Daily Cardiology Research Analysis
Three impactful cardiology studies advance arrhythmia prevention and management. A pooled participant-level analysis shows finerenone reduces new-onset atrial fibrillation across cardio-kidney-metabolic spectra, while a multicenter PFA study demonstrates favorable safety and one-year effectiveness for posterior wall plus pulmonary vein ablation in persistent AF. Proactive electroanatomical mapping with preventive ablation in repaired tetralogy of Fallot markedly lowers primary-prevention ICD can
Summary
Three impactful cardiology studies advance arrhythmia prevention and management. A pooled participant-level analysis shows finerenone reduces new-onset atrial fibrillation across cardio-kidney-metabolic spectra, while a multicenter PFA study demonstrates favorable safety and one-year effectiveness for posterior wall plus pulmonary vein ablation in persistent AF. Proactive electroanatomical mapping with preventive ablation in repaired tetralogy of Fallot markedly lowers primary-prevention ICD candidacy with excellent VT-free outcomes.
Research Themes
- AF prevention across cardio-kidney-metabolic disease
- Pulsed field ablation safety and efficacy in persistent AF
- Preventive substrate ablation to reduce ICD implantation in congenital heart disease
Selected Articles
1. Finerenone Reduces New-Onset Atrial Fibrillation Across the Spectrum of Cardio-Kidney-Metabolic Syndrome: The FINE-HEART Pooled Analysis.
In a prespecified participant-level pooled analysis of 14,581 patients across CKM conditions, finerenone reduced new-onset AF/AFL versus placebo (3.9% vs 4.7%; HR 0.83, 95% CI 0.71-0.97). Benefits were consistent across CKM burden; predictors of incident AF included age, HF history, BMI, region, and albuminuria.
Impact: This is the first robust participant-level pooled evidence that a nonsteroidal MRA reduces incident AF across diverse CKM phenotypes, linking antifibrotic/anti-inflammatory modulation to arrhythmia prevention.
Clinical Implications: Finerenone may be considered for AF prevention in CKM populations already meeting indications for MRA, potentially lowering arrhythmic risk alongside renal and HF benefits.
Key Findings
- Across 14,581 CKM patients without baseline AF/AFL, finerenone lowered incident AF/AFL vs placebo (3.9% vs 4.7%; HR 0.83, 95% CI 0.71-0.97; P=0.019).
- Effect was consistent across the spectrum of CKM conditions and independent of the number of CKM components.
- Predictors of incident AF/AFL included older age, HF history, higher BMI, geographic region, and higher urine albumin-to-creatinine ratio.
Methodological Strengths
- Prespecified participant-level pooled analysis across three large randomized trials
- Blinded clinical event adjudication and stratified Cox modeling by region and trial
Limitations
- AF/AFL was a secondary outcome across included trials
- Mechanistic biomarkers linking finerenone to AF reduction were not assessed
Future Directions: Prospective trials designed with AF prevention as a primary endpoint in CKM populations and mechanistic substudies (fibrosis, inflammation, atrial remodeling) are warranted.
BACKGROUND: Mineralocorticoid receptor antagonists (MRA) modulate cardiac and systemic pathways such as fibrosis and inflammation, which may contribute to the onset of atrial fibrillation (AF) or atrial flutter (AFL). OBJECTIVES: In this participant-level pooled analysis of 3 large clinical trials, the authors evaluated the effect of the nonsteroidal MRA finerenone on incident AF/AFL across the cardio-kidney-metabolic (CKM) spectrum. METHODS: In this prespecified analysis, we pooled participants from 2 trials of chronic kidney disease and type 2 diabetes (FIDELIO-DKD and FIGARO-DKD) and a trial of heart failure (HF) with mildly reduced or preserved ejection fraction (FINEARTS-HF). Patients were randomized 1:1 to finerenone or placebo. New-onset AF/AFL was prospectively adjudicated in all trials by blinded clinical event committees. The risk of new-onset AF/AFL was evaluated using Cox regression models stratified by region and trial. RESULTS: Among 14,581 patients who were free of AF/AFL at trial enrollment, 631 (4.3%) experienced new-onset AF/AFL during follow-up. Predictors of new-onset AF/AFL included older age, history of HF, higher body mass index, geographic region, and higher levels of urine albumin-to-creatinine ratio. During 2.9 years of median follow-up, new-onset AF/AFL occurred in 286 (3.9%) participants receiving finerenone and 345 (4.7%) assigned to placebo (HR: 0.83; 95% CI: 0.71-0.97; P = 0.019). Risk reductions were consistent irrespective of number of CKM conditions (P
2. Pulsed Field Ablation for Persistent Atrial Fibrillation: 1-Year Results of ADVANTAGE AF.
In 339 PerAF patients, PFA-guided PVI plus posterior wall ablation achieved 99.7% acute success with a 2.3% primary safety event rate and 63.5% one-year freedom from arrhythmia or escalation endpoints. Symptomatic AF freedom reached 85.3%, and no tamponade, stroke, PV stenosis, or atrioesophageal fistula occurred.
Impact: This large multicenter study demonstrates favorable one-year effectiveness and a reassuring safety profile of PFA for posterior wall plus PVI in persistent AF, informing broader adoption and trial designs.
Clinical Implications: PFA with PVI+posterior wall isolation is a viable option for PerAF with low acute complications and meaningful one-year rhythm control; operator experience may influence outcomes.
Key Findings
- Acute success for both PVI and posterior wall ablation was 99.7% in 339 patients.
- Primary safety endpoint occurred in 2.3% with no tamponade, stroke, PV stenosis, or atrioesophageal fistula.
- Primary one-year effectiveness (freedom from atrial arrhythmia/redo ablation/cardioversion/AAD escalation after blanking) was 63.5%; symptomatic AF freedom was 85.3%.
Methodological Strengths
- Prospective multicenter pivotal IDE design with predefined safety and effectiveness goals
- Systematic rhythm surveillance (Holter at 6/12 months and frequent transtelephonic monitoring)
Limitations
- Single-arm design without randomized comparator
- Effectiveness varied by operator experience, potentially limiting generalizability
Future Directions: Randomized trials comparing PFA strategies vs thermal ablation in PerAF, and optimization of posterior wall lesion sets and operator training standards.
BACKGROUND: Pulsed field ablation (PFA) has gained prominence for pulmonary vein isolation (PVI) to treat atrial fibrillation, but there are limited outcome data on PFA to treat persistent atrial fibrillation (PerAF). OBJECTIVES: This study sought to determine the safety and efficacy of PVI + posterior wall ablation (PWA) with PFA in PerAF. METHODS: ADVANTAGE AF (A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects with Persistent Atrial Fibrillation) is a prospective, single-arm, multicenter pivotal investigational device exemption study of PerAF patients undergoing PVI+PWA with the pentaspline PFA catheter. One-year follow-up included 24-hour Holter monitoring at 6 and 12 months and twice monthly and symptomatic transtelephonic monitoring. The primary safety endpoint was incidence of predefined adverse events. The primary effectiveness endpoint included acute success and postblanking 1-year freedom from atrial tachyarrhythmia recurrence (>30 seconds), redo ablation, cardioversion, or antiarrhythmic drug escalation. Endpoint analysis used Kaplan-Meier methodology with 97.5% 1-sided confidence limits compared with a 12% safety and 40% effectiveness goals, with 85% power. RESULTS: PFA in 339 patients (260 treatment and 79 roll-in) resulted in 99.7% success for both PVI and PWA. The primary safety endpoint was 2.3% (5.1% upper confidence limit), including 1 with pericarditis, 1 with myocardial infarction, and 4 with pulmonary edema; no tamponade, stroke, pulmonary vein stenosis, or esophageal fistula occurred. Primary effectiveness was 63.5% (57.3% lower confidence limit) at 1 year, with 8.5% patients having a single, isolated atrial fibrillation recurrence. Freedom from symptomatic atrial fibrillation was 85.3%; efficacy varied by operator experience. CONCLUSIONS: ADVANTAGE AF, the first large prospective study of PFA to treat PerAF using a strategy of PVI and posterior wall isolation, revealed favorable safety and effectiveness outcomes. (A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects with Persistent Atrial Fibrillation [ADVANTAGE AF]; NCT05443594).
3. Proactive Mapping and Preventive Ablation Reduce Defibrillator Implantation Rates in Tetralogy of Fallot.
Among 97 rTOF patients without prior VT, proactive electroanatomical mapping identified SCAI in 34% and inducible SCAI-dependent VT in 17/19. Preventive SCAI transection (87% success) reduced primary-prevention ICD candidacy to 11% versus 25–51% by guideline/risk score, with only 4% VT events (all after ablation failure) over a 58-month median follow-up.
Impact: This study challenges guideline-driven ICD implantation by demonstrating that substrate-directed preventive ablation can markedly downselect candidates while maintaining low VT event rates.
Clinical Implications: In rTOF without prior VT, proactive mapping with preventive SCAI ablation can be integrated into shared decision-making to avoid unnecessary ICDs, reserving devices for residual substrates or ventricular dysfunction.
Key Findings
- SCAI present in 33/97 (34%); inducible monomorphic VT in 19 (20%), 17 of which were SCAI-dependent.
- Preventive SCAI transection succeeded in 26/30 attempts (87%) without complications.
- ICD eligibility reduced to 11% after mapping/ablation vs 25–51% by contemporary risk tools; VT events occurred in 4% over 58 months, all after ablation failure.
Methodological Strengths
- Consecutive cohort with long median follow-up (58 months)
- Direct comparison of mapping-based selection versus multiple guideline-based risk methods
Limitations
- Nonrandomized design from a specialized center may limit generalizability
- Some ICD decisions involved shared decision-making, potentially introducing selection bias
Future Directions: Multicenter randomized or pragmatic studies comparing preventive ablation versus device-first strategies and validation of mapping-guided risk stratification.
BACKGROUND: In patients with repaired tetralogy of Fallot (rTOF) and spontaneous ventricular tachycardia (VT), transection of slow-conducting anatomical isthmus (SCAI) by ablation results in excellent long-term VT-free survival. In patients without prior VT, proactive electroanatomical mapping and preventive SCAI ablation may impact patient selection for primary prevention implantable cardioverter-defibrillator (ICD) implantation. OBJECTIVES: The purpose of this study was to evaluate long-term outcomes after proactive electroanatomical mapping and ablation of SCAI and its impact on patient selection for primary prevention ICD implantation, compared with current risk stratification methods in rTOF patients without prior VT. METHODS: Consecutive rTOF patients without prior VT who underwent electroanatomical mapping for VT substrate identification were included (2005-2020). After successful SCAI ablation, ICD implantation was offered but was subject to shared decision making. The potential eligibility for ICD implantation was retrospectively determined using the following: 1) a clinical risk score; 2) guideline-recommended risk factors (American Heart Association [AHA] 2018 guidelines without late gadolinium enhancement [LGE] on cardiac magnetic resonance [CMR] information, AHA 2018 guidelines with LGE-CMR information, European Society of Cardiology [ESC] 2022 guidelines); and 3) electroanatomical mapping and SCAI ablation results. In the latter, patients with a nontransected SCAI, VT substrates remote from anatomical isthmuses, or severe right-/left ventricular dysfunction qualified for ICDs. RESULTS: A total of 97 patients were included (age 35 ± 16 years, 57 men); 33 patients (34%) had SCAI and 19 (20%) had inducible monomorphic VT (17 of 19 SCAI-dependent VT). Successful SCAI transection was achieved in 87% (26 of 30 patients) in whom attempted, without complications. In total, 13 patients received an ICD implantation. During a median follow-up of 58 months (Q1-Q3: 30-99 months), 4 patients (4%) had VT, all after ablation failure. According to clinical risk score, AHA 2018 guidelines without LGE-CMR information, AHA 2018 guidelines with LGE-CMR information, and ESC 2022 guidelines, 49 (51%), 24 (25%), 31 (32%), and 48 patients (49%) would have qualified for ICDs, respectively. After proactive mapping and preventive ablation, 11 patients (11%) remained ICD candidates, including all 4 with a VT event during the follow-up (annual VT risk 7%/y). CONCLUSIONS: Long-term outcome of rTOF patients without SCAI is excellent. Proactive electroanatomical mapping and preventive SCAI ablation may significantly reduce primary prevention ICD implantation rates compared with current risk prediction methods.