Biomarkers in Acute Heart Failure: Diagnosis, Prognosis, and Treatment

Abstract

Heart failure is a global health problem. An episode of acute heart failure (AHF) is a period of substantial morbidity and mortality with few advances in the management of an episode that have improved outcomes. The measurement of multiple biomarkers has become an integral adjunctive tool for the management of AHF. Many biomarkers are now well established in their ability to assist with diagnosis and prognostication of an AHF patient. There are also emerging biomarkers that are showing significant promise in the areas of diagnosis and prognosis. For improving the management of AHF, both established and novel biomarkers may assist in guiding medical therapy and subsequently improving outcomes. Thus, it is important to understand the different abilities and limitations of established and emerging biomarkers in AHF so that they may be correctly interpreted and integrated into clinical practice for AHF. This knowledge may improve the care of AHF patients. This review will summarize the evidence of both established and novel biomarkers for diagnosis, prognosis and management in AHF so that the treating clinician may become more comfortable incorporating these biomarkers into clinical practice in an evidence-based manner.

Keywords: Biomarkers; Diagnosis; Heart failure; Prognosis; Therapy.

Conflict of interest statement

Conflict of Interest: The author has no financial conflicts of interest.

Copyright © 2021. Korean Society of Heart Failure.

Figures

Figure 1. Pathway for using BNP and NT-proBNP in diagnosis, prognosis and management of acute heart failure.

In patients with suspected acute heart failure, check a BNP or NT-proBNP and the value can help determine if acute heart failure is unlikely, likely or in the ‘gray zone.’ If a diagnosis of acute heart failure is certain based on history and exam findings, assessment of BNP or NT-proBNP can still be helpful for prognosis as the degree of BNP or NT-proBNP elevation is prognostic for in-hospital outcomes. After a patient has reached clinical stability and is felt ready for discharge, recheck a BNP or NT-proBNP to see if there has been >30% decline from admission. If this has not been achieved, prognosis is guarded, and further interventions should be attempted to see if BNP/NT-proBNP can be further lowered. If the value still cannot be lowered despite further interventions, this identifies a high-risk patient population for higher mortality and heart failure readmission. These patients should be more closely monitored. Boxes are colored to reflect severity of illness at each step with green reflective of a good outcome, yellow is cautionary status and red is area of significant concern for poor outcomes. BNP = B-type natriuretic peptide; NT-proBNP = N-terminal fragment of pro-B-type natriuretic peptide.

Figure 2. The J or U shape of sST2. Serially checking sST2 with admission to the hospital, at discharge and post-discharge can give a trajectory of sST2.

This trajectory may appear U-shaped, which is associated with an increased risk of subsequent death or heart failure readmission, or J-shaped, which is associated with a low risk for these outcomes. sST2 = soluble suppressor of tumorigenicity-2.

Figure 3. Integration of NPs, hs-cTn, and sST2 into acute heart failure management.

Values for these biomarkers should be checked on admission with each individual biomarker associated with worse outcomes when values are elevated. Serial measures of hs-cTn may identify high risk individuals, while serially sampling NPs and sST2 can substantially improve risk stratification. sST2 should be monitored after discharge as well for determining a J or U shape as in Figure 2. Boxes are colored to reflect severity of illness at each step with green reflective of a good outcome, yellow is cautionary status and red is area of significant concern for poor outcomes. hs-cTn = high-sensitivity cardiac troponin; NP = natriuretic peptide; sST2 = soluble suppressor of tumorigenicity-2.

Figure 4. A potential pathway for using NPs, CA-125, and bio-ADM in acute heart failure for management.

NPs correlate with intravascular congestion and studies have shown improved outcomes when the discharge value is ≥30% lower than the admission value; however, these studies did not specify this reduction was only from decongesting the intravascular compartment. NPs also reflect neurohormonal activation so other biomarkers may be beneficial for monitoring this compartment. bio-ADM shows promise as a biomarker of tissue congestion and levels are prognostic for heart failure outcomes; however, its use is still being defined. Given its short half-life though, serial monitoring might be beneficial during acute heart failure. CA-125 correlates with tissue congestion and prognosis. It has a longer half-life so assessment at admission and near discharge are more useful to assess for residual congestion. Studies support titrating therapy based on CA-125 levels with levels >35 U/mL associated with residual congestion. bio-ADM = bio-adrenomedullin; CA-125 = cancer antigen 125; NP = natriuretic peptide.

Figure 5. The different biomarkers through the spectrum of heart failure from diagnosis, prognosis, and management to cardiogenic shock.

bio-ADM = bio-adrenomedullin; CA-125 = cancer antigen 125; DPP3 = dipeptidyl peptidase 3; Gal-3 = galectin-3; hs-cTn = high-sensitivity cardiac troponin; IGFBP7 = Insulin-like growth factor-binding protein 7; MR-proANP = mid-regional pro-atrial natriuretic peptide; NP = natriuretic peptide; sST2 = soluble suppressor of tumorigenicity-2.