Heart
Heart transplant
Chronic allograft vasculopathy

Editor-in-Chief: Debra Zynger, M.D.
Alexis Musick, B.S.
Carolyn Glass, M.D., Ph.D.

Revised: 14 August 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: Chronic allograft vasculopathy heart


Alexis Musick, B.S.
Carolyn Glass, M.D., Ph.D.
Page views in 2019 to date: 83
Cite this page: Musick A, Glass C. Chronic allograft vasculopathy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/chronicgraftvasculopathy.html. Accessed August 25th, 2019.
Definition / general
  • Diffuse, concentric hyperplasia of the coronary vasculature after orthotopic heart transplantation, resulting in progressive luminal narrowing, ischemic injury and allograft failure
Essential features
  • Long term complication after heart transplantation
  • Invasive coronary angiography is diagnostic
  • Concentric intimal hyperplasia of the epicardial arteries / veins and medial disease of the intramyocardial microvasculature
ICD coding
  • ICD-9: 996.83 – complications of transplanted heart
  • ICD-10: T86.290 – cardiac allograft vasculopathy
Epidemiology
Sites
Pathophysiology
  • Host allorecognition of donor HLA on coronary endothelium → T cell activation → altered cytokine expression → endothelial activation, vascular smooth muscle proliferation and extracellular matrix deposition → intimal (epicardial) or medial (microvasculature) thickening and vasculopathy (Circulation 2007;116:1274)
  • Formation of anti HLA or anti endothelial antibodies → increased risk of chronic allograft vasculopathy and cardiovascular mortality (J Heart Lung Transplant 2006;25:1277, J Heart Lung Transplant 2010;29:717, Circulation 1989;80:III122)
  • Nonimmunological factors (e.g., coronary artery disease, tobacco use) → endothelial dysfunction and vascular inflammation → enhanced graft immunogenicity (Croat Med J 2014;55:562)
Etiology
  • Interplay between immunologic (cellular / antibody mediated rejection and HLA matching) and nonimmunologic (e.g., recipient hyperlipidemia, donor hypertension) factors
Diagrams / tables

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Arteriographic classification

Clinical features
  • Rarely present with angina due to allograft denervation
  • Arrhythmia, diaphoresis, exertional dyspnea, gastrointestinal distress, progressive heart failure, sudden cardiac death or syncope (Croat Med J 2014;55:562)
Radiology description
Radiology images

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Coronary angiography

CT angiography

Intravascular ultrasound

Coronary angiography

Optical coherence tomography

Prognostic factors
Case reports
Treatment
Gross description
Gross images

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Coronary artery hyperplasia

Microscopic (histologic) description
  • Endomyocardial biopsy of intramyocardial arteries (J Heart Lung Transplant 2011;30:1044):
    • Concentric fibromuscular intimal and medial thickening with luminal stenosis
    • Subendothelial lymphocytic accumulation
    • Perivascular fibrosis
  • Epicardial artery and vein sections (Catheter Cardiovasc Interv 2018;92:E527):
    • Concentric intimal thickening (proliferation of smooth muscle cells and myofibroblasts) along vessel length with luminal stenosis
    • Variable mononuclear inflammatory infiltrate (T lymphocytes, macrophages and foam cells) in the intima, media, or adventitia
    • May have fibrinoid necrosis of the media and damage to the inner elastic lamina
  • Myocardial sections (Arch Pathol Lab Med 2007;131:1169):
    • Bilateral, patchy ischemic injury (acute and healing) with myocytolysis, coagulative necrosis and interstitial fibrosis
  • May have coincident atheromatous plaques, usually eccentric and proximal
Microscopic (histologic) images

Contributed by Carolyn Glass, M.D., Ph.D.

Explant, concentric intimal hyperplasia

Explant, diffuse intimal hyperplasia

Explant, coronary artery stenosis

Explant, coronary artery occlusion

Positive stains
Negative stains
Sample pathology report
  • Heart, explant:
    • Multifocal mild acute cellular allograft rejection with focal myocyte necrosis (ISHLT Grade 1R; 1990 Grade 2)
    • pAMR 0: no significant evidence of antibody mediated rejection on immunohistology.
    • Quilty effect: moderate focal endocardial inflammatory cell aggregate with myocardial encroachment.
  • Clinical Information
    • Cardiac allograft vasculopathy status post orthotopic heart transplant
Differential diagnosis
Board review question #1
A 34 year old Hispanic man underwent an orthotopic heart transplantation six years ago following intractable idiopathic restrictive cardiomyopathy where he received a heart from a 25 year old white woman. Routine posttransplant endomyocardial biopsies showed no histological evidence of rejection but surveillance coronary angiography and intravascular ultrasound recently revealed diffuse, circumferential thickening of the left anterior descending artery with significant intimal thickening and 70% luminal stenosis. The patient has no history of dyslipidemia, diabetes, or CMV infection. Which of the following is a significant risk factor in the development of this patient's disease?

  1. Absence of histological evidence of rejection
  2. Donor female sex
  3. Donor white race
  4. Donor young age
  5. Recipient CMV IgG/IgM seronegativity
Board review answer #1
C. This patient has chronic allograft vasculopathy as indicated by diffuse concentric intimal hyperplasia and 70% stenosis of a single primary vessel (left anterior descending) on angiography. White race of the donor is associated with an increased incidence of cardiac allograft vasculopathy in the recipient. Recipient CMV IgG/IgM seropositivity, not seronegativity, is also associated with an increased risk of disease. Absence of histological evidence of rejection has no effect on incidence and may be reflective of sampling error (i.e., biopsies did not capture diseased microvasculature). Donor old age and male sex, not young age and female sex, are risk factors for the development of cardiac allograft vasculopathy.

Reference: Heart - Chronic allograft vasculopathy

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Board review question #2
A 51 year old woman received an orthotopic heart transplant four years ago due to end stage dilated cardiomyopathy. One year ago, she began experiencing mild exertional dyspnea. At that time, invasive angiography demonstrated 60% stenosis and diffuse narrowing of the left circumflex artery. Over time, the patient developed progressive heart failure and required a repeat transplantation. A representative section of her explanted heart is shown below.

Which of the following statements about this disease is true?

  1. Although donor vasculature is affected, recipient vasculature is spared
  2. Characteristic mononuclear inflammatory infiltrate is limited to the adventitia
  3. Concentric intimal thickening and luminal stenosis is found in epicardial arteries but not epicardial veins
  4. Development of the disease is closely associated with EBV seroconversion or reactivation of anti-EBV IgM
  5. Positive immunofluorescence for IgG, IgM, or IgA is diagnostic of the disease
Board review answer #2
A. This patient has chronic allograft vasculopathy as indicated by diffuse concentric intimal hyperplasia and 60% stenosis of a single primary vessel (left main coronary artery) on angiography. The patient's biopsy also shows severe intimal hyperplasia with marked luminal stenosis. In this disease, the donor coronary vasculature is affected while the recipient vasculature is spared. EBV seroconversion or reactivation is more associated with posttransplant lymphoproliferative disease. While acute antibody mediated rejection events (indicated by immunofluorescence in choice B) may occur in the context of cardiac allograft vasculopathy, it is not diagnostic. The inflammatory infiltrate seen in the disease may occur in any layer of the vessel and concentric intimal thickening may occur in both epicardial arteries and veins.

Reference: Heart - Chronic allograft vasculopathy

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