Plasma trimethylamine levels predict adverse cardiovascular events in sudden cardiac arrest Survivors: A prospective cohort study.

BACKGROUND

The trimethylamine N-oxide (TMAO) pathway has been associated with multiple cardiovascular diseases, yet its prognostic value for sudden cardiac arrest (SCA) survivors remains unknown.

METHODS

Patients who survived SCA and received implantable cardioverter defibrillators (ICDs) were prospectively enrolled. We evaluated the associations between plasma concentrations of TMAO-related metabolites and long-term adverse clinical events, including recurrent lethal ventricular arrhythmia (VA).

RESULTS

A total of 75 SCA survivors were included in the study. During a median follow-up of 1099 days, 34 (45.3 %) patients experienced adverse clinical events, including 24 (32.2 %) with life-threatening VA, 12 (16.0 %) with heart failure rehospitalization, and 5 (6.7 %) with cardiovascular death. Trimethylamine (TMA), carnitine, choline, and creatinine showed strong correlations with clinically significant parameters such as left ventricular ejection fraction (LVEF), New York Heart Association functional class, and N-terminal pro-brain natriuretic peptide (NT-proBNP). These four metabolites demonstrated positive associations with adverse clinical events, with higher median level of TMA associated with more than a threefold increased risk after adjusting for age, sex, LVEF, kidney function, and NT-proBNP levels (hazard ratio = 3.36, 95 % confidence interval [CI]: 1.18-9.59; P = 0.024). A scoring system, VT-C3, incorporating LVEF, TMA, and the weighted sum of TMA-related metabolites (Choline, Carnitine, Creatinine), showed significant predictive capacity for both adverse events (area under the curve [AUC]: 0.75, 95 % CI: 0.64-0.85) and recurrent lethal VA (AUC: 0.73, 95 % CI: 0.62-0.84). No significant prognostic values were observed for TMAO and betaine.

CONCLUSIONS

Our findings suggest that plasma concentrations of TMA, choline, carnitine, and creatinine are associated with an increased risk of subsequent adverse clinical events among SCA survivors. A simple scoring system comprising LVEF and these biomarkers could enhance current risk stratification and improve secondary prevention strategies based on ICD implantation.