Page 162 - Biomarkers for risk stratification and guidance in heart failure

1,000 pg/ml but decreasing, diuretic dosage could be reduced and evidence based HF medication should be uptitrated to recommended dosages. Such decision-making algorithm should be investigated in future trials.
Clinical challenges of NT-proBNP-guided therapy: cardiorenal interaction.
When treating HF, clinicians may encounter conflicting prognostic information by
evaluating changes in renal function and natriuretic peptides over time. In other
words: how should outpatient change in renal function in relation to change in
natriuretic peptides be interpreted? In chapter 5 we already demonstrated that
both the absolute outpatient NT-proBNP level, as change in NT-proBNP early
after hospital discharge after admission because of acute HF have independent
prognostic impact. Although not entirely uniform,83,84 most studies showed
increased risk of worsening renal function (WRF) in heart failure patients. In
a recently performed meta-analysis, presence of worsening renal function in
both acute and chronic HF was associated with increased risk for mortality
(OR 1.81, 95% CI 1.55-2.12, P<0.001)85. The prognostic impact of improvement
of renal function (IRF) is less well known and mainly investigated in acute HF,
where it has been associated with worse outcome.86,87 In contrast in chronic HF, improvement in renal function defined as a decrease in creatinine of >0.3 mg/dl
predicted lower mortality (HR 0.8, 95% CI 0.6-1.0).88 In chapter 6 we investigated
the prognostic impact of change in renal function in addition to change in NT-
proBNP early after hospital discharge after admission because of acute heart
failure. We found that early changes in NT-proBNP after hospital discharge due to
acute HF had significant prognostic impact whereas changes in renal function did
not. This finding might lead to the assumption that i) treatment of heart failure 7 should be focused on improvement in cardiac function in such patients even if
renal function slightly deteriorates and ii) there are multiple triggers for changes in renal function with different pathophysiologic and prognostic backgrounds. Worsening renal function in HF patients can be caused by ominous processes like forward failure, venous congestion, neurohumoral activation, and release of vasoactive substances resulting in low renal perfusion.89 On the contrary, WRF can also be caused by factors that are associated with favorable outcome like titration of evidence based HF medication like ACE-inhibitors, AT-2 antagonist and aldosterone receptor blockers.90-94 WRF can also reflect intravascular volume depletion caused by diuretic treatment of HF.95 On the other hand; improvement in renal function might reflect an increase in renal perfusion as a result of
General Discussion
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