Page 157 - Biomarkers for risk stratification and guidance in heart failure
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                                Chapter 7
7.3 GUIDED THERAPY OF HEART FAILURE: APPLICABLE TO ALL PATIENTS?
One possible explanation of the apparent dependency of the efficacy of NP- guided treatment upon age is that comorbidities, which are more common with increasing age, may limit HF therapy titration and / or reduce benefits of treatment. Another interesting finding of the previously mentioned meta-analysis was that, as only 10% of the trial participants had heart failure with preserved left ventricular ejection fraction (HFpEF), the effect of natriuretic peptide-guided therapy in this patient group still remained to be assessed. These findings have led to debate whether there are potential differences in treatment response between HFrEF and HFpEF, as well as potential interactions between comorbidities and age with treatment response in patients included in randomized trials of (NT-pro) BNP-guided therapy in HF.
In chapter 4 of this thesis, we address these questions in a meta-analysis consisting of the previously mentioned cohort61 with the addition of the HFpEF subgroup in TIME-CHF62. We found that (i) positive effects of natriuretic peptide- guided therapy were indeed only seen in patients with reduced EF and (ii) comorbidities strongly influenced the response to guided therapy and explained the lower efficacy of this approach in elderly patients. In patients with reduced EF, natriuretic peptide-guided therapy only led to mortality reduction in patients with none or only one of the following comorbidities: CVA/TIA, diabetes, COPD or peripheral vascular disease.
Natriuretic peptide-guided therapy in HFpEF
In HPEF patients, no positive effect of natriuretic peptide-guided therapy was seen. Strikingly: in patients with preserved ejection fraction without hypertension and in patients with renal dysfunction, natriuretic peptide-guided therapy even increased mortality.
Compared to HFrEF, patients with HFpEF have substantially different demographics.63 In addition to the notion that HFrEF and HFpEF may be two distinct diseases,62 several other concepts may be relevant to the finding that natriuretic peptide-guided therapy is ineffective in HFpEF. Until today, no prospective large randomized therapeutic trial has demonstrated positive results of HF therapies.64-66 In contrast, medical and device treatment has markedly improved prognosis in HFrEF over the last decades.67 It is therefore not surprising
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