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Risk Stratification for Developing Cardiovascular Allograft Vasculopathy in Heart Transplant Recipients: Evaluation by Annual Intravascular Ultrasound
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The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
Conclusion: In our patients an additional application of cardioplegic solution did not positively influence the outcome after htx. However, as we observed reduced myocardial damage and improved clinical course in patients with prolonged graft ischemia and supplemental cardioplegia, this approach may be useful in selected patients and should be validated in further prospective studies. 5( 21) Risk Stratification for Developing Cardiovascular Allograft Vasculopathy in Heart Transplant Recipients: Evaluation by Annual Intravascular Ultrasound T. Sato ,1 O. Seguchi,1 H. Ishibashi-Ueda,2 M. Yanase,1 N. Okada,1 K. Kuroda,1 E. Hisamatsu,1 H. Sunami,1 T. Watanabe,1 S. Nakajima,1 H. Hata,3 T. Fujita,1 N. Fukushima,1 J. Kobayashi,3 T. Nakatani.1 1Transplantation, National Cardiovascular Center, Osaka, Japan; 2Pathology, National Cardiovascular Center, Osaka, Japan; 3Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan. Purpose: Heart transplantation (HTx) remains the treatment of choice for patients with end stage heart failure. While progress has been made, longterm success after HTx is primarily limited by the development of cardiac allograft vasculopathy (CAV). The purpose of this study was to assess the influence and interdependence of immunologic and non-immunologic risk factors in the development of CAV after HTx in patients undergoing annual intravascular ultrasound (IVUS) examination. Methods: We conducted a single-center, retrospective, observational analysis. Fifty four consecutive patients who underwent HTx from May 1999 to December 2013 were included in this study. Endomyocardial biopsies were performed for surveillance of acute cellular rejection (ACR) and specimens were graded per the ISHLT classification. Cardiovascular risk factors were also collected, including donor and recipient age at transplant, obesity (body mass index ≥ 25) at 1 year after transplant, diabetes, and dyslipidemia during the follow up period after HTx. A baseline IVUS was conducted each year within 5 to 11 weeks after HTx. Patients were divided into two groups based on whether or not there was CAV progression. Results: CAV progression was detected in 25 patients (46.2%). Univariate and multivariate analysis indicated a history of ACR ≥ grade 2 (ACR ≥ 2) and donor age were significantly associated with CAV progression. Of the 54 patients, 18 experienced ACR ≥ 2 during the follow-up period, 77% of whom developed CAV. In addition, patients with a donor age > 50 had a significant association with CAV development. However, there was no significant difference between the groups in cardiac event-free survival or overall mortality. Conclusion: In this study, donor age and a history of ACR ≥ 2 were independent risk factors associated with the development of CAV. However, overall mortality and cardiac events did not differ in acute or long-term survival, possibly reflecting the benefit of annual IVUS with prompt therapeutic intervention to minimize further development. Identification of patients at risk of developing CAV may have relevant implications in appropriately guiding resources and intensive follow-up. However, patients without these risks may be able to avoid frequent invasive testing that increases costs and complication risks for the patient. 5( 22) Perfusion Cardiac Magnetic Resonance Imaging in Cardiac Allograft Vasculopathy S. Chih ,1 A.M. Crean,2 A.C. Alba,2 C.S. Fan,3 C. Manlhiot,3 H.J. Ross.2 1University of Ottawa Heart Institute, Ottawa, ON, Canada; 2Toronto General Hospital - University Health Network, Toronto, ON, Canada; 3Cardiovascular Data Management Centre - University of Toronto, Toronto, ON, Canada. Purpose: Cardiac allograft vasculopathy (CAV) is a leading cause of mortality after heart transplantation. Non-invasive imaging has poor sensitivity and specificity for CAV. Cardiac magnetic resonance imaging (CMR) provides integrated assessment of cardiac anatomy, function, perfusion, and fibrosis. We investigated the accuracy of perfusion CMR to detect CAV.
Methods: Between 2011 and 2014, 29 patients scheduled for coronary angiography (20 for CAV surveillance) completed evaluation by CMR 20 ± 12 days apart. Angiograms were analyzed by quantitative coronary angiography and disease severity graded according to ISHLT CAV 0-3. Intravascular ultrasound (IVUS, n = 27) was performed in the left anterior descending artery (LAD) and CAV defined as maximal intimal thickness (MIT) > 0.5 mm. Perfusion CMR was performed using dipyridamole (0.14 mg/kg/min) and Gadobutrol (0.05 mmol/kg). Myocardial perfusion reserve index (MPR) was calculated from normalized stress:rest upslopes of myocardial signal intensity-time curves. We analyzed accuracy metrics of CMR to detect CAV based on optimal MPR cut-off as determined by receiving operating characteristic curves. Results: Average time post-transplant was 5 ± 4 years (18 male, mean age 45 ± 16 years). CAV was present in the majority: 20 (69%) and 19 (70%) patients had disease on angiography (all CAV grade 1) and IVUS (mean MIT 0.82 ± 0.42 mm), respectively. Only 2 and 4 patients had perfusion defects on rest- and stress-imaging, respectively. In contrast, MPR was globally reduced: 1.44 ± 0.35. Mean LAD territory MPR was lower in patients with MIT ≥ 0.50 mm: 1.35 ± 0.23 vs. 1.71 ± 0.45, p = 0.013. There was moderate inverse correlation between LAD MPR and MIT (figure). An optimal MPR ≤ 1.68 cut-off predicting CAV was determined yielding: sensitivity 100%, specificity 63%, negative predictive value (NPV) 100%, positive predictive value 86%, positive likelihood ratio 2.7. Conclusion: MPR is reduced in patients with CAV. An MPR ≤ 1.68 has high NPV, suggesting potential value as a rule out test for CAV.
5( 23) What Are the Important Factors for Cardiac Vasculopathy Development After Heart Transplantation? M. Sobieszczanska-Malek ,1 J. Korewicki,1 M. Karczmarz,1 K. Komuda,1 S. Szymanska,2 P. Bekta,3 A. Parulski,4 M. Jasinska,5 M. Kuśmierczyk,4 T. Zielinski.1 1Heart Failure and Transplantology, Institute of Cardiology, Warsaw, Poland; 2Pathology, The Children’s Memorial Health Institute, Warsaw, Poland; 3Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland; 4Cardiosurgery and Transplantology, Institute of Cardiology, Warsaw, Poland; 5Anesthesiology, Institute of Cardiology, Warsaw, Poland. Purpose: Heart transplantation (HT) is a lifesaving therapy for patients with end-stage heart disease. Cardiac allograft vasculopathy (CAV) is still an important problem. The aim of the study was to compare the influence of immunologic and nonimmunologic risk factors on the development of vasculopathy in patients with transplanted heart in a single center. Methods: 147 patients mean age 45.8 ± 15.3 who underwent HT were studied. All of them were examined at least once by coronary angiography after HT. We analysed following risk factors: nonimmunologic - age of transplantation, smoking, hypertension, lipids, diabetes, obesity and weight gain after HT, immunologic - ACR, AMR, CMV episodes, donor related risk factors - age, sex, catecholamines usage, ischemic time, compatibility of sex and blood groups, cause of death, cardiac arrest.
The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
Conclusion: In our patients an additional application of cardioplegic solution did not positively influence the outcome after htx. However, as we observed reduced myocardial damage and improved clinical course in patients with prolonged graft ischemia and supplemental cardioplegia, this approach may be useful in selected patients and should be validated in further prospective studies. 5( 21) Risk Stratification for Developing Cardiovascular Allograft Vasculopathy in Heart Transplant Recipients: Evaluation by Annual Intravascular Ultrasound T. Sato ,1 O. Seguchi,1 H. Ishibashi-Ueda,2 M. Yanase,1 N. Okada,1 K. Kuroda,1 E. Hisamatsu,1 H. Sunami,1 T. Watanabe,1 S. Nakajima,1 H. Hata,3 T. Fujita,1 N. Fukushima,1 J. Kobayashi,3 T. Nakatani.1 1Transplantation, National Cardiovascular Center, Osaka, Japan; 2Pathology, National Cardiovascular Center, Osaka, Japan; 3Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan. Purpose: Heart transplantation (HTx) remains the treatment of choice for patients with end stage heart failure. While progress has been made, longterm success after HTx is primarily limited by the development of cardiac allograft vasculopathy (CAV). The purpose of this study was to assess the influence and interdependence of immunologic and non-immunologic risk factors in the development of CAV after HTx in patients undergoing annual intravascular ultrasound (IVUS) examination. Methods: We conducted a single-center, retrospective, observational analysis. Fifty four consecutive patients who underwent HTx from May 1999 to December 2013 were included in this study. Endomyocardial biopsies were performed for surveillance of acute cellular rejection (ACR) and specimens were graded per the ISHLT classification. Cardiovascular risk factors were also collected, including donor and recipient age at transplant, obesity (body mass index ≥ 25) at 1 year after transplant, diabetes, and dyslipidemia during the follow up period after HTx. A baseline IVUS was conducted each year within 5 to 11 weeks after HTx. Patients were divided into two groups based on whether or not there was CAV progression. Results: CAV progression was detected in 25 patients (46.2%). Univariate and multivariate analysis indicated a history of ACR ≥ grade 2 (ACR ≥ 2) and donor age were significantly associated with CAV progression. Of the 54 patients, 18 experienced ACR ≥ 2 during the follow-up period, 77% of whom developed CAV. In addition, patients with a donor age > 50 had a significant association with CAV development. However, there was no significant difference between the groups in cardiac event-free survival or overall mortality. Conclusion: In this study, donor age and a history of ACR ≥ 2 were independent risk factors associated with the development of CAV. However, overall mortality and cardiac events did not differ in acute or long-term survival, possibly reflecting the benefit of annual IVUS with prompt therapeutic intervention to minimize further development. Identification of patients at risk of developing CAV may have relevant implications in appropriately guiding resources and intensive follow-up. However, patients without these risks may be able to avoid frequent invasive testing that increases costs and complication risks for the patient. 5( 22) Perfusion Cardiac Magnetic Resonance Imaging in Cardiac Allograft Vasculopathy S. Chih ,1 A.M. Crean,2 A.C. Alba,2 C.S. Fan,3 C. Manlhiot,3 H.J. Ross.2 1University of Ottawa Heart Institute, Ottawa, ON, Canada; 2Toronto General Hospital - University Health Network, Toronto, ON, Canada; 3Cardiovascular Data Management Centre - University of Toronto, Toronto, ON, Canada. Purpose: Cardiac allograft vasculopathy (CAV) is a leading cause of mortality after heart transplantation. Non-invasive imaging has poor sensitivity and specificity for CAV. Cardiac magnetic resonance imaging (CMR) provides integrated assessment of cardiac anatomy, function, perfusion, and fibrosis. We investigated the accuracy of perfusion CMR to detect CAV.
Methods: Between 2011 and 2014, 29 patients scheduled for coronary angiography (20 for CAV surveillance) completed evaluation by CMR 20 ± 12 days apart. Angiograms were analyzed by quantitative coronary angiography and disease severity graded according to ISHLT CAV 0-3. Intravascular ultrasound (IVUS, n = 27) was performed in the left anterior descending artery (LAD) and CAV defined as maximal intimal thickness (MIT) > 0.5 mm. Perfusion CMR was performed using dipyridamole (0.14 mg/kg/min) and Gadobutrol (0.05 mmol/kg). Myocardial perfusion reserve index (MPR) was calculated from normalized stress:rest upslopes of myocardial signal intensity-time curves. We analyzed accuracy metrics of CMR to detect CAV based on optimal MPR cut-off as determined by receiving operating characteristic curves. Results: Average time post-transplant was 5 ± 4 years (18 male, mean age 45 ± 16 years). CAV was present in the majority: 20 (69%) and 19 (70%) patients had disease on angiography (all CAV grade 1) and IVUS (mean MIT 0.82 ± 0.42 mm), respectively. Only 2 and 4 patients had perfusion defects on rest- and stress-imaging, respectively. In contrast, MPR was globally reduced: 1.44 ± 0.35. Mean LAD territory MPR was lower in patients with MIT ≥ 0.50 mm: 1.35 ± 0.23 vs. 1.71 ± 0.45, p = 0.013. There was moderate inverse correlation between LAD MPR and MIT (figure). An optimal MPR ≤ 1.68 cut-off predicting CAV was determined yielding: sensitivity 100%, specificity 63%, negative predictive value (NPV) 100%, positive predictive value 86%, positive likelihood ratio 2.7. Conclusion: MPR is reduced in patients with CAV. An MPR ≤ 1.68 has high NPV, suggesting potential value as a rule out test for CAV.
5( 23) What Are the Important Factors for Cardiac Vasculopathy Development After Heart Transplantation? M. Sobieszczanska-Malek ,1 J. Korewicki,1 M. Karczmarz,1 K. Komuda,1 S. Szymanska,2 P. Bekta,3 A. Parulski,4 M. Jasinska,5 M. Kuśmierczyk,4 T. Zielinski.1 1Heart Failure and Transplantology, Institute of Cardiology, Warsaw, Poland; 2Pathology, The Children’s Memorial Health Institute, Warsaw, Poland; 3Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland; 4Cardiosurgery and Transplantology, Institute of Cardiology, Warsaw, Poland; 5Anesthesiology, Institute of Cardiology, Warsaw, Poland. Purpose: Heart transplantation (HT) is a lifesaving therapy for patients with end-stage heart disease. Cardiac allograft vasculopathy (CAV) is still an important problem. The aim of the study was to compare the influence of immunologic and nonimmunologic risk factors on the development of vasculopathy in patients with transplanted heart in a single center. Methods: 147 patients mean age 45.8 ± 15.3 who underwent HT were studied. All of them were examined at least once by coronary angiography after HT. We analysed following risk factors: nonimmunologic - age of transplantation, smoking, hypertension, lipids, diabetes, obesity and weight gain after HT, immunologic - ACR, AMR, CMV episodes, donor related risk factors - age, sex, catecholamines usage, ischemic time, compatibility of sex and blood groups, cause of death, cardiac arrest.