Cardiac rehabilitation before and after cardiac transplantation

Author(s): Maricarmen Cruz, MD, Isabel Borras-Fernandez, MD, Xavier Aviles-Guzman, MD, Cristina Isabel Sepulveda-Alamo

Originally published:09/20/2013

Last updated:09/20/2013



Heart transplantation (HT) is the procedure in which a failing heart is replaced by a healthy heart from a suitable donor in order to re-extablish myocardial function.


Common causes leading to a heart transplantation are: nonischemic cardiomyopathy (54%), ischemic cardiomyopathy (37%), valvular heart disease (3%), congenital heart disease (3%), hypertension (HTN), infections, alcohol/drug use, and unknown.1

Epidemiology including risk factors and primary prevention

There are approximately 2300 new cases of HT in the United States yearly, and 3742 worldwide.2 The median heart allograft donor age in 2010 was 31 years in the U.S. compared to 42 years in Europe.3 Seventy five percent of heart transplant candidates are men. Recipients’ survival risk is affected by the need of requiring a ventilator or left ventricular assist device prior to transplantation, a previous transplant, coronary artery disease or cardiomyopathy, and older age.


Asthe heart is failing, the musculoskeletal system is subject todeconditioning and muscle atrophy associated withdecreased mitochondrial content, decreased oxidative enzymes, and a shift toward less fatigue-resistant type IIb fibers.4In the lungs,there is ventilation/perfusion mismatch with a severity related to the same as heart failure (HF); after transplant, forced expiratory volume at1 second(FEV1),forced vital capacity, and total lung capacity normalize; however, decreased diffusing capacity may persistbecause ofvascular and parenchymal abnormalities.5

Cardiac transplantation results in postganglionic denervation, leading to the inability to respond to the parasympathetic nervous system.The denervated heartpresents with higher systolic and diastolic blood pressures, elevated heart rate (HR) at rest, lower maximal myocardial oxygen consumption, lower heart rate reserve, and decreased exercise duration.6Physiologic changes in exercise response are catecholamine dependent, thus delaying recovery after exercise.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

HT candidates present with deteriorating cardiac function that has not responded to conventional medical therapy and fall into the New York Heart Association (NYHA) disease class III (moderate) or IV (severe).7

Outcomes after transplantation have improved significantly: the 1-year survival rate is about 81.8%, and the 5-year survival rate is 69.8%.3 Patients’ outcomes are affected by pre-existing conditions, especially HTN, diabetes mellitus (DM) and obesity, and the development of secondary complications.7 Other factors that influence the evolution of the disease are immunosuppressive therapies. In general, the overall 10-year mortality is about 50%. From a functional and emotional point of view, the patients quality of life is significantly improved, and approximately 90% of patients report not having any activity limitations within the first 5 years after a HT.3

Specific secondary or associated conditions and complications

Expected conditions and complications include: pulmonary HTN, DM, HTN, acute rejection, cardiac allograft vasculopathy, renal dysfunction/failure, opportunistic infection, wound dehiscence, peripheral neuropathy and myopathy, obesity, severe peripheral vascular or cerebrovascular disease, and malignancy.



Symptoms that should be pursued include the following:

  1. Pain
  2. Breathlessness
  3. Persistent cough
  4. Fatigue
  5. Palpitations
  6. Limitations in physical activity, associated with angina or not
  7. Anxiety
  8. Depression
  9. Sleeping problems
  10. Nausea
  11. Constipation
  12. Edema

History also should include the following: duration of symptoms, prior functional level, home and community environmental barriers, musculoskeletal complaints, symptoms consistent with neurologic and/or vascular diseases, a psychosocial assessment, use of assistive devices, and postsurgical complications.

Physical examination

Signs observed during the examination reflect the physiologic changes of deconditioning and of a denervated heart and should include monitoring of the following:

  1. General medical status including hypotension, fever, shortness of breath, edema, and fatigue (signs of acute rejection).4
  2. Hemodynamic status including resting HTN, elevated resting HR, and decreased chronotropic response.
  3. Cardiopulmonary status including jugular-venous distention, rales, displaced apical pulse, third and fourth heart sounds, hepatomegaly, edema, abdominal distension, and hyperventilation.
  4. Musculoskeletal status including decreased muscle mass and strength, contractures and pain, proximal weakness (myopathy secondary to corticosteroid use), edema, pigmentation of skin, and diminished pulses (peripheral vascular resistance).
  5. Neurologic status including decreased reflexes, impaired sensation, proximal muscles weakness, and impaired balance.

Functional assessment

Tools used for clinical functional assessments in HF patients mostly focus on measuring quality of life and symptoms, such as the Minnesota Living with Heart Failure Questionnaire, the Sickness Impact Profile, and the Sense of Coherence Scale.8

Laboratory studies

Side effects related to chronic immunosuppression should be followed (leukopenia, thrombocytopenia, renal dysfunction, hyperglycemia, hyperlipidemia, opportunistic infection, and malignancies) using the following tests:

  1. Complete blood count
  2. Comprehensive metabolic panel
  3. Lipid profile
  4. Trough levels of immunosuppresive medications (eg, calcineurin inhibitors and target of rapamycin; maintenance doses are adjusted using the trough level).


Essential imaging studies include: electrocardiogram (previous myocardial infarct), echocardiograms (cardiac structure and function), heart catheterizations (including right atrial and ventricular assessment), metabolic stress tests (severity of cardiac functional impairment and risk stratification pretransplant), holter monitoring (arrhythmias), endomyocardial biopsy, and coronary angiography (acute rejection and accelerated atherosclerosis posttransplant).9

Supplemental assessment tools

  1. The six-minute walk test measures functional exercise capacity.
  2. The Borg Rate of Perceived Exertion Scale determines the perceived exertion during various levels of exercise intensity.4

Early predictions of outcomes

No single tool has enough predictive power to stratify patients in advanced HF, in part related to the variability in the clinical course previous to cardiac transplant. Bad prognostic factors are: peak oxygen consumption of less than 14 mL/kg/min, or less than 50% of predictive value for older age (>70 y); being a woman (worse prognosis); age (>70 y); etiology of heart disease (coronary artery disease, cardiomyopathy); longer duration of illness; obesity (body mass index >30); active infections; severe DM with end organ damage; peripheral vascular or cerebrovascular diseases; creatinine greater than 2.5 mg/dL or creatinine clearance less than 25 mL/min; bilirubin greater than 2.5 mg/dL; serum transaminases greater than 3 times the reference ranges; international numeric ratio greater than 1.5 off warfarin; severe pulmonary dysfunction with FEV1 less than 40% predicted; recent pulmonary infarction within 6 to 8 weeks; uncontrolled HTN; neuromuscular disorders; mental illness; substance abuse; and reduced functional capacity whether estimated by NYHA class or exercise testing.10,11


Explore architectural (stairs, hills), transportation, and mobility barriers.

Social role and social support system

A holistic approach, including psychologic, social, and spiritual assessment is recommended. Depression, anxiety, sleeping difficulties, and adjustment disorders are commonly seen. Psychiatric history or history of substance abuse may contribute to functional limitations and affect compliance to treatment posttransplant. Transportation barriers can interfere with continuity of care; family involvement is key home management support. Poor medical compliance after the postoperative recovery may account for significant morbidity and for up to 25% of deaths.12

Professional Issues

Only 2200 transplants are performed each year in the U.S., because there is a shortage of donors, making research and follow-up challenging.10


Available or current treatment guidelines

Heart transplant candidates should initiate an exercise routine prior to surgery. Posttransplant, patients will be deconditioned, with impaired functionally capacity, decreased cardiac output, and decreased maximal oxygen capacity.

There are several reasons for persistent abnormal exercise capacity early after cardiac transplantation:

  1. Marked deconditioning before heart transplant
  2. Surgical denervation
  3. Skeletal muscle weakness
  4. Corticosteroids

Cardiac rehabilitation programs could extend from 4 weeks to 6 months, depending on the patient’s postoperative course.

At different disease stages

  1. Pretransplant stage8:
    • Left ventricular assist devices (LVADs) can serve as a viable bridge before tranplantation, allowing an opportunity to recondition through aerobic training that can include treadmill or free ambulation.
  2. New onset/acute13:
    • Physical conditioning should begin during the inpatient phase, once hemodynamic stabilization has been achieved.
    • Exercise programs should include aerobic exercises in cycle-ergometer or walking with progressive increase on duration and intensity and articular mobility, flexibility, and resistance of large muscular groups. Monitoring should include HR and blood pressure, and subjective fatigue with the Borg Scale.
    • On discharge, patients should be stable walking on level surfaces; sternum is essential, limiting the use of the upper limb to sit-to-stand and transfers.
  3. Subbacute14:
    • Programs can begin as early as 2 weeks postsurgery. Structured-supervised programs demonstrate superior outcomes over home-based programs in a physical work capacity and activities of daily living.
    • Walking is recommended on alternate days; the exercise program should progress to include: closed-chain resistive activities (bridging, half squats, toe raises), abdominal exercises (curl ups and pelvic tilts), flexibility exercises (chest expansion and thoracic mobility, side stretch, trunk twist, scapular squeezes, shoulder rolls), and aerobic exercises (treadmill walking or pedaling on bicycle ergometer). The duration and intensity shall progressively increase to meet the patient’s tolerance with a goal of 30 minutes of continuous aerobic exercise at moderate intensity for each session.
    • Patients suspected of organ rejection must be halted from training until endomyocardial biopsy shows resolution of rejection.
  4. Chronic/stable:
    • Cardiac transplant patients may survive for more than 25 years.
    • Chronic immunosuppression may lead to infections, malignancy, and renal deterioration.
    • Exercise routines should be adopted daily.
    • Exercise must be halted if organ rejection is suspected.
  5. Preterminal or end of life care13:
    • An interdisciplinary approach is used to address patient and family needs.
    • Providers need to educate patient/family about disease progression, functional decline, advanced care planning, and end of life decisions.
    • Goals are targeted to maximize quality of life, focusing on symptoms management. These include: pain relief, affirming life and regarding dying as a normal process, and offering a support system to help patients live as actively as possible.

Coordination of care

Coordination of care seems challenging with great opportunity for improvement.15 Disease unpredictability challenges providers in forming enduring relationships.16 Interdisciplinary coordination of care should begin pretransplant before end-stage heart disease occurs, and is led by a physician. The team should include specialists in HF, rehabilitation, palliative care, social work, and a spiritual and psychologic counselor.12Coordination should integrate both hospitalized and community-based patients.

Patient & family education

Education needs assessment must include the patient and family. It must integrate symptoms management and avoid unnecessary admissions. Models in palliative care in the United Kingdom and Switzerland train nurses in community skills that provide symptom management support at home.12

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

HT patients require an effective education program where they become aware of the course of their recovery, including understanding of the medication regimes need and potential side effects. Clinicians need to closely monitor medications interaction and their side effects. Unusual neuropathies can be observed postsurgically, such as peroneal, axillary, and radial, among others.


Cutting edge concepts and practice

Stem-cell therapy in treatment for heart failure:

The STAR-HEART clinical trial by Strauer et al17 showed that intracoronary infusion of CD 34+/CD 133 stem cells improved myocardial function and patients’ exercise capacity, with persistent benefits for 5 years.


Gaps in the evidence-based knowledge

It is recognized that the incidence and types of immune suppression-associated malignancies vary with extent and completeness of follow-up.18

There are concerns about the risk of adverse events, including bleeding and thromboembolic events with recent miniaturization of the LVADs. More experience is needed.19


1. Jurt U, Delgado D, Malhotra K, Bishop H, Ross H. Cardiology patient pages. Heart transplant: what to expect. Circulation. 2002;106:1750-1752.

2. United Network of Organ Sharing (UNOS) and The Registry of the International Society of Heart and Lung Transplantation (ISHLT) ( registry.asp). The registry of the International Society of Heart and Lung Transplantation: twenty-fifth annual report. J Heart Lung Transplant. 2008;27:937-983.

3. Stehlik J, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society of Heart and Lung Transplantation MS: 29th official adult heart transplant report–2012. J Heart Lung Transplant. 2012:31:1052-1064.

4. Cordes C. Rehabilitation after cardiac transplantation. In: Perk J, Mathes P, Gohlke H, et al, eds. Cardiovascular Prevention and Rehabilitation. London, UK: Springer-Verlag; 2007:407-415.

5. Ravenscraft SA, Gross CR, Kubo SH, et al. Pulmonary function after successful heart transplantation–one year follow up. Chest. 1993;103:54-58.

6. Wilson RF, Johnson, TH, Haidet GC, et al. Sympathetic reinnervation of the sinus node and exercise hemodynamics after cardiac transplantation. Circulation. 2000;101:2727-2733.

7. Botta DM, Mancini M. Heart transplantation. 2012. Available at: Accessed June 14, 2012.

8. Piña IL, Apstein CS, Balady GJ, et al. Exercise and heart failure: a statement from the American Heart Association committee on exercise, rehabilitation and prevention. Circulation. 2003;107:1210-1225.

9. Abrahams Z, Mullens W, Boyle A. Cardiac transplantation. In: Griffin BP, Topol EJ, eds. Manual of Cardiovascular Medicine. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:171-190.

10. Mancini, D, Lietz K. Contemporary reviews in cardiovascular medicine: selection of cardiac transplant patients 2010. Circulation. 2010;122:173-183.

11. Constanzo MR, Augustine S, Bourge R, et al. Selection and treatment of candidates for heart transplantation. Circulation. 1995;92:3593-3612.

12. Jaarsma T, Beattie JM, Ryder M, et al. Palliative care in heart failure: a position statement from the palliative care workshop of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2009;11:433-443.

13. Guimaraes GV, d’Avila VM, Chizzola PR, et al. Physical rehabilitation in heart transplantation. Revista Brasileira de Medcina do Esporte. 2004;10:412-415.

14. Kobashigawa JA, Leaf DA, Lee N, et al. A controlled trial of exercise rehabilitation after heart transplantation. N Engl J Med. 1999;340:272-277.

15. Engelhardt JB, Rizzo VM, Della Penna RD, et al. Effectiveness of care coordination and health counseling in advancing illness. Am J Manage Care. 2009;15:817-825.

16. Stewart S, McMurray JJ. Palliative care for heart failure. Editorial. Br Med J. 2002;325:915-916.

17. Strauer BE, Yousef M, Schannwell CM. The acute and long-term effects of intracoronary stem cell trasnplantation in 191 patients with chronic heart failure: the STAR-heart study. Eur J Heart Fail. 2010;12:721-729.

18. Strecker T, Rösch J, Weyand M, Agaimy A. Frequency and spectrum of metachronous malignancies in heart transplant recipients: a 11-year-experience at a German heart center. Int J Clin Exp Pathol. 2013;6:411-420.

19. Heack ML, Hoogslag GE, Rodrigo SF et al. Treatment options in end-stage heart failure: where to go from here? Neth Heart J. 2012;20:167-175.

Author Disclosure

Maricarmen Cruz, MD
Nothing to Disclose

Isabel Borras-Fernandez, MD
Nothing to Disclose

Xavier Aviles-Guzman, MD
Nothing to Disclose

Cristina Isabel Sepulveda-Alamo, MD
Nothing to Disclose

Related Articles