Cardiac allograft vasculopathy: A review.
cardiac allograft vasculopathy
cardiac transplantation
graft survival
paediatrics
pediatric heart transplant
Journal
Pediatric transplantation
ISSN: 1399-3046
Titre abrégé: Pediatr Transplant
Pays: Denmark
ID NLM: 9802574
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
11
11
2021
received:
08
06
2021
accepted:
26
11
2021
pubmed:
6
1
2022
medline:
23
4
2022
entrez:
5
1
2022
Statut:
ppublish
Résumé
Heart transplantation has become the standard of care for pediatric patients with end-stage heart disease, and outcomes have consistently improved over the last few decades. CAV, however, remains a leading cause of morbidity and mortality in heart transplantation and is the leading cause of death beyond 3 years post-transplantation. We sought out to provide an in-depth overview of CAV in the pediatric heart transplant population. Database searches were conducted in both Medline and Embase on the topic of cardiac vasculopathy in pediatric heart transplant recipients. The search used five broad concept terms: heart transplant; pediatric; CAV; diagnosis, prognosis, and risk factors; and guidelines and reviews. References were captured if there was at least one term in each of the concepts. The search was limited to articles in the English language. A total of 148 articles were identified via the literature search with further articles identified via review of references. Pediatric data regarding the etiology and development of CAV remain limited although knowledge about the immune and non-immune factors playing a role are increasing. CAV continues to be difficult to detect with many invasive and non-invasive methods available, yet their effectiveness in the detection of CAV remains suboptimal. There remains no proven medical intervention to treat or reverse established CAV disease, and CAV is associated with high rates of graft loss once detected. However, several medications are used in hopes of preventing, slowing progression, or modifying the outcomes. This review provides a comprehensive overview of CAV, discusses its clinical presentation, risk factors, diagnostic tools used to identify CAV in the pediatric population, and highlights the current therapeutic options and the need for ongoing research.
Sections du résumé
BACKGROUND
Heart transplantation has become the standard of care for pediatric patients with end-stage heart disease, and outcomes have consistently improved over the last few decades. CAV, however, remains a leading cause of morbidity and mortality in heart transplantation and is the leading cause of death beyond 3 years post-transplantation. We sought out to provide an in-depth overview of CAV in the pediatric heart transplant population.
METHODS
Database searches were conducted in both Medline and Embase on the topic of cardiac vasculopathy in pediatric heart transplant recipients. The search used five broad concept terms: heart transplant; pediatric; CAV; diagnosis, prognosis, and risk factors; and guidelines and reviews. References were captured if there was at least one term in each of the concepts. The search was limited to articles in the English language.
RESULTS
A total of 148 articles were identified via the literature search with further articles identified via review of references. Pediatric data regarding the etiology and development of CAV remain limited although knowledge about the immune and non-immune factors playing a role are increasing. CAV continues to be difficult to detect with many invasive and non-invasive methods available, yet their effectiveness in the detection of CAV remains suboptimal. There remains no proven medical intervention to treat or reverse established CAV disease, and CAV is associated with high rates of graft loss once detected. However, several medications are used in hopes of preventing, slowing progression, or modifying the outcomes.
CONCLUSION
This review provides a comprehensive overview of CAV, discusses its clinical presentation, risk factors, diagnostic tools used to identify CAV in the pediatric population, and highlights the current therapeutic options and the need for ongoing research.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14218Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
Singh TP, Hsich E, Cherikh WS, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: 23rd pediatric heart transplantation report-2020; focus on deceased donor characteristics. J Heart Lung Transplant. 2020;39(10):1028-1037.
Rossano JW, Singh TP, Cherikh WS, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: twenty-second pediatric heart transplantation report - 2019; focus theme: donor and recipient size match. J Heart Lung Transplant. 2019;38(10):1028-1041. 10.1016/j.healun.2019.08.002
Dipchand AI, Laks JA. Pediatric heart transplantation: long-term outcomes. Indian J Thorac Cardiovasc Surg. 2020;36:175-189.
Kindel SJ, Pahl E. Current therapies for cardiac allograft vasculopathy in children. Congenit Heart Dis. 2012;7(4):324-335.
Badano LP, Miglioranza MH, Edvardsen T, et al. European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation. Eur Heart J Cardiovasc Imaging. 2015;16(9):919-948.
Vassalli G, Gallino A, Weis M, et al. Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy. Eur Heart J. 2003;24(13):1180-1188.
Daly KP, Seifert ME, Chandraker A, et al. VEGF-C, VEGF-A and related angiogenesis factors as biomarkers of allograft vasculopathy in cardiac transplant recipients. J Hear Lung Transplant. 2013;32(1):120-128. 10.1016/j.healun.2012.09.030
Daly KP, Stack M, Eisenga MF, et al. Vascular endothelial growth factor A is associated with the subsequent development of moderate or severe cardiac allograft vasculopathy in pediatric heart transplant recipients. J Hear Lung Transplant. 2017;36(4):434-442.
Watanabe K, Karimpour-Fard A, Michael A, Miyamoto SD, Nakano SJ. Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children. J Hear Lung Transplant. 2018;37(9):1075-1082.
Jeewa AM, Dreyer WJM, Kearney DLM, Denfield SWM. The presentation and diagnosis of coronary. Journals@Ovid Table ContentsCongenital Hear Dis. 2012;7(4):302-311.
Mehra MR, Crespo-Leiro MG, Dipchand A, et al. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010. J Hear Lung Transplant. 2010;29(7):717-727.
Price JF, Towbin JA, Dreyer WJ, et al. Symptom complex is associated with transplant coronary artery disease and sudden death/resuscitated sudden death in pediatric heart transplant recipients. J Hear Lung Transplant. 2005;24(11):1798-1803.
Daly KP, Chakravarti SB, Tresler M, et al. Sudden death after pediatric heart transplantation: analysis of data from the Pediatric Heart Transplant Study Group. J Heart Lung Transplant. 2011;30(12):1395-1402. 10.1016/j.healun.2011.08.015
Chantranuwat C, Blakey JD, Kobashigawa JA, et al. Sudden, unexpected death in cardiac transplant recipients: an autopsy study. J Hear Lung Transplant. 2004;23(6):683-689.
Taylor DO, Stehlik J, Edwards LB, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-sixth official adult heart transplant report-2009. J Heart Lung Transplant. 2009;28(10):1007-1022. 10.1016/j.healun.2009.08.014
Alba AC, Foroutan F, Ng Fat Hing NKV, Fan CPS, Manlhiot C, Ross HJ. Incidence and predictors of sudden cardiac death after heart transplantation: a systematic review and meta-analysis. Clin Transplant. 2018;32(3):1-16.
Su JA, Baxter-Lowe LA, Kantor PF, Szmuszkovicz JR, Menteer JD. The clinical impact of donor-specific antibodies on antibody-mediated rejection and long-term prognosis after heart transplantation. Curr Opin Organ Transplant. 2019;24(3):245-251.
Svobodova E, Gazdic T, Kubanek M, et al. Novel insights into pretransplant allosensitization in heart transplant recipients in the contemporary era of immunosuppression and rejection surveillance. Transpl Int. 2016;29:63-72.
Barten MJ, Schulz U, Beiras-Fernandez A, et al. The clinical impact of donor-specific antibodies in heart transplantation. Transplant Rev. 2018;32(4):207-217.
Asimacopoulos EP, Garbern JC, Gauvreau K, Blume ED, Daly KP, Singh TP. Association of clinical rejection versus rejection on protocol biopsy with cardiac allograft vasculopathy in pediatric heart transplant recipients. Transplantation. 2020;104(1):E31-E37.
Frank R, Molina MR, Goldberg LR, Wald JW, Kamoun M, Lal P. Circulating donor-specific anti - human leukocyte antigen antibodies and complement C4d deposition are associated with the development of cardiac allograft vasculopathy. Am J Clin Pathol. 2014;142:809-815.
Asante-Korang A, Amankwah EK, Lopez-Cepero M, et al. Outcomes in highly sensitized pediatric heart transplant patients using current management strategies. J Hear Lung Transplant. 2015;34(2):175-181.
Young JB. Perspectives on cardiac allograft vasculopathy. Curr Atheroscler Rep. 2000;2(3):259-271.
Costello JP, Mohanakumar T, Nath DS. Mechanisms of chronic cardiac allograft rejection. Texas Hear Inst J. 2013;40(4):395-399.
Seipelt IM, Crawford SE, Rodgers S, et al. Hypercholesterolemia is common after pediatric heart transplantation: initial experience with pravastatin. J Hear Lung Transplant. 2004;23(3):317-322.
Pietra BA, Boucek MM. Coronary artery vasculopathy in pediatric cardiac transplant patients: the therapeutic potential of immunomodulators. Pediatr Drugs. 2003;5(8):513-524.
Asante-Korang A, Carapellucci J, Krasnopero D, Doyle A, Brown B, Amankwah E. Conversion from calcineurin inhibitors to mTOR inhibitors as primary immunosuppressive drugs in pediatric heart transplantation. Clin Transplant. 2017;31(10):e13054.
Valantine HA. The role of viruses in cardiac allograft vasculopathy. Am J Transplant. 2004;4(2):169-177.
Shirali GS, Ni J, Chinnock RE, et al. Association of viral genome with graft loss in children after cardiac transplantation. N Engl J Med. 2001;344(20):1498-1503.
Mahle WT, Fourshee MT, Naftel DM, et al. Does cytomegalovirus serology impact outcome after pediatric heart transplantation? J Heart Lung Transplant. 2009;28(12):1299-1305. 10.1016/j.healun.2009.07.011
Pahl E, Naftel DC, Kuhn MA, et al. The impact and outcome of transplant coronary artery disease in a pediatric population: a 9-year multi-institutional study. J Hear Lung Transplant. 2005;24(6):645-651.
Kobayashi D, Du W, Tj LE. Predictors of cardiac allograft vasculopathy in pediatric heart transplant recipients. Pediatr Transplant. 2013;17:436-440.
Rossano JW, Cherikh WS, Chambers DC, et al. The Registry of the International Society for Heart and Lung Transplantation: twentieth pediatric heart transplantation report-2017 ; Focus theme: allograft ischemic time. J Hear Lung Transplant. 2017;36(10):1060-1069. 10.1016/j.healun.2017.07.018
Dipchand AI. Current state of pediatric cardiac transplantation. Ann Cardiothorac Surg. 2018;7(1):31-55.
Reinhardt Z. Paediatric heart transplantation: an update. Arch Dis Child. 2019;104(12):1216-1222.
Soslow JH, Samyn MM. Multi-modal imaging of the pediatric heart transplant recipient. Transl Pediatr. 2019;8(4):322-338.
Kuhn MA, Jutzy KR, Deming DD, et al. The medium-term findings in coronary arteries by intravascular ultrasound in infants and children after heart transplantation. J Am Coll Cardiol. 2000;36(1):250-254. 10.1016/S0735-1097(00)00701-4
Kuhn MA, Gordon BM, Razzouk AJ, Bock MJ, Chinnock RE, Bailey LL. Intravascular ultrasound in the diagnosis of cardiac allograft vasculopathy in pediatric heart transplant recipients: a 20 year single center review. J Hear Lung Transplant. 2018;37(4):S191.
Cote AT, Hosking M, Voss C, et al. Coronary artery intimal thickening and ventricular dynamics in pediatric heart transplant recipients. Congenit Heart Dis. 2018;13:663-670.
Dedieu N, Silva Vieira M, Fenton M, et al. The importance of qualitative and quantitative regional wall motion abnormality assessment at rest in pediatric coronary allograft vasculopathy. Pediatr Transplant. 2018;22(5):1-8.
Hussain T, Fenton M, Peel SA, et al. Detection and grading of coronary allograft vasculopathy in children with contrast-enhanced magnetic resonance imaging of the coronary vessel wall. Circ Cardiovasc Imaging. 2013;6:91-98.
Dipchand AI, Bharat W, Manlhiot C, et al. A prospective study of dobutamine stress echocardiography for the assessment of cardiac allograft vasculopathy in pediatric heart transplant recipients. Pediatr Transplant. 2008;12:570-576.
Larsen RL, Applegate PM, Dyar DA, et al. Dobutamine stress echocardiography for assessing coronary artery disease after transplantation in children. J Am Coll Cardiol. 1998;32(2):515-520. 10.1016/S0735-1097(98)00260-5
Zoeller BB, Miyamoto SD, Younoszai AK, Landeck BF. Longitudinal strain and strain rate abnormalities precede invasive diagnosis of transplant coronary artery vasculopathy in pediatric cardiac transplant patients. Pediatr Cardiol. 2016;37(4):656-662.
Clemmensen TS, Eiskjaer H, Løgstrup BB, et al. Noninvasive detection of cardiac allograft vasculopathy by stress exercise echocardiographic assessment of myocardial deformation. J Am Soc Echocardiogr. 2016;29(5):480-490.
Gebska MA, Williford NN, Schadler AJ, et al. Pharmacological vs exercise stress echocardiography for detection of cardiac allograft vasculopathy. Mayo Clin Proc Innov Qual Outcomes. 2020;4(1):65-75.
Mehra MR, Uber PA, Potluri S, Ventura HO, Scott RL, Park MH. Usefulness of an elevated B-type natriuretic peptide to predict allograft failure, cardiac allograft vasculopathy, and survival after heart transplantation. Am J Cardiol. 2004;94(4):454-458.
Bjerre KP, Clemmensen TS, Poulsen SH, et al. Micro- and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients-an exploratory study. Clin Transplant. 2021;35(1):1-11.
Claudius I, Lan YT, Chang RK, Wetzel GT, Alejos J. Usefulness of B-type natriuretic peptide as a noninvasive screening tool for cardiac allograft pathology in pediatric heart transplant recipients. Am J Cardiol. 2003;92(11):1368-1370.
Rossano JW, Denfield SW, Kim JJ, et al. B-Type natriuretic peptide levels late after transplant predict graft survival in pediatric heart transplant patients. J Heart Lung Transplant. 2010;29(3):385-386. 10.1016/j.healun.2009.06.002
Miller RJH, Manabe O, Tamarappoo B, et al. Comparative prognostic and diagnostic value of myocardial blood flow and myocardial flow reserve after cardiac transplantation. J Nucl Med. 2020;61(2):249-255.
Bravo PE, Bergmark BA, Vita T, et al. Diagnostic and prognostic value of myocardial blood flow quantification as non-invasive indicator of cardiac allograft vasculopathy. Eur Heart J. 2018;39(4):316-323.
Nandi D, Chin C, Schumacher KR, et al. Surveillance for cardiac allograft vasculopathy: practice variations among 50 pediatric heart transplant centers. J Hear Lung Transplant. 2020;39(11):1260-1269.
Chin C, Gamberg P, Miller J, Luikart H, Bernstein D. Efficacy and safety of atorvastatin after pediatric heart transplantation. J Heart Lung Transplant. 2002;21(11):1213-1217. 10.1016/S1053-2498(02)00455-2
Mahle WT, Vincent RN, Berg AM, Kanter KR. Pravastatin therapy is associated with reduction in coronary allograft vasculopathy in pediatric heart transplantation. J Hear Lung Transplant. 2005;24(1):63-66.
Greenway SC, Butts R, Naftel DC, et al. Statin therapy is not associated with improved outcomes after heart transplantation in children and adolescents. J Hear Lung Transplant. 2016;35(4):457-465.
October VMC. Immunosuppressants in Organ Transplantation. 2007;1-4. Available from: myvmc.com/treatments/immunosuppressants-in-organ-transplantation
Ansari D, Höglund P, Andersson B, Nilsson J. Comparison of basiliximab and anti-thymocyte globulin as induction therapy in pediatric heart transplantation: a survival analysis. J Am Heart Assoc. 2016;5(1):1-8.
Singh TP, Faber C, Blume ED, et al. Safety and early outcomes using a corticosteroid-avoidance immunosuppression protocol in pediatric heart transplant recipients. J Hear Lung Transplant. 2010;29(5):517-522.
Denfield SW. Strategies to prevent cellular rejection in pediatric heart transplant recipients. Pediatr Drugs. 2010;12(6):391-403.
Kaczmarek I, Ertl B, Schmauss D, et al. Preventing cardiac allograft vasculopathy: long-term beneficial effects of mycophenolate mofetil. J Hear Lung Transplant. 2006;25(5):550-556.
Eisen HJ, Kobashigawa J, Keogh A, Bourge R, Renlund D. Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac methods: results. J Hear Lung Transplant. 2005;24(5):517-525.
Dipchand AI, Benson L, McCrindle BW, Coles J, West L. Mycophenolate mofetil in pediatric heart transplant recipients: a single-center experience. Pediatr Transplant. 2001;5(2):112-118.
Keogh A, Richardson M, Ruygrok P, et al. Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial. Circulation. 2004;110(17):2694-2700.
Eisen HJ, Tuzcu EM, Dorent R, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med. 2003;349(9):847-858.
Arora S, Ueland T, Wennerblom B, et al. Effect of everolimus introduction on cardiac allograft vasculopathy-results of a randomized, multicenter trial. Transplantation. 2011;92(2):235-243.
Matsuo Y, Cassar A, Yoshino S, et al. Attenuation of cardiac allograft vasculopathy by sirolimus: relationship to time interval after heart transplantation. J Hear Lung Transplant. 2013;32(8):784-791. 10.1016/j.healun.2013.05.015
Gonzalez-Vilchez F, Vazquez de Prada J, Paniagua M, et al. Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: calcineurin-inhibitors conversion or minimization? Int J Cardiol. 2014;171(1):15-23. 10.1016/j.ijcard.2013.11.036
Ganschow R, Pape L, Sturm E, et al. Growing experience with mTOR inhibitors in pediatric solid organ transplantation. Pediatr Transplant. 2013;17(7):694-706.
Turner ME, Addonizio LJ, Richmond ME, et al. Percutaneous coronary artery revascularization procedures in pediatric heart transplant recipients: a large single center experience. Catheter Cardiovasc Interv. 2016;88(5):797-803.
Sachdeva R, Seib PM, Frazier EA, Sachdeva R. Percutaneous coronary intervention using drug-eluting stents in pediatric heart transplant recipients. Pediatr Transplant. 2009;13(8):1014-1019.
Jeewa A, Chin C, Pahl E, et al. Outcomes after percutaneous coronary artery revascularization procedures for cardiac allograft vasculopathy in pediatric heart transplant recipients: a multi-institutional study. J Heart Lung Transplant. 2015;34(9):1163-1168. 10.1016/j.healun.2014.11.011
Conway J, Manlhiot C, Kirk R, Edwards LB, McCrindle BW, Dipchand AI. Mortality and morbidity after retransplantation after primary heart transplant in childhood: an analysis from the registry of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2014;33(3):241-251. 10.1016/j.healun.2013.11.006
Dipchand AI, Edwards LB, Kucheryavaya AY, et al. The registry of the international society for heart and lung transplantation: seventeenth official pediatric heart transplantation report - 2014; focus theme: retransplantation. J Hear Lung Transplant. 2014;33(10):985-995.
Chin C, Naftel D, Pahl E, et al. Cardiac re-transplantation in pediatrics: a multi-institutional study. J Hear Lung Transplant. 2006;25(12):1420-1424.
Barghash MH, Pinney SP. Heart retransplantation: candidacy, outcomes, and management. Curr Transplant Reports. 2020;7(1):12-17.
Scott E, Loya K, Mountford J, Milligan G, Baker AH. MicroRNA regulation of endothelial homeostasis and commitment-implications for vascular regeneration strategies using stem cell therapies. Free Radic Biol Med. 2013;64:52-60. 10.1016/j.freeradbiomed.2013.04.037
Singh N, Heggermont W, Fieuws S, Vanhaecke J, Van Cleemput J, De Geest B. Endothelium-enriched microRNAs as diagnostic biomarkers for cardiac allograft vasculopathy. J Heart Lung Transplant. 2015;34(11):1376-1384. 10.1016/j.healun.2015.06.008
Nog R, Gupta CA, Panza JA. Role of micro RNA in heart transplant. Cardiol Rev. 2021. 10.1097/CRD.0000000000000393. Online ahead of print.
Neumann A, Napp LC, Kleeberger JA, et al. MicroRNA 628-5p as a novel biomarker for cardiac allograft vasculopathy. Transplantation. 2017;101(1):e26-e33.
Heggermont WA, Delrue L, Dierickx K, et al. Low MicroRNA-126 levels in right ventricular endomyocardial biopsies coincide with cardiac allograft vasculopathy in heart transplant patients. Transplant Direct. 2020;6:1-7.
Jordan SC, Ammerman N, Choi J, et al. Interleukin-6: an important mediator of allograft injury. Transplantation. 2020;104(12):2497-2506.
Miller CL, Madsen JC. IL-6 directed therapy in transplantation. Curr Transplant Reports. 2021;8(3):191-204.
Birgit F, Tai Y, Chen W, et al. Neutralizing IL-6 reduces human arterial allograft rejection by allowing emergence of CD161(+) CD4(+) T regulatory cells. J Immunol. 2011;15(187):6268-6280.
Targeting Inflammation and Alloimmunity in Heart Transplant Recipients With Tocilizumab.