Evaluation Criteria for the Pretransplant Patient

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Heart Transplantation

Evaluation Criteria for the Pretransplant Patient Sandra A. Cupples, DNSc, RN, and Linden C. Spruill, MSW, ACSW, LICSW

O ver the course of the last 30 years, heart transplantation has progressed from a rare ,experimental procedure to a well-accepted treatment modality for end-stage heart failure (HF). 19. 46 The success of this procedure has resulted in an increased number of heart transplant centers and an expansion of the waiting list. 19• 30 There has been no corresponding increase, however, in the number of available donor hearts. In fact, the number of cardiac donors has remained relatively constant over the past 10 years. 19 As a result, each month transplant centers add approximately 200 more candidates to the waiting list than there are available donor hearts.36 This excess of demand over supply has resulted in the following sobering statistics: (1) the current average waiting time in the United States now exceeds 300 days 36 ; (2) the median heart transplant waiting time almost doubled between 1988 (11 7 days) and 1996 (224 days) 56 ; (3) the mortality rate for patients on the list is between 10% and 30%19· 36 ; and (4) the percentage of hospitalized candidates receiving transplants averages more than 60% but is as

From the Heart Transplant Program (SAC) and the Social Work Department (LCS), Washington Hospital Center, Washington , DC

high as 80% in certain regions. 36 Stevenson and colleagues 53 have argued that in the next century, only those hospitalized patients dependent on inotropic or circulatory support will actually undergo transplantation. Regarding these statistics, Miller36 noted that ". . . these data emphasize the need to establish uniform criteria to limit the number of waiting list patients to those who have refractory HF and have the greatest survival advantage. " Currently, there are no formally established and uniformly accepted listing criteria for patients referred for heart transplant evaluation39 ; however, given that the selection of appropriate heart transplant candidates is a serious ethical and societal issue ,24 virtually all transplant centers have physiologic and psychosocial guidelines that govern the evaluation process. These guidelines are used to identify those patients who have the greatest need for transplantation11 and who will derive the greatest benefit from transplantation with respect to survival and quality of life. 1• 22 • 43 The purpose of this article is to review these selection criteria in terms of the following: (1) indications for heart transplantation; (2) severity and prognosis of HF; (3) assessment of physiologic contraindications and comorb id conditions; (4) psychosocial criteria; and (5) care of the candidate on the waiting list.

CRITICAL CARE NURSING CLINICS OF NORTH AMERICA I Volume 12 I Number 1 I March 2000

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Indications for Heart Transplantation Diagnoses Most adult patients who are referred for heart transplant evaluation have either ischemic cardiomyopathy ( 44.8%) or nonischemic cardiomyopathy (46.2%) .23 Nonischemic cardiomyopathies are further classified according to their causes: peripartum, inflammatory, familial, toxic (e.g., induced by ethanol or chemotherapeutic agents), or idiopathic (cause is unknown). 22 The remaining patients are referred for congenital abnormalities, valvular disease, or refractory ventricular dysrhythmias.11· 22 Patients typically are considered for heart transplant evaluation if they have one or more of the following : (1) end-stage HF that is not amenable to any medical or surgical options 1· 3· 22 ; (2) New York Heart Association (NYHA) Class III or IV symptoms on optimal medical therapy 1· 3· 22; (3) prognosis for 1 year survival less than or equal to 50°!o3; (4) recurrent, symptomatic refractory ventricular dysrhythmias9· 38 • 51; or (5) refractory angina not amenable to medical or surgical therapy.38

Search for Possible Options Because transplantation is considered a treatment of last resort, the evaluation team must first determine if there are any medical or surgical options that will offer the patient better long-term survival. 1 This is particularly true for patients with ischemic cardiomyopathy.43 In summarizing the recommendations of a recent American Society of Transplant Physicians-National Institutes of Health conference, Miller36 states, "There was consensus that all patients with ischemic etiology should undergo evaluation for reversible ischemia and viable or hibernating myocardium that would be amenable to surgical or catheter interventional techniques as an alternative to transplantation. " Radionuclide studies such as planar rest and redistribution 201 thallium imaging, 99mtechnetium-labeled tetrofosmin, or 99 mtechnetium-labeled sestamibi imaging and positron emission tomography are useful in detecting myocardial viability. 4· 11 As Olivari43 notes , because of improvements in myocardial preservation, operative techniques, and pre- and postoperative medical and surgical management, certain patients with low ejec-

tion fractions but viable myocardium can achieve short- and long-term outcomes with bypass graft surgery that are similar to outcomes achieved with transplantation. Patients with nonischemic heart disease should be given a trial of optimal medical therapy before proceeding with transplant evaluation. This medical therapy may include vasodilators, angiotensin-converting enzyme inhibitors, diuretics, digoxin, and betablocking agents. 9· 13 It has been estimated that more than 60% of patients referred for heart transplant evaluation may be stabilized by hemodynamically guided and individually tailored therapy designed to reduce preload and afterload. 16 Valve replacement should be considered for critical aortic valve disease; valve replacement or repair should be considered for severe mitral regurgitation. 37

Transplant Evaluation Process After it is determined that a patient has no other medical or surgical options that offer better long-term survival than transplantation, the transplant team begins the evaluation process. This process is designed to answer two specific questions: (1) Will the patient be able to resume an active , functional, and relatively normal lifestyle following transplantation? and (2) Is the patient capable of complying with a strict medical regimen that involves daily medications (many w ith unpleasant side-effects) and frequent follow-up visits?1 The list that follows outlines the standard selection criteria for heart transplantation. Whereas certain of these criteria are objective (e.g., age and absence of end-organ disease), others are fairly subjective and more difficult to evaluate (e.g., adequacy of social support). For this reason, heart transplant evaluation is usually conducted by a multidisciplinary team consisting of a transplant cardiologist, surgeon, nurse coordinator, social worker, dietitian, psychologist, or psychiatrist. In addition, other consultants may be called in as necessary (e.g., an infectious disease specialist, gastroenterologist, neuropsychologist, and so forth) .19 • End-stage heart disease not amenable to medical or surgical therapy. • NYHA Class III-IV symptoms on optimal medical therapy with :5 50% 1-year survival.

EVALUATION CRITERIA FOR THE PRETRANSPLANT PATIENT

• Age generally :'.5 60 years. • Absence of irreversible end-organ damage or systemic illness that limits longterm survival. • Stable psychosocial status; motivation to resume active lifestyle. • Willingness to comply with medical advice. • Adequate family and social support.

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The first step in the evaluation process is to establish the severity of functional impairment and prognosis. This is performed by assessing the patient's NYHA classification, hemodynamic parameters, exercise tolerance, and neurohumoral factors.

25%. 19· 22 The prognostic value of LVEF, however, has been equivocal. In one study of patients with coronary artery disease, an LVEF of less than 22% was associated with a 3-year survival of less than 40%. 19 In patients with NYHA Class III and IV symptoms, however, LVEF does not differentiate between survivors and nonsurvivors , and further stratification tests are necessary.11· 1s Other hemodynamic measurements are obtained after optimal reductions in preload and afterload are achieved. In most studies of patients with HF, poor survival has been associated with elevated LV end-diastolic pressure, right atrial pressure, pulmonary artery wedge pressure and systemic vascular resistance, low cardiac output, and low stroke work index.11· 19, 22

NYHA Classification

Exercise Tolerance

The NYHA classification is widely used to estimate disability; however, its usefulness may be limited by its subjectivity. 19 Symptoms range from Class I (no limitations of physical activity and no undue symptoms) to Class IV (symptoms at rest or with minimal physical activity). Patients with Class IV symptoms are readily identified; however, it is oftentimes more difficult to discriminate between Class II and Class III symptoms. Furthermore, there is no direct correlation between severity of symptoms and left ventricular (LV) dysfunction. Thus, for example, some patients may be in Class I or II and may have severe LV dysfunction or life-threatening symptoms. 3 Generally, patients with Class IV symptoms have a worse prognosis than patients with Class I through III symptoms. 22 • 46

Metabolic exercise testing determines peak oxygen consumption-that is, oxygen uptake at the patient's anaerobic threshold.12• 44 Oxygen consumption equals the product of cardiac output and the arterial-venous oxygen (A-VOJ difference-that is, the difference of oxygen delivery minus oxygen extraction. Oxygen delivery is dependent on three factors: cardiac output, pulmonary function , and hemoglobin concentration. Oxygen extraction is dependent on vasodilatation and the oxidative capacity of muscle. 34 The measurement of oxygen consumption in HF patients was first described by Weber in 1982.58 Since that time, the metabolic exercise test has become the gold standard for stratifying patients referred for heart transplantation; it is the most accurate prognosticator of survival. The metabolic exercise test should be performed after the ambulatory patient has been stabilized on optimal medical therapy for at least 2 weeks. 19• 36 Exercise testing is contraindicated in patients with cardiogenic shock, inotropic or mechanical circulatory support, unstable angina, refractory ventricular dysrhythmias, or certain hypertrophic or restrictive cardiomyopathies. 36 During a metabolic exercise test, the patient exercises on a bicycle or treadmill and breathes through a low-resistance nonrebreathing valve or a disposable pneumotach cylinder. A closed-system metabolic cart analyzes exhaled breath. 34 Results are expressed

Severity and Prognosis of Disease

Hemodynamic Parameters

Hemodynamic parameters consist of LV ejection fraction (LVEF) , LV end-diastolic pressure, right atrial pressure, pulmonary capillary wedge pressure, cardiac output, and stroke work index. LVEF, a measure of global ventricular function, can be determined noninvasively by echocardiography, radionuclide ventriculography, or MR imaging, or invasively by cardiac catheterization. 11 Normal LVEF ranges between 40% and 65%. Patients typically referred for heart transplantation evaluation have LVEFs less than 20% to

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as milliliters of oxygen consumed per kilogram per minute. The Bethesda Conference Task Force on Recipient Guidelines for Cardiac Transplantation stipulated that a maximal oxygen consumption of less than 10 mL/kg/ min with the achievement of anaerobic metabolism is an accepted indication for transplantation. A maximal oxygen consumption of less than 14 mL/kg/min accompanied by major limitations in a patient's daily activities is a probable indication for transplantation. A maximal oxygen consumption of more than 15 mL/kg/min without other symptoms is an inadequate indication for transplantation.40 Given the dynamic nature of HF, patients with an oxygen consumption of more than 14 mL/ kg/min typically have repeat metabolic exercise testing every 6 months.;4 Neurohumoral Factors

In an attempt to maintain homeostasis, patients with HF develop several seemingly compensatory neurohumoral mechanisms. For example, activation of the renin-angiotensin system increases intravascular volume and improves renal perfusion. Similarly, increased production of norepinephrine increases cardiac contractility. 2;· 54 Over time, these mechanisms become counterproductive. Volume overload decreases serum sodium levels and persistent elevation of catecholamines contributes to peripheral vasoconstriction. 12· ;4 This neurohumoral activation is associated with the progression of LV dysfunction and poor prognosis.11 • 22 For example, Cohn and colleagues8 reported an 80% 2-year mortality rate among HF patients with norepinephrine levels of 1200 pg/mL, whereas patients who had norepinephrine levels of 200 pg/rnL had a 50% 2-year mortality rate.

Assessment of Contraindications and Comorbid Conditions After it is determined that the severity of disease and prognosis warrant transplantation, the next step in the evaluation process is to ascertain whether the patient has any contraindications to transplantation. Kao and colleagues2; define a contraindication as ". . . any condition that would place a recipient at excessive risk of morbidity due to transplantrelated interventions such as immunosup-

pression, or limit survival independent of the transplantation. " The following list provides the generally accepted contraindications to heart transplantation.1, 3, 6, 9, 11, 12, 22, 37, 4o, 43 • Advanced age (typically> 60- 65). • Pulmonary hypertension with irreversibly high pulmonary vascular resistance. • Coexistent systemic illness with poor prognosis. • Irreversible pulmonary disease. • Acute pulmonary embolism. • Pulmonary infarction. • Irreversible renal dysfunction (typically with serum creatinine 2 mg/dL or creatinine clearance < 50 mL/min.) • Irreversible hepatic dysfunction. • Acquired immunodeficiency disorder (AIDS). • Severe peripheral or cerebrovascular obstructive disease. • Insulin-dependent diabetes mellitus (IDDM) with end-organ damage. • Active infection. • Coexisting neoplasm. • Active peptic ulcer disease, diverticulosis, or diverticulitis. • Myocardial infiltrative and inflammatory disease (e.g., sarcoidosis, amyloidosis, and so forth) . • Severe obesity. • Cachexia. • Severe osteoporosis. • Psychosocial instability. • Current substance abuse (drugs, alcohol , tobacco) . • Behavior pattern or psychiatric illness likely to preclude compliance. The following list highlights commonly recommended evaluation tests and procedures. 22, 28, 4o • Comprehensive history and physical examination • Cardiovascular studies ECG Metabolic exercise test 24-hour Holter monitoring* Echocardiogram CM-mode and twodimensional; Doppler) Right heart catheterization Left heart catheterization* Radionuclide ventriculography* Multigated blood panel imaging scan* Endomyocardial biopsy* • Laboratory Studies Blood chemistries Renal and liver function panels Lipid profile

EVALUATION CRITERIA FOR THE PRETRANSPLANT PATIENT

Complete blood count with differential Prothrombin time, partial thromboplastin time, fibrinogen Glycosylated hemoglobin • Urinalysis • 24-hour urine collection for creatinine clearance and protein excretion • Serology HIV

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• • • • • • • • • • • • •

Cytomegalovirus IgG and IgM antibodies Rapid plasma reagin test Hepatitis B surface antibody and antigen; Hepatitis C antibody Epstein Barr IgG and IgM antibodies Herpes group virus Varicella-Zoster virus Toxoplasmosis Fungal antibody screen Lyme titres* Immunologic data Blood type and antibody screen Human leukocyte antigen typing Panel reactive antibody screen Abdominal ultrasonography Carotid and peripheral Doppler flow studies* Chest radiograph Pulmonary function tests Tuberculin purified protein derivative Skin test anergy battery Mammography Papanicolaou (PAP) smear Stool for occult blood* Digital rectal examination Sigmoidoscopy* Prostate specific antigen (PSA) Consultations Dental Social work Psychiatry* Neuropsychology* Nutrition Ophthalmology* Gynecology*

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heart transplantation in selected individuals older than age 55 who have no comorbidities. I, 5• I2, 48 For example, Coffman and colleagues7 compared two groups of heart transplant recipients, 71 patients younger than age 60 and 40 patients between ages 60 and 69. These investigators found no significant differences between the two groups with respect to 1-, 2-, 3-, or 4-year survival rates, incidence of treated rejection, incidence of infection, intensive care unit days or total hospital length-of-stay, number of rehospitalizations during the first postoperative year, or return to work rates. Moreover, patients in the older age group reported significantly greater improvement in posttransplant quality of life and had significantly fewer rejection episodes at 1 year. Currently, there is no universally agreed on upper age limit for heart transplantation.I, 9 Most heart transplant programs consider physiologic and chronologic age.I Even though septuagenarians have successfully undergone heart transplantation,9• I3 many centers do not consider patients who are older than 65 years.19• 43 As the potential for comorbid conditions increases with age, more stringent selection criteria are typically applied to older patients.38 The current critical shortage of donor organs also raises ethical issues regarding older heart transplant candidates. Expansion of the upper age limit increases the discrepancy between supply and demand for donor hearts. 11 Stevenson and colleagues53 recently estimated that imposing an age limit of 55 years would reduce the number of patients currently on the waiting list by 30%. In response to these ethical issues, a few transplant centers have established an alternate waiting list for older candidates. These candidates agree and are eligible to receive hearts from older donorsmarginal organs that would have otherwise been wasted. 22• 43 Several small studies have demonstrated excellent short-term results from this alternate donor program. 29, 32. so

• If indicated

Pulmonary Hypertension Advanced Age

Age is one of the most controversial aspects of candidate selection. 36- 38· 43• 5I In the past, age 55 was the upper age limit established for heart transplantation; however, a number of single center studies have reported successful

Patients who have had severe HF over a prolonged period are at risk for developing irreversible pulmonary hypertension (HTN). Pulmonary HTN results from several factors including increased LV end-diastolie- pressures (caused by LV systolic dysfunction), elevated circulating catecholamines (caused by

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neurohumoral activation), pulmonary vasoconstriction (caused by chronic hypoxia) , changes in the pulmonary vascular structure, and parenchymal factors associated with alveolar hypoventilation and interstitial edema.II , 54 · 59 At the time of transplantation, fixed pulmonary HTN can lead to acute right HF of the donor heart because the musculature of the unconditioned, thin-walled right ventricle cannot pump against the high pulmonary vascular resistance (PVR) 1· 11 • 37 , 40· 54 Indeed, pulmonary HTN is a leading cause of perioperative death following orthotopic heart transplantation.19· 30· 36· 43 Calculation of pulmonary pressures is an essential component of transplant evaluation. The transpulmonary gradient (TPG) is the difference between the mean pulmonary artery pressure and the pulmonary capillary wedge pressure. PVR expressed as Wood units is calculated by dividing the TPG by cardiac output. Pulmonary pressure criteria vary from center to center; however, patients with a TPG less than 12 to 15 or a PVR less than 5 to 8 Wood units are generally considered to have acceptable pulmonary pressures.1· 19· 40· 43 If a patient's initial pulmonary pressures are elevated, pharmacologic agents are administered to determine if these pressures are reversible or fixed. These pulmonary vasodilators may include nitroglycerine, nitroprusside, isoproterenol, prostaglandins, nitric oxide, or oxygen.19• 26· 36· 54 As the vasodilator dose is increased, inotropic agents such as dobutamine may be simultaneously administered to counteract systemic hypotension. If hemodynamic maneuvering fails to immediately decrease PVR, the patient may be admitted to the coronary care unit for administration of additional diuretics, inotropic agents, or vasodilators over a period of several days before pulmonary pressures are reassessed. 19 Patients who have a PVR greater than 5 Wood units or a TPG greater than 15 with a systolic pressure of more than 90 mm Hg after an aggressive pharmacologic challenge are typically considered to have irreversible pulmonary HTN and are excluded from orthotopic heart transplantation. 36 Renal Dysfunction

Renal dysfunction in patients with congestive HF may be caused by intrinsic kidney disease ,

low cardiac output, chronic hypertension, generalized atherosclerosis, or medications such as diuretics and angiotensin-converting enzyme inhibitors.25· 36· 43 Potential nephrotoxicity associated with posttransplant immunosuppressive agents makes it essential for the health care team to identify the cause and reversibility of any renal impairment. Diagnostic tests may include urinalysis , creatinine clearance, renal ultrasound, CT, and renal biopsy.25· 43 These tests are performed after the patient achieves maximal hemodynamic status.43 Small, shrunken kidneys typically are associated with end-organ disease.25 In normal sized kidneys, an improvement in function following the administration of inotropes usually indicates that renal dysfunction is a result of low cardiac output. 11 A creatinine clearance of less than 50 mL per minute is an exclusion criterion in many transplant centers. 40 Pulmonary Disease

Patients with severe end-stage HF often have coexistent pulmonary complications such as pulmonary embolism and infarction (attributed to low cardiac output and inactivity) 1· 11 and irreversible changes in the pulmonary vasculature (attributed to chronically elevated pulmonary pressures).25 Recent pulmonary embolism and infarction predispose patients to recurrent embolization and posttransplant abscess formation. Chronic bronchitis or obstructive pulmonary disease are associated with an increased risk of pulmonary infections and ventilator dependence. 11 • 25 Screening tests typically include a chest radiograph, tuberculin purified protein derivative, and pulmonary function tests (PFTs). Any radiographic abnormality must be fully investigated with follow-up procedures such as CT or biopsy. PFTs should be performed after the patient's HF has been treated with maximal medical therapy. Patients with a forced expiratory volume in 1 second (FEV1) of less than 50% of predicted norms or patients with a ratio of FEV1to forced vital capacity of less than 40% to 50% of predicted norms are at increased risk for posttransplant morbidity and mortality. 11 • 19· 25 The lungs are the most common site of opportunistic infections in heart transplant recipients, 19 making pul-

EVALUATION CRITERIA FOR THE PRETRANSPLANT PATIENT

monary screening an essential component of the evaluation process. Hepatobiliary Disease

Because HF itself may cause hepatic dysfunction, it is important to determine whether this dysfunction is caused by HF or primary liver disease. Screening tests typically include liver function tests; hepatobiliary ultrasonography; coagulation studies; serologies for hepatitis A, B, and C; and liver biopsy if cirrhotic liver disease is suspected. Because many posttransplant medications are hepatotoxic, irreversible hepatic disease is generally considered to be a contraindication to heart transplantation.11' 19 Cholelithiasis is common among HF patients. Pretransplant laparoscopic cholecystectomy may be performed to prevent potential life-threatening emergencies such as biliary tract obstruction and cholecystitis. 19 Gastrointestinal Disease

A number of gastrointestinal (GI) diseases require resolution during the transplant evaluation process. These diseases include gastritis, ulcerating or diffuse peptic disease, and diverticular disease. 3' 11 • 22, 25 Active peptic ulcer disease may precipitate GI hemorrhaging during cardiopulmonary bypass at the time of transplantation or in the postoperative period.11 Posttransplant corticosteroid therapy may exacerbate peptic disease. 25 Diverticular disease, particularly diverticulitis, places the immunocompromised recipient at great risk for posttransplant superinfections with enteric organisms. 3, 25 Pretransplant evaluation for patients with a history of GI disease may include endoscopy, upper and lower GI series, and abdominal ultrasonography. 1 Treatment with H2 inhibitors is often initiated, and pretransplant endoscopy is typically required to confirm the effectiveness of therapy for gastritis or peptic ulcer disease.11 Other Systemic Disease

The term other systemic disease includes any coexistent condition that could affect the transplant recipient with respect to morbidity, mortality, or quality of life. Diseases such as

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insulin-dependent diabetes mellitus (IDDM), peripheral and cerebrovascular atherosclerosis, amyloidosis, and sarcoidosis are typically included in this category. 1 IDDM was once considered to be an absolute contraindication to heart transplantation because of concerns about posttransplant steroid-induced exacerbation of this disease and increased risk of infection and vasculopathy.3·6· 22 Today, however, IDDM patients without end-organ damage are considered for transplantation3· 9· 11 · 22 • 40 and many have successfully undergone this procedure. Several studies have demonstrated similar survival and complication rates in diabetic and nondiabetic patients. 23, 41 · 48 The advent of steroidfree immunosuppression regimens has also made transplantation a more realistic option for selected patients with IDDM.1 Diabetic patients are carefully screened for end-organ damage such as retinopathy, nephropathy, peripheral neuropathy, and diffuse vascular disease. 43 Diagnostic tests may include fundoscopic examination, fluorescein angiography, electromyography, and peripheral vascular studies. Kidney biopsy may be required to determine whether nephropathy is caused by diabetes or HF. 25 Peripheral and cerebrovascular atherosclerosis is particularly common among older patients with ischemic cardiomyopathy and a history of cigarette smoking. 19 Patients with" this disease have an increased risk for perioperative thrombotic or embolic events. 11 After transplantation, corticosteroids can accelerate the progression of atherosclerotic vascular disease. Patients who present with a history of a cerebrovascular event must be evaluated in terms of their capacity to follow the posttransplant medical regimen and participate in rehabilitation. 11 Pretransplant revascularization procedures such as carotid endarterectomy or peripheral vascular bypass grafting may be performed in selected patients.11, 19 Other systemic diseases are potential contraindications to transplantation because they can recur in the transplanted heart, impose severe posttransplant limitations, or increase mortality independent of transplantation. 38 These diseases include but are not limited to the following: amyloidosis, l , 11 · 19· 38 sarcoidosis, 1· 11 · 19' 38 scleroderma,22• 38 Becker's or Duchenne's muscular dystrophy,38 lupus erythematosus,1· 22• 38 hemochromatosis, 19 multi-

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ple sclerosis,1 familial hyperlipidemia,22 and certain rheumatologic disorders.19 Because patients with these conditions will have increased posttransplant morbidity, they typically are considered for transplantation only if the progression of the disease has been halted. 19 However, Grady 22 notes that as the waiting list lengthens, patients with these types of comorbidities are increasingly excluded as candidates. Infectious Disease

Active infection is a contraindication to transplantation because of the deleterious effects of immunosuppression. Pretransplant screening for active infection includes a thorough history of previous infections, particularly recurrent pneumonia, bronchitis, sinusitis, or urinary tract infections. The patient's immunization record is carefully reviewed including travel history and previous exposure to endemic mycoses. Specific screening tests may include urine cultures; stool examination for enteric pathogens, ova, and parasites; and tuberculosis testing.19 Any active infection must be treated and completely resolved before transplantation. 6· 19 Pretransplant serologic testing is performed to identify latent infections and determine the patient's susceptibility to primary infections after transplantation. These tests include screening for the following: herpes simplex virus , Epstein-Barr virus, Varicella-Zoster virus, cytomegalovirus, Hepatitis B and C, HIV, toxoplasma gondii, and rapid plasma reagin. 19 Acquired immunodeficiency disorder is an absolute contraindication to transplantation.22 Malignancy

The issue of whether patients with a history of malignancy can be considered for transplantation is extremely controversial. 1·38 In the past, preexisting malignancy was considered to be an absolute contraindication to transplantation because of concerns that immunosu ppressive therapy would precipitate a recurrence.22 Today, some transplant centers are willing to consider patients who have a remote history of malignancy. 3 Indeed, a number of these patients have successfully undergone heart transplantation.17· 18· 21· 49 Armitage and colleagues2 reported on a series of 11

heart transplant recipients who had a remote history of lymphoma, sarcoma, or carcinoma. At a mean posttransplant follow-up time of 18 months (range 4 to 41 months) , all 11 patients were alive, active, and had no tumor recurrence. More recently, Koerner and coworkers27 reported survival data on 20 heart transplant recipients who had a history of malignant neoplasms. There were two early (less than 30 days posttransplant) and six late deaths. The remaining 12 recipients had a mean survival time of 35 months (range: 2 to 72 months). Miller36 recommends that patients with a history of noncutaneous malignancy obtain an oncology consult to document the grade of malignancy, duration of remission, and prognosis. Because posttransplant immunosuppressive therapy can increase the rate of progression of occult neoplasms and limit posttransplant survival,25· 36 the transplantation evaluation process includes screening for malignancy. This screening typically includes a carcinoembryonic antigen test, chest radiograph, stool for occult blood, and rectal and colon examinations. Gender-specific tests consist of mammograms, PAP smears, and pelvic examinations for women and prostatespecific antigen testing and prostate examinations for men. 11 • 19·36 Patients with active malignancy, with the exception of primary tumors of the heart or nonmelanoma cutaneous carcinoma, are typically excluded from transplantation.11 Other Conditions

Patients with morbid obesity are generally poor candidates for any type of surgery. 43 Morbid obesity is a comorbidity that can negatively impact posttransplant outcomes. This risk increases when the patient is more than 120% of ideal body weight. A body weight that is more than 140% of ideal is typically considered to be a serious contraindication to transplantation. 9· 36 Posttransplant consequences of obesity may include limited functional recovery,6 hypertension, 36· 43 wound infection,3 and allograft vasculopathy .19· 36 Moreover, obesity itself may be exacerbated by immunosuppressive medications. Pretransplant management of obesity provides an opportunity to monitor and evaluate the patient's compliance. Given the difficulty as-

EVALUATION CRITERIA FOR THE PRETRANSPLANT PATIENT

sociated with procuring a donor organ of the appropriate size, some transplant centers make placement on the waiting list contingent on weight loss. 19 Patients with cachexia are also poor surgical candidates. 43 Cachexia has been associated with impaired wound healing and increased risk of postoperative infection.6 Serial prealbumin levels may be obtained to monitor the patient's pretransplant nutritional status. Severe osteoporosis places patients at significantly increased risk for posttransplant morbidity because of corticosteroid therapy.11·19·36 Some transplant centers obtain pretransplant bone density scans on all patients, whereas others screen selected patients such as those older than 60 years, those already diagnosed with osteoporosis, and immobile or obese patients at high risk for osteoporosis. Patients with a bone density more than two standard deviations below normal have a significantly increased risk of bone fracture. 36 Pretransplant strategies to increase bone mass include calcium supplementation, hormonal replacement, alendronate (Fosamax) therapy, and regular exercise. 19 Severe osteoporosis, however, cannot be ameliorated. 13 Panel Reactive Antibodies

Patients who meet all selection criteria undergo screening for preformed human leukocyte antigen antibodies. The purpose of this test is to detect the candidate's preexisting sensitization to potential donor antigens. The candidate's serum is tested against a panel of sera from random individuals. Those candidates who are highly sensitized have a greater risk of posttransplant rejection, morbidity, and mortality. Multiparous women and individuals who have previously received blood transfusions may be highly sensitized to potential donor antigens. A prospective crossmatch with potential donors may be required for highly sensitized candidates. This requirement can extend the wait for an organ from a crossmatch-negative donor. 3· 19

Psychosocial Criteria

A psychosocial assessment is an important component of the evaluation process, 31 and most transplant programs consider psychosocial criteria when selecting potential candi-

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dates. 20·33 The scarcity of donor organs and the significant stress of the transplant experience mandate that recipients be able to cope with the lifestyle changes that transplant imposes. Patients are typically screened with respect to their support systems, emotional stability, substance abuse history, compliance history, and commitment to the transplantation process. The importance of this evaluation is evidenced by the findings of a recent study by Paris and colleagues47 who noted that "most patients who have any history of psychosocial factors before heart transplantation will continue to have them after heart transplantation, although sometimes they may exhibit in a different form. " The pretransplant evaluation serves as a baseline for comparison purposes if psychosocial problems arise after transplantation.57 At many transplant centers, potential candidates are assessed by a clinical social worker. The major focus of the psychosocial evaluation is a systems-oriented analysis of factors that would influence the patient's emotional and psychologic adjustments and the family's ability to participate in the transplantation process and support the patient. Individuals who have emotional and physical support from family or friends are generally better able to cope with the stressors associated with transplantation and are more likely to be compliant.10 These supports enable recipients to face the surgery and aftercare with increased self-esteem and increased likelihood of reliability in self-care. 35 Tangible support is also required for transportation to and from the transplant center for follow-up visits and for assistance with the day-to-day care of the patient in the first several weeks after transplantation. The transplant evaluation process is inherently stressful. Individuals who use drugs or alcohol as coping mechanisms strain the resources of the health care system. Substance abuse may obfuscate symptoms, decrease compliance, and interfere with the postoperative treatment of infection and rejection.35 Potential candidates are also assessed for their commitment to the transplantation process and to basic health and well-being. Behaviors such as smoking are not consistent with this commitment. Patients are typically required to demonstrate a given period of substancefree living through random drug and nicotine

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screening. Transplant teams often recommend that patients enroll in formal drug and tobacco cessation programs. Unmanaged mental illness is a contraindication to transplantation. Patients with mental illness are typically required to be under treatment and be cleared by a psychiatrist before placement on the waiting list. A recent worldwide survey of 204 heart transplant centers indicated that major psychopathology such as active schizophrenia, dementia, severe mental retardation, current suicidal ideation or history of multiple suicide attempts, and severe alcohol abuse and drug addiction were considered to be contraindications to transplantation. 42 The long-term success of transplantation depends on the cooperation and compliance of the recipient. Although it may be difficult to predict which patients may be noncompliant after surgery, those patients who have a pretransplant history of noncompliance would seem to have an increased likelihood of posttransplant noncompliance. 35 The patient's ability to comply with medical regimens in the past (e.g., taking medications, keeping appointments, following a diet, maintaining ideal body weight) is a useful benchmark. Some transplant centers enroll patients with marginal compliance history in end-stage heart disease research protocols. This strategy affords the transplant team the opportunity to assess the patient's motivation and compliance over time. 3 Many transplant centers offer monthly support group programs designed to increase transplant candidates' and families ' level of knowledge about transplantation and provide an opportunity for them to meet other candidates and recipients. Attendance at these meetings also serves as an indication of the patient's level of commitment to the transplantation process. Some heart transplant programs have added a neuropsychologic assessment to the evaluation process. A comprehensive neuropsychologic evaluation can document the patient's intellectual functioning and cognitive strengths and weaknesses. Specific domains that can be assessed include intelligence, academic skills, reading comprehension, attention, concentration, learning, memory, language ability, and motor functioning. In addition, a neuropsychologist can provide patient-specific suggestions for tailoring edu-

cational material so that it is congruent with the patient's cognitive functioning, thereby potentially increasing understanding and compliance.14 Heart transplantation is an expensive procedure. Costs include those related to evaluation testing, possible pretransplant hospitalization, surgery, follow-up care, and medications. The first-year costs for transplantation have been estimated at $253,200. 55 Medications alone can exceed $10,000 per year. Lack of medical insurance or limited insurance is rarely considered to be a contraindication to transplantation.37 An additional aspect of the social worker's role, however, is to advise patients of these costs, explain insurance benefits, obtain insurance (e.g., Medical Assistance) for those individuals who are uninsured, and develop a realistic plan for bridging gaps in insurance coverage.

Care of the Transplant Candidate Patients who meet all selection criteria are placed on the waiting list; however, because HF is a dynamic disease process,54 transplant candidates require periodic reassessment while they are on the transplant list. This reassessment may include examination by the transplant team physicians, metabolic exercise testing, reevaluation of LVEF by echocardiography or nuclear scans, and serial hemodynamic measurements by way of right heart catheterizations to determine current PVR and refine medical therapy.11· 19• 36· 37 Periodic reassessment also provides an opportunity for the transplant team to determine the patient's current level of compliance and psychosocial status. 19 Because candidates may spend months to years on the waiting list, certain tests should be repeated at regular intervals. These include panel reactive antibody testing and routine cancer screening. Candidates should be questioned about any interim blood transfusions, infections, travel, allergic reactions, and weight changes.19 Outpatient transplant candidates are frequently encouraged to enroll in formal cardiac rehabilitation programs to maximize their physical functioning. The exercise prescription is based on the candidate's oxygen con-

EVALUATION CRITERIA FOR THE PRETRANSPLANT PATIENT

sumption test and recommendations of the heart failure specialist.36 A significant subset of candidates will improve while on the waiting list. 19 Stevenson and colleagues52 recently reported on the reassessment of 68 transplant candidates who were placed on the waiting list with a peak oxygen consumption of less than 14 ml/ kg/ min. Thirty-one of these clinically stable patients were subsequently removed from the

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waiting list because their repeat MV02 tests indicated a 2 ml/ kg/min or greater improvement in oxygen consumption. Over the next 2 years, there were no deaths in this group of patients; two patients were relisted and subsequently underwent transplantation. Studies such as this clearly demonstrate the efficacy of periodic reassessment to detect substantial clinical improvement that may obviate the need for transplantation.

SUMMARY

As Achuff1 notes, transplant evaluation can be a lengthy and difficult process for patients and transplant personnel; however, the scarcity of donor organs mandates that heart transplant teams carefully evaluate all relevant physiologic and psychosocial data. By doing so, transplant professionals enhance their ability to select patients who are most likely to benefit from transplantation in terms of survival and quality of life, thereby making prudent use of a limited societal resource.

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