Skip to main content
Top
Published in: BMC Infectious Diseases 1/2015

Open Access 01-12-2015 | Research article

Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients

Authors: Inger Johansson, Rune Andersson, Vanda Friman, Nedim Selimovic, Lars Hanzen, Salmir Nasic, Ulla Nyström, Vilborg Sigurdardottir

Published in: BMC Infectious Diseases | Issue 1/2015

Login to get access

Abstract

Background

Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx.

Methods

A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 ± 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed.

Results

Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0–7.4) compared with CMV disease (4.2 years; CI, 3.2–5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3–6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant.

Conclusions

CAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.
Literature
1.
go back to reference Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI, et al. The registry of the international society for heart and lung transplantation: 29th official adult heart transplant report - 2012. J Heart Lung Transplant. 2012;31:1052–64.PubMedCrossRef Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI, et al. The registry of the international society for heart and lung transplantation: 29th official adult heart transplant report - 2012. J Heart Lung Transplant. 2012;31:1052–64.PubMedCrossRef
2.
go back to reference Colvin-Adams M, Harcourt N, Duprez D. Endothelial Dysfunction and Cardiac Allograft Vasculopathy. Journal of Cardiovascular Translational Research. 2013;6:263–77.PubMedCrossRef Colvin-Adams M, Harcourt N, Duprez D. Endothelial Dysfunction and Cardiac Allograft Vasculopathy. Journal of Cardiovascular Translational Research. 2013;6:263–77.PubMedCrossRef
3.
go back to reference Hannah V. Cardiac allograft vasculopathy after heart transplantation: risk factors and management. J Heart Lung Transplant. 2004;23:S187–93.CrossRef Hannah V. Cardiac allograft vasculopathy after heart transplantation: risk factors and management. J Heart Lung Transplant. 2004;23:S187–93.CrossRef
4.
go back to reference Crespo-Leiro MG, Marzoa-Rivas R, Barge-Caballero E, Paniagua-Martín MJ. Prevention and treatment of coronary artery vasculopathy. Current Opinion in Organ Transplantation. 2012;17:546–50.PubMedCrossRef Crespo-Leiro MG, Marzoa-Rivas R, Barge-Caballero E, Paniagua-Martín MJ. Prevention and treatment of coronary artery vasculopathy. Current Opinion in Organ Transplantation. 2012;17:546–50.PubMedCrossRef
5.
go back to reference Koskinen PK, Kallio EA, Tikkanen JM, Sihvola RK, Häyry PJ, Lemström KB. Cytomegalovirus infection and cardiac allograft vasculopathy. Transplant Infectious Disease. 1999;1:115–26.PubMedCrossRef Koskinen PK, Kallio EA, Tikkanen JM, Sihvola RK, Häyry PJ, Lemström KB. Cytomegalovirus infection and cardiac allograft vasculopathy. Transplant Infectious Disease. 1999;1:115–26.PubMedCrossRef
6.
go back to reference Potena L, Grigioni F, Ortolani P, Magnani G, Marrozzini C, Falchetti E, et al. Relevance of cytomegalovirus infection and coronary-artery remodeling in the first year after heart transplantation: A prospective three-dimensional intravascular ultrasound study. Transplantation. 2003;75:839–43.PubMedCrossRef Potena L, Grigioni F, Ortolani P, Magnani G, Marrozzini C, Falchetti E, et al. Relevance of cytomegalovirus infection and coronary-artery remodeling in the first year after heart transplantation: A prospective three-dimensional intravascular ultrasound study. Transplantation. 2003;75:839–43.PubMedCrossRef
7.
go back to reference Potena L, Valantine HA. Cytomegalovirus-associated allograft rejection in heart transplant patients. Curr Opin Infect Dis. 2007;20:425–31.PubMedCrossRef Potena L, Valantine HA. Cytomegalovirus-associated allograft rejection in heart transplant patients. Curr Opin Infect Dis. 2007;20:425–31.PubMedCrossRef
9.
go back to reference Grattan MT, Moreno-Cabral CE, Starnes VA, Oyer PE, Stinson EB, Shumway NE. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. Journal of the American Medical Association. 1989;261:3561–6.PubMedCrossRef Grattan MT, Moreno-Cabral CE, Starnes VA, Oyer PE, Stinson EB, Shumway NE. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. Journal of the American Medical Association. 1989;261:3561–6.PubMedCrossRef
10.
go back to reference Koskinen PK, Nieminen MS, Krogerus LA, Lemstrom KB, Mattila SP, Hayry PJ, et al. Cytomegalovirus infection accelerates cardiac allograft vasculopathy: Correlation between angiographic and endomyocardial biopsy findings in heart transplant patients. Transpl Int. 1993;6:341–7.PubMedCrossRef Koskinen PK, Nieminen MS, Krogerus LA, Lemstrom KB, Mattila SP, Hayry PJ, et al. Cytomegalovirus infection accelerates cardiac allograft vasculopathy: Correlation between angiographic and endomyocardial biopsy findings in heart transplant patients. Transpl Int. 1993;6:341–7.PubMedCrossRef
11.
go back to reference Sharples LD, Jackson CH, Parameshwar J, Wallwork J, Large SR. Diagnostic accuracy of coronary angiography and risk factors for post-heart-transplant cardiac allograft vasculopathy. Transplantation. 2003;76:679–82.PubMedCrossRef Sharples LD, Jackson CH, Parameshwar J, Wallwork J, Large SR. Diagnostic accuracy of coronary angiography and risk factors for post-heart-transplant cardiac allograft vasculopathy. Transplantation. 2003;76:679–82.PubMedCrossRef
12.
go back to reference Luckraz H, Charman SC, Wreghitt T, Wallwork J, Parameshwar J, Large SR. Does cytomegalovirus status influence acute and chronic rejection in heart transplantation during the ganciclovir prophylaxis era? J Heart Lung Transplant. 2003;22:1023–7.PubMedCrossRef Luckraz H, Charman SC, Wreghitt T, Wallwork J, Parameshwar J, Large SR. Does cytomegalovirus status influence acute and chronic rejection in heart transplantation during the ganciclovir prophylaxis era? J Heart Lung Transplant. 2003;22:1023–7.PubMedCrossRef
13.
go back to reference Mahle WT, Fourshee MT, Naftel DM, Alejos JC, Caldwell RL, Uzark K, et al. Does Cytomegalovirus Serology Impact Outcome After Pediatric Heart Transplantation? J Heart Lung Transplant. 2009;28:1299–305.PubMedCrossRef Mahle WT, Fourshee MT, Naftel DM, Alejos JC, Caldwell RL, Uzark K, et al. Does Cytomegalovirus Serology Impact Outcome After Pediatric Heart Transplantation? J Heart Lung Transplant. 2009;28:1299–305.PubMedCrossRef
14.
go back to reference Fearon WF, Potena L, Hirohata A, Sakurai R, Yamasaki M, Luikart H, et al. Changes in coronary arterial dimensions early after cardiac transplantation. Transplantation. 2007;83:700–5.PubMedCrossRef Fearon WF, Potena L, Hirohata A, Sakurai R, Yamasaki M, Luikart H, et al. Changes in coronary arterial dimensions early after cardiac transplantation. Transplantation. 2007;83:700–5.PubMedCrossRef
15.
go back to reference Mendez-Eirin E, Paniagua-Martín MJ, Marzoa-Rivas R, Barge-Caballero E, Grille-Cancela Z, Cañizares A, et al. Cumulative incidence of cytomegalovirus infection and disease after heart transplantation in the last decade: Effect of preemptive therapy. Transplant Proc. 2012;44:2660–2.PubMedCrossRef Mendez-Eirin E, Paniagua-Martín MJ, Marzoa-Rivas R, Barge-Caballero E, Grille-Cancela Z, Cañizares A, et al. Cumulative incidence of cytomegalovirus infection and disease after heart transplantation in the last decade: Effect of preemptive therapy. Transplant Proc. 2012;44:2660–2.PubMedCrossRef
16.
go back to reference Ljungman P, Griffiths P, Paya C: Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002, 34:1094-7.PubMedCrossRef Ljungman P, Griffiths P, Paya C: Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002, 34:1094-7.PubMedCrossRef
17.
go back to reference Costanzo MR, Naftel DC, Pritzker MR, Heilman 3rd JK, Boehmer JP, Brozena SC, et al. Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database. J Heart Lung Transplant. 1998;17:744–53.PubMed Costanzo MR, Naftel DC, Pritzker MR, Heilman 3rd JK, Boehmer JP, Brozena SC, et al. Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database. J Heart Lung Transplant. 1998;17:744–53.PubMed
18.
go back to reference Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. 2005;24:1710–20.PubMedCrossRef Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. 2005;24:1710–20.PubMedCrossRef
19.
go back to reference Raichlin E, Edwards BS, Kremers WK, Clavell AL, Rodeheffer RJ, Frantz RP, et al. Acute Cellular Rejection and the Subsequent Development of Allograft Vasculopathy After Cardiac Transplantation. J Heart Lung Transplant. 2009;28:320–7.PubMedCrossRef Raichlin E, Edwards BS, Kremers WK, Clavell AL, Rodeheffer RJ, Frantz RP, et al. Acute Cellular Rejection and the Subsequent Development of Allograft Vasculopathy After Cardiac Transplantation. J Heart Lung Transplant. 2009;28:320–7.PubMedCrossRef
20.
go back to reference Petrakopoulou P, Kübrich M, Pehlivanli S, Meiser B, Reichart B, Von Scheidt W, et al. Cytomegalovirus infection in heart transplant recipients is associated with impaired endothelial function. Circulation. 2004;110:II207–12.PubMedCrossRef Petrakopoulou P, Kübrich M, Pehlivanli S, Meiser B, Reichart B, Von Scheidt W, et al. Cytomegalovirus infection in heart transplant recipients is associated with impaired endothelial function. Circulation. 2004;110:II207–12.PubMedCrossRef
21.
go back to reference McDonald K, Rector TS, Braulin EA, Kubo SH, Olivari MT. Association of coronary artery disease in cardiac transplant recipients with cytomegalovirus infection. Am J Cardiol. 1989;64:359–62.PubMedCrossRef McDonald K, Rector TS, Braulin EA, Kubo SH, Olivari MT. Association of coronary artery disease in cardiac transplant recipients with cytomegalovirus infection. Am J Cardiol. 1989;64:359–62.PubMedCrossRef
22.
go back to reference Wahlers T, Fieguth HG, Jurmann M, Albes J, Hausen B, Demertzis S, et al. Graft coronary vasculopathy in cardiac transplantation--evaluation of risk factors by multivariate analysis. Eur J Cardiothorac Surg. 1996;10:1–5.PubMedCrossRef Wahlers T, Fieguth HG, Jurmann M, Albes J, Hausen B, Demertzis S, et al. Graft coronary vasculopathy in cardiac transplantation--evaluation of risk factors by multivariate analysis. Eur J Cardiothorac Surg. 1996;10:1–5.PubMedCrossRef
23.
go back to reference Sagedal S, Hartmann A, Nordal KP, Osnes K, Leivestad T, Foss A, et al. Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival. Kidney Int. 2004;66:329–37.PubMedCrossRef Sagedal S, Hartmann A, Nordal KP, Osnes K, Leivestad T, Foss A, et al. Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival. Kidney Int. 2004;66:329–37.PubMedCrossRef
24.
go back to reference Delgado JF, Reyne AG, de Dios S, Lopez-Medrano F, Jurado A, Juan RS, et al. Influence of cytomegalovirus infection in the development of cardiac allograft vasculopathy after heart transplantation. J Heart Lung Transplant. 2015;34:1112–9.PubMedCrossRef Delgado JF, Reyne AG, de Dios S, Lopez-Medrano F, Jurado A, Juan RS, et al. Influence of cytomegalovirus infection in the development of cardiac allograft vasculopathy after heart transplantation. J Heart Lung Transplant. 2015;34:1112–9.PubMedCrossRef
25.
go back to reference Potena L, Holweg CTJ, Chin C, Luikart H, Weisshaar D, Narasimhan B, et al. Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation. 2006;82:398–405.PubMedCrossRef Potena L, Holweg CTJ, Chin C, Luikart H, Weisshaar D, Narasimhan B, et al. Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation. 2006;82:398–405.PubMedCrossRef
26.
go back to reference Potena L, Grigioni F, Magnani G, Lazzarotto T, Musuraca AC, Ortolani P, et al. Prophylaxis versus preemptive anti-cytomegalovirus approach for prevention of allograft vasculopathy in heart transplant recipients. J Heart Lung Transplant. 2009;28:461–7.PubMedCrossRef Potena L, Grigioni F, Magnani G, Lazzarotto T, Musuraca AC, Ortolani P, et al. Prophylaxis versus preemptive anti-cytomegalovirus approach for prevention of allograft vasculopathy in heart transplant recipients. J Heart Lung Transplant. 2009;28:461–7.PubMedCrossRef
27.
go back to reference Stoica SC, Cafferty F, Pauriah M, Taylor CJ, Sharples LD, Wallwork J, et al. The cumulative effect of acute rejection on development of cardiac allograft vasculopathy. J Heart Lung Transplant. 2006;25:420–5.PubMedCrossRef Stoica SC, Cafferty F, Pauriah M, Taylor CJ, Sharples LD, Wallwork J, et al. The cumulative effect of acute rejection on development of cardiac allograft vasculopathy. J Heart Lung Transplant. 2006;25:420–5.PubMedCrossRef
28.
go back to reference Gao SZ, Schroeder JS, Hunt SA, Valantine HA, Hill IR, Stinson EB. Influence of graft rejection on incidence of accelerated graft coronary artery disease: a new approach to analysis. J Heart Lung Transplant. 1993;12:1029–35.PubMed Gao SZ, Schroeder JS, Hunt SA, Valantine HA, Hill IR, Stinson EB. Influence of graft rejection on incidence of accelerated graft coronary artery disease: a new approach to analysis. J Heart Lung Transplant. 1993;12:1029–35.PubMed
29.
go back to reference Stovin PG, Sharples LD, Schofield PM, Cary NR, Mullins PA, English TA, et al. Lack of association between endomyocardial evidence of rejection in the first six months and the later development of transplant-related coronary artery disease. J Heart Lung Transplant. 1993;12:110–6.PubMed Stovin PG, Sharples LD, Schofield PM, Cary NR, Mullins PA, English TA, et al. Lack of association between endomyocardial evidence of rejection in the first six months and the later development of transplant-related coronary artery disease. J Heart Lung Transplant. 1993;12:110–6.PubMed
30.
go back to reference Caforio AL, Tona F, Fortina AB, Angelini A, Piaserico S, Gambino A, et al. Immune and nonimmune predictors of cardiac allograft vasculopathy onset and severity: multivariate risk factor analysis and role of immunosuppression. Am J Transplant. 2004;4:962–70.PubMedCrossRef Caforio AL, Tona F, Fortina AB, Angelini A, Piaserico S, Gambino A, et al. Immune and nonimmune predictors of cardiac allograft vasculopathy onset and severity: multivariate risk factor analysis and role of immunosuppression. Am J Transplant. 2004;4:962–70.PubMedCrossRef
31.
go back to reference Braga JR, Santos IS, McDonald M, Shah PS, Ross HJ. Factors associated with the development of cardiac allograft vasculopathy--a systematic review of observational studies. Clin Transplant. 2012;26:E111–124.PubMedCrossRef Braga JR, Santos IS, McDonald M, Shah PS, Ross HJ. Factors associated with the development of cardiac allograft vasculopathy--a systematic review of observational studies. Clin Transplant. 2012;26:E111–124.PubMedCrossRef
32.
go back to reference Dahlman S, Jeppsson A, Nyström U, Bergh CH, Sigurdardottir V, Nilsson F: Coronary Angiography or not for older heart donors? Abstract published in Transplantmed, June 10, 2011. Abstract published in Transplantmed, June 10, 2011. Dahlman S, Jeppsson A, Nyström U, Bergh CH, Sigurdardottir V, Nilsson F: Coronary Angiography or not for older heart donors? Abstract published in Transplantmed, June 10, 2011. Abstract published in Transplantmed, June 10, 2011.
Metadata
Title
Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients
Authors
Inger Johansson
Rune Andersson
Vanda Friman
Nedim Selimovic
Lars Hanzen
Salmir Nasic
Ulla Nyström
Vilborg Sigurdardottir
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2015
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-015-1321-1

Other articles of this Issue 1/2015

BMC Infectious Diseases 1/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.