Biomarkers for predicting atrial fibrillation: An explorative sub-analysis of the randomised SCREEN-AF trial

Abstract

Background

Atrial fibrillation (AF) is a common treatable risk factor for stroke. Screening for paroxysmal AF in general practice is difficult, but biomarkers might help improve screening strategies.

Objectives

We investigated six blood biomarkers for predicting paroxysmal AF in general practice.

Methods

This was a pre-specified sub-study of the SCREEN-AF RCT done in Germany. Between 12/2017-03/2019, we enrolled ambulatory individuals aged 75 years or older with a history of hypertension but without known AF. Participants in the intervention group received active AF screening with a wearable patch, continuous ECG monitoring for 2x2 weeks and usual care in the control group. The primary endpoint was ECG-confirmed AF within six months after randomisation. High-sensitive Troponin I (hsTnI), brain natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), N-terminal pro atrial natriuretic peptide (NT-ANP), mid-regional pro atrial natriuretic peptide (MR-pro ANP) and C-reactive protein (CRP) plasma levels were investigated at randomisation for predicting AF within six months after randomisation.

Results

Blood samples were available for 291 of 301 (96.7%) participants, including 8 with AF (3%). Five biomarkers showed higher median results in AF-patients: BNP 78 vs. 41 ng/L (p = 0.012), NT-pro BNP 273 vs. 186 ng/L (p = 0.029), NT-proANP 4.4 vs. 3.5 nmol/L (p = 0.027), MR-pro ANP 164 vs. 125 pmol/L (p = 0.016) and hsTnI 7.4 vs. 3.9 ng/L (p = 0.012). CRP levels were not different between groups (2.8 vs 1.9 mg/L, p = 0.1706).

Conclusion

Natriuretic peptide levels and hsTnI are higher in patients with AF than without and may help select patients for AF screening, but larger trials are needed.

KEY MESSAGES

• BNP, NT-pro BNP, NT-ANP and MR-pro ANP and hsTnI levels are higher in patients with AF than without AF

• With a sensitivity at 100%, BNP had the highest specificity of 60% (BNP level 50.1ng/L), followed by NT-pro BNP with a specificity of 53% (179ng/l)

Trial Registration:

• ClinicalTrials.gov Identifier: NCT02392754
• www.DZHK.de: SCREEN-AF DZHK15

Keywords:

• Atrial fibrillation
• natriuretic peptides
• screening
• prediction
• primary care

Acknowledgements

The authors thank all participating primary care physicians and their teams.

Disclosure statement

JH has research grants and speaking fees from Medtronic, Boston Scientific, BMS/Pfizer, Servier and consulting fees from Bayer. DG reported receiving an operating grant from the Canadian Stroke Prevention Intervention Network (C-SPIN) during the conduct of the main SCREEN-AF trial (C-SPIN is a peer-reviewed national network grant funded by the Canadian Institutes of Health Research [CIHR]). He was supported by a Mid-Career Investigator Award from the Heart and Stroke Foundation (Canada) and the Department of Medicine and Bastable-Potts Chair at Sunnybrook Health Sciences Centre, Toronto. He serves as a Canadian national co-leader for the ARCADIA trial. He received an honorarium for participation in ad hoc advisory board for HLS Therapeutics Inc. He has had no personal financial relationships with cardiac monitoring device manufacturers or pharmaceutical companies related to AF in the past 6+ years. RW reports receiving grants from Deutsches Zentrum für Herz-/Kreislaufforschung for the conduct of the study, Deutsche Forschungsgemeinschaft, European Union, Bundesministerium für Bildung und Forschung, Boehringer Ingelheim and Medtronic; personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, Daiichi-Sankyo, BMS, Medtronic, Novartis, Pfizer, Pharmacosmos, sciarc and Servier outside the submitted work.

Additional information

Funding

The study was funded by the Canadian Stroke Prevention Intervention Network (C-SPIN), a peer-reviewed national network grant from the Canadian Institutes of Health Research (CIHR), a peer-reviewed operating grant (FKZ 81 × 1300111) from the German Centre for Cardiovascular Research (DZHK) [31], supplemented by funding from Boehringer Ingelheim and in-kind support from Microlife Corp, ManthaMed, and iRhythm. Financial support was also received from the Open Access Publication Fund of the UKE. No funding was received from the manufacturers of the used assays.