• Open Access

Recommendations for Screening and Detection of Connective Tissue Disease–Associated Pulmonary Arterial Hypertension

Authors

  • Dinesh Khanna,

    Corresponding author
    1. University of Michigan, Ann Arbor
    • University of Michigan, Division of Rheumatology, Department of Internal Medicine, Suite 7C27, 300 North Ingalls Street, SPC 5422, Ann Arbor, MI 48109. E-mail: khannad@med.umich.edu

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    • Dr. Khanna has received consulting fees, speaking fees, and/or honoraria from United Therapeutics, Roche, Bristol-Myers Squibb, Gilead, Pfizer, Digna Biotech, and Impact Pharmaceutical Services (less than $10,000 each) and from Actelion (more than $10,000).

  • Heather Gladue,

    1. University of Michigan, Ann Arbor
    Current affiliation:
    1. Emory University, Atlanta, Georgia
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  • Richard Channick,

    1. Massachusetts General Hospital, Boston
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    • Dr. Channick has received consulting fees, speaking fees, and/or honoraria from Actelion, United Therapeutics, and Bayer (less than $10,000 each).

  • Lorinda Chung,

    1. Stanford University School of Medicine, Stanford, California
    2. Palo Alto VA Health Care System, Palo Alto, California
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    • Dr. Chung has received consulting fees, speaking fees, and/or honoraria from Gilead (less than $10,000).

  • Oliver Distler,

    1. University Hospital Zurich, Zurich, Switzerland
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    • Dr. Distler has received consulting fees, speaking fees, and/or honoraria from Bayer, Pfizer, ErgoNex, Bristol-Myers Squibb, Sanofi-Aventis, Sinoxa, United BioSource, Medac, Swedish Orphan Biovitrum, Boehringer Ingelheim Pharma, Novartis, and Active Biotech (less than $10,000 each) and from Actelion and 4D Science (more than $10,000 each); he also has a patent for the use of microRNA-29 for the treatment of systemic sclerosis.

  • Daniel E. Furst,

    1. David Geffen School of Medicine at University of California, Los Angeles
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  • Eric Hachulla,

    1. Université Lille 2 and Hôpital Claude Huriez, Lille, France
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    • Dr. Hachulla has received consulting fees, speaking fees, and/or honoraria from Actelion, Pfizer, Lilly, United Therapeutics, and GlaxoSmithKline (less than $10,000 each).

  • Marc Humbert,

    1. Université Paris-Sud, INSERM U999, AP-HP, and Hôpital Bicêtre, Le Kremlin-Bicêtre, France
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    • Dr. Humbert has received consulting fees, speaking fees, and/or honoraria from Actelion, Aires Pharmaceuticals, Bayer, GlaxoSmithKline, Novartis, and Pfizer (less than $10,000 each).

  • David Langleben,

    1. Jewish General Hospital and McGill University, Montreal, Quebec, Canada
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    • Dr. Langleben has received consulting fees, speaking fees, and/or honoraria from Actelion, Bayer, Novartis, Pfizer, GlaxoSmithKline, Lilly, and United Therapeutics (less than $10,000 each).

  • Stephen C. Mathai,

    1. Johns Hopkins University School of Medicine, Baltimore, Maryland
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    • Dr. Mathai has received consulting fees, speaking fees, and/or honoraria from Bayer Healthcare, United Therapeutics, and Actelion (less than $10,000 each).

  • Rajeev Saggar,

    1. St. Joseph's Hospital and Medical Center, Phoenix, Arizona
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    • Dr. Saggar has received consulting fees, speaking fees, and/or honoraria from United Therapeutics, Gilead, Actelion, and Bayer (less than $10,000 each).

  • Scott Visovatti,

    1. University of Michigan, Ann Arbor
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  • Nezam Altorok,

    1. University of Michigan, Ann Arbor
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  • Whitney Townsend,

    1. University of Michigan, Ann Arbor
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  • John FitzGerald,

    1. David Geffen School of Medicine at University of California, Los Angeles
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  • Vallerie V. McLaughlin

    1. University of Michigan, Ann Arbor
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    • Dr. McLaughlin has received consulting fees, speaking fees, and/or honoraria from Merck (less than $10,000) and from Actelion, Bayer, Gilead, and United Therapeutics (more than $10,000 each); she also has received institutional grants and research support from Actelion, Bayer, and Novartis.


Abstract

Objective

Pulmonary arterial hypertension (PAH) affects up to 15% of patients with connective tissue diseases (CTDs). Previous recommendations developed as part of larger efforts in PAH did not include detailed recommendations for patients with CTD-associated PAH. Therefore, we sought to develop recommendations for screening and early detection of CTD-associated PAH.

Methods

We performed a systematic review of the literature on the screening and diagnosis of PAH in CTD. Using the RAND/University of California, Los Angeles consensus methodology, we developed case scenarios followed by 2 stages of voting. First, international experts from a variety of specialties voted anonymously on the appropriateness of each case scenario. The experts then met face-to-face to discuss and resolve discrepant votes to arrive at consensus recommendations.

Results

The key recommendation stated that all patients with systemic sclerosis (SSc) should be screened for PAH. In addition, patients with mixed connective tissue disease or other CTDs with scleroderma features (scleroderma spectrum disorders) should be screened for PAH. It was recommended that screening pulmonary function tests (PFTs) with single-breath diffusing capacity for carbon monoxide, transthoracic echocardiogram, and measurement of N-terminal pro–brain natriuretic peptide (NT-proBNP) be performed in all patients with SSc and scleroderma spectrum disorders. In patients with SSc and scleroderma spectrum disorders, transthoracic echocardiogram and PFTs should be performed annually. The full screening panel (transthoracic echocardiogram, PFTs, and measurement of NT-proBNP) should be performed as soon as any new signs or symptoms are present.

Conclusion

We provide consensus-based, evidence-driven recommendations for screening and early detection of CTD-associated PAH. It is our hope that these recommendations will lead to earlier detection of CTD-associated PAH and ultimately improve patient outcomes.

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