Evidence mapPaperPMID 42331613Full record

ReviewJournal of cardiovascular pharmacology2026

Pitfalls of Therapies Targeting the Nitric Oxide Signaling Pathway in Heart Failure With Preserved Ejection Fraction.

Skylar A Loeb, Darla L Tharp, Scott D Zawieja, Soumiya Pal, Antonio Abbate, Brant E Isakson

Abstract readReview
In one paragraph

Review in Journal of cardiovascular pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Skylar A LoebRobert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA.
Darla L TharpDepartment of Pathobiology and Integrative Biomedical Sciences, University of Missouri, Columbia, MO.
Scott D ZawiejaDepartment of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO.
Soumiya PalDepartment of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO.
Antonio AbbateRobert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA.
Brant E IsaksonRobert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA.

Funding

NHLBI NIH HHS HL007284NHLBI NIH HHS HL137112NHLBI NIH HHS HL171997NHLBI NIH HHS HL175083NHLBI NIH HHS HL176103
6 · The paper itself

Abstract

abstractOver 30 million individuals globally are afflicted with heart failure with preserved ejection fraction (HFpEF). Despite this substantial figure, treatment options for HFpEF remain limited. This is largely attributed to the variability in disease features and comorbidities with which patients present in the clinic. A common feature among patients with HFpEF is reduced nitric oxide (NO) bioavailability-a finding which prompted the use of therapeutics targeting the NO signaling pathway in HFpEF preclinical and clinical trials. Although many of these therapeutics were successful in animal models, clinical trials have yielded neutral, negative, or contradictory results. In this review, we will summarize the outcomes of HFpEF clinical trials investigating drugs that target the NO signaling pathway (nitrates, nitrites, soluble guanylyl cyclase stimulators, and phosphodiesterase 5 inhibitors) and discuss potential pitfalls underlying the neutral or negative results, as well as considerations for the design of future studies.

Indexed as

Cardiovascular AgentsHeart FailureNitric OxideStroke VolumeVentricular Function, LeftAnimalsHumansMolecular Targeted TherapyPhosphodiesterase 5 InhibitorsSignal TransductionSoluble Guanylyl CyclaseTreatment OutcomeCardiovascular AgentsNitric OxidePhosphodiesterase 5 InhibitorsSoluble Guanylyl Cyclaseheart failure with preserved ejection fractionnitratenitric oxidenitritephosphodiesterase inhibitorsoluble guanylyl cyclase stimulator

Identifiers

PMID42331613
PMCPMC13440607

What Socratic holds

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Registered trials

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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.