Heart transplantation associated arrhythmias

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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):
    • 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:
    • 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.
    • 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).

Techniques of HT

• John, R et al.  guide about techniques of HT:
  • 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
  • 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

• 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.
  1. Tachyarrhythmias
     1. 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.
• [Disease name] may be classified according to [classification method] into [number] subtypes/groups:

• [group1]
• [group2]
• [group3]

• Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

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].

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.
  • 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].