Progress in Cardiovascular Diseases Volume 53, Issue 6, May-June 2011, Pages 429-436 Exercise and Cardiovascular Diseases doi:10.1016/j.pcad.2011.03.

010 | How to Cite or Link Using DOI Permissions & Reprints Exercise Therapy for Cardiac Transplant Recipients Ray W. Squires
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Cardiovascular Health and Rehabilitation, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN 55905 Available online 3 May 2011.

Abstract
Heart transplantation (HT) is an attractive treatment for patients with terminal heart failure from a variety of causes. Survival at 1- and 5 years after HT averages 90% and 70%, respectively. The physiologic response to exercise is abnormal after HT presumably because the transplanted heart is surgically denervated, although a minority of patients demonstrate signs of partial cardiac reinnervation several months after surgery. The heart rate response to exercise is typically blunted, and exercise capacity is below average for most HT recipients. Multiple studies have demonstrated the benefits of exercise training (ET) after HT. Peak exercise oxygen uptake improves by an average of 24% after 2 to 3 months of ET. Resistance training results in increased skeletal muscle mass and strength. Early mobilization and low-level ET may begin in the hospital after extubation. Outpatient ET, ideally in a supervised environment for at least several weeks, should begin immediately after hospital dismissal. Exercise prescription for HT patients is similar to that for other patients who have undergone cardiothoracic surgery, with the exception of a target heart rate. Ratings of perceived exertion are useful for prescribing exercise intensity. Exercise training does not affect the frequency or severity of episodes of acute rejection. There are no data regarding the effect of ET on survival after HT.

Abbreviations and Acronyms: HT, heart transplantation; ET, exercise training; HF, heart failure Keywords: Heart transplantation; Exercise therapy; Cardiac transplant recipients

Article Outline
Background information Responses to exercise Heart rate and exercise Blood, intracardiac, and vascular pressures Left ventricular function Exercise cardiac output Skeletal muscle structure and biochemistry Pulmonary function and arterial oxygenation

 Oxygen extraction by exercising skeletal muscle Oxygen uptake kinetics, peak exercise VO2 Partial cardiac reinnervation Graded exercise testing Responses to ET Aerobic ET Resistance exercise Effect of ET on immune function and longevity Exercise programming suggestions Pretransplant graded exercise testing and training Early mobilization and inpatient ET Outpatient ET Statement of Conflict of Interest References

Background information
The first successful human heart transplantation (HT) was performed by Barnard1 in Cape Town, South Africa, in 1967. Although the patient lived only 18 days, the resulting publicity and enthusiasm spurred a number of surgical centers to perform the operation. Long-term survival was poor, and the procedure did not enjoy widespread application during the 1960s and 1970s. Developments at Stanford University, including improved techniques for preservation of the donor organ, the transvenous right ventricular endomyocardial biopsy technique for early detection of acute rejection, and the introduction of the powerful immunosuppressant cyclosporine in the 1980s resulted in marked improvement in survival.2 These important advances and eventual insurance funding of the operation and aftercare in the United States made the procedure an attractive treatment for patients with terminal heart failure (HF). The 2010 report of the Registry of the International Society for Heart and Lung Transplantation listed 225 transplant centers worldwide, with the majority located in North America.3 Approximately 3000 heart and heart/lung transplants per year are reported to the registry with estimates of 5000 total transplants performed worldwide each year. The most common reasons for HT include nonischemic cardiomyopathy, ischemic cardiomyopathy, retransplantation, adult congenital heart disease, and valvular heart disease.3 Most recipients are men, approximately 10% of all recipients are 65 years or older, and 20% of patients are treated with a ventricular assist device before HT. Immunosuppression is achieved with a variety of drugs, including combinations of tacrolimus, sirolimus, mycophenolate mofetil, mycophenolic acid, and prednisone. [3] and [4] The goal of immunosuppression is to prevent acute rejection while minimizing the risks of infection and malignancy. Common comorbidities associated with immunosuppressant use include hypertension, diabetes mellitus, and hyperlipidemia.3 Median survival is approximately 10 years after HT.3 Survival at 1 and 5 years averages 90% and 70%, respectively.5 The highest mortality occurs in the first 6 months after surgery, with a fairly constant annual mortality rate of 3% to 4% after the first year.3 The most common causes of death include graft failure (antibody-mediated rejection, allograft vasculopathy), malignancy (aggressive skin cancers, lymphoproliferative cancers), and infection. In general, most patients report a favorable quality of life after HT.3 Many patients return to work, school, and their usual avocational activities, although exercise capacity remains below normal for most individuals.6

Responses to exercise
The responses of HT recipients to acute exercise is unique and related, in part, to the following factors [7] , [8] and [9] : 1 The transplanted heart is surgically denervated and receives no direct efferent input from the . autonomic nervous system and provides no direct afferent signals to the central nervous system. Months after HT, some patients demonstrate signs of partial cardiac reinnervation. This will be discussed later. 2. During organ harvesting and with transplantation, the donor heart has experienced ischemic time and reperfusion. 3. There is no intact pericardium. 4.Diastolic dysfunction (elevated filling pressures at rest and with exercise) is common. Reasons for this include hypertension, acute rejection episodes resulting in myocardial scarring and fibrosis, and allograft vasculopathy. 5. Abnormal skeletal muscle histology and energy metabolism, developed during the course of chronic HF, may continue after HT. 6. Peripheral and coronary vasodilatory capacity may be impaired, in part, due to endothelial dysfunction. Heart rate and exercise As a result of the loss of parasympathetic innervation of the donor heart, heart rate at rest is elevated to approximately 95 to 115 beats/min and represents the inherent rate of depolarization of the sinoatrial node.10 With graded exercise, the heart rate typically does not increase during the first several minutes (delayed increase), followed by a gradual rise with peak heart rates slightly lower than normal (approximately 150 beats/min) due to sympathetic nervous system denervation. Many patients achieve their highest exercise heart rate during the first few minutes of recovery from exercise, rather that at the point of maximal exercise intensity. Heart rate may remain near peak values for several minutes during recovery before gradually returning to resting levels (delayed decrease). The chronotropic reserve (the difference between the maximal and resting heart rates) is less than normal. Regulation of heart rate during exercise is dependent on circulating catecholamines. Fig 1 shows the heart rate response to graded exercise of the same patient 1 year before and 3 months after orthotopic HT.

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High-quality image (95K) Fig 1. Heart rates measured during graded exercise in the same patient 1 year before and 3 months after orthotopic cardiac transplantation. Note the elevated resting heart rate and the delayed increase in heart rate during exercise after transplantation consistent with complete denervation. Reprinted with permission from Squires.7

Blood, intracardiac, and vascular pressures Blood pressure at rest is often mildly elevated, even though most patients receive antihypertensive medications. During exercise, blood pressure generally increases appropriately, although peak exercise blood pressure is slightly lower than expected for normal persons.11 Vascular resistance and intracardiac and pulmonary vascular pressures (particularly right-sided pressures) are elevated.12 Left ventricular function For most HT patients, left ventricular ejection fraction is normal at rest and during exercise.12 However, as mentioned previously, left ventricular diastolic function is often impaired, as evidenced by an elevated filling pressure for a given end-diastolic volume. This impairment results in a belownormal increase in stroke volume during exercise. The impaired rise in stroke volume, coupled with the below-normal heart rate reserve, results in an impaired exercise cardiac output. Exercise cardiac output With the onset of exercise, cardiac output in HT recipients with complete cardiac denervation increases because of the augmentation of stroke volume via the Frank-Starling mechanism. Later in exercise, increased heart rate also contributes to augmentation of cardiac output.13Fig 2 demonstrates the greater increase, relative to controls, in left ventricular end-diastolic volume index during exercise in HT patients that results in an enhanced Frank-Starling effect. However, at rest and during exercise, the cardiac index is lower for HT recipients than for normal persons (Fig 3).

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High-quality image (90K) Fig 2. The change in left ventricular end-diastolic volume index (LVEDVI) during graded, supine exercise in cardiac transplant recipients compared with healthy persons. Reprinted with permission from Pflugfelder PW, Purves PD, McKenzie FN, et al: Cardiac dynamics during supine exercise in cyclosporine-treated orthotopic heart transplant recipients: assessment by radionuclide angiography. J Am Coll Cardiol 1987;10:336-341. 1987 American College of Cardiology Foundation.

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High-quality image (91K) Fig 3. The change in cardiac index (CI) during graded, supine exercise in cardiac transplant recipients compared with healthy persons. Reprinted with permission from Pflugfelder PW, Purves PD,

McKenzie FN, et al: Cardiac dynamics during supine exercise in cyclosporine-treated orthotopic heart transplant recipients: assessment by radionuclide angiography. J Am Coll Cardiol 1987;10:336-341. 1987 American College of Cardiology Foundation. Skeletal muscle structure and biochemistry During the clinical course of chronic HF, several skeletal muscle structural and biochemical abnormalities develop and include reduced aerobic metabolic enzyme activity, lower capillary density, endothelial dysfunction with impaired vasodilation during exercise, and conversion of some slowtwitch motor units to fast twitch motor units with greater reliance on anaerobic than aerobic energy production. These abnormalities generally persist after HT, with partial improvement after several months for some patients. [14] , [15] and [16] Pulmonary function and arterial oxygenation The efficiency of pulmonary ventilation during exercise may be below normal during the first several months after HT, illustrated by an elevation in the ratio of minute ventilation to carbon dioxide production (the ventilatory equivalent for CO2, VE/VCO2).7 This excess ventilation results in a heightened sense of shortness of breath during exercise. The normal increase in tidal volume during exercise is blunted, probably as a result of respiratory muscle weakness, deconditioning, and the effects of corticosteroid medications.17 Alveolar gas diffusion impairment is present in approximately 40% of patients. However, arterial oxygen saturation at rest and during exercise is normal for most patients.18 A minority of patients with pre-HT diffusion abnormalities experience mild arterial desaturation (to approximately 90%) with exercise.19 Oxygen extraction by exercising skeletal muscle Extraction of oxygen from the arterial blood by metabolically active body tissues, as indicated by the arterial-mixed venous oxygen difference, is normal at rest after HT. However, during exercise, the arterial-mixed venous oxygen difference does not increase in a normal manner and reflects abnormalities with both the delivery of capillary blood to the exercising skeletal muscle and impairment of the oxidative capacity of the muscle.12 Oxygen uptake kinetics, peak exercise VO2 With the onset of exercise, the rate of increase in VO2 (oxygen uptake kinetics) is slower than normal as a result of both an impaired rise in cardiac output and a diminished oxidative capacity of the skeletal muscle (reduced arterial-mixed venous oxygen difference).20Fig 4 shows oxygen uptake vs cycle ergometer power output during graded exercise for the same patient measured 1 year before and 3 months after HT. Although peak VO2 was 18% higher after transplantation, for any given submaximal power output, oxygen uptake was consistently lower than before HT, consistent with slower VO2 kinetics.

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High-quality image (112K) Fig 4. Oxygen uptake vs cycle ergometer power output for the same patient measured 1 year before and 3 months after orthotopic cardiac transplantation. Reprinted with permission from Squires.7 Because of the dual abnormalities of an impaired exercise cardiac output and a reduced arterial-mixed venous oxygen difference described above, peak exercise oxygen uptake (peak VO2) is usually below normal for HT patients. In a series of 95 patients with a mean age of 49 years who performed a cardiopulmonary exercise test approximately 1 year after HT, the mean peak VO2 was 20 mL kg1 min1 (62% of age- and sex-predicted).21 Marked variability in response was evident with a range for peak VO2 of 11 to 38 mL kg1 min1 (39%-110% of age- and sex-predicted). Selected, highly trained HT patients may achieve much higher values: mean peak VO2 of 40 mL kg1 min1 in 14 men (mean age, 43 years), with highest value of 54 mL kg1 min1,22 and mean peak VO2 of 45 mL kg1 min1 in 12 men (mean age, 47 years).23 Rarely, highly motivated and well-trained transplant recipients are able to perform impressive athletic feats. For example, a 20-year-old elite soccer player returned to competition after HT.24 A woman in her 40s, after surgery, climbed both Mt Kilimanjaro (5895 m) and the iconic Matterhorn (4478 m; considered much more technically difficult than Kilimanjaro).25 The upper limit of endurance exercise performance after HT is probably the report of a 49-year-old man, 22 years after surgery, who completed an ironman triathlon (3.8 km swim, 180 km cycle, 42.2 km run) in 15.6 hours, finishing 1881 of 2067 athletes.26 Partial cardiac reinnervation Occasionally, HT patients with graft vessel disease resulting in myocardial ischemia will report typical anginal symptoms, suggesting at least partial afferent cardiac reinnervation.27 It also seems that partial cardiac sympathetic efferent reinnervation occurs in many patients during the first several months to years after surgery. The evidence for this statement is based on neurochemical evaluation of autonomic nervous system activity in the heart and the observation of improved responsiveness of the heart rate during exercise. [28] and [29] The heart rate reserve (also called chronotropic response), defined as the difference between the heart rate at rest and the highest value during maximal exercise, increases during the first 6 weeks after surgery in many patients.29 In a subset of HT patients, the heart rate reserve increases further over the next 6 to 12 months. A more rapid decline in heart rate from peak exercise to baseline is observed in some patients at 1 to 2 years after HT. Heart rate responsiveness to maximal graded exercise was assessed in a group of 95 HT recipients at 1 year after surgery.21 Partial normalization of the heart rate response to exercise was defined as an increase in heart rate for each minute of graded exercise, maximal heart rate occurring at peak exercise, and a decrease in heart rate during each minute of recovery. By this definition, 32 subjects

(33.7%) exhibited partial normalization of the heart rate response. Maximal heart rate was higher (147 vs 134 beats/min, P < .008), and exercise test duration was longer (8.2 vs 7.2 minutes, P < .05), although peak VO2 was similar (20.9 vs 19.4 mL kg1 min1; P, nonsignificant). Fig 5 shows the heart rate responses to graded exercise for the same patient at 3 and 12 months after HT. The finding of the lack of improvement in peak VO2 with a larger heart rate reserve has been reported for pediatric HT recipients.30 Furthermore, in adult HT patients, increasing the heart rate reserve with a novel high-intensity warm-up did not result in an increase in peak VO2.31

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High-quality image (115K) Fig 5. Heart rate responses to graded exercise in the same patient at 3 months and 12 months after cardiac transplantation demonstrating both denervation (at 3 months) and partial reinnervation (at 24 months). Reprinted with permission from Squires et al.21

Graded exercise testing

Exercise testing after HT is helpful in determining the exercise capacity, prescribing exercise training (ET), and in counseling patients regarding the timing of return to work or school, or resumption of avocational pursuits. The electrocardiogram (ECG) of HT recipients commonly demonstrates right bundle-branch block and nonspecific repolarization abnormalities. The sensitivity of the exercise ECG in detecting ischemia due to the presence of allograft vasculopathy is poor (<25%), unless combined with myocardial imaging.32 Because of the healing and recovery process after surgery and the usual deconditioned state before surgery, it is best to wait 6 to 8 weeks after surgery before performing graded exercise testing to maximal effort. For patients with more complicated postoperative courses, an even longer period of recovery is recommended before performance of an exercise test. Treadmill or cycle ergometer protocols, with continuous exercise (2 or 3 minute stages or ramp tests), may be used. Arm cranking protocols may also be used after adequate sternal healing, for a specific upper extremity fitness evaluation or an arm cranking exercise prescription.33 The initial exercise intensity should be approximately 2 metabolic equivalents (METs), with 1- to 2-MET increments in intensity per stage. [27] and [33] Continuous multilead ECG monitoring with blood pressure measurement and Borg perceived exertion ratings for each stage is recommended. For precise determination of aerobic capacity, direct measurement of VO2 and associated variables is highly desirable. The end points of the graded exercise test should be maximal effort (symptom-limited maximum) or standard signs of exertional intolerance.34

Responses to ET
Recipients of HT are excellent candidates for progressive ET for several reasons: pre-HT syndrome of chronic HF with poor exercise capacity due to central and peripheral circulatory abnormalities,

skeletal muscle pathology, deconditioning, the healing process with open-heart surgery similar to that observed with coronary or valvular surgery, and post-HT use of corticosteroid medications with resultant skeletal muscle atrophy and weakness. Aerobic ET The literature contains multiple reports demonstrating the benefits of aerobic ET for patients after HT. [35] , [36] , [37] , [38] , [39] , [40] , [41] and [42] In general, HT recipients respond to training in a similar fashion to other cardiac patients. Peak VO2 improves by an average of 24% after 2 to 6 months of ET, and this training improves mitochondrial oxidative capacity but apparently does not increase skeletal muscle capillary density as it does in healthy subjects.43 Potential additional benefits of regular HT for HT recipients include the following: The first study of ET after HT was published in 1983 and included only 2 subjects in a case presentation format.35 After a 6-week period of ET, ratings of perceived exertion and systolic blood pressure were consistently lower for all submaximal exercise intensities comparing pretraining and posttraining graded exercise test results. Early investigations were limited to fewer than 20 subjects. The first larger study was that of Niset and colleagues37 in 1988, who studied 62 patients at approximately 1 month after HT and again at the 1-year anniversary. Patients were instructed in ET principles and were started in a supervised program. No control group was used. A precise description of the ET prescriptions and patient compliance with the program were not available. However, directly measured peak VO2 did increase by 33% (P < .01). In 1988, Kavanagh and associates39 reported the results of a 16-month ET program in 36 HT recipients (no control group): ET (walk/jog) began approximately 7 months after surgery and was carefully supervised. Patients demonstrated an average of 27% increase in peak VO2. Some of the limitations of these earlier investigations were overcome in a 6-month long study reported in 1999 by Kobashigawa and colleagues.42 Twenty-seven HT patients were randomized to an ET or control group early after surgery. The ET group underwent supervised ET (aerobic and strengthening exercises), whereas the control group performed an unstructured home walking program. Peak VO2 improved more in the supervised ET group (+4.4 vs +1.9 mL kg1 min1, P < . 01). There were no differences between the 2 groups for number of episodes of acute rejection or infection. Supervised ET programs seem to improve fitness to a greater extent than less structured Improved submaximal exercise endurance Increased peak treadmill exercise workload or peak cycle power output Increased maximal heart rate Decreased exercise heart rate at the same absolute submaximal workload Increased ventilatory (anaerobic) threshold Decreased submaximal exercise minute ventilation Reduced exercise ventilatory equivalent for CO2 Lessened symptoms of fatigue and/or dyspnea Reduced rest and submaximal exercise systolic and diastolic blood pressure Decreased peak exercise diastolic blood pressure Reduced submaximal exercise ratings of perceived exertion Improved psychosocial function Increased lean body mass Reduced body fat mass Increased bone mineral content

approaches. As mentioned previously, some patients after HT may develop outstanding aerobic fitness (2 to 3 times the usual age and sex average peak VO2 for transplant recipients), although they seem to be a small minority. Twelve men (average age of 47 years) who trained for 2 years, 7 to 20 hours per week of jogging or cycling, achieved an average peak VO2 of 45 mL kg1 min1.23 Another study of 14 male HT patients (average age, 43 years) who competed in a 600-km relay running race reported an average peak VO2 of 42 mL kg1 min1 (range, 32-54 mL kg1 min1).22 Resistance exercise Most HT patients require prednisone, at least during the first several months after surgery, for immunosuppression. Skeletal muscle atrophy and weakness are common adverse effects related to prednisone. Resistance ET partially reverses corticosteroid-related myopathy and improves skeletal muscle strength. Horber and associates44 found definite evidence of skeletal muscle wasting and weakness in the lower extremities of renal transplant patients who received prednisone. Fifty days of isokinetic strength training substantially increased muscle mass and strength in these patients. In addition, strength training has been shown to improve bone density and to reduce the potential development of osteoporosis (also caused by prednisone) in HT recipients.45 Effect of ET on immune function and longevity An obvious and important question concerning ET in immunosuppressed HT recipients is the effects of training on immune function. Traditional, moderate ET does not increase or decrease the number or severity of episodes of acute rejection. [42] and [46] In addition, ET does not require changes in immunosuppressant dosage or treatment. Infection risk is not changed by ET. There are no data regarding the effect of ET on survival after HT.

Exercise programming suggestions

Pretransplant graded exercise testing and training As part of the evaluation process for HT, ambulatory patients undergo cardiopulmonary exercise testing. Peak VO2 is a powerful prognostic indicator: patients with an aerobic capacity of 14 mL kg1 min1 (4 METs) or below experience a markedly reduced 1-year survival, independent of left ventricular ejection fraction.47 Based on the results of the exercise test, an ET prescription may be developed for the patient with the goal of maintaining or even improving cardiorespiratory fitness while waiting for a donor organ. Ideally, the exercise program should be carried out under medical supervision, although many patients have performed home-based, independent exercise successfully. Early mobilization and inpatient ET After surgery, patients are extubated expeditiously, usually within 24 hours. Passive range-of-motion exercises for both the upper and lower extremities, sitting up in a chair, and slow ambulation may begin and progress gradually after extubation.48 Walking or cycle ergometry may be increased in duration to 20 to 30 minutes, as tolerated. Exercise intensity is guided using the Borg perceived exertion scale ratings of 11 to 13 (fairly light to somewhat hard; Table 1), keeping the respiratory rate below 30 breaths/min and arterial oxygen saturation above 90%. Exercise frequency is 2 to 3 sessions per day.7 Patients whose postoperative courses are uncomplicated remain hospitalized for 7

to 10 days. Table 1. The Borg perceived exertion scale 6 7 Very, very light 8 9 Very light 10 11 Fairly light 12 13 Somewhat hard 14 15 Hard 16 17 Very hard 18 19 Very, very hard 20 From Borg G. Physical Performance and Perceived Exertion. Lund, Sweden: Gleerup, 1962. During inpatient rehabilitation, as well as during the outpatient phases, episodes of acute rejection of a moderate or greater severity may require alteration of the ET plan. If the rejection episode is graded as moderate, activity may be continued at the current level, but should not progress until after the rejection has been adequately treated. Severe acute rejection necessitates suspension of all physical activity with the exception of passive range-of-motion exercises. Outpatient ET Recipients of HT may enter an outpatient cardiac rehabilitation program as soon as they are dismissed from the hospital.7 Patients are generally required by the HT team to remain near the transplant center for close follow-up for approximately 3 months. Ideally, they should exercise in both a supervised environment (3 sessions per week) and independently (at least 3 sessions per week). Continuous monitoring of the ECG during the first few supervised ET sessions is standard practice, although many weeks of ECG monitored ET is seldom useful. It is not necessary to perform graded exercise testing before beginning the outpatient exercise program. Performance of a 6-minute walk is helpful in assessing functional capacity, however. Graded exercise testing should be performed 6 to 8 weeks after surgery for patients without complicated recoveries, when the patient has recovered sufficiently from surgery to assess the cardiopulmonary responses to exercise and to refine the exercise prescription. Exercise prescription for cardiac transplant patients is similar to methods used with patients who have undergone coronary bypass, coronary valve, or other cardiothoracic surgery. The one exception is that a target heart rate is not used, unless the patient exhibits a partially normalized heart rate response to exercise as discussed previously. The typical denervated heart increases in rate slowly during submaximal exercise, and the heart rate may either drift gradually higher during steady-state exercise or plateau after several minutes.20 Borg perceived exertion scale ratings of 12 to 14 (somewhat hard) may be used to prescribe exercise intensity.7 The ET prescription should include standard warm-up and cool-down activities, a gradual increase in aerobic exercise duration to 30 to 60 minutes, with a frequency of 4 to 6 sessions per week. Typical modes of aerobic ET used during the early outpatient recovery period include walking outdoors (or shopping centers, schools), treadmill

walking, cycle ergometry, and stair climbing. Because of the sternal incision, special emphasis on upper extremity active range-of-motion exercises is required. At approximately 6 weeks after surgery, when sternal healing is nearly completed, rowing, arm cranking, combination arm/leg ergometry, outdoor cycling, hiking, jogging, and swimming (and other water-based exercise) become additional options, depending on the patients' fitness levels. Sports such as tennis and golf may be performed as early as 6 weeks after surgery if patient fitness is adequate (5 METs or greater) and sternal healing is nearly complete. Skeletal muscle weakness in HT recipients is very common and is related to skeletal muscle atrophy due to advanced HF, pre-HT deconditioning, and corticosteroid use post-HT as part of the immunosuppressant regimen. Muscle strengthening exercises should be incorporated into the ET program to counteract these factors. For the first 6 weeks after surgery, bilateral arm lifting is restricted to less than 10 lb to avoid sternal nonunion. During this early stage of rehabilitation, light hand weights are an excellent method of introducing resistance ET. After at least 6 weeks of healing, patients may be started on standard weight machines, emphasizing moderate resistance, 10 to 20 slow repetitions per set, 1 to 3 sets of exercises for the major muscle groups, with a frequency of 2 or 3 sessions per week. [7] and [21] We recommend Borg perceived exertion scale ratings of 12 to 14 to gauge the intensity of lifting. Strength gains of 25% to 50% or greater commonly occur after 8 weeks of strength ET in these patients. Performance of the strengthening exercises immediately after the aerobic portion of the exercise prescription (after the cool-down) is recommended. Because HT recipients are likely to require antihypertensive medications, periodic blood pressure measurement during both aerobic and strengthening ET is recommended. Encouragement to continue a lifelong exercise program should be a consistent message from the HT team and the primary health care provider. Patients should continue in a supervised ET program indefinitely, or exercise independently, or use a combination of supervised and unsupervised ET. We recommend annual graded exercise tests with revision of the ET prescription, as necessary.

Statement of Conflict of Interest

The author declares that there is no conflict of interest.

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32 J.K. Ehrman, S.J. Keteyian and A.B. Levine, et al. Exercise stress tests after cardiac transplantation. Am J Cardiol, 71 (1993), pp. 13721373. 33 S.J. Keteyian and C. Brawner, Cardiac transplant American College of Sports Medicine. ACSM's exercise management for persons with chronic diseases and disabilities, (2nd ed.), Human Kinetics, Champaign, IL (2003), pp. 7075. 34 R.J. Gibbons, G.J. Balady and J.W. Beasley, et al. ACC/AHA guidelines for exercise testing: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee on exercise testing). J Am Coll Cardiol, 30 (1997), pp. 260315. 35 R.W. Squires, P.A. Arthur and G.T. Gau, et al. Exercise after cardiac transplantation: a report of two cases. J Cardiopulmonary Rehabil, 3 (1983), pp. 570574. 36 S. Degre, G. Niset and J.M. Desmet, et al. Effets de l'entrainement physique sur le coeur humain denerve apres transplantation cardiaque orthotopique. Ann Cardiol Angeol (Paris), 35 (1986), pp. 147149. 37 G. Niset, C. Cousty-Degre and S. Degre, Psychological and physical rehabilitation after heart transplantation: 1 year follow-up. Cardiology, 75 (1988), pp. 311317. 38 P. Sieurat, J.P. Roquebrune and D. Grinneiser, et al. Surveillance et readaptation des transplantes cardiaques heterotopiques a la periode de convalescence. Arch Mal Coeur, 79 (1986), pp. 210216. 39 T. Kavanagh, M.H. Yacoub and D.J. Mertens, et al. Cardiorespiratory responses to exercise training after orthotopic cardiac transplantation. Circulation, 77 (1988), pp. 162171. 40 T. Kavanagh, M.H. Yacoub and D.J. Mertens, et al. Exercise rehabilitation after heterotopic cardiac transplantation. J Cardiopulmonary Rehabil, 9 (1989), pp. 303310. 41 S. Keteyian, R. Shepard and J. Ehrman, et al. Cardiovascular responses of heart transplant patients to exercise training. J Appl Physiol, 70 (1991), pp. 26272631. 42 J.A. Kobashigawa, D.A. Leaf and N. Lee, et al. A controlled trial of exercise rehabilitation after heart transplantation. N Engl J Med, 340 (1999), pp. 272277. 43 E. Lampert, B. Mettauer and H. Hoppeler, et al. Skeletal muscle response to short endurance training in heart transplantation recipients. J Am Coll Cardiol, 32 (1998), pp. 420426. 44 F.F. Horber, J.R. Scheidegger and B.F. Grunig, et al. Evidence that prednisone-induced myopathy is reversed by physical training. J Clin Endocrinol Metab, 61 (1985), pp. 8388. 45 R.W. Braith, R.M. Mills and M.A. Welsch, et al. Resistance exercise training restores bone mineral density in heart transplant recipients. J Am Coll Cardiol, 28 (1996), pp. 14711477. Article | PDF (735 K) | | View Record in Scopus | | Cited By in Scopus (79) 46 Q.M. Zhao, B. Mettauer and E. Epailly, et al. Effect of exercise training on leukocyte

subpopulations and clinical course in cardiac transplant patients. Transplant Proc, 30 (1998), pp. 172175. Article | PDF (194 K) | | View Record in Scopus | | Cited By in Scopus (5)

47 D.M. Mancini, H. Eisen and W. Kussmaul, et al. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation, 83 (1991), pp. 778786. 48 C.G.A. McGregor, Cardiac transplantation: Surgical considerations and early postoperative management. Mayo Clin Proc, 67 (1992), pp. 577585. Statement of Conflict of Interest: see page 435.

Address reprint requests to Ray W. Squires, PhD, Program Director, Cardiovascular Health and Rehabilitation, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN 55905. Copyright 2011 Published by Elsevier Inc.

Otro articulo:

Transplantation Proceedings Volume 43, Issue 7, September 2011, Pages 2714-2717 doi:10.1016/j.transproceed.2011.04.025 | How to Cite or Link Using DOI Permissions & Reprints

Thoracic The Effect of Early Cardiac Rehabilitation on Health-Related Quality of Life among Heart Transplant Recipients and Patients with Coronary Artery Bypass Graft Surgery C.-J. Hsua, b, c, S.-Y. Chena, e, S. Suc, M.-C. Yangc, C. Lana, e, N.-K. Choud, e, R.-B. Hsue, J.-S. Laia, e, S.-S. Wangd, e,
a b c d e ,

Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan Keelung Hospital, Department of Health, Keelung City, Taiwan Institute of Health Policy and Management, College of Public Health, National Taiwan University, Taipei, Taiwan Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

National Taiwan University College of Medicine, Taipei, Taiwan Available online 10 September 2011.

Abstract
Purpose To investigate the effect of an early postoperative outpatient cardiac rehabilitation program to healthrelated quality of life among heart transplantation recipients (HTR) and patients with coronary artery bypass graft (CABG) surgery. Methods The study included 45 clinically stable HTR (age: 47 14 years; 36 men, 9 women) and 34 patients with CABG (age: 57.2 12.5 years; 27 men, 7 women). HTR started rehabilitation 70 33 days after transplantation; patients with CABG started training 36 18 days after surgery. Patients participated in a 12-week supervised exercise training program three times per week. Each training session comprised 10 minutes of warm-up, 25 to 30 minutes of cycling or treadmill walking, and 10 minutes of cooldown. The exercise intensity was set at 50% to 80% of peak oxygen uptake (VO2peak) according to the patient's condition. The health-related quality of life of subjects was evaluated by the Medical Outcomes Trust 36-item health survey (SF-36) at baseline and upon the completion of rehabilitation. Results At baseline, the HTR group showed lower VO2peak than the CABG group, but the health-related quality of life was similar between the two groups. After training, both groups exhibited an increase of 3.6 mL kg1 min1 in VO2peak and improvement of physical component in health-related quality of life. The HTR group showed a significant increase of SF-36 scores in physical functioning (59.7 18.9 to 77.0 14.0), physical role (21.1 34.1 to 38.3 37.9), bodily pain (57.4 24.3 to 73.6 21.5), social functioning (63.6 23.4 to 72.8 22.1), emotional role (59.2 43.7 to 76.3 37.4), and mental health (67.1 17.9 to 73.4 14.6). The CABG group only exhibited increased scores in physical functioning (60.0 22.9 to 73.4 18.0), physical role (19.1 24.9 to 27.9 38.3), bodily pain (57.1 20.0 to 70.3 16.1), and social functioning (54.0 21.3 to 69.9 21.1).

Conclusions Early postoperative cardiac rehabilitation significantly improved physical capacity and quality of life among heart transplant recipients and patients with CABG. Additionally, HTR showed greater improvement in health-related quality of life than patients with CABG regardless of lower physical capacity.

Article Outline
Subjects and Methods Exercise Testing Exercise Protocol Quality of Life Data Analysis Results Discussion References Exercise intolerance is a common symptom among patients with heart disease. Low exercise capacity leads to poor clinical outcome and quality of life. Thereby, exercise training is crucial to heart patients with low functional capacity. Some specific groups of heart patients, such as heart transplant recipients (HTR) or those with congestive heart failure, displayed very low exercise capacity. Though exercise training may modestly improve their exercise tolerance, the physical capacity remains far lower than normal people. For those patients, the goal of exercise training is not only to enhance the physical capacity, but also to improve the quality of life. In recent years, increasing use of more patient-focused outcome, such as health-related quality of life, has been applied in cardiac rehabilitation. Health-related quality of life may be disease specific or generic. Disease-specific measures focus on the complaints that are attributable to a specific patient population. In contrast, the generic quality-oflife measures may be applied to patients with different diseases.1 Previous study has demonstrated that a common generic measure, the Short Form 36 (SF-36), showed higher sensitivity than diseasespecific measures in cardiac patients.2 The SF-36 is a multipurpose health survey with only 36 questions. It yields an eight-scale profile of functional health and well-being scores as well as physical and mental health summary measures. Studies of exercise training for cardiac patients usually reported significant improvement in scores of SF-36.3 However, whether the improvement of health-related quality of life is related to absolute increase in physical capacity or to peak aerobic capacity achieved is not clear. In this study, we recruited two groups of patients, including HTR and patients with coronary artery bypass graft (CABG). Previous studies have shown that exercise training may improve physical capacity in both groups, but the HTR group displays significant lower peak oxygen uptake than the CABG group, even after intensive training. [4] and [5] The purpose of this study was to investigate the effect of an outpatient phase 2 cardiac rehabilitation exercise program, which aimed to improve exercise capacity and health-related quality of life. Additionally, we intended to test the hypothesis that the peak physical capacity achieved after training is not a major determinant of health-related quality of life.

Subjects and Methods

The study included 45 clinically stable orthotopic HTR (age: 47 14 years; 36 men, 9 women) and 34 CABG patients (age: 57.2 12.5 years; 27 men, 7 women) completed a phase II cardiac rehabilitation program. HTR started rehabilitation 70 33 days after transplantation; patients with CABG started training 46 28 days after surgery. The reason for heart transplantation included 23 dilated cardiaomyopathy, 19 ischemic cardiomyopathy, and three other cause. Patients were excluded if they had: (1) active congestive heart failure, (2) significant myocardial ischemia during exercise, (3) unstable dysrhythmias, and (4) uncontrolled diabetes and/or hypertension. Active rejection or recent infection was also excluded in the HTR group. All procedures were fully explained to the patients, and written consents were obtained. This study was approved by the Human Research Committee of the National Taiwan University Hospital. Exercise Testing Exercise testing was performed before and after 12-week exercise training. Continuous electrocardiographic monitoring and analysis of expired gases were performed during the exercise testing. Blood pressure (BP) was measured before testing by the standard cuff method after each subject sat quietly for 5 minutes. Subjects used a cycle ergometer to perform a symptom-limited exercise test. Patients exercised in an upright position until the appearance of symptoms (ie, fatigue, angina, undue dyspnea, claudication, and cerebral symptoms) or signs (2-mm ST depression over resting electrocardiogram, significant ectopic activity, inappropriate BP response). Inappropriate BP responses included: (1) a drop in systolic BP of 20 mm Hg or more, (2) systolic BP drop below the value obtained before testing, (3) an increase in systolic BP to 260 mm Hg or an increase in diastolic BP to 115 mm Hg.6 The workload was 10 W for the first 3 minutes (familiarization period), and then increased in 10-W increments every minute. The pedaling cadence was maintained between 50 and 70 rpm. Breath-by-breath analysis of expired gas was performed by an automated system. Exercise Protocol Patients in both groups entered an outpatient cardiac rehabilitation program within 6 months after surgical operation. Exercise workouts were conducted three times a week. Each session included a 10-minute warm-up, 25 to 30 minutes of bicycle exercise combined with treadmill walking, and a 10minute cooldown. The exercise intensity was set at 50% to 80% of peak oxygen uptake (VO2peak) according to the patient's condition. The exercise session was supervised by a physical therapist and the heart rate and BP were monitored during the exercise. A home-based walking program with similar intensity of the outpatient program was recommended to all patients. Quality of Life General health-related quality of life was evaluated by the Chinese version of the SF-36.7 The SF-36 comprises 36 items that cover the domains of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Individual subscales scores and two summary scores, defined as physical component score (PCS) and mental component score (MCS), may be computed. Patients were tested by the SF-36 before participation in the cardiac rehabilitation program and after its completion. Data Analysis A paired t test was performed to compare the variables of pretraining and posttraining measurements within group. An unpaired t test was performed to analyze the variables between groups. A two-tailed p value of less than .05 was considered to be indicative of statistical significance.

Results
Eighty-nine subjects completed a 12-week exercise program. The HTR group included 45 subjects, and the CABG group comprised 34 subjects. Table 1 lists the baseline demographic and clinical characteristics of the subjects. Both groups were similar in body size, resting ejection fraction, and days of training. The CABG group was older than the HTR group. Table 1. Baseline Demographic and Clinical Characteristics Group CABG (n = 34) HT (n = 45) Age (y) 57.2 12.5 47.3 14.5* Gender (M/F) 27/7 36/9 Body height (cm) 165.6 9.7 166.3 7.5 Body weight (kg) 65.8 11.6 63.5 11/9 Resting heart rate (bpm) 83.4 11.0 103.3 9.9 Resting BP (mm Hg) 124.7 17.9 128.0 17.6 Resting ejection fraction (%) 63.5 12.6 61.3 9.6 Medical history Myocardial infarction (%) 85.3 42.2 Hypertension (%) 64.7 35.5 Diabetes (%) 35.3 17.7 Current smoking (%) 6.5 4.4 Mean time from surgery (wk) 6.5 2.3 10.1 4.5 Days of training 104 31 99 34 Data are listed as mean standard deviation. BP, blood pressure; CABG, coronary artery bypass grafting; HT, heart transplant recipients. Table 2 lists the variables of functional capacity and health-related quality of life before and after training. Before training, the HTR group showed 24.8% lower VO2peak than the CABG group. After training, the HTR group showed significant improvement in VO2peak and five subscales of the Chinese version of SF-36. The VO2peak increased 24% from 14.9 to 18.5 mL kg1 min1. Additionally, patients displayed significantly improved SF-36 scores in physical functioning, physical role, bodily pain, social functioning, and emotional role. The scores of general health, vitality and mental health showed a trend of improvement, but it did not reach statistical significance. Subjects also showed significant improvement in the physical component summary, but the metal component summary did not show significant change. Table 2. Functional Capacity and Quality of Life Before and After Training CABG (n = 34) HT (n = 45) Variables VO2peak (mL kg1 min1) Short Form 36 Physical functioning Role-physical Bodily pain General health Pretraining Posttraining P Value Pretraining Posttraining P Value 16.6 4.5 20.2 5.7* <.0001 14.9 3.5 18.5 4.7* <.0001

60.0 22.9 19.1 24.9 54.1 20.2 56.2 19.1

73.4 18.0* 27.9 38.3* 70.3 16.1* 59.4 21.1

.0001 .0173 .0001 .1858

59.7 18.9 21.1 34.1 57.4 24.3 64.0 17.8

77.0 14.0* 38.3 37.9* 73.6 21.5* 67.6 18.7

<.0001 .0496 .0011 .2461

CABG (n = 34)

HT (n = 45)

Variables Pretraining Posttraining P Value Pretraining Posttraining P Value Vitality 53.3 15.5 59.6 19.1 .5550 55.7 19.9 61.9 17.3 .0543 Social functioning 54.0 21.3 69.9 21.1* .0002 63.6 23.4 72.8 22.1* .0147 Role-emotional 43.3 43.7 55.9 43.2 .1896 59.2 43.7 76.3 37.4* .0464 Mental health 61.5 18.0 65.1 17.4 .2162 67.1 17.9 73.4 14.6* .0137 PCS 32.5 8.9 39.9 10.0* .0001 35.4 9.8 43.2 8.9* <.0001 MCS 43.0 9.3 45.6 9.4 .1795 47.5 10.8 50.2 9.0 .1035 Data are listed as mean standard deviation. CABG, coronary artery bypass grafting surgery; HT, heart transplantation; VO2peak, peak oxygen uptake; PCS, standardized physical component scale; MCS, standardized mental component scale. In the CABG group, the VO2peak and four subscales of the SF36 showed significant increase after training. The VO2peak increased 19.4% from 18.6 to 22.2 mL kg1 min1. In addition, patients displayed significantly improved SF-36 scores in physical functioning, physical role, bodily pain, and social functioning. The scores of general health, vitality, emotional role, and mental health did not show significant change. Subjects also showed significant improvement in the physical component summary, but they did not show significant change in the mental component summary. Compared with the age-matched norm of Taiwanese,7 the HTR group before training showed significant lower scores of SF-36 in seven subscales, except general health subscale. After training, general health, emotion role, and mental health subscales reached the age-matched normal standard. The CABG group showed significantly lower scores of SF-36 in all subscales than the norm before training. Although four subscales of SF-36 improved after training, no subscale attained the normal standard.

Discussion
This study showed two important findings. First, an early outpatient cardiac rehabilitation program significantly improved exercise capacity and health-related quality of life among HTR and patients with CABG surgery. Second, though the HTR group displayed lower aerobic capacity at baseline and after training, they exhibited greater improvement in health-related quality of life than the CABG group after cardiac rehabilitation. The results implied that the relative increase of physical capacity, rather than the absolute increase of VO2peak, is the major determinant of health-related quality of life. Poor exercise capacity plays a major role in preventing patients from performing daily activities or returning to work. Previous studies have reported exercise programs, initiated from several weeks to 18 months after operation, with training period duration from 6 weeks to 16 months, showed increased physical capacity in patients with heart diseases. [4] , [5] and [8] In this study, the baseline VO2peak was significantly lower in the HTR group than the CABG group, and both groups exhibited significantly lower VO2peak than the age-matched healthy populations. After training, the HTR group increased 24.2% in VO2peak from 14.9 3.5 to 18.5 4.7 mL kg1 min1. Meanwhile, the CABG group increased 19.3% in VO2peak from 18.6 4.5 to 22.2 5.7 mL kg1 min1. Both groups displayed an increase of 3.6 mL kg1 min1 in VO2peak after 3 months of training, and the increase was similar to previous studies in HTR and patients after CABG. [4] and [5] Upon the termination of cardiac rehabilitation, the VO2peak reaches 6.3 metabolic equivalent (MET) for the CABG group and 5.3 MET for the HTR group. Because the exercise intensity of most daily activities is lower than 4

MET, the results implied that both groups will not encounter major difficulties in activities of daily living. The significant increase of VO2peak may explain the significant improvement in physical function, role-physical, and physical component scores in both groups. Before participation in the exercise program, seven subscales of the Chinese version of the SF-36 in the HTR group were significantly lower than the age-matched norm, and all subscales of the SF-36 in the CABG group were lower than the normal standard. The results showed poorer health-related quality of life for both groups in comparison with normal people. After 3 months of cardiac rehabilitation, the HTR group displayed significant improvement in six subscales in the SF-36, but the CABG group only showed improvement in four subscales. In the HTR group, all scores among the eight subscales were above 60, except role-physical. In the CABG group, only scores of four subscales were above 60 (physical function, pain, social function, and mental health). After training, general health, emotion role, and mental health subscales in HTR reached scores of the normal standard, but patients with CABG still showed significantly lower scores of SF-36 in all subscales. These findings indicated that exercise training improved health-related quality of life much greater among HTR than patients with CABG. Before training, the scores of PCS were lower than 40 and the MCS were lower than 50 in both groups. The scores PCS and MCS were standardized to a mean of 50, with a score above 50 representing better than average function and below 50, poorer than average function.9 After training, both groups showed significant increase in scores of PCS, but the score of PCS in the CABG group remained below 40. The MCS did not show significant change in both groups, but HTR achieved a score above 50. Previous studies found that the scores of PCS displayed large differences between patients with chronic disease and the normal standard, but differences of the MCS were usually small.10 According to a recent study,11 physical function could be severely affected by chronic diseases, but mental health remained relatively high and stable. This may explain the small change of MCS after exercise training. There were some limitations in this study. First, the most prominent improvement of health-related quality of life may be found between pre- and postoperation, but this study did not interview patients preoperatively. Second, although both groups received thoracotomy and extracorporeal circulation during operation, the HTR group was more severe in medical condition and displayed denervated heart rate responses in comparison with the CABG group. However, the lower physical capacity and more severe medical condition did not resulted in poorer improvement in health-related quality of life. In conclusion, early postoperative outpatient rehabilitation program is beneficial to exercise capacity and health-related quality of life among heart transplant recipients and patients with CABG. Although the HTR group showed lower physical capacity than the CABG at baseline, both groups displayed similar increase of VO2peak after training. Additionally, HTR showed greater improvement in health related quality of life than patients with CABG regardless of poorer physical capacity.

References
1 J.E. Ware, K.K. Snow and M. Kosinski, SF-36 Health Survey: Manual and Interpretation Guide, The Health Institute, New England Medical Center, Boston, Mass (1993). 2 G.M. Kiebzak, L.M. Pierson and M. Campbell, et al. Use of the SF36 general health status survey to document health-related quality of life in patients with coronary artery disease. Heart Lung, 31 (2002), p. 207. 3 K. Brown, A review to examine the use of SF-36 in cardiac rehabilitation. Br J Nurs, 12 (2003), p.

904. 4 H. Karapolat, S. Eyigor and M. Zoghi, et al. Comparison of hospital-supervised exercise versus home-based exercise in patients after orthotopic heart transplantation. Transplant Proc, 39 (2007), p. 1586. 5 H.M. Arthur, K.M. Smith and J. Kodis, et al. A controlled trial of hospital versus home-based exercise in cardiac patients. Med Sci Sports Exerc, 34 (2002), p. 1544. 6 V.F. Froelicher, J. Myers and W.P. Follansbee, et al. Exercise and the Heart, Mosby, St Louis, Mo (1993). 7 P.H. Tseng, S.S. Wang and C.L. Chang, et al. Perceived health-related quality of life in heart transplant recipients with vs without preoperative ECMO in Taiwan. Transplant Proc, 42 (2010), p. 923. 8 Y.T. Wu, C.L. Chein and N.K. Chou, et al. Efficacy of a home-based exercise program for orthotopic heart transplant recipients. Cardiology, 111 (2008), p. 87. 9 J.E. Ware, K.K. Snow and M. Kosinski, SF-36 physical and mental health summary scales: a user manual and interpretation guide, The Health Institude, New England Medical Center, Boston, Mass (1994). 10 H.J. Smith, R. Taylor and A. Mitchell, A comparison of four quality of life instruments in cardiac patients: SF-36, QLI, QLMI, and SEIQoL. Heart, 84 (2000), p. 390. | View Record in Scopus | | Full Text via CrossRef | Cited By in Scopus (77) 11 W.M. Hopman, M.B. Harrison, H. Coo and E. Friedberg, et al. Associations between chronic disease, age and physical and mental health status. Chronic Dis Can, 29 (2009), p. 108. | View Record in Scopus | | Cited By in Scopus (6) Address correspondence to Shoei-Shen Wang, Chung-Shan South Road, Taipei 100, Taiwan (R.O.C.) Copyright 2011 Elsevier Inc. All rights reserved. Transplantation Proceedings Volume 43, Issue 7, September 2011, Pages 2714-2717

Otro articulo

El trasplante cardaco es la nica teraputica, junto con los inhibidores de la enzima conversiva de la angiotensina, capaz de cambiar en forma sustancial la evolucin natural de los pacientes con insuficiencia cardaca grave. Sin embargo, debido al limitado nmero de donantes, su impacto es escaso en comparacin con la magnitud del problema. Hasta finales de 1998 se han registrado 48.541 trasplantes cardacos ortotpicos en todo el mundo, y unos 2.510 de corazn y ambos pulmones. En Espaa se han efectuado 2.780 en los ltimos 15 aos. La supervivencia esperada para un paciente trasplantado es del 75% despus del primer ao y 60% a los 5 aos. La duracin media del injerto es de 8 aos y 6 meses. El trasplante cardaco est indicado en pacientes jvenes y de mediana edad con procesos cardacos irreversibles en mala situacin clnica, sin otras posibilidades de tratamiento mdico o quirrgico alternativo y con una expectativa de vida limitada en el tiempo. El mayor debate a la hora de indicar esta teraputica se establece en torno a los enfermos crticos, enfermos de edad superior a 65 aos y algunos enfermos con determinadas enfermedades sistmicas. La gran demanda de trasplantes obliga a los equipos a extender los criterios de aceptacin de donantes. Al mismo tiempo, un mayor conocimiento sobre la transmisibilidad de determinadas infecciones, preferentemente virales, obliga da a da a replantearse estos criterios. El control del rechazo se persigue con el uso de diversas estrategias inmunosupresoras. La ms empleada es la denominada triple terapia (ciclosporina, azatioprina y esteroides). El uso de anticuerpos antilinfocitarios como tratamiento de induccin citoltica no es unnimemente aceptado. Algunos de los nuevos inmunosupresores como el micofenolatomofetil y el tacrolimus parecen ofrecer ventajas sobre todo por su mayor potencia. Dado que el trasplante es una actividad limitada en s misma, cuya prctica afecta a la totalidad del sistema sanitario de un pas, se hace obligada una correcta planificacin y adecuacin de los centros, as como el establecimiento de reglas claras para la utilizacin de donantes y priorizacin de los trasplantes. Finalmente, el paciente debe ser informado de

forma extensa, clara y comprensible de los riesgos, limitaciones y expectativas de estos complejos procedimientos. Palabras clave: Guas clnicas. Trasplante cardaco. Trasplante cardiopulmonar. GUIDELINES OF THE SPANISH SOCIETY OF CARDIOLOGY. CARDIAC TRANSPLANTATION AND HEART-LUNG TRANSPLANTATION Cardiac transplantation is the only therapy that is able to substantially modify the natural evolution of patients with severe heart failure, along with angiotensin conversive enzime inhibitors. Nevertheless, because of the limited number of donors, its impact is scarce compared to the magnitude of the problem. Up to the end of 1998, 48,541 orthotopic cardiac transplantations and about 2,510 heart and both lung transplantations have been registered throughout the world. In Spain 2,780 procedures have been performed in the last 15 years. The survival expectations for a transplanted patient is 75% after the first year and 60% the following 5 years. The average duration of the graft is 8 years and 6 months. Cardiac transplantation is indicated for young and middle-age patients with irreversible cardiac process in bad clinical condition, with no other possibility of medical or surgical management and with a limited life expectancy. The major debate when choosing this therapy appears with the critical patients, patients older than 65 years, and some patients with systemic diseases. The great demand of transplantation obliges the teams to enlarge the criteria for donors acceptance. At the same time, the increase of the knowledge about the transmission of some infections, mainly viral, forces to review those criteria day-to-day. The use of different immunosuppressive strategies pursues the control of rejection. The most commonly used is the so-called triple therapy (cyclosporineazatioprine and steroids). The use of an821 Guas de actuacin clnica de la Sociedad Espaola de Cardiologa. Trasplante cardaco y de corazn-pulmones Luis Alonso-Pulpn (coordinador), Luis Almenar, Mara G. Crespo, Lorenzo Silva, Javier Segovia, Nicols Manito, Jos Joaqun Cuenca, Alberto Juff y Federico Valls Sociedad Espaola de Cardiologa. Correspondencia: Dr. L. Alonso Pulpn. Unidad de Insuficiencia Cardaca y Trasplante Cardaco. Servicio de Cardiologa. Hospital Puerta de Hierro. San Martn de Porres, 4. 28035 Madrid.

alcoholismo / angiografa coronaria / azatioprina / biopsia / calidad asistencial / ciclosporina A / ecocardiografa / electrocardiografa / enfermedad vascular del injerto / factores de riesgo / factores pronsticos / grupos de edad / guas de prctica clnica tilinfocitary antibodies such as citolitic induction treatment is not unanimously accepted. Some of the new immunosuppressive agents such as myphenolatemofetil and tacrolimus seem to offer advantages mainly due to their greater potency. Since transplantation is a limited procedure, of which its practise has an effect on the whole health system of a country, a perfect planning and adequacy of the Centers is compulsory, as well as the setting-up of clear rules for the use of donors and priority of transplantation. Finally, the patient must be informed cleary and comprehensively at length of the risks, limitations and expectations of these complex procedures. Key words: Guidelines. Heart transplantation. Heartlung transplantation. (Rev Esp Cardiol 1999; 52: 821-839) 1. RESULTADOS DEL TRASPLANTE CARDACO EN ESPAA Y EN EL RESTO DEL MUNDO INTRODUCCIN En el paciente con insuficiencia cardaca terminal, el trasplante cardaco es la nica opcin teraputica disponible en la actualidad que ha demostrado poseer un impacto positivo de gran magnitud sobre la supervivencia. Por ello, en los pases que disponen de cierto nivel econmico, se ha extendido y generalizado su uso, considerndose el tratamiento de eleccin ante cardiopatas evolucionadas en situacin funcional avanzada, no mejorables de forma suficiente con otros procedimientos mdicos y/o quirrgicos. RESULTADOS EN EL MBITO NACIONAL DEL TRASPLANTE CARDACO Y CARDIOPULMONAR En Espaa, el primer trasplante cardaco con xito se realiz en mayo de 1984. Desde entonces el nmero de procedimientos ha ido incrementndose de tal forma que, en 1997 se realizaron 318 trasplantes, alcanzndose la cifra global de 2.406. Esta cifra tiene tendencia a ir incrementndose con los aos; as, en 1998 se realizaron 349 trasplantes en 14 centros distribuidos por la geografa nacional. El sistema de coordinacin nacional y local ha hecho posible incrementar el nmero de donantes para poder realizar ms trasplantes. No obstante, no existen suficientes rganos para todos los pacientes que los necesitan; por ello, pese a tener unos criterios de seleccin de los receptores ms bien estrictos, slo se

trasplantan al ao el 80% de los pacientes que se incluyen en lista de espera. En nuestro medio, la cardiopata que con ms frecuencia motiva el trasplante de los pacientes es la cardiopata isqumica (42%). El segundo lugar lo ocupa la miocardiopata dilatada idioptica (34%) y las valvulopatas (11%). El resto de indicaciones son muy variadas, encontrando, en porcentaje relativo y por orden de frecuencia decreciente, a las cardiopatas congnitas, miocardiopata hipertrfica, miocardiopata dilatada alcohlica, miocardiopata restrictiva idioptica y miocarditis como ms frecuentes. Existe una gran disparidad en el sexo del paciente trasplantado, la mayora son varones (84%) con edad media de 48 16 aos. En ocasiones, los pacientes tienen tal situacin clnica y/o presentan un deterioro fsico tan rpido que obliga a intentar trasplantarlos con extrema urgencia. Ello implica que, tras la aparicin de un rgano compatible en cualquier zona del territorio nacional, tengan preferencia para realizarles el trasplante antes que a cualquier paciente incluido previamente en la lista, pero en situacin ms estable . Esta situacin no es, ni mucho menos, infrecuente. El porcentaje de pacientes trasplantados de forma urgente en nuestro pas oscila entre el 20 y el 25%. El trasplante cardaco es un procedimiento que lleva consigo una mortalidad elevada, probablemente mayor que las tcnicas quirrgicas cardacas convencionales. No obstante, sus resultados son espectaculares, siendo capaz de mantener vivo a la mayora de pacientes a corto y medio plazo que, por otra parte, tendran un pronstico fatal de necesidad. El perodo de mximo riesgo es el primer mes, en el que la supervivencia desciende bruscamente al 85%. Posteriormente, existe un descenso ms gradual de tal forma que el 75% de pacientes estn vivos al ao y el 60% a los 5 aos. La vida media, es decir, el momento en el que la supervivencia es del 50% est en 8 aos y 6 meses. No obstante, stos son datos globales, que incluyen todos los perodos desde que se inici el trasplante y todos los tipos de trasplante (cardiopulmonar, retrasplante, neonatos, trasplantes heterotpicos y urgentes), sea cual sea el riesgo de ste. Actualmente, y para el trasplante cardaco estndar, la supervivencia es mucho mayor. En la etapa precoz, la causa ms frecuente de mortalidad es el fallo primario del injerto, seguido de infeccin y fallo multiorgnico. El fallo primario del injerto es una situacin de etiologa multifactorial en la que existe una imposibilidad del corazn recin implantado para mantener un gasto cardaco adecuado. El fallo multiorgnico es la consecuencia de complicaciones que acaban por producir un fracaso de varios rganos

o sistemas a la vez. En el primer ao, las causas ms frecuentes de mortalidad son el rechazo y la infeccin. A largo plazo, las dos causas que producen el fallecimiento de los pacientes trasplantados con ms frecuencia son la enfermedad vascular del injerto, que consiste en un estrechamiento rpidamente progresivo de las arterias coronarias, y las neoplasias. REVISTA ESPAOLA DE CARDIOLOGA. VOL. 52, NM. 10, OCTUBRE 1999 822 No todos los factores, prequirrgicos, quirrgicos y posquirrgicos, que existen en un trasplante influyen en el mismo grado sobre el xito o fracaso del procedimiento. De hecho, se han identificado una serie de condiciones que afectan de manera negativa a la supervivencia1. La experiencia con el trasplante cardiopulmonar en nuestro pas es todava muy limitada. Ello se debe a que el nmero de procedimientos no es elevado. Los problemas principales son: dificultad para conseguir donantes adecuados, problemas tcnicos quirrgicos y alta incidencia de complicaciones a medio y largo plazo. El nmero total de trasplantes cardiopulmonares realizados hasta el 31 de diciembre de 1998 es de 24. RESULTADOS EN EL MBITO MUNDIAL DEL TRASPLANTE CARDACO Y CARDIOPULMONAR De los registros internacionales, el que goza de ms prestigio es el Registro de la Sociedad Internacional de Trasplante Cardaco y Pulmonar. Se publica anualmente en el Journal of Heart and Lung Transplantation y es de referencia obligada para todos los grupos de trasplante2. Este registro recoge los trasplantes realizados desde 1982, actualizndose cada ao. El nmero de procedimientos que recoge, en la ltima publicacin, es de 45.993 trasplantes cardacos realizados en 301 centros y 2.428 trasplantes cardiopulmonares de 122 hospitales. El nmero de trasplantes cardacos ha ido incrementndose desde el inicio, alcanzndose aproximadamente los 4.000 trasplantes anuales; no obstante, desde 1995 est experimentando un ligero, aunque progresivo descenso, de tal forma que en 1997 se realizaron 3.471. La patologa cardaca que motiv el trasplante con ms frecuencia es la miocardiopata (46%), seguida de la cardiopata isqumica (45%) y las valvulopatas (4%). Es importante tener en cuenta que este registro no es comparable con el espaol y que no es tan homogneo, ya que no incluye todos los centros que realizan trasplantes, sino los que voluntariamente les envan sus datos. La mayora de pacientes trasplantados estn entre 18 y 65 aos, fuera de estas edades, el trasplante es menos frecuente. La supervivencia anual que se presenta

en este registro es del 80% al ao, del 65% a los 5 aos y del 45% a los 10 aos. La vida media es de 8 aos y 7 meses. El 90% de los supervivientes permanecen en buena clase funcional y sin limitaciones en su vida diaria. El trasplante cardiopulmonar tambin experiment un importante incremento inicial. El ao que se realizaron ms trasplantes de este tipo fue en 1990, con 241. A partir de aqu, fue descendiendo el nmero de procedimientos; en 1997 se realizaron 151. Las dos patologas que indican el trasplante cardiopulmonar con ms frecuencia es la cardiopata congnita (28%) y la hipertensin pulmonar primaria (26%). Como en el resto de trasplantes, las causas de muerte suelen variar segn el tiempo que ha transcurrido desde el trasplante. As, en el primer mes suelen ser muertes sbitas, infecciones y hemorragias masivas relacionadas con la intervencin. En el primer ao, infecciones, hemorragias y rechazo. A partir del ao, bronquiolitis e infecciones. 2. INDICACIONES DEL TRASPLANTE CARDACO ORTOTPICO Y DE TRASPLANTE CORAZN-PULMN TRASPLANTE CARDACO ORTOTPICO La indicacin de trasplante cardaco (TC) es una cardiopata grave en situacin terminal, sin otra opcin teraputica posible y sin contraindicaciones para el mismo. La mejora en el pronstico de la insuficiencia cardaca tras un tratamiento mdico adecuado y la limitada fuente de donantes hacen que los criterios de seleccin de pacientes para TC tengan como objetivo primordial identificar a aquellos pacientes con la mayor necesidad de TC y que, adems, tengan el mximo beneficio con la realizacin del mismo2,3. Aunque no se pueden imponer unos criterios homogneos de seleccin del receptor, dado que el nmero de donantes es limitado, se hace imprescindible un consenso entre todos los grupos de trasplante para evitar disfunciones del sistema. La evaluacin tiene como objetivos bsicos4-8: 1. Confirmar la gravedad de la cardiopata. 2. Descartar otras terapias posibles: a) revascularizacin de isquemia significativa reversible; b) reemplazo valvular de valvulopata artica crtica, y c) reemplazo valvular o reparacin de regurgitacin mitral severa. 3. Verificar la ausencia de contraindicaciones. 4. Estimar el pronstico a corto plazo, que ayude a decidir en qu momento el paciente debe ser incluido en lista de espera para TC. Una vez que la necesidad de TC ha sido establecida, debern de ser excluidas aquellas condiciones que incrementen la morbimortalidad post-TC. Muchas de

ellas se podran considerar como una variable continua y a veces es difcil establecer el punto en el que la supervivencia post-TC se ve afectada negativamente. De forma general seran contraindicaciones absolutas: 1. Enfermedades que pudieran acortar la esperanza de vida. 2. Pacientes con adiccin actual al alcohol, tabaco o drogas. L. ALONSO-PULPN ET AL. GUAS DE ACTUACIN CLNICA DE LA SOCIEDAD ESPAOLA DE CARDIOLOGA. TRASPLANTE CARDACO Y DE CORAZN-PULMONES 823 3. Demostrado mal cumplimiento del tratamiento mdico. No obstante, actualmente no suele hablarse de contraindicaciones absolutas ni relativas sino de condiciones que aumentan la morbimortalidad tras el TC (tabla 1). Las cardiopatas inflamatorias son una contraindicacin relativa. Aunque un subgrupo de pacientes con miocarditis o miocardiopata periparto mejora la funcin ventricular, se desconoce la duracin en la que se puede esperar dicha mejora antes de decidir incluir a estos pacientes en lista de TC. Adems, en el caso de miocarditis aguda se sabe que existe un aumento de riesgo en el nmero de rechazos tras el TC que pueden acortar la supervivencia. Las cardiopatas infiltrativas como la sarcoidosis y la amiloidosis pueden recurrir en el corazn trasplantado y las manifestaciones sistmicas de dichas enfermedades pueden limitar la recuperacin funcional y la supervivencia a largo plazo. En el caso de la amiloidosis, en la actualidad puede decirse que el TC es una terapia experimental y paliativa911. En ambas entidades, no obstante, la experiencia mundial es tan limitada que impide establecer recomendaciones taxativas12. La hipertensin pulmonar es una causa importante de morbimortalidad post-TC por el riesgo de fracaso del ventrculo derecho (ya que el ventrculo derecho de un donante sano no est preparado para soportar presiones pulmonares elevadas) y disfuncin precoz del injerto. Por encima de 2,5 unidades Wood ya se considera un factor de riesgo de mortalidad y que aumenta progresivamente. La mayora de los centros excluyen a los pacientes con una resistencia vascular pulmonar tras el estudio de reversibilidad superior a 4 o 6 unidades Wood o un gradiente transpulmonar mayor de 15. Para determinar dicha reversibilidad se utilizan distintos protocolos con vasodilatadores pulmonares e inotrpicos incluyendo oxgeno, xido ntrico inhalado, nitroprusiato, milrinona, adenosina o prostaciclina.

La funcin pulmonar deber ser valorada tras un adecuado tratamiento del edema pulmonar, ya que puede alterar los resultados de los estudios de funcin pulmonar. Una enfermedad obstructiva crnica significativa, con un volumen expiratorio forzado < 50% del predicho aumenta el riesgo de complicaciones pulmonares tras el TC. La presencia de bronquitis crnica y bronquiectasias aumenta el riesgo de complicaciones infecciosas tras el TC. El embolismo pulmonar y/o infarto pulmonar aumentan el riesgo de neumona o fstula bronquiopleural. La lcera pptica activa es una contraindicacin temporal para el TC por la anticoagulacin requerida para la circulacin extracorprea. Los antecedentes de diverticulitis recurrente y las colecistitis aumentan el riesgo de infecciones intraabdominales severas, a menudo fatales. La exposicin previa al virus de la hepatitis C en el receptor aumenta el riesgo de hepatopata tras el TC pero en la experiencia conocida no parece afectar a la supervivencia global. La disfuncin renal en pacientes con insuficiencia cardaca puede deberse a hipoperfusin, tratamiento mdico o enfermedad renal parenquimatosa. Es necesario definir la etiologa y reversibilidad de la disfuncin renal antes de contraindicar el TC y/o indicar un trasplante renal asociado. En este sentido, el tratamiento corto con dopamina a bajas dosis u otro inotrpico positivo puede identificar a pacientes con insuficiencia renal por hipoperfusin. La ecografa renal en la que se observen unos riones de pequeo tamao sugiere enfermedad intrnseca renal crnica. La diabetes mellitus era en el pasado una contraindicacin absoluta de TC, pero en la actualidad la mayora de los programas de TC excluyen nicamente a los pacientes diabticos con evidencia de disfuncin de rganos diana, es decir, retinopata, nefropata y neuropata. Las infecciones bacterianas suponen una complicacin grave tras el TC, por lo que ste debera evitarse en pacientes con infeccin aguda. La presencia de neoplasias es una contraindicacin por el riesgo de progresin tumoral con la inmunosupresin. Se desconoce el efecto de la inmunosupresin sobre neoplasias tericamente curadas y algunos centros recomiendan de forma intuitiva un perodo mayor de 5 aos antes del TC13. No obstante, dado que por ahora la experiencia es escasa, cada paciente debera ser considerado de forma individual. Los tumores cardacos primarios son una entidad rara y aunque se han comunicado casos con xito, la mayora fallecen a medio plazo tras el trasplante por REVISTA ESPAOLA DE CARDIOLOGA. VOL. 52, NM. 10, OCTUBRE 1999

824 TABLA 1 Condiciones que pueden aumentar la morbimortalidad tras el trasplante cardaco Edad Enfermedad sistmica coexistente de mal pronstico Miocardiopata infiltrativa o inflamatoria Hipertensin arterial pulmonar irreversible Enfermedad parenquimatosa pulmonar irreversible Tromboembolismo pulmonar agudo Enfermedad vascular cerebral o perifrica severa Disfuncin renal irreversible Disfuncin heptica irreversible lcera pptica activa Diverticulitis o diverticulitis activa Diabetes insulinodependiente con afectacin visceral Obesidad severa Osteoporosis severa Infeccin activa Neoplasia coexistente Inestabilidad psicosocial, toxicomana o ambas diseminacin metastsica, por lo que la indicacin deber ser muy cautelosa14-16. La presencia de enfermedad carotdea o vascular perifrica aumenta el riesgo intraoperatorio de accidentes vasculares cerebrales y complicaciones en la insercin de baln intraartico de contrapulsacin. Adems, probablemente los efectos aterognicos de los esteroides podran acelerar la progresin de la arteriosclerosis con sus riesgos asociados. La obesidad aumenta la morbimortalidad post-TC y hace difcil a veces la concordancia de peso/superficie corporal con el donante, lo que puede ser un factor de riesgo de enfermedad vascular del injerto. Se considera que un peso superior al 150% del ideal es un factor de riesgo de complicaciones post-TC. La osteoporosis puede verse acelerada tras el tratamiento con esteroides post-TC y puede limitar de forma significativa la capacidad funcional. Los factores psicolgicos y sociales desempean un papel crucial en el xito del TC a largo plazo. Se deber descartar la presencia de enfermedad mental o drogadiccin y cualquier aspecto que predisponga a un mal cumplimiento del tratamiento y que pudiera aumentar la mortalidad. La edad avanzada es un factor de riesgo de morbimortalidad tras el TC, pero el establecer un lmite de edad que lo contraindique es un tema de debate. Dificultades adicionales son la frecuente disparidad entre la edad cronolgica y fisiolgica y que muchas veces la morbimortalidad asociada con la edad se debe a la presencia concomitante de otras condiciones comrbidas

que son conocidos factores de riesgo de complicaciones post-TC y cuya prevalencia aumenta con la edad. Por ello, en muchos centros que de forma individualizada han incluido pacientes de edad superior a 60-65 aos, pero con ausencia de otras contraindicaciones relativas, se ha visto que los resultados son superponibles a la serie global de pacientes. Por otra parte, a medida que se ampla la edad del receptor aumenta el nmero de potenciales receptores para TC. Por tanto, aunque no existe base cientfica que contraindique el TC exclusivamente por la edad, el limitado nmero de donantes disponible recomienda a los centros de trasplante el establecer un lmite no superior a los 65 aos. DETERMINAR EL MOMENTO DE INCLUSIN EN LISTA DE ESPERADE TRASPLANTE CARDACO Determinar cundo la cardiopata est en situacin terminal es difcil de definir exactamente pero, en general, se refiere a una enfermedad cardaca en clase funcional IV de la New York Hearth Association (NYHA) a pesar de tratamiento mdico ptimo y con una meticulosa monitorizacin del peso, estado general, electrlitos y funcin renal. De hecho, muchos centros de trasplante han encontrado que entre un 30 y un 50% de los pacientes remitidos para TC, tras tratamiento agresivo de la insuficiencia cardaca pueden ser estabilizados o incluso hacer regresar su situacin de insuficiencia cardaca. Todos los pacientes evaluados para TC debern tener una limitacin importante de la capacidad funcional. Sin embargo, aun en presencia de una disfuncin cardaca avanzada, pueden existir otras causas de disnea de esfuerzo, como enfermedad pulmonar o muscular, esta ltima muchas veces en relacin con el descondicionamiento muscular motivado por las recomendaciones de minimizar el ejercicio a pacientes de insuficiencia cardaca. Para valorar la capacidad funcional de los pacientes se utilizan la ergometra convencional, el test de los 6 minutos y la ergometra con anlisis directo del intercambio de gases respiratorios, para medir el consumo mximo de oxgeno. Si el paciente es incapaz de caminar 300 metros en el test de los 6 minutos o si el consumo mximo de oxgeno es inferior a 10 ml/kg/min, el pronstico a corto plazo es malo y debera ser ya incluido en lista de espera de trasplante17. Sin embargo, la utilizacin del valor del consumo mximo de oxgeno como valor absoluto tiene potenciales limitaciones, ya que la capacidad de esfuerzo estimada vara con la edad, el sexo y la superficie corporal. Se ha visto que cuando el valor del consumo mximo de oxgeno era inferior al 50% del estimado para su peso, edad y sexo aumentaba la sensibilidad

para predecir eventos cardacos como muerte sbita o ingresos hospitalarios por descompensacin de IC. Adems, como en todos los tests funcionales, las determinaciones seriadas ayudan a identificar a aquellos pacientes que mejoran tras tratamiento mdico y/o programas de rehabilitacin o se deterioran mientras estn en lista de espera. Los criterios que se utilizan para decidir el momento de inclusin en lista de espera se basan en los propuestos por la Conferencia de Bethesda sobre TC y quedan recogidos en la tabla 2. CRITERIOS DE PRIORIZACIN Trasplante cardaco urgente Pacientes con retrasplante por fallo primario del injerto en el perodo inicial. Pacientes en situacin de shock cardiognico y con baln intraartico de contrapulsacin y/o ventilacin mecnica y/o asistencia mecnica circulatoria. Pacientes con arritmias malignas incontroladas situacin de tormenta arritmognica. Trasplante cardaco electivo Todos los pacientes en lista de espera que no cumplan los criterios anteriores. L. ALONSO-PULPN ET AL. GUAS DE ACTUACIN CLNICA DE LA SOCIEDAD ESPAOLA DE CARDIOLOGA. TRASPLANTE CARDACO Y DE CORAZN-PULMONES 825 TRASPLANTE DE CORAZN Y PULMN Las indicaciones de trasplante de corazn y ambos pulmones (TCP) han evolucionado con la mejora en los resultados del trasplante pulmonar, cuyas indicaciones, por otra parte, tanto de trasplante uni como bipulmonar, estn aumentando a expensas de enfermedades para las que slo el trasplante cardiopulmonar era una opcin. Adems, la creciente demanda de donantes para el TC reduce el nmero de bloques corazn-pulmn. Actualmente la necesidad de realizar un TCP viene determinada por el grado de disfuncin cardaca derecha y/o izquierda, la presencia o ausencia de enfermedad coronaria severa y la complejidad de la cardiopata congnita, en conjuncin con enfermedad pulmonar en situacin terminal. Indicaciones18 Hipertensin pulmonar primaria Presiones de arteria pulmonar iguales o por encima de dos tercios de las sistmicas. Insuficiencia cardaca derecha severa tras altas dosis de diurticos. Insuficiencia tricuspdea de grados 3 o 4. Fraccin de eyeccin de ventrculo derecho menor del 20%. Sndrome de Eisenmenger Defecto cardaco irreparable.

Insuficiencia cardaca derecha severa. Enfermedad parenquimatosa pulmonar Enfermedad pulmonar progresiva con: a) cor pulmonale, o b) disfuncin ventricular izquierda severa secundaria a enfermedad coronaria avanzada, valvulopata o miocardiopata. 3. SELECCIN DE DONANTES. CRITERIOS GENERALES DE ACEPTABILIDAD. EMPAREJAMIENTO DE DONANTE Y RECEPTOR. CRITERIOS DE URGENCIA EN TRASPLANTE CARDACO Una vez establecido el diagnstico de muerte enceflica es prioritaria una valoracin clnica completa para establecer la idoneidad del fallecido como donante de rganos y tejidos. La valoracin del donante de rganos aborda dos temas fundamentales: 1. Estudio morfolgico y funcional del rgano. 2. Descartar enfermedades transmisibles del donante. Para este fin es necesario: 1. Revisin pormenorizada de la historia clnica. 2. Exploracin clnica detallada. 3. Estudio analtico, pruebas complementarias y estudios serolgicos. 4. Evaluar el rgano durante el proceso de extraccin. Entre un 15 y un 35% de los fallecidos en situacin de muerte enceflica se excluyen como potenciales donantes tras la mencionada evaluacin. Sin embargo, debemos recordar que tan importante como la exclusin de estos fallecidos es no descartar a un donante potencial por desconocimiento de los criterios de aceptacin y de las pruebas diagnsticas que podemos realizar. Criterios de donante ptimo19-22 Edad menor de 40 aos. Sin antecedentes de parada cardaca. Serologa negativa para VIH y hepatitis B. Sin infeccin activa o neoplasia con posibilidad de metstasis. REVISTA ESPAOLA DE CARDIOLOGA. VOL. 52, NM. 10, OCTUBRE 1999 826 TABLA 2 Indicaciones de trasplante cardaco (Conferencia de Bethesda, 1993) Indicaciones definitivas para trasplante 1. Consumo mximo de oxgeno < 10 ml/kg/min habiendo alcanzado el umbral anaerbico 2. Clase funcional IV de la NYHA 3. Historia de hospitalizaciones recurrentes por insuficiencia cardaca congestiva 4. Isquemia severa que limita la actividad diaria y no es susceptible de revascularizacin quirrgica ni angioplastia y con FE < 20%

5. Arritmias ventriculares sintomticas recurrentes refractarias a todas las modalidades teraputicas aceptadas Indicaciones probables para trasplante 1. Consumo mximo de oxgeno < 14 ml/kg/min y limitacin significativa de la actividad diaria 2. NYHA clase III-IV 3. Hospitalizaciones recientes por insuficiencia cardaca congestiva. Inestabilidad entre el balance de lquidos y la funcin renal no debida a mal cumplimiento por parte del paciente del control del peso, tratamiento diurtico y restriccin de sal 4. Isquemia inestable recurrente no susceptible de revascularizacin quirrgica ni angioplastia con FE < 30% 5. Actividad ectpica ventricular de alto grado con historia familiar de muerte sbita Indicaciones inadecuadas para trasplante 1. Baja fraccin de eyeccin < 20% aislada 2. NYHA clase I-II 3. Angina de esfuerzo estable con fraccin de eyeccin de ventrculo izquierdo > 20% 4. Arritmias ventriculares previas 5. Consumo mximo de oxgeno > 14 ml/kg/min sin otras indicaciones