1
Hjertesviktforum 2015
Langtidseffekter av trening etter
hjertetransplantasjon
PhD-stipendiat/ lege Marianne Yardley
Veileidere: Professor Dr. med Lars Gullestad, Post doc Kari Nytrøen.
Hjertesviktforum 2015
3
Disposisjon
• Hjerte/karsykdom- Status i dag
• Tiden etter treningsintervensjon- nytter det?
• Kronotrop insuffisiens og intervalltrening
• Oksygenopptak som en prediktor for langtidsoverlevelse etter
hjertetransplantasjon
• Overlevelsesstatistikk- Resultater fra Norge
Marianne Yardley
Marianne Yardley
Status 2015
• Dødelighet av hjerte/kar sykdom er stadig synkende
• Økende andel hjertesvikt pasienter
• Forebygging og behandling er fremdeles viktig!
Marianne Yardley
6
Marianne Yardley
7
Marianne Yardley
8
Tiden etter
treningsintervensjon
Marianne Yardley
9
Langtidsoppfølging
• 2 Meta analyser – tiden etter hjertesviktrehabilitering
• Minimalt som er gjort etter høy intensitetstrening (HIT)
• 41 HTx pasienter har vært til 5 års follow- up etter HIT
– TEX studien (Kari Nytrøen)
Marianne Yardley
10
Mueller L, Myers J, Kottman W, Oswald U, Boesch C, Arbrol N, et al. Exercise capacity,
physical activity patterns and outcomes six years after cardiac rehabilitation in patients
with heart failure. Clinical rehabilitation. 2007;21(10):923-31 9p.
Vo2
mL/kg/min
Exercise group
Control group
Baseline
Post training Follow up
Baseline
Post
training
Follow up
22.0±3.4
26.7*±4.3
19.9±2.7
20.9±2.9
20.3±4.5
* P verdi < 0.05
Marianne Yardley
23.6±5.8
11
Piepoli MF, Davos C, Francis DP, Coats AJ.
Exercise training meta-analysis of trials in patients with chronic heart failure
(ExTraMATCH). BMJ. 2004;328(7433):189.
Marianne Yardley
12
Sagar VA, Davies EJ, Briscoe S, Coats AJS, Dalal HM, Lough F, et al. Exercise-based
rehabilitation for heart failure: systematic review and meta-analysis. Open Heart.
2015;2(1).
• Lavere andel re- innleggelser
• Bedre selvrapportert livskvalitet
• Lenger langtidsoverlevelse
Marianne Yardley
13
Re- innleggelser
Marianne Yardley
Sagar VA, Davies EJ, Briscoe S, Coats AJS, Dalal HM, Lough F, et
al. Exercise-based rehabilitation for heart failure: systematic
review and meta-analysis. Open Heart. 2015;2(1).
14
Moholdt T, Aamot IL, Granoien I, Gjerde L, Myklebust G, Walderhaug L, et al. Long-term
follow-up after cardiac rehabilitation: a randomized study of usual care exercise
training versus aerobic interval training after myocardial infarction. International
journal of cardiology. 2011;152(3):388-90.
Marianne Yardley
15
Tilbakemeldinger- TEX 5 år
• Bidra til ny kunnskap
• Gøy
• Kjempetøft
• ”Kjøpte meg tredemølle”
• Mulig å delta på gruppe
rehabilitering med HIT
Marianne Yardley
16
…..hva med den trege pulsen og HIT??
Marianne Yardley
17
Marianne Yardley
18
Marianne Yardley
19
Marianne Yardley
20
Oksygenopptak og selvrapportert fysisk helse
som prediktorer for langtidsoverlevelse
etter hjertetransplantasjon
[email protected]
21
Hva påvirker langtidsoverlevelse etter HTx?
•Årsak til hjertesvikt
•Donors alder
•Mottakers alder
•Iskemitid
•Utvikling av vaskulopati i koronarkar (CAV/ graftsklerose)
•Mekanisk støtte på venteliste
•VO2peak??
Marianne Yardley
Survival curves for cardiac deaths, based on VO2peak at referral.
Terence Kavanagh et al. Circulation. 2002;106:666-671
Marianne Yardley
Copyright © American Heart Association, Inc. All rights reserved.
23
Keteyian SJ, Brawner CA, Savage PD, Ehrman JK, Schairer J, Divine G, et al.
Peak aerobic capacity predicts prognosis in patients with coronary heart disease.
American heart journal. 2008;156(2):292-300.
Marianne Yardley
24
VO2peak som prognostisk faktor
•
Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, Asumi M, et al. Cardiorespiratory fitness
as a quantitative predictor of all-cause mortality and cardiovascular events in
healthy men and women: a meta-analysis. Jama. 2009:301:2024-35.
•
Cahalin LP, Chase P, Arena R, Myers J, Bensimhon D, Peberdy MA, et al. A meta-analysis
of the prognostic significance of cardiopulmonary exercise testing in patients with
heart failure. Heart failure reviews. 2013:18:79-94.
•
Costanzo MR, Augustine S, Bourge R, Bristow M, O'Connell JB, Driscoll D, et al.
Selection and treatment of candidates for heart transplantation. Circulation.
1995:92:3593-612.
Marianne Yardley
25
Overlevelses statistikk – 2 HTx populasjoner
•
CPET kohort
– Lars Gullestad et al.
– 178 pasienter fullført VO2peak test (1990-2003)
– Gjennomsnitt observasjonstid: 11 år
– Events: 128
•
SF-36 kohort
– Odd E Havik et al. (1998-2000)
– 133 pas fullført spørreskjema om livskvalitet
– Gjennomsnitt observasjonstid 10 år
– Events: 87
Marianne Yardley
26
SF- 36 spørreskjema
•
Mål på selvrapportert livskvalitet
– fysisk og mental helse
•
SF-36 score korrelerer med O2 opptak
•
Inaktivitet er estimert til å forklare 9% av tidlig død på verdensbasis
Lee et al. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life
expectancy. Lancet 2012
•
Sammenheng mellom selvrapportert fysisk helse og prognose
– HUNT undersøkelsen
– Oslo undersøkelsen
Marianne Yardley
27
Marianne Yardley
28
Resultater
Marianne Yardley
29
CPET kohort- Karakteristika overlevende / døde
Variable
Survivors
Non- survivors
n= 42
Mean± SD,
Median [Q1,Q3]
n=128
Mean± SD,
Median[Q1,Q3] P-value
HR [95% CI]
Gender (% men)
86%
89%
0.559
1.181 [0.678-2.059] 0.557
Age at CPET
(years)
Weight (kg)
45 [36, 56]
56 [51, 56]
<0.001
1.051 [1.031-1.072] <0.001
77± 11
82± 13
0.032
1.014 [1.000-1.028] 0.042
Donor age (years) 28± 9
29± 11
0.752
1.001 [0.983-1.020] 0.892
Ischemic time
(min)
Etiology of
heart failure
107± 70
127± 66
0.103
1.002 [0.999-1.005] 0.205
Other 9%
CMP 60%
CAD 31%
Other 6%
CMP 32%
CAD 62%
0.002
ref
0.001
0.953 [0.427-2.129] 0.907
1.939 [0.892-4.213] 0.094
Smoking (% yes)
24%
41%
0.064
1.435 [0.998-2.065] 0.051
Marianne Yardley
Compare Univariate cox- regression
groups
n=170
n=178
P-value
Variable
n= 42
8%
Non- survivors Compare Univariate cox- regression
groups
n=128
n=170
n=178
35%
0.001
2.415 [1.620-3.599] <0.001
2 [1, 6]
3 [1, 6]
0.274
1.040 [0.993-1.016] 0.177
Ejection fraction (%) 78 [72, 82]
74 [69, 83]
0.870
1.004 [0.993-1.016] 0.487
Cardiac Index
2.6± 0.6
0.609
1.039 [0.751-1.438] 0.817
Hemoglobine (g/Dl) 13.4± 1.4
12.9± 1.5
0.133
0.925 [0.808-1.058] 0.253
Creatinine (µmol/L) 111± 30
126± 33
0.011
1.008 [1.003-1.013] 0.003
Cya dosage (mg)
250 [200, 300] 225 [195, 275] 0.177
0.998 [0.996-1.001] 0.141
Prednisolone
dosage (mg)
7.5 [7.5, 7.5]
CAV after HTx
(% yes)
Years since HTx at
inclusion
Survivors
2.6± 0.7
Imurel dosage (mg) 95± 51
Marianne Yardley
7.5 [7.5, 7.5]
0.398
1.028 [0.885-1.194] 0.720
110± 50
0.106
1.002 [0.998-1.006] 0.264
31
Exercise variables Survivors
n= 42
1.77± 0.52
Non- survivors Compare
groups
n=128
n=170
0.001
1.50± 0.44
VO2peak
(mL/kg/min)
VO2peak
<mediana (%)
23.08± 6.05
18.20± 4.58
<0.001
0.901 [0.866-0.937] <0.001
44%
56%
0.006
1.848 [1.296-2.633] 0.001
VO2peak (% )b
58.9± 13.4
52.5± 11.5
0.003
0.974 [0.960-0.989] 0.001
Heart rate max
147± 26
146± 20
0.853
0.997 [0.990-1.005] 0.473
RER
1.21± 0.14
1.19± 0.12
0.277
0.416 [0.099-1.758] 0.233
SBP rest (mmHg)
127± 21
135± 20
0.028
1.007 [0.999-1.016] 0.096
SBP max (mmHg)
183± 26
193± 31
0.089
1.004 [0.997-1.011] 0.230
V max (L)
71± 22
64± 19
0.053
0.988 [0.980-0.997] 0.010
Watt max
159± 46
131± 39
<0.001
0.990 [0.986-0.995] <0.001
VO2peak (L/min)
a Median value = 19,6
b Age predicted values for VO2peak, based on reference values presented by Åstrand et al.
Marianne Yardley
Univariate coxP-value
regression
n=178
0.449 [0.298-0.676] <0.001
32
SF-36 kohort: Karakteristika overlevende / døde
Variable
Survivors
Nonsurvivors
n=46
Gender (% men)
Age at time of
SF- 36 (years)
Weight (kg)
Body mass index
(kg/m2)
Donor age(years)
Ischemic time
(min)
Etiology of heart
failure
Compare
groups
n=133
Univariate cox- regression
P- value
HR [95% CI]
P-value
0.643
<0.001
1.085 [0.631-1.867]
1.076 [1.048-1.105]
0.768
<0.001
n=133
Mean± SD
Median
[Q1,Q3]
78%
46 ±13
n=87
Mean± SD
Median
[Q1,Q3]
82%
59 ±7
78± 13
25± 3
86± 14
27± 4
0.009
0.003
1.020 [1.005-1.035]
1.071[1.023-1.122]
0.011
0.004
30± 10
114± 65
31± 13
141 ±72
0.859
0.031
1.001 [0.982-1.020]
1.003 [1.000-1.006]
0.948
0.053
Other 14%
CMP 62%
CAD 24%
Other 29%
CMP 7%
CAD 64%
<0.001
ref
1.051 [0.431-2.563]
2.494 [1.070-5.813]
0.001
0.913
0.034
Marianne Yardley
33
Variable
Survivors
Compare
groups
n=133
0.141
Univariate cox- regression
n=46
15%
Nonsurvivors
n=87
26%
Smoking (% yes)
9%
32%
0.003
2.721 [1.721-4.304]
<0.001
Years since HTx (at 3 [2, 6]
inclusion)
6 [3, 9]
0.003
1.086 [1.034-1.141]
0.001
Hemoglobine
(g/Dl)
13.6± 1.2
13.4± 1.4
0.522
0.982 [0.836-1.154]
0.824
Creatinine
(µmol /L)
107± 27
124± 66
0.038
1.003 [1.000-1.006]
0.028
Cardiac Index
Cya dosage (mg)
Prednisolone
dosage (mg)
2.7± 0.6
231± 75
7.3± 1.2
2.6± 0.5
196± 49
7.4± 1.2
0.291
0.006
0.629
0.726 [0.431-1.224] 0.229
0.994 [0.990-0.998] 0.003
1.055 [0.883- 1.260] 0.555
Imurel dosage
(mg)
92± 45
99± 50
0.434
1.002 [0.998-1.007]
CAV after HTx
(% yes)
Marianne Yardley
n=133
1.560 [0.968- 2.514] 0.068
0.317
34
Variable
Compare
groups
n=133
Univariate coxregression
n=133
P-value
n=46
Nonsurvivors
n=87
5 [2, 7]
6 [4, 11]
0.011
1.029[1.002- 1.057]
0.033
95 [89, 96]
80 [60, 94]
<0.001
0.977 [0.969- 0.985]
<0.001
PF-score <median 37%
(%)a
63%
<0.001
2.604 [1.677- 4.044]
<0.001
Role Physical (RP)
Bodily pain (BP)
General health
(GH)
Mental health
(MH)
Vitality (VT)
Social functioning
(SF)
100 [75, 100]
84 [62, 100]
77 [61, 92]
50 [0,94]
72 [41, 84]
62 [45, 82]
0.003
0.013
0.006
0.991 [0.986- 0.996]
0.989 [0.982- 0.997]
0.985 [0.976-0.995]
0.001
0.004
0.002
88 [76, 94]
82 [68, 92]
0.300
0.996 [0.984-1.008]
0.476
70 [55, 80]
88 [67, 89]
60 [40, 75]
78 [56, 89]
0.003
0.087
0.987 [0.978-0.997]
0.992 [0.983- 1.001]
0.008
0.088
Role Emotional
(RE)
100 [67, 100]
67 [33, 100]
0.001
0.990 [0.984-0.996]
0.001
BDI score
SF- 36 variables;
Physical
functioning (PF)
Survivors
Marianne Yardley
35
Forklaringsmodell med VO2peak og PF-score
•Andre variabler som forklarer overlevelse ytterligere
•Vurdert potensielle confoundere
– Påvirker både VO2peak/PF-score og overlevelse
– tommelfingel regel- endrer estimatet med 10 %
Marianne Yardley
36
CPET kohort; multippel cox regresjon
Variables
HR [95% CI]
P- value
VO2peak
0.917 [0.876-0.960]
<0.001
Age at CPET
1.045 [1.020-1.070]
<0.001
CAV
1.968 [1.314- 2.948]
0.001
SF-36 kohort; multippel cox regresjon
Variables
HR [95% CI]
P- value
Physical Functioning
0.983 [0.975-0.992]
<0.001
Age
1.077 [1.046-1.108]
<0.001
Smoking
1.878 [1.123-3.141]
0.016
CAV
1.674 [1.025-2.732]
0.039
Marianne Yardley
37
Overlevelseskurver
Marianne Yardley
38
Overlevelse
•
Median overlevelse Norge: 12 år
•
CPET kohort
– 12 år
– VO2peak under median: 9 (7, 11)
– VO2peak over median: 16 (14, 18)
•
SF-36 kohort
– 10 år
– PF score under median: 8 (6, 10)
– PF score over median: 12 (10, 13)
Marianne Yardley
39
Overlevelseskurver
•VO2peak og selvrapportert fysisk helse utpeker seg som viktige prediktorer på langtidsoverlevelse.
•Fysisk kapasitet bør måles oftere, også etter hjertetransplantasjon.
Marianne Yardley