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Larry R Jackson II,1 Daniel J Friedman,1 Diane M Francis,2 Sonia Maccioni,2 Vincent C Thomas,3 Paul Coplan,4 Rahul Khanna,4 Charlene Wong,4 Neloufar Rahai,4 Jonathan P Piccini1 1Division of Cardiology, Duke University Medical Center & Duke Clinical Research Institute, Durham, NC, USA; 2Health Economics and Market Access, Johnson & Johnson Medical Devices, Irvine, CA, USA; 3Medical Safety, Biosense Webster, Irvine, CA, USA; 4Medical Device Epidemiology and Real-World Data Sciences, Johnson & Johnson, New Brunswick, NJ, USACorrespondence: Larry R Jackson II, Duke Clinical Research Institute, 300 W. Morgan Street, Durham, NC, 27701, USA, Tel +1 919-684-9940, Email larry.jackson@duke.eduBackground: Atrial fibrillation (AF) is associated with considerable morbidity and mortality. Timely management and treatment is critical in alleviating AF disease burden. Variation in treatment by race and ethnic and sex could lead to inequities in health outcomes.Objective: To identify racial and ethnic and sex differences in rhythm treatment for patients with incident AF.Methods: Using 2010– 2019 Optum Clinformatics database, an administrative claims data for commercially insured patients in the United States (US), incident AF patients ≥ 20 years old who were continuously enrolled 12-months pre- and post-index diagnosis were identified. Rhythm control treatment (ablation, antiarrhythmic drugs [AAD], and cardioversion) for AF were compared by patient race and ethnicity (Asian, Hispanic, Black vs White) and sex (female vs male). Multivariable regression analysis was used to examine the relationship of race and ethnicity and sex with rhythm control AF treatment.Results: A total of 77,932 patients were identified with incident AF. Black and Hispanic female patients had the highest CHA2DS2VASc scores (4.3 ± 1.8) and Elixhauser scores (4.1 ± 2.8 and 4.0 ± 6.7), respectively. Black males were less likely to receive AAD treatment (adjusted odds ratio [aOR] 0.87; 95% confidence interval [CI], 0.79– 0.96) or ablation (aOR, 0.72; 95% CI, 0.58– 0.90). Compared to White males, all groups had lower likelihood of receiving cardioversion with Asian females having the lowest [aOR, 0.48; 95% CI, (0.37– 0.63)].Conclusion: Black patients were less likely to receive pharmacologic and procedural rhythm control therapies. Further research is needed to understand the drivers of undertreatment among racial and ethnic groups and females with AF.Keywords: race, sex, atrial fibrillation, catheter ablation

The complete amino acid sequence of the Drosophila melanogaster Cu,Zn superoxide dismutase subunit has been determined by automated Edman degradation. Sequence analyses were performed on the intact S-carboxymethylated protein, two fragments derived from CNBr cleavage, and three peptides recovered from mouse submaxillary protease digestion of the reduced and S-carboxymethylated enzyme. The peptides were aligned by characterizing peptides yielded by trypsin and Staphylococcus aureus V8 protease. All the peptides studied were purified exclusively by reverse-phase columns of HPLC and were analyzed with an improved liquid-phase sequencer. A molecular weight of 15,750 (subunit) was calculated from the 151 residues sequenced. The amino acid sequence of the Drosophila superoxide dismutase subunit is compared with that of four other eucaryotes: man, horse, cow, and yeast. Comparison of the five primary structures reveals very different rates of evolution at different times. Copper-zinc superoxide dismutase appears to be a very erratic evolutionary clock. Val-Val-Lys-Ala- Val-Cys-Val-Ile-Asn-Gly-Asp-Ala-Lys-Gly-Thr-Val-Phe-Phe-Glu-Gln- Glu-Ser-Ser-Gly-Thr-Pro-Val-Lys-Val-Ser-Gly-Glu-Val-Cys-Gly-Leu- Ala-Lys-Gly-Leu-His-Gly-Phe-His-Val-His-Glu-Phe-Gly-Asp-Asn-Thr- Asn-Gly-Cys-Met-Ser-Ser-Gly-Pro-His-Phe-Asn-Pro-Tyr-Gly-Lys-Glu- His-Gly-Ala-Pro-Val-Asp-Glu-Asn-Arg-His-Leu-Gly-Asp-Leu-Gly-Asn- Ile-Glu-Ala-Thr-Gly-Asp-Cys-Pro-Thr-Lys-Val-Asn-Ile-Thr-Asp-Ser- Lys-Ile-Thr-Leu-Phe-Gly-Ala-Asp-Ser-Ile-Ile-Gly-Arg-Thr-Val-Val-Val- His-Ala-Asp-Ala-Asp-Asp-Leu-Gly-Gln-Gly-Gly-His-Glu-Leu-Ser-Lys- Ser-Thr-Gly-Asn-Ala-Gly-Ala-Arg-Ile-Gly-Cys-Gly-Val-Ile-Gly-Ile- Ala-Lys.

We have obtained the complete amino acid sequence of copper/zinc-containing superoxide dismutase (SOD, superoxide:superoxide oxidoreductase, EC 1.15.1.1) from Drosophila melanogaster. The sequence of this enzyme is also known for man, horse, cow, and the yeast Saccharomyces cerevisiae. The rate of evolution of this enzyme is far from constant. The number of amino acid substitutions per 100 residues per 100 million years is 30.9 when the three mammals are compared to each other, 10.6 when Drosophila is compared to the three mammals, and 5.8 when the yeast is compared to the four animals. The first value represents one of the fastest evolutionary rates for any protein, the second is similar to the globin rate, and the third is similar to some cytochromes and other slowly evolving proteins. Hence, SOD is not an acceptable evolutionary clock. Another peculiarity of this enzyme is that a two-amino-acid deletion must have occurred independently in the lineages going to the cow and to Drosophila. We conclude that using the primary structure of a single gene or protein to time evolutionary events or to reconstruct phylogenetic relationships is potentially fraught with error.

Suprascapular neuropathy has often been overlooked as a source of shoulder pain. The condition may be more common than once thought as it is being diagnosed more frequently. Etiologies for suprascapular neuropathy may include repetitive overhead activities, traction from a rotator cuff tear, and compression from a space-occupying lesion at the suprascapular or spinoglenoid notch. Magnetic resonance imaging is useful for visualizing space-occupying lesions, other pathological entities of the shoulder, and fatty infiltration of the rotator cuff. Electromyography and nerve conduction velocity studies remain the standard for diagnosis of suprascapular neuropathy; however, data on interobserver reliability are limited. Initial treatment of isolated suprascapular neuropathy is typically nonoperative, consisting of physical therapy, nonsteroidal anti-inflammatory drugs, and activity modification; however, open or arthroscopic operative intervention is warranted when there is extrinsic nerve compression or progressive pain and/or weakness. More clinical data are needed to determine if treatment of the primary offending etiology in cases of traction from a rotator cuff tear or compression from a cyst secondary to a labral tear is sufficient or whether concomitant decompression of the nerve is warranted for management of the neuropathy. [ABSTRACT FROM AUTHOR]

The long head of the biceps tendon is a known pain generator of the shoulder. There are numerous pathologic entities that may affect this tendon, including tendonitis, partial tearing, and subluxation. These conditions are often associated with rotator cuff tears, especially those involving the subscapularis. Operative interventions include tenotomy and tenodesis. Tenodesis can be preformed in a proximal or distal location. Subpectoral tenodesis may have a lower recurrence rate than proximal-based techniques. [ABSTRACT FROM AUTHOR]

Based on a review of state public health department Web sites, this article describes Web-based Data Query Systems (WDQSs) currently used in 27 US states. In addition, functionalities of selected well-established state WDQSs are defined as major functionalities (11), subfunctionalities (21), and specific functionalities (141), on the basis of a consensus process with participants from states and national organizations in the United States and Canada. Also, on the basis of the consensus process, specific functionalities are categorized as core, enhanced, and expert. Key terms relevant to WDQSs are defined. The information contained in this article should prove useful to public health agencies developing, revising, or evaluating the WDQS. [ABSTRACT FROM AUTHOR]

This article explores factors that facilitate or impede data sharing and linkage collaborations between state public health agencies and managed care organizations (MCOs). The exploration is based upon a review of both recent literature and the four years' experience of the Massachusetts Health Assessment Partnership (MHAP). MHAP has undertaken six collaborative data sharing and linkage projects that have involved diverse topics and methods. This article summarizes both exogenous and endogenous factors that have affected MHAP as a successful collaboration and indicates those factors that might be replicated in future collaborations between public health agencies and MCOs in other locations. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study assessed the impact of the Office of Management and Budget's (OMB's) 1997 revised standards for the collection of race and ethnicity data on state health departments, using the Massachusetts Department of Public Health (MDPH) as the primary example, and we make recommendations for states' implementation of these standards. METHODS: After analyzing the revised OMB standards, existing MDPH data sets were assessed for the impact of the revised standards on data collection, tabulation, analysis, and reporting for state health departments. RESULTS: The revised OMB standards will have an impact on the MDPH and other state health departments. Similarities and differences exist between federal and state health agencies regarding the purpose of data collection, tabulation, analysis, and reporting. These similarities and differences will affect state implementation of the revised OMB standards. CONCLUSIONS: States need to plan for the implementation of the revised OMB standards and to understand the impact of this revision on the collecting and reporting of public health data. The revised OMB standards will introduce added complexities to the collection and analysis of race and ethnicity data, but they will also produce a more nuanced understanding of the relationship of race and ethnicity to the health of the American people. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) and kidney failure with replacement therapy (KFRT) are prevalent in patients with atrial fibrillation (AF)., Objective: The purpose of this study was to analyze procedural and long-term outcomes in AF patients with underlying CKD and KFRT after left atrial appendage occlusion (LAAO) device implantation., Methods: Data were extracted from the National Cardiovascular Data Registry LAAO Registry from January 2017 to December 2019 and linked to Centers for Medicare & Medicaid Services billing claims. Patients were stratified into 3 groups: no CKD, CKD, and KFRT. Multivariate analyses were used to assess the associations of CKD and KFRT with procedural and long-term outcomes, respectively., Results: A total of 59,190 patients were enrolled in our study. CKD and KFRT were found to be independently associated with any complication from the procedure (odds ratio [OR] 1.149, 95% confidence interval [CI] 1.058-1.;247 and OR 2.163, 95% CI 1.763-2.652) and in-hospital death (OR 1.603, 95% CI 1.054-2.437; and OR 5.488, 95% CI 2.686-11.213). At 1 year, CKD and KFRT were associated with a higher risk of any major adverse event (hazard ratio [HR] 1.402, 95% CI 1.333-1.474; and HR 2.506, 95% CI 2.236-2.809) and death (HR 1.662, 95% CI 1.553-1.779; and HR 3.422, 95% CI 2.989-3.919), but no difference in the competing risk of stroke (HR 0.972, 95% CI 0.819-1.152; and HR 0.794, 95% CI 0.434-1.451)., Conclusion: CKD and KFRT were associated with higher rates of procedural complications and 1-year adverse events and death, but no difference in the 1-year rate of stroke., Competing Interests: Disclosures Dr Friedman has received research grants from the American Heart Association, National Cardiovascular Data Registry, Boston Scientific, Abbott, Medtronic, Merit Medical, and Biosense Webster; and receives consulting fees from Abbott, AtriCure, and Sanofi. Dr Curtis has an institutional contract with the American College of Cardiology for his role as senior scientific advisor of the NCDR; and has equity interest in Medtronic. Dr Freeman has received consulting fees from Medtronic, Boston Scientific, Pacemate, Abbott, and Biosense Webster; and has received equity from Pacemate. Dr Pun has received research grants from Medtronic. All other authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The first commercial systems for pulsed field ablation (PFA) were recently approved by the Food and Drug Administration, but their safety profile in nationwide practice remains underexplored., Objectives: This study aimed to describe reported adverse events with PFA systems after their market release and to compare the relative proportion of complications associated with PFA vs radiofrequency (RF) ablation catheters., Methods: We conducted a search of the Manufacturer and User Facility Device Experience database for adverse event reports involving Food and Drug Administration-approved PFA and RF catheters from January 1, 2024, to July 31, 2024., Results: A total of 1237 reports detailing clinical complications (n=156 for PFA and n=315 for RF) or catheter malfunctions (n=336 for PFA and n=430 for RF) were analyzed. The most common adverse events reported for PFA were pericardial effusion, vasovagal response, and hemolysis, and these were pericardial effusion, ischemic stroke, and esophageal damage for RF ablation. The proportion of reported adverse events that were deaths was lower in PFA than in RF (2.6% vs 8.9%; P=.010). Hemolysis (9.0% vs 0%), coronary events (5.8% vs 0.6%), and vasovagal responses (14.1% vs 0%) were reported more frequently after PFA (P<.001 for all). In contrast, esophageal damage (0% vs 4.1%; P<.001) and pulmonary vein stenosis (0% vs 1.9%; P=.184) were not reported with PFA, but only with RF. Regarding catheter malfunctions, mechanical problems were reported in higher proportion after PFA than after RF (87.2% vs 17.2%; P<.001)., Conclusion: The reported complications associated with PFA and RF ablation differ significantly. Close attention to PFA-specific complications is essential for ensuring the safe use of PFA and for mitigating risk., Competing Interests: Disclosures Dr Piccini is supported by grant R01AG074185 from the National Institutes of Aging. He also receives grants for clinical research from Abbott, the American Heart Association, Boston Scientific, iRhythm, and Philips and serves as a consultant for ABVF, Abbott, Boston Scientific, Kardium, Medtronic, Milestone Pharmaceuticals, Sanofi, Philips, and UpToDate. Dr Loring has received grant support from Boston Scientific and the Department of Veterans Affairs and serves as a consultant for Huxley Medical and Boston Scientific. Dr Pokorney reports research support from Milestone Pharmaceuticals, Boston Scientific, and Medtronic and speaker/consultant/advisory board support from Boston Scientific, Medtronic, Philips, Zoll, Bristol Myers Squibb, Pfizer, Johnson & Johnson, and Milestone Pharmaceuticals. Drs Cho, Lee, and Black-Maier had no relevant disclosures., (Copyright © 2024. Published by Elsevier Inc.)

Background: Data on whether cardiac resynchronization therapy (CRT) results in better clinical and echocardiographic outcomes in patients with nonischemic cardiomyopathy (NICM) vs ischemic cardiomyopathy (ICM) are conflicting., Objectives: The authors conducted this meta-analysis of 7 clinical trials of CRT to determine the association between etiology of cardiomyopathy and clinical and echocardiographic outcomes., Methods: The authors analyzed patient-level data using Bayesian Hierarchical Weibull survival regression modeling to determine the association between etiology of cardiomyopathy and time to all-cause death or heart failure hospitalization (HFH). Linear regression was used to assess the association between etiology of cardiomyopathy and echocardiographic measurements., Results: Of 6,252 patients included, 4,717 (75%) were men, median age was 66 years (IQR: 58-73 years), 3,704 (59%) had ICM, and 3,778 (60%) received CRT. CRT increased the time to HFH or all-cause death (HR: 0.67; 95% credible interval [CrI]: 0.56-0.82; P < 0.001) with no difference by etiology of cardiomyopathy (HR ratio: 1.06 [95% CrI: 0.87-1.29]; P = 0.57). Likewise, CRT increased the time to all-cause death (HR: 0.71 [95% CrI: 0.55-0.93]; P = 0.019) with no difference by etiology of cardiomyopathy (HR ratio: 1.06 [95% CrI: 0.80-1.43]; P = 0.70). Echocardiographic data that were available for 2,430 (39%) patients showed that CRT improvements in left ventricular ejection fraction, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter were larger for patients with NICM., Conclusions: Although CRT led to greater increases in left ventricular ejection fraction and reductions in ventricular dimensions for patients with NICM compared with those with ICM, CRT significantly increased the time to HFH or all-cause death independently of the etiology of cardiomyopathy. Further studies on improving patient selection for CRT are needed., Competing Interests: Funding Support and Author Disclosures Primary funding was provided by the National Heart, Lung, and Blood Institute (NHLBI) (1R01HL131754). Dr Cleland has received grants and personal fees from Pharmacosmos; personal honoraria from Abbott, AstraZeneca, Idorsia, Myokardia, NI Medical, Novartis, Servier, and Torrent Pharmaceuticals; grants and personal honoraria from Amgen/Cytokinetics, Bayer, Bristol Myers Squibb, Johnson & Johnson, Medtronic, Vifor, and Viscardia; and personal honoraria and nonfinancial support from Boehringer-Ingelheim outside of the submitted work. Dr Curtis serves on medical advisory boards for Janssen Pharmaceuticals, Medtronic, Abbott, Milestone Pharmaceuticals, and Eagle Pharmaceuticals; and she has received honoraria for speaking from Abbott and Medtronic. Dr Friedman has received research support from the American Heart Association, Boston Scientific, Biosense Webster, Merit Medical, Medtronic, National Institutes of Health, and Abbott; and consulting fees from Abbott, AtriCure, Microport, NI Medical, and Sanofi. Dr Gold serves on a medical advisory board for CVRx and EBR; has received research support to his institution from Boston Scientific, Abbott, and Medtronic; and is a consultant to Boston Scientific, Abbott, and Medtronic. Dr Linde has received research support to her institution from the Swedish Heart-Lung Foundation, Swedish Academy of Science, Roche Diagnostics, AstraZeneca, and Stockholm County Council; and speaker honoraria from Medtronic, Impulse Dynamics, Bayer, Boeringer Ingelheim, Novartis, Vifor Pharma, and Microport. Dr Al-Khatib has received research funding from Medtronic and Boston Scientific through grants to her institution. 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.)

Background: Percutaneous left atrial appendage occlusion (LAAO) is indicated in patients with atrial fibrillation for whom long-term oral anticoagulation is contraindicated. Whether outcomes are different based on operator certification [interventional cardiology (IC) versus electrophysiology (EP)] is unclear., Objectives: To compare LAAO outcomes by physician certification (EP versus IC) in the NCDR LAAO Registry., Methods: We identified patients from 2020-2022 undergoing implantation of a Watchman FLX or Amulet LAAO device and stratified patients by primary operator certification. Outcomes of interest included: (1) any major adverse event (MAE), 2) mortality, 3) ischemic stroke, and 4) major bleeding during the initial hospitalization and at 45 days. We performed multivariable Cox proportional hazards regression analysis to determine the risk of adverse events by physician certification., Results: A total of 1,638 physicians (57% electrophysiologists) performing 91,711 procedures during the study period were included. EPs were more likely to use intracardiac echocardiography (25.2% vs 9.7%, p<0.001) and had lower radiation total (235 mGy vs 305 mGy, p<0.001). EPs were more likely than ICs to discharge patients on DOAC+aspirin, whereas ICs were more likely to discharge patients on single or dual antiplatelet therapy (all p<0.001). In-hospital death (0.1% vs. 0.1%, p=0.46) and MAE (1.5% vs 1.6%, p=0.42) were similar by physician certification. At 45 days, there was no difference in death [HR death 1.03, 95% CI (0.89-1.2)] or MAE [HR MAE 0.97, 95% CI (0.91-1.03)] after multivariable regression., Conclusions: Contemporary LAAO is safe with low rates of procedural complications and no significant differences in procedural outcomes by operator subspecialty after multivariable adjustment. Continued utilization of technology by EPs and ICs is necessary to allow for broad access to this treatment for eligible patients., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Conduction system pacing (CSP), often accomplished with lumenless pacing leads, is increasingly employed to achieve physiologic ventricular activation. There are limited data on the extraction of these leads. The objective of this study was to describe the safety and efficacy of extraction of CSP pacing leads and compare outcomes with extraction of non-CSP lumenless leads., Methods: Patients undergoing CSP/non-CSP lumenless lead removal were included. Outcomes of interest included rates of complete procedural success, complications, and successful reimplantation., Results: Overall, 23 patients were included (n = 14 with CSP and n = 9 with non-CSP lumenless leads implanted in the right atrium, right ventricle, or septum). The mean age was 52.7 ± 24.0 years, 30% were female, and the mean lead age was 4.5 ± 4.4 years. The complete procedural success rate was 100%. One serious complication occurred in the non-CSP group but was unrelated to the lead of interest. Manual traction alone was successful in 57% of CSP cases (mean lead age 2.4 ± 1.7 years) and in 11% of non-CSP cases (mean lead age 7.9 ± 5.3 years). Laser sheaths were used in 43% of CSP cases and 89% of non-CSP cases; rotational cutting tools were used in no CSP cases and in 33% of non-CSP cases. Reimplantation in the conduction system was attempted with a left bundle branch pacing lead and successful in 80% (n = 4/5)., Conclusion: Extraction of CSP and non-CSP lumenless leads is feasible with a high success rate and a good safety profile. CSP reimplantation after extraction is also feasible with good electrical performance., (© 2024 Wiley Periodicals LLC.)

Genetic research presents numerous ethical, legal, and social implications (ELSI), particularly when the research involves collaborations between investigators in high and low-income countries. Some ELSI issues are universal, and others are specific to context and culture. This study investigates perceptions of genetic research in Nicaragua, Central America, where local and U.S. based researchers have collaborated for over a decade. A total of 43 residents from northwestern Nicaragua, a region with high mortality rates attributed to chronic kidney disease of non-traditional causes (CKDnt), were interviewed, including research participants in ongoing studies (n = 36), health professionals (n = 3), labor leaders (n = 2), and family members of research participants (n = 2). Questions focused on informed consent, data-sharing, and post-study expectations. Audio recordings of interviews conducted in Spanish were transcribed and translated into English. English transcripts were coded and analyzed using NVivo 12 software. The lack of familiarity with terms in the consent form presented a barrier to participant comprehension of key elements of the genetic research study, raising concerns about the validity of informed consent. Research participants often viewed their participation as access to health care. Health professionals emphasized the importance of long-term partnerships between foreign-based researchers and local health institutions. Leaders and family members recommended that they be informed of research studies and allowed the opportunity to consent, as they felt the benefits and risks of research also apply to them. Our findings identified genetic research practices to be improved upon in order to be more responsive to the contextual realities of collaborators living in low-resource settings., (© 2023. The Author(s).)

Apolipoprotein L1 (APOL1) variants G1 and G2 contribute to the excess risk of kidney disease in individuals of recent African ancestry. Since disease mechanisms and optimal treatments remain controversial, we study the effect of current standard-of-care drugs in mouse models of APOL1 kidney disease. Experiments were performed in APOL1 BAC-transgenic mice, which develop proteinuria and glomerulosclerosis following injection with a pCpG-free IFN-γ plasmid. Proteinuric, plasmid injected G1/G1 and G2/G2 mice were randomized to drug treatment or no treatment. Lisinopril, dapagliflozin, and hydralazine were administered in drinking water starting day seven. The urine albumin/creatinine ratio was measured twice weekly, and the kidneys examined histologically with the focal segmental glomerulosclerosis score computed from periodic acid-Shiff-stained sections. The angiotensin converting enzyme inhibitor lisinopril, at standard dose, reduced proteinuria by approximately 90-fold and reduced glomerulosclerosis in the APOL1 G1/G1 BAC-transgenic mice. These effects were independent of blood pressure. Dapagliflozin did not alter disease progression in either G1/G1 or G2/G2 mice. Proteinuria reduction and glomerulosclerosis in G2/G2 BAC-transgenic mice required lisinopril doses two times higher than were effective in G1/G1 mice but achieved a much smaller benefit. Therefore, in these BAC-transgenic mouse models of APOL1 disease, the anti-proteinuric and anti-glomerulosclerotic effects of standard dose lisinopril were markedly effective in G1/G1 compared with G2/G2 APOL1 mice. Comparable reduction in blood pressure by hydralazine treatment provided no such protection. Neither G1/G1 nor G2/G2 mice showed improvement with the sodium-glucose cotransporter-2 inhibition dapagliflozin. Thus, it remains to be determined if similar differences in ACE inhibitor responsiveness are observed in patients., (Published by Elsevier Inc.)

Background: Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation., Methods and Results: In this meta-analysis, we pooled patient-level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE-ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all-cause mortality, and time to all-cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all-cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64-0.99]; posterior probability or P =0.044), with a similar association with time to all-cause mortality (aHR, 0.78 [95% CI, 0.59-1.03]; P =0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30-1.27]; P =0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35-1.34]; P =0.27 for all-cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes., Conclusions: Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Competing Interests: Funding Support and Author Disclosures Dr Friedman has received research grants from Abbott, the American Heart Association, Biosense Webster, Boston Scientific, Medtronic, Merit Medical, National Cardiovascular Data Registry, Phillips, and the National Institutes of Health; and has received consulting fees from Abbott, Alleviant, Boston Scientific, NI Medical, Microport, and Sanofi.

Background: Skin rejuvenation is a widely sought-after goal, prompting advancements in laser technology for noninvasive and effective treatments. Ablative lasers, in particular, have evolved to address diverse skin concerns, with fractional ablative lasers offering better-tolerated outcomes. The introduction of a novel ablative Thulium pulsed laser, based on Thulium-doped Yttrium aluminum Perovskite (Tm:YAP) crystal, delivers precise and controlled skin rejuvenation by allowing customization of ablative microcolumns., Methods: A pilot in vivo study was conducted on the abdominal skin of a live female pig. Using the Laser Team Medical (LTM) prototype laser, treatments were administered with varying coagulation settings (minimal and maximum) and energies (32, 80, 120, and 160 mJ per microcolumn). Biopsies were harvested, fixed, and stained for subsequent analysis. The penetration depth and width of the microcolumns were evaluated., Results: Low coagulation settings produced ablative microcolumns with thermal affected zones of 160 µm width, while high coagulation settings resulted in wider zones of 400-530 µm. The ablation cavities' width was estimated to be less than 100 µm in both settings. The novel 1940 nm pulsed laser demonstrated superior microcolumn properties, offering potential advantages such as shorter downtime and increased efficacy compared to existing fractional ablative lasers., Conclusion: This study presents encouraging preliminary results regarding the efficacy and safety of the first ablative 1940 nm pulsed laser. The results show ablative microcolumns thinner than the counterpart devices, showing the device safety and potential higher efficacy along with short downtime. The LTM novel ablative 1940 nm pulsed laser holds immense potential for enhancing skin rejuvenation treatments due to its superior microcolumns properties. The versatility of this laser can open new treatment procedures and may extend to different areas of dermatology., (© 2024 The Author(s). Lasers in Surgery and Medicine published by Wiley Periodicals LLC.)

Background: Implantable cardioverter-defibrillator (ICD) shocks are a common complication after left ventricular assist device (LVAD) implantation; however, data on their frequency and causes are limited., Objective: The purpose of this study was to define the incidence, programming, patient characteristics, and factors associated with appropriate and inappropriate ICD shocks in persons with LVADs., Methods: We performed a retrospective review at Duke University Hospital of all LVAD recipients implanted between January 1, 2013, to June 30, 2019, with a preexisting ICD. ICD shocks were adjudicated by the treating physician and a second reviewer for the purpose of this study., Results: Among 421 patients with an ICD in situ undergoing LVAD implant, 147 (33.9%) had at least 1 shock after LVAD implantation. Among 134 patients with complete device history, a total of 330 shock episodes occurred: 255 (77.3%) appropriate and 75 (22.7%) inappropriate. Etiologies for inappropriate shocks included supraventricular tachycardia (n = 66 [20.0%]), physiological oversensing (n = 1 [0.3%]), and nonphysiological oversensing (n = 8 [2.4%]) including LVAD electromagnetic interference (n = 1 [0.3%]). ICD programming with shorter detection delay (P <.001) and absence of antitachycardia pacing programming (P = .001) in high-rate zones was seen more commonly in inappropriate shock than appropriate shock., Conclusions: The rate of inappropriate shocks in LVAD recipients is very high and most often is due to supraventricular arrhythmias. LVAD electromagnetic interference is a rare cause of ICD shock. Implementation of current consensus American Heart Association recommendations for LVAD programming with long detection delays and high rate cutoffs may help prevent inappropriate ICD shocks., Competing Interests: Disclosures Drs Katz and Koontz receive research support from Abbott. Dr Sun serves as a consultant to Biosense Webster, Medtronic, and Merit Medical. Dr Russell is a former consultant at Medtronic and DSMB Abbott. Dr Milano has received research support from Abbott and Medtronic. Dr Piccini receives grants for clinical research from Abbott, American Heart Association, Boston Scientific, iRhythm, and Philips; and serves as a consultant to ABVF, Abbott, Abbvie, Boston Scientific, Element Science, ElectroPhysiology Frontiers, Kardium, Medtronic, Milestone, Sanofi, Pacira, Philips, and Up-to-Date. All other authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: The association of hospital and physician procedure volume with outcome has not been well evaluated for atrial fibrillation (AF) ablation in contemporary practice., Objective: This study aimed to determine the association between hospital and physician AF ablation volume and procedural success (isolation of all pulmonary veins) and major adverse events (MAEs)., Methods: Procedures reported to the National Cardiovascular Data Registry AFib Ablation Registry between July 2019 and June 2022 were included. Hospital and physician procedural volumes were annualized and stratified into quartiles to compare outcomes. Three-level hierarchical (patient, hospital, and physician) models were used to assess the procedural volume-outcome relationship., Results: A total of 70,296 first-time AF ablations at 186 US hospitals were included. Overall, procedural success and MAE rates were 98.5% and 1.0%, respectively. With hospital volume (Q4) as a reference, the likelihood of procedural success was lower for Q1 (odds ratio [OR], 0.44; 95% CI, 0.29-0.68), Q2 (OR, 0.50; 95% CI, 0.33-0.75), and Q3 (OR, 0.60; 95% CI, 0.40-0.89); the results were similarly significant for physician volume. With MAE for hospitals, there was an inverse procedural volume relationship for Q1 (OR, 1.78; 95% CI, 1.26-2.52) but not for Q2 (OR, 1.06; 95% CI, 0.77-1.46) or Q3 (OR, 1.19; 95% CI, 0.89-1.58) and similarly for physicians in Q1 and Q2 but not in Q3. An adjusted MAE ≤1% was predicted by an annual volume of approximately 190 for hospitals and 60 for physicians., Conclusion: In this national cohort, hospital and physician AF ablation procedural volumes were directly related to acute procedural success and inversely related to rates of MAE., Competing Interests: Disclosures Dr Freeman reports advisory board/consulting fees from Boston Scientific, Medtronic, Biosense Webster, and PaceMate; and equity in PaceMate. Dr Zeitler reports nonfinancial research support from Biosense Webster, Boston Scientific, and Sanofi; travel/speaking for Abbott, Biosense Webster, Medtronic, and Philips; and advisory board/consulting fees from Biosense Webster and Medtronic. Dr Zei reports consulting fees from Biosense Webster, Abbott, Volta Medical, and Medtronic. Dr Sanders served on the advisory board of Medtronic, Abbott, Boston Scientific, PaceMate, and CathRx; the University of Adelaide, Australia has received on his behalf lecture, research funding, and/or consulting fees from Medtronic, Abbott, Boston Scientific, and Becton-Dickenson., (Published by Elsevier Inc.)

Background: Women might benefit more than men from cardiac resynchronization therapy (CRT) and do so at shorter QRS durations., Objective: This meta-analysis was performed to determine whether sex-based differences in CRT effects are better accounted for by height, body surface area (BSA), or left ventricular end-diastolic dimension (LVEDD)., Methods: We analyzed patient-level data from CRT trials (MIRACLE, MIRACLE ICD, MIRACLE ICD II, REVERSE, RAFT, COMPANION, and MADIT-CRT) using bayesian hierarchical Weibull regression models. Relationships between QRS duration and CRT effects were examined overall and in sex-stratified cohorts; additional analyses indexed QRS duration by height, BSA, or LVEDD. End points were heart failure hospitalization (HFH) or death and all-cause mortality., Results: Compared with men (n = 5628), women (n = 1439) were shorter (1.62 [interquartile range, 1.57-1.65] m vs 1.75 [1.70-1.80] m; P < .001), with smaller BSAs (1.76 [1.62-1.90] m 2 vs 2.02 [1.89-2.16] m 2 ; P < .001). In adjusted sex-stratified analyses, the reduction in HFH or death was greater for women (hazard ratio, 0.54; credible interval, 0.42-0.70) than for men (hazard ratio, 0.77; credible interval, 0.66-0.89; P interaction = .009); results were similar for all-cause mortality even after adjustment for height, BSA, and LVEDD. Sex-specific differences were observed only in nonischemic cardiomyopathy. The effect of CRT on HFH or death was observed at a shorter QRS duration for women (126 ms) than for men (145 ms). Indexing QRS duration by height, BSA, or LVEDD attenuated sex-specific QRS duration thresholds for the effects of CRT on HFH or death but not on mortality., Conclusion: Although body size partially explains sex-specific QRS duration thresholds for CRT benefit, it is not associated with the magnitude of CRT benefit. Indexing QRS duration for body size might improve selection of patients for CRT, particularly with a "borderline" QRS duration., (Copyright © 2024. Published by Elsevier Inc.)

Background: Procedure volumes are associated with outcomes for many cardiovascular procedures, leading to guidelines on minimum volume thresholds for certain procedures; however, the volume-outcome relationship with left atrial appendage occlusion is poorly understood. As such, we sought to determine the relationship between hospital and physician volume and WATCHMAN left atrial appendage occlusion procedural success overall and with the new generation WATCHMAN FLX device., Methods: We performed an analysis of WATCHMAN procedures (January 2019 to October 2021) from the National Cardiovascular Data Registry LAAO Registry. Three-level hierarchical generalized linear models were used to assess the adjusted relationship between procedure volume and procedural success (device released with peridevice leak <5 mm, no in-hospital major adverse events)., Results: Among 87 480 patients (76.2±8.0 years; 58.8% men; mean CHA 2 DS 2 -VASc score, 4.8±1.5) from 693 hospitals, the procedural success rate was 94.2%. With hospital volume Q4 (greatest volume) as the reference, the likelihood of procedural success was significantly less among Q1 (odds ratio [OR], 0.66 [CI, 0.57-0.77]) and Q2 (OR, 0.78 [CI, 0.69-0.90]) but not Q3 (OR, 0.95 [CI, 0.84-1.07]). With physician volume Q4 (greatest volume) as the reference, the likelihood of procedural success was significantly less among Q1 (OR, 0.72 [CI, 0.63-0.82]), Q2 (OR, 0.79 [CI, 0.71-0.89]), and Q3 (OR, 0.88 [CI, 0.79-0.97]). Among WATCHMAN FLX procedures, there was attenuation of the volume-outcome relationships, with statistically significant but modest absolute differences of only ≈1% across volume quartiles., Conclusions: In this contemporary national analysis, greater hospital and physician WATCHMAN volumes were associated with increased procedure success. The WATCHMAN FLX transition was associated with increased procedural success and less heterogeneity in outcomes across volume quartiles. These findings indicate the importance of understanding the volume-outcome relationship for individual left atrial appendage occlusion devices., Competing Interests: Disclosures Dr Friedman has received research grants from Abbott, American Heart Association, Biosense Webster, Boston Scientific, Medtronic, Merit Medical, National Cardiovascular Data Registry, and the National Institutes of Health (NIH) and consulting fees from Abbott, AtriCure, NI Medical, Microport, and Sanofi. Dr Freeman reported receiving consulting fees from Medtronic, Boston Scientific, Pacemate, and Biosense Webster; equity from Pacemate; and funding from the NIH. JPC reported an institutional contract with the American College of Cardiology for his role as Senior Scientific Advisor of the National Cardiovascular Data Registry (NCDR) and equity interest in Medtronic. Dr Curtis is supported by R01AG074185 from the National Institutes of Aging. He also receives grants for clinical research from Abbott, the American Heart Association, the Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, iRhythm, and Philips and serves as a consultant to Abbott, Abbvie, ARCA Biopharma, Bayer, Boston Scientific, Bristol Myers Squibb (Myokardia), Element Science, Itamar Medical, LivaNova, Medtronic, Milestone, ElectroPhysiology Frontiers, ReCor, Sanofi, Philips, and UpToDate. Dr Masoudi reported an institutional contract with the American College of Cardiology for his role as Chief Scientific Advisor of the NCDR. Dr Vemulapalli has received grants from the American College of Cardiology, Society of Thoracic Surgeons, Cytokinetics, Abbott Vascular, Boston Scientific, NIH (R01 and SBIR [Small Business Innovation Research]) and Food and Drug Administration (NEST cc [National Evaluation System for Health Technology Coordinating Center]) and serves as a consultant for Medtronic, Edwards Lifesciences, Total CME, and American College of Physicians. The other authors report no conflicts.

Background: Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs/AVRT)., Methods: We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies., Results: Analyses comprised 2384 AVNRT cases and 106 489 referents, and 2811 AVAP/AVRT cases and 1,483 093 referents. We identified 2 significant loci for AVNRT, which implicate NKX2-5 and TTN as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of NKX2-5 and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicate SCN5A , SCN10A , and TTN/CCDC141 . Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals., Conclusions: Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility., Competing Interests: Disclosures Dr Lubitz is a full-time employee of Novartis as of July 2022. Previously, Dr Lubitz received research support from Bristol Myers Squibb/Pfizer, Bayer AG, Boehringer Ingelheim, Fitbit, IBM, Medtronic, and Premier, Inc, and consulted for Bristol Myers Squibb/Pfizer, Bayer AG, Blackstone Life Sciences, and Invitae. Dr Ellinor receives research support from Bayer AG, IBM, and Bristol Myers Squibb/Pfizer and has consulted for Novartis, MyoKardia, and Bayer AG. Dr Damrauer receives research support for RenalytixAI and has consulted for Calico Labs. Dr Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic outside this work. Dr Cutler has consulted for Janssen Scientific. Dr Roselli is supported by a grant from Bayer AG to the Broad Institute focused on the development of therapeutics for cardiovascular disease. The other authors report no conflicts.

Introduction: Peak frequency (PF) mapping is a novel method that may identify critical portions of myocardial substrate supporting reentry. The aim of this study was to describe and evaluate PF mapping combined with omnipolar voltage mapping in the identification of critical isthmuses of left atrial (LA) atypical flutters., Methods and Results: LA omnipolar voltage and PF maps were generated in flutter using the Advisor HD-Grid catheter (Abbott) and EnSite Precision Mapping System (Abbott) in 12 patients. Normal voltage was defined as ≥0.5 mV, low-voltage as 0.1-0.5 mV, and scar as <0.1 mV. PF distributions were compared with ANOVA and post hoc Tukey analyses. The 1 cm radius from arrhythmia termination was compared to global myocardium with unpaired t-testing. The mean age was 65.8 ± 9.7 years and 50% of patients were female. Overall, 34 312 points were analyzed. Atypical flutters most frequently involved the mitral isthmus (58%) or anterior wall (25%). Mean PF varied significantly by myocardial voltage: normal (335.5 ± 115.0 Hz), low (274.6 ± 144.0 Hz), and scar (71.6 ± 140.5 Hz) (p < .0001 for all pairwise comparisons). All termination sites resided in low-voltage regions containing intermediate or high PF. Overall, mean voltage in the 1 cm radius from termination was significantly lower than the remaining myocardium (0.58 vs. 0.95 mV, p < .0001) and PF was significantly higher (326.4 vs. 245.1 Hz, p < .0001)., Conclusion: Low-voltage, high-PF areas may be critical targets during catheter ablation of atypical atrial flutter., (© 2024 Wiley Periodicals LLC.)

Introduction: Mesoamerican nephropathy (MeN) is a chronic kidney disease (CKD) which may be caused by recurrent acute kidney injury (AKI). We investigated urinary quinolinate-to-tryptophan ratio (Q/T), a validated marker of nicotinamide adenine dinucleotide (NAD+) biosynthesis that is elevated during ischemic and inflammatory AKI, in a sugarcane worker population in Nicaragua with high rates of MeN., Methods: Among 693 male sugarcane workers studied, we identified 45 who developed AKI during the harvest season. We matched them 1:1 based on age and job category with 2 comparison groups: (i) "no kidney injury," active sugarcane workers with serum creatinine (sCr) <1.1 mg/dl; and (ii) "CKD," individuals no longer working in sugarcane due to their CKD, who had additional 1:1 matching for sCr. We measured urine metabolites using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) and compared Q/T and other metabolic features between the AKI and comparison groups., Results: Urine Q/T was significantly higher in workers with AKI than in those with no kidney injury (median interquartile Range [IQR]: 0.104 [0.074-0.167] vs. 0.060 [0.045-0.091], P  < 0.0001) and marginally higher than in workers with CKD (0.086 [0.063-0.142], P  = 0.059). Urine levels of the NAD+ precursor nicotinamide were lower in the AKI group than in comparison groups., Conclusion: Workers at risk for MeN who develop AKI demonstrate features of impaired NAD+ biosynthesis, thereby providing new insights into the metabolic mechanisms of injury in this population. Therapeutic use of oral nicotinamide, which may ameliorate NAD+ biosynthetic derangement and fortify against kidney injury, should be investigated to prevent AKI in this setting., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background: The National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry (LAAO) includes the vast majority of transcatheter LAAO procedures performed in the United States. The objective of this study was to develop a model predicting adverse events among patients undergoing LAAO with Watchman FLX., Methods: Data from 41 001 LAAO procedures with Watchman FLX from July 2020 to September 2021 were used to develop and validate a model predicting in-hospital major adverse events. Randomly selected development (70%, n=28 530) and validation (30%, n=12 471) cohorts were analyzed with 1000 bootstrapped samples, using forward stepwise logistic regression to create the final model. A simplified bedside risk score was also developed using this model., Results: Increased age, female sex, low preprocedure hemoglobin, no prior attempt at atrial fibrillation termination, and increased fall risk most strongly predicted in-hospital major adverse events and were included in the final model along with other clinically relevant variables. The median in-hospital risk-standardized adverse event rate was 1.50% (range, 1.03%-2.84%; interquartile range, 1.42%-1.64%). The model demonstrated moderate discrimination (development C-index, 0.67 [95% CI, 0.65-0.70] and validation C-index, 0.66 [95% CI, 0.62-0.70]) with good calibration. The simplified risk score was well calibrated with risk of in-hospital major adverse events ranging from 0.26% to 3.90% for a score of 0 to 8, respectively., Conclusions: A transcatheter LAAO risk model using National Cardiovascular Data Registry and LAAO Registry data can predict in-hospital major adverse events, demonstrated consistency across hospitals and can be used for quality improvement efforts. A simple bedside risk score was similarly predictive and may inform shared decision-making., Competing Interests: Disclosures Dr Faridi receives research funding from the National Institutes of Health (NIH)/National Heart, Lung and Blood Institute (NHLBI;K23HL161424). Dr Friedman reports receiving research grants from Abbott, American Heart Association, Biosense Webster, Boston Scientific, Medtronic, Merit Medical, National Cardiovascular Data Registry, Phillips, and NIH, and consulting fees from Abbott, NI Medical, Microport, and Sanofi. Dr Hsu reports receiving honoraria from Medtronic, Abbott, Boston Scientific, Biotronik, Janssen Pharmaceuticals, Bristol-Myers Squibb, Pfizer, Sanofi, Altathera, Zoll Medical, Hillrom, iRhythm, Acutus Medical, Galvanize Therapeutics, and Biosense-Webster, research grants from Biotronik and Biosense-Webster, and has equity interest in Vektor Medical. Dr Mortazavi receives research funding from the National Science Foundation (IIS #2014475) and the NIH (R21EB028486, R01HL151240, R01EB028106, and R01HL142765). Dr Lakkireddy reports being a consultant for Abbott, Boston Sci, Atricure, Biosense Webster, and Acutus. Dr Curtis has a contract with the American College of Cardiology (ACC) for his role as Chief Scientific Advisor of the ACC’s National Cardiovascular Data Registry. He holds equity interest in Medtronic. Dr Freeman reports receiving research grants from the N NHLBI and the ACC National Cardiovascular Data Registry and consulting/advisory board fees from Boston Scientific, Biosense Webster, Medtronic, and PaceMate. and equity in PaceMate.

Catheter ablation of atrial fibrillation (AF) is an established therapy that reduces AF burden, improves quality of life, and reduces the risks of cardiovascular outcomes. Although there are clear guidelines for the application of de novo catheter ablation, there is less evidence to guide recommendations for repeat catheter ablation in patients who experience recurrent AF. In this review, we examine the rationale for repeat ablation, mechanisms of recurrence, patient selection, optimal timing, and procedural strategies. We discuss additional important considerations, including treatment of comorbidities and risk factors, risk of complications, and effectiveness. Mechanisms of recurrent AF are often due to non-pulmonary vein (non-PV) triggers; however, there is insufficient evidence supporting the routine use of empiric lesion sets during repeat ablation. The emergence of pulsed field ablation may alter the safety and effectiveness of de novo and repeat ablation. Extrapolation of data from randomized trials of de novo ablation does not optimally inform efficacy in cases of redo ablation. Additional large, randomized controlled trials are needed to address important clinical questions regarding procedural strategies and timing of repeat ablation., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT)., Methods and Results: Original patient-level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK-HF, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, RAFT, COMPANION, MADIT-CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (n = 920), coronary artery disease (n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1-2, or ≥3. The outcomes of interest were time to all-cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all-cause mortality. Outcomes were evaluated within each comorbidity group using a Bayesian hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1-2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all-cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68-0.93) (p = 0.010); for no comorbidities the aHR was 0.54 (95% CI 0.34-0.86), for 1-2 comorbidities was 0.81 (95% CI 0.67-0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64-1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all-cause mortality, the aHR for the overall cohort was 0.74 (95% CI 0.65-0.84) (p = 0.001), for no comorbidities was 0.69 (95% CI 0.50-0.94), for 1-2 comorbidities was 0.77 (95% CI 0.66-0.90) and for ≥3 comorbidities was 0.68 (95% CI 0.55-0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081)., Conclusion: In a meta-analysis of patient-level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all-cause mortality even when several comorbid diseases are present., Clinical Trial Registration: NCT00271154, NCT00251251, NCT00267098, NCT00180271., (© 2023 European Society of Cardiology.)

Patients with severe mental illness (SMI) including schizophrenia and bipolar disorder die on average 15-20 years earlier than the general population often due to sudden death that, in most cases, is caused by cardiovascular disease. This state-of-the-art review aims to address the complex association between SMI and cardiovascular risk, explore disparities in cardiovascular care pathways, describe how to adequately predict cardiovascular outcomes, and propose targeted interventions to improve cardiovascular health in patients with SMI. These patients have an adverse cardiovascular risk factor profile due to an interplay between biological factors such as chronic inflammation, patient factors such as excessive smoking, and healthcare system factors such as stigma and discrimination. Several disparities in cardiovascular care pathways have been demonstrated in patients with SMI, resulting in a 47% lower likelihood of undergoing invasive coronary procedures and substantially lower rates of prescribed standard secondary prevention medications compared with the general population. Although early cardiovascular risk prediction is important, conventional risk prediction models do not accurately predict long-term cardiovascular outcomes as cardiovascular disease and mortality are only partly driven by traditional risk factors in this patient group. As such, SMI-specific risk prediction models and clinical tools such as the electrocardiogram and echocardiogram are necessary when assessing and managing cardiovascular risk associated with SMI. In conclusion, there is a necessity for differentiated cardiovascular care in patients with SMI. By addressing factors involved in the excess cardiovascular risk, reconsidering risk stratification approaches, and implementing multidisciplinary care models, clinicians can take steps towards improving cardiovascular health and long-term outcomes in patients with SMI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: M.R.P. and D.J.F. report research support from Vertex. The remaining authors declare no competing interests.

Background: Cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations (HFH) and mortality for guideline-indicated patients with heart failure (HF). Most patients with HF are aged ≥70 years but such patients are often under-represented in randomized trials., Methods: Patient-level data were combined from 8 randomized trials published 2002-2013 comparing CRT to no CRT (n = 6,369). The effect of CRT was estimated using an adjusted Bayesian survival model. Using age as a categorical (<70 vs ≥70 years) or continuous variable, the interaction between age and CRT on the composite end point of HFH or all-cause mortality or all-cause mortality alone was assessed., Results: The median age was 67 years with 2436 (38%) being 70+; 1,554 (24%) were women; 2,586 (41%) had nonischemic cardiomyopathy and median QRS duration was 160 ms. Overall, CRT was associated with a delay in time to the composite end point (adjusted hazard ratio [aHR] 0.75, 95% credible interval [CI] 0.66-0.85, P = .002) and all-cause mortality alone (aHR of 0.80, 95% CI 0.69-0.96, P = .017). When age was treated as a categorical variable, there was no interaction between age and the effect of CRT for either end point (P > .1). When age was treated as a continuous variable, older patients appeared to obtain greater benefit with CRT for the composite end point (P for interaction = .027) with a similar but nonsignificant trend for mortality (P for interaction = .35)., Conclusion: Reductions in HFH and mortality with CRT are as great or greater in appropriately indicated older patients. Age should not be a limiting factor for the provision of CRT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele., (© 2023. The Author(s).)

Background: Left ventricular (LV) lead implantation is often the most challenging aspect of cardiac resynchronization therapy (CRT) procedures; early studies reported implant failure rates in ∼10% of cases., Objective: The purpose of this study was to define rates, reasons for, and factors independently associated with LV lead implant failure., Methods: We studied patients with left bundle branch block and ejection fraction ≤ 35% who underwent planned de novo transvenous CRT implantation (2010-2016) and were reported to the National Cardiovascular Data Registry ICD Registry. Independent predictors of LV lead implant failure were determined using logistic regression; age, sex, and variables with a univariable P value of <.15 were considered for inclusion in the model., Results: Of the 111,802 patients who underwent a planned CRT procedure, 3.6% of patients (n = 3979) had LV lead implant failure. Reasons for implant failure included venous access (7.5%), coronary sinus access (64.3%), tributary vein access (13.5%), coronary sinus dissection (7.6%), unacceptable threshold (4.4%), and diaphragmatic stimulation (1.7%). Significant independent predictors of LV lead implant failure included younger age (odds ratio [OR] 1.01; 95% confidence interval [CI] 0.1.01-1.02), female sex (OR 1.38; 95% CI 1.29-1.47), black race (vs white, OR 1.44; 95% CI 1.32-1.57), Hispanic ethnicity (OR 1.23; 95% CI 1.08-1.40), QRS duration (OR 1.055 per 10 ms; 95% CI 1.038-1.072 per 10 ms), obstructive sleep apnea (OR 1.14; 95% CI 1.04-1.24), and implantation by a physician without specialized training (vs electrophysiology trained, OR 1.53; 95% CI 1.34-1.76)., Conclusion: LV lead implant failure is uncommon in the current era and is most commonly due to coronary sinus access failure. Predictors of LV lead implant failure included younger age, female sex, black race, Hispanic ethnicity, increased QRS duration, sleep apnea, and absence of electrophysiology training., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF)., Methods: Individual-patient-data from four randomized trials investigating CRT-Defibrillators (COMPANION, MADIT-CRT, REVERSE) or CRT-Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all-cause mortality or to all-cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian-Weibull survival regression model adjusting for baseline characteristics., Results: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56-0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55-1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55-0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66-1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70-1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60-0.97)., Conclusion: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF., (© 2023 Wiley Periodicals LLC.)