To evaluate the effectiveness and safety of cryoballoon ablation (CBA) compared with radiofrequency ablation (RFA) for symptomatic paroxysmal or drug-refractory persistent atrial fibrillation (AF). Prospective cluster cohort study in experienced CBA and RFA centres. Primary endpoint was ‘atrial arrhythmia recurrence’, secondary endpoints were as follows: procedural results, safety, and clinical course. A total of 4189 patients were included: CBA 2329 (55.6%) and RFA 1860 (44.4%). Cryoballoon ablation population was younger, with fewer comorbidities. Procedure time was longer in the RFA group (P = 0.01). Radiation exposure was 2487 (CBA) and 1792 cGycm² (RFA) (P < 0.001). Follow-up duration was 441 (CBA) and 511 days (RFA) (P < 0.0001). Primary endpoint occurred in 30.7% (CBA) and 39.4% patients (RFA) [adjusted hazard ratio (adjHR) 0.85, 95% confidence interval (CI) 0.70–1.04; P = 0.12). In paroxysmal AF, CBA resulted in a lower risk of recurrence (adjHR 0.80, 95% CI 0.64–0.99; P = 0.047). In persistent AF, the primary outcome was not different between groups. Major adverse cardiovascular and cerebrovascular event rates were 1.0% (CBA) and 2.8% (RFA) (adjHR 0.53, 95% CI 0.26–1.10; P = 0.088). Re-ablations (adjHR 0.46, 95% CI 0.34–0.61; P < 0.0001) and adverse events during follow-up (adjHR 0.64, 95% CI 0.48–0.88; P = 0.005) were less common after CBA. Higher rehospitalization rates with RFA were caused by re-ablations. The primary endpoint did not differ between CBA and RFA. Cryoballoon ablation was completed rapidly; the radiation exposure was greater. Rehospitalization due to re-ablations and adverse events during follow-up were observed significantly less frequently after CBA than after RFA. Subgroup analysis suggested a lower risk of recurrence after CBA in paroxysmal AF. ClinicalTrials.gov (NCT01360008), https://clinicaltrials.gov/ct2/show/NCT01360008.

Ischemic stroke cause remains undetermined in 30% of cases, leading to a diagnosis of cryptogenic stroke. Paroxysmal atrial fibrillation (AF) is a major cause of ischemic stroke but may go undetected with short periods of ECG monitoring. The Cryptogenic Stroke and Underlying Atrial Fibrillation trial (CRYSTAL AF) demonstrated that long-term electrocardiographic monitoring with insertable cardiac monitors (ICM) is superior to conventional follow-up in detecting AF in the population with cryptogenic stroke. We evaluated the sensitivity and negative predictive value (NPV) of various external monitoring techniques within a cryptogenic stroke cohort. Simulated intermittent monitoring strategies were compared to continuous rhythm monitoring in 168 ICM patients of the CRYSTAL AF trial. Short-term monitoring included a single 24-hour, 48-hour, and 7-day Holter and 21-day and 30-day event recorders. Periodic monitoring consisted of quarterly monitoring through 24-hour, 48-hour, and 7-day Holters and monthly 24-hour Holters. For a single monitoring period, the sensitivity for AF diagnosis was lowest with a 24-hour Holter (1.3%) and highest with a 30-day event recorder (22.8%). The NPV ranged from 82.3% to 85.6% for all single external monitoring strategies. Quarterly monitoring with 24-hour Holters had a sensitivity of 3.1%, whereas quarterly 7-day monitors increased the sensitivity to 20.8%. The NPVs for repetitive periodic monitoring strategies were similar at 82.6% to 85.3%. Long-term continuous monitoring was superior in detecting AF compared to all intermittent monitoring strategies evaluated (p <0.001). Long-term continuous electrocardiographic monitoring with ICMs is significantly more effective than any of the simulated intermittent monitoring strategies for identifying AF in patients with previous cryptogenic stroke.

Background: Impedance-based remote monitoring (RM) failed to reduce clinical events in the OptiLink heart failure (HF) trial. However, rates of alert-driven interventions triggered by intrathoracic fluid index threshold crossings (FTC) were low indicating physicians’ inappropriate reactions to alerts. Methods: We separated appropriate from inappropriate contacts to FTC transmissions in the OptiLink HF trial (Optimization of Heart Failure Management Using OptiVol™ Fluid Status Monitoring and CareLink™). Appropriate contacts had to meet the following criteria: (1) initial telephone contact within 2 working days after FTC transmission, (2) follow-up contacts according to study protocol, and (3) medical intervention initiated after FTC due to cardiac decompensation. We compared time to cardiovascular death or HF hospitalization between RM patients contacted appropriately or inappropriately and patients with usual care. Results: In the RM group, at least one FTC alert was transmitted in 356 patients (70.5%; n=505). Of note, only 55.5% (n=758) of all transmitted FTCs (n=1365) were followed by an appropriate contact. While 113 patients (31.7%; n=356) have been contacted appropriately after every FTC, in 243 patients (68.3%; n=356) at least one FTC was not responded by an appropriate contact. Compared with usual care, RM with appropriate contacts to FTC alerts independently reduced the risk of the primary end point (hazard ratio, 0.61 [95% CI, 0.39–0.95]; P =0.027). Conclusions: RM appropriate reactions to FTC alerts are associated with significantly improved clinical outcomes in patients with advanced HF and implantable cardioverter-defibrillators.

The Official Journal of EuroPCR and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Although cardiac resynchronization therapy (CRT) is effective in most patients with heart failure (HF) and ventricular dyssynchrony, a significant minority of patients (approximately 30%) are non-responders. Optimal atrioventricular and interventricular delays often change over time and reprogramming these intervals might increase CRT effectiveness. The SonR algorithm automatically optimizes atrioventricular and interventricular intervals each week using an accelerometer to measure change in the SonR signal, which was shown previously to correlate with hemodynamic improvement (left ventricular [LV] dP/dtmax). The RESPOND CRT trial will evaluate the effectiveness and safety of the SonR optimization system in patients with HF New York Heart Association class III or ambulatory IV eligible for a CRT-D device. Enrolled patients will be randomized in a 2:1 ratio to either SonR CRT optimization or to a control arm employing echocardiographic optimization. All patients will be followed for at least 24 months in a double-blinded fashion. The primary effectiveness end point will be evaluated for non-inferiority, with a nested test of superiority, based on the proportion of responders (defined as alive, free from HF-related events, with improvements in New York Heart Association class or improvement in Kansas City Cardiomyopathy Questionnaire quality of life score) at 12 months. The required sample size is 876 patients. The two primary safety end points are acute and chronic SonR lead-related complication rates, respectively. Secondary end points include proportion of patients free from death or HF hospitalization, proportion of patients worsened, and lead electrical performance, assessed at 12 months. The RESPOND CRT trial will also examine associated reverse remodeling at 1 year.

Extracellular vesicles (EVs) have emerged as essential mediators of intercellular communication, transporting a complex repertoire of lipids, proteins, and nucleic acids that mirror the physiological and pathological status of their parent cells. This review provides a comprehensive overview of EVs from their biogenesis and molecular composition to their translational potential in human disease. This review outlines the major classes of EVs, including exosomes, microvesicles, apoptotic bodies, and oncosomes, together with recent developments in their isolation, molecular characterization, and omics-based profiling. Special focus is given to the role of EVs in viral infection, inflammation, and immune regulation, as well as their contribution to disease development and cancer biology. Moreover, we highlight the emerging clinical applications of mesenchymal stem cell-derived EVs (MSC-EVs) in regenerative medicine and oncology, alongside the therapeutic modulation of EV signaling by photobiomodulation (PBM). Finally, we address key translational challenges related to standardization, scalability, and regulatory validation. As exosome-based therapeutics fall under strict FDA and EMA oversight, their translation further depends on harmonized quality controls and robust safety evaluation. By integrating molecular mechanisms with clinical applications, this review emphasizes the transformative potential of EVs as next-generation diagnostic and therapeutic tools in precision medicine.