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Common Carotid Artery Wall Rigidity Index Is a Marker of Cardiac Allograft Rejection
S298
The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
8( 18) Vessel Shrinkage (Negative Remodeling) Is the Main Mechanism of Lumen Compromise in Allograft Vasculopathy - A Long-Term Serial Intravascular Ultrasound Study K. Goto,1 I. Iakovou,2 A. Gkouziouta ,2 A. Maehara,1 G.S. Mintz,1 G. Karavolias,2 V. Leontiadis,2 V. Voudris,2 G. Pavlides,2 S. Adamopoulos.2 1Cardiovascular Research Foundation, Clinical Trial Center, Columbia University Medical Center, Center for Interventional Vascular Therapy, New York USA, NY; 2Cardiology Department, Onassis Cardiac Surgery Centre, Athens, Greece. Purpose: There is limited long-term data on the mechanism of lumen compromise in cardiac allograft vasculopathy (CAV). Methods: We performed serial intravascular ultrasound (IVUS) evaluation of the LAD in 66 consecutive heart transplant recipients. Baseline and follow-up (mean duration= 3.2 years) proximal LAD segments were matched; and a ≥ 20mm long proximal segment was analyzed every 1mm, and results normalized for analysis length and reported as mm3/mm. Results: Overall, the change of mean lumen area was well correlated to the change in mean vessel area (r= 0.94, p< 0.01), but not to the change in mean plaque area (p= 0.16) . Twenty two pts (33.3 %) had a history of cellular rejection. Clinical characteristics, baseline IVUS, and follow up IVUS were similar between pts with vs without rejection. During follow up, vessel area decreased in pts with and without rejection (-0.25±1.62 vs -0.08±1.17 mm3/mm, p= 0.62). And plaque area increased in both groups (0.27±0.68 vs 0.09±0.33 mm3/mm, p= 0.16). As a result, lumen area decreased in both groups, and there was no significant difference between them (-0.53±1.67 vs -0.16±1.12 mm3/mm, p= 0.3). Furthermore, the correlations between mean lumen areas vs mean vessel or plaque areas were similar in pts with or without rejection. Conclusion: Lumen loss occurs in long term follow up of CAV pts with and without rejection. Although plaque increase contributes to lumen loss, the main mechanism is vessel negative remodeling. 8( 19) Potential Value of C4d Capillary Deposition in Myocardial Biopsies and NTproBNP, hs CRP in Serum as Markers of Prognosis in Patients After Heart Transplantation T. Zielinski ,1 M. Sobieszczanska- Malek,1 K. Komuda,1 M. Karczmarz,1 A. Browarek,1 W. Grajkowska,2 P. Kluge,2 M. Pronicki,1 S. Szymanska,2 A. Parulski,3 P. Bekta,4 M. Karcz,4 J. Wisniewska,1 J. Rozanski,3 J. Korewicki.1 1Heart Failure and Transplantology, Institute of Cardiology, Warsaw, Poland; 2Pathology Department, Children Health Memorial Hospital, Warsaw, Poland; 3Cardiac Surgery and Transplantation, Institute of Cardiology, Warsaw, Poland; 4Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland. Purpose: Despite advances in development of biomarkers of cardiac graft dysfunction there is a controversy about their role in long term prognosis. The aim of the study was to determine whether a single marker approach can be used to prognose a long term survival of patients after OHT Methods: 217 consecutive pts (175 men) from a single center operated up to 2013 in which at least one myocardial biopsy was available were included in the analyses. Mean age of pts was 46 ± 15 years, 104 pts with ischemic,and 113 non ischemic etiology. Multiple NTproBNP and hs CRP levels measurements in serum at different time points ranging from 3 months up to 10 years after OHT were determined and averaged , all available biopsies were analyzed for the intracapillary deposition of C4d in transplanted hearts (1345 biopsies in 217 pts). ROC curves analyses were performed for determine the cut-off value for hs CRP and NTproBNP for the best prediction of survival. Based on those cutoff values survival Kaplan Meier curves with log-rank test were designed to analyze differences in survival according to the levels of hs CRP, NTproBNP and the presence of C4d deposition in myocardial capillaries. A multivariate Cox survival proportional hazard regression model was used to determine a significance of analyzed markers and other factors. Analyses were done using STATISTICA 10 software. Results: The survival follow up was 100% complete and lasted median time 1896 (interquartile range ±2402) days. During long term observation 66 pts died. Capillary deposition of C4d was found in 42 patients (in 14”
protracted”- in at least two biopsies). The presence of C4d however has no significant influence on long term survival. Increase of NTproBNP and hs CRP levels were independently correlated with poor long term outcome in pts after OHT in multivariate Cox analysis. The cut off values determined by AUC analyses for NTproBNP were 5141 pg/ml and hsCRP> 0,698 mg/dl. Pts with higher levels of NtproBNP or hsCRP had significantly shorter survival (log rank respectively p< 0.0001 and p< 0.0002). Conclusion: 1. Averaged increased post transplantation serum levels of NTproBNP and hs CRP are independent markers of long term worsened survival of pts after heart transplantation. 2. C4d deposition in myocardial capillaries in myocardial biopsies is of limited prognostic value. 8( 20) Common Carotid Artery Wall Rigidity Index Is a Marker of Cardiac Allograft Rejection A.O. Shevchenko ,1 I.U. Tunyuaeva,2 A.A. Nasyrova,2 I.M. Ilynsky,3 O.P. Shevchenko,4 S.V. Gautier,5 V.N. Poptzov.6 1Cardiology Dept., Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 2Functional Diagnostics Dept., Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 3Pathology Dept., Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 4Science Dept., Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 5Transplantology Dept., Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 6Intensive Care Unit, Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation. Purpose: Our goal was to analyze the clinical utility of carotid artery wall rigidity index (CAWRI) measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients. Methods: Seventy five consecutive heart transplant recipients (12 females and 63 males, mean age 44.9±15.1 y) 9-5307 days after cardiac transplantation (mean 565.2 days) were included. Carotid triplex ultrasound was performed prior to planned endomyocardial biopsy. CAWRI was estimated using empirical equation: CWRI= ([Vs-Vd]/aT)*(Dd2/[Dd2-Ds2]), where Vs, Vd, Ds, and Dd are systolic and diastolic common carotid artery blood flow velocities and diameters, respectively, and aT is carotid flow acceleration time. Results: Antibody-mediated and cellular rejection were found in 10 (13.3%) and 14 (18.7%) patients, respectively. Mean CWRI in patients without rejection was significantly lower in comparison to antibody-mediated rejection (5681.5±799.7 vs 11071±2262.3 cm/sec2, p= 0.046) and cell-mediated rejection (5681.5±799.7 vs 11641.0±1946.2 cm/sec2, p= 0.002). Area under ROC for CWRI was 0.65±0.07 (p= 0.03 when compared to 0.5 value). Analysis showed that in patients with CWRI > 7000 cm/sec2 relative risk of any type of rejection was 2.23 (95%CI 1.06-4.7, p= 0.03) with true positive rate 0.71, specificity - 0.57, negative predictive value - 0.8. Conclusion: Increased common carotid wall stiffness is found in patients with both antibody-mediated and cellular cardiac allograft rejection. Non-invasive measurement of carotid artery wall rigidity index using triplex ultrasound is a simple screening tool for risk stratification. Having a functional marker would enable preventive measures to be taken at the early stages. 8( 21) Anti-Human Leukocyte Antigen Antibody Class Affects Outcomes After Heart Transplant F. Liou , M. Kittleson, J. Patel, S. Siddiqui, M. Luu, B. Kearney, D. Ramzy, D.H. Chang, L. Czer, N. Reinsmoen, J.A. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA. Purpose: The development of donor-specific antibodies (DSA) after heart transplant has been correlated to the subsequent development of graft rejection. The development of donor specific antibodies (DSA) are divided into class I and class II anti-HLA antibodies. It is not clear as to whether each
The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
8( 18) Vessel Shrinkage (Negative Remodeling) Is the Main Mechanism of Lumen Compromise in Allograft Vasculopathy - A Long-Term Serial Intravascular Ultrasound Study K. Goto,1 I. Iakovou,2 A. Gkouziouta ,2 A. Maehara,1 G.S. Mintz,1 G. Karavolias,2 V. Leontiadis,2 V. Voudris,2 G. Pavlides,2 S. Adamopoulos.2 1Cardiovascular Research Foundation, Clinical Trial Center, Columbia University Medical Center, Center for Interventional Vascular Therapy, New York USA, NY; 2Cardiology Department, Onassis Cardiac Surgery Centre, Athens, Greece. Purpose: There is limited long-term data on the mechanism of lumen compromise in cardiac allograft vasculopathy (CAV). Methods: We performed serial intravascular ultrasound (IVUS) evaluation of the LAD in 66 consecutive heart transplant recipients. Baseline and follow-up (mean duration= 3.2 years) proximal LAD segments were matched; and a ≥ 20mm long proximal segment was analyzed every 1mm, and results normalized for analysis length and reported as mm3/mm. Results: Overall, the change of mean lumen area was well correlated to the change in mean vessel area (r= 0.94, p< 0.01), but not to the change in mean plaque area (p= 0.16) . Twenty two pts (33.3 %) had a history of cellular rejection. Clinical characteristics, baseline IVUS, and follow up IVUS were similar between pts with vs without rejection. During follow up, vessel area decreased in pts with and without rejection (-0.25±1.62 vs -0.08±1.17 mm3/mm, p= 0.62). And plaque area increased in both groups (0.27±0.68 vs 0.09±0.33 mm3/mm, p= 0.16). As a result, lumen area decreased in both groups, and there was no significant difference between them (-0.53±1.67 vs -0.16±1.12 mm3/mm, p= 0.3). Furthermore, the correlations between mean lumen areas vs mean vessel or plaque areas were similar in pts with or without rejection. Conclusion: Lumen loss occurs in long term follow up of CAV pts with and without rejection. Although plaque increase contributes to lumen loss, the main mechanism is vessel negative remodeling. 8( 19) Potential Value of C4d Capillary Deposition in Myocardial Biopsies and NTproBNP, hs CRP in Serum as Markers of Prognosis in Patients After Heart Transplantation T. Zielinski ,1 M. Sobieszczanska- Malek,1 K. Komuda,1 M. Karczmarz,1 A. Browarek,1 W. Grajkowska,2 P. Kluge,2 M. Pronicki,1 S. Szymanska,2 A. Parulski,3 P. Bekta,4 M. Karcz,4 J. Wisniewska,1 J. Rozanski,3 J. Korewicki.1 1Heart Failure and Transplantology, Institute of Cardiology, Warsaw, Poland; 2Pathology Department, Children Health Memorial Hospital, Warsaw, Poland; 3Cardiac Surgery and Transplantation, Institute of Cardiology, Warsaw, Poland; 4Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland. Purpose: Despite advances in development of biomarkers of cardiac graft dysfunction there is a controversy about their role in long term prognosis. The aim of the study was to determine whether a single marker approach can be used to prognose a long term survival of patients after OHT Methods: 217 consecutive pts (175 men) from a single center operated up to 2013 in which at least one myocardial biopsy was available were included in the analyses. Mean age of pts was 46 ± 15 years, 104 pts with ischemic,and 113 non ischemic etiology. Multiple NTproBNP and hs CRP levels measurements in serum at different time points ranging from 3 months up to 10 years after OHT were determined and averaged , all available biopsies were analyzed for the intracapillary deposition of C4d in transplanted hearts (1345 biopsies in 217 pts). ROC curves analyses were performed for determine the cut-off value for hs CRP and NTproBNP for the best prediction of survival. Based on those cutoff values survival Kaplan Meier curves with log-rank test were designed to analyze differences in survival according to the levels of hs CRP, NTproBNP and the presence of C4d deposition in myocardial capillaries. A multivariate Cox survival proportional hazard regression model was used to determine a significance of analyzed markers and other factors. Analyses were done using STATISTICA 10 software. Results: The survival follow up was 100% complete and lasted median time 1896 (interquartile range ±2402) days. During long term observation 66 pts died. Capillary deposition of C4d was found in 42 patients (in 14”
protracted”- in at least two biopsies). The presence of C4d however has no significant influence on long term survival. Increase of NTproBNP and hs CRP levels were independently correlated with poor long term outcome in pts after OHT in multivariate Cox analysis. The cut off values determined by AUC analyses for NTproBNP were 5141 pg/ml and hsCRP> 0,698 mg/dl. Pts with higher levels of NtproBNP or hsCRP had significantly shorter survival (log rank respectively p< 0.0001 and p< 0.0002). Conclusion: 1. Averaged increased post transplantation serum levels of NTproBNP and hs CRP are independent markers of long term worsened survival of pts after heart transplantation. 2. C4d deposition in myocardial capillaries in myocardial biopsies is of limited prognostic value. 8( 20) Common Carotid Artery Wall Rigidity Index Is a Marker of Cardiac Allograft Rejection A.O. Shevchenko ,1 I.U. Tunyuaeva,2 A.A. Nasyrova,2 I.M. Ilynsky,3 O.P. Shevchenko,4 S.V. Gautier,5 V.N. Poptzov.6 1Cardiology Dept., Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 2Functional Diagnostics Dept., Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 3Pathology Dept., Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 4Science Dept., Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 5Transplantology Dept., Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 6Intensive Care Unit, Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation. Purpose: Our goal was to analyze the clinical utility of carotid artery wall rigidity index (CAWRI) measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients. Methods: Seventy five consecutive heart transplant recipients (12 females and 63 males, mean age 44.9±15.1 y) 9-5307 days after cardiac transplantation (mean 565.2 days) were included. Carotid triplex ultrasound was performed prior to planned endomyocardial biopsy. CAWRI was estimated using empirical equation: CWRI= ([Vs-Vd]/aT)*(Dd2/[Dd2-Ds2]), where Vs, Vd, Ds, and Dd are systolic and diastolic common carotid artery blood flow velocities and diameters, respectively, and aT is carotid flow acceleration time. Results: Antibody-mediated and cellular rejection were found in 10 (13.3%) and 14 (18.7%) patients, respectively. Mean CWRI in patients without rejection was significantly lower in comparison to antibody-mediated rejection (5681.5±799.7 vs 11071±2262.3 cm/sec2, p= 0.046) and cell-mediated rejection (5681.5±799.7 vs 11641.0±1946.2 cm/sec2, p= 0.002). Area under ROC for CWRI was 0.65±0.07 (p= 0.03 when compared to 0.5 value). Analysis showed that in patients with CWRI > 7000 cm/sec2 relative risk of any type of rejection was 2.23 (95%CI 1.06-4.7, p= 0.03) with true positive rate 0.71, specificity - 0.57, negative predictive value - 0.8. Conclusion: Increased common carotid wall stiffness is found in patients with both antibody-mediated and cellular cardiac allograft rejection. Non-invasive measurement of carotid artery wall rigidity index using triplex ultrasound is a simple screening tool for risk stratification. Having a functional marker would enable preventive measures to be taken at the early stages. 8( 21) Anti-Human Leukocyte Antigen Antibody Class Affects Outcomes After Heart Transplant F. Liou , M. Kittleson, J. Patel, S. Siddiqui, M. Luu, B. Kearney, D. Ramzy, D.H. Chang, L. Czer, N. Reinsmoen, J.A. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA. Purpose: The development of donor-specific antibodies (DSA) after heart transplant has been correlated to the subsequent development of graft rejection. The development of donor specific antibodies (DSA) are divided into class I and class II anti-HLA antibodies. It is not clear as to whether each