Redefining the role of biomarkers in heart failure trials: expert consensus document

Sabbah, Hani N.; Zannad, Faı̈ez; Tintelen, J. Peter van; Schelbert, Erik B.; Kim, Raymond J.; Milting, Hendrik; Vonk, Richardus; Neudeck, Brien L.; Clark, Richard L.; Witte, Klaus K.; Dinh, Wilfried; Pieske, Burkert; Butler, Javed; Gheorghiade, Mihai

doi:10.1007/s10741-017-9608-5

Cited by 19 publications

(13 citation statements)

References 91 publications

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“…26 NT-proBNP is a biomarker reflecting myocardial strain with an established clinical value in the diagnosis and management of patients with HF. 27 Other phase II clinical trials in HFpEF (eg, sacubitril-valsartan 28 ) have used NT-proBNP level reductions as primary end points. Despite the lower values of NT-proBNP in patients with HFpEF, as compared with HF with reduced EF, natriuretic peptides maintain their prognostic value.…”

Section: Discussionmentioning

confidence: 99%

IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction

Tassell

Trankle

Canada

et al. 2018

Circ: Heart Failure

148

120

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BACKGROUND: Enhanced inflammation may lead to exercise intolerance in heart failure with preserved ejection fraction. The aim of the current study was to determine whether IL (interleukin)-l blockade with anakinra improved cardiorespiratory fitness in heart failure with preserved ejection fraction. METHODS AND RESULTS: Thirty-one patients with heart failure with preserved ejection fraction and CRP (C-reactive protein) >2 mg/L were randomized to anakinra (100 mg subcutaneously daily, N=21) or placebo (N=10) for 12 weeks. We measured peak oxygen consumption (Vo2), ventilatory efficiency (VE/Vco2 slope), and high-sensitivity CRP and NT-proBNP (N-terminal pro-B-type natriuretic peptide) at 4, 12, and 24 weeks. Twenty-eight patients completed ≥2 visits, 18 women (64%), 27 (96%) obese. There were no differences in peak Vo2 or VE/Vco2 slope between groups at baseline. Peak Vo2 was not changed after 12 weeks of anakinra (from 13.6 [11.8–18.0] to 14.2 [11.2–18.5] mL-kg−1-min−1, P=0.89), or placebo (14.9 [11.7–17.2] to 15.0 [13.8–16.9] mL-kg−1-min−1, P=0.40), without significant between-group differences in changes at 12 weeks (−0.4 [95% CI, −2.2 to +1.4], P=0.64). VE/Vco2 slope was also unchanged with anakinra (from 28.3 [27.2–33.0] to 30.5 [26.3–32.8], P=0.97) or placebo (from 31.6 [27.3–36.9] to 31.2 [27.8–33.4], P=0.78), without significant between-group differences in changes at 12 weeks (+1.2 [95% CI, −1.8 to +4.3], P=0.97). Within the anakinra-treated patients, high-sensitivity CRP and NT-proBNP levels were lower at 4 weeks compared with baseline (P=0.026 and P=0.022 versus placebo [between-group analysis], respectively). CONCLUSIONS: Treatment with anakinra for 12 weeks failed to improve peak Vo2 and VE/Vco2 slope in a group of obese heart failure with preserved ejection fraction patients. The favorable trends in high-sensitivity CRP and NT-proBNP with anakinra deserve exploration in future studies. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: .

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Section: Discussionmentioning

confidence: 99%

IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction

Tassell

Trankle

Canada

et al. 2018

Circ: Heart Failure

148

120

View full text Add to dashboard Cite

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“…Because of its aggressive behavior and frequently late diagnosis, research aiming at early diagnosis of pancreatic cancer or its precursors is crucial. Molecular biomarkers play an important role in early diagnosis, and the rapid development of high-throughput technologies has resulted in an increasing number of biomarkers being screened for disease progression [37] , [38] . Biomarkers enable the identification of genes, miRNAs, LncRNAs, and so on for early diagnosis, treatment, and prognosis of the disease, including pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of Prognostic Biomarkers by Combined mRNA and miRNA Expression Microarray Analysis in Pancreatic Cancer

Liu

Yang

Taher

et al. 2018

Translational Oncology

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Pancreatic cancer is the fourth leading cause for cancer-related death, and early diagnosis is one key to improve the survival rate of this disease. Molecular biomarkers are an important method for diagnostic use in pancreatic cancer. We used data from three mRNA microarray datasets and a microRNA dataset (GSE16515, GSE15471, GSE28735, and GSE41372) to identify potential key genes. Differentially expressed genes (DEGs) and microRNAs (DEMs) were identified. Functional, pathway enrichment, and protein-protein interaction analyses were performed on common DEGs across all datasets. The target genes of the DEMs were identified. DEMs targets that were also DEGs were further scrutinized using overall survival analysis. A total of 236 DEGs and 21 DEMs were identified. There were a total of four DEGs (ECT2, NR5A2, NRP2, and TGFBI), which were also predicted target genes of DEMs. Overall survival analysis showed that high expression levels of three of these genes (ECT2, NRP2, and TGFBI) were associated with poor overall survival for pancreatic cancer patients. The basic expression of DEGs in pancreas stood lower level in various organ tissues. The expression of ECT2 and NRP2 was higher in different pancreatic cancer cell lines than normal pancreas cell line. Knockout of ECT2 by Crispr Cas9 gene editing system decreased proliferation and migration ability in pancreatic cancer cell line MiaPaCa2. In conclusion, we think that data mining method can do well in biomarker screening, and ECT2 and NRP2 can play as potential biomarker or therapy target by Crispr Cas9 in pancreatic cancer.

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“…Anticipation is extremely valuable in the management of BPSDs. New terms illustrating this technological reality are emerging in medical research: “digital biomarker” (Kramer et al, 2017; Califf, 2018), “electronic biomarker” (Faurholt-Jepsen et al, 2015), or “digital phenotyping” (Insel, 2017) ( Box 1 ). These sensitive and continuous measures may even reveal subtle intraindividual changes or modified variability over time and may constitute new early biomarkers of mental health (Kaye, 2008; Dodge et al, 2014).…”

Section: Future Directions For the Management Of Bpsds In The Patientmentioning

confidence: 99%

Information and Communication Technologies, a Promising Way to Support Pharmacotherapy for the Behavioral and Psychological Symptoms of Dementia

et al. 2019

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Health care systems face an expansion in the number of older individuals with a high prevalence of neurodegenerative diseases and related behavioral and psychological symptoms of dementia (BPSDs). Health care providers are expected to develop innovative solutions to manage and follow up patients over time in the community. To date, we are unable to continuously and accurately monitor the nature, frequency, severity, impact, progression, and response to treatment of BPSDs after the initial assessment. Technology could address this need and provide more sensitive, less biased, and more ecologically valid measures. This could provide an opportunity to reevaluate therapeutic strategies more quickly and, in some cases, to treat earlier, when symptoms are still amenable to therapeutic solutions or even prevention. Several studies confirm the relationship between sensor-based data and cognition, mood, and behavior. Most scientific work on mental health and technologies supports digital biomarkers, not so much as diagnostic tools but rather as monitoring tools, an area where unmet needs are significant. In addition to the implications for clinical care, these real-time measurements could lead to the discovery of new early biomarkers in mental health. Many also consider digital biomarkers as a way to better understand disease processes and that they may contribute to more effective pharmaceutical research by (i) targeting the earliest stage, (ii) reducing sample size required, (iii) providing more objective measures of behaviors, (iv) allowing better monitoring of noncompliance, (v) and providing a better understanding of failures. Finally, communication technologies provide us with the opportunity to support and renew our clinical and research practices.

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Redefining the role of biomarkers in heart failure trials: expert consensus document

Cited by 19 publications

References 91 publications

IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction

IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction

Identification of Prognostic Biomarkers by Combined mRNA and miRNA Expression Microarray Analysis in Pancreatic Cancer

Information and Communication Technologies, a Promising Way to Support Pharmacotherapy for the Behavioral and Psychological Symptoms of Dementia

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