Subclinical Myocardial Injury and the Phenotype of Clinical Congestion in Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction

Published:September 14, 2021DOI:

      Bullet Points

      • Clinical congestion is a complex phenotype consisting of a combination of elevated ventricular filling pressures, natriuretic peptide levels, and subclinical myocardial injury as measured by high sensitivity troponin levels.
      • Subclinical myocardial injury was associated with clinical congestion in multivariable models despite adjustment for resting ventricular filling pressures and natriuretic peptide levels.
      • These data strengthen the evidence base linking subclinical myocardial injury to clinical congestion and suggest it may be an important contributor to the pathophysiology of the congested state.



      Clinical congestion is associated with adverse outcomes in patients with heart failure. The pathophysiological mediators of this association remain uncertain.

      Methods and Results

      We prospectively enrolled a cohort of patients with heart failure and reduced left ventricular ejection fraction and performed a detailed clinical examination followed on the same day by an invasive right heart catheterization and blood sampling for biomarkers. High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured. A clinical congestion score was calculated based on jugular venous pressure (cm H20 <10 = 0, 10–14 = 1, >14 = 2 points), bendopnea (0 vs 1), a third heart sound (0 vs 1), or peripheral edema (0–2). Congestion was categorized into tiers as absent (0 points), mild (1 point), or moderate to severe (≥ 2 points). We tested for associations of high-sensitivity troponin T, NT-proBNP, and elevated ventricular filling pressures with clinical congestion in both univariate and multivariable analyses. Of 153 participants, 65 (42%) had absent, 35 mild (23%), and 53 (35%) had moderate to severe clinical congestion. Congestion tier was associated with higher NT-proBNP and hs-troponin levels, and the right atrial pressure and pulmonary capillary wedge pressure (P < .001 for each). Increased congestion tier was also associated with the coexistent presence of elevated troponin T (≥52 ng/L), NT-proBNP (≥1000 pg/mL), and pulmonary capillary wedge pressure (≥22 mm Hg). Specifically, 78% of those with absent clinical congestion had 0 to 1 of these findings, whereas 75% of those with moderate-severe congestion had 2 or all 3 of these abnormalities (P < .001). An elevated hs-troponin was associated with mild or greater clinical congestion (odds ratio 3, 95% confidence interval 1.2–7.5, P = .02) in multivariable analysis adjusting for potential confounders including the right atrial pressure, pulmonary capillary wedge pressure, and NT-proBNP levels.


      Clinical congestion is a phenotype in which there is a high coexistent presence of elevated ventricular filling pressures, elevated natriuretic peptide levels, and subclinical myocardial injury. An elevated troponin was associated with clinical congestion in multivariable models that adjusted for ventricular filling pressures and natriuretic peptide levels. These data strengthen the evidence base for an association of elevated troponin with clinical congestion, suggesting that subclinical myocardial injury may be an important contributor to the pathophysiology of the congested state.

      Graphical abstract

      Key Words

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        • Gheorghiade M
        • Filippatos G
        • De Luca L
        • Burnett J.
        Congestion in acute heart failure syndromes: an essential target of evaluation and treatment.
        Am J Med. 2006; 119 (Epub 2006/11/23. PubMed PMID: 17113398): S3-S10
        • Drazner MH
        • Rame JE
        • Stevenson LW
        • Dries DL.
        Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure.
        N Engl J Med. 2001; 345 (Epub 2001/09/01. PubMed PMID: 11529211): 574-581
        • Ambrosy AP
        • Pang PS
        • Khan S
        • Konstam MA
        • Fonarow GC
        • Traver B
        • et al.
        Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial.
        Eur Heart J. 2013; 34 (Epub 2013/01/08. PubMed PMID: 23293303): 835-843
        • Caldentey G
        • Khairy P
        • Roy D
        • Leduc H
        • Talajic M
        • Racine N
        • White M
        • et al.
        Prognostic value of the physical examination in patients with heart failure and atrial fibrillation: insights from the AF-CHF trial (atrial fibrillation and chronic heart failure).
        JACC Heart Fail. 2014; 2 (Epub 2014/03/14. PubMed PMID: 24622114): 15-23
        • Nohria A
        • Tsang SW
        • Fang JC
        • Lewis EF
        • Jarcho JA
        • Mudge GH
        • et al.
        Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure.
        J Am Coll Cardiol. 2003; 41 (Epub 2003/05/28. PubMed PMID: 12767667): 1797-1804
        • Hollenberg SM
        • Warner Stevenson L
        • Ahmad T
        • Amin VJ
        • Bozkurt B
        • Butler J
        • et al.
        2019 ACC Expert Consensus Decision Pathway on Risk Assessment, Management, and Clinical Trajectory of Patients Hospitalized With Heart Failure: a report of the American College of Cardiology Solution Set Oversight Committee.
        J Am Coll Cardiol. 2019; 74 (Epub 2019/09/19. PubMed PMID: 31526538): 1966-2011
        • Selvaraj S
        • Claggett B
        • Pozzi A
        • McMurray J
        • Jhund P
        • Packer M
        • et al.
        The Prognostic Implications of Congestion on Physical Examination among Contemporary Patients with Heart Failure and Reduced Ejection Fraction: PARADIGM-HF.
        Circulation. 2019; 140 (. PubMed PMID: 31220936): 1369-1379
        • Yancy CW
        • Jessup M
        • Bozkurt B
        • Butler J
        • Casey Jr., DE
        • Colvin MM
        • et al.
        2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.
        Circulation. 2017; 136 (Epub 2017/04/30. PubMed PMID: 28455343): e137-ee61
        • Drazner MH
        • Stevenson LW.
        Relief and prevention of congestion in heart failure enhance quality and length of life.
        Circulation. 2019; 140 (Epub 2019/10/22. PubMed PMID: 31634006): 1380-1382
        • Pham DD
        • Drazner MH
        • Ayers CR
        • Grodin JL
        • Hardin EA
        • Garg S
        • et al.
        Identifying discordance of right- and left-ventricularfilling pressures in patients with heart failure by the clinical examination.
        Circ Heart Fail. 2021; (PMID: 34503353)
        • Thibodeau JT
        • Turer AT
        • Gualano SK
        • Ayers CR
        • Velez-Martinez M
        • Mishkin JD
        • et al.
        Characterization of a novel symptom of advanced heart failure: bendopnea.
        JACC Heart Fail. 2014; 2 (Epub 2014/03/14. PubMed PMID: 24622115): 24-31
        • Hashim IA
        • Vigen R
        • Fernandez F
        • Yu A
        • Bertulfo B
        • Thibodeaux L
        • Das SR
        • et al.
        Validation and implementation of the fifth-generation high sensitivity Troponin T (hs-TnT) assay at a large teaching county hospital. A laboratory-driven multi-specialty effort.
        Clin Chim Acta. 2019; 495 (Epub 2019/03/31. PubMed PMID: 30926278): 85-87
        • Vigen R
        • Kutscher P
        • Fernandez F
        • Yu A
        • Bertulfo B
        • Hashim IA
        • et al.
        Evaluation of a novel rule-out myocardial infarction protocol incorporating high-sensitivity troponin T in a US hospital.
        Circulation. 2018; 138 (Epub 2018/10/30. PubMed PMID: 30372140): 2061-2063
        • Drazner MH.
        Is the inferior vena cava really superior?.
        JACC Cardiovasc Imaging. 2013; 6 (Epub 2013/01/19. PubMed PMID: 23328558): 29-31
        • Thibodeau JT
        • Drazner MH.
        The role of the clinical examination in patients with heart failure.
        JACC Heart Fail. 2018; 6 (Epub 2018/06/11. PubMed PMID: 29885957): 543-551
        • Weil BR
        • Suzuki G
        • Young RF
        • Iyer V
        • Canty Jr, JM
        Troponin release and reversible left ventricular dysfunction after transient pressure overload.
        J Am Coll Cardiol. 2018; 71 (Epub 2018/06/23. PubMed PMID: 29929614; PMCID: PMC6020832): 2906-2916
        • Horwich TB
        • Patel J
        • MacLellan WR
        • Fonarow GC.
        Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure.
        Circulation. 2003; 108 (Epub 2003/08/13. PubMed PMID: 12912820): 833-838
        • Negi S
        • Sawano M
        • Kohsaka S
        • Inohara T
        • Shiraishi Y
        • Kohno T
        • et al.
        Prognostic implication of physical signs of congestion in acute heart failure patients and its association with steady-state biomarker levels.
        PLoS One. 2014; 9 (Epub 2014/05/08. PubMed PMID: 24802880; PMCID: PMC4011709): e96325
        • Aimo A
        • Januzzi Jr., JL
        • Vergaro G
        • Ripoli A
        • Latini R
        • Masson S
        • et al.
        Prognostic value of high-sensitivity troponin T in chronic heart failure: an individual patient data meta-analysis.
        Circulation. 2018; 137 (Epub 2018/01/18. PubMed PMID: 29335288): 286-297
        • Rorth R
        • Jhund PS
        • Kristensen SL
        • Desai AS
        • Kober L
        • Rouleau JL
        • et al.
        The prognostic value of troponin T and N-terminal pro B-type natriuretic peptide, alone and in combination, in heart failure patients with and without diabetes.
        Eur J Heart Fail. 2019; 21 (Epub 2018/12/12. PubMed PMID: 30537261; PMCID: PMC6607514): 40-49