The Diagnostic and Therapeutic Value of Multimarker Analysis in Heart Failure. An Approach to Biomarker-Targeted Therapy

Abstract

Background: Heart failure is a pathophysiological state, which is still associated with high morbidity and mortality despite established therapies. Diverse well-known biomarkers fail to assess the variety of individual pathophysiology in the context of heart failure. Methods: An analysis of prospective, multimarker-specific therapeutic approaches to heart failure based on studies in current literature was performed. A total of 159 screened publications in the field of biomarkers in heart failure were hand-selected and found to be eligible for this study by a team of experts. Results: Established biomarkers of the inflammatory axis, matrix remodeling, fibrosis and oxidative stress axis, as well as potential therapeutic interventions were investigated. Interaction with end organs, such as cardio-hepatic, cardio-renal and cardio-gastrointestinal interactions show the complexity of the syndrome and could be of further therapeutic value. MicroRNAs are involved in a wide variety of physiologic and pathophysiologic processes in heart failure and could be useful in diagnostic as well as therapeutic setting. Conclusion: Based on our analysis by a biomarker-driven approach in heart failure therapy, patients could be treated more specifically in long term with a consideration of different aspects of heart failure. New studies evaluating a multimarker - based therapeutic approach could lead in a decrease in the morbidity and mortality of heart failure patients.

Keywords: biomarkers; cardiovascular medicine; heart failure; multimarker analysis; targeted therapy.

Figure 1

Pathophysiological processes relevant in heart failure and their interaction with end organs. Inflammatory processes with following remodeling and fibrosis, neuroendocrine activation, myocardial injury, oxidative stress and myocardial stretch contribute to heart failure. Heart failure might cause damage in end organs, but on the other hand failure of end organs induces heart failure.

Figure 2

Flowchart outlining the protocol adopted in this systematic review for literature selection.

Figure 3

Biomarkers and therapy options in the inflammatory/matrix remodeling/fibrosis axis. Hypertension, obesity and myocyte injury cause inflammatory processes with following remodeling and fibrosis as an end result. Inflammatory markers are important for the detection and antibodies, including Canakinumab and Anakinra are prospective therapy options. sST-2 and Galectin indicate remodeling processes. The most important marker of cardiac fibrosis is TGF-ß. Losmapimod and ALK5 inhibitors are the most promising therapeutic interventions.

Figure 4

Biomarkers and potential therapy options of the oxidative stress axis. Existing heart failure, mechanical stretch, neurohumoral activation and inflammatory processes induce the excess of oxidative stress. Oxidative stress itself causes cardiac fibrosis and myocardial injury. The best investigated biomarkers, indicating an excess of oxidative stress, are uric acid and myeloperoxidase. Oxypurinol, Allopurinol, N-Acetylcystein and Vitamin A,C,E are the most promising therapeutic approaches.

Figure 5

Cardio-renal interaction. Heart failure can cause renal hypoperfusion, increased vascular resistance and therefore results in an impairment of renal function. Unlike, chronic kidney disease may cause volume overload and results in a myocardial stretch. Uremic toxins provoke inflammatory processes and are reported to worsen heart failure. Oxidative stress, inflammatory processes and neurohumoral activation may independently by its origin impair cardiac and renal function.