Relevance of cytomegalovirus infection and coronary-artery remodeling in the first year after heart transplantation: a prospective three-dimensional intravascular ultrasound study

Potena, Luciano; Grigioni, Francesco; Ortolani, Paolo; Magnani, Gaia; Marrozzini, Cinzia; Falchetti, Elena; Barbieri, Anna Maria; Reggiani, Maria Letizia Bacchi; Lazzarotto, Tiziana; Marzocchi, Antonío; Magelli, Carlo; Landini, Maria Paola; Branzi, Angelo

doi:10.1097/01.tp.0000054231.42217.a5

Cited by 63 publications

(45 citation statements)

References 24 publications

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“…Power calculations were based on the reported increase in intimal area during the first post-HT year (31), and on an expected coefficient of variability of the measurements of 0.9. We estimated a baseline intimal area of 2.0 ± 1.8 mm 2 , and expected an increase in intimal area of at least 1.…”

Section: Discussionmentioning

confidence: 99%

“…corticosteroids and/or adjustments of oral medication doses. Surveillance for cytomegalovirus (CMV) infection was performed using the pp65 antigenemia test at scheduled times and CMV infection was treated preemptively, as previously reported (31). All patients received counseling for a low-fat mediterranean-style diet (32).…”

Section: Concurrent Treatments and Proceduresmentioning

confidence: 99%

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Homocysteine‐Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS‐Based Study

Potena

Grigioni

Magnani

et al. 2005

American Journal of Transplantation

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Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n = 22), or standard therapy (control group, n = 22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p < 0.001), coronary intimal area increased similarly in the two groups (p > 0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p < 0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n = 19; p = 0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p = 0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia.Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.

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Section: Discussionmentioning

confidence: 99%

Section: Concurrent Treatments and Proceduresmentioning

confidence: 99%

Homocysteine‐Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS‐Based Study

Potena

Grigioni

Magnani

et al. 2005

American Journal of Transplantation

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“…16 This association in adult recipients has been confirmed subsequently. [17][18][19][20][21][22][23][24] Furthermore, documented CMV infection has been shown to be associated with impaired coronary endothelial function in heart transplant recipients. 25 A number of reasons can be offered why it is important to consider the role of CMV in the development of vasculopathy in children separately.…”

Section: Editorial P 1701 Clinical Perspective P 1805mentioning

confidence: 99%

Positive Pretransplantation Cytomegalovirus Serology Is a Risk Factor for Cardiac Allograft Vasculopathy in Children

et al. 2007

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Background-Cytomegalovirus (CMV) infection has been implicated as a cause of posttransplantation coronary artery disease in adults. The purpose of this retrospective observational study was to evaluate the effect of CMV on outcome after heart transplantation in children. Methods and Results-Risk factors tested were recipient age, sex, and pretransplantation CMV serology; use of anti-CMV prophylaxis; posttransplantation evidence of CMV infection; and donor CMV serology. Transplantations were stratified traditionally according to CMV risk as low risk (recipient negative/donor negative), intermediate risk (recipient positive), and high risk (recipient negative/donor positive). Primary outcome measures were (1) development of coronary artery vasculopathy, (2) mortality (or graft loss) that occurred outside the early postoperative period, and (3) death (or graft loss) due to vasculopathy. Analysis was by proportional hazards modeling. A total of 165 children underwent heart transplantation, with a mean age at transplantation of 7.8 (SD 5.6) years. Thirty-two children had laboratory evidence of CMV infection after transplantation, but only 6 developed CMV disease or syndrome. Traditional CMV risk stratification correlated well with CMV infection but did not predict mortality, coronary artery disease, or coronary death. In contrast, positive recipient CMV was the only independent predictor of all 3 outcome measures: coronary artery disease (hazard ratioϭ3.6), all-cause mortality (partial hazard ratioϭ4.1), and coronary death (hazard ratioϭ4.6). Conclusions-In children, pretransplantation recipient CMV status is a more powerful predictor for the development of clinically significant vasculopathy and subsequent death than traditional risk stratification. This phenomenon warrants further investigation.

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“…11,12 The pathogenesis of this disease is complex, multifactorial, and currently incompletely understood. However, studies have highlighted the relationship between CMV and allograft vasculopathy in adults 1,2,13 and, more recently, in children. 3 One of the hallmarks of allograft vasculopathy is endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…Human cytomegalovirus (CMV) is associated with increased risk of posttransplantation coronary vasculopathy. 1,2 We have shown CMV serology to be an important factor in allograft vasculopathy of pediatric recipients. 3 Coronary endothelial dysfunction is associated with CMV infection 4 and the later development of transplant vasculopathy.…”

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confidence: 99%

Endothelial Dysfunction and Cytomegalovirus Replication in Pediatric Heart Transplantation

et al. 2008

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Background-Cardiac allograft vasculopathy is the major limiting factor to the long-term success of pediatric heart transplantation. Cytomegalovirus (CMV) has been shown to be a significant risk factor for the development of cardiac allograft vasculopathy. Recent work has demonstrated CMV DNA in leukocytes in the absence of direct allograft infection, suggesting that vascular changes may not be limited to the allograft. Method and Results-Systemic arterial endothelial function was assessed with high-resolution ultrasound to determine brachial artery flow-mediated dilation in 50 pediatric heart transplant recipients (8 to 17 years of age; 27 male). Patients were separated into 2 groups according to CMV status: those without evidence of CMV replication after transplantation (nϭ38; 19 male) and patients with evidence of viremia after transplantation (nϭ12; 8 male). No patient had detectable viremia at the time of study. Flow-mediated dilation was significantly impaired in patients with evidence of CMV replication after transplantation (6.64Ϯ1.12%, meanϮSE) compared with those without (9.48Ϯ0.56%; Pϭ0.02). This difference remained after adjustment for age, time since transplantation, and medication. Pretransplantation recipient and donor CMV status and traditional CMV risk were not associated with flow-mediated dilation. Conclusions-CMV replication after cardiac transplantation is associated with chronic endothelial dysfunction in the systemic circulation in children. The implication for both systemic and coronary vascular health requires prospective evaluation.

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Relevance of cytomegalovirus infection and coronary-artery remodeling in the first year after heart transplantation: a prospective three-dimensional intravascular ultrasound study

Cited by 63 publications

References 24 publications

Homocysteine‐Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS‐Based Study

Homocysteine‐Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS‐Based Study

Positive Pretransplantation Cytomegalovirus Serology Is a Risk Factor for Cardiac Allograft Vasculopathy in Children

Endothelial Dysfunction and Cytomegalovirus Replication in Pediatric Heart Transplantation

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