This document discusses rehabilitation in heart transplant patients. It provides statistics on heart transplants performed from 1988-2006, including the most common causes of heart disease. It also discusses treatment at the time of transplant, trends in recipient characteristics, and survival rates post-transplant. Complications after transplant like hypertension, renal dysfunction, hyperlipidemia, diabetes and coronary altery disease are common. Exercise intolerance is also discussed. Rehabilitation including exercise training can help increase VO2 max and reduce complications like osteoporosis and obesity. Safety precautions during rehabilitation are also recommended.

1. Indicazioni e stratificazione diagnostica alla
riabilitazione nel paziente post-trapianto di cuore
Dipartimento di Scienze Cardiotoraciche
Seconda Università di Napoli
Dipartimento di Chirurgia Cardiovascolare e Trapianti
Azienda Ospedaliera Monaldi
Napoli

3. Il Trapianto Cardiaco
Casistica Chirurgica 1988 - 2006
430 trapianti in 425 pazienti
40 39
38 37 36
35 34
32 32
30
28 27 28
25
22
20 20
15
12
10 10
8 8 9
6
5
3
0
'88 '90 '92 '94 '96 '98 2000 2002 2004 2006

5. Cardiopatia di base in 418 trapianti cardiaci
Pz. %
Primitiva 184 44 %
Post-ischemica 149 35.7 %
Da valvulopatia 33 7.9 %
Miocarditica 32 7.6 %
Congenita 4 0.96 %
Restrittiva 2 0.6 %
Re-tx 5 1.3 %
Miscellanea 9 2.3 %

6. Il Trapianto Cardiaco
Trattamento terapeutico al momento del trapianto
Pz. Mortalità osp.
Terapia orale 336 9.8 %
Terapia inotropa ev 60 22.0 %
Inotropi + supp. mecc. 22 31.8 %
 IABP 14
 IABP + RVAD 1
 LVAD 7
 ECMO 2

7. Età del ricevente
Range 5 – 68 anni

8. Etiologia della cardiomiopatia
60 53%
50 42,9% 42,9% 40,9%
40 36,6%
30 24,8%
16,5%
20 12,8%
9,4%
10 6,1% 5,7%
8,6%
0
Primitiva Ischemica Valvolare Altro
1988-1995 1996-2000 2001-2005

9. Trend caratteristiche cliniche del ricevente
40
29,9
30
22,8
22 22
20 17,4 21,3
14,8
11,4 10,5 10,5 12,8
9,5 9,8
10 6,7
0 0
1988-1995 1996-2000 2001-2005
Mism atch di peso Status I Diabete Pregressa CCH PVR>5 UW

10. Trend età del donatore
Uso di donatori ≥ 50 anni: -1988-1995 4/105 (3.8%) P = 0.013
-1996-2000 16/149 (10.7%)
-2001-2005 25/164 (15.2%)

11. Cause di morte del donatore
70 64,7
62,9
60 55,5
50
35,3 36,6
40
30,3
30
20
10 5,5
0 0 0 3,4 3,4
0 1,2 1,2
0
1988-1995 1996-2000 2001-2005
Trauma cranico Emorragia cerebrale
Ischemia cerebrale Arma da fuoco
Neoplasia cerebrale

12. Sopravvivenza dopo trapianto cardiaco
Decessi totali: 136 / 418 procedure (32.5%) mortalità ospedaliera inclusa
100% 100,0%
87,8%
90% 82,4% 80,8%
89,6% 75,9%
80% 83,0% 70,0%
80,0%
70% 72,7%
55,1%
60%
58,8% 46,5%
50%
40% 47,1%
30%
28,9%
20% 24,0%
10%
0%
0 1m 6m 1a 3a 5a 10a 15a 17a
Sopravvivenza attuariale ISHLT Survival curve 1982-2001

13. Sopravvivenza dopo trapianto cardiaco
Decessi totali: 136 / 418 procedure (32.5%)
100,0%
100% 90,8% 89,5% 88,5%
90% 83,5% 84,6% 84,6%
79,7%
80% 77,4%
71,4% 75,8%
70% 64,7%
69,1%
60%
60% 63,8%
59,0%
50%
40%
30%
p = 0.001 A vs C
20%
10%
p = 0.042 B vs C
0%
0 1 mese 6 mesi 1a 3a 5a
1988-1995 1996-2000 2001-2005

14. Classe funzionale NYHA
di 284 pazienti sopravvissuti
 I classe 255
 II classe 19
 III classe 8
 IV classe 2

15. ADULT HEART RECIPIENTS
Functional Status of Surviving Recipients
(Follow-ups: April 1994 - June 2004)
100%
80%
60%
40%
20%
No Activity Limitations Performs with Some Assistance Requires Total Assistance
0%
1 Year (N = 15,901) 3 Years (N = 13,954) 5 Years (N = 11,872) 7 Years (N = 9,144)
ISHLT 2005
J Heart Lung Transplant 2005;24: 945-982

16. ADULT HEART RECIPIENTS
Employment Status of Surviving Recipients
(Follow-ups: April 1994 - June 2004)
100%
80% Retired
60% Not Working
Working Part Time
40%
Working Full Time
20%
0%
1 Year (N = 14,888) 3 Year (N = 12,842) 5 Year (N = 10,848) 7 Year (N = 8,371)
ISHLT 2005
J Heart Lung Transplant 2005;24: 945-982

17. Exercise intolerance in heart transplant
• I pazienti trapiantati che non effettuano un
ciclo di riabilitazione cardiorespiratoria
presentano una VO2 max ridotta rispetto ai
controlli di pari età.

18. Causes of Exercise Intolerance in Heart Transplant Patients
Altered Anatomy and Physiology
Functional denervation
Chronotropic incompetence
Decreased chronotropic reserve
Slower kinetics of the chronotropic response
Heart rate increased at rest
Heart rate decreased at peak exercise
Abnormal circulatory response to exercise
Lowered cardiac output
Diastolic dysfunction

19. Effects of Previous Cardiac Illness
Deconditioning
Diminished pulmonary diffusion
Skeletal muscle metabolism
Skeletal muscle strength
Peripheral circulation
Effects of Immunosuppressive Agents
Cyclosporine induced diastolic dysfunction
Osteopenia
Osteoporosis
Myopathy
Infections

22. Attivazione adreno-midollare e ANP

23. VO2 max

24. Efficacia sull’incremento della VO2 max

25. Efficacia sull’incremento della VO2 max

26. Efficacia sull’incremento della VO2 max

27. POST-HEART TRANSPLANT MORBIDITY FOR ADULTS
Cumulative Prevalence in Survivors within 1 Year Post-Transplant (Follow-ups: April 1994 - June 2003)
Within 1 Total number with
Outcome
Year known response
Hypertension 73.2% (N = 15,305)
Renal Dysfunction 26.2% (N = 15,249)
Abnormal Creatinine < 2.5 mg/dl 16.2%
Creatinine > 2.5 mg/dl 8.6%
Chronic Dialysis 1.3%
Renal Transplant 0.2%
Hyperlipidemia 52.0% (N = 16,178)
Diabetes 25.0% (N = 15,300)
CAV 7.9% (N = 13,812)

28. POST-HEART TRANSPLANT MORBIDITY FOR ADULTS
Cumulative Prevalence in Survivors within 5 Years Post-Transplant (Follow-ups: April 1994 - June 2003)
Within 5 Total number with
Outcome
Years known response
Hypertension 94.2% (N = 5,172)
Renal Dysfunction 31.8% (N = 5,571)
Abnormal Creatinine < 2.5 mg/dl 19.6%
Creatinine > 2.5 mg/dl 9.4%
Chronic Dialysis 2.4%
Renal Transplant 0.4%
Hyperlipidemia 84.0% (N = 5,753)
Diabetes 32.8% (N = 5,128)
CAV 32.9% (N = 3,644)

29. POST-HEART TRANSPLANT MORBIDITY FOR ADULTS
Cumulative Prevalence in Survivors within 7 Years Post-Transplant (Follow-ups: April 1994 - June 2003)
Within 7 Total number with
Outcome
Years known response
Hypertension 97.0% (N = 2,366)
Renal Dysfunction 35.5% (N = 2,657)
Abnormal Creatinine < 2.5 mg/dl 20.2%
Creatinine > 2.5 mg/dl 10.4%
Chronic Dialysis 4.0%
Renal Transplant 0.9%
Hyperlipidemia 89.1% (N = 2,701)
Diabetes 35.0% (N = 2,362)
CAV 43.0% (N = 1,510)

30. Incidenza cumulativa di complicanze post-trapianto
Variabile 1 anno 5 anni
Ipertensione 36.8% (92/250) 57.6% (136/236)
Iperlipidemia 54.4% (136/250) 62.5% (148/236)
Diabete 19.6% (49/250) 26.7% (63/236)
100% 100,00%
94,80% 94,80%
93,20% 93,20% 93,20%
96,30%
90% 92,10% 92,10%
87,00%
80%
80,0%
p = 0.11
70%
0
1a
2a
3a
4a
5a
Creatinina < 1,5 Creatinina > 1,5

31. Pre-op. Cr-Cl
80
6 months Cr-Cl
60
80 5 Years Cr-Cl
1 Year Cr-Cl 30
70
60
40
60
3 Years Cr-Cl
40
40 50
20 20
40 30
Dev. Stand = ,79
Media = ,9
20 30
Frequence
0 N = 160,00
Dev. Stand = ,78
0,0 1,0 2,0 3,0 4,0
20
20 Media = 1,0
Frequence
0 N = 150,00
Clearance
Dev. Stand = ,79
0,0 1,0
10 2,0 3,0 4,0
10 Media = 1,3
10
Frequence
Clearance
0 N = 132,00
Dev. Stand = ,80
Frequence
0,0 1,0 2,0 3,0 4,0
Media = 1,4
Dev. Stand = ,86
Clearance
0 N = 88,00
0,0 1,0 2,0 3,0 4,0 Media = 1,5
0 N = 55,00
Clearance
0,0 1,0 2,0 3,0 4,0
Clearance

32. Hyperlipidemia.
1. An elevation in blood lipids is documented in almost 50% of cardiac
recipients by 5 years posttransplantation.
2. Both steroids and CsA are thought to contribute to this problem.
3. Hyperlipidemia is also associated with posttransplant obesity.[38]
During the first months posttransplantation, patients gain weight
rapidly. Along with the gain in body weight, both serum cholesterol
and triglycerides rise.
4. Management of hyperlipidemia begins with attention to diet and
exercise. Lipid-lowering agents, especially the HMG-CoA inhibitors
or "statins," are used routinely. It is reported that recipients started on
these drugs within the first 6 weeks posttransplantation have a lower
incidence of CAD, fewer serious acute rejection episodes, and
improved survival.

33. Osteoporosis.
1. Osteoporosis is a common problem, with the incidence of fractures
reported to be 35% within the first year after heart transplantation.
Immunosuppressive drug therapy contributes to osteoporosis.
Corticosteroids are the most problematic, as they reduce calcium
absorption, increase excretion, and interfere with skeletal growth
factors. CsA and TAC further inhibit calcineurin
phosphate, amplifying the problem.
2. Periodic bone mineral density evaluations are recommended along
with assessment of estrogen and testosterone levels. Prevention
begins with administration of calcium, vitamin D, and sex hormone
replacementTreatment with bisphosphonates and calcitonin may be
added. An endocrinology consultation may benefit patients at risk
and prevent the devastating effects of pathologic fractures.
3. The pain and physical disability that result from osteoporosis have a
negative impact on quality of life posttransplantation.

34. Effect of training on Osteoporosis

35. Effect of training on obesity

36. Recommendations
Suggested Safety Precautions for Heart Transplant Rehabilitation
Allow 6 to 8 weeks for healing of the sternum and taper of steroids.
Discontinue resistance training during acute episodes of rejection.
Utilize “perceived exertion” to adjust exercise intensity.
Utilize conservative initial resistances to avoid compression
fractures.
Ensure adequate systemic blood pressure (transient hypotension is
common).
Alternate upper body exercise with lower body exercises
Symptomatic patients should walk for 2 minutes between exercise or
perform standing calf raises
Include a cool-down walk at the end of each exercise session

37. Libertà attuariale da rigetto acuto (>1B)
100,0% 98,0%
100% 91,5% 90,7% 89,7% 89,7%
90%
83,5%
80% 79,7%
71,4% 77,4% 73,7% 73,7%
70% 64,7% 60%
70,1% 68,5%
60%
50%
40%
30%
p = 0.001 C vs A & B
20%
10%
0%
0 1 mese 6 mesi 1a 3a 5a
1988-1995 1996-2000 2001-2005

38. Protocollo di immunosoppressione 1
Gennaio 1988 - Dicembre2000
• Induzione: Thymoglobuline 2.5mg/Kg/24h per 5 giorni
ATG 2.5mg/Kg/24h per 7 giorni
- sospensione in caso di : anafilassi/ leucopenia
(<2000/µl)/ trombocitopenia (<50000/µl)
• Metilprednisolone 500 mg e.v. in S.O. → 125 mg/12h per 2 gg
• Prednisone: 1 mg/kg os → décalage → 0.1 mg/kg/24h (12 mese)
• Azatioprina: 2 mg/kg/24h → WBC 4000–6000/µl
• Ciclosporina:
- 3 mg/kg/24h (dopo stabilizzazione emodinamica e
con funzione renale soddisfacente)
- ciclosporinemia 300 ng/dl 1 anno
- ciclosporinemia 150-200 ng/dl dopo 1 anno
De Santo LS et al. Transpl Proc 2005, in press

39. Protocollo di immunosoppressione 2
da Gennaio 2001
• Induzione Thymoglobuline 1.5mg/Kg/24h per 5 giorni
- sospensione in caso di : anafilassi/ leucopenia
(<2000/µl)/ trombocitopenia (<50000/µl)
• Metilprednisolone 500 mg e.v. in S.O. → 125 mg/12h per 2 gg
• Prednisone: 1 mg/kg os → décalage → 0.1 mg/kg/24h (12 mese)
• Mycophenolate mofetil: 1500mg x 2/24h
• Ciclosporina:
- 3 mg/kg/24h (dopo stabilizzazione emodinamica e
con funzione renale soddisfacente)
- ciclosporinemia 300 ng/dl 1 anno
- ciclosporinemia 150-200 ng/dl dopo 1 anno
De Santo LS et al. Transpl Proc 2005, in press

40. Protocollo di immunosoppressione 3
dal Maggio 2005
• Induzione ATG 1.5mg/Kg/24h per 5 giorni
- sospensione in caso di : anafilassi/ leucopenia
(<2000/µl)/ trombocitopenia (<50000/µl)
• Metilprednisolone 500 mg e.v. in S.O. → 125 mg/12h per 2 gg
• Prednisone: 1 mg/kg os → décalage → 0.1 mg/kg/24h (6 mese)
• Everolimus: 1,5 mg/die
• Ciclosporina:
- 3 mg/kg/24h (dopo stabilizzazione emodinamica e
con funzione renale soddisfacente)
- ciclosporinemia 300 ng/dl 1 anno
- ciclosporinemia 150-200 ng/dl dopo 1 anno

41. POST-HEART TRANSPLANTATION REHABILITATION
AND PHYSICAL CONDITIONING HANDBOOK
Class I – Conditions in which there are evidences and/or agreement
that some procedure is effective or useful:
1) early physical rehabilitation;
2) aerobic physical activity;
3) resistance-exercise physical activity;
4) supervised physical activity program;
5) exercise test, preferably cardiopulmonary exercise test.

44. Class II – Condition in which there are conflicting evidences and/or
divergence of opinion with regard to the usefulness and effectiveness of
some procedure or treatment:
a) Evidence or opinion that favors the utilization of the treatment:
1) non-supervised physical activity program;
2) physical activity in heated swimming pool;
3) recreative activities.
b) Evidence of less established opinion:
1) participation in competitive games without supervision;
2) high-intensity sporadic physical activity.

46. Class III – Condition in which there are evidences and/or
agreement that the procedure/treatment is not useful and in some
cases, it may even be harmful:
1) hemodynamic instability;
2) light or severe rejection episodes;
3) infection process;
4) clinical, orthopedic or neurological limitation that disables
physical activity.

47. Program Format
Phase I Cardiac Rehabilitation
Phase I of Cardiac Rehabilitation begins during hospitalization.
A cardiac nurse visits each patient to provide education and nutrition
counseling in preparation for discharge.
Patients may also receive physical therapy during the hospital stay.

48. Phase II Cardiac Rehabilitation
Phase II is a 4 to 12 week exercise program, with three sessions per
week.
Exercise sessions include several components: warm up walking or
biking; aerobic exercise on treadmills, exercise bikes, stair-steps, and
rowing machines to help the heart use oxygen more efficiently and
improve blood flow; resistance training to increase strength and
stamina; and cool down stretching for flexibility. Small group sessions
provide heart monitoring during exercise, individualized care, and
frequent blood pressure checks by the Cardiac Rehabilitation Staff.

49. Phase III Cardiac Rehabilitation
Phase III is designed to maintain cardiovascular fitness through
prescribed exercise. Candidates or Phase III include individuals who
have a prior history of heart disease, those who are at high risk of
developing heart disease, and graduates of Phase II Cardiac
Rehabilitation.

52. Efficacia sulla vasculopatia del graft?
Profilo lipidico
Ipertensione arteriosa
Aumento ponderale

53. Conclusioni
♦ Il trapianto ortotopico di cuore è allo stato attuale l’unica terapia
valida dello scompenso terminale in grado di restituire una
buona qualità di vita al 70% dei pazienti per cinque anni, al 55%
per 10 anni ed al 46,5% per 17 anni.
♦ La prevenzione e la cura del rigetto acuto hanno raggiunto
soddisfacenti livelli di efficacia. Lo stesso puo’ dirsi per le
complicanze infettive ivi comprese quelle virali.
♦ Il miglioramento del trattamento delle comorbidità raggiunto
mediante l’inserimento di un medico internista nella gestione del
programma trapianti ha offerto un miglioramento della qualità di
vità del paziente trapiantato.

54. Conclusioni
♦ Tutti i pazienti sottoposti a trapianto di
cuore necessiterebbero di una valutazione
delle indicazioni ad un ciclo di
riabilitazione prima della dimissione
ospedaliera.