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One of the fundamental unmet clinical needs within cardiac electrophysiology is intraoperative assessment of catheter ablation, which can lead to recurrent arrhythmias and subsequent complications if ineffective. This work demonstrates photoacoustic imaging (PAI) of radiofrequency ablation (RFA) lesions in an in vivo swine model (n=3). Spectral unmixing of PAI data provides local myocardial characterization (e.g., oxygen saturation & tissue ablation) by overlaying unmixed PAI images with B-mode ultrasound imaging (PAI/US), with the latter providing anatomical context. Based on stained gross pathology, areas of central tissue necrosis coincided with increases in unmixed ablated regions of the myocardium. An average contrast-to-noise ratio of 2.8±0.2 confirmed lesion detectability, while the lesion dimensions quantified from PAI and pathology did not present significant differences. In vivo PAI of RFA lesions to determine ablation characteristics could lead to a paradigm shift in catheter ablation assessment and improve clinical outcomes.

Background: The increasing prevalence of atrial fibrillation (AF) and chronic kidney diseases highlights the need for a deeper comprehension of the molecular mechanisms linking them. Mutations in PKD1, the gene encoding Polycystin-1 (PKD1 or PC1), account for 85% of autosomal dominant polycystic kidney disease (ADPKD) cases. This disease often includes cardiac complications such as AF. In cardiomyocytes, PC1 deletion reduces hypertrophic response to pressure overload but promotes baseline ventricular dysfunction, while deletion in fibroblasts ameliorates post-myocardial infarction fibrosis. Despite its known cardiac impact, the role of PC1 in atrial cardiomyocytes and arrhythmias is less understood. Here, we sought to investigate the role of PC1 in AF., Methods: We used intracardiac programmed stimulation and optical mapping to evaluate AF inducibility in two mouse models, Pkd1 R3277C, which recapitulates human ADPKD progression, and cardiomyocyte-specific Pkd1 deletion, and their respective controls. Isolated adult mouse atrial cardiomyocytes, human iPSC-derived atrial cardiomyocytes (hiPSC-aCM), and HL-1 cells served as in vitro cellular models. Molecular mechanisms were evaluated using optical mapping and molecular and biochemical approaches., Results: Loss-of-function PC1 mutations significantly increased AF susceptibility in vivo and facilitated local reentry in ex vivo left atrial appendages. Comprehensive in vitro experiments supported a direct effect of PC1 in atrial cardiomyocytes. PC1-deficient monolayers exhibited increased arrhythmic events, escalating into reentrant spiral waves post-tachypacing. Transcriptomics analysis revealed PC1-dependent regulation of DNA repair, with PC1 deficiency leading to increased DNA damage under stress. PARP1 inhibitors or nicotinamide riboside, which counteract DNA damage-related metabolic consequences, reduced in vitro arrhythmias PC1-deficient monolayers. Overexpression of the C-terminus of PC1 had the opposite effects in DNA repair genes, suggesting its regulatory effects in atrial cardiomyocytes through retinoblastoma/E2F. Analyses of human atrial tissue from non-ADPKD patients showed reduced levels of mature PC1, suggesting a broader relevance of impaired PC1 in AF., Conclusions: Impaired PC1 increases in vivo AF inducibility under programmed electrical stimulation and promotes in vitro arrhythmias in hiPSC-aCM and HL-1 cells. Our findings indicate that PC1 protects against DNA damage to reduce AF susceptibility.

Competing Interests: Disclosures Dr Turagam has served as a consultant for Biosense Webster and Boston Scientific. Dr Nair has served as a consultant for Boston Scientific and Johnson & Johnson. Dr Doshi has served as a consultant for Boston Scientific and Abbott Vascular. Dr Valderrabano has served as a consultant for Biosense Webster and Abbott. Dr Natale has served as a consultant for Abbott, Biosense Webster, and Boston Scientific. Dr Halperin has served as a consultant for Abbott and Bayer HealthCare. Dr Mansour has received consulting fees from Biosense Webster and Boston Scientific. Dr Reddy has served as an unpaid consultant for Boston Scientific, Biosense Webster, and Abbott. Dr Reddy has served as a consultant to Boston Scientific and Abbott; and unrelated to this manuscript, he has served as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Anumana, Apama Medical-Boston Scientific, APN Health, Append Medical, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, Cardiofocus, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EP Frontiers, Farapulse-Boston Scientific, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Laminar Medical, LuxMed, Medlumics, Neutrace, Nuvera-Biosense Webster, Oracle Health, Pulse Biosciences, Restore Medical, Sirona Medical, SoundCath; and unrelated to this work, has served as a consultant for Adagio Medical, AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Cairdac, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Novo Nordisk, Philips; and has equity in Atraverse, DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The Kunming-Montreal Global Biodiversity Framework (GBF) of the UN Convention on Biological Diversity set the agenda for global aspirations and action to reverse biodiversity loss. The GBF includes an explicit goal for maintaining and restoring biodiversity, encompassing ecosystems, species and genetic diversity (goal A), targets for ecosystem protection and restoration and headline indicators to track progress and guide action 1 . One of the headline indicators is the Red List of Ecosystems 2 , the global standard for ecosystem risk assessment. The Red List of Ecosystems provides a systematic framework for collating, analysing and synthesizing data on ecosystems, including their distribution, integrity and risk of collapse 3 . Here, we examine how it can contribute to implementing the GBF, as well as monitoring progress. We find that the Red List of Ecosystems provides common theory and practical data, while fostering collaboration, cross-sector cooperation and knowledge sharing, with important roles in 16 of the 23 targets. In particular, ecosystem maps, descriptions and risk categories are key to spatial planning for halting loss, restoration and protection (targets 1, 2 and 3). The Red List of Ecosystems is therefore well-placed to aid Parties to the GBF as they assess, plan and act to achieve the targets and goals. We outline future work to further strengthen this potential and improve biodiversity outcomes, including expanding spatial coverage of Red List of Ecosystems assessments and partnerships between practitioners, policy-makers and scientists., (© 2024. Springer Nature Limited.)

Background: Strokes after left atrial appendage closure (LAAC) prophylaxis are generally less severe than those after warfarin prophylaxis-thought to be secondary to more hemorrhagic strokes with warfarin. Hemorrhagic strokes are similarly infrequent with direct oral anticoagulant (DOAC) prophylaxis, so the primary subtype after either LAAC or DOAC prophylaxis is ischemic stroke (IS)., Objectives: The purpose of this study was to compare the severity of IS using the modified Rankin Scale in atrial fibrillation patients receiving prophylaxis with DOACs vs LAAC., Methods: A retrospective analysis was performed of consecutive patients undergoing LAAC at 8 centers who developed an IS (IS LAAC ) compared with contemporaneous consecutive patients who developed IS during treatment with DOACs (IS DOAC ). The primary outcome was disabling/fatal stroke (modified Rankin Scale 3-5) at discharge and 3 months later., Results: Compared with IS DOAC patients (n = 322), IS LAAC patients (n = 125) were older (age 77.2 ± 13.4 years vs 73.1 ± 11.9 years; P = 0.002), with higher HAS-BLED scores (3.0 vs 2.0; P = 0.004) and more frequent prior bleeding events (54.4% vs 23.6%; P < 0.001), but similar CHA 2 DS 2 -VASc scores (5.0 vs 5.0; P = 0.28). Strokes were less frequently disabling/fatal with IS LAAC than IS DOAC at both hospital discharge (38.3% vs 70.3%; P < 0.001) and 3 months later (33.3% vs 56.2%; P < 0.001). Differences in stroke severity persisted after propensity score matching. By multivariate regression analysis, IS LAAC was independently associated with fewer disabling/fatal strokes at discharge (OR: 0.22; 95% CI: 0.13-0.39; P < 0.001) and 3 months (OR: 0.25; 95% CI: 0.12-0.50; P < 0.001), and fewer deaths at 3 months (OR: 0.28; 95% CI: 0.12-0.64; P < 0.001)., Conclusions: Ischemic strokes in patients with atrial fibrillation are less often disabling or fatal with LAAC than DOAC prophylaxis., Competing Interests: Funding Support and Author Disclosures Dr Turagam has served as a consultant for Biosense Webster and Sanofi. Dr Nair has served as a consultant for and receives honoraria for speaking engagements from Boston Scientific, Johnson and Johnson, and Medtronic. Dr Doshi has served as a consultant to Boston Scientific, Biosense Webster, and Abbott Vascular. Dr Valderrabano has received scientific research support from and served as a consultant to Circa; has received research support from and served as a consultant to Biosense Webster; and has served as a consultant to Abbott. Dr Dukkipati has received payment for Farapulse acquisition from Boston Scientific; and has equity in Manual Surgical Sciences. Dr Natale has served as a consultant for Abbott, Baylis, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. Dr Reddy has served as an unpaid consultant to Boston Scientific; unrelated to this paper, he has served as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Apama Medical-Boston Scientific, Anumana, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, and Valcare; unrelated to this work, has served as a consultant for Abbott, AtriAN, Biosense Webster, BioTel Heart, Biotronik, Cairdac, Cardiofocus, Cardionomic, CoreMap, Fire1, Gore and Associates, Impulse Dynamics, Medtronic, Novartis, Philips, and Pulse Biosciences; and has equity in DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: QDOT MICRO (QDM) is a novel contact force-sensing catheter optimized for temperature-controlled radiofrequency (RF) ablation. The very high-power short-duration (vHPSD) algorithm modulates power, maintaining target temperature during 90 W ablations for ≤4 seconds., Objectives: This study aims to evaluate safety and 12-month effectiveness of the QDM catheter in paroxysmal atrial fibrillation (AF) ablation using the vHPSD mode combined with conventional-power temperature-controlled (CPTC) mode., Methods: In this prospective, multicenter, nonrandomized study, patients with drug-refractory, symptomatic paroxysmal AF underwent pulmonary vein (PV) isolation with QDM catheter with vHPSD as primary ablation mode, with optional use of the CPTC mode (25 to 50 W) for PV touch-up or non-PV ablation. The primary safety endpoint was incidence of primary adverse events within ≤7 days of ablation. The primary effectiveness endpoint was freedom from documented atrial tachyarrhythmia recurrence and acute procedural, repeat ablation, and antiarrhythmic drug failure., Results: Of 191 enrolled participants, 166 had the catheter inserted, received RF ablation, and met eligibility criteria. Median procedural, RF application for ablating PVs, and fluoroscopy times were 132.0, 8.0, and 9.1 minutes, respectively. The primary adverse event rate was 3.6%. Imaging conducted in a subset of participants (n = 40) at 3 months did not show moderate or severe PV stenosis. The Kaplan-Meier estimated 12-month rate for primary effectiveness success was 76.7%; freedom from atrial tachyarrhythmia recurrence was 82.1%; clinical success (freedom from symptomatic recurrence) was 86.0%; and freedom from repeat ablation was 92.1%., Conclusions: Temperature-controlled paroxysmal AF ablation with the novel QDM catheter in vHPSD mode (90 W, ≤4 seconds), alone or with CPTC mode (25 to 50 W), is highly efficient and effective without compromising safety. (Evaluation of QDOT MICRO Catheter for Pulmonary Vein Isolation in Subjects With Paroxysmal Atrial Fibrillation [Q-FFICIENCY]; NCT03775512)., Competing Interests: Funding Support and Author Disclosures This study was supported by Biosense Webster, Inc. Dr Osorio has received grants from Biosense Webster, Inc, and Abbott; has received consulting fees from Biosense Webster, Inc, Boston Scientific, and Medtronic; and has received payments or honoraria for lectures/presentations/Speakers Bureau from Biosense Webster, Inc, and Boston Scientific. Dr Hussein has received steering committee funding from Biosense Webster, Inc. Dr Delaughter has received consulting fees and advisory board payments from Biosense Webster, Inc. Dr Natale has received consulting fees from Abbott, Baylis, Biosense Webster, Inc, Boston Scientific, Biotronik, and Medtronic. Dr Dukkipati has received grants from Biosense Webster, Inc. Dr Oza has received consulting fees from Biosense Webster, Inc and Atricure. Dr Daoud has received consulting fees from Biosense Webster, Inc, Medtronic, and S4 Medical; has received payments or honoraria for lectures/presentations/Speakers Bureau from ABIM, Western AF, and JACC: Clinical Electrophysiology; has patents planned, issued, or pending; has a leadership role in S4 Medical; and has stock/stock options from S4 Medical. Dr Di Biase has received consulting fees from Biosense Webster, Inc, Stereoataxis, and Rhythm Management; and has received speaker honoraria/travel from Biosense Webster, Inc, St Jude Medical (now Abbott), Boston Scientific, Medtronic, Biotronik, Atricure, Baylis, and Zoll. Dr Mansour has received grants from Biosense Webster, Inc, and Boston Scientific; has received consulting fees from Biosense Webster, Inc, Boston Scientific, Philips, and Medtronic; has received support for attending meetings/travel from Biosense Webster, Inc, and Boston Scientific; and has stock/stock options from New Pace Limited and EPD Solutions. Dr Valderrabano has received consulting fees from Baylis and Circa; and has received payments or honoraria for lectures/presentations/speakers’ bureaus from Biosense Webster, Inc. Dr Ellenbogen has received grants, consulting fees, and payment for lectures and advisory board from Biosense Webster, Inc, and has leadership positions at the American College of Cardiology and Heart Rhythm Society. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The need to mitigate the CO 2 emissions deriving from the cement industry becomes imperative as the climate crisis advances. An effective strategy to achieve this is increasing the replacement level of cement clinkers by waste-derived supplementary cementitious materials (SCMs). In this study, the use of mechanochemically activated biomass ash for high-volume (up to 40%) substitution of cement is investigated. The effect of mineral carbonation treatment on the performance of the mechanochemically treated biomass ash as SCM was also examined. The results showed that the mechanochemically treated biomass ash was the most effective SCM, with the respective samples at 40% cement replacement reaching 63% of the strength at 28 days as compared to samples with 100% Portland cement, while only 17% of the strength was achieved in samples with 40% untreated biomass ash. As suggested by the isothermal calorimetry, XRD, FTIR, and TG analysis, the mechanochemical treatment enhanced the reactivity and the filler effect of the biomass ash, leading to improved mechanical performances of these mortars compared to those containing untreated biomass ash. Mineral carbonation reduced the reactivity of the mechanochemically treated biomass ash but still led to better strength performances in comparison to the untreated biomass ash.

Background: Left atrial appendage closure (LAAC) is usually performed under the guidance of transesophageal echocardiography (TEE). Data on the safety of intracardiac echocardiogram (ICE)-guided LAAC from a real-world population in the United States remain limited. In this study, the aim was to evaluate the trends and outcomes of ICE-guided LAAC procedures using the US National Inpatient Sample., Methods: This study used the National Inpatient Sample database from quarter 4 of 2015 to 2019. We used a propensity-matched analysis and adjusted odds ratios for in-hospital outcomes/complications. A P value of <.05 was considered significant., Results: We identified 61,995 weighted LAAC cases. Of these, 1410 patients had ICE-guided LAAC with a lower median age than the patients who had TEE-guided LAAC (75 vs 77 years; P ≤ .01). The use of ICE-guided LAAC increased from 1.7% in 2015 to 2.2% in 2019 ( P trend = .75). Major, cardiovascular, neurologic, and pulmonary complications were similar for ICE-guided and TEE-guided LAAC on adjusted analysis. On propensity-matched analysis, the overall vascular complication rates were similar. However, retroperitoneal bleeding remained significantly higher (0.7% vs 0%) with ICE. Gastrointestinal bleeding complications were more frequent in TEE-guided LAAC (3.5% vs 2.1%). The length of stay was similar for both groups (median = 1 day; P = .23); however, ICE was associated with $1769 excess cost of hospitalization ($25,112 vs $23,343; P = .04)., Conclusions: ICE-guided LAAC is safer than TEE-guided LAAC, with similar rates of major complications. However, ICE use was associated with lower rates of gastrointestinal bleeding and higher rates of retroperitoneal bleeding. In addition, ICE-guided LAAC is associated with a similar length of stay but higher costs of hospitalization., (© 2022 The Author(s).)

Background: Accurate localization of premature ventricular contractions (PVC) focus is a prerequisite to successful catheter ablation., Objective: The objective was to evaluate the software View Into Ventricular Onset (VIVO) accuracy at locating the anatomical origins for premature ventricular contractions. The VIVO device noninvasively creates a model of the patient's heart and torso, with exact locations of 12‑lead ECG electrodes, and applies a mathematical algorithm from surface signals to determine the origin of the arrhythmia. We sought to compare the agreement between VIVO-predicted locations to invasive electroanatomical mapping results., Methods: 51 consecutive patients who presented for PVC ablations at the study centers were recruited. VIVO images were collected at baseline preprocedure and all patients underwent invasive electroanatomical activation mapping of the clinical arrhythmia. Pacing was performed in pre-specified locations in the right and/or left ventricle. The successful sites of ablation and the pacing locations were compared to VIVO predicted locations. The results were adjudicated by physician experts in a blinded fashion., Results: Seven patients were excluded from analyses. VIVO accurately identified the origin of the clinical premature ventricular contractions in 44/44 patients (100.00%). The accuracy in identifying the paced location for all patients (right and left sides of the heart) was 99.5% using the VIVO system. No adverse events were reported., Conclusions: VIVO is a novel noninvasive system that could be used to help guide ablation procedures with a high degree of accuracy. The VIVO algorithm is easy to use and may be useful in the workflow for ventricular arrhythmia ablation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Atrial fibrillation induced stroke accounts for up to 15% of all strokes. These strokes are caused approximately 90% of the time by clot formation in the left atrial appendage (LAA). To prevent these clots, the most common approach is to administer blood thinners. However, contraindications prevent some people from being able to have blood thinners. Devices have been developed to seal the LAA to prevent clot formation in these patients. Current devices, such as the LARIAT® tie off the LAA theoretically preventing blood from entering the LAA. These have had limited clinical success mainly due to failure to completely close the LAA leaving holes and orifices for thrombi to form. To overcome this lack of complete closure, many surgeons use off-label approaches, classically filling the LAA filamentous coils, to cover these holes. Although this usually helps largely cover the holes, placement is challenging, the coils can migrate, the holes are not fully closed as there is space within and around the coils that don't fully mold to the LAA geometry. Furthermore, the coils can develop device related thrombi defeating their purpose. Therefore, these are not fully sufficient to complement the closure techniques in closing the LAA. To address limitation of the closure devices and coil sealing of remaining holes, we developed a thermally responsive hydrogel (Thermogel) that solidifies once injected into the LAA to uniformly and fully close off the LAA thus preventing clot formation and device related thrombi. This Thermogel consists of three portions: 1) a structural component composed of thiolated Pluronic F127 for gel to solid transition following injection, 2) Heparin for anticoagulation, and 3) Dopamine for adhesion to the surrounding endothelium in the turbulent flow encountered in cardiovascular applications. Here we have demonstrated that Thermogel, in conjunction with the LARIAT®, is capable of filling the defects in small and large animals through catheter injection. Thermogel was biocompatible and led to atrophy of the LAA at 5 weeks in a large animal model. Given the advantages of this Thermogel for sealing this defect and ability to be delivered through an endovascular approach, Thermogel presents a viable adjuvant to current occlusion-based treatments for sealing cardiovascular defects., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ennio Tasciotti, Francesca Taraballi, Miguel Valderrabano has patent Thermosensitive Hydrogel Sealing of the Left Atrial Appendage to Prevent Thromboembolism in Atrial Fibrillation pending to Ennio Tasciotti, Francesca Taraballi, Miguel Valderrabano.

Background: Device-related thrombus (DRT) has been considered an Achilles' heel of left atrial appendage occlusion (LAAO). However, data on DRT prediction remain limited., Objectives: This study constructed a DRT registry via a multicenter collaboration aimed to assess outcomes and predictors of DRT., Methods: Thirty-seven international centers contributed LAAO cases with and without DRT (device-matched and temporally related to the DRT cases). This study described the management patterns and mid-term outcomes of DRT and assessed patient and procedural predictors of DRT., Results: A total of 711 patients (237 with and 474 without DRT) were included. Follow-up duration was similar in the DRT and no-DRT groups, median 1.8 years (interquartile range: 0.9-3.0 years) versus 1.6 years (interquartile range: 1.0-2.9 years), respectively (P = 0.76). DRTs were detected between days 0 to 45, 45 to 180, 180 to 365, and >365 in 24.9%, 38.8%, 16.0%, and 20.3% of patients. DRT presence was associated with a higher risk of the composite endpoint of death, ischemic stroke, or systemic embolization (HR: 2.37; 95% CI, 1.58-3.56; P < 0.001) driven by ischemic stroke (HR: 3.49; 95% CI: 1.35-9.00; P = 0.01). At last known follow-up, 25.3% of patients had DRT. Discharge medications after LAAO did not have an impact on DRT. Multivariable analysis identified 5 DRT risk factors: hypercoagulability disorder (odds ratio [OR]: 17.50; 95% CI: 3.39-90.45), pericardial effusion (OR: 13.45; 95% CI: 1.46-123.52), renal insufficiency (OR: 4.02; 95% CI: 1.22-13.25), implantation depth >10 mm from the pulmonary vein limbus (OR: 2.41; 95% CI: 1.57-3.69), and non-paroxysmal atrial fibrillation (OR: 1.90; 95% CI: 1.22-2.97). Following conversion to risk factor points, patients with ≥2 risk points for DRT had a 2.1-fold increased risk of DRT compared with those without any risk factors., Conclusions: DRT after LAAO is associated with ischemic events. Patient- and procedure-specific factors are associated with the risk of DRT and may aid in risk stratification of patients referred for LAAO., Competing Interests: Funding Support and Author Disclosures Dr Maarse has received an unrestricted grant from Boston Scientific. Dr Pérez de Prado has served as a proctor for Boston Scientific. Dr Gupta has served as a proctor for Abbott. Dr Sanchez has served as a speaker and proctor for Boston Scientific. Dr Demkow has served as a proctor for Abbott and Boston Scientific. Dr Alkhouli has served as a consultant for Boston Scientific. Dr Wang has been a consultant for Edwards LifeSciences, Boston Scientific, and Neochord; and has received research grant support from Boston Scientific assigned to employer Henry Ford health system. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Managing arrhythmias from the left ventricular summit and interventricular septum is a major challenge for the clinical electrophysiologist requiring intimate knowledge of cardiac anatomy, advanced training and expertise. Novel mapping and ablation strategies are needed to treat arrhythmias originating from these regions given the current suboptimal long-term success rates with standard techniques. Herein, we describe innovative approaches to improve acute and long-term clinical outcomes such as mapping and ablation using the septal coronary venous system and the septal coronary arteries, alcohol ablation, coil embolization, and ablation of all early sites among others., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Intramural origin of ventricular arrhythmias is one of the reasons for failure of catheter ablation, especially in nonischemic substrates. Conventional unipolar ablation has limited efficacy for the creation of deep transmural lesions in the ventricular myocardium, and alternative ablation strategies have been developed to overcome this problem. These novel approaches include simultaneous unipolar ablation, bipolar ablation, use of low-ionic irrigant solution, needle ablation, and ethanol ablation. This review provides an overview of each one of these techniques, including their main advantages and limitations., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Ethanol infusion (EI) in the vein of Marshall (VOM) has multifactorial effects that could be synergistic to pulmonary vein isolation (PVI) in ablation of atrial fibrillation (AF). The efficacy of radiofrequency (RF) versus cryoablation when combined with a VOM-EI has never been investigated. The aim of this study is to evaluate outcome differences of AF ablation using RF versus cryoablation when combined with a VOM-EI., Materials and Methods: Consecutive patients (n=132) underwent catheter ablation of paroxysmal AF with either RF or cryoballoon (CB) for PVI combined with VOM-EI. Bi-directional conduction block at the mitral isthmus was attempted. The end-point was the freedom from any atrial arrhythmias documented after a blanking period of 90 days after the procedure., Results: Kaplan-Meier estimates of the arrhythmia-free survival after 1 year were 63.8 (RF + VOM), and 82.7 % (CB + VOM), respectively. Comparison between CB + VOM versus RF + VOM reached a significance (p=0.0292). The periprocedural complication rate was comparable in both groups (5.0 % RF, 5.8 % CB; p=0.14) with a significant difference in the incidence of phrenic nerve palsy (0 % RF, 2.0 % CB; p<0.05)., Conclusions: PVI with a CB had an increased freedom from AF recurrence compared to RF combined with VOM-EI. The present results suggest a potential additive effect of a VOM-EI to CB application.

Implantable cardioverter-defibrillators (ICDs) are a powerful tool in preventing sudden cardiac death due to ventricular arrhythmias in ischemic cardiomyopathy. ICD indications and timing in acute coronary syndromes are unclear. PURPOSE OF REVIEW: We reviewed several trials that delineated the indications for a cardiac defibrillator in patients with coronary artery disease. RECENT FINDINGS: The role of cardiac defibrillators in secondary prevention has been well established by AVID, CIDS, and CASH trials. AVID showed reduction in both all-cause mortality and arrhythmic death while the two smaller trials showed only improvement in arrhythmic death. Similarly, trials like MADIT, CABG Patch, MUSTT, MADIT-II, DINAMIT, and the IRIS trial have fine-tuned the indications for ICD in primary prevention of sudden cardiac death. Benefits of an ICD were most pronounced in those with reduced ejection fraction and 40 days or more since myocardial infarction or in those who were not immediately post revascularization. The recent VEST trial aimed to study wearable cardioverter-defibrillators (WCDs) in patients who did not have an indication for an implantable defibrillator. The arrhythmic deaths (1.6% vs. 2.4%) were not reduced by the WCD. Based on consistent reduction in arrhythmic death in all primary and secondary prevention trials, defibrillators are effective in carefully selected patients.

Background: Numerous studies investigated cell-based therapies for myocardial infarction (MI). The conflicting results of these studies have established the need for developing innovative approaches for applying cell-based therapy for MI. Experimental studies on animal models demonstrated the potential of fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) for treating acute MI. In contrast, studies on the treatment of chronic MI (CMI; > 4 wk post-MI) with UA-ADRCs have not been published so far. Among several methods for delivering cells to the myocardium, retrograde delivery into a temporarily blocked coronary vein has recently been demonstrated as an effective option., Aim: To test the hypothesis that in experimentally-induced chronic myocardial infarction (CMI; > 4 wk post-MI) in pigs, retrograde delivery of fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) into a temporarily blocked coronary vein improves cardiac function and structure., Methods: The left anterior descending (LAD) coronary artery of pigs was blocked for 180 min at time point T0. Then, either 18 × 10 6 UA-ADRCs prepared at "point of care" or saline as control were retrogradely delivered via an over-the-wire balloon catheter placed in the temporarily blocked LAD vein 4 wk after T0 (T1). Effects of cells or saline were assessed by cardiac magnetic resonance (CMR) imaging, late gadolinium enhancement CMR imaging, and post mortem histologic analysis 10 wk after T0 (T2)., Results: Unlike the delivery of saline, delivery of UA-ADRCs demonstrated statistically significant improvements in cardiac function and structure at T2 compared to T1 (all values given as mean ± SE): Increased mean LVEF (UA-ADRCs group: 34.3% ± 2.9% at T1 vs 40.4 ± 2.6% at T2, P = 0.037; saline group: 37.8% ± 2.6% at T1 vs 36.2% ± 2.4% at T2, P > 0.999), increased mean cardiac output (UA-ADRCs group: 2.7 ± 0.2 L/min at T1 vs 3.8 ± 0.2 L/min at T2, P = 0.002; saline group: 3.4 ± 0.3 L/min at T1 vs 3.6 ± 0.3 L/min at T2, P = 0.798), increased mean mass of the left ventricle (UA-ADRCs group: 55.3 ± 5.0 g at T1 vs 71.3 ± 4.5 g at T2, P < 0.001; saline group: 63.2 ± 3.4 g at T1 vs 68.4 ± 4.0 g at T2, P = 0.321) and reduced mean relative amount of scar volume of the left ventricular wall (UA-ADRCs group: 20.9% ± 2.3% at T1 vs 16.6% ± 1.2% at T2, P = 0.042; saline group: 17.6% ± 1.4% at T1 vs 22.7% ± 1.8% at T2, P = 0.022)., Conclusion: Retrograde cell delivery of UA-ADRCs in a porcine model for the study of CMI significantly improved myocardial function, increased myocardial mass and reduced the formation of scar tissue., Competing Interests: Conflict-of-interest statement: Schmitz C has served as consultant of SciCoTec (Grünwald, Germany), the principal shareholder of InGeneron, Inc. (Houston, TX, United States). Alt EU is Chairman of the Board of Isar Klinikum and of InGeneron, Inc., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Atrial fibrillation (AF) triggers within the coronary sinus (CS)/great cardiac vein (GCV) and the left atrial appendage (LAA) have been recognized as nonpulmonary vein triggers of AF., Objective: The aim of this study was to describe an electrical connection between the LAA and CS/GCV and its importance in achieving LAA electrical isolation (LAAEI)., Methods: A total of 488 consecutive patients undergoing catheter ablation for persistent or long-standing persistent AF who showed firing from the LAA and/or from the CS/GCV were enrolled in this multicenter prospective study. In all patients, potential defragmentation of the CS/GCV to achieve isolation and LAAEI was attempted with both endocardial and epicardial ablation., Results: In 7% (n = 34) of these patients, after attempting endocardial LAAEI, the LAA was isolated during epicardial ablation in the GCV. In 8% (n = 39) of patients after attempting endocardial LAA isolation, the LAA was isolated during ablation along the endocardial aspect of the GCV. The presence of a venous branch connecting the GCV with the LAA was found in all these patients. In 23% (n = 112) of patients, the isolation of the LAA also isolated the GCV. In all these patients, LAA dissociated firing was present together with the CS/GCV recordings., Conclusion: These findings suggest the presence of a distinct electrical connection between the GCV and the LAA. The clinical relevance of our results requires further investigation. Ablation in the CS/GCV can result in inadvertent isolation of the LAA. Ablation of the GCV is relevant to achieve LAAEI. Considering the potential long-term implications, ablation in the distal CS/GCV should prompt assessment of LAA conduction., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Pharmacological therapies for cardiovascular diseases are limited by short-term pharmacokinetics and extra-cardiac adverse effects. Improving delivery selectivity specifically to the heart, wherein therapeutic drug levels can be maintained over time, is highly desirable. Nanoparticle (NP)-based pericardial drug delivery could provide a strategy to concentrate therapeutics within a unique, cardiac-restricted compartment to allow sustained drug penetration into the myocardium. Our objective was to explore the kinetics of myocardial penetration and retention after pericardial NP drug delivery. Fluorescently-tagged poly(lactic-co-glycolic acid) (PLGA) NPs were loaded with BODIPY, a fluorophore, and percutaneously administered into the pericardium via subxiphoid puncture in rabbits. At distinct timepoints hearts were examined for presence of NPs and BODIPY. PLGA NPs were found non-uniformly distributed on the epicardium following pericardial administration, displaying a half-life of ~2.5days in the heart. While NPs were mostly confined to epicardial layers, BODIPY was capable of penetrating into the myocardium, resulting in a transmural gradient. The distinct architecture and physiology of the different regions of the heart influenced BODIPY distribution, with fluorophore penetrating more readily into atria than ventricles. BODIPY proved to have a long-term presence within the heart, with a half-life of ~7days. Our findings demonstrate the potential of utilizing the pericardial space as a sustained drug-eluting reservoir through the application of nanoparticle-based drug delivery, opening several exciting avenues for selective and prolonged cardiac therapeutics., (Copyright © 2017 Elsevier B.V. All rights reserved.)