Search

Introduction: Little is known regarding the prevalence and prognostic implications of non-sustained ventricular tachycardia (NSVT) in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA). We aimed to investigate the prevalence of NSVT in patients with ATTRwr-CA, and the association of NSVT with sustained ventricular arrhythmias (VA) and all-cause mortality., Methods: In a cohort of ATTRwt-CA patients from 2011 to 2022 without prior sustained VA, we ascertained the presence and characteristics of NSVT during clinically indicated ambulatory Holter monitoring. Patients were stratified based on the presence of NSVT at baseline. The primary and secondary endpoints of sustained VA and all-cause mortality, respectively, were assessed during follow-up., Results: The cohort included 217 patients with ATTRwt-CA (95% males, median age 75 years; median NYHA class 2). Baseline Holter monitoring demonstrated NSVT in 116 (53%) patients. During a median follow-up of 27 months (IQR 16-45) after the index Holter monitor, 11 (5.1%) patients reached the primary endpoint of sustained VA (incidence 1.8 per 100 person-years, all monomorphic VT), and 46 (21%) patients died. In univariable Cox proportional hazard model, NYHA class 3 or 4 heart failure (p = .048), the presence of NSVT (p = .04), the duration of longest NSVT run (p = .029), and the percentage of ventricular ectopy (p < .001) were associated with the primary outcome. When adjusting for age and NYHA class 3 or 4 heart failure, the presence of NSVT remained associated with the primary outcome (p = .03). All-cause mortality was not significantly different between patients with and without NSVT. A cutoff for ventricular ectopy burden of 0.5%, the median for all patients in this study, was associated with increased risk in sustained VA (log-rank p = .004) and mortality (log-rank p = .02)., Conclusion: NSVT is highly prevalent among ATTRwt-CA patients undergoing clinically indicated Holter monitoring and may confer an increased risk of incident sustained VA., (© 2024 Wiley Periodicals LLC.)

Background: Despite effectiveness of the implantable cardioverter-defibrillator (ICD) in saving patients with life-threatening ventricular arrhythmias (VAs), the temporal occurrence of VA after ICD implantation is unpredictable., Objective: The study aimed to apply machine learning (ML) to intracardiac electrograms (IEGMs) recorded by ICDs as a unique biomarker for predicting impending VAs., Methods: The study included 13,516 patients who received Biotronik ICDs and enrolled in the CERTITUDE registry between January 1, 2010, and December 31, 2020. Database extraction included IEGMs from standard quarterly transmissions and VA event episodes. The processed IEGM data were pulled from device transmissions stored in a centralized Home Monitoring Service Center and reformatted into an analyzable format. Long-range (baseline or first scheduled remote recording), mid-range (scheduled remote recording every 90 days), or short-range predictions (IEGM within 5 seconds before the VA onset) were used to determine whether ML-processed IEGMs predicted impending VA events. Convolutional neural network classifiers using ResNet architecture were employed., Results: Of 13,516 patients (male, 72%; age, 67.5 ± 11.9 years), 301,647 IEGM recordings were collected; 27,845 episodes of sustained ventricular tachycardia or ventricular fibrillation were observed in 4467 patients (33.0%). Neural networks based on convolutional neural networks using ResNet-like architectures on far-field IEGMs yielded an area under the curve of 0.83 with a 95% confidence interval of 0.79-0.87 in the short term, whereas the long-range and mid-range analyses had minimal predictive value for VA events., Conclusion: In this study, applying ML to ICD-acquired IEGMs predicted impending ventricular tachycardia or ventricular fibrillation events seconds before they occurred, whereas midterm to long-term predictions were not successful. This could have important implications for future device therapies., Competing Interests: Disclosures A.L. receives consulting fees from SHL Telemedicine. A number of AI ECG algorithms have been licensed by Mayo Clinic to Anumana, Eko Health, and AliveCor; Mayo Clinic, P.A.F., I.Z.A., and S.J.A. may benefit financially from their commercialization. G.A.U. receives consulting and speaking fees from Biotronik, St Jude Medical, Medtronic, Boston Scientific, Philips BioTel, and Zoll Medical. S.J.A. receives honoraria and consulting and speaking fees from Biotronik, St Jude Medical, Medtronic, Boston Scientific, BioSig Technologies, and MediLynx. All other authors have no relevant relationships to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Immunity to SARS-CoV-2 vaccination and infection differs considerably among individuals. We investigate the critical pathways that influence vaccine-induced cross-variant serological immunity among individuals at high-risk of COVID-19 complications., Methods: Neutralizing antibodies to the wild-type SARS-CoV-2 virus and its variants (Beta, Gamma, Delta and Omicron) were analyzed in patients with autoimmune diseases, chronic comorbidities (multimorbidity), and healthy controls. Antibody levels were assessed at baseline and at different intervals up to 12 months following primary and booster vaccination with either BNT162b2 or mRNA-1273. Immunity induced by vaccination with and without infection (hybrid immunity) was compared with that of unvaccinated individuals with recent SARS-CoV-2 infection. Plasma cytokines were analyzed to investigate variations in antibody production following vaccination., Results: Patients with autoimmune diseases (n = 137) produced lesser antibodies to the wild-type SARS-CoV-2 virus and its variants compared with those in the multimorbidity (n = 153) and healthy groups (n = 229); antibody levels were significantly lower in patients with neuromyelitis optica and those on prednisolone, mycophenolate or rituximab treatment. Multivariate logistic regression analysis identified neuromyelitis optica (odds ratio 8.20, 95% CI 1.68-39.9) and mycophenolate (13.69, 3.78-49.5) as significant predictors of a poorer antibody response to vaccination (i.e, neutralizing antibody <40%). Infected participants exhibited antibody levels that were 28.7% higher (95% CI 24.7-32.7) compared to non-infected participants six months after receiving a booster vaccination. Individuals infected during the Delta outbreak generated cross-protective neutralizing antibodies against the Omicron variant in quantities comparable to those observed after infection with the Omicron variant itself. In contrast, unvaccinated individuals recently infected with the wild-type (n = 2390) consistently displayed lower levels of neutralizing antibodies against both the wild-type virus and other variants. Pathway analyses suggested an inverse relationship between baseline T cell subsets and antibody production following vaccination., Conclusion: Hybrid immunity confers a robust protection against COVID-19 among immunocompromised individuals., Competing Interests: Declaration of Competing Interest Paul A. MacAry, Bhuvaneshwari Shunmuganathan, and Rashi Gupta are co-inventors of the ELISA-based surrogate viral neutralization test, which has been commercialized and branded as the ImTracker MULTI COVID-19 viral variant neutralization test by Gen-Y Biologics (for more information, visit https://genybiologics.com/imtracker/). The remaining authors have no competing interests to declare and affirm that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cardiac electrophysiology involves the diagnosis and management of arrhythmias. CT and MRI play an increasingly important role in cardiac electrophysiology, primarily in preprocedural planning of ablation procedures but also in procedural guidance and postprocedural follow-up. The most common applications include ablation for atrial fibrillation (AF), ablation for ventricular tachycardia (VT), and for planning cardiac resynchronization therapy (CRT). For AF ablation, preprocedural evaluation includes anatomic evaluation and planning using CT or MRI as well as evaluation for left atrial fibrosis using MRI, a marker of poor outcomes following ablation. Procedural guidance during AF ablation is achieved by fusing anatomic data from CT or MRI with electroanatomic mapping to guide the procedure. Postprocedural imaging with CT following AF ablation is commonly used to evaluate for complications such as pulmonary vein stenosis and atrioesophageal fistula. For VT ablation, both MRI and CT are used to identify scar, representing the arrhythmogenic substrate targeted for ablation, and to plan the optimal approach for ablation. CT or MR images may be fused with electroanatomic maps for intraprocedural guidance during VT ablation and may also be used to assess for complications following ablation. Finally, functional information from MRI may be used to identify patients who may benefit from CRT, and cardiac vein mapping with CT or MRI may assist in planning access. © RSNA, 2024 Supplemental material is available for this article.

The introduction of pulsed field ablation (PFA) in electrophysiology marks a significant advancement, promising efficacy comparable to thermal ablation methods while potentially providing safety advantages. Despite a generally favorable safety profile in human trials and postmarket registries, cautious evaluation of PFA's safety is essential. This review provides a comprehensive overview of key safety considerations as we discuss a myriad of considerations ranging from thermal effects, gaseous microbubble formation, muscle contractions, and proarrhythmia to procedural techniques. We explore specific safety concerns with phrenic nerve injury, cerebral lesions, coronary artery spasm, hemolysis and pulmonary bleeding. Vigilance in safety monitoring, coupled with advancements in procedural techniques and understanding of PFA's unique effects, is crucial for optimizing the safe and effective use of PFA., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)

Objective: To review the salient features of multimodality cardiovascular imaging in patients with disseminated Mycobacterium chimaera (MC) infections after exposure to contaminated heater-cooler units during cardiopulmonary bypass., Patients and Methods: Twelve patients with confirmed MC infection were retrospectively identified after a review from January 1, 2010, to April 30, 2021. The electronic medical records were examined with a focus on transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography (CT), cardiac magnetic resonance imaging, and positron emission tomography-CT., Results: Three (27.3%) patients had diagnostic findings of endocarditis on transthoracic echocardiography, with most patients having nonspecific abnormalities including elevated prosthetic valve gradients or prosthetic leaflet thickening. Transesophageal echocardiography identified 4 (36.7%) patients with vegetations and 3 (27.3%) with aortic root abscess or pseudoaneurysm, with more common findings such as mild aortic root or prosthetic leaflet thickening. Six (50%) patients underwent cardiac CT imaging, which found aortic root pseudoaneurysms or abscesses, prosthetic ring dehiscence, and leaflet thickening. Three (25%) patients underwent cardiac magnetic resonance imaging demonstrating prosthetic valve vegetations, leaflet thickening, and abnormal myocardial delayed enhancement in a noncoronary distribution, suggesting myocarditis. Ten (83%) patients underwent positron emission tomography-CT, 4 (40%) had an abnormal fluorodeoxyglucose uptake around the cardiac prosthetic material, and 7 (70%) had a fluorodeoxyglucose uptake in other organs, suggesting concomitant multiorgan involvement., Conclusion: Multimodality cardiovascular imaging is central to the management of patients with disseminated MC and can help establish a preliminary diagnosis while awaiting confirmatory microbiological data, potentially reducing the time to diagnosis. Imaging findings are subtle and atypical, not always meeting classically modified Duke's criteria for infectious endocarditis. Clinicians should have a high index of suspicion for the disease and a low threshold for repeat imaging when initial testing is equivocal., Competing Interests: Dr Bennett reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events as a Course Director from Society of Critical Care Medicine, Critical Care Echo Board Review, and Mayo Clinic Foundation, Heart to Heart: Advances in Cardiac Critical Care and Resuscitation. The other authors report no competing interests., (© 2024 The Authors.)

Background: The incidence and prognosis of right bundle branch block (RBBB) following transcatheter aortic valve replacement (TAVR) are unknown. Hence, we sought to characterize the incidence of post-TAVR RBBB and determine associated risks of permanent pacemaker (PPM) implantation and mortality., Methods: All patients 18 years and above without preexisting RBBB or PPM who underwent TAVR at US Mayo Clinic sites and Mayo Clinic Health Systems from June 2010 to May 2021 were evaluated. Post-TAVR RBBB was defined as new-onset RBBB in the postimplantation period. The risks of PPM implantation (within 90 days) and mortality following TAVR were compared for patients with and without post-TAVR RBBB using Kaplan-Meier analysis and Cox proportional hazards modeling. The risks of PPM implantation (within 90 days) and mortality following TAVR were compared for patients with and without post-TAVR RBBB using Kaplan-Meier analysis and Cox proportional hazards modeling., Results: Of 1992 patients, 15 (0.75%) experienced new RBBB post-TAVR. There was a higher degree of valve oversizing among patients with new RBBB post-TAVR versus those without (17.9% versus 10.0%; P =0.034). Ten patients (66.7%) with post-TAVR RBBB experienced high-grade atrioventricular block and underwent PPM implantation (median 1 day; Q1, 0.2 and Q3, 4), compared with 268/1977 (13.6%) without RBBB. Following propensity score adjustment for covariates (age, sex, balloon-expandable valve, annulus diameter, and valve oversizing), post-TAVR RBBB was significantly associated with PPM implantation (hazard ratio, 8.36 [95% CI, 4.19-16.7]; P <0.001). No statistically significant increase in mortality was seen with post-TAVR RBBB (hazard ratio, 0.83 [95% CI, 0.33-2.11]; P =0.69), adjusting for age and sex., Conclusions: Although infrequent, post-TAVR RBBB was associated with elevated PPM implantation risk. The mechanisms for its development and its clinical prognosis require further study., Competing Interests: Disclosures None.

Outflow tract ventricular arrhythmias are the most common type of idiopathic ventricular arrhythmia. A systematic understanding of the outflow tract anatomy improves procedural efficacy and enables electrophysiologists to anticipate and prevent complications. This review emphasizes the three-dimensional spatial relationships between the ventricular outflow tracts using seven anatomical principles. In turn, each principle is elaborated on from a clinical perspective relevant for the practicing electrophysiologist. The developmental anatomy of the outflow tracts is also discussed and reinforced with a clinical case., (© 2023 American Association of Clinical Anatomists.)

Background: The outcomes of catheter ablation for atrial fibrillation in adults with congenital heart disease are not well described., Methods: In a retrospective study of adult patients with congenital heart disease who underwent catheter ablation for atrial fibrillation between 2000 and 2020 at Mayo Clinic, procedural characteristics and outcomes were collected. The primary outcomes were atrial arrhythmia (AA) recurrence following a 3-month blanking period and repeat ablation. An arrhythmia clinical severity score was assessed pre- and post-ablation based on the duration of arrhythmia episodes, symptoms, cardioversion frequency, and antiarrhythmic drug use., Results: One hundred forty-five patients (age, 57±12 years; 28% female; 63% paroxysmal atrial fibrillation) underwent 198 ablations with a median follow-up of 26 months (interquartile range, 14-69). One hundred ten, 26, and 9 patients had simple, moderate, and complex congenital heart disease, respectively. All patients underwent pulmonary vein isolation, and non-pulmonary vein targets were ablated in 79 (54%). AA recurrence at 12 months was 37% (95% CI, 29%-45%). On univariate analysis, increasing left atrial volume index was associated with higher odds of AA recurrence (odds ratio, 1.03 [1.00-1.06] per 1 mL/m 2 increment; P =0.05). Noninducibility of atrial flutter was predictive of decreased odds of AA recurrence (odds ratio, 0.43 [0.21-0.90]; P =0.03). A second ablation was performed in 43 patients after a median of 20 (interquartile range, 8-37) months. Arrhythmia clinical severity scores improved following ablation, reflecting a decrease in symptoms, cardioversions, and antiarrhythmic drugs., Conclusions: Catheter ablation of atrial fibrillation is feasible and effective in patients with adult congenital heart disease and reduces symptoms. Recurrence of AA frequently requires repeat ablation., Competing Interests: Disclosures Dr Madhavan receives research funding from Boston Scientific, BMS/Pfizer, and Convatec, Inc; speaker honorarium from Biosense Webster; and she is on the steering committee of CERTITUDE Registry, Biotronik, Inc. Dr Asirvatham receives speaking/honoraria from Abbott, Biosense Webster, Biotronik, Boston Scientific, Medtronic, and Zoll. All other authors have no conflicts to disclose.

Background: Labor pain intensity is known to predict persistent postpartum pain, whereas acute postpartum pain may interfere with maternal postpartum physical, mental, and emotional well-being. Nevertheless, there is little research studying the association between labor pain intensity and acute postpartum pain. This study investigated the associations between labor pain intensity and psychological factors with acute postpartum pain., Methods: We included women with American Society of Anesthesiologists (ASA) physical status II, having ≥ 36 gestational weeks and a singleton pregnancy. We investigated the association between labor pain intensity (primary exposure) and high acute postpartum pain at 0 to 24 h after delivery (Numeric Rating Scale (NRS) ≥ 3 of 10; primary outcome). Pre-delivery questionnaires including Angle Labor Pain Questionnaire (A-LPQ), Pain Catastrophizing Scale (PCS), Fear Avoidance Components Scale (FACS) and State Trait Anxiety Inventory (STAI) were administered. Demographic, pain, obstetric and neonatal characteristics were also collected accordingly., Results: Of the 880 women studied, 121 (13.8%) had high acute postpartum pain at 0 to 24 h after delivery. A-LPQ total, PCS, FACS and STAI scores were not significantly associated with acute postpartum pain. Greater A-LPQ subscale on birthing pain (adjusted odds ratio (aOR) 1.03, 95% CI 1.01-1.05, p = 0.0008), increased blood loss during delivery (for every 10ml change; aOR 1.01, 95% CI 1.00-1.03, p = 0.0148), presence of shoulder dystocia (aOR 10.06, 95% CI 2.28-44.36, p = 0.0023), and use of pethidine for labor analgesia (aOR 1.74, 95% CI 1.07-2.84, p = 0.0271) were independently associated with high acute postpartum pain. "Sometimes" having nausea during menstruation before current pregnancy (aOR 0.34, 95% CI 0.16-0.72, p = 0.0045) was found to be independently associated with reduced risk of high acute postpartum pain., Conclusions: Pre-delivery pain factor together with obstetric complications (shoulder dystocia, blood loss during delivery) were independently associated with high acute postpartum pain., Trial Registration: This study was registered on clinicaltrials.gov registry (NCT03167905) on 30/05/2017., (© 2023. The Author(s).)

Background: Ventricular fibrillation (VF) is a lethal cardiac arrhythmia that is a significant cause of sudden cardiac death. Comprehensive studies of spatiotemporal characteristics of VF in situ are difficult to perform with current mapping systems and catheter technology., Objective: The goal of this study was to develop a computational approach to characterize VF using a commercially available technology in a large animal model. Prior data suggests that characterization of spatiotemporal organization of electrical activity during VF can be used to provide better mechanistic understanding and potential ablation targets to modify VF and its substrate. We therefore evaluated intracardiac electrograms during biventricular mapping of the endocardium (ENDO) and epicardium (EPI) in acute canine studies., Methods: To develop thresholds for organized and disorganized activity, a linear discriminant analysis (LDA)-based approach was performed to the known organized and disorganized activities recorded in ex vivo Langendorff-perfused rat and rabbit hearts using optical mapping experiments. Several frequency- and time-domain approaches were used as individual and paired features to identify the optimal thresholds for the LDA approach. Subsequently, VF was sequentially mapped in 4 canine hearts, using the CARTO mapping system with a multipolar mapping catheter in the ENDO left and right ventricles and EPI to capture the progression of VF at 3 discrete post-induction time intervals: VF period 1 (just after induction of VF to 15 min), VF period 2 (15 to 30 min), and VF period 3 (30 to 45 min). The developed LDA model, cycle lengths (CL), and regularity indices (RI) were applied to all recorded intracardiac electrograms to quantify the spatiotemporal organization of VF in canine hearts., Results: We demonstrated the presence of organized activity in the EPI as VF progresses, in contrary to the ENDO, where the activity stays disorganized. The shortest CL always occurred in the ENDO, especially the RV, indicating a faster VF activity. The highest RI was found in the EPI in all hearts for all VF stages, indicating spatiotemporal consistency of RR intervals., Conclusion: We identified electrical organization and spatiotemporal differences throughout VF in canine hearts from induction to asystole. Notably, the RV ENDO is characterized by a high level of disorganization and faster VF frequency. In contrast, EPI has a high spatiotemporal organization of VF and consistently long RR intervals., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Living structures constantly interact with the biotic and abiotic environment by sensing and responding via specialized functional parts. In other words, biological bodies embody highly functional machines and actuators. What are the signatures of engineering mechanisms in biology? In this review, we connect the dots in the literature to seek engineering principles in plant structures. We identify three thematic motifs-bilayer actuator, slender-bodied functional surface, and self-similarity-and provide an overview of their structure-function relationships. Unlike human-engineered machines and actuators, biological counterparts may appear suboptimal in design, loosely complying with physical theories or engineering principles. We postulate what factors may influence the evolution of functional morphology and anatomy to dissect and comprehend better the why behind the biological forms.

Background: The prevention of stroke in patients with atrial fibrillation (AF) and cancer is challenging because patients are at increased bleeding and thrombotic risk., Objectives: The authors sought to assess left atrial appendage occlusion (LAAO) as a safe and effective strategy for reducing stroke at no increased bleeding risk in cancer patients with AF., Methods: We reviewed patients with nonvalvular AF who underwent LAAO at Mayo Clinic sites from 2017 to 2020 and identified those who had undergone prior or current treatment for cancer. We compared the incidence of stroke, bleeding, device complications, and death with a control group who underwent LAAO without malignancy., Results: Fifty-five patients were included; 44 (80.0%) were male, and the mean age was 79.0 ± 6.1 years. The median CHA 2 Ds 2 -VASc score was 5 (Q1-Q3: 4-6), with 47 (85.5%) having a prior bleeding event. Over the first year, ischemic stroke occurred in 1 (1.4%) patient, bleeding complications in 5 (10.7%) patients, and death in 3 (6.5%) patients. Compared with controls who underwent LAAO without cancer, there was no significant difference in ischemic stroke (HR: 0.44; 95% CI: 0.10-1.97; P = 0.28), bleeding complication (HR: 0.71; 95% CI: 0.28-1.86; P = 0.19), or death (HR: 1.39; 95% CI: 0.73-2.64; P = 0.32)., Conclusions: Within our cohort, LAAO in cancer patients was achieved with good procedural success and offered a reduction in stroke at no increased bleeding risk similar to noncancer patients., Competing Interests: This study was funded by the National Institutes of Health/National Cancer Institute (R01CA233601) and the Miami Heart Foundation. Dr Holmes is a member of the advisory board (unpaid) for Boston Scientific. Dr Herrmann is on the advisory board (unrelated to the topic of this study) for Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

The co-morbidities and long-term complications of spontaneous coronary artery dissection (SCAD) are incompletely understood. This study investigated the association of atrial arrhythmias (AA), defined as atrial fibrillation and atrial flutter, with SCAD in a patient registry and population-based cohort. This observational study was performed in 2 parts. The first was a retrospective study reviewing patients diagnosed with AA in the Mayo Clinic SCAD Registry. The second was a population-based, case-control study to assess AA in patients with SCAD compared with age- and gender-matched controls. Of 1,214 patients in the Mayo Clinic SCAD Registry, 45 patients (3.7%) with SCAD were identified with an AA. A total of 8 of those patients (17.8%) had a pre-SCAD AA; 20 (44.4%) had a peri-SCAD AA; and 17 (37.8%) had a post-SCAD AA. The univariate analysis did not reveal significant associations with traditional cardiovascular risk factors. In the population-based cohort, 5 patients with SCAD (4%) and 4 controls (1%) developed an AA before the date of SCAD for each patient (odds ratio 4.5, 95% confidence interval [CI] 1.05 to 19.0, p = 0.04). A total of 5 patients with SCAD (4%) and 3 controls (1%) developed an AA in the 10 years after SCAD (hazard ratio 6.3, 95% CI 1.2 to 32.8, p = 0.03). A subgroup of patients with SCAD experienced AA before and after SCAD. Patients with a history of SCAD were more likely to develop AA in the next 10 years than were age- and gender-matched healthy controls., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In the pivotal WATCHMAN trials, warfarin was used for post-procedural anticoagulation in the first 45 days after left atrial appendage closure. We aimed to investigate the efficacy and safety of direct oral anticoagulant (DOAC) versus warfarin after WATCHMAN. We performed a literature search of 5 electronic databases to identify studies comparing DOAC with warfarin after WATCHMAN. We pooled outcomes for the efficacy (thromboembolism, device-related thrombus [DRT], peridevice leak [PDL] >5 mm) and safety endpoints (bleeding, mortality). Thromboembolism was defined as ischemic stroke, transient ischemic attack, or systemic embolism. We included 10 cohort studies with 2,440 patients, of whom 1,397 (57.3%) received DOAC. Concerning periprocedural outcomes (within 7 days following implantation), DOAC was associated with a reduction in major bleeding (Risk ratio [RR] 0.32; 95% confidence interval [CI] 0.11-0.92) compared with warfarin, without significant differences in all bleeding (RR 0.46; 95% CI 0.15-1.42) and thromboembolism (RR 0.93; 95% CI 0.21-4.16). On first follow-up transesophageal echocardiography, DRT (RR 0.79; 95% CI 0.39-1.60) and PDL>5 mm (RR 0.44; 95% CI 0.16-1.20) were comparable among groups. With a mean follow-up of 1.5-12 months, DOAC was associated with reductions in major bleeding (RR 0.52; 95% CI 0.30-0.89) and all bleeding (RR 0.38; 95% CI 0.25-0.58) compared with warfarin. The outcomes of thromboembolism (RR 0.79; 95% CI 0.36-1.73) and all-cause mortality (RR 0.49; 95% CI 0.19-1.28) were not significantly different between the 2 groups. Following WATCHMAN implantation, DOAC was associated with reductions in major bleeding and all bleeding compared with warfarin at mid-term follow-up. The outcomes of thromboembolism, all-cause mortality, DRT, and PDL >5 mm were comparable among groups., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Pulsed electric field (PEF) ablation is an emerging modality for the treatment of cardiac arrhythmias. Data regarding effects on the interventricular septum are limited, and the optimal delivery protocol and electrode configuration remain undefined., Objectives: This study sought to evaluate the electrophysiological, imaging, and histological characteristics of bipolar direct-current PEF delivered across the interventricular septum., Methods: PEF was applied between identical solid-tip ablation catheters positioned on either side of the septum in a chronic canine model. Intracardiac and surface electrophysiological data were recorded following delivery. In 4 animals, cardiac magnetic resonance (CMR) was performed early (6 ± 2 days) and late (30 ± 2 days) postablation. After 4 weeks of survival, cardiac specimens were sectioned for histopathological analysis., Results: In 8 canines, PEF was delivered in 27 separate septal sites (45 ± 17 J/site) with either microsecond or nanosecond PEF. Acute complications included transient complete atrioventricular block in 5 animals (63%) after delivery at the anterobasal septum, with right bundle branch block persisting in 3 (38%). Ventricular fibrillation occurred in 1 animal during microsecond but not nanosecond PEF. Postprocedural CMR showed prominent edema and significant left ventricular systolic dysfunction, which recovered with late imaging. At 4 weeks, 36 individual well-demarcated lesions were demonstrated by CMR and histopathology. Lesion depth measured by histology was 2.6 ± 2.1 mm (maximum 10.9 mm and near transmural)., Conclusions: Bipolar PEF ablation of the interventricular septum is feasible and can produce near transmural lesions. Myocardial stunning, edema, and conduction system injury may occur transiently. Further studies are required to optimize safe delivery and efficacious lesions., Competing Interests: Funding Support and Author Disclosures Funding for this work was provided through benefactor endowment to the Mayo Clinic Department of Cardiovascular Medicine and intramural funding (awarded to Dr Asirvatham). Drs Tri, Desimone, Killu, Maor, and Asirvatham have intellectual property claims involving the techniques used in this study. Mrs Danitz and Uecker are employed by Pulse Biosciences Inc, the manufacturer of the nanosecond pulse generator used in this study. Dr Asirvatham has received speaking/honoraria from Abbott, Biosense Webster, Biotronik, Boston Scientific, Medtronic, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: While the triggers for ventricular fibrillation (VF) are well-known, the substrate required for its maintenance remains elusive. We have previously demonstrated dynamic spatiotemporal changes across VF from electrical induction of VF to asystole. Those data suggested that VF drivers seemed to reside in the distal RV and LV. However, signals from these areas were not recorded continuously. The aim of this study was to map these regions of significance with stationary basket electrodes from induction to asystole to provide further insights into the critical substrate for VF rhythm sustenance in canines., Methods: In six healthy canines, three multipolar basket catheters were positioned in the distal right ventricle (RV), RV outflow tract, and distal left ventricle (LV), and remained in place throughout the study. VF was induced via direct current application from an electrophysiologic catheter. Surface and intracardiac electrograms were recorded simultaneously and continuously from baseline, throughout VF, and until asystole, in order to get a complete electrophysiologic analysis of VF. Focused data analysis was also performed via two defined stages of VF: early VF (immediately after induction of VF to 10 min) and late VF (after 10 min up to VF termination and asystole)., Results: VF was continuously mapped for a mean duration of 54 ± 9 min (range 42-70 min). Immediately after initiation of VF in the early phase, the distal LV region appeared to drive the maintenance of VF. Towards the terminal stage of VF, the distal RV region appeared to be responsible for VF persistence. In all canines, we noted local termination of VF in the LV, while VF on surface ECG continued; conversely, subsequent spontaneous termination of VF in the RV was associated with termination of VF on surface ECG into a ventricular escape rhythm. Continuous mapping of VF showed trends towards an increase in peak-to-peak ventricular electrogram cycle length (p = 0.06) and a decrease in the ventricular electrogram amplitude (p = 0.06) after 40 min. Once we could no longer discern surface QRS activity, we demonstrated local ventricular myocardial capture in both the RV and LV but could not reinitiate sustained VF despite aggressive ventricular burst pacing., Conclusions: This study describes the evolution of VF from electrical initiation to spontaneous VF termination without hemodynamic support in healthy canines. These data are hypothesis-generating and suggest that critical substrate for VF maintenance may reside in both the distal RV and LV depending on stage of VF. Further studies are needed to replicate these findings with hemodynamic support and to translate such findings into clinical practice. Ventricular fibrillation maintenance may be dependent on critical structures in the distal RV. ECG: electrocardiogram; LV: left ventricle; RV: right ventricle; RVOT: right ventricular outflow tract; VF: ventricular fibrillation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Optimal management of cardiac implantable electronic devices (CIEDs) in patients with Ebstein anomaly during tricuspid valve (TV) surgery is unknown. Thus, we aimed to characterize CIED management/outcomes in patients with Ebstein anomaly undergoing TV surgery., Methods: Patients at the Mayo Clinic from 1987 to 2020 with Ebstein anomaly and CIED procedure were reviewed for procedural details, complications, echocardiogram, and lead parameters. Five-year cumulative incidence of CIED complications were estimated using the Kaplan-Meier method., Results: Ninety-three patients were included; 51 were female, and mean age was 40.7±17.5 years. A new CIED was implanted in 45 patients at the time of TV surgery with the majority receiving an epicardial (n=37) CIED. Among 34 patients who had preexisting CIED (11 epicardial, 23 transvenous) at time of TV surgery, 20 had a transvenous right ventricular lead managed by externalizing the lead to the TV (n=15) or extracting the transvenous lead with epicardial lead implantation (n=5). Fourteen patients underwent CIED implantation (4 epicardial, 10 transvenous) without concurrent surgery. Placement of lead across the TV was avoided in 85% of patients. The 5-year cumulative incidence of CIED complications was 24% with no significant difference between epicardial and transvenous CIEDs (26% versus 23%, P =0.96). Performance of lead parameters was similar in epicardial and transvenous leads during median (interquartile range) follow-up of 44.5 (61.1) months., Conclusions: In patients with Ebstein anomaly undergoing TV surgery, the use of epicardial leads and externalization of transvenous leads to the TV can avoid lead placement across the valve leaflets. Lead performance and CIED complications was similar between epicardial and transvenous CIEDs.

Background: Mid-myocardial ventricular arrhythmias are challenging to treat. Cardiac electroporation via pulsed electric fields (PEFs) offers significant promise. We therefore tested PEF delivery using screw-in pacemaker leads as proof-of-concept., Methods: In 5 canine models, we applied nanosecond PEF (pulse width 300 ns) across the right ventricular (RV) septum using a single lead bipolar configuration (n = 2) and between two leads (n = 3). We recorded electrograms (EGMs) prior to, immediately post, and 5 min after PEF. Cardiac magnetic resonance imaging (cMRI) and histopathology were performed at 2 weeks and 1 month., Results: Nanosecond PEF induced minimal extracardiac stimulation and frequent ventricular ectopy that terminated post-treatment; no canines died with PEF delivery. With 1 lead, energy delivery ranged from 0.64 to 7.28 J. Transient ST elevations were seen post-PEF. No myocardial delayed enhancement (MDE) was seen on cMRI. No lesions were noted on the RV septum at autopsy. With 2 leads, energy delivery ranged from 56.3 to 144.9 J. Persistent ST elevations and marked EGM amplitude decreases developed post-PEF. MDE was seen along the septum 2 weeks and 1 month post-PEF. There were discrete fibrotic lesions along the septum; pathology revealed dense connective tissue with < 5% residual cardiomyocytes., Conclusions: Ventricular electroporation is feasible and safe with an active fixation device. Reversible changes were seen with lower energy PEF delivery, whereas durable lesions were created at higher energies. Central illustration: pulsed electric field delivery into ventricular myocardium with active fixation leads., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background The epidemiology of ventricular arrhythmias (VAs) in patients with advanced heart failure (HF) is not well defined. Methods and Results Residents of Olmsted County, Minnesota, with advanced HF from 2007 to 2017 were identified using the 2018 European Society of Cardiology criteria. Billing codes were used to capture VAs; severe VAs requiring emergency care were defined as events associated with emergency department visits or hospitalizations. The cumulative incidence of VAs postadvanced HF was estimated with the Kaplan-Meier method. Multivariable Cox analyses were used to determine the following: (1) Predictors of severe VAs postadvanced HF; and (2) Impact of severe VAs on mortality. Of 936 patients with advanced HF, 261 (27.9%) had a history of VA. The 1-year cumulative incidence of severe VAs postadvanced HF was 5.4%. Prior VAs (hazard ratio [HR] 2.22 [95% CI, 1.26-3.89], P =0.006) and left ventricular ejection fraction <40% (HR, 3.79 [95% CI, 1.72-8.39], P <0.001) were independently associated with increased severe VA risk postadvanced HF. New-onset severe VAs were associated with increased mortality (HR, 4.41 [95% CI, 2.80-6.94]; P <0.001), whereas severe VAs in patients with prior VAs had no significant association with mortality risk (HR, 1.08 [95% CI, 0.65-1.78]; P =0.77). Severe VAs were associated with increased mortality in patients without implantable cardioverter defibrillators (HR, 4.89 [95% CI, 2.89-8.26]; P <0.001), but not in patients with implantable cardioverter defibrillators (HR, 1.42 [95% CI, 0.92-2.19]; P =0.11). Conclusions Patients with left ventricular ejection fraction <40% and prior VAs have increased risk of severe VA postadvanced HF. New-onset severe VAs or severe VAs without implantable cardioverter defibrillators postadvanced HF are associated with increased mortality.

[Figure: see text].

Background: Despite safety communications from the Food and Drug Administration (FDA) regarding the outbreak of Mycobacterium chimaera infections (MCIs) from contaminated heater-cooler devices, new cases continue to be identified., Methods: We retrospectively reviewed confirmed cases of MCI that were managed at Mayo Clinic sites (Arizona, Florida, and Minnesota) from 09/2015 to 01/2021. Clinical histories including prior cardiovascular surgery were recorded. Diagnostic workup including ophthalmologic examination, imaging, and laboratory testing was reviewed. Treatment and survival outcomes on follow-up were obtained., Results: Twelve patients with MCI were included. All patients had aortic valve or graft replacement. Five patients had their surgical procedures following the 10/15/2015 FDA safety communication. The mean time from surgery to symptom onset (range) was 32 (13-73) months. Ten of 11 patients who underwent ophthalmologic examination had chorioretinal abnormalities. Three patients who underwent microbial cell-free deoxyribonucleic acid sequencing tested positive for M. chimaera, which was subsequently confirmed with blood culture growth. Echocardiography and positron emission tomography/computed tomography (PET/CT) revealed evidence of prosthetic valve/graft infection in 7/12 (58.3%) and 6/10 (60.0%) of cases, respectively. Seven patients (58.3%) underwent redo cardiovascular surgery. Of these, 1 patient died 2 days postdischarge, 1 experienced spinal osteomyelitis relapse, and another had interval prosthetic valve fluorodeoxyglucose (FDG) uptake on PET/CT suspicious for recurrent infection. Among 4 patients on medical therapy only, 3 expired or transitioned to hospice during follow-up., Conclusions: MCI continues to occur despite the FDA communications. Incorporation of ophthalmologic examination and use of advanced tools may improve MCI diagnosis. The mortality in these patients is high even with aggressive surgical/medical management., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Deficiencies in DNA repair and DNA degrading nucleases lead to accumulation of cytosolic DNA. cGAS is a critical DNA sensor for the detection of cytosolic DNA and subsequent activation of the STING signaling pathway. Here, we show that the cGAS-STING pathway was unresponsive to STING agonists and failed to induce type I interferon (IFN) expression in many tested human tumor cells including DU145 prostate cancer cells. Inhibition of IL-6 or the downstream JAK2/STAT3 signaling restored responsiveness to STING agonists in DU145 cells. STING activity in murine TRAMP-C2 prostate cancer cells was critical for tumor rejection and immune cell infiltration. Endogenous STING agonists including double-stranded DNA and RNA:DNA hybrids present in TRAMP-C2 cells contribute to tumor rejection, but tumor growth was further suppressed by administration of cGAMP. Intratumoral co-injections of IL-6 significantly reduced the anti-tumor effects of cGAMP. In summary, STING in tumor cells contributes to tumor rejection in prostate cancer cells, but its functions are frequently suppressed in tumor cells in part via JAK2 and STAT3 pathways.

Objective: To assess 4 adverse renal outcomes in a heterogeneous cohort of patients with systolic heart failure (HF) who were prescribed sacubitril-valsartan vs angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB)., Patients and Methods: The OptumLabs Database Warehouse, which contains linked administrative claims and laboratory results, was used to identify patients with systolic HF who were prescribed sacubitril-valsartan or ACEi/ARB between July 1, 2015, and September 30, 2019. One-to-one propensity score matching and inverse probability of treatment weighting was used to balance baseline variables. Cox proportional hazards modeling was performed to compare renal outcomes in both medication groups, including 30% or more decline in estimated glomerular filtration rate (eGFR), doubling of serum creatinine, acute kidney injury (AKI), and kidney failure (eGFR < 15 mL/min per 1.73 m 2 , kidney transplant, or dialysis initiation)., Results: A total of 4667 matched pairs receiving sacubitril-valsartan or ACEi/ARB were included; the mean follow-up period was 7.8±7.8 months. The mean age was 69.4±11 years; 35% were female, 19% black, and 15% Hispanic. The cumulative risk at 1 year was 6% for 30% or more decline in eGFR, 2% for doubling of serum creatinine, 3% for AKI, and 2% to 3% for kidney failure. Furthermore, no significant differences in risk were observed with sacubitril-valsartan compared with ACEi/ARB for a 30% or more decline in eGFR (hazard ratio [HR], 0.96; 95% CI, 0.79 to 1.10), doubling of serum creatinine (HR, 0.94; 95% CI, 0.69 to 1.27); AKI (HR, 0.80; 95% CI, 0.63 to 1.03), and kidney failure (HR 0.80; 95% CI, 0.59 to 1.08)., Conclusion: Among patients with systolic HF, the risk of adverse renal outcomes was similar between patients prescribed sacubitril-valsartan and those prescribed ACEi/ARB., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Objective: To investigate the clinical presentation, pathophysiology, and treatment for "paroxysmal severe mitral regurgitation" (MR), which is an underappreciated cause of heart failure with preserved left ventricular ejection fraction., Methods: We retrospectively reviewed cases of transient severe MR that were evaluated at Mayo Clinic in Rochester, Minnesota, between January 1, 2006, and December 31, 2019. Paroxysmal severe MR was defined as the appearance of transient severe MR in patients with mild MR at rest, normal left ventricle (LV) size, left ventricular ejection fraction greater than 40%, and absence of obstructive coronary artery disease., Results: We identified 6 patients (5 women) with a median age of 68 years. There were 3 distinct mechanisms of paroxysmal severe MR, which we labeled types 1, 2, and 3. Type 1 MR was caused by LV dyssynchrony from a rate-dependent left bundle branch block, which led to apical leaflet tenting and incomplete coaptation. Type 2 MR occurred from mitral annular dilatation during maneuvers that increased left-sided volume. Type 3 MR was caused by coronary artery vasospasm with apical leaflet tenting. Treatments varied depending on the underlying cause and included cardiac resynchronization therapy for type 1, surgical valve replacement for type 2, and medical therapy for type 3., Conclusion: Paroxysmal severe MR is a rare cause of heart failure in patients with preserved LV function. We have identified 3 distinct mechanisms that can lead to this dynamic process, with treatments varying based on the underlying cause., (Copyright © 2020. Published by Elsevier Inc.)

Background: Case reports and referral-based studies suggest spontaneous coronary artery dissection (SCAD) is associated with autoimmune diseases and causes 2% to 4% of acute coronary syndromes., Objectives: This study determined the association of SCAD with autoimmune diseases, together with incidence and recurrence, in a population-based study., Methods: This case-control study took place from 1995 to 2018 within the Rochester Epidemiology Project. The study identified cases with SCAD from diagnosis codes and verified them using coronary angiography images, matching each case to 3 control subjects on age, sex, county, and years of medical history. Autoimmune disease history came from a validated, code-based definition. A multivariable logistic regression model calculated the odds ratio (OR) for SCAD among patients with a history of autoimmune disease, adjusting for race and body mass index., Results: The study identified 114 cases with SCAD (mean age 51 years and 90% women) and 342 matched control subjects. Autoimmune disease occurred in 13 (11%) cases with SCAD and 40 (12%) control subjects (p = 0.93). Even after adjustment, autoimmune diseases were not associated with SCAD (OR: 0.81; 95% confidence interval [CI]: 0.40 to 1.66). SCAD incidence between 2010 and 2018 (2.7 per 100,000; 95% CI: 1.7 to 3.7) was 10-fold higher than the incidence between 1995 and 2009 (0.3 per 100,000; 95% CI: 0.0 to 0.6). SCAD recurrence was 10% (95% CI: 3% to 16%) at 5 years., Conclusions: These findings suggested SCAD pathogenesis is noninflammatory and screening for autoimmune diseases based on SCAD alone is not warranted. The code-based incidence of SCAD has increased over time, highlighting the importance of considering SCAD among patients with acute coronary syndromes., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Genome-wide association studies have identified several genes associated with glaucoma. However, their roles in the pathogenesis of glaucoma remain unclear, particularly their effects on retinal nerve fiber layer (RNFL) thickness. The aim of this study was to investigate the associations between the identified glaucoma risk genes and RNFL thickness., Methods: A total of 3843 participants (7,020 healthy eyes) were enrolled from the Singapore Epidemiology of Eye Diseases (SEED) study, a population-based study composing of three major ethnic groups-Malay, Indian, and Chinese-in Singapore. Ocular examinations were performed, and spectral-domain optical coherence tomography (SD-OCT) was used to measure circumpapillary RNFL thickness. We selected 35 independent glaucoma-associated genetic loci for analysis. An linear regression model was conducted to determine the association of these variants with circumpapillary RNFL, assuming an additive genetic model. We conducted association analysis in each of the three ethnic groups, followed by a meta-analysis of them., Results: The mean age of the included participants was 59.4 ± 8.9 years, and the mean RFNL thickesss is 92.3 ± 11.2 µm. In the meta-analyses, of the 35 glacuoma loci, we found that only SIX6 was significantly associated with reduction in global RNFL thickness (rs33912345; β = -1.116 um per risk allele, P = 1.64E-05), and the effect size was larger in the inferior RNFL quadrant (β = -2.015 µm, P = 2.9E-6), and superior RNFL quadrant (β = -1.646 µm, P = 6.54E-5). The SIX6 association were consistently observed across all three ethnic groups. Other than RNFL, we also found several genetic varaints associated with vertical cuo-to-disc ratio (ATOH7, CDKN2B-AS1, and TGFBR3-CDC7), rim area (SIX6 and CDKN2B-AS1), and disc area (SIX6, ATOH7, and TGFBR3-CDC7). The association of SIX6 rs33912345 with NRFL thickness remained similar after further adjusting for disc area and 3 other disc parameter associated SNPs (ATOH7, CDKN2B-AS1, and TGFBR3-CDC7)., Conclusions: Of the 35 glaucoma identified risk loci, only SIX6 is significantly and independently associated with thinner RNFL. Our study further supports the involvement of SIX6 with RNFL thickness and pathogensis of glaucoma.

Left bundle branch block may be due to conduction system degeneration or a reflection of myocardial pathology. Left bundle branch block may also develop following aortic valve disease or cardiac procedures. Patients with heart failure with reduced ejection fraction and left bundle branch block may respond positively to cardiac resynchronization therapy. Lead placement via the coronary sinus is the mainstay approach of cardiac resynchronization therapy. However, other options, including physiological pacing, are being explored. In this review, we summarize the salient pathophysiologic and clinical aspects of left bundle branch block, as well as current and future strategies for management.

Purpose: The aim of this study was to determine whether cataract surgery was associated with age-related macular degeneration (AMD) development in Asian patients., Design: Longitudinal cohort study., Methods: Participants from the Singapore Malay and Indian Eye Studies were recruited between 2004 and 2015. A total of 6790 late-AMD-free eyes from 3475 individuals were followed for 6 years on average. Multivariable regression analysis using generalized estimating equations determined associations between cataract surgery and the incidence of any, early, and late AMD., Results: The mean age (SD) of participants was 55.5 (9.1) years; 48.1% were male; 11.3% of eyes had cataract surgery recorded; incident any, early, and late AMD developed in 238 (3.6%), 222 (3.4%), and 29 (0.4%) eyes, respectively. Operated eyes had higher incidence of late AMD [1.4% vs 0.3%; adjusted risk ratio (RR): 3.47, 95% confidence interval (CI) 1.40-8.57], but not early AMD (6.0% vs 3.0%, adjusted RR: 1.12, 95% CI 0.76-1.64) or any AMD (6.9 vs 3.2%, adjusted RR: 1.23, 95% CI 0.85-1.78)., Conclusions: Our data are consistent with findings in population-based Caucasian studies that cataract surgery may be associated with incidence of late AMD. However, the absolute risk of late AMD development remains low and physicians should continue to balance the benefits and risks of cataract surgery in elderly patients.

Objectives: This paper aims to compare the effectiveness of sacubitril-valsartan and angiotensin-converting enzyme inhibitor (ACE)/angiotensin receptor blocker (ARB) in systolic heart failure (HF)., Background: Sacubitril-valsartan reduced risks of death and hospitalization for HF versus enalapril in ambulatory patients with HF and reduced ejection fraction in the PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor with Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in HF) trial. However, the comparative effectiveness of sacubitril-valsartan and ACE/ARB in patients treated in routine clinical practice is unclear., Methods: We identified patients with systolic HF in a U.S. administrative claims database treated with sacubitril-valsartan or ACE/ARB from July 1, 2015, to February 2, 2018. One-to-one propensity score matching was used to balance patients on 29 clinical variables. Cox models were used to compare outcomes between treatment groups., Results: A total of 7,893 matched pairs were included; mean (SD) follow-up was 6.3 (5.4) months. Sacubitril-valsartan was associated with lower risks of all-cause mortality or all-cause hospitalization (hazard ratio [HR]: 0.86, 95% confidence interval (CI): 0.81 to 0.91; p < 0.001), all-cause mortality (HR: 0.80, 95% CI: 0.66 to 0.97; p = 0.027), and all-cause hospitalization (HR: 0.86, 95% CI: 0.80 to 0.91; p < 0.001), but not HF hospitalization (HR: 1.07, 95% CI: 0.96 to 1.19; p = 0.26). A lower risk of the primary outcome with sacubitril-valsartan was observed in white patients (HR: 0.83, 95% CI: 0.76 to 0.90) but not black patients (21% of population, HR: 1.00, 95% CI: 0.88 to 1.15; interaction p = 0.032). No statistically significant differences in treatment response by sex or age were observed., Conclusions: Sacubitril-valsartan was associated with lower risks of death and hospitalization compared with ACE/ARB in a heterogeneous cohort of patients with systolic HF. However, our finding that outcomes with sacubitril-valsartan and ACE/ARBs were similar in black patients warrants further evaluation., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Mechanisms and risk factors for cerebrovascular accidents (CVAs) in Ebstein's anomaly (EA) are not well understood; hence, we aimed to clarify these in a large cohort of EA patients., Methods: Patients with a confirmed diagnosis of EA were retrospectively reviewed. Baseline characteristics were compared between patients with and without a prior history of CVA using logistic regression modeling. Cox regression analysis was used to identify predictors of CVA following initial evaluation. CVA incidence from birth and following tricuspid valve surgery were estimated using the Kaplan-Meier method., Results: Nine hundred sixty-eight patients (median age 21.1 years, 41.5% male) were included, in which, 87 patients (9.0%) had a history of CVA (54 strokes, 33 transient ischemic attacks; 5 associated with brain abscesses) prior to their initial evaluation. The odds of atrial septal defect/patent foramen ovale (odds ratio [OR] 4.91; 95% CI 2.60-21.22; p = .0002) and migraines/headaches (OR 2.38; 95% CI 1.40-4.04; p = .0013) but not atrial arrhythmias (OR 0.75; 95% CI 0.44-1.30; p = .31) were significantly higher among patients with prior CVA following multivariable adjustment. Seventeen patients experienced CVA following initial evaluation; no examined variables including atrial arrhythmias (HR 2.38; 0.91-6.19; p = .076) were predictive of CVA risk. The 10-year, 50-year, and 70-year incidences of CVA were 1.4%, 15.9%, and 23.5%, respectively, with paradoxical embolism heavily implicated., Conclusion: Patients with EA are at substantive risk for CVA. Histories of migraines/headaches and interatrial shunts should prompt concern for paradoxical embolic CVAs. This has significant implications for all patients with atrial-level shunting., (© 2019 Wiley Periodicals, Inc.)

Introduction : Spontaneous coronary artery dissection (SCAD) is an increasingly appreciated cause of acute myocardial infarction (AMI) and sudden cardiac death most often affecting young to middle-aged women with few conventional cardiovascular risk factors. Areas covered : A literature search was performed using MedLine, PubMed, and Google Scholar (dating to 04/30/2019). Authors review the key clinical features of SCAD and highlight what is known regarding its pathophysiology and associated factors. The relationship between SCAD and other systemic vasculopathies, notably fibromuscular dysplasia (FMD) is also discussed. Authors also mention the management of acute SCAD along with considerations for long term follow-up such as chest pain syndrome, extracoronary vasculopathy screening, and recurrent SCAD. Expert opinion : Our understanding regarding the association of SCAD and other arteriopathies such as FMD is anticipated to grow. In addition, progress is likely to be made in our efforts to predict recurrent SCAD risk and define potential preventative strategies, possibly through the incorporation of adjunctive imaging.

Purpose: The evolution of heart rhythm monitoring technology over the past few decades has seen a decline in the use and need of transtelephonic monitoring (TTM). We sought to establish a predicted date for the sun setting of TTM at our institution, as well as establish the current demographics of the patients still using this technology., Methods: We retrospectively reviewed all patients with permanent pacemakers receiving routine device follow-up at our institution (Mayo Clinic-Rochester) between 2015 and 2018. From this cohort, we reviewed and analyzed patients using TTM for device follow-up and utilized projected battery longevity to determine cessation date. Pacemaker implantation date, underlying arrhythmia, and most recent device interrogation reports were also collected., Results: As of March 2018, a total of 3543 patients with permanent pacemakers were being followed at our institution and 289 (8.2%) are using TTM for monitoring device function (147 male, mean age 79.9 ± 12.0 years). Of those currently using TTM, by January of 2020, only 122 (42.2%) are predicted to be using this technology for device follow-up, 40 (13.8%) by January 2022, with zero patients by November of 2024., Conclusions: The use of TTM will continue to significantly diminish over the next few years. Based on battery longevity estimates, we predict that by the end of 2024 TTM will no longer be used for device follow-up at our institution.

Cardiac magnetic resonance (CMR) has significant diagnostic and prognostic utility in myocardial infarction evaluation. However, its application in spontaneous coronary artery dissection (SCAD) is not described. Patients with confirmed SCAD who had CMR performed within 8 days of the index SCAD were reviewed. Clinical variables including demographics and medical history were recorded. CMR indexes, including myocardial delayed enhancement (MDE), microvascular obstruction, perfusion defects, left ventricular ejection fraction, and wall motion score index were measured. A total of 18 patients (all women, mean age 47.1 years) were included. Overall burden of atherosclerotic risk factors was low; 3 had a previous SCAD. Two patients underwent CMR before coronary angiography, whereas the others received CMR thereafter. Mean time between SCAD diagnosis and CMR completion was 2.7 days (range 0 to 8). Mean left ventricular ejection fraction and wall motion score index were 56.1% and 1.27, respectively. A total of 15 patients had MDE consistent with myocardial infarction in the SCAD distribution(s) identified on coronary angiography, with 8 patients having concomitant microvascular obstruction. Ten patients had transmural MDE. At follow-up (mean 386 days), all patients were alive; extracoronary vascular abnormalities were identified in 14; 6 had recurrent chest pain; and 2 had recurrent SCAD. Both patients with recurrent SCAD had no unique features on CMR to predict a future event. In conclusion, CMR provided significant value in clarifying the diagnosis and assessing for adverse sequelae after acute SCAD. Further studies are needed to determine its role in SCAD prognostication., (Copyright © 2018. Published by Elsevier Inc.)

Aims: Ventricular dysfunction or structural alteration of either ventricle is a well-established risk factor for sudden death (SD). Ebstein anomaly (EA) can present with both right and left heart abnormalities; however, predictors of SD have not been described. We therefore sought to characterize the incidence and risk factors of SD among a large cohort of patients with EA., Methods and Results: All EA patients who underwent evaluation at a high-volume institution over a 4-decade period were retrospectively reviewed. Clinical variables, cardiovascular surgical procedure(s), and cause of death were recorded. Sudden death incidence from birth and following tricuspid valve (TV) surgery were estimated using the Kaplan-Meier method. Cox regression analysis was used to identify clinical and surgical predictors of SD. The cohort comprised of 968 patients [mean age 25.3 years, 41.5% male; 79.8% severe EA, 18.6% accessory pathway, 0.74% implantable cardioverter-defibrillator (ICD) placement]. The 10-, 50-, and 70-year cumulative incidences of SD from birth were 0.8%, 8.3%, and 14.6%, respectively. Prior ventricular tachycardia [hazard ratio (HR) 6.37, P < 0.001)], heart failure (HR 5.64, P < 0.001), TV surgery (HR 5.94, P < 0.001), syncope (HR 2.03, P = 0.019), pulmonic stenosis (HR 3.42, P = 0.001), and haemoglobin > 15 g/dL (HR 2.05, P = 0.026) were multivariable predictors of SD. In a similar subgroup analysis of patients who underwent TV surgery, all of the above factors except syncope were significantly associated with post-operative SD on multivariable analysis., Conclusion: Patients with EA are at significant risk for SD. Key clinical SD predictors identified can aid in risk stratification and potentially guide primary prevention ICD implantation.

The left atrial appendage has been implicated as a major nidus for thrombus formation, particularly in atrial fibrillation. This discovery has prompted substantial interest in the development of left atrial appendage exclusion devices aimed at decreasing systemic thromboembolism risk. Its deceptively simple appearance belies the remarkable complexity that characterizes its anatomy and physiology. We highlight the key anatomic features and variations of the left atrial appendage as well as its relationships with surrounding structures. We also summarize crucial anatomic factors that should be taken into account by the interventional cardiologist when planning for or performing left atrial appendage exclusion procedures., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Mesalamine, or 5-aminosalicylic acid, is a frequently used medication for the treatment of inflammatory bowel disease (IBD). We report the case of a 40-year-old woman recently diagnosed with IBD and started on mesalamine, who presented with new onset tender skin lesions 3 days following medication administration. One day following the onset of skin lesions, the patient developed acute chest pain, shortness of breath, ECG changes, troponemia, C-reactive protein elevation and pericardial enhancement on cardiac MRI consistent with myopericarditis. Subsequent skin biopsy confirmed the diagnosis of Sweet's syndrome. On cessation of the drug, both the skin lesions and the cardiac symptoms resolved in combination with anti-inflammatory therapy. While mesalamine has been previously associated with myocarditis and pericarditis, to our knowledge this is the first case of coexisting Sweet's syndrome with myopericarditis in the context of mesalamine therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)