<div><h4>Predictors of major adverse cardiac events among patients with chest pain and low HEART score in the emergency department.</h4><i>Ho AFW, Yau CE, Ho JS, Lim SH, ... Doevendans PA, de Kleijn DPV</i><br /><b>Aim</b><br />For patients who present to the emergency departments (ED) with undifferentiated chest pain, the risk of major adverse cardiac events (MACE) may be underestimated in low-HEART score patients. We aimed to identify characteristics of patients who were classified as low risk by HEART score but subsequently developed MACE at 6 weeks.<br /><b>Methods</b><br />We studied a multiethnic cohort of patients who presented with chest pain arousing suspicion of acute coronary syndrome to EDs in the Netherlands and Singapore. Patients were risk-stratified using HEART score and followed up for MACE at 6 weeks. Risk factors of developing MACE despite low HEART scores (scores 0-3) were identified using logistic and Cox regression models.<br /><b>Results</b><br />Among 1376 (39.8%) patients with low HEART scores, 63 (4.6%) developed MACE at 6 weeks. More males (53/806, 6.6%) than females (10/570, 2.8%) with low HEART score developed MACE. There was no difference in outcomes between ethnic groups. Among low-HEART score patients with 2 points for history, 21% developed MACE. Among low-HEART score patients with 1 point for troponin, 50% developed MACE, while 100% of those with 2 points for troponin developed MACE. After adjusting for HEART score and potential confounders, male sex was independently associated with increased odds (OR 4.12, 95%CI 2.14-8.78) and hazards (HR 3.93, 95%CI 1.98-7.79) of developing MACE despite low HEART score.<br /><b>Conclusion</b><br />Male sex, highly suspicious history and elevated troponin were disproportionately associated with MACE. These characteristics should prompt clinicians to consider further investigation before discharge.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 04 Nov 2023:131573; epub ahead of print</small></div>

<div><h4>Comparison of diagnostic accuracy of current left bundle branch block and ventricular pacing ECG criteria for detection of occlusion myocardial infarction.</h4><i>Lindow T, Mokhtari A, Nyström A, Koul S, Smith SW, Ekelund U</i><br /><b>Background</b><br />Electrocardiographic detection of patients with occlusion myocardial infarction (OMI) can be difficult in patients with left bundle branch block (LBBB) or ventricular paced rhythm (VPR) and several ECG criteria for the detection of OMI in LBBB/VPR exist. Most recently, the Barcelona criteria, which includes concordant ST deviation and discordant ST deviation in leads with low R/S amplitudes, showed superior diagnostic accuracy but has not been validated externally. We aimed to describe the diagnostic accuracy of four available ECG criteria for OMI detection in patients with LBBB/VPR at the emergency department.<br /><b>Methods</b><br />The unweighted Sgarbossa criteria, the modified Sgarbossa criteria (MSC), the Barcelona criteria and the Selvester criteria were applied to chest pain patients with LBBB or VPR in a prospectively acquired database from five emergency departments.<br /><b>Results</b><br />In total, 623 patients were included, among which 441 (71%) had LBBB and 182 (29%) had VPR. Among these, 82 (13%) patients were diagnosed with AMI, and an OMI was identified in 15 (2.4%) cases. Sensitivity/specificity of the original unweighted Sgarbossa criteria were 26.7/86.2%, for MSC 60.0/86.0%, for Barcelona criteria 53.3/82.2%, and for Selvester criteria 46.7/88.3%. In this setting with low prevalence of OMI, positive predictive values were low (Sgarbossa: 4.6%; MSC: 9.4%; Barcelona criteria: 6.9%; Selvester criteria: 9.0%) and negative predictive values were high (all >98.0%).<br /><b>Conclusions</b><br />Our results suggests that ECG criteria alone are insufficient in predicting presence of OMI in an ED setting with low prevalence of OMI, and the search for better rapid diagnostic instruments in this setting should continue.<br /><br />Copyright © 2023 The Author. Published by Elsevier B.V. All rights reserved.<br /><br /><small>Int J Cardiol: 04 Nov 2023:131569; epub ahead of print</small></div>

<div><h4>Impact of temporal and spatial resolution on atrial feature tracking cardiovascular magnetic resonance imaging.</h4><i>Schmidt-Rimpler J, Backhaus SJ, Hartmann FP, Schaten P, ... Kelle S, Schuster A</i><br /><b>Background</b><br />Myocardial deformation assessment by cardiovascular magnetic resonance-feature tracking (CMR-FT) has incremental prognostic value over volumetric analyses. Recently, atrial functional analyses have come to the fore. However, to date recommendations for optimal resolution parameters for accurate atrial functional analyses are still lacking.<br /><b>Methods</b><br />CMR-FT was performed in 12 healthy volunteers and 9 ischemic heart failure (HF) patients. Cine sequences were acquired using different temporal (20, 30, 40 and 50 frames/cardiac cycle) and spatial resolution parameters (high 1.5 × 1.5 mm in plane and 5 mm slice thickness, standard 1.8 × 1.8 × 8 mm and low 3.0 × 3.0 × 10 mm). Inter- and intra-observer reproducibility were calculated.<br /><b>Results</b><br />Increasing temporal resolution is associated with higher absolute strain and strain rate (SR) values. Significant changes in strain assessment for left atrial (LA) total strain occurred between 20 and 30 frames/cycle amounting to 2,5-4,4% absolute changes depending on spatial resolution settings. From 30 frames/cycle onward, absolute strain values remained unchanged. Significant changes of LA strain rate assessment were observed up to the highest temporal resolution of 50 frames/cycle. Effects of spatial resolution on strain assessment were smaller. For LA total strain a general trend emerged for a mild decrease in strain values obtained comparing the lowest to the highest spatial resolution at temporal resolutions of 20, 40 and 50 frames/cycle (p = 0.006-0.046) but not at 30 frames/cycle (p = 0.140).<br /><b>Conclusion</b><br />Temporal and to a smaller extent spatial resolution affect atrial functional assessment. Consistent strain assessment requires a standard spatial resolution and a temporal resolution of 30 frames/cycle, whilst SR assessment requires even higher settings of at least 50 frames/cycle.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 03 Nov 2023:131563; epub ahead of print</small></div>

<div><h4>Incidence and outcomes of high bleeding risk patients with type 1 and type 2 myocardial infarction in a community-based cohort: Application of the Academic Research Consortium High Bleeding Risk Criteria.</h4><i>Breen TJ, Raphael CE, Ingraham B, Lane C, ... Gulati R, Singh M</i><br /><b>Background:</b><br/>and aims</b><br />The incidence and outcomes of high bleeding risk (HBR) patients in a community cohort according to the Academic Research Consortium (ARC) criteria is not known. We hypothesized that HBR is common and associated with worse outcomes for all-comers with myocardial infarction.<br /><b>Methods</b><br />We prospectively collected all patients with cardiac troponin T > 99th percentile upper limit of normal (≥0.01 ng/mL) in Olmsted County between 2003 and 2012. Events were retrospectively classified as type 1 myocardial infarction (T1MI), type 2 myocardial infarction (T2MI), or myocardial injury. Patients were further classified as HBR based on the \"ARC-HBR definition.\" Outcomes included all-cause mortality, cardiovascular mortality, recurrent MI, stroke, and major bleeding.<br /><b>Results</b><br />2419 patients were included in the final study; 1365 were classified as T1MI and 1054 as T2MI. Patients were followed for a median of 5.5 years. ARC-HBR was more common in T2MI than T1MI (73% vs 46%, p < 0.001). Among patients with T1MI, HBR was associated with higher all-cause mortality (HR 3.7, 95% CI 3.2-4.5, p < 0.001), cardiovascular mortality (4.7, 3.6-6.3, p < 0.001), recurrent MI (2.1, 1.6-2.7, p < 0.001), stroke (4.9, 2.9-8.4, p < 0.001), and major bleeding (6.5, 3.7-11.4, p < 0.001). For T2MI, HBR was similarly associated with higher all-cause mortality (HR 2.1, 95% CI 1.8-2.5, p < 0.001), cardiovascular mortality (2.7, 1.8-4.0, p < 0.001), recurrent MI (1.7, 1.1-2.6, p = 0.02) and major bleeding (HR 15.6, 3.8-63.8, p < 0.001).<br /><b>Conclusion</b><br />HBR is common among unselected patients with T1MI and T2MI and is associated with increased overall and cardiovascular mortality, recurrent cardiovascular events, and major bleeding on long-term follow up.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 30 Oct 2023:131565; epub ahead of print</small></div>

<div><h4>Commissural alignment during TAVR reduces the risk of overlap to coronary ostia.</h4><i>Nicole C, Siller-Matula Jolanta M, Fabiola B, Giuseppe P, ... Daniele T, Salvatore R</i><br /><b>Background</b><br />Transcatheter aortic valve replacement (TAVR) showed safety and efficacy in patients with severe aortic stenosis. Commissural alignment (CA) during TAVR has the potential to reduce the impact of the prostheses on accessibility of coronary arteries, as misalignment of the neocommissures could cause partial overlap with coronary ostia. Therefore, the aim of this study was to investigate the impact of CA on coronary overlap rates.<br /><b>Methods</b><br />We examined the techniques of CA and their impact on coronary access. Eligible studies were searched for on Pubmed, SCOPUS and DOAJ and selected using PRISMA guidelines. The primary endpoint was the incidence of a severe coronary overlap or failed coronary re-access. Results of the analysis are expressed as Risk Ratio (RR) with 95% CI.<br /><b>Results</b><br />Four studies were included in this analysis. Of these, 681 patients underwent TAVR with CA and 210 underwent TAVR without CA. We examined Evolut valves and Acurate Neo valves. The primary endpoint occurred in 138 patients undergoing TAVR with CA and in 154 patients without CA (RR = 0.279; 95% CI 0.201-0.386; p < 0.001). Neither prosthesis-related, nor patient-related factors had a significant interaction with the analyses.<br /><b>Conclusions</b><br />Commissural alignment was associated with significantly lower rates of commissure-to coronary-ostia overlap and failure of coronary access. Consequently, a modified insertion technique could reduce coronary overlap and coronary occlusion, particularly in supra-annular valves. Therefore, controlled orientation of prostheses by CA during TAVR could favour coronary access, especially in younger patients that could require coronary re-access after TAVR.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 30 Oct 2023:131572; epub ahead of print</small></div>

<div><h4>Left ventricular strain-volume loops and myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy.</h4><i>Kerstens TP, van Everdingen WM, Ten Cate FEAU, Thijssen DHJ</i><br /><b>Background</b><br />The left ventricular strain-volume loop (SVL) combines changes in global longitudinal strain (GLS) and LV volume across a cardiac cycle, providing insight into cardiac dynamics. This study explored the association between left ventricular SVL and presence of fibrosis, assessed with late gadolinium enhancement, in patients with Duchenne muscular dystrophy (DMD).<br /><b>Methods and results</b><br />34 pediatric patients with DMD were included. Feature tracking analysis was used to assess endocardial GLS and volumetric measurements to construct the SVL. Mean age at the time of assessment was 14 ± 3 and 11 ± 2 years old (p < 0.01) in the group with (n = 18) versus without fibrosis (n = 16), respectively. Left ventricular ejection fraction was not significantly different between groups (fibrosis 56.4 ± 3.8% versus without fibrosis 54.0 ± 6.3%, p = 0.18). After adjusting for age, the late diastolic slope of the SVL was significantly associated with presence of fibrosis (OR 0.39 [95% CI 0.18-0.85]; area under the receiver operating characteristic curve: 0.83 [95% CI 0.70-0.97]) No significant association was observed for peak strain and fibrosis (OR 1.15 [95% CI 0.86-1.546]).<br /><b>Conclusion</b><br />A lower late diastolic slope of the left ventricular SVL, related to the interplay between longitudinal deformation and volume changes late in diastole, is associated with presence of myocardial fibrosis in pediatric patients with DMD.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 30 Oct 2023:131568; epub ahead of print</small></div>

<div><h4>Alerting trends in epidemiology for non-rheumatic degenerative mitral valve disease, 1990-2019: An age-period-cohort analysis for the Global Burden of Disease Study 2019.</h4><i>Liu Z, Wei P, Jiang H, Zhang F, ... Fang F, Pan X</i><br /><b>Background</b><br />The global and national burden of rheumatic mitral valve disease (MVD) has been well studied and estimated before. However, little is known about non-rheumatic degenerative MVD. Therefore, this study aimed to assess the trends in non-rheumatic degenerative MVD (NRDMVD) epidemiology, with an emphasis on NRDMVD mortality, leading risk factors, and their associations with age, period, and birth cohort.<br /><b>Methods</b><br />Using the data derived from the Global Burden of Disease Study 2019, including prevalence, mortality, and disability-adjusted life years, we analyzed the burden of NRDMVD and the detailed trends of NRDMVD mortality over the past 30 years in 204 countries and territories by implementing the age-period-cohort framework.<br /><b>Results</b><br />Globally, the number of deaths due to NRDMVD increased from 5695.89 (95% uncertainty interval [UI]: 5405.19 to 5895.4) × 1000 in 1990 to 9137.79 (95% UI: 8395.68 to 9743.55) × 1000 in 2019. The all-age mortality rate increased from 106.47 (95% UI: 101.03 to 110.2) per 100,000 to 118.1 (95% UI: 108.51 to 125.93) per 100,000, whereas the age-standardized mortality rate decreased from 170.45 (95% UI: 159.61 to 176.94) per 100,000 to 117.95 (95% UI: 107.83 to 125.92) per 100,000. The estimated net drift of mortality per year was -1.1% (95% confidence interval: -1.17 to -1.04). The risk of death due to NRDMVD increased with age, reaching its peak after 85 years old globally. Despite female patients being associated with lower local drift than male patients, no significant gender differences were observed in the age effect across countries and regions for all sociodemographic index (SDI) levels, except low-SDI regions.<br /><b>Conclusions</b><br />We estimated the global disease prevalence of and mortality due to NRDMVD over approximately a 30-year period. The health-related burden of NRDMVD has declined worldwide; however, the condition persisted in low-SDI regions. Moreover, higher attention should be paid to female patients.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 30 Oct 2023:131561; epub ahead of print</small></div>

<div><h4>Applicability and performance of heart failure prognostic scores in dilated cardiomyopathy: The real-world experience of an Italian referral center for cardiomyopathies.</h4><i>Masè M, Rossi M, Setti M, Barbati G, ... Merlo M, Sinagra G</i><br /><b>Background</b><br />The performance of heart failure (HF) risk models is validated in the general population with HF but in specific aetiological settings, and specifically in dilated cardiomyopathy (DCM), has scarcely been explored. We tested eight of the main prognostic scores used in HF in a large real-world population of patients with DCM.<br /><b>Methods</b><br />We included 784 consecutive DCM patients enrolled, both inpatients and outpatients, enrolled between January 2000 and December 2017. The risk of 1 and/or 3-year all-cause mortality/heart transplantation/durable left ventricular assist device (LVAD) implantation (D/HTx/LVAD) was estimated in our cohort according to the following risk scores SHFM, 3-CHF, CHARM, MAGGIC, GISSI-HF, MECKI, Barcelona Bio-HF, Krakow score and their accuracy calculated through the receiver operator characteristic (ROC) curve analysis.<br /><b>Results</b><br />During a median follow-up of 5.8 years (Interquartile Range 3.2-7.6 years), 191 patients (20%) died or underwent HTx/LVAD (158 deaths, 30 heart transplantations, and 3 LVAD implantations). The high missing rate allowed to calculated only four prognostic models (MAGGIC, CHARM, 3-CHF and SHFM). All the scores overestimated the rate of D/HTx/LVAD. The prognostic accuracy was suboptimal for MAGGIC (AUC 0.754) and CHARM (AUC 0.720) scores and only modest for 3-CHF (AUC 0.677) and SHFM (AUC 0.667).<br /><b>Conclusions</b><br />Main prognostic scores for the risk stratification of HF are only partially applicable to real-world patients with DCM. MAGGIC and CHARM scores showed the best accuracy, despite the overestimation of risk. Our findings corroborate the need of specific risk scores for the prognostic stratification of DCM.<br /><b>Clinical perspective</b><br />What is new? The present study is the largest analyses in literature which investigate how the main existing heart failure prognostic risk scores performed in a real-world of dilated cardiomyopathy population, both in- and outpatients. What are the clinical implications? DCM is a stand-alone model of heart failure, where the performance of multiple heart failure prognostic scores for the risk stratification is quite limited. The need for contemporary, dedicated prognostic scores in this disease is increasingly evident.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 Oct 2023:131562; epub ahead of print</small></div>

<div><h4>Dysbiosis of gut microbiota in patients with protein-losing enteropathy after the Fontan procedure.</h4><i>Go K, Horiba K, Yamamoto H, Morimoto Y, ... Takahashi Y, Kato T</i><br /><b>Background</b><br />There is a lack of predictive biomarkers for the onset or activity of protein-losing enteropathy (PLE), a Fontan procedure-associated complication. Here, we aimed to identify the gut microbiota composition of patients with active PLE and investigate its relationship with PLE activity.<br /><b>Methods</b><br />This multicenter case-control study involved patients who developed PLE (n = 16) after the Fontan procedure and those who did not (non-PLE; n = 20). Patients with PLE who maintained a serum albumin level of ≥3 g/dL for >1 year were included in the remissive-stage-PLE group (n = 9) and those who did not maintain this level were included in the active-PLE group (n = 7). 16S rRNA gene sequencing analysis of fecal samples was performed using QIIME2 pipeline. Alpha (Shannon and Faith\'s phylogenetic diversity indices) and beta diversity was assessed using principal coordinate analysis based on unweighted UniFrac distances.<br /><b>Results</b><br />Shannon and Faith\'s phylogenetic diversity indices were lower in the active-PLE group than in the remissive-stage- (q = 0.028 and 0.025, respectively) and non-PLE (q = 0.028 and 0.017, respectively) groups. Analysis of beta diversity revealed a difference in the microbiota composition between the active-PLE and the other two groups. Linear discriminant effect size analysis demonstrated differences in the relative abundance of Bifidobacterium and Granulicatella spp., and Ruminococcus torques between patients with active- and those with remissive-stage-PLE.<br /><b>Conclusions</b><br />Gut microbiota dysbiosis was observed in patients with active PLE. Changes in the bacterial composition of the gut microbiota and decreased diversity may be associated with the severity of PLE.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 22 Oct 2023:131554; epub ahead of print</small></div>

<div><h4>Prevalence of respiratory failure and use of mechanical ventilation in heart failure patients undergoing left atrial appendage occlusion device implantation.</h4><i>Seri A, Rabadi A, Baral N, Andi K, ... Mehta A, Vallabhajosyula S</i><br /><b>Background</b><br />We sought to evaluate respiratory complications in heart failure patients undergoing left atrial appendage occlusion (LAAO) for stroke prevention in atrial fibrillation.<br /><b>Methods</b><br />Adult admissions (>18 years) undergoing LAAO during 2016-2020 were identified from the National Inpatient Sample. Heart failure (HF) was stratified into systolic (SHF) and diastolic heart failure (DHF) and were compared to those without HF. Outcomes of interested included acute respiratory failure, use of non-invasive and invasive mechanical ventilation, and in-hospital mortality.<br /><b>Results</b><br />Of 74,440 admissions for atrial fibrillation undergoing LAAO, SHF and DHF were noted in 8335 (11.2%) and 10,925 (14.7%), respectively. The SHF cohort was predominantly male (78%) whereas DHF cohort were female (53%). Compared to those without HF, presence of SHF (2.3% vs. 0.6%; adjusted odds ratio [OR] 1.61 [95% confidence interval {CI} 1.10-2.36]; p = 0.01) and DHF (2.8% vs. 0.6%; adjusted OR 2.20 [95% CI 1.58-3.06]; p < 0.001) were associated with higher rates of acute respiratory failure. SHF (1.7% vs. 0.6%; adjusted OR 1.70 [95% CI 1.07-2.71]; p = 0.02) group but not DHF (1.2% vs. 0.6%; adjusted OR 1.21 [95% CI 0.78-1.89]; p = 0.39) was associated with higher rates of non-invasive ventilation, whereas the DHF group (0.9% vs. 0.2%; adjusted OR 1.91 [95% CI 1.08-3.34]; p = 0.02) but not SHF (0.8% vs. 0.2%; adjusted OR 1.54 [95% CI 0.83-2.84]; p = 0.17) was associated with higher rates of invasive mechanical ventilation use. In-hospital mortality was comparable between cohorts.<br /><b>Conclusion</b><br />Compared to those without HF, atrial fibrillation admissions with HF undergoing LAAO had higher rates of acute respiratory failure and mechanical ventilation rates without differences in in-hospital mortality.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 21 Oct 2023:131552; epub ahead of print</small></div>

<div><h4>Contribution of reduced skeletal muscle perfusion reserve to exercise intolerance in heart failure with preserved ejection fraction.</h4><i>Serafin A, Jasic-Szpak E, Marwick TH, Przewlocka-Kosmala M, Ponikowski P, Kosmala W</i><br /><b>Background</b><br />Skeletal muscle (SM)-associated mechanisms of exercise intolerance in HFpEF are insufficiently defined, and inadequate augmentation of SM blood flow during physical effort may be one of the contributors. Therefore, we sought to investigate the association of SM perfusion response to exertion with exercise capacity in this clinical condition.<br /><b>Methods</b><br />Echocardiography and SM microvascular perfusion by contrast-enhanced ultrasound were performed at rest and immediately post-exercise test in 77 HFpEF patients in NYHA class II and III, and in 25 subjects with normal exercise tolerance (stage B). Exercise reserve of cardiac function and SM perfusion was calculated by subtracting resting value from exercise value.<br /><b>Results</b><br />In addition to decreased cardiac functional reserve, HFpEF patients demonstrated significantly reduced SM perfusion reserve as compared to HF stage B, with the degree of impairment being greater in the subgroup with more profound left ventricular (LV) diastolic abnormalities (E/e\' > 15 and TRV > 2.8 m/s). SM perfusion reserve was significantly associated with exercise capacity (beta = 0.33; SE 0.11; p = 0.003), cardiac output reserve (beta = 0.24; SE 0.12; p = 0.039), resting E/e\' (beta = -0.33; SE 0.11; p = 0.006), and patient frailty expressed by the PRISMA 7 score (beta = -0.30; SE 0.11; p = 0.008). In multivariable analysis including clinical, demographic and cardiac functional variables, SM perfusion reserve was in addition to patient frailty, sex and LV longitudinal strain reserve among the independent correlates of exercise capacity.<br /><b>Conclusions</b><br />SM perfusion reserve is impaired in HFpEF, and is associated with reduced exercise capacity independent of clinical, demographic and \"central\" cardiac factors. This supports the need to consider the SM domain in patient management strategies in HFpEF.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 21 Oct 2023:131553; epub ahead of print</small></div>

<div><h4>Evaluation of the anatomic sinus after transcatheter aortic valve replacement.</h4><i>Moscarelli M, Prestera R, Fiore C, Pernice V, ... Speziale G, Fattouch K</i><br /><b>Background</b><br />Following transcatheter aortic valve replacement (TAVI), the newly formed \'anatomic sinus\'. may contribute to the formation of subclinical leaflet thrombosis (SLT).The evaluation of root geometry after TAVI is generally performed using multi-detector computed tomography (MDCT), and the role of transthoracic echocardiography (2D TTE) requires further validation. Thus, we aimed to test the reproducibility of 2D TTE assessment of the anatomic sinus with MDCT as a reference and its association with SLT.<br /><b>Methods</b><br />2D TTE was performed in 90 patients, and the echocardiograms were analyzed offline. Both sinus of Valsalva (SOV) and prosthesis diameters were assessed in the long- and short-axis parasternal views (PLAX/PSAX), and the anatomic sinus area was calculated. Inter- and intra-observer reproducibility were assessed using the interclass correlation coefficient (ICC). MDCT was performed in 50 individuals to evaluate concordance with 2D TTE and to detect SLT.<br /><b>Results</b><br />There was excellent correlation regarding the diameter of the SOV and the prosthesis in PLAX (ICC: 0.93 (95% CI: 0.76,0.97); ICC: 0.80 (95% CI: 0.63,0.96)) and PSAX view (ICC: 0.90 (95% CI: 0.68,0.97); ICC: 0.88 (95% CI: 0.63,0.96)). Bland-Altman analysis of 2D TTE and MDCT anatomic sinus areas indicated a high level of agreement. SLT was detected in 8 individuals (16%); 3 patients had severe SLT at the level of 1 cusp.<br /><b>Conclusions</b><br />2D TTE might play a role in the evaluation of the anatomic sinus after TAVI. The importance of this space and its effects on the SLT remain uncertain.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 20 Oct 2023:131551; epub ahead of print</small></div>

<div><h4>Microparticles and cardiotoxicity secondary to doxorubicin-based chemotherapy in breast cancer patients.</h4><i>Pestana RMC, Teixeira-Carvalho A, Dos Santos LI, de Oliveira AN, ... Simões R, Gomes KB</i><br /><AbstractText>Doxorubicin (DOXO)-cardiotoxicity is a limiting factor for breast cancer chemotherapy. The relationship between microparticles (MPs) and cardiotoxicity remains unclear. MPs can be released under varying pathophysiological conditions. Thereby, this study aimed to assess MPs derived from cardiomyocytes (CardioMPs), platelets (PMPs) and those that expresses tissue factor (TFMPs) in 80 women with breast cancer undergoing DOXO-based chemotherapy, with or without cardiotoxicity in a one-year follow-up. We observed in the cardiotoxicity group higher count of total-MPs at T0 (prior chemotherapy) (p = 0.034), CardioMPs at T0 and T1 (just after chemotherapy) (p = 0.009 and p = 0.0034) and TFMPs at T0 (p = 0.011) compared to non-cardiotoxicity group. The results suggest that MPs could be associated to cardiotoxicity due to DOXO treatment in breast cancer patients.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Oct 2023:131435; epub ahead of print</small></div>

<div><h4>Aging and atrial fibrillation: A vicious circle.</h4><i>Gao P, Gao X, Xie B, Tse G, Liu T</i><br /><AbstractText>Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia observed in clinical practice. Its prevalence increases dramatically with advancing age. This review article discusses the recent advances in studies investigating the relationship between aging and AF and the possible underlying mechanisms.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 15 Oct 2023:131445; epub ahead of print</small></div>

<div><h4>Accuracy of lung ultrasound examinations of residual congestion performed by novice residents in patients with acute heart failure.</h4><i>Imanishi J, Iwasaki M, Ujiro S, Nakano T, ... Todoroki T, Okuda M</i><br /><b>Aims</b><br />The popularity of B-line-guided congestion assessment by lung ultrasound (LUS) has been increasing. However, the ability of novice residents to detect residual congestion with B-line-guided assessment by LUS after decongestion treatment is poorly understood. In this study, we investigated whether novice residents (no prior echocardiography experience) can acquire the skills for B-line-guided residual congestion assessment and whether the range of variation in assessment is acceptable in actual clinical use.<br /><b>Methods and results</b><br />The study included 30 postgraduate first-year novice residents and an expert. The residents underwent training for LUS. At the end of the training session, a set of 15 LUS videos was provided to the residents, and they were asked to estimate the number of B-lines in each video. When the residents\' answers greatly differed from the correct answer, we provided feedback to raise awareness of the discrepancies. After the training session, the residents performed residual congestion assessment by LUS after decongestion treatment in patients hospitalized with acute heart failure. The residents identified residual congestion in 57% of the patients. The sensitivity and specificity to identify residual congestion by the residents were 90% and 100%, respectively. The inter-operator agreement between the residents and the expert was substantial (κ = 0.86). The Spearman rank correlation coefficient for the B-lines between the expert and each resident was very high at 0.916 (P < 0.0001).<br /><b>Conclusions</b><br />After a brief lecture, novice residents can achieve proficiency in quantifying B-lines on LUS and can reliably identify residual congestion on LUS.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 14 Oct 2023:131446; epub ahead of print</small></div>

<div><h4>Proposed diagnostic criteria for arrhythmogenic cardiomyopathy. European Task Force consensus report.</h4><i>Domenico C, Aris A, Cristina B, Barbara B, ... Arthur W, Alessandro Z</i><br /><AbstractText>Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent \"non-ischemic\" myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the \"Padua criteria\" were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late‑gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other \"non-scarring\" myocardial disease. The \"ring-like\' pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 14 Oct 2023:131447; epub ahead of print</small></div>

<div><h4>Outpatient tricuspid regurgitation in the community: Clinical context and outcome.</h4><i>Leonardi D, Bursi F, Fanti D, Dotto A, ... Ribichini FL, Benfari G</i><br /><b>Background:</b><br/>and aims</b><br />Epidemiology of tricuspid regurgitation (TR) is poorly known and its burden in the community is challenging to define. We aimed to evaluate the prevalence of TR in a geographically defined area and its outcome, in particular overall survival and hospitalization, considering different clinical contexts.<br /><b>Methods</b><br />We retrospectively analyzed consecutive outpatients referred between 2006 and 2013 for echocardiography and clinical evaluation. Patients with at least moderate TR were included and five different clinical settings were defined: concomitant significant left-sided valvular heart disease (LVHD-TR), heart failure (HF-TR), previous open-heart valvular surgery (postop-TR), pulmonary hypertension (PHTN-TR) and isolated TR (isolated-TR). Primary endpoint was a composite outcome of all-cause mortality or first hospitalization for HF.<br /><b>Results</b><br />Of 6797 consecutive patients with a clinical visit and echocardiograms performed in routine practice in a geographically defined community, moderate or severe TR was found in 4.8% of patients (327) . During median follow-up of 6.1 years, TR severity was a determinant of event-free survival. Analyzed for each clinical subset, eight-year event-free survival was 87 ± 7% for postop-TR subgroup, 75 ± 7% for isolated-TR, 67 ± 6% for PHTN-TR, 58 ± 6% for LHVD -TR and 52 ± 11% for HF-TR.<br /><b>Conclusion</b><br />Moderate or more TR is a notable finding in the community and has impact on event-free survival in all clinical settings, with the worst outcomes when associated with relevant left-sided valvular heart disease and HF.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 14 Oct 2023:131443; epub ahead of print</small></div>

<div><h4>Treatment effect of canagliflozin for patients on therapy for heart failure: Pooled analysis of the CANVAS program and CREDENCE trial.</h4><i>Jain SS, Yu J, Arnott C, Neal B, ... Jardine M, Mahaffey KW</i><br /><b>Background</b><br />Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that has been shown to reduce cardiovascular events in diabetic patients with and without heart failure (HF). Whether the clinical benefits and safety profile of canagliflozin are different in those on a beta blocker and an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (BB + RAASi) is unknown.<br /><b>Methods</b><br />We pooled participants with HF at baseline from the CANVAS Program and CREDENCE trial and assessed major adverse cardiovascular events and its components; hospitalization for heart failure (HHF); HHF or CV death; all-cause mortality; a renal composite; and a combined renal and CV composite.<br /><b>Results</b><br />Of 14,543 participants, 2113 had HF at baseline, and 1280 were on BB + RAASi. In those with a history of HF, participants on BB + RAASi therapy were more likely to have coronary atherosclerotic disease (82 vs 72%, p < 0.001), history of myocardial infarction (42 vs 29%, p < 0.001), higher mean body mass index (34 vs 32 kg/m<sup>2</sup>, p < 0.001), and lower mean estimated glomerular filtration rate (67 vs 70 mL/min/1.73 m<sup>2</sup>, p < 0.01). They were also more likely to be on insulin, a statin, antithrombotic agent, and a diuretic (all p < 0.001). In unadjusted analysis and when adjusted for selected baseline factors, there was no heterogeneity in canagliflozin treatment effect except for HHF/CV death in those on baseline BB + RAASi vs. those not on baseline BB + RAASi (P<sub>heterogeneity</sub> = 0.02).<br /><b>Conclusion</b><br />Canagliflozin mostly improved CV and kidney outcomes in participants with a history of HF irrespective of use of BB + RAASi at baseline, with possible greater benefit on HHF/CV death in participants on BB + RAASi.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 14 Oct 2023:131444; epub ahead of print</small></div>

<div><h4>Self-expanding and balloon-expandable valves in low risk TAVR patients.</h4><i>Bhogal S, Waksman R, Shea C, Zhang C, ... Satler LF, Rogers T</i><br /><b>Background</b><br />Recent randomized studies have broadened the indication of transcatheter aortic valve replacement (TAVR) to also include low-surgical-risk patients. However, the data on self-expanding (SE) and balloon-expandable (BE) valves in low-risk patients remain sparse.<br /><b>Methods</b><br />The current study is a post hoc analysis of combined data from both LRT 1,0 and 2.0 trials comparing BE and SE transcatheter heart valves.<br /><b>Results</b><br />A total of 294 patients received a BE valve, and 102 patients received an SE valve. The 30-day clinical outcomes were similar across both groups except for stroke (4.9% vs. 0.7%, p = 0.014) and permanent pacemaker implantation (17.8% vs. 5.8%, p < 0.001), which were higher in the SE cohort than the BE cohort. No difference was observed in the terms of paravalvular leak (≥moderate) between the groups (0% vs. 1.5%, p = 0.577). SE patients had higher aortic valve area (1.92 ± 0.43 mm<sup>2</sup> vs. 1.69 ± 0.45 mm<sup>2</sup>, p < 0.001) and lower mean gradient (8.93 ± 3.53 mmHg vs. 13.41 ± 4.73 mmHg, p < 0.001) than BE patients. In addition, the rate of subclinical leaflet thrombosis was significantly lower in SE patients (5.6% vs. 13.8%, p = 0.038).<br /><b>Conclusion</b><br />In this non-randomized study assessing SE and BE valves in low-risk TAVR patients, SE valves are associated with better hemodynamics and lesser leaflet thrombosis with increased rates of stroke and permanent pacemaker implantation at 30 days; however, this could be due to certain patient-dependent factors not fully evaluated in this study. The long-term implications of these outcomes on structural valve durability remain to be further investigated. Clinical Trial Registry LRT 1.0: NCT02628899 LRT 2.0: NCT03557242.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 11 Oct 2023:131431; epub ahead of print</small></div>

<div><h4>Development and validation of a postoperative bleeding complications prediction model in infective endocarditis.</h4><i>Wang J, Hou J, Feng K, Wu H, ... Huang S, Wu Z</i><br /><b>Objectives</b><br />Bleeding complications are one of the most serious postoperative complications after cardiac surgery and are associated with high mortality, especially in patients with infective endocarditis (IE). Our objectives were to identify the risk factors and develop a prediction model for postoperative bleeding complications in IE patients.<br /><b>Methods</b><br />The clinical data of IE patients treated from October 2013 to January 2022 were reviewed. Multivariate logistic regression analysis was used to evaluate independent risk factors for postoperative bleeding complications and develop a prediction model accordingly. The prediction model was verified in a temporal validation cohort. The performance of the model was evaluated in terms of its discrimination power, calibration, precision, and clinical utility.<br /><b>Results</b><br />A total of 423 consecutive patients with IE who underwent surgery were included in the final analysis, including 315 and 108 patients in the training cohort and validation cohort, respectively. Four variables were selected for developing a prediction model, including platelet counts, systolic blood pressure, heart failure and vegetations on the mitral and aortic valves. In the training cohort, the model exhibited excellent discrimination power (AUC = 0.883), calibration (Hosmer-Lemeshow test, P = 0.803), and precision (Brier score = 0.037). In addition, the model also demonstrated good discrimination power (AUC = 0.805), calibration (Hosmer-Lemeshow test, P = 0.413), and precision (Brier score = 0.067) in the validation cohort.<br /><b>Conclusions</b><br />We developed and validated a promising risk model with good discrimination power, calibration, and precision for predicting postoperative bleeding complications in IE patients.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Oct 2023:131432; epub ahead of print</small></div>

<div><h4>Prenatal diagnosis of coarctation: Impact on early and late cardiovascular outcome.</h4><i>da Mata MF, Anjos R, Lemos M, Nelumba T, ... Teixeira A, Abecasis M</i><br /><b>Background</b><br />Prenatal diagnosis (PND) of aortic coarctation (AoCo) has been associated with a significant improvement in early results, but there is limited information on the long-term cardiovascular outcome.<br /><b>Methods</b><br />We studied 103 patients with simple AoCo, operated in the neonatal period, with a median follow-up of 8,5 years (2 to 23,7 years), with 47% followed for over 10 years. PND was made in 35%. The primary aim was to determine the short and long-term cardiovascular impact of PND of AoCo.<br /><b>Results</b><br />Neonates with PND had less preoperative neonatal complications, with only 2,8% incidence of a composite preoperative severe morbidity course, compared to 28% in the postnatal group. PND patients underwent surgery 8 days earlier and had a shorter length of stay in ICU. PND did not impact the incidence of post-operative complications. On the long-term, prevalence of hypertension, left ventricular hypertrophy and rate of recoarctation were not influenced by PND. The PND group had mean 24 h diastolic BP 9 mmHg lower and mean daytime BP 11 mmHg lower. In the final multivariable model, PND was the single independent variable correlating with daytime diastolic BP.<br /><b>Conclusion</b><br />PND of AoCo effectively leads to a better pre-operative course with less pre-operative morbidity. We found no significant differences in immediate post-operative cardiovascular outcomes. A better initial course of patients with PND does not have a major long-term impact on cardiovascular outcomes, nevertheless, at late follow-up PND patients had lower diastolic BP values on ambulatory monitoring, which may have an impact on long-term cardiovascular risk.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Oct 2023:131430; epub ahead of print</small></div>

<div><h4>Twenty-five-year trends in incidence, angiographic appearance, and management of spontaneous coronary artery dissection.</h4><i>Würdinger M, Schweiger V, Gilhofer T, Cammann VL, ... Ghadri JR, Templin C</i><br /><b>Background</b><br />Spontaneous coronary artery dissection (SCAD) has been described as an infrequent cause of acute coronary syndrome (ACS). Knowledge about the disease is still limited and SCAD might still be underdiagnosed.<br /><b>Objectives</b><br />Trends in incidence, presentation, angiographic appearance, management, and outcomes of SCAD over 25 years were analyzed.<br /><b>Methods</b><br />Patients with SCAD between 1997 and 2021 at the University Hospital Zurich, Switzerland, were included. Incidences were assessed as total numbers and proportions of ACS cases. Clinical data were collected from medical records and angiographic findings were reviewed. Major adverse cardiac events (MACE) were defined as the composite of all-cause death, cardiac arrest, SCAD recurrence or progression, other myocardial infarction, and stroke.<br /><b>Results</b><br />One hundred fifty-six SCAD cases were included in this study. The incidence increased significantly in total (p < 0.001) and relative to ACS cases (p < 0.001). This was based on an increase of shorter lesions (p = 0.004), SCAD type 2 (p < 0.001), and lesions in side branches (p = 0.014), whereas lesions in the left main coronary artery and proximal segments were decreasing (p-values 0.029 and < 0.001, respectively). There was an increase in conservative therapy (p < 0.001). The rate of MACE (24%) was stable, however, there was a reduced proportion of patients with a need for intensive care treatment (p = 0.017).<br /><b>Conclusions</b><br />SCAD represents an important entity of ACS that still might be underappreciated. The increasing incidence of SCAD is likely based on better awareness and familiarity with the disease. A lower need for intensive care treatment suggests positive effects of the increasing implementation of conservative management.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Oct 2023:131429; epub ahead of print</small></div>

<div><h4>Long-term outcome after surgical correction of sinus venosus defect in a nationwide register-based cohort study.</h4><i>Muroke V, Jalanko M, Haukka J, Anttila V, Pätilä T, Sinisalo J</i><br /><b>Objectives</b><br />Long-term results after sinus venosus defect (SVD) closure are sparse and many studies lack a proper control cohort. This nationwide cohort evaluated the long-term outcome after SVD surgery.<br /><b>Methods</b><br />The study enrolled every surgical SVD correction from the nationwide hospital discharge registry (FHDR) and surgical registries of two tertiary centers. Patients with more complex congenital heart defects were excluded. Surgeries were performed from 1969 to 2019. Five sex and birth-year-matched controls per SVD patient were gathered from the general population.<br /><b>Results</b><br />In total, 182 surgical SVD corrections were performed during the study period. The median age at the time of surgery was 8.3 years (range 0.06-75.7), and the majority (77.5%, n = 141) were under 18 years old. The median follow-up period was 18 years (range 0.1-53). There was no significant difference in mortality during the follow-up (logrank p = 0.62, MRR 0.78, 95% CI: 0.30-2.0). However, SVD patients had elevated risk for new-onset atrial fibrillation (RR 4.9, 95% CI: 2.2-10.9), heart failure (RR 4.0, 95% CI: 1.2-13.2), ischemic heart disease (4.3, 95% CI, 1.5-11.7), migraine (RR 3.6, 95% CI: 1.5-9.1) and sick sinus syndrome, II- or III-degree AV-block or pacemaker implantation (RR 11.3, 95% CI: 2.9-43.8).<br /><b>Conclusion</b><br />Young patients with SVD have an excellent survival prognosis after the surgery. Risk for sick sinus syndrome or conduction disorders, atrial fibrillation, and heart failure remains elevated in the long-term follow-up.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Oct 2023:131433; epub ahead of print</small></div>

<div><h4>Oral anticoagulation in heart failure complicated by atrial fibrillation: A nationwide routine data study.</h4><i>Möckel M, Pudasaini S, Baberg HT, Levenson B, ... Günster C, Jeschke E</i><br /><b>Background</b><br />This nationwide routine data analysis evaluates if oral anticoagulant (OAC) use in patients with heart failure (HF) and atrial fibrillation (AF) leads to a lower mortality and reduced readmission rate. Superiority of new oral anticoagulants (NOACs), compared to vitamin K antagonists (VKA), was analyzed for these endpoints.<br /><b>Methods</b><br />Anonymous data of patients with a health insurance at the Allgemeine Ortskrankenkasse and a claims record for hospitalization with the main diagnosis of HF and secondary diagnosis of AF (2017-2019) were included. A hospital stay in the previous year was an exclusion criterion. Mortality and readmission for all-cause and stroke/intracranial bleeding (ICB) were analyzed 91-365 days after the index hospitalization. Kaplan-Meier survival curves and multivariable Cox regression models were used to evaluate the impact of medication on outcome.<br /><b>Results</b><br />180,316 cases were included [81 years (IQR 76-86), 55.6% female, CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥ 2 (96.81%)]. In 80.6%, OACs were prescribed (VKA: 21.7%; direct factor Xa inhibitors (FXaI): 60.0%; direct thrombin inhibitors (DTI): 3.4%; with multiple prescriptions per patient included). Mortality rate was 19.1%, readmission rate was 29.9% and stroke/ICB occurred in 1.9%. Risk of death was lower with any OAC (HR 0.77, 95% CI [0.75-0.79]) but without significant differences in OAC type (VKA: HR 0.73, [0.71-0.76]; FXaI: HR 0.77, [0.75-0.78]; DTI: HR 0.71, [0.66-0.77]). The total readmission rate (HR 0.97, [0.94 to 0.99]) and readmission for stroke/ICB (HR 0.71, [0.65-0.77]) was lower with OAC.<br /><b>Conclusions</b><br />Nationwide data confirm a reduction in mortality and readmission rate in HF-AF patients taking OACs, without NOAC superiority.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Oct 2023:131434; epub ahead of print</small></div>

<div><h4>Comparison of mid-term mortality after surgical, supported or unsupported percutaneous revascularization in patients with severely reduced ejection fraction: A direct and network meta-analysis of adjusted observational studies and randomized-controlled.</h4><i>Iannaccone M, Barbero U, Franchin L, Montabone A, ... Brilakis ES, Chieffo A</i><br /><b>Introduction</b><br />The optimal revascularization strategy in patients with heart failure with reduced ejection fraction (HFrEF) remains to be elucidated. The aim of this paper is to compare the mid-term mortality rate among patients with severely reduced ejection fraction (EF) and complex coronary artery disease who underwent coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) with Impella support, or without.<br /><b>Methods</b><br />Randomized control trials and propensity-adjusted observational studies including patients with ischemic cardiomyopathy (ICM) and severe EF reduction undergoing revascularization were selected. Different revascularization strategies (CABG, supported PCI, and PCI without Impella) were compared in pairwise and network meta-analysis. The primary endpoint was mid-term mortality (within the first year after revascularization).<br /><b>Results</b><br />Fifteen studies, mostly observational (17,841 patients; 6779 patients treated with CABG, 8478 treated with PCI without Impella, and 2584 treated with Impella-supported PCI) were included in this analysis. The median age was 67.8 years (IQR 65-70.1), 21.2% (IQR 16.4-26%) of patients were female sex, and a high prevalence of cardiovascular risk factors was noted across the entire population. At pairwise analysis, CABG and PCI without Impella showed similar one-year all-cause mortality (10.6% [IQR 7.5-12.6%] vs 12% [IQR 8.4-11.5%]) RR 0.85 CI 0.67-1.09, while supported PCI reduced one-year all-cause mortality compared to PCI without Impella (9.4% [IQR 5.7-12.5%] vs 10.6% [IQR 8.9-10.7%]) RR 0.77 CI 0.6-0.89. At network meta-analysis, supported PCI showed better results (RR 0.75, 95% CI 0.59-0.94) compared to CABG.<br /><b>Conclusion</b><br />Our analysis found that supported PCI may have a benefit over standard PCI in patients in direct comparison, and over CABG from indirect comparison, and with HFrEF undergoing revascularization. Further RCTs are needed to confirm this result. (PROSPERO CRD42023425667).<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 09 Oct 2023:131428; epub ahead of print</small></div>

<div><h4>Loganin protects against myocardial ischemia-reperfusion injury by modulating oxidative stress and cellular apoptosis via activation of JAK2/STAT3 signaling.</h4><i>Xia B, Ding J, Li Q, Zheng K, ... You Q, Yuan X</i><br /><b>Background</b><br />Myocardial ischemia-reperfusion injury (MIRI) is a pathological process that follows immediate revascularization of myocardial infarction and is characterized by exacerbation of cardiac injury. Loganin, a monoterpene iridoid glycoside derived from Cornus officinalis Sieb. Et Zucc, can exert cardioprotective effects in cardiac hypertrophy and atherosclerosis. However, its role in ischemic heart disease remains largely unknown.<br /><b>Methods</b><br />Considering that Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) has a protective effect on the heart, we developed a mouse model of MIRI to investigate the potential role of this pathway in loganin-induced cardioprotection.<br /><b>Results</b><br />Our results showed that treatment with loganin (20 mg/kg) prevented the enlargement of myocardial infarction, myocyte destruction, serum markers of cardiac injury, and deterioration of cardiac function induced by MIRI. Myocardium subjected to I/R treatment exhibited higher levels of oxidative stress, as indicated by an increase in malondialdehyde (MDA) and dihydroethidium (DHE) density and a decrease in total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD), whereas treatment with loganin showed significant attenuation of I/R-induced oxidative stress. Loganin treatment also increased the expression of anti-apoptotic Bcl-2 and reduced the expression of caspase-3/9, Bax, and the number of TUNEL-positive cells in ischemic cardiac tissue. Moreover, treatment with loganin triggered JAK2/STAT3 phosphorylation, and AG490, a JAK2/STAT3 inhibitor, partially abrogated the cardioprotective effects of loganin, indicating the essential role of JAK2/STAT3 signaling in the cardioprotective effects of loganin.<br /><b>Conclusions</b><br />Our data demonstrate that loganin protects the heart from I/R injury by inhibiting I/R-induced oxidative stress and cellular apoptosis via activation of JAK2/STAT3 signaling.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 07 Oct 2023:131426; epub ahead of print</small></div>

<div><h4>Temporary mechanical circulatory support with Impella in cardiac surgery: A systematic review.</h4><i>Pieri M, D\'Andria Ursoleo J, Nardelli P, Ortalda A, ... Fominskiy E, Scandroglio AM</i><br /><b>Introduction</b><br />Perioperative cardiogenic shock in cardiac surgery is still burdened by a high mortality risk. The introduction of Impella pumps in the therapeutic armory of temporary mechanical circulatory support (tMCS) has potential implications to improve the management of complex cases, although it has never been systematically addressed. We performed a systematic review of the reported use of tMCS with Impella in cardiac surgery.<br /><b>Methods</b><br />We searched PubMed for all original studies on the Impella use in adult patients in cardiac surgery.<br /><b>Results</b><br />Nineteen studies (out of 151 identified by search string) were included. All studies were observational and all but one (95%) were retrospective. Seven studies focused on the implantation of Impella in the pre-operative setting (coronary or valvular surgery), either as a prophylactic device in high-risk cases (3 studies) or in patients with CS as stabilization tool prior to cardiac surgery procedure (4 studies). Three studies reported the use of Impella as periprocedural support for percutaneous valvular procedure, three as bridge to heart replacement, and six for postcardiotomy CS. Impella support had a low complication rate and was successful in supporting hemodynamics pre-, intra- and postoperatively. Most consistently reported data were left-ventricular ejection fraction at implant, short-term survival and weaning rate.<br /><b>Conclusions</b><br />tMCS with Impella in cardiac surgery patients is feasible and successful. It can be applied in selected cardiac surgery patients and presents advantages over other types of support. Systematic prospective studies are needed to standardize indications for implant and management of surgical issues, and to identify which patients may benefit.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 07 Oct 2023:131418; epub ahead of print</small></div>

<div><h4>Percutaneous coronary intervention can be safely performed with left ventricular thrombus without increasing stroke risk: A 5-year retrospective review using real-world data.</h4><i>Shehadeh M, Rahhal A, Shunnar K, Ahmed AO, ... Alyafei S, Arabi A</i><br /><b>Introduction</b><br />Left ventricular thrombus (LVT) increases the risk of ischemic stroke. However, it remains uncertain if the percutaneous coronary intervention (PCI) in the confirmed LVT setting further augments the stroke risk. Therefore, in this study, we evaluated the risk of stroke among patients with LVT undergoing CAG +/- PCI.<br /><b>Methods</b><br />This retrospective observational cohort study included all the patients encountered with LVT from 1st of April 2015, to 31st of March 2020. The study population was divided into two groups: Longobardo et al. (2018) [1] patients with LVT who underwent CAG +/- PCI; Solheim et al. (2010) [2] patients with LVT who did not undergo CAG +/- PCI. The primary outcome evaluated was stroke during the index admission, and the secondary outcomes included in-hospital mortality, all-cause mortality, and stroke at 12 months post-discharge. Logistic regression was used to determine the risk of stroke associated with PCI among patients with LVT, and a p-value<0.05 indicated statistical significance.<br /><b>Results</b><br />Of the 210 patients included, 119 underwent CAG +/- PCI, while 91 patients did not undergo CAG +/- PCI. Most of the patients were Asian (67%), male (96%), with a mean age of 56 years. Ischemic cardiomyopathy was the primary etiology of LVT in both groups (96% in the CAG +/- PCI group and 80% in non CAG +/- PCI group). During the index admission, stroke among patients with LVT did not differ between the CAG +/- PCI and non CAG +/- PCI groups (5% versus 3.3%; odds ratio (OR) 1.6, 95% confidence interval (CI) 0.34-6.4, p = 0.539; adjusted OR 0.9, 95% CI 0.09-10.6, p = 0.968). Similarly, in-hospital mortality, all-cause mortality, and stroke at 12 months did not differ between the study groups.<br /><b>Conclusion</b><br />Performing CAG +/- PCI among patients with LVT was not associated with an increased risk of stroke during admission or within 12 months in comparison to patients who did not undergo CAG +/- PCI, which may reassure cardiologists to perform CAG +/- PCI among patients with LVT safely.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 04 Oct 2023:131415; epub ahead of print</small></div>

<div><h4>The challenge of risk stratification in hypertrophic cardiomyopathy: Clinical, genetic and imaging insights from a quaternary referral centre.</h4><i>Paratz ED, Stub D, Sutherland N, Gutman S, ... Taylor A, Ellims A</i><br /><b>Background</b><br />Hypertrophic cardiomyopathy (HCM) is the commonest genetic cardiomyopathy and may result in sudden cardiac death (SCD). Clinical risk stratification scores are utilised to estimate SCD risk and determine potential utility of a primary prevention implantable cardioverter defibrillator (ICD).<br /><b>Methods</b><br />Patients with a confirmed diagnosis of HCM from a quaternary HCM service were defined according to clinical characteristics, genetic profiles and cardiac imaging results. European Risk-SCD score and American Heart Association / American College of Cardiology (AHA/ACC) Score were calculated. The primary outcome was cardiac arrest.<br /><b>Results</b><br />380 patients with HCM were followed up for a median of 6.4 years. 18 patients (4.7%) experienced cardiac arrest, with predictive factors being younger age (37.2 vs 54.4 years, p = 0.0041), unexplained syncope (33.3% vs 9.4%, p = 0.007), non-sustained ventricular tachycardia (50.0% vs 12.7%, p < 0.0001), increased septal thickness (21.5 vs 17.5 mm, p = 0.0003), and presence of a sarcomeric gene mutation (100.0% vs 65.8%, p = 0.038). The Risk-SCD and AHA/ACC scores had poor agreement (kappa coefficient 0.38). Risk-SCD score had poor sensitivity (44.4%), classifying 55.6% of patients with cardiac arrest as low-risk but was highly specific (93.7%). AHA/ACC risk score did not discriminate between groups significantly. 20 patients (5.3%) died, with most >60-year-olds having a non-cardiac cause of death (p = 0.0223).<br /><b>Conclusion</b><br />This study highlights limited (38%) agreement between the Risk-SCD and AHA/ACC scores. Most cardiac arrests occurred in ostensibly low or medium-risk patients under both scores. Appropriate ICD selection remains challenging. Incorporating newer risk markers such as HCM genotyping and myocardial fibrosis quantification by cardiac MRI may assist future risk refinement.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 04 Oct 2023:131416; epub ahead of print</small></div>

<div><h4>Impact of chronic obstructive pulmonary disease on right ventricular function and remodeling after aortic valve replacement.</h4><i>Myagmardorj R, Stassen J, Nabeta T, Hirasawa K, ... Delgado V, Bax JJ</i><br /><b>Background</b><br />Both chronic obstructive pulmonary disease (COPD) and right ventricular (RV) dysfunction are common factors that have been associated with poor prognosis after aortic valve replacement (AVR). Since there is still uncertainty about the impact of COPD on RV function and dilatation in patients undergoing AVR, we sought to explore RV function and remodeling in the presence and absence of COPD as well as their prognostic implications.<br /><b>Methods</b><br />Patients who received surgical or transcatheter AVR due to severe AS were screened for COPD. Demographic and clinical data were collected at baseline while echocardiographic measurements were performed at baseline and 1 year after AVR. The study end-point was all-cause mortality.<br /><b>Results</b><br />In total 275 patients were included, with 90 (33%) patients having COPD. At 1-year follow-up, mild worsening of tricuspid annular planar systolic excursion and RV dilatation were observed in patients without COPD, while there were significant improvements in RV longitudinal strain, RV wall thickness but dilatation of RV outflow tract distal dimension in the COPD group compared to the baseline. On multivariable analysis, the presence of COPD provided significant incremental prognostic value over RV dysfunction and remodeling.<br /><b>Conclusions</b><br />At 1-year after AVR, RV function and dimensions mildly deteriorated in non-COPD group whereas COPD group received significant benefit of AVR in terms of RV function and hypertrophy. COPD was independently associated with >2-fold all-cause mortality and had incremental prognostic value over RV dysfunction and remodeling.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 04 Oct 2023:131414; epub ahead of print</small></div>

<div><h4>Association of the monocytes to high-density lipoprotein cholesterol ratio with in-stent neoatherosclerosis and plaque vulnerability: An optical coherence tomography study.</h4><i>Rong J, Gu N, Tian H, Shen Y, ... Zhao R, Shi B</i><br /><b>Background</b><br />Monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is an independent predictor of atherosclerosis and in-stent restenosis (ISR). However, the association between MHR and the incidence of in-stent neoatherosclerosis (ISNA) remains to be validated.<br /><b>Methods</b><br />This study included 216 patients with acute coronary syndrome who had 220 ISR lesions and had undergone optical coherence tomography (OCT). All eligible patients were divided into three groups according to their MHR tertile level. OCT characteristics were comparatively analyzed between groups of different MHR levels, and univariate and multivariate logistic regression analyses were constructed to assess correlations between MHR level and ISNA as well as in-stent thin-cap fibroatheroma (TCFA). A receiver operating characteristic curve was used to determine the optimal MHR thresholds for predicting ISNA and in-stent TCFA.<br /><b>Results</b><br />The incidence of ISNA (70.3% vs. 61.1% vs. 20.3%, P < 0.001) and in-stent TCFA (40.5% vs. 31.9% vs. 6.8%, P < 0.001) was the highest in the third tertile, followed by the second and first tertiles, respectively. Multivariate analysis revealed that MHR was independently associated with ISNA (odds ratio [OR], 7.212; 95% confidence interval [CI], 1.287-40.416; P = 0.025) and in-stent TCFA (OR, 5.610; 95% CI, 1.743-18.051; P = 0.004) after adjusting for other clinical factors. The area under the curve was 0.745 (95% CI, 0.678-0.811; P < 0.001) for the prediction of ISNA and 0.718 (95% CI, 0.637-0.778; P < 0.001) for the prediction of in-stent TCFA.<br /><b>Conclusion</b><br />MHR levels are an independent risk factor for ISNA.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 04 Oct 2023:131417; epub ahead of print</small></div>

<div><h4>Trends in ischemic heart disease among females in low-and middle-income countries from 1990 to 2019.</h4><i>Makuvire TT, Latif Z, Kumar P, Samad Z, Warraich HJ</i><br /><b>Background</b><br />Ischemic heart disease (IHD) is a major contributor to mortality in low-and middle-income-countries (LMICs). However, trends in IHD in females in LMICs are not well described.<br /><b>Methods</b><br />We analyzed the Global Burden of Disease (GBD) Study from 1990 to 2019 for males and females with IHD from the ten most-populous LMICs (India, Indonesia, Pakistan, Nigeria, Ethiopia, Philippines, Egypt, Vietnam, Iran, and Afghanistan).<br /><b>Results</b><br />In females, IHD incidence increased from 950,000 cases/year to 1.6 million/year, IHD prevalence increased from 8 million to 22.5 million (181% increase) and IHD mortality from 428,320 to 1,040,817 (143% increase). IHD accounted for 6.2% of all deaths among females in 1990, doubling to 13.2% in 2019. IHD mortality for each country increased with the greatest shift in AAPC seen in the Philippines (5.8%, 95% CI 5.4-6.1) and India (3.7%, 95% CI 3.0-4.4). Notably, reductions in ASMR were greater for males than females in Afghanistan, Iran, Egypt, Ethiopia and Nigeria. (all p < 0.001).<br /><b>Conclusions</b><br />The burden of IHD among females in LMIC has increased considerably in LMICs from 1990 to 2019. While the ASMR from IHD across most countries is declining, this was not uniformly noted. Furthermore, several countries noted lesser improvement in ASMR among females compared to males.<br /><br />Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 01 Oct 2023; 388:131113</small></div>

<div><h4>Sudden cardiac death in childhood RASopathy-associated hypertrophic cardiomyopathy: Validation of the HCM risk-kids model and predictors of events.</h4><i>Boleti OD, Roussos S, Norrish G, Field E, ... Wolf CM, Kaski JP</i><br /><b>Background</b><br />RASopathies account for nearly 20% of cases of childhood hypertrophic cardiomyopathy (HCM). Sudden cardiac death (SCD) occurs in patients with RASopathy-associated HCM, but the risk factors for SCD have not been systematically evaluated.<br /><b>Aim</b><br />To validate the HCM Risk-Kids SCD risk prediction model in children with RASopathy-associated HCM and investigate potential specific SCD predictors in this population.<br /><b>Methods</b><br />Validation of HCM Risk-Kids was performed in a retrospective cohort of 169 patients with a RASopathy-associated HCM from 15 international paediatric cardiology centres. Multiple imputation by chained equations was used for missing values related to the HCM Risk-Kids parameters.<br /><b>Results</b><br />Eleven patients (6.5%) experienced a SCD or equivalent event at a median age of 12.5 months (IQR 7.7-28.64). The calculated SCD/equivalent event incidence was 0.78 (95% CI 0.43-1.41) per 100 patient years. Six patients (54.54%) with an event were in the low-risk category according to the HCM Risk-Kids model. Harrell\'s C index was 0.60, with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 91%; with a poor distinction between the different risk groups. Unexplained syncope (HR 42.17, 95% CI 10.49-169.56, p < 0.001) and non-sustained ventricular tachycardia (HR 5.48, 95% CI 1.58-19.03, p < 0.007) were predictors of SCD on univariate analysis.<br /><b>Conclusion</b><br />Unexplained syncope and the presence of NSVT emerge as predictors for SCD in children with RASopathy-associated HCM. The HCM Risk-Kids model may not be appropriate to use in this population, but larger multicentre collaborative studies are required to investigate this further.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 28 Sep 2023:131405; epub ahead of print</small></div>

<div><h4>Left atrial pump strain predicts long-term survival after transcatheter aortic valve implantation.</h4><i>Winkler NE, Anwer S, Rumpf PM, Tsiourantani G, ... Kasel AM, Tanner FC</i><br /><b>Background</b><br />This study aims at investigating left atrial (LA) deformation by left atrial reservoir (LARS) and pump strain (LAPS) and its implications for long-term survival in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI).<br /><b>Methods</b><br />Speckle tracking echocardiography was performed in 198 patients with severe AS undergoing TAVI. Association of strain parameters with cardiovascular mortality was determined.<br /><b>Results</b><br />Over a follow-up time of 5 years, 49 patients (24.7%) died. LAPS was more impaired in non-survivors than survivors (P = 0.010), whereas no difference was found for LARS (P = 0.114), LA ejection fraction (P = 0.241), and LA volume index (P = 0.292). Kaplan-Meier analyses yielded a reduced survival probability according to the optimal threshold for LAPS (P = 0.002). A more impaired LAPS was associated with increased mortality risk (HR 1.12 [95% CI 1.02-1.22]; P = 0.014) independent of LVEF, LAVI, age, and sex. Addition of LAPS improved multivariable echocardiographic (LVEF, LAVI) and clinical (age, sex) models with potential incremental value for mortality prediction (P = 0.013 and P = 0.031, respectively). In contrast, LARS and LAVI were not associated with mortality.<br /><b>Conclusions</b><br />In patients undergoing aortic valve replacement for severe AS, LAPS was impaired in patients dying during long-term follow-up after TAVI, differentiated survivors from non-survivors, was independently associated with long-term mortality, and yielded potential incremental value for survival prediction after TAVI. LAPS seems useful for risk stratification in severe AS and timely valve replacement.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 28 Sep 2023:131403; epub ahead of print</small></div>

<div><h4>Mitral regurgitation outcomes after transcatheter atrial septal defect closure.</h4><i>Yamano M, Yamano T, Nakamura T, Zukeran T, ... Shiraishi H, Matoba S</i><br /><b>Background</b><br />Worsening mitral regurgitation (MR) is a complication of intervention for atrial septal defect (ASD). Little is known about mitral valve (MV) characteristics associated with worsening MR. We aimed to elucidate MR outcomes and predictors of worsening MR after transcatheter ASD closure.<br /><b>Methods</b><br />We analyzed changes in MR from prior to transcatheter ASD closure to 6 months after the procedure and predictors of worsening MR via baseline transthoracic echocardiography in 238 patients (64.7% females; mean age, 53 ± 22 years).<br /><b>Results</b><br />Worsening MR was defined as worsening to moderate in patients with less than or equal to mild MR at baseline or vena contracta width increasing of ≥2 mm by 6-month follow-up in patients with moderate MR. Worsening MR was observed in 29 patients (12.2%). The associated echocardiographic findings were pseudoprolapse, hamstringing, stiffness, and anteroposterior and intercommissural mitral annulus diameter in the univariable logistic regression analysis (all P < 0.05). Multivariable analysis after adjusting for age; long-standing persistent atrial fibrillation; and ASD size showed that models combining MV leaflet findings such as pseudoprolapse or hamstringing, or anterior leaflet stiffness with the ratio of the sum of anterior and posterior leaflet lengths to intercommissural mitral annulus diameter were statistically significant for predicting worsening MR (R<sup>2</sup> = 0.393, P < 0.001 and R<sup>2</sup> = 0.385, P < 0.001, respectively).<br /><b>Conclusions</b><br />Worsening MR after transcatheter ASD closure might depend on MV leaflet findings and annulus size in patients with long-standing persistent atrial fibrillation.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 28 Sep 2023:131404; epub ahead of print</small></div>

<div><h4>Prognostic role of inferior vena collapsibility index in congenital heart disease: A validation study.</h4><i>Egbe AC, Abozied O, Miranda WR, Younis A, ... Karnakoti S, Connolly HM</i><br /><b>Background</b><br />A recent study showed that inferior vena cava collapsibility index (IVCCI) <60% had better prognostic performance as compared to the American Society of Echocardiogram (ASE) criteria for estimating right atrial pressure (RAP). However, this study was based on a selected cohort of adults with congenital heart disease (CHD) that underwent right heart catheterization and limiting the generalizability of the results. The purpose of this study was, therefore, to validate the prognostic performance of IVCCI in a more representative sample of adults with CHD, which would in turn, improve generalizability of the results.<br /><b>Methods</b><br />Retrospective cohort study of adults with CHD that underwent echocardiogram at Mayo Clinic (2003-2021). Elevated RAP was defined as RAP >10 mmHg, and was estimated using IVCCI <60% or the ASE criteria (maximum IVC diameter < 2.1 cm and IVCCI <50%). Cardiovascular event was defined as heart failure hospitalization, heart transplant or cardiovascular death.<br /><b>Results</b><br />Of the 4029 patients, 754 (19%) and 601 (15%) had elevated RAP (RAP >10 mmHg) based on IVCCI <60%, and the ASE criteria, respectively. Of the 4029 patients, 374 (9%) had cardiovascular events during 7.6 (4.4-10.5) years of follow-up. IVCCI <60% was independently associated with cardiovascular events (adjusted HR 2.08, 95% CI 1.75-2.42; C-statistic 0.708, 95%CI 0.688-0.728), and provided improved prognostic performance as compared to the ASE criteria (C-statistic difference 0.036, 95%CI 0.017-0.055, P = 0.008).<br /><b>Conclusions</b><br />IVCCI had superior prognostic performance as compared to the ASE criteria.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 27 Sep 2023:131399; epub ahead of print</small></div>

<div><h4>Overview of SARS-CoV-2 infection and vaccine associated myocarditis compared to non-COVID-19-associated myocarditis: A systematic review and meta-analysis.</h4><i>Ishisaka Y, Watanabe A, Aikawa T, Kanaoka K, ... Yasuhara J, Kuno T</i><br /><b>Background</b><br />Previous literature suggests that both SARS-CoV-2 infection and COVID-19 mRNA vaccine are associated with myocarditis, in which the incidence is higher in the infection group. COVID-19 mRNA vaccine-related myocarditis is noted to have a more benign course. Despite these findings, there is a need for a larger population systematic review that compares the outcomes to pre-pandemic acute myocarditis to better understand the extent of the current post-COVID state.<br /><b>Methods</b><br />We performed a literature search with PubMed and EMBASE and identified studies investigating COVID-19 and its vaccinated population, and the population prior to the pandemic (control group) who had myocarditis. We performed a one-group meta-analysis of the incidence, baseline demographics, and outcomes of myocarditis for each group.<br /><b>Results</b><br />The incidence in the SARS-CoV-2 infection group was 2.76 per thousand (95% CI, 0.85-8.92), 19.7 per million (95% CI, 12.3-31.6) in the vaccine group, and 0.861 per million (95% CI, 0.04-16.7) in the control group. The majority of patients were male, with the highest proportion in the vaccine group. The mean age was the youngest in the vaccine group (24.8, 95% CI, 19.1-30.6). The vaccine group had the lowest mortality (2.0%, 95% CI, 1.3-2.7) followed by the control and the SARS-CoV-2 infection group. The vaccine group had the lowest proportion of immunoglobulin and glucocorticoid use, mechanical circulatory support, and cardiogenic shock.<br /><b>Conclusion</b><br />Our study showed favorable outcomes of myocarditis in patients with COVID-19 mRNA vaccination, despite a higher incidence than pre-COVID controls. Further studies with standardized myocarditis diagnostic criteria assessing long-term outcomes are necessary.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 27 Sep 2023:131401; epub ahead of print</small></div>

<div><h4>Associations between systemic immunity-inflammation index and heart failure: Evidence from the NHANES 1999-2018.</h4><i>Zheng H, Yin Z, Luo X, Zhou Y, Zhang F, Guo Z</i><br /><b>Background</b><br />Heart failure (HF) is a disease closely associated with inflammation, and the systemic immune-inflammation index (SII) is a novel inflammatory marker. Therefore, this study aims to explore the relationship between SII and HF.<br /><b>Methods</b><br />We used National Health and Nutrition Examination Survey data from 1998 to 2018 to include adults who reported a diagnosis of HF and complete information on the calculation of SII. SII was calculated as platelet count × neutrophil count/lymphocyte count. We used multiple linear regression models to examine the association between SII and HF and explored possible influencing factors by subgroup analysis. In addition, we performed smoothed curve fitting and threshold effect analysis to describe the nonlinear relationship.<br /><b>Results</b><br />The population-based study involved a total of 48,155 adults ages 20-85. Multivariate logistic regression showed that participants with the highest SII had a statistically significant 32% increased risk of HF prevalence compared to those with the lowest SII (OR = 1.32; 95% CI, 1.06-1.65, P = 0.0144) in a fully adjusted model. Subgroup analysis revealed no significant interactions between SII and specific subgroups (p > 0.05 for all interactions). Furthermore, the association between SII and HF was non-linear; the inflection point was 1104.78 (1000 cells/μl).<br /><b>Conclusions</b><br />Based on our findings, elevated SII levels were found to be strongly associated with the risk of HF, and SII was nonlinearly associated with HF. To validate these findings, a larger prospective investigation is needed to support the results of this study and investigate potential problems.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 26 Sep 2023:131400; epub ahead of print</small></div>

<div><h4>Association of sex with major bleeding risks in sub-Saharian anticoagulated patients with mechanical heart valves: A cohort study from the Khartoum emergency Salam Centre.</h4><i>Erba N, Tosetto A, Abdallah SA, Langer M, ... Lip GYH, Poli D</i><br /><b>Background</b><br />Rheumatic heart disease (RHD) with mechanical heart valve (MHV) replacement is common in Africa. However, MHV requires lifelong anticoagulation that could have a particular impact in women in reproductive age.<br /><b>Methods</b><br />We report data of a prospective observational cohort study conducted between August 2018 and September 2019 in MHV patients in the Salam Centre for Cardiac Surgery built in Khartoum by Emergency, an Italian Non-Governmental Organization, to evaluate bleeding risk, its associated determinants, and the impact of lifelong anticoagulation in fertile women.<br /><b>Results</b><br />We studied 3647 patients (median age 25.1 years; 53.9% female). During follow-up [median time 1.1 (0.1-1.2) years], we recorded 85 major bleedings (rate 2.16 × 100 pt-years), Major bleedings occurred more frequently among women (64/85 cases, 75.3%; rate 3.0 × 100 pt-years), compared to men (21/85 cases, 24.7%; rate 1.16 × 100 pt-years) (RR 2.6; 95% CI 1.6-4.5; p = 0.0001). Multivariate analysis was performed to identify variables associated with major bleeding, and female sex was the only risk factor significantly associated, whereas aspirin treatment and higher INR target showed a non-significant trend for higher bleeding risk. Thirty-two/85 (37.6%) of major bleedings were metrorrhagias. When we calculate the incidence of major bleedings after the exclusion of gynecological events, no sex differences in the bleeding risk were found (HR 1.3, 95% CI 0.8-2.3; p = 0.3).<br /><b>Conclusions</b><br />Bleeding risk of young MHV patients on oral anticoagulant therapy is higher among women, mainly due to metrorrhagia. Women in the reproductive life are at high risk for gynecological bleeding when treated with anticoagulants.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 26 Sep 2023:131398; epub ahead of print</small></div>

<div><h4>Impacts of high sensitivity troponin T reporting on care and outcomes in clinical practice: Interactions between low troponin concentrations and participant sex within two randomized clinical trials.</h4><i>Lambrakis K, Khan E, van den Merkhof A, Papendick C, ... Cullen L, Chew DP</i><br /><b>Background</b><br />The impacts of high sensitivity cardiac troponin (hs-cTn) reporting on downstream interventions amongst suspected acute coronary syndrome (ACS) in the emergency department (ED), especially amongst those with newly identified hs-cTn elevations and in consideration of well-established sex-related disparities, has not been critically evaluated to date. This investigation explores the impact of hs-cTnT reporting on care and outcomes, particularly by participant sex.<br /><b>Methods</b><br />Two similarly ED-based randomized controlled trials conducted between July 2011 to March 2013 (n = 1988) and August 2015 to April 2019 (n = 3378) were comparatively evaluated. Clinical outcomes were adjudicated to the Fourth Universal Definition of MI. Changes in practice were assessed at 30 days, and death or MI were explored to 12 months.<br /><b>Results</b><br />The HS-Troponin study demonstrated no difference in death or MI with unmasking amongst those with hs-cTnT <30 ng/L, whereas the RAPID TnT study demonstrated a significantly higher rate. In RAPID TnT, there was significant increase in death or MI associated with unmasking for females with hs-cTnT <30 ng/L (masked: 11[1.5%], unmasked: 25[3.4%],HR: 2.27,95%C.I.:1.87-2.77,P < 0.001). Less cardiac stress testing with unmasking amongst those <30 ng/L was observed in males in both studies, which was significant in RAPID TnT (masked: 92[12.0%], unmasked: 55[7.0%], P = 0.008). In RAPID TnT, significantly higher rates of angiography in males were observed with unmasking, with no such changes amongst females <30 ng/L (masked: 28[3.7%], unmasked: 51[6.5%],P = 0.01).<br /><b>Conclusion</b><br />Compared with males, there were no evident impacts on downstream practices for females with unmasking in RAPID TnT, likely representing missed opportunities to reduce late death or MI.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 26 Sep 2023:131396; epub ahead of print</small></div>

<div><h4>Immediate versus staged complete revascularization in acute coronary syndrome: A meta-analysis of randomized controlled trials.</h4><i>Bujak K, Rinaldi R, Vidal-Cales P, Montone RA, ... Sabaté M, Brugaletta S</i><br /><b>Background</b><br />Clinical guidelines recommend a complete revascularization (CR) in patients with acute coronary syndromes (ACS) and multivessel disease (MVD). However, its optimal timing is unclear. The aim of this meta-analysis was to compare the clinical outcomes following immediate versus staged CR in ACS.<br /><b>Methods</b><br />PubMed and Scopus were searched until March 2023 for randomized controlled trials (RCTs) comparing immediate versus staged CR. The primary endpoint was major adverse cardiovascular event (MACE) at the longest follow-up. Secondary outcomes were all-cause death, cardiovascular death, myocardial infarction (MI), any unplanned revascularization, target-vessel revascularization (TVR), and stent thrombosis. Safety outcomes were major bleeding, contrast volume, procedure duration, and length of hospitalization.<br /><b>Results</b><br />Eight RCTs were included (3559 patients, weighted mean follow-up 12.5 months). There were no differences in the primary endpoint (OR 0.74, 95%CI: 0.54-1.01) and in the secondary endpoints of death, and stent thrombosis between the two CR strategies. Immediate CR was associated with a lower risk of recurrent MI (OR 0.51, 95% CI 0.34-0.76), any unplanned revascularization (OR 0.59, 95%CI: 0.43-0.80), and TVR (OR 0.61, 95% CI 0.45-0.84) compared to staged CR. Immediate CR was also associated with lower total contrast volume and shorter total procedure duration and hospitalization length compared to staged CR without differences in major bleedings.<br /><b>Conclusion</b><br />No difference was found between immediate and staged CR regarding MACE, or deaths rates at one year. Immediate CR may be associated with a lower risk of recurrent MI and unplanned coronary revascularization than staged CR.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 26 Sep 2023:131397; epub ahead of print</small></div>

<div><h4>Improved assessment of left ventricular ejection fraction using artificial intelligence in echocardiography: A comparative analysis with cardiac magnetic resonance imaging.</h4><i>Sveric KM, Ulbrich S, Dindane Z, Winkler A, ... Heidrich F, Linke A</i><br /><b>Background</b><br />Left ventricular ejection fraction (LVEF) measurement in echocardiography (Echo) using the recommended modified biplane Simpson (MBS) method is operator-dependent and exhibits variability. We aimed to assess the accuracy of a novel fully automated (Auto) artificial intelligence (AI) in view selection and biplane LVEF calculation compared to MBS-Echo, with cardiac magnetic resonance imaging (CMR) as reference.<br /><b>Methods</b><br />Each of the 301 consecutive patients underwent CMR and Echo on the same day. LVEF was measured independently by Auto-Echo, MBS-Echo and CMR. Interobserver (n = 40) and test-retest (n = 14) analysis followed.<br /><b>Results</b><br />A total of 229 patients (76%) underwent complete analysis. Auto-Echo and MBS-Echo showed high correlations with CMR (R = 0.89 and 0.89) and with each other (R = 0.93). Auto underestimated LVEF (bias: 2.2%; limits of agreement [LOA]: -13.5 to 17.9%), while MBS overestimated it (bias: -2.2%; LOA: 18.6 to 14.1%). Despite comparable areas under the curves of Auto- and MBS-Echo (0.93 and 0.92), 46% (n = 70) of MBS-Echo misclassified LVEF by ≥5% units in patients with a reduced CMR-LVEF <51%. Although LVEF bias variability across different LV function ranges was significant (p < 0.001), Auto-Echo was closer to CMR for patients with reduced LVEF, wall motion abnormalities, and poor image quality than MBS-Echo. The interobserver correlation coefficient of Auto-Echo was excellent compared Auto-Echo (1.00 vs. <0.91) for different readers. True test-retest variability was higher for MBS-Echo than for Auto-Echo (7.9% vs. 2.5%).<br /><b>Conclusion</b><br />The tested AI has the potential to improve the clinical utility of Echo by reducing user-related variability, providing more accurate and reliable results than MBS.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 25 Sep 2023:131383; epub ahead of print</small></div>

<div><h4>Forecasting the mortality burden of coronary heart disease and stroke in Germany: National trends and regional inequalities.</h4><i>Emmert-Fees KMF, Luhar S, O\'Flaherty M, Kypridemos C, Laxy M</i><br /><b>Background</b><br />The decline of cardiovascular disease (CVD) mortality has slowed in many countries, including Germany. We examined the implications of this trend for future coronary heart disease (CHD) and stroke mortality in Germany considering persistent mortality inequalities between former East and West Germany.<br /><b>Methods</b><br />We retrieved demographic and mortality data from 1991 to 2019 from the German Federal Statistical Office. Using a Bayesian age-period-cohort framework, we projected CHD and stroke mortality from 2019 to 2035, stratified by sex and German region. We decomposed annual changes in deaths into three components (mortality rates, population age structure and population size) and assessed regional inequalities with age-sex-standardized mortality ratios.<br /><b>Results</b><br />We confirmed that declines of CVD mortality rates in Germany will likely stagnate. From 2019 to 2035, we projected fewer annual CHD deaths (114,600 to 103,500 [95%-credible interval: 81,700; 134,000]) and an increase in stroke deaths (51,300 to 53,700 [41,400; 72,000]). Decomposing past and projected mortality, we showed that population ageing was and is offset by declining mortality rates. This likely reverses after 2030 leading to increased CVD deaths thereafter. Inequalities between East and West declined substantially since 1991 and are projected to stabilize for CHD but narrow for stroke.<br /><b>Conclusions</b><br />CVD deaths in Germany likely keep declining until 2030, but may increase thereafter due to population ageing if the reduction in mortality rates slows further. East-West mortality inequalities for CHD remain stable but may converge for stroke. Underlying risk factor trends need to be monitored and addressed by public health policy.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 25 Sep 2023:131359; epub ahead of print</small></div>

<div><h4>Impact of sacubitril/valsartan and gliflozins on cardiac resynchronization therapy response in ischemic and non-ischemic heart failure patients.</h4><i>Fonderico C, Pergola V, Faccenda D, Salucci A, ... Rapacciuolo A, Strisciuglio T</i><br /><b>Aims</b><br />Angiotensin receptor-neprilysin inhibitor (ARNi) and sodium-glucose co-transporter 2 inhibitor (SGLT2i) improve outcomes in heart failure with reduced ejection fraction (HFrEF) patients, however their effects in cardiac resynchronization therapy (CRT) recipients have been scarcely explored. This study investigated whether ARNi and SGLT2i 1) improve the rate of clinical and echocardiographic CRT response and 2) have different impact based on the ischemic or non-ischemic etiology.<br /><b>Methods</b><br />HFrEF patients referred for CRT implant were grouped in no treatment (group 1), only ARNi (group 2) and both ARNi and SGLT2i (group 3). Clinical and echocardiographic responsewere evaluated at 12 months.<br /><b>Results</b><br />A total of 178 patients were enrolled. At one-year follow-up, 74.4% patients in group 2 (p = 0.031) and 88.9% in group 3 (p = 0.014) were classified as clinical responders vs 54.5% in the no treatments group. In multivariable analysis, ARNi/SGLT2i use was an independent predictor of CRT response (OR 3.72; CI 95%, 1.40-10.98; p = 0.011), confirmed in both groups 2 and 3. At 12 months, the median Δ LVEF increase was 6% and 8.5% in groups 2 and 3 respectively, vs 4.5% in group 1 (p = 0.042 and p = 0.029) with significantly more echocardiographic responders in groups 2 and 3 (76% and 78% vs 50%, p = 0.003 and p = 0.036). Significantly more ischemic HFrEF patients than non-ischemic were considered clinical and echocardiographic responders in the treatment group.<br /><b>Conclusions</b><br />ARNi alone or in combination with SGLT2iin CRT patients improves the clinical and echocardiographic response at 12 months. Ischemic patients seem to benefit more from these treatments.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 23 Sep 2023:131391; epub ahead of print</small></div>

<div><h4>N-ammonia positron emission tomography for diagnosis and monitoring of ischemia without obstructive coronary artery disease.</h4><i>Sakai A, Nagao M, Yamamoto A, Nakao R, ... Sato K, Yamaguchi J</i><br /><b>Background</b><br />Ischemia with no obstructive coronary arteries (INOCA), a chronic disorder with a poor prognosis, remains challenging to diagnose. <sup>13</sup>N-ammonia positron emission tomography (13NH3 PET), which can quantify microcirculation, is its most reliable detection method. We aimed to investigate the differences in 13NH3 PET findings between INOCA and coronary artery disease (CAD).<br /><b>Methods</b><br />Overall, consecutive 433 patients with known or suspected CAD underwent adenosine-stress 13NH3 PET. Based on the European Society of Cardiology guidelines, INOCA was defined as typical angina without coronary stenosis (INOCA n = 45, CAD n = 293, no CAD n = 95). Papillary muscle ischemia (PMI) and global myocardial flow reserve (MFR) were examined as microvascular injuries using 13NH3 PET.<br /><b>Results</b><br />PMI was observed significantly more frequently in patients with INOCA than in those with CAD (40.0% vs. 11.6%, respectively; p = 0.02). Global MFR (1.84 ± 0.54 vs. 2.08 ± 0.66, respectively; p < 0.0001) and reactive hyperemia index were significantly lower in patients with INOCA than in those with CAD. Forty-five major adverse cardiac events (MACE) were recorded in a median follow-up time of 827 days. Kaplan-Meier analysis revealed that the survival rate worsened in patients with INOCA and PMI (log-rank test, p = 0.001). In the Cox proportional hazards model, PMI was an independent predictive factor for MACE (odds ratio, 4.16; 95% confidence interval, 2.13-8.15; p < 0.0001).<br /><b>Conclusions</b><br />PMI presence and decreased MFR were 13NH3 PET findings characteristic of INOCA. 13NH3 PET can be used to monitor the treatment course.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 23 Sep 2023:131392; epub ahead of print</small></div>

<div><h4>Sex-related differences in non-ischemic myocardial injury in the emergency department: A real-world perspective.</h4><i>Golino M, Morello M, Marazzato J, Blasi F, ... Angeli F, De Ponti R</i><br /><b>Background</b><br />Myocardial injury is associated with adverse outcomes. No data are reported about sex differences in incidence and factors associated with myocardial injury in an emergency department (ED) setting from a real-world perspective. We aimed to assess whether sex plays a major role in the diagnosis of myocardial injury in the ED.<br /><b>Methods</b><br />In this subanalysis of a retrospective study, patients presenting at the ED with at least one high-sensitivity cardiac troponin T (hs-cTnT) value and without acute coronary syndromes diagnosis were compared.<br /><b>Results</b><br />31,383 patients were admitted to the ED, 4660 had one hs-cTnT value, and 3937 were enrolled: 1943 females (49.4%) and 1994 males (50.6%). The diagnosis of myocardial injury was higher among men (36.8% vs. 32.9%, p < 0.01). Male sex was independently associated with myocardial injury. An older age, an elevated NT-proB-type Natriuretic Peptide and a lower estimated glomerular filtrate rate were independently associated with myocardial injury in both sexes.<br /><b>Conclusions</b><br />In the ED, from a real-world perspective, myocardial injury occurred more frequently in males, and it was associated with older age and the presence of cardiac, lung, and kidney disease but not higher hs-cTnT values.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 23 Sep 2023:131394; epub ahead of print</small></div>

<div><h4>Excessive daytime sleepiness, morning tiredness, and prognostic biomarkers in patients with chronic coronary syndrome.</h4><i>Olszowka M, Hagström E, Hadziosmanovic N, Ljunggren M, ... Held C, STABILITY Investigators</i><br /><b>Background</b><br />Sleep-related breathing disorders (SRBD) are related to cardiovascular outcomes in patients with chronic coronary syndrome (CCS). Whether SRBD-related symptoms are associated with prognostic biomarkers in patients with CCS is not established.<br /><b>Methods</b><br />Associations between frequency (never/rarely, sometimes, often, always) of self-reported SRBD-related symptoms (excessive daytime sleepiness [EDS]; morning tiredness [MT]; loud snoring; multiple awakenings/night; gasping, choking, or apnea when asleep) and levels of biomarkers related to cardiovascular prognosis (high-sensitivity C-reactive protein [hs-CRP], interleukin 6 [IL-6], high-sensitivity cardiac troponin T [hs-cTnT], N-terminal pro B-type natriuretic peptide [NT-proBNP], cystatin C, growth differentiation factor 15 [GDF-15] and lipoprotein-associated phospholipase A<sub>2</sub> activity) were assessed at baseline in 15,640 patients with CCS on optimal secondary preventive therapy in the STABILITY trial. Cross-sectional associations were assessed by adjusted linear regression models testing for trends with the never/rarely category serving as reference.<br /><b>Results</b><br />EDS was associated (geometric mean ratio, 95% confidence interval) with increased levels of IL-6 (often 1.07 [1.03-1.10], always 1.15 [1.10-1.21]), GDF-15 (often 1.03 [1.01-1.06], always 1.07 [1.03-1.11]), NT-proBNP (always 1.22 [1.12-1.33]), and hs-cTnT (always 1.07 [1.01-1.12]). MT was associated with increased levels of IL-6 (often 1.05 [1.01-1.09], always 1.09 [1.04-1.15]), and GDF-15 (always 1.06 [1.03-1.10]). All biomarkers were to some degree associated with higher levels of hs-CRP and loud snoring was also associated with decreased levels of NT-proBNP and hs-cTnT.<br /><b>Conclusions</b><br />In patients with CCS, stepwise increased frequency of SRBD-related symptoms, such as EDS and MT, were associated with gradually higher levels of IL-6 and GDF-15, each reflecting distinct pathophysiological pathways.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 23 Sep 2023:131395; epub ahead of print</small></div>

<div><h4>Short-term follow-up of proximal aorta remodeling after zone 2 thoracic endovascular aortic repair for acute type B aortic dissection.</h4><i>Wang Z, Fang C, Song H, Wei D, ... Ma Z, Zhao X</i><br /><b>Background</b><br />To evaluate the early remodeling of the proximal aorta in patients with acute type B aortic dissection (ATBAD) after zone 2 thoracic endovascular aortic repair (TEVAR).<br /><b>Methods</b><br />From January 2016 to May 2022, 53 ATBAD patients underwent zone 2 TEVAR were divided into two groups, the Castor single-branched stent-graft (CSS) group (n = 26) and the common stent-graft group (n = 27). Three-dimensional imaging created by computed tomography angiography was used to measure different parameters of the aorta, such as angulation, cross-sectional area (CSA), length and tortuosity. Early remodeling of the proximal aorta was evaluated by comparing geometric parameters of the proximal aorta before and 3 months after surgery.<br /><b>Results</b><br />In terms of angle, the postoperative angle of aortic arch to ascending aorta, descending aorta increased in all patients compared with that before surgery (all P < 0.05), while the angle of aortic arch to left subclavian artery increased after surgery only in the CSS group (P < 0.001); As for CSA, the CSA of distal aortic arch and true lumen increased (all P < 0.05), while the CSA of false lumen decreased in both groups after operation (all P < 0.05); Only in CSS group, the CSA of the ascending aorta, proximal aortic arch and total descending thoracic aorta decreased after surgery (all P < 0.05); In terms of length, the aortic arch prolonged after operation in both groups (P = 0.018 and P = 0.004, respectively). In addition, the ascending aorta tortuosity decreased in the CSS group after surgery (P = 0.011). There was no significant difference in the alterations of other aortic parameters after operation (P > 0.05).<br /><b>Conclusions</b><br />The CSS implantation provided a more relatively safe and effective treatment for acute type B aortic dissection patients with unfavorable proximal landing zone. It can promote the earlier remodeling of the proximal aorta compared with the common stent-graft implantation after zone 2 TEVAR.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 23 Sep 2023:131393; epub ahead of print</small></div>

<div><h4>Clinical characteristics and prognosis of patients with heart failure and high concentrations of interleukin-17D.</h4><i>Baumhove L, Bomer N, Tromp J, van Essen BJ, ... van der Meer P, Voors AA</i><br /><b>Aims</b><br />Heart failure (HF) is associated with cytokine activation and inflammation. Experimental evidence suggests that plasma interleukin-17 (IL-17) is associated with myocardial fibrosis and cardiac dysfunction in HF. IL-17D, a subtype of IL-17 originates from particular tissues such as the heart. However, there is very limited data on the IL-17 cytokine family in patients with HF. Therefore, we investigated the association between circulating IL-17D levels, clinical characteristics and outcome in a large cohort of patients with heart failure.<br /><b>Methods and results</b><br />Plasma IL-17D was measured in 2032 patients with HF from 11 European countries using a proximity extension assay. The primary outcome was a composite of HF hospitalization or all-cause mortality. Patients with higher plasma IL-17D concentrations were more likely to have atrial fibrillation (AF), renal dysfunction and heart failure with preserved ejection fraction (HFpEF) and had higher plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations (all p < 0.001). IL-17D was not associated with interleukin-6 (IL-6) or C-reactive protein (CRP) concentrations. After adjustment for confounders in a multivariable Cox regression analysis, patients in the highest quartile of plasma IL-17D had a significantly increased risk of the composite outcome of HF hospitalization or all-cause mortality compared to patients in the lowest quartile [Hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.05-1.57].<br /><b>Conclusion</b><br />In patients with HF, elevated plasma IL-17D concentrations are associated with higher plasma NT-proBNP concentrations and a higher prevalence of AF and renal dysfunction. High IL-17D concentrations are independently associated with worse outcome.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 21 Sep 2023:131384; epub ahead of print</small></div>

<div><h4>Galectin-3 contributes to acute cardiac dysfunction and toxicity by increasing oxidative stress and fibrosis in doxorubicin-treated mice.</h4><i>Seropian IM, Fontana Estevez FS, Villaverde A, Cacciagiú L, ... Miksztowicz V, González GE</i><br /><b>Background</b><br />Doxorubicin (DOX) leads to cardiovascular toxicity through direct cardiomyocyte injury and inflammation. We aimed to study the role of Galectin-3 (Gal-3), a β-galactosidase binding lectin associated with inflammation and fibrosis in DOX-induced acute cardiotoxicity in mice.<br /><b>Methods</b><br />Male C57 and Gal-3 knockout (KO) mice were given a single dose of DOX (15 mg/kg, i.p) or placebo. Serum creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and cardiac thiobarbituric acid-reactive substance (TBARS) were measured at 3 days to assess cardiac injury and oxidative stress. Cardiac remodeling and function were studied by echocardiography and catheterization at 7 days. Myocardial fibrosis was quantified in picrosirius red stained slices.<br /><b>Results</b><br />Absence of Gal-3 tended to reduce the mortality after DOX. DOX significantly increased CPK, LDH, AST and TBARS while treated Gal-3 KO mice showed reduced injury and oxidative stress. After 7 days, adverse remodeling, fibrosis and dysfunction in treated-C57 mice were severely affected while those effects were prevented by absence of Gal-3.<br /><b>Conclusion</b><br />In summary, genetic deletion of Gal-3 prevented cardiac damage, adverse remodeling and dysfunction, associated with reduced cardiac oxidative stress and fibrosis. Understanding the contribution of GAL-3 to doxorubicin-induced cardiac toxicity reinforces its potential use as a therapeutic target in patients with several cancer types.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 21 Sep 2023:131386; epub ahead of print</small></div>

<div><h4>Cardiac magnetic resonance assessment of athletic myocardial fibrosis; Benign bystander or malignant marker?</h4><i>Javed W, Malhotra A, Swoboda P</i><br /><AbstractText>The benefits of exercise are irrefutable with a well-established dose-dependent relationship between exercise intensity and reduction in cardiovascular disease. Differentiating the physiological adaptation to exercise, termed the \"athlete\'s heart\" from cardiomyopathies, has been advanced by the advent of more sophisticated imaging modalities such as cardiac magnetic resonance imaging (CMR). Myocardial fibrosis on CMR is a mutual finding amongst seemingly healthy endurance athletes and individuals with cardiomyopathy. As a substrate for arrhythmias, fibrosis is traditionally associated with increased cardiovascular risk. In this article, we discuss the aetiologies, distribution and potential implications of myocardial fibrosis in athletes.</AbstractText><br /><br />Copyright © 2023 The Author. Published by Elsevier B.V. All rights reserved.<br /><br /><small>Int J Cardiol: 21 Sep 2023:131382; epub ahead of print</small></div>

<div><h4>Hemoglobin to red cell distribution width ratio: A predictor of clinical outcome and diuretic response in patients with acute heart failure.</h4><i>Chen H, Zhen Z, Dong Y, Liu C, Dong B, Xue R</i><br /><b>Background</b><br />Hemoglobin to Red Cell Distribution Width Ratio (HRR) is a novel inflammatory marker in the prognostic assessment of tumors. Nevertheless, its focus on the cardiovascular field is relatively limited, particularly regarding its correlation with diuretic responses and clinical outcomes.<br /><b>Methods</b><br />This is a secondary analysis of the Renal Optimization Strategies Evaluation (ROSE AHF) clinical trial. The outcomes of interest included all-cause death, rehospitalization and diuretic responses. Multivariable Cox proportional hazard regression and linear regression models were performed, respectively. Prognostic outcomes and diuretic response were further evaluated in ejection fraction (EF) subgroups (preserved EF ≥ 50% and reduced EF<50%).<br /><b>Results</b><br />A total of 351 patients were included in the present study and further categorized according to HRR median (0.7131) value at admission: low HRR group (n = 176) and high HRR group (n = 175). High HRR were found to be independently associated with decreased risk of all-cause death (HR = 0.51; 95% CI,0.30-0.87, P = 0.013), reduced risk of developing all-caused death or rehospitalization (HR = 0.62; 95% CI,0.39-0.98, P = 0.039). Furthermore, high HRR indicated lower cumulative urine output (OR: -992.33, P = 0.004) and less weight loss (OR: 3.08, P < 0.001) within 72 h after diuresis. Subgroup analysis revealed no significant interaction effect between EF and HRR in prognostic impact or diuretic responses, and HRR was negatively correlated with plasma volume.<br /><b>Conclusion</b><br />High HRR demonstrated a lower risk of developing adverse clinical outcomes and a poorer diuretic response that might be due to less volume overload in AHF patients.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 20 Sep 2023:131368; epub ahead of print</small></div>

<div><h4>ICD outcome in pediatric arrhythmogenic cardiomyopathy.</h4><i>Cicenia M, Silvetti MS, Cantarutti N, Battipaglia I, ... Baban A, Drago F</i><br /><b>Background</b><br />Arrhythmogenic cardiomyopathy (ACM) is a very rare condition among pediatric patients. Sudden cardiac death (SCD) is the main complication and often requires ICD implantation. Aim of the study is the evaluation of the outcomes of ICD implanted ACM pediatric patients in terms of safety, efficacy and complications.<br /><b>Methods</b><br />All pediatric patients (<18 y.o.) diagnosed with ACM and who were implanted with ICD since 2009 in Our Institution were collected. Implantation was decided according to current recommendations/ guidelines, and outcome was recorded during follow-up.<br /><b>Results</b><br />Nineteen consecutive ACM patients were implanted with ICD. Subcutaneous ICDs (S-ICD) were implanted in 15 patients (79%) while transvenous ICDs (TV-ICD) in 4 patients (21%). Mean age at implantation was 14.3 ± 2.1 y.o. ICDs were implanted for secondary prevention in 4 (21%) patients, and for primary prevention in 15 (79%). During the follow-up (5.59 ± 3.4 years), appropriate ICD interventions were delivered in 4 (21%) patients for sustained VTs, [2 implanted in primary prevention (13%) and 2 in secondary prevention (50%)]. No defibrillation failures occurred. Inappropriate shocks occurred in 2 cases (10.5%). Device-related complications requiring device revision occurred in 3 (16%): lead dislodgement, surgical skin erosion and sensing defect.<br /><b>Conclusions</b><br />In a pediatric ACM cohort, appropriate ICD therapies occurred in a minority of primary prevention patients and frequently in secondary prevention patients. The rate of inappropriate shocks and device-related complications were even more rare and mostly wound related. Therefore, ICD therapy in pediatric ACM is effective and safe.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 20 Sep 2023:131381; epub ahead of print</small></div>

<div><h4>The value of using left ventricular pressure-strain loops to evaluate myocardial work in predicting heart failure with improved ejection fraction.</h4><i>Li T, Li Z, Guo S, Jiang S, ... Wu Y, Tian J</i><br /><b>Background</b><br />The ultrasound left ventricular pressure-strain loop (LV PSL) was applied to evaluate myocardial work in heart failure with improved ejection fraction (HFimpEF) versus patients with persistent heart failure with reduced ejection fraction (HFrEF) to investigate the value of myocardial work parameters in predicting HFimpEF.<br /><b>Methods</b><br />We collected 120 patients with HFrEF and recorded clinical characteristics and echocardiographic parameters (PSL technique) of patients. Patients were divided into HFimpEF group or persistent HFrEF group according to outcome of follow-up. Furthermore, differential clinical and echocardiographic parameters were determined by Student\'s t-test. We recognized the important echocardiographic parameters to predict whether patients would recover to HFimpEF using the univariate logistic regression analysis and ROC curves. In addition, the multivariate logistic regression models were constructed and evaluated using Delong test and decision curve analysis.<br /><b>Results</b><br />Firstly, the HFimpEF group had a higher prevalence of hypertension and higher systolic blood pressure (P-values <0.05). In terms of echocardiographic parameters, HFimpEF group also had higher LVEF, LV GLS, GCW, GWE, and GWI and lower LVEDD (P-values <0.01). In particular, LVEF, LVEDD, GLS, GWI, and GCW were robust predictors of the conversion of HFrEF patients to HFimpEF (AUC > 0.70, P-values <0.05). Finally, we determined that the predictive Model 4 (LVEF, LVEDD, GLS, and GCW) had the optimal diagnostic power.<br /><b>Conclusion</b><br />The model constructed by GCW with LVEF, LVEDD, and GLS has important predictive value for HFimpEF, which is an effective clinical decision-making tool for providing disease assessment.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 19 Sep 2023:131366; epub ahead of print</small></div>

<div><h4>Screening for - and prevalence of - anxiety and depression in cardiac rehabilitation in the post-COVID era. An observational study.</h4><i>Helmark C, Harrison A, Pedersen SS, Doherty P</i><br /><b>Background</b><br />Approximately 20-30% of patients with a cardiac disease suffer from anxiety and/or depression, leading to poor health outcomes. To identify this subgroup, clinical guidelines recommend screening for anxiety and depression in cardiac rehabilitation (CR). It is unknown how screening practice is delivered post-COVID.<br /><b>Methods</b><br />This observational study used data from the National Audit of Cardiac Rehabilitation from April 2018-March 2022. Descriptive statistics were used to assess screening rates and prevalence, while a multivariate logistic regression model was performed to analyse determinants for screening for anxiety and depression among patients participating in cardiac rehabilitation.<br /><b>Results</b><br />The population consisted of 245,705 patients, where 128,643 (52.4%) were screened and 117,062 (47.6%) were not. Patients attending CR during first year of COVID-19 were less likely to be screened. Patients with female gender, living alone, non-white ethnicity, living in the most deprived areas, current smoking, and physical inactivity were less likely to be screened, while patients who were revascularized, having an objective physical fitness test, and attending a certified CR center were more likely to be screened. For patients attending CR during COVID-19, the prevalence of anxiety and depression decreased significantly. For anxiety the prevalence dropped from 34.4% to 15.8%, for depression the prevalence dropped from 33.5% to 16.5%.<br /><b>Conclusion</b><br />CR service provision was negatively impacted during COVID-19, leading to much lower screening for anxiety and depression in the CR setting. Prevalence of anxiety and depression decreased during COVID-19 for this population, possibly because psychologically affected patients refrained from attending CR.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 19 Sep 2023:131379; epub ahead of print</small></div>

<div><h4>Signal intensity coefficient as a detector of aortic stenosis-induced myocardial fibrosis and its correlation to the long term outcome.</h4><i>Chang WT, Lin CH, Lee WC, Kan WC, ... Huang PS, Wu NC</i><br /><b>Objective</b><br />Despite advanced aortic valve replacement techniques, aortic stenosis (AS)-induced irreversible myocardial fibrosis contributes to poorer outcomes. Therefore, in addition to early diagnosis of AS, detecting myocardial fibrosis is crucial for physicians to determine the timing of surgery. The Signal Intensity Coefficient (SIC) was used to detect subtle myocardial deformation. Hence, we aimed to investigate whether SIC correlated with myocardial dysfunction and fibrosis from both clinical and preclinical perspectives.<br /><b>Methods</b><br />We collected medical records and echocardiography images, including the SIC of patients who underwent surgical aortic valve replacement (AVR) for AS from 2010 to 2015. The endpoint of the study was mortality. Median follow-up period was 80 months.<br /><b>Results</b><br />Among 109 patients, 15 died due to cardiovascular causes. Although SIC decreased in all patients post-AVR, patients with an SIC ≥0.34 before surgeries presented with a higher probability of cardiovascular death. In contrast, changes in the left ventricular (LV) ejection fraction, LV mass index, and LV volume failed to predict outcomes. Similarly, SIC was obtained in mice undergoing aortic banding and debanding surgery for comparison with the degree of myocardial fibrosis. SIC was continuously elevated after aortic banding and declined gradually after debanding surgery in mice. Debanding surgery indicated the regression of aortic banding-induced myocardial fibrosis.<br /><b>Conclusion</b><br />Pre-AVR SIC was associated with the risk of cardiovascular death and reflected the degree of myocardial fibrosis. Further investigations are required to study the clinical application of SIC in patients with AS.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 17 Sep 2023:131367; epub ahead of print</small></div>

<div><h4>ISCHEMIC STROKE AND MAJOR BLEEDING WHILE ON DIRECT ORAL ANTICOAGULANTS IN NAÏVE PATIENTS WITH ATRIAL FIBRILLATION: IMPACT OF RESUMPTION OR DISCONTINUATION OF ANTICOAGULANT TREATMENT. A population-based study.</h4><i>Gennaro N, Ferroni E, Zorzi M, Denas G, Pengo V</i><br /><b>Aims</b><br />We assessed the cumulative incidence of recurrent stroke, major bleeding and all-cause mortality associated with restarting antithrombotic treatment, in patients experiencing an anticoagulation-related event (stroke or major bleeding), occurred during anticoagulation therapy for AF.<br /><b>Methods and results</b><br />We performed a retrospective population-based analysis on linked claims data of patients resident in the Veneto Region, treated with DOACs for AF and discharged (2013-2020) from the hospital for stroke, intracranial haemorrhage (ICH), and major bleeding. To adjust for competing risk of death and reduce confounding, we started the follow up after a 120-days blanking period, counting events in patients resuming oral anticoagulation versus those that did not. Risks of all-cause mortality, ischemic stroke (IS)intracranial haemorrhage (ICH), and other major bleeding events (MB) were estimated with multivariable Cox proportional hazard models and propensity score to adjust for differences in baseline characteristics. Overall, 1029 patients (mean age 77 years) were included in the final cohort: 23% experienced an IS, 18% an ICH, and 59% MB. Of these, 77% resumed anticoagulation. The cumulative incidence of events was significantly lower in patients resuming therapy. In the multivariable analysis considering age, sex and propensity score as covariates, resumption of anticoagulation significantly reduced the risk of a cumulative event (HR 0.45, 95%CI 0.35-0.57, p < 0.01). Stratifying for the index event, among patients with IS (92% resumed therapy), we observed a risk reduction of 81%; in patients with ICH (64% resumed therapy), we observed a risk reduction of 64% and for patients with MB (76% resuming therapy), we observed a risk reduction of 49%.<br /><b>Conclusions</b><br />In patients with AF who experienced an anticoagulation-related event, resuming oral anticoagulation was associated with better outcomes for all-cause mortality and subsequent events as compared with patients who did not resume treatment.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Sep 2023:131369; epub ahead of print</small></div>

<div><h4>LKB1 delays atherosclerosis by inhibiting phenotypic transformation of vascular smooth muscle cells.</h4><i>Chen K, Zhu C, Zhang Q, Zeng Z, ... Zhou Z, Zeng R</i><br /><b>Background:</b><br/>and objective</b><br />Although liver kinase B1 (LKB1) is a well-known tumor suppressor gene, and its encoded protein has important biological functions, it is not clear whether LKB1 can inhibit atherosclerosis by regulating vascular smooth muscle cells (VSMCs). The purpose of this study is to explore the relationship among LKB1, VSMCs and atherosclerosis.<br /><b>Methods and results</b><br />ApoE<sup>-/-</sup> mice with VSMCs-specific overexpression of LKB1 were constructed by adeno-associated virus transfection technique, and then fed with high-fat diet for eight weeks. The effect of LKB1 overexpression on atherosclerosis in mice was investigated by oil red O staining, HE staining, immunofluorescence and Western Blot. The results showed that the expression of LKB1 mRNA and protein in arterial tissue of mice increased significantly after overexpression of LKB1. The degree of atherosclerosis, smooth muscle fiber proliferation and lipid accumulation were significantly alleviated in the overexpression group. The results of Western Blot showed that the expression of α-SMA was increased, while the expression of OPN and CD68 was significantly decreased in the overexpression group (P < 0.05). The Immunofluorescence results of Image Pro Plus software analysis showed that the co-localization relationship between α-SMA and CD68 was more obvious in the control group (P < 0.01).<br /><b>Conclusion</b><br />Our results suggested that LKB1 can delay the progression of atherosclerosis by inhibiting the phenotypic transition of VSMCs.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Sep 2023:131363; epub ahead of print</small></div>

<div><h4>Increased incidence risks of cardiovascular disease among cancer patients: Evidence from a population-based cohort study in China.</h4><i>He D, Qin K, Li J, Li Y, ... Xu J, Zhu Y</i><br /><b>Background</b><br />Cardiovascular disease (CVD) is becoming a major concern among cancer patients, leading to the development of a new field named cardio-oncology. However, previous studies were mainly based on the western population and focused on CVD mortality. Evidence from the Chinese population is limited. Furthermore, few studies investigated the incidence risks of CVD among cancer patients.<br /><b>Methods</b><br />85,787 eligible cancer patients were included from Hangzhou city, China. Age-standardized standard incidence ratio (SIR) was used to reflect the incidence risks of CVD among cancer patients as compared with the standard population, which was defined as all residents in Hangzhou city during the same period.<br /><b>Results</b><br />After three years of follow-up, cancer patients showed elevated incidence risks of CVD (SIR = 1.41, 95%CI: 1.35-1.47) as compared with the standard population. The elevated risks of CVD were highest in the first year after cancer diagnosis (SIR = 1.68, 95%CI: 1.58-1.78), then followed by the second (SIR = 1.21, 95%CI: 1.11-1.31) and the third (SIR = 1.18, 95%CI: 1.07-1.29) year. These results were consistent in males and females. Furthermore, different risks of CVD were observed among different cancer sites. Patients with pancreatic cancer showed the highest risks of CVD, then followed by liver cancer, lung cancer, kidney cancer, gastric cancer, bladder cancer, prostate cancer, and colorectal cancer.<br /><b>Conclusions</b><br />Cancer patients have increased incidence risks of CVD, especially in the first year after cancer diagnosis. The increased risks of CVD vary by different cancer sites. Our findings highlight the importance of paying close attention to the CVD risks among cancer patients.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Sep 2023:131362; epub ahead of print</small></div>

<div><h4>Factors that predict compliance in a virtual cardiac rehabilitation program.</h4><i>Eichner NZM, Zhu QM, Granados A, Berry NC, Saha SK</i><br /><b>Background</b><br />Despite the well-established benefits of cardiac rehabilitation (CR) for patients with cardiovascular disease (CVD), participation in CR remain low. Virtual CR programs present a unique opportunity to promote utilization. To date, few virtual CR cohorts have been analyzed for compliance. This study aims to determine factors that predict compliance within a large virtual CR program in the United States.<br /><b>Methods</b><br />We analyzed 1409 patients enrolled in the Kaiser Permanente Mid-Atlantic States Virtual CR program that consists of 12 CR sessions via telephone. Demographic characteristics, as well as body weight, blood pressure, HbA1c level, and smoking status were collected at admission. Patients were further classified by CVD diagnosis codes. Compliance was defined as at least 75% (9/12 sessions) attendance. Data was analyzed using simple and multiple regression models with significance defined as P < 0.05.<br /><b>Results</b><br />Age was the single strongest predictor for virtual CR compliance (adjusted R<sup>2</sup> = 0.58; P < 0.001), and non-compliant patients were younger. HbA1C level, CVD diagnosis codes, and smoking status each moderately predicted compliance (adjusted R<sup>2</sup> = 0.48, 0.42, and 0.31, respectively; P < 0.001). Smoking and HbA1C level combined in a multiple regression model significantly improved prediction of compliance (adjusted R<sup>2</sup> = 0.79, P < 0.01). Sex, baseline weight or hypertension were not significant predictors of CR compliance.<br /><b>Conclusions</b><br />Age, diabetes, CVD diagnoses, smoking status at admission are independent predictors of compliance in a large virtual CR program. Targeted intervention could be designed accordingly to improve CR compliance.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Sep 2023:131364; epub ahead of print</small></div>

<div><h4>Clinical evaluation of Sepsis-1 and Sepsis-3 in infective endocarditis.</h4><i>Wang Q, Fu B, Hu P, Liao X, ... Wang Z, Wei X</i><br /><b>Background</b><br />Sepsis is associated with poor survival outcomes in patients with infective endocarditis (IE). However, the prognostic value of the Sepsis-1 and Sepsis-3 criteria of sepsis for IE patients is unclear.<br /><b>Methods</b><br />A total of 1354 patients with IE was enrolled and classified into the sepsis and non-sepsis groups according to the Sepsis-1 and Sepsis-3. Multivariate regression analysis was performed to test the predictive performances of the Sepsis-1 and Sepsis-3 in assessing the risk of mortality in patients with IE.<br /><b>Results</b><br />Sepsis was diagnosed in 347 (25.6%) patients according to the Sepsis-1 and 496 (36.6%) patients with the Sepsis-3. The in-hospital mortality rate was 11.5% in the Sepsis-1 group and 14.3% in the Sepsis-3 group. Kaplan-Meier survival curve analysis showed that both Sepsis-1 (Log-rank = 17.2, p < 0.001) and Sepsis-3 (Log-rank = 94.3, p < 0.001) were significantly associated with 6-month mortality. Multivariate regression analysis demonstrated that the Sepsis-3 were independently associated with the in-hospital mortality (odds ratio = 2.89, 95% CI 1.68-4.97, p < 0.001) and the 6-month mortality (hazard ratio = 3.24, 95% CI 2.08-5.04, p < 0.001).<br /><b>Conclusions</b><br />Sepsis-3 showed better predictive performance than the Sepsis-1 criteria in assessing the risk of mortality in patients with IE.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Sep 2023:131365; epub ahead of print</small></div>

<div><h4>Assessment of the left atrial volume and function following percutaneous mitral balloon valvuloplasty: Insights into acute and late impact of atrial fibrillation on atrial remodeling.</h4><i>Soares JR, Carvalho VT, Lodi-Junqueira L, Fonseca IMG, ... Hung J, Nunes MCP</i><br /><b>Background</b><br />Rheumatic mitral stenosis (MS) leads to LA remodeling with disordered electrical activation that may revert with valve intervention. This study aimed to assess the acute and late impact of percutaneous mitral balloon valvuloplasty (PMBV) on LA volume and function in patients with atrial fibrillation (AF) compared with sinus rhythm.<br /><b>Methods</b><br />A total of 167 patients with severe MS undergoing PMBV were prospectively enrolled. LA volumes and function were measured by three-dimensional echocardiography (3DE) pre PMBV, within 24 to 48 h after PMBV, and at 1 year.<br /><b>Results</b><br />Mean age was 43.5 ± 11.8 years old, and 142 (85%) patients were women. At baseline, 46 patients (27.5%) were in permanent AF, and 62 (37.1%) classified as New York Heart Association functional class III or IV. In sinus rhythm population, LA volumes decreased immediately after PMBV and continue to decrease at 1-year follow-up. LA emptying fraction increased from 23.6 ± 10.4% to 33.8 ± 11.9% acutely after the procedure (p < 0.001), and to 37.2 ± 13.2% at 1-year follow-up (p = 0.028). Patients with AF only had a significant decrease in LA minimum volume immediately after PMBV, with no significant changes in maximum volume either immediately or at follow-up. In these patients, LA emptying fraction increased immediately after the procedure from 15.8 ± 9.9% to 22.8 ± 9.8 (p = 0.001) with no evidence for additional improvement at the 1-year follow-up. Age, and post-procedural mean gradient were identified as the most significant factors associated with the absolute changes in LA function between baseline and the 1-year follow-up.<br /><b>Conclusions</b><br />In patients with severe MS, the impact of PMBV on LA volume and function varies according to cardiac rhythm. In patients in sinus rhythm, the procedure leads to improvement of LA volumes and function both acutely and at 1-year follow-up. Patients with AF had a lesser improvement in LA function immediately after the procedure, without further improvement over time despite adequate relief of valve obstruction.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 12 Sep 2023:131361; epub ahead of print</small></div>

<div><h4>Higher-risk SIPAT score predicts increased risk of long-term mortality in orthotopic heart transplant recipients.</h4><i>Kosaraju R, Vandenbogaart E, Core E, Livingston N, ... Kamath M, Deng M</i><br /><b>Background</b><br />Orthotopic heart transplantation (OHT) improves survival in eligible patients. Organ scarcity necessitates extensive clinical and psychosocial evaluations before listing. The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) predicts risk for poor psychosocial outcomes and morbidity in the first year post-transplant, yet it is unknown whether it predicts long-term outcomes.<br /><b>Methods</b><br />Blinded examiners obtained data from a retrospective cohort of 51 OHT recipients from a high-volume center. Patients with \"Excellent\" or \"Good\" SIPAT score indicating low psychosocial risk for transplant (E/G) were compared with those who met \"Minimum Acceptable Criteria\" or were \"High Risk\" (MAC/HR). Associations were examined between SIPAT group and outcomes.<br /><b>Results</b><br />MAC/HR versus E/G recipients had significantly reduced survival in the 10 years post-OHT (mean 6.7 vs 8.8 years, p = 0.027; 55% vs 82% survival proportions, p = 0.037). MAC/HR patients were more likely to live in a county with greater income inequality (p = 0.025) and have psychiatric history pre-OHT (p = 0.046). Both groups had otherwise similar demographics and medical history. A lower proportion of MAC/HR patients adhered to medications post-OHT and a greater proportion had psychiatric illness, though differences were not significant.<br /><b>Conclusions</b><br />Higher-risk SIPAT scores predict reduced long-term survival post-OHT. Further efforts are crucial to improve outcomes in higher-risk patients.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 12 Sep 2023:131360; epub ahead of print</small></div>

<div><h4>Echocardiography assessment of right ventricular-pulmonary artery coupling: Validation of surrogates and clinical utilities.</h4><i>Li Q, Zhang M</i><br /><AbstractText>Right ventricular-pulmonary artery (RV-PA) coupling indicates efficiency of energy transfer from the right ventricle to the pulmonary circulation. The gold standard measurement, end-systolic elastance/arterial elastance ratio (Ees/Ea), is derived from invasive pressure-volume loop, which is technically demanding, expensive and limited in clinical practice. Recent studies have proposed various non-invasive surrogates of Ees/Ea based on echocardiography assessment, of which TAPSE/PASP ratio is an easily-obtained and validated parameter in severe pulmonary hypertension and rapidly applicated in the diagnosis and risk evaluation of various diseases and cardiac intervention. In this review, we summarized principles and validations of echocardiographic surrogates, and their clinical utilities and also limitations. The goal is to systematically review the research advances of echocardiography assessment of RV-PA coupling and help to guide clinical practice.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 11 Sep 2023:131358; epub ahead of print</small></div>

<div><h4>Transaxillary versus transfemoral access as default access in TAVI: A propensity matched analysis.</h4><i>van Wely M, van Nieuwkerk AC, Rooijakkers M, van der Wulp K, ... Delewi R, van Royen N</i><br /><b>Background</b><br />Transfemoral (TF) access is default in transcatheter aortic valve implantation (TAVI). Transaxillary (TAx) access has been shown to be a safe alternative in case of prohibitive iliofemoral anatomy, but whether TAx as preferred access has similar safety and efficacy as TF access is unknown. The aim of this study was to compare outcomes between patients treated with self-expanding devices using TF or TAx route as preferred access in TAVI.<br /><b>Methods</b><br />A single center cohort of 354 patients treated using TAx as preferred access and a multi-center cohort of 5980 patients treated using TF access were compared. Propensity score matching was used to reduce selection bias and potential confounding. After propensity score matching, each group consisted of 322 patients. Clinical outcomes according to VARC-2 were compared using chi-square test.<br /><b>Results</b><br />In 6334 patients undergoing TAVI, mean age was 81.4 ± 7.0 years, 57% was female and median logistic EuroSCORE was 14.7% (IQR 9.5-22.6). In the matched population (age 79.3 ± 7.0, 50% female, logistic EuroSCORE 13.4%, IQR 9.0-21.5), primary outcomes 30-day and one-year all-cause mortality were similar between Tax and TF groups (30 days: 5% versus 6%, p = 0.90; 1 year: 20% versus 16%, p = 0.17). Myocardial infarction was more frequent in patients undergoing Tax TAVI compared with TF (4% versus 1%, p = 0.05), but new permanent pacemakers were less frequently implanted (12% versus 21%, p = 0.001).<br /><b>Conclusion</b><br />TAx as preferred access is feasible and safe with outcomes that are comparable to TF access.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 09 Sep 2023:131353; epub ahead of print</small></div>

<div><h4>Left atrial remodeling in hypertrophic cardiomyopathy and Fabry disease: A CMR-based head-to-head comparison and outcome analysis.</h4><i>Moroni A, Tondi L, Milani V, Pieroni M, ... Lombardi M, Camporeale A</i><br /><b>Background</b><br />Hypertrophic cardiomyopathy (HCM) and Fabry disease cardiomyopathy (FD) are phenocopies, as they show left ventricular hypertrophy (LVH). The left atrium (LA) is emerging as a potential marker of disease severity in both cardiomyopathies. The present study compares HCM and FD cardiomyopathy with similar degree of LVH, exploring LA morpho-functional parameters and the correlates of clinical outcome.<br /><b>Methods</b><br />We performed a comprehensive CMR-based comparison between 30 HCM and 30 FD patients matched on age, sex, BSA, LV mass and major cardiovascular risk factors affecting LA remodeling (arterial hypertension and diabetes). 30 healthy controls were also included. CMR feature tracking (CMR-FT) analysis, T1 mapping and conventional parameters were evaluated. Patients also underwent transthoracic echocardiography for LV diastolic function assessment. Clinical events at follow-up were collected (atrial and ventricular events, bradyarrhythmia, heart failure (HF) hospitalization and death).<br /><b>Results</b><br />HCM patients showed greater LA remodeling compared to FD patients, namely higher LA end-systolic volume index (LAVi max), lower LA-ejection fraction (LA-EF) and worse reservoir (εs) and booster function (εa) (all p < 0.05). Accordingly, these parameters have demonstrated good potential for distinguishing between FD and HCM (AUC 0.68-0.73, all p < 0.05), with LAVi max being an independent predictor for HCM diagnosis (OR 1.07, 95%CI 1.011-1.132, p 0.02). Moreover, in HCM patients a significant association between εs and HF occurrence was observed at 2-year follow-up (OR 0.85, 95%CI 0.72-0.99, p 0.04).<br /><b>Conclusions</b><br />In HCM, LA remodeling is greater than in FD cardiomyopathy with similar LVH, and reservoir strain is associated with HF at follow-up.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 09 Sep 2023:131357; epub ahead of print</small></div>

<div><h4>Changes of left atrial morphology and function evaluated with four-dimensional automated left atrial quantification echocardiography in patients with coronary slow flow phenomenon and preserved left ventricular ejection fraction.</h4><i>Xing Y, Zhang Y, Zhao R, Shi J, ... Chen L, Pan C</i><br /><b>Background</b><br />Coronary slow flow phenomenon (CSFP) can cause left ventricular diastolic dysfunction (LVDD). In multiple studies, the left atrial (LA) strain has been reported to be an excellent parameter for assessing LVDD. The 4-dimensional automated LA quantification (4D Auto LAQ) dedicated to the LA was recently available. Our study aimed to evaluate subclinical changes in LA morphology and function with 4D Auto LAQ in patients with CSFP and preserved left ventricular ejection fraction (LVEF).<br /><b>Methods</b><br />Forty-eight patients with CSFP confirmed with coronary angiography and 46 age and gender-matched controls with normal coronary flow were enrolled. The thrombolysis in myocardial infarction frame count (TFC) method was used to record coronary blood flow velocities for each major coronary artery. LA volume, LA longitudinal and circumferential strains during each of the three LA phases (reservoir, conduit, and contraction), LA total emptying fraction (LATEF), LA active emptying fraction (LAAEF), and LA passive emptying fraction (LAPEF) were quantified with 4D Auto LAQ analysis.<br /><b>Results</b><br />Compared with controls, LA longitudinal reservoir strain (LASr), LA longitudinal strain during the conduit phase (LAScd), LA contraction strain (LASct), LA conduit circumferential strain (LAScd-c), LATEF, LAPEF decreased significantly in individuals with CSFP. Of the 4D- LAQ parameters, only LASr [odds ratio (OR): 0.773, P < 0.001] and LATEF [OR: 0.762, P < 0.001] were associated with CSFP in multivariate analysis. A LASr ≤23.00% can differentiate CSFP from controls [sensitivity, 66.7%; specificity, 93.5%; area under the curve (AUC), 0.823; P < 0.001]. A LASr of ≤19.00% could predict the elevation of LV filling pressure in the CSFP cohort [sensitivity, 76.9%; specificity, 74.3%; area under the curve (AUC), 0.792; P < 0.001]. LASr was the only index to demonstrate significant changes compared to controls in single-vessel CSFP. Compared to the right coronary artery (RCA) and left circumflex (LCX), TFC of the left anterior descending (LAD) artery was the only independent variable of LASr (Standardized Coefficients: -0.386, P = 0.037).<br /><b>Conclusions</b><br />Impairment of LA reservoir function reflected by changes of LASr and LATEF can be seen in patients with CSFP. LASr could predict the elevation of LV filling pressure in CSFP individuals. LASr is more sensitive than LATEF in detecting LA reservoir dysfunction in single-vessel CSFP. CSFP in LAD exerts a more prominent influence on LASr than RCA or LCX.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 09 Sep 2023:131351; epub ahead of print</small></div>

<div><h4>Prognostic impact of treatments evolution in STEMI.</h4><i>Fabris E, Boldrin C, Gregorio C, Pezzato A, ... Perkan A, Sinagra G</i><br /><b>Objective</b><br />To evaluate in a real-world primary percutaneous coronary intervention (pPCI) registry the impact of the evolution of evidence-based treatments on prognosis.<br /><b>Methods</b><br />STEMI patients undergoing pPCI at the University Hospital of Trieste, Italy, were enrolled. The first cohort (old treatments cohort) included STEMI patients treated between January-2007 and December-2012, and the second cohort (new treatments cohort), between January-2013 and December-2020. Inverse Probability of Treatment Weighting (IPTW) Cox regression models as well as multivariable Cox regression models were performed to assess the risk of a composite primary endpoint (PE) of all cause death, reinfarction and re-PCI at 5 years.<br /><b>Results</b><br />A total of 2425 STEMI patients were enrolled. At multivariable Cox regression, the new-treatments cohort had lower risk of PE and mortality. Weighted (IPTW) Cox proportional hazard models confirmed the lower risk of the new treatments cohort for PE (HR 0.72; 95% CI 0.56-0.91, p = 0.007) and 5-year mortality (HR 0.70, 95%CI 0.54-0.91, p = 0.009). When considering both clinical and procedural variables, complete revascularization (HR 0.46, 95%CI 0.27-0.80, p = 0.006) and the administration of prasugrel or ticagrelor (HR 0.72, 95%CI 0.52-0.99, p = 0.013) were independent predictors of PE as well as of 5-year mortality. Patients receiving prasugrel or ticagrelor or drug eluting stent were at lower risk of 1-year stent thrombosis (HR 0.50, 95%CI 0.28-0.90, p = 0.021).<br /><b>Conclusions</b><br />In a real-word STEMI population the prognosis of patients is improved in the last decades, and this was associated to the use of new antithrombotic treatments and to the implementation of complete revascularization.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 09 Sep 2023:131352; epub ahead of print</small></div>

<div><h4>Electrocardiographic heterogeneity of patients with variant transthyretin amyloid cardiomyopathy: Genotype-phenotype correlations.</h4><i>Russo D, Cappelli F, Di Bella G, Tini G, ... Rapezzi C, Musumeci MB</i><br /><b>Backgorund</b><br />Hereditary transthyretin(vATTR) cardiac amyloidosis has extremely different features according to the type of transthyretin(TTR) mutation. Data about electrocardiographic findings(ECG) in vATTR are limited and not informative of genotype correlation. Aim of this study is to analyze ECG characteristics and their correlation to clinical and echocardiographic aspects in patients with vATTR, focusing on different TTR mutations.<br /><b>Methods and results</b><br />This is a multicentric, retrospective, observational study performed in six Italian referral centres. We divided patients in two groups, according to the previously described phenotypic manifestations of the TTR mutation. Of 64 patients with vATTR, 23(36%) had prevalent cardiac(PC) TTR mutations and 41(64%) patients had a prevalent neurological(PN) TTR mutations. Patients with PC mutations were more frequently males and older, with advanced NAC staging. At baseline ECG, atrial fibrillation was more common in patients with PC, while pacemaker induced rhythm in PN mutations. PQ and QRS durations were longer and voltage to mass ratio was lower in PC mutations. Different TTR mutations tend to have distinctive ECG features.<br /><b>Conclusions</b><br />ECG in vATTR is extremely heterogeneous and the specific mutations are associated with distinct instrumental and clinical features. The differences between PN and PC vATTR are only partially explained by the different degree of cardiac infiltration.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 09 Sep 2023:131354; epub ahead of print</small></div>

<div><h4>Clinical characteristics and outcomes in patients with acute type a aortic intramural hematoma.</h4><i>Kanagami T, Saito Y, Hashimoto O, Nakayama T, ... Himi T, Kobayashi Y</i><br /><b>Background</b><br />Although type A acute aortic dissection (AAD) including classic double-channel aorta and intramural hematoma (IMH) is a life-threatening condition, the prognostic impact and predictors of IMH remain to be established. The present study evaluated the prevalence, baseline characteristics, and outcomes of IMH as compared with classic non-thrombosed type A AAD.<br /><b>Methods</b><br />This multicenter registry in Japan retrospectively included 703 patients with type A AAD. IMH was defined as a crescentic or circular area along the ascending aortic wall without contrast enhancement on computed tomography (CT). Non-thrombosed type A AAD was defined as the classic double-channel ascending aorta on contrast-enhanced CT. The primary endpoint was in-hospital mortality.<br /><b>Results</b><br />Of the 703 patients with type A AAD, 312 (44.3%) had IMH. Older age was an only baseline patient factor significantly associated with the presence of IMH in the multivariable analysis. The longitudinal extent of dissection was greater in patients with classic non-thrombosed AAD than those with IMH, resulting in an increased risk of end-organ malperfusion in the classic AAD group. During the hospitalization, 41 (13.1%) and 85 (21.7%) patients with and without IMH died (p < 0.001). IMH was associated with lower in-hospital mortality in a multivariable model, irrespective of age and the implementation of surgery.<br /><b>Conclusions</b><br />The present study showed that IMH on CT was frequent among patients with type A AAD. Although IMH was more likely to be present in the elderly, its effect on the better survival was independent of age and surgical treatment.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 09 Sep 2023:131355; epub ahead of print</small></div>

<div><h4>Fractal analysis: Left ventricular trabecular complexity cardiac MRI adds independent risks for heart failure with preserved ejection fraction in participants with end-stage renal disease.</h4><i>Zhang TY, An DA, Zhou H, Ni Z, ... Mou S, Wu LM</i><br /><b>Purpose</b><br />To measure left ventricular (LV) trabecular complexity by fractal dimension (FD) in patients with end-stage renal disease (ESRD), and assess whether FD was an independent risk factor for heart failure with preserved ejection fraction (HFpEF), or a significant predictor for adverse outcome in this population.<br /><b>Methods</b><br />The study retrospectively enrolled 104 participants with ESRD who underwent 3.0 T cardiac magnetic resonance imaging (MRI) from June 2018 to November 2020. LV trabeculation was quantified with fractal analysis of short-axis cine slices to estimate the FD. Logistic regression analyses were used to evaluate FD and cardiac MRI parameters and to find independent risk predictors. Cox proportional hazard regression was used to investigate the association between FD and MACE.<br /><b>Results</b><br />LV FD was higher in in the HFpEF group than those in the non-HFpEF group, with the greatest difference near the base of the ventricle. Age, minimum left atrial volume index, and LV mean basal FD were independent predictors for HFpEF in patients with ESRD. Combining the mean basal FD with typical predictive factors resulted in a C-index (0.902 vs 0.921), which was not significantly higher. Same improvements were found for net reclassification improvement [0.642; 95% confidence interval (CI), 0.254-1.029] and integrated discrimination index (0.026; 95% CI, 0.008-0.061). Participants with a LV global FD above the cutoff value (1.278) had higher risks of MACE in ESRD patients.<br /><b>Conclusions</b><br />LV trabecular complexity measured by FD was an independent risk factor for HFpEF, and a significant predictor for MACE among patients with ESRD.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 09 Sep 2023:131334; epub ahead of print</small></div>

<div><h4>Left cardiac vagotomy rapidly reduces contralateral cardiac vagal electrical activity in anesthetized Göttingen minipigs.</h4><i>Vallone F, Dushpanova A, Leali M, Strauss I, ... Micera S, Lionetti V</i><br /><b>Background</b><br />The impact of acute unilateral injury on spontaneous electrical activity in both vagus nerves at the heart level is poorly understood. We investigated the immediate neuroelectrical response after right or left cardiac vagal nerve transection (VNTx) by recording spiking activity of each heart vagus nerve (VN).<br /><b>Methods</b><br />Fourteen male Göttingen minipigs underwent sternotomy. Multi-electrode cuffs were implanted below the cut level to record vagal electroneurographic signals during electrocardiographic and hemodynamic monitoring, before and immediately after cardiac VNTx (left: L-cut, n = 6; right: R-cut, n = 8).<br /><b>Results</b><br />Left cardiac VNTx significantly reduced multi-unit electrical activity (MUA) firing rate in the vagal stump (-30.7% vs pre-cut) and intact right VN (-21.8% vs pre-cut) at the heart level, without affecting heart rate, heart rate variability, or hemodynamics. In contrast, right cardiac VNTx did not acutely alter MUA in either VN but slightly increased (p < 0.022) the root mean square of successive RR interval differences (rMSSD), an index of parasympathetic outflow, without affecting hemodynamics.<br /><b>Conclusions</b><br />Our study reveals an early left-lateralized pattern in vagal spiking activity following unilateral cardiac vagotomy. These findings enhance understanding of the neuroelectrical response to vagal injury and provide insights into preserving vagal outflow after unilateral cardiac vagotomy. Importantly, monitoring spiking activity of the cardiac right VN may predict onset of left vagal pathway injury, which is detrimental to cardiac patients and can occur as a complication of catheter ablation for atrial fibrillation.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 07 Sep 2023:131349; epub ahead of print</small></div>

<div><h4>Incidence and determinants of atrial fibrillation in patients with wild-type transthyretin cardiac amyloidosis.</h4><i>Carlo F, Mattia Z, Alessia A, Luigi T, ... Federico P, Francesco C</i><br /><b>Background</b><br />Data on the incidence and factors associated with de novo atrial fibrillation (AF) in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is limited. We described the incidence and factors associated with de novo AF in patients diagnosed with ATTRwt-CA to drive tailored arrhythmia screening.<br /><b>Methods</b><br />Multicenter, retrospective, observational cohort study performed in six referral centers for CA. All consecutive patients diagnosed with ATTRwt-CA between 2004 and 2020 with >6-month follow up (FU) were enrolled and divided into three groups according to presence of AF: (1)patients with \'known AF\'; (2)patients in \'sinus rhythm\' and (3)patients developing \'de novo AF\' during FU. Incidence and factors associated with AF in patients with ATTRwt were the primary outcomes.<br /><b>Results</b><br />Overall, 266 patients were followed for a median of 19 [11-33] months: 148 (56%) with known AF, 84 (31.6%) with sinus rhythm, and 34 (12.8%) with de novo AF. At Fine-Gray competing risk analysis to account for mortality, PR (sub-distribution hazard ratio [SHR] per Δms: 1.008, 95% C.I. 1.001-1.013, p = 0.008), QRS (SHR per Δms: 1.012, 95% C.I. 1.001-1.022, p = 0.046) and left atrial diameter ≥ 50 mm (SHR: 2.815,95% C.I. 1.483-5.342, p = 0.002) were associated with de novo AF. Patients with at least two risk factors (PR ≥ 200 ms, QRS ≥ 120 ms or LAD≥50 mm) had a higher risk of developing de novo AF compared to patients with no risk factors (HR 14.918 95% C.I. 3.242-31.646, p = 0.008).<br /><b>Conclusions</b><br />At the end of the study almost 70% patients had AF. Longer PR and QRS duration and left atrial dilation are associated with arrhythmia onset.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 07 Sep 2023:131346; epub ahead of print</small></div>

<div><h4>Yeo\'s index: A novel index that combines anatomic and haemodynamic assessment of the severity of mitral stenosis.</h4><i>Leow R, Kong WKF, Li TY, Poh KK, Sia CH, Yeo TC</i><br /><b>Background</b><br />A mitral leaflet separation index (MLSI), measuring the anatomical separation of the mitral valve (MV) leaflet tips in diastole, was previously described as an accurate method of assessing mitral stenosis (MS). We propose a novel modification of the MLSI by including a hemodynamic assessment which we term Yeo\'s index that may improve its diagnostic performance.<br /><b>Methods and results</b><br />We retrospectively studied 174 patients with varying severity of MS without significant mitral regurgitation, aortic valve disease or ventricular septal defect. MLSI was measured in 2 orthogonal views on transthoracic echocardiography as previously described. MV dimensionless index (DI) was calculated by dividing the left ventricular outflow tract pulsed-wave Doppler time velocity integral (TVI) by the MV continuous-wave Doppler TVI. We defined Yeo\'s index as the product of MLSI and DI. With linear correlation, Yeo\'s index demonstrated good correlation against MVA by planimetry (r = 0.728), pressure half-time (r = 0.677), and continuity equation (r = 0.829), with improved performance over the MLSI. Using ROC analysis, Yeo\'s index demonstrated good ability to correctly classify MS as severe (MVA ≤1.5cm<sup>2</sup>) (AUC 0.874, 95% CI 0.816-0.920). Yeo\'s index ≤0.260 cm correctly classified severe MS with sensitivity of 82% and specificity of 80%. Presence of AF did not affect the performance of Yeo\'s index. Yeo\'s index ≤0.147 cm also identified very severe MS (MVA ≤ 1.0 cm<sup>2</sup>) with specificity of 94% and sensitivity of 78%.<br /><b>Conclusion</b><br />Yeo\'s index performed well in identifying severe MS and may be a useful adjunct to existing measures of MS severity.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 07 Sep 2023:131350; epub ahead of print</small></div>

<div><h4>Impact of eccentric jet on outcomes in patients with atrial functional mitral regurgitation: An echocardiographic study.</h4><i>Hasegawa H, Kuwajima K, Kagawa S, Yamane T, ... Siegel RJ, Shiota T</i><br /><b>Background</b><br />Previous studies have reported the mechanisms underlying atrial functional mitral regurgitation (A-FMR). Recently, A-FMR subtypes based on mitral regurgitation (MR) mechanisms were proposed: \"central jet\" due to insufficient leaflet remodeling and \"eccentric jet\" due to atriogenic tethering. However, their prognostic value remains unclear. Therefore, this study investigated the impact of A-FMR subtypes on clinical outcomes.<br /><b>Methods</b><br />Outpatients with significant A-FMR between January 2013 and December 2016 were retrospectively reviewed. They were classified into two subtypes according to the MR jet\'s direction. All-cause mortality, heart failure hospitalization, and any mitral valve interventions were the primary composite endpoint.<br /><b>Results</b><br />Among 101 patients with significant A-FMR, 32% had eccentric jet. The primary endpoint was observed in 56 patients during the follow-up period (median 0.7 years, range 0.1-4.2 years). Kaplan-Meier curves demonstrated that the composite endpoint was higher among patients with eccentric jet than those with central jet (log-rank p < 0.001). Eccentric jet (hazard ratio [HR] 2.46, 95% confidence interval [CI] 1.28-4.73; p = 0.007), age (HR 1.06, 95% CI 1.02-1.11; p = 0.002), symptoms (HR 6.22, 95% CI 2.18-17.8; p < 0.001), severe MR (HR 3.97, 95% CI 1.92-8.18; p < 0.001), and significant tricuspid regurgitation (TR; HR 2.00, 95% CI 1.01-3.97; p = 0.047) were independent predictors of the composite endpoint.<br /><b>Conclusions</b><br />Patients with eccentric jet had poorer outcomes than those with central jet. Eccentric jet, age, symptoms, severe MR, and significant TR were independently associated with poor outcomes.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 05 Sep 2023:131342; epub ahead of print</small></div>

<div><h4>Long-term intracoronary imaging and physiological measurements of bioresorbable scaffolds and untreated atherosclerotic plaques.</h4><i>Fezzi S, Pighi M, Del Sole PA, Scarsini R, ... Pesarini G, Ribichini FL</i><br /><b>Background</b><br />Bioresorbable scaffolds (BRS) provide the prospect of restoring the anatomic and physiologic characteristics of the vascular wall.<br /><b>Objective</b><br />This study sought to examine the long-term outcomes of BRS-based coronary intervention in a young population with diffuse and severe coronary atherosclerotic disease (CAD) and to compare the long-term evolution of treated segments versus the natural progression of untreated non-flow limiting stenoses.<br /><b>Methods</b><br />Observational, single-center cohort study that prospectively included patients that underwent percutaneous coronary intervention with implantation of ABSORB BRS (Abbott Vascular). The clinical endpoint was the incidence of device-oriented composite endpoint (DoCE) up to 5 years follow-up. A subgroup of patients with baseline intracoronary imaging assessment of long lesions and/or multivessel disease underwent elective angiographic (70 patients, 129 lesions) and intracoronary imaging (55 patients, 102 lesions) follow-up. Paired intravascular ultrasound (IVUS) and quantitative flow reserve (QFR) were analyzed.<br /><b>Results</b><br />Between 2012 and 2017, 159 patients (mean age 54.0 ± 11.1) with native CAD were treated with BRS on 247 lesions. Patients were mainly at their first cardiac event, mostly acute coronary syndromes (86.5%). At the median follow-up time of 56 months [41-65], DoCE occurred in 15/159 (9.4%) patients, while non-target vessel-oriented composite endpoint occurred in 16 patients (10.4%). A significant atherosclerotic progression was detected on residual non-flow limiting plaques as per IVUS and QFR assessment, while no significant change was detected in the treated segment.<br /><b>Conclusions</b><br />Mild-to-moderate asymptomatic CAD progressed significantly at 5-year despite OMT. BRS-treated segments had a less aggressive progression at 5-year despite more severe and symptomatic CAD at baseline.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 05 Sep 2023:131341; epub ahead of print</small></div>

<div><h4>Temporal variations in ischemic and bleeding event risks after acute coronary syndrome during dual antiplatelet therapy.</h4><i>Fujii T, Kasai S, Kawamura Y, Yoshimachi F, Ikari Y</i><br /><b>Background</b><br />This study estimates the temporal risk variations of ischemic and bleeding events during dual antiplatelet therapy (DAPT) among patients stratified according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria, suggesting the optimal period for DAPT after acute coronary syndrome (ACS).<br /><b>Methods</b><br />A total of 1264 ACS patients receiving either clopidogrel or prasugrel with aspirin were classified by ARC-HBR; HBR (n = 574) and non-HBR groups (n = 690). This study was designed as a multicenter observation to evaluate the primary endpoints of ischemic, including cardiovascular death, myocardial infarction, or ischemic stroke, and bleeding events, defined as Bleeding Academic Research Consortium type 3/5. The temporal risk variations were estimated using the Cox hazard and Royston-Parmar models.<br /><b>Results</b><br />Ischemic and bleeding events were observed in 9.4% and 7.4%, respectively, during an average observation period of 313 days. The HBR group had a higher incidence of both events than the non-HBR group (15.3% vs. 4.5%, P < 0.01 for ischemic; 11.9% vs. 3.8%, P < 0.01 for bleeding). The estimated risk curves for both events revealed peaks and steep declines in the first few days, followed by constant declines. The peak of risk was higher for bleeding than for ischemic events, but this relationship reversed early, with ischemic events displaying a higher risk in both the HBR and non-HBR groups until at least 60 days.<br /><b>Conclusions</b><br />A 60-day period of DAPT is appropriate to balance the risks of adverse events after ACS, regardless of ARC-HBR criteria.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 05 Sep 2023:131340; epub ahead of print</small></div>

<div><h4>Prediction of clinical outcomes after percutaneous coronary intervention: Machine-learning analysis of the National Inpatient Sample.</h4><i>Galimzhanov A, Matetic A, Tenekecioglu E, Mamas MA</i><br /><b>Background</b><br />This study aimed to develop a multiclass machine-learning (ML) model to predict all-cause mortality, ischemic and hemorrhagic events in unselected hospitalized patients undergoing percutaneous coronary intervention (PCI).<br /><b>Methods</b><br />This retrospective study included 1,815,595 unselected weighted hospitalizations undergoing PCI from the National Inpatient Sample (2016-2019). Five most common ML algorithms (logistic regression, support vector machine (SVM), naive Bayes, random forest (RF), and extreme gradient boosting (XGBoost)) were trained and tested with 101 input features. The study endpoints were different combinations of all-cause mortality, ischemic cerebrovascular events (CVE) and major bleeding. An area under the curve (AUC) with 95% confidence interval (95% CI) was selected as a performance metric.<br /><b>Results</b><br />The study population was split to a training cohort of 1,186,880 PCI discharges, validation cohort (for calibration) of 296,725 hospitalizations and a test cohort of 331,990 PCI discharges. A total of 98,180 (5.4%) hospital entries included study outcomes. Logistic regression, SVM, naive Bayes, and RF model demonstrated AUCs of 0.83 (95% CI 0.82-0.84), 0.84 (95% CI 0.83-0.86), 0.81 (95% CI 0.80-0.82), and 0.83 (95% CI 0.81-0.84), retrospectively. The XGBoost classifier performed the best with an AUC of 0.86 (95% CI 0.85-0.87) with excellent calibration. We then built a web-based application that provides predictions based on the XGBoost model.<br /><b>Conclusion</b><br />We derived the multi-task XGBoost classifier based on 101 features to predict different combinations of all-cause death, ischemic CVE and major bleeding. Such models may be useful in benchmarking and risk prediction using routinely collected administrative data.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 05 Sep 2023:131339; epub ahead of print</small></div>

<div><h4>Myocardial extracellular volume fraction is positively associated with activated monocyte subsets among cART-treated persons living with HIV in South Africa.</h4><i>Peterson TE, Shey M, Masina N, Wong LY, ... Ntsekhe M, Baker JV</i><br /><b>Background</b><br />Despite treatment with combination antiretroviral therapy (cART), persons living with HIV (PLWH) are at higher risk of cardiac structural abnormalities that may presage clinical heart failure, including myocardial fibrosis. This study assessed whether circulating cellular and soluble protein markers of immune activation cross-sectionally associate with myocardial fibrosis among cART-treated PLWH in South Africa.<br /><b>Methods</b><br />Participants were enrolled in Khayelitsha township near Cape Town, SA. Cardiac magnetic resonance imaging was performed. Plasma protein biomarkers were measured using enzyme-linked immunoassays and monocyte phenotypes were evaluated using flow cytometry. Associations were assessed using multivariable linear and logistic regression.<br /><b>Results</b><br />Among 69 cART-treated PLWH, mean (SD) age was 48 (10) years, 71% were female, and time since HIV diagnosis was 9 (6) years. Evidence of left ventricular fibrosis by late gadolinium enhancement was present in 74% of participants and mean (SD) extracellular volume fraction (ECV) was 30.9 (5.9)%. Degree of myocardial fibrosis/inflammation measured by ECV was positively associated with percentages of circulating non-classical and intermediate monocyte phenotypes reflecting inflammation and tissue injury.<br /><b>Conclusion</b><br />These data generate hypotheses on possible immune mechanisms of HIV-associated non-ischemic myocardial disease, specifically among cART-treated PLWH in sub-Saharan Africa, where the majority of the HIV burden exists globally.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 04 Sep 2023:131332; epub ahead of print</small></div>

<div><h4>Comparison of different treatment strategies in patients with chronic thromboembolic pulmonary hypertension: A single centre real-world experience.</h4><i>Dardi F, Rotunno M, Guarino D, Suarez SM, ... Galiè N, Palazzini M</i><br /><b>Background</b><br />Pulmonary endarterectomy (PEA) has been the most effective therapy for chronic thromboembolic pulmonary hypertension (CTEPH). However, there is a substantial proportion of patients deemed not operable in whom other treatment strategies are available: medical therapy and balloon pulmonary angioplasty (BPA). We aimed to compare different CTEPH treatment strategies effect in a real-world setting.<br /><b>Methods</b><br />All patients with CTEPH referred to our centre were included. We compare the short-term clinical, functional, exercise and haemodynamic effect of medical therapy (irrespective of subsequent treatment strategies), PEA and BPA (irrespective of previous/subsequent treatment strategies); we also describe the long-term outcome of the different patient groups.<br /><b>Results</b><br />We included 467 patients (39% were treated only with medical therapy, 43% underwent PEA, 13% underwent BPA and 5% were not treated with any therapy). Patients treated only with medical therapy were the oldest; compared to patients undergoing PEA, they had a lower exercise capacity, a higher risk profile and gained a lower haemodynamic, functional and survival benefit from the treatment. Patients undergoing BPA had a lower haemodynamic improvement but a comparable functional, exercise and risk improvement and a similar survival compared to patients undergoing PEA; their survival is anyway better than patients undergoing only medical treatment. Untreated historical control patients had the worst survival.<br /><b>Conclusions</b><br />We confirm the superiority of PEA compared to any alternative treatment in CTEPH patients and we observe that BPA, in patients deemed not operable or with persistent/recurrent PH after PEA, leads to a better outcome than medical therapy alone.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 04 Sep 2023:131333; epub ahead of print</small></div>

<div><h4>Possibilities of dapagliflozin-induced cardioprotection on doxorubicin + cyclophosphamide mode of chemotherapy-induced cardiomyopathy.</h4><i>Avagimyan A, Sheibani M, Nana P, Mkrtchyan L, ... Shafie D, Sarrafzadegan N</i><br /><b>Rationale</b><br />The global burden of cardiovascular (CV) and oncological diseases continues to increase. In this regard, the prevention of CV diseases (CVD) before and after cancer treatment is an urgent and unsolved problem in medicine. For this reason, our research group aimed to investigate the possibility of dapagliflozin-related cardioprotection, using an experimental model of chronic Doxorubicin (Adriamycin) + Cyclophosphamide (AC)-mode of chemotherapy-induced cardiomyopathy.<br /><b>Objective</b><br />The redox balance, lipid metabolism, endothelial dysfunction, and myocardial damage parameters were measured to evaluate the pathways of dapagliflozin-induced stabilization of CV homeostasis.<br /><b>Methods</b><br />For this study, 80 inbred Wistar rats were randomly assigned to four equally sized groups. A model of chronic cardiotoxicity was attained by using doxorubicin and cyclophosphamide co-administration. In the case, the markers of redox-balance, cholesterol metabolism, endothelial dysfunction, myocardial alteration, and morphological examination were assessed.<br /><b>Results</b><br />For all parameters, statistically significant deviations were obtained, emphasizing the sequel of AC-mode chemotherapy-related detergent effect on CV system (group 2). Moreover, the data obtained from dapagliflozin-treated groups (group 3) showed that this strategy provide limitation of lipid peroxidation, cholesterol metabolism and endothelial function normalization, with subsequent morphological preservation of myocardium.<br /><b>Conclusion</b><br />Dapagliflozin has a broad spectrum of pleiotropic influences, namely cholesterol-lowering, anti-inflammatory, and endothelium-stabilizing properties. These properties provide a favorable environment for the prevention of chemotherapy-related cardiomyopathy.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 02 Sep 2023:131331; epub ahead of print</small></div>

<div><h4>Effect of PCSK9 antibodies on coronary plaque regression and stabilization derived from intravascular imaging in patients with coronary artery disease: A meta-analysis.</h4><i>Liu S, Wang P, Liu C, Jin M, ... Liu Z, Fu Z</i><br /><b>Background</b><br />Despite extensive evidence demonstrating the beneficial effects of the additional PCSK9 antibodies with high-density statins treatment on cardiovascular clinical outcomes, the potent causes underlying these effects remain elusive. This meta-analysis aimed at exploring the underlying causes to assess the effect of PCSK9 antibodies on the regression and stabilization of coronary plaque derived from intravascular imaging in statin-treated patients with coronary artery disease (CAD).<br /><b>Methods</b><br />PubMed, Embase, and Cochrane Library were searched from inception to February 1, 2023, for randomized controlled trials (RCTs), nonrandomized studies without language restrictions if they described the association between PCSK9 antibodies with coronary plaque regression and stabilization evaluated by intravascular imaging in statin-treated patients with CAD. Meta-analyses were performed for mean difference (MD) and odds ratio (OR) using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.<br /><b>Results</b><br />A total of 9 studies (7 RCTs and 2 non-RCTs) with 2290 CAD patients were identified and included. Among statin-treated CAD patients, the addition use of PCSK9 antibodies was associated with IVUS-derived percent atheroma volume (PAV) (4 studies with 1875 participants; MD, -1.26; 95% CI, -1.51 to -1.00; P < 0.01), total atheroma volume (TAV) (4 studies with 1875 participants; MD, -7.23; 95% CI, -11.28 to -3.18; P < 0.01), incidence of PAV regression (4 studies with 1875 participants; OR, 2.24; 95% CI, 1.81 to 2.77; P < 0.01) and incidence of TAV regression (3 studies with 1256 participants; OR, 1.66; 95% CI, 1.33 to 2.09; P < 0.01) in Caucasians instead of Asians from multiple countries; OCT-derived minimum fibrous cap thickness (FCT) (6 studies with 841 participants; MD, 25.16; 95% CI, 14.06 to 36.27; P < 0.01), incidence of thin-capped fibroatheroma (TCFA) regression (2 studies with 222 participants; OR, 2.56; 95% CI, 1.42 to 4.61; P < 0.01) and maximum lipid arc (4 studies with 280 participants; MD, -14.96; 95% CI, -22.10 to -7.83; P < 0.01) in Asians and Caucasians without races restrictions.<br /><b>Conclusions</b><br />PCSK9 antibodies resulted in significantly greater coronary plaque regression and stabilization in statin-treated CAD patients, mostly Caucasians from multiple countries. Further studies are needed to assess the effect for Asian patients.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 02 Sep 2023:131330; epub ahead of print</small></div>

<div><h4>Mortality after catheter ablation of structural heart disease related ventricular tachycardia.</h4><i>Bennett RG, Garikapati K, Campbell TG, Kotake Y, ... Wong MS, Kumar S</i><br /><b>Background</b><br />There is a paucity of data describing mortality after catheter ablation of ventricular tachycardia (VT).<br /><b>Objectives</b><br />We describe the causes and predictors of cardiac transplant and/or mortality following catheter ablation of structural heart disease (SHD) related VT.<br /><b>Methods</b><br />Over 10-years, 175 SHD patients underwent VT ablation. Clinical characteristics, and outcomes, were compared between patients undergoing transplant and/or dying and those surviving.<br /><b>Results</b><br />During 2.8 (IQR 1.9-5.0) years follow-up, 37/175 (21%) patients underwent transplant and/or died following VT ablation. Prior to ablation, these patients were older (70.3 ± 11.1 vs. 62.1 ± 13.9 years, P = 0.001), had lower left ventricular ejection fraction ([LVEF] 30 ± 12% vs. 44 ± 14%, P < 0.001), and were more likely to have failed amiodarone (57% vs. 39%, P = 0.050), compared to those that survived. Predictors of transplant and/or mortality included LVEF≤35% (HR 4.71 [95% CI 2.18-10.18], P < 0.001), age ≥ 65 years (HR 2.18 [95% CI 1.01-4.73], P = 0.047), renal impairment (HR 3.73 [95% CI 1.80-7.74], P < 0.001), amiodarone failure (HR 2.67 [95% CI 1.27-5.63], P = 0.010) and malignancy (HR 3.09 [95% CI 1.03-9.26], P = 0.043). Ventricular arrhythmia free survival at 6-months was lower in the transplant and/or deceased, compared to non-deceased group (62% vs. 78%, P = 0.010), but was not independently associated with transplant and/or mortality. The risk score, MORTALITIES-VA, accurately predicted transplant and/or mortality (AUC: 0.872 [95% CI 0.810-0.934]).<br /><b>Conclusions</b><br />Cardiac transplant and/or mortality after VT ablation occurred in 21% of patients. Independent predictors included LVEF≤35%, age ≥ 65 years, renal impairment, malignancy, and amiodarone failure. The MORTALITIES-VA score may identify patients at high-risk of transplant and/or dying after VT ablation.<br /><br />Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.<br /><br /><small>Int J Cardiol: 01 Sep 2023; 386:50-58</small></div>

<div><h4>Cardiac amyloidosis in patients with spinal stenosis and yellow ligament hypertrophy.</h4><i>Martín NC, Aurelio RM, María GA, Ángel RM, ... Emilio BL, Jesús PF</i><br /><b>Background</b><br />Spinal stenosis (SS) is a manifestation associated with cardiac amyloidosis (CA). However, there is a lack of studies assessing the prevalence of CA among patients with SS. We aimed to address the prevalence of CA among patients with SS and YLH.<br /><b>Methods</b><br />We performed a cross-sectional study of consecutive patients older than 65 years with SS and yellow ligament hypertrophy (YLH). All the patients were assessed with an electrocardiogram, echocardiogram and biohumoral evaluation. Patients with CA red flags was further studied with cardiac magnetic resonance and 99mTc-DPD scintigraphy. A cohort of patients with confirmed CA and SS was used to assess clinical features associated with CA.<br /><b>Results</b><br />105 patients (75.0 ± 6.6 years old; 45.7% males) with SS and YLH [5.5 [5-7] mm] were screened. Prevalence of red flags of CA was high and 58 patients presented clinical suspicion of CA. One patient (0.95%) was finally diagnosed of CA. Patients with confirmed CA presented a more expressive phenotype than the screened population. Patients with suspected CA had greater YLH than patients without suspicion of CA (6.4 ± 1.3 vs. 5.0 ± 0.8 mm; p < 0.001) and patients with confirmed CA presented greater YLH than the screening population (6.7 ± 1.8 vs. 5.7 ± 1.2 mm; p = 0.018).<br /><b>Conclusion</b><br />Despite red flags of CA are common among patients with SS, the prevalence of confirmed CA was low in our sample of screened patients.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 30 Aug 2023:131301; epub ahead of print</small></div>

<div><h4>Is there a reduced confidence towards direct oral anticoagulants compared to vitamin K antagonists in patients scheduled for an elective electrical cardioversion? The results of the BLITZ-AF study.</h4><i>Cemin R, Maggioni AP, Boriani G, Di Pasquale G, ... Gulizia MM, on the behalf of BLITZ-AF Investigators</i><br /><b>Objective</b><br />To study the confidence of cardiologists in performing an electrical cardioversion in patients on oral anticoagulation (OA) with or without transoesophageal echocardiography (TOE).<br /><b>Methods</b><br />Data about atrial fibrillation (AF) patients admitted to cardiology wards for elective cardioversion (ECV) were extrapolated from the BLITZ-AF study. Percentage of vitamin K antagonists (VKAs), direct oral anticoagulants (DOAC) and heparin prescription were analysed in relation to the use of TOE before ECV.<br /><b>Results</b><br />Overall rate of TOE was 33.7% (240/713); it was used before ECV in 124/313 (39.6%) of DOACs patients and in 96/372 (25.8%) of the patients on VKAs, showing a significant reduced resort to TOE in VKAs patients (p = 0.0001). Among non-valvular patients TOE was more frequently performed in males, at younger ages and in patients on heparin when compared to patients treated with OA. TOE was also more frequently performed in tertiary hospitals and in hospitals with cardiology wards and electrophysiology labs, when compared to hospital provided only with cardiology wards. At multivariable analysis there was a significant less recourse to TOE in patients on VKAs (OR 0.47; 95% CI: 0.33-0.67) and higher recourse in the heparin group (OR: 3.85; 95% CI:1.59-9.28) with respect to patients on DOACs; a higher recourse to TOE was observed also in tertiary hospitals (OR 4.25; 95% CI 2.69-6.69) and in hospitals with cardiology wards and electrophysiology (EP) labs (OR 1.87; 95% CI 1.23-2.82).<br /><b>Conclusion</b><br />our study shows the reluctance in cardioverting patients on DOACs respect to VKAs without a previous TOE, despite adequate anticoagulant treatment.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 Aug 2023:131302; epub ahead of print</small></div>

<div><h4>Blockade of CXCR4 promotes macrophage autophagy through the PI3K/AKT/mTOR pathway to alleviate coronary heart disease.</h4><i>Li F, Peng J, Lu Y, Zhou M, ... Luo P, Xia B</i><br /><b>Objective</b><br />Autophagy is important in regulating inflammation and cholesterol efflux, suggesting that targeting autophagy may slow down atherosclerosis (AS). Since the pathological basis of coronary artery disease (CAD) is atherosclerosis, it is crucial to investigate the role of autophagy in atherosclerosis. This study aimed to investigate the role of the chemokine CXC chemokine receptor 4 (CXCR4) in promoting macrophage autophagy through the phosphoinositide-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway to alleviate coronary artery disease.<br /><b>Methods</b><br />The human left coronary artery and myocardium were collected to detect CXCR4, MAP1LC3(LC3) and SQSTM1(p62) expression. ApoE-/- mice were used to establish an atherosclerosis mice model, while human monocytes (THP-1) were used to establish a foam cell model and co-cultured with foam cells using siRNACXCR4. Western blotting was conducted to quantify CXCR4, PI3K/AKT/mTOR pathway protein, LC3, Beclin1 and p62 protein levels. The left coronary artery from humans and mouse aorta and myocardium were stained with Hematoxylin and Eosin (H&E), macrophages with Oil Red O staining and foam cells were assessed by Movat\'s staining. CXCR4 levels, PI3K/AKT/mTOR pathway protein, LC3 and p62 were detected by immunohistochemistry (IHC) and immunofluorescence assays. Detection of autophagosomes in macrophages using transmission electron microscopy. We further assessed whether the effect of CXCR4-mediated macrophage autophagy on the formation of atherosclerosis and structural changes in the myocardium was mediated via the PI3K/AKT/mTOR signaling pathway.<br /><b>Results</b><br />CXCR4 and p62 proteins were upregulated in human coronary lesions, mouse aorta, myocardial tissue, and foam cells, while LC3II/LC3I was downregulated. p85 (P-PI3K), Ser473 (P-AKT), and Ser2448 (P-mTOR) phosphorylated proteins associated with the PI3K/AKT/mTOR pathway were detected in AS and foam cell models. Upregulated CXCR4 inhibited autophagy of macrophages and increased the severity of atherosclerotic lesions. After specific knockdown of CXCR4 by adeno-associated virus (AAV9-CXCR4-RNAi) and siRNACXCR4, the above indicators were reversed, macrophage autophagy was promoted, the severity of atherosclerotic lesions was reduced, and the disorganized arrangement of myocardial architecture was improved.<br /><b>Conclusion</b><br />Knockdown of CXCR4 reduces the extent of coronary artery disease by promoting macrophage autophagy through the PI3K/AKT/mTOR pathway to attenuate atherosclerosis.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 Aug 2023:131303; epub ahead of print</small></div>

<div><h4>Association between SARS-CoV-2 infection and new-onset atrial fibrillation.</h4><i>Rosh B, Naoum I, Barnett-Griness O, Najjar-Debbiny R, Saliba W</i><br /><b>Background</b><br />Atrial fibrillation (AF) is associated with substantial morbidity and mortality. New-onset AF (NOAF) has been related recently to SARS-CoV-2 infection; however, the evidence supporting this link is still scarce. We aimed to examine the association between SARS-CoV-2 infection and NOAF.<br /><b>Methods</b><br />We conducted a nested-case control study in a cohort of 2,931,046 adults from the largest healthcare provider in Israel. Subjects were followed from March 1st, 2020, until June 30th, 2022, for the occurrence of NOAF. Ten randomly selected controls were matched to each case of NOAF on age, sex, and duration of follow-up. Exposure to SARS-CoV-2 infection in the prior 30 days was assessed in cases and controls. To account for surveillance bias we performed a lag-time analysis and assessed the association with a negative control exposure (low back pain). Data was analyzed using conditional logistic regression.<br /><b>Results</b><br />During the follow-up 18,981 patients developed NOAF and were matched to 189,810 controls. The mean age of cases and matched controls was 73.8 ± 13 years, and 51.1% of them were women. Multivariable analysis showed that SARS-CoV-2 infection was associated with an increased risk of NOAF; adjusted-OR, 4.24 (95% CI, 3.89-4.62). The association remained significant on lag-time analysis; however, the strength of the association was gradually attenuated with increasing lag-time but stabilized around a lag-time of 20 days. The negative control exposure (low back pain) was associated only with small increased risk of NOAF; adjusted-OR of 1.13 (95% CI, 1.02-1.26).<br /><b>Conclusion</b><br />SARS-CoV-2 infection appears to be associated with increased risk of NOAF.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 Aug 2023:131298; epub ahead of print</small></div>