Evidence map›Paper›PMID 26754625›Full record

Trial reportCirculation. Heart failure2016

Plasma Biomarkers Reflecting Profibrotic Processes in Heart Failure With a Preserved Ejection Fraction: Data From the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction Study.

Michael R Zile, Pardeep S Jhund, Catalin F Baicu, Brian L Claggett, Burkert Pieske, Adriaan A Voors, Margaret F Prescott, Victor Shi, Martin Lefkowitz, John J V McMurray and 2 more

2 registry-linked trialsAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
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 2 registered trials, which are not on this map. Cited by 48 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 4 pooled it
6.5field-weighted citation impact, top 3% 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.

NCT00887588 phase2completednot on this map

A 36-week, Randomized, Double-blind, Multi-center, Parallel Group, Active Controlled Study to Evaluate the Efficacy, Safety and Tolerability of LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction

TypeinterventionalSponsorNovartis PharmaceuticalsRan2009 to 2011Enrolled307ConditionsChronic Heart FailureArmsLCZ696, Valsartan, Placebo
NCT04857931 phase2terminatednot on this mapstarted 2022, after this paper: background citation

A Biomarker Study Assessing the Effects of Colchicine on Inflammation and Extra-Cellular Matrix Turnover in Patients With Heart Failure and Preserved Ejection Fraction.

TypeinterventionalSponsorMontreal Heart InstituteRan2022 to 2023Enrolled14ConditionsHeart Failure, Inflammation, ColchicineArmsColchicine, Placebo
3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 4 syntheses or guidelines pooled it, 113 citations in OpenAlex.

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  12. Rewiring the scar: translational advances in cardiac fibrosis.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025
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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

12 authors at 6 institutions in 5 countries.

Michael R ZileFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.). zilem@musc.edu.
Pardeep S JhundFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
Catalin F BaicuFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
Brian L ClaggettFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
Burkert PieskeFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
Adriaan A VoorsFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
Margaret F PrescottFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
Victor ShiFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
Martin LefkowitzFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
John J V McMurrayFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
Scott D SolomonFrom the Department of Medicine, Medical University of South Carolina, Charleston (M.R.Z., C.F.B.); RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z., C.F.B.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., S.D.S.); BHF Glasgow Cardiovascular Research Center, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.M.); Department of Cardiology, Medical University of Graz, Graz, Austria (B.P.); Department of Internal Medicine and Cardiology, Charité, Campus Virchow Klinikum, Berlin, Germany (B.P.); Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany (B.P.); Department of Cardiology, University of Groningen, Groningen, The Netherlands (A.A.V.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) Investigators
Brigham and Women's Hospital · USMedical University of Graz · ATMedical University of South Carolina · USUniversity of Groningen · NLDeutsches Herzzentrum der Charité · DEUniversity of Glasgow · GB

Funding

Extracellular Matrix in Hypertensive Heart Disease & Transition to Heart FailureR01HL123478 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ZILE, MICHAEL R · 2015 to 2018
$1.5M
NHLBI NIH HHS R01 HL123478
6 · The paper itself

Abstract

backgroundHeart failure with preserved ejection fraction is a clinical syndrome that has been associated with changes in the extracellular matrix. The purpose of this study was to determine whether profibrotic biomarkers accurately reflect the presence and severity of disease and underlying pathophysiology and modify response to therapy in patients with heart failure with preserved ejection fraction. METHODS AND

resultsFour biomarkers, soluble form of ST2 (an interleukin-1 receptor family member), galectin-3, matrix metalloproteinase-2, and collagen III N-terminal propeptide were measured in the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) trial at baseline, 12 and 36 weeks after randomization to valsartan or LCZ696. We examined the relationship between baseline biomarkers, demographic and echocardiographic characteristics, change in primary (change in N-terminal pro B-type natriuretic peptide) and secondary (change in left atrial volume) end points. The median (interquartile range) value for soluble form of ST2 (33 [24.6-48.1] ng/mL) and galectin 3 (17.8 [14.1-22.8] ng/mL) were higher, and for matrix metalloproteinase-2 (188 [155.5-230.6] ng/mL) lower, than in previously published referent controls; collagen III N-terminal propeptide (5.6 [4.3-6.9] ng/mL) was similar to referent control values. All 4 biomarkers correlated with severity of disease as indicated by N-terminal pro B-type natriuretic peptide, E/E', and left atrial volume. Baseline biomarkers did not modify the response to LCZ696 for lowering N-terminal pro B-type natriuretic peptide; however, left atrial volume reduction varied by baseline level of soluble form of ST2 and galectin 3; patients with values less than the observed median (<33 ng/mL soluble form of ST2 and <17.8 ng/mL galectin 3) had reduction in left atrial volume, those above median did not. Although LCZ696 reduced N-terminal pro B-type natriuretic peptide, levels of the other 4 biomarkers were not affected over time.

conclusionsIn patients with heart failure with preserved ejection fraction, biomarkers that reflect collagen homeostasis correlated with the presence and severity of disease and underlying pathophysiology, and may modify the structural response to treatment. CLINICAL

trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00887588.

Indexed as

Stroke VolumeVentricular Function, LeftAgedAged, 80 and overAminobutyratesAngiotensin II Type 1 Receptor BlockersAngiotensin Receptor AntagonistsBiomarkersBiphenyl CompoundsBlood ProteinsDouble-Blind MethodDrug CombinationsFemaleFibrosisGalectin 3GalectinsAminobutyratesAngiotensin II Type 1 Receptor BlockersAngiotensin Receptor AntagonistsBiomarkersBiphenyl CompoundsBlood ProteinsDrug CombinationsGalectin 3GalectinsIL1RL1 protein, humanInterleukin-1 Receptor-Like 1 ProteinLGALS3 protein, humanMatrix Metalloproteinase 2MMP2 protein, humanPeptide FragmentsProcollagenprocollagen Type III-N-terminal peptideReceptors, Cell Surfacesacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartanbiomarkersextracellular matrixheart failurehomeostasispathophysiology

Identifiers

PMID26754625
PMCPMC5485256
OpenAlexW2573482863

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.