Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND: Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation are not known. METHODS: In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events. RESULTS: A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999). CONCLUSIONS: Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.).

Arrhythmic Risk in Biventricular Pacing Compared With Left Bundle Branch Area Pacing: Results From the I-CLAS Study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy. We sought to compare the occurrence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP. METHODS: The I-CLAS study (International Collaborative LBBAP Study) included patients with left ventricular ejection fraction ≤35% who underwent BVP or LBBAP for cardiac resynchronization therapy between January 2018 and June 2022 at 15 centers. We performed propensity score-matched analysis of LBBAP and BVP in a 1:1 ratio. We assessed the incidence of VT/VF and new-onset AF among patients with no history of AF. Time to sustained VT/VF and time to new-onset AF was analyzed using the Cox proportional hazards survival model. RESULTS: Among 1778 patients undergoing cardiac resynchronization therapy (BVP, 981; LBBAP, 797), there were 1414 propensity score-matched patients (propensity score-matched BVP, 707; propensity score-matched LBBAP, 707). The occurrence of VT/VF was significantly lower with LBBAP compared with BVP (4.2% versus 9.3%; hazard ratio, 0.46 [95% CI, 0.29-0.74]; P<0.001). The incidence of VT storm (>3 episodes in 24 hours) was also significantly lower with LBBAP compared with BVP (0.8% versus 2.5%; P=0.013). Among 299 patients with cardiac resynchronization therapy pacemakers (BVP, 111; LBBAP, 188), VT/VF occurred in 8 patients in the BVP group versus none in the LBBAP group (7.2% versus 0%; P<0.001). In 1194 patients with no history of VT/VF or antiarrhythmic therapy (BVP, 591; LBBAP, 603), the occurrence of VT/VF was significantly lower with LBBAP than with BVP (3.2% versus 7.3%; hazard ratio, 0.46 [95% CI, 0.26-0.81]; P=0.007). Among patients with no history of AF (n=890), the occurrence of new-onset AF >30 s was significantly lower with LBBAP than with BVP (2.8% versus 6.6%; hazard ratio, 0.34 [95% CI, 0.16-0.73]; P=0.008). The incidence of AF lasting >24 hours was also significantly lower with LBBAP than with BVP (0.7% versus 2.9%; P=0.015). CONCLUSIONS: LBBAP was associated with a lower incidence of sustained VT/VF and new-onset AF compared with BVP. This difference remained significant after adjustment for differences in baseline characteristics between patients with BVP and LBBAP. Physiological resynchronization by LBBAP may be associated with lower risk of arrhythmias compared with BVP.

Left bundle branch area pacing using a lumenless lead: A systematic literature review and meta-analysis.

BACKGROUND: Although left bundle branch area pacing (LBBAP) has been shown to be a feasible option for delivering physiological pacing, data are largely limited to single-center reports. The aim of this analysis was to systematically assess the safety and efficacy of LBBAP with the Model 3830 lead among primarily bradycardia patients. METHODS AND RESULTS: PubMed, Embase, Cochrane Library, and Google Scholar were searched for full-text articles on LBBAP using the SelectSecure Model 3830 lumenless lead. Rates and means were estimated using random- and mixed-effects models. Of 3395 articles, 53 met inclusion criteria, representing 6061 patients undergoing an implant attempt. Average patient age was 68.1 years (95% CI: 66.6, 69.6) and 53.1% were male (95% CI: 50.5%, 55.7%). The average implant success rate among bradycardia-indicated patients was 92.7% (95% CI: 89.5%, 94.9%). The overall estimated procedural adverse event rate was 2.5% (95% CI: 1.1%, 5.4%). The estimated septal perforation rate at implant was 1.6% (95% CI: 1.0%, 2.6%) with no adverse clinical sequelae reported. Pacing thresholds were low at implant (0.67 V [95% CI: 0.64, 0.70]) and remained stable through 12 months (0.76 V [95% CI: 0.72, 0.80]). Among bradycardia-indicated patients, LVEF remained stable from baseline to post-implant (59.5% [95% CI: 57.9%, 61.1%] vs. 60.1% [95% CI: 58.5%, 61.7%]). CONCLUSION: This meta-analysis including 6061 patients implanted with a Model 3830 lead for LBBAP found an average implant success rate of 92.7% and a procedural adverse event rate of 2.5% with stable electrical parameters and LVEF post-implant.

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.

Institutional experience report on the target contouring workflow in the radiotherapy department for stereotactic arrhythmia radioablation delivered on conventional linear accelerators.

PURPOSE: In stereotactic arrhythmia radioablation (STAR), the target is defined using multiple imaging studies and a multidisciplinary team consisting of electrophysiologist, cardiologist, cardiac radiologist, and radiation oncologist collaborate to identify the target and delineate it on the imaging studies of interest. This report describes the workflow employed in our radiotherapy department to transfer the target identified based on electrophysiology and cardiology imaging to the treatment planning image set. METHODS: The radiotherapy team was presented with an initial target in cardiac axes orientation, contoured on a wideband late gadolinium-enhanced (WB-LGE) cardiac magnetic resonance (CMR) study, which was subsequently transferred to the computed tomography (CT) scan used for treatment planning-i.e., the average intensity projection (AIP) image set derived from a 4D CT-via an axial CMR image set, using rigid image registration focused on the target area. The cardiac and the respiratory motion of the target were resolved using ciné-CMR and 4D CT imaging studies, respectively. RESULTS: The workflow was carried out for 6 patients and resulted in an internal target defined in standard anatomical orientation that encompassed the cardiac and the respiratory motion of the initial target. CONCLUSION: An image registration-based workflow was implemented to render the STAR target on the planning image set in a consistent manner, using commercial software traditionally available for radiation therapy.

Stepping back for good reasons: a reappraisal of the DF-1 connector for defibrillator leads.

The DF-4 defibrillator standard has been rapidly adopted due to its convenience at implantation. There are however trade-offs compared to the traditional DF-1 standard that are underappreciated. This viewpoint outlines the advantages and limitations of current defibrillator lead standards that should be kept in mind, as they impact the options that are available to deal with issues that may arise.

Rationale and design of a randomized study comparing the Watchman FLX device to DOACs in patients with atrial fibrillation.

BACKGROUND: Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy. STUDY DESIGN: A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding. CONCLUSIONS: This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF. CLINICAL TRIAL REGISTRATION: NCT04394546.

Ex-vivo histopathologic examination of irrigated radiofrequency ablation utilizing half-normal saline of the human heart.

INTRODUCTION: Radiofrequency ablation (RFA) utilizing half-normal saline (HNS) irrigation is a promising intervention to circumvent commonly encountered limitations during radiofrequency ablation of deep myocardial substrate. Few studies to date have analyzed the morphologic changes in the human myocardium following HNS RFA. METHODS AND RESULTS: Three patients with symptomatic ventricular tachycardia (VT) who underwent RFA with HNS irrigation underwent pathological specimen examination at time of autopsy or following native heart explant at the time of cardiac transplantation. Gross evaluation of the heart was performed fresh and after fixation in 10% formalin. A routine examination was performed with fixation in 10% formalin. Sections of lesioned tissue were paraffin embedded and evaluated using standard hematoxylin and eosin (H&E) staining. CONCLUSION: Irrigated RF ablation with HNS irrigant produces coagulative necrosis as well as several delayed histopathological changes with a deeper field of effective ablation. Transmurality may not be obtained in the ventricular myocardium with endocardial, epicardial, or sequential unipolar HNS ablation.

Clinical outcomes of conduction system pacing versus biventricular pacing for cardiac resynchronization therapy: A systematic review and meta-analysis.

INTRODUCTION: Conduction system pacing (CSP) is observed to produce greater improvements in echocardiographic and hemodynamic parameters as compared to conventional biventricular pacing (BiVP). However, whether these surrogate endpoints directly translate to improvements in hard clinical outcomes such as death and heart failure hospitalization (HFH) with CSP remains uncertain as studies reporting these outcomes are scarce. The aim of this meta-analysis was to analyze the existing data to compare the clinical outcomes of CSP versus BiVP. METHODS: A systematic search of the Embase and PubMed database was performed for studies comparing CSP and BiVP for patients indicated to receive a CRT device. The coprimary endpoints were all-cause mortality and HFH. Other secondary outcomes included change in left ventricular ejection fraction (LVEF), change in NYHA class, and increase in NYHA class ≥1. A random-effects model was chosen a priori to analyze the composite effects given the anticipated heterogeneity of included trials. RESULTS: Twenty-one studies (4 randomized and 17 observational) were identified reporting either primary outcome and were included in the meta-analysis. In total 1960 patients were assigned to CSP and 2367 to BiVP. Median follow-up time was 10.1 months (ranging 2-33 months). CSP was associated with a significant reduction in all-cause mortality (odds ratio [OR] 0.68, 95% confidence interval [CI]: 0.56-0.83) and HFH (OR 0.52, 95% CI: 0.44-0.63). Mean improvement in LVEF was also greater with CSP (mean difference 4.26, 95% CI: 3.19-5.33). Reduction in NYHA class was significantly greater with CSP (mean difference -0.36, 95% CI: -0.49 to -0.22) and the number of patients with an increase in NYHA class ≥1 was significantly greater with CSP (OR 2.02, 95% CI: 1.70-2.40). CONCLUSIONS: CSP was associated with a significant reduction in all-cause mortality and HFH when compared to conventional BiVP for CRT. Further large-scale randomized trials are needed to verify these observations.

Paroxysmal atrial fibrillation ablation with a novel temperature-controlled CF-sensing catheter: Q-FFICIENCY clinical and healthcare utilization benefits.

INTRODUCTION: The prospective, nonrandomized, multicenter Q-FFICIENCY study demonstrated the safety and 12-month efficacy of paroxysmal atrial fibrillation (AF) ablation with the novel QDOT MICRO temperature-controlled, contact force-sensing, radiofrequency (RF) catheter. Participants underwent pulmonary vein isolation with very high-power short-duration (vHPSD) mode (90 W, ≤4 s) alone or combined with conventional-power temperature-controlled (CPTC) mode (25-50 W). This study aimed to assess quality-of-life (QOL) and healthcare utilization (HCU) benefits experienced by Q-FFICIENCY study participants. METHODS: Besides evaluating procedural efficiency, QOL and HCU were assessed through 12 months postablation via Atrial Fibrillation Effect on Quality-of-Life Tool (AFEQT) score, antiarrhythmic drug (AAD) use, and incidence of cardioversion and cardiovascular hospitalization. RESULTS: Of 191 participants enrolled, 166 were ablated with the new catheter. Compared to baseline, statistically significant, clinically meaningful improvements in composite and subcategories of AFEQT scores were observed at 3 months and sustained through 12 months (12-month increase, 29.3-44.2 points). Class I/III AAD use decreased from 97.6% (162/166) at baseline to 19.6% (31/158) during Months 6-12, representing a significant 79.9% reduction. The cardioversion rate significantly declined by 93.9% from 31.3% (12 months preablation) to 1.9% (evaluation period). One-year Kaplan-Meier estimates of freedom from all-cause and cardiovascular hospitalization were 80.9% (95% confidence interval [CI], 74.8%-86.9%) and 88.8% (95% CI, 84.0%-93.7%), respectively. CONCLUSIONS: Paroxysmal AF ablation with the novel temperature-controlled RF catheter in vHPSD mode, alone or with CPTC mode, led to clinically meaningful improvement in QOL and significant reduction in AAD use, cardioversion, and cardiovascular hospitalization.

Conventional biventricular pacing is still preferred to conduction system pacing for atrioventricular block in patients with reduced ejection fraction and narrow QRS.

It is well established that right ventricular pacing is detrimental in patients with reduced cardiac function who require ventricular pacing (VP), and alternatives nowadays are comprised of biventricular pacing (BiVP) and conduction system pacing (CSP). The latter modality is of particular interest in patients with a narrow baseline QRS as it completely avoids, or minimizes, ventricular desynchronization associated with VP. In this article, experts debate whether BiVP or CSP should be used to treat these patients.

The evolving state of cardiac resynchronization therapy and conduction system pacing: 25 years of research at EP Europace journal.

Cardiac resynchronization therapy (CRT) was proposed in the 1990s as a new therapy for patients with heart failure and wide QRS with depressed left ventricular ejection fraction despite optimal medical treatment. This review is aimed first to describe the rationale and the physiologic effects of CRT. The journey of the landmark randomized trials leading to the adoption of CRT in the guidelines since 2005 is also reported showing the high level of evidence for CRT. Different alternative pacing modalities of CRT to conventional left ventricular pacing through the coronary sinus have been proposed to increase the response rate to CRT such as multisite pacing and endocardial pacing. A new emerging alternative technique to conventional biventricular pacing, conduction system pacing (CSP), is a promising therapy. The different modalities of CSP are described (Hirs pacing and left bundle branch area pacing). This new technique has to be evaluated in clinical randomized trials before implementation in the guidelines with a high level of evidence.

Conduction system pacing: overview, definitions, and nomenclature.

Pacing from the right ventricle is associated with an increased risk of development of congestive heart failure, increases in total and cardiac mortality, and a worsened quality of life. Conduction system pacing has become increasingly realized as an alternative to right ventricular apical pacing. Conduction system pacing from the His bundle and left bundle branch area has been shown to provide physiologic activation of the ventricle and may be an alternative to coronary sinus pacing. Conduction system pacing has been studied as an alternative for both bradycardia pacing and for heart failure pacing. In this review, we summarize the clinical results of conduction system pacing under a variety of different clinical settings. The anatomic targets of conduction system pacing are illustrated, and electrocardiographic correlates of pacing from different sites in the conduction system are defined. Ultimately, clinical trials comparing conduction system pacing with standard right ventricular apical pacing and cardiac resynchronization therapy pacing will help define its benefit and risks compared with existing techniques.

Hemodynamic response and safety of vasodilator stress cardiovascular magnetic resonance in patients with permanent pacemakers or implantable cardioverter-defibrillators.

INTRODUCTION: Vasodilator stress cardiovascular magnetic resonance (CMR) is a powerful diagnostic modality, but data toward its use in patients with permanent pacemakers (PPMs) or implantable cardioverter-defibrillators (ICDs) is limited. METHODS AND RESULTS: Patients with ICDs (>1% pacing) or PPMs who underwent regadenoson single photon emission computed tomography (SPECT) and all patients with ICDs or PPMs who underwent stress CMR were retrospectively identified. SPECT tests were analyzed for hemodynamic responses and new pacing requirements; CMR studies were examined for safety, device characteristics and programming, hemodynamic responses, and image quality. Changes from baseline were evaluated with the Related-Samples Wilcoxon Signed Rank Test. Of 67 patients (median age 65 [IQR 58-72] years, 31 [46%] female, 31 [46%] Black), 47 underwent SPECT and 20 CMR. With regadenoson SPECT, 89% of patients experienced tachycardic responses above resting heart rates (+19 [13-32] beats per minute, p < .01). During stress CMR, 10 (50%) devices were asynchronously paced approximately 10 beats per minute above resting rates, and the remaining were temporarily deactivated. Those with asynchronous pacing had no changes in heart rates, whereas patients with deactivated devices had near uniform heart rate accelerations. Image quality was diagnostic in the majority of stress CMR sequences, with nonconditional ICDs contributing 40 of 57 (70%) of nondiagnostic segments. CONCLUSION: This data supports the safety of vasodilator stress CMR with promising diagnostic quality images in patients with CMR conditional ICDs and PPMs. Despite a near uniform tachycardic response to regadenoson in the SPECT environment, high rates of asynchronous pacing during vasodilator stress CMR did not result in competitive pacing or adverse arrhythmic events. Further studies are needed to validate these findings and confirm the diagnostic and prognostic performance of stress CMR in these individuals.

Cardiac resynchronization therapy via left bundle branch pacing vs. optimized biventricular pacing with adaptive algorithm in heart failure with left bundle branch block: a prospective, multi-centre, observational study.

AIMS: The purpose of our study was to evaluate the feasibility and efficacy of cardiac resynchronization therapy (CRT) via left bundle branch pacing (LBBP-CRT) compared with optimized biventricular pacing (BVP) with adaptive algorithm (BVP-aCRT) in heart failure with reduced left ventricular ejection fraction ≤35% (HFrEF) and left bundle branch block (LBBB). METHODS AND RESULTS: One hundred patients with HFrEF and LBBB undergoing CRT were prospectively enrolled in a non-randomized fashion and divided into two groups (LBBP-CRT, n = 49; BVP-aCRT, n = 51) in four centres. Implant characteristics and echocardiographic parameters were accessed at baseline and during 6-month and 1-year follow-up. The success rate for LBBP-CRT and BVP-aCRT was 98.00% and 91.07%. Fused LBBP had the greatest reduced QRS duration compared to BVP-aCRT (126.54 ± 11.67 vs. 102.61 ± 9.66 ms, P < 0.001). Higher absolute left ventricular ejection fraction (LVEF) and △LVEF was also achieved in LBBP-CRT than BVP-aCRT at 6-month (47.58 ± 12.02% vs. 41.24 ± 10.56%, P = 0.008; 18.52 ± 13.19% vs. 12.89 ± 9.73%, P = 0.020) and 1-year follow-up (49.10 ± 10.43% vs. 43.62 ± 11.33%, P = 0.021; 20.90 ± 11.80% vs. 15.20 ± 9.98%, P = 0.015, P = 0.015). There was no significant difference in response rate between two groups while higher super-response rate was observed in LBBP-CRT as compared to BVP-aCRT at 6 months (53.06% vs. 36.59%, P = 0.016) and 12 months (61.22% vs. 39.22%, P = 0.028) during follow-up. The pacing threshold was lower in LBBP-CRT at implant and during 1-year follow-up (both P < 0.001). Procedure-related complications and adverse clinical outcomes including heart failure hospitalization and mortality were not significantly different in two groups. CONCLUSIONS: The feasibility and efficacy of LBBP-CRT demonstrated better electromechanical resynchronization and higher clinical and echocardiographic response, especially higher super-response than BVP-aCRT in HFrEF with LBBB.

Interleukin-1 blockade in cardiac sarcoidosis: study design of the multimodality assessment of granulomas in cardiac sarcoidosis: Anakinra Randomized Trial (MAGiC-ART).

BACKGROUND: Sarcoidosis is an inflammatory disease characterized by the formation of granulomas, which involve the heart in up to 25% of patients. Cardiac sarcoidosis can lead to life threatening arrhythmias and heart failure. While corticosteroids have been used as a treatment for over 50 years, they are associated with hypertension, diabetes, and weight gain, further increasing cardiovascular risk. Interleukin-1 (IL-1) is the prototypical proinflammatory cytokine that works to activate the nuclear transcription factor NF-kB, one of the targets of glucocorticoids. IL-1 also plays an important role also in the pathophysiology of heart disease including atherosclerosis, myocardial infarction, and myocarditis. METHODS: Building on a network of research collaborators developed in the Cardiac Sarcoidosis Consortium, we will investigate the feasibility and tolerability of treatment of CS with anakinra at two National Institute of Health Clinical and Translational Science Award (CTSA) hubs with expertise in cardiac sarcoidosis. In this pilot study, up to 28 patients with cardiac sarcoidosis will be recruited to compare the administration of an IL-1 blocker, anakinra, 100 mg daily on top of standard of care versus standard of care only for 28 days and followed for 180 days. Utilizing surrogate endpoints of changes in systemic inflammatory biomarkers and cardiac imaging, we aim to determine whether IL-1 blockade with anakinra can combat systemic and cardiac inflammation in patients with cardiac sarcoidosis. DISCUSSION: The current trial demonstrates an innovative collaborative approach to clinical trial development in a rare, understudied disease that disproportionately affects females and minorities. Trial Registration The trial was registered prospectively with ClinicalTrials.gov on July 12, 2019, identifier NCT04017936.

Procedure characteristics and outcomes of atrial fibrillation ablation procedures using cryoballoon versus radiofrequency ablation: A report from the GWTG-AFIB registry.

INTRODUCTION: Cryoballoon ablation (CBA) is an alternative to radiofrequency ablation (RFA) for ablation of atrial fibrillation (AF) and real-world comparisons of this strategy are lacking. As such, we sought to compare patient and periprocedural characteristics and outcomes of CBA versus RFA in the Get With the Guidelines AFIB Registry. METHODS: Categorical variables were compared via the χ2 test and continuous variables were compared via the Wilcoxon rank-sum test. Adjusted analyses were performed using overlap weighting of propensity scores. RESULTS: A total of 5247 (1465 CBA, 3782 RFA) ablation procedures were reported from 33 sites. Those undergoing CBA more often had paroxysmal AF (60.0% vs. 48.8%) and no prior AF ablation (87.5% vs. 73.8%). CHA2 DS2 -VASc scores were similar. Among de novo ablations, most ablations involved intracardiac echocardiography and electroanatomic mapping, but both were less common with CBA (87.3% vs. 93.9%, p < .0001, and 87.7% vs. 94.6%, p < .0001, respectively). CBA was associated with shorter procedures (129 vs. 179 min, p < .0001), increased fluoroscopy use (19 vs. 11 min, p < .0001), and similar ablation times (27 vs. 35 min, p = .15). Nonpulmonary vein ablation was common with CBA: roof line 38.6%, floor line 20.4%, cavotricuspid isthmus 27.7%. RFA was associated with more total complications compared to CBA (5.4% vs. 2.3%, p < .0001), due to more volume overload and "other" events, although phrenic nerve injury was more common with CBA (0.9% vs 0.1%, p = .0001). In the adjusted model, any complication was less common among CBA cases (odds ratio, 0.45; confidence interval, 0.25-0.79, p = .0056). CONCLUSION: CBA was associated with fewer complications, and shorter procedure times, and greater fluoroscopy times, compared to RFA. Nonpulmonary vein ablation and electroanatomic mapping system use was common with CBA.

Safety and feasibility of left bundle branch area pacing following valvular interventions: Multicenter study.

OBJECTIVES: To evaluate the safety and feasibility of left bundle branch area pacing (LBBAP) in patients with valvular interventions. METHODS: Eighty-four patients were included in this study. All patients underwent recent surgical or percutaneous valvular interventions. LBBAP was attempted in all patients. Implant success rates, peri- and postprocedure electrocardiogram, pacing parameters, and complications were assessed at implant, and during follow-up. RESULTS: LBBAP implantation was successful in 80/84 (95%) patients. Mean age was 74.1 ± 13.8 years and 56% patients were male. Prior valvular replacements included: percutaneous aortic (26), surgical aortic (36), combined surgical aortic plus mitral (6), MVR (10), tricuspid (1), and pulmonic (1). Average LVEF was 52.6 ± 11%. Majority of patients underwent LBBAP due to atrioventricular block (76%) and sinus node disease (13%). Total procedure duration was 74.1 ± 12.5 min and fluoroscopic duration was 9.7 ± 6.8 min. Pacing parameters were stable during follow-up period of 10.0 ± 6.3 months. Pacing QRS duration was significantly narrower than baseline QRS duration (131.5 ± 31.4 ms vs. 114.3 ± 13.7 ms, p < .001, respectively). No acute complications were observed. Mean follow-up was 10.0 ± 6.3 months (median: 8.4 months, min: 1 and max: 24 months). During follow-up, there were three device infections and two patients had loss of LBBA capture within 1 month of implant. CONCLUSIONS: LBBAP is a feasible and safe pacing modality in patients with prior interventions for valvular heart disease.

Electrocardiographic characteristics and ablation of ventricular arrhythmias originating from the basal inferoseptal area.

AIMS: Ventricular arrhythmias (VAs) from the basal inferoseptal (BIS) area are rare and can pose unique challenges during catheter ablation (CA) due to the anatomic complexity. The study sought to describe the electrocardiographic and clinical characteristics of VAs originating from the BIS area. METHODS AND RESULTS: Patients with VAs and successful ablation at the BIS area from 2016 to 2020 were included. The 12-lead electrocardiogram (ECG), intracardiac findings, and outcomes were analysed. Of 482 patients with VAs referred for CA, 17 (3.5%) had successful ablation at BIS area. There were 12 males, mean age was 66.7 ± 9 years, 82% had ejection fraction <50%. Mean baseline premature ventricular complex burden was 28.6 ± 9%. All patients had a leftward superior axis. Left bundle branch block (LBBB) with early transition in V2 was noted in eight patients and right bundle branch block (RBBB) in nine patients. Detailed mapping of the right ventricle (RV) was performed in 15 patients (88%), coronary sinus (CS)/middle cardiac vein (MCV) in 13 (76%), right atrium (RA) adjacent to the inferoseptal process (ISP) of left ventricle (LV) in 5 (29%), ISP-LV in 13 (76%), and epicardium in 2 (12%). Successful ablation site was in LV in 10 (59%), RV in 2 (12%), CS/MCV in 1 (6%), RA in 1 (6%), and epicardium in 2 (12%). Fifteen patients (88%) required mapping in at least two chambers (range 2-5) and seven patients (41%) required ablation in at least two chambers (range 2-3). CONCLUSIONS: Ventricular arrhythmias originating in the BIS are uncommon. The most common ECG patterns were leftward superior axis, LBBB with transition in V2 or RBBB. The VA foci can be endocardial or epicardial and meticulous mapping/ablation from multiple chambers is often required to eliminate these foci successfully.

Anatomy of the cardiac conduction system.

The specialized cardiomyocytes that constitute the conduction system in the human heart, initiate the electric impulse and result in rhythmic and synchronized contraction of the atria and ventricles. Although the atrioventricular (AV) conduction axis was described more than a century ago by Sunao Tawara, the anatomic pathway for propagation of impulse from atria to the ventricles has been a topic of debate for years. Over the past 2 decades, there has been a resurgence of conduction system pacing (CSP) by implanting pacing leads in the His bundle region in lieu of chronic right ventricular pacing that is associated with worse clinical outcomes. The inherent limitations of implanting the leads in the His bundle region has led to the emergence of left bundle branch area pacing in the past 3 years as an alternative strategy for CSP. The clinical experience from performing CSP has helped electrophysiologists gain deeper insight into the anatomy and physiology of cardiac conduction system. This review details the anatomy of the cardiac conduction system, and highlights some of the recently published articles that aid in better understanding of the AV conduction axis and its variations, the knowledge of which is critical for CSP. The remarkable evolution in technology has led to visualization of the cardiac conduction system using noninvasive, nondestructive high-resolution contrast-enhanced micro-computed tomography imaging that may aid in future CSP. We also discuss from anatomical perspective, the differences seen clinically with His bundle pacing and left bundle branch area pacing.