Daily Cardiology Research Analysis
Prospective continuous monitoring after coronary artery bypass grafting revealed a much higher incidence but extremely low long-term burden of new-onset atrial fibrillation, challenging routine prolonged anticoagulation. Mechanistic work uncovered neutrophil S100a9 lactylation as a driver of myocardial ischemia/reperfusion injury and a DLAT-dependent, druggable axis. A prospective cardio-oncology study characterized the high early incidence of cancer therapy–related cardiac dysfunction with BRAF
Summary
Prospective continuous monitoring after coronary artery bypass grafting revealed a much higher incidence but extremely low long-term burden of new-onset atrial fibrillation, challenging routine prolonged anticoagulation. Mechanistic work uncovered neutrophil S100a9 lactylation as a driver of myocardial ischemia/reperfusion injury and a DLAT-dependent, druggable axis. A prospective cardio-oncology study characterized the high early incidence of cancer therapy–related cardiac dysfunction with BRAF/MEK inhibitors and identified simple baseline markers to guide surveillance.
Research Themes
- Postoperative atrial fibrillation incidence versus burden and anticoagulation strategy after CABG
- Immunometabolic lactylation mechanisms driving myocardial ischemia/reperfusion injury
- Prospective cardio-oncology surveillance for BRAF/MEK inhibitor–associated cardiotoxicity
Selected Articles
1. Long-Term Continuous Monitoring of New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting.
In a prospective cohort with insertable cardiac monitors implanted at CABG, 48% developed new-onset AF within 1 year, but the median AF burden was only 0.07% and essentially zero beyond 30 days. Only three patients had AF episodes longer than 24 hours after discharge. These data challenge routine prolonged anticoagulation solely for postoperative AF in CABG patients.
Impact: This study provides high-quality, continuous-monitoring evidence that postoperative AF is common but fleeting, directly informing anticoagulation decisions after CABG. It addresses a guideline area based largely on nonrandomized evidence.
Clinical Implications: Consider prioritizing short-term monitoring and individualized stroke risk assessment rather than routine 60-day anticoagulation for all new-onset AF after CABG. Shared decision-making should weigh extremely low AF burden beyond 30 days against bleeding risk.
Key Findings
- One-year cumulative incidence of new-onset AF after CABG was 48% (95% CI 41–55%).
- Median AF burden over 1 year was 0.07% (370 minutes), with 3.65% burden in days 1–7, 0.04% in days 8–30, and 0% in days 31–365.
- Only 3 patients experienced AF episodes longer than 24 hours after discharge.
Methodological Strengths
- Prospective multicenter design with continuous insertable cardiac monitor surveillance
- Clearly defined outcomes with 1-year follow-up and time-resolved AF burden analysis
Limitations
- Modest sample size and two-center design may limit generalizability
- Not powered to adjudicate thromboembolic events or net clinical benefit of anticoagulation
Future Directions: Trials that randomize anticoagulation duration based on AF burden thresholds after CABG are warranted. Integration of continuous monitoring with stroke risk stratification could refine post-CABG AF management.
2. S100a9 lactylation triggers neutrophil trafficking and cardiac inflammation in myocardial ischemia/reperfusion injury.
Using lactyl-proteomics and knock-in mice, the authors show that neutrophil S100a9 K26 lactylation drives migration, cardiac recruitment, and NETosis-mediated cardiomyocyte injury after MI/R. DLAT functions as the lactyltransferase, and α-lipoic acid attenuates this modification, reducing neutrophil burden and improving cardiac function. Plasma S100a9K26la correlates with cardiac death in AMI, nominating a mechanistic target and biomarker.
Impact: This study reveals a previously unrecognized lactylation-dependent program connecting neutrophil metabolism to post-MI inflammation with clear translational levers (DLAT/α-lipoic acid). It advances mechanistic understanding and proposes actionable biomarkers/targets.
Clinical Implications: S100a9K26 lactylation may serve as a prognostic biomarker in AMI and a targetable pathway to reduce MI/R injury. Repurposing α-lipoic acid or developing DLAT/S100a9 pathway inhibitors could complement reperfusion strategies by limiting neutrophil-driven damage.
Key Findings
- Neutrophil S100a9 is lactylated at K26 in AMI patients and MI/R mice; knock-in models show causality in MI/R progression.
- Lactylated S100a9 translocates to the nucleus, co-activating migration gene promoters and enhancing neutrophil trafficking and recruitment.
- DLAT acts as the lactyltransferase for S100a9K26la; α-lipoic acid restrains this modification, reducing neutrophil burden and improving cardiac function.
- Plasma S100a9K26la levels correlate positively with cardiac death in AMI patients.
Methodological Strengths
- Integrated lactyl-proteomics, gene-edited knock-in mice, and human patient correlates
- Mechanistic dissection including nuclear translocation, promoter binding, and identification of the responsible lactyltransferase
Limitations
- Translational efficacy of targeting DLAT/S100a9 axis not yet tested in humans
- Sample sizes for human correlates and long-term outcomes are not fully detailed
Future Directions: First-in-human studies of α-lipoic acid or selective DLAT/S100a9 inhibitors to reduce MI/R injury; validation of plasma S100a9K26la as a prognostic biomarker and companion diagnostic.
3. Prospective Evaluation of the Cardiovascular Effects of BRAF and MEK Inhibitors in Patients With Melanoma.
In a prospective cohort of melanoma patients on BRAF/MEK inhibitors, hypertension and CTRCD each occurred in 45.9%; moderate-to-severe CTRCD manifested by 4 weeks and was at least partially reversible. No moderate/severe CTRCD occurred in patients deemed low risk at baseline, and higher baseline NT-proBNP predicted CTRCD.
Impact: This study provides real-world, time-resolved incidence and predictors of cardiotoxicity under BRAF/MEK inhibitors with multimodality imaging, informing surveillance timing and risk stratification.
Clinical Implications: Implement early echocardiographic surveillance (by 4 weeks) in patients at higher baseline cardiotoxicity risk and consider NT-proBNP to refine risk assessment. Many CTRCD cases are mild and partially reversible, supporting continued therapy with close monitoring when appropriate.
Key Findings
- Incidence of hypertension and CTRCD were each 45.9% over 24 weeks of BRAF/MEK inhibitor therapy.
- All moderate/severe CTRCD occurred by 4 weeks and showed at least partial reversibility.
- No moderate/severe CTRCD occurred in patients classified as low baseline risk; higher baseline NT-proBNP predicted CTRCD.
Methodological Strengths
- Prospective longitudinal design with predefined cardio-oncology risk stratification
- Comprehensive multimodality assessment (home/clinic BP, echocardiography, stress perfusion CMR, biomarkers)
Limitations
- Modest sample size in a regional network limits precision and generalizability
- Observational design without randomized cardio-protective interventions
Future Directions: Randomized trials testing early surveillance strategies and cardioprotective interventions guided by baseline NT-proBNP and risk stratification in BRAF/MEK-treated patients.