Heart transplantation associated arrhythmias: Difference between revisions

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{{Heart transplantation}}
{{Heart transplantation}}
{{CMG}}
{{CMG}}
==Overview==
==Overview   ==


* Patients with end-stage cardiac disease who are managed with heterotopic [[heart transplantation]], very commonly have [[arrhythmias]] post-transplantation, especially in the early postoperative period.
* Patients with end stage cardiac disease can be managed with heterotopic  heart transplantation, which is the most effective long term therapy, while  implantable left ventricular assisted devices have also shown desirable outcomes.  
* Most [[arrhythmias]] are benign like [[premature atrial complex]]<nowiki/>es and [[premature ventricular complexes]] that do not result in symptoms.
* The short term mortality in these patients has been decrease due to more refined surgical techniques, as well as the use of more advanced immunosuppressive regimen, but the morbidity in these patients has increased due to repeated transplant rejection episodes, and Cardiac allograft vasculopathy, which usually manifest as arrhythmia.
* More dangerous and life-threatening arrhythmias may also occur, which result in significant [[Morbidity & Mortality|morbidity]] and [[mortality]].


==Mechanisms and Risk Factors==
==Historical Perspective==
Various mechanisms are involved in both Bradyarrhythmias and Tachyarrythmias. Some of them are-
===Graft ischemia time===
Patients with graft [[ischemia]] time >4 hours are classified as high risk. Subsequent [[Endomyocardial fibrosis|endocardial fibrosis]] also contributes to arrhythmias.


===Bicaval and Biatrial Anastomosis===
* Brink J et al (2009) reports about the first human-to-human Heart Transplant (HT) : <ref name="pmid192878133">{{cite journal |vauthors=Brink JG, Hassoulas J |title=The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town - with reference to : the operation. A human cardiac transplant : an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town |journal=Cardiovasc J Afr |volume=20 |issue=1 |pages=31–5 |date=2009 |pmid=19287813 |pmc=4200566 |doi= |url=}}</ref>
*''' Biatrial method:'''
** Performed by a team led by Dr Christiaan Barnard in 1967, at the Groote Schuur Hospital and the University of Cape Town.
** His first patient was 53 years old Louis Washkansky with a history of smoking, diabetes and  severe coronary insufficiency.
** Donor heart was from a young lady who had  succumbed due to a lethal brain injury from a road traffic accident.
** Post operative course: after successful orthotopic HT procedure Washkansky continued to  recover progressively until he suddenly developed infiltrates in the lungs. Since the cause of infiltrates was not clear he was initially treated for rejection with immunosuppressive therapy, which aggravated his bilateral pneumonia and he died on 18th postoperative day due to severe pneumonia and septicemia.
* Subsequent orthotopic HTs were reported by Brink J et al. (2009) as: <ref name="pmid192878132">{{cite journal |vauthors=Brink JG, Hassoulas J |title=The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town - with reference to : the operation. A human cardiac transplant : an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town |journal=Cardiovasc J Afr |volume=20 |issue=1 |pages=31–5 |date=2009 |pmid=19287813 |pmc=4200566 |doi= |url=}}</ref>
** Barnard performed  10 more orthotopic HTs between 1967 to 1974, two of whom survived for 13 and 23 years respectively.
** Dr Shumway from Stanford University and Dr. Juro Wada at Sapporo Medical University in Japan performed the first HT in the United States (US) and Japan respectively, in 1968.
** 166 transplants  were performed globally between 1968 to 1970, however due to complications such as severe graft rejection reaction and infection, the 2-year survival rate was reported to be only 11%.
* Heterotopic HTs:
** Due to poor survival rate post orthotopic HT Barnard considered heterotopic ''(piggy-back)''  HT as a possibility to improve patient survival rate in 1974.<ref name="pmid192878134">{{cite journal |vauthors=Brink JG, Hassoulas J |title=The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town - with reference to : the operation. A human cardiac transplant : an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town |journal=Cardiovasc J Afr |volume=20 |issue=1 |pages=31–5 |date=2009 |pmid=19287813 |pmc=4200566 |doi= |url=}}</ref>
** Heterotopic heart transplantation allows the recipient's heart to maintain circulation while rejection reaction is reversed with immunosuppressive therapy.
** Advent of cyclosporine in 1980 was a much needed addition to post-operative management which contributed greatly to reduce incidence of severe life-threatening rejection episodes, hence Barnard’s group was able to resume orthotopic heart transplantation(OHT).<ref name="pmid29968430">{{cite journal |vauthors=Kim IC, Youn JC, Kobashigawa JA |title=The Past, Present and Future of Heart Transplantation |journal=Korean Circ J |volume=48 |issue=7 |pages=565–590 |date=July 2018 |pmid=29968430 |pmc=6031715 |doi=10.4070/kcj.2018.0189 |url=}}</ref>


Part of the recipient right and left atria are retained which is sutured to respective atrial of the donor.
=== '''Techniques of HT''' ===
This allows surgeons to preserve the recipient's sinus node, however, due to disruption of blood supply and denervation, this is rendered non-functional.
There is a complete conduction block across the suture line in the [[right atrium]].
*'''Bicaval method:'''


An [[anastomosis]] is made at the level of two [[Vena cavae|vena cava]]<nowiki/>e, the great vessels, and the left atrial cuff around the [[pulmonary vein]].
* John, R et al.  guide about techniques of HT:<ref name="JohnLiao2010">{{cite journal|last1=John|first1=Ranjit|last2=Liao|first2=Kenneth|title=Orthotopic Heart Transplantation|journal=Operative Techniques in Thoracic and Cardiovascular Surgery|volume=15|issue=2|year=2010|pages=138–146|issn=15222942|doi=10.1053/j.optechstcvs.2010.04.001}}</ref>
There is less [[Sinoatrial node|sinus nodal]] injury, [[tricuspid regurgitation]], and atrial dilatation making it the preferred technique of the current times.
** Preoperative preparation:
Potential advantages: associated with a reduced hospital stay, decreased incidence of atrial dysrhythmias and conduction disturbances, less mitral and tricuspid incompetence secondary to atrioventricular (AV) geometry distortion and right ventricular failure.
*** Successful HT requires very close coordination between the donor and recipient surgical team.
Potential disadvantages: increased ischemic time and the possibility of narrowing of the caval anastomosis.
*** Preoperative assessment includes: following considerations are critical to success of HT
 
**** Assessing compatibility of the donor heart.
===Denervation and Reinnervation===
**** Surgical team ensures optimum health of the recipient by ruling out any ongoing coagulation defect or infection.
Complete denervation of the donor heart is done and during the process of renevervation may be nonuniform.
** Intra-operative phase is planned to limit donor ischemic time to less than six hours; preferably less than four hours in case of old donor or increased pulmonary vascular resistance.
 
* John, R et al. report  Bicaval and Biatrial anastomosis are two most common techniques of HT<ref name="JohnLiao20102">{{cite journal|last1=John|first1=Ranjit|last2=Liao|first2=Kenneth|title=Orthotopic Heart Transplantation|journal=Operative Techniques in Thoracic and Cardiovascular Surgery|volume=15|issue=2|year=2010|pages=138–146|issn=15222942|doi=10.1053/j.optechstcvs.2010.04.001}}</ref>
===[[Cardiac allograft vasculopathy|Cardiac Allograft Vasculopathy]]/ Cardiac transplant Atherosclerosis===
** Biatrial method:
<ref name="VenturaMehra1995">{{cite journal|last1=Ventura|first1=Hector O.|last2=Mehra|first2=Mandeep R.|last3=Smart|first3=Frank W.|last4=Stapleton|first4=Dwight D.|title=Cardiac allograft vasculopathy: Current concepts|journal=American Heart Journal|volume=129|issue=4|year=1995|pages=791–799|issn=00028703|doi=10.1016/0002-8703(95)90331-3}}</ref>
*** Part of the recipient right and left atria is retained which is sutured to respective atrial of the donor.
 
*** This allows surgeons to preserve the recipient's sinus node, however due to disruption of  blood supply and denervation this is rendered non-functional.
===[[Rejection]]===
*** There is a complete conduction block across the suture line in the right atrium.
Maybe the cause in both early and late postoperative periods. Persistent AF warrants an evaluation for ongoing rejection.
** Bicaval method:
*** Anastomosis is made at the level of two vena cavae, the great vessels and the left atrial cuff around the pulmonary vein.  
*** There is less sinus nodal injury, tricuspid regurgitation, and atrial dilatation making it the preferred technique of the current times.
*** Potential advantages: associated with reduced hospital stay,decreased incidence of atrial dysrhythmias and conduction disturbances, less mitral and tricuspid incompetence secondary to atrioventricular (AV)  geometry distortion and right ventricular failure.
*** Potential disadvantages: increased ischemic time and the possibility of narrowing of the caval anastomosis.  


==Classification==
==Classification==
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|6.  Early rejection
|6.  Early rejection
|-
|-
|7.  Ionotrpes
|7.  Inotrpes
|-
|-
|Atrial flutter
|Atrial flutter
|Common  in the immediate  postoperative period  (>1 month)<br />Over all frequency 7.6%  
|Common  in immediate  postoperative period  (>1 month)<br />Over all frequency 7.6%  
(Elkaryoni et al.)
(Elkaryoni et al.)
|1.  AR - 28% cases  
|1.  AR - 28% cases  
2. Remodeling of atria (late-onset)
2. Remodelling of atria (late onset )
3. Atrial suture lines - conduction barriers
3. Atrial suture lines - conduction barriers
4. Recipient to donor atrial conduction
4. Recipient to donor atrial conduction
Line 79: Line 87:
|Focal atrial tachycardia
|Focal atrial tachycardia
|
|
|Formation of depolarization foci near the atrial scar that takes control of the heart rhythm. Foci can be found in donor atrium or in the atrial remnant of the recipient which passes into the donor.
|Formation of depolarization foci near the atrial scar that take control of the heart rhythm. Foci can be found in donor atrium or in the atrial remnant of recipient which passes into the donor.
|Focal  catheter ablation
|Focal  catheter ablation
|-
|-
|Atrial reentrant tachycardia & Nodal  reentrant tachycardia
|Atrial reenterant tachycardia & Nodal  reenterant tachycardia
|
|
|Requires a preexisting route in the donor that allows a macroreentrant.
|Requires a preexisting route in the donor that allows a macroreentrant.
|Radiofrequency  ablation (RFA)
|Radiofrequency  ablation (RFA)
|-
|-
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|Recipient-to-donor atrial conduction  tachycardia
|Recipient-to-donor atrial conduction  tachycardia
|
|
|Site of origin usually right atrial anastomosis.  
|site  of origin usually right atrial anastomosis.  
|Radiofrequency  ablation (RFA)
|Radiofrequency  ablation (RFA)
|-
|-
Line 100: Line 108:
(Elkaryoni et al.)
(Elkaryoni et al.)
|Non-sustained  
|Non-sustained  
|Early  post-transplant period
|Early  post-transplat period
|1.Acute  rejection
|1.Acute  rejection
2. Graft vasculopathy  
2. Graft vasculopathy  
Line 107: Line 115:
|-
|-
|Sustained
|Sustained
|Early  post-transplant period
|Early  post-transplat period
|1.  Acute rejection (if presenting during immediate postoperative period)
|1.  Acute rejection (if presenting during immediate post operative period)
2. Allopathic vasculopathy
2. Allopathic vasculopathy
3. LV dysfunction
3. LV dysfunction
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| rowspan="3" |Bradyarrhytmia
| rowspan="3" |Bradyarrhytmia
| rowspan="3" |
| rowspan="3" |
|Sinus Bradycardia
|Sick  sinus syndrome (SSS)
|0.5  %  
|0.5  %  
(Elkaryoni et al.)
(Elkaryoni et al.)
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|
|
|-
|-
|Sinus Node dysfunction
|Sudden cardiac arrrest
|3.7%   
|3.7%   
(Elkaryoni et al.)
(Elkaryoni et al.)
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|}
|}


*
*
*
*
*
*Post heart transplant Arrhythmias can be divided into tachyarrhythmias (heart rate > 100/min)  and bradyarrhythmia (heart rate < 60 /min). Tachycardias are further classified based on place of origin, such as supraventricular arrhythmias originate between sinus node and the AV node, where as ventricular arrhythmias originate below the AV node at the ventricular level.
**'''Tachyarrhythmias'''
** Supraventricular tachyarrhythmias (SVT)
*** Are most common POA noticed after HT.
*** Overall AF is reported to be more common as compared to AFl (47.3% vs 7.6%).
*** However older studies report AF (0.3 to 24%)  second after AFl (2.8 to 30%)
**Atrial Fibrillation (AF)
***EKG findings: irregularly irregular rhythm, absent [[P wave|P waves]], ventricular rate of 100-180 beats/minute, variability in QRS complexes intervals, narrow QRS complexes. 
***Mechanism:
****Early postoperative period: associated with pericardial inflammation, graft manipulation, primary graft failure, allograft rejection (AR) (37.5%), and autonomic changes(such as due to denervation), ischemia, and inotropes.<ref name="ThajudeenStecker2012">{{cite journal|last1=Thajudeen|first1=Anees|last2=Stecker|first2=Eric C.|last3=Shehata|first3=Michael|last4=Patel|first4=Jignesh|last5=Wang|first5=Xunzhang|last6=McAnulty|first6=John H.|last7=Kobashigawa|first7=Jon|last8=Chugh|first8=Sumeet S.|title=Arrhythmias After Heart Transplantation: Mechanisms and Management|journal=Journal of the American Heart Association|volume=1|issue=2|year=2012|issn=2047-9980|doi=10.1161/JAHA.112.001461}}</ref>
****Postoperative period (> 1 month): seen to be associated with allograft vasculopathy (in 21% cases), rejection (in 46% cases) or infection.<ref name="BoyleShivkumar20142">{{cite journal|last1=Boyle|first1=Noel G|last2=Shivkumar|first2=Kalyanam|last3=Vaseghi|first3=Marmar|last4=Taleski|first4=Jane|last5=Hamon|first5=David|title=Arrhythmias in the Heart Transplant Patient|journal=Arrhythmia & Electrophysiology Review|volume=3|issue=3|year=2014|pages=149|issn=2050-3377|doi=10.15420/aer.2014.3.3.149}}</ref>
***Occurrence:
****In relation to technique of heart transplantation: meta-analysis reports pooled estimated incidence of AF:<ref name="ChokesuwattanaskulBathini2018">{{cite journal|last1=Chokesuwattanaskul|first1=Ronpichai|last2=Bathini|first2=Tarun|last3=Thongprayoon|first3=Charat|last4=Preechawat|first4=Somchai|last5=O'Corragain|first5=Oisin A.|last6=Pachariyanon|first6=Pavida|last7=Ungprasert|first7=Patompong|last8=Cheungpasitporn|first8=Wisit|title=Atrial fibrillation following heart transplantation: A systematic review and meta-analysis of observational studies|journal=Journal of Evidence-Based Medicine|volume=11|issue=4|year=2018|pages=261–271|issn=17565391|doi=10.1111/jebm.12323}}</ref>
****# Biatrial technique: 18.7% (95%CI: 10.3%-31.5%)
****#Bicaval technique: 11.1% (95%CI: 6.5%-18.4%)
****Frequency in relation to timing of onset postoperative period:
*****POAF (</= 1 month): 6.2%
*****POAF (> 1 month): 4%
****#
*
==Pathophysiology==
*The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
*The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].


Post heart transplant Arrhythmias can be divided into tachyarrhythmias (heart rate > 100/min)  and bradyarrhythmia (heart rate < 60 /min). Tachycardias are further classified based on place of origin, such as supraventricular arrhythmias originate between the sinus node and the AV node, whereas ventricular arrhythmias originate below the AV node at the ventricular level.
==Clinical Features== 


===Tachyarrhythmias===
==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]
==Epidemiology and Demographics==


====Supraventricular tachyarrhythmias (SVT)====
** The International Society for Health and Lung Transplantation (ISHLT) reports over 5,500 annual transplants (all ages) performed globally, most in  North America. Increased number of deaths due to drug overdose in the US, an improvement in reporting of transplants globally and increasing use of “higher-risk” donor hearts are thought to be the main reasons for annual increase in number of reported HTs.  Figure 1: Number of heart transplants (adult and pediatric) by year (transplants: 1988−2017) and geographic region.<ref name="pmid19287813">{{cite journal |vauthors=Brink JG, Hassoulas J |title=The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town - with reference to : the operation. A human cardiac transplant : an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town |journal=Cardiovasc J Afr |volume=20 |issue=1 |pages=31–5 |date=2009 |pmid=19287813 |pmc=4200566 |doi= |url=}}</ref>
It includes-
** Age & gender breakdown: 36th report of ISHLT estimates that:
*[[Premature atrial contraction|Atrial Premature Complexes]] (benign)
*** Median recipient age for HT is 55 years.
*[[Atrial fibrillation|Atrial Fibrillation]]
*** Donor median range falls in the range of 28 years in North America to 45 years in Europe.
**Atrial Fibrillation is the most common and mostly occur in the early postoperative period, mostly within the first 7 days. <ref name="CreswellSchuessler1993">{{cite journal|last1=Creswell|first1=Lawrence L.|last2=Schuessler|first2=Richard B.|last3=Rosenbloom|first3=Michael|last4=Cox|first4=James L.|title=Hazards of postoperative atrial arrhythmias|journal=The Annals of Thoracic Surgery|volume=56|issue=3|year=1993|pages=539–549|issn=00034975|doi=10.1016/0003-4975(93)90894-N}}</ref>
*** Gender breakdown amongst donor and recipient groups is reported to have  67.9% and 74.4% male population respectively.  
** Occurence of Atrial Fibrillation >30 days postoperatively is a marker of higher long‐term mortality rate <ref name="ThajudeenStecker2012">{{cite journal|last1=Thajudeen|first1=Anees|last2=Stecker|first2=Eric C.|last3=Shehata|first3=Michael|last4=Patel|first4=Jignesh|last5=Wang|first5=Xunzhang|last6=McAnulty|first6=John H.|last7=Kobashigawa|first7=Jon|last8=Chugh|first8=Sumeet S.|title=Arrhythmias After Heart Transplantation: Mechanisms and Management|journal=Journal of the American Heart Association|volume=1|issue=2|year=2012|issn=2047-9980|doi=10.1161/JAHA.112.001461}}</ref>
** HT outcome:
*[[Atrial flutter|Atrial Flutter]]- Most common > 3 weeks postoperatively
*** Survival rate amongst 1-year survivors is reported to be 14.8 years, which is relatively higher for patients with primary diagnosis of  congenital heart disease followed by non-ischemic and ischemic cardiomyopathy, as worse for patients with diagnosis of re-transplants.  
* Others like AV Reentrant Tachycardias, Atrial reentrant tachycardia
*** Higher recipients and donor age are also associated with early post operative mortality.  
*** Female gender is associated with significantly higher post-transplant survival than men (median survival 12.2 years in women, 11.4 years in men).
*** Stehlik et al. report that most of the patients during the immediate postoperative period patients undergoing HT do not require hospitalisation. The functional status of 80% of the HT recipients is ≥80% on the Karnofsky Score (range, 10%–100%). Many HT recipients return to work.  Figure 2 : 5 Kaplan-Meier survival by era (adult heart transplants: January 1982−June 2017). NA, not available.


====Ventricular Arrythmias====
** Elkaryoni et al analysed Nationwide Inpatient Sample 2002-2014 to identify OHT recipients by using ICD-9 codes. Out of the 175,845 HT, 21,613 patients (12.3%)  recipients presented with arrhythmia
It includes-
*** Mean age was 60.8 ± 13.8 years, 73.1% were males and 63.8% were white.
*[[Premature ventricular contraction|Ventricular premature beats]]- seen in upto 100% of the patients in the early postoperative period <ref name="ScottDark1992">{{cite journal|last1=Scott|first1=Christopher D.|last2=Dark|first2=John H.|last3=McComb|first3=Janet M.|title=Arrhythmias after cardiac transplantation|journal=The American Journal of Cardiology|volume=70|issue=11|year=1992|pages=1061–1063|issn=00029149|doi=10.1016/0002-9149(92)90361-2}}</ref>
*** Overall most common POA reported was Atrial fibrillation (AF) (47.3%) followed by atrial flutter (AFl) (7.6%), ventricular tachycardia (4.7%), Paroxysmal supraventricular tachycardia (1.6%), sudden cardiac arrest (3.7%) and ventricular fibrillation (1.1%), sick sinus syndrome (0.5%), complete heart block (0.3%) and other dysrhythmias (33.2%). Frequencies reported are not associated with timing of onset.
* Nonsustained [[Ventricular tachycardia|Ventricular Tachycardia]]
*** Congestive heart failure (CHF) and Orthotopic HT complications  such as cellular rejection and cardiac allograft vasculopathy were the most predictors for POA (OR 2.33, OR 1.65 res[ectively).
*[[Ventricular Tachycardia|Sustained Ventricular Tachycardia]]
*[[Ventricular fibrillation|Ventricular Fibrillation]]


===Bradyarrhythmias===
*The international Society of Heart and Lung Transplant (ISHLT) reports over 5,500 annual transplant Heart transplant performed globally, most in North America. Increased number of  deaths due to drug overdose in the US, an improvement in reporting of transplant globally and increasing use of "high-risk" donor hearts are thought to be the main reasons for annual increase in number of reported heart transplants.8
*
*
*
*prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].
===Age===
*Patients of all age groups may develop [disease name].
*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].
===Gender===
*[Disease name] affects men and women equally.
*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.
===Race===
*There is no racial predilection for [disease name].
*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name].


====[[Sinus bradycardia|Sinus Bradycardia]]====
==Risk Factors==
Posttransplantation [[bradycardia]] is caused by- <ref name="JacquetZiady1990">{{cite journal|last1=Jacquet|first1=Luc|last2=Ziady|first2=Galal|last3=Stein|first3=Keith|last4=Griffith|first4=Bartley|last5=Armitage|first5=John|last6=Hardesty|first6=Robert|last7=Kormos|first7=Robert|title=Cardiac rhythm disturbances early after orthotopic heart transplantation: Prevalence and clinical importance of the observed abnormalities|journal=Journal of the American College of Cardiology|volume=16|issue=4|year=1990|pages=832–837|issn=07351097|doi=10.1016/S0735-1097(10)80330-4}}</ref>
*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
*Prolonged organ [[Ischemia|ischemic]] time
*[[Antiarrhythmic agents|Antiarrhythmic]] drug effects
*Surgical [[trauma]] and surgical [[Sutures|suture lines]]


====[[Sinus Node|Sinus Node Dysfunction]]====
== Natural History, Complications and Prognosis==
====Complete [[Heart block|Heart Block]]====
*The majority of patients with [disease name] remain asymptomatic for [duration/years].
<ref name="ThajudeenStecker2012">{{cite journal|last1=Thajudeen|first1=Anees|last2=Stecker|first2=Eric C.|last3=Shehata|first3=Michael|last4=Patel|first4=Jignesh|last5=Wang|first5=Xunzhang|last6=McAnulty|first6=John H.|last7=Kobashigawa|first7=Jon|last8=Chugh|first8=Sumeet S.|title=Arrhythmias After Heart Transplantation: Mechanisms and Management|journal=Journal of the American Heart Association|volume=1|issue=2|year=2012|issn=2047-9980|doi=10.1161/JAHA.112.001461}}</ref>
*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].


== Treatment ==
== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]
=== Symptoms ===
*[Disease name] is usually asymptomatic.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]
=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]


The treatment of posttransplant arrhythmias depends on the type and etiology.
=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].


* '''[[Catheter ablation]]/ [[Radiofrequency ablation]]''' - Employed in various tachyarrythmias.
*A  [positive/negative] [test name] is diagnostic of [disease name].
* '''[[Pacemaker]] insertion'''- Considered in persistent bradyarrythmias and heart block.
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
* '''[[Implantable cardioverter defibrillator|ICD]] insertion''' - For prevention of Sudden Cardiac Death (SCD)
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].
*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].


== Treatment ==
=== Medical Therapy ===
=== Medical Therapy ===
*[[Empiric therapy|Empiric]] treatment of rejection with [[steroid]] therapy is done when the suspected [[etiology]] is [[rejection]].
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.
* Limited evidence is present but the use of [[Antiarrhythmic agents|antiarrhythmic]] therapy can be employed with careful consideration of safety and tolerability.
*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].
   
   
=== Prevention ===
=== Prevention ===
Preventive care can be taken by targeting the etiology of the arrhythmias. This involves-
*There are no primary preventive measures available for [disease name].
* Detection and prompt treatment of rejection.
* Prevention of cardiac [[allograft]] [[vasculopathy]].
*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
* Limited data is available on [[Implantable cardioverter defibrillator|ICD]] implantation for prevention of [[sudden cardiac death]]. <ref name="McDowellHauptman2009">{{cite journal|last1=McDowell|first1=Deryk L.|last2=Hauptman|first2=Paul J.|title=Implantable Defibrillators and Cardiac Resynchronization Therapy in Heart Transplant Recipients: Results of a National Survey|journal=The Journal of Heart and Lung Transplantation|volume=28|issue=8|year=2009|pages=847–850|issn=10532498|doi=10.1016/j.healun.2009.04.016}}</ref>
 
*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].


==References==
==References==

Revision as of 17:27, 17 June 2020


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

  • Patients with end stage cardiac disease can be managed with heterotopic  heart transplantation, which is the most effective long term therapy, while  implantable left ventricular assisted devices have also shown desirable outcomes.
  • The short term mortality in these patients has been decrease due to more refined surgical techniques, as well as the use of more advanced immunosuppressive regimen, but the morbidity in these patients has increased due to repeated transplant rejection episodes, and Cardiac allograft vasculopathy, which usually manifest as arrhythmia.

Historical Perspective

  • Brink J et al (2009) reports about the first human-to-human Heart Transplant (HT) : [1]
    • Performed by a team led by Dr Christiaan Barnard in 1967, at the Groote Schuur Hospital and the University of Cape Town.
    • His first patient was 53 years old Louis Washkansky with a history of smoking, diabetes and  severe coronary insufficiency.
    • Donor heart was from a young lady who had  succumbed due to a lethal brain injury from a road traffic accident.
    • Post operative course: after successful orthotopic HT procedure Washkansky continued to  recover progressively until he suddenly developed infiltrates in the lungs. Since the cause of infiltrates was not clear he was initially treated for rejection with immunosuppressive therapy, which aggravated his bilateral pneumonia and he died on 18th postoperative day due to severe pneumonia and septicemia.
  • Subsequent orthotopic HTs were reported by Brink J et al. (2009) as: [2]
    • Barnard performed  10 more orthotopic HTs between 1967 to 1974, two of whom survived for 13 and 23 years respectively.
    • Dr Shumway from Stanford University and Dr. Juro Wada at Sapporo Medical University in Japan performed the first HT in the United States (US) and Japan respectively, in 1968.
    • 166 transplants  were performed globally between 1968 to 1970, however due to complications such as severe graft rejection reaction and infection, the 2-year survival rate was reported to be only 11%.
  • Heterotopic HTs:
    • Due to poor survival rate post orthotopic HT Barnard considered heterotopic (piggy-back)  HT as a possibility to improve patient survival rate in 1974.[3]
    • Heterotopic heart transplantation allows the recipient's heart to maintain circulation while rejection reaction is reversed with immunosuppressive therapy.
    • Advent of cyclosporine in 1980 was a much needed addition to post-operative management which contributed greatly to reduce incidence of severe life-threatening rejection episodes, hence Barnard’s group was able to resume orthotopic heart transplantation(OHT).[4]

Techniques of HT

  • John, R et al.  guide about techniques of HT:[5]
    • Preoperative preparation:
      • Successful HT requires very close coordination between the donor and recipient surgical team.
      • Preoperative assessment includes: following considerations are critical to success of HT
        • Assessing compatibility of the donor heart.
        • Surgical team ensures optimum health of the recipient by ruling out any ongoing coagulation defect or infection.
    • Intra-operative phase is planned to limit donor ischemic time to less than six hours; preferably less than four hours in case of old donor or increased pulmonary vascular resistance.
  • John, R et al. report  Bicaval and Biatrial anastomosis are two most common techniques of HT[6]
    • Biatrial method:
      • Part of the recipient right and left atria is retained which is sutured to respective atrial of the donor.
      • This allows surgeons to preserve the recipient's sinus node, however due to disruption of  blood supply and denervation this is rendered non-functional.
      • There is a complete conduction block across the suture line in the right atrium.
    • Bicaval method:
      • Anastomosis is made at the level of two vena cavae, the great vessels and the left atrial cuff around the pulmonary vein.
      • There is less sinus nodal injury, tricuspid regurgitation, and atrial dilatation making it the preferred technique of the current times.
      • Potential advantages: associated with reduced hospital stay,decreased incidence of atrial dysrhythmias and conduction disturbances, less mitral and tricuspid incompetence secondary to atrioventricular (AV)  geometry distortion and right ventricular failure.
      • Potential disadvantages: increased ischemic time and the possibility of narrowing of the caval anastomosis.  

Classification

Types of Arrhythmias Occurrence Common mechanism Treatment
Tachyarrhythmias Supra-ventricular tachy- arrthymia

(SVT)

Atrial fibrillation Common in early postoperative period
Over all frequency 47.3%

(Elkaryoni et al.)

1. Graft manipulation (primary graft failure) 1. Evaluate and manage the trigger

2. Persistent cases: Catheter ablation

2. Inflammatory changes (pericardial inflammation)
3. Autonomic hypersensitivity  
4. Ischemia
5. Denervation
6. Early rejection
7. Inotrpes
Atrial flutter Common in immediate  postoperative period (>1 month)
Over all frequency 7.6%

(Elkaryoni et al.)

1. AR - 28% cases

2. Remodelling of atria (late onset ) 3. Atrial suture lines - conduction barriers 4. Recipient to donor atrial conduction 5. Increased risk with bi-atrial method 6. Increased risk with older donor age

1. Evaluate and manage the trigger

2. Persistent cases: Radiofrequency ablation

Other SVTs Focal atrial tachycardia Formation of depolarization foci near the atrial scar that take control of the heart rhythm. Foci can be found in donor atrium or in the atrial remnant of recipient which passes into the donor. Focal catheter ablation
Atrial reenterant tachycardia & Nodal reenterant tachycardia Requires a preexisting route in the donor that allows a macroreentrant. Radiofrequency ablation (RFA)
Atrial macro-reentrant tachycardia site of origin is mostly in the upper right atrium, around the native and donor suture line Radiofrequency ablation (RFA)
Recipient-to-donor atrial conduction tachycardia site of origin usually right atrial anastomosis. Radiofrequency ablation (RFA)
Ventricular tachycardias
Over all frequency 7.6%

(Elkaryoni et al.)

Non-sustained Early post-transplat period 1.Acute rejection

2. Graft vasculopathy 3. Severe cardiac allograft vasculopathy (in symptomatic cases)

 ICD placement (in symptomatic cases)
Sustained Early post-transplat period 1. Acute rejection (if presenting during immediate post operative period)

2. Allopathic vasculopathy 3. LV dysfunction

Prompt for coronary angiography and cardiac biopsy
Ventricular fibrillation 1.1% Transplant coronary artery disease
Bradyarrhytmia Sick sinus syndrome (SSS) 0.5  %

(Elkaryoni et al.)

1. Sympathetic denervation

2. Ischemic injury to the sinus node 3. Graft ischemia or rejection 4. Drug effects  

Sudden cardiac arrrest 3.7%

(Elkaryoni et al.)

1. SSS

2. Cardiac allograft vasculopathy 3. Transplant coronary artery disease

Heart Block 0.3%

(Elkaryoni et al.)

1. Postoperative injury

2. Progressive conduction system disease associated with coronary artery disease 3. LV dysfunction 4. Chronic rejection 5. Injury from endomyocardial biopsies.
  • Post heart transplant Arrhythmias can be divided into tachyarrhythmias (heart rate > 100/min)  and bradyarrhythmia (heart rate < 60 /min). Tachycardias are further classified based on place of origin, such as supraventricular arrhythmias originate between sinus node and the AV node, where as ventricular arrhythmias originate below the AV node at the ventricular level.
    • Tachyarrhythmias
    • Supraventricular tachyarrhythmias (SVT)
      • Are most common POA noticed after HT.
      • Overall AF is reported to be more common as compared to AFl (47.3% vs 7.6%).
      • However older studies report AF (0.3 to 24%)  second after AFl (2.8 to 30%)
    • Atrial Fibrillation (AF)
      • EKG findings: irregularly irregular rhythm, absent P waves, ventricular rate of 100-180 beats/minute, variability in QRS complexes intervals, narrow QRS complexes. 
      • Mechanism:
        • Early postoperative period: associated with pericardial inflammation, graft manipulation, primary graft failure, allograft rejection (AR) (37.5%), and autonomic changes(such as due to denervation), ischemia, and inotropes.[7]
        • Postoperative period (> 1 month): seen to be associated with allograft vasculopathy (in 21% cases), rejection (in 46% cases) or infection.[8]
      • Occurrence:
        • In relation to technique of heart transplantation: meta-analysis reports pooled estimated incidence of AF:[9]
          1. Biatrial technique: 18.7% (95%CI: 10.3%-31.5%)
          2. Bicaval technique: 11.1% (95%CI: 6.5%-18.4%)
        • Frequency in relation to timing of onset postoperative period:
          • POAF (</= 1 month): 6.2%
          • POAF (> 1 month): 4%

Pathophysiology

  • The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
  • The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
  • On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
  • On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Clinical Features

Differentiating [disease name] from other Diseases

  • [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
  • [Differential dx1]
  • [Differential dx2]
  • [Differential dx3]

Epidemiology and Demographics

    • The International Society for Health and Lung Transplantation (ISHLT) reports over 5,500 annual transplants (all ages) performed globally, most in  North America. Increased number of deaths due to drug overdose in the US, an improvement in reporting of transplants globally and increasing use of “higher-risk” donor hearts are thought to be the main reasons for annual increase in number of reported HTs. Figure 1: Number of heart transplants (adult and pediatric) by year (transplants: 1988−2017) and geographic region.[10]
    • Age & gender breakdown: 36th report of ISHLT estimates that:
      • Median recipient age for HT is 55 years.
      • Donor median range falls in the range of 28 years in North America to 45 years in Europe.
      • Gender breakdown amongst donor and recipient groups is reported to have  67.9% and 74.4% male population respectively.
    • HT outcome:
      • Survival rate amongst 1-year survivors is reported to be 14.8 years, which is relatively higher for patients with primary diagnosis of  congenital heart disease followed by non-ischemic and ischemic cardiomyopathy, as worse for patients with diagnosis of re-transplants.
      • Higher recipients and donor age are also associated with early post operative mortality.
      • Female gender is associated with significantly higher post-transplant survival than men (median survival 12.2 years in women, 11.4 years in men).
      • Stehlik et al. report that most of the patients during the immediate postoperative period patients undergoing HT do not require hospitalisation. The functional status of 80% of the HT recipients is ≥80% on the Karnofsky Score (range, 10%–100%). Many HT recipients return to work. Figure 2 : 5 Kaplan-Meier survival by era (adult heart transplants: January 1982−June 2017). NA, not available.
    • Elkaryoni et al analysed Nationwide Inpatient Sample 2002-2014 to identify OHT recipients by using ICD-9 codes. Out of the 175,845 HT, 21,613 patients (12.3%)  recipients presented with arrhythmia
      • Mean age was 60.8 ± 13.8 years, 73.1% were males and 63.8% were white.
      • Overall most common POA reported was Atrial fibrillation (AF) (47.3%) followed by atrial flutter (AFl) (7.6%), ventricular tachycardia (4.7%), Paroxysmal supraventricular tachycardia (1.6%), sudden cardiac arrest (3.7%) and ventricular fibrillation (1.1%), sick sinus syndrome (0.5%), complete heart block (0.3%) and other dysrhythmias (33.2%). Frequencies reported are not associated with timing of onset.
      • Congestive heart failure (CHF) and Orthotopic HT complications  such as cellular rejection and cardiac allograft vasculopathy were the most predictors for POA (OR 2.33, OR 1.65 res[ectively).
  • The international Society of Heart and Lung Transplant (ISHLT) reports over 5,500 annual transplant Heart transplant performed globally, most in North America. Increased number of deaths due to drug overdose in the US, an improvement in reporting of transplant globally and increasing use of "high-risk" donor hearts are thought to be the main reasons for annual increase in number of reported heart transplants.8
  • prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
  • In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

  • Patients of all age groups may develop [disease name].
  • [Disease name] is more commonly observed among patients aged [age range] years old.
  • [Disease name] is more commonly observed among [elderly patients/young patients/children].

Gender

  • [Disease name] affects men and women equally.
  • [Gender 1] are more commonly affected with [disease name] than [gender 2].
  • The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

  • There is no racial predilection for [disease name].
  • [Disease name] usually affects individuals of the [race 1] race.
  • [Race 2] individuals are less likely to develop [disease name].

Risk Factors

  • Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

  • The majority of patients with [disease name] remain asymptomatic for [duration/years].
  • Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
  • If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
  • Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
  • Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

Diagnosis

Diagnostic Criteria

  • The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
  • [criterion 1]
  • [criterion 2]
  • [criterion 3]
  • [criterion 4]

Symptoms

  • [Disease name] is usually asymptomatic.
  • Symptoms of [disease name] may include the following:
  • [symptom 1]
  • [symptom 2]
  • [symptom 3]
  • [symptom 4]
  • [symptom 5]
  • [symptom 6]

Physical Examination

  • Patients with [disease name] usually appear [general appearance].
  • Physical examination may be remarkable for:
  • [finding 1]
  • [finding 2]
  • [finding 3]
  • [finding 4]
  • [finding 5]
  • [finding 6]

Laboratory Findings

  • There are no specific laboratory findings associated with [disease name].
  • A [positive/negative] [test name] is diagnostic of [disease name].
  • An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
  • Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings

  • There are no [imaging study] findings associated with [disease name].
  • [Imaging study 1] is the imaging modality of choice for [disease name].
  • On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
  • [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

  • [Disease name] may also be diagnosed using [diagnostic study name].
  • Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

  • There is no treatment for [disease name]; the mainstay of therapy is supportive care.
  • The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
  • [Medical therapy 1] acts by [mechanism of action 1].
  • Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Surgery

  • Surgery is the mainstay of therapy for [disease name].
  • [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
  • [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention

  • There are no primary preventive measures available for [disease name].
  • Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
  • Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

References

  1. ↑ Brink JG, Hassoulas J (2009). "The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town - with reference to : the operation. A human cardiac transplant : an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town". Cardiovasc J Afr. 20 (1): 31–5. PMC 4200566. PMID 19287813.
  2. ↑ Brink JG, Hassoulas J (2009). "The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town - with reference to : the operation. A human cardiac transplant : an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town". Cardiovasc J Afr. 20 (1): 31–5. PMC 4200566. PMID 19287813.
  3. ↑ Brink JG, Hassoulas J (2009). "The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town - with reference to : the operation. A human cardiac transplant : an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town". Cardiovasc J Afr. 20 (1): 31–5. PMC 4200566. PMID 19287813.
  4. ↑ Kim IC, Youn JC, Kobashigawa JA (July 2018). "The Past, Present and Future of Heart Transplantation". Korean Circ J. 48 (7): 565–590. doi:10.4070/kcj.2018.0189. PMC 6031715. PMID 29968430.
  5. ↑ John, Ranjit; Liao, Kenneth (2010). "Orthotopic Heart Transplantation". Operative Techniques in Thoracic and Cardiovascular Surgery. 15 (2): 138–146. doi:10.1053/j.optechstcvs.2010.04.001. ISSN 1522-2942.
  6. ↑ John, Ranjit; Liao, Kenneth (2010). "Orthotopic Heart Transplantation". Operative Techniques in Thoracic and Cardiovascular Surgery. 15 (2): 138–146. doi:10.1053/j.optechstcvs.2010.04.001. ISSN 1522-2942.
  7. ↑ Thajudeen, Anees; Stecker, Eric C.; Shehata, Michael; Patel, Jignesh; Wang, Xunzhang; McAnulty, John H.; Kobashigawa, Jon; Chugh, Sumeet S. (2012). "Arrhythmias After Heart Transplantation: Mechanisms and Management". Journal of the American Heart Association. 1 (2). doi:10.1161/JAHA.112.001461. ISSN 2047-9980.
  8. ↑ Boyle, Noel G; Shivkumar, Kalyanam; Vaseghi, Marmar; Taleski, Jane; Hamon, David (2014). "Arrhythmias in the Heart Transplant Patient". Arrhythmia & Electrophysiology Review. 3 (3): 149. doi:10.15420/aer.2014.3.3.149. ISSN 2050-3377.
  9. ↑ Chokesuwattanaskul, Ronpichai; Bathini, Tarun; Thongprayoon, Charat; Preechawat, Somchai; O'Corragain, Oisin A.; Pachariyanon, Pavida; Ungprasert, Patompong; Cheungpasitporn, Wisit (2018). "Atrial fibrillation following heart transplantation: A systematic review and meta-analysis of observational studies". Journal of Evidence-Based Medicine. 11 (4): 261–271. doi:10.1111/jebm.12323. ISSN 1756-5391.
  10. ↑ Brink JG, Hassoulas J (2009). "The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town - with reference to : the operation. A human cardiac transplant : an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town". Cardiovasc J Afr. 20 (1): 31–5. PMC 4200566. PMID 19287813.

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