<div><h4>Mesoscopic mapping of hemodynamic responses and neuronal activity during pharmacologically induced interictal spikes in awake and anesthetized mice.</h4><i>Li J, Yang F, Zhan F, Estin J, ... Ma H, Schwartz TH</i><br /><AbstractText>Imaging hemodynamic responses to interictal spikes holds promise for presurgical epilepsy evaluations. Understanding the hemodynamic response function is crucial for accurate interpretation. Prior interictal neurovascular coupling data primarily come from anesthetized animals, impacting reliability. We simultaneously monitored calcium fluctuations in excitatory neurons, hemodynamics, and local field potentials (LFP) during bicuculline-induced interictal events in both isoflurane-anesthetized and awake mice. Isoflurane significantly affected LFP amplitude but had little impact on the amplitude and area of the calcium signal. Anesthesia also dramatically blunted the amplitude and latency of the hemodynamic response, although not its area of spread. Cerebral blood volume change provided the best spatial estimation of excitatory neuronal activity in both states. Targeted silencing of the thalamus in awake mice failed to recapitulate the impact of anesthesia on hemodynamic responses suggesting that isoflurane\'s interruption of the thalamocortical loop did not contribute either to the dissociation between the LFP and the calcium signal nor to the alterations in interictal neurovascular coupling. The blood volume increase associated with interictal spikes represents a promising mapping signal in both the awake and anesthetized states.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 01 Jun 2024; 44:911-924</small></div>

<div><h4>NCAM mimetic peptide P2 synergizes with bone marrow mesenchymal stem cells in promoting functional recovery after stroke.</h4><i>Lan XY, Liang XS, Cao MX, Qin HM, ... Boltze J, Li S</i><br /><AbstractText>The neural cell adhesion molecule (NCAM) promotes neural development and regeneration. Whether NCAM mimetic peptides could synergize with bone marrow mesenchymal stem cells (BMSCs) in stroke treatment deserves investigation. We found that the NCAM mimetic peptide P2 promoted BMSC proliferation, migration, and neurotrophic factor expression, protected neurons from oxygen-glucose deprivation through ERK and PI3K/AKT activation and anti-apoptotic mechanisms <i>in vitro</i>. Following middle cerebral artery occlusion (MCAO) in rats, P2 alone or in combination with BMSCs inhibited neuronal apoptosis and induced the phosphorylation of ERK and AKT. P2 combined with BMSCs enhanced neurotrophic factor expression and BMSC proliferation in the ischemic boundary zone. Moreover, combined P2 and BMSC therapy induced translocation of nuclear factor erythroid 2-related factor, upregulated heme oxygenase-1 expression, reduced infarct volume, and increased functional recovery as compared to monotreatments. Treatment with LY294002 (PI3K inhibitor) and PD98059 (ERK inhibitor) decreased the neuroprotective effects of combined P2 and BMSC therapy in MCAO rats. Collectively, P2 is neuroprotective while P2 and BMSCs work synergistically to improve functional outcomes after ischemic stroke, which may be attributed to mechanisms involving enhanced BMSC proliferation and neurotrophic factor release, anti-apoptosis, and PI3K/AKT and ERK pathways activation.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 01 Jul 2024; 44:1128-1144</small></div>

<div><h4>The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia.</h4><i>Wu CY, Zhang Y, Xu L, Huang Z, ... Zhang Q, Lee RH</i><br /><AbstractText>Cardiopulmonary arrest (CA) is a major cause of death/disability in the U.S. with poor prognosis and survival rates. Current therapeutic challenges are physiologically complex because they involve hypoperfusion (decreased cerebral blood flow), neuroinflammation, and mitochondrial dysfunction. We previously discovered novel serum/glucocorticoid-regulated kinase 1 (SGK1) is highly expressed in brain of neurons that are susceptible to ischemia (hippocampus and cortex). We inhibited SGK1 and utilized pharmacological (specific inhibitor, GSK650394) and neuron-specific genetic approaches (shRNA) in rodent models of CA to determine if SGK1 is responsible for hypoperfusion, neuroinflammation, mitochondrial dysfunctional, and neurological deficits after CA. Inhibition of SGK1 alleviated cortical hypoperfusion and neuroinflammation (via Iba1, GFAP, and cytokine array). Treatment with GSK650394 enhanced mitochondrial function (via Seahorse respirometry) in the hippocampus 3 and 7 days after CA. Neuronal injury (via MAP2, dMBP, and Golgi staining) in the hippocampus and cortex was observed 7 days after CA but ameliorated with SGK1-shRNA. Moreover, SGK1 mediated neuronal injury by regulating the Ndrg1-SOX10 axis. Finally, animals subjected to CA exhibited learning/memory, motor, and anxiety deficits after CA, whereas SGK1 inhibition via SGK1-shRNA improved neurocognitive function. The present study suggests the fundamental roles of SGK1 in brain circulation and neuronal survival/death in cerebral ischemia-related diseases.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 01 Jul 2024; 44:1145-1162</small></div>

<div><h4>Vitamin D deficiency promotes intracranial aneurysm rupture.</h4><i>Kimura T, Rahmani R, Miyamoto T, Kamio Y, ... Lawton MT, Hashimoto T</i><br /><AbstractText>Intracranial aneurysm rupture causes severe disability and high mortality. Epidemiological studies show a strong association between decreased vitamin D levels and an increase in aneurysm rupture. However, the causality and mechanism remain largely unknown. In this study, we tested whether vitamin D deficiency promotes aneurysm rupture and examined the underlying mechanism for the protective role of vitamin D against the development of aneurysm rupture utilizing a mouse model of intracranial aneurysm. Mice consuming a vitamin D-deficient diet had a higher rupture rate than mice with a regular diet. Vitamin D deficiency increased proinflammatory cytokines in the cerebral arteries. Concurrently, vitamin D receptor knockout mice had a higher rupture rate than the corresponding wild-type littermates. The vitamin D receptors on endothelial and vascular smooth muscle cells, but not on hematopoietic cells, mediated the effect of aneurysm rupture. Our results establish that vitamin D protects against the development of aneurysmal rupture through the vitamin D receptors on vascular endothelial and smooth muscle cells. Vitamin D supplementation may be a viable pharmacologic therapy for preventing aneurysm rupture.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 01 Jul 2024; 44:1174-1183</small></div>

<div><h4>Limitations of apical sparing pattern in cardiac amyloidosis: a multicentre echocardiographic study.</h4><i>Cotella J, Randazzo M, Maurer MS, Helmke S, ... Slivnick JA, Lang RM</i><br /><b>Aims</b><br />Although impaired left ventricular (LV) global longitudinal strain (GLS) with apical sparing is a feature of cardiac amyloidosis (CA), its diagnostic accuracy has varied across studies. We aimed to determine the ability of apical sparing ratio (ASR) and most common echocardiographic parameters to differentiate patients with confirmed CA from those with clinical and/or echocardiographic suspicion of CA but with this diagnosis ruled out.<br /><b>Methods and results</b><br />We identified 544 patients with confirmed CA and 200 controls (CTRLs) as defined above (CTRL patients). Measurements from transthoracic echocardiograms were performed using artificial intelligence software (Us2.AI, Singapore) and audited by an experienced echocardiographer. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance and optimal cut-offs for the differentiation of CA patients from CTRL patients. Additionally, a group of 174 healthy subjects (healthy CTRL) was included to provide insight on how patients and healthy CTRLs differed echocardiographically. LV GLS was more impaired (-13.9 ± 4.6% vs. -15.9 ± 2.7%, P < 0.0005), and ASR was higher (2.4 ± 1.2 vs. 1.7 ± 0.9, P < 0.0005) in the CA group vs. CTRL patients. Relative wall thickness and ASR were the most accurate parameters for differentiating CA from CTRL patients [area under the curve (AUC): 0.77 and 0.74, respectively]. However, even with the optimal cut-off of 1.67, ASR was only 72% sensitive and 66% specific for CA, indicating the presence of apical sparing in 32% of CTRL patients and even in 6% healthy subjects.<br /><b>Conclusion</b><br />Apical sparing did not prove to be a CA-specific biomarker for accurate identification of CA, when compared with clinically similar CTRLs with no CA.<br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 31 May 2024; 25:754-761</small></div>

<div><h4>Biatrial arrhythmogenic substrate in patients with hypertrophic obstructive cardiomyopathy.</h4><i>Ramdat Misier NL, Amesz JH, Taverne YJHJ, Nguyen H, ... Brundel BJJM, de Groot NMS</i><br /><b>Background</b><br />Atrial fibrillation (AF) in patients with hypertrophic obstructive cardiomyopathy (HOCM) may be caused by a primary atrial myopathy. Whether HOCM-related atrial myopathy affects mainly electrophysiological properties of the left atrium (LA) or also the right atrium (RA) has never been investigated.<br /><b>Objective</b><br />The purpose of this study was to characterize atrial conduction and explore differences in the prevalence of conduction disorders, potential fractionation, and low-voltage areas (LVAs) between the RA and LA during sinus rhythm (SR) as indicators of potential arrhythmogenic areas.<br /><b>Methods</b><br />Intraoperative epicardial mapping of both atria during SR was performed in 15 HOCM patients (age 50 ± 12 years). Conduction delay (CD) and conductin block (CB), unipolar potential characteristics (voltages, fractionation), and LVA were quantified.<br /><b>Results</b><br />Conduction disorders and LVA were found scattered throughout both atria in all patients and did not differ between the RA and LA (CD: 2.9% [1.9%-3.6%] vs 2.6% [2.1%-6.4%], P = .541; CB: 1.7% [0.9%-3.1%] vs 1.5% [0.5%-2.8%], P = .600; LVA: 4.7% [1.6%-7.7%] vs 2.9% [2.1%-7.1%], P = .793). Compared to the RA, unipolar voltages of single potentials (SPs) and fractionated potentials (FPs) were higher in the LA (SP: P75 7.3 mV vs 10.9 mV; FP: P75 2.0 mV vs 3.7 mV). FP contained low-voltage components in only 18% of all LA sites compared to 36% of all RA sites.<br /><b>Conclusion</b><br />In patients with HOCM, conduction disorders, LVA, and FP are equally present in both atria, supporting the hypothesis of a primary atrial myopathy. Conceptually, the presence of a biatrial substrate and high-voltage FP may contribute to failure of ablative therapy of atrial tachyarrhythmias in this population.<br /><br />Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Heart Rhythm: 01 Jun 2024; 21:819-827</small></div>

<div><h4>Clinical and prognostic implications of left ventricular dilatation in heart failure.</h4><i>Kasa G, Teis A, Juncà G, Aimo A, ... Bayés-Genis A, Delgado V</i><br /><b>Aims</b><br />To assess the agreement between left ventricular end-diastolic diameter index (LVEDDi) and volume index (LVEDVi) to define LV dilatation and to investigate the respective prognostic implications in patients with heart failure (HF).<br /><b>Methods and results</b><br />Patients with HF symptoms and LV ejection fraction (LVEF) < 50% undergoing cardiac magnetic resonance were evaluated retrospectively. LV dilatation was defined as LVEDDi or LVEDVi above the upper normal limit according to published reference values. Patients were followed up for the combined endpoint of cardiovascular death or HF hospitalization during 5 years. A total of 564 patients (median age 64 years; 79% men) were included. LVEDDi had a modest correlation with LVEDVi (r = 0.682, P < 0.001). LV dilatation was noted in 84% of patients using LVEDVi-based definition and in 73% using LVEDDi-based definition, whereas 20% of patients displayed discordant definitions of LV dilatation. During a median follow-up of 2.8 years, patients with both dilated LVEDDi and LVEDVi had the highest cumulative event rate (HR 3.00, 95% CI 1.15-7.81, P = 0.024). Both LVEDDi and LVEDVi were independently associated with the primary outcome (hazard ratio 3.29, 95%, P < 0.001 and 2.8, P = 0.009; respectively).<br /><b>Conclusion</b><br />The majority of patients with HF and LVEF < 50% present both increased LVEDDi and LVEDVi whereas 20% show discordant linear and volumetric definitions of LV dilatation. Patients with increased LVEDDi and LVEDVi have the worst clinical outcomes suggesting that the assessment of these two metrics is needed for better risk stratification.<br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 31 May 2024; 25:849-856</small></div>

<div><h4>Depleting inositol pyrophosphate 5-InsP7 protected the heart against ischaemia-reperfusion injury by elevating plasma adiponectin.</h4><i>Fu L, Du J, Furkert D, Shipton ML, ... Zhu Y, Fu C</i><br /><b>Aims</b><br />Adiponectin is an adipocyte-derived circulating protein that exerts cardiovascular and metabolic protection. Due to the futile degradation of endogenous adiponectin and the challenges of exogenous administration, regulatory mechanisms of adiponectin biosynthesis are of significant pharmacological interest.<br /><b>Methods and results</b><br />Here, we report that 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) generated by inositol hexakisphosphate kinase 1 (IP6K1) governed circulating adiponectin levels via thiol-mediated protein quality control in the secretory pathway. IP6K1 bound to adiponectin and DsbA-L and generated 5-InsP7 to stabilize adiponectin/ERp44 and DsbA-L/Ero1-Lα interactions, driving adiponectin intracellular degradation. Depleting 5-InsP7 by either IP6K1 deletion or pharmacological inhibition blocked intracellular adiponectin degradation. Whole-body and adipocyte-specific deletion of IP6K1 boosted plasma adiponectin levels, especially its high molecular weight forms, and activated AMPK-mediated protection against myocardial ischaemia-reperfusion injury. Pharmacological inhibition of 5-InsP7 biosynthesis in wild-type but not adiponectin knockout mice attenuated myocardial ischaemia-reperfusion injury.<br /><b>Conclusion</b><br />Our findings revealed that 5-InsP7 is a physiological regulator of adiponectin biosynthesis that is amenable to pharmacological intervention for cardioprotection.<br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Cardiovasc Res: 02 Jul 2024; 120:954-970</small></div>

<div><h4>Myosin light chain 6 (Myl6) interacts with kindlin-3 and is required to support integrin αβ activation in platelets in mice.</h4><i>Xu Z, Zhou Y, Yu H, Chen X, Ma YQ</i><br /><b>Background</b><br />Kindlin-3 in platelets plays an essential role in supporting integrin α<sub>IIb</sub>β<sub>3</sub> activation, platelet spreading, aggregation, and clot retraction by binding to the integrin β<sub>3</sub> cytoplasmic tail. However, the mechanism by which kindlin-3 mediates the crosstalk between integrin α<sub>IIb</sub>β<sub>3</sub> and myosin in platelets remains unknown.<br /><b>Objectives</b><br />To examine the role of myosin light chain 6 (Myl6) in supporting integrin α<sub>IIb</sub>β<sub>3</sub> activation in platelets.<br /><b>Methods</b><br />Myl6<sup>fl/fl</sup>PF4-Cre mice with a deficiency of Myl6 in the megakaryocyte lineage were generated, and integrin α<sub>IIb</sub>β<sub>3</sub> activation in Myl6-deficient platelets was analyzed.<br /><b>Results</b><br />We identified a novel kindlin-3 binding protein, Myl6, an essential light chain of myosin in platelets. Myl6<sup>fl/fl</sup>PF4-Cre mice exhibited significant macrothrombocytopenia resulting from defective proplatelet formation. In the absence of Myl6, integrin α<sub>IIb</sub>β<sub>3</sub> activation in platelets was significantly suppressed, and platelet aggregation was substantially impaired. Interestingly, the deficiency of Myl6 in platelets preferentially affected the binding of a multivalent ligand compared to a monovalent ligand to integrin α<sub>IIb</sub>β<sub>3</sub> upon activation, indicating that Myl6 may contribute to the avidity modulation of integrin α<sub>IIb</sub>β<sub>3</sub> by binding to kindlin-3. Furthermore, blood coagulation ability was impaired in Myl6<sup>fl/fl</sup>PF4-Cre mice, and consistently, these mice exhibited defects in both hemostatic and thrombotic functions.<br /><b>Conclusion</b><br />In summary, these results suggest that Myl6, as a novel kindlin-3 binding partner, is required to support integrin α<sub>IIb</sub>β<sub>3</sub> activation in platelets, which plays an important role in both hemostasis and thrombosis.<br /><br />Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Thromb Haemost: 01 Jul 2024; 22:2009-2017</small></div>

<div><h4>Left atrial appendage closure in patients with left atrial appendage thrombus guided by intracardiac echocardiography.</h4><i>Wang B, Chu H, Wang Z, Fu G, ... Feng M, Du X</i><br /><b>Background</b><br />Data regarding left atrial appendage closure (LAAC) in patients with left atrial appendage (LAA) thrombus are limited. Recently published cases have mostly been guided by transesophageal echocardiography. Intracardiac echocardiography (ICE) is now widely used during LAAC procedures.<br /><b>Objective</b><br />This is the first study to report the feasibility of LAAC in patients with LAA thrombus guided by ICE.<br /><b>Methods</b><br />Patients with persistent LAA thrombus despite anticoagulation or contraindications to anticoagulation who underwent a modified ICE-guided LAAC procedure between June 2021 and April 2023 were included. Periprocedural events and clinical outcomes during follow-up were recorded.<br /><b>Results</b><br />A total of 12 patients (mean age 65 ± 7 years; 92% male) were included: 10 with persistent LAA thrombus and 2 with contraindications to anticoagulation. Most of the thrombus was at the apex (n = 6), followed by the body (n = 3) and the ostium (n = 3). A LAmbre device was used and successfully implanted in all patients with the guidance of ICE. No thrombotic material was retrieved from patients with the protection of cerebral protection device (n = 11). No patient experienced severe periprocedural complications. All patients completed transesophageal echocardiography follow-up, and no device-related thrombus or peridevice leak > 3 mm was detected. None of the patients experienced stroke/transient ischemic attack, systemic embolism, or major bleeding events during a median follow-up of 147 days (interquartile range 80-306 days).<br /><b>Conclusion</b><br />LAAC using the LAmbre device guided by ICE may be feasible in patients with LAA thrombus when performed by experienced operators.<br /><br />Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Heart Rhythm: 01 Jun 2024; 21:812-818</small></div>

<div><h4>Remnant cholesterol as a new lipid-lowering target to reduce cardiovascular events.</h4><i>Raggi P, Becciu ML, Navarese EP</i><br /><b>Purpose of review</b><br />Remnant cholesterol has become increasingly recognized as a direct contributor to the development of atherosclerosis and as an additional marker of cardiovascular risk. This review aims to summarize the pathophysiological mechanisms, and the current evidence base from epidemiological investigations and genetic studies that support a causal link between remnant cholesterol and atherosclerotic cardiovascular disease. Current and novel therapeutic approaches to target remnant cholesterol are discussed.<br /><b>Recent findings</b><br />A recent Mendelian randomization study of over 12 000 000 single-nucleotide polymorphisms associated with high levels of remnant cholesterol, demonstrated a genetic association between remnant cholesterol and adverse cardiovascular events among 958 434 participants.<br /><b>Summary</b><br />In this light, the emerging role of remnant cholesterol as an independent lipid risk marker warrants a reevaluation of lipid management guidelines and underscores the potential for novel therapeutic targets in cardiovascular disease prevention.<br /><br />Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.<br /><br /><small>Curr Opin Lipidol: 01 Jun 2024; 35:110-116</small></div>

<div><h4>C-reactive protein, pharmacological treatments and diet: how to target your inflammatory burden.</h4><i>Bay B, Arnold N, Waldeyer C</i><br /><b>Purpose of review</b><br />This article focuses on pharmacological agents as well as dietary changes aimed at the reduction of the inflammatory burden measured by circulating C-reactive protein concentrations.<br /><b>Recent findings</b><br />Over the last years, repurposed as well as new anti-inflammatory agents have been investigated in outcome trials in the cardiovascular field. Currently, a specific inhibition of the inflammatory cascade via the interleukin-6 ligand antibody ziltivekimab is being explored in large-scale outcome trials, after the efficacy of this agent with regard to the reduction of inflammatory biomarkers was proven recently. Next to the investigated pharmacological agents, specific dietary patterns possess the ability to improve the inflammatory burden. This enables patients themselves to unlock a potential health benefit ahead of the initiation of a specific medication targeting the inflammatory pathway.<br /><b>Summary</b><br />Both pharmacological agents as well as diet provide the opportunity to improve the inflammatory profile and thereby lower C-reactive protein concentrations. Whilst advances in the field of specific anti-inflammatory treatments have been made over the last years, their broad implementation is currently limited. Therefore, optimization of diet (and other lifestyle factors) could provide a cost effective and side-effect free intervention to target low-grade vascular inflammation.<br /><br />Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.<br /><br /><small>Curr Opin Lipidol: 01 Jun 2024; 35:141-148</small></div>

<div><h4>PCSK9-directed therapies: an update.</h4><i>Katzmann JL, Laufs U</i><br /><b>Purpose of review</b><br />Two large cardiovascular outcomes trials of monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) demonstrated that therapeutic inhibition of extracellular PCSK9 markedly reduces LDL cholesterol concentration and cardiovascular risk. Several novel strategies to inhibit PCSK9 function are in development. Different mechanisms of action may determine specific properties with potential relevance for patient care.<br /><b>Recent findings</b><br />For the monoclonal antibodies evolocumab und alirocumab as first-generation PCSK9 inhibitors, follow-up data of up to 8 years of exposure complement the information on efficacy and safety available from outcome trials. For the small-interfering RNA inclisiran as second-generation PCSK9 inhibitor, several phase III trials have been published and a cardiovascular outcome trial has completed recruitment and is ongoing. Third-generation PCSK9 inhibitors encompass, among others, orally available drugs such as MK-0616 and the fusion protein lerodalcibep. Additional strategies to inhibit PCSK9 include vaccination and gene editing.<br /><b>Summary</b><br />Long-term inhibition of PCSK9 with monoclonal antibodies is safe and conveys sustained cardiovascular benefit. Novel strategies to inhibit PCSK9 function such as orally available drugs, RNA targeting, and one-time treatment with gene editing may further enhance the therapeutic armamentarium and enable novel preventive strategies.<br /><br />Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.<br /><br /><small>Curr Opin Lipidol: 01 Jun 2024; 35:117-125</small></div>

<div><h4>Minimally invasive epicardial surgical left atrial appendage exclusion for atrial fibrillation patients at high risk for stroke and for bleeding.</h4><i>Rose DZ, DiGiorgi P, Ramlawi B, Pulungan Z, Teigland C, Calkins H</i><br /><b>Background</b><br />Atrial fibrillation (AF) patients at high risk for stroke and for bleeding may be unsuitable for either oral anticoagulation or endocardial left atrial appendage (LAA) occlusion. However, minimally invasive, epicardial left atrial appendage exclusion (LAAE) may be an option.<br /><b>Objective</b><br />The purpose of this study was to evaluate outcomes of LAAE in high-risk AF patients not receiving oral anticoagulation.<br /><b>Methods</b><br />A retrospective analysis of Medicare claims data was conducted to evaluate thromboembolic events in AF patients who underwent LAAE compared to a 1:4 propensity score-matched group of patients who did not receive LAAE (control). Neither group was receiving any oral anticoagulation at baseline or follow-up. Fine-Gray models estimated hazard ratios and evaluated between-group differences. Bootstrapping was applied to generate 95% confidence intervals (CIs).<br /><b>Results</b><br />The LAAE group (n = 243) was 61% male (mean age 75 years). AF was nonparoxysmal in 70% (mean CHA<sub>2</sub>DS<sub>2</sub>-VASc score 5.4; mean HAS-BLED score 4.2). The matched control group (n = 972) had statistically similar characteristics. One-year adjusted estimates of thromboembolic events were 7.3% (95% CI 4.3%-11.1%) in the LAAE group and 12.1% (95% CI 9.5%-14.8%) in the control group. Absolute risk reduction was 4.8% (95% CI 0.6%-8.9%; P = .028). Adjusted hazard ratio for thromboembolic events for LAAE vs non-LAAE was 0.672 (95% CI 0.394-1.146).<br /><b>Conclusion</b><br />In AF patients not taking oral anticoagulation who are at high risk for stroke and for bleeding, minimally invasive, thoracoscopic, epicardial LAAE was associated with a lower rate of thromboembolic events.<br /><br />Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Heart Rhythm: 01 Jun 2024; 21:771-779</small></div>

<div><h4>Atrial electrofunctional predictors of incident atrial fibrillation in cardiac amyloidosis.</h4><i>Sinigiani G, De Michieli L, Porcari A, Zocchi C, ... Cappelli F, Cipriani A</i><br /><b>Background</b><br />Atrial fibrillation (AF) is common in patients with cardiac amyloidosis (CA) and is a significant risk factor for heart failure hospitalization and thromboembolic events.<br /><b>Objective</b><br />This study was designed to investigate the atrial electrofunctional predictors of incident AF in CA.<br /><b>Methods</b><br />A multicenter, observational study was conducted in 4 CA referral centers including sinus rhythm patients with light-chain (AL) and transthyretin (ATTR) CA undergoing electrocardiography and cardiac magnetic resonance imaging. The primary end point was new-onset AF occurrence.<br /><b>Results</b><br />Overall, 96 patients (AL-CA, n = 40; ATTR-CA, n = 56) were enrolled. During an 18-month median follow-up (Q1-Q3, 7-29 months), 30 patients (29%) had incident AF. Compared with those without AF, patients with AF were older (79 vs 73 years; P = .001). They more frequently had ATTR (87% vs 45%; P < .001); electrocardiographic interatrial block (IAB), either partial (47% vs 21%; P = .011) or advanced (17% vs 3%; P = .017); and lower left atrial ejection fraction (LAEF; 29% vs 41%; P = .004). Age (hazard ratio [HR], 1.059; 95% CI, 1.002-1.118; P = .042), any type of IAB (HR, 2.211; 95% CI, 1.03-4.75; P = .041), and LAEF (HR, 0.967; 95% CI, 0.936-0.998; P = .044) emerged as independent predictors of incident AF. Patients exhibiting any type of IAB, LAEF <40%, and age >78 years showed a cumulative incidence for AF of 40% at 12 months. This risk was significantly higher than that carried by 1 (8.5%) or none (7.6%) of these 3 risk factors.<br /><b>Conclusion</b><br />In patients with CA, older age, IAB on 12-lead electrocardiography, and reduced LAEF on cardiac magnetic resonance imaging are significant and independent predictors of incident AF. A closer screening for AF is advisable in CA patients carrying these features.<br /><br />Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Heart Rhythm: 01 Jun 2024; 21:725-732</small></div>

<div><h4>Atherosclerotic Coronary Plaque Features in Patients with Chronic Obstructive Pulmonary Disease and Acute Coronary Syndrome.</h4><i>Russo M, Camilli M, La Vecchia G, Rinaldi R, ... Crea F, Montone RA</i><br /><AbstractText>Previous studies reported a robust relationship between chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD). Systemic inflammation has been proposed as possible pathogenetic mechanism linking these two entities, although data on atherosclerotic coronary features in COPD patients are lacking. We studied atherosclerotic coronary plaque features in COPD patients presenting with acute coronary syndromes (ACS) by using optical coherence tomography (OCT). ACS patients undergoing intracoronary OCT imaging of the culprit vessel were enrolled. Coronary plaque characteristics and OCT-defined macrophage infiltration (MØI) were assessed by OCT. ACS patients were divided into two groups according to the presence of an established diagnosis of COPD, and plaque features at the culprit site and along the culprit vessel were compared between the groups. Among 146 ACS patients (mean age:66.1±12.7 years, 109 males), 47 (32.2%) had COPD. Patients with COPD had significantly higher prevalence of MØI (78.7% vs. 54.5%, p=0.005) and thin cap fibroatheroma (TCFA) (48.9% vs. 22.2%, p=0.001) at the culprit site. In the multivariate logistic regression, COPD was independently associated with MØI (OR:21.209, CI95%:1.679;267.910, p=0.018) and TCFA at the culprit site (OR:5.345, CI95%:1.386;20.616, p=0.015). Similarly, COPD was independently associated with both MØI (OR:3.570, CI95%:1.472;8.658, p=0.005) and TCFA (OR:4.088, CI95%:1.584;10.554, p=0.004) along the culprit vessel. In conclusion, in ACS patients undergoing OCT imaging of the culprit vessel, COPD was an independent predictor of plaque inflammation and vulnerability. These results may suggest that a higher inflammatory milieu in COPD patients might enhance local coronary inflammation, promoting CAD development and plaque vulnerability.</AbstractText><br /><br />Copyright © 2024. Published by Elsevier Inc.<br /><br /><small>Am J Cardiol: 11 Jun 2024; epub ahead of print</small></div>