Daily Cardiology Research Analysis
Analyzed 196 papers and selected 3 impactful papers.
Summary
A multicenter randomized trial (PRO-TAVI) found that deferring PCI in TAVI candidates with coronary disease was non-inferior to routine pre-TAVI PCI at 1 year, potentially shifting revascularization strategy. An integrative preclinical–clinical study showed GLP-1 receptor agonists reduce atherosclerosis progression and inflammatory biomarkers, with clinical benefits independent of hyperglycemia or obesity. In cardio-oncology, clonal hematopoiesis markedly increased trastuzumab-related cardiotoxicity risk, supported by a complementary Tet2-deficient mouse model.
Research Themes
- Optimizing coronary revascularization strategy around TAVI
- Anti-inflammatory and anti-atherosclerotic mechanisms of GLP-1 receptor agonists beyond glycemic control
- Genomic risk stratification for cardiotoxicity in cardio-oncology (clonal hematopoiesis)
Selected Articles
1. Deferral of percutaneous coronary intervention in patients undergoing transcatheter aortic valve implantation (PRO-TAVI): an investigator-initiated, multicentre, open-label, non-inferiority, randomised controlled trial.
In 466 TAVI candidates with coronary artery disease, deferring PCI was non-inferior to routine pre-TAVI PCI for a 1-year composite of death, MI, stroke, or major bleeding. The hazard ratio was 0.89 with a non-inferiority p value of 0.0008, suggesting an initial conservative approach may be appropriate in selected patients.
Impact: This pragmatic multicenter RCT challenges the routine practice of pre-TAVI PCI, offering high-level evidence to support a conservative, anatomy-guided approach without compromising 1-year outcomes.
Clinical Implications: For TAVI candidates with stable coronary disease, routine PCI before TAVI may be avoided in favor of deferral with individualized decision-making, potentially reducing procedural complexity and bleeding risk without worsening major outcomes.
Key Findings
- Deferral of PCI was non-inferior to pre-TAVI PCI for the 1-year composite endpoint (24% vs 26%; HR 0.89; non-inferiority p=0.0008).
- Randomization was stratified by proximal LAD disease; median age 81 years, reflecting real-world TAVI demographics.
- Results support initial conservative management with tailored revascularization decisions.
Methodological Strengths
- Multicenter randomized controlled non-inferiority design with prespecified margin
- Intention-to-treat analysis with clinically meaningful composite endpoint
Limitations
- Open-label design may introduce performance bias
- Follow-up limited to 1 year; long-term ischemic risk remains to be clarified
Future Directions: Longer-term follow-up and subgroup analyses (e.g., high-risk anatomy, fractional flow reserve-guided strategies) could refine selection criteria for deferral.
BACKGROUND: Coronary artery disease is common in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to assess whether deferral of percutaneous coronary intervention (PCI) is non-inferior to routine PCI before TAVI in patients with coronary artery disease. METHODS: In this investigator-initiated, open-label, randomised controlled trial, done at 12 hospitals in the Netherlands, TAVI patients with coronary artery disease were randomly assigned in a 1:1 ratio to deferral of PCI or PCI before TAVI. Randomisation was done by use of a web-based system with random block sizes of 2 and 4, and stratification by presence of coronary artery disease involving proximal left anterior descending artery. The primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, and major bleeding at 1 year. Non-inferiority testing was done in the intention-to-treat population against the prespecified margin of 11 percentage points. The study is registered with ClinicalTrials.gov (NCT05078619) and long-term follow-up is ongoing. FINDINGS: Between Oct 7, 2021, and Nov 19, 2024, 466 patients were enrolled: 233 were assigned to deferral of PCI and 233 to PCI before TAVI. Median age was 81 years (IQR 78-84), and 166 (36%) of 466 patients were female. The primary endpoint occurred in 56 (24%) of 233 patients in the deferral group as compared with 60 (26%) of 233 patients in the PCI group (rate difference -1·7% [95% CI -9·5 to 6·2]; hazard ratio 0·89 [95% CI 0·62-1·28]; p=0·0008 for non-inferiority; p=0·68 for superiority). INTERPRETATION: In patients with coronary artery disease undergoing TAVI, deferral of PCI was non-inferior to PCI before TAVI for the 1-year composite of all-cause mortality, myocardial infarction, stroke, and major bleeding. These findings suggest that an initial conservative strategy can be appropriate in selected patients, although patient-tailored treatment decisions remain essential. FUNDING: ZonMw.
2. Clonal Hematopoiesis and Risk of Trastuzumab-Related Cardiotoxic Effects.
Across UK Biobank and SNUH cohorts, CHIP positivity nearly doubled the risk of trastuzumab-related cardiotoxicity by ESC criteria (adjusted sHR 1.91). In Tet2-deficient bone marrow chimeric mice, trastuzumab led to a significant LVEF decline, supporting a causal link between CHIP-related inflammation and cardiotoxicity.
Impact: This study bridges human genomics and mechanistic validation to identify CHIP as a high-risk feature for cardiotoxicity, enabling potential pre-treatment risk stratification in HER2+ breast cancer.
Clinical Implications: Screening for CHIP (e.g., via peripheral blood sequencing) could inform cardioprotective strategies and surveillance intensity during trastuzumab therapy, especially in patients with additional risk factors or prior anthracycline exposure.
Key Findings
- CHIP positivity (VAF ≥1.0%) was associated with higher 2-year trastuzumab cardiotoxicity by ESC, Canadian, and CREC criteria (e.g., ESC adjusted sHR 1.91; 95% CI 1.32-2.76).
- Tet2-deficient chimeric mice displayed a significant LVEF reduction after trastuzumab (effect size −4.2%; P=0.03), while controls did not.
- Competing-risk and multivariable models adjusted for age, CV risk factors, and anthracyclines supported robustness.
Methodological Strengths
- Large-scale population cohort with external validation in a tertiary cohort
- Mechanistic corroboration using Tet2-deficient mouse model
Limitations
- Observational design susceptible to residual confounding
- Heterogeneity in cardiotoxicity definitions and treatment exposures across cohorts
Future Directions: Prospective studies integrating CHIP screening to tailor cardioprotection and therapy choices; explore CHIP clone-specific risks and interventional modulation.
IMPORTANCE: Clonal hematopoiesis of indeterminate potential (CHIP) is linked to an increased incidence of cardiovascular and malignant diseases. OBJECTIVE: To determine whether CHIP is associated with cardiotoxic effects in patients with breast cancer receiving trastuzumab. DESIGN, SETTING, AND PARTICIPANTS: Analyses of human cohorts with complementary animal experimentation were performed using a nationwide population-based cohort (UK Biobank), 1 tertiary referral center (Seoul National University Hospital [SNUH]), and a controlled laboratory setting. UK Biobank participants were enrolled between 2006 and 2010, and SNUH patients were enrolled from January 2004 to March 2024. Data were analyzed from March 2021 to February 2026. MAIN OUTCOME MEASURES: Incident heart failure (HF) in the UK Biobank cohort and trastuzumab-related cardiotoxic effects in the SNUH cohort were the main outcome measures. Trastuzumab-related cardiotoxic effects were defined using established clinical criteria (European Society of Cardiology [ESC], Canadian Trastuzumab Working Group, and Cardiac Review and Evaluation Committee [CREC]). Fine-Gray competing risk models were used to account for death and myocardial infarction; multivariable models were adjusted for age and cardiovascular risk factors in both cohorts, with additional adjustment for anthracycline use in the SNUH cohort. Changes in left ventricular ejection fraction (LVEF) were assessed in Tet2-deficient bone marrow chimeric mice following trastuzumab exposure. RESULTS: Overall, 15 729 patients with breast cancer from the UK Biobank cohort (mean [SD] age, 58.8 [7.3] years; 107 [0.68%] male) and 454 female patients with breast cancer who received trastuzumab from the SNUH cohort (mean [SD] age, 52.0 [9.6] years) were included. The corresponding 2-year cumulative incidence values for trastuzumab-related cardiotoxic effects were 15.7% vs 5.0% by ESC criteria (Gray test P = .001), 19.9% vs 10.8% by Canadian criteria (P = .01), and 20.9% vs 11.3% by CREC criteria (P = .02). Using the ESC definition, CHIP positivity (variant allele frequency ≥1.0%) was associated with cardiotoxic effects in multivariable competing risk analysis (adjusted subdistribution hazard ratio, 1.91; 95% CI, 1.32-2.76). Tet2-deficient mice demonstrated a significant LVEF reduction following trastuzumab treatment (effect size, -4.2%; 95% CI, -7.91 to -0.49; P = .03); other experimental groups showed no significant change. CONCLUSIONS AND RELEVANCE: In this cohort study, the presence of CHIP was associated with increased susceptibility to trastuzumab-related cardiotoxic effects.
3. Glucagon-like peptide-1 receptor agonists reduce experimental atherosclerosis progression, inflammatory biomarkers and cardiovascular events, irrespective of hyperglycaemia and obesity.
In normoglycemic, non-obese rabbits, liraglutide reduced percent atheroma volume (−7.8%) and plaque cathepsin activity, macrophage content, and plasma CRP. In a 47,324-participant biobank, GLP-1 RA prescriptions were associated with lower inflammatory biomarkers and reduced MACE, independent of BMI or HbA1c levels, with mediation by inflammatory markers.
Impact: By integrating advanced in vivo imaging, histology, in vitro macrophage assays, and large-scale human data, this study provides mechanistic evidence that GLP-1 RAs confer anti-atherosclerotic and anti-inflammatory benefits beyond glycemic or weight effects.
Clinical Implications: Supports expanding GLP-1 RA use for cardiovascular risk reduction irrespective of diabetes/obesity, and motivates inflammation-targeted patient selection and endpoint design in future trials.
Key Findings
- Liraglutide inhibited atherosclerosis progression in rabbits (IVUS Δ percent atheroma volume: −7.8%, 95% CI −11.3 to −4.2; P<0.001).
- NIRF-OCT demonstrated reduced plaque cathepsin activity (−9.8 nM; P=0.028) and histology showed lower cathepsin S and macrophage content.
- In 47,324 biobank participants, GLP-1 RA prescriptions associated with lower inflammatory biomarkers and fewer MACE, independent of BMI/HbA1c; mediation analysis implicated inflammation.
Methodological Strengths
- Multimodal translational design (IVUS/NIRF-OCT, histology, in vitro, large biobank with PSM and mediation)
- Consistent effects across glycemic and obesity strata
Limitations
- Observational prescription data subject to confounding by indication despite PSM
- Rabbit model and short treatment duration may not fully generalize to humans
Future Directions: Randomized trials powered for inflammatory endpoints and plaque biology, and mechanistic work on cathepsin modulation in humans.
BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular events. However, their impact on atherosclerosis and inflammation, regardless of diabetes or obesity, is unknown. Here, GLP-1 RA effects were investigated on (i) atherosclerosis burden and inflammation in vivo in rabbits and (ii) inflammatory biomarkers and major adverse cardiovascular events (MACE) in clinical subjects, adjusted for glycaemic and obesity status. METHODS: Rabbits with atherosclerosis received liraglutide (0.1 mg/kg/day) or saline for 4 weeks. Serial intravascular ultrasound (IVUS) and near-infrared fluorescence-optical coherence tomography (NIRF-OCT) assessed plaque burden and cathepsin activity. Histological, plasma, and in vitro analyses assessed GLP-1 RA effects on atheroinflammation. A clinical study of 47,324 participants from the Mass General Brigham Biobank evaluated the association between GLP-1 RA prescription and inflammatory biomarkers [lymphocyte-based ratios and C-reactive protein (CRP)], and MACE. Analyses included multivariable regression, propensity score matching (PSM), and mediation analysis. RESULTS: In 28 normoglycaemic, non-obese rabbits, liraglutide significantly inhibited atherosclerosis progression compared with controls [IVUS Δ percent atheroma volume: -7.8%, 95% confidence interval (CI) -11.3 to -4.2; P < .001], and reduced NIRF-OCT plaque cathepsin activity (-9.8 nM, 95% CI -18.5 to -1.1; P = .028). Liraglutide further reduced plaque cathepsin S, macrophage content, and plasma CRP levels. In vitro, multiple GLP-1 RAs suppressed cathepsin activity and inflammatory mediators in macrophages. In biobank patients, GLP-1 RA prescription associated with significantly lower levels of inflammatory biomarkers and MACE in regression and PSM analyses, with benefits persisting in subgroups stratified by body mass index or glycated haemoglobin. Mediation analysis showed inflammatory biomarkers partly contributed to this effect. CONCLUSIONS: This integrative preclinical-clinical study demonstrates that GLP-1 RAs reduce atherosclerosis progression, inflammatory biomarkers and MACE, irrespective of hyperglycaemia or obesity.