Page 94 - Biomarkers for risk stratification and guidance in heart failure

Which heart failure patients profit from natriuretic peptide-guided therapy?
In HFrEF patients forming the majority of the study population, comorbidities including diabetes, PVD, CVI/TIA and COPD influenced the effects of NT-proBNP- guided therapy upon mortality. Diabetes mellitus and COPD are frequent comorbidities in HF.22 They are of independent prognostic importance23 and might, therefore, influence prognosis such that NT-proBNP-guided therapy has less effect. Interestingly, no interaction was seen with renal failure, which is in line with the recent finding that intensifying HFrEF therapy may reduce the negative effects of worsening renal failure on prognosis.24 This might be related to the fact that renal dysfunction is often an expression of poor cardiac function in patients with HFrEF, whereas this is not so much the case in HFpEF.
In addition to a better understanding of the effects of (NT-pro) BNP-guided
therapy in HF, our results shed new light on HF treatment in general. Only a
minority of real-life HF patients fulfil the enrolment criteria of landmark HF trials25 4 because patients with comorbidities have often been excluded. In contrast, most
of the (NT-pro)BNP-guided HF trials did not have similarly restrictive inclusion
criteria, resulting in recruitment of more ‘real world’ patients. Our results on comorbidities might explain why in daily practice, recommended therapies are
often not used in adequate doses. It might be speculated that in elderly multi-
morbid patients, use of biomarkers may help to identify patients in whom
avoiding up-titration or down-titration may be superior to the current approach.
The effect of HF medication in patients with combined comorbidities and the
feasibility and wisdom of titrating to currently recommended target doses in such
patients remains to be assessed in future trials.
Heart failure with preserved vs. reduced left ventricular ejection fraction
Compared with patients with HFrEF, patients with HFpEF have substantially different demographics.26-28 Previous data suggest lower event rates among those with HFpEF compared with HFrEF even after correction for other significant predictors.7,26 However, in our cohort, patients with HFpEF and HFrEF had comparable mortality rates and the combined endpoint of hospitalization because of HF or death was more often reached in HFpEF patients. This difference might be partly explained by the fact that the studies which included HFpEF (TIME-CHF, PRIMA, BATTLESCARRED and Vienna) included patients (recently) hospitalized for acutely decompensated HF.8,9,12,17 As survival differences between HFrEF and HFpEF diminish with increasing age,26 inclusion of the generally more aged HFpEF group of TIME-CHF17 could also have contributed to this finding. Finally, guided
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