Heart transplantation pathophysiology: Difference between revisions

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{{Heart transplantation}}
{{Heart transplantation}}


{{CMG}}; {{AE}}  
{{CMG}}; {{AE}} {{IF}}
==Overview==
==Overview==
The exact pathogenesis of [disease name] is not fully understood.
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.
 
OR
 
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
 
OR
 
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
 
OR
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Pathophysiology==
==Pathophysiology==


===Pathogenesis===
===Pathogenesis===
Cardiac Transplantation is the end result of intractable heart failure.  
Cardiac Transplantation is the treatment for patients with intractable heart failure, not amenable to medical and device therapy.


*[[Heart failure]] is a complex syndrome whereby there is an inadequate output of the heart to meet the metabolic demands of the body. Heart failure is caused by abnormal function of different parts of the heart including the [[pericardium]], the [[myocardium]], the [[endocardium]], the [[heart valves]] and the great vessels.  
*[[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 and indications that result 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>
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 Left Ventricular Ejection Fraction less than 35%
*Systolic Heart Failure with a low Left Ventricular Ejection Fraction( <35%) may be caused by
**Ischemic [[cardiomyopathy]]
**Ischemic [[cardiomyopathy]]
**Dilated cardiomyopathy
**Dilated cardiomyopathy
**[[Valvular heart disease]]
**[[Valvular heart disease]]
**[[Hypertensive heart disease]]
**[[Hypertensive heart disease]]
**Etiologies which are excluded are [[amyloid]], [[HIV]], and cardiac [[sarcoma]]
*Ischemic Coronary Artery Disease with Refractory [[Angina]]
*Ischemic Coronary Artery Disease with Refractory [[Angina]]
*Intractable life-threatening [[Arrhythmias]]
*Long-standing Intractable life-threatening [[Arrhythmias]]
**Ventricular arrhythmias which are not controlled by an implantable cardioverter-defibrillator
**Ventricular arrhythmias
*Cardiomyopathies
*Cardiomyopathies
**Restrictive and Hypertrophic Cardiomyopathies with [[NYHA]] Class IV [[heart failure]] symptoms
**Restrictive and Hypertrophic Cardiomyopathies  
**Non-dilated cardiomyopathies  
**Non-dilated cardiomyopathies  
*Congenital Heart Disease
*Congenital Heart Disease
** New York Heart Association functional class IV [[Heart Failure]] not amenable to surgery.
** Many congenital heart defects that are not amenable to surgery lead to New York Heart Association functional class IV [[Heart Failure]]


==Genetics==
==Gross Pathology==
[Disease name] is transmitted in [mode of genetic transmission] pattern.
===Pre-transplantation or Recipient Heart===


OR
On gross pathology, features of '''chronic heart failure''' are seen- 
*Biventricular [[Hypertrophy (medical)|hypertrophy]]
*Moderate to severe four-chamber [[dilatation]] are characteristic findings
*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 <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>


Genes involved in the pathogenesis of [disease name] include:
===Post-transplantation or Donor Heart===
*[Gene1]
*[Gene2]
*[Gene3]


OR
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>


The development of [disease name] is the result of multiple genetic mutations such as:
==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]]<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>


*[Mutation 1]
Features of moderate acute rejection include-
*[Mutation 2]
* Dense collection of [[inflammatory cells]], associated with involvement of adjacent myocytes.
*[Mutation 3]
*[[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>


==Associated Conditions==
Features of severe acute rejection ''additionally'' include-
Conditions associated with [disease name] 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>


*[Condition 1]
Features of chronic rejection include-
*[Condition 2]
*[[Concentric hypertrophy|Concentric]] [[intimal]] thickening
*[Condition 3]
* Reservation of internal elastic lamina


==Gross Pathology==
===Types of rejection===
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
{| 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]])
|}


==Microscopic Pathology==
==== Nonrejection changes====
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
* 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.

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 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-

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

Post-transplantation or Donor Heart

Changes associated with Rejection

Features of mild acute rejection include [4]-

Features of moderate acute rejection include-

Features of severe acute rejection additionally include-

Features of chronic rejection include-

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

  1. ↑ 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. ↑ 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. ↑ 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.
  4. ↑ 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. ↑ 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.
  6. ↑ 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.

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