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Pulmonary arterial hypertension with below threshold pulmonary vascular resistance


Seshika Ratwatte, James Anderson, Geoffrey Strange, Carolyn Corrigan, Nicholas Collins, David S. Celermajer, Nathan Dwyer, John Feenstra, Dominic Keating, Eugene Kotlyar, Melanie Lavender,Helen Whitford, Ken Whyte, Trevor Williams, Jeremy P. Wrobel, Anne Keogh, Edmund M. Lau on behalf of the PHSANZ Registry

European Respiratory Journal 2020 56: 1901654; DOI: 10.1183/13993003.01654-2019

Abstract

Pulmonary vascular resistance (PVR) >3 Wood units is a criterion of the haemodynamic definition of pulmonary arterial hypertension (PAH). However, this cut-off is conservative and arbitrarily defined. Data is lacking on the natural history, response to therapy and survival of patients diagnosed with precapillary pulmonary hypertension (PH) with mild or borderline elevation of PVR.

In Australia, PAH therapy could be prescribed solely on mean pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) criteria. Using the Australian and New Zealand Pulmonary Hypertension Registry, we aimed to study a population diagnosed with PAH between January 2004 and December 2017 with the pre-defined haemodynamic characteristics of mean PAP ≥25 mmHg, PAWP ≤15 mmHg and PVR <3 Wood units.

Eighty-two patients met the pre-defined haemodynamic inclusion criteria (mean age 63±11 years; 67 females). Underlying aetiologies included idiopathic disease (n=39), connective tissue disease (CTD; n=42) and HIV infection (n=1). At diagnosis, mean PAP was 27 mmHg (interquartile range (IQR) 25–30 mmHg), PAWP 13 mmHg (IQR 11–14 mmHg) and PVR 2.2 Wood units (IQR 1.9–2.7 Wood units). Baseline 6-min walk distance (6MWD) was 352 m (IQR 280–416 m) and 77% of subjects were in New York Heart Association (NYHA) functional class 3 or 4. All patients were commenced on initial monotherapy with an endothelin receptor antagonist (ERA; n=66) or phosphodiesterase type-5 inhibitor (PDE5i; n=16). At first re-evaluation, 6MWD increased by 46 m (IQR 7–96 m) and 35% of subjects demonstrated improvement in NYHA functional class. After a median follow-up of 65 months (IQR 32–101 months), 18 out of 82 subjects (22.0%) had died, with estimated 1-year and 5-year survival rates of 98% and 84%, respectively. Death attributed to PAH occurred in six out of these 18 patients (33.3%, 7% of total cohort).

Patients with precapillary PH and “borderline” PVR falling outside the current definition have adverse outcomes. Such patients appear to respond to PAH therapy; however, this requires further study in randomised trials.

Selected patients with precapillary PH and “borderline” PVR, who fail to meet the current threshold of 3 Wood units, have functional limitation and adverse outcomes, and may potentially benefit from PAH therapy https://bit.ly/2QYaQrC

Footnotes

  • This article has an editorial commentary: https://doi.org/10.1183/13993003.00962-2020

  • This article has supplementary material available from erj.ersjournals.com

  • Conflict of interest: J. Anderson reports research support from GlaxoSmithKline and travel grants from Actelion and Bayer.

  • Conflict of interest: G. Strange reports grants from Actelion, Bayer, Pfizer Pharmaceuticals and GlaxoSmithKline, and personal fees from Actelion, Arena Pharmaceuticals, Bayer and GlaxoSmithKline, outside the submitted work.

  • Conflict of interest: C. Corrigan has nothing to disclose.

  • Conflict of interest: N. Collins reports fees for lectures from Actelion, outside the submitted work.

  • Conflict of interest: D.S. Celermajer has nothing to disclose.

  • Conflict of interest: N. Dwyer has participated in advisory board work for Actelion, GlaxoSmithKline and Bayer, outside the submitted work.

  • Conflict of interest: J. Feenstra has nothing to disclose.

  • Conflict of interest: D. Keating reports personal fees for lectures from GlaxoSmithKline, Actelion and Novartis, outside the submitted work.

  • Conflict of interest: E. Kotlyar reports personal fees for lectures from Actelion, Bayer, Novartis, Servier and GlaxoSmithKline, as well as advisory board work for GlaxoSmithKline, Actelion and Bayer, outside the submitted work.

  • Conflict of interest: M. Lavender has been consultant to and received grants from GlaxoSmithKline, Actelion and Bayer, outside the submitted work.

  • Conflict of interest: H. Whitford reports fees for lectures, advisory board work and travel grants from Actelion, GlaxoSmithKline and Bayer, outside the submitted work.

  • Conflict of interest: K. Whyte has nothing to disclose.

  • Conflict of interest: T. Williams reports advisory board work for Actelion, GlaxoSmithKline and Bayer, as well as grants from Actelion, outside the submitted work.

  • Conflict of interest: J.P. Wrobel reports fees for lectures, advisory board work and travel grants from Actelion, Boehringer Ingelheim, GlaxoSmithKline and Roche, outside the submitted work.

  • Conflict of interest: A. Keogh reports advisory board work for Actelion, GlaxoSmithKline and Bayer, as well as grants from Actelion, Bayer, Pfizer, Gilead, Arena, Respira, Acceleron, Pfizer and Bellerophon, outside the submitted work.

  • Conflict of interest: E.M. Lau reports speaking and consultancy fees from Actelion and Menarini Pharmaceuticals, as well as research support from Actelion and GlaxoSmithKline.

  • Conflict of interest: S. Ratwatte has nothing to disclose.

  • Support statement: Funding support for the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) Registry was provided by Actelion Pharmaceuticals, Allied Healthcare, Bayer, GlaxoSmithKline, Novartis and Pfizer. GlaxoSmithKline provided research funding support for the primary author, but were not involved in conceptualisation, analysis or manuscript preparation. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received August 21, 2019.
  • Accepted March 24, 2020.
  • Copyright ©ERS 2020

sumber : https://erj.ersjournals.com/content/56/1/1901654

 
 

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