Cardiac allograft vasculopathy pathophysiology: Difference between revisions
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Acute phase reactants may be elevated and is thought to be a marker of progression of CAV. | Acute phase reactants may be elevated and is thought to be a marker of progression of CAV. | ||
* HLA mismatch: | * HLA mismatch: | ||
Studies have reported a higher incidence of CAV in recipients with HLA mismatch. HLA-DR and HLA-A mismatches have been more strongly associated with occurrence of CAV <ref name="pmid16278580">{{cite journal| author=Tambur AR, Pamboukian SV, Costanzo MR, Herrera ND, Dunlap S, Montpetit M et al.| title=The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome. | journal=Transplantation | year= 2005 | volume= 80 | issue= 8 | pages= 1019-25 | pmid=16278580 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16278580 }} </ref>. | Studies have reported a higher incidence of CAV in recipients with HLA mismatch. HLA-DR and HLA-A mismatches have been more strongly associated with occurrence of CAV <ref name="pmid16278580">{{cite journal| author=Tambur AR, Pamboukian SV, Costanzo MR, Herrera ND, Dunlap S, Montpetit M et al.| title=The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome. | journal=Transplantation | year= 2005 | volume= 80 | issue= 8 | pages= 1019-25 | pmid=16278580 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16278580 }} </ref>. Moreover presence of [[HLA]] class I and class II antibodies by solid phase, flow cytometry, panel reactive antibody (PRA) assay post heart transplant co-relate with worse graft outcomes. Tambur et al. showed that class II HLA specific antibodies were associated with [[IVUS]] evidence of severe vasculopathy. | ||
==References== | ==References== |
Revision as of 22:48, 5 August 2014
Cardiac allograft vasculopathy Microchapters |
Differentiating Cardiac allograft vasculopathy from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]; Raviteja Guddeti, M.B.B.S. [3]
Overview
Cardiac allograft vasculopathy (CAV) is a fibro-proliferative disorder of graft coronary arteries in heart transplant recipients. It is characterized by longitudinal concentric intraluminal narrowing secondary to intimal proliferation in epicardial coronary arteries. There is also concentric medial hyperplasia in the myocardial microvasculature. In contrast, native atherosclerotic process is non-circumferential, focal and localized to epicardial coronary vessels.
Pathophysiology
Pathology
The pathogenesis of CAV is believed to be an interplay between immunological and non-immunological factors. Histologically, immunological and non-immunological factors cause sub-endothelial inflammation resulting in migration of lymphocytes (T cells especially), proliferation of smooth muscle cells, formation of lipid laden foam cells and fibrosis. This further accelerates the process of endothelial dysfunction. The end result is progressive luminal compromise, reduced coronary blood flow and vasodilatory capacity leading to ischemia and chronic ventricular dysfunction [1].
Early-CAV is associated with thickening of the intima with or without expansion of external elastic lamina (positive remodeling) and is not accompanied by decrease in the intraluminal diameter. This is followed by concentric remodeling and luminal compromise (negative remodeling). There may also be associated mural thrombi which may lead to acute myocardial infarction. Early clots are platelet rich which may later be replaced by organized thrombus rich in fibrin. Increased platelet activation with expression of surface membrane glycoproteins has been linked to accelerated progression of CAV. Serial intravascular ultrasound imaging has demonstrated that majority of the intraluminal narrowing occurs in the first year after transplant.
In the early post-transplant period, lesions tend to be non-circumferential, focal, composed of fibrous and fibro-fatty material. This fibro-fatty tissue may represent either CAV or traditional atherosclerosis, and represents the most common lesions found on IVUS studies. However, presence of necrotic core may be in this period may be associated with graft atherosclerotic coronary artery disease, donor age, male gender, and other traditional risk factors [1] [2]. Calcified lesions and necrotic core begin to appear within 2 years of transplantation.
Immunologic and non-immunologic risk factors | |||||||||||||||||||||||||||||||
Persistent enthothelial injury and dysfunction | |||||||||||||||||||||||||||||||
Subendothelial accumulation of lymphocytes, myointimal proliferation, formation of foam cells and fibrosis | |||||||||||||||||||||||||||||||
Concentric intimal hyperplasia and luminal narrowing | |||||||||||||||||||||||||||||||
Decreased coronary blood flow and reduced vasodilatory capacity | |||||||||||||||||||||||||||||||
Myocardial ischemia and ventricular dysfunction | |||||||||||||||||||||||||||||||
Pathogenesis
The pathogenesis of CAV appears to multifactorial with immunological and non-immunological factors both contributing to the process. Predominant factors include donor specific HLA antibodies, cellular mediated injury, cytomegalovirus infection and hypercholesterolemia. Immunological insult is the most accepted theory owing to the fact that CAV develops in donor arteries only.
Acute phase reactants may be elevated and is thought to be a marker of progression of CAV.
- HLA mismatch:
Studies have reported a higher incidence of CAV in recipients with HLA mismatch. HLA-DR and HLA-A mismatches have been more strongly associated with occurrence of CAV [3]. Moreover presence of HLA class I and class II antibodies by solid phase, flow cytometry, panel reactive antibody (PRA) assay post heart transplant co-relate with worse graft outcomes. Tambur et al. showed that class II HLA specific antibodies were associated with IVUS evidence of severe vasculopathy.
References
- ↑ 1.0 1.1 Pollack A, Nazif T, Mancini D, Weisz G (2013). "Detection and imaging of cardiac allograft vasculopathy". JACC Cardiovasc Imaging. 6 (5): 613–23. doi:10.1016/j.jcmg.2013.03.001. PMID 23680373.
- ↑ Billingham ME (1992). "Histopathology of graft coronary disease". J Heart Lung Transplant. 11 (3 Pt 2): S38–44. PMID 1622997.
- ↑ Tambur AR, Pamboukian SV, Costanzo MR, Herrera ND, Dunlap S, Montpetit M; et al. (2005). "The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome". Transplantation. 80 (8): 1019–25. PMID 16278580.