Heart transplantation pathophysiology: Difference between revisions
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{{Heart transplantation}} | {{Heart transplantation}} | ||
{{CMG}}; {{AE}} | {{CMG}}; {{AE}} {{IF}} | ||
==Overview== | ==Overview== | ||
The pathogenesis leading to a cardiac transplant involves the mechanisms leading up to heart failure. | The [[pathogenesis]] leading to a [[cardiac transplant]] involves the mechanisms leading up to [[heart failure]]. [[Heart failure]] leads to an inadequate output of the heart to meet the [[metabolic]] demands of the body. Features of chronic heart failure like biventricular [[hypertrophy]], four-chamber [[dilatation]], fibrotic scars, myofibrillar loss, sarcoplasmic vacuolation, [[interstitial fibrosis]] may be seen in the diseased heart. Post-transplantation changes indicating acute or chronic [[rejection]] may be seen. Non-rejection changes include [[coronary artery disease]] (eccentric), Quilty effect, [[interstitial fibrosis]], nodular [[lymphocytic]] endomyocardial infiltrates, and posttransplant [[lymphoproliferative]] disorder in the transplanted heart. | ||
==Pathophysiology== | ==Pathophysiology== | ||
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Cardiac Transplantation is the treatment for patients with intractable heart failure, not amenable to medical and device therapy. | Cardiac Transplantation is the treatment for patients with intractable heart failure, not amenable to medical and device therapy. | ||
*[[Heart failure]] | *[[Heart failure]] results when there is an inadequate output of the heart to meet the metabolic demands of the body. Heart failure can be caused by abnormal function of any part of the heart like the [[pericardium]], the [[myocardium]], the [[endocardium]], the [[heart valves]] and the great vessels- the [[aorta]] and [[pulmonary artery]]. | ||
*Heart failure is characterized by decreased [[cardiac output]] but not necessarily decreased [[ejection fraction]]. | *Heart failure is characterized by decreased [[cardiac output]] but not necessarily decreased [[ejection fraction]]. | ||
*[[Symptoms]] of heart failure are due to a lack of both forward blood flow to the body, and backward flow into the [[lungs]]. The body tries to compensate for the low [[cardiac output]] by mechanisms that increase the [[preload]] and [[afterload]]. These mechanisms lead to exacerbation of the [[cardiac]] malfunction and symptoms associated with heart failure. | *[[Symptoms]] of heart failure are due to a lack of both forward blood flow to the body, and backward flow into the [[lungs]]. The body tries to compensate for the low [[cardiac output]] by mechanisms that increase the [[preload]] and [[afterload]]. These mechanisms lead to exacerbation of the [[cardiac]] malfunction and symptoms associated with heart failure. | ||
It is understood that heart failure is the end result of many causes- | It is understood that heart failure is the end result of many causes- | ||
Common causes | Common causes whose pathogenesis results in the need for cardiac transplantation may include:<ref name="pmid26776864">{{cite journal| author=Mehra MR, Canter CE, Hannan MM, Semigran MJ, Uber PA, Baran DA | display-authors=etal| title=The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update. | journal=J Heart Lung Transplant | year= 2016 | volume= 35 | issue= 1 | pages= 1-23 | pmid=26776864 | doi=10.1016/j.healun.2015.10.023 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26776864 }} </ref> | ||
*Systolic Heart Failure with a low Left Ventricular Ejection Fraction( <35%) may be caused by | *Systolic Heart Failure with a low Left Ventricular Ejection Fraction( <35%) may be caused by | ||
**Ischemic [[cardiomyopathy]] | **Ischemic [[cardiomyopathy]] | ||
| Line 36: | Line 35: | ||
On gross pathology, features of '''chronic heart failure''' are seen- | On gross pathology, features of '''chronic heart failure''' are seen- | ||
*Biventricular hypertrophy | *Biventricular [[Hypertrophy (medical)|hypertrophy]] | ||
*Moderate to severe four-chamber dilatation are characteristic findings | *Moderate to severe four-chamber [[dilatation]] are characteristic findings | ||
*Remnant fibrotic scars from previous myocardial | *Remnant fibrotic scars from previous [[myocardial infarction]]<nowiki/>s- [[Transmural care|transmural]] or [[subendocardial]] | ||
*Mural thrombus- most commonly in the left ventricle but may be present in any chamber | *[[Mural thrombus]]- most commonly in the [[left ventricle]] but may be present in any chamber <ref name="pmid2981905">{{cite journal| author=Pomerance A, Stovin PG| title=Heart transplant pathology: the British experience. | journal=J Clin Pathol | year= 1985 | volume= 38 | issue= 2 | pages= 146-59 | pmid=2981905 | doi=10.1136/jcp.38.2.146 | pmc=499095 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2981905 }} </ref> <ref name="pmid1434905">{{cite journal| author=Tazelaar HD, Edwards WD| title=Pathology of cardiac transplantation: recipient hearts (chronic heart failure) and donor hearts (acute and chronic rejection). | journal=Mayo Clin Proc | year= 1992 | volume= 67 | issue= 7 | pages= 685-96 | pmid=1434905 | doi=10.1016/s0025-6196(12)60726-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1434905 }} </ref> | ||
===Post-transplantation or Donor Heart=== | ===Post-transplantation or Donor Heart=== | ||
On gross pathology, features of '''acute or chronic rejection''' may be seen, if the patient is not on adequate immunosuppressive therapy. | On gross pathology, features of '''acute or chronic rejection''' may be seen, if the patient is not on adequate [[Immunosuppressive therapy|immunosuppressive]] therapy. <ref name="pmid1434905">{{cite journal| author=Tazelaar HD, Edwards WD| title=Pathology of cardiac transplantation: recipient hearts (chronic heart failure) and donor hearts (acute and chronic rejection). | journal=Mayo Clin Proc | year= 1992 | volume= 67 | issue= 7 | pages= 685-96 | pmid=1434905 | doi=10.1016/s0025-6196(12)60726-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1434905 }} </ref> | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
=== Pre-transplantation or Recipient Heart=== | === Pre-transplantation or Recipient Heart=== | ||
*Hypertrophy of myocytes | *[[Hypertrophy]] of [[myocytes]] | ||
*Myofibrillar loss | *Myofibrillar loss | ||
* Sarcoplasmic vacuolation | * Sarcoplasmic vacuolation | ||
*Interstitial fibrosis | *[[Interstitial]] [[fibrosis]] | ||
*Deposition of collagen, mostly in the subendocardial region. | *Deposition of [[collagen]], mostly in the [[subendocardial]] region. | ||
* Variable degree of myocarditis | * Variable degree of [[myocarditis]]<ref name="pmid1434905">{{cite journal| author=Tazelaar HD, Edwards WD| title=Pathology of cardiac transplantation: recipient hearts (chronic heart failure) and donor hearts (acute and chronic rejection). | journal=Mayo Clin Proc | year= 1992 | volume= 67 | issue= 7 | pages= 685-96 | pmid=1434905 | doi=10.1016/s0025-6196(12)60726-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1434905 }} </ref> | ||
===Post-transplantation or Donor Heart=== | |||
====Changes associated with Rejection==== | |||
Features of mild acute rejection include <ref name="pmid17683180">{{cite journal| author=Tan CD, Baldwin WM, Rodriguez ER| title=Update on cardiac transplantation pathology. | journal=Arch Pathol Lab Med | year= 2007 | volume= 131 | issue= 8 | pages= 1169-91 | pmid=17683180 | doi=10.1043/1543-2165(2007)131[1169:UOCTP]2.0.CO;2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17683180 }} </ref>- | |||
* Focal [[mononuclear cells]] infiltrate, without the involvement of adjacent [[myocytes]].<ref name="pmid21727202">{{cite journal| author=Boilson BA, McGregor CG, Kushwaha SS| title=Pathophysiological changes after cardiac transplantation: the role of chronic inflammation and rejection. | journal=Heart | year= 2011 | volume= 97 | issue= 20 | pages= 1634-5 | pmid=21727202 | doi=10.1136/heartjnl-2011-300526 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21727202 }} </ref> | |||
Features of moderate acute rejection include- | |||
* Dense collection of [[inflammatory cells]], associated with involvement of adjacent myocytes. | |||
*[[Eosinophils]] and also [[mononuclear cells]] are also seen in the infiltrate. <ref name="pmid21727202">{{cite journal| author=Boilson BA, McGregor CG, Kushwaha SS| title=Pathophysiological changes after cardiac transplantation: the role of chronic inflammation and rejection. | journal=Heart | year= 2011 | volume= 97 | issue= 20 | pages= 1634-5 | pmid=21727202 | doi=10.1136/heartjnl-2011-300526 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21727202 }} </ref> | |||
Features of severe acute rejection ''additionally'' include- | |||
*[[Hemorrhage]] | |||
*[[Edema]] | |||
*[[Vasculitis]] | |||
*[[Neutrophil|Neutrophilic]] infiltrate <ref name="pmid2981905">{{cite journal| author=Pomerance A, Stovin PG| title=Heart transplant pathology: the British experience. | journal=J Clin Pathol | year= 1985 | volume= 38 | issue= 2 | pages= 146-59 | pmid=2981905 | doi=10.1136/jcp.38.2.146 | pmc=499095 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2981905 }} </ref> | |||
Features of chronic rejection include- | |||
*[[Concentric hypertrophy|Concentric]] [[intimal]] thickening | |||
* Reservation of internal elastic lamina | |||
===Types of rejection=== | |||
{| class="wikitable" | |||
| Type (grade) | |||
| Description | |||
| Details of microscopic pathology | |||
|- | |||
| antibody-mediated rejection (acute vascular) | |||
| edema, dilated small vessels | |||
| scant inflammation | |||
|- | |||
| normal (0R) | |||
| normal | |||
| no extravascular monocytes | |||
|- | |||
| acute cellular (1R) | |||
| (perivascular) inflammatory infiltrate, myocyte damage | |||
| scant interstitial infiltrate (lymphoplasmacytic), scant damage | |||
|- | |||
| acute cellular (2R) | |||
| (perivascular) inflammatory space-occupying lesion | |||
| diffuse interstitial infiltrate displaces parenchyma (lymphoplasmacytic), obvious damage (myocyte eosinophilia or drop-out) | |||
|- | |||
| acute cellular (3R) | |||
| disruption of normal arch. | |||
| diffuse interstitial infiltrate disrupts parenchyma (lymphoplasmic & [[PMN]]s), fibre loss/damage | |||
|- | |||
| chronic | |||
| concentric intimal thicking | |||
| internal elastic lamina preserved (unlike [[atherosclerosis]]) | |||
|} | |||
==== Nonrejection changes==== | |||
* Coronary Artery Disease- Arteriosclerosis- '''[[concentric]]''' intimal thickening associated with endovasculitis. This is to be compared with ordinary [[atherosclerosis]] where lipids are deposited mainly in the [[endothelium]] and subendothelium in an '''eccentric''' pattern. | |||
* Other changes like- <ref name="pmid1434905">{{cite journal| author=Tazelaar HD, Edwards WD| title=Pathology of cardiac transplantation: recipient hearts (chronic heart failure) and donor hearts (acute and chronic rejection). | journal=Mayo Clin Proc | year= 1992 | volume= 67 | issue= 7 | pages= 685-96 | pmid=1434905 | doi=10.1016/s0025-6196(12)60726-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1434905 }} </ref> | |||
**[[Ischemic]] changes | |||
** Interstitial [[fibrosis]] | |||
** Mycoytes- hypertrophy, calcification | |||
** Nodular [[lymphocytic]] endomyocardial infiltrates- Seen with the use of Cyclosporin, known as '''Quilty effect''' <ref name="pmid1756159">{{cite journal| author=Pardo-Mindán FJ, Lozano MD| title="Quilty effect" in heart transplantation: is it related to acute rejection? | journal=J Heart Lung Transplant | year= 1991 | volume= 10 | issue= 6 | pages= 937-41 | pmid=1756159 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1756159 }} </ref> | |||
** Posttransplant [[Lymphoproliferative disorders|lymphoproliferative]] disorder- Similar to large cell lymphoma | |||
==References== | ==References== | ||
Latest revision as of 19:38, 15 July 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ifrah Fatima, M.B.B.S[2]
Overview
The pathogenesis leading to a cardiac transplant involves the mechanisms leading up to heart failure. Heart failure leads to an inadequate output of the heart to meet the metabolic demands of the body. Features of chronic heart failure like biventricular hypertrophy, four-chamber dilatation, fibrotic scars, myofibrillar loss, sarcoplasmic vacuolation, interstitial fibrosis may be seen in the diseased heart. Post-transplantation changes indicating acute or chronic rejection may be seen. Non-rejection changes include coronary artery disease (eccentric), Quilty effect, interstitial fibrosis, nodular lymphocytic endomyocardial infiltrates, and posttransplant lymphoproliferative disorder in the transplanted heart.
Pathophysiology
Pathogenesis
Cardiac Transplantation is the treatment for patients with intractable heart failure, not amenable to medical and device therapy.
- Heart failure results when there is an inadequate output of the heart to meet the metabolic demands of the body. Heart failure can be caused by abnormal function of any part of the heart like the pericardium, the myocardium, the endocardium, the heart valves and the great vessels- the aorta and pulmonary artery.
- Heart failure is characterized by decreased cardiac output but not necessarily decreased ejection fraction.
- Symptoms of heart failure are due to a lack of both forward blood flow to the body, and backward flow into the lungs. The body tries to compensate for the low cardiac output by mechanisms that increase the preload and afterload. These mechanisms lead to exacerbation of the cardiac malfunction and symptoms associated with heart failure.
It is understood that heart failure is the end result of many causes- Common causes whose pathogenesis results in the need for cardiac transplantation may include:[1]
- Systolic Heart Failure with a low Left Ventricular Ejection Fraction( <35%) may be caused by
- Ischemic cardiomyopathy
- Dilated cardiomyopathy
- Valvular heart disease
- Hypertensive heart disease
- Ischemic Coronary Artery Disease with Refractory Angina
- Long-standing Intractable life-threatening Arrhythmias
- Ventricular arrhythmias
- Cardiomyopathies
- Restrictive and Hypertrophic Cardiomyopathies
- Non-dilated cardiomyopathies
- Congenital Heart Disease
- Many congenital heart defects that are not amenable to surgery lead to New York Heart Association functional class IV Heart Failure
Gross Pathology
Pre-transplantation or Recipient Heart
On gross pathology, features of chronic heart failure are seen-
- Biventricular hypertrophy
- Moderate to severe four-chamber dilatation are characteristic findings
- Remnant fibrotic scars from previous myocardial infarctions- transmural or subendocardial
- Mural thrombus- most commonly in the left ventricle but may be present in any chamber [2] [3]
Post-transplantation or Donor Heart
On gross pathology, features of acute or chronic rejection may be seen, if the patient is not on adequate immunosuppressive therapy. [3]
Microscopic Pathology
Pre-transplantation or Recipient Heart
- Hypertrophy of myocytes
- Myofibrillar loss
- Sarcoplasmic vacuolation
- Interstitial fibrosis
- Deposition of collagen, mostly in the subendocardial region.
- Variable degree of myocarditis[3]
Post-transplantation or Donor Heart
Changes associated with Rejection
Features of mild acute rejection include [4]-
- Focal mononuclear cells infiltrate, without the involvement of adjacent myocytes.[5]
Features of moderate acute rejection include-
- Dense collection of inflammatory cells, associated with involvement of adjacent myocytes.
- Eosinophils and also mononuclear cells are also seen in the infiltrate. [5]
Features of severe acute rejection additionally include-
- Hemorrhage
- Edema
- Vasculitis
- Neutrophilic infiltrate [2]
Features of chronic rejection include-
- Concentric intimal thickening
- Reservation of internal elastic lamina
Types of rejection
| Type (grade) | Description | Details of microscopic pathology |
| antibody-mediated rejection (acute vascular) | edema, dilated small vessels | scant inflammation |
| normal (0R) | normal | no extravascular monocytes |
| acute cellular (1R) | (perivascular) inflammatory infiltrate, myocyte damage | scant interstitial infiltrate (lymphoplasmacytic), scant damage |
| acute cellular (2R) | (perivascular) inflammatory space-occupying lesion | diffuse interstitial infiltrate displaces parenchyma (lymphoplasmacytic), obvious damage (myocyte eosinophilia or drop-out) |
| acute cellular (3R) | disruption of normal arch. | diffuse interstitial infiltrate disrupts parenchyma (lymphoplasmic & PMNs), fibre loss/damage |
| chronic | concentric intimal thicking | internal elastic lamina preserved (unlike atherosclerosis) |
Nonrejection changes
- Coronary Artery Disease- Arteriosclerosis- concentric intimal thickening associated with endovasculitis. This is to be compared with ordinary atherosclerosis where lipids are deposited mainly in the endothelium and subendothelium in an eccentric pattern.
- Other changes like- [3]
- Ischemic changes
- Interstitial fibrosis
- Mycoytes- hypertrophy, calcification
- Nodular lymphocytic endomyocardial infiltrates- Seen with the use of Cyclosporin, known as Quilty effect [6]
- Posttransplant lymphoproliferative disorder- Similar to large cell lymphoma
References
- ↑ Mehra MR, Canter CE, Hannan MM, Semigran MJ, Uber PA, Baran DA; et al. (2016). "The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update". J Heart Lung Transplant. 35 (1): 1–23. doi:10.1016/j.healun.2015.10.023. PMID 26776864.
- ↑ 2.0 2.1 Pomerance A, Stovin PG (1985). "Heart transplant pathology: the British experience". J Clin Pathol. 38 (2): 146–59. doi:10.1136/jcp.38.2.146. PMC 499095. PMID 2981905.
- ↑ 3.0 3.1 3.2 3.3 Tazelaar HD, Edwards WD (1992). "Pathology of cardiac transplantation: recipient hearts (chronic heart failure) and donor hearts (acute and chronic rejection)". Mayo Clin Proc. 67 (7): 685–96. doi:10.1016/s0025-6196(12)60726-5. PMID 1434905.
- ↑ Tan CD, Baldwin WM, Rodriguez ER (2007). "Update on cardiac transplantation pathology". Arch Pathol Lab Med. 131 (8): 1169–91. doi:10.1043/1543-2165(2007)131[1169:UOCTP]2.0.CO;2. PMID 17683180.
- ↑ 5.0 5.1 Boilson BA, McGregor CG, Kushwaha SS (2011). "Pathophysiological changes after cardiac transplantation: the role of chronic inflammation and rejection". Heart. 97 (20): 1634–5. doi:10.1136/heartjnl-2011-300526. PMID 21727202.
- ↑ Pardo-Mindán FJ, Lozano MD (1991). ""Quilty effect" in heart transplantation: is it related to acute rejection?". J Heart Lung Transplant. 10 (6): 937–41. PMID 1756159.