ReviewCirculation. Heart failure2017
INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction): Rationale and Design.
Registry-linked trialAbstract readReview
In one paragraph
Review in Circulation. Heart failure, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02742129 (Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF), which is not on this map. Cited by 32 papers.
0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
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.
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.
Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF
Who cites it
32 citing papers in PubMed.
- Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure With Preserved Ejection Fraction: The INABLE-Training Trial.Mayo Clinic proceedings · 2024Trial
- Trial
- Inorganic nitrate supplementation enhances functional capacity and lower-limb microvascular reactivity in patients with peripheral artery disease.Nitric oxide : biology and chemistry · 2018Trial
- Effect of organic and inorganic nitrates on cerebrovascular pulsatile power transmission in patients with heart failure and preserved ejection fraction.Physiological measurement · 2018Trial
- Cardiopulmonary Exercise Testing and HFpEF: Diagnostic and Therapeutic Perspectives.Healthcare (Basel, Switzerland) · 2025Review
- Dysregulated ProteinCirculation research · 2025Article
- The NO Pathway as a Target in Patients with Stable and Advanced Heart Failure: An Additional Arrow in Our Quiver!Biomolecules · 2025Review
- The Heart Has Intrinsic Ketogenic Capacity that Mediates NADCirculation research · 2025Article
- Calcitriol Concentration in the Early Phase of Myocardial Infarction and Its Relation to Left Ventricular Ejection Fraction.Metabolites · 2024Article
- From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease.European journal of medical research · 2023Review
- Review
- Combination Sodium Nitrite and Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity in a "2-Hit" Murine Model.Journal of the American Heart Association · 2023Article
- Adiposity and clinical outcomes in East Asian patients with heart failure and preserved ejection fraction.International journal of cardiology. Heart & vasculature · 2023Article
- Right atrial pressure represents cumulative cardiac burden in heart failure with preserved ejection fraction.ESC heart failure · 2022Article
- Myofilament Phosphorylation in Stem Cell Treated Diastolic Heart Failure.Circulation research · 2021Article
- Myocardial Tissue Characterization in Heart Failure with Preserved Ejection Fraction: From Histopathology and Cardiac Magnetic Resonance Findings to Therapeutic Targets.International journal of molecular sciences · 2021Review
- Heart Failure Syndrome With Preserved Ejection Fraction Is a Metabolic Cluster of Non-resolving Inflammation in Obesity.Frontiers in cardiovascular medicine · 2021Review
- Efficacy and Safety of Qishen Yiqi Dripping Pill for Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2020Review
- Inorganic nitrate and nitrite supplementation fails to improve skeletal muscle mitochondrial efficiency in mice and humans.The American journal of clinical nutrition · 2020Article
- The vasculature in HFpEF vs HFrEF: differences in contractile protein expression produce distinct phenotypes.Heliyon · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Yogesh N V ReddyFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.).
Gregory D LewisFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.).
Sanjiv J ShahFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.).
Martin LeWinterFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.).
Marc SemigranFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.).
Victor G Davila-RomanFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.).
Kevin AnstromFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.).
Adrian HernandezFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.).
Eugene BraunwaldFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.).
Margaret M RedfieldFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.).
Barry A BorlaugFrom the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., M.M.R., B.A.B.); Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Boston (G.D.L., M.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiology Unit, University of Vermont College of Medicine, Burlington (M.L.W.); Cardiovascular Division, Washington University School of Medicine, St. Louis, MO (V.G.D.-R.); Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (K.A., A.H.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.). borlaug.barry@mayo.edu.
Funding
Washington University Nutrition Obesity Research CenterP30DK056341 · WASHINGTON UNIVERSITY · 1999 to 2025
$5.7MNHLBI NIH HHS R01 HL128526NHLBI 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 HL110342NIDDK NIH HHS P30 DK056341
Abstract
Approximately half of patients with heart failure have preserved ejection fraction. There is no proven treatment that improves outcome. The pathophysiology of heart failure with preserved ejection fraction is complex and includes left ventricular systolic and diastolic dysfunction, pulmonary vascular disease, endothelial dysfunction, and peripheral abnormalities. Multiple lines of evidence point to impaired nitric oxide (NO)-cGMP bioavailability as playing a central role in each of these abnormalities. In contrast to traditional organic nitrate therapies, an alternative strategy to restore NO-cGMP signaling is via inorganic nitrite. Inorganic nitrite, previously considered to be an inert byproduct of NO metabolism, functions as an important in vivo reservoir for NO generation, particularly under hypoxic and acidosis conditions. As such, inorganic nitrite becomes most active at times of greater need for NO signaling, as during exercise when left ventricular filling pressures and pulmonary artery pressures increase. Herein, we present the rationale and design for the INDIE-HFpEF trial (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure with Preserved Ejection Fraction), which is a multicenter, randomized, double-blind, placebo-controlled cross-over study assessing the effect of inhaled inorganic nitrite on peak exercise capacity, conducted in the National Heart, Lung, and Blood Institute-sponsored Heart Failure Clinical Research Network. CLINICAL
trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02742129.
Indexed as
Exercise TestExercise ToleranceHeart FailureHumansNitratesRandomized Controlled Trials as TopicStroke VolumeVentricular Function, LeftNitratesclinical trialexerciseheart failureheart failure with preserved ejection fractionmetabolismnitric oxide
Identifiers
What Socratic holds
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Registered trials
NCT02742129ClinicalTrials.gov
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 Socratic graph.