AK underwent heart transplantation in 2007 for arrhythmogenic right ventricular cardiomyopathy. Just two years later she completed the 1500 meter final at the World Transplant Games in Gold Coast, Australia in a record time of 07:19:07 for the women's 50-59 year old age group. Her gold medal is displayed in the entrance to our clinic as an incentive to our patients. Every year since 1987 the World Transplant Games have been held to showcase the athletic achievements of patients who have undergone organ transplantation. Review of these results reveals competitive times and feats of strength by age group.¹

With approximately 5,000 heart transplants performed worldwide each year, and the median survival after transplantation now exceeding 10 years, the number of living transplant recipients continues to grow.² Unfortunately, some heart transplant recipients have complex post-operative courses requiring extensive medical care, including treatment for early rejection,³ making physical rehabilitation post-transplant more difficult. However, when the rehabilitation process does start many patients set a goal of returning to a level of physical fitness at which they performed prior to the onset of heart disease, or in some cases to even exceed their previous level of athletic performance. In the majority of heart transplant recipients, quality of life greatly exceeds that experienced with advanced heart failure, and most patients are able to return to normal functional activity after recovery from transplant surgery.⁴ A select group of transplant recipients have pushed the envelope and with aggressive training have participated in highly competitive sports.⁵

The transplanted heart responds differently to exercise than the native heart due to multiple factors which can include autonomic denervation, ischemic time and reperfusion during transplant, diastolic dysfunction secondary to rejection and allograft vasculopathy, altered metabolism and skeletal muscle histology which may be acquired due to severe heart failure prior to transplant and other factors.^6-8 The diastolic dysfunction of the allograft and skeletal muscle pathology may improve initially after transplant, but see minimal improvement over subsequent years. Factors such as chronotropic response from denervation during surgery and peripheral oxygen uptake assessed by the maximal rate of oxygen uptake (VO₂ max) have been shown to improve over time and through structured rehabilitation programs.⁹

Immediately following cardiac transplantation, the allograft lacks both parasympathetic and sympathetic innervation, and as a result both resting heart rate and chronotropic response to exercise differ in the transplant patient as compared to age-matched controls. The inherent rate of sinus node depolarization in most adults ranges from 95-115bpm, and without parasympathetic innervation this represents the baseline heart rate immediately following transplantation.¹⁰ Lack of sympathetic innervation results in a slower rise to peak heart rate during exercise, a slower decline following exercise, and a less significant difference between resting heart rate and maximal rate during exercise.⁸ However, partial reinnervation, predominantly sympathetic, occurs in many patients in the months to years following transplant.^11-15 Reinnervation as demonstrated via positron-emission tomography has been associated with increased heart rate at maximal exercise and increased duration of exercise at peak heart rate.^16,17 Furthermore, at least one-third to as many as two-thirds of subjects exhibit a partial normalization of heart rate response to exercise from six months to one year after surgery.^18,19 The transplanted heart increases stroke volume with exercise significantly more than control subjects allowing cardiac output to be increased in light of the blunted heart rate response. While it has been postulated that circulating norepinephrine levels are responsible for augmenting heart rate and stroke volume during exercise in the transplant recipient, and that use of beta blockade can blunt this response,¹⁵ some studies have failed to show the rise in serum catecholamines that would account for this augmentation.²⁰

Cardiac transplant recipients also demonstrate differences from normal individuals in regards to net oxygen uptake in peripheral tissues as well as ventilation response to exercise.²¹ Peak VO₂ measured during maximum effort exercise testing is arguably the most objective measure of functional capacity and is a strong predictor of mortality in patients with heart failure.²² Peak VO₂ is measured during a maximum effort, symptom limited cardiopulmonary exercise test.

VO₂ max = Q x (C_aO₂ – C_vO₂)
Q = cardiac output calculated by (maximum heart rate) x (maximum stroke volume)
C_aO₂ – C_vO₂ is the arterial oxygen content – venous oxygen content, which assesses the maximum net oxygen uptake of end organ tissues.

Numerous studies have shown that in heart transplant recipients, maximum oxygen uptake with exercise averages 40-70% of that of age matched controls but appears to increase over time, as does the ventilation threshold with training.^23-26 It is known that standardized exercise training can significantly improve peak VO₂ by increasing the mitochondrial oxygen capacity of skeletal muscle cells. This increase in peak VO₂ with training may explain why some transplant recipients are able to participate in competitive sports while others do not reach the degree of function they enjoyed prior to transplant.6 Multiple studies have demonstrated that both moderate-intensity and high-intensity exercise programs can increase VO₂ max as compared to control groups.⁹ While most post-transplant rehabilitation programs recommend standardized moderate-intensity exercise, it is possible that programs with a greater level of intensity may offer superior results in increasing exercise capacity. A recent study investigating high-intensity interval training as compared to a moderate training regimen showed that the more intense program resulted in significantly greater increases in VO₂ max as well as both peak heart rate and heart rate recovery, thus demonstrating the effects of such a regimen on both chronotropic response and skeletal muscle oxidative capacity.²⁷

Another challenge to the competitive athlete following heart transplant may be expanded plasma volume. In one study of transplant recipients plasma volume was found to be higher than in normal controls by 12%.²⁰ The expansion of plasma volume has been hypothesized to allow for augmented stroke volume in the transplanted heart by increasing venous return during exercise. This may indicate that in order to maximally increase cardiac output and stroke volume with exercise, transplant recipients may need to balance a relatively expanded blood volume and yet not burden their circulatory system with excess volume in the form of edema, pulmonary or otherwise.

Exercise therapy after heart transplant is feasible and can be started as early as 6-8 weeks after surgery when sternal healing is nearly completed.⁸ Formal outpatient cardiac rehabilitation may begin at the time of discharge from the hospital. Transplant recipients undergoing exercise therapy should begin in a monitored setting with continuous ECG monitoring. Though not necessary at the start of exercise therapy, graded exercise testing should be performed 6-8 weeks after transplant to determine the individual's response to exercise and modify the exercise therapy regimen. Maintaining exercise capacity by ongoing exercise therapy, whether performed in a supervised or unsupervised setting, is useful for maintaining functional capacity in the setting of deconditioning from advanced heart failure, the perioperative period, hemodynamic alterations of the transplanted heart, and chronic steroid use. There may be a role for interval graded exercise tests to monitor exercise capacity and allow modification of exercise regimen.

There have been numerous reports in both the popular media and in the medical literature of people whom are able to perform at an impressive level of physical fitness post heart transplant. From competitive cycling, grueling endurance competitions,^28-30 climbing the world's tallest peaks,³¹ and participation in the national and international Transplant Games, we know that some transplant recipients are able to achieve a level of physical fitness that allows them to participate in competitive athletic events. It is also possible that as future studies better elucidate the most effective intensity, duration, and timing of exercise training post-transplantation that a greater number of patients may be able to participate in competitive athletics than previously thought possible.

References

1. World Transplant Games Federation. 2016; wtgf.org. Accessed 10/30/2016.
2. Stehlik J, Edwards LB, Kucheryavaya AY, et al. The registry of the international society for heart and lung transplantation: twenty-eight adult heart transplant report--2011. J Heart Lung Transplant 2011;30:1078-94.
3. Squires RW. Exercise training after cardiac transplantation. Med Sci Sports Exerc 1991;23:686-94.
4. Lund LH, Edwards LB, Kucheryavaya AY, et al. The registry of the international society for heart and lung transplantation: thirtieth official adult heart transplant report--2013; focus theme: age. J Heart Lung Transplant 2013;32:951-64.
5. Haykowsky MJ, Riess KJ, Schneider CA. Ironman triathlon performance pre- and post-heart transplant. J Heart Lung Transplant 2015;34:756.
6. Lampert E, Mettauer B, Hoppeler H, Charloux A, Charpentier A, Lonsdorfer J. Structure of skeletal muscle in heart transplant recipients. J Am Coll Cardiol 1996;28:980-4.
7. Lampert E, Mettauer B, Hoppeler H, Charloux A, Charpentier A, Lonsdorfer J. Skeletal muscle response to short endurance training in heart transplant recipients. J Am Coll Cardiol 1998;32:420-6.
8. Squires RW. Exercise therapy for cardiac transplant recipients. Prog Cardiovasc Dis 2011;53:429-36.
9. Nytroen K, Yardley M, Rolid K, et al. Design and rational of the HITTS randomized controlled trial: Effect of High-intensity Interval Training in de novo Heart Transplant Recipients in Scandinavia. Am Heart J 2016;172:96-105.
10. Squires R. Transplant. In: Pashkow FJ, Dafoe WA, editors. Clinical cardiac rehabilitation: a cardiologist's guide, 2nd ed. Baltimore, MD: Williams and Wilkins; 1999. P. 175-91.
11. Stark RP, McGinn AL, Wilson RF. Chest pain in cardiac-transplant recipients--evidence of sensory reinnervation after cardiac transplantation. N Engl J Med 1991;324:1791-4.
12. Lord SW, Brady S, Holt ND, Mitchell L, Dark JH, McComb JM. Exercise response after cardiac transplantation: correlation with sympathetic reinnervation. Heart 1996;75:40-3.
13. Estorch M, Camprecios M, Flotats A, et al. Sympathetic reinnervation of cardiac allografts evaluated by 123I-MIBG imaging. J Nucl Med 1999;40:911-6.
14. Bengel FM, Ueberfuhr P, Schiepel N, Nekolla SG, Reichart B, Schwaiger M. Myocardial efficiency and sympathetic reinnervation after orthotopic heart transplantation: a noninvasive study with positron emission tomography. Circulation 2001;103:1881-6.
15. Bngel FM, Ueberfuhr P, Karja J, et al. Sympathetic reinnervation, exercise performance and effects of beta-adrenergic blockade in cardiac transplant recipients. Eur Heart J 2004;25:1726-33.
16. Bengel FM, Ueberfuhr P, Schiepel N, Nekolla SG, Reichart B, Schwaiger M. Effect of sympathetic reinnervation on cardiac performance after heart transplantation. N Engl J Med 2001;345:731-8.
17. Schwaiblmair M, von Scheidt W, Uberfuhr P, et al. Functional significance of cardiac reinnervation in heart transplant recipients. J Heart Lung Transplant 1999;18:838-45.
18. Squires RW, Leung TC, Cyr NS, et al. Partial normalization of the heart rate response to exercise after cardiac transplantation: frequency and relationship to exercise capacity. Mayo Clin Proc 2002;77:1295-300.
19. Nytroen K, Myers J, Chan KN, Geiran OR, Gullestad L. Chronotropic responses to exercise in heart transplant recipients: 1-yr follow-up. Am J Phys Med Rehabil 2011;90:579-88.
20. Braith RW, Plunkett MB, Mills RM. Cardiac output responses during exercise in volume-expanded heart transplant recipients. Am J Cardiol 1998;81:1152-6.
21. Savin WM, Haskell WL, Schroeder JS, Stinson EB. Cardiorespiratory responses of cardiac transplant patients to graded, symptom-limited exercise. Circulation 1980;62:55-60.
22. Balady GJ, Arena R, Sietsema K, et al. Clinician's guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation 2010;122:191-225.
23. Nytroen K, Gullestad L. Exercise after heart transplantation: an overview. World J Transplant 2013;3:78-90.
24. Borrelli E, Pogliaghi S, Molinello A, Diciolla F, Maccherini M, Grassi B. Serial assessment of peak VO₂ and VO₂ kinetics early after heart transplantation. Med Sci Sports Exerc 2003;35:1798-804.
25. Marconi C. Pathophysiology of cardiac transplantation and the challenge of exercise. Int J Sports Med 2000;21:S106-8.
26. Braith RW, Edwards DG. Exercise following heart transplantation. Sports Med 2000;30:171-92.
27. Dall CH, Snoer M, Christensen S, et al. Effect of high-intensity training versus moderate training on peak oxygen uptake and chronotropic response in heart transplant recipients: a randomized crossover trial. Am J Transplant 2014;14:2391-9.
28. Patterson JA, Walton NG. Exercise limitations in a competitive cyclist twelve months post heart transplantation. J Sports Sci Med 2009;8:696-701.
29. Haykowsky MJ, Riess K, Burton I, Jones L, Tymchak W. Heart transplant recipient completes ironman triathlon 22 years after surgery. J Heart Lung Transplant 2009;28:415.
30. Richard R, Verdier JC, Duvallet A, et al. Chronotropic competence in endurance trained heart transplant recipients: heart rate is not a limiting factor for exercise capacity. J Am Coll Cardiol 1999;33:192-7.
31. Kapp C. Heart transplant recipient climbs the Matterhorn. 42-year-old Kelly Perkins becomes the first person with a heart transplant to ascend the 4478-m peak. Lancet 2003;362:880-1.

Keywords: Allografts, Arrhythmogenic Right Ventricular Dysplasia, Athletes, Autonomic Denervation, Cardiac Output, Catecholamines, Denervation, Edema, Electrocardiography, Exercise, Exercise Therapy, Exercise Test, Heart Failure, Heart Rate, Heart Transplantation, Norepinephrine, Perioperative Period, Physical Fitness, Plasma Substitutes, Plasma Volume, Positron-Emission Tomography, Quality of Life, Sinoatrial Node, Stroke Volume, Transplantation

< Back to Listings