Abstract
Biomarkers have become an integral part of practicing medicine, especially in heart failure. The natriuretic peptides are commonly used in the evaluation of heart failure, but their role extends beyond diagnosis and includes risk stratification and management of heart failure patients. Newer biomarkers have arrived and are becoming part of routine care of heart failure patients. Both ST2 and high-sensitivity troponin have significant prognostic value for mortality, but also may assist in the titration of medical therapy. Procalcitonin can help guide appropriate antibiotic use in patients with heart failure. The ability to appropriately use and interpret these biomarkers is imperative to the care of heart failure patients, especially as these newer biomarkers become widely used.
Clinical Scenario
Mrs. Smith is a 70-year-old woman with a history of heart failure with reduced ejection fraction secondary to ischemic cardiomyopathy and chronic obstructive pulmonary disease who presents with shortness of breath. She has been hospitalized 3 times this year. Findings are notable for tachycardia, elevated jugular venous pressure, lower extremity edema, and an elevated white count. Things you consider are:
1)Is this heart failure, and if so, how severe is it?
2)Should I start antibiotics for a possible pneumonia?
3)How can I possibly know it’s safe to discharge the patient and reduce the risk of readmission?
4)What is the patient’s long-term prognosis?
Background
Heart failure is a common condition, with over 5.7 million afflicted and over 1 million hospitalizations annually. Almost all medical practitioners will interact with heart failure patients and should be familiar with their care. Biomarkers have become an integral part of medicine, aiding in the diagnosis and treatment of numerous conditions. This review provides a focused update on biomarkers that are and will soon be regularly used in the management of heart failure. Table 1 depicts an opinion of an ideal biomarker in heart failure. We will discuss biomarkers that are either diagnostic for heart failure, one of its comorbidities such as bacterial pneumonia, or surrogates for underlying pathology. In these situations, the biomarkers may lead to specific treatments, and improvements may be reflected by a drop in the biomarker. Figure 1 displays an overview of underlying pathophysiological disorders in heart failure with resultant surrogate biomarkers. Table 2 denotes the major utility of the biomarkers that will be discussed.
Natriuretic Peptides: B-Type Natriuretic Peptide and N-Terminal Prohormone B-Type Natriuretic Peptide
B-type natriuretic peptide (BNP) is a neurohormone synthesized and released primarily from the ventricles of the heart. It is initially synthesized as pre-proBNP, cleaved to proBNP, and subsequently to the biologically active 32-amino acid BNP and the inactive 76-amino acid N-terminal fragment (NTproBNP). BNP is synthesized and released in response to pressure and volume overload and results in vasodilation, natriuresis, and diuresis. BNP’s half-life is approximately 20 minutes, and it is cleared primarily by neutral endopeptidase and natriuretic peptide (NP) receptors with potentially some clearance by renal filtration. NTproBNP has a half-life of 1 to 2 hours and is more dependent on renal filtration for elimination. Both of these NPs are helpful in the diagnosis, prognosis, and management of heart failure.
The first and most common use of NPs is assisting in the diagnosis of heart failure in patients with dyspnea. In the Breathing Not Properly study, BNP accurately diagnosed heart failure in patients presenting to the emergency department with dyspnea, with a sensitivity of 90% and specificity of 76% at a cut-off of 100 pg/mL. In the N-terminal Pro-BNP Investigation of Dyspnea in the Emergency Department Study (PRIDE), NTproBNP had a similar sensitivity for excluding heart failure at a cut-off of 300 pg/mL. Importantly, NTproBNP’s sensitivity and specificity vary based on age, with age-related cut-offs of 450 pg/mL for <50 years, 900 pg/mL for 50-75 years, and 1800 pg/mL for >75 years.
The diagnostic strength of NPs is their high sensitivity for “ruling out” heart failure; however, as the value increases, heart failure becomes more likely. Defining “rule in” cut-offs for heart failure is complicated as multiple factors influence NP levels (details below). Proposed rule-in cut-offs are the age-related values presented earlier for NTproBNP and a value >400 pg/mL for BNP.
In patients admitted with acute heart failure and volume overload, NPs are excellent surrogates of volume status except when superimposed on severe kidney disease. Table 3 delineates that a second measurement early during treatment can inform whether the NP level is heading in the right direction (ie, toward a euvolemic state). This should be measured in the same manner we measure a white blood cell count after treatment for an infection is initiated. A lack of drop of the NP level following a significant diuresis may represent “third space” movement of water, without affecting the preload and afterload of the ventricles. NP levels at the time of anticipated discharge may be informative as to whether patients have reached an optivolemic status. The NP level at discharge should be used as a basis for following the patient in the outpatient setting, not only to titrate therapy but to judge whether future symptoms (and NP levels) are likely due to decompensation.
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-Nicholas Wettersten, MD, Alan S. Maisel, MD
This article originally appeared in the June 2016 issue of The American Journal of Medicine.
