Evidence map›Paper›PMID 27179829›Full record

ArticleJACC. Heart failure2016

Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance.

Anthony J A Molina, Manish S Bharadwaj, Cynthia Van Horn, Barbara J Nicklas, Mary F Lyles, Joel Eggebeen, Mark J Haykowsky, Peter H Brubaker, Dalane W Kitzman

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. 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 NCT05888688 (The Imaging Assessment of Sarcopenia Across the Heart Failure Spectrum), which is not on this map. Cited by 131 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 3 pooled it
13.5field-weighted citation impact, top 1% 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.

NCT05888688 recruitingnot on this mapstarted 2023, after this paper: background citation

The Imaging Assessment of Sarcopenia Across the Heart Failure Spectrum

Typeobservational_patient_registrySponsorUniversity of LeicesterRan2023 to 2026Enrolled80ConditionsHeart Failure, Sarcopenia, Heart Failure With Reduced Ejection Fraction, Heart Failure With Preserved Ejection Fraction
3 · Its place in the literature

Who cites it

131 citing papers in PubMed, 3 syntheses or guidelines pooled it, 195 citations in OpenAlex.

  1. Pooled it
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  9. Assessment of Exercise Intolerance and Evaluation for HFpEF: A Literature Review of Pathophysiology, Diagnosis, and Management.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
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71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Anthony J A MolinaGerontology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Manish S BharadwajGerontology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Cynthia Van HornGerontology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Barbara J NicklasGerontology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Mary F LylesGerontology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Joel EggebeenCardiology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Mark J HaykowskyCollege of Nursing and Health Innovation, University of Texas at Arlington, Arlington, Texas.
Peter H BrubakerDepartment of Exercise and Health Science, Wake Forest University, Winston-Salem, North Carolina.
Dalane W KitzmanCardiology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address: dkitzman@wakehealth.edu.
Wake Forest University · USThe University of Texas at Arlington · US

Funding

Wake Forest Claude D. Pepper OAIC - RenewalP30AG021332 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Jamie Nicole Justice · 2002 to 2026
$36.4M
WORKER PROTECTION AGAINST AIRBORNE INFLUENZA - A PILOT STUDYM01RR007122 · NCRR · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI HUNDLEY, WILLIAM GREGORY · 1992 to 2010
$35.2M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
REHAB-HF: A Trial of Rehabilitation Therapy in Older Acute Heart Failure PatientsR01AG045551 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI KITZMAN, DALANE W · 2014 to 2018
$6.8M
Exercise Intolerance in Older HFPEF PatientsR01AG018915 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI KITZMAN, DALANE W · 2001 to 2019
$5.2M
Loss of fat tissue and functional responses to exercise in older, obese adultsR01AG020583 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI NICKLAS, BARBARA J · 2002 to 2013
$4.0M
Exercise Intolerance in Elderly Diastolic Heart FailureR37AG018915 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI KITZMAN, DALANE W · 2005 to 2013
$3.4M
NCATS NIH HHS UL1 TR001420NCRR NIH HHS M01 RR007122NIA NIH HHS P30 AG021332NIA NIH HHS R01 AG018915NIA NIH HHS R01 AG020583NIA NIH HHS R01 AG045551NIA NIH HHS R37 AG018915
6 · The paper itself

Abstract

objectivesThe aim of this study was to examine skeletal muscle mitochondria content, oxidative capacity, and the expression of key mitochondrial dynamics proteins in patients with heart failure with preserved ejection fraction (HFpEF), as well as to determine potential relationships with measures of exercise performance.

backgroundMultiple lines of evidence indicate that severely reduced peak exercise oxygen uptake (peak VO2) in older patients with HFpEF is related to abnormal skeletal muscle oxygen utilization. Mitochondria are key regulators of skeletal muscle metabolism; however, little is known about how these organelles are affected in HFpEF.

methodsBoth vastus lateralis skeletal muscle citrate synthase activity and the expression of porin and regulators of mitochondrial fusion were examined in older patients with HFpEF (n = 20) and healthy, age-matched control subjects (n = 17).

resultsCompared with age-matched healthy control subjects, mitochondrial content assessed by porin expression was 46% lower (p = 0.01), citrate synthase activity was 29% lower (p = 0.01), and Mfn2 (mitofusin 2) expression was 54% lower (p <0.001) in patients with HFpEF. Expression of porin was significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.48, p = 0.003 and r = 0.33, p = 0.05, respectively). Expression of Mfn2 was also significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.40, p = 0.02 and r = 0.37, p = 0.03 respectively).

conclusionsThese findings suggest that skeletal muscle oxidative capacity, mitochondrial content, and mitochondrial fusion are abnormal in older patients with HFpEF and might contribute to their severe exercise intolerance.

Indexed as

Oxygen ConsumptionStroke VolumeAgedAge FactorsCase-Control StudiesCitrate (si)-SynthaseExercise ToleranceFemaleGTP PhosphohydrolasesHeart FailureHumansMaleMiddle AgedMitochondrial DynamicsMitochondrial ProteinsMitochondria, MuscleCitrate (si)-SynthaseGTP PhosphohydrolasesMFN2 protein, humanMitochondrial ProteinsVDAC1 protein, humanVoltage-Dependent Anion Channel 1agingexerciseheart failuremitochondriapreserved ejection fractionskeletal muscle

Identifiers

PMID27179829
PMCPMC4967040
OpenAlexW2364050795

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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.