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.
IMPORTANCE: The incidence and burden of new-onset atrial fibrillation (AF) after coronary artery bypass grafting (CABG) are not known. Nevertheless, North American guidelines state that it is reasonable to administer 60 days of oral anticoagulation to patients with new-onset AF after CABG, a moderate-strength recommendation (class 2a) based on evidence derived from nonrandomized clinical studies. OBJECTIVE: To test the hypothesis that the incidence of new-onset AF within the first year after CABG is higher than suggested in the current literature and to assess AF burden. DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter cohort study in 2 academic cardiac surgery centers in Germany that involved 198 patients with 3-vessel coronary artery disease or left main disease and no history of arrhythmias who received an insertable cardiac monitor during CABG for long-term continuous electrocardiographic monitoring. Patients were enrolled from November 2019 through November 2023 and were followed up for 1 year. EXPOSURES: Atrial fibrillation detected within a year of continuous monitoring using insertable cardiac monitors implanted during CABG. MAIN OUTCOMES AND MEASURES: Cumulative incidence of new-onset AF within a year of surgery. Secondary outcomes were AF burden and clinical outcomes. RESULTS: A total of 1217 patients were assessed, and 1008 were excluded. Of the 198 patients enrolled (173 male [87.4%]; 25 female [12.6%]; mean age, 66 [SD, 9] years), 95 patients developed new-onset AF within the first year after CABG (cumulative incidence, 48%; 95% CI, 41%-55%). The median AF burden during the first year was 0.07% (IQR, 0.02%-0.23%) or 370 minutes. The median AF burden on days 1 through 7 was 3.65% (IQR, 0.95%-9.09%); on days 8 through 30, 0.04% (IQR, 0%-1.21%); and on days 31 through 365, 0% (IQR, 0%-0.0003%), corresponding to 368, 13, and 0 minutes, respectively. After discharge, 3 patients had an AF episode longer than 24 hours. CONCLUSIONS AND RELEVANCE: Although the incidence of new-onset AF after CABG in this study was higher than previously reported, the AF burden in these patients was very low, especially after 30 days. The very low AF burden questions the current guideline recommendations that long-term oral anticoagulation should be considered in patients with new-onset AF after CABG.
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.
Lactylation, a post-translational modification derived from glycolysis, plays a pivotal role in ischemic heart diseases. Neutrophils are predominantly glycolytic cells that trigger intensive inflammation of myocardial ischemia reperfusion (MI/R). However, whether lactylation regulates neutrophil function during MI/R remains unknown. Employing lactyl proteomics analysis, S100a9 was lactylated at lysine 26 (S100a9K26la) in neutrophils, with elevated levels observed in both acute myocardial infarction (AMI) patients and MI/R model mice. S100a9K26la was demonstrated driving the development of MI/R using mutant knock-in mice. Mechanistically, lactylated S100a9 translocated to the nucleus of neutrophils, where it binded to the promoters of migration-related genes, thereby enhancing their transcription as a co-activator and promoting neutrophil migration and cardiac recruitment. Additionally, lactylated S100a9 was released during NETosis, leading to cardiomyocyte death by disrupting mitochondrial function. The enzyme dihydrolipoyllysine-residue acetyltransferase (DLAT) was identified as the lactyltransferase facilitating neutrophil S100a9K26la post-MI/R, a process that could be restrained by α-lipoic acid. Consistently, targeting DLAT/S100a9K26la axis suppressed neutrophil burden and improved cardiac function post-MI/R. In patients with AMI, elevated S100a9K26la levels in plasma were positively correlated with cardiac death. These findings highlight S100a9 lactylation as a potential therapeutic target for MI/R and as a promising biomarker for evaluating poor prognosis of MI/R.
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.
BACKGROUND: Rapidly accelerated fibrosarcoma B-type (BRAF) and MEK inhibitors have revolutionized outcomes for patients with BRAF-mutated melanoma. However, they are associated with cardiovascular adverse effects. The real-world incidence and risk factors for these effects are poorly described. OBJECTIVES: The aim of this study was to characterize the incidence and risk factors for BRAF inhibitor- and MEK inhibitor-associated hypertension and cancer therapy-related cardiac dysfunction (CTRCD) in a real-world setting. METHODS: A prospective, longitudinal, cohort study was undertaken among patients with melanoma treated with BRAF and MEK inhibitors in a regional cancer network (March 2021 to March 2023). Baseline cardiotoxicity risk stratification was assessed using the European Society of Cardiology cardio-oncology guideline-recommended tool. Comprehensive cardiovascular assessment was performed at baseline and at 4, 12, and 24 weeks, including home and clinic blood pressure, echocardiography, stress perfusion cardiovascular magnetic resonance imaging and blood biomarkers. CTRCD was defined using International Cardio-Oncology Society definitions. RESULTS: A total of 61 participants were enrolled. Twenty-eight participants (45.9%) developed hypertension and 45.9% developed CTRCD: 24 (85.7%) mild, 3 (10.7%) moderate, and 1 (3.6%) severe. All moderate or severe CTRCD was evident by 4 weeks and at least partially reversible. No patient at low baseline risk developed moderate or severe CTRCD. Patients with CTRCD had higher median baseline N-terminal pro-B-type natriuretic peptide compared with those without (109 pg/mL [Q1-Q3: 51-380 pg/mL] vs 54 pg/mL [Q1-Q3: 29-149 pg/mL]; P = 0.047). There were no robust associations between hypertension nor cardiovascular magnetic resonance imaging-derived myocardial or perfusion characteristics and incident CTRCD. CONCLUSIONS: BRAF inhibitor- and MEK inhibitor-associated hypertension and CTRCD are common. The present results reinforce the utility of baseline cardiotoxicity risk stratification, including assessment of N-terminal pro-B-type natriuretic peptide. Future guidelines should consider recommending early surveillance echocardiography for higher risk patients.