Novel heart failure biomarkers: why do we fail to exploit their potential?

Piek, Arnold; Du, Weijie; Boer, Rudolf A. de; Silljé, Herman H W

doi:10.1080/10408363.2018.1460576

Cited by 82 publications

(94 citation statements)

References 198 publications

(240 reference statements)

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“…However, many of the biomarkers identified in our study have also been connected with noncardiac diseases [24]. As Piek et al [24] demonstrated the challenge to find specific biomarkers of heart failure, we also suppose that the biomarkers investigated in our study are probably not AF or cardiac specific; they likely represent the different underlying pathological processes in AF [8]. As shown in our model, we suppose that the combination of different molecular biomarkers would probably increase their specificity for cardiac diseases, especially AF, even though the individual AUCs were also discriminative.…”

Section: Resultsmentioning

confidence: 77%

Biomarkers Associated with Atrial Fibrillation in Patients with Ischemic Stroke: A Pilot Study from the NOR-FIB Study

Lambert¹,

Kong²,

Ratajczak-Tretel³

et al. 2020

Cerebrovasc Dis Extra

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Background and Purpose: Cardioembolic stroke due to paroxysmal atrial fibrillation (AF) may account for 1 out of 4 cryptogenic strokes (CS) and transient ischemic attacks (TIAs). The purpose of this pilot study was to search for biomarkers potentially predicting incident AF in patients with ischemic stroke or TIA. Methods: Plasma samples were collected from patients aged 18 years and older with ischemic stroke or TIA due to AF (n = 9) and large artery atherosclerosis (LAA) with ipsilateral carotid stenosis (n = 8) and age-and sex-matched controls (n = 10). Analyses were performed with the Olink technology simultaneously measuring 184 biomarkers of cardiovascular disease. For bioinformatics, acquired data were analyzed using gene set enrichment analysis (GSEA). Selected proteins were validated using ELISA. Individual receiver operating characteristic (ROC) curves and odds ratios from logistic regression were calculated. A randomForest (RF) model with out-of-bag estimate was applied for predictive modeling. Results: GSEA indicated enrichment of proteins related to inflammatory response in the AF group. Interleukin (IL)-6, growth differentiation factor (GDF)-15, and pentraxin-related protein PTX3 were the top biomarkers on the ranked list for the AF group compared to the LAA group and the control group. ELISA validated increased expression of all tested proteins (GDF-15, PTX3, and urokinase plasminogen activator surface receptor [U-PAR]), except for IL-6. 19 proteins had the area under the ROC curve (AUC) over 0.85 including all of the proteins with significant evolution in the logistic regression. AUCs were very discriminant in distinguishing patients with and without AF (LAA and control group together). GDF-15 alone reached AUC of 0.95. Based on RF model, all selected participants in the tested group were classified correctly, and the most important protein in the model was GDF-15. Conclusions: Our results demonstrate an association between inflammation and AF and that multiple proteins alone and in combination may potentially be used as indicators of AF in CS and TIA patients. However, further studies including larger samples sizes are needed to support these findings. In the ongoing NOR-FIB study, we plan further biomarker assessments in patients with CS and TIA undergoing long-term cardiac rhythm monitoring with insertable cardiac monitors.

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Section: Resultsmentioning

confidence: 77%

Biomarkers Associated with Atrial Fibrillation in Patients with Ischemic Stroke: A Pilot Study from the NOR-FIB Study

Lambert¹,

Kong²,

Ratajczak-Tretel³

et al. 2020

Cerebrovasc Dis Extra

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“…Nevertheless, none of these biomarkers, despite sound pathophysiological concepts, was shown to be useful in the guidance of HF therapy . In opposite, also others used biomarkers to identify patients who may benefit from advanced therapy like rolofylline, a selective A1 adenosine receptor antagonist, investigated for HF treatment in the PROTECT trial.…”

Section: Discussionmentioning

confidence: 99%

“…HF therapy. 32 In opposite, also others used biomarkers to identify patients who may benefit from advanced therapy like rolofylline, a selective A1 adenosine receptor antagonist, investigated for HF treatment in the PROTECT trial. The authors conclude that biomarkers are superior to clinical characteristics.…”

Section: Biomarkersmentioning

confidence: 99%

Biomarker guidance allows a more personalized allocation of patients for remote patient management in heart failure: results from the TIM‐HF2 trial

Möckel

Koehler

Anker

et al. 2019

European J of Heart Fail

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Aims The TIM‐HF2 study showed less days lost due to unplanned cardiovascular hospitalization or all‐cause death and improved survival in patients randomly assigned to remote patient management (RPM) instead of standard of care. Methods and results This substudy explored whether the biomarkers mid‐regional pro‐adrenomedullin (MR‐proADM) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) could be used to identify low‐risk patients unlikely to benefit from RPM, thereby allowing more efficient allocation of the intervention. For 1538 patients of the trial (median age 73 years, interquartile range 64–78 years, 30% female), baseline biomarkers were used to select subpopulations recommended for RPM with various safety endpoints (100%, 98%, 95% sensitivity), and efficacy of RPM was assessed. Both biomarkers were strongly associated with events. The primary endpoint of lost days increased from 1.0% (1.4%) in the lowest to 17.3% (17.6%) in the highest quintile of NT‐proBNP (MR‐proADM). After combining biomarkers to identify patients recommended for RPM with 95% sensitivity, in the most efficient scenario (excluding 27% of patients; NT‐proBNP < 413.7 pg/mL and MR‐proADM < 0.75 nmol/L), the effect of RPM on patients was highly similar to the original trial (ratio of lost days: 0.78, hazard ratio for all‐cause death: 0.68). Number needed to treat for all‐cause death was lowered from 28 to 21. Rates of emergencies and telemedical efforts were significantly lower among patients not recommended for RPM. Biomarker guidance would have saved about 150 h effort/year per 100 patients of the eligible population. Conclusions The combined use of MR‐proADM and NT‐proBNP may allow safe, more precise, effective and cost‐saving allocation of patients with heart failure to RPM and warrants further prospective studies.

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“…Based on the observed changes, the authors suggest that the ST2/IL‐33 system might be the link between oxidative stress and fibrosis. Stressed cardiomyocytes and fibroblasts produce IL‐33 and interaction of IL‐33 with ST2L appears to be cardioprotective by, amongst others, reducing myocardial fibrosis . Meanwhile, stressed cardiomyocytes and fibroblasts also produce sST2, which competitively binds to ST2L, thereby preventing the cardioprotective effects of the IL‐33/ST2 interaction.…”

mentioning

confidence: 99%