Heart
Cardiac transplantation
General

Author: R. Amita, M.D.(see Authors page)

Revised: 29 December 2015, last major update December 2015

Copyright: (c) 2015, PathologyOutlines.com, Inc.

PubMed Search: Heart [title] transplant pathology
Cite this page: General (transplant). PathologyOutlines.com website. http://pathologyoutlines.com/topic/hearttransplant.html. Accessed February 26th, 2017.
Definition / General
  • First human heart transplantation was performed in 1967 (S Afr Med J 2011;101:97)
  • Heart transplantation remains the most effective therapy for end stage heart disease of coronary and noncoronary etiology
Epidemiology
  • More than 73,000 heart transplants have been performed worldwide to date
Pathophysiology
  • Donor heart dysfunction results from the "catecholamine storm" (hypertension, tachycardia and intense vasoconstriction) that produces an increase in myocardial oxygen demand and potential myocardial ischemia
  • These phenomena may mediate myofibrillar degeneration, a process characterized by injury and death of myofibers in a hypercontracted state
  • After dissipation of this intense sympathetic activity, there is loss of sympathetic tone with a massive reduction in systemic vascular resistance, which may contribute to a second phase of potential myocardial injury, precipitated by abnormal myocardial loading conditions and impaired coronary perfusion
  • Myocardial injury interacts with other factors such as older donor age and longer ischemic time, increasing the probability of post-operative primary graft dysfunction
Etiology
  • Risk factors for graft failure:
    • Older donor age
    • Donor left ventricular (LV) dysfunction
    • Longer ischemic time
    • Size mismatch (smaller donor to a larger recipient)
  • Indications include coronary heart disease, non ischemic cardiomyopathies, congenital heart disease
Diagnosis
  • Endomyocardial biopsy (EMB) remains the gold standard for rejection surveillance in the heart transplant patient
Prognostic Factors
  • 10 year survival rate after cardiac transplantation currently approaches 50% and more in high volume centers
Micro Description
  • Quilty lesions, also known as endocardial lymphocytic infiltrates, are collections of predominantly T lymphocytes with admixed B cells, occasional macrophages and plasma cells seen in the endocardium of transplanted hearts that vary in size from 0.007 to 1.89 mm
  • Acute cellular rejection consists of a mononuclear inflammatory infiltrate that is predominantly a T cell mediated response directed against the cardiac allograft
  • The grades proposed in the ISHLT-WF1990 were mainly based on the amount of inflammatory infiltrate and the presence of myocyte damage

  • 1990 Grading System of the International Society of Heart and Lung Transplantation for Acute Cellular Rejection:
    • Grade 0 (no acute rejection)
    • Grade 1A (focal, mild acute rejection)
    • Grade 1B (diffuse, mild acute rejection)
    • Grade 2 (focal, moderate acute rejection)
    • Grade 3A (multifocal moderate rejection)
    • Grade 3B (diffuse, borderline severe acute rejection)
    • Grade 4 (severe acute rejection)

  • 2004 Grading System of the International Society of Heart and Lung Transplantation for Acute Cellular Rejection:
    • Grade 0R (no acute cellular rejection)
    • Grade 1R (mild, low grade, acute cellular rejection): interstitial and/or perivascular infiltrate with up to 1 focus of myocyte damage
    • Grade 2R (moderate, intermediate grade, acute cellular rejection): 2 or more foci of infiltrate with associated myocyte damage
    • Grade 3R (severe, high grade, acute cellular rejection): diffuse infiltrate with multifocal myocyte damage +/- edema, +/- hemorrhage +/- vasculitis
Micro Images

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Grades of cellular rejection

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Endocardial lymphocytic infiltrates versus cellular rejection

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Ischemic injury

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Previous biopsy sites

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Various grading images

Differential Diagnosis
  • Ischemic injury:
    • Should be differentiated from cellular rejection
    • The extent of myocyte necrosis is usually out of proportion to the inflammatory infiltrate in ischemic injury, with the infiltrates consisting mostly of neutrophils and macrophages
    • In cellular rejection, the infiltrates are predominantly lymphocytic
  • Previous biopsy site:
    • Will show several stages of healing
    • Recent biopsy sites will show thrombus and granulation tissue
    • Late findings include fibrosis with entrapped myocytes that often exhibit disarray and a variable amount of mononuclear cell infiltrate
    • Old biopsy sites present as endocardial scars