Cardiac allograft vasculopathy: A review

Abstract

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.

Adult and late adolescent complications of pediatric solid organ transplantation

“…25 Despite this, many pediatric heart transplant programs incorporate statin therapy into their post-transplant protocols. 22 Recent research is focused on the immune mechanisms of CAV and the role of interleukin-6 (IL-6) in mediating CAV; a randomized controlled trial of tocilizumab, an IL-6 receptor antagonist, in adult heart transplant recipients is ongoing with estimated completion in April 2025. 26…”

“…21 CAV is a progressive form of vascular intimal proliferation that leads to obliteration of the vascular lumen. 22 The causes of CAV are poorly understood but likely include some combination of immune mechanisms (e.g., antibody-mediated rejection) in addition to traditional nonimmune cardiac risk factors, including dyslipidemia, hypertension, diabetes, and obesity. mTOR inhibitors have been proposed as an alternative immunosuppressive agent to decrease the onset or progression of CAV, but a recent retrospective review of showed increased rates of rejection and CAV in children treated with mTOR inhibitors, though the authors did not feel the association with CAV was likely to be causal.…”

Repeat pediatric heart transplantation: A united network for organ sharing database analysis

“…Cardiac allograft vasculopathy is the leading cause of graft failure, affecting almost 50% of pediatric heart transplant recipients by 15 years post‐transplant 2 . There has been no significant improvement in the prevention or treatment of this complication over the past 20 years, with repeat transplantation representing the only viable management option 3,4 . Despite this, repeat transplantation is rare, accounting for less than 5% of all pediatric transplants 1,5 .…”

“…2 There has been no significant improvement in the prevention or treatment of this complication over the past 20 years, with repeat transplantation representing the only viable management option. 3,4 Despite this, repeat transplantation is rare, accounting for less than 5% of all pediatric transplants. 1,5 A diagnosis of congenital heart disease and a history of previous transplantation are each independently associated with worse survival following pediatric heart transplantation.…”

Recurrent Mild Acute Rejections and Donor-specific Antibodies as Risk Factors for Cardiac Allograft Vasculopathy in a National Pediatric Heart Transplant Cohort

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C hronic rejection in heart transplant (HTx) presents as cardiac allograft vasculopathy (CAV), manifesting as progressive and diffuse intimal proliferative arteriosclerosis. 1 CAV can cause late graft failure and death after pediatric HTx. Approximately half of pediatric HTx recipients develop CAV during the first 15 posttransplant years.

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