cardiovascular response to exercise and rehabilitation in the heart failure patient
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Cardiovascular response to exercise and Rehabilitation in the
Heart Failure patientAlain COHEN SOLAL
Hôpital Lariboisière, Paris
Bruxelles, 14.10.06
• Rest is the first treatment of chronic heart failure …..
E Braunwald, Textbook of Internal Medicine, WB Saunders Ed, 1986
Peripheral abnormalities
Cardiac dysfunction
Fatigue
Physical deconditioning
Vicious circle of CHF
No relationship between LVEF and exercise capacity
0
10
20
30P
eak
VO
2 (m
l/m
in/k
g)
0% 10% 20% 30% 40% 50%
LV EJECTION FRACTIONCohen Solal A et al. Heart 1996
VO2max(ml/min/kg)
The O2/CO2 transport chain in CHF
LungsHeart
Peripheralcirculation
Musclemetabolism
O2 transport
CO2 elimination
Training
Vascular abnormalities :Major endothelial
dysfunction in CHF
B Hornig et al, Circulation, 1995;1996:210B Hornig et al, Circulation, 1995;1996:210
p<0.05
* *
0
5
10
15
20
Normals CHF
% change in arterial diameter before L-NMMA
after L-NMMA
- 50%
Morphologic abnormalities of peripheral muscles in CHF
H Drexler et al
CHF Normals
Mitochondrial density and exercise capacity in CHF
H Drexler et al, Circulation 1992 ; 85 : 1751H Drexler et al, Circulation 1992 ; 85 : 1751
Peak VO2
ml/kg/mn
CHFControls
0 2 4 6 8
Mitochondrial density
p< 0.0001r = 0. 57n = 60
05
101520253035404550
Comparison ACE-I/physical training in CHF
T Meyer et alInt J Cardiol
Physical rehabilitation
Princeps study in London
• 20 patients
• LVEF < 35%
• NYHA III
• 3 months of home training (cycle) vs 3 months of inactivity (cross over)
Effets de 6 semaines d'entrainement physiqueà domicile chez l'insuffisant cardiaque
Duré
e d
'eff
ort
(m
in)
10
20
Avant Réadaptation Inactivité
² = +20% p<0.05
d'après AJS Coats et al, Lancet 1989
Overall effects of rehabilitation on peak VO2
(10 controlled studies)
0
10
20
30
40
50
Control Trained
Gain in peak VO2 (%)
Exercise training and peak VO2
Circulation 2003; 107: 1210-25
Peak VO2: OKbut what about Quality of Life ?
from R Belardinelli et al
Is it dangerous to train CHF patients ?
• No,– If contra-indications related to the cause of HF
are respected– (major hypotension, invalidating angina,
uncontrolled ventricular arrhythmias, PHT? cardiac thrombus ?)
– Far from an episode of decompensation– On optimal treatment(at least ACE-I/diu + BB
++ ..)
Mechanisms of action of cardiac rehabilitations ?
• Heart
• Vessels
• Muscle
• Autonomic nervous system
• Lung
Effects on the heart
• Improvement in myocardia perfusion (1)
• Decrease in myocardial ischemia (2)
• Improvement in ED vasodilatation (5)
• Increase in exercise CO (3)
• No deleterious effect on cardiac remodeling (4)
(1) V. Froelicher et al, JAMA 1984; 10: 1291(2) AA. Ehsani et al, Am J Cardiol 1982; 50: 246
(3) AJS. Coats et al,Circulation 1992; 85: 2119P. Dubach et al, JACC 1997; 29: 1591
(4) P. Giannuzzi et al (Etude EAMI), JACC 1993; 22: 1821(5) R. Hambrecht et al, JACC 1993; 22: 468
The PET Study100 CAD pts, PTCA-stent based therapy vs exercise training6 months follow up
Hambrecht R et al. Circulation 2004
Exercise
PTCA/Stent
Benefits of training in HF
Sullivan MJ - Circulation 1988; 78: 506-15 * e 1989; 79: 324-9 **
Anaerobic treshold **Exercise *
4 - 6 months
EDV ml/mEDV ml/m22
EVS ml/mEVS ml/m22
EF %EF %
LV Function and RemodelingLV Function and RemodelingELVD - CHFELVD - CHF
BaselineBaseline
147 147 41 41
110 110 34 34
25 25 4 4
6 Months6 Months
156 156 42*† 42*†
118 118 34‡ 34‡
25 25 5‡ 5‡
BaselineBaseline
142 142 26 26
107 107 24 24
25 25 4 4
6 Months6 Months
135 135 2* 2*
97 97 24* 24*
29 29 4* 4*
Exercise Training GroupExercise Training Group(n=45)(n=45)
Control GroupControl Group(n=44)(n=44)
* p<0.01 time effect within group; † p<0.001 interaction; ‡ p<0.01 interaction* p<0.01 time effect within group; † p<0.001 interaction; ‡ p<0.01 interaction
LV remodeling & exercise training
Afzal A - Progress Cardiov Dis 1998: 41: 175-90
JACC, 1997
Circulation, 1997
JACC, 1993
Am Heart J, 1996
Effects on the vessels
• Rest and exercise vasodilatation improved (1)
• Improvement in endothelium-dependent vasodilatation (2)
(1) AJS. Coats et al, Circulation 1996; 85: 2119(1) AJS. Coats et al, Circulation 1996; 85: 2119
(2) B. Hornig et al, Circulation 1996; 93: 210(2) B. Hornig et al, Circulation 1996; 93: 210
R. Hambrecht et al, Circulation 1998;98: 2709R. Hambrecht et al, Circulation 1998;98: 2709
Effects of training on endothelial function in CHF pts
B Hornig et al, Circulation, 1995;1996:210B Hornig et al, Circulation, 1995;1996:210
p<0.05 p<0.05
0
5
10
15
20
Controls CHF Trained CHF
Change in diameter (%)
Mechanisms of the effects of training on peripheral
vasodilatation
• Increased eNOS ?
• Increased VEGF ?
• Decrease in oxydative stress ?
Effects on the muscle
R Hambrecht et al
CHF CHF trained
Effects on the autonomic nervous system
• Decrease in sympathetic tone and increase in parasympathetic tone (1)
• Decrease in plasma norepinephrine, improvement in MIBG uptake (2)
• Increases HR variability (3)
(1) AJS. Coats et al, Circulation 1992; 85: 2119(1) AJS. Coats et al, Circulation 1992; 85: 2119(2) R. Hambrecht et, JACC 1995; 25: 1239, Agostini D, 2000(2) R. Hambrecht et, JACC 1995; 25: 1239, Agostini D, 2000
(3) AJS. Coats et al, Circulation 1992; 85: 2119(3) AJS. Coats et al, Circulation 1992; 85: 2119
Effects on HRV
AJS. Coats et al, Circulation 1992; 85: 2119AJS. Coats et al, Circulation 1992; 85: 2119
Electric myocardial stability and exercise training
Groups VFT (mV)
ERP (msec)
HW/BW
LVP (mm Hg)
dP/dT max
Control (n=10)
3.1±1.6** 48±8 4.9±0.8* 112±32 4,075±
1,128
Exercise (n=5)
9.6±0.8** 50±10 3.7±0.3 119±18 5,462
±1,528
(*p<0.05, ** p<0.01)Male rats, treadmill, 8 weeks H Dor-Haim, Israel Heart Society 06
Exercise ventilation and training
0
10
20
30
40
50
Repos 25 W 50 W Max
Ventilation (l/min)
BeforeTrained
AJS Coats et al, Circulation 1992; 85: 2119AJS Coats et al, Circulation 1992; 85: 2119
*
*
* p < 0.05
17 patients -Lactate-PWP?+ diaphragm- ergoreflex
Training and BNP in CHF
Passino et al. JACC 06
Other possibles mechanisms of action potentially beneficial
• Increase in cardiac NO synthase
• Reduction in oxidative stress
• Anti-inflammatory action (TNF alpha, interleukins)
• ……
Which patients ?
• Patients in NYHA class II-III
• Class IV ?
• Patients on a transplant list ?
• Class I patients ?
• Women ?
• Which peak VO2?
Which protocol ?
• High (usually, 60-70% peak VO2) vs low (40% peak VO2) level exercise training – Low level : periphery +++, autonomic tone– High level : heart
• Anaerobic threshold based • Interval training vs usual training • Segmental training vs dynamic training • Home-based or hospital-based training • 3 or 5 days per weeks ? 2, 3 or 6 months
Compliance and training response
AJS. Coats et al, Circulation 1990;85:2119-31AJS. Coats et al, Circulation 1990;85:2119-31
-10
-20
-30
-400 20 40 60 80 100 120
Observance (%)
0
10
20
30
40
50
60
70 % increase in exercise tolerance
r = 0.74, p< 0.01
Duration of the effect
• Most of the studies have used 3-6 month periods of training
• Improvement seems to level off after the 1st-3rd month
• Acceptability of a long-term training program ? Phase III remains a major problem
Other questions
• Do betablockers limit benefit ?
• Should we systematically propose a rehab programme to a patient on a transplant list?
• Can we remove from the transplant list a patient significantly improved by training?
• Effects on outcome ?
Van Bortel L.M.A.B. 1992 Cardiovascular Drugs and Therapy 6:239-247
Du
rée
(min
.)
p<0.01 vs placebo
20
30
40
50
60
70
Placebo Atenolol 50mg Nebivolol 5mg
Effects of betablockers on exercise toleranceEffects of betablockers on exercise tolerance
nTA 70% VO2 max
Effects of traing in CRT patientsEffects of traing in CRT patients
VO
2max
(m
l/kg
/min
) P = 0.003
10
12
14
16
18
20
baseline 1 mth 3 mths 5 mths
l CRT +
n CRT -
VO
2pea
k (m
l/kg/
min
)
Conraads V et al. WCC 06
Am J Cardiol 2005;95:734–741
Conclusions
3. Patients who improved to low risk for peak VO2 had a 1-year survival, but patients who improved to low risk and were treated with blockers had a 1-year survival rate (83%) comparable to that after transplant (84%).
• 227 advanced HF adults referred for initial HxT evaluation• 52 ± 10 years old• 2nd evaluation: > 60 days after initial evaluation (352±238 days)
Effects on outcome
EXTRAMATCH
RRR 95% CI p
Deaths 35% 0.46-0.92 0.015
Deaths+
Hospitalisations
28% 0.56-0.93 0.011
NNT during 2 years to save 1 life: 17
ExtraMATCH : mortality
HR 95% CI p
Ischemic 0.54 0.35-0.83 0.01
Male 0.60 0.41-0.87 0.01
NYHA III-IV 0.63 0.40-0.99 0.05
EF<25% 0.59 0.38-0.92 0.02
VO2m<15 0.63 0.42-0.96 0.03
Duration > 28weeks
0.64 0.41-0.99 0.04
ExTraMATCH coll BMJ 16.01.2004
Unsustained effects of Exercise on mortality (EXERT Study, Montreal)
McKelvie RS et al. Am Heart J. 2002;144:23-30McKelvie RS et al. Am Heart J. 2002;144:23-30
N=181N=181
Heart Failure - A Controlled Trial Investigating Outcomes of exercise
TraiNing
Randomized trial, 3 000 pts NYHA class II–IV,
EF<35%
ET + usual care vs usual care - 2 years
intervention
52 centres in US (44 centres), Canada (8
centres), 5 in France Expecting to find a 20 % reduction in death and
hospitalization rates
HF – Action NHLBI initiative and funding
Subject Demographics
Age Median (25th, 75th) 59 (51, 68)
Sex Female Male
507 (29%) 1235 (71%)
Ethnicity Hispanic or Latino Not Hispanic or Latino
58 (3%) 1673 (97%)
Race Asian Black or African American White Other2
28 (2%) 595 (34%)
1085 (62%) 63 (4%)
BMI Median (25th, 75th) 30 (26, 35)
Prior Cardiac Procedures
CABG 450 (26%)
PCI 399 (23%)
CABG or PCI 669 (38%)
Valve surgery 99 (6%)
Pacemaker 319 (18%)
AICD 635 (36%)
CRT 287 (17%)
AICD or CRT 703 (40%)
AICD and CRT 219 (13%)
Cost-effectiveness
• Data lacking in CHF
Circulation 2003; 107: 1210-25
Recommendation ESC : IC
CONCLUSION• Importance of the peripheral abnormalities in
CHF• Physical activity beneficial in stable patients• Mechanism of action mainly peripheral and
neurohormonal with current protocols• Unequaled effect on symptoms, mood and QOL • Long term effects on morbimortality unknown • Could (should) be proposed to all CHF patients
with systolic dysfunction
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