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Novel Applications of Cardiac Biomarkers in Heart Failure
NT-proBNP. If a robust decrease is not observed, intensification of heart among patients admitted with acute decompensated heart failure were
failure treatment would be indicated. associated with adverse outcomes. In a similar fashion, Sakhuja and
colleagues showed that cTnT was prognostic for short-term mortality, and
Chronic Heart Failure was additive to results for either BNP or NT-proBNP for this application.
37
In patients with chronic heart failure, both natriuretic peptides have Recently, Peacock et al.
38
analyzed the Acute Decompensated Heart
shown to remain prognostically meaningful despite available results
from other measures of prognostication such as LV function, signs
and symptoms, and even peak oxygen consumption (VO
2
).
26,27
Similar
to acute heart failure, patterns of BNP or NT-proBNP over time are
The utility of markers of cardiomyocyte
more indicative of risk than are single measurements;
28
changes in
injury or necrosis in heart failure remain
natriuretic peptides appear to parallel the benefit of therapeutic
interventions for chronic heart failure, with a gradual change in
unclear, but preliminary data in this area
response to therapy most apparent approximately two weeks
are compelling.
following treatment changes.
29
Given these facts, the use of BNP or NT-proBNP as an adjunct to
management in chronic heart failure appears logical. Troughton et al.
30
Failure National Registry (ADHERE) and found the adjusted odds ratio
first demonstrated that an NT-proBNP level below approximately for in-hospital death associated with a measurable cTnI was 2.33
1,700ng/l was associated with fewer combined events of heart failure (95% confidence interval [C] 1.98–2.75; p<0.001).
decompensation, hospitalization, and mortality (19 versus 54; p=0.02)
during a median 9.5 months of follow-up. Importantly, this study was Hudson et al.
39
analyzed cTnT levels on 136 ambulatory patients with
small and the medical management was not optimal with regard to chronic stable heart failure and found that elevated cTnT levels
β-blockers. The Systolic Heart Failure Treatment Supported by BNP >0.02ng/ml were associated with increased relative risks (RR) of death
(STARS-BNP)
31
study further explored the concept of BNP-guided or heart failure hospitalization (RR 2.7, 95% CI 1.7–4.3, p<0.001) and
heart failure management among 220 patients with class II–IV death alone (RR 4.2, 95% CI 1.8–9.5; p<0.001) during a median
symptoms who were randomized to BNP (target value <100ng/l) and follow-up of 14 months. Similarly, Sato et al.
40
observed that
clinically guided treatment. In this study with 15 months of follow-up, persistently elevated cTnT levels >0.02ng/ml had deterioration of left
primary end-points (unplanned hospital stays for heart failure or ventricular ejection fraction (LVEF). Lastly, Miller and colleagues
death related to heart failure) were observed in 24% of the BNP group showed that serial sampling of cTnT provided superior prognostication
versus 52% of the clinical group. for adverse outcome, with a rising pattern associated with the greatest
risk; this risk was independent of that of BNP and was superior to this
Several larger randomized trials are ongoing to examine NT-proBNP latter marker for prognosis.
41
Thus, available data support the use of
guidance for heart failure therapy as outpatients. Method papers have cTn methods for risk assessment in acute and chronic heart failure;
been published for the BNP-Assisted Treatment To Lessen Serial what remains less clear is the therapeutic imperative associated with
Cardiovascular Readmissions and Death (BATTLE-SCARRED)
32
and Trial of an elevated cTn value in this setting.
Intensified versus Standard Medical Therapy in Elderly Patients With
Congestive Heart Failure (TIME-CHF) studies,
33
and both trials have been Novel Applications of Established Cardiac
presented. In both, the use of NT-proBNP guidance for heart failure Biomarkers—Inflammatory Markers
management was associated with significant improvements in mortality Inflammation plays a pivotal role in heart failure, and there is an
(BATTLESCARRED) or heart-failure-free survival (TIME-CHF); however, emerging appreciation for the role of inflammatory marker
these benefits were most obvious among those <75 years of age. measurement for risk assessment in heart failure patients.
Accordingly, more information is necessary regarding the specific
benefits of natriuretic-peptide-guided heart failure management before C-reactive Protein
it becomes standard of care in heart failure. C-reactive protein (CRP) is a member of the pentraxin family
of inflammatory markers, and represents the prototypical biomarker of
Novel Applications of Established Cardiac inflammation.
42
Synthesized by the liver in response to numerous
Biomarkers—Markers of Myocyte Injury stimuli, CRP has been shown to be powerfully prognostic for
The utility of markers of cardiomyocyte injury or necrosis in heart failure the development of heart failure and is also predictive of risk across the
remain unclear, but preliminary data in this area are compelling. It is well spectrum of heart failure.
known that cardiac-specific troponin (cTn) levels may be elevated in
patients with heart failure without overt ischemia.
34–35
Elevated cTnI and In the Framingham Heart Study, Vasan et al.
43
reported that elevated
cTnT levels among patients with both acute and chronic heart failure have CRP (5mg/dl) had near-tripling of heart failure risk, while Anand et al.
44
been associated with both short- and long-term adverse outcomes. demonstrated that chronic stable heart failure patients with CRP
above the median value of 3.23mg/l had features of more severe heart
In the context of acute decompensated heart failure, Del Carlo et al.
36
failure than those with CRP levels below the median. Multivariate
demonstrated that persistently measurable levels of cTnT by day seven analysis also indicated that increased CRP was an independent
US CARDIOLOGY 43
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