Wolfgang Dichtl

Background and Aims: Population aging is increasing the prevalence of atrial fibrillation (AF). In elderly patients with persistent AF, pulmonary vein isolation (PVI) has limited success, but is widely used. Pacemaker-implantation with atrioventricular-node ablation (PM+AVNA) provides effective symptom control, but the relative effects of PM+AVNA vs PVI on hospitalizations and other outcomes in the elderly remain unknown. Methods: This investigator-initiated, multicenter, open-label trial randomized patients aged ≥75 years with symptomatic persistent AF and normal left ventricular ejection fraction to PM+AVNA or PVI treatment strategies. The primary endpoint was a composite of hospitalization for atrial arrhythmia or heart failure, outpatient electrical cardioversion or upgrade to cardiac resynchronization therapy for left ventricular dysfunction. Secondary endpoints included all-cause death, stroke, treatment-related complications and quality of life. Results: Twelve centers in Germany and Austria randomized 196 patients (median age 81 years). At 12 months, a first primary endpoint event occurred in 24 of 98 patients (24%) assigned to PM+AVNA and 45 of 98 patients (46%) assigned to PVI (hazard ratio 0.45, 95% confidence interval 0.27 to 0.74; P = .002). A total of 29 and 84 primary endpoint events occurred respectively, consisting principally of arrhythmia-related hospitalizations and cardioversions in the PVI group (54 and 19 respectively, vs 3 and 1 in the PM+AVNA group) and of heart failure-related hospitalizations in the PM+AVNA group (23, vs 11 in PVI group). Mortality, stroke, treatment-related complications, and quality-of-life changes did not show between-group differences. Conclusions: In elderly patients with persistent AF, PM+AVNA was associated with fewer primary endpoint events than PVI over a 12-month follow-up period.

Background: Pacemakers enable continuous long-term surveillance of atrial fibrillation detected by implanted devices. Circulating biomarkers reflecting endothelial dysfunction, inflammation, and myocardial stress may help identify patients at risk for atrial fibrillation (AF) progression and higher arrhythmic burden. Methods: This analysis included patients from the prospective ACaSA study (NCT05127720) with a dual chamber pacemaker (Microport^® BOREA DR or TEO DR) and monitored weekly via remote monitoring technology (SMARTVIEW^®). Individuals with permanent AF or single-chamber systems were excluded. Baseline plasma concentrations of angiopoietin-2 (ANGPT2), growth differentiation factor-15 (GDF-15), fibroblast growth factor-23 (FGF-23), bone morphogenetic protein-10 (BMP10), and tumor necrosis factor–related apoptosis-inducing ligand receptor-2 (TRAIL-R2) were quantified using enzyme-linked immunosorbent assays. N-terminal pro-B-type natriuretic peptide (NT-proBNP) was measured using electrochemiluminescence immunoassay. Biomarkers were log₂-transformed, with values below assay detection limits imputed at half the lower limit of detection. Two endpoints were assessed following a 30-day blanking period: (1) progression to persistent AF, defined as ≥7 consecutive days with >99% daily AF burden, analyzed using Cox regression; and (2) AF burden, calculated as total AF time normalized to monitored days and categorized as 75%, analyzed using multinomial logistic regression. Multivariable models were adjusted for age, sex, heart failure, diabetes, and prior myocardial infarction; Cox models were limited to age, sex, and heart failure due to fewer events. Results: A total of 223 patients were included (median age 75 years; 37.2% women). During follow-up, 28 patients (13.3%) progressed to persistent AF. Higher baseline ANGPT2 was the strongest predictor of progression (HR per doubling 1.83, 95% CI 1.27–2.66, p = 0.001), followed by GDF-15 (HR 1.52, 95% CI 1.03–2.24, p = 0.036). In the burden analysis, ANGPT2 demonstrated a pronounced graded relationship with arrhythmic load, with markedly increased odds of high (>75%) AF burden (OR 8.31, 95% CI 2.63–26.26, p < 0.001). GDF-15 independently predicted both medium (OR 2.05, p = 0.025) and high burden (OR 2.32, p = 0.037). NT-proBNP displayed a borderline association with high burden (OR 2.02, p = 0.061). No significant associations were observed for FGF-23, BMP10, or TRAIL-R2. Conclusions: In continuously monitored pacemaker patients, ANGPT2 and GDF-15 emerged as key biomarkers associated with AF disease severity. ANGPT2 was strongly linked to both progression to persistent AF and high AF burden, whereas GDF-15 consistently predicted higher AF burden and also contributed to risk of progression. These findings highlight endothelial and inflammatory pathways as potential markers of atrial disease progression.

Atrial fibrillation (AF) is a growing unmet medical need. To reduce its impact on patients’ lives, improvements in stroke prevention therapy, treatment of concomitant conditions, and rhythm control therapy are actively developed: Innovations in anti-thrombotic agents, new anti-arrhythmic drugs (AADs), and novel interventional rhythm control therapies emerge alongside AF-reducing effects of general cardiometabolic therapies. Simple risk scores are slowly replaced by personalized AF risk estimation using quantifiable features. These developments were discussed by over 80 experts from academia and industry during the 10th Atrial Fibrillation NETwork /European Heart Rhythm Association consensus conference from 5 to 7 May 2025. The emerging consensus, described here, is multi-domain therapy combining stroke prevention, rhythm control, and therapy of concomitant cardiovascular conditions. This combines anti-coagulants, AADs, and AF ablation with old and new cardiometabolic drugs that can reduce AF risk, AF burden, and AF-related complications at scale. The paper furthermore describes quantitative traits that may enable a shift towards risk-driven therapy based on AF phenotypes. These can enable adjusted therapy strategies that are safe, accessible, and patient-centred. Applying modern data science and artificial intelligence methods to quantitative phenotypic and genetic features can further improve risk estimation and personalized therapy selection. At the same time, translational and clinical research into reversing the drivers of AF and into improved stroke prevention through new drugs and through combination therapies is needed. Together, these efforts offer pathways towards personalized, patient-centred, multi-modal, and accessible AF management that integrates rhythm control, stroke prevention, and therapy of concomitant conditions to bridge today’s practical needs with tomorrow’s therapeutic innovation.

Structured Background: Arrhythmia-risk assessment in congenital long-QT syndrome (LQTS) and drug-induced QT prolongation (diQTP) is primarily based on clinical, genetic, and electrical parameters. Electromechanical window (EMW; aortic-valve closure time minus QT interval) assessment outperformed QTc as a predictor of symptomatic status in LQTS. The relationship between QTc and EMW dynamics, and ventricular tachyarrhythmia (VT) timing in LQTS and diQTP is unknown. Methods: 47 LQTS/-VT, 18 LQTS/+VT (3 LQT1, 5 LQT2, 4 LQT3, 3 LQT7, 3 genotype-negative), nine diQTP/+VT and 26 controls were included. QTc and EMW were obtained from standard 12-lead ECGs and ECG-echocardiograms at two or three time points. +VT patients were included if EMW/QTc assessments were performed within two weeks before or after torsades de pointes, ventricular fibrillation, monomorphic or bidirectional VT. Results: Median age was 42 (27-57) years, and 70% were female. In control subjects, EMW remained stably positive over time. In LQTS/-VT patients, EMW was negative without significant variation. In LQTS/+VT and diQTP/+VT patients, transient accentuations of EMW negativity were observed at the time point closest to VT (2 (1 to 7) days to arrhythmia), regardless of whether measured before or after VT. Temporary EMW negativity accentuation was driven by foreshortening of mechanical systole despite concurrent QT prolongation. EMW recovery after VT was similar for patients with or without beta-blocker therapy. Multiple logistic regression analysis identified EMW negativity and EMW dynamics (ΔEMW) as independent predictors of imminent VT in LQTS. An EMW of −75 ms and ΔEMW of −39 ms were optimal cut-offs to predict emergent arrhythmic deterioration in the LQTS cohort. Conclusion: Temporary accentuation of EMW negativity is a marker of impending VT in LQTS and diQTP patients. EMW negativity ≤ −75 ms and a ΔEMW ≥ −39 ms best differentiated LQTS patients with imminent or very recent VT from those not at acute risk.

Background: While epicardial adipose tissue (EAT) is a known predictor of adverse cardiovascular outcomes, lipomatous hypertrophy of the interatrial septum (LHIS) is composed of metabolically active fat such as brown adipose tissue, which may exert a different effect. This study investigates the coronary atherosclerosis profile in patients with LHIS using CTA, compared with a propensity score-matched control group. Methods: A total of 142 patients were included (n = 71 with LHIS and n = 71 controls) and propensity score-matched for age, gender, BMI, and the major CV risk factors (matching level, 2 +/− 4.99. HRP prevalence was significantly lower in LHIS patients vs. controls (21.1% vs. 40.8%; p < 0.011), while CAC (p = 0.827) and CADRADS (p = 0.329) were not different, and there was no difference in the obstructive disease rate. There was no difference in lipid panels (cholesterol, LDL, HDL, TG) and statin intake rate. Conclusions: HRP prevalence is lower in patients with LHIS than controls, while coronary stenosis severity and CAC score are not different. Clinical relevance: LHIS may serve as imaging biomarker for reversed CV risk.

Using continuous thoracic impedance measurements, sleep apnea can be long‐time monitored via an electronic device sensor. In the ACaSA trial, 233 patients implanted with a cardiac pacemaker (MicroPort CRM, Clamart, France) were prospectively observed between March 2022 and July 2024. For each night of follow‐up, the burden of device‐detected sleep apnea (DDSA) was measured via transthoracic impedance, defined by a respiratory disturbance index (RDI) ≥ 20 events per sleeping hour. Local meteorological data including maximum ambient diurnal temperature, humidity, precipitation and air pressure change were extracted from the national weather system and linked to the individual patient's place of residence. The association between these weather conditions and RDI in the following night was estimated using a generalised linear mixed effects model. Overall, 74,031 patient‐nights of 210 individuals (median age 75.7 years [IQR 69.9–81.3], 77 [36.7%] female) with a median follow up of 593 nights (IQR 348–755) were analysed. In a multivariate regression analysis, ambient maximum diurnal temperature was independently associated with presence of DDSA. Following days with a maximum of 30°C, the odds of experiencing severe DDSA increased by 1.34 (95% CI: 1.17–1.54, p < 0.001) compared to days with only 10°C. Higher relative humidity increased the odds for suffering from severe DDSA as well (OR 1.19 [1.07–1.33] in 90% relative humidity vs. 65% humidity; p = 0.007). These associations of ambient maximum diurnal temperature and relative humidity with severe DDSA the following night need further investigations, in particular in view of upcoming global climate changes.