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Table of Contents
Year : 2020  |  Volume : 8  |  Issue : 4  |  Page : 164-166

Biomarkers in heart failure: Work still half done?

1 Department of Cardiology, JSS Medical College and JSSAHER, Mysuru; Namana Medical Centre, Bengaluru, Karnataka, India
2 Department of Medicine, JSSMC and Hospital JSSAHER, Mysuru, Karnataka, India

Date of Submission23-Aug-2020
Date of Decision14-Sep-2020
Date of Acceptance27-Sep-2020
Date of Web Publication23-Oct-2020

Correspondence Address:
Prof. Nagaraj Desai
Namana Medical Centre, New BEL Road, RMV 2nd Stage, RMV Extension, Bengaluru - 560 094, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajim.ajim_61_20

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How to cite this article:
Desai N, Venkatesh C R. Biomarkers in heart failure: Work still half done?. APIK J Int Med 2020;8:164-6

How to cite this URL:
Desai N, Venkatesh C R. Biomarkers in heart failure: Work still half done?. APIK J Int Med [serial online] 2020 [cited 2021 Sep 24];8:164-6. Available from: https://www.ajim.in/text.asp?2020/8/4/164/298940

To carefully observe the phenomena of life in all its phases, normal and perverted, to make perfect that most difficult of all arts, the art of observation, to call to aid the science of experimentation, to cultivate the reasoning faculty, so as to be able to know the true from the false–these are our methods .

William Osler (1849-1919)

Estimation of biomarkers to aid the diagnosis and predict the prognosis of a patient with heart failure (HF) is a well-accepted strategy in clinical practice. All major clinical guidelines on HF[1],[2],[3] recommend the incorporation of estimation of biomarkers used in the optimum and appropriate management.

The syndrome of HF manifests as a result of chronic cardiac overwork or acute myocardial injury. This is caused by several mechanisms, including inflammation, activation of several neurohormonal systems, and biochemical changes influencing the multiple organ systems including myocardial cell and interstitium itself. These complex interactions result in the abnormal production of several biochemical substances, which have been called cardiac biomarkers of HF.[4] Several candidates have been participants of a variety of investigations to be labeled as a biomarker. Of them, natriuretic peptides that are released due to cardiac stretch have been well established in clinical practice. Recently, some biomarkers such as ST2, Galectin 3 have also garnered increasing attention.

The utility of a molecule as “Biomarker” in the management of HF may be based on certain clinical principles as suggested by Morrow and Lemos.[5] They are: a potential candidate biomarker should be measurable, it should be able to provide new information, and importantly, it should aid the clinician to manage his patient better. Other equally important points of practical value are its assay should be accurate and quantitative with a faster turn around time to make a meaningful clinical decision. Above all, it should represent in an important way the biological underpinnings of the syndrome of HF.

Indeed, several biomarkers, each one addressing/involved in a pathobiological process which may be at work in HF, have been investigated. The list is long. Moreover, possibly, many will fall wayside while only some will find a place in routine clinical practice. For instance, the mediators of inflammation like C-reactive protein, the markers of myocyte injury such as cardiac-specific Troponins I and T, the markers of myocyte stress such as Brain natriuretic peptide (BNP), N-terminal pro–BNP (NT-proBNP), and ST2 have been studied. The molecules which represent oxidative stress such as oxidized low-density lipoproteins, myeloperoxidase, and others have been also examined. Extracellular matrix remodeling matrix metalloproteinases, tissue inhibitors of metalloproteinases have also been investigated. Finally, the neurohormones such as norepinephrine, renin, angiotensin II, aldosterone, arginine vasopressin, and endothelin have been studied.[4],[6] In a nutshell, the approach to evaluate a molecule as a biomarker involved in the syndrome of HF has resulted in a basket of molecules.[6] Neither it is wise nor is it recommended to measure any biomarker without evidence emanating from clinical studies.

The current issue of the journal carries an article by Bhai and Biradar evaluating the relevance of serum Gamma-glutamyl transferase in patients with HF.[7] In a cohort of fifty patients of HF, there was a significant increase in the levels of the enzyme in patients with valvular heart disease. Moreover, the authors could not demonstrate the same in patients with coronary artery disease. There was no control group in this hospital-based observational study. Furthermore, they did not measure serum natriuretic peptides. This piece of work may have to be taken to the next levels in a more rigorous manner to understand the importance of this molecule in HF. We already have gained some knowledge in this area. Gamma-glutamyl transferase, an inexpensive molecule to measure, has been evaluated to explore its utility in atherosclerosis, arrhythmias, HF, and predicting prognosis including sudden cardiac death and the need for heart transplantation in observational and community-based studies, and has been found to have significant associations. However, the causal mechanistic underpinnings of these associations are poorly understood. Associated hepatic congestion and hepatic dysfunction is an attractive explanation. In this present study, it would have been interesting to know some more details of echocardiography, including a right ventricular function, for instance, the range of values of Tricuspid annular plane systolic excursion and markers of hepatic congestion and their relation to the biomarker under evaluation.

All clinical practice guidelines for HF, including American,[1] European,[2] Indian,[3] and several others recommend strongly, the measurement of biomarkers in the algorithms of management of the patient with HF, alhough with certain clinical caveats. All these guidelines recommend, with Class I and level of evidence A (highest grade), measurement of natriuretic peptides in several clinical scenarios. A substantial evidence base exists that supports the use of natriuretic peptide biomarkers to assist in the diagnosis or exclusion of HF as a cause of symptoms (e.g., dyspnea and weight gain) in the setting of chronic ambulatory HF or the setting of acute care with decompensated HF, especially when the cause of dyspnea is unclear. The role of natriuretic peptide biomarkers in population screening to detect incident HF is emerging. Pre-discharge estimation has been found to be useful in both reduced as well as preserved ejection fraction; however, routine serial estimations of natriuretic peptides on follow-up is not found in favor. It's worth remembering that many cardiac and noncardiac causes increase plasma levels of natriuretic peptide biomarkers. Hence, the laboratory reports should be interpreted cautiously. Other biomarkers such as troponins are also mentioned. Increased troponins in the context of acute HF are reported to be associated with worse outcomes and an important clinical caveat is a possible associated acute coronary syndrome. Furthermore, elevated troponins in chronic HF portends a poorer prognosis. Newer biomarkers of myocardial fibrosis, soluble ST2 receptor, and galectin-3 are predictive of hospitalization and death and may provide incremental information, on prognosis, over natriuretic peptide levels in patients with HF.[8] Further, studies evaluating a strategy of multimarker biomarkers estimation, including natriuretic peptides, troponins, and others instead of a single biomarker, have also been shown to improve the risk stratification of patients with chronic HF.[9] This finding supports the concept that evaluating multiple biomarkers has some advantages and predict the risks better. One should wait for the outcomes of larger studies before such a concept can be put to extensive clinical use.

Dyspnea, a cardinal symptom of HF, is difficult to assess in a patient of “mixed syndrome of HF and airways disease.” Airways disease is an important comorbid condition which may militate against satisfactory clinical status. Indeed, we reported a prevalence rate of nearly 30% of patients with stable heart disease to have associated airways disease.[10] The evaluation of airways disease and its optimum management resulted in the improvement in symptoms and several other parameters, including lung function tests. This underscores the importance of comprehensive care of a patient with dyspnea rather than a cookbook approach.

With the widespread use of angiotensin-neprilysin inhibitor in the management of HF, which is guidelines recommended, one should carefully interpret the laboratory reports of natriuretic peptides. BNP values are higher as it is a substrate for neprilysin and one should rely on NT-ProBNP for decision-making.

The availability of “Point of Care devices” that can generate reports of biomarkers, quantitatively, in a “jiffy” is serving the clinical practice well. Usage of these tests has taken it to the next level. The emergency and chronic care physicians should be using them smartly in making clinical decisions.

For a long time, we all trusted clinical evaluation to diagnose HF. Indeed, HF diagnosis is clinical. Subsequently, an era of laboratory medicine emerged where the emphasis was to look for confirmatory/objective/quantitative evidence. Biochemical tests and imaging techniques have become part of our analytical approach in decision-making to an unprecedented extent. Indeed, these approaches can provide anatomical, pathological, and physiological diagnosis, and in some cases, able to provide prognostic information. Further, some of these tools have been proposed as a screening method to diagnose a subclinical disease. Unless one is vigilant, there is a lurking danger that these technologies may override one's clinical decisions. This is where clinical errors may occur. Welcoming new thought is always exciting; however, vigilance should be our watchword.

There is a cost attached to all our clinical decisions. It is a cliché to state that the widespread use of estimation of biomarkers to diagnose and prognosticate a patient with HF and screen for high-risk patients in clinical practice will be driven by the costs of tests involved necessitating the application of clinical judgment, especially in a cost-sensitive environment.[11]

The key takeaway seems to revolve around the right clinical question…asking ourselves.

  References Top

Yancy CW, Jessup M, Bozkurt B, Butler J, Casey Jr DE, Colvin MM,et al . 2017 ACCF/ACC/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guidelines for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol 2017;70:776-803.  Back to cited text no. 1
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al . 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. The task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology. Eur Heart J 2016;37:2129-200.  Back to cited text no. 2
Guha S, Harikrishnan S, Ray S, Sethi R, Ramakrishnan S, Banerjee S. CSI position statement CSI position statement on management of heart failure in India. Indian Heart J 2018;70S: S1-72.  Back to cited text no. 3
Braunwald E. “Biomarkers in heart failure.” N Engl J Med 2008;358:2148-59.   Back to cited text no. 4
Morrow DA, de Lemos JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation 2007;115:949-52.  Back to cited text no. 5
Ghashghaei R, Arbit B, Maisel AS. Current and novel biomarkers in heart failure: bench to bedside. Curr Opin Cardiol 2016;31:191-5.  Back to cited text no. 6
Bhai FH, Biradar S. To study Gamma-Glutamyl transferase levels in heart failure. APIK J Int Med 2020;8:179-83.  Back to cited text no. 7
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Felker GM, Ahmad T. Biomarkers for the prevention of heart failure. JACC 2018;72:3255-8.  Back to cited text no. 8
Ky B, French B, Levy WC, Sweitzer NK, Fang JC, Wu AH, et al . Multiple biomarkers for risk prediction in chronic heart failure. Circ Heart Fail 2012;5:183-90.  Back to cited text no. 9
Mahendra M, S SK, Desai N, Bs J, Pa M. Evaluation for airway obstruction in adult patients with stable ischemic heart disease. Indian Heart J 2018;70:266-71.  Back to cited text no. 10
Satyamurthy I, Dalal JJ, Sawhney JP, Mohan JC, Choglee SA, Desai N, et al . The Indian consensus document on cardiac biomarker. Indian Heart J 2014;66:73-82.  Back to cited text no. 11


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