Atrial fibrillation (AF) is a prevalent heart rhythm disorder significantly impacting quality of life, morbidity, and mortality. Catheter ablation using thermal energy is an effective treatment, but its indiscriminate tissue destruction poses safety risks, including pulmonary vein stenosis, stroke, phrenic nerve palsy, and the life-threatening atrio-esophageal fistula. Pulsed field ablation (PFA) is an emerging modality showing promise due to its preferential myocardial tissue damage, minimizing harm to surrounding structures. Pre-clinical and early clinical trials with the pentaspline PFA catheter demonstrated feasibility and safety in smaller patient cohorts, but large-scale real-world safety data were lacking. Following European regulatory approval, the MANIFEST-PF survey showed promising safety results in a smaller group, prompting the MANIFEST-17K study to assess PFA safety in a substantially larger, real-world setting.

The literature review section cites several studies supporting the efficacy and safety of catheter ablation for atrial fibrillation. However, it emphasizes the limitations of thermal ablation due to its non-selective tissue damage. Previous studies, including the MANIFEST-PF survey and the ADVENT trial, are highlighted, demonstrating the early promise of PFA. The review also acknowledges the possibility of unforeseen adverse events emerging only after thousands of procedures, emphasizing the need for large-scale, real-world data like that provided by the MANIFEST-17K study.

MANIFEST-17K is a retrospective, observational, multicenter study encompassing 17,642 consecutive patients undergoing PFA with a pentaspline catheter at 106 centers (91.4% of centers using this catheter). Data were collected from center-level databases, including center characteristics, limited patient baseline data, procedure parameters, and all adverse events (AEs). Major and minor AEs were prospectively defined. For specific AEs like stroke and coronary spasm, root cause analyses were performed. Data were analyzed using descriptive statistics, with continuous variables compared using t-tests or Mann-Whitney U tests, and categorical variables compared using chi-squared or Fisher exact tests. The study excluded the initial 1,758 patients from the MANIFEST-PF survey, focusing on data from 2022 onward.

The MANIFEST-17K study found no esophageal complications, pulmonary vein stenosis, or persistent phrenic nerve injury, highlighting PFA's tissue selectivity. The overall major complication rate was low at 0.98%, primarily consisting of pericardial tamponade (0.36%), vascular complications (0.30%), and stroke (0.12%). Mortality was rare (0.03%). Unexpected findings included coronary artery spasm (0.14%), predominantly proximity-related, and hemolysis-related acute renal failure requiring hemodialysis in five patients (0.03%). A learning curve was observed, with lower rates of pericardial tamponade and stroke in the MANIFEST-17K cohort compared to the initial MANIFEST-PF cohort, suggesting improvements in technique over time. In a subset of patients with post-procedural brain MRI, asymptomatic abnormalities were observed in 9.4%.

The findings of the MANIFEST-17K study support the favorable safety profile of PFA for atrial fibrillation treatment. The absence of esophageal complications, PV stenosis, and persistent phrenic nerve injury in a large, real-world cohort strongly suggests PFA's tissue-selective nature. The low rates of major complications, especially when compared to historical thermal ablation data, further support this conclusion. While unexpected complications such as coronary spasm and hemolysis-related renal failure occurred, their low incidence and generally benign outcomes suggest that PFA remains a safe and effective procedure. The learning curve observed emphasizes the importance of experience and training in minimizing complications.

The MANIFEST-17K study, the largest registry to date on PFA for AF, confirms a favorable safety profile in a real-world setting. PFA demonstrated tissue selectivity with minimal esophageal complications. Although rare complications exist, such as hemolysis-related renal failure and coronary spasm, their low frequency and often manageable nature do not negate the overall benefit of the procedure. Further research should focus on optimizing techniques to reduce the incidence of these rare but potentially serious complications.

The retrospective observational design of MANIFEST-17K is a limitation, as it's susceptible to biases inherent in such studies. The possibility of subclinical events not captured in the data cannot be ruled out. The determination of coronary spasm relied on clinical judgment, potentially impacting accuracy. The study's cohort of operators may be skewed towards greater expertise, affecting generalizability. Furthermore, the findings relate specifically to the pentaspline PFA catheter and may not be directly applicable to other PFA technologies.