Blood-biomarkers and devices for atrial fibrillation screening: Lessons learned from the AFRICAT (Atrial Fibrillation Research In CATalonia) study

Q: What does this research mean for the field?

NT-proBNP is an independent biomarker for detecting atrial fibrillation in high-risk elderly patients, and a screening strategy combining high NT-proBNP levels with rhythm detection devices is feasible. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Elena Palà; Alejandro Bustamante; Josep Lluís Clua‐Espuny; Juan Acosta; Felipe Anastacio González González; Sara Dos Santos; Domingo Ribas-Segui; Juan Ballesta-Ors; Anna Peñalba; Marina Giralt; Íñigo Lechuga-Durán; Delicia Gentille-Lorente; Alonso Pedrote; Miguel Ángel Muñoz; Joan Montaner

doi:10.1371/journal.pone.0273571

August 23, 2022PLoS ONEOpen Access

Blood-biomarkers and devices for atrial fibrillation screening: Lessons learned from the AFRICAT (Atrial Fibrillation Research In CATalonia) study

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Why the study?

The study aimed to develop an AF screening program combining blood markers, rhythm detection devices, and long-term monitoring, validating NT-proBNP and evaluating novel biomarkers and wearable devices.

Does a screening strategy combining blood biomarkers and rhythm detection devices improve atrial fibrillation detection in subjects aged 65-75 years with hypertension and diabetes?

Key Points

To evaluate circulating blood biomarkers, including NT-proBNP, and compare wearable rhythm detection devices against continuous Holter monitoring for community atrial fibrillation screening.
Conducted a two-phase prospective cohort study enrolling 359 hypertensive and diabetic patients aged 65–75 years (Phase I: n = 100; Phase II: n = 259).
Screened participants using baseline 12-lead ECG, 4 weeks of continuous Holter monitoring (Nuubo), and four detection devices (AliveCor, WatchBP, MyDiagnostick, and Fibricheck).
Profiled 1310 serum proteins using an aptamer array in 26 participants, followed by verification and validation of candidate biomarkers alongside NT-proBNP.
Diagnosed atrial fibrillation in 34 of 359 participants (9.47%), with log-transformed NT-proBNP confirmed as the only independent predictive biomarker (OR = 1.934; p < 0.001).
Identified 41 differentially expressed proteins via aptamer array, but primary verification candidates TIMP-2 and ST-2 failed subsequent validation.
Compared against ECG, WatchBP achieved the highest sensitivity (84.6%) and AUC (0.895 [95% CI, 0.780–1.000]), whereas MyDiagnostick demonstrated the highest specificity (97.10%).

Structured PICO

Does a screening strategy combining blood biomarkers and rhythm detection devices improve atrial fibrillation detection in subjects aged 65-75 years with hypertension and diabetes?

P

Population

359 subjects aged 65-75 years with hypertension and diabetes

I

Intervention

Blood biomarkers (NT-proBNP, aptamer array) and rhythm detection devices (AliveCor, Watch BP, MyDiagnostick, Fibricheck) with 4 weeks of Holter monitoring

C

Comparator

Baseline 12-lead ECG and/or medical history

O

Outcome

Atrial fibrillation detectionsurrogate

An atrial fibrillation screening strategy using rhythm detection devices and short monitoring periods among high-risk patients with high NT-proBNP levels is feasible and effective.

Implication

NT-proBNP and WatchBP may support targeted AF screening in older hypertensives with diabetes; hypothesis-generating, requiring randomized trials before practice change.

Abstract

BACKGROUND AND OBJECTIVE: AFRICAT is a prospective cohort study intending to develop an atrial fibrillation (AF) screening program through the combination of blood markers, rhythm detection devices, and long-term monitoring in our community. In particular, we aimed to validate the use of NT-proBNP, and identify new blood biomarkers associated with AF. Also, we aimed to compare AF detection using various wearables and long-term Holter monitoring. METHODS: 359 subjects aged 65-75 years with hypertension and diabetes were included in two phases: Phase I (n = 100) and Phase II (n = 259). AF diagnosis was performed by baseline 12-lead ECG, 4 weeks of Holter monitoring (NuuboTM), and/or medical history. An aptamer array including 1310 proteins was measured in the blood of 26 patients. Candidates were selected according to p-value, logFC and biological function to be tested in verification and validation phases. Several screening devices were tested and compared: AliveCor, Watch BP, MyDiagnostick and Fibricheck. RESULTS: AF was present in 34 subjects (9.47%). The aptamer array revealed 41 proteins with differential expression in AF individuals. TIMP-2 and ST-2 were the most promising candidates in the verification analysis, but none of them was further validated. NT-proBNP (log-transformed) (OR = 1.934; p<0.001) was the only independent biomarker to detect AF in the whole cohort. Compared to an ECG, WatchBP had the highest sensitivity (84.6%) and AUC (0.895 [0.780-1]), while MyDiagnostick showed the highest specificity (97.10%). CONCLUSION: The inclusion and monitoring of a cohort of primary care patients for AF detection, together with the testing of biomarkers and screening devices provided useful lessons about AF screening in our community. An AF screening strategy using rhythm detection devices and short monitoring periods among high-risk patients with high NT-proBNP levels could be feasible.