Evidence map›Paper›PMID 27072860›Full record

Trial reportCirculation. Heart failure2016

Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) Trial.

Imad Hussain, Selma F Mohammed, Paul R Forfia, Gregory D Lewis, Barry A Borlaug, Dianne S Gallup, Margaret M Redfield

Registry-linked trialOpen access · bronzeAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation. Heart failure, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00763867 (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure), which is not on this map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
9.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00763867 phase3completednot on this map

Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (RELAX)

TypeinterventionalSponsorDuke UniversityRan2008 to 2012Enrolled216ConditionsHeart FailureArmsPlacebo, Sildenafil
3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 91 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Novel Therapies for Right Ventricular Failure.Current cardiology reports · 2025
    Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Phosphodiesterase inhibitor for heart failure with preserved ejection fraction: A systematic review and meta-analysis.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Imad HussainFrom the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (I.H., S.F.M., B.A.B., M.M.R.); Temple University, Philadelphia, PA (P.R.F.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L.); Duke Clinical Research Institute, Durham, NC (D.S.G.).
Selma F MohammedFrom the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (I.H., S.F.M., B.A.B., M.M.R.); Temple University, Philadelphia, PA (P.R.F.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L.); Duke Clinical Research Institute, Durham, NC (D.S.G.).
Paul R ForfiaFrom the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (I.H., S.F.M., B.A.B., M.M.R.); Temple University, Philadelphia, PA (P.R.F.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L.); Duke Clinical Research Institute, Durham, NC (D.S.G.).
Gregory D LewisFrom the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (I.H., S.F.M., B.A.B., M.M.R.); Temple University, Philadelphia, PA (P.R.F.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L.); Duke Clinical Research Institute, Durham, NC (D.S.G.).
Barry A BorlaugFrom the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (I.H., S.F.M., B.A.B., M.M.R.); Temple University, Philadelphia, PA (P.R.F.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L.); Duke Clinical Research Institute, Durham, NC (D.S.G.).
Dianne S GallupFrom the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (I.H., S.F.M., B.A.B., M.M.R.); Temple University, Philadelphia, PA (P.R.F.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L.); Duke Clinical Research Institute, Durham, NC (D.S.G.).
Margaret M RedfieldFrom the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (I.H., S.F.M., B.A.B., M.M.R.); Temple University, Philadelphia, PA (P.R.F.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L.); Duke Clinical Research Institute, Durham, NC (D.S.G.). redfield.margaret@mayo.edu.
Massachusetts General Hospital · USHarvard University · USTemple University · US

Funding

Heart Failure Clinical Research Network Coordinating CenterU10HL084904 · NHLBI · DUKE UNIVERSITY · PI ANSTROM, KEVIN J, HERNANDEZ, ADRIAN · 2012 to 2018
$38.0M
Mayo Heart Failure Regional Clinical CenterU10HL110262 · NHLBI · MAYO CLINIC ROCHESTER · PI REDFIELD, MARGARET M · 2012 to 2018
$3.6M
Heart Failure Clinical Research Network Regional Clinical Center (U10)U10HL110312 · NHLBI · DUKE UNIVERSITY · PI FELKER, GARY M · 2012 to 2018
$3.5M
SALsalate to Improve Exercise toleraNce and LVDD in T2dm-DHF (SALIENT-DHF trial)U10HL110309 · NHLBI · WASHINGTON UNIVERSITY · PI DAVILA-ROMAN, VICTOR G., MANN, DOUGLAS L · 2012 to 2018
$3.5M
Harvard Regional Clinical Center of the NHLBI Heart Failure NetworkU10HL110337 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI GIVERTZ, MICHAEL M, LEWIS, GREGORY DYER · 2012 to 2018
$3.5M
Renal Sympathetic Denervation in Congestive Heart FailureU10HL110336 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI STARLING, RANDALL CARSON, TANG, WAI HONG WILSON · 2012 to 2018
$2.5M
Heart Failure Clinical Trials NetworkU10HL110302 · NHLBI · EMORY UNIVERSITY · PI SMITH, ANDREW · 2012 to 2018
$2.5M
Mayo Heart Failure Regional Clinical CenterU01HL084907 · NHLBI · MAYO CLINIC ROCHESTER · PI REDFIELD, MARGARET M · 2006 to 2011
$2.4M
Mid Atlantic Heart Failure NetworkU10HL110338 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI CAPPOLA, THOMAS P., MARGULIES, KENNETH BER · 2012 to 2018
$2.4M
New England, New York and Quebec Regional Clinical CenterU10HL110342 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI HUGGINS, GORDON S, VANBUREN, PETER C · 2012 to 2018
$2.3M
The Jefferson Regional Clinical Center for Heart Failure NetworkU10HL110297 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI WHELLAN, DAVID J · 2012 to 2018
$2.0M
The Texas Medical Center Regional Coordinating Center for Heart FailureU01HL084890 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI DESWAL, ANITA · 2006 to 2011
$1.8M
NHLBI NIH HHS U01 HL084861NHLBI NIH HHS U01 HL084889NHLBI NIH HHS U01 HL084890NHLBI NIH HHS U01 HL084891NHLBI NIH HHS U01 HL084907NHLBI NIH HHS U01 HL084931NHLBI NIH HHS U109 HL110337NHLBI NIH HHS U10 HL084904NHLBI NIH HHS U10 HL110262NHLBI NIH HHS U10 HL110297NHLBI NIH HHS U10 HL110302NHLBI NIH HHS U10 HL110309NHLBI NIH HHS U10 HL110312NHLBI NIH HHS U10 HL110336NHLBI NIH HHS U10 HL110337NHLBI NIH HHS U10 HL110338NHLBI NIH HHS U10 HL110342
6 · The paper itself

Abstract

backgroundRight ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function indexed to load (RV-pulmonary arterial [PA] coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV-PA coupling may be uniquely sensitive to sildenafil. METHODS AND

resultsIn a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial, physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD (tricuspid annular plane systolic excursion [TAPSE]) and according to impairment in RV-PA coupling (TAPSE/pulmonary artery systolic pressure) ratio. The prevalence of atrial fibrillation and diuretic use, n-terminal probrain natriuretic peptide levels, renal dysfunction, neurohumoral activation, myocardial necrosis and fibrosis biomarkers, and the severity of diastolic dysfunction all increased with severity of RVD. Peak oxygen consumption decreased and ventilatory inefficiency (VE/VCO2 slope) increased with increasing severity of RVD. Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio. Compared with placebo, at 24 weeks, TAPSE decreased, and peak oxygen consumption and VE/CO2 slope were unchanged with sildenafil. There was no interaction between RV-PA coupling and treatment effect, and sildenafil did not improve TAPSE, peak oxygen consumption, or VE/VCO2 in patients with pulmonary hypertension and RVD.

conclusionsHFpEF patients with RVD and impaired RV-PA coupling have more advanced heart failure. In RELAX patients with RVD and impaired RV-PA coupling, sildenafil did not improve RV function, exercise capacity, or ventilatory efficiency. CLINICAL

trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867.

Indexed as

AgedAged, 80 and overDiastoleExercise ToleranceFemaleHeart FailureHumansMaleMiddle AgedOxygen ConsumptionPhosphodiesterase 5 InhibitorsPulmonary ArteryPulmonary CirculationPulmonary VentilationRecovery of FunctionSeverity of Illness IndexPhosphodiesterase 5 InhibitorsSildenafil Citratediastoleexerciseheart failurehypertensionpulmonary hypertension

Identifiers

PMID27072860
PMCPMC4831074
OpenAlexW2547798696

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.