associated PAH (APAH) cohorts are well studied, patients with drugs and toxins associated (D⫹T APAH), especially those with methamphetamine use, are not as well characterized.Recent studies have shown an association between iPAH and methamphetamine exposure.Based on our clinical experience, we hypothesized that D⫹T APAH is a distinct entity with a more progressive course than iPAH. In this study, we sought to characterize baseline and clinical outcomes in D⫹T APAH as compared to iPAH. Methods and Materials: Demographic, clinical, and outcomes data were gathered from the Vera Moulton Wall Center Pulmonary Vascular Disease Database and analyzed. Results: We compared 34 iPAH to 45 D⫹T APAH patients. Reported exposures included cocaine (21%), methamphetamines (40%), and diet-pills (30.6%). Combined exposure to stimulants and diet-pills accounted for 22.2% of our cohort. Surprisingly, we found an 8.5 years reported mean exposure time to stimulants and 1.7 years to anorexigens. Patients with D⫹T APAH were older (42.8⫾7.7 vs 38⫾7.6 yrs, p⫽0.007) and more obese (31.9⫾6.2 vs 28.4⫾7.6 kg/m2,
Purpose: Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis and an activator of tissue transforming growth factor 1 (TGF-1). Analysis with genetically modified mice suggested that TSP-1 had a protective role to the infiltration and tissue remodelling responses after infarction. The expression levels of TSP-1 and its putative role in ventricular remodelling have not been determined in human heart failure. Methods and Materials: We analysed the expression of TSP-1, TGF-1 and eNOS mRNA in myocardial biopsies from 34 patients (pts) with end-stage HF undergoing heart transplantation and 13 controls (donors without cardiopathy). Total RNA was extracted from the left ventricle and 1g was retrotranscribed. mRNA expression levels were quantified by Real-time PCR and are given as ng-equivalents of cDNA. Results: Pts mean age was 54⫾2 years and was similar to controls (51⫾72 years). Mean ejection fraction was 21⫾5%, end-diastolic diameter and end-systolic diameter were 73⫾10 and 61⫾11 mm, respectively. HF ethiology was ischemic in 18 pts and non ischemic in the remaining 16. TSP-1 mRNA expression in ventricular tissue from heart failure patients was lower (159.04⫾14.55 ng-equivalents(ngequi) of cDNA), than in control ventricles (234⫾30.66 ng-equi, p⬍0.05). Failing hearts also had lower levels of TGF-1 (68.42⫾4.36 vs 80.58⫾5.26 ng-equi, p⬍0.05) and eNOS (16.9⫾1.11 vs 24.14⫾1.92 ng-equi, p⬍0.002) mRNA expression than in control tissues. TSP-1 mRNA levels correlated with TGF-1 (p⫽0.001, R2⫽ 0.2). Conclusions: 1/ Decreased TSP-1 mRNA levels in failing hearts is in agreement with published results of lower circulating TSP-1 in such patients. 2/ The ventricular dilatation found in these patients could be due to lower expression of TSP-1. 3/ Surprisingly, TGF-1 mRNA levels were lower in failing hearts, which indicates that fibrogenesis takes place in earlier phases of heart failure. 129 Treatment of Endothelial Cells with ATG Prevents Transendothelial Migration of Leukocytes A. Beiras-Fernandez, I. Hartmann, I. Kaczmarek, G. Eissner, B. Reichart LM-University, Munich, Germany