Does Cytomegalovirus Serology Impact Outcome After Pediatric Heart Transplantation?

Mahle, William T.; Fourshee, Margaret T.; Naftel, D.; Alejos, Juan; Caldwell, Randall L.; Uzark, Karen; Berg, Alexandria M.; Kanter, Kirk R.

doi:10.1016/j.healun.2009.07.011

Cited by 44 publications

(43 citation statements)

References 16 publications

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“…CMV disease and infection predispose adult heart transplant recipients to development of CAV 30 and there have been conflicting reports regarding the association between pre-transplant CMV positivity and risk of CAV in pediatric recipients. 31,32 Our study did not identify any significant differences in VEGF concentration based on recipient and donor cytomegalovirus status at transplant. The incidence of CAV in pediatric recipients increases with time from transplant 7,28,29 ; nevertheless, VEGF levels are unchanged based on number of years post-transplant and similar VEGF criteria may be applicable regardless of time post-transplant.…”

Section: Discussioncontrasting

confidence: 52%

Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children

Watanabe

Karimpour-Fard

Michael

et al. 2018

The Journal of Heart and Lung Transplantation

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BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of retransplantation and death in pediatric heart transplant recipients. Our aim was to evaluate the association between serum vascular endothelial growth factor-A (VEGF) and CAV development in the pediatric heart transplant population. METHODS: In this retrospective study performed at a university hospital, VEGF concentrations were measured by enzyme-linked immunosorbent assay in banked serum from pediatric heart transplant recipients undergoing routine cardiac catheterization. In subjects with CAV (n = 29), samples were obtained at 2 time-points: before CAV diagnosis (pre-CAV) and at the time of initial CAV diagnosis (CAV). In subjects without CAV (no-CAV, n = 16), only 1 time-point was used. VEGF concentrations (n = 74) were assayed in duplicate. RESULTS: Serum VEGF is elevated in pediatric heart transplant recipients before catheter-based diagnosis of CAV (no-CAV mean: 144.0 ± 89.05 pg/ml; pre-CAV mean: 316.2 ± 118.3 pg/ml; p = 0.0002). Receiver-operating characteristic curve analysis of pre-CAV VEGF levels demonstrated an area under the curve of 87.7% (p = 0.0002), with a VEGF level of 226.3 pg/ml predicting CAV development with 77.8% sensitivity and 91.7% specificity. VEGF is similarly elevated in subjects with angiographically diagnosed CAV and in those with normal angiography but intravascular ultrasound (IVUS) evidence of CAV. CONCLUSIONS: The increase in serum VEGF before onset of detectable CAV is fundamental to its utility as a predictive biomarker and suggests further investigations of VEGF in the pathogenesis of CAV are warranted in the pediatric heart transplant population.

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Section: Discussioncontrasting

confidence: 52%

Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children

Watanabe

Karimpour-Fard

Michael

et al. 2018

The Journal of Heart and Lung Transplantation

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“…In heart transplantation, CMV prophylaxis with either CMV Ig or antiviral agents was associated with decreased mortality (227). Others have reported association between CMV seropositivity and coronary artery vasculopathy (228), yet data from the multicenter Pediatric Heart Transplant Study did not demonstrate this association (229). The lack of evidence that CMV has substantial indirect deleterious effects in pediatric transplantation recipients coupled with the more limited pharmacokinetic studies and the potential toxicities associated with antiviral therapy in the developing child provide a less compelling rationale for prolonged antiviral prophylaxis in children.…”

Section: Indirect Effects Of CMV In Pediatricsmentioning

confidence: 99%

Updated International Consensus Guidelines on the Management of Cytomegalovirus in Solid-Organ Transplantation

et al. 2013

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Cytomegalovirus (CMV) continues to be one of the most common infections after solid-organ transplantation, resulting in significant morbidity, graft loss, and adverse outcomes. Management of CMV varies considerably among transplant centers but has been become more standardized by publication of consensus guidelines by the Infectious Diseases Section of The Transplantation Society. An international panel of experts was reconvened in October 2012 to revise and expand evidence and expert opinion-based consensus guidelines on CMV management, including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues. The following report summarizes the recommendations.

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“…Bacterial infections, especially in the first month post-transplant, were the most common cause of severe infections with an overall mortality of 34% (63). Cytomegalovirus has been purported to be possibly associated with acute rejection, CAV and graft loss, but this was not born out in the PHTS analysis should no demonstrable association with death or CAV (64). Regarding infections, the type, severity, risk factors, prophylaxis, management strategies, and impact on outcomes vary and are beyond the scope of this chapter though excellent summaries and guidelines exist in the literature (65).…”

Section: Other Post-transplant Complicationsmentioning

confidence: 99%

Current state of pediatric cardiac transplantation

Dipchand

2018

Ann. Cardiothorac. Surg.

102

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Pediatric heart transplantation is standard of care for children with end-stage heart failure. The diverse age range, diagnoses, and practice variations continue to challenge the development of evidence-based practices and new technologies. Outcomes in the most recent era are excellent, especially with the more widespread use of ventricular assist devices (VADs). Waitlist mortality remains high and knowledge of risk factors for death while waiting and following transplantation contributes to decision-making around transplant candidacy and timing of listing. The biggest gap impacting both waitlist and overall survival remains mechanical support options for infants and patients with single ventricle physiology. Though acute rejection has decreased progressively, both diagnosis and management of antibody-mediated rejection has become increasingly challenging and complex, as has the ability to understand the implication of anti-HLA antibodies detected both pre-and post-transplantation-including when and how to intervene. Trends in immunosuppression protocols include more use of induction therapy and steroid avoidance or withdrawal protocols. Common long-term morbidities include renal insufficiency, which can be mitigated with surveillance and renal-sparing strategies, and infections. Functional outcomes are excellent, but significant psychosocial challenges exist in relation to neurodevelopment, non-adherence, and transition from childcentered to adult-centered care. Cardiac allograft vasculopathy (CAV) remains a barrier to long-term survival, though it is more apparent that objective evidence of an impact on the allograft is important with regards to impact on outcomes. Retransplantation is rare in pediatric heart transplant recipients. Pediatric heart transplantation continues to evolve in order to address the challenges of the diverse group of patients that reach end-stage heart failure during childhood.

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Does Cytomegalovirus Serology Impact Outcome After Pediatric Heart Transplantation?

Cited by 44 publications

References 16 publications

Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children

Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children

Updated International Consensus Guidelines on the Management of Cytomegalovirus in Solid-Organ Transplantation

Current state of pediatric cardiac transplantation

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