Gas exchange measurements during exercise show early pulmonary

Daniel Dumitrescu, Cathérine Seck, Pia Moinzadeh, Nicolas Hunzelmann, Stephan Rosenkranz

Klinik III für Innere Medizin, Klinik für Dermatologie und Venerologie

Herzzentrum der Universität zu Köln, Universitätsklinikum Köln

[email protected]

Gas exchange measurements during exercise

show early pulmonary arterial hypertension

in scleroderma patients

Annual Congress of the

European Society of Cardiology

Munich, August 26 2012

Conflict of Interest - Disclosure

Within the past 12 months, I or my spouse/partner have had a financial

interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

1. Honoraria for lectures Actelion, GSK, Lilly, Pfizer

2. Honoraria for advisory board activities

3. Participation in clinical trials Actelion, Bayer, GSK, Novartis

4. Research support Actelion, Pfizer,

3-Year Survival in Patients with Systemic Sclerosis:

The French ItinérAIR-Sclérodermie Study

Hachulla-E et al, Rheumatology 2009; 48: 304-308

546 pts. with systemic sclerosis (w/o pulmonary fibrosis or left heart disease) Overall 3-year Survival: 91.1%

94.4%

56.3%

Relationship between Pulmonary Microcirculation

Loss and Pulmonary Artery Pressure at Rest

Lau et al., Eur Heart J 2011; published on-line May 26

mean PAP

Froim: Kroidl et al. Kursbuch Spiroergometrie. 2006

normal normal

pulmonary

vascular

disease

pulmonary

vascular

disease

Mismatch between

perfusion and ventilation:

Poor perfusion, good ventilation

PaCO2 > PETCO2

Rationale for measurement of PETCO2 during exercise

PaCO2 = arterial pCO2

PETCO2 = end-tidal PCO2

Normal value slightly < 40 mmHg

Normal value around 40 mmHg

Pulmonary ventilation-/perfusion mismatch, reflected by ventilatory efficiency:

VE/VCO2(left) and PETCO2 (right)

Likelihood of PAH, estimated by ventilatory equivalents and

end-tidal CO2 at the anaerobic threshold

Yasunobu Y, Oudiz RJ, Sun XG, Hansen JE, Wasserman K. End-tidal PCO2 abnormality and exercise limitation in patients

with primary pulmonary hypertension. Chest. 2005 May;127(5):1637-1646.

N=60

9 healthy controls

52 PAH patients

Study design

•Consecutive referrals from scleroderma clinic

•SSc and dyspnea (known or new onset)

•No PH diagnosed or known from medical history

n = 45

Non-invasive diagnostic work-up:

•Echocardiography

•Lung function testing

•6 minute walking distance

•NTproBNP

•Cardiopulmonary exercise testing

RIGHT HEART CATHETERIZATION

Group 1: No PAH

PAPmean < 25 mmHg

n=23

Group 2: Mild PAP elevation

PAPmean 25-35 mmHg

n=9

Group 3: High PAP elevation

PAPmean > 35 mmHg

n=13

Calculation of gas exchange parameters

Measurement Calculation algorithm

Peak VO2 (ml/min) Highest average during a complete 30-s

period, to the nearest 10 mL/min

Peak Heart rate (1/min) Highest average during the same

complete 30-s period

Peak O2 pulse (ml/beat) Peak VO2 ÷ peak heart rate,

to the nearest 0,1 ml/beat

AT (ml/min) Primarily V-slope method, but may also

use end-tidal and ventilatory equivalent

data, to the nearest 10 mL/min

PETCO2@AT (mmHg) Average for the 60-s period at and

immediately after the AT

VE/VCO2@AT (mmHg) Average for the 60-s period at and

immediately after the AT

Hansen et al. Reproducibility of Cardiopulmonary Exercise Measurements in patients with pulmonary arterial

hypertension. CHEST 2004;126: 816-824

Patient Characteristics

Total Group 1 Group 2 Group 3

n 45 23 9 13

M/F 9/36 6/17 2/7 1/12

Age (years) 59 ± 13 55 ± 13 62 ± 10 65 ± 12

BMI 24.8 ± 3.7 24.7 ± 3.8 25.4 ± 3.9 24.6 ± 3.7

FVC (% predicted) 84.1 ± 20.5 83.6 ± 4.9 81.8 ± 17.2 86.4 ± 18.4

DLCO (% predicted) 55.2 ± 16.3 61.4 ± 15.1 52.3 ± 14.5 40.5 ± 17.1

PAPmean (mmHg) 28.7 ± 13.4 18.6 ± 5.0 27.8 ± 2.6 45.8 ± 8.6

PCWP (mmHg) 10.7 ± 3.5 10.3 ± 4.0 11.4 ± 2.8 10.9 ± 3.2

CO (L/Min) 4.9 ± 1.3 5.4 ± 1.1 4.8 ± 1.3 4.0 ± 1.0

PVR (Wood units) 4.4 ± 4.0 1.6 ± 0.7 3.6 ± 0.8 9.4 ± 3.4

Diagnostic accuracy of PETCO2 vs tricuspid pressure gradient

true negative false negative

false positive true positive












AT 31 mmHg

AT 26 mmHg

AT 27 mmHg


Relevance of non-invasive diagnostic procedures

Mean ±SD Significance (ANOVA): p < 0,05

Groups (1,2,3) 1 vs 2 1 vs 3 2 vs 3

Tricuspid pressure gradient on echocardiography (mmHg)

1: 26,7±7,9

2: 35,8±14,8

3: 57,9±23,5

no yes no

Peak oxygen consumption (ml/min/kg)

1: 15,8±3,1

2: 12,6±2,1

3: 10,3±2,9

yes yes no

Anaerobic threshold (AT) (ml/min/kg)

1: 11,3±2,2

2: 9,9±2,1

3: 7,8±1,4

no yes no

VE/VCO2 at the AT (no unit)

1: 31,4±3,6

2: 41,3±1,9

3: 45,2±9,3

yes yes no

PETCO2 at the AT (mmHg)

1: 36,1±4,0

2: 26,5±0,9

3: 25,7±5,4

yes yes no

PETCO2 difference between start of exercise and AT (mmHg)

1: 3,9±2,3

2: 0,4±3,5

3: -2,5±1,4

yes yes yes

Patient Characteristics

Total Group 1 Group 2 Group 3

n 45 23 9 13

M/F 9/36 6/17 2/7 1/12

Age (years) 59 ± 13 55 ± 13 62 ± 10 65 ± 12

BMI 24.8 ± 3.7 24.7 ± 3.8 25.4 ± 3.9 24.6 ± 3.7

FVC (% predicted) 84.1 ± 20.5 83.6 ± 4.9 81.8 ± 17.2 86.4 ± 18.4

DLCO (% predicted) 55.2 ± 16.3 61.4 ± 15.1 52.3 ± 14.5 40.5 ± 17.1

PAPmean (mmHg) 28.7 ± 13.4 18.6 ± 5.0 27.8 ± 2.6 45.8 ± 8.6

PCWP (mmHg) 10.7 ± 3.5 10.3 ± 4.0 11.4 ± 2.8 10.9 ± 3.2

CO (L/Min) 4.9 ± 1.3 5.4 ± 1.1 4.8 ± 1.3 4.0 ± 1.0

PVR (Wood units) 4.4 ± 4.0 1.6 ± 0.7 3.6 ± 0.8 9.4 ± 3.4

Correlation of DLCO with invasive hemodynamic measurements

Clinical importance of PETCO2 measurement -

Inclusion of postcapillary PH (PCWP > 15 mmHg)

Clinical importance of PETCO2 measurement

Inclusion of borderline PAH (PAPmean 21-24 mmHg)

Conclusions

- CPET is able to detect PAH in scleroderma patients.

- PETCO2 is an important parameter to detect PAH in early and late stages.

- PETCO2 is better able to detect early PAH than the estimated PAP by echo.

- The PETCO2 difference adds relevant information to the AT value.

- CPET might be considered for routine screening in scleroderma patients.

THANK YOU FOR YOUR ATTENTION!

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Gas exchange measurements during exercise show early pulmonary