Key result
Elevated miR-145-5p linked to ~4.3-fold higher odds of symptoms in Brugada syndrome.
Why the study?
Risk stratification for sudden cardiac death in Brugada syndrome remains challenging and contemporary models show modest predictive value, leading researchers to assess peripheral blood micro-RNAs as candidate biomarkers.
Does leucocyte-derived miRNA profiling identify distinct biomarker signatures that predict symptom status and arrhythmogenic risk in patients with Brugada syndrome?
Case-Control (n=51)
No
Does leucocyte-derived miRNA profiling identify distinct biomarker signatures that predict symptom status and arrhythmogenic risk in patients with Brugada syndrome?
Odds Ratio: 4.3 (95% CI 1.1–16.8)
p-value: p=0.04
Leucocyte-derived miRNAs, particularly miR-145-5p and miR-585-3p, provide a novel, non-invasive biomarker strategy capable of accurately discriminating symptomatic from asymptomatic patients with Brugada syndrome.
May support miRNA profiling for symptom stratification in Brugada syndrome; hypothesis-generating and requires prospective validation.
AIMS: Risk stratification for sudden cardiac death in patients with Brugada syndrome remains a major challenge. Contemporary risk prediction models have only modest predictive value. The aim of this study was to assess the role of micro-RNAs from peripheral blood as candidate biomarkers in Brugada syndrome. METHODS AND RESULTS: In this prospective study, Brugada patients and unaffected control individuals were enrolled for analysis of leucocyte-derived microRNAs (miRNAs) levels. Expression levels of 798 different circulating miRNAs were analysed on the NanoString® nCounter platform. All results were cross-validated by using a quantitative polymerase chain reaction. Micro-RNA expression levels of Brugada patients were compared with clinical data. A total of 21 definite Brugada patients (38% with a history of ventricular arrhythmia or cardiac arrest) and 30 unaffected control individuals were included in the study. Micro-RNA analysis showed a distinct expression profile in Brugada patients with 42 differentially expressed markers (38 up-regulated, 4 down-regulated miRNAs). The symptom status of Brugada patients was associated with a distinct miRNA signature. Micro-RNAs 145-5p and 585-3p were significantly up-regulated in symptomatic Brugada patients (P = 0.04). Incorporating miRNAs 145-5p and 585-3p into a multivariable model demonstrated significantly increased symptom prediction (area under the curve = 0.96; 95% confidence interval: 0.88-1.00). CONCLUSION: Brugada patients display a distinct miRNA expression profile compared with unaffected control individuals. There is also evidence that certain miRNAs (miR-145-5p and miR-585-3p) are associated with the symptom status of Brugada patients. The results suggest the principal utility of leucocyte-derived miRNAs as prognostic biomarkers for Brugada syndrome.
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Steinberg et al. (2023) conducted a case-control in Brugada syndrome (n=51). Brugada syndrome and symptomatic status vs. Unaffected control individuals and asymptomatic Brugada patients was evaluated on Symptomatic status (associated with miR-145-5p expression) (OR 4.3, 95% CI 1.1-16.8, p=0.04). In Brugada syndrome patients, elevated leucocyte-derived expression of miR-145-5p was associated with a 4.3-fold increased odds of being symptomatic, which combined with miR-585-3p yielded an AUC of 0.96 for symptom prediction.
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