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Indicazioni e stratificazione diagnostica alla riabilitazione nel paziente post-
trapianto di cuoreDipartimento di Scienze Cardiotoraciche
Seconda Università di NapoliDipartimento di Chirurgia Cardiovascolare e Trapianti
Azienda Ospedaliera MonaldiNapoli
108
68 9
12
20
32
38
28 27
22
34
28
37
32
3639
30
5
10
15
20
25
30
35
40
'88 '90 '92 '94 '96 '98 2000 2002 2004 2006
Il Trapianto CardiacoCasistica Chirurgica 1988 - 2006
430 trapianti in 425 pazienti
Il Trapianto CardiacoCasistica Chirurgica 1988 - 2006
430 trapianti in 425 pazienti
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 %
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 %
Cardiopatia di base in 418 trapianti cardiaci Cardiopatia di base in 418 trapianti cardiaci
Il Trapianto CardiacoTrattamento terapeutico al momento del trapianto
Il Trapianto CardiacoTrattamento 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 7ECMO 2
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 7ECMO 2
Età del riceventeEtà del ricevente
Range 5 – 68 anni
42,9%
53%
36,6%
42,9%
24,8%
40,9%
8,6%
9,4%6,1% 5,7%
12,8%16,5%
0
10
20
30
40
50
60
Primitiva Ischemica Valvolare Altro
Etiologia della cardiomiopatia
1988-1995 1996-2000 2001-2005
0
11,4 10,59,5
10,5
6,7
22,8
12,814,8
17,4
9,8
22 2221,3
29,9
0
10
20
30
40
1988-1995 1996-2000 2001-2005
Mismatch di peso Status I Diabete Pregressa CCH PVR>5 UW
Trend caratteristiche cliniche del riceventeTrend caratteristiche cliniche del ricevente
Trend età del donatoreTrend 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%)
64,7
35,3
0 0 0
62,9
30,3
3,4 3,40
55,5
36,6
5,5
1,2 1,20
10
20
30
40
50
60
70
1988-1995 1996-2000 2001-2005
Trauma cranico Emorragia cerebraleIschemia cerebrale Arma da fuocoNeoplasia cerebrale
Cause di morte del donatoreCause di morte del donatore
Sopravvivenza dopo trapianto cardiacoDecessi totali: 136 / 418 procedure (32.5%) mortalità ospedaliera inclusa
Sopravvivenza dopo trapianto cardiacoDecessi totali: 136 / 418 procedure (32.5%) mortalità ospedaliera inclusa
100,0%
87,8%82,4% 80,8%
75,9%70,0%
55,1%
46,5%
89,6%
83,0%80,0%
72,7%
58,8%
47,1%
28,9%24,0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1m 6m 1a 3a 5a 10a 15a 17a
Sopravvivenza attuariale ISHLT Survival curve 1982-2001
100,0%
87,8%82,4% 80,8%
75,9%70,0%
55,1%
46,5%
89,6%
83,0%80,0%
72,7%
58,8%
47,1%
28,9%24,0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1m 6m 1a 3a 5a 10a 15a 17a
Sopravvivenza attuariale ISHLT Survival curve 1982-2001
Sopravvivenza dopo trapianto cardiacoDecessi totali: 136 / 418 procedure (32.5%)
Sopravvivenza dopo trapianto cardiacoDecessi totali: 136 / 418 procedure (32.5%)
63,8%59,0%
75,8%
69,1%
100,0%90,8% 89,5% 88,5%
84,6% 84,6%
71,4%
64,7% 60%
83,5%
79,7% 77,4%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1 mese 6 mesi 1a 3a 5a
1988-1995 1996-2000 2001-2005
63,8%59,0%
75,8%
69,1%
100,0%90,8% 89,5% 88,5%
84,6% 84,6%
71,4%
64,7% 60%
83,5%
79,7% 77,4%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1 mese 6 mesi 1a 3a 5a
1988-1995 1996-2000 2001-2005
p = 0.001 A vs C
p = 0.042 B vs C
p = 0.001 A vs C
p = 0.042 B vs C
Classe funzionale NYHA
di 284 pazienti sopravvissuti Classe funzionale NYHA
di 284 pazienti sopravvissuti
I classe 255 II classe 19 III classe 8 IV classe 2
I classe 255 II classe 19 III classe 8 IV classe 2
ADULT HEART RECIPIENTS Functional Status of Surviving Recipients
(Follow-ups: April 1994 - June 2004)
0%
20%
40%
60%
80%
100%
1 Year (N = 15,901) 3 Years (N = 13,954) 5 Years (N = 11,872) 7 Years (N = 9,144)
No Activity Limitations Performs with Some Assistance Requires Total Assistance
ISHLT 2005J Heart Lung Transplant 2005;24: 945-982
ADULT HEART RECIPIENTSEmployment Status of Surviving Recipients
(Follow-ups: April 1994 - June 2004)
ISHLT 2005J Heart Lung Transplant 2005;24: 945-982
0%
20%
40%
60%
80%
100%
1 Year (N = 14,888) 3 Year (N = 12,842) 5 Year (N = 10,848) 7 Year (N = 8,371)
Retired
Not Working
Working Part Time
Working Full Time
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.
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
Effects of Previous Cardiac IllnessDeconditioning
Diminished pulmonary diffusion Skeletal muscle metabolism
Skeletal muscle strength Peripheral circulation
Effects of Immunosuppressive AgentsCyclosporine induced diastolic dysfunction
Osteopenia Osteoporosis
Myopathy Infections
Attivazione adreno-midollare e ANP
VO2 max
Efficacia sull’incremento della VO2 max
Efficacia sull’incremento della VO2 max
Efficacia sull’incremento della VO2 max
POST-HEART TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 Year Post-Transplant (Follow-ups: April 1994 - June 2003)
Outcome Within 1
Year Total number with 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)
POST-HEART TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 5 Years Post-Transplant (Follow-ups: April 1994 - June 2003)
Outcome Within 5
Years Total number with 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)
POST-HEART TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 7 Years Post-Transplant (Follow-ups: April 1994 - June 2003)
Outcome Within 7
Years Total number with 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)
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)
100,00%
94,80% 94,80%93,20% 93,20%
96,30%
92,10%
87,00%
80,0%
93,20%
92,10%
70%
80%
90%
100%
0
1a
2a
3a
4a
5a
Creatinina < 1,5 Creatinina > 1,5
100,00%
94,80% 94,80%93,20% 93,20%
96,30%
92,10%
87,00%
80,0%
93,20%
92,10%
70%
80%
90%
100%
0
1a
2a
3a
4a
5a
Creatinina < 1,5 Creatinina > 1,5
Incidenza cumulativa di complicanze post-trapiantoIncidenza cumulativa di complicanze post-trapianto
p = 0.11
Clearance
4,03,02,01,00,0
Pre-op. Cr-ClF
requ
ence
80
60
40
20
0
Dev. Stand = ,79
Media = ,9
N = 160,00
Clearance
4,03,02,01,00,0
6 months Cr-ClF
requ
ence
80
60
40
20
0
Dev. Stand = ,78
Media = 1,0
N = 150,00
Clearance
4,03,02,01,00,0
1 Year Cr-ClF
requ
ence
70
60
50
40
30
20
10
0
Dev. Stand = ,79
Media = 1,3
N = 132,00
Clearance
4,03,02,01,00,0
3 Years Cr-Cl
Fre
quen
ce40
30
20
10
0
Dev. Stand = ,80
Media = 1,4
N = 88,00
Clearance
4,03,02,01,00,0
5 Years Cr-Cl
Fre
quen
ce
30
20
10
0
Dev. Stand = ,86
Media = 1,5
N = 55,00
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.
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.
Effect of training on Osteoporosis
Effect of training on obesity
RecommendationsSuggested Safety Precautions for Heart Transplant RehabilitationAllow 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
70,1% 68,5%
73,7% 73,7%
100,0% 98,0%91,5% 90,7% 89,7% 89,7%
71,4%
64,7% 60%
83,5%
79,7%77,4%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1 mese 6 mesi 1a 3a 5a
1988-1995 1996-2000 2001-2005
70,1% 68,5%
73,7% 73,7%
100,0% 98,0%91,5% 90,7% 89,7% 89,7%
71,4%
64,7% 60%
83,5%
79,7%77,4%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1 mese 6 mesi 1a 3a 5a
1988-1995 1996-2000 2001-2005
Libertà attuariale da rigetto acuto (>1B)Libertà attuariale da rigetto acuto (>1B)
p = 0.001 C vs A & Bp = 0.001 C vs A & B
Protocollo di immunosoppressione 1Gennaio 1988 - Dicembre2000
Protocollo di immunosoppressione 1Gennaio 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
• 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
Protocollo di immunosoppressione 2
da Gennaio 2001
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
• 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
Protocollo di immunosoppressione 3
dal Maggio 2005
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
• 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
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.
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.
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.
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.
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.
Phase III Cardiac RehabilitationPhase 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.
Efficacia sulla vasculopatia del graft?
Profilo lipidico
Ipertensione arteriosa
Aumento ponderale
ConclusioniConclusioni
♦ 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.
ConclusioniConclusioni
♦Tutti i pazienti sottoposti a trapianto di cuore necessiterebbero di una valutazione delle indicazioni ad un ciclo di riabilitazione prima della dimissione ospedaliera.