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Heart Transplantation

  • Author: Donald M Botta, Jr, MD; Chief Editor: John Geibel, MD, DSc, MSc, MA  more...
 
Updated: Feb 26, 2016
 

Background

Heart transplantation is the procedure by which the failing heart is replaced with another heart from a suitable donor.[1] It is generally reserved for patients with end-stage congestive heart failure (CHF) who are estimated to have less than 1 year to live without the transplant and who are not candidates for or have not been helped by conventional medical therapy. In addition, most candidates are excluded from other surgical options because of the poor condition of the heart.

Candidacy determination and evaluation are key components of the process, as are postoperative follow-up care and immunosuppression management. Proper execution of these steps can culminate in an extremely satisfying outcome for both the physician and patient.[2]

Candidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III (moderate) symptoms or class IV (severe) symptoms.[3] Evaluation demonstrates ejection fractions of less than 25%. Attempts are made to stabilize the cardiac condition while the evaluation process is undertaken.

Interim therapy can include oral agents as well as inotropic support. Mechanical support with the intra-aortic balloon pump (IABP) or implantable assist devices may be appropriate in some patients as a bridge to transplantation.[4, 5, 6] However, mechanical support does not improve waiting list survival in adult patients with congenital heart disease.[7]

The annual frequency of heart transplantation is about 1% of the general population with heart failure, both candidates and noncandidates. Improved medical management of CHF has decreased the candidate population; however, organ availability remains an issue.[8, 9] Further information on organ availability and waiting lists is available from the United Network for Organ Sharing.

For patient education resources, see the Heart Center, as well as Heart and Lung Transplant and Congestive Heart Failure.

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Practice Essentials

Heart transplantation is the replacement of a failing heart with a heart from a suitable donor. The 1-year survival rate after cardiac transplantation is as high as 81.8%, with a 5-year survival rate of 69.8%. A significant number of recipients survive more than 10 years after the procedure. See the image below.

Completed operation. Note suture lines on now-impl Completed operation. Note suture lines on now-implanted heart.

Indications for heart transplantation

Heart transplantation is generally reserved for patients with end-stage congestive heart failure (CHF) who are estimated to have less than 1 year to live without the transplant and who are not candidates for or have not been helped by conventional medical therapy. Because of the poor condition of their heart, most heart transplantation candidates are excluded from other surgical options. Specific indications for a transplant include the following:

  • Dilated cardiomyopathy
  • Ischemic cardiomyopathy
  • Congenital heart disease for which no conventional therapy exists or for which conventional therapy has failed
  • Ejection fraction of less than 20%
  • Intractable angina or malignant cardiac arrhythmias for which conventional therapy has been exhausted
  • Pulmonary vascular resistance of less than 2 Wood units
  • Age younger than 65 years
  • Ability to comply with medical follow-up care

Workup

Evaluation of the heart transplant candidate includes laboratory tests, imaging studies, and other tests as appropriate.

Laboratory studies

  • Virus: Including hepatitis viruses, human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV); used to determine past exposure and currently active disease
  • Fungus and tuberculosis (TB): Used to determine past exposure and to predict reactivation
  • Prostate-specific antigen (PSA): If positive, initiate appropriate evaluation and therapy before completing the evaluation for transplantation
  • Papanicolaou test: Results should be negative before listing for transplantation
  • Complete blood count (CBC): With differential, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and a complete chemistry profile (including liver panel, lipid profile, and urinalysis)
  • Blood typing and screening, panel-reactive antibody (PRA) testing, and tissue typing: Used to determine the immunologic suitability of the patient for transplantation and donor matching

Imaging studies

  • Coronary arteriography: Performed in cases of cardiomyopathy to determine if the cause of the cardiac dysfunction may be amenable to conventional therapies
  • Echocardiography: Used to determine the cardiac ejection fraction and to monitor the cardiac function of patients on the transplantation waiting list
  • Posteroanterior and lateral chest radiographs: Used to screen for other thoracic pathologies that may preclude transplantation.
  • Bilateral mammograms: Should reveal no abnormalities before listing for transplantation

Cardiac and pulmonary evaluation

  • Maximal venous oxygen consumption (MVO 2): Used to assess overall cardiac function and as a predictor of the severity of congestive heart failure and survival
  • Right- and left-heart catheterization: Used to determine if the disease process is reversible or treatable by more conventional therapy
  • Pulmonary vascular resistance: Patients with fixed resistances above 4 Wood units are not candidates for heart transplantation

Biopsy

Endomyocardial biopsy of the potential candidate is not routinely performed. The procedure may be considered if a systemic process involving the heart is thought to be the cause of the cardiomyopathy.

Perform biopsies of appropriate areas if the patient exhibits symptoms of systemic disease. Biopsies are used to determine the extent and activity of the disease process. Systemic disease processes are a contraindication to cardiac transplantation.

Transplantation procedures

During the cardiac transplantation procedure, the ventricles are excised, leaving the great vessels, right atrium, and left atrium of the recipient. The donor heart is then sewn to these areas. A cardiac allograft can be sewn in either a heterotopic or an orthotopic position.

Heterotopic heart transplantation

Heterotopic transplantation is an excellent technique for patients with severe pulmonary hypertension. Inherent problems with the technique, however, include pulmonary compression of the recipient, difficulty obtaining an endomyocardial biopsy, and the need for anticoagulation.

Orthotopic heart transplantation

Orthotopic heart transplantation is performed with either of the following techniques:

  • Shumway-Lower technique: This method is simpler and saves perhaps 10-15 minutes of ischemic time
  • Bicaval anastomosis: One advantage of the bicaval method is that, by avoiding a large right atrium, the surgeon can maintain better atrial transport; another claimed advantage of this technique is a lower reported incidence of tricuspid regurgitation

Immunosuppressive therapy

Immunosuppression is started soon after surgery. Several regimens can be used, including pretransplantation induction therapy and simple postoperative maintenance therapy; the choice of regimen depends on the training and experience of the transplant center.[10, 11]

Complications

Posttransplant complications can include the following:

  • Bleeding from suture lines
  • Hyperacute rejection
  • Infection
  • Psychiatric disturbances from steroid therapy
  • Cardiac rejection
  • Allograft vascular disease
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Disease Processes Necessitating Heart Transplantation

The disease processes that necessitate cardiac transplantation can be divided into the following categories:

  • Dilated cardiomyopathy (54%) - This often has an unclear origin
  • Ischemic cardiomyopathy (45%) - This percentage is rising because of the increase in coronary artery disease (CAD) in younger age groups
  • Congenital heart disease and other diseases not amenable to surgical correction (1%)

The pathophysiology of cardiomyopathy that may necessitate cardiac replacement depends on the primary disease process. Chronic ischemic conditions precipitate myocardial cell damage, with progressive enlargement of the myocyte followed by cell death and scarring. The condition can be treated with angioplasty or bypass; however, the small-vessel disease is progressive and thus causes progressive loss of myocardial tissue. This eventually results in significant functional loss and progressive cardiac dilatation.

The pathologic process involved in the functional deterioration of a dilated cardiomyopathy is still unclear. Mechanical dilatation and disruption of energy stores appear to play roles.

The pathophysiology of the transplanted heart is unique. The denervation of the organ makes it dependent on its intrinsic rate. As a result of the lack of neuronal input, some left ventricular hypertrophy results. The right-side function is directly dependent on the ischemic time before reimplantation and the adequacy of preservation. The right ventricle is easily damaged and may initially function as a passive conduit until recovery occurs.

The rejection process that can occur in the allograft has 2 primary forms, cellular and humoral. Cellular rejection is the classic form of rejection and is characterized by perivascular infiltration of lymphocytes with subsequent myocyte damage and necrosis if left untreated.

Humoral rejection is much more difficult to characterize and diagnose. It is thought to be a generalized antibody response initiated by several unknown factors. The antibody deposition into the myocardium results in global cardiac dysfunction. This diagnosis is generally made on the basis of clinical suspicion and exclusion; endomyocardial biopsy is of little value in this context.

CAD is a late pathologic process common to all cardiac allografts, characterized by myointimal hyperplasia of small and medium-sized vessels. The lesions are diffuse and may appear any time from 3 months to several years after implantation. The inciting causes are unclear, though cytomegalovirus (CMV) infection and chronic rejection have been implicated. The mechanism of the process is thought to depend on growth-factor production in the allograft initiated by circulating lymphocytes. Currently, there is no treatment other than retransplantation.

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Future and Controversies

The future of cardiac transplantation will be determined by the outcomes of several issues. One is the ongoing shortage of donor organs, which has fueled a search for alternative therapies for the failing heart. Such therapies include artificial assist devices, dual-chamber pacing, new drug interventions, and genetic therapy.[12] These efforts have proven to be successful in reducing the need for transplantation. Research in the area of xenografts continues.[13, 14]

Another issue is the prevention of allograft vascular disease, which remains a paramount challenge. The pathology of allograft vascular disease is clearly multifactorial in origin, making the research and therapy equally complex. Resolution of this issue will prolong graft survival and lives.

A third issue is the question of recipient selection and listing status, which continues to pose medical and ethical dilemmas. If the donor situation were not an issue, then the listing of potential recipients would not be troublesome.

The final issue is financial. In this era of cost containment in health care, the escalating costs of heart transplantation raises the questions of who should pay for the therapy and whether the procedure should be available on demand.

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Indications

The general indications for cardiac transplantation include deteriorating cardiac function and a prognosis of less than 1 year to live. Specific indications include the following:

  • Dilated cardiomyopathy
  • Ischemic cardiomyopathy
  • Congenital heart disease for which no conventional therapy exists or for which conventional therapy has failed
  • Ejection fraction less than 20%
  • Intractable angina or malignant cardiac arrhythmias for which conventional therapy has been exhausted
  • Pulmonary vascular resistance of less than 2 Wood units
  • Age younger than 65 years
  • Ability to comply with medical follow-up care

The 2016 International Society for Heart Lung Transplantation updated criteria for heart transplantation are as follows[15, 16] :

  • Heart failure prognosis scores should be performed along with cardiopulmonary exercise testing to determine prognosis and guide listing for transplantation for ambulatory patients. An estimated 1-yr survival of <80%, as calculated by the Seattle Heart Failure Model (SHFM), or a Heart Failure Survival Score (HFSS) in the high/medium risk range should be considered as reasonable cut points for listing
  • Patients should not be listed solely on the criteria of heart failure survival prognostic scores
  • Right heart catheterization (RHC) should be performed on all adult candidates in preparation for listing for cardiac transplantation and periodically until transplantation .
  • After left ventricular assist device (LVAD), reevaluation of hemodynamics should be done after 3-6 mo to ascertain reversibility of pulmonary hypertension
  • Pre-transplant body mass index (BMI) >35 kg/m 2 is associated with a worse outcome after cardiac transplantation; for such obese patients, it is reasonable to recommend weight loss to achieve a BMI of ≤35 kg/m 2 before listing for cardiac transplantation.
  • It is reasonable to consider the presence of irreversible renal dysfunction (epidermal growth factor receptor [eGFR] <30 ml/min/1.73 m 2) as a relative contraindication for heart transplantation alone.
  • Clinically severe symptomatic cerebrovascular disease may be considered a contraindication to transplantation
  • Assessment of frailty (3 of 5 possible symptoms, including unintentional weight loss of ≥10 lb within the past year, muscle loss, fatigue, slow walking speed, and low levels of physical activity) could be considered when assessing candidacy
  • Use of mechanical circulatory support should be considered for patients with potentially reversible or treatable comorbidities, such as cancer, obesity, renal failure, tobacco use, and pharmacologically irreversible pulmonary hypertension, with subsequent reevaluation to establish candidacy
  • Any patient for whom social supports are deemed insufficient to achieve compliant care in the outpatient setting may be regarded as having a relative contraindication to transplant. The benefit of heart transplantation in patients with severe cognitive-behavioral disabilities or dementia (eg, self-injurious behavior, inability to ever understand and cooperate with medical care) has not been established and has the potential for harm; therefore, heart transplantation cannot be recommended for this subgroup of patients
  • Retransplantation is indicated for those patients who develop significant cardiac allograft vasculopathy (CAV) with refractory cardiac allograft dysfunction, without evidence of ongoing rejection
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Contraindications

Contraindications for heart transplantation include the following:

  • Age greater than 65 years - This is a relative contraindication; patients who are older than 65 years are evaluated on an individual basis
  • Fixed pulmonary vascular resistance of greater than 4 Wood units
  • Active systemic infection
  • Active systemic disease such as collagen-vascular disease or sickle cell disease
  • Active malignancy - Patients with malignancies who have demonstrated a 3- to 5-year disease-free interval may be considered, depending on the tumor type and the evaluating program
  • An ongoing history of substance abuse (eg, alcohol, drugs, or tobacco)
  • Psychosocial instability
  • Inability to comply with medical follow-up care [17]
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Outcomes

The 1-year survival rate after cardiac transplantation is as high as 81.8%, with a 5-year survival rate of 69.8%. A significant number of recipients survive more than 10 years after the procedure. After transplantation, adult patients with congenital heart disease have high 30-day mortality but better late survival.[7] The functional status of the recipient after the procedure is generally excellent, depending on the his or her level of motivation.

In patients with severe biventricular failure who received pneumatic biventricular assist devices as a bridge to transplant, the 1-year actuarial survival rate was 89%, compared with 92% in patients without a ventricular assist device.[18]

Hypertension, diabetes mellitus, and obesity are associated with exponential increases in postoperative mortality rates. Heart transplant recipients with all three of these metabolic risk factors were found to have a 63% increased mortality compared to patients without any of the risk factors.[19]

Arnaoutakis et al found that high-risk patients had better 1-year survival rates at high-volume centers (ie, centers that perform more than 15 procedures per year) than at lower volume centers (79% vs 64%, respectively). These differences dissipated among lower-risk patients. Based on these findings, the authors recommended that all high-risk heart transplantation procedures be performed at higher-volume centers.[20]

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Contributor Information and Disclosures
Author

Donald M Botta, Jr, MD Assistant Professor, Department of Surgery, Section of Cardiac Surgery, Surgical Director, Cardiac Transplantation, Director of Mechanical Circulatory Support, Yale University School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Mary C Mancini, MD, PhD, MMM Professor and Chief of Cardiothoracic Surgery, Department of Surgery, Louisiana State University School of Medicine in Shreveport

Mary C Mancini, MD, PhD, MMM is a member of the following medical societies: American Association for Thoracic Surgery, American College of Surgeons, American Surgical Association, Society of Thoracic Surgeons, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

John Geibel, MD, DSc, MSc, MA Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director, Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow

John Geibel, MD, DSc, MSc, MA is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, Society for Surgery of the Alimentary Tract

Disclosure: Received royalty from AMGEN for consulting; Received ownership interest from Ardelyx for consulting.

Acknowledgements

Deepak M Gangahar, MBBS, MD Professor, Department of Surgery, Chief, Section of Cardiovascular and Thoracic Surgery, Surgical Director, Heart Transplant and VAD Services, University of Nebraska Medical Center

Deepak M Gangahar, MBBS, MD is a member of the following medical societies: American College of Cardiology, American College of Chest Physicians, American College of Surgeons, American Medical Association, International Society for Heart and Lung Transplantation, International Society for Minimally Invasive Cardiothoracic Surgery, Nebraska Medical Association, and Society of Thoracic Surgeons

Disclosure: Nothing to disclose.

Shreekanth V Karwande, MBBS Chair, Professor, Department of Surgery, Division of Cardiothoracic Surgery, University of Utah School of Medicine and Medical Center

Shreekanth V Karwande, MBBS is a member of the following medical societies: American Association for Thoracic Surgery, American College of Chest Physicians, American College of Surgeons, American Heart Association, Society of Critical Care Medicine, Society of Thoracic Surgeons, and Western Thoracic Surgical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Richard Thurer, MD B and Donald Carlin Professor of Thoracic Surgical Oncology, University of Miami, Leonard M Miller School of Medicine

Richard Thurer, MD is a member of the following medical societies: American Association for Thoracic Surgery, American College of Chest Physicians, American College of Surgeons, American Medical Association, American Thoracic Society, Florida Medical Association, Society of Surgical Oncology, and Society of Thoracic Surgeons

Disclosure: Nothing to disclose.

References
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  28. Khan MS, Mery CM, Zafar F, Adachi I, Heinle JS, Cabrera AG, et al. Is mechanically bridging patients with a failing cardiac graft to retransplantation an effective therapy? Analysis of the United Network of Organ Sharing database. J Heart Lung Transplant. 2012 Aug 17. [Medline].

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  30. Tambur AR, Pamboukian SV, Costanzo MR, et al. The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome. Transplantation. 2005 Oct 27. 80(8):1019-25. [Medline].

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  33. Tremmel JA, Ng MK, Ikeno F, Hunt SA, Lee DP, Yeung AC, et al. Comparison of drug-eluting versus bare metal stents in cardiac allograft vasculopathy. Am J Cardiol. 2011 Sep 1. 108(5):665-8. [Medline].

  34. Ford MA, Almond CS, Gauvreau K, Piercey G, Blume ED, Smoot LB, et al. Association of graft ischemic time with survival after heart transplant among children in the United States. J Heart Lung Transplant. 2011 Nov. 30(11):1244-9. [Medline].

  35. Miller CA, Sarma J, Naish J, Yonan N, Williams SG, Shaw SM, et al. Multiparametric Cardiovascular Magnetic Resonance Assessment of Cardiac Allograft Vasculopathy. J Am Coll Cardiol. 2013 Dec 9. [Medline].

 
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View of the recipient's chest after the heart is removed, with the patient on cardiopulmonary bypass.
Suturing of the donor heart. Note that the left atrial anastomosis is performed first.
Completed operation. Note suture lines on now-implanted heart.
Heterotopic transplantation.
View after cardiectomy, showing cuffs for bicaval anastomosis.
Completed bicaval transplantation technique.
 
 
 
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