TY - JOUR
T1 - Risk of bias in studies investigating novel diagnostic biomarkers for heart failure with preserved ejection fraction. A systematic review
AU - Henkens, Michiel T. H. M.
AU - Remmelzwaal, Sharon
AU - Robinson, Emma L.
AU - van Ballegooijen, Adriana J.
AU - Aizpurua, Arantxa Barandiaran
AU - Verdonschot, Job A. J.
AU - Raafs, Anne G.
AU - Weerts, Jerremy
AU - Hazebroek, Mark R.
AU - Wijk, Sandra Sanders-van
AU - Handoko, M. Louis
AU - den Ruijter, Hester M.
AU - Lam, Carolyn S. P.
AU - de Boer, Rudolf A.
AU - Paulus, Walter J.
AU - van Empel, Vanessa P. M.
AU - Vos, Rein
AU - Brunner-La Rocca, Hans-Peter
AU - Beulens, Joline W. J.
AU - Heymans, Stephane R. B.
N1 - Funding Information:
This work was supported by the European Union Commission's Horizon 2020, and IMI2‐CARDIATEAM [N°821508]. We acknowledge the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON2015‐RECONNECT, CVON2016‐Early HFPEF and CVON 2017‐ShePREDICTS. Additionally, J.W.J.B. is supported by a ZonMw VIDI grant.
Funding Information:
This work was supported by the European Union Commission's Horizon 2020, and IMI2-CARDIATEAM [N?821508]. We acknowledge the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON2015-RECONNECT, CVON2016-Early HFPEF and CVON 2017-ShePREDICTS. Additionally, J.W.J.B. is supported by a ZonMw VIDI grant. Conflict of interest: none declared.
Publisher Copyright:
© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
PY - 2020/9
Y1 - 2020/9
N2 - Aim Diagnosing heart failure with preserved ejection fraction (HFpEF) in the non-acute setting remains challenging. Natriuretic peptides have limited value for this purpose, and a multitude of studies investigating novel diagnostic circulating biomarkers have not resulted in their implementation. This review aims to provide an overview of studies investigating novel circulating biomarkers for the diagnosis of HFpEF and determine their risk of bias (ROB). Methods and results A systematic literature search for studies investigating novel diagnostic HFpEF circulating biomarkers in humans was performed up until 21 April 2020. Those without diagnostic performance measures reported, or performed in an acute heart failure population were excluded, leading to a total of 28 studies. For each study, four reviewers determined the ROB within the QUADAS-2 domains: patient selection, index test, reference standard, and flow and timing. At least one domain with a high ROB was present in all studies. Use of case-control/two-gated designs, exclusion of difficult-to-diagnose patients, absence of a pre-specified cut-off value for the index test without the performance of external validation, the use of inappropriate reference standards and unclear timing of the index test and/or reference standard were the main bias determinants. Due to the high ROB and different patient populations, no meta-analysis was performed. Conclusion The majority of current diagnostic HFpEF biomarker studies have a high ROB, reducing the reproducibility and the potential for clinical care. Methodological well-designed studies with a uniform reference diagnosis are urgently needed to determine the incremental value of circulating biomarkers for the diagnosis of HFpEF.
AB - Aim Diagnosing heart failure with preserved ejection fraction (HFpEF) in the non-acute setting remains challenging. Natriuretic peptides have limited value for this purpose, and a multitude of studies investigating novel diagnostic circulating biomarkers have not resulted in their implementation. This review aims to provide an overview of studies investigating novel circulating biomarkers for the diagnosis of HFpEF and determine their risk of bias (ROB). Methods and results A systematic literature search for studies investigating novel diagnostic HFpEF circulating biomarkers in humans was performed up until 21 April 2020. Those without diagnostic performance measures reported, or performed in an acute heart failure population were excluded, leading to a total of 28 studies. For each study, four reviewers determined the ROB within the QUADAS-2 domains: patient selection, index test, reference standard, and flow and timing. At least one domain with a high ROB was present in all studies. Use of case-control/two-gated designs, exclusion of difficult-to-diagnose patients, absence of a pre-specified cut-off value for the index test without the performance of external validation, the use of inappropriate reference standards and unclear timing of the index test and/or reference standard were the main bias determinants. Due to the high ROB and different patient populations, no meta-analysis was performed. Conclusion The majority of current diagnostic HFpEF biomarker studies have a high ROB, reducing the reproducibility and the potential for clinical care. Methodological well-designed studies with a uniform reference diagnosis are urgently needed to determine the incremental value of circulating biomarkers for the diagnosis of HFpEF.
KW - Heart failure with preserved ejection fraction
KW - Diagnosis
KW - Biomarker
KW - Bias
KW - QUADAS-2
KW - VENTRICULAR DIASTOLIC FUNCTION
KW - NATRIURETIC PEPTIDE LEVELS
KW - DIFFERENTIATION FACTOR 15
KW - CELL DISTRIBUTION WIDTH
KW - ATRIAL-FIBRILLATION
KW - PREDICTIVE-VALUE
KW - ECHOCARDIOGRAPHY
KW - RECOMMENDATIONS
KW - ASSOCIATION
KW - PREVALENCE
U2 - 10.1002/ejhf.1944
DO - 10.1002/ejhf.1944
M3 - (Systematic) Review article
C2 - 32592317
SN - 1388-9842
VL - 22
SP - 1586
EP - 1597
JO - European journal of heart failure
JF - European journal of heart failure
IS - 9
ER -