Cardiovascular response to exercise and Rehabilitation in the Heart Failure patient
description
Transcript of Cardiovascular response to exercise and Rehabilitation in the Heart Failure patient
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