Heart Transplantation

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Chapter 14 Heart Transplantation

The first human heart transplant was performed in 1967 by Christian Barnard in South Africa. After this landmark operation there was a burst of activity, and 101 such operations were performed by 54 teams in 22 countries within a year. As a result of acute graft failure and rejection, however, outcomes were poor, and patients rarely survived longer than 1 year. Over the next decade very few heart transplant operations were performed. As with lung transplantation, it was not until the introduction of cyclosporine in the early 1980s that outcomes improved and heart transplantation became a viable treatment option for patients with end-stage heart failure.¹

Current survival rates after heart transplantation are 90% at 3 months, 87% at 1 year, 78% at 3 years, and 70% at 5 years.² These figures are substantially better than those observed after lung transplantation (see Chapter 13). It is important to note that quality of life is significantly improved by heart transplantation, with most patients being able to resume a relatively normal life, including return to work, leisure activities, and study.³

The number of patients on the waiting list for heart transplantation in the United States is slightly over 3000,⁴ with approximately 2000 undergoing the procedure in the United States each year (4000 worldwide).⁵ The waiting time for heart transplantation has risen considerably in the past few years. US Registry data has shown that in 2003, 49% of patients waited more than 2 years for a transplant, up from 23% in 1994.² In the year to July 2004, 494 patients died while awaiting heart transplantation,² about 16% of the patients on the waiting list.

These figures do not provide a fair assessment of the discrepancy between the number of donors and the number of patients with end-stage heart failure who may benefit from transplantation because not all suitable candidates are listed. A mere 10% of suitable candidates may actually undergo heart transplantation.

In this chapter, the preoperative evaluation and perioperative management of heart transplant recipients are described, with particular emphasis on early postoperative hemodynamic stabilization. Heterotopic heart transplantation, in which a donor heart is used as support for the native heart, is rarely performed now and is not discussed. Heart-lung transplantation is also infrequently performed; it is discussed briefly in Chapter 13.

SELECTION CRITERIA

Recipient Criteria and Preoperative Assessment

Patients undergoing heart transplantation must have end-stage cardiac disease with limited life expectancy. Management options other than transplantation should be fully explored. These include optimization of medical therapy; coronary artery bypass graft surgery for patients with suitable coronary anatomy and reversible ischemia on viability testing; mitral valve repair for patients with severe mitral regurgitation; insertion of an implantable defibrillator for those with recurrent arrhythmias; and biventricular pacing for patients with prolonged intraventricular conduction. In addition, because of the shortage of suitable donors, patients with end-stage heart failure may be offered a ventricular-assist device as “destination” therapy (see Chapter 22).

The two main pathologies that give rise to end-stage cardiac failure necessitating heart transplantation are ischemic cardiomyopathy and the nonischemic cardiomyopathies (dilated, hypertrophic, restrictive), which make up about 45% of cases each.⁵ The remaining cases include valvular heart disease, congenital heart disease, and primary heart transplant failure. Inclusion and exclusion criteria for recipients of heart transplantation are outlined in Table 14-1.⁶

Table 14-1 Recipient Selection Criteria for Heart Transplantation

Severe end-stage heart failure with NYHA functional class III-IV

VO_{2 max} <14 ml/kg/min^*

Age <65 years

Normal function or reversible renal/hepatic dysfunction

Absence of active infection

Compliance with medication

Psychological stability with social support

Absence of malignancy

Absence of significant coexisting systemic conditions

Abstinence from alcohol and recreational drug use

Cross-match compatibility

Absence of significant peripheral or cerebrovascular disease

Pulmonary vascular resistance <5 Wood units

Nonobese

* Mancini DM, Eisen H, Kussmaul W, et al: Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation 83:778-786, 1991. NYHA, New York Heart Association; VO₂ _max, maximal exercise.

(Modified from Costanzo MR, Augustine S, Bourge R, et al: Selection and treatment of candidates for heart transplantation: a statement for health professionals from the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association. Circulation 92:3539-3612, 1995.)

The assessment of a patient’s suitability for heart transplantation includes a right heart catheter study (see Chapter 5). This is a critical investigation because the presence of elevated pulmonary vascular resistance (>5 Wood units) contraindicates heart transplantation. A resistance level above 3 Wood units indicates an increased risk for postoperative right ventricular dysfunction.

A potential recipient is tested for ABO blood group and for the presence of antibodies to human leukocyte antigens (HLA). The latter is referred to as panelreactive antibodies and is expressed as the percentage of volunteer donor blood to which the patient’s serum reacts. A potential recipient with a high percentage of panel-reactive antibodies is less likely to have a negative (i.e., acceptable) cross-match with a potential organ donor and is therefore likely to have to wait longer for a suitable heart. Such a patient is also more likely to develop rejection following transplantation (see Hyperacute Rejection in the subsequent material).

Patients undergoing heart transplantation in the United States are typically extremely unwell: 70% are hospitalized; 25% require some form of mechanical cardiac support (ventricular-assist device or intraaortic balloon pump); and almost half are undergoing intravenous inotropic infusions.⁵ For patients with decompensated heart failure who are receiving inotropic drugs, the insertion of a ventricular-assist device prior to transplantation (i.e., as a bridge to transplantation rather than as destination therapy) may improve outcome after surgery.⁷

Evaluation of potential heart transplant recipients should be undertaken by a multidisciplinary team that is experienced in the management of severe heart failure and transplantation. This team includes cardiologists, cardiac surgeons, transplant coordinators, psychologists, social workers, dieticians, physiotherapists and, for critically ill patients, intensivists.

Donor Criteria and Management

As well as recipient criteria, donor criteria are vital in the decision to proceed with transplantation. An important criterion is the absence or low probability of coronary artery disease in the donor heart. For this reason, the upper donor age limit in most transplant units is 55 to 60 years.⁸ An echocardiogram is performed to assess valvular and ventricular function. The presence of segmental wall motion abnormalities is suggestive of myocardial ischemia or infarction and precludes the use of the organ. In some centers, coronary angiography is performed in potential donors who have risk factors for coronary artery disease.

The requirement for high-dose inotropic support in a donor is a relative contraindication to use of the heart for transplantation, particularly if it is associated with echocardiographic evidence of impaired ventricular function. The neuroendocrine failure that accompanies brain death is associated with marked vasodilation (see Chapter 38), and it usual for there to be some requirement for a vasopressor. The effects of neuroendocrine failure may be ameliorated by employing hormonal therapy (vasopressin, cortisol, triiodothyronine, insulin-glucose) in the donor. This regime may increase the number and quality of organs available for use in heart transplantation.

Ideally, the donor heart’s ischemic time should be less than 6 hours. In one study, an ischemic time greater than 4 hours was associated with increased rates of early mortality.⁹ In an attempt to extend the safe ischemic time, continuous perfusion systems (as opposed to standard cold storage) have been developed. These systems are complicated and have not been widely adopted.

Recipient-Donor Matching

The matching of recipients and donor organs within a particular country (or group of countries) is typically under the control of a single allocation agency; in the United States, it is the United Network of Organ Sharing (UNOS). Based on UNOS criteria, thoracic organs are offered on the basis of geography, donor-recipient compatibility, and medical urgency:

• Organs are offered first to all transplant centers within 500 miles of the donor hospital, then sequentially to more distant zones

• Compatibility testing is performed on the basis of donor-recipient ABO compatibility, cross-match testing, and size matching. ABO matching is usually typespecific, O to O, A to A, B to B, and AB to AB, although an O blood group heart can be offered to a critically ill non-O patient. Typically, there is a predominance of O blood group candidates waiting for transplantation. Cross-matching is essential for candidates who have a high percentage of panel-reactive antibodies (>10%) in order to minimize the risk for hyperacute (antibody-mediated) and acute (cell-mediated) rejection. Recipient and donor are also matched for body weight as an approximation of heart size; a desired donor weight falls within 20% of that of the recipient. In practice, however, a donor body weight similar to or heavier than that of the recipient is preferred, particularly if the recipient has increased pulmonary vascular resistance.

• Once this iterative matching process has occurred, the remaining potential candidates for the donor heart are prioritized on the basis of medical urgency. In the United States, thoracic organ recipients are prioritized according to the three-tiered UNOS criteria.¹⁰ Status 1A patients are those on mechanical circulatory support for fewer than 30 days; mechanical circulatory support for longer than 30 days and with device-related complications, mechanical ventilation, high-dose intravenous inotropic support, or with a life expectancy of fewer than 7 days. Status 1B patients are those on mechanical circulatory support for longer than 30 days and without device-related complications and those on low-dose inotropic support. Status 2 patients are all other patients on the active transplant waiting list.

INTRAOPERATIVE MANAGEMENT

Patient monitoring during heart transplantation includes an arterial line, central venous and pulmonary artery catheters, and transesophageal echocardiography (TEE). The right internal jugular vein is avoided as a location of line placement because it is the usual site of access for subsequent endomyocardial biopsies. Strict attention to aseptic technique is essential for all invasive procedures.

Surgical access is made by means of a standard midline sternotomy. Cardiopulmonary bypass (CPB) is established by employing bicaval cannulation (see Chapter 9). Myocardial protection of the native heart is not required, but perfusion of the donor coronary arteries with cardioplegia solution is commonly performed prior to implantation, particularly if the ischemic time is prolonged. The conventional heart transplant operation involves four suture lines: the aortic, pulmonary artery, and left and right atrial anastomoses. Recently, the single right atrial anastomosis has been modified to include separate anastomoses of the superior and inferior vena cavae. This modification reduces the incidence of atrial arrhythmias and, by minimizing distortion of the tricuspid valve, decreases the incidence of tricuspid regurgitation.¹¹ Separate pulmonary venous anastomoses are also performed in some centers in an attempt to reduce the incidence of left atrial thrombus formation. Together, these modifications to the atrial anastomoses are known as total heart transplant.

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