Introduction
Cardiac transplantation is a widely accepted therapy for the treatment of end-stage congestive heart failure. Most candidates for cardiac transplantation have not been helped by conventional medical therapy and are excluded from other surgical options because of the poor condition of the heart. About 45% of the candidates have ischemic cardiomyopathy; however, this percentage is rising because of the increase in coronary artery disease in younger age groups. Of the candidates, 54% have some form of dilated cardiomyopathy, which often has an unclear origin. The remaining 1% of candidates fall into the category of other diseases, including congenital heart disease, that are not amenable to surgical correction.
Candidacy determination and evaluation are key components of the process, as is 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.
History of the Procedure
Christian Barnard performed the first successful heart transplant in a human in 1967 in South Africa. The origins of the procedure date to 1905, when Alexis Carrel transplanted a puppy's heart into the neck of a dog. Because of the lack of immunosuppression, the experiment was unsuccessful; however, the work spurred numerous investigations that culminated in the success the procedure has today. Early investigators included Frank C. Mann of the Mayo Clinic, V.P. Demikov of the Soviet Union, and Marcus Wong. These early efforts in transplantation were thwarted by the infancy of cardiopulmonary bypass and a lack of understanding of the immune system. As knowledge in these areas advanced, so did the field of cardiac transplantation.
The clinical use of cyclosporine as an immunosuppressant revolutionized the field of cardiac transplantation in 1983. Recipient survival rates improved, thus producing an explosive increase in the number of transplant centers offering cardiac transplantation. The remaining limiting factor was the number of available organ donors.1
Problem
Cardiac transplantation is the procedure by which the failing heart is replaced with another heart from a suitable donor. The procedure is generally reserved for patients with end-stage congestive heart failure with a prognosis of less than a year to live without the transplant and who are not candidates for conventional medical therapy or have not been helped by conventional medical therapy.
As of April 24, 2009, 2,787 individuals are waiting for hearts. In 2008, about 1,800 heart transplants were performed nationwide. The improved medical management of congestive heart failure has decreased the candidate population; however, organ availability remains an issue.2,3 For more information on organ availability and waiting lists, visit the United Network for Organ Sharing.
Frequency
The annual frequency of the procedure is about 1% of the general population with heart failure, both candidates and noncandidates.
Etiology
The disease processes that require cardiac transplantation can be divided into the following categories:
- Idiopathic cardiomyopathy - 54%
- Ischemic cardiomyopathy - 45%
- Congenital heart disease and other diseases - 1%
Pathophysiology
The pathophysiology of cardiomyopathy that may require cardiac replacement is dependent upon 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 procedures; however, the small-vessel disease is progressive in nature, resulting in 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 the dilated cardiomyopathy is still unclear. Mechanical dilatation and disruption of energy stores appear to play a role.
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-sided function is directly dependent upon the ischemic time incurred prior to 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 is primarily of 2 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. Humoral rejection 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 because endomyocardial biopsy is of little value.
Coronary artery disease is a late pathologic process common to all cardiac allografts. The pathology is characterized by myointimal hyperplasia of the small- and medium-sized vessels. The lesions are diffuse in nature. The lesions may appear any time from 3 months to several years after implantation. The inciting causes are still unclear, though cytomegalovirus (CMV) infection and chronic rejection have been implicated. The mechanism of the process is thought to be dependent upon growth-factor production in the allograft initiated by circulating lymphocytes. Currently, the process has no treatment other than retransplantation.
Presentation
Candidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III (moderate) symptoms or class IV (severe) symptoms.4 Evaluation demonstrates ejection fractions of less than 25%. Attempts are made to stabilize the cardiac condition while the evaluation process is undertaken. The interim therapy can include oral agents as well as inotropic support. Mechanical support with the intra-aortic balloon pump or implantable assist devices may be appropriate in some patients as a bridge to transplantation.5,6
Indications
The general indications for cardiac transplantation include deteriorating cardiac function and having a prognosis of less than 1 year to live.
Specific indications
- Dilated cardiomyopathy
- Ischemic cardiomyopathy
- Congenital heart disease for which no conventional therapy exists or that 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
Relevant Anatomy
During the cardiac transplantation procedure, the ventricles are excised, leaving the great vessels, right atrium, and left atrium of the recipient.
View of the recipient's chest after the heart is removed, with the patient on cardiopulmonary bypass.
The donor heart is then sewn to these areas.
Suturing of the donor heart. Note that the left atrial anastomosis is performed first.
The completed operation. Note the suture lines on the now-implanted heart.
A recent trend has been to revert to bicaval anastomoses rather than right atrial anastomoses in an attempt to decrease the incidence of postoperative tricuspid insufficiency.
In the transplantation process, the sinoatrial nodes of the donor and recipient remain intact, and both are present within the recipient. For approximately 3 weeks after surgery, the electrocardiogram demonstrates 2 P waves; however, the heart rate and electrical activity of the new heart are purely dependent on the intrinsic electrical system of the heart and not on the neurological input from the recipient.
Contraindications
- Age (>65 y): This is a relative issue; 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 upon the tumor type and the evaluating program.
- An ongoing history of substance abuse (eg, alcohol, drugs, tobacco)
- Psychosocial instability
- Inability to comply with medical follow-up care7
More on Heart Transplantation |
 Overview: Heart Transplantation |
| Workup: Heart Transplantation |
| Treatment: Heart Transplantation |
| Follow-up: Heart Transplantation |
| Multimedia: Heart Transplantation |
| References |
| Next Page » |
References
Griepp RB, Ergin MA. The history of experimental heart transplantation. J Heart Transplant. 1984;3:145.
Kramer BL, Massie BM, Topic N. Controlled trial of captopril in chronic heart failure: a rest and exercise hemodynamic study. Circulation. Apr 1983;67(4):807-16. [Medline].
Overcast TD, Evans RW, Bowen LE, et al. Problems in the identification of potential organ donors. Misconceptions and fallacies associated with donor cards. JAMA. Mar 23-30 1984;251(12):1559-62. [Medline].
Heart Failure Society of America. The Stages of Heart Failure – New York Heart Association (NYHA) Classification. Heart Failure Society of America Web site. Available at http://www.abouthf.org/questions_stages.htm. Accessed May 1, 2009.
Hill JD. Bridging to cardiac transplantation. Ann Thorac Surg. Jan 1989;47(1):167-71. [Medline].
Portner PM, Oyer PE, Pennington DG, et al. Implantable electrical left ventricular assist system: bridge to transplantation and the future. Ann Thorac Surg. Jan 1989;47(1):142-50. [Medline].
Copeland JG, Emery RW, Levinson MM, et al. Selection of patients for cardiac transplantation. Circulation. Jan 1987;75(1):2-9. [Medline].
Chan MC, Giannetti N, Kato T, et al. Severe tricuspid regurgitation after heart transplantation. J Heart Lung Transplant. Jul 2001;20(7):709-17. [Medline].
McGee E, McCarthy PM, Hoercher KJ, et al. Donor Tricuspid Annuloplasty Reduces Post-Transplant Tricuspid Regurgitation (Abstract 22). The Kaufman Center for Heart Failure, The Cleveland Clinic. International Society for Heart and Lung Transplantation Meeting, San Francisco,. April 21-24, 2004.
Caves PK, Stinson EB, Billingham M, Shumway NE. Percutaneous transvenous endomyocardial biopsy in human heart recipients. Experience with a new technique. Ann Thorac Surg. Oct 1973;16(4):325-36. [Medline].
Hunt J, Lerman M, Magee MJ, et al. Improvement of renal dysfunction by conversion from calcineurin inhibitors to sirolimus after heart transplantation. J Heart Lung Transplant. Nov 2005;24(11):1863-7. [Medline].
Kaczmarek I, Sadoni S, Schmoeckel M, et al. The need for a tailored immunosuppression in older heart transplant recipients. J Heart Lung Transplant. Nov 2005;24(11):1965-8. [Medline].
Hofflin JM, Potasman I, Baldwin JC, et al. Infectious complications in heart transplant recipients receiving cyclosporine and corticosteroids. Ann Intern Med. Feb 1987;106(2):209-16. [Medline].
Penn I. Cancers following cyclosporine therapy. Transplantation. Jan 1987;43(1):32-5. [Medline].
Tambur AR, Pamboukian SV, Costanzo MR, et al. The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome. Transplantation. Oct 27 2005;80(8):1019-25. [Medline].
Ramakrishna H, Jaroszewski DE, Arabia FA. Adult cardiac transplantation: A review of perioperative management Part - I. Ann Card Anaesth. Jan-Jun 2009;12(1):71-8. [Medline].
Holman WL, Kormos RL, Naftel DC, Miller MA, Pagani FD, Blume E, et al. Predictors of death and transplant in patients with a mechanical circulatory support device: a multi-institutional study. J Heart Lung Transplant. Jan 2009;28(1):44-50. [Medline].
Sauer H. Recent advances using stem cell-derived cardiac and vascular cells for cardiomyoplasty. Xenotransplantation. Sep 2008;15(5):306. [Medline].
Reichart B, Brandl U. 40 years of heart transplantation and the DFG-Transregio Research Group Xenotransplantation. Xenotransplantation. Sep 2008;15(5):293-294. [Medline].
Griffith BP, Hardesty RL, Deeb GM, et al. Cardiac transplantation with cyclosporin A and prednisone. Ann Surg. Sep 1982;196(3):324-9. [Medline].
Kfoury AG, Renlund DG, Snow GL, Stehlik J, Folsom JW, Fisher PW, et al. A clinical correlation study of severity of antibody-mediated rejection and cardiovascular mortality in heart transplantation. J Heart Lung Transplant. Jan 2009;28(1):51-7. [Medline].
Pedotti P, Mattucci DA, Gabbrielli F, Venettoni S, Costa AN, Taioli E. Analysis of the complex effect of donor's age on survival of subjects who underwent heart transplantation. Transplantation. Oct 27 2005;80(8):1026-32. [Medline].
Schuh A, Liehn EA, Sasse A, Schneider R, Neuss S, Weber C, et al. Improved left ventricular function after transplantation of microspheres and fibroblasts in a rat model of myocardial infarction. Basic Res Cardiol. Jan 12 2009;[Medline].
Sweeney MS, Macris MP, Frazier OH, et al. The treatment of advanced cardiac allograft rejection. Ann Thorac Surg. Oct 1988;46(4):378-81. [Medline].
Ye F, Ying-Bin X, Yu-Guo W, Hetzer R. Tacrolimus versus cyclosporine microemulsion for heart transplant recipients: a meta-analysis. J Heart Lung Transplant. Jan 2009;28(1):58-66. [Medline].
Further Reading
Keywords
cardiac replacement, cardiac transplantation, cardiac allograft, cardiopulmonary bypass, cyclosporine, intra-aortic balloon pump, implantable assist devices, coronary artery angioplasty, coronary artery bypass surgery, CABG, valve repair, allografts, xenografts, end-stage congestive heart failure, CHF, ischemic cardiomyopathy, angina, pulmonary disease, malignant cardiac arrhythmias, coronary artery disease, CAD, congenital heart disease, CHD, cytomegalovirus, CMV, rejection, organ donors, organ donation
