Daily Cardiology Research Analysis
A stepped-wedge cluster-randomized trial across 12 Asian emergency departments validated the ESC 0/1-hour high-sensitivity troponin algorithm as safe while markedly increasing early discharge. Methodologically, a 5,158-patient TAVI cohort showed that modeling hs-cTnT as a continuous, time-dependent variable outperforms the dichotomous VARC-3 PPMI definition for prognostication. In primary prevention, a 375,544-participant UK Biobank study confirmed that ApoB better captures cardiovascular risk t
Summary
A stepped-wedge cluster-randomized trial across 12 Asian emergency departments validated the ESC 0/1-hour high-sensitivity troponin algorithm as safe while markedly increasing early discharge. Methodologically, a 5,158-patient TAVI cohort showed that modeling hs-cTnT as a continuous, time-dependent variable outperforms the dichotomous VARC-3 PPMI definition for prognostication. In primary prevention, a 375,544-participant UK Biobank study confirmed that ApoB better captures cardiovascular risk than LDL-C in discordant states, partially mediated by VLDL particles.
Research Themes
- Rapid ACS triage and implementation science
- Biomarker-driven prognosis in structural heart interventions
- Lipoprotein metrics and mechanisms for primary prevention
Selected Articles
1. Validation of the European Society of Cardiology 0/1-hour algorithm for chest pain triage in Asian emergency departments: a multinational stepped-wedge cluster-randomised trial.
In a 12-hospital, five-country stepped-wedge cluster randomized trial of 3,869 chest pain patients, the ESC 0/1-hour hs-cTnT algorithm was non-inferior for 30-day MACE vs usual care and significantly increased ED discharge rates (60% vs 35%). Low-risk classifications had extremely low event rates with no non-fatal MI, supporting broader implementation across Asian EDs.
Impact: This pragmatic, multinational cluster RCT delivers high-level evidence that a widely recommended hs-cTn rapid rule-in/rule-out algorithm is safe and operationally superior in Asian EDs, addressing a crucial implementation gap.
Clinical Implications: Adopting the ESC 0/1-hour hs-cTn algorithm can safely increase early ED discharges and reduce downstream testing for NSTE-ACS evaluation in diverse Asian settings. Hospitals should standardize hs-cTn pathways, lab turnaround, and clinician education to realize these benefits.
Key Findings
- 30-day MACE was 1.4% with the 0/1-hour pathway vs 1.7% with usual care, meeting non-inferiority (upper one-sided 95% CI −0.3%).
- ED discharge rate increased from 35% to 60% under the 0/1-hour algorithm (p<0.001).
- Among 941 low-risk patients, only 3 MACE events occurred (no non-fatal MI), indicating excellent safety of early discharge decisions.
Methodological Strengths
- Stepped-wedge cluster-randomized design across 12 hospitals enhances external validity and implementation relevance.
- Prospective protocolized hs-cTnT testing with prespecified non-inferiority margin ensures rigorous safety assessment.
Limitations
- Algorithm performance was evaluated with hs-cTnT and may not generalize to all hs-cTn assays.
- Short-term (30-day) outcomes were assessed; longer-term downstream effects were not captured.
Future Directions: Evaluate cost-effectiveness, patient-centered outcomes, and scalability to lower-resource EDs; assess performance with different hs-cTn assays and extended follow-up.
2. Time- and dose-dependent high-sensitivity cardiac troponin-T to improve outcome prediction after TAVI: a multicenter cohort study.
In 5,158 TAVI patients, the VARC-3 dichotomous PPMI definition did not predict 1-year mortality, whereas modeling hs-cTnT as a continuous, time-dependent variable showed clear prognostic gradients, with early post-procedural elevations carrying the highest short-term hazard. These results support abandoning binary thresholds in favor of dynamic risk models.
Impact: This study challenges a widely used endpoint (VARC-3 PPMI) and introduces a dynamic biomarker framework that more accurately stratifies risk after TAVI, with immediate implications for surveillance and intervention timing.
Clinical Implications: Replace binary PPMI cutoffs with continuous, time-aware hs-cTnT trajectories to identify high-risk patients early after TAVI, personalize monitoring intensity, and guide targeted interventions or imaging.
Key Findings
- In 5,158 TAVI patients, VARC-3-defined PPMI was not associated with 1-year all-cause mortality.
- Higher pre- and post-procedural hs-cTnT, modeled continuously, were linked to increased 1-year mortality risk.
- Royston–Parmar time-dependent models showed the greatest hazard early after the procedure for higher hs-cTnT values, declining over time.
Methodological Strengths
- Large multicenter cohort with contemporary TAVI practice and systematic hs-cTnT measurements.
- Advanced flexible parametric survival modeling addressing non-linearity and non-proportional hazards.
Limitations
- Observational design; potential for residual confounding.
- Generalizability beyond two tertiary centers requires external validation.
Future Directions: Prospective validation of hs-cTnT dynamic risk models; integration with imaging and clinical variables; assessment of interventional thresholds that trigger intensified surveillance or therapy.
3. Impact of LDL-C and Apolipoprotein B Level Discordance and associated Lipoprotein Particle Alterations on Cardiovascular Outcomes in a large primary prevention population.
Among 375,544 primary prevention participants, discordantly high ApoB versus LDL-C was associated with higher MACE risk and discordantly low ApoB with lower risk, independent of absolute lipid levels. NMR profiling showed increased VLDL burden in high-ApoB discordance, with VLDL particles and triglycerides mediating about one-quarter of the excess risk.
Impact: This very large cohort integrates NMR lipoprotein profiling to clarify mechanisms behind ApoB-LDL-C discordance, reinforcing ApoB as a primary risk metric and informing triglyceride/VLDL-targeted prevention strategies.
Clinical Implications: Routine ApoB measurement can refine risk stratification when LDL-C is misleading; consider intensifying therapy when ApoB is high despite modest LDL-C, and target triglyceride/VLDL biology (e.g., lifestyle, omega-3, fibrates, emerging agents).
Key Findings
- Discordantly high ApoB (vs LDL-C) was associated with increased MACE risk (HR 1.11; 95% CI 1.06–1.15), while discordantly low ApoB was protective (HR 0.87; 95% CI 0.83–0.93).
- NMR showed highest VLDL-C, VLDL-CE, and VLDL particle concentrations in high-ApoB discordance, but lower CE content per particle.
- Mediation analysis indicated VLDL particles and triglycerides mediated 25.5% and 26.6% of excess MACE risk, respectively.
Methodological Strengths
- Very large primary prevention cohort with harmonized NMR lipoprotein profiling.
- Robust multivariable Cox modeling and mediation analysis to probe mechanisms.
Limitations
- UK Biobank volunteer bias may limit generalizability.
- Observational design cannot establish causality; residual confounding possible.
Future Directions: Test whether ApoB-guided therapy improves outcomes versus LDL-C-guided care; evaluate agents specifically lowering ApoB and VLDL in discordant individuals.