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