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OP0036 An Evidence-Based Tool for Detection of Pulmonary Arterial Hypertension in Systemic Sclerosis: The Detect Study
  1. C. P. Denton1,
  2. J. G. Coghlan1,
  3. E. Grünig2,
  4. D. Bonderman3,
  5. O. Distler4,
  6. D. Khanna5,
  7. U. Müller-Ladner6,
  8. J. E. Pope7,
  9. M. C. Vonk8,
  10. M. Doelberg9,
  11. H. Chadha-Boreham9,
  12. H. Heinzl3,
  13. D. M. Rosenberg9,
  14. V. V. McLaughlin5,
  15. J. R. Seibold10
  1. 1Royal Free Hospital, London, United Kingdom
  2. 2University Hospital Heidelberg, Heidelberg, Germany
  3. 3Medical University of Vienna, Vienna, Austria
  4. 4University Hospital Zurich, Zurich, Switzerland
  5. 5University of Michigan, Ann Arbor, United States
  6. 6Kerckhoff Clinic, Bad Nauheim, Germany
  7. 7Western University of Canada, St Joseph’s Health Care, London, Ontario, Canada
  8. 8Radboud University Medical Centre, Nijmegen, Netherlands
  9. 9Actelion Pharmaceuticals Ltd, Allschwil, Switzerland
  10. 10Scleroderma Research Consultants LLC, Avon, Connecticut, United States

Abstract

Background Diagnosis of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) requires right heart catheterisation (RHC). Current screening recommendations are consensus-based and focus on echocardiography and symptoms. While false positives are common, the rate of false negatives (missed diagnoses) has never been determined.

Objectives The DETECT study aimed to develop the first comprehensive evidence-based tool for detection of PAH in SSc patients that would limit the number of missed PAH diagnoses.

Methods In this multicentre, cross-sectional cohort study (NCT00706082), patients with SSc for >3 years, a diffusing capacity of the lung for carbon monoxide (DLCO) <60% of predicted, and no previous diagnosis of pulmonary hypertension underwent multiple non-invasive screening tests (112 total) followed by RHC. Univariable and multivariable analyses selected the best discriminatory variables for identifying PAH. These variables were assessed for clinical plausibility and feasibility and incorporated into an internally validated detection algorithm. Tools for application in clinical practice were developed.

Results 466 SSc patients underwent RHC. Of these, 19% (n=87) had RHC-confirmed PAH and 69% (n=321) had normal pulmonary arterial pressure (PAP). PAH was mild (mean PAP 32.5 [30.7−34.3] mmHg; 64% WHO functional class I or II). Eight variables were included in a two-step algorithm. To align the algorithm with real-world practice where non-echocardiographic data might be evaluated first, six accessible clinical variables (forced vital capacity % predicted/DLCO % predicted; current/past telangiectasias; anti-centromere antibody; N-terminal pro-brain natriuretic peptide; uric acid; right axis deviation on electrocardiography) were used in step 1 to inform referral to echocardiography. Right atrial area and tricuspid regurgitation jet velocity were added in step 2 to determine referral to RHC. The DETECT algorithm, with pre-defined step 1 sensitivity 97% and step 2 specificity 35%, resulted in 4% missed PAH diagnoses, requiring RHC in 62% of patients. When the current ESC/ERS1 screening recommendations were applied, missed diagnoses and RHC referral rates were 29% and 40%, respectively. Paper-based and electronic tools for application of the DETECT algorithm in clinical practice are available.

Conclusions The two-step DETECT algorithm is a sensitive, non-invasive tool to facilitate early detection of PAH in SSc patients with a low DLCO, addressing resource utilisation of echocardiography and RHC and, most importantly, minimising missed diagnoses. This is an evidence-based approach to improving standards of care for SSc.

References

  1. Galiè N et al. Eur Heart J 2009;30:2493–537.

Acknowledgements Actelion Pharmaceuticals Ltd was responsible for designing the study protocol, data collection, and statistical analysis under the leadership of an independent Study Scientific Committee (non-Actelion authors, apart from HH). The authors would like to thank all investigators and patients involved in the DETECT study. They would also like to thank Fabrice Kiefer, PhD and Aisha Rashid, BSc (Actelion Pharmaceuticals Ltd) and Outcome Europe SARL (St-Prex, Switzerland) for their operational support, Juan-Vicente Torres-Martin, MSc (Actelion Pharmaceuticals Ltd) for support of the statistical analyses, Martin Schumacher, PhD (University of Freiburg, Germany) for statistical consultancy, and Julia Heagerty, PhD (Elements Communications Ltd, Westerham, UK) for medical writing support funded by Actelion Pharmaceuticals Ltd.

Disclosure of Interest C. Denton Grant/research support from: Actelion, Pfizer, GSK, Sanofi-Aventis, Novartis, Consultant for: Actelion, Pfizer, GSK, Sanofi-Aventis, Novartis, J. Coghlan Grant/research support from: Actelion, Pfizer, GSK, United Therapeutics, Consultant for: Actelion, Pfizer, GSK, United Therapeutics, Speakers bureau: Actelion, Pfizer, GSK, United Therapeutics, E. Grünig Grant/research support from: Actelion, Bayer, GSK, Encysive, Lilly, Pfizer, Consultant for: Actelion, Bayer, Gilead, GSK, Lilly, Milteney, Novartis, Pfizer, Rotex Medica, Speakers bureau: Actelion, Bayer, Gilead, GSK, Lilly, Milteney, Novartis, Pfizer, Rotex Medica, D. Bonderman Grant/research support from: Actelion, Consultant for: Actelion, O. Distler Grant/research support from: Actelion, Pfizer, Ergonex, Sanofi-Aventis, Consultant for: Actelion, Pfizer, Boehringer-Ingelheim, Bayer, Roche, Ergonex, BMS, Sanofi-Aventis, United Biosource Corporation, Medac, Biovitrium, Novartis, Active Biotech, 4D Science, Sinoxa, Speakers bureau: Actelion, Pfizer, Ergonex, D. Khanna Grant/research support from: Actelion, BMS, Gilead, Genentech, ISDIN, United Therapeutics, Consultant for: Actelion, BMS, Gilead, Genentech, ISDIN, United Therapeutics, Bayer, Sanofi-Aventis, Merck, Roche, Speakers bureau: Actelion, United Therapeutics, U. Müller-Ladner Grant/research support from: Actelion, Consultant for: Actelion, Speakers bureau: Actelion, Pfizer, GSK, J. Pope Grant/research support from: Actelion, Amgen, Abbott, BMS, UCB, Janssen, Roche, Celgene, Teva, Consultant for: Actelion, Amgen, Abbott, BMS, Pfizer, UCB, Janssen, Roche, GSK, Speakers bureau: Amgen, BMS, Pfizer, M. Vonk Grant/research support from: Actelion, Pfizer, GSK, United Therapeutics, Therabel Pharma, Consultant for: Actelion, Pfizer, Speakers bureau: Actelion, Pfizer, M. Doelberg Shareholder of: Actelion, Employee of: Actelion, H. Chadha-Boreham Shareholder of: Actelion, Employee of: Actelion, H. Heinzl Grant/research support from: Roche Austria, Consultant for: Actelion, D. Rosenberg Shareholder of: Actelion, Employee of: Actelion, V. McLaughlin Grant/research support from: Actelion, Bayer, Novartis, United Therapeutics, Consultant for: Actelion, Bayer, Gilead, United Therapeutics, Speakers bureau: Actelion, Gilead, United Therapeutics, J. Seibold Grant/research support from: Actelion, Gilead, United Therapeutics, Consultant for: Actelion, Pfizer, Gilead, United Therapeutics, Boehringer-Ingelheim, Bayer, Sigma Tau, FibroGen, Sanofi-Aventis, Celgene, MedImmune, Genentech, InterMune

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