Research Article| Volume 47, ISSUE 6, P565-575, November 2018

Download started.


Comparative symptom biochemistry between moderate and advanced heart failure

Published:October 09, 2018DOI:



      We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF).


      The purpose of this paper was to compare relationships between peripheral biomarkers of HF pathogenesis and physical symptoms between patients with advanced versus moderate HF.


      This was a two-stage phenotype sampling cohort study wherein we examined patients with advanced HF undergoing ventricular assist device implantation in the first stage, and then patients with moderate HF (matched adults with HF not requiring device implantation) in the second stage. Linear modeling was used to compare relationships among biomarkers and physical symptoms between cohorts.


      Worse myocardial stress, systemic inflammation and endothelial dysfunction were associated with worse physical symptoms in moderate HF (n=48), but less physical symptom burden in advanced HF (n=48).


      Where patients are in the HF trajectory needs to be taken into consideration when exploring biological underpinnings of physical HF symptoms.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Heart & Lung: The Journal of Cardiopulmonary and Acute Care
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Yancy CW
        • Jessup M
        • Bozkurt B
        • et al.
        2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American college of cardiology foundation/American heart association task force on practice guidelines.
        Circulation. 2013; 128: 1810
        • Lindenfeld J
        • Albert NM
        • Boehmer JP
        • et al.
        HFSA 2010 comprehensive heart failure practice guideline.
        J Card Fail. 2010; 16: 1
        • Adams KF
        • Fonarow GC
        • Emerman CL
        • et al.
        Characteristics and outcomes of patients hospitalized for heart failure in the united states: Rationale, design, and preliminary observations from the first 100,000 cases in the acute decompensated heart failure national registry (ADHERE).
        Am Heart J. 2005; 149: 209-216
        • Goldberg RJ
        • Spencer FA
        • Mariana Szklo‐Coxe
        • et al.
        Symptom presentation in patients hospitalized with acute heart failure.
        Clin Cardiol. 2010; 33: E80
        • Bekelman DB
        • Havranek EP
        • Becker DM
        • et al.
        Symptoms, depression, and quality of life in patients with heart failure.
        J Card Fail. 2007; 13 (S1071-9164(07)00167-4[pii]): 643-648
        • Zambroski CH
        • Moser DK
        • Bhat G
        • Ziegler C
        Impact of symptom prevalence and symptom burden on quality of life in patients with heart failure.
        Eur J Cardiovasc Nurs. 2005; 4 (S1474-5151(05)00034-4[pii]): 198-206
        • Shah MR
        • Hasselblad V
        • Stinnett SS
        • et al.
        Dissociation between hemodynamic changes and symptom improvement in patients with advanced congestive heart failure.
        Eur J Heart Fail. 2002; 4 (S1388984201002021[pii]): 297-304
        • Rector TS
        • Anand IS
        • Cohn JN
        Relationships between clinical assessments and patients' perceptions of the effects of heart failure on their quality of life.
        J Card Fail. 2006; 12 (S1071-9164(05)01322-9[pii]): 87-92
        • Myers J
        • Zaheer N
        • Quaglietti S
        • Madhavan R
        • Froelicher V
        • Heidenreich P
        Association of functional and health status measures in heart failure.
        J Card Fail. 2006; 12 (S1071-9164(06)00213-2[pii]): 439-445
        • Lewis EF
        • Lamas GA
        • O'Meara E
        • et al.
        Characterization of health-related quality of life in heart failure patients with preserved versus low ejection fraction in CHARM.
        Eur J Heart Fail. 2007; 9 (S1388-9842(06)00339-4[pii]): 83-91
        • Bhardwaj A
        • Rehman SU
        • Mohammed AA
        • et al.
        Quality of life and chronic heart failure therapy guided by natriuretic peptides: Results from the ProBNP outpatient tailored chronic heart failure therapy (PROTECT) study.
        Am Heart J. 2012; 164: 799.e1
        • Guglin M
        • Patel T
        • Darbinyan N
        Symptoms in heart failure correlate poorly with objective haemodynamic parameters.
        Int J Clin Pract. 2012; 66: 1224-1229
        • Lee CS
        • Hiatt SO
        • Denfeld QE
        • Chien CV
        • Mudd JO
        • Gelow JM
        Gender-specific physical symptom biology in heart failure.
        J Cardiovasc Nurs. 2015; 30: 517-521
        • Denfeld QE
        • Mudd JO
        • Gelow JM
        • Chien C
        • Hiatt SO
        • Lee CS
        Physical and psychological symptom biomechanics in moderate to advanced heart failure.
        J Cardiovasc Nurs. 2015; 30: 346-350
        • Denfeld QE
        • Mudd JO
        • Hasan W
        • et al.
        Exploring the relationship between beta-adrenergic receptor kinase-1 and physical symptoms in heart failure.
        Heart Lung. 2018; (S0147-9563(18)30107-9[pii])
        • Lee CS
        • Mudd JO
        • Gelow JM
        • et al.
        Background and design of the profiling biobehavioral responses to mechanical support in advanced heart failure study.(report).
        J Cardiovasc Nurs. 2014; 29: 405
        • Li D
        • Lewinger JP
        • Gauderman WJ
        • Murcray CE
        • Conti D
        Using extreme phenotype sampling to identify the rare causal variants of quantitative traits in association studies.
        Genet Epidemiol. 2011; 35: 790-799
        • Kirklin JK
        • Naftel DC
        • Pagani FD
        • et al.
        Seventh INTERMACS annual report: 15,000 patients and counting.
        J Heart Lung Transplant. 2015; 34: 1495-1504
        • Levy WC
        • Mozaffarian D
        • Linker DT
        • et al.
        The seattle heart failure model: prediction of survival in heart failure.
        Circulation. 2006; 113: 1424
        • Allen LA
        • Felker GM
        Multi-marker strategies in heart failure: clinical and statistical approaches.
        Heart Fail Rev. 2010; 15: 343-349
        • Bettencourt P
        • Azevedo A
        • Pimenta J
        • Fries F
        • Ferreira S
        • Ferreira A
        N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients.
        Circulation. 2004; 110: 2168
        • Rauchhaus M
        • Doehner W
        • Francis DP
        • et al.
        Plasma cytokine parameters and mortality in patients with chronic heart failure.
        Circulation. 2000; 102: 3060
        • Potapov EV
        • Hennig F
        • Wagner FD
        • et al.
        Natriuretic peptides and E-selectin as predictors of acute deterioration in patients with inotrope-dependent heart failure.
        Eur J Cardiothorac Surg. 2005; 27 (S1010-7940(05)00126-0[pii]): 899-905
        • Felker GM
        • Fiuzat M
        • Thompson V
        • et al.
        Soluble ST2 in ambulatory patients with heart failure: association with functional capacity and long-term outcomes.
        Circ Heart Fail. 2013; 6: 1172-1179
        • Tamura T
        • Furukawa Y
        • Taniguchi R
        • et al.
        Serum adiponectin level as an independent predictor of mortality in patients with congestive heart failure.
        Circ J. 2007; 71 (JST.JSTAGE/circj/71.623[pii]): 623-630
        • Chung I
        • Choudhury A
        • Lip GY
        Platelet activation in acute, decompensated congestive heart failure.
        Thromb Res. 2007; 120 (S0049-3848(07)00012-6[pii]): 709-713
        • Jurgens CY
        • Lee CS
        • Riegel B
        Psychometric analysis of the heart failure somatic perception scale as a measure of patient symptom perception.
        J Cardiovasc Nurs. 2017; 32: 140
        • Cleeland CS
        • Ryan KM
        Pain assessment: Global use of the brief pain inventory.
        Ann Acad Med Singap. 1994; 23: 129-138
        • Johns MW.
        A new method for measuring daytime sleepiness: the epworth sleepiness scale.
        Sleep. 1991; 14 (10.1093/sleep/14.6.540): 540-545
        • de Bold AJ
        • Bruneau BG
        • Kuroski de Bold ML
        Mechanical and neuroendocrine regulation of the endocrine heart.
        Cardiovasc Res. 1996; 31 (0008-6363(95)00121-2[pii]): 7-18
        • Ogawa T
        • Linz W
        • Stevenson M
        • et al.
        Evidence for load-dependent and load-independent determinants of cardiac natriuretic peptide production.
        Circulation. 1996; 93: 2059-2067
        • Eurlings LW
        • Sanders-van Wijk S
        • van Kraaij DJ
        • et al.
        Risk stratification with the use of serial N-terminal pro-B-type natriuretic peptide measurements during admission and early after discharge in heart failure patients: Post hoc analysis of the PRIMA study.
        J Card Fail. 2014; 20: 881-890
        • Torre-Amione G
        Immune activation in chronic heart failure.
        Am J Cardiol. 2005; 95 (S0002-9149(05)00385-1 40C[pii])
        • Aukrust P
        • Gullestad L
        • Ueland T
        • Damas JK
        • Yndestad A
        Inflammatory and anti-inflammatory cytokines in chronic heart failure: potential therapeutic implications.
        Ann Med. 2005; 37: 74-85
        • Leung L
        • Cahill CM
        TNF-alpha and neuropathic pain–a review.
        J Neuroinflammation. 2010; 7 ([doi]): 27
        • Yin WH
        • Chen JW
        • Jen HL
        • et al.
        The prognostic value of circulating soluble cell adhesion molecules in patients with chronic congestive heart failure.
        Eur J Heart Fail. 2003; 5 (S1388984203000096[pii]): 507-516
        • Chong AY
        • Lip GY
        • Freestone B
        • Blann AD
        Increased circulating endothelial cells in acute heart failure: Comparison with von willebrand factor and soluble E-selectin.
        Eur J Heart Fail. 2006; 8 (S1388-9842(05)00164-9[pii]): 167-172
        • Shantsila E
        • Wrigley BJ
        • Blann AD
        • Gill PS
        • Lip GY
        A contemporary view on endothelial function in heart failure.
        Eur J Heart Fail. 2012; 14: 873-881
        • Ky B
        • French B
        • McCloskey K
        • et al.
        High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure.
        Circ Heart Fail. 2011; 4: 180-187
        • Shah RV
        • Chen-Tournoux AA
        • Picard MH
        • van Kimmenade RR
        • Januzzi JL
        Serum levels of the interleukin-1 receptor family member ST2, cardiac structure and function, and long-term mortality in patients with acute dyspnea.
        Circ Heart Fail. 2009; 2: 311-319
        • Szabo T
        • Scherbakov N
        • Sandek A
        • et al.
        Plasma adiponectin in heart failure with and without cachexia: catabolic signal linking catabolism, symptomatic status, and prognosis.
        Nutr Metab Cardiovasc Dis. 2014; 24: 50-56
        • Van Berendoncks AM
        • Garnier A
        • Beckers P
        • et al.
        Functional adiponectin resistance at the level of the skeletal muscle in mild to moderate chronic heart failure.
        Circ Heart Fail. 2010; 3: 185-194
        • Kistorp C
        • Faber J
        • Galatius S
        • et al.
        Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure.
        Circulation. 2005; 112 (CIRCULATIONAHA.104.530972[pii]): 1756-1762
        • Chung I
        • Choudhury A
        • Patel J
        • Lip GY
        Soluble, platelet-bound, and total P-selectin as indices of platelet activation in congestive heart failure.
        Ann Med. 2009; 41: 45-51
        • Whitaker KL
        • Scott SE
        • Wardle J
        Applying symptom appraisal models to understand sociodemographic differences in responses to possible cancer symptoms: A research agenda.
        Br J Cancer. 2015; 112: 27