Daily Cardiology Research Analysis
A first-in-human study shows high-voltage pulsed field ablation efficiently creates transmural lesions for scar-related ventricular tachycardia with high acute success. A large, multinational analysis finds SCORE2 risk charts overestimate cardiovascular risk and broaden treatment eligibility compared with the unrounded online calculator. A meta-analysis of RCTs suggests clopidogrel monotherapy after DAPT post-PCI lowers stroke and MI versus aspirin without increasing bleeding or mortality.
Summary
A first-in-human study shows high-voltage pulsed field ablation efficiently creates transmural lesions for scar-related ventricular tachycardia with high acute success. A large, multinational analysis finds SCORE2 risk charts overestimate cardiovascular risk and broaden treatment eligibility compared with the unrounded online calculator. A meta-analysis of RCTs suggests clopidogrel monotherapy after DAPT post-PCI lowers stroke and MI versus aspirin without increasing bleeding or mortality.
Research Themes
- Nonthermal pulsed field ablation for ventricular tachycardia
- Cardiovascular risk assessment calibration and implementation
- Post-PCI antiplatelet monotherapy optimization
Selected Articles
1. High-Voltage Focal Pulsed Field Ablation to Treat Scar-Related Ventricular Tachycardia: The First-in-Human
In a two-center, first-in-human series of 26 patients with scar-related VT, a high-voltage (>10 kV), short-duration, QRS-synchronized focal PFA catheter achieved 92% acute success with a median ablation time of 31 minutes and marked suppression of inducible clinical VT (88% to 6%). Epicardial-endocardial mapping in a sub-cohort supported transmural lesion formation.
Impact: Introduces a novel high-voltage PFA approach demonstrating efficient transmural lesion formation in thick, fibrotic ventricular scar, addressing a major unmet need in VT ablation.
Clinical Implications: If validated in larger trials, high-voltage focal PFA could offer a faster, safer, and more effective strategy for scar-related VT, potentially reducing thermal injury risks and procedural time.
Key Findings
- Acute procedural success was 92% (24/26 patients) with a median 21 lesions and 31 minutes of ablation time.
- Inducible clinical VT decreased from 88% pre-ablation (14/16) to 6% post-ablation (1/16; p<0.001).
- QRS-synchronized, >10 kV monophasic pulses with short durations produced transmural ventricular lesions confirmed by epi-endo mapping in a sub-cohort.
Methodological Strengths
- Prospective first-in-human multicenter design with standardized high-voltage PFA protocol
- Epi-endo high-density voltage mapping to assess transmurality; force-sensing catheter and impedance navigation for precision
Limitations
- Single-arm study with small sample size (n=26) and short follow-up (6 months)
- Incomplete reporting of long-term VT freedom and durability across all patients
Future Directions: Randomized comparisons with radiofrequency/cryoablation and dose-finding studies are needed to confirm efficacy, safety, lesion durability, and optimal pulse parameters.
BACKGROUND: Unlike the tremendous progress made in atrial fibrillation ablation, the greatest unmet clinical need is for innovative ablation treatments for scar-related ventricular tachycardia (VT) - particularly given the thick, often fibrotic tissue characteristic of the scarred substrate. A focal pulsed field ablation (PFA) catheter with a novel waveform was designed: high-voltage to provide tissue penetration, and low-energy (using short duration pulses) to avoid tissue overheating. We present the outcomes of METHODS: An investigational 8.5-French force-sensing PFA catheter was used for scar-VT ablation in ischemic or non-ischemic substrates. PF lesions consisted of 5 applications, each <200 msec, of a high-voltage (>10 kV) monophasic waveform with QRS-synchronization. The PFA catheter was localized by electrical impedance-based navigation. A sub-cohort of patients without prior cardiac surgery underwent epicardial ventricular mapping - at baseline and after endocardial PFA - to assess for transmurality of endocardial PF lesions. Study endpoints included procedural efficiency, safety and effectiveness to final follow-up of 6 months. RESULTS: At 2 centers, 26 patients underwent ablation: age 66 ± 9; 4% female; left ventricular ejection fraction 32 ± 10%; VT storm 42%; prior VT ablation 42%. Acute procedural success, achieved in 24 (92%) patients, required 21 [IQR 14-24] lesions per patient, with a transpired ablation time of 31 minutes [19-42]. The clinical VT was induced in 14 of 16 patients (88%) pre-ablation, and 1 of 16 patients (6%; p < 0.001) post-ablation. High-density epi-endo voltage mapping was performed in 10 patients [42%]; of the 9 patients undergoing CONCLUSIONS: In this first-in-human study, the high-voltage PFA catheter efficiently delivered transmural ventricular lesions to treat scar-related VT.
2. Using SCORE2 with a risk chart or online calculator: Impact on model performance, treatment eligibility and cardiovascular disease prevention.
Across nearly one million UK primary care individuals and an Eastern European cohort, SCORE2 risk charts overestimated 10-year risk and increased treatment eligibility compared to the unrounded online calculator. The online calculator modestly improved discrimination while maintaining acceptable calibration, translating to slightly more events prevented per 1000 treated in modeled scenarios.
Impact: Clarifies a practical implementation issue in European prevention guidelines, demonstrating that unrounded online estimation enhances discrimination and avoids overtreatment driven by risk chart rounding.
Clinical Implications: Clinicians and health systems should preferentially use the SCORE2 online calculator rather than paper charts to improve risk classification and more appropriately target preventive therapies.
Key Findings
- Risk charts yielded higher predicted risks than the online calculator in both low- and high/very-high-risk regions.
- Chart-based assessment increased treatment eligibility (6.3% vs 4.0% in low-risk; 51% vs 43% in high/very-high-risk regions).
- Online calculator improved discrimination (C-statistic +0.010 and +0.008) with adequate calibration for both methods.
- Modeled preventive impact favored the calculator (e.g., 53 vs 46 events prevented per 1000 treated in low-risk regions).
Methodological Strengths
- Very large, contemporary primary care dataset with external high-risk regional cohort
- Direct head-to-head comparison of chart rounding vs unrounded algorithm with discrimination, calibration, and eligibility impacts
Limitations
- Observational design with potential residual confounding and coding/misclassification in routine data
- Assumed relative risk reduction (50%) in prevention modeling may not generalize across populations
Future Directions: Prospective implementation studies testing calculator-first workflows, patient-level clinical outcomes, and health economic impacts across regions and health systems.
BACKGROUND: Current European Cardiovascular Disease (CVD) prevention guidelines recommend 10-year risk assessment using the SCORE2 model to identify individuals eligible for preventive treatment. Risk can be estimated using conventional risk charts or online calculators, though these methods may differ in precision and treatment classification. METHODS AND RESULTS: Individuals without established CVD or diabetes mellitus were included from CPRD (United Kingdom, Europe's low risk region, n=977,616) and HAPIEE (Czech Republic and Poland, high risk region and Lithuania, very high risk region, n=11,739). During median 8.4 years (IQR 5.0-10.4), 22,898 CVD events occurred. SCORE2 risk was estimated via two methods: an online calculator (unrounded SCORE2 algorithm) and risk charts from the 2021 ESC Prevention Guidelines. Predicted risks were higher with the risk charts than with the online calculator. In the low risk region, the median 10-year risk was 4.0% (IQR 2.0-6.0) with the risk charts versus 3.7% (IQR 2.3-5.8) with the calculator. In the high/very high-risk region, risk was 9.0% (IQR 5.0-15.0) and 8.4% (IQR 4.5-13.9), respectively. Chart-based risk assessment resulted in higher treatment eligibility (6.3% versus 4.0% in the low risk region; 51% versus 43% in high/very high risk region). Discrimination was higher with the online calculator: difference in C-statistic +0.010 (95%CI 0.008-0.012) in low risk region, +0.008 (95%CI 0.005-0.010) in high/very high risk region. Calibration was adequate for both approaches. Assuming a 50% relative risk reduction for preventive treatment, this corresponded to 53 vs. 46 events prevented per 1000 treated in the low-risk region and 80 vs. 74 in the high/very-high-risk region (calculator vs. risk charts). CONCLUSION: Risk assessment using SCORE2 risk charts yields too high predicted risks and too broad treatment eligibility. By avoiding rounding of risk factors, the online calculator shows better discrimination.
3. Efficacy of clopidogrel monotherapy versus aspirin monotherapy after percutaneous coronary intervention.
Across four RCTs including 19,554 post-PCI patients transitioning from DAPT, clopidogrel monotherapy reduced stroke (HR 0.69) and MI (HR 0.71) compared with aspirin without differences in all-cause or CV mortality, major bleeding, or stent thrombosis.
Impact: Synthesizes randomized evidence supporting clopidogrel as a preferable monotherapy option after DAPT, with potential to inform antiplatelet de-escalation strategies post-PCI.
Clinical Implications: For stable post-DAPT PCI patients, clopidogrel monotherapy may be favored over aspirin to lower ischemic events without added bleeding; implementation should consider genotype, adherence, and cost.
Key Findings
- Clopidogrel monotherapy lowered stroke risk vs aspirin (HR 0.69; 95% CI 0.51–0.94; I²=28%).
- Myocardial infarction risk was reduced with clopidogrel (HR 0.71; 95% CI 0.51–0.99; I²=48%).
- No significant differences in all-cause mortality, cardiovascular death, major bleeding, revascularization, or stent thrombosis.
Methodological Strengths
- Meta-analysis restricted to randomized controlled trials with large aggregated sample size
- Prespecified outcomes with random-effects modeling and heterogeneity assessment
Limitations
- Only four RCTs; moderate heterogeneity for some endpoints and lack of individual patient data
- Follow-up durations and DAPT durations varied across trials
Future Directions: Head-to-head trials stratified by CYP2C19 genotype and bleeding risk, plus cost-effectiveness analyses to guide personalized monotherapy selection.
Following percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is standard to reduce thrombotic complications. However, the optimal monotherapy after DAPT remains debated. Clopidogrel may offer better protection than aspirin. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing clopidogrel versus aspirin monotherapy after DAPT in PCI patients. Searches were performed in MEDLINE, Embase, Scopus, CENTRAL, and ClinicalTrials.gov up to April 12, 2025. Outcomes included stroke, myocardial infarction (MI), all-cause mortality, and cardiovascular (CV) death. Hazard ratios (HRs) were pooled using random-effects models. Four RCTs comprising 19,554 patients (clopidogrel: 9,846; aspirin: 9,708) were included. Clopidogrel was associated with a significantly lower risk of stroke (HR: 0.69; 95% CI: 0.51-0.94; p = 0.02; I² = 28%) and MI (HR: 0.71; 95% CI: 0.51-0.99; p = 0.05; I² = 48%) compared with aspirin. There was no significant difference between clopidogrel and aspirin in terms of all-cause mortality (HR: 0.99; 95% CI: 0.78-1.25; p = 0.92; I² = 55%), CV death (HR: 0.87; 95% CI: 0.70-1.08; p = 0.22; I² = 0%), coronary revascularization (HR: 0.95; 95% CI: 0.83-1.09; p = 0.44; I² = 0%), major bleeding (HR: 0.97; 95% CI: 0.70-1.35; p = 0.87; I² = 57%), or stent thrombosis (HR: 0.66; 95% CI: 0.38-1.15; p = 0.15; I² = 0%). Clopidogrel monotherapy post-DAPT after PCI reduces stroke and MI risk compared to aspirin, without increasing mortality or bleeding. These findings support clopidogrel as a favorable alternative for monotherapy.