Piergiuseppe Agostoni, MD, PhD
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Transcript of Piergiuseppe Agostoni, MD, PhD
Piergiuseppe Agostoni, MD, PhD
Centro Cardiologico Monzino, Istituto di Cardiologia, Università di Milano, Milano
Division of Respiratory Disease, University of Washington, Seattle, WA.
Physiological bases of clinical exercise testing: choosing and performing the proper
test
Gas diffusion
O2 transport
Cardiac output
O2 extraction
Ventilation
muscle
Why a cardiopulmonary exercise test?
Etiology of exercise limitation is unknown
Disease prognosis (CHF)
Effectiveness of therapeutic intervention
Exercise prescription
Transplant evaluation
Research!
Modalities
ERGOMETER Treadmill Cycloergometer Armometer
Cardiopulmonary exercise test
GAS ANALYSIS (indirect calorimetry)
Douglas bag procedure Time-averaged systems
Breath-by-breath systems
Treadmill Cycloergometer
• Hystorical • Easy to be performed • VO2max > 5-10%• Expensive, noisy• Dangerous for some
categories of patients• Not suitable for
hemodynamic measurements
• Difficulties in assessing workrate
• Easy to assess workrate• Less expensive, less
noise
• Easy to assess VO2/WR
• Suitable for hemodynamic measurements
• VO2max 89%-95% vs treadmill
Cardiopulmonary Exercise
Test ProtocolsCostant Workload
Step Incremental Workload
Ramp Incremental Workload
VO2
Time3’ 6’ Gas kinetics Analysis
- phase 1 linked to cardiac output
- phase 2 related to exercise capacity
(Tau: 63% VO2max; T1/2)
- phase 3 (Delta 6°e 3° minute)
• Above or below Anaerobic Threshold
• Response to therapeutic intervention
CONSTANT WORKLOAD PROTOCOLS
Zhang et al.
Ramp
1-min step 3-min step
2-min step
Time (min)Time (min)
VO
VO
22 (
L•m
in (
L•m
in-1-1))
Work
Rate
(W
)W
ork
Rate
(W
)
INCREMENTAL PROTOCOLSDid the different work rate step patterns affect aerobic function parameters?
What is a Ramp What is a Ramp Protocol?Protocol?
Constant and continuous work increasesConstant and continuous work increases
Can be easily individualizedCan be easily individualized
Test duration may be better targetedTest duration may be better targeted
May better elicit a “true” VOMay better elicit a “true” VO22maxmax
2’-3’ step incremental protocol useful 2’-3’ step incremental protocol useful only if intermediate steady state needing only if intermediate steady state needing (i.e. blood sampling, haemodinamic (i.e. blood sampling, haemodinamic measures)measures)
CARDIOPULMONARY EXERCISE TESTOPTIMAL LENGHT
J Appl Physiol 1983
- What is the ideal maximal exercise test? Mode that progressively increases total body and myocardial demand in reasonable time- What is an optimal time duration?- What is an optimal time duration? 8 to 12 minutes
50
100
150
200
C B A
5 min 10 min 15 min
0
10
20
30
C B A
5 min 10 min 15 min
Peak WRWatts
Peak VO2ml/min/Kg
*
* **
*
Agostoni PG et al. Eur J Heart Fail 2005
They are influenced
Effects of work-rate ramp on peak exercise parameters in heart failure
20
60
100
140
C B A
5 min 10 min 15 min
0
10
20
C B A
5 min 10 min 15 min
Work rate ATWatts
VO2 ATml/min/Kg
*
*
*
Agostoni PG et al. Eur J Heart Fail 2005
It is not influencedIt is influenced
Effects of work-rate ramp on AT parameters in heart failure
20
30
40
50
C B A
VE
/VCO
2 slop
e
5 min 10 min 15 min
Agostoni PG et al. Eur J Heart Fail 2005
Effects of work-rate ramp on VE/VCO2 slope in heart failure
It is not influenced
Agostoni PG et al. Eur J Heart Fail 2005
Effects of work-rate ramp on VO2/WR slope in heart
failure
It is influenced
>VO2/WR slope > lenght
• Match the Person, Match the Person, Protocol, and Purpose of Protocol, and Purpose of the Test !!!!the Test !!!!
• Major Parameters.Major Parameters.
CARDIOPULMONARY EXERCISE TEST: WHICH MEASUREMENTS DOES IT SUPPLY?
Wasserman K. Priciples Exercise Testing and Interpretation. Third Edition Lippincott Williams &
Wilkins
VO2max
VO2 = SV x HR x a-vO2diff
VO2/WORK SLOPE
O2 consumption vs work
match o2 delivery and o2 utilization.
VO2/ WR Clinical Relevance
VO2
Work
obese normal
CAD, MI
N.V. 10 ml/min/W
1. Position (ie overweight)2. slope (ie heart failure)3. Linearity (ie coronary artery disease)
CHF, reduced O2 utlization
O2 Pulse
HD: heart disease; OAD: obstructive airway disease
O2Pulse = SV x HR x a-vO2diff HR
It reflects SV and…is affected by:- anemia- hypoxemia- heart failure - deconditioning
ANAEROBIC THRESHOLD IDENTIFICATION
V-SLOPE METHOD
Normal
>40% del V’O2 MAX
BEHIND ANAEROBIC THRESHOLD IDENTIFICATION
END OF RESPIRATORY COMPENSATION IDENTIFICATION
VE/VCO2 SLOPE
Ventilatory Efficiency
! overestimated VE/VCO2 slope
Tidal volume & Respiratory frequency
• VT
non-linearly– may plateau in some– ventilatory limitation
• VT > 55% of VC
• RF– slow initially– sharp
• hyperventilation– ventilatory limitation
• RR > 55 b/min
k x VCO2[PaCO2 x (1-Vd/Vt)]
VE=
…beyond VO2… the future of CPET…
Piergiuseppe Agostoni, MD, PhDGaia Cattadori, Anna Apostolo, Mauro Contini,
Pietro Palermo, Giancarlo Marenzi, Karlman Wasserman.
VO2 = VE (FiO2 – FeO2)
VO2 = Q (CaO2 – CvO2)
VO2 = D (PcapO2 – PmitO2)
Fick
a) Cardiac output
b) A-V O2 difference- hemoglobin- Hb O2 sat
- pO2
0
2,5
5
7,5
10
12,5
15
2,5 5 7,5 10 12,5 15 17,5 20
2,00
1,75
1,50
1,25
1,00
0,75
0,50
0,25
VO2 = C.O. x C(a-v)O2
A-V Content Difference (ml/100 ml)
Card
iac O
utp
ut
(L/m
in)
0
2,5
5
7,5
10
12,5
15
2,5 5 7,5 10 12,5 15 17,5 20
2,00
1,75
1,50
1,25
1,00
0,75
0,50
0,25
VO2 = C.O. x C(a-v)O2
A-V Content Difference (ml/100 ml)
Card
iac O
utp
ut
(L/m
in)
HealthyHealthy
+ Hb
COPD
HF
Anemia
Stringer WW et al. J Appl Physiol. 82(3): 908-912
CO estimated noninvasively from oxygen uptake during exercise.
Method: INERT GAS REBREATHING
Spontaneous rebreathe (for 10-20 sec.) from a bag prefilled with an oxygen enriched mixture containing two foreign gases Nitrous oxide (N2O) is soluble in blood and its concentration decreases during rebreathing with a rate proportional to CO Sulphur hexafluoride (SF6) is insoluble in blood and is used to determine the lung volume Population:
20 CHF pts (VO2max 16.62.9 ml/min/Kg)Study Design:
1. CPET (ramp protocol) to assess functional capacity2. CPET (incremental protocol) with CO determination at each step by
- Inert Gas Rebreathing method (R) 3. CPET (incremental protocol) with CO determination at each step by
- Inert Gas Rebreathing method (R) - Direct Fick method - Thermodilution method
y = 0.779x + 2.1037R = 0.9382
0
4
8
12
16
20
0 4 8 12 16 20
Thermodilution (L/min)
Reb
rea
th
ing
(L
/min
)
y = 1.1425x - 1.3518R = 0.9465
0
4
8
12
16
20
0 4 8 12 16 20
Direct Fick (L/min)
Th
erm
od
ilu
tio
n (
L/m
in)
Conclusions:
Agreement (vs Fick and vs Thermodilution)
In CHF CO measurement during exerciseby Inert Gas Rebreathing technique provides repeatable measurements
that agree with Direct Fick and Thermodilution methods
y = 0.9504x + 0.5366R= 0.9482
0
4
8
12
16
20
0 4 8 12 16 20
Direct Fick (L/min)
Reb
rea
th
ing
(L
/min
)
F vs TR= 0.95
R vs FR= 0.95
R vs TR= 0.94
0
2
4
6
8
10
12
14
16
18
20
22
0 2 4 6 8 10 12 14 16 18 20
Artero-venous oxygen difference (ml/100ml)
Car
dia
cO
utp
ut
(L/m
in)
1,5
1
0,50,3
VO2
(L/min)
VO2 Pred = 2695 VO2 Measured 2079 (83%)
0
2
4
6
8
10
12
14
16
18
20
22
0 2 4 6 8 10 12 14 16 18 20
Artero-venous oxygen difference (ml/100ml)
Car
dia
c O
utp
ut
(L/m
in)
1,5
1
0,50,3
VO2
(L/min)
VO2 Pred = 1676 VO2 Measured 947 (57%)
0
2
4
6
8
10
12
14
16
18
20
22
0 2 4 6 8 10 12 14 16 18 20
Artero-venous oxygen difference (ml/100ml)
Car
dia
c O
utp
ut
(L/m
in)
1,5
1
0,50,3
VO2
(L/min)
PRE riab VO2p=713 (8.6) POST riab VO2p=806 (9.7)
0
2
4
6
8
10
12
14
16
18
20
22
0 2 4 6 8 10 12 14 16 18 20
Artero-venous oxygen difference (ml/100ml)
Car
dia
c O
utp
ut
(L/m
in)
1,5
1
0,50,3
VO2
(L/min)
PRE riab VO2p=911 (12.7) POST riab VO2p=1413 (19.6)
However, we have to account for Cardiac Output distribution,
exercise hemoconcentration and
anemia…
Agostoni et al Am J Cardiol 2001
Agostoni et al Am J Cardiol 2001
CO distribution improves in severe HF
STUDY SAMPLE
21 patients with thalassemia intermedia
10 with previuos splenectomy
Agostoni PG et al. Brit J Haematol 2005
VO2 peak (ml/kg/min) 24.3±6.9 22.5±4.4
Δ Hb (g/dl) 0.95±0.37 0.4±0.2*
Δ Haematocrit (%) 3.03±1.33 1.38±0.82*
Δ Plasma Proteins (g/dl)
0.5±0.4 0.42±0.28
Δ Red Cells 0.46±0.25 0.17±0.1*
Plasmatic Albumin 0.25±0.2 0.2±0.2
VE/VCO2 32.2±6.9 29±2.6
VO2/WORK 9.39±0.68 9.1±0.82
Without splenectomy
Splenectomized
*p<0.01 vs pts without splenectomy Agostoni PG et al. Brit J Haematol 2005
How much is anaemia relevant ?
if Hb sat 100%CaO2 = 1.34 ml x gr Hb
if peripheral O2 extraction 70%
1 gr Hb provides to the tissues
1 ml O2 x dl of blood.
….clinical use
VO2max predicted 2695 (ml/min)HRmax predicted 169 (b/min)COmax predicted 16.6 (L/min) {(≥5xVO2)+3}
Hb predicted 15 (g/dl)diffAV predicted 16.4 (ml/100ml)
Step CO L/min
HR b/min
SV ml/b
VO2 ml/min
Diff AV
Basal 5.9 90 66 208 3.5
40 % 10.1 101 100 1155 11.4
Peak 15.3 166 92 2310 15
Peak pred
16.6 169 98 2695 16.4
Peak % 92 98 94 86 91
Hb 15 gr/dl
ml VO2 due to anemia 0 ml
ml VO2 due to deconditioning [(16.4-15.0)x153]=214 ml
ml VO2 due to CO 166 – 153 = 13 x 16.4 = 213 ml
Deficit VO2 calcolated 427 ml/min
Deficit VO2 observed 385 ml/min
CONCLUSIONS: Test indicative of good functional capacity (VO2 max 86% of the predicted). Minimal deficit due to:
- anemia (0%)
- deconditioning (50%)
- cardiogenic (50%)
VO2max predicted 2120 (ml/min)HRmax predicted 154 (b/min)COmax predicted 13.6 (L/min) {(≥5xVO2)+3}
Hb predicted 15 (g/dl)diffAV predicted 16 (ml/100ml)
Step CO (L/min)
HR (b/min)
SV (ml/b)
VO2 (ml/min
Diff AV
Basal 4.5 75 60 220 5
40 watt
5.9 102 58 604 10
Peak 7.9 109 72 1080 14
Peak pred
13.6 154 88 2120 16
Peak %
58 71 82 51 88
Hb 11 gr/dl
ml VO2 due to anemia 4gr x 79 = 316 ml
ml VO2 due to deconditioning [(16-14)x79] – 316=-158 ml
ml VO2 due to CO 136 – 79 = 57 x 16 = 912 ml
Deficit VO2 calculated 1070 ml/min
Deficit VO2 observed 1040 ml/min
DEFICIT VO2 considering an over-extraction due to compensation mechanisms: 1228 ml/VO2CONCLUSIONS: Test
indicative of reduced functional capacity (VO2max 51% of predicted) due to:
- anemia (-26%)
- deconditioning (+13%)
- cardiogenic (-74%)
mainly due to the reduced increase of HR (71% of predicted) with a good stroke volume max (80% of predicted).
VO2max predicted 1676 (ml/min)HRmax predicted 154 (b/min)COmax predicted 11.4 (L/min) {(≥5xVO2)+3}
Hb predicted 15 (g/dl)diffAV predicted 14.7 (ml/100ml)
Step CO (L/min)
HR (b/min)
SV (ml/b)
VO2 (ml/min
Diff AV
Basal 4.0 76 50 250 6.2
40 % 5.8 84 69 569 9.8
Peak 7.8 110 71 947 12.1
Peak pred
11.4 154 74 1676 14.7
Peak %
68 71 96 57 82
Hb 15 gr/dl
ml VO2 due to anemia 0 ml
ml VO2 due to deconditioning [(14.7-12.1)x78] = 202 ml
ml VO2 due to CO 114 – 78 = 36 x 14.7 = 529 ml
Deficit VO2 calculated 731 ml/min
Deficit VO2 observed 729 ml/min
CONCLUSIONS: Test indicative of reduced functional capacity (VO2 max 57% of predicted) due to:
- anemia (0%)
- deconditioning (28%)
- cardiogenic (72%)
mainly due to the reduced increase of HR