Page 67 - Biomarkers for risk stratification and guidance in heart failure

Chapter 3
Whether clinicians need a biomarker to guide heart failure therapy is a question that has generated considerable debate in the last decade.1,2 The concept of tailoring heart failure treatment to achieve a target level of B-type natriuretic peptide (BNP) and thereby reduce cardiovascular event rates was first tested in the late 1990s.3,4 Since then, a series of studies using a variety of study designs have addressed this strategy in small and moderate-sized cohorts.5-8
The rationale for attempting to improve the treatment of heart failure is undisputed: heart failure prevalence is increasing, and associated mortality and hospitalization rates remain high even with modern therapies and multidisciplinary care.9,10 There is currently no reliable objective guide to optimal pharmacotherapy of heart failure that can be easily applied to individual patients in the ambulant chronic heart failure setting. Additionally, despite clear treatment guidelines, target doses for medications that have been shown in controlled trials to improve clinical outcomes are frequently not achieved in the real world. This undertreatment is not explained simply by differences in patient populations.10-12 The reasons for suboptimal treatment are many, but of particular importance is the fact that clinical assessment is insensitive and frequently does not identify hemodynamic decompensation or allow accurate assessment of filling pressures, making it an inexact guide to diuretic dosing.13 Treatment options for systolic heart failure have become complex, and a range of medications and devices with proven efficacy now need to be considered, often in combination.10 In contrast, the optimal choice of treatment and dosing in heart failure with preserved ejection fraction remains uncertain.14 There is also inherent and understandable hesitancy when it comes to up-titration of treatment in apparently stable patients, especially when there are concerns about hypotension, azotemia, or other adverse medication effects.
The B-type natriuretic peptides (BNP and N-terminal pro–B-type natriuretic peptide \[NT-proBNP\]) stand out as biomarkers with the potential to guide therapy. Commercial assays for both peptides are readily available and analytical variation is minimal, particularly for NT-proBNP.15 Plasma levels of both peptides reflect cardiac function and filling pressures and are powerful predictors of mortality and clinical outcome.16 Irrespective of innate within-patient variation, serial peptide measurements provide incremental prognostic value in both the in- and out-patient setting, with a fall in peptide levels being associated with better outcomes.17,18 Additionally, plasma levels of both peptides fall during treatment with proven therapies and mirror beneficial changes in left ventricular structure and function.19,20
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