Table of Contents
Definition / general | Epidemiology | Pathophysiology | Etiology | Diagnosis | Prognostic factors | Microscopic (histologic) description | Differential diagnosis | Additional referencesCite this page: Amita R. General (transplant). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/hearttransplant.html. Accessed December 3rd, 2024.
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 postoperative 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
Microscopic (histologic) 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
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
Additional references