Cardiac transplantation is now an accepted treatment for end-stage heart disease, relieving symptoms, increasing exercise tolerance, and improving survival. A number of studies have demonstrated that exercise training can further improve exercise capacity and quality of life. The atypical response of the denervated heart to exercise requires that training intensity be based on metabolic measurements and/or perceived exertion rather than heart rate, in order to ensure efficacy and safety.
HosenpudJDNovickRJBreenTJKeckBDailyOP: The Registry of the International Society for Heart and Lung Transplantation: Twelfth Official Report. J Heart Lung Transplant1995; 1:805–815.
2.
YoungJBWintersWLBougeRUretskyBF: Task Force 4: Function of the heart transplant recipientJ Am Coll Cardiol1993, 22:31–41. Oneof a series of task force statements developed by the American College of Cardiology. This contains an excellent summary of the physiology and pathophysiology of the denervated heart, and also deals with assessment of quality of life after heart transplantation.
3.
HausdorfGBannerNRMitchellAKhaghaniAMartinMYacoubM: Diastolic function after cardiac and heart-lung transplantationBr Heart J1989, 62:123–132.
4.
PaulusWJBronzwaerJGFFeliceHKishanNWellensF: Deficient acceleration of left ventricular relaxation during exercise after heart transplantationCirculation1992, 86:1175–1185. Ahaemodynamic study of 27 orthotopic transplant recipients showing diastolic dysfunction in the cardiac allograft due, according to the authors, to decreased adrenergic tone, ischaemic injury, or cyclosporin-induced hypertension.
5.
KavanaghTYacoubMHCampbellRBMertensD: Marathon running after cardiac transplantation: A case historyJ Cardiopulmonary Rehabil1986, 6:16–20.
6.
PeriniROrizioCGambaAVeicsteinasA: Kinetics of heart rate and catecholamines during exercise in humansEur J Appl Physiol1993, 66:500–506. Furtherconfirmation of the denervated heart's catecholamine-mediated response to prolonged exercise. Frequent blood sampling (12 in all) coupled with beat-to-beat heart rate analysis characterises this report.
7.
KaoACVan TrigtPShaeffer-McCallGSShawJPKuzilBBPageRD: Central and peripheral limitations to upright exercise in untrained cardiac transplant recipientsCirculation1994, 89:2605–2615. Uprightexercise on the cycle ergometer was carried out on 30 cardiac transplant patients, 3–16 months after surgery, and 30 controls. The patients had a significantly reduced peak work rate, oxygen intake, and cardiac index. Pulmonary capillary wedge pressure, right atrial, and mean pulmonary arterial pressures were also elevated. Arteriovenous oxygen difference was 24% lower at peak effort in the transplant group. The authors attribute the limited exercise tolerance to a combination of chronotropic incompetence and diastolic dysfunction limiting the appropriate compensatory use of the Starling mechanism. They also speculate that there is a peripheral abnormality in oxygen transport or utilisation.
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BraithRWLimacherMCMillsRMLeggettSHPollockMLStaplesED: Exercise-induced hypoxemia in heart transplant recipientsJ Am Coll Cardiol1993, 22:767–776.
9.
StrattonJRKempGJDalyRCYacoubMRajagopalanB: Effects of cardiac transplantation on bioenergetic abnormalities of skeletal muscle in congestive heart failureCirculation1994, 89:1624–1631. Magneticresonance spectroscopy studies of forearm muscle during exercise revealed the presence of metabolic abnormalities before cardiac transplantation, and demonstrated their partial persistence for more than six months after surgery. This partially explains the exercise limitation experienced by long-term heart transplant patients. It also makes a case for the early introduction of exercise training after surgery.
10.
HaskellWLSavinWMSchroederJSAldermanEAInglesNBDaughtersGTStinsonEB: Cardiovascular responses to handgrip isometric exercise in patients following cardiac transplantationCirc Res Supp I1981, 48:1156–1161.
11.
KayeMPEsterM: Chronology and mode of reinnervention of the surgically denervated canine heart: Functional and chemical correlatesAm J Physiol1977, 2:431–437.
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RowanRABillinghamME: Myocardial innervation in long-term heart transplant survivors: A quantitative ultrastructural surveyJ Heart Transplant1988, 7:448–452.
13.
StarkRPMcGinnALWilsonRF: Chest pain in cardiac-transplant recipientsN Engl J Med1991, 324:1791–1794. Theearliest report of anginal-type chest pain in two cardiac transplantation patients with documented severe coronary heart disease. Both patients were also found to have significant release of myocardial norepinephrine in response to a tyramine challenge, an indicator of sympathetic reinnervation. By contrast, three other transplant patients, also with severe coronary disease, did not have any evidence of reinnervation from tyramine challenge, and did not experience anginal symptoms.
14.
FallenELKamathMVGhistaDNFitchettD: Spectral analysis of heart rate variability following human heart transplantation: Evidence for functional reinnervationJ Autonomic Nervous System1988, 23:199–206. Powerspectral analysis demonstrated normal heart rate variability in one of nine cardiac transplant recipients, 33 months after surgery. However, persistence of a resting tachycardia (94 beats per minute) suggests that only partial reinnervation had occurred.
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RudasLPflugfelderPWMenkisAHNovickRJMcKenzieFNKostukWJ: Evolution of heart rate responsiveness after orthotopic cardiac transplantationAm J Cardiol1991, 68:232–236. Across-sectional study of patients tested at two, 15, and 42 months after transplantation showed increasingly normal heart rate responses to (1) assuming the standing position, and (2) exercise testing; both indicators of autonomic reinnervation.
16.
FolinoAFBujaGMiorelliMLiviUNavaAThieneG: Heart rate variability in patients with orthotopic heart transplantation: Long-term follow-upClin Cardiol1993, 16:539–542.
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SchwaigerMHutchinsGDKalffVRosenspireKHakaMSMalletteS: Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomographyJ Clin Invest1991, 87:1681–1690.
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KayeDMEslerMKingwellBMcPhersonGEsmoreDJenningsG: Functional and neurochemical evidence for partial cardiac sympathetic reinnervation after cardiac transplantation in humansCirculation1993, 88:1110–1118. Across-sectional study comprising ten ‘early’ (mean 24 weeks) and five ‘late’ (mean 210 weeks) post-transplant patients, which measured cardiac norepinephrine release, as well as heart rate variability. The results provide evidence of partial sympathetic reinnervation.
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WilsonRFChristensenBVOlivariMTSimonAWhiteCWLaxsonDD: Evidence for structural sympathetic reinnervation after orthotopic cardiac transplantation in humansCirculation1991, 83:1210–1220.
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WilsonRFLaxsonDDChristensenBVMcGinnALKuboSH: Regional differences in sympathetic reinnervation after human orthotopic cardiac transplantationCirculation1993, 88:165–171. Byinjecting tyramine into the left main and right coronary arteries and later into the left anterior descending or circumflex branch it was possible to demonstrate, in long-term heart transplants (1 year) that (1) sympathetic reinnervation to the sinus node occurs frequently and (2) left ventricular reinnervation may occur in a patchy manner and through multiple pathways.
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WhartonJPolakJMGordonLBannerNRSpringallDRRoseM: Immunohistochemical demonstration of human cardiac innervation before and after transplantationCirculation Research1990, 66:900–912.
22.
LordSWBradySHoltNDMitchellLDarkJHMcCombJM: Exercise response after cardiac transplantation: Correlation with sympathetic reinnervationHeart1996, 75:40–43. Eightorthoptic heart transport patients in whom intracoronary injection of tyramine resulted in a greater than 25% increase in heart rate were also shown to achieve on exercise testing an associated higher work rate and peak heart rate, as well as a more rapid recovery rate than patients in whom response to tyramine was less marked. The authors conclude that sympathetic efferent sinus node reinnervation can occur, and can result in a increased exercise time and total workloads, although not to normal levels.
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McGregorCGA: Cardiac transplantation: Surgical considerations and early postoperative managementMayo Clin Proc1992, 67:577–585. Acomprehensive and well-written review of the Mayo Clinic Heart Transplant Program.
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SavinWMHaskellWLSchroederJSStinsonEB: Cardiorespiratory responses of cardiac transplant patients to graded, symptom-limited exerciseCirculation1980, 62:55–60.
25.
NaugthonJPHaiderR: Methods of exercise testing. In Exercise testing and exercise training in coronary heart disease. New York: Academic Press; 1973:79–91.
26.
LermanJBruceRASivarajonEPettetGEMTrimbleS: Low-level dynamic exercises for earlier cardiac rehabilitation: Aerobic and hemodynamic responsesArch Phys Med Rehabil1976, 57:355–360.
27.
KavanaghTYacoubMHMertensDJKennedyJCampbellRBSawyerP.Cardiorespiratory responses to exercise training after orthotopic cardiac transplantationCirculation1988, 77:162–171. Thelargest heart transplant patients training study to date. The achievement of a training bradycardia, particularly in the highly compliant subjects, is attributed to the duration of the programme, with the likely mechanisms (1) a reduction in serum norepinephrine levels, (2) an increase in myocardial -receptor density and/or affinity, and (3) an increase in skeletal muscle mass. Unfortunately, the study lacks a control group (see Table 1).
28.
KavanaghT: Exercise and therapy of the cardiac transplant patient In Exercise and the Heart in Health and Cardiac Disease. Edited by MillerHCShephardRJ.New York: Marcel Dekker, Inc.; 1991:257–282. Acomprehensive review of rehabilitation after heart transplantation.
29.
KavanaghTYacoubMH: The benefits of exercise for heart transplant patientsPerspect Cardiol1988, 4:21–37.
30.
BrubakerPHBerryMJBrozenaSCMorleyDLWalterJDPaoloneAM: Relationship of lactate and ventilatory thresholds in cardiac transplant patientsMed Sci Sports Exerc1993, 25:191–196. Acomparison between the invasive (blood lactates) and non-invasive (ventilatory) determination of anaerobic threshold in cardiac transplant patients and normal controls. There was no significant difference between the oxygen intake at which both lactate threshold and ventilatory threshold occurred in heart transplants. The same was true for normals, although the absolute values were higher than in the transplants. Neither was there any difference between the relative oxygen intake (% peak) at which lactate threshold and ventilatory threshold occurred in transplants and normals. The authors conclude that exercise training intensity at or below the ventilatory threshold can be used with safety in cardiac transplant patients.
31.
BraithRWWoodCELimacherMCPollockMLLowenthalDTPhillipsMI: Abnormal neuroendocrine responses during exercise in heart transplant recipientsCirculation1992, 86:1453–1463. Changesin plasma norepinephrine, vasopressin, and renin activity from rest to exercise were found to be similar in heart transplant patients and normal controls at an exercise intensity of 40% of VO2max, but significantly greater in the patients when exercise intensity was increased to 70% VO2max. The authors hypothesised that this chronic neuroendocrine hyperactivity may be a major contributor to post-transplant hypertension.
32.
WinderWHagbergJHicksonREhsaniAMcLaneJ: Time course of sympathoadrenal adaptation to endurance exercise training in manJ Appl Physiol1978, 45:370–374.
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DuncanJJFarrJEUptonSJHaganRDOglesbyMEBlairSN: The effects of aerobic exercise on plasma catecholamines and blood pressure in patients with mild hypertensionJAMA1985, 254:2609–2613. Mildlyhypertensive men obtained benefit from a 16-week aerobic exercise training programme in terms of fitness level and reduced systolic and diastolic blood pressures, the reductions in systolic pressure being 6.3 mmHg, 10.3 mmHg, and 15.5 mmHg for normals, normoadrenergic, and hyperadrenergic groups respectively.
34.
SmartFWBallantyneCMCocanougherBFarmerJASekelaMENoonGP: Insensitivity of noninvasive tests to detect coronary artery vasculopathy after heart transplantAm J Cardiol1991, 67:243–247. Annualnon-invasive surveillance of 73 heart transplant patients, 19 of whom went on to develop coronary artery vasculopathy, proved to be ineffectual in predicting the development of disease. The tests employed included two-dimensional resting echocardiography, rest and exercise wall motion studies, dipyridamole-thallium scintigraphy, and 48-hour ambulatory monitoring. Ambulatory monitoring gave the highest positive predictive value of 53% (arrhythmia, and not ST segment depression, being the predictive feature) with exercise testing the lowest at 21 %. These values are no better than chance in diagnosing disease.
35.
EhrmanJKKeteyianSJLevineABRhoadsKLElderLRLevineB: Exercise stress tests after cardiac transplantationAm J Cardiol1993, 71:1372–1373. Exercisetesting was carried out on 36 heart transplant patients (28 men, eight women), followed by coronary angiography. Three patients had ST-segment depression ≥ 0.5 mm, but none had coronary stenosis. Seven patients had significant coronary disease on angiography, but none had ST-segment depression. The authors point out that the inability of the exercise test to detect ischaemia may have been due to (1) the patient's failure to reach 90% of their predicted heart rate, and (2) the prevalence of right bundle branch block in 60% of the tests.
36.
KavanaghTYacoubMH: Exercise and cardiac rehabilitation In Current Therapy in Sports Medicine. Edited by TorgJSSheppardRC.St Louis: Mosby Year Book; 1995:663–668.
37.
SquiresRWArthurPRGauGTMuriALambertWB: Exercise after cardiac transplantation: A report of two casesJ Cardiac Rehabil1983, 3:570–574. Asmall study, with limited measurements, but the first to demonstrate that an early out-patient exercise training programme for heart transplant patients is feasible and safe (see Table 1).
38.
SavinWMGordonEGreenSHaskellWKantrowitzNLunbergM: Comparison of exercise training effects in cardiac denervated and innervated humans [abstract]J Am Coll Cardiol1983, 1:722. Theconclusions drawn from this study were that innervation was not required to obtain a training-induced increase in work capacity and decrease in submaximal heart rates, but is required to produce a resting bradycardia, at least when the training duration is only four months (see Table 1).
39.
SieuratPRoquebruneJPGrinneiserDBourrionFElbezeJPJourdanJ: Monitoring and rehabilitation of heterotropic transplantation patients during the period of convertescence [in French]Arch Mal Coeur1986, 2:210–216.
40.
DegréSNisetGDesmetJMAbramonicaMIbrahimTStoupelE: The effect of physical training on the human denervated heart after cardiac transplantation [in French]Ann Cardiol Angeiol1986, 35:147–149.
41.
NisetGCousty-DegréCDegréS: Psychosocial and physical rehabilitation after heart transplantation: 1 -year follow-upCardiology1988, 75:311–317.
42.
KavanaghTYacoubMHMertensDJCampbellRBSawyerP: Exercise rehabilitation after heterotopic cardiac transplantationJ Cardiopulmonary Rehabil1989, 9:303–310. An18-month training programme resulted in a training bradycardia in the recipient but not the donor heart.
43.
KeteyianSEhrmanJFedelFRhoadsK: Heart rate-perceived exertion relationship during exercise in orthotopic heart transplant patientsJ Cardiopulmonary Rehabil1990, 10:287–293. Thepurpose of the study was to compare ratings of perceived exertion and heart rate responses during exercise training and exercise testing. The conclusions were that exercise training intensity held at an RPE of 12–14 throughout the training period is both safe and effective.
44.
KeteyianSShepardREhrmanJFedelFGlickCRhoodesK: Cardiovascular responses of heart transplant patients to exercise trainingJ Appl Physiol1991, 70:2627–2631.
45.
EhrmanJKeteyianSFedelFRhoadsKLevineBShepardR: Ventilatory threshold after exercise training in orthotopic heart transplant patientsJ Cardiopulmonary Rehabil1992, 12:126–130. Theprime purpose of this study was to determine the effect of an 8–10 week training programme on the ventilatory threshold. The absolute ventilatory threshold was found to increase significantly, but there was no change in the relative ventilatory threshold (training heart rate = VO2 at VT/Peak VO2×100).
46.
BraithRWLimacherMCLeggettSHPollockML: Skeletal muscle strength in heart transplant patientsJ Heart Lung Transplant1993, 12:1018–1023. Theauthors demonstrate that there is a high correlation (r = 0.90) between quadriceps strength and peak oxygen intake in heart transplant patients, and consequently weak leg musculature contributes to reduced exercise performance.
47.
HorberFFScheideggerJRGrunigBFFreyFJ: Evidence that prednisoneinduced myopathy is reversed by physical trainingJ Clin Endocrinol Metab1985, 6:83–88. Twelverenal transplant patients receiving prednisone immunosuppressant therapy, when compared with 12 normal subjects, were found to have a 20% reduction in muscle, a 36% increase in fat to muscle ratio, and a 20% reduction in total work output in the mid-thigh area. After 90 days of isokinetic training muscle area increased, fat area decreased, and total work output normalised.
