RNA Interference With Zilebesiran for Mild to Moderate Hypertension: The KARDIA-1 Randomized Clinical Trial.

Importance: Angiotensinogen is the most upstream precursor of the renin-angiotensin-aldosterone system, a key pathway in blood pressure (BP) regulation. Zilebesiran, an investigational RNA interference therapeutic, targets hepatic angiotensinogen synthesis. Objective: To evaluate antihypertensive efficacy and safety of different zilebesiran dosing regimens. Design, Setting, and Participants: This phase 2, randomized, double-blind, dose-ranging study of zilebesiran vs placebo was performed at 78 sites across 4 countries. Screening initiation occurred in July 2021 and the last patient visit of the 6-month study occurred in June 2023. Adults with mild to moderate hypertension, defined as daytime mean ambulatory systolic BP (SBP) of 135 to 160 mm Hg following antihypertensive washout, were randomized. Interventions: Randomization to 1 of 4 subcutaneous zilebesiran regimens (150, 300, or 600 mg once every 6 months or 300 mg once every 3 months) or placebo (once every 3 months) for 6 months. Main Outcomes and Measures: The primary end point was between-group difference in least-squares mean (LSM) change from baseline to month 3 in 24-hour mean ambulatory SBP. Results: Of 394 randomized patients, 377 (302 receiving zilebesiran and 75 receiving placebo) comprised the full analysis set (93 Black patients [24.7%]; 167 [44.3%] women; mean [SD] age, 57 [11] years). At 3 months, 24-hour mean ambulatory SBP changes from baseline were -7.3 mm Hg (95% CI, -10.3 to -4.4) with zilebesiran, 150 mg, once every 6 months; -10.0 mm Hg (95% CI, -12.0 to -7.9) with zilebesiran, 300 mg, once every 3 months or every 6 months; -8.9 mm Hg (95% CI, -11.9 to -6.0) with zilebesiran, 600 mg, once every 6 months; and 6.8 mm Hg (95% CI, 3.6-9.9) with placebo. LSM differences vs placebo in change from baseline to month 3 were -14.1 mm Hg (95% CI, -19.2 to -9.0; P < .001) with zilebesiran, 150 mg, once every 6 months; -16.7 mm Hg (95% CI, -21.2 to -12.3; P < .001) with zilebesiran, 300 mg, once every 3 months or every 6 months; and -15.7 mm Hg (95% CI, -20.8 to -10.6; P < .001) with zilebesiran, 600 mg, once every 6 months. Over 6 months, 60.9% of patients receiving zilebesiran had adverse events vs 50.7% patients receiving placebo and 3.6% had serious adverse events vs 6.7% receiving placebo. Nonserious drug-related adverse events occurred in 16.9% of zilebesiran-treated patients (principally injection site reactions and mild hyperkalemia) and 8.0% of placebo-treated patients. Conclusions and Relevance: In adults with mild to moderate hypertension, treatment with zilebesiran across a range of doses at 3-month or 6-month intervals significantly reduced 24-hour mean ambulatory SBP at month 3. Trial Registration: ClinicalTrials.gov Identifier: NCT04936035.

Transcatheter Leadless Pacemaker for the Treatment of Vasovagal Syncope.

Vasovagal syncope (VVS) is largely a benign condition focused on patient education, lifestyle modification, and avoidance of triggers. However, a subset of patients may benefit from permanent pacemaker placement. Commonly, patients with VVS are younger and those requiring pacing have symptoms associated with severe cardioinhibitory syncope. With the advent of leadless pacemaker systems, a lot of the risks associated with traditional transvenous pacemaker systems are mitigated. In this article, we provide a comprehensive review of the data available for the treatment of cardioinhibitory vasovagal syncope using leadless pacemaker systems.

Same-Day Discharge After Left Bundle Area Pacing.

BACKGROUND: Left bundle area pacing (LBAP) has emerged as an area that appears to be an attractive alternative to other forms of physiological pacing owing to its ease and favorable pacing parameters. Same-day discharge after conventional pacemakers, implantable cardioverter defibrillators, and more recently leadless pacemakers have become routine, especially after the COVID-19 pandemic. With the advent of LBAP, the safety and feasibility of same-day discharge remain unclear. METHODS: This is a retrospective, observational case series of consecutive, sequential patients undergoing LBAP at Baystate Medical Center, an academic teaching hospital. We included all patients who underwent LBAP and were discharged on the same day of procedure completion. Safety parameters included any procedure-related complications including pneumothorax, cardiac tamponade, septal perforation, and lead dislodgement. Pacemaker parameters included pacing threshold, R-wave amplitude, and lead impedance pre-discharge the following day of implantation and up to 6 months of follow-up. RESULTS: A total of 11 patients were included in our analysis, the average age was 70.3 ± 6.74 years. The most common indication for pacemaker insertion was AV block (73%). No complications were seen in any of the patients. The average time between the procedure and discharge was 5.6 hours. Pacemaker and lead parameters were stable after 6 months of follow-up. CONCLUSIONS: In this case series, we find that same-day discharge after LBAP for any indication is a safe and feasible option. As this mode of pacing becomes increasingly more common, larger prospective studies evaluating the safety and feasibility of early discharge after LBAP will be needed.

Periprocedural anticoagulation therapy in patients undergoing micra leadless pacemaker implantation.

Over the past decade, there has been significant improvement in the treatment cardiac diseases and symptomatic bradyarrhythmias with the development of leadless pacemaker systems. The Micra transcatheter pacemaker system has been shown to mitigate a lot of the complications associated with traditional pacing systems, which are notably skin pocket and lead-related complications. Numerous studies have shown the low complication rates associated with Micra procedure; however, there have been no specific guidelines or recommendations surrounding periprocedural anticoagulant therapy. This is important because a significant percentage of patients requiring pacemaker therapy have an indication for anticoagulation therapy as well. Multiple studies have shown the safety of uninterrupted anticoagulation during Micra implant, however, there is insufficient high-quality data to recommend periprocedural systemic use of anticoagulation. In this paper, we review the available data surrounding anticoagulation therapy in patients undergoing Micra implantation and the potential bleeding risks associated with this procedure.

Very low tidal volume, high-frequency ventilation in atrial fibrillation ablation: a systematic review.

BACKGROUND: Ventilation strategies in atrial fibrillation ablation affect procedure outcomes by influencing catheter stability. Studies have highlighted favorable atrial fibrillation (AF) ablation outcomes with the use of high-frequency jet ventilation (HFJV) which has been shown to improve lesion durability, energy delivery, and tissue contact. However, this mode of ventilation is not readily available. In this systematic review, we highlight the available data on the use of very low tidal volume, high-frequency ventilation using standard ventilators that aim to provide settings similar to HFJV during AF ablations. METHODS: Using a combination of search terms in databases and manual searches in bibliographies of identified articles, we reviewed all published data reported in the English language on the use of very low tidal volume with high-frequency ventilation during atrial fibrillation ablation. RESULTS: A total of 4 manuscripts were identified; 3 cohort studies and 1 case report. The utilization of standard ventilators with a high-frequency, very low tidal volume ventilation strategy appears to closely mimic the catheter stability benefits that HFJV ventilators provide. Across the 3 cohort identified studies, the use of this ventilation strategy was associated with improved catheter stability, tissue contact, and a decrease in radiofrequency time. No increased risk was identified compared to standard ventilation. CONCLUSION: With a purpose of limiting thoracic excursion and cardiac movement, limited and sparse studies have shown improved outcomes with a very low tidal volume, high-frequency ventilation strategy. Additional studies are needed to solidify this easily accessible and widely available mode of ventilation.

A Novel Annotation Technique During Mapping to Facilitate the Termination of Atrial Tachycardia Following Ablation for Atrial Fibrillation.

INTRODUCTION: The treatment of atrial tachycardia (AT) occurring after ablation for atrial fibrillation (AF) is challenging. The most common ablation strategy relies on entrainment, and electroanatomic activation mapping (EAM) using a conventional window of interest (WOI), centered on the easily detectable atrial signal on the coronary sinus catheter. We describe a novel EAM annotation technique that uses a WOI starting 40 milliseconds prior to the P wave in order to detect the reentrant AT exit site. This WOI timing is based on the similarity between scar-related reentrant AT and scar-related ventricular tachycardia. METHODS: Patients with AT after prior ablation for AF were included. The EAM of the AT was performed using the novel mapping annotation technique. The ablation was considered successful if the AT terminated during ablation at the site identified by this strategy. RESULTS: Twenty-eight patients with 36 ATs were included. The ATs were classified as follows: mitral annulus (13/36), roof (11/36), anterior/posterior/lateral left atrial wall (10/36), and RA (2/36). A complete EAM using the novel annotation technique was achieved in 34 of 36 AT's, encompassing 94 ± 6.5% of the cycle length. Low amplitude pre-P fractionated electrograms were found in 34 of 36 (94%) ATs and these occurred at a mean distance of 1.8 ± 1.2 mm from the "early-meets-late" line. Ablation at these areas resulted in termination of 34 of 36 ATs (94%). CONCLUSION: The novel EAM annotation allows the accurate detection of the critical isthmus of post-AF ablation AT. Ablation of these isthmuses results in termination of the AT in the vast majority of patients.

Feasibility and safety of uninterrupted rivaroxaban for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry.

OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety of uninterrupted rivaroxaban therapy during atrial fibrillation (AF) ablation. BACKGROUND: Optimal periprocedural anticoagulation strategy is essential for minimizing bleeding and thromboembolic complications during and after AF ablation. The safety and efficacy of uninterrupted rivaroxaban therapy as a periprocedural anticoagulant for AF ablation are unknown. METHODS: We performed a multicenter, observational, prospective study of a registry of patients undergoing AF ablation in 8 centers in North America. Patients taking uninterrupted periprocedural rivaroxaban were matched by age, sex, and type of AF with an equal number of patients taking uninterrupted warfarin therapy who were undergoing AF ablation during the same period. RESULTS: A total of 642 patients were included in the study, with 321 in each group. Mean age was 63 ± 10 years, with 442 (69%) males and 328 (51%) patients with paroxysmal AF equally distributed between the 2 groups. Patients in the warfarin group had a slightly higher mean HAS- BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) score (1.70 ± 1.0 vs. 1.47 ± 0.9, respectively; p = 0.032). Bleeding and embolic complications occurred in 47 (7.3%) and 2 (0.3%) patients (both had transient ischemic attacks) respectively. There were no differences in the number of major bleeding complications (5 [1.6%] vs. 7 [1.9%], respectively; p = 0.772), minor bleeding complications (16 [5.0%] vs. 19 [5.9%], respectively; p = 0.602), or embolic complications (1 [0.3%] vs. 1 [0.3%], respectively; p = 1.0) between the rivaroxaban and warfarin groups in the first 30 days. CONCLUSIONS: Uninterrupted rivaroxaban therapy appears to be as safe and efficacious in preventing bleeding and thromboembolic events in patients undergoing AF ablation as uninterrupted warfarin therapy.

Comparison of electroanatomical mapping systems: accuracy in left atrial mapping.

BACKGROUND: Current 3D mapping systems have difficulty rendering complex cardiac structures. Different electroanatomical mapping software has been recently developed which uses a mathematical algorithm to improve interpolation between mapped points and delineation of closely spaced structures. This study tested the feasibility and accuracy of this software in comparison to traditional software. METHODS: In vivo 3D impedance-based mapping using a multielectrode catheter with a single geometry point cloud was performed in the left atria and pulmonary veins (PV) in 23 patients undergoing catheter ablation for atrial fibrillation. The maps were analyzed with traditional (NavX, St. Jude Medical, Minnetonka, MN, USA), either with or without multichamber mapping versus St. Jude OneModel™ software and dimensions of cardiac chambers in human studies were compared to preprocedural computed tomographic (CT) or magnetic resonance (MR) scans to determine the relative accuracy of the maps. RESULTS: Maps created by the OneModel software provided greater detail of complex cardiac structures compared to traditional software. Comparison of the left atrial/pulmonary vein electroanatomical maps with the CT and MR scans as reference standard demonstrated significantly less error in measurement of all PV ostial long- and short-axis dimensions, inter-PV distance, and ridge width (left PV to left atrial appendage) with the OneModel versus traditional software (P < 0.001 for all dimensions measured). CONCLUSIONS: The OneModel software produces maps that are more accurate in rendering complex cardiac structures compared to traditional software.

Rapid acquisition of high-resolution electroanatomical maps using a novel multielectrode mapping system.

PURPOSE: Conventional electroanatomical mapping systems employ roving catheters with one or a small number of electrodes. Maps acquired using these systems usually contain a small number of points and take a long time to acquire. Use of a multielectrode catheter could facilitate rapid acquisition of higher-resolution maps through simultaneous collection of data from multiple points in space; however, a large multielectrode array could potentially limit catheter maneuverability. The purpose of this study was to test the feasibility of using a novel, multielectrode catheter to map the right atrium and the left ventricle. METHODS: Electroanatomical mapping of the right atrium and the left ventricle during both sinus and paced rhythm were performed in five swine using a conventional mapping catheter and a novel, multielectrode catheter. RESULTS: Average map acquisition times for the multielectrode catheter (with continuous data collection) ranged from 5.2 to 9.5 min. These maps contained an average of 2,753 to 3,566 points. Manual data collection with the multielectrode catheter was less rapid (average map completion in 11.4 to 18.1 min with an average of 870 to 1,038 points per map), but the conventional catheter was slower still (average map completion in 28.6 to 32.2 min with an average 120 to 148 points per map). CONCLUSIONS: Use of this multielectrode catheter is feasible for mapping the left ventricle as well as the right atrium. The multielectrode catheter facilitates acquisition of electroanatomical data more rapidly than a conventional mapping catheter. This results in shorter map acquisition times and higher-density electroanatomical maps in these chambers.

Predictors of atrial fibrillation termination and clinical success of catheter ablation of persistent atrial fibrillation.

The termination of persistent atrial fibrillation (AF) during catheter ablation has been associated in some, but not all, studies with reduced arrhythmia during clinical follow-up. We sought to determine the rate of persistent AF termination achievable with a stepwise ablation strategy, the predictors of AF termination, and the clinical outcomes associated with termination and nontermination. A total of 143 consecutive patients (age 62 ± 9 years, AF duration 5.7 ± 5.2 years) with persistent and longstanding persistent AF resistant to antiarrhythmic medication who presented in AF for catheter ablation were studied. Ablation was done with a stepwise approach, including pulmonary vein isolation, followed by complex fractionated atrial electrogram ablation and ablation of resultant atrial tachycardias. Clinical follow-up was then performed after a 2-month blanking period to assess arrhythmia recurrence, defined as AF or atrial tachycardia lasting ≥ 30 seconds. AF termination by ablation was achieved in 95 (66%) of the 143 patients. Multivariate predictors of AF termination included longer baseline AF cycle length (p <0.001) and smaller left atrial size (p = 0.002). AF termination by ablation was associated with both a lower incidence of arrhythmia recurrence after a single procedure without antiarrhythmic drugs (p = 0.01) and overall clinical success (single or multiple procedures, with or without antiarrhythmic drugs; p = 0.005). On multivariate analysis, the predictors of overall clinical success included AF termination by ablation (p = 0.001), a shorter ablation duration (p = 0.002), younger age (p = 0.02), male gender (p = 0.03), and the presence of hypertension (p = 0.03). In conclusion, among patients with persistent AF, termination of AF by ablation can be achieved in most patients and is associated with reduced recurrence of arrhythmia.

Feasibility and safety of dabigatran versus warfarin for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry.

OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety of periprocedural dabigatran during atrial fibrillation (AF) ablation. BACKGROUND: AF ablation requires optimal periprocedural anticoagulation for minimizing bleeding and thromboembolic complications. The safety and efficacy of dabigatran as a periprocedural anticoagulant for AF ablation are unknown. METHODS: We performed a multicenter, observational study from a prospective registry including all consecutive patients undergoing AF ablation in 8 high-volume centers in the United States. All patients receiving dabigatran therapy who underwent AF ablation on periprocedural dabigatran, with the dose held on the morning of the procedure, were matched by age, sex, and type of AF with an equal number of patients undergoing AF ablation with uninterrupted warfarin therapy over the same period. RESULTS: A total of 290 patients, including 145 taking periprocedural dabigatran and an equal number of matched patients taking uninterrupted periprocedural warfarin, were included in the study. The mean age was 60 years with 79% being male and 57% having paroxysmal AF. Both groups had a similar CHADS(2) score, left atrial size, and left ventricular ejection fraction. Three thromboembolic complications (2.1%) occurred in the dabigatran group compared with none in the warfarin group (p = 0.25). The dabigatran group had a significantly higher major bleeding rate (6% vs. 1%; p = 0.019), total bleeding rate (14% vs. 6%; p = 0.031), and composite of bleeding and thromboembolic complications (16% vs. 6%; p = 0.009) compared with the warfarin group. Dabigatran use was confirmed as an independent predictor of bleeding or thromboembolic complications (odds ratio: 2.76, 95% confidence interval: 1.22 to 6.25; p = 0.01) on multivariate regression analysis. CONCLUSIONS: In patients undergoing AF ablation, periprocedural dabigatran use significantly increases the risk of bleeding or thromboembolic complications compared with uninterrupted warfarin therapy.