Annual Congress of the European Society of Cardiology Munich, August

Annual Congress of the European Society of Cardiology Munich, August 26 2012 Gas exchange measurements during exercise show early pulmonary arterial hypertension in scleroderma patients 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 daniel.dumitrescu@uk-koeln.de

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 546 pts. with systemic sclerosis (w/o pulmonary fibrosis or left heart disease) Overall 3-year Survival: 91.1% 94.4% 56.3% Hachulla-E et al, Rheumatology 2009; 48: 304-308

Relationship between Pulmonary Microcirculation Loss and Pulmonary Artery Pressure at Rest mean PAP Lau et al., Eur Heart J 2011; published on-line May 26

Rationale for measurement of PETCO 2 during exercise pulmonary vascular disease Mismatch between perfusion and ventilation: Poor perfusion, good ventilation PaCO 2 > PETCO 2 pulmonary vascular disease PaCO2 = arterial pco2 PETCO2 = end-tidal PCO2 Normal value slightly < 40 mmhg Normal value around 40 mmhg normal Pulmonary ventilation-/perfusion mismatch, reflected by ventilatory efficiency: VE/VCO 2 (left) and PETCO 2 (right) normal Froim: Kroidl et al. Kursbuch Spiroergometrie. 2006

Likelihood of PAH, estimated by ventilatory equivalents and end-tidal CO 2 at the anaerobic threshold N=60 9 healthy controls 52 PAH patients 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.

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 VO 2 (ml/min) Highest average during a complete 30-s period, to the nearest 10 ml/min Peak Heart rate (1/min) Peak O 2 pulse (ml/beat) AT (ml/min) PETCO2@AT (mmhg) VE/VCO2@AT (mmhg) Highest average during the same complete 30-s period Peak VO2 peak heart rate, to the nearest 0,1 ml/beat Primarily V-slope method, but may also use end-tidal and ventilatory equivalent data, to the nearest 10 ml/min Average for the 60-s period at and immediately after the AT 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 PETCO 2 vs tricuspid pressure gradient true negative false negative false positive true positive false positive true positive true negative false negative

Diagnostic accuracy of PETCO 2 vs tricuspid pressure gradient true negative false negative AT 26 mmhg AT 31 mmhg AT 27 mmhg false positive true positive false positive true positive true negative false negative

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) Peak oxygen consumption (ml/min/kg) Anaerobic threshold (AT) (ml/min/kg) VE/VCO2 at the AT (no unit) PETCO2 at the AT (mmhg) PETCO2 difference between start of exercise and AT (mmhg) 1: 26,7±7,9 2: 35,8±14,8 3: 57,9±23,5 1: 15,8±3,1 2: 12,6±2,1 3: 10,3±2,9 1: 11,3±2,2 2: 9,9±2,1 3: 7,8±1,4 1: 31,4±3,6 2: 41,3±1,9 3: 45,2±9,3 1: 36,1±4,0 2: 26,5±0,9 3: 25,7±5,4 1: 3,9±2,3 2: 0,4±3,5 3: -2,5±1,4 no yes no yes yes no no yes no yes yes no yes yes no yes yes yes

Correlation of DLCO with invasive hemodynamic measurements

Clinical importance of PETCO 2 measurement - Inclusion of postcapillary PH (PCWP > 15 mmhg)

Clinical importance of PETCO 2 measurement Inclusion of borderline PAH (PAPmean 21-24 mmhg)

Conclusions - CPET is able to detect PAH in scleroderma patients. - PETCO 2 is an important parameter to detect PAH in early and late stages. - PETCO 2 is better able to detect early PAH than the estimated PAP by echo. - The PETCO 2 difference adds relevant information to the AT value. - CPET might be considered for routine screening in scleroderma patients.

THANK YOU FOR YOUR ATTENTION!