One-year outcomes of pulmonary vein isolation with a novel cryoballoon: Primary results of the FROZEN AF trial.

INTRODUCTION: Cryoablation therapy for pulmonary vein isolation (PVI) to treat paroxysmal atrial fibrillation (PAF) is well established. A novel 28 mm cryoballoon system designed to operate under low pressure to safely reach a lower nadir temperature and maintain constant balloon size during cooling has not been prospectively studied in a large patient population for safety and efficacy. The FROZEN AF (NCT04133168) trial was an international multicenter, open-label, prospective, single-arm study on the safety and performance of a novel cryoballoon system for treatment of PAF. METHODS AND RESULTS: The study enrolled patients at 44 sites in 10 countries across North America, Europe, and Asia. Subjects were indicated for PVI treatment of PAF and had failed or were intolerant of one or more antiarrhythmic drugs. Procedural outcomes were defined based on the 2017 HRS consensus statement. Follow-up was performed at 7 days, 3, 6, and 12 months. Data are reported as mean ± SD or median (IQR). PVI was performed with a 28 mm cryoballoon in 325 drug refractory PAF patients. Complete PVI was achieved in 95.7% of patients. In cryoablation lesions longer than 60 s, 60.1% of PV isolations required only a single cryoballoon application. Procedure related complications included: phrenic nerve palsy [temporary 4 (1.2%), persistent 0 (0.0%)], cardiac tamponade/perforation 2 (0.6%), and air embolism 1 (0.3%). Freedom from documented atrial arrhythmia recurrence at 12 months was 79.9% (AF 82.7%, AFL 96.5%, AT 98.1%), antiarrhythmic drugs (AAD) were continued or re-initiated in 26.8% of patients after the 3-month blanking period. Additionally, an extension arm enrolled 50 pts for treatment with 28/31 mm variable size cryoballoon. A single temporary PNP occurred in this group, which resolved before discharge. Freedom from documented recurrence at 12 months in these pts was 82.0%. CONCLUSIONS: This novel cryoballoon may facilitate PVI to treat PAF, providing more options to address the variety of anatomies present in patients with PAF. This cryoballoon system proved to be safe and effective for treatment of patients with drug refractory or drug intolerant PAF.

Improved diagnostic performance of insertable cardiac monitors by an artificial intelligence-based algorithm.

AIMS: The increasing use of insertable cardiac monitors (ICM) produces a high rate of false positive (FP) diagnoses. Their verification results in a high workload for caregivers. We evaluated the performance of an artificial intelligence (AI)-based ILR-ECG Analyzer™ (ILR-ECG-A). This machine-learning algorithm reclassifies ICM-transmitted events to minimize the rate of FP diagnoses, while preserving device sensitivity. METHODS AND RESULTS: We selected 546 recipients of ICM followed by the Implicity™ monitoring platform. To avoid clusterization, a single episode per ICM abnormal diagnosis (e.g. asystole, bradycardia, atrial tachycardia (AT)/atrial fibrillation (AF), ventricular tachycardia, artefact) was selected per patient, and analyzed by the ILR-ECG-A, applying the same diagnoses as the ICM. All episodes were reviewed by an adjudication committee (AC) and the results were compared. Among 879 episodes classified as abnormal by the ICM, 80 (9.1%) were adjudicated as 'Artefacts', 283 (32.2%) as FP, and 516 (58.7%) as 'abnormal' by the AC. The algorithm reclassified 215 of the 283 FP as normal (76.0%), and confirmed 509 of the 516 episodes as abnormal (98.6%). Seven undiagnosed false negatives were adjudicated as AT or non-specific abnormality. The overall diagnostic specificity was 76.0% and the sensitivity was 98.6%. CONCLUSION: The new AI-based ILR-ECG-A lowered the rate of FP ICM diagnoses significantly while retaining a > 98% sensitivity. This will likely alleviate considerably the clinical burden represented by the review of ICM events.

Wearable Devices, Health Care Use, and Psychological Well-Being in Patients With Atrial Fibrillation.

BACKGROUND: Wearables are increasingly used by patients with atrial fibrillation (AF) for symptom monitoring and health management, but their impact on patient health care use and psychological well-being is not well understood. METHODS AND RESULTS: In this retrospective, propensity-matched study of patients with AF, survey and electronic health record data were merged to compare AF-specific health care use (outpatient/inpatient visits, rhythm-related testing, and procedures) and informal health care use (telephone calls and patient portal messages) over a 9-month period between wearable users and nonusers. We also examined the effects of wearable cardiac monitoring features (eg, heart rate alerts, irregular rhythm notification, and ECG) on patient behavior and well-being. Of 172 patients with AF in this analysis (age, 72.6±9.0 years; 42% women), 83 used a wearable. Compared with nonusers, wearable users reported higher rates of symptom monitoring and preoccupation (P=0.03) and more AF treatment concerns (P=0.02). Moreover, 20% of wearable users experienced anxiety and always contacted their doctors in response to irregular rhythm notifications. After matching, AF-specific health care use was significantly greater among wearable users compared with nonusers (P=0.04), including significantly higher rates of ECGs, echocardiograms/transesophageal echocardiogram, and ablation. Wearable users were also significantly more likely to use informal health care resources compared with nonusers (P=0.05). CONCLUSIONS: Wearables were associated with higher rates of symptom monitoring and preoccupation, AF treatment concerns, AF-specific health care use, and use of informal health care resources. Prospective, randomized studies are needed to understand the net effects of wearables and their alerts on patients, providers, and the health care system.

Promises and Perils of Consumer Mobile Technologies in Cardiovascular Care: JACC Scientific Statement.

Direct-to-consumer (D2C) wearables are becoming increasingly popular in cardiovascular health management because of their affordability and capability to capture diverse health data. Wearables may enable continuous health care provider-patient partnerships and reduce the volume of episodic clinic-based care (thereby reducing health care costs). However, challenges arise from the unregulated use of these devices, including questionable data reliability, potential misinterpretation of information, unintended psychological impacts, and an influx of clinically nonactionable data that may overburden the health care system. Further, these technologies could exacerbate, rather than mitigate, health disparities. Experience with wearables in atrial fibrillation underscores these challenges. The prevalent use of D2C wearables necessitates a collaborative approach among stakeholders to ensure effective integration into cardiovascular care. Wearables are heralding innovative disease screening, diagnosis, and management paradigms, expanding therapeutic avenues, and anchoring personalized medicine.

Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial.

BACKGROUND: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. METHODS AND RESULTS: This is a post hoc analysis of the MORE-CRT MPP (More Response on Cardiac Resynchronization Therapy with Multipoint Pacing)  trial (n=3739, 28% women), with a subgroup analysis of patients with nonischemic cardiomyopathy and left bundle-branch block (n=1308, 41% women) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/left ventricular end-diastolic volume (LVEDV). Women had a higher CRT response rate than men (70.1% versus 56.8%, P<0.0001). In subgroup analysis, regression analysis of the nonischemic cardiomyopathy left bundle-branch block subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (P<0.0039). QRSd/LVEDV was significantly higher in women (0.919) versus men (0.708, P<0.001). CRT response was 78% for female patients with QRSd/LVEDV greater than the median value, compared with 68% with QRSd/LVEDV less than the median value (P=0.012). The association between CRT response and QRSd/LVEDV was strongest at QRSd <150 ms. CONCLUSIONS: In the nonischemic cardiomyopathy left bundle-branch block population, increased relative dyssynchrony in women, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150 ms. Women may benefit from CRT at a QRSd <130 ms, opening the debate on whether sex-specific QRSd cutoffs or QRS/LVEDV measurement should be incorporated into clinical guidelines.

High initial heart rate score is an independent predictor of new atrial high-rate episodes in pacemaker patients with sinus node dysfunction.

BACKGROUND: Heart rate score (HRSc), the percentage of atrial depolarizations in the largest paced and sensed 10-beats/min histogram bin recorded in cardiac devices, is associated with several adverse outcomes, but it remains uncertain whether HRSc independently predicts atrial high-rate episodes (AHREs) in patients with sinus node dysfunction (SND) undergoing pacemaker (PM) implantation. OBJECTIVE: This study aimed to determine whether initial HRSc after PM implantation predicts new-onset AHREs in patients with SND. METHODS: Patients had Boston Scientific PMs implanted for SND from 2012 to 2021 at Cleveland Clinic, University of Occupational and Environmental Health, Japan, Kyushu Rosai Hospital, and JCHO Kyushu Hospital. Patients were excluded if they had atrial fibrillation before PM implantation or AHREs within 3 months after implantation. Subsequent AHREs after implantation were evaluated and correlated with HRSc. RESULTS: During 48.9 (interquartile range, 25.7-50.4) months, 130 consecutive PM patients (76 ± 10 years; 40% male) had a median initial HRSc of 74% (57%-86%). AHREs defined by >1%, >6 h/d burden, and atrial tachycardia response events >24 hours developed in 27 of 130 (21%), 15 of 130 (12%), and 9 of 130 (7%), respectively. For each definition, patients with HRSc ≥80% had higher occurrence of AHREs than those with HRSc <80% (both P = .008, log-rank test). After adjustment for age, race, comorbidities, left ventricular ejection fraction, left atrial diameter, and cumulative percentage of right atrial and right ventricular pacing, initial HRSc ≥80% (hazard ratio, 3.33; 95% CI, 1.35-8.18; P = .009) and male sex (hazard ratio, 2.59; 95% CI, 1.06-6.33; P = .04) independently predicted AHREs. CONCLUSION: HRSc ≥80% is associated with new-onset, device-determined AHREs for patients undergoing PM implantation for SND. HRSc may have prognostic and therapeutic implications.

Left Ventricular Mass as a Modulator of Ventricular Arrhythmia Risk and Sex Differences Following CRT for Non-Ischemic Cardiomyopathy and LBBB.

BACKGROUND: Risk for ventricular arrhythmias (VA) following cardiac resynchronization therapy (CRT) has been associated with ischemic disease/scar, sex, and possibly left ventricular mass (LVM). OBJECTIVE: To evaluate sex differences and baseline/post-implant change [Δ] of LVM on VA risk after CRT implant among patients with non-ischemic cardiomyopathy (NICM) and left bundle branch block. METHODS: Among patients meeting the criteria, baseline and follow-up echocardiographic images were obtained for LVM assessment. VA events were reported from device diagnostics and therapies. VA risk was stratified by ROC (Youden-index cut-point) for baseline LVM and ΔLVM, and baseline patient characteristics using a multivariable Cox regression model. RESULTS: 118 patients (71[60.2%] female, age 60.5 ±11.3 years, LVEF 19.2 ±7.0%, QRS 165.6 ±20 ms, LVM 313.9 ±108.8 g) were enrolled and followed for median 90 (IQR 44-158) months. Thirty-five (29.6%) patients received appropriate shocks or anti-tachycardia pacing at a median of 73.5 (IQR 25-130) months post-implant. Males had a higher VA incidence (male 18/47 [38.3%] vs. female 17/71 [23.9%], P=0.02). Baseline LVM >308.9g separated patients with higher VA risk (P=0.001). Less than a 20% decrease in LVM increased VA risk (P<0.001). Baseline LVM was the only baseline characteristic predicting VA events in the Cox regression model (Hazard ratio 1.01 [95%CI, 1.001-1.009], Log-rank P=0.003). Sex differences in VA risk were eliminated by the baseline LVM parameters. CONCLUSION: VA risk after CRT in NICM was associated with baseline LV >308.9g and a decrease in LVM ≤ 20%, without sex differences.

Heart size disparity drives sex-specific response to cardiac resynchronization therapy: a post-hoc analysis of the MORE-MPP CRT trial.

Background: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased "relative dyssynchrony" at given QRS durations (QRSd). Objective: To investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. Methods: A post-hoc analysis of the MORE-CRT MPP trial (n=3739, 28% female), with a sub-group analysis of patients with non-ischaemic cardiomyopathy (NICM) and left bundle branch block (LBBB) (n=1308, 41% female) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/LVEDV (left ventricular end-diastolic volume). Results: Females had a higher CRT response rate than males (70.1% vs. 56.8%, p<0.0001). Subgroup analysis: Regression analysis of the NICM LBBB subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (p<0.0039). QRSd/LVEDV was significantly higher in females (0.919) versus males (0.708, p<0.001). CRT response was 78% for female patients with QRSd/LVEDV>median value, compared to 68% < median value (p=0.012). Association between CRT response and QRSd/LVEDV was strongest at QRSd<150ms. Conclusions: In the NICM LBBB population, increased relative dyssynchrony in females, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150ms. Females may benefit from CRT at a QRSd <130ms, opening the debate on whether sex-specific QRSd cut-offs or QRS/LVEDV measurement should be incorporated into clinical guidelines.