Figure 3.
Exercise-induced cardiac biomarkers in four domains: present constraints and potential remedies. Clinical (no sport-specific cutoffs, 76–96% of athletes exceeding myocardial infarction thresholds, multi-marker strategies adding no value, absence of validated return-to-play algorithms); methodological/design (small sample sizes, short follow-up durations, lack of comparison with CMR gold standard); technical (non-standardized pre-analytical protocols, variability in EV and miRNA methods, requirement for invasive blood sampling); and individual diversity (high inter-individual variability, lack of re-regulation data, no personalized baseline reference values). Athlete-specific 99th percentiles, multifaceted ML models, AI-driven decision support, large multicenter cohorts with 5–10 year follow-up, direct biomarker comparison with CMR (T1 mapping and late gadolinium enhancement), MISEV-aligned guidelines, locked-in assays, and saliva-based POC testing (validated for cTnI, emerging for miRNAs) are some of the suggested solutions. Prevention-first personalized sports medicine, which integrates individual molecular profiles, individualized exercise prescriptions, personalized monitoring, and real-time feedback, is the ultimate long-term aim (with a ten-plus-year horizon). Without thorough prospective validation, all potential applications remain hypothetical (Hacker et al., 2023; Su and Chen, 2025; Zheng et al., 2025; Dinc and Ardic, 2026; Greco et al., 2026; Kasiak, 2026; Liu et al., 2026; Shen et al., 2026).
