Heart Transplant

Updated: April 10, 2020

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Cardiac Pacemaker

https://link.springer.com/chapter/10.1007/978-3-319-43773-6_8

In addition, the depolarization of the remaining native heart is not transmitted beyond the anastomotic suture line to the donor heart.

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Postoperative Cardiovascular Physiology

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Heart Rate

Immediately post-operatively, the transplanted heart is bradycardic likely from sinus node

dysfunction (myocardial ischemia and surgical manipulation) and can last for 1-2 weeks. 

The sinus node dysfunction is usually transient but a 2-5% prevalence of permanent pacemaker

placement has been report (1).

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In time, the transplanted heart will have a higher heart rate, between 90-110 beats per minute, likely related to the loss of vagal tone from denervation (134). With exercise, heart rate may increases slightly (likely due to Bainbridge reflex). 

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Stroke Volume (Diastolic Dysfunction)

• due to reperfusion stunning usually for the first 24 hours

• causes impaired filling

• filling pressures of 10-15 mmHg may be required

• if does not resolve within 1 week, suspect acute rejection in your differential diagnosis

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Cardiac Output

Because of the impaired heart rate and diastolic dysfunction, adequate heart rate and

atrio-ventricular synchrony are often required to maintain cardiac output. 

A minimum heart rate of 90 beats per minute is usually maintained using:

• epicardial pacing

• isoproterenol infusion

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In addition, Frank-Starling mechanisms and its affect on end-diastolic volume are further implored to maximize the cardiac output. Because of this, heart transplant patients become preload dependent with higher filling pressures needed a concept that is very important especially before the use of anesthesia. 

 

Maximizing the heart rate and stroke volume ensures an adequate cardiac output. 

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The normal response to changes in position (eg. sitting, standing, walking) are lost as are the variations in response to stimuli such as valsalva maneuver, carotid sinus massage, body position as well as normal response to laryngoscopy and intubation.

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Additionally, especially with exercise, left ventricular end-diastolic volume remains the main mechanism of increasing stroke volume and thus cardiac output. Relying on circulating catecholamines would have a delayed chronotropic response and thus not an adequate compensatory mechanism. Remember, normally an innervated heart that undergoes a sudden reduction in intravascular volume will have a simultaneous increase in both heart rate and contractility. In the denervated heart, the initial response is only dependent on Frank-Starling mechanisms.

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Certain medications that will not work:

• phenylephrine

• atropine

• amyl nitrate 

• digoxin

• neostigmine

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Adenosine has an exaggerated response - use 1 mg

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Reference: (1) Chinnock et al, Pacing Clin Electrophysiol, 1996, (134) Beck, Circulation, 1969

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Donor-Recipient Size Mismatch

Mismatch can affect cardiovascular function

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Immune System

Histocompatibility complexes: protect an individual from organism or toxins that might cause damage (77-78). All cells and toxins possess specific antigens that uniquely identify them. Antigens provoke the immune system and once activated it functions in two different pathways:

• innate immune system

• adaptive (acquired) immune system - this is responsible for allograft rejection

  • cell-mediated​ immune system (T cells)

  • humoral-mediated immune system (B-cells)

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Innate Immune System

• Complement system consists of 3 pathways:

  • Classical

  • Lectin

  • Alternative

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Adaptive Immune System

T lymphocytes are activated by antigen which causes a proliferation and release of a

vast quantity of different types of T cells (helper T, cytotoxic T, and suppressor

T cells).

• Helper T cells predominate and are primarily responsible for regulating

immune function by producing lymphokines (eg. IL, IF). Its these lymphokines

that facilitate or inhibit both B and T cells. 

• Cytotoxic T cells directly attack the offending antigen (especially foreign cells)

• Suppressor T cells are believed to modulate by releasing chemicals that turn "off" the immune reactions; might also play a role in autoimmune disorders

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Antigen can directly activate B lymphocytes (plasma cells) which are responsible

for antibody production and activation of the complement system (C3-->C3b) which

will be responsible for neutralizing the antigens by means of: agglutination,

precipitation, opsonization or lysis. 

 

Allograft Rejection

Almost all cardiac transplant recipients will experience episodes of graft rejection at some point. 

Immune activation, unless suppressed, will damage and ultimately destroy the transplanted donor heart. 

Acute cardiac rejection manifestations is quite variable: 

• malaise

• reduced exercise tolerance

• low grade fever

Rejection is best diagnosed by means of periodic endomyocardial biopsies. After the initial biopsy, routine biopsies are performed biweekly for the first three months, monthly for 6 months and then every 3 months; after the first 2 years, biopsies are performed on an annual basis. Episodes of rejection can alter this schedule and the number of biopsies that may be required. 

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Chronic rejection manifests as an accelerated graft atherosclerosis. Incidence is about 10-15% by the end of the first year and 35-50% by the fifth year. Evidence suggests that denervation causes an up-regulation of muscarinic receptors that promotes an influx of calcium in the transplanted hearts coronary arteries causing a circumferential, diffuse narrowing of the intraluminal diameter. Calcium channel blockers may ameliorate this problem. 

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Immunosuppressive Therapy

Most centers use a "triple-drug" regimen which consists of:

• glucocorticoids

• antiproliferative

  • mycophenolate​

  • azathioprine

  • cyclophosphamide

  • chlorambucil

  • methotrexate

• calcineurin inhibitors

  • tacrolimus (prograf, FK506)

  • cyclosporin

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References: (77) Barry et al, Cirulation, 1999, (78) Hanto et al, Surgery Scientific Principles and practices, 1993, 

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Infection​

Infection is the leading cause of death among cardiac transplant patients, between 1 month and 1 year, and is usually caused by:

• mediastinitis

• pneumonia

• urinary tract infection

• central-line induced sepsis

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The most frequent infecting organism is cytomegalovirus.

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Despite advances in antimicrobial prophylaxis, infection continues to be one of the most important barriers for long-term survival. Methods to identify heart recipients at risk of infection could allow physicians to make targeted adjustments to immunosuppressive strategy and prophylaxis aimed at decreasing patient morbidity (2). 

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Immunoglobulin G (IgG)

• investigated as a risk factor for infection 

• < 400 mg/dL is a risk factor for infection with:

  • respiratory infection​

  • cytomegalovirus (CMV)

  • aspergillus and other fungal infections

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References: (2) Carbone et al, J Neurol Neurosurg Psychiatry, 1999

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Complications

• primary graft failure

• rejection

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Primary Graft Failure

• poor cardiac output with adequate filling pressures

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Rejection

• hyperacute 

  • usually happens within the first few hours of transplant​

  • antibody mediated

• acute

  • usually happens after the first week​

  • T-mediated

• Treatment

  • high dose methylprednisolone pulse therapy ​

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