<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>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>

<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>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>Transcatheter aortic valve implantation in severe aortic stenosis does not necessarily reverse left ventricular myocardial damage: data of long-term follow-up.</h4><i>Myon F, Marut B, Kosmala W, Auffret V, ... Oger E, Donal E</i><br /><b>Aims</b><br />Aortic stenosis (AS) is causing myocardial damage and replacement is mainly indicated based on symptoms. Non-invasive estimation of myocardial work (MW) provides a less afterload-dependent too for assessing myocardial function. We sought to look at the impact of transcatheter aortic valve implantation (TAVI) on the myocardium at long-term follow-up and according to current indications.<br /><b>Methods and results</b><br />We conducted an observational, cross-sectional, single-centre study. Patients were selected based on the validated indication for a TAVI. Standardized echocardiographies were repeated. A total of 102 patients were included. The mean age was 85 years, 45% were female, 68% had high blood pressure, and 52% had a coronary disease. One-fifth was suffering from low-flow-low-gradient AS. A follow-up was performed at 22 ± 9.5 months after the TAVI. No TAVI dysfunction was observed. Left ventricular (LV) ejection fraction was stable (62 ± 8%), and global longitudinal strain had improved (-14.0 ± 3.7 vs. -16.0 ± 3.6%, P < 0.0001). No improvement of the MW parameters was noticed (LV global work index 2099 ± 692 vs. 2066 ± 706 mmHg%, P = 0.8, LV global constructive 2463 ± 736 vs. 2463 ± 676 mmHg%, P = 0.8). Global wasted work increased [214 (149; 357) vs. 247 (177; 394) mmHg%, P = 0.0008].<br /><b>Conclusion</b><br />In a population of severe symptomatic AS patients who had undergone a TAVI, the non-invasive myocardial indices that assess the LV performance at long-term follow-up did not improve. These results are questioning the timing of the intervention and the need for more attention in the pharmacological management of these AS patients.<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; 25:821-828</small></div>

<div><h4>Acute Response of the Noninfarcted Myocardium and Surrounding Tissue Assessed by T2 Mapping After STEMI.</h4><i>Bergamaschi L, Landi A, Maurizi N, Pizzi C, ... Valgimigli M, Pavon AG</i><br /><b>Background</b><br />ST-segment elevation myocardial infarction (STEMI) is associated with a systemic and local inflammatory response with edema. However, their role at the tissue level is poorly characterized.<br /><b>Objectives</b><br />This study aims to characterize T2 values of the noninfarcted myocardium (NIM) and surrounding tissue and to investigate prognostic relevance of higher NIM T2 values after STEMI.<br /><b>Methods</b><br />A total of 171 consecutive patients with STEMI without prior cardiovascular events who underwent cardiac magnetic resonance after primary percutaneous coronary intervention were analyzed in terms of standard infarct characteristics. Edema of the NIM, liver, spleen, and pectoralis muscle was assessed based on T2 mapping. Follow-up was available for 130 patients. The primary endpoint was major adverse cardiac events (MACE), defined as cardiovascular death, myocardial infarction, unplanned coronary revascularization or rehospitalization for heart failure. The median time from primary percutaneous coronary intervention to cardiac magnetic resonance was 3 days (IQR: 2-5 days).<br /><b>Results</b><br />Higher (above the median value of 45 ms) T2 values in the NIM area were associated with larger infarct size, microvascular obstruction, and left ventricular dysfunction and did not correlate with C-reactive protein, white blood cells, or T2 values of the pectoralis muscle, liver, and spleen. At a median follow-up of 17 months, patients with higher (>45 ms) NIM T2 values had increased risk of MACE (P < 0.001) compared with subjects with NIM T2 values ≤45 ms, mainly caused by a higher rate of myocardial reinfarction (26.3% vs 1.4%; P < 0.001). At multivariable analysis, higher NIM T2 values independently predicted MACE (HR: 2.824 [95% CI: 1.254-6.361]; P = 0.012).<br /><b>Conclusions</b><br />Higher NIM T2 values after STEMI are independently associated with worse cardiovascular outcomes, mainly because of higher risk of myocardial infarction.<br /><br />Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jun 2024; 17:610-621</small></div>

<div><h4>Sex-based differences in the phenotypic expression and prognosis of idiopathic non-ischaemic cardiomyopathy: a cardiovascular magnetic resonance study.</h4><i>Mallabone M, Labib D, Abdelhaleem A, Dykstra S, ... Fine NM, White JA</i><br /><b>Aims</b><br />We sought to characterize sex-related differences in cardiovascular magnetic resonance-based cardiovascular phenotypes and prognosis in patients with idiopathic non-ischaemic cardiomyopathy (NICM).<br /><b>Methods and results</b><br />Patients with NICM enrolled in the Cardiovascular Imaging Registry of Calgary (CIROC) between 2015 and 2021 were identified. Z-score values for chamber volumes and function were calculated as standard deviation from mean values of 157 sex-matched healthy volunteers, ensuring reported differences were independent of known sex-dependencies. Patients were followed for the composite outcome of all-cause mortality, heart failure admission, or ventricular arrhythmia. A total of 747 patients were studied, 531 (71%) males. By Z-score values, females showed significantly higher left ventricular (LV) ejection fraction (EF; median difference 1 SD) and right ventricular (RV) EF (difference 0.6 SD) with greater LV mass (difference 2.1 SD; P < 0.01 for all) vs. males despite similar chamber volumes. Females had a significantly lower prevalence of mid-wall striae (MWS) fibrosis (22% vs. 34%; P < 0.001). Over a median follow-up of 4.7 years, 173 patients (23%) developed the composite outcome, with equal distribution in males and females. LV EF and MWS were significant independent predictors of the outcome (respective HR [95% CI] 0.97 [0.95-0.99] and 1.6 [1.2-2.3]; P = 0.003 and 0.005). There was no association of sex with the outcome.<br /><b>Conclusion</b><br />In a large contemporary cohort, NICM was uniquely expressed in females vs. males. Despite similar chamber dilation, females demonstrated greater concentric remodelling, lower reductions in bi-ventricular function, and a lower burden of replacement fibrosis. Overall, their prognosis remained similar to male patients with NICM.<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; 25:804-813</small></div>

<div><h4>Contemporary Trends and Outcomes of Intravascular Lithotripsy in Percutaneous Coronary Intervention: Insights From BMC2.</h4><i>Sukul D, Seth M, Madder RD, Basir MB, ... Lee D, Gurm HS</i><br /><b>Background</b><br />With an aging population and an increase in the comorbidity burden of patients undergoing percutaneous coronary intervention (PCI), the management of coronary calcification for optimal PCI is critical in contemporary practice.<br /><b>Objectives</b><br />This study sought to examine the trends and outcomes of coronary intravascular lithotripsy (IVL), rotational/orbital atherectomy, or both among patients who underwent PCI in Michigan.<br /><b>Methods</b><br />We included all PCIs between January 1, 2021, and June 30, 2022, performed at 48 Michigan hospitals. Outcomes included in-hospital major adverse cardiac events (MACEs) and procedural success.<br /><b>Results</b><br />IVL was used in 1,090 patients (2.57%), atherectomy was used in 1,743 (4.10%) patients, and both were used in 240 patients (0.57% of all PCIs). IVL use increased from 0.04% of PCI cases in January 2021 to 4.28% of cases in June 2022, ultimately exceeding the rate of atherectomy use. The rate of MACEs (4.3% vs 5.4%; P = 0.23) and procedural success (89.4% vs 89.1%; P = 0.88) were similar among patients treated with IVL compared with atherectomy, respectively. Only 15.6% of patients treated with IVL in contemporary practice were similar to the population enrolled in the pivotal IVL trials. Among such patients (n = 169), the rate of MACEs (0.0%) and procedural success (94.7%) were similar to the outcomes reported in the pivotal IVL trials.<br /><b>Conclusions</b><br />Since its introduction in February 2021, coronary IVL use has steadily increased, exceeding atherectomy use in Michigan by February 2022. Contemporary use of IVL and atherectomy is generally associated with high rates of procedural success and low rates of complications.<br /><br />Published by Elsevier Inc.<br /><br /><small>JACC Cardiovasc Interv: 13 Jun 2024; epub ahead of print</small></div>

<div><h4>The premise, promise, and perils of artificial intelligence in critical care cardiology.</h4><i>Huerta N, Rao SJ, Isath A, Wang Z, Glicksberg BS, Krittanawong C</i><br /><AbstractText>Artificial intelligence (AI) is an emerging technology with numerous healthcare applications. AI could prove particularly useful in the cardiac intensive care unit (CICU) where its capacity to analyze large datasets in real-time would assist clinicians in making more informed decisions. This systematic review aimed to explore current research on AI as it pertains to the CICU. A PRISMA search strategy was carried out to identify the pertinent literature on topics including vascular access, heart failure care, circulatory support, cardiogenic shock, ultrasound, and mechanical ventilation. Thirty-eight studies were included. Although AI is still in its early stages of development, this review illustrates its potential to yield numerous benefits in the CICU.</AbstractText><br /><br />Copyright © 2024. Published by Elsevier Inc.<br /><br /><small>Prog Cardiovasc Dis: 25 Jun 2024; epub ahead of print</small></div>