Shen, Win K.

Background: A blanking period allowing for atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has historically been standardized to 90 days. With the recent introduction of pulsed field ablation (PFA) for PVI and emerging in vitro data suggesting a shorter inflammatory timeframe, it remains unclear whether recurrences during this 90-days period reflect incomplete procedural success or merely transient inflammatory changes. Research Question: In patients undergoing PVI with PFA, do early AF recurrences at 30, 60, and 90 days predict late AF recurrences beyond the standardized 90-day blanking period? Methods: Patients undergoing PFA for AF were retrospectively included. Procedures were performed under general anesthesia, and high-density (HD) mapping, with PVI and additional ablation lines applied at the operator’s discretion. PFA catheters included Farawave, PulseSelect, and Sphere-9. AF recurrences were defined as documented episodes on 12-lead ECG or cardiac monitoring devices, confirmed by interpretation from an experienced cardiologist. Survival analyses were conducted based on the occurrence of early recurrences at 30, 60, and 90 days post-ablation. Kaplan-Meier curves and hazard ratios were reported. This study was approved by our institutional review board. Results: To the best of our knowledge, this is the largest real-world study reporting outcomes of PFA for AF in the United States. A total of 1,214 patients were included in the analysis. Mean age was 66.4 years; 31.9% were female, and 22.4% underwent redo PVI. Six-month AF recurrence-free survival was 79% (95% CI, 75–83%) for the overall cohort. Patients experiencing early recurrence at 30, 60, and 90 days had a significantly higher risk of AF recurrence beyond the standardized 90-day blanking period (HR 4.0, 95% CI 2.7–5.9, P < 0.01; HR 5.0, 95% CI 3.6–7.1, P < 0.01; and HR 6.9, 95% CI 4.9–9.6, P < 0.01, respectively). Conclusion: Early recurrences at 30, 60, and 90 days post-ablation are strongly associated with atrial fibrillation recurrence beyond the 90-day blanking period. These findings challenge the traditional concept of blanking period after PFA and suggest that early recurrence may indicate incomplete procedural success rather than transient inflammation.

Background: Patients with cardiac implantable electronic devices (CIEDs) undergoing radiation therapy face potential risks of device malfunction. Proton beam therapy (PBT), with its reduced neutron scatter, has emerged as a potentially safer alternative, yet real-world safety data remain scarce. Methods: We conducted a retrospective cohort study of 100 patients with CIEDs (76 pacemakers, 24 ICDs) who underwent PBT from 2016 to 2023 at a quaternary center. Baseline and serial device interrogations were performed before, during, and after treatment to assess lead impedance, capture thresholds, battery function, and arrhythmic events. Patients were stratified by pacemaker dependence and monitored accordingly. Primary outcomes included device malfunction and new-onset arrhythmias during treatment. Secondary outcomes included device parameter changes, one-year arrhythmia incidence, and cardiac-related hospitalizations. Results: No treatment-related deaths or major device failures occurred. Device malfunction was rare (2 pacemaker patients, 2.6%), with no malfunctions in ICD recipients. Transient, non-clinically significant changes in lead impedance and capture thresholds were observed. Arrhythmias during treatment occurred in 26% of pacemaker and 25% of ICD patients, but only 4% developed new arrhythmias. At one year, device-related complications and cardiac outcomes remained comparable across groups. Independent predictors of arrhythmias during treatment included a higher radiation dose per fraction (OR 1.45; p=0.001), a longer treatment duration (OR 1.12; p=0.04), and a higher number of fractions (OR 1.20; p=0.01). Conclusion: Proton beam therapy appears safe in patients with CIEDs, with a low incidence of clinically significant device malfunctions or arrhythmias. These findings support the integration of PBT into routine practice for this population and underscore the importance of structured monitoring protocols and prospective guideline refinement.

Background: Syncope is a leading cause of transient loss of consciousness, especially in older adults. Post-syncopal driving restrictions are widely recommended, but the required duration varies by state. The impact of these policies on motor vehicle crash outcomes remains unclear. Methods: We conducted a cross-sectional analysis of 45 U.S. states, comparing crash and fatality data between states requiring < 6 months vs. ≥ 6 months of driving restriction following a syncopal episode. Data were obtained from Fatality Analysis Reporting System, National Highway Traffic Safety Administration, state Department of Motor Vehicles, and medical boards. Crash rates were normalized by licensed drivers and population. Statistical comparisons were made using Welch’s t-tests. Results: States with ≥ 6-month restrictions had significantly lower crash rates among older drivers (0.0171 vs. 0.0256, p = 0.0076). Relative crash ratios comparing older to younger drivers were also lower (0.220 vs. 0.306, p = 0.067). Overall crash rates trended lower in states with ≥ 6-month restrictions in both per licensed driver ( p = 0.054) and per population ( p = 0.099). No significant differences were observed in fatality rates. Conclusions: Longer post-syncope driving restriction durations (≥ 6 months) are associated with reduced crash risk among older drivers and a narrowing of age-related disparities in crash rates. These findings suggest potential public health value in adopting more uniform, evidence-based restriction policies following syncopal events for older drivers.

Background: Cavotricuspid isthmus ablation (CTI) is a first line therapy in patients with typical atrial flutter. With the advent of Pulsed Field (PF) as a new energy source, we sought to evaluate the use of PF for CTI ablation. A systematic literature search was conducted on the use of PF for CTI-flutter up to December 2024. A meta-analysis was performed for studies reporting pooled data, while a patient-level summary was done for reports with available individual data. The mean number of PF applications, acute success rate, and prevalence of coronary vasospasm were evaluated. Results: Eleven studies with pooled data from 155 patients were included. All patients had an acute block of the CTI. The mean number of PFA applications was 7.78 (95% CI 6.53–9.48). The incidence of ST-elevation was 0.04% (95% CI 0-2.23%). Subclinical vasospasm was documented in 45% (95% CI 32%–59%) of patients who underwent periprocedural coronary angiography. Prophylactic use of nitrates showed a trend toward reducing the incidence of subclinical vasospasm (RR 0.24, 95% CI 0.06–1.06, p=0.059). Twelve cases with patient-level data were included; six reported complications, including ST elevation and conduction disturbances. Conclusion: PFA for CTI flutter demonstrates high acute success; however, evidence regarding the durability of the block is limited. Clinical vasospasm with ST segment elevation is uncommon but can lead to life-threatening complications. The incidence of subclinical vasospasm is high, and nitrates trend toward reducing this phenomenon. To date, the role of PFA for this condition appears to be limited.

Abstract Aims Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although lipoprotein(a) [Lp(a)] is known to be a well-established risk factor for atherosclerotic cardiovascular disease, its role in the development of AF, independent of this association, remains unclear. Methods and results Adult patients from the three Mayo Clinic sites with a baseline Lp(a) and without AF history were included. Patients were categorized into two groups based on their Lp(a) levels: high Lp(a) (≥50 mg/dL) and low Lp(a) (&lt;50 mg/dL). Survival probabilities free from incident AF were compared between Lp(a) groups, during a follow-up period up to 15 years, using the Kaplan–Meier curve and the log-rank test. Multivariable Cox regression analysis was also conducted. A total of 75 376 patients were included (median age: 55 years, 59% males), with a median follow-up duration of 8.8 (inter-quartile range: 3.4, 14.8) years. Incident AF was detected in 5738 (7.6%) patients. Survival probability free from incident AF was significantly lower in patients with elevated Lp(a) (86%) compared with those with low Lp(a) (88%, log-rank P &lt; 0.001). Multivariable analysis adjusted for potential risk factors of AF showed a statistically significant association of elevated Lp(a) with an 11% increase in AF risk (adjusted hazard ratio: 1.11, 95% confidence interval: 1.05–1.18). Conclusion Our study suggests that elevated Lp(a) (≥50 mg/dL) is an independent risk factor for incident AF. Future prospective studies are warranted to validate our results and to test if reducing Lp(a) could mitigate the burden of AF.

Background: Recognition of the causes of early mortality after ventricular tachycardia (VT) ablation in patients with reduced left ventricular ejection fraction is an essential step toward improving post-procedural outcomes. Objective: This study sought to determine the causes of early mortality (≤30-days) after VT ablation in patients with reduced left ventricular ejection fraction and to understand further the circumstances surrounding death after the procedure. Methods: We performed a retrospective analysis of all patients undergoing VT ablation in patients with reduced left ventricular ejection fraction from January 1, 2013, to November 10, 2021, at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a detailed chart review of the electronic health record within the Mayo Clinic system and outside records. Results: A total of 503 patients (mean age 63 ± 13 years, 11.2% female) with EF <50% were included in the study. The 30-day all-cause mortality rate was 5% (n=25), and the mortality rate due to a procedural complication was 0.4%. Among all 30-day deaths, recurrent VT was the most common primary cause of death (44%). This was followed by decompensated heart failure (28%), procedure-related death (8%), cerebrovascular accident (CVA) (4%), and infection (4%). Most patients (91%) who died from VT had the VT recurrence within three days of the ablation. 76% of patients with early mortality had delayed referral for VT ablation, and 72% opted for comfort care before death. Conclusions: The overall early mortality (≤30-days) rate after catheter ablation of VT in patients with reduced left ventricular ejection fraction was 5%, but the death rate directly due to a procedural complication was only 0.4%. The most common cause of death was recurrent VT, followed by heart failure. Further research into ablation strategies is vital to improving the safety, efficacy, and durability of VT ablation.

Introduction: Multiple supervised machine learning (ML) models have been used to assess the outcomes in patients who underwent transcatheter aortic valve replacement (TAVR) procedure, however, supervised ML requires significant expert time for annotation and labeling. Unsupervised ML can provide insight into the dataset without this process. Hypothesis: We hypothesized that unsupervised k-means ML can identify distinct phenogroups in TAVR patients that can predict prognosis without a priori knowledge. Methods: A retrospective study of patients who underwent TAVR (Jan 2012-Dec 2017) at Mayo Clinic sites was performed. Baseline demographics, EKG, cardiac computed tomography, and echocardiographic data were abstracted. Variables with ≥ 20% missing data were excluded. Prior to the k-means clustering algorithm, principal component analysis was used for dimensionality reduction. Input variables were analyzed according to k-means determined clusters. Kaplan-Meier survival analysis was used to assess the survival of each cluster. Results: A total of 1071 consecutive patients were included in the final analysis. A total of 141 unique variables were used. The mean age was 80.7±8.6 years, 58.2% were male. Patients were divided into 2 distinct phenogroups. In the two phenogroups, cluster 0 (n=639) has significantly better survival than cluster 1 (n= 432) (log-rank p=0.0002) (Figure 1). Cluster 1 has features of low flow-low gradient (LFLG) hemodynamic profile, including lower systolic blood pressure, mean aortic valve gradient, peak aortic valve velocity, and worse LV ejection fraction. Conclusions: Unsupervised ML can identify distinct phenotype features with prognostic significance in TAVR patients. Our results suggest that patients with LFLG hemodynamic features are intrinsically different from other TAVR patients and require more attention to avoid adverse outcomes.

Introduction: Syncope was reported to be associated with sudden cardiac death in heart failure patients regardless of the etiology of syncope. We attempted to use unsupervised machine learning to identify the prognostically distinct phenotypes in a large population of heart failure patients presenting with syncope. Hypothesis: Unsupervised machine learning can identify prognostically distinct phenotypes in a large population of heart failure patients presenting with syncope. Methods: Patients with a diagnosis of systolic or diastolic heart failure and syncope at Mayo Clinic sites were identified for baseline and follow-up data. Variables with ≥ 20% missing data were excluded; a total of 57 variables were used for k-means clustering analysis. Patients were grouped according to 4 distinct k-means determined clusters for statistical analysis. Results: A total of 3,557 patients with proper follow-up and echocardiography data were included in the final analysis. The median follow-up duration was 36.3 months, and 2908 (81.7%) patients died. Cluster 2 (n= 680) was identified as the cluster with the highest mortality (92%), which contained patients with high proportions of cardiovascular comorbidities, especially chronic kidney disease. The Kaplan-Meier survival curves are shown in Figure 1. In multivariate Cox regression analysis, the presence of CKD independently predicts mortality (HR 1.62, 95%CI 1.50-1.76, p <0.0001) after adjusting for age and sex. Conclusions: Unsupervised machine learning identified patients with CKD, CAD and DM are high-risk phenotypes in heart failure patients with syncope, and can be used to guide future studies in this highly heterogeneous, unexplored population.

Introduction: Unsupervised machine learning (ML) can provide insight into a dataset without significant expert time for annotation and labeling, but was never used to assess the heterogeneous MitraClip population. Hypothesis: We hypothesized that unsupervised k-means ML could identify prognostically-distinct phenogroups in MitraClip patients without a priori knowledge of the dataset. Methods: Patients who underwent MitraClip (June 2014-September 2020) at Mayo Clinic sites were identified from the Mayo institutional NCDR database for baseline and follow-up data. Variables with ≥ 50% missing data were excluded. A k-means algorithm was used for clustering analysis. Input variables were grouped according to 4 distinct k-means determined clusters. Kaplan-Meier survival analysis was used to assess the survival of each cluster. Results: A total of 389 consecutive patients were included in the final analysis, and 95 unique variables were used. The mean age was 80.3±8.7 years; 256 (65.8%) were male. The mean STS MV Replace score was 9.1±5.7. Fifty-five (14.5%) patients died during the mean follow duration (185 days). Kaplan-Meier analysis showed significant survival differences among clusters (Figure 1). The cluster (cluster 2, n=120) with best survival performance (all-cause mortality 3.3%) had features of non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation. Cluster 3 (n=66) had the worst survival performance (all-cause mortality 27.3%) and opposite features than cluster 2. Conclusions: Unsupervised ML can identify distinct phenotype clusters with prognostic significance in MitraClip patients. Patients with non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation are intrinsically different from other MitraClip patients and should be considered the potential optimal candidates.

Background : Lipid lowering therapy reduces mortality in patients with both ischemic and nonischemic cardiomyopathies and recently has been shown to decrease ICD shocks. Radiofrequency ablation (RFA) of recurrent VT in patients with an ICD also reduces shocks following intervention. It is unclear if statin therapy after VT RFA will further impact ICD shock rates. Methods : All patients from 1993–2005 who underwent a RFA procedure for recurrent VT at the Mayo Clinic with an ICD were included. Patient records were extracted for medical and procedural details and all ICD interrogations were reviewed for VT recurrence and therapies. Results: 63 patients (age 62±15 years) were followed over 3.9±3.6 years. Comorbid diseases included: coronary artery disease 37(58%, 34 prior myocardial infarction), ARVD/C 6(10%), nonischemic dilated cardiomyopathy 7(11%), moderate-severe valve disease 14(22%), hypertension 34(54%), and hyperlipidemia 35(56%). Ejection fraction was <0.35 in 34(56%). VT was induced in all patients (LV 55 (LVOT 1), RV 8 (RVOT 3) with multiple inducible VTs in 21(33%). VT was noninducible after RFA in 39(62%) patients. Dismissal medications included: statins 19(30%), beta blockers 40(66%), ACE/ARB 37(61%), diuretics 34(55%), and digoxin 23(37%). 5-year overall survival was 63%(95% CI 55–71). Age, diabetes, and renal insufficiency were associated with increased post ablation mortality, with no medication improving survival. 5-year survival free of ICD shocks was 31%(95% CI 24–38). Only statin therapy at discharge was associated with a decreased risk of ICD shocks [5(26%) versus 26(59%), p=0.020]. 7 additional patients received statins during follow-up, but not at discharge, of these 5(71%) had shocks. Conclusion : Statin use at discharge in patients with an ICD undergoing RFA for refractory VT significantly reduced recurrent ventricular arrhythmias and ICD shocks. Although the mechanism underlying the effects of statins on arrhythmic recurrence early after RFA requires further study, these data support aggressive therapy of the underlying substrate responsible for the VT.