Journal: Int J Cardiol

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Abstract
<div><h4>A comprehensive meta-analysis comparing radiofrequency ablation versus pharmacological therapy for the treatment of atrial fibrillation in patients with heart failure.</h4><i>Casula M, Pignalosa L, Quilico F, Scajola LV, Rordorf R</i><br /><b>Background</b><br />Atrial fibrillation (AF) and heart failure (HF) are both associated with worse prognosis and often coexist in the same patients. Whether catheter ablation (CA) is superior to pharmacological therapy in reducing major clinical endpoints in patients with AF and HF is still unsettled.<br /><b>Objective</b><br />To conduct a comprehensive meta-analysis comparing CA with medical therapy (MT) in this population.<br /><b>Methods</b><br />We systematically searched for randomized and observational studies comparing clinical outcomes between patients with AF and HF treated with CA or MT. The studied outcomes were mortality, hospitalization, left ventricle ejection fraction (LVEF) and 6-min walking test (6MWT) improvement.<br /><b>Results</b><br />A total of 12 studies counting 41,377 patients (3611 treated with CA and 37,766 with MT) were included in the analysis. The random-effect model revealed a clear trend in favor of CA in reducing unexpected HF hospitalization (RR 0.72; 95%CI 0.51-1.00; P = 0.05), all-cause death (RR 0.77; 95%CI 0.59-1.01; P = 0.06), all-cause hospitalization (RR 0.84; 95%CI 0.68-1.03; P = 0.09), and the composite of HF hospitalization and death (RR 0.77; 95%CI 0.58-1.02; P = 0.07), compared with MT. Patients treated with CA experienced a better improvement in LVEF (mean difference 6.17; 95%CI 2.98-9.37; P = 0.0002) and 6MWT (mean difference 13.70; 95%CI 3.95-23.45; P = 0.006). When the analysis was limited to randomized controlled trial, CA was found to significantly reduce all-cause death (RR 0.68; 95%CI 0.54-0.86; P = 0.001).<br /><b>Conclusion</b><br />As compared to MT, CA is associated with a better improvement in functional capacity and LVEF, and with a reduction in major clinical endpoints in patients with HF and AF.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 26 Jan 2023; epub ahead of print</small></div>
Casula M, Pignalosa L, Quilico F, Scajola LV, Rordorf R
Int J Cardiol: 26 Jan 2023; epub ahead of print | PMID: 36709925
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<div><h4>Severe mitral regurgitation in nonagenarians: Impact of symptomatic status, frailty and etiology on management and outcomes.</h4><i>Crane AD, Saijo Y, Kocyigit D, Tharwani A, ... Griffin BP, Xu B</i><br /><b>Background</b><br />Data regarding mitral regurgitation (MR) in extremely elderly patients are limited. The aim of the present study was to assess symptomatic status, frailty, etiology and outcomes for nonagenarians with severe MR.<br /><b>Methods</b><br />Single-center cohort study of patients ≥90 years of age with at least 3+ MR on echocardiography between September 2010 and August 2018. Out of a total of 11,998 patients with at least 3+ MR, 267 patients were included in the present study.<br /><b>Results</b><br />The average age was 93.5 ± 2.6 years, and 57% were female. At baseline, 88% were symptomatic, with mean Charlson co-morbidity index of 6 ± 2 points, and mean frailty score of 2.9 ± 1.4 points. Primary MR was present in 50%, secondary in 47%, and prosthetic valve dysfunction in 3%. Among patients with primary MR, the most common etiology was mitral annular calcification (58%). In comparison, the most common etiology of secondary MR was atrial functional MR (52%). Of all, 95% were treated conservatively, and 5% underwent interventional management. Among 253 patients who had follow-up data with a median follow-up of 14 months (25th-75th interquartile range: 3-31 months), 191 patients (75%) died. Mortality trended higher in the conservative group versus the interventional group (60% vs. 22%, log-rank P = 0.063).<br /><b>Conclusions</b><br />Most nonagenarians with significant MR were symptomatic at presentation, had elevated Charlson co-morbidity index and frailty score. Etiologies of MR were almost equally distributed between primary and secondary causes. The vast majority of nonagenarians with significant MR were conservatively managed.<br /><br />Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 23 Jan 2023; epub ahead of print</small></div>
Crane AD, Saijo Y, Kocyigit D, Tharwani A, ... Griffin BP, Xu B
Int J Cardiol: 23 Jan 2023; epub ahead of print | PMID: 36702362
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<div><h4>Comparison of vessel fractional flow reserve with invasive resting full-cycle ratio in patients with intermediate coronary lesions.</h4><i>Lake P, Halbach M, Kardasch M, Mauri V, ... Adam M, Wienemann H</i><br /><b>Background</b><br />Vessel fractional flow reserve (vFFR) is a novel angiography-derived index for the assessment of myocardial ischemia without the need for pressure wires and hyperemic agents. vFFR has demonstrated very good diagnostic performance compared with the hyperemic index fractional flow reserve (FFR). The aim of this study was to compare vFFR to the non-hyperemic pressure ratio resting full-cycle ratio (RFR).<br /><b>Methods</b><br />This was a retrospective, observational, single-center study of an all-comer cohort undergoing RFR assessment. Invasive coronary angiography was obtained without a dedicated vFFR acquisition protocol, and vFFR calculation was attempted in all vessels interrogated by RFR (1483 lesions of 1030 patients).<br /><b>Results</b><br />vFFR could be analyzed in 986 lesions from 705 patients. Median diameter stenosis was 37% (interquartile range (IQR): 30.0-44.0%), vFFR 0.86 (IQR: 0.81-0.91) and RFR 0.94 (IQR: (0.90-0.97). The correlation between vFFR and RFR was strong (r = 0.70, 95% confidence interval (CI): 0.66-0.74, p < 0.001). Using RFR ≤0.89 as reference, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy for vFFR were 77%, 93%, 77%, and 92% and 89%. vFFR yielded a high area under the curve (AUC) of 0.92 (95% CI: 0.90-0.94). The good diagnostic performance of vFFR was confirmed among subgroups of patients with diabetes, severe aortic stenosis, female gender and lesions located in the left anterior descending.<br /><b>Conclusion</b><br />vFFR has a high diagnostic performance taking RFR as the reference standard for evaluating the functional significance of coronary stenoses.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 21 Jan 2023; epub ahead of print</small></div>
Lake P, Halbach M, Kardasch M, Mauri V, ... Adam M, Wienemann H
Int J Cardiol: 21 Jan 2023; epub ahead of print | PMID: 36693476
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<div><h4>Association with carotid plaque parameters detected on contrast-enhanced ultrasound and coronary artery plaque progression in non-culprit lesions: A retrospective study.</h4><i>Ren L, Han Y, Long M, Yan L, ... Fei X, Luo Y</i><br /><b>Aim</b><br />To investigate the correlation between carotid plaque parameters detected on contrast-enhanced ultrasound(CEUS) and the plaque progression in non-culprit coronary lesions (NCCLs) after percutaneous coronary intervention (PCI).<br /><b>Methods</b><br />In this retrospective cross-sectional study, we analyzed 173 patients who underwent PCI. Patients were stratified into two groups (progression and non-progression groups) by comparing the coronary angiography (CAG) results at baseline and follow-up. The correlation between carotid plaque parameters and plaque progression in NCCLs was analyzed by multivariate logistic regression analysis. A logistic regression model was established to predict NCCLs progression.<br /><b>Results</b><br />Overall, 55 of 173 patients exhibited NCCLs progression (31.79%). Univariate comparisons showed that plaque thickness, plaque length, and IPN score were significantly higher in the progressive group than in the non-progressive group (P < 0.01). Multivariate logistic regression analysis revealed that carotid plaque length (OR = 3.418, 95% CI =1.101-10.610) and IPN score (OR = 7.395, 95% CI =3.154-17.342) were strongly associated with plaque progression in NCCLs. After adjusting for confounders, the history of previous PCI, plaque length, and IPN score were independent predictors of the NCCLs progression (P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the logistic regression model in predicting the NCCLs progression were 62.50%, 90.53%, 81.12%, 76.92%, and 82.69%, respectively, and the area under the receiver operating characteristic (ROC) curve was 0.882 (95% CI: 0.826-0.939).<br /><b>Conclusions</b><br />Carotid plaque length and IPN score were strongly correlated with plaque progression in NCCLs. Combining the history of previous PCI can reasonably predict the NCCLs progression.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 19 Jan 2023; epub ahead of print</small></div>
Ren L, Han Y, Long M, Yan L, ... Fei X, Luo Y
Int J Cardiol: 19 Jan 2023; epub ahead of print | PMID: 36682688
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<div><h4>Neonatal systemic hypertension across the PHIS database: An update.</h4><i>AlMaazmi A, Hagan J, Fernandes CJ, Gowda SH</i><br /><b>Background</b><br />The definition of systemic hypertension in the neonatal population remains elusive given the variability of normative blood pressure measurements. Inadequate literature exists about incidence, therapy and long-term management of systemic hypertension in neonates. We aimed to describe the current incidence of neonatal systemic hypertension, differences in demographic and risk factors data.<br /><b>Methods</b><br />Retrospective cohort of neonates (≤28 days) admitted to a neonatal intensive care unit participating in Pediatric Health Information System (PHIS) between Jan 2010 and December 2020 with an ICD 9/10 code for hypertension. Patients were excluded if they had congenital heart disease lesions that might contribute to systemic hypertension or had incomplete data.<br /><b>Results</b><br />There were a total of 2494 hypertensive patients among the 432,367 NICU patients meeting the study inclusion criteria, with an incidence of 0.6%. Patients with hypertension were significantly more likely to die before discharge compared to patients without HTN (8.4% versus 3.8%, respectively, p < 0.001). Of the 2494, 52.8% received at least one antihypertensive agent, with hydralazine being the most prescribed agent (29.7%).<br /><b>Conclusion</b><br />Diagnosis of Systemic hypertension continues to increase in the neonatal population, despite absence of well-defined criteria necessitating targeted medical management. A consensus guideline which addresses this very important condition is beneficial.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 19 Jan 2023; epub ahead of print</small></div>
AlMaazmi A, Hagan J, Fernandes CJ, Gowda SH
Int J Cardiol: 19 Jan 2023; epub ahead of print | PMID: 36682689
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<div><h4>PASCAL repair system for patients with mitral regurgitation: A systematic review.</h4><i>Srinivasan A, Brown J, Ahmed H, Daniel M</i><br /><b>Background</b><br />Transcatheter edge-to-edge repair (TEER) of the mitral valve has emerged as the standard treatment for patients with mitral regurgitation (MR) with high surgical risk. Even though MitraClip is widely used, the novel PASCAL device system offers distinct technical features. We aim to study the safety and efficacy of the PASCAL repair system in clinically significant MR.<br /><b>Methods</b><br />PubMed, Medline, Cochrane Central Register of Controlled Trials, and EMBASE were searched for articles published from August 2016 until June 2022 to identify studies that investigated the safety and efficacy of PASCAL for patients with degenerative, functional and mixed MR. Primary performance endpoints were technical, device, and procedural successes. Primary safety endpoint was composite 30 day major adverse events (MAE). Secondary endpoints were MR grade at discharge and 30 days, 30 day postprocedural NYHA functional class, left ventricular ejection fraction (LVEF), change in 6-min walk distance (6MWD), 30-day and 12-month all-cause mortality.<br /><b>Results</b><br />We included twelve retrospective and prospective observational studies and one randomized controlled study consisting of 1028 patients with severe, symptomatic MR (NYHA III-IV: 84.0%, MR ≥ 3+: 99.7%) and high surgical risk (mean logistic EuroSCORE of 16.4).Technical success was 95.7%, procedural success was 95.2%, and device success was 86.1% relative to the weighted average. MR grade was ≤2+ in 94.7% of patients at discharge and 94.0% patients at 30-day follow-up. Mean 30-day and 12-month mortality after device implantation were 4.54% and 12.2%.<br /><b>Conclusion</b><br />The PASCAL repair system appears to be a safe and effective therapeutic option to treat severe, symptomatic MR in high surgical risk patients.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 18 Jan 2023; epub ahead of print</small></div>
Srinivasan A, Brown J, Ahmed H, Daniel M
Int J Cardiol: 18 Jan 2023; epub ahead of print | PMID: 36681242
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<div><h4>Handheld echocardiographic screening for rheumatic heart disease by non-experts in rural South Kordofan, Sudan: Supporting task shifting for control of a serious disease.</h4><i>Elazrag A, Altahir A, Abbas A, Hasabo E, ... Elnaiem W, Ali S</i><br /><b>Background</b><br />Rheumatic heart disease (RHD) is a major and preventable cause of cardiac morbidity in Sudan. It can be detected early with a handheld echocardiography (HHE) machine. Our study aimed to screen for RHD in rural South Kordofan and to investigate the ability of non-experts to obtain good quality HHE records.<br /><b>Methods</b><br />A cross-sectional study was conducted in South Kordofan, Sudan. A team of non-experts was trained for two weeks on handheld echocardiographic screening for RHD using a simplified protocol. Cases were recorded and reviewed by a pediatric cardiologist. Demographic and clinical features of screened subjects were studied. Descriptive statistics were presented as \"number (%)\" or \"mean ± SD\". RHD frequency was expressed as cases per 1000, and the Chi-Square test/Fisher\'s Exact test was used to compare RHD findings between different groups.<br /><b>Results</b><br />A total of 467 subjects were screened. Echocardiographic quality was acceptable in 93% of recorded studies, hence 452 cases were included in the analysis. The disease frequency was found to be 50 per 1000. Out of 452 screened subjects (age 10-25 years), 23 were found to have RHD. The disease was mild in 70% and moderate or involving two valves in 30% of patients. Risk factors for the disease included the father\'s occupation and the village of residence.<br /><b>Conclusion</b><br />Shortly trained non-expert medicals can assist in RHD surveillance in remote areas using HHE for early detection and management. South Kordofan state is highly endemic to RHD and a control program needs to be implemented.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 18 Jan 2023; epub ahead of print</small></div>
Elazrag A, Altahir A, Abbas A, Hasabo E, ... Elnaiem W, Ali S
Int J Cardiol: 18 Jan 2023; epub ahead of print | PMID: 36681245
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<div><h4>Cardiac computed tomography based analysis of mitral annulus, coronary sinus and left circumflex artery in patients with mitral regurgitation: Implications for transcatheter mitral annuloplasty techniques.</h4><i>Lin F, Wang Q, Meng L, Liang Y, ... Zhang Q, Gu X</i><br /><b>Introduction</b><br />CT imaging analysis of mitral annulus (MA), coronary sinus (CS) and left circumflex artery (LCX) is critical to transcatheter mitral annuloplasty (TMA), which, however, is scantly reported. We aimed to comprehensively assess MA, CS and LCX anatomy and geometry in mitral regurgitation (MR) based on 3-D reconstruction of cardiac CT images.<br /><b>Methods</b><br />Patients with primary or secondary MR and patients without MR were recruited and underwent cardiac CT examination. MR severity was evaluated by echocardiography. 3-D reconstruction of cardiac CT images was done by the Mimics Research 21.0 software. A MA-centered two dimensional coordinate system, a CS plane, a MA plane and a series of auxiliary planes along the posterior MA were created for the measurement of parameters defining MA, CS and LCX anatomy and geometry during the cardiac cycle.<br /><b>Results</b><br />The secondary MR group had a significantly higher MA perimeter index than the other two groups during the cardiac cycle. The CS diameters at most sites, and the posterior MA radian were substantially greater in the two MR groups. Distances between the CS and MA at some locations were significant different among the three groups. The secondary MR group had a significantly smaller CS-MA plane angle than the other two groups during systole, and than control group during diastole. The site where the CS crossed LCX was pinpointed.<br /><b>Conclusion</b><br />The comprehensive information from this study may help improve the results of TMA and enhance the design of devices for a better annuloplasty effect.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 18 Jan 2023; epub ahead of print</small></div>
Abstract
<div><h4>Transcatheter valve-in-valve or valve-in-ring implantation with a novel balloon-expandable device in patients with bioprosthetic left side heart valves failure: 1-year follow-up from a multicenter experience.</h4><i>Moscarella E, Ielasi A, Mussayev A, Montorfano M, ... Bedogni F, Tespili M</i><br /><b>Background</b><br />Transcatheter aortic and mitral valve-in-valve (ViV) or valve-in-ring (ViR) implantation into failed bioprosthetic heart valves (BHVs) or rings represents an appealing, less invasive, treatment option for patients at high surgical risk. Nowadays, few data have been reported on the use of balloon-expandable Myval (Meril Life Science, Vapi, India) transcatheter heart valve (THV) for the treatment of degenerated BHVs or rings. We aimed at evaluating the early and mid-term clinical outcomes of patients with left side heart bioprosthesis deterioration treated with transcatheter ViV/ViR implantation using Myval THV.<br /><b>Methods</b><br />97 consecutive patients with symptomatic, severe aortic(n=33) and mitral(n=64) BHVs/ring dysfunction underwent transcatheter aortic ViV and mitral ViV/ViR implantation with Myval THV.<br /><b>Results</b><br />Technical success was achieved in 95 (98%) of the patients. Two cases of acute structural trans-catheter mitral ViV/ViR dysfunction requiring a second THV implantation were reported. At 30-day, a significant reduction in prosthetic trans-valvular pressure gradients and increase in valve areas were seen following both aortic and mitral ViV/ViR implantation. Overall survival at 15 months (IQR 8-21) was 92%. Patients undergoing mitral ViV/ViR had a relatively worse survival compared with those undergoing aortic ViV implantation (89% vs. 97% respectively; HR:2.7,CI:0.33-22.7;p=0.34). At longest follow-up available a significant improvement in NYHA functional class I and II was observed in patients with aortic and mitral ViV/ViR implantation(93.8% and 92.1%).<br /><b>Conclusions</b><br />Despite high surgical risk, transcatheter ViV/ViR implantation for failed left side heart bioprosthesis can be performed safely using Myval THV with a high success rate and low early and mid-term mortality and morbidity.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Jan 2023; epub ahead of print</small></div>
Moscarella E, Ielasi A, Mussayev A, Montorfano M, ... Bedogni F, Tespili M
Int J Cardiol: 16 Jan 2023; epub ahead of print | PMID: 36657566
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<div><h4>Immature neutrophil is associated with coronary plaque vulnerability based on optical coherence tomography analysis.</h4><i>Wan M, Lu Y, Mao B, Yu S, ... Li X, Zhuang J</i><br /><b>Introduction</b><br />High neutrophil to lymphocyte ratio is considered to predict poor prognosis of acute coronary syndrome (ACS). However, the association of neutrophil subpopulation with plaque vulnerability and the incidence of ACS remains unknown.<br /><b>Methods and results</b><br />Blood samples from 48 patients with unstable angina (UA), 31 with ST-segment elevation myocardial infarction (STEMI) and 33 healthy controls were collected at admission. The morphology of coronary plaques in 48 UA patients were further evaluated by optical coherence tomography (OCT). According to maturation stages of neutrophils and the expression of CD10 and CD101, circulating neutrophils could be divided into pre-neutrophils (CD101<sup>-</sup>CD10<sup>-</sup>), immature neutrophils (CD101<sup>+</sup>CD10<sup>-</sup>) and mature neutrophils (CD101<sup>+</sup>CD10<sup>+</sup>). While the number of pre-neutrophil was quite low in blood and comparable among three groups, the absolute counts and percentage of CD10<sup>-</sup> immature neutrophils were higher in peripheral bloods of UA and STEMI patients compared with those in healthy controls. The concentration of plasma myeloperoxidase was positively associated with the percentage of CD10<sup>-</sup> immature neutrophils. Furthermore, UA patients with thin-cap fibroatheroma (TCFA) observed by OCT had a higher proportion and larger number of immature neutrophils as compared to those without TCFA. The percentage of immature neutrophils also closely correlated with plaque rupture and the feature of vulnerable plaque, including thinner fibrous cap and larger lipid core, but did not associate with percent lumen stenosis.<br /><b>Conclusion</b><br />Our findings emphasize that the abnormally increased level of CD10<sup>-</sup> immature neutrophils may sever as a promising marker of the incidence of ACS and plaque vulnerability.<br /><br />Copyright © 2023 The Author. Published by Elsevier B.V. All rights reserved.<br /><br /><small>Int J Cardiol: 14 Jan 2023; epub ahead of print</small></div>
Wan M, Lu Y, Mao B, Yu S, ... Li X, Zhuang J
Int J Cardiol: 14 Jan 2023; epub ahead of print | PMID: 36649888
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<div><h4>Estimation of adverse events associated with P2Y12 receptor inhibitors stratified by academic research consortium for high bleeding risk criteria in acute coronary syndrome.</h4><i>Fujii T, Endo S, Tsuchiya R, Nagamatsu H, ... Yoshimachi F, Ikari Y</i><br /><b>Background</b><br />The usefulness of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria in the selection of P2Y12 receptor inhibitors for acute coronary syndrome is unknown. This study investigated whether the selection of antiplatelet agents according to the ARC-HBR criteria could improve clinical outcomes.<br /><b>Methods</b><br />This multicenter retrospective study included 1261 patients with acute coronary syndrome who received dual antiplatelet therapy, namely clopidogrel (75 mg, n = 529) or prasugrel (3.75 mg, n = 732) in addition to aspirin. The primary endpoint was net adverse clinical events (NACE) after hospital admission, including ischemic (death, myocardial infarction, ischemic stroke) and bleeding events (Bleeding Academic Research Consortium 3 or 5). Secondary outcomes were ischemic and bleeding events. For each patient, the observation period was defined as the duration of dual antiplatelet therapy after admission.<br /><b>Results</b><br />During the observation period (average: 313 days), the rate of NACE was lower in the prasugrel group than the clopidogrel group (20.6% vs. 12.6%, respectively, P < 0.01). In patients who satisfied or did not satisfy the ARC-HBR criteria, prasugrel was associated with a 3.7% and 2.1% lower incidence of NACE, respectively, versus clopidogrel. Ischemic and bleeding events were less frequent in the prasugrel group than the clopidogrel group (11.5% vs. 7.9%, respectively, P = 0.03; 10.6% vs. 5.2%, respectively, P < 0.01). The estimated incidence models for NACE suggested that the difference between clopidogrel and prasugrel was greater in patients who satisfied the ARC-HBR criteria than in those who did not.<br /><b>Conclusions</b><br />Prasugrel is preferable to clopidogrel regardless of the ARC-HBR.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 14 Jan 2023; epub ahead of print</small></div>
Fujii T, Endo S, Tsuchiya R, Nagamatsu H, ... Yoshimachi F, Ikari Y
Int J Cardiol: 14 Jan 2023; epub ahead of print | PMID: 36649890
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<div><h4>Invasive management of significant tricuspid regurgitation in clinical practice.</h4><i>Moral S, Abulí M, Méndez I, González-Gómez A, ... Brugada R, Evangelista A</i><br /><b>Background</b><br />Tricuspid regurgitation (TR) is a prevalent condition inside valvular heart disease (VHD) with relevant prognosis implications. However, concordance between real management in clinical practice and invasive treatment recommendations of European Society of Cardiology (ESC) guidelines is unknown.<br /><b>Methods</b><br />A substudy of ESC VHD II survey was performed to evaluate the real treatment of TR compared to the clinical ESC guidelines recommendations published in 2012, 2017 and 2021 was performed. TR cases with surgical indication were divided in 3 groups: 1: severe isolated TR without previous left VHD; 2: moderate/severe TR and concomitant severe left VHD; 3: severe TR plus previous left VHD surgery.<br /><b>Results</b><br />Of 902 patients assessed, 123 had significant TR. Fifty (41%) cases demonstrated ESC guidelines 2012-2017 Class I or IIa recommendations for invasive treatment: 9(18%) of group 1, 37(74%) of group 2 and 4(8%) of group 3. Surgery was performed in 24 patients (48%); 1 in group 1(4%), 22 in group 2(92%) and 1 in group 3(4%). Overall concordance was 48% (group 1: 11%; group 2: 59%; group 3: 25%). Regarding the 2021 ESC guidelines only one patient changed groups with an overall concordance of 47% (group 1: 10%; group 2: 59%; group 3: 25%).<br /><b>Conclusion</b><br />Concordance between 2012, 2017 and 2021 ESC guidelines recommendations and clinical practice for TR surgical intervention is low, especially in those without concomitant severe left VHD. These results suggest the need to improve further guideline implementation and alternative treatments, such as percutaneous, which could resolve potential discrepancies in those clinical scenarios.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 12 Jan 2023; epub ahead of print</small></div>
Moral S, Abulí M, Méndez I, González-Gómez A, ... Brugada R, Evangelista A
Int J Cardiol: 12 Jan 2023; epub ahead of print | PMID: 36642332
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<div><h4>Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension: Relationship between treated branches and outcome.</h4><i>D\'Armini AM, Pin M, Celentano A, Te Masiglat LJ, ... Pellegrini C, Ghio S</i><br /><b>Background</b><br />In patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA) it is important to minimize residual obstructions, in order to achieve low postoperative pulmonary vascular resistances and better clinical results. The aim of the study was to test the hypothesis that the greater the number of pulmonary artery branches treated at surgery, the better the hemodynamic and clinical outcome after PEA.<br /><b>Methods</b><br />In 564 consecutive CTEPH patients undergoing PEA the count of the number of treated branches was performed directly on the surgical specimens. Post-operative follow-up visits were scheduled at 3 months and 12 months after surgery including right heart catheterization and Bruce test.<br /><b>Results</b><br />The population was divided into tertiles based on the number of treated branches: Group 1 (from 4 to 30 treated branches, n = 194 patients); Group 2 (from 31 to 43 treated branches, n = 190 patients); Group 3 (from 44 to 100 treated branches, n = 180 patients). At 3 and at 12 months after PEA, after adjustment for confounders, patients in the highest tertile of treated branches had significantly lower values of PVR and of pulmonary arterial compliance (PCa) as compared to the other two groups (p < 0.002). Hospital mortality was 3% in Group 3, 6% in Group 2 and 10% in Group 1 (overall p = 0.035).<br /><b>Conclusions</b><br />In CTEPH patients undergoing PEA, a higher number of treated pulmonary artery branches is associated with a better hemodynamic and a better clinical outcome at 3 months and 12 months after surgery.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 12 Jan 2023; epub ahead of print</small></div>
D'Armini AM, Pin M, Celentano A, Te Masiglat LJ, ... Pellegrini C, Ghio S
Int J Cardiol: 12 Jan 2023; epub ahead of print | PMID: 36642333
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<div><h4>Thrombospondin-1 plasma levels associated with in-hospital major adverse cardiovascular events in patients with acute coronary syndrome.</h4><i>Ma Z, Wang M, Xu X, Zhang Y, ... Su P, Zhao L</i><br /><b>Background</b><br />Thrombospondin-1, a large matricellular glycoprotein, exerts multifaced biological effects on the cardiovascular system and is correlated with cardiovascular diseases. Its plasma levels and correlation with in-hospital prognosis are yet unclear in the acute coronary syndrome population. The present study aimed to evaluate the correlation between thrombospondin-1 plasma levels and in-hospital adverse events in patients with acute coronary syndrome.<br /><b>Methods</b><br />This is a cross-sectional study. A total of 341 inpatients with acute coronary syndrome were recruited in Beijing Chaoyang Hosipital from May 2021 to November 2021. The thrombospondin-1 plasma levels were measured, and the in-hospital major adverse cardiovascular events, including all-cause death, recurrent ischemia, arrhythmias, and heart failure, were recorded. This correlation was assessed by logistic regression analysis.<br /><b>Results</b><br />The thrombospondin-1 plasma levels were higher in patients with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction compared to those in unstable angina (P < 0.001), while the differences between the two different types of myocardial infarction were not statistically different. Thrombospondin-1 plasma levels were correlated with GRACE score, leukocytes, neutrophils, platelets, troponin I, creatine kinase-MB, D-dimer, C-reactive protein, erythrocyte sedimentation rate, and log10 brain natriuretic peptide. Furthermore, thrombospondin-1 plasma levels were associated with the in-hospital major adverse cardiovascular events in patients with acute coronary syndrome (P = 0.001).<br /><b>Conclusions</b><br />Thrombospondin-1 plasma levels were higher in patients with myocardial infarction than those in unstable angina. The high thrombospondin-1 plasma levels were associated with in-hospital major adverse cardiovascular events.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 11 Jan 2023; epub ahead of print</small></div>
Ma Z, Wang M, Xu X, Zhang Y, ... Su P, Zhao L
Int J Cardiol: 11 Jan 2023; epub ahead of print | PMID: 36640963
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<div><h4>Impact of core laboratory assessment on treatment decisions and clinical outcomes using combined fractional flow reserve and coronary flow reserve measurements - DEFINE-FLOW core laboratory sub-study.</h4><i>van de Hoef TP, Stegehuis VE, Madera-Cambero MI, van Royen N, ... Escaned J, Piek JJ</i><br /><b>Objective</b><br />The role of combined FFR/CFR measurements in decision-making on coronary revascularization remains unclear. DEFINE-FLOW prospectively assessed the relationship of FFR/CFR agreement with 2-year major adverse cardiac event (MACE) and target vessel failure (TVF) rates, and uniquely included core-laboratory analysis of all pressure and flow tracings. We aimed to document the impact of core-laboratory analysis on lesion classification, and the relationship between core-laboratory fractional flow reserve (FFR) and coronary flow reserve (CFR) values with clinical outcomes and angina burden during follow-up.<br /><b>Methods</b><br />In 398 vessels (348 patients) considered for intervention, ≥1 coronary pressure/flow tracing was approved by the core-laboratory. Revascularization was performed only when both FFR(≤0.80) and CFR(<2.0) were abnormal, all others were treated medically.<br /><b>Results</b><br />MACE was lowest for concordant normal FFR/CFR, but was not significantly different compared with either discordant group (low FFR/normal CFR: HR:1.63; 95%CI:0.61-4.40; P = 0.33; normal FFR/low CFR: HR:1.81; 95%CI:0.66-4.98; P = 0.25). Moreover, MACE did not differ between discordant groups treated medically and the concordant abnormal group undergoing revascularization (normal FFR/low CFR: HR:0.63; 95%CI:0.23-1.73;P = 0.37; normal FFR/low CFR: HR:0.70; 95%CI:0.22-2.21;P = 0.54). Similar findings applied to TVF.<br /><b>Conclusions</b><br />Patients with concordantly normal FFR/CFR have very low 2-year MACE and TVF rates. Throughout follow-up, there were no differences in event rates between patients in whom revascularization was deferred due to preserved CFR despite reduced FFR, and those in whom PCI was performed due to concordantly low FFR and CFR. These findings question the need for routine revascularization in vessels showing low FFR but preserved CFR.<br /><b>Clinical trial registration</b><br />ClinicalTrials.govNCT02328820.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 11 Jan 2023; epub ahead of print</small></div>
van de Hoef TP, Stegehuis VE, Madera-Cambero MI, van Royen N, ... Escaned J, Piek JJ
Int J Cardiol: 11 Jan 2023; epub ahead of print | PMID: 36640965
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<div><h4>Reducing cardiac tamponade caused by temporary pacemaker perforation in transcatheter aortic valve replacement.</h4><i>Feldt K, Dalén M, Meduri CU, Kastengren M, ... Linder R, Settergren M</i><br /><b>Background</b><br />Cardiac tamponade caused by temporary right ventricular (RV) pacemaker perforation is a rare but serious complication in transcatheter aortic valve replacement (TAVR).<br /><b>Aims</b><br />To study the incidence of temporary pacemaker related cardiac tamponade in TAVR, and the relation to the type of pacemaker lead used in periprocedural temporary transvenous pacing.<br /><b>Methods</b><br />A single center registry of transfemoral TAVRs in 2014-2020. Main inclusion criterion was peri-operative use of a temporary RV pacing lead. Main exclusion criteria were a preoperatively implanted permanent pacemaker or the exclusive use of left ventricular guidewire pacing. Incident cardiac tamponade were classified as pacemaker lead related, or other. Patients were grouped according to type of temporary RV pacing wire.<br /><b>Results</b><br />810 patients were included (age 80.5 ± 7.3 [mean ± standard deviation], female 319, 39.4%). Of these, 566 (69.9%) received a standard RV temporary pacing wire (RV-TPW), and 244 (30.1%) received temporary RV pacing through a permanent, passive pacemaker lead (RV-TPPL). In total, 18 (2.2%) events of cardiac tamponade occurred, 12 (67%) were pacemaker lead related. All pacemaker lead-related cardiac tamponades occurred in the group who received a standard RV-TPW and none in the group who received RV-TPPL (n = 12 [2.1%] vs. n = 0 [0%], p = 0.022). No difference in cardiac tamponade due to other causes was seen between the groups (p = 0.82).<br /><b>Conclusions</b><br />The use of soft-tip RV-TPPL was associated with a lower risk of pacemaker related cardiac tamponade in TAVR. When perioperative pacing is indicated, temporary RV-TPPL may contribute to a significant reduction of cardiac tamponade in TAVR.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 11 Jan 2023; epub ahead of print</small></div>
Feldt K, Dalén M, Meduri CU, Kastengren M, ... Linder R, Settergren M
Int J Cardiol: 11 Jan 2023; epub ahead of print | PMID: 36640966
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<div><h4>Infective endocarditis in adults with congenital heart disease: Contemporary management and related outcomes in Central and South-Eastern European region.</h4><i>Study Group on Adult Congenital Heart Disease in Central and South-Eastern Europe</i><br /><b>Background</b><br />Infective endocarditis (IE) remains major cause of morbidity and mortality in adult congenital heart disease (ACHD). Limited data exists on ACHD with IE in Central and South-Eastern European (CESEE) countries. The aim of this study is to characterize contemporary management and assess outcomes of ACHD with IE in CESEE region.<br /><b>Methods</b><br />Data on ACHD patients with IE from 9 tertiary centres in 9 different CESEE countries between 2015 and 2020 was included. Baseline demographics, clinical presentation, indication for surgery, outcomes, hospital and all-cause-1-year mortality were studied.<br /><b>Results</b><br />A total of 295 ACHD patients (mean age 40 ± 14 years) with IE were included. Median time from symptoms onset to establishing diagnosis was 25 (11-59) days. The majority of patients (203, 68.8%) received previous empiric oral antibiotic therapy. The highest incidence of IE was observed on native and left sided valves, 194(65.8%) and 204(69.2%), respectively. More than half had a vegetation size ≥10 mm (164, 55.6%); overall 138 (46.8%) had valve complications and 119 (40.3%) had heart failure. In-hospital mortality was 26 (8.8%).<br /><b>Conclusion</b><br />There is clear delay in establishing IE diagnosis amongst ACHD patients in CESEE countries. Adequate diagnosis is hampered by common prescription of empiric antibiotics before establishing formal diagnosis. Hence, patients commonly present with associated complications requiring surgery. Hospital treatment and survival are, nevertheless, comparable to other Western European countries. Improved awareness and education of patients and medical profession regarding IE preventive measures, risks, signs, and symptoms are urgently needed. Empiric antibiotic prescription before blood cultures are taken must be omitted.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Jan 2023; epub ahead of print</small></div>
Study Group on Adult Congenital Heart Disease in Central and South-Eastern Europe
Int J Cardiol: 10 Jan 2023; epub ahead of print | PMID: 36638916
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<div><h4>Association between atrial fibrillation burden and cognitive function in patients with atrial fibrillation.</h4><i>Tang SC, Liu YB, Lin LY, Huang HC, ... Ho YL, Yu CC</i><br /><b>Background</b><br />Accumulating evidence has demonstrated an association between clinical atrial fibrillation (AF) and cognitive impairment. This study aimed to further clarify the impact of AF burden on cognitive function based on detailed electrophysiological recordings and standardized assessments of cognitive function.<br /><b>Methods</b><br />This prospective cohort study, conducted at the Cardiac Electrophysiology Clinic of a tertiary center, included patients with non-valvular AF. AF burden was evaluated using 14-day patch-based electrocardiography. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA).<br /><b>Results</b><br />Enrolled patients (n = 253) were grouped according to the median AF burden (13.52%). Patients with higher AF burden were significantly older and had larger left atrium size, a worse ejection fraction, and a lower MoCA score than those with lower AF burden. Predictors of MoCA score included age, CHA<sub>2</sub>DS<sub>2</sub>-VASc score, AF burden, and Center for Epidemiologic Studies Depression Scale scores. The association between MoCA scores and AF burden remained significant after adjustment for demographic characteristics, underlying diseases, and echocardiographic parameters (standardized beta coefficient: -0.159, 95% confidence interval: -0.020 to -0.004, p = 0.004).<br /><b>Conclusion</b><br />AF burden is associated with cognitive function in patients with AF. Further studies are required to determine whether reducing AF burden can preserve cognitive function in these patients.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Jan 2023; epub ahead of print</small></div>
Tang SC, Liu YB, Lin LY, Huang HC, ... Ho YL, Yu CC
Int J Cardiol: 10 Jan 2023; epub ahead of print | PMID: 36638917
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<div><h4>Relationship between atrial fibrillation and a liver fibrogenesis marker in patients with acute heart failure.</h4><i>Miyamoto R, Nagao K, Matsuto K, Hata R, ... Sato Y, Inada T</i><br /><b>Background</b><br />Hemodynamic disturbance in heart failure (HF) induces extra-cardiac organ injury. Atrial fibrillation (AF) is common in patients with HF. The relationship between AF and organ injury in HF remains unclear. We investigated the relationship between AF and the liver fibrosis marker, type IV collagen 7S (P4NP 7S) in patients with HF.<br /><b>Methods and results</b><br />From a pooled dataset of 3 observational cohorts of hospitalized HF, 720 patients in whom P4NP 7S was measured before discharge were included. Median P4NP 7S were 5.1, 5.3, and 6.2 ng/mL in the sinus rhythm (SR) (n = 368), paroxysmal AF (n = 67), and persistent AF (n = 285) groups, respectively (P < 0.001). In the multiple linear regression analysis, the significant association with P4NP 7S was found for persistent AF (P < 0.001). The cumulative 1-year incidence of the primary composite endpoint of cardiac death and HF hospitalization were 27.6, 24.1, and 34.5% in the SR, paroxysmal AF, and persistent AF groups, respectively (Log-rank P = 0.07) and 25.3 and 34.5% in the low (below median) and high P4NP 7S groups, respectively (Log-rank P = 0.005). The adjusted risks of persistent AF versus SR and high P4NP 7S versus low P4NP 7S for the primary endpoint were 1.38 (95% confidence interval 1.02-1.89) and 1.52 (1.14-2.03), respectively. When patients were divided based on a combination of AF and P4NP 7S, concomitant persistent AF and high P4NP 7S portended a dismal prognosis.<br /><b>Conclusion</b><br />AF is associated with an increase in the liver fibrosis marker. Co-presence of persistent AF and P4NP 7S may portend adverse clinical outcomes.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Jan 2023; epub ahead of print</small></div>
Miyamoto R, Nagao K, Matsuto K, Hata R, ... Sato Y, Inada T
Int J Cardiol: 10 Jan 2023; epub ahead of print | PMID: 36638918
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<div><h4>Predictors of in-hospital heart failure in patients with acute anterior wall ST-segment elevation myocardial infarction.</h4><i>Liang J, Zhang Z</i><br /><b>Background</b><br />Heart failure (HF) is a severe complication of acute ST-segment elevation myocardial infarction (STEMI). Its incidence is associated with myocardial infarction location, and it occurs frequently after acute anterior wall STEMI due to the larger infarct size. However, predictors of in-hospital HF in patients with acute anterior wall STEMI are inadequately defined. We aimed to determine potential predictors of HF in patients with acute anterior wall STEMI during hospitalization.<br /><b>Methods</b><br />A total of 714 consecutive patients who were diagnosed with acute anterior wall STEMI and underwent primary percutaneous coronary intervention (pPCI) between January 2013 to August 2019 were enrolled retrospectively. We assigned the patients to HF and non-HF groups. The clinical parameters were subjected to univariate analysis and logistic regression analysis to obtain the independent predictors.<br /><b>Results</b><br />Among the 714 patients enrolled in the present study (mean age 61.0 ± 13.8 years, men 80.7%), 387 (54.2%) had in-hospital HF. According to a multivariate logistic regression analysis, ventricular fibrillation (VF, OR: 5.66, 95% CI: 2.25-14.23, P < 0.001) was the most striking independent predictor of in-hospital HF. Community-acquired pneumonia (CAP, OR: 4.72, 95% CI: 2.44-9.10, P < 0.001), age (OR: 1.03, 95% CI: 1.01-1.04, P < 0.001), left ventricular ejection fraction (LVEF, OR: 0.96, 95% CI: 0.93-0.97, P < 0.001), and peak N-terminal pro-brain natriuretic peptide (NT-pro-BNP, OR: 1.06, 95% CI: 1.02-1.11, P = 0.006) were also independently associated with in-hospital HF.<br /><b>Conclusion</b><br />VF, CAP, age, LVEF, and peak NT-pro-BNP were independently associated with in-hospital HF in patients with acute anterior wall STEMI.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Jan 2023; epub ahead of print</small></div>
Liang J, Zhang Z
Int J Cardiol: 10 Jan 2023; epub ahead of print | PMID: 36638919
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<div><h4>Cardiotoxicity with human epidermal growth factor receptor-2 inhibitors in breast cancer: Disproportionality analysis of the FDA adverse event reporting system.</h4><i>Zhao M, Chen C, Zhang C, Xu X, ... Wu B, Xu T</i><br /><b>Background</b><br />The cardiotoxicity induced by human epidermal growth factor receptor-2 (HER-2) inhibitors in patients with breast cancer has been reported widely. However, these data sources were largely limited to fewer patients in clinical trials and case reports, lacking more comprehensive analysis from real-world data.<br /><b>Methods</b><br />The cases diagnosed with breast cancer from January 2004 to December 2021 were extracted from the FDA adverse event database and further divided into 3 groups (the HER-2 inhibitor group, the positive control group, and the control group). The association between HER-2 inhibitors and cardiovascular adverse events was evaluated using the reporting odds ratio (ROR), a disproportionality method.<br /><b>Results</b><br />A total of 167,639 breast cancer patients were included, including 18,615 cases in the HER-2 inhibitor drug group, 2568 cases in the positive control group, and 146,456 cases in the control group. A total of 2529 cases (13.5%) treated with HER-2 inhibitors experienced cardiovascular adverse events, mainly reported by health professionals (81.5%). The disproportionality analysis showed that cardiomyopathy was observed in all HER-2 inhibitors except trastuzumab deruxtecan. Trastuzumab-related CVAEs were most frequently reported (N = 2075), and the median time was 80.50 days (IQR: 8.00 to 206.75 days).<br /><b>Conclusion</b><br />Based on real-world data analysis, our study demonstrated a significant association between HER-2 inhibitors and cardiovascular toxicity. Cardiac function in patients with breast cancer should be monitored early during anti-HER therapy, especially within six months.<br /><br />Copyright © 2022 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 09 Jan 2023; epub ahead of print</small></div>
Zhao M, Chen C, Zhang C, Xu X, ... Wu B, Xu T
Int J Cardiol: 09 Jan 2023; epub ahead of print | PMID: 36634822
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<div><h4>Clinical scenarios of HCM-related mortality: Relevance of age and stage of disease at presentation.</h4><i>Zampieri M, Salvi S, Fumagalli C, Argirò A, ... Cappelli F, Olivotto I</i><br /><b>Unlabelled</b><br />The evolving epidemiology of hypertrophic cardiomyopathy (HCM) has progressively changed our perception of HCM-related mortality. However, recent studies detailing individual causes of death based on age and clinical setting are lacking. Thus, the present study aimed to describe the modes of death in a consecutive cohort of HCM patients based on presenting clinical features and stage of disease.<br /><b>Methods</b><br />By retrospective analysis of a large HCM cohort, we identified 161 patients with >1 year follow-up who died between 2000 and 2020 and thoroughly investigated their modes of death. HCM stage at presentation was defined as \"classic\", \"adverse remodeling\" or \"overt dysfunction\".<br /><b>Results</b><br />Of the 161 patients, 103 (64%) died of HCM-related causes, whereas 58 (36%) died of non-HCM-related causes. Patients who died of HCM-related causes were younger than those who died of non-HCM related causes. The most common cause of death was heart failure (HF). Sudden cardiac death (SCD) ranked third, after non cardiovascular death, and mostly occurred in young individuals. The proportion of HF related death and SCD per stage of disease was 14% and 27% in \"classic\", 38% and 21% in \"adverse remodeling\" and 74% and 10% in \"overt dysfunction\".<br /><b>Conclusions</b><br />Most HCM patients die due to complications of their own disease, mainly in the context of HF. While SCD tends to be juvenile, HF related deaths often occur in age groups no longer amenable to cardiac transplant. Modes of death vary with the stage of disease, with SCD becoming less prevalent in more advanced phases, when competitive risk of HF becomes overwhelming.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 05 Jan 2023; epub ahead of print</small></div>
Zampieri M, Salvi S, Fumagalli C, Argirò A, ... Cappelli F, Olivotto I
Int J Cardiol: 05 Jan 2023; epub ahead of print | PMID: 36621577
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<div><h4>Prognostic implications of post-discharge hemodynamic congestion assessed by peripheral venous pressure among patients discharged from acute heart failure.</h4><i>Matsuto K, Maruichi-Kawakami S, Aida K, Imamoto K, ... Inada T, Nagao K</i><br /><b>Background</b><br />Congestion is a major cause of hospitalization for heart failure (HF). Peripheral venous pressure (PVP) strongly correlates with right atrial pressure. We recently reported that high PVP at discharge portends a poor prognosis in patients hospitalized for HF. In the same population, we aimed to analyze changes in PVP after discharge and to evaluate prognostic implications of post-discharge PVP.<br /><b>Methods</b><br />PVP was measured at the forearm vein of 163 patients in the 1-month post-discharge follow-up visit. The primary outcome was a composite of cardiovascular death or re-hospitalization for HF after the 1-month follow-up visit up to 1 year after discharge.<br /><b>Results</b><br />Post-discharge PVP correlated with jugular venous pressure, the inferior vena cava diameter, and brain-type natriuretic peptide levels. The cumulative incidence of the primary outcome event was significantly higher in patients with PVP above the median (6 mmHg) than in those with median PVP or lower (39.8% versus 16.9%, Log-rank P = 0.04). Age- and sex-adjusted risk of PVP per 1 mmHg for the primary outcome measure was significant (hazard ratio: 1.12 [95% confidence interval 1.03-1.21]). 35% of patients who had PVP ≤6 mmHg at discharge had PVP >6 mmHg at the 1-month follow-up. PVP significantly decreased from discharge to 1-month follow-up in patients without the primary outcome event (from 6 [4-10] to 6 [4-8] mmHg, P=0.01), but remained high in those with the primary outcome event (from 8 [5-11] to 7 [5-10.5] mmHg, P = 0.9).<br /><b>Conclusions</b><br />PVP measurements during the early post-discharge period may be useful to identify high risk patients.<br /><b>Trial registration number</b><br />UMIN000034279.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 04 Jan 2023; epub ahead of print</small></div>
Matsuto K, Maruichi-Kawakami S, Aida K, Imamoto K, ... Inada T, Nagao K
Int J Cardiol: 04 Jan 2023; epub ahead of print | PMID: 36610550
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<div><h4>Not baseline but time-dependent erythropoiesis-stimulating agent responsiveness predicts cardiovascular disease in hemodialysis patients receiving epoetin beta pegol: A multicenter prospective PARAMOUNT-HD Study.</h4><i>Fujii H, Hamano T, Tsuchiya K, Kuragano T, ... Nitta K, PARAMOUNT Study Investigators</i><br /><b>Background</b><br />Responsiveness to erythropoiesis-stimulating agents (ESAs) has been reported to be associated with increased cardiovascular disease (CVD) and mortality in patients undergoing hemodialysis (HD). However, the association between hyporesponsiveness to the long-acting ESA, epoetin beta pegol (CERA) and CVD remains unknown.<br /><b>Methods</b><br />This multicenter prospective study included 4034 patients undergoing maintenance HD. After shifting from prior ESA to CERA, we studied the association between erythropoietin resistance index (ERI), including cardiac events, major adverse cardiovascular events (MACE), and all-cause mortality, using Cox proportional hazards models (Landmark analyses) and marginal structural models to adjust for time-dependent confounding factors, including iron-containing medications and hemodiafiltration (HDF).<br /><b>Results</b><br />The median dialysis vintage and the observational period were 5.0 years and 22.1 months, respectively. The landmark analyses revealed that the highest tertile of baseline ERI (T3) was associated with a significantly higher all-cause mortality than the lowest tertile (T1) (hazard ratio [HR]: 1.48, 95% CI: 1.03-2.13). Furthermore, marginal structural models revealed that time-dependent ERI T3 was significantly associated with increased cardiac events (HR: 1.59, 95% CI: 1.14-2.23), MACE (HR: 1.60, 95% CI: 1.19-2.15), all-cause mortality (HR: 1.97, 95% CI: 1.40-2.77), and heart failure (HF) (HR: 2.05, 95% CI: 1.23-3.40) compared to T1. A linear mixed effects model showed that iron-containing medications and HDF are negatively associated with time-dependent ERI.<br /><b>Conclusions</b><br />Baseline ERI at six months predicted only all-cause mortality; however, time-dependent ERI was a predictor of cardiac events, all-cause mortality, MACE, and HF. The widespread use of iron-containing medications and HDF would ameliorate ESA hyporesponsiveness.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 30 Dec 2022; epub ahead of print</small></div>
Fujii H, Hamano T, Tsuchiya K, Kuragano T, ... Nitta K, PARAMOUNT Study Investigators
Int J Cardiol: 30 Dec 2022; epub ahead of print | PMID: 36592827
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<div><h4>Evolving epidemiology of transthyretin amyloid cardiomyopathy due to increased recognition in women.</h4><i>Prasad M, Kim M, Chandrashekar P, Zhao Y, ... Nazer B, Masri A</i><br /><b>Background</b><br />Transthyretin amyloid cardiomyopathy (ATTR-CM), particularly wild type (wtATTR-CM), is thought to mainly affect men. Non-invasive diagnosis and approved therapeutics have been associated with increased disease recognition. We investigated the trajectory of ATTR-CM diagnosis in women.<br /><b>Methods</b><br />This observational study utilized data collected on 140 consecutive ATTR-CM patients diagnosed between 2005 and 2022 who are followed at the Oregon Health and Science University Amyloidosis Clinic. Subgroup analysis was performed on patients with wtATTR-CM which included 113 subjects (80.1%). The proportion of women among patients diagnosed with ATTR-CM prior to 2019 was compared with that of those diagnosed 2019-2022 (2019 was the year of tafamidis approval by the FDA). The clinical characteristics of male and female ATTR-CM patients were compared as well.<br /><b>Results</b><br />Of the 140 ATTR-CM patients, 16 (11.4%) were women (age 77 ± 9 years) and 124 (88.6%) were men (age 76 ± 9 years). There was an increase in the rate of women diagnosed with ATTR-CM from pre 2019 to 2019-2022 in the overall cohort (4/68 [5.9%] vs 12/72 [16.7%]) and wild type subgroup (0/51 [0%] vs 7/62 [11.3%]). There were several differences in baseline clinical characteristics between women and men in this cohort, yet all women had a clear clinical phenotype of ATTR-CM.<br /><b>Conclusions</b><br />There has been a significant increase in the rate of wtATTR-CM diagnoses in women, who presented with clear phenotypes of ATTR-CM. Further studies are needed to understand the effect of increased recognition of ATTR-CM in women on disease epidemiology, natural history, and outcomes.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 Dec 2022; epub ahead of print</small></div>
Prasad M, Kim M, Chandrashekar P, Zhao Y, ... Nazer B, Masri A
Int J Cardiol: 29 Dec 2022; epub ahead of print | PMID: 36587655
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<div><h4>Chiari network for the interventional cardiologist: A hidden enemy at the heart gate - A systematic review of the literature.</h4><i>Ali H, Lupo P, Cristiano E, Nicolì L, ... Butera G, Cappato R</i><br /><b>Background</b><br />This study aimed to collect and analyze the literature data regarding Chiari network (CN) and other right atrium (RA) remnants comprising the Eustachian and Thebesian valves (EV, ThV) as a potential entrapment site during different percutaneous cardiac procedures (PCP).<br /><b>Methods and results</b><br />A systematic search was conducted using Pubmed and Embase databases following the PRISMA guidelines to obtain available data concerning PCP associated with entrapment of inserted materials within CN-EV-ThV. The final analysis included 41 patients who underwent PCP with reported material entrapment within these RA remnants. The PCP was atrial septal defect (ASD)/patent foramen ovale (PFO) closure, catheter ablation, and pacemaker/defibrillator implantation in 44%, 22%, and 17% of patients, respectively. The entrapped materials were ASD/PFO devices, multipolar electrophysiology catheters, passive-fixation pacing leads, and J-guidewires in about 30%, 20%, 15%, and 10% of patients, respectively. Intraprocedural transthoracic, transoesophageal and intracardiac echocardiography showed sensitivity to reveal these structures of 20%, ~95%, and 100%, respectively. A percutaneous approach successfully managed 70% of patients, while cardiovascular surgery was required in 20% and three patients died (7.3%).<br /><b>Conclusions</b><br />CN and other RA remnants may cause entrapment of various devices or catheters during PCP requiring right heart access. The percutaneous approach, guided by intraprocedural imaging, appears safe and effective in managing most patients. Prevention includes recognizing these anatomical structures at baseline cardiac imaging and intraprocedural precautions. Further studies are needed to analyze the actual incidence of this condition, its clinical impact and appropriate management.<br /><br />Copyright © 2022 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 29 Dec 2022; epub ahead of print</small></div>
Ali H, Lupo P, Cristiano E, Nicolì L, ... Butera G, Cappato R
Int J Cardiol: 29 Dec 2022; epub ahead of print | PMID: 36587656
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<div><h4>Right ventricular strain in Fabry disease: Prognostic implications.</h4><i>Meucci MC, Lillo R, Mango F, Lombardo A, ... Crea F, Graziani F</i><br /><b>Introduction</b><br />Left ventricular (LV) hypertrophy is the main feature of cardiac involvement in Anderson-Fabry disease (FD), but the right ventricle (RV) is also frequently affected. Previous studies failed to demonstrate an independent association between conventional parameters of RV performance and outcomes in FD. Nevertheless, if RV free wall strain (RV-FWS), assessed by 2D speckle tracking analysis, may provide a better prognostication is currently unknown.<br /><b>Methods</b><br />We retrospectively evaluated the association between RV-FWS and the occurrence of cardiovascular events in a cohort of 56 patients with FD. The study endpoint comprises cardiovascular mortality, severe heart failure symptoms, new-onset atrial fibrillation and major arrhythmias requiring device implantation.<br /><b>Results</b><br />Reduced RV-FWS, defined by values lower than 23%, was found in 25 (45%) patients. During a median follow-up of 47 months, 16 (29%) patients met the study endpoint. A ROC-curve analysis confirmed the threshold of reduced RV-FWS (<23%) as the best cut-off for predicting cardiovascular events, but with a lower power compared to left-sided parameters. On univariable Cox regression analysis, RV-FWS, expressed as continuous variable, was significantly associated with the study endpoint (HR: 0.795, 95% CI: 0.710-0.889, p < 0.001). However, RV-FWS did not retain a significant association with outcomes, after adjustment for LV global longitudinal strain or indexed left atrial volume (p = 0.340 and p = 0.289 respectively).<br /><b>Conclusions</b><br />RV-FWS was not independently associated with the occurrence of cardiovascular events in FD, confirming previous observations that prognosis is mainly driven by the severity of LV cardiomyopathy.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 28 Dec 2022; epub ahead of print</small></div>
Meucci MC, Lillo R, Mango F, Lombardo A, ... Crea F, Graziani F
Int J Cardiol: 28 Dec 2022; epub ahead of print | PMID: 36586515
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<div><h4>Effect of eplerenone on clinical stability of Japanese patients with acute heart failure.</h4><i>Kobayashi M, Ferreira JP, Matsue Y, Chikamori T, ... Yamashina A, Kitakaze M</i><br /><b>Background</b><br />In the EARLIER (Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure) trial, eplerenone did not reduce heart failure (HF) hospitalizations or all-cause mortality in 300 patients admitted for acute HF (AHF). However, the trial might have been underpowered for these endpoints, and a comprehensive overview of the effect of eplerenone on diuretic doses and patients\' clinical stability is warranted.<br /><b>Methods</b><br />The EARLIER trial included Japanese patients hospitalized for AHF randomly assigned to eplerenone or placebo over 6 months. Cox proportional hazards and mixed-effects models were used for analyses.<br /><b>Results</b><br />Three hundred patients were included (mean age, 67 ± 13 years; 73% males). The median furosemide equivalent dose was 40 (20-62) mg at randomization. Patients with higher furosemide-equivalent doses had more severe signs and symptoms of congestion and a higher risk of all-cause mortality or HF hospitalization during 6-month follow-up (adjusted-hazard ratio per 10 mg/day increase = 1.25, 95% confidence interval: 1.05-1.49). Eplerenone significantly decreased furosemide-equivalent diuretic doses and b-type natriuretic levels throughout the follow-up (overall-joint-p < 0.05 for both) and reduced E/e\' and inferior vena cava diameter at 4 weeks (both p < 0.05). Additionally, eplerenone significantly reduced left ventricular (LV) end-diastolic diameter at 24 weeks (p < 0.05).<br /><b>Conclusions</b><br />Eplerenone treatment improved the clinical stability particularly during short period following hospitalization for AHF, translated by lower diuretic doses, natriuretic peptide levels, indirect markers of filling pressure and venous congestion, and a smaller LV volume.<br /><br />Copyright © 2022 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 28 Dec 2022; epub ahead of print</small></div>
Kobayashi M, Ferreira JP, Matsue Y, Chikamori T, ... Yamashina A, Kitakaze M
Int J Cardiol: 28 Dec 2022; epub ahead of print | PMID: 36586516
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<div><h4>Trajectory of serum chloride levels during decongestive therapy in acute heart failure.</h4><i>Kurashima S, Kitai T, Matsue Y, Nogi K, ... Saito Y, Izumi C</i><br /><b>Background</b><br />Hypochloremia is a risk factor for poor outcomes in patients with acute heart failure (AHF). However, the changes in serum chloride levels during decongestion therapy and their impact on prognosis remain unknown.<br /><b>Methods</b><br />In total, 2798 patients with AHF were retrospectively studied and divided into four groups according to their admission and discharge serum chloride levels: (1) normochloremia (n=2,192, 78%); (2) treatment-associated hypochloremia, defined as admission normochloremia with a subsequent decrease (<98 mEq/L) during hospitalization (n=335, 12%); (3) resolved hypochloremia, defined as admission hypochloremia that disappeared at discharge (n=128, 5%); (4) persistent hypochloremia, defined as chloride <98 mEq/L at admission and discharge (n = 143, 5%). The primary outcome was all-cause death, and the secondary outcomes were cardiovascular death and a composite of cardiovascular death and rehospitalization for heart failure after discharge.<br /><b>Results</b><br />The mean age was 76 ± 12 years and 1584 (57%) patients were men. The mean left ventricular ejection fraction was 46 ± 16%. During a median follow-up period of 365 days, persistent hypochloremia was associated with an increased risk of all-cause death (adjusted hazard ratio [95% confidence interval]: 2.27 [1.53-3.37], p < 0.001), cardiovascular death (2.38 [1.46-3.87], p < 0.001), and a composite of cardiovascular death and heart failure rehospitalization (1.47 [1.06-2.06], p = 0.022). However, the outcomes were comparable between patients with resolved hypochloremia and normochloremia.<br /><b>Conclusions</b><br />Persistent hypochloremia was associated with worse clinical outcomes, while resolved hypochloremia and normochloremia showed a comparable prognosis. Changes in serum chloride levels can help identify patients with poor prognoses and can be used to determine subsequent treatment strategies.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 27 Dec 2022; epub ahead of print</small></div>
Kurashima S, Kitai T, Matsue Y, Nogi K, ... Saito Y, Izumi C
Int J Cardiol: 27 Dec 2022; epub ahead of print | PMID: 36584943
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<div><h4>Detrimental effect of high social risk on the cardiovascular health status of community-dwelling older adults living in rural settings. A population-based, longitudinal prospective study.</h4><i>Del Brutto OH, Mera RM, Rumbea DA, Recalde BY, Sedler MJ</i><br /><b>Background</b><br />Information of the effect of social risk on the cardiovascular health (CVH) status among individuals living in rural settings is limited. We aim to assess this effect in participants of the Three Villages Study cohort.<br /><b>Methods</b><br />Following a longitudinal prospective design, older adults living in rural Ecuador received baseline social risk determinations by means of social determinants of health components included in the Gijon\'s Social-Familial Evaluation Scale (SFES) together with clinical interviews and procedures to determine CVH status included in the Life\'s Simple 7 construct. Those who also received CVH assessment at the end of the study were included. Random-effects generalized least square and mixed logistic regression models were fitted to assess the longitudinal effect of social risk on CVH metrics, after adjusting for relevant covariates.<br /><b>Results</b><br />The study included 443 community dwellers (mean age: 67 ± 7 years). The Gijon\'s SFES mean score was 9.8 ± 2.7 points. The mean number of ideal CVH metrics at baseline was 3.1 ± 1.3, which decreased to 2.6 ± 1.2 (β: -0.467; 95% C.I.: -0.588 to -0.346), after a mean of 7.31 ± 3.26 years of follow-up. The total Gijon\'s SFES score was higher among individuals with a worsening CVH status compared to those who did not (10.4 ± 2.6 versus 9.3 ± 2.6; p < 0.001). The ideal CVH status declined 1.23 (95% C.I.: 1.13-1.34) times per point of change in the total Gijon\'s SFES score.<br /><b>Conclusion</b><br />Study results indicate a deleterious effect of high social risk on CVH status at follow-up in this underserved population.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 26 Dec 2022; epub ahead of print</small></div>
Del Brutto OH, Mera RM, Rumbea DA, Recalde BY, Sedler MJ
Int J Cardiol: 26 Dec 2022; epub ahead of print | PMID: 36581111
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<div><h4>Real-world abdominal aorta aneurysm screening patterns among patients with new or worsening of symptomatic peripheral artery disease.</h4><i>Lee M, Pichert MD, Tran AT, Farooq A, ... Mena-Hurtado CI, Smolderen KG</i><br /><b>Background</b><br />Patients with peripheral artery disease (PAD) have an increased risk of abdominal aortic aneurysms (AAA), but it remains unclear whether practitioners are screening patients for AAA as part of routine PAD management.<br /><b>Methods</b><br />The Patient-centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease (PORTRAIT) Registry is an international prospective registry of patients with new or worsening PAD symptoms presenting to 16 specialty centers in the United States, Netherlands, and Australia, from June 2011 to December 2015. Patients were stratified by AAA screening or AAA positivity. An adjusted median odds ratio was calculated for AAA screening rates across sites.<br /><b>Results</b><br />Of the 1275 patients in the study, 871 (68%) were screened for AAA, with 53 (6.1%) having AAA. AAA screening rates did not differ significantly by country (p = 0.36), but there was a large variation across sites for documentation of AAA screening with an adjusted median odds ratio 12.0 (95% CI 4.7-93.1), with AAA screening rates ranging from 7% to 100% across vascular specialty centers.<br /><b>Conclusions</b><br />Among patients with PAD in a multicenter registry, over two-thirds were screened for AAA, with 6% having documented aneurysms. A large variation was seen across clinical sites, suggesting efforts are needed to increase awareness for guideline implementation and establish new benefit-risk evidence inclusive of high-risk populations such as patients with PAD.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 25 Dec 2022; epub ahead of print</small></div>
Lee M, Pichert MD, Tran AT, Farooq A, ... Mena-Hurtado CI, Smolderen KG
Int J Cardiol: 25 Dec 2022; epub ahead of print | PMID: 36577485
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<div><h4>Phenotyping for percutaneous coronary intervention and long-term recurrent weighted outcomes.</h4><i>Galimzhanov A, Sabitov Y, Guclu E, Tenekecioglu E, Mamas MA</i><br /><b>Introduction</b><br />Percutaneous coronary interventions (PCI) are often performed in multimorbid patients with heterogeneous characteristics and variable clinical outcomes. We aimed to identify distinct clinical phenotypes utilizing machine learning and explore their relationship with long-term recurrent and weighted outcomes.<br /><b>Methods</b><br />This prospective observational cohort study enrolled all-comer PCI patients in 2020-2021. Multiple imputation k-means clustering was utilized to detect specific phenotypes. The study endpoints were patient-oriented and device oriented composite endpoints (POCE, DOCE), its individual components, and major bleeding. We applied semiparametric regression models for recurrent and weighted endpoints.<br /><b>Results</b><br />The study included a total of 643 patients. We unveiled three phenotype clusters: 1) inflammatory (n = 44, with high white blood cell counts, high values of C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio), 2) high erythrocyte sedimentation rate (ESR) (n = 204), and 3) non-inflammatory (n = 395). For ACS-only population, we four distinct phenotypes (high-CRP, high-ESR, high aspartate-aminotransferase, and normal). For all-comer PCI patients, identified phenotypes had a higher risk of POCE (mean ratio (MR) 1.42 (95% confidence interval (CI) 1.11-1.81) and MR 2.01 (95% CI 1.58-2.56), respectively), DOCE (MR 1.61 (95% CI 1.20-2.16), MR 2.60 (95%CI 1.94-3.48), respectively), and stroke (hazard ratio (HR) 2.86 (95% CI 1.10-7.4), 6.83 (95% CI 2.01-23.2)). Similarly, high-ESR and high-CRP phenotypes of ACS patients were significantly associated with the development of clinical composite outcomes.<br /><b>Conclusion</b><br />Machine learning unveiled three distinct phenotype clusters in patients after PCI that were linked with the risk of recurrent and weighted clinical endpoints. German Clinical Trial Registry number: DRKS00020892.<br /><br />Copyright © 2022 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 24 Dec 2022; epub ahead of print</small></div>
Galimzhanov A, Sabitov Y, Guclu E, Tenekecioglu E, Mamas MA
Int J Cardiol: 24 Dec 2022; epub ahead of print | PMID: 36574846
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<div><h4>Identifying and comparing low-value care recommendations for coronary heart disease prevention, diagnosis, and treatment in the US and China.</h4><i>Su W, Song S, Dong H, Wu H, Meng Z</i><br /><b>Background</b><br />Low-value care provides little or no benefit, causes harm and incurs unnecessary costs. Low-value care for coronary heart disease (CHD) is particularly prevalent in the US and China. Identifying low-value care services is the first step in reducing these services. There is currently limited data on identifying a comprehensive CHD low-value care list in the US and China. We aimed to identify and compare low-value care recommendations for CHD prevention, diagnosis, and treatment in the US and China.<br /><b>Methods</b><br />Clinical practice guidelines (CPGs) related to CHD in the US and China were screened for do-not-do recommendations stating that specific services should be avoided. The similarities and discrepancies of low-value care recommendations for CHD between the two countries were then compared.<br /><b>Results</b><br />We found a total of 38 low-value care recommendations in 6 Chinese CPGs and 98 recommendations in 11 US CPGs. In the US, the most common types of low-value care recommendations were therapeutic medications (44, 44.9%), followed by therapeutic procedures (27, 27.6%), diagnostic imaging (16, 16.3%), diagnostic testing (9, 9.2%) and primary prevention (2, 2.0%). In China, the most common types were therapeutic medications (18, 47.4%), followed by therapeutic procedures (13, 34.2%), diagnostic testing (4, 10.5%), and diagnostic imaging (3, 7.9%).<br /><b>Conclusion</b><br />In this study, a comprehensive list of low-value care for CHD in the US and China was established and potentially become the important targets for de-implementation for both countries. The findings may have important implications for other countries, especially low-and middle-income countries, to reduce low-value care for CHD.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 22 Dec 2022; epub ahead of print</small></div>
Su W, Song S, Dong H, Wu H, Meng Z
Int J Cardiol: 22 Dec 2022; epub ahead of print | PMID: 36566783
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<div><h4>External validation of the PROGRESS-CTO complication risk scores: Individual patient data pooled analysis of 3 registries.</h4><i>Simsek B, Tajti P, Carlino M, Ojeda S, ... Brilakis ES, Azzalini L</i><br /><b>Background</b><br />Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is associated with a considerable risk of complications, and risk stratification is of utmost importance.<br /><b>Aims</b><br />To assess the clinical usefulness of the recently developed PROGRESS-CTO (NCT02061436) complication risk scores in an independent cohort.<br /><b>Methods</b><br />Individual patient data pooled analysis of 3 registries was performed.<br /><b>Results</b><br />Of the 4569 patients who underwent CTO PCI, 102 (2.2%) had major adverse cardiovascular events (MACE). Patients with MACE were older (69 ± 11 vs. 65 ± 10, p < 0.001), more likely to have a history of prior coronary artery bypass graft surgery, and unfavorable angiographic characteristics J-CTO score (2.4 ± 1.2 vs. 2.1 ± 1.3, p = 0.007), including blunt stump (59% vs. 49%, p = 0.047). Technical success was lower in patients with MACE (59% vs. 86%, p < 0.001). The area under the receiver operating characteristic curve of the PROGRESS-CTO complication risk models were as follows: MACE 0.72 (95% confidence interval [CI], 0.67-0.76), mortality 0.73 (95% CI, 0.61-0.85), and pericardiocentesis 0.69 (95% CI, 0.62-0.77) in the validation dataset. The observed complication rates increased with higher PROGRESS-CTO complication scores. The PROGRESS-CTO MACE score showed good calibration in this external cohort, with MACE rates similar to the original study: 0.7% (score 0-1), 1.5% (score 2), 2.2% (score 3), 3.8% (score 4), 4.9% (score 5), 5.8% (score 6-7).<br /><b>Conclusion</b><br />Given the good discriminative performance, calibration, and ease of calculation, the PROGRESS-CTO complication scores could help assess the risk of complications in patients undergoing CTO PCI.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 21 Dec 2022; epub ahead of print</small></div>
Simsek B, Tajti P, Carlino M, Ojeda S, ... Brilakis ES, Azzalini L
Int J Cardiol: 21 Dec 2022; epub ahead of print | PMID: 36565956
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<div><h4>Characteristics of exercise intolerance in different subgroups of pulmonary arterial hypertension associated with congenital heart disease.</h4><i>Zhang HD, Yan Y, He YY, Liu QQ, ... Yan XX, Han ZY</i><br /><b>Background</b><br />Exercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD.<br /><b>Methods</b><br />We retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak V̇o<sub>2</sub>), anaerobic threshold, and the slope of ventilatory equivalent for carbon dioxide (V̇e/V̇co<sub>2</sub> slope), were recorded.<br /><b>Results</b><br />The median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak V̇o<sub>2</sub> was reduced in patients compared to healthy controls (median, 14.8 ml/kg/min versus 26.9 ml/kg/min, p < 0.001). Of all 171 patients, 60 (35.1%) had Eisenmenger syndrome, 35 (20.5%) had PAH associated with systemic-to-pulmonary shunts (PAH-SP), 39 (22.8%) had PAH with small defects (PAH-SD), and 37 (21.6%) had PAH after cardiac defect correction (PAH-CD). Patients with Eisenmenger syndrome had the lowest peak V̇o<sub>2</sub> (p = 0.003) and the highest V̇e/V̇co<sub>2</sub> slope (p = 0.012), compared with other patients, representing the worst exercise capacity and ventilatory efficiency. Patients with PAH-SP had the best exercise capacity among the four groups, indicated by the highest peak V̇o<sub>2</sub> (p = 0.003) compared with other patients. Peak V̇o<sub>2</sub> was negatively correlated with pulmonary vascular resistance (r = -0.411, p < 0.001).<br /><b>Conclusions</b><br />Exercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 21 Dec 2022; epub ahead of print</small></div>
Zhang HD, Yan Y, He YY, Liu QQ, ... Yan XX, Han ZY
Int J Cardiol: 21 Dec 2022; epub ahead of print | PMID: 36565957
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<div><h4>Machine learning-based prediction of infarct size in patients with ST-segment elevation myocardial infarction: A multi-center study.</h4><i>Xin A, Li K, Yan LL, Chandramouli C, ... Qian G, Chen Y</i><br /><b>Background</b><br />Cardiac magnetic resonance imaging (CMR) is the gold standard for measuring infarct size (IS). However, this method is expensive and requires a specially trained technologist to administer. We therefore sought to quantify the IS using machine learning (ML) based analysis on clinical features, which is a convenient and cost-effective alternative to CMR.<br /><b>Methods and results</b><br />We included 315 STEMI patients with CMR examined one week after morbidity in final analysis. After feature selection by XGBoost on fifty-six clinical features, we used five ML algorithms (random forest (RF), light gradient boosting decision machine, deep forest, deep neural network, and stacking) to predict IS with 26 (selected by XGBoost with information gain greater than average level of 56 features) and the top 10 features, during which 5-fold cross-validation were used to train and optimize models. We then evaluated the value of actual and ML-IS for the prediction of adverse remodeling. Our finding indicates that MLs outperform the linear regression in predicting IS. Specifically, the RF with five predictors identified by the exhaustive method performed better than linear regression (LR) with 10 indicators (R<sup>2</sup> of RF: 0.8; LR: 0). The finding also shows that both actual and ML-IS were independently associated with adverse remodeling. ML-IS ≥ 21% was associated with a twofold increase in the risk of LV remodeling (P < 0.01) compared with patients with reference IS (1st tertile).<br /><b>Conclusion</b><br />ML-based methods can predict IS with widely available clinical features, which provide a proof-of-concept tool to quantitatively assess acute phase IS.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 21 Dec 2022; epub ahead of print</small></div>
Xin A, Li K, Yan LL, Chandramouli C, ... Qian G, Chen Y
Int J Cardiol: 21 Dec 2022; epub ahead of print | PMID: 36565958
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<div><h4>Microalbuminuria during acute coronary syndrome: Association with 22-year mortality and causes of death. The ABC-8* study on heart disease. (*ABC is an acronym for Adria, Bassano, Conegliano, and Padova Hospitals).</h4><i>Mahmoud HT, Berton G, Cordiano R, Palmieri R, Petucco S, Bagato F</i><br /><b>Background</b><br />Microalbuminuria is associated with adverse outcomes in acute coronary syndrome (ACS) patients.<br /><b>Methods</b><br />To evaluate the very long-term association between Microalbuminuria and the overall mortality and causes of death in this clinical setting, we prospectively studied 579 unselected ACS patients admitted to three hospitals. The baseline albumin-to-creatinine ratio (ACR) was measured on days 1, 3, and 7 in 24-h urine samples. Patients were followed for 22 years or until death.<br /><b>Results</b><br />Virtually all patients completed follow-up; 449(78%) had died: 41% due to non-sudden cardiac death (non-SCD), 19% sudden cardiac death (SCD), 40% due to non-cardiac (non-CD) death. Using unadjusted Cox regression analysis, ACR was a significant predictor of all-cause mortality (hazard ratio [HR] 1.26;95%confidence interval [CI] 1.22-1.31; p˂0.0001) and the three causes of death (HR 1.40;95%CI 1.32-1.48; p˂0.0001), (HR 1.22;95%CI 1.12-1.32; p˂0.0001) and (HR 1.16;95%CI 1.09-1.23; p˂0.0001) for non-SCD, SCD and non-CD respectively. Using a fully adjusted model, ACR was a significant independent predictor of all-cause mortality (HR 1.12; 95%CI 1.08-1.16; p˂0.0001) and only non-SCD (HR 1.21; 95%CI 1.14-1.29; p˂0.0001). There was a positive interaction between ACR level and history of AMI (HR 1.15; 95%CI 1.03-1.29; p = 0.01) and the presence of heart failure at admission (HR 1.11; 95%CI 1.01-1.24; p = 0.04), and negative interaction with higher than median LVEF (HR 0.89; 95%CI 0.80-0.99; p = 0.03) for all-cause mortality at the multivariable level.<br /><b>Conclusion</b><br />Based on the present analysis, baseline urinary albumin excretion during ACS is a strong independent predictor of the very long-term mortality risk, chiefly due to non-sudden cardiac death.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Dec 2022; epub ahead of print</small></div>
Abstract
<div><h4>Role of cardiac magnetic resonance in the differential diagnosis between arrhythmogenic cardiomyopathy with left ventricular involvement and previous infectious myocarditis.</h4><i>Colombo D, Turco A, Lomi S, Valentini A, ... Preda L, Ghio S</i><br /><b>Aims</b><br />Arrhythmogenic cardiomyopathy with left ventricular involvement (ACM-LV), particularly in case of isolated left ventricular involvement (i.e. left dominant arrhythmogenic cardiomyopathy, LDAC) and previous infectious myocarditis (pIM) may have overlapping clinical and cardiac magnetic resonance (CMR) features. To date, there are no validated CMR criteria for the differential diagnosis between these conditions. The present study aimed to identify CMR characteristics to distinguish ACM-LV from pIM.<br /><b>Methods and results</b><br />This observational, retrospective, single-centre study included 30 pIM patients and 30 ACM-LV patients. In ACM-LV patients CMR was performed at diagnosis; in patients with pIM, CMR was performed six months after acute infection. CMR analysis included quantitative assessment of left ventricle (LV) volumes, systolic function and wall thicknesses, qualitative and quantitative assessment of late gadolinium enhancement (LGE) sequences. Compared with pIM, ACM-LV patients showed slightly larger LV volumes, more frequent regional wall motion anomalies and reduced wall thicknesses. ACM-LV patients had higher amounts of LV LGE and extension. Notably, the LDAC subgroup had the highest amount of LV LGE. LV LGE amount > 15 g and a LV LGE percentage > 30% of LV mass discriminated ACM-LV from pIM with a 100% specificity. LGE segmental distribution was superimposable among the groups, except for septal segments that were more frequently involved in ACM-LV and LDAC patients.<br /><b>Conclusions</b><br />A great extension of LV LGE (a cut-off of LGE >15 g and a percentage above 30% of LV LGE in relation to total myocardial mass) discriminates ACM-LV from pIM with extremely high specificity.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Dec 2022; epub ahead of print</small></div>
Colombo D, Turco A, Lomi S, Valentini A, ... Preda L, Ghio S
Int J Cardiol: 16 Dec 2022; epub ahead of print | PMID: 36535562
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<div><h4>Correlation between the level of evidence and the class of recommendations concerning the pharmacological aspects of the Guidelines of the European Society of Cardiology.</h4><i>Milbradt S, Eichhorn J, Fetzner U, Fietz R, ... Saely C, Drexel H</i><br /><AbstractText><br /><b>Background:</b><br/>The reliability of the recommendations affecting the clinical decisions is being continuously weighed in everyday practice (Gershlick, 2018). The objective of our study was to assess the consistency of the evidence behind the recommendations. Methods We narrowed our focus on the pharmacotherapeutic aspects of the most recent 38 European Society of Cardiology guidelines and analyzed the correlation between the level of evidence (LoE) classified as A, B and C and the class of recommendations (CoR) subdivided into I, IIa, IIb and III. Results Contrary to the majority of recommendations based on a LoE C (43,0%), fewer recommendations were proposed on heavily evidence-supported LoE A (23.8%), which percentage increased with subsequent updates of the guidelines. The most common recommendation was CoR I (44,9%), while the least common recommendation was CoR III (9,2%). While a similar share of A (39,1%) and C (30,1%) LoE shaped the CoR I nearly half (48,8%) of the CoR III were based on LoE C. Conversely, the overwhelming majority of the recommendations within the scope of LoE A were indisputably strong and classified as CoR I (73,7%). <br /><b>Conclusion:</b><br/>The pharmacological aspects of the ESC guidelines are predominantly based on LoE C. A greater number of pharmacological recommendations are based on LoE A in comparison to the general ones. Various constraints significantly skew the credibility due to paucity of scientific data. A more nuanced approach is needed, as the guidelines cannot completely substitute the clinical experience and the patient-centered approach in shaping the optimal therapeutic outcome.</AbstractText><br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Dec 2022; epub ahead of print</small></div>
Milbradt S, Eichhorn J, Fetzner U, Fietz R, ... Saely C, Drexel H
Int J Cardiol: 16 Dec 2022; epub ahead of print | PMID: 36535563
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<div><h4>Increased risk of acute myocardial infarction after COVID-19 recovery: A systematic review and meta-analysis.</h4><i>Zuin M, Rigatelli G, Battisti V, Costola G, Roncon L, Bilato C</i><br /><b>Background</b><br />Few studies have analyzed the incidence and the risk of acute myocardial infarction (AMI) during the post-acute phase of COVID-19 infection.<br /><b>Objective</b><br />To assess the incidence and risk of AMI in COVID-19 survivors after SARS-CoV-2 infection by a systematic review and meta-analysis of the available data.<br /><b>Methods</b><br />Data were obtained searching MEDLINE and Scopus for all studies published at any time up to September 1, 2022 and reporting the risk of incident AMI in patients recovered from COVID-19 infection. AMI risk was evaluated using the Mantel-Haenszel random effects models with Hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins and Thomson I<sup>2</sup> statistic.<br /><b>Results</b><br />Among 2765 articles obtained by our search strategy, four studies fulfilled the inclusion criteria for a total of 20,875,843 patients (mean age 56.1 years, 59.1% males). Of them, 1,244,604 had COVID-19 infection. Over a mean follow-up of 8.5 months, among COVID-19 recovered patients AMI occurred in 3.5 cases per 1.000 individuals compared to 2.02 cases per 1.000 individuals in the control cohort, defined as those who did not experience COVID-19 infection in the same period). COVID-19 patients showed an increased risk of incident AMI (HR: 1.93, 95% CI: 1.65-2.26, p < 0.0001, I<sup>2</sup> = 83.5%). Meta-regression analysis demonstrated that the risk of AMI was directly associated with age (p = 0.01) and male gender (p = 0.001), while an indirect relationship was observed when the length of follow-up was utilized as moderator (p < 0.001).<br /><b>Conclusion</b><br />COVID-19 recovered patients had an increased risk of AMI.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Dec 2022; epub ahead of print</small></div>
Zuin M, Rigatelli G, Battisti V, Costola G, Roncon L, Bilato C
Int J Cardiol: 16 Dec 2022; epub ahead of print | PMID: 36535564
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<div><h4>Drivers of mortality in patients with chronic coronary disease in the low-dose colchicine 2 trial.</h4><i>Opstal TSJ, Nidorf SM, Fiolet ATL, Eikelboom JW, ... El Messaoudi S, Cornel JH</i><br /><b>Background</b><br />Low-dose colchicine significantly reduces the risk of cardiovascular events in patients with chronic coronary disease. An increase of non-cardiovascular death raised concerns about its safety. This study reports cause-specific mortality and baseline predictors of mortality in the Low-Dose Colchicine 2 (LoDoCo2) trial.<br /><b>Methods</b><br />Patients with chronic coronary disease were randomly allocated to colchicine 0.5 mg once daily or placebo on a background of optimal medical therapy. Cause-specific mortality data were analysed, stratified by treatment status. Multivariate analyses were performed to examine the predictors of mortality as well as cardiovascular and non-cardiovascular death.<br /><b>Results</b><br />After a median 28.6 months follow-up, 133 out of 5522 participants (2.4%) died. Forty-five deaths were cardiovascular (colchicine versus placebo: 20 [0.7%] versus 25 [0.9%], HR, 0.80; 95% CI, 0.44-1.44), while eighty-eight deaths were non-cardiovascular (53 [1.9%] versus 35 [1.3%]; HR, 1.51; 95% CI, 0.99-2.31). Forty-eight deaths were due to cancer (26 [0.9%] versus 22 [0.8%]), thirteen end-stage pulmonary disease (9 [0.3%] versus 4 [0.1%]), eight infection (4 [0.1%] versus 4 [0.1%]), five dementia (4 [0.1%] versus 1 [0.0%]) and five related multiple organ failure (3 [0.1%] versus 2 [0.1%]). Multivariable analysis demonstrated age > 65 years was the only independent baseline characteristic associated with non-cardiovascular death (HR, 3.65; 95% CI, 2.06-6.47).<br /><b>Conclusions</b><br />During the LoDoCo2 trial, assignment to colchicine was not associated with an adverse effect on any specific causes of death. Most deaths were related to non-cardiovascular causes, underscoring the importance of comorbidities as drivers of all-cause mortality in patients with chronic coronary disease.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 15 Dec 2022; epub ahead of print</small></div>
Opstal TSJ, Nidorf SM, Fiolet ATL, Eikelboom JW, ... El Messaoudi S, Cornel JH
Int J Cardiol: 15 Dec 2022; epub ahead of print | PMID: 36529304
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<div><h4>Machine learning-based predictive risk models for 30-day and 1-year mortality in severe aortic stenosis patients undergoing transcatheter aortic valve implantation.</h4><i>Lertsanguansinchai P, Chokesuwattanaskul R, Petchlorlian A, Suttirut P, Buddhari W, Chula TAVI Team</i><br /><b>Background</b><br />Predictive risk score for mortality plays an important role in the decision-making in patient selection and risk stratification for TAVI. Existing established predictive risk scores had poor discrimination performance in the prediction of mortality after the TAVI.<br /><b>Objectives</b><br />The present study aimed to develop machine learning-based predictive models for 30-day and 1-year mortality in severe aortic stenosis patients undergoing TAVI.<br /><b>Methods</b><br />A total of 186 patients in a retrospective cohort study were analyzed. The models were fitted by a decision tree. Each model was tested in 100 iterations of 80:20 stratified random splitting into training/testing samples and 10-fold cross-validation.<br /><b>Results</b><br />Variables that predict 30-day mortality are a set of factors driven mainly by height, chronic lung disease, STS score, preoperative LVEF, age, and preoperative LVOT VTI. Variables that predict 1-year mortality are a set of factors consisting of preoperative LVEF, STS score, heart rate, systolic blood pressure, home oxygen use, serum creatinine level, and preoperative LVOT Vmax. This decision tree-generated predictive models for 30-day and 1- year mortality provided the most precise accuracy of 0.97 and 0.90 with the AUC-ROC curves of 0.83 and 0.71 on 30-day and 1-year mortality on testing data and had better discrimination performance compared to the existing established TAVI predictive risk scores.<br /><b>Conclusions</b><br />These machine learning models show excellent accuracy and have a better prediction for 30-day and 1-year mortality than the existing established TAVI predictive risk scores. A customized predictive model deems to be properly developed for better risk discrimination among cohorts.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 15 Dec 2022; epub ahead of print</small></div>
Lertsanguansinchai P, Chokesuwattanaskul R, Petchlorlian A, Suttirut P, Buddhari W, Chula TAVI Team
Int J Cardiol: 15 Dec 2022; epub ahead of print | PMID: 36529306
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<div><h4>LncRNA HOTAIR promotes myocardial fibrosis in atrial fibrillation through binding with PTBP1 to increase the stability of Wnt5a.</h4><i>Tan W, Wang K, Yang X, Wang K, Wang N, Jiang TB</i><br /><b>Background</b><br />Atrial fibrillation (AF) is one of the most common arrhythmia in clinical practice, and atrial fibrosis is the important mediator in AF. LncRNA HOTAIR was reported to be up-regulated in AF, while the underlying mechanism of HOTAIR in AF remains unclear.<br /><b>Methods</b><br />In vitro and in vivo AF model was established. qRT-PCR and Western blotting were used to assess the mRNA expression (HOTAIR, Wnt5a and PTBP1) and protein levels (Wnt5a, collagen I/III, α-SMA, CTGF, p-ERK, ERK, p-JNK, and JNK), respectively. MTT, CCK8, transwell assay was used to test cell viability, proliferation and migration, respectively. RIP assay assessed the correlation among HOTAIR, PTBP1 and Wnt5a. The level of α-SMA was detected by immunofluorescence. HE and Masson staining detected the histological changes and fibrosis in mouse heart tissues.<br /><b>Results</b><br />Ang II significantly increased the viability of atrial fibroblasts. The levels of HOTAIR and Wnt5a in fibroblasts were up-regulated by Ang II. HOTAIR silencing or Wnt5a significantly inhibited Ang II-induced proliferation, migration and fibrosis in fibroblasts. HOTAIR silencing repressed Wnt5a-mediated ERK and JNK signaling pathway, and Wnt5a partially abolished the effect of HOTAIR silencing on cell proliferation, migration and fibrosis. Meanwhile, HOTAIR could increase the mRNA stability of Wnt5a via recruiting PTBP1. Furthermore, HOTAIR knockdown notably inhibited the fibrosis in heart tissues of AF mice via regulation of Wnt signaling.<br /><b>Conclusion</b><br />HOTAIR could promote atrial fibrosis in AF through binding with PTBP1 to increase Wnt5a stability. Our study might shed new insights on exploring new strategies against AF.<br /><br />Copyright © 2022 Elsevier B.V. All rights reserved.<br /><br /><small>Int J Cardiol: 15 Dec 2022; 369:21-28</small></div>
Tan W, Wang K, Yang X, Wang K, Wang N, Jiang TB
Int J Cardiol: 15 Dec 2022; 369:21-28 | PMID: 35787431
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<div><h4>A machine learning approach to identifying patients with pulmonary hypertension using real-world electronic health records.</h4><i>Kogan E, Didden EM, Lee E, Nnewihe A, ... Chehoud C, Bridges C</i><br /><b>Background</b><br />This study aimed to develop a machine learning (ML) model to identify patients who are likely to have pulmonary hypertension (PH), using a large patient-level US-based electronic health record (EHR) database.<br /><b>Methods</b><br />A gradient boosting model, XGBoost, was developed using data from Optum\'s US-based de-identified EHR dataset (2007-2019). PH and disease control adult patients were identified using diagnostic, treatment and procedure codes and were randomly split into the training (90%) or test set (10%). Model features included patient demographics, physician visits, diagnoses, procedures, prescriptions, and laboratory test results. Shapley Additive exPlanations values were used to determine feature importance.<br /><b>Results</b><br />We identified 11,279,478 control and 115,822 PH patients (mean age, respectively: 62 and 68 years, both 53% female). The final model used 165 features, with the most important predictive features including diagnosis of heart failure, shortness of breath and atrial fibrillation. The model predicted PH with an area under the receiver operating characteristic curve (AUROC) of 0.92. AUROC remained above 0.80 for the prediction of PH up to and beyond 18 months before diagnosis. Among the PH patients, we also identified 955 pulmonary arterial hypertension (PAH) and 1432 chronic thromboembolic pulmonary hypertension (CTEPH) patients, and the range of AUROCs obtained for these cohorts was 0.79-0.90 and 0.87-0.96, respectively.<br /><b>Conclusions</b><br />This model to detect PH based on patients\' EHR records is viable and performs well in subgroups of PAH and CTEPH patients. This approach has the potential to improve patient outcomes by reducing diagnostic delay in PH.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 14 Dec 2022; epub ahead of print</small></div>
Kogan E, Didden EM, Lee E, Nnewihe A, ... Chehoud C, Bridges C
Int J Cardiol: 14 Dec 2022; epub ahead of print | PMID: 36528138
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<div><h4>Pregnancy outcomes of women with Eisenmenger syndrome: A single-center study.</h4><i>Liu Y, Li Y, Zhang J, Zhao Y, ... Fan X, Wang J</i><br /><b>Background</b><br />To explore the outcomes of mothers with Eisenmenger syndrome (ES) and their offspring.<br /><b>Methods</b><br />Pregnant women with ES admitted to the Beijing Anzhen Hospital between 2010 and 2019 were retrospectively analyzed and followed up.<br /><b>Results</b><br />Forty-two parturient women with ES were recruited, with an average age of 26.7 years (standard deviation [SD], ±4.0 years). The average gestational age was 33.7 weeks (SD, ±2.5 weeks). The average percutaneous oxygen saturation was 84.1 (±9.2), and 40 (95.2%) had caesarean delivery. The average pulmonary artery systolic pressure was 107.5 mmHg (SD, ±20.3 mmHg). Twelve (28.6%) women experienced pulmonary hypertensive crisis; 11 (26.2%) of these women died. Regarding the offspring, the average fetal weight was 1778.1 g (SD, ±555.3 g), six (14.3%) died, and congenital heart disease was diagnosed in three (7.1%). There were significant differences in age, gestational age, percutaneous oxygen saturation, Apgar score, and heart failure between the maternal death and non-death groups (P < 0.05). Death was mainly related to pulmonary hypertensive crisis and heart failure.<br /><b>Conclusions</b><br />We recommend pregnancy termination if ES occurs during early pregnancy; however, patients should be informed of the risks if it occurs during late pregnancy. Multidisciplinary cooperation should be strengthened to improve the prognosis of the mothers and their offspring.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 13 Dec 2022; epub ahead of print</small></div>
Liu Y, Li Y, Zhang J, Zhao Y, ... Fan X, Wang J
Int J Cardiol: 13 Dec 2022; epub ahead of print | PMID: 36526021
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<div><h4>Layman electrocardiographic screening using smartphone-based multiple‑lead ECG device in school children.</h4><i>Maurizi N, Fumagalli C, Skalidis I, Muller O, ... Marchionni N, Olivotto I</i><br /><b>Background</b><br />Pre-partecipation ECG screening of large populations has a significant socioeconomic impact. Technological progress now allows for high-tech-low-cost ECG screening using validated smartphone-based devices capable of guiding to the correct performance of a 12‑lead ECG by layman with no medical background.<br /><b>Methods</b><br />We enrolled 728 (364, 52% males) individuals, aged 12-13 years who underwent ECG screening with a smartphone 12‑lead ECG during school hours by layman volunteers. Correct electrodes placement was provided by a validated image-processing algorithm by the smartphone camera in the App. ECG interpretation was via a telecardiology platform and alterations classified following current standards.<br /><b>Results</b><br />A total of 741 ECGs were recorded, of which 13(2%) were technically not interpretable. Mean PR, QRS and QTc were: 145 ± 22, 85 ± 19 and 387 ± 57 msec. No QTc prolongation was observed. Mean QRS axis was 15°; 26 (4%) patients presented an iRBB. T-wave inversion from V1-V3 was present in 145 (21%) subjects. Twenty-one(3%) patients were referred to second level examination: deep Q-waves in inferior leads in 12(1.6%), ventricular ectopics in 5(0.7%), anterior T-waves inversions V1-V4 in 3(0.4%); extreme right axis deviation in 1(0.3%). Second line investigations did not provide any definitive diagnosis. Total project costs (material equipment and human cost) was 14.460€, 19.51€ per individual. The potential net saving with respect to current pre-participation screening cost was 19%.<br /><b>Conclusions</b><br />Layman 12‑lead Smartphone-ECG population screening proved feasible and effective, with a rate of non-interpretable ECG of <5%. Potential cost-saving in ECG screening and recording was 19%, providing an appealing opportunity when large campaigns should be addressed also in developing countries.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Dec 2022; epub ahead of print</small></div>
Maurizi N, Fumagalli C, Skalidis I, Muller O, ... Marchionni N, Olivotto I
Int J Cardiol: 10 Dec 2022; epub ahead of print | PMID: 36513281
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<div><h4>Chemokine-like receptor 1 deficiency impedes macrophage phenotypic transformation and cardiac repair after myocardial infarction.</h4><i>Wang C, Zhang M, Yan J, Wang R, ... Sun X, Dong S</i><br /><b>Background</b><br />Timely and appropriate transformation of macrophage phenotypes from proinflammatory to anti-inflammatory is essential for cardiac repair after myocardial infarction (MI). Chemokine-like receptor 1 (CMKLR1), which is expressed on macrophages, is regulated by proinflammatory and anti-inflammatory stimuli. However, the contribution of CMKLR1 to macrophage phenotypic transformation and the role it plays in modulating cardiac repair after MI remain unclear.<br /><b>Methods</b><br />CMKLR1 knockout (CMKLR1<sup>-/-</sup>) mice were generated by CRISPR/Cas-mediated genome engineering. A model of murine MI was induced by permanent ligation along the left anterior descending artery. Cardiac function was evaluated by echocardiography. Infarct size and collagen deposition were detected by Masson\'s trichrome staining. Cardiac macrophages were obtained by fluorescence-activated cell sorting. The protein and mRNA expression of associated molecules was determined by Western blotting and qRT-PCR.<br /><b>Results</b><br />We demonstrated that macrophages highly expressed CMKLR1 and accumulated in murine infarcted hearts during the anti-inflammatory reparative phase of MI. CMKLR1 deficiency impaired cardiac function, increased infarct size, induced maladaptive cardiac remodeling, and decreased long-term survival after MI. Furthermore, CMKLR1 deficiency impeded macrophage phenotypic transformation from M1 to M2 in vivo and in vitro. In addition, we demonstrated that CMKLR1 signaling through the PI3K/Akt/mTOR pathway stimulated C/EBPβ activation while simultaneously limiting NF-κB activation, thereby promoting anti-inflammatory and prohibiting proinflammatory macrophage polarization.<br /><b>Conclusions</b><br />Our results reveal that CMKLR1 deficiency impedes macrophage phenotypic transformation and cardiac repair after MI involving the PI3K/AKT/mTOR pathway. CMKLR1 may thus represent a potential therapeutic target for MI.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Dec 2022; epub ahead of print</small></div>
Wang C, Zhang M, Yan J, Wang R, ... Sun X, Dong S
Int J Cardiol: 10 Dec 2022; epub ahead of print | PMID: 36513282
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<div><h4>Risk factors for early death after surgery in patients with acute Stanford type A aortic dissection: A systematic review and meta-analysis.</h4><i>Zhang Y, Yang Y, Guo J, Zhang X, ... Sun T, Lin L</i><br /><b>Background</b><br />There are many risk factors related to early death after surgery among patients with acute Stanford type A aortic dissection (ATAAD) that have been analyzed in previous studies, but no evidence-based study has been conducted to confirm these risk factors.<br /><b>Aims</b><br />The aims of this study were to investigate risk factors for early death after surgery in patients with ATAAD via systematic review and meta-analysis and assess evidence-based strategies for preventing adverse events.<br /><b>Methods</b><br />The protocol for this study was prospectively registered with PROSPERO (CRD 42022332772). The authors systematically searched PubMed, Ovid, Scopus, Web of Science and Cochrane Library following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines from database construction to May 2021. Studies that met the selection criteria were determined by two independent researchers, and the odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported for the risk factors and were pooled using Stata 15.0.<br /><b>Results</b><br />A total of 23 studies including 5510 patients met the inclusion criteria, and 10 risk factors were analyzed in this meta-analysis. The preoperative risk factors for early death after surgery in patients with ATAAD were age [(OR: 1.03, 95% CI (1.01, 1.06)], male sex [(OR: 1.43, 95% CI (1.06, 1.92)], shock [(OR: 1.91, 95% CI (1.06, 3.45)], malperfusion [(OR: 3.45, 95% CI (2.24, 5.31)] and cardiac tamponade [(OR: 3.89, 95% CI (1.17, 12.98)].<br /><b>Conclusion</b><br />Patients with ATAAD who have an older age, male sex, shock, malperfusion and cardiac tamponade have a higher risk for early death after surgery. However, more highly homogenous studies are needed to demonstrate these results. Clinical staff should pay more attention to these factors and take individual actions to reduce mortality after surgery in patients with ATAAD.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Dec 2022; epub ahead of print</small></div>
Zhang Y, Yang Y, Guo J, Zhang X, ... Sun T, Lin L
Int J Cardiol: 10 Dec 2022; epub ahead of print | PMID: 36513283
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<div><h4>Acute pericarditis as a major clinical manifestation of long COVID-19 syndrome.</h4><i>Dini FL, Baldini U, Bytyçi I, Pugliese NR, Bajraktari G, Henein MY</i><br /><b>Background</b><br />The long COVID-19 syndrome has been recently described and some reports have suggested that acute pericarditis represents important manifestation of long COVID-19 syndrome. The aim of this study was to identify the prevalence and clinical characteristics of patients with long COVID-19, presenting with acute pericarditis.<br /><b>Methods</b><br />We retrospectively included 180 patients (median age 47 years, 62% female) previously diagnosed with COVID-19, exhibiting persistence or new-onset symptoms ≥12 weeks from a negative naso-pharyngeal SARS CoV2 swamp test. The original diagnosis of COVID-19 infection was determined by a positive swab. All patients had undergone a thorough physical examination. Patients with suspected heart involvement were referred to a complete cardiovascular evaluation. Echocardiography was performed based on clinical need and diagnosis of acute pericarditis was achieved according to current guidelines.<br /><b>Results</b><br />Among the study population, shortness of breath/fatigue was reported in 52%, chest pain/discomfort in 34% and heart palpitations/arrhythmias in 37%. Diagnosis of acute pericarditis was made in 39 patients (22%). Mild-to-moderate pericardial effusion was reported in 12, while thickened and bright pericardial layers with small effusions (< 5 mm) with or without comet tails arising from the pericardium (pericardial B-lines) in 27. Heart palpitations/arrhythmias (OR:3.748, p = 0.0030), and autoimmune disease and allergic disorders (OR:4.147, p = 0.0073) were independently related to the diagnosis of acute pericarditis, with a borderline contribution of less likelihood of hospitalization during COVID-19 (OR: 0.100, p = 0.0512).<br /><b>Conclusion</b><br />Our findings suggest a high prevalence of acute pericarditis in patients with long COVID-19 syndrome. Autoimmune and allergic disorders, and palpitations/arrhythmias were frequently associated with pericardial disease.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Dec 2022; epub ahead of print</small></div>
Dini FL, Baldini U, Bytyçi I, Pugliese NR, Bajraktari G, Henein MY
Int J Cardiol: 10 Dec 2022; epub ahead of print | PMID: 36513284
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<div><h4>A prospective study on the association between atrial fibrillation and blood pressure in an elderly Chinese population.</h4><i>Chen Y, Zhang W, Sheng CS, Huang QF, ... Freedman B, Wang JG</i><br /><b>Background</b><br />Intensive BP lowering in patients with hypertension has been associated with a lowered risk of AF. It is still uncertain what is the optimal BP levels to prevent AF in the general elderly population. In the present prospective study, we investigated the association between incident AF and BP in an elderly Chinese population.<br /><b>Methods and findings</b><br />Elderly (≥65 years) residents were recruited from 6 communities in Shanghai. 9019 participants who did not have AF at baseline and had at least one ECG recording during follow-up were included in the present analysis. During a median of 3.5 years follow-up, the overall incidence rate of AF was 5.6 per 1000 person-years (n = 178). Systolic BP was associated with increased AF risk (age- and sex-adjusted hazard ratio [HR] per 20-mmHg increase for systolic BP 1.21, 95% CI 1.04-1.39, P = 0.01), but risk estimate was attenuated after adjustment for common AF risk factors. In categorical analyses, statistical significance was achieved for HR relative to optimal BP only in stage 2 or 3 systolic and diastolic hypertension (multivariate-adjusted HR 1.76, 95% CI 1.00-3.08, P = 0.05). The association between AF incidence and BP status tended to be stronger in the absence than presence of a history of cardiovascular disease at baseline (P for interaction = 0.06).<br /><b>Conclusion</b><br />In this Chinese population of 65 years and older, linear increases in systolic and diastolic BP were not independently associated with increased risk of AF, and only exposure to stage 2 or 3 hypertension carries a higher risk of AF.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Dec 2022; epub ahead of print</small></div>
Chen Y, Zhang W, Sheng CS, Huang QF, ... Freedman B, Wang JG
Int J Cardiol: 10 Dec 2022; epub ahead of print | PMID: 36513285
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<div><h4>Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocytes.</h4><i>Wang IC, Lin JH, Lee WS, Liu CH, Lin TY, Yang KT</i><br /><b>Background</b><br />Ischemia/reperfusion (I/R) is associated with severe cellular damage and death. Ferroptosis, a new form of regulated cell death caused by the accumulation of iron-mediated lipid peroxidation, has been found in several diseases including I/R injury, which was reported to be suppressed by flavonoids. Baicalein (BAI) and luteolin (Lut) are flavonoids and were shown to reduce the myocardial I/R injury. BAI was found to suppress ferroptosis in cancer cells via reducing reactive oxygen species (ROS) generation. However, the anti-ferroptosis effect of Lut on ferroptosis has not been reported. This study aimed to investigate whether ferroptosis reduction contributes to the BAI- and Lut-protected cardiomyocytes.<br /><b>Methods</b><br />This research used erastin, RSL3, and Fe-SP to induce ferroptosis. Cell viability was examined using MTT assay. Annexin V-FITC, CM-H<sub>2</sub>DCFDA, and Phen Green SK diacetate (PGSK) fluorescent intensity were detected to analyze apoptotsis, ROS levels, and Fe<sup>2+</sup> concentrations, respectively. qPCR and Western blot analysis were conducted to detect the levels of mRNA and protein, respectively.<br /><b>Results</b><br />Our data show that BAI and Lut protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both BAI and Lut decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. BAI and Lut reduced the I/R-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA.<br /><b>Conclusions</b><br />BAI and Lut could protect the cardiomyocytes against the I/R-induced ferroptosis via suppressing accumulation of ROS and MDA.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Dec 2022; epub ahead of print</small></div>
Wang IC, Lin JH, Lee WS, Liu CH, Lin TY, Yang KT
Int J Cardiol: 10 Dec 2022; epub ahead of print | PMID: 36513286
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<div><h4>Risk of bleeding after percutaneous coronary intervention and its impact on further adverse events in clinical trial participants with comorbid peripheral arterial disease.</h4><i>Pinxterhuis TH, Ploumen EH, Zocca P, Doggen CJM, ... Geelkerken RH, von Birgelen C</i><br /><b>Background</b><br />Both patients with obstructive coronary artery disease (CAD) and patients with peripheral arterial disease (PADs) have an increased bleeding risk. Information is scarce on bleeding in CAD patients, treated with percutaneous coronary intervention (PCI), who have comorbid PADs. We assessed whether PCI patients with PADs have a higher bleeding risk than PCI patients without PADs. Furthermore, in PCI patients with PADs we evaluated the extent by which bleeding increased the risk of further adverse events.<br /><b>Methods</b><br />Three-year pooled patient-level data of two randomized PCI trials (BIO-RESORT, BIONYX) with drug-eluting stents were analyzed to assess mortality and the composite endpoint major adverse cardiac events (MACE: all-cause mortality, any myocardial infarction, emergent coronary artery bypass surgery, or target lesion revascularization).<br /><b>Results</b><br />Among 5989 all-comer patients, followed for 3 years, bleeding occurred in 7.7% (34/440) with comorbid PADs and 5.0% (279/5549) without PADs (HR: 1.59, 95%CI:1.11-2.23, p = 0.010). Of all PADs patients, those with a bleeding had significantly higher rates of all-cause mortality (HR: 4.70, 95%CI:2.37-9.33, p < 0.001) and MACE (HR: 2.39, 95%CI:1.23-4.31, p = 0.003). Furthermore, PADs patients with a bleeding were older (74.4 ± 6.9 vs. 67.4 ± 9.5, p < 0.001). After correction for age and other potential confounders, bleeding remained independently associated with all-cause mortality (adj.HR: 2.97, 95%CI:1.37-6.43, p = 0.006) while the relation of bleeding with MACE became borderline non-significant (adj.HR: 1.85, 95%CI:0.97-3.55, p = 0.06).<br /><b>Conclusion</b><br />PCI patients with PADs had a higher bleeding risk than PCI patients without PADs. In PADs patients, bleeding was associated with all-cause mortality, even after adjustment for potential confounders.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 07 Dec 2022; epub ahead of print</small></div>
Pinxterhuis TH, Ploumen EH, Zocca P, Doggen CJM, ... Geelkerken RH, von Birgelen C
Int J Cardiol: 07 Dec 2022; epub ahead of print | PMID: 36496036
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<div><h4>The interaction of persistent antiphospholipid antibodies positivity and cigarette smoking is associated with an increased risk of cardiovascular events: Cross-sectional and longitudinal analysis.</h4><i>Xu J, Fan Y, Zhou R, Shao J, ... Liu Y, Lin W</i><br /><b>Background</b><br />The antiphospholipid antibody (aPL)-positivity was suggested as a nontraditional risk of coronary artery disease (CAD) and it was associated with cigarette smoking. The co-occurrence of them was usually reported in individuals with cardiovascular diseases. This study was to demonstrate their interaction on the increasing risk of cardiovascular events.<br /><b>Methods and results</b><br />A total of 826 consecutive male individuals who underwent coronary angiography/percutaneous coronary intervention (PCI) were prospectively followed and classified into three groups based on different smoking statuses. The current smoking subjects had the highest occurrence of aPL-positivity, including aCL IgM (20.1%) and aβ2GP1 IgM (15.5%). IgM isotype positivity was an independent risk factor of CAD in the multivariate model, OR: 2.70 (1.52-4.80) for aCL IgM and OR:2.50 (1.35-4.63) for aβ2GP1 IgM.The interaction of current smoking and IgM isotype positivity was significantly associated with increased risk of CAD, OR: 8.75(4.59-16.66) for aCL IgM and OR: 8.78(4.28-17.98) for aβ2GP1 IgM. During about 3 years of follow-up, the smoking patients carrying persistent aPL positivity had the highest cumulative incidence of recurrent myocardial infarction and in-stent restenosis after CAD.<br /><b>Conclusion</b><br />The interaction of current smoking and IgM isotype positivity was significantly associated with the increased risk of CAD, including positive aCL IgM and aβ2GP1 IgM. Cigarette smoking elevated the risk of subsequent cardiovascular events in the presence of IgM isotype positivity, including recurrent myocardial infarction and in-stent restenosis.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 07 Dec 2022; epub ahead of print</small></div>
Abstract
<div><h4>Registered prodromal symptoms of out-of-hospital cardiac arrest among patients calling the medical helpline services.</h4><i>Zylyftari N, Lee CJ, Gnesin F, Møller AL, ... Gislason G, Torp-Pedersen C</i><br /><AbstractText><br /><b>Background:</b><br/>Early identification of warning symptoms among out-of-hospital cardiac arrest (OHCA) patients remains challenging. Thus, we examined the registered prodromal symptoms of patients who called medical helpline services within 30-days before OHCA. Methods Patients unwitnessed by emergency medical services (EMS) aged ≥18 years during their OHCA were identified from the Danish Cardiac Arrest Registry (2014-2018) and linked to phone records from the 24-h emergency helpline (1-1-2) and out-of-hours medical helpline (1813-Medical Helpline) in Copenhagen before the arrest. The registered symptoms were categorized into chest pain; breathing problems; central nervous system (CNS)-related/unconsciousness; abdominal/back/urinary; psychiatric/addiction; infection/fever; trauma/exposure; and unspecified (diverse from the beforementioned categories). Analyses were divided by the time-period of calls (0-7 days/8-30 days preceding OHCA) and call type (1-1-2/1813-Medical Helpline). Results Of all OHCA patients, 18% (974/5442) called helpline services (males 56%, median age 76 years[Q1-Q3:65-84]). Among these, 816 had 1145 calls with registered symptoms. The most common symptom categories (except for unspecified, 33%) were breathing problems (17%), trauma/exposure (17%), CNS/unconsciousness (15%), abdominal/back/urinary (12%), and chest pain (9%). Most patients (61%) called 1813-Medical Helpline, especially for abdominal/back/urinary (17%). Patients calling 1-1-2 had breathing problems (24%) and CNS/unconsciousness (23%). Nearly half of the patients called within 7 days before their OHCA, and CNS/unconsciousness (19%) was the most registered. The unspecified category remained the most common during both time periods (32%;33%) and call type (24%;39%). <br /><b>Conclusions:</b><br/>Among patients who called medical helplines services up to 30-days before their OHCA, besides symptoms being highly varied (unspecified (33%)), breathing problems (17%) were the most registered symptom-specific category.</AbstractText><br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 07 Dec 2022; epub ahead of print</small></div>
Zylyftari N, Lee CJ, Gnesin F, Møller AL, ... Gislason G, Torp-Pedersen C
Int J Cardiol: 07 Dec 2022; epub ahead of print | PMID: 36496039
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<div><h4>Systematic review and meta-analysis of the association between all-cause mortality and statin therapy in patients with preserved ejection fraction heart failure (HFpEF).</h4><i>Kaur G, Jones M, Howes L, Hattingh HL</i><br /><b>Background</b><br />Heart failure (HF) is a growing global health burden increasing in prevalence as the average age of the population rises. HF with preserved ejection fraction (HFpEF) is defined as EF that is ≥50% and represents almost half of the population with HF.<br /><b>Methods</b><br />We conducted a systematic review and meta-analysis exploring an association between HFpEF and statin use on all-cause mortality and cardiovascular rehospitalisation. Searches were conducted in MEDLINE via Ovid, The Cochrane Library for clinical trials in CENTRAL and Embase via Ovid for articles published between 1 January 2000 and 2 July 2021. Risk of bias was assessed using the Newcastle-Ottawa Scale and evidence rated for quality using the GRADE approach.<br /><b>Results</b><br />A total of 19 studies were included in the review. The analysis suggests a risk reduction of 27% for the statin exposed participants compared to the statin non-exposed participants (HR 0.73, 95% CI: 0.68-0.79) with regard to all-cause mortality. There is a low level of heterogeneity (I<sup>2</sup> = 38%) associated with this result that has been accounted for by using a random effects model, however given the included studies are observational, the quality of the evidence is rated as low. Information on rehospitalisation was insufficient for determining the impact of statin use on rehospitalisations.<br /><b>Conclusion</b><br />Our meta-analysis revealed a reduction in all-cause mortality in patients with HFpEF on statin therapy. Considering the outcomes from this meta-analysis there is a need for high level studies to provide quality evidence on the use of statins in patients with HFpEF.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 07 Dec 2022; epub ahead of print</small></div>
Abstract
<div><h4>A simplified echocardiographic formula to estimate cardiac index in the intensive care unit.</h4><i>Gaspardone C, Romagnolo D, Baldetti L, Fasolino A, ... Ajello S, Scandroglio AM</i><br /><b>Background:</b><br/>and aim</b><br />Measurement of cardiac index (CI) is crucial in the hemodynamic assessment of critically ill patients in the intensive care unit (ICU). The most reliable trans-thoracic echocardiography (TTE) technique for CI estimation is the left ventricular outflow tract (LVOT) Doppler method that requires, among other parameters, the LVOT cross-sectional area (CSA) measurement. However, inherent and practical disadvantages, mostly related to the ICU setting, hamper LVOT-CSA assessment. In this study, we aimed to validate a simplified formula, leveraging on LVOT-velocity time integral (VTI) and heart rate (HR) only, for non-invasive estimation of CI in ICU patients.<br /><b>Methods and results</b><br />We prospectively enrolled 50 consecutive patients admitted to our ICU requiring pulmonary artery catheterization (PAC) over a one-year period. For each patient we measured the CI by PAC (CI<sub>PAC</sub>) and TTE. The latter was obtained both with the \"traditional formula\" (traditional CI<sub>TTE</sub>), requiring LVOT-CSA assessment, and our new \"simplified formula\" (simplified CI<sub>TTE</sub>). The correlation between the simplified CI<sub>TTE</sub> and CI<sub>PAC</sub> was strong (r = 0.81) and resulted significantly greater than the traditional CI<sub>TTE</sub> and CI<sub>PAC</sub> correlation (r = 0.70; p < 0.05 for Pearson r coefficients comparison). Both TTE-based CI showed an acceptable agreement (+0.19 ± 0.48 L/min/m<sup>2</sup> for simplified CI<sub>TTE</sub> and - 0.18 ± 0.58 L/min/m<sup>2</sup> for traditional CI<sub>TTE</sub>) with the reference CI<sub>PAC</sub>.<br /><b>Conclusion</b><br />In this study, we validated a practical approach, leveraging on TTE LVOT-VTI and HR only, for non-invasive estimation of CI in ICU patients.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 07 Dec 2022; epub ahead of print</small></div>
Gaspardone C, Romagnolo D, Baldetti L, Fasolino A, ... Ajello S, Scandroglio AM
Int J Cardiol: 07 Dec 2022; epub ahead of print | PMID: 36496041
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<div><h4>Ferulic acid attenuates high glucose-induced MAM alterations via PACS2/IP3R2/FUNDC1/VDAC1 pathway activating proapoptotic proteins and ameliorates cardiomyopathy in diabetic rats.</h4><i>Salin Raj P, Nair A, Preetha Rani MR, Rajankutty K, Ranjith S, Raghu KG</i><br /><b>Background</b><br />Diabetic cardiomyopathy (DCM) is one of the severe complications of diabetes with no known biomarkers for early detection. Mitochondria-associated endoplasmic reticulum membranes (MAM) are less studied subcellular targets but an emerging area for exploration in metabolic disorders including DCM. We herein studied the role of MAMs and downstream mitochondrial functions in DCM. We also explored the efficacy of ferulic acid (FeA) against DCM via modulation of MAM and its associated signaling pathway.<br /><b>Methods</b><br />The H9c2 cardiomyoblast cells were incubated with high d-glucose for 48 h to create a high glucose ambience in vitro. The expression of various critical proteins of MAM, mitochondrial function, oxidative phosphorylation (OxPhos) and the genesis of apoptosis were examined. The rats fed with high fat/high fructose/streptozotocin (single dose, i.p.) were used as a diabetic model and analyzed the insulin resistance and markers of cardiac hypertrophy and apoptosis.<br /><b>Results</b><br />High glucose conditions caused the upregulation of MAM formation via PACS2, IP3R2, FUNDC1, and VDAC1 and decreased mitochondrial biogenesis, fusion and OxPhos. The upregulation of mitochondria-driven SMAC-HTRA2-ARTS-XIAP apoptosis and other cell death pathways indicates their critical roles in the genesis DCM at the molecular level. The diabetic rats also showed cardiomyopathy with increased heart mass index, TNNI3K, troponin, etc. FeA effectively prevented the high glucose-induced MAM alterations and associated cellular anomalies both in vitro and in vivo.<br /><b>Conclusion</b><br />High glucose-induced MAM distortion and subsequent mitochondrial dysfunctions act as the stem of cardiomyopathy. MAM could be explored as a potential target to treat diabetic cardiomyopathy. Also, the FeA could be an attractive nutraceutical agent for diabetic cardiomyopathy.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 05 Dec 2022; epub ahead of print</small></div>
Salin Raj P, Nair A, Preetha Rani MR, Rajankutty K, Ranjith S, Raghu KG
Int J Cardiol: 05 Dec 2022; epub ahead of print | PMID: 36481261
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<div><h4>Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function.</h4><i>Mörtberg J, Salzinger B, Lundwall K, Edfors R, ... Lindahl B, Spaak J</i><br /><b>Background</b><br />Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction.<br /><b>Methods</b><br />Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 mL/min/1.73 m<sup>2</sup> was tested.<br /><b>Results</b><br />Tissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 mL/min/ 1.73 m<sup>2</sup>.<br /><b>Conclusions</b><br />Adrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 04 Dec 2022; epub ahead of print</small></div>
Mörtberg J, Salzinger B, Lundwall K, Edfors R, ... Lindahl B, Spaak J
Int J Cardiol: 04 Dec 2022; epub ahead of print | PMID: 36476672
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<div><h4>Outcomes of atrial septostomy and effect on long-term survival in patients with idiopathic pulmonary arterial hypertension: A single-center cohort.</h4><i>Xing C, Wang X, Pan X, Yu J, ... Shen L, He B</i><br /><b>Objective</b><br />Pulmonary arterial hypertension (PAH) is a chronic progressive disease that may lead to right heart failure (RHF) and early death. Balloon atrial septostomy (BAS) may be used for the palliative treatment of RHF from PAH. We present our contemporary institutional experience of utilizing BAS in idiopathic PAH (IPAH) patients with refractory RHF to investigate the effect on the safety, efficacy and long-term survival.<br /><b>Methods</b><br />This retrospective analysis included 12 IPAH patients with severe RHF from March 2017 to May 2019 who were assessed as high risk. All patients received standard treatment including combination of PAH-specific drugs. Graded BAS was performed on these patients due to unsatisfactory clinical response. Clinical, functional and hemodynamic variables before and immediately after the procedure were collected. 1-year follow-up outcomes and 3-year survival rate were further analyzed.<br /><b>Results</b><br />Successful septostomy was achieved in cases with no procedure-related complications. All patients obtained hemodynamic improvement immediately after the procedure. The WHO functional class and exercise endurance improved at 1-year follow-up, 7 of 12 patients achieved intermediate-low risk status, while the rest remained at intermediate-high risk. 2 patients died at 18 and 20 months due to malignant arrhythmia and advanced heart failure, respectively. Survival at 1 year and 3 years was 100% and 83.3%.<br /><b>Conclusions</b><br />In selected IPAH patients with refractory RHF, BAS is an additional therapeutic strategy, especially when PAH-specific drugs could not achieve the treatment target. BAS can improve hemodynamic variables, bring clinical and cardiac functional benefits and increase the 3-year survival.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 04 Dec 2022; epub ahead of print</small></div>
Xing C, Wang X, Pan X, Yu J, ... Shen L, He B
Int J Cardiol: 04 Dec 2022; epub ahead of print | PMID: 36476671
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<div><h4>Screening of Fabry disease in patients with an implanted permanent pacemaker.</h4><i>Fingrova Z, Havranek S, Sknouril L, Bulava A, ... Germain DP, Linhart A</i><br /><b>Background</b><br />Anderson-Fabry disease (AFD) is an X-linked inherited lysosomal disease caused by a defect in the gene encoding lysosomal enzyme α-galactosidase A (GLA). Atrio-ventricular (AV) nodal conduction defects and sinus node dysfunction are common complications of the disease. It is not fully elucidated how frequently AFD is responsible for acquired AV block or sinus node dysfunction and if some AFD patients could manifest primarily with spontaneous bradycardia in general population. The purpose of study was to evaluate the prevalence of AFD in male patients with implanted permanent pacemaker (PM).<br /><b>Methods</b><br />The prospective multicentric screening in consecutive male patients between 35 and 65 years with implanted PM for acquired third- or second- degree type 2 AV block or symptomatic second- degree type 1 AV block or sinus node dysfunction was performed.<br /><b>Results</b><br />A total of 484 patients (mean age 54 ± 12 years at time of PM implantation) were enrolled to the screening in 12 local sites in Czech Republic. Out of all patients, negative result was found in 481 (99%) subjects. In 3 cases, a GLA variant was found, classified as benign: p.Asp313Tyr, p.D313Y). Pathogenic GLA variants (classical or non-classical form) or variants of unclear significance were not detected.<br /><b>Conclusion</b><br />The prevalence of pathogenic variants causing AFD in a general population sample with implanted permanent PM for AV conduction defects or sinus node dysfunction seems to be low. Our findings do not advocate a routine screening for AFD in all adult males with clinically significant bradycardia.<br /><br />Copyright © 2022 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 03 Dec 2022; epub ahead of print</small></div>
Fingrova Z, Havranek S, Sknouril L, Bulava A, ... Germain DP, Linhart A
Int J Cardiol: 03 Dec 2022; epub ahead of print | PMID: 36473604
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Abstract
<div><h4>Research advances in drug therapy for abdominal aortic aneurysms over the past five years: An updated narrative review.</h4><i>Li R, Liu Y, Jiang J</i><br /><b>Background</b><br />Abdominal aortic aneurysms (AAA) rupture can lead to patient death. Surgical treatment is currently the optimal treatment for AAA with large diameter (≥50 mm) . For AAA with small diameter (30-50 mm), how to administer effective pharmacological treatment to reduce aneurysm expansion rate and rupture risk is the current focus in the field of vascular surgery. There is still no effective drug for the treatment of asymptomatic AAA.<br /><b>Methods</b><br />This article searches the PubMed, Web of Science, Embase, and Cochrane databases for clinical studies on the drug treatment of abdominal aortic aneurysms in the past 5 years. The latest progress in the drug treatment of AAA was reviewed, including antibiotics, antihypertensive drugs, antiplatelet drugs, hypoglycemic drugs, hypolipidemic drugs, mast cell inhibitors and corticosteroids.<br /><b>Results</b><br />25 studies were included in this narrative review. Among them, metformin revealed therapeutic effect in 2 prospective cohort study and 3 retrospective cohort study. The therapeutic effect of statins was controversial in 3 retrospective cohort study. However, the definite therapeutic effects of antihypertensive agents, antibiotics, mast cell inhibitors, antiplatelet agents and corticosteroids on abdominal aortic aneurysms have not been verified in prospective studies.<br /><b>Conclusion</b><br />Metformin provided a positive effect in reducing expansion rate, rupture risk, and perioperative mortality. The therapeutic effect of statins was controversial, which warrant further validation in prospective cohorts. However, there is still a lack of effective agents for the treatment of AAA based on recent studies.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 30 Nov 2022; epub ahead of print</small></div>
Li R, Liu Y, Jiang J
Int J Cardiol: 30 Nov 2022; epub ahead of print | PMID: 36462700
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<div><h4>Circulating progenitor cells and outcomes in patients with coronary artery disease.</h4><i>Dhindsa DS, Desai SR, Jin Q, Sandesara PB, ... Waller EK, Quyyumi AA</i><br /><b>Background</b><br />Low quantities of circulating progenitor cells (CPCs), specifically CD34+ populations, reflect impairment of intrinsic regenerative capacity. This study investigates the relationship between subsets of CPCs and adverse outcomes.<br /><b>Methods</b><br />1366 individuals undergoing angiography for evaluation of coronary artery disease (CAD) were enrolled into the Emory Cardiovascular Biobank. Flow cytometry identified CPCs as CD45med blood mononuclear cells expressing the CD34 epitope, with further enumeration of hematopoietic CPCs as CD133+/CXCR4+ cells and endothelial CPCs as vascular endothelial growth factor receptor-2 (VEGFR2+) cells. Adjusted Cox or Fine and Gray\'s sub-distribution hazard regression models analyzed the relationship between CPCs and 1) all-cause death and 2) a composite of cardiovascular death and non-fatal myocardial infarction (MI).<br /><b>Results</b><br />Over a median 3.1-year follow-up period (IQR 1.3-4.9), there were 221 (16.6%) all-cause deaths and 172 (12.9%) cardiovascular deaths/MIs. Hematopoietic CPCs were highly correlated, and the CD34+/CXCR4+ subset was the best independent predictor. Lower counts (≤median) of CD34+/CXCR4+ and CD34+/VEGFR2+ cells independently predicted all-cause mortality (HR 1.46 [95% CI 1.06-2.01], p = 0.02 and 1.59 [95% CI 1.15-2.18], p = 0.004) and cardiovascular death/MI (HR 1.50 [95% CI 1.04-2.17], p = 0.03 and 1.47 [95% CI 1.01-2.03], p = 0.04). A combination of low CD34+/CXCR4+ and CD34+/VEGFR2+ CPCs predicted all-cause death (HR 2.1, 95% CI 1.4-3.0; p = 0.0002) and cardiovascular death/MI (HR 2.0, 95% CI 1.3-3.2; p = 0.002) compared to those with both lineages above the cut-offs.<br /><b>Conclusions</b><br />Lower levels of hematopoietic and endothelial CPCs indicate diminished endogenous regenerative capacity and independently correlate with greater mortality and cardiovascular risk in patients with CAD.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 Nov 2022; epub ahead of print</small></div>
Dhindsa DS, Desai SR, Jin Q, Sandesara PB, ... Waller EK, Quyyumi AA
Int J Cardiol: 29 Nov 2022; epub ahead of print | PMID: 36460208
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<div><h4>Implantable cardioverter defibrillator lead performance: A systematic review and individual patient data Meta-analysis.</h4><i>Giacopelli D, Azzolina D, Comoretto RI, Quartieri F, ... Gargaro A, Gregori D</i><br /><b>Background</b><br />Reliable post-approval surveillance of implantable cardioverter-defibrillator (ICD) lead performance remains a challenge. In the past, two ICD leads were recalled due to a high frequency of failures. In this meta-analysis, we sought to provide a combined estimate of failure-free rate for ICD leads by reconstructing individual patient data from published Kaplan-Meier (KM) curves and to investigate whether estimates could be influenced by the characteristics of the study.<br /><b>Methods</b><br />Observational studies assessing failure-free estimates of transvenous ICD leads with KM method, were identified through a systematic search up to November 2021.<br /><b>Results</b><br />Forty-four studies were eligible that included 41,870 (63.1%) non-recalled leads and 24,493 (36.9%) recalled leads. The 8-year cumulative failure-free rate was 94.1% (CI, 93.6% - 94.6%) for contemporary non-recalled leads and 81.2% (80.3% - 82.0%) for recalled leads (hazard ratio [HR], 3.15 [2.85-3.47], p < 0.001). Failure-free rate was lower in single-center studies in both the non-recalled (HR, 0.28 [0.15-0.51], p < 0.001) and recalled (HR, 0.54 [0.33-0.88], p = 0.014) group compared with multicenter studies. Similarly, estimates were significantly lower in small (i.e. extracted KM curve with <312 leads) versus large studies (HR non-recalled group, 0.54 [CI, 0.33-0.89], p = 0.015; HR recalled group, 0.62 [CI, 0.43-0.89], p = 0.009).<br /><b>Conclusions</b><br />In this meta-analysis including >66,000 leads, we provide pooled survival curves that may play a role in generating evidence-based standards for assessing clinically acceptable failure rates for ICD leads. Lead performance was underestimated with single-center and small-sized studies; multicenter studies remain the main tool to reliably conduct post-market surveillance of ICD leads.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 Nov 2022; epub ahead of print</small></div>
Giacopelli D, Azzolina D, Comoretto RI, Quartieri F, ... Gargaro A, Gregori D
Int J Cardiol: 29 Nov 2022; epub ahead of print | PMID: 36460209
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<div><h4>Peratrial device closure of perimembranous ventricular septal defects via a small right subaxillary incision: Midterm results in patients <12 months of age.</h4><i>Song S, Shao Z, Liang W, Dong H, ... Li M, Fan T</i><br /><b>Background</b><br />Both percutaneous and perventricular device closures of perimembranous ventricular septal defects (Pm-VSDs) are alternatives to surgical procedures,but they all present certain drawbacks.<br /><b>Objective</b><br />To report our clinical experiences and midterm follow-up results of minimally invasive peratrial device closure of Pm-VSDs under the guidance of transesophageal echocardiography(TEE) in patients <12 months of age.<br /><b>Methods</b><br />Between January 2015 and December 2020,268 patients <12 months of age with Pm-VSDs underwent peratrial device closure in our institute. The procedure was performed under TEE guidance via a small right subaxillary incision. The delivery pathways is established by manipulating the hollow probe, and then the device is installed.<br /><b>Results</b><br />A total of 263 cases (98.1%) underwent successful closure, whereas five cases failed and were converted to cardiopulmonary bypass operation via the original incision during the procedure. The mean age was 9.5 ± 2.0 months and the mean body weight was 8.8 ± 1.4 kg. The mean diameter of the VSD was 4.4 ± 0.5 mm. One patient (0.4%) underwent a second thoracotomy for postoperative intercostal hemorrhage on the second day after surgery. The mean diameter of the occluder size was 5.5 ± 0.6 mm. During the follow-up (4.3 ± 1.4 y), there was no mortality, no new aortic valve regurgitation and atrioventricular block.<br /><b>Conclusion</b><br />Peratrial device closure of Pm-VSDs via the right subaxillary route under TEE guidance is safe and effective at midterm follow-up, confirming this is an valuable alternative method for patients <12 months of age.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 Nov 2022; epub ahead of print</small></div>
Song S, Shao Z, Liang W, Dong H, ... Li M, Fan T
Int J Cardiol: 29 Nov 2022; epub ahead of print | PMID: 36460210
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<div><h4>Scar imaging in the dyssynchronous left ventricle: Accuracy of myocardial metabolism by positron emission tomography and function by echocardiographic strain.</h4><i>Larsen CK, Galli E, Duchenne J, Aalen JM, ... Hopp E, Smiseth OA</i><br /><b>Purpose</b><br />Response to cardiac resynchronization therapy (CRT) is reduced in patients with high left ventricular (LV) scar burden, in particular when scar is located in the LV lateral wall or septum. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can identity scar, but is not feasible in all patients. This study investigates if myocardial metabolism by <sup>18</sup>F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contractile function by echocardiographic strain are alternatives to LGE-CMR.<br /><b>Methods</b><br />In a prospective multicenter study, 132 CRT candidates (91% with left bundle branch block) were studied by speckle tracking strain echocardiography, and 53 of these by FDG-PET. Regional myocardial FDG metabolism and peak systolic strain were compared to LGE-CMR as reference method.<br /><b>Results</b><br />Reduced FDG metabolism (<70% relative) precisely identified transmural scars (≥50% of myocardial volume) in the LV lateral wall, with area under the curve (AUC) 0.96 (95% confidence interval (CI) 0.90-1.00). Reduced contractile function by strain identified transmural scars in the LV lateral wall with only moderate accuracy (AUC = 0.77, CI 0.71-0.84). However, absolute peak systolic strain >10% could rule out transmural scar with high sensitivity (80%) and high negative predictive value (96%). Neither FDG-PET nor strain identified septal scars (for both, AUC < 0.80).<br /><b>Conclusions</b><br />In CRT candidates, FDG-PET is an excellent alternative to LGE-CMR to identify scar in the LV lateral wall. Furthermore, preserved strain in the LV lateral wall has good accuracy to rule out transmural scar. None of the modalities could identify septal scar.<br /><b>Clinical trial registration</b><br />The present study is part of the clinical study \"Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy (CRID-CRT)\", which was registered at clinicaltrials.gov (identifier NCT02525185).<br /><br />Copyright © 2022 The Author. Published by Elsevier B.V. All rights reserved.<br /><br /><small>Int J Cardiol: 29 Nov 2022; epub ahead of print</small></div>
Larsen CK, Galli E, Duchenne J, Aalen JM, ... Hopp E, Smiseth OA
Int J Cardiol: 29 Nov 2022; epub ahead of print | PMID: 36460211
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<div><h4>Efficacy of SGLT2 inhibitors in patients with heart failure: An overview of systematic reviews.</h4><i>Sephien A, Ghobrial M, Reljic T, Prida X, Nerella N, Kumar A</i><br /><b>Aims</b><br />Sodium-Glucose transporter 2 inhibitors (SGLT2i) have been shown to have benefit in patients with heart failure (HF). Multiple systematic reviews and meta-analyses (SR and MA) of randomized control trials (RCTs) comparing SGLT2i to placebo have been performed. However, there is uncertainty in the quality of the evidence and associated efficacy. We performed an overview of SR and MA of RCTs to summarize the evidence related to the efficacy of SGLT2i for the management of HF.<br /><b>Methods and results</b><br />A comprehensive search of three databases (the Cochrane Library, EMBASE, and PubMed) was conducted until February 21, 2021. All SRs and MA of RCTs evaluating the efficacy of SGLT2i in patients with HF were eligible for inclusion. The primary outcome was all-cause mortality. Methodological quality was evaluated using the AMSTAR-2 assessment tool. The overall quality of evidence was summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. The initial search yielded 3431 references, of which, eight SRs and MA met the inclusion criteria. The methodological quality ranged from critically low to high. The overall quality of evidence ranged from very low to moderate. Most of the SRs and MA showed benefits in all-cause mortality, HF-related hospitalizations, and change in Kansas City Questionnaire Score.<br /><b>Conclusions</b><br />SGLT2i are possibly beneficial in patients with HF, however, none of the SRs and MA compared the efficacy between different types of SGLT2i. Furthermore, this paper emphasizes the need for consistent reproducible conduct and reporting of SRs to generate high-quality evidence and facilitate clinical decision-making.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 28 Nov 2022; epub ahead of print</small></div>
Sephien A, Ghobrial M, Reljic T, Prida X, Nerella N, Kumar A
Int J Cardiol: 28 Nov 2022; epub ahead of print | PMID: 36455697
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<div><h4>Renin-angiotensin system inhibitor exerts prognostic effects in HFpEF patients with low baseline chloride level.</h4><i>Shirotani S, Jujo K, Takada T, Abe T, ... Murasaki S, Yamaguchi J</i><br /><b>Background</b><br />Few interventions have shown improved prognosis in patients with heart failure and preserved ejection fraction (HFpEF). Serum chloride levels, which are affected by serum renin secretion, are associated with the prognosis of HFpEF patients. However, the relationship between serum chloride levels and the effects of renin-angiotensin system inhibitors (RASi) in HFpEF patients remains unclear. We investigated whether the prognostic benefit of RASi depends on baseline serum chloride levels in HFpEF patients.<br /><b>Methods</b><br />This observational study included 506 hospitalized patients with HFpEF (ejection fraction >50%) who were discharged. They were divided into two categories based on serum chloride levels at admission (cutoff level: 101 mEq/L) according to previous reports. In each chloride category, all-cause mortality, the primary endpoint, was compared between patients who received RASi and those who did not.<br /><b>Results</b><br />Patients who received RASi had a significantly lower mortality rate after discharge than those who did not, but only in the lower chloride category (log-rank, p = 0.001). Multivariable Cox regression analysis confirmed the effect of risk reduction by RASi on all-cause mortality in the lower chloride category (adjusted hazard ratio: 0.31, 95% confidence interval: 0.11-0.84). The prognostic advantages of RASi were evident in the lower chloride category, but not in the higher chloride category, at admission (P for interaction = 0.027).<br /><b>Conclusion</b><br />RASi administration was associated with an improved prognosis only in HFpEF patients with a low baseline serum chloride level. Clinicians should consider RASi administration if patients\' serum chloride levels are low, to improve the long-term prognosis of HFpEF patients.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 28 Nov 2022; epub ahead of print</small></div>
Shirotani S, Jujo K, Takada T, Abe T, ... Murasaki S, Yamaguchi J
Int J Cardiol: 28 Nov 2022; epub ahead of print | PMID: 36455698
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<div><h4>Long-term use of an ankle-foot orthosis intervention in patients with peripheral artery disease using the integrated promoting action on research implementation in health services (i-PARIHS) framework.</h4><i>Bashir AZ, Dinkel DM, Pipinos II, Estabrooks PA, Johanning JM, Myers SA</i><br /><b>Background</b><br />Peripheral artery disease (PAD) is a cardiovascular disease that limits patients\' walking ability. Persistent ankle-foot orthosis (AFO) use may increase the distance patients can walk as well as physical activity.<br /><b>Purpose</b><br />The purpose of the study was to determine the implementation and patients\' perspectives related to the use or disuse of the AFO intervention six months post-intervention. This study was guided by a semi-structured interview and survey based on the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) constructs.<br /><b>Design</b><br />A convergent mixed methods design was used to evaluate participants\' perceptions six months following a three-month AFO intervention. A survey and semi-structured questionnaire based on the i-PARIHS constructs were administered and analyzed.<br /><b>Setting</b><br />Vascular surgery clinic and biomechanics research laboratory.<br /><b>Participants</b><br />Patients (N = 7; male, 100%; age, 71.9 ± 0.6.7y; body mass index, 29.0 ± 0.5.5; ankle brachial index 0.50 ± 0.17) with claudication completed the study.<br /><b>Interventions</b><br />A certified orthotist fit participants with an AFO that was worn for 3 months.<br /><b>Main outcome measures</b><br />Qualitative analysis of semi-structured interviews and quantitative analysis of the survey.<br /><b>Results</b><br />The highest positive ratings were seen in the dimensions of usability and cost-effectiveness. The patients found the AFO device and instructions to wear, easy when starting the intervention and there were no out-of-pocket costs. The lower scores and challenges faced with observability and relative advantage domains indicated issues related to motivation for sustained use of the AFO.<br /><b>Conclusions</b><br />Barriers associated with AFO function that prevent common activities and poor health seem to be the biggest issue for not wanting to wear the AFO after the 3-month intervention. Addressing patients\' perceptions and challenges to wearing the AFO is essential to increasing compliance and physical activity. Future research should concentrate on understanding the compatibility of orthotic device interventions with the subject\'s lifestyle.<br /><b>Clinical trial registration no</b><br />NCT02902211.<br /><br />Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 28 Nov 2022; epub ahead of print</small></div>
Bashir AZ, Dinkel DM, Pipinos II, Estabrooks PA, Johanning JM, Myers SA
Int J Cardiol: 28 Nov 2022; epub ahead of print | PMID: 36455699
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<div><h4>Surgical edge-to-edge repair for tricuspid regurgitation: Impact of the concomitant annuloplasty.</h4><i>Lee H, Kim J, Jung JH, Yoo JS</i><br /><b>Background</b><br />Surgical edge-to-edge repair has been suggested for tricuspid regurgitation (TR) with complex tricuspid valve (TV) pathologies. Nevertheless, the impact of concomitant TAP has not been well established. This study aimed to compare the outcomes of tricuspid edge-to-edge repair according to the implementation of concomitant TAP.<br /><b>Methods</b><br />A total of 264 patients who underwent tricuspid edge-to-edge repair between January 2001 and December 2020 were enrolled in the study, and 23 patients who had undergone previous TV repair were excluded. The remaining 241 patients were categorized into two groups: TAP (n = 190) and non-TAP (n = 51). Inverse probability of treatment weighting (IPTW) was used to adjust the baseline differences between the two groups.<br /><b>Results</b><br />Early mortality and morbidity did not differ between the two groups. The mean follow-up duration was 111.5 ± 72.4 months. IPTW-adjusted survival analysis did not reveal a difference between the two groups in late significant tricuspid stenosis (trans-tricuspid pressure gradient ≥5 mmHg) and TV reoperations. However, freedom from overall mortality and late severe TR were significantly higher in the TAP group (p = 0.033 and 0.006, respectively). The sensitivity analysis, including propensity score matching, showed consistent results.<br /><b>Conclusion</b><br />The long-term outcomes of surgical tricuspid edge-to-edge repair were better when performed with concomitant TAP.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 28 Nov 2022; epub ahead of print</small></div>
Lee H, Kim J, Jung JH, Yoo JS
Int J Cardiol: 28 Nov 2022; epub ahead of print | PMID: 36455700
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<div><h4>Pre-procedural oral anticoagulant use is associated with cardiovascular events in women after transcatheter aortic valve replacement: An analysis from the WIN-TAVI cohort.</h4><i>van Bergeijk KH, Wykrzykowska JJ, Sartori S, Snyder C, ... Voors AA, Mehran R</i><br /><b>Background</b><br />Transcatheter aortic valve implantation (TAVI) has become an accepted treatment for patients with severe aortic stenosis (AS). Predicting which patients are at risk for adverse clinical outcomes after TAVI remains difficult, especially in women.<br /><b>Aim</b><br />To identify predictors of adverse events in the WIN-TAVI cohort.<br /><b>Methods</b><br />The WIN-TAVI study is an observational registry of 1019 women undergoing TAVI for severe symptomatic AS. Follow-up was 1 year. The primary outcome was defined according to VARC-2: a composite of mortality, stroke, myocardial infarction or hospitalization for valve related symptoms or heart failure. The secondary outcome was a composite of cardiovascular mortality or hospitalization for valve-related symptoms or heart failure.<br /><b>Results</b><br />We included 1019 women with severe AS (mean age of 82.5 ± 6.3 years). At 1 year, 16.4% of the patients experienced the primary endpoint and 12.6% the secondary endpoint. The use of oral anticoagulants (OAC) was the strongest independent predictor of the primary outcome (adjusted hazard ratio [aHR] 1.51, 95% confidence interval [CI] 1.079-2.106, p = 0.016). Independent predictors of the secondary endpoint were age (aHR 1.04 per year, 95% CI 1.01-1.074, p = 0.016) and use of OAC (aHR: 1.79, 95% CI 1.24-2.60, p = 0.002). OAC use was not associated with higher bleeding risk.<br /><b>Conclusion</b><br />Pre-procedural use of OAC was the strongest predictor of adverse outcomes during 1-year follow-up, likely reflecting a combination of high-risk factors and comorbidities, but was not related to increased bleeding risk.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 28 Nov 2022; epub ahead of print</small></div>
van Bergeijk KH, Wykrzykowska JJ, Sartori S, Snyder C, ... Voors AA, Mehran R
Int J Cardiol: 28 Nov 2022; epub ahead of print | PMID: 36455701
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<div><h4>Risks associated with prior oral anticoagulation use in hospitalized COVID-19 patients - A retrospective cohort study on 5392 patients from a tertiary centre.</h4><i>Bistrovic P, Sabljic A, Kovacevic I, Cikara T, ... Manola S, Lucijanic M</i><br /><b>Introduction</b><br />There are conflicting data on prior oral-anticoagulant (OAC) use and outcomes of hospitalized COVID-19 patients. Due to uncertainties regarding associated risks with the prior OAC use, we have investigated this issue in a large cohort of hospitalized COVID-19 patients from our institution.<br /><b>Methods</b><br />We have retrospectively evaluated a total of 5392 consecutive COVID-19 patients hospitalized in our tertiary center institution in period 3/2020 to 6/2021. Majority of patients received low-molecular-weight-heparin thromboprophylaxis and corticosteroids during hospitalization. Patients\' characteristics and clinical outcomes were documented as a part of a hospital registry project and were evaluated according to the prior non-OAC, warfarin and direct oral anticoagulants (DOAC) use.<br /><b>Results</b><br />Median age was 72 years, median Charlson comorbidity index (CCI) was 4 points. There were 56.2% male patients. Majority of patients had severe (70.5%) or critical (15.8%) COVID-19 on admission. A total of 84.8% patients did not receive prior OAC, 9% were previously anticoagulated with warfarin and 6.2% were previously anticoagulated with DOACs. In the multivariate regression analyses, prior warfarin use was associated increased in-hospital mortality (OR 1.24, P = 0.048) independently of older age (OR 2.12, P < 0.001), male sex (OR 1.27, P < 0.001), higher CCI (OR 1.26, P < 0.001) and severe or critical COVID-19 on admission (OR 22.66, P < 0.001). Prior DOAC use was associated with higher occurrence of major bleeding (OR 1.72, P = 0.045) independently of higher CCI (OR 1.08, P = 0.017).<br /><b>Conclusion</b><br />Prior OAC use could be associated with worse clinical outcomes during COVID-19 hospitalization. These phenomena might be OAC type specific and persist after multivariate adjustments.<br /><br />Copyright © 2022 Elsevier B.V. All rights reserved.<br /><br /><small>Int J Cardiol: 28 Nov 2022; epub ahead of print</small></div>
Bistrovic P, Sabljic A, Kovacevic I, Cikara T, ... Manola S, Lucijanic M
Int J Cardiol: 28 Nov 2022; epub ahead of print | PMID: 36471534
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<div><h4>The prognostic value of right ventricular strain and mechanical dispersion on mortality in patients with normal left ventricle function.</h4><i>Rothschild E, Baruch G, Kaplan A, Laufer-Perl M, ... Kapusta L, Topilsky Y</i><br /><b>Aims</b><br />We aimed to assess if right ventricular (RV) 4-chamber longitudinal strain (RV4CLS), RV free wall longitudinal strain (RVFWLS) and RV mechanical dispersion index (RVMDI) have prognostic independent value in patients with preserved ejection fraction (pEF), without clearly elevated LV filling pressure.<br /><b>Methods</b><br />Retrospective analysis of Peak RV4CLS, RVFWLS, RVMDI and comprehensive echocardiographic assessment including left ventricle (LV), atrium (LA) strain and RV parameters in patients with pEF (EF ≥ 50%; E/e\' < 14). Multivariate Cox regression hazards model were used to determine the independent association between RV strain parameters to all-cause mortality and cardiovascular events.<br /><b>Results</b><br />We analyzed 224 consecutive patients with pEF (age 65.2 ± 19.8, 44% female, Charlson Comorbidity Index median = 3.8), with all-cause mortality of 64 patients and 28 cardiovascular events, during a median follow-up of 8.2 years (interquartile range: 6.8 to 8.4 years). The best strain univariate predictors of mortality were RV4CSL [1.16 (1.07-1.26); p = 0.0001] and RVMDI [1.01 (1.001-1.02); p = 0.02] being superior to LV and LA strain, or other RV functional indices. Moreover, after adjustment for clinical (age, gender, Charlson Comorbidity Index), conventional echocardiographic parameters (LA volume, E/e\' average, LVEDD, routine RV functional indices), LV and LA STE, RV4CLS and RVFWLS remained statistically significant associates of all-cause mortality and cardiac events. RV4CLS, or RVFWLS remained statistically significant associated for all-cause mortality, after additional adjustment for RVFAC and RVMDI.<br /><b>Conclusions</b><br />RV4CSL and RVMDI provide significant prognostic additive value in patients with preserved ejection fraction with excellent reproducibility, incremental to routine clinical, hemodynamic and LV and LA STE parameters.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 27 Nov 2022; epub ahead of print</small></div>
Rothschild E, Baruch G, Kaplan A, Laufer-Perl M, ... Kapusta L, Topilsky Y
Int J Cardiol: 27 Nov 2022; epub ahead of print | PMID: 36450336
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<div><h4>Impact of transcatheter tricuspid valve replacement for tricuspid regurgitation on hepatic, cardiac, and venous structure.</h4><i>Ning X, Cao J, Wang W, Xu Z, ... Qiao F, Lu F</i><br /><b>Background</b><br />Patients with long-term tricuspid regurgitation (TR) are mostly accompanied by hepatic, cardiac, and venous remodeling. Transcatheter tricuspid valve replacement (TTVR) device has emerged as a promising alternative to open-heart surgery for TR patients. No study has assessed the impact of TTVR on hepatic, cardiac, and venous remodeling.<br /><b>Methods</b><br />Twenty-two patients with TR enrolled in this study underwent TTVR between October 2020 and January 2021. Liver, heart, and veins were reconstructed by three-dimensional computed tomography reconstruction software at baseline and 6 months follow-up.<br /><b>Results</b><br />Twenty-two patients were enrolled in this study. The mean age was 64.8 ± 8.2 years, and all patients had severe or greater TR with multiple comorbidities. The left hepatic lobe volume decreased from 518.8 ± 171.9 ml to 470.4 ± 179.6 ml at 6 months during follow-up (p = 0.049). Evidence of a decrease in three hepatic veins parameters and splenic vein parameters was noted from baseline to 6 months. And a significant decrease in right atrial volume (317.5 ml [interquartile range: 216.1 to 497.3 ml] vs. 266.7 ml [interquartile range: 178.7 to 480.7 ml]; p = 0.003) were observed in the study.<br /><b>Conclusions</b><br />Six-month outcomes show that TR elimination by LuX-Valve is associated with the reverse remodeling of liver, heart, and veins. Accordingly, LuX-Valve is a promising alternative for patients presenting with severe TR.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 27 Nov 2022; epub ahead of print</small></div>
Ning X, Cao J, Wang W, Xu Z, ... Qiao F, Lu F
Int J Cardiol: 27 Nov 2022; epub ahead of print | PMID: 36450337
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<div><h4>The kinesthetic diagnosis in a homeric item of pathological heartbeat: An overview in the history of ancient greek medicine.</h4><i>Cilione M, Gazzaniga V, Martini M</i><br /><AbstractText>The Iliad, by the Greek poet Homer, is a precious mine of examples of war traumatology. In the specific case of spear wounds in the chest, the death of the Trojan warrior Alcathous is particularly interesting from the point of view of the history of medicine and the evolution of cardiology and knowledge of the heart at the time of ancient Greece. In particular this paper aims to evidence and reconstruct the main anatomical and physiological knowledge of the heart at that time. Indeed, a historical-linguistic analysis of the Greek text prompts some reflections and thoughts on the heartbeat in pathological conditions and on the function of the heart as a hematopoietic organ. Furthermore, Homer\'s account is a critical text that highlights the relevance of the use of the senses in the ancient description of nosological pictures and it allows us an interesting and suggestive approach to reconstruction from the historical and historiographical point of view.</AbstractText><br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 26 Nov 2022; epub ahead of print</small></div>
Cilione M, Gazzaniga V, Martini M
Int J Cardiol: 26 Nov 2022; epub ahead of print | PMID: 36503672
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<div><h4>Identification of echocardiographic subgroups in patients with coronary heart disease combined with heart failure based on latent variable stratification.</h4><i>Du Y, Yuan N, Yan J, Han G, ... Zhang Y, Tian J</i><br /><b>Background</b><br />The prognosis of chronic heart failure is poor, and it remains a challenge to classify patients for better personalized intervention. This study aimed to explore potential subgroups in patients with coronary heart disease and chronic heart failure using comprehensive echocardiographic indices.<br /><b>Methods</b><br />5126 patients with coronary heart disease with chronic heart failure were included. Latent class analysis was applied to identify the grouping patterns of patients based on echocardiographic indices. Network maps and radar charts of echocardiographic indices were drawn to visualize the distribution of echocardiographic findings. The incidence of adverse outcomes was presented on the Kaplan-Meier curve and compared using the log-rank test. The Cox regression model was used to analyze the relationship between subgroups and mortality.<br /><b>Results</b><br />Three groups were identified: eccentric hypertrophy, concentric hypertrophy, and decreased diastolic function. Network plots showed a higher correlation between left atrial diameter, left ventricular mass index, and left ventricle ejection fraction in the eccentric hypertrophy group than in the other groups. The Kaplan-Meier curve showed a significant difference in mortality between the three subgroups (P < 0.001). Multivariate Cox analysis indicated that the eccentric hypertrophy group had the highest risk of death (HR = 1.586, 95% CI: 1.310-1.921, P < 0.001) compared with the other groups.<br /><b>Conclusion</b><br />Patients with coronary heart disease and chronic heart failure can be classified into three subgroups based on echocardiographic indices. This grouping has been shown to be an independent risk factor for mortality in these patients. Accurate subgrouping based on echocardiographic indices is important for identifying high-risk patients.<br /><br />Copyright © 2022 The Author. Published by Elsevier B.V. All rights reserved.<br /><br /><small>Int J Cardiol: 25 Nov 2022; epub ahead of print</small></div>
Du Y, Yuan N, Yan J, Han G, ... Zhang Y, Tian J
Int J Cardiol: 25 Nov 2022; epub ahead of print | PMID: 36442673
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<div><h4>Vessel fractional flow reserve-based non-culprit lesion reclassification in patients with ST-segment elevation myocardial infarction: Impact on treatment strategy and clinical outcome (FAST STEMI I study).</h4><i>Groenland FTW, Huang J, Scoccia A, Neleman T, ... Van Mieghem NM, Daemen J</i><br /><b>Background</b><br />Complete revascularization in patients with ST-segment elevation myocardial (STEMI) improves clinical outcome. Vessel fractional flow reserve (vFFR) has been validated as a non-invasive physiological technology to evaluate hemodynamic lesion significance without need for a dedicated pressure wire or hyperemic agent. This study aimed to assess discordance between vFFR reclassification and treatment strategy in intermediate non-culprit lesions of STEMI patients and to assess the clinical impact of this discordance.<br /><b>Methods</b><br />This was a single-center, retrospective cohort study. From January 2018 to December 2019, consecutive eligible STEMI patients were screened based on the presence of a non-culprit vessel with an intermediate lesion (30-80% angiographic stenosis) feasible for offline vFFR analysis. The primary outcome was the percentage of non-culprit vessels with discordance between vFFR and actual treatment strategy. The secondary outcome was two-year vessel-oriented composite endpoint (VOCE), a composite of vessel-related cardiovascular death, vessel-related myocardial infarction, and target vessel revascularization.<br /><b>Results</b><br />A total of 441 patients (598 non-culprit vessels) met the inclusion criteria. Median vFFR was 0.85 (0.73-0.91). Revascularization was performed in 34.4% of vessels. Discordance between vFFR and actual treatment strategy occurred in 126 (21.1%) vessels. Freedom from VOCE was higher for concordant vessels (97.5%) as compared to discordant vessels (90.6%)(p = 0.003), particularly due to higher adverse event rates in discordant vessels with a vFFR ≤0.80 but deferred revascularization.<br /><b>Conclusions</b><br />In STEMI patients with multivessel disease, discordance between vFFR reclassification and treatment strategy was observed in 21.1% of non-culprit vessels with an intermediate lesion and was associated with increased vessel-related adverse events.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 24 Nov 2022; epub ahead of print</small></div>
Groenland FTW, Huang J, Scoccia A, Neleman T, ... Van Mieghem NM, Daemen J
Int J Cardiol: 24 Nov 2022; epub ahead of print | PMID: 36436683
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<div><h4>Echocardiographic detection of heart valve disease in a community cohort of asymptomatic Australians > 65 years with cardiovascular risk factors.</h4><i>D\'Elia N, Gall S, Potter E, Wright L, Yang H, Marwick TH</i><br /><b>Background</b><br />Valvular heart disease is becoming an increasingly prevalent with population ageing. We sought to define the current prevalence of valvular heart disease in Australia.<br /><b>Methods</b><br />The TasELF and VicELF studies prospectively recruited 962 asymptomatic participants ≥65 years, with at least one cardiovascular risk factor, from the Tasmanian and Victorian communities. People were excluded if they had a previous diagnosis of heart failure, or a life expectancy <1 year. All underwent baseline echocardiography. Those with moderate or severe valvular disease were identified. The current prevalence of clinically significant valve disease was applied to the Australian Bureau of Statistics population projections.<br /><b>Results</b><br />Echocardiograms were interpretable in 943 participants (98%). Clinically significant valve disease was present in 5% of the population, and mitral regurgitation was the most common overall valvular lesion, present in 36% of the population. The projected numbers of people with clinically significant valvular disease is expected to increase significantly across all age groups by the year 2060.<br /><b>Conclusions</b><br />Clinically significant yet asymptomatic valvular disease was prevalent in a large community cohort of participants with at least one risk factor. The total burden of valvular heart disease is expected to increase dramatically over the coming decades.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 24 Nov 2022; epub ahead of print</small></div>
D'Elia N, Gall S, Potter E, Wright L, Yang H, Marwick TH
Int J Cardiol: 24 Nov 2022; epub ahead of print | PMID: 36436684
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<div><h4>Prevalence and determinants of tricuspid regurgitation after repair of tetralogy of Fallot.</h4><i>Offen SM, Puranik R, Baker D, Cordina R, Chard R, Celermajer DS</i><br /><b>Background</b><br />The prevalence and determinants of tricuspid regurgitation (TR) in patients with repaired Tetralogy of Fallot (rTOF) remain incompletely understood.<br /><b>Objectives</b><br />To explore the prevalence of and factors associated with TR in patients with rTOF, specifically, the relationship of right ventricular (RV) dilatation with TR severity.<br /><b>Methods</b><br />Patients (≥17 yrs) with rTOF referred to our service (2000-2019) were identified. Those with severe pulmonary stenosis, significant shunt, or previous tricuspid valve surgery were excluded. Using standard cardiac MRI protocols, RV, right atrial (RA) and tricuspid valve (TV) parameters were measured and compared.<br /><b>Results</b><br />68 consecutively eligible patients with rTOF were included in the study (27 ± 9 yrs., 35% female). Despite substantial RV volume overload (mean RVEDVi 153 mL/m<sup>2</sup>), the majority of the cohort (78%) had no or only mild TR. RA volumes, tenting height/area and annular diameter were normal (4.9 ± 2.0 mm, 1.1 ± 1.0 cm<sup>2</sup> and 32.4 ± 6.2 mm, respectively). There was no significant correlation of TR fraction with RVEDVi (r = 0.13; p = 0.30), RVEF (r = 0.09; p = 0.44) or tricuspid annular diameter (r = 0.07; p = 0.62). Only RAVi showed a weak but significant correlation with TR fraction (0.29; p = 0.03). In a pooled cohort analysis, including both rTOF patients and adults with a dilated RV from pre-tricuspid shunt lesions, rTOF was independently associated with higher TR fraction (p = 0.017).<br /><b>Conclusion</b><br />Despite substantial RV dilatation in a cohort with rTOF, there was surprisingly little TR. We found poor correlation between RVEDVi, RA volumes, tricuspid annular dilatation and the presence of significant TR. These findings question commonly held notions regarding the pathophysiology of functional TR in these patients.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 24 Nov 2022; epub ahead of print</small></div>
Offen SM, Puranik R, Baker D, Cordina R, Chard R, Celermajer DS
Int J Cardiol: 24 Nov 2022; epub ahead of print | PMID: 36436685
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<div><h4>Spontaneous coronary artery dissection and ST-segment elevation myocardial infarction: Does clinical presentation matter?</h4><i>García-Guimarães M, Sanz-Ruiz R, Sabaté M, Velázquez-Martín M, ... Alfonso F, Spanish Registry on SCAD investigators</i><br /><b>Background</b><br />Some patients with spontaneous coronary artery dissection (SCAD) present as ST-segment-elevation myocardial infarction (STEMI). This study evaluates the characteristics, management and outcomes of SCAD patients presenting as STEMI compared to non-ST-segment elevation myocardial infarction (NSTEMI).<br /><b>Methods</b><br />We analysed data from consecutive patients included in the prospective Spanish Registry on SCAD. All coronary angiograms were centrally reviewed. All adverse events were adjudicated by an independent Clinical Events Committee.<br /><b>Results</b><br />Between June 2015 to December 2020, 389 patients were included. Forty-two percent presented with STEMI and 56% with NSTEMI. STEMI patients showed a worse distal flow (TIMI flow 0-1 38% vs 19%, p < 0.001) and more severe (% diameter stenosis 85 ± 18 vs 75 ± 21, p < 0.001) and longer (42 ± 23 mm vs 35 ± 24 mm, p = 0.006) lesions. Patients with STEMI were more frequently treated with percutaneous coronary intervention (PCI) (31% vs 16%, p < 0.001) and developed more frequently left ventricular systolic dysfunction (21% vs 8%, p < 0.001). No differences were found in combined major adverse events during admission (7% vs 5%, p = 0.463), but in-hospital reinfarctions (5% vs 1.4%, p = 0.039) and cardiogenic shock (2.6% vs 0%, p = 0.019) were more frequently seen in the STEMI group. At late follow-up (median 29 months) no differences were found in the incidence of major adverse cardiac and cerebrovascular events (13% vs 13%, p-value = 0.882) between groups.<br /><b>Conclusions</b><br />Patients with SCAD and STEMI had a worse angiographic profile and were more frequently referred to PCI compared to NSTEMI patients. Despite these disparities, both short and long-term prognosis were similar in STEMI and NSTEMI SCAD patients.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 23 Nov 2022; epub ahead of print</small></div>
García-Guimarães M, Sanz-Ruiz R, Sabaté M, Velázquez-Martín M, ... Alfonso F, Spanish Registry on SCAD investigators
Int J Cardiol: 23 Nov 2022; epub ahead of print | PMID: 36435331
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<div><h4>Effectiveness of statins for the primary prevention of cardiovascular disease in the Asian elderly population.</h4><i>Lin YW, Wang CC, Wu CC, Hsu YT, Lin FJ</i><br /><b>Background</b><br />Population aging is a global trend, and the elderly have a higher risk of atherosclerotic cardiovascular disease (ASCVD) and related mortality. Statins have been observed to reduce cardiovascular events in patients with ASCVD. However, compared with secondary prevention, the benefits of statins for primary prevention are undetermined among the elderly.<br /><b>Aims</b><br />This study aimed to evaluate the effectiveness of statins in an elderly population without a history of cardiovascular disease (CVD).<br /><b>Methods</b><br />The study was carried out using the National Taiwan University Hospital Integrated Medical Database and the National Health Insurance Research Database in Taiwan. Patients aged 65 years and older without a history of CVD were identified between 1 February 2008 and 31 December 2015. New statin users were 1:4 matched to nonusers based on certain variables. The risks of major adverse cardiovascular events (MACEs) and all-cause mortality were estimated using Cox proportional hazards models. Further, we applied marginal structural models to account for time-varying low-density lipoprotein cholesterol (LDL-C) levels.<br /><b>Results</b><br />A total of 2761 new statin users and 9503 nonusers were selected after matching; the mean age was 71.8 years, and 63% were women. At a median follow-up of 4.8 years, statin use was associated with reduced risk of MACEs (hazard ratio [HR]: 0.75; 95% confidence interval [CI], 0.52-0.98) and mortality (HR: 0.72, 95% CI: 0.55-0.93) when accounting for time-varying LDL-C. No significant differences in effect were detected between subgroups.<br /><b>Conclusion</b><br />Statin use could be beneficial for the primary prevention of CVD in elderly Asians.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 23 Nov 2022; epub ahead of print</small></div>
Lin YW, Wang CC, Wu CC, Hsu YT, Lin FJ
Int J Cardiol: 23 Nov 2022; epub ahead of print | PMID: 36435332
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<div><h4>Percutaneous coronary intervention from COURAGE to ISCHEMIA and beyond.</h4><i>Weintraub WS, Mancini GBJ, Boden WE</i><br /><AbstractText>Multiple randomized clinical trials and observational studies in patients with chronic coronary artery disease have evaluated whether revascularization, in particular PCI, can reduce the incidence of future cardiovascular events and relieve angina. Perhaps the two most widely quoted trials are COURAGE and ISCHEMIA. In both trials revascularization did not reduce the incidence of cardiovascular death or non-fatal events. In both, revascularization did relieve angina, particularly in patients with severe pain. From the time of COURAGE to ISCHEMIA there were also multiple developments. In particular improved stent technology with second and third generation drug eluting stents in ISCHEMIA compared to bare metal stents in COURAGE. There was also the development of new methods to evaluate ischemia, in particular the potential surrogate fractional flow reserve. This period also saw improvement and maturation of coronary computed tomography angiography to assess coronary anatomy non-invasively. There was also greater emphasis on more intensive, guideline directed medical therapy to treat dyslipidemia and hypertension. There has also been greater recognition that not all angina is due to epicardial obstructive disease. Microvascular disease and coronary spasm are responsible for much of the symptom burden of ischemia. These data have led to a paradigm shift toward a more nuanced approach to treating stable ischemic heart disease, with less need for revascularization except in cases of particularly severe anatomic disease or unremitting symptoms while on optimal medial therapy. In recognition of the importance of disparities in cardiovascular health, it is crucial to implement preventive strategies with optimal medical therapy in the community.</AbstractText><br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 22 Nov 2022; epub ahead of print</small></div>
Weintraub WS, Mancini GBJ, Boden WE
Int J Cardiol: 22 Nov 2022; epub ahead of print | PMID: 36427605
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<div><h4>Sex differences in patients with acute coronary syndromes and non-obstructive coronary arteries: Presentation and outcome.</h4><i>Williams MGL, Dastidar A, Liang K, Johnson TW, ... Plein S, Bucciarelli-Ducci C</i><br /><b>Background</b><br />A substantial number of patients present with a suspected ACS and non-obstructive coronary arteries; sex differences in these patients are not well understood. This study aims to evaluate the impact of sex on clinical presentation and outcome in patients with suspected acute coronary syndrome (ACS) and non-obstructive coronary arteries with a final diagnosis confirmed by cardiovascular magnetic resonance imaging (CMR).<br /><b>Methods</b><br />Consecutive patients with ACS and non-obstructive coronary arteries (n = 719) with an unclear cause from a single tertiary centre who were referred for CMR were included. The primary endpoint was all-cause mortality.<br /><b>Results</b><br />CMR was performed at a median time of 30 days after presentation and identified a diagnosis in 74% of patients. All-cause mortality was 9.5% over a median follow up of 4.9 years, with no significant difference between sexes (8.8% versus 10.1%; p = 0.456). Men were more likely to have non-ischaemic aetiology on CMR than women (55% v 41%, p < 0.001), but were equally likely to have an ischaemic cause (25% v 27%, p = 0.462). Age group (HR 1.58, p < 0.001) and LV ejection fraction (HR 0.98, p = 0.023) were independent predictors of mortality.<br /><b>Conclusions</b><br />There is no difference in all-cause mortality between sexes in patients presenting with suspected ACS and non-obstructive coronary arteries.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 22 Nov 2022; epub ahead of print</small></div>
Williams MGL, Dastidar A, Liang K, Johnson TW, ... Plein S, Bucciarelli-Ducci C
Int J Cardiol: 22 Nov 2022; epub ahead of print | PMID: 36427606
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<div><h4>Incremental value of left ventricular global longitudinal strain in moderate aortic stenosis and reduced left ventricular ejection fraction.</h4><i>Stassen J, Singh GK, Pio SM, Chimed S, ... Marsan NA, Bax JJ</i><br /><b>Background</b><br />Moderate aortic stenosis (AS) often coexists with left ventricular (LV) systolic dysfunction and may affect survival through afterload mismatch. Because outcomes are ultimately driven by the condition of the LV, accurate assessment of LV performance is crucial to improve risk stratification. This study investigated the prognostic value of LV global longitudinal strain (GLS) in patients with moderate AS and reduced LV systolic dysfunction.<br /><b>Methods</b><br />Patients with moderate AS (aortic valve area 1.0-1.5 cm<sup>2</sup>) and reduced LV ejection fraction (EF) (<50%) were identified. LVGLS was evaluated with speckle-tracking echocardiography. Patients were divided into 2 groups according to an LVGLS value of 11%, based on spline curve analysis. The primary endpoint was all-cause mortality.<br /><b>Results</b><br />A total of 166 patients (mean age 73 ± 11 years, 71% male) were included. The cumulative 1- and 5-year mortality rates were higher in patients with LVGLS <11% (25% and 60%) versus LVGLS ≥11% (10% and 27%) (p < 0.001). On multivariable analysis, LVGLS as a continuous variable (HR 0.753; 95% CI 0.673-0.843; p < 0.001) and as a categorical variable (<11%) (HR 3.028; 95% CI 1.623-5.648; p < 0.001) were independently associated with outcomes, whereas LVEF was not. LVGLS provided additional prognostic information in patients with/without coronary artery disease and with mildly versus severely reduced LVEF. In addition, LVGLS had incremental prognostic value over established risk factors, including LVEF.<br /><b>Conclusion</b><br />The combination of moderate AS and reduced LV systolic dysfunction is associated with a high mortality risk. LVGLS, but not LVEF, is independently associated with mortality and provides incremental prognostic value over established risk factors in patients with moderate AS and reduced LVEF.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 22 Nov 2022; epub ahead of print</small></div>
Stassen J, Singh GK, Pio SM, Chimed S, ... Marsan NA, Bax JJ
Int J Cardiol: 22 Nov 2022; epub ahead of print | PMID: 36427607
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<div><h4>Genomic and RNA-Seq profiling of patients with HFrEF unraveled OAS1 mutation and aggressive expression.</h4><i>Li X, Shen Y, Xu X, Guo G, ... He K, Liu C</i><br /><b>Background</b><br />Heart failure (HF) is a complex pathophysiological state characterized by inadequate delivery of blood and nutrients to the cardiac tissues. It is rarely curable and is commonly associated with a poor prognosis. In this study, we aimed to analyse exomic and RNA-Seq data from patients with HF to identify the key altered pathways in HF.<br /><b>Methods</b><br />Whole blood samples were collected from patients with HF and subjected to whole exome sequencing (WES) and RNA-Seq analysis. The gene expression and RNA-Seq data obtained were verified using gene chip analysis and RT-PCR.<br /><b>Results</b><br />Both exomic and RNA-Seq data confirmed the dysregulation of phosphorylation and immune signalling in patients with HF. Specifically, exomic analysis showed that TITIN, OBSCURIN, NOD2, CDH2, MAP3K5, and SLC17A4 mutations were associated with HF, and RNA-Seq revealed that S100A12, S100A8, S100A9, PFDN5, and TMCC2, were upregulated in patients with HF. Additionally, comparison between RNA-seq and WES data showed that OAS1 mutations are associated with HF.<br /><b>Conlcusion</b><br />Our findings indicated that patients with HF show an overall disruption of key phosphorylation and immune signalling pathways. Based on RNA-seq and WES, OAS1 mutations may be primarily responsible for these changes.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 19 Nov 2022; epub ahead of print</small></div>
Li X, Shen Y, Xu X, Guo G, ... He K, Liu C
Int J Cardiol: 19 Nov 2022; epub ahead of print | PMID: 36414043
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<div><h4>Relationship between sexual differences and cardiovascular risk factors in the prevalence of asymptomatic coronary disease.</h4><i>Yoon YH, Park GM, Lee JY, Lee JH, ... Kim YH, Lee SW</i><br /><b>Background</b><br />This study investigated the sexual differences of coronary artery disease (CAD) prevalence and its association with cardiovascular risk factors in the asymptomatic population.<br /><b>Methods</b><br />In total 6434 asymptomatic participants without known CAD (1740 women and 4694 men) underwent coronary computed tomography angiography (CCTA). The prevalence of significant CAD (diameter stenosis ≥50%) and other CCTA findings were compared by sex, and its influence on CAD was investigated in groups stratified by the number of cardiovascular risk factors, including age (>55 years), hypertension, diabetes, dyslipidemia, and current smoking.<br /><b>Results</b><br />The prevalence of current smokers, hypertension, and diabetes were higher in men than women. The mean coronary artery calcium score was 13.1 ± 58.4 for women and 51.1 ± 158.2 for men; the coronary atherosclerosis burden indices were significantly higher in men than women. Significant CAD was identified in 65 women (3.7%) and 429 men (9.1%), showing a significant association (adjusted odds ratio [OR] 2.38, P < 0.001). The relatively higher risk for significant CAD in men was observed in patients with fewer risk factors, and the risk difference was not significant in patients with many risk factors (adjusted ORs: 7.69, 3.37, 1.71, 1.31, and 0.88 in patients with 0, 1, 2, 3, and 4-5 risk factors, respectively). The association between sex and risk factor groups was significant (P < 0.001).<br /><b>Conclusions</b><br />In the asymptomatic population, a significantly higher CAD prevalence was noted in men than women. However, women with a high number of cardiovascular risk factors showed a CAD prevalence similar to that of men.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 19 Nov 2022; epub ahead of print</small></div>
Yoon YH, Park GM, Lee JY, Lee JH, ... Kim YH, Lee SW
Int J Cardiol: 19 Nov 2022; epub ahead of print | PMID: 36414046
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<div><h4>Sex disparities and dyslipidemic control in a coronary rehabilitation program.</h4><i>Proença T, Pinto RA, Carvalho MM, Rocha A, Dias P, Macedo F</i><br /><AbstractText>Lipid control is one of the most important secondary cardiovascular prevention targets. Although cardiovascular disease is the most common cause of death in both sexes, women are less likely to receive guideline-recommended secondary prevention medications. To compare sex disparities in dyslipidemia control in a secondary prevention population, we retrospectively analysed all patients who participated in a Coronary Rehabilitation Program (CRP) after an acute coronary syndrome (ACS) from January 2011 to October 2019. Of a total of 881 patients enrolled, mean age 55.0-year-old, 16.1% were female. At hospital admission, females and males had similar mean LDL-levels. Female patients received more high intensity therapy during follow-up (67.8% vs 53.9% at baseline, p = 0.015; 75.6% vs 59.0% after CRP, p = 0.003; and 79.8% vs 65.1% at 1-year-follow-up, p = 0.007). At the end of the CRP, male patients exhibit a better control of LDL [82.0 vs 75.6 mg/dL, t(597) = 2.4, p = 0.016)] with 12.8% vs 16.4% below 55 mg/dL and 29.8% vs 44.5% below 70 mg/dL (p = 0.008). At 1-year follow-up, both sexes exhibited similar LDL-control thanks to a worsening control of the male population (81.9 vs 80.6 mg/dL, t(540) = 0.52, p = 0.605). Only 13.3% of females had LDL below 55 mg/dL (vs 12.9%, p = 0.921) and 32.5% below 70 mg/dL (vs 37.0%, p = 0.432). This real-life study showed that guideline recommended LDL target is not achieved in the majority of patients. Unlike other reports, there were more women receiving more potent anti-dyslipidemic therapy. Nevertheless, women showed a poor control of LDL-concentration after three months of ACS and a similar control after 1-year.</AbstractText><br /><br />Copyright © 2022 Elsevier Ireland Ltd. All rights reserved.<br /><br /><small>Int J Cardiol: 18 Nov 2022; epub ahead of print</small></div>
Proença T, Pinto RA, Carvalho MM, Rocha A, Dias P, Macedo F
Int J Cardiol: 18 Nov 2022; epub ahead of print | PMID: 36410542
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<div><h4>Aortic size predicts aortic dissection in turner syndrome - A 25-year prospective cohort study.</h4><i>Thunström S, Thunström E, Naessén S, Berntorp K, ... Bryman I, Landin-Wilhelmsen K</i><br /><b>Background</b><br />Women with Turner syndrome (TS) have an increased risk of aortic dissection. The current recommended cutoff to prevent aortic dissection in TS is an aortic size index (ASI) of ≥2.5 cm/m<sup>2</sup>. This study estimated which aortic size had the best predictive value for the risk of aortic dissection, and whether adjusting for body size improved risk prediction.<br /><b>Methods</b><br />A prospective, observational study in Sweden, of women with TS, n = 400, all evaluated with echocardiography of the aorta and data on medical history for up to 25 years. Receiver operating characteristic (ROC) curves, sensitivity and specificity were calculated for the absolute ascending aortic diameter (AAD), ascending ASI and TS specific z-score.<br /><b>Results</b><br />There were 12 patients (3%) with aortic dissection. ROC curves demonstrated that absolute AAD and TS specific z-score were superior to ascending ASI in predicting aortic dissection. The best cutoff for absolute AAD was 3.3 cm and 2.12 for the TS specific z-score, respectively, with a sensitivity of 92% for both. The ascending ASI cutoff of 2.5 cm/m<sup>2</sup> had a sensitivity of 17% only. Subgroup analyses in women with an aortic diameter ≥ 3.3 cm could not demonstrate any association between karyotype, aortic coarctation, bicuspid aortic valve, BMI, antihypertensive medication, previous growth hormone therapy or ongoing estrogen replacement treatment and aortic dissection. All models failed to predict a dissection in a pregnant woman.<br /><b>Conclusions</b><br />In Turner syndrome, absolute AAD and TS-specific z-score were more reliable predictors for aortic dissection than ASI. Care should be taken before and during pregnancy.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 18 Nov 2022; epub ahead of print</small></div>
Thunström S, Thunström E, Naessén S, Berntorp K, ... Bryman I, Landin-Wilhelmsen K
Int J Cardiol: 18 Nov 2022; epub ahead of print | PMID: 36410543
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<div><h4>Polygenic risk in Type III hyperlipidaemia and risk of cardiovascular disease: An epidemiological study in UK Biobank and Oxford Biobank.</h4><i>Pieri K, Trichia E, Neville MJ, Taylor H, ... Karpe F, Koivula RW</i><br /><b>Background</b><br />Type III hyperlipidaemia (T3HL) is characterised by equimolar increases in plasma triglycerides (TG) and cholesterol in <10% of APOE22 carriers conveying high cardiovascular disease (CVD) risk. We investigate the role of a weighted triglyceride-raising polygenic score (TG.PS) precipitating T3HL.<br /><b>Methods</b><br />The TG.PS (restricted to genome-wide significance and weighted by published independent effect estimates) was applied to the Oxford Biobank (OBB, n = 6952) and the UK Biobank (UKB, n = 460,037), to analyse effects on plasma lipid phenotypes. Fasting plasma lipid, lipoprotein biochemistry and NMR lipoprotein profiles were analysed in OBB. CVD prevalence/incidence was examined in UKB.<br /><b>Results</b><br />One TG.PS standard-deviation (SD) was associated with 13.0% (95% confidence-interval 12.0-14.0%) greater TG in OBB and 15.2% (15.0-15.4%) in UKB. APOE22 carriers had 19.0% (1.0-39.0%) greater TG in UKB. Males were more susceptible to TG.PS effects (4.0% (2.0-6.0%) greater TG with 1 TG.PS SD in OBB, 1.6% (1.3-1.9%) in UKB) than females. There was no interaction between APOE22 and TG.PS, BMI, sex or age on TG. APOE22 carriers had lower apolipoprotein B (apoB) (OBB; -0.35 (-0.29 to -0.40)g/L, UKB; -0.41 (-0.405 to -0.42)g/L). NMR lipoprotein lipid concentrations were discordant to conventional biochemistry in APOE22 carriers. In APOE22 compared with APOE33, CVD was no more prevalent in similarly hypertriglyceridaemic participants (OR 0.97 95%CI 0.76-1.25), but was less prevalent in normolipidaemia (OR 0.81, 95%CI 0.69-0.95); no differences were observed in CVD incidence.<br /><b>Conclusions</b><br />TG.PS confers an additive risk for developing T3HL, that is of comparable effect size to conventional risk factors. The protective effect of APOE22 for prevalent CVD is consistent with lower apoB in APOE22 carriers.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 18 Nov 2022; epub ahead of print</small></div>
Pieri K, Trichia E, Neville MJ, Taylor H, ... Karpe F, Koivula RW
Int J Cardiol: 18 Nov 2022; epub ahead of print | PMID: 36410544
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<div><h4>Machine learning approach in diagnosing Takotsubo cardiomyopathy: The role of the combined evaluation of atrial and ventricular strain, and parametric mapping.</h4><i>Cau R, Pisu F, Porcu M, Cademartiri F, ... Suri JS, Saba L</i><br /><b>Background</b><br />Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is a key diagnostic tool in the differential diagnosis between non-ischemic cause of cardiac chest pain. Some patients are not eligible for a gadolinium contrast-enhanced CMR; in this scenario, the diagnosis remains challenging without invasive examination. Our purpose was to derive a machine learning model integrating some non-contrast CMR parameters and demographic factors to identify Takotsubo cardiomyopathy (TTC) in subjects with cardiac chest pain.<br /><b>Material and methods</b><br />Three groups of patients were retrospectively studied: TTC, acute myocarditis, and healthy controls. Global and regional left ventricular longitudinal, circumferential, and radial strain (RS) analysis included were assessed. Reservoir, conduit, and booster bi-atrial functions were evaluated by tissue-tracking. Parametric mapping values were also assessed in all the patients. Five different tree-based ensemble learning algorithms were tested concerning their ability in recognizing TTC in a fully cross-validated framework.<br /><b>Results</b><br />The CMR-based machine learning (ML) ensemble model, by using the Extremely Randomized Trees algorithm with Elastic Net feature selection, showed a sensitivity of 92% (95% CI 78-100), specificity of 86% (95% CI 80-92) and area under the ROC of 0.94 (95% CI 0.90-0.99) in diagnosing TTC. Among non-contrast CMR parameters, the Shapley additive explanations analysis revealed that left atrial (LA) strain and strain rate were the top imaging markers in identifying TTC patients.<br /><b>Conclusions</b><br />Our study demonstrated that using a tree-based ensemble learning algorithm on non-contrast CMR parameters and demographic factors enables the identification of subjects with TTC with good diagnostic accuracy.<br /><b>Translational outlook</b><br />Our results suggest that non-contrast CMR features can be implemented in a ML model to accurately identify TTC subjects. This model could be a valuable tool for aiding in the diagnosis of subjects with a contraindication to the contrast media. Furthermore, the left atrial conduit strain and strain rate were imaging markers that had a strong impact on TTC identification. Further prospective and longitudinal studies are needed to validate these findings and assess predictive performance in different cohorts, such as those with different ethnicities, and social backgrounds and undergoing different treatments.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 18 Nov 2022; epub ahead of print</small></div>
Cau R, Pisu F, Porcu M, Cademartiri F, ... Suri JS, Saba L
Int J Cardiol: 18 Nov 2022; epub ahead of print | PMID: 36410545
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<div><h4>Therapy with high-dose statins reduces soluble P-selectin: The impact on plasma fibrin clot properties.</h4><i>Siudut J, Pudło J, Konieczyńska M, Polak M, Jawień J, Undas A</i><br /><b>Objective</b><br />Studies on the effect of statins on platelets in patients with coronary artery disease (CAD) yielded inconsistent results. We sought to investigate whether high-dose statin therapy reduces plasma concentrations of soluble P-selectin (sP-selectin), a well-established platelet activation marker and if such changes can affect fibrin clot properties, which are unfavorably altered in CAD patients.<br /><b>Methods</b><br />We studied 130 consecutive patients with advanced CAD who did not achieve the target LDL cholesterol on statins. At baseline and after 6-12 months of treatment with atorvastatin 80 mg/day or rosuvastatin 40 mg/day, soluble plasma sP-selectin, along with plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation and fibrinolysis proteins were determined.<br /><b>Results</b><br />Before high-intensity statin treatment, lower Ks and longer CLT values were associated with increased sP-selectin (β -0.27 [95% CI -0.44 to -0.10] and β 0.21 [95% CI 0.01 to 0.41]; both p < 0.05, respectively) also after adjustment for potential confounders. sP-selectin, alongside fibrin features and other variables at baseline showed no association with lipid profile. On high-dose statin therapy, there was 32% reduction in sP-selectin levels (p < 0.001). On-treatment change (Δ) in sP-selectin correlated with ΔKs and ΔCLT (r = -0.32, p < 0.001 and r = 0.22, p = 0.011, respectively), but not with cholesterol and C-reactive protein lowering. We did not observe any associations between post-treatment sP-selectin levels and lipids, fibrin clot properties or thrombin generation.<br /><b>Conclusions</b><br />High-dose statin therapy reduces markedly sP-selectin levels in association with improved fibrin clot phenotype, which highlights the contribution of platelet-derived proteins to a prothrombotic state in hypercholesterolemia and statin-induced antithrombotic effects.<br /><br />Copyright © 2022. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 18 Nov 2022; epub ahead of print</small></div>
Siudut J, Pudło J, Konieczyńska M, Polak M, Jawień J, Undas A
Int J Cardiol: 18 Nov 2022; epub ahead of print | PMID: 36410546
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