Topic: Journal Club Selection

Abstract
<div><h4>Artificial intelligence-derived risk score for mortality in secondary mitral regurgitation treated by transcatheter edge-to-edge repair: the EuroSMR risk score.</h4><i>Hausleiter J, Lachmann M, Stolz L, Bedogni F, ... Rudolph V, EuroSMR Investigators </i><br /><b>Background:</b><br/>and aims</b><br />Risk stratification for mitral valve transcatheter edge-to-edge repair (M-TEER) is paramount in the decision-making process to appropriately select patients with severe secondary mitral regurgitation (SMR). This study sought to develop and validate an artificial intelligence-derived risk score (EuroSMR score) to predict 1-year outcomes (survival or survival + clinical improvement) in patients with SMR undergoing M-TEER.<br /><b>Methods</b><br />An artificial intelligence-derived risk score was developed from the EuroSMR cohort (4172 and 428 patients treated with M-TEER in the derivation and validation cohorts, respectively). The EuroSMR score was validated and compared with established risk models.<br /><b>Results</b><br />The EuroSMR risk score, which is based on 18 clinical, echocardiographic, laboratory, and medication parameters, allowed for an improved discrimination of surviving and non-surviving patients (hazard ratio 4.3, 95% confidence interval 3.7-5.0; P < .001), and outperformed established risk scores in the validation cohort. Prediction for 1-year mortality (area under the curve: 0.789, 95% confidence interval 0.737-0.842) ranged from <5% to >70%, including the identification of an extreme-risk population (2.6% of the entire cohort), which had a very high probability for not surviving beyond 1 year (hazard ratio 6.5, 95% confidence interval 3.0-14; P < .001). The top 5% of patients with the highest EuroSMR risk scores showed event rates of 72.7% for mortality and 83.2% for mortality or lack of clinical improvement at 1-year follow-up.<br /><b>Conclusions</b><br />The EuroSMR risk score may allow for improved prognostication in heart failure patients with severe SMR, who are considered for a M-TEER procedure. The score is expected to facilitate the shared decision-making process with heart team members and patients.<br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 14 Mar 2024; 45:922-936</small></div>
Hausleiter J, Lachmann M, Stolz L, Bedogni F, ... Rudolph V, EuroSMR Investigators
Eur Heart J: 14 Mar 2024; 45:922-936 | PMID: 38243773
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<div><h4>Legacy benefits of blood pressure treatment on cardiovascular events are primarily mediated by improved blood pressure variability: the ASCOT trial.</h4><i>Gupta A, Whiteley WN, Godec T, Rostamian S, ... Sever PS, ASCOT-10 Investigators </i><br /><b>Background:</b><br/>and aims</b><br />Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure (BP) control, but with differential BPV, is uncertain. Morbidity and mortality follow-up of UK participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm has been extended for up to 21 years to determine the CV impact of mean systolic blood pressure (SBP) control and BPV during the trial, and amongst those allocated to amlodipine- and atenolol-based treatment.<br /><b>Methods</b><br />Eight thousand five hundred and eighty hypertensive participants (4305 assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period (median 5.5 years) were followed for up to 21 years (median 17.4 years), using linked hospital and mortality records. A subgroup of participants (n = 2156) was followed up 6 years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean SBP and standard deviation of visit-to-visit SBP as a measure of BPV, were measured using >100 000 BP measurements. Cox proportional hazard models were used to estimate the risk [hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes.<br /><b>Results</b><br />Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes {HR per 10 mmHg, 1.14 [95% confidence interval (CI) 1.10-1.17], P < .001}, systolic BPV independent of mean SBP was a strong predictor of CV events [HR per 5 mmHg 1.22 (95% CI 1.18-1.26), P < .001] and predicted events even in participants with well-controlled BP. During 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of stroke [HR 0.82 (95% CI 0.72-0.93), P = .003], total CV events [HR 0.93 (95% CI 0.88-0.98), P = .008], total coronary events [HR 0.92 (95% CI 0.86-0.99), P = .024], and atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = .030], with weaker evidence of a difference in CV mortality [HR 0.91 (95% CI 0.82-1.01), P = .073]. There was no significant difference in the incidence of non-fatal myocardial infarction and fatal coronary heart disease, heart failure, and all-cause mortality.<br /><b>Conclusions</b><br />Systolic BPV is a strong predictor of CV outcome, even in those with controlled SBP. The long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing CV events appear to be primarily mediated by an effect on systolic BPV during the trial period.<br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 31 Jan 2024; epub ahead of print</small></div>
Gupta A, Whiteley WN, Godec T, Rostamian S, ... Sever PS, ASCOT-10 Investigators
Eur Heart J: 31 Jan 2024; epub ahead of print | PMID: 38291599
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<div><h4>Clinical Presentation, Classification, and Outcomes of Cardiogenic Shock in Children.</h4><i>Puri K, Jentzer JC, Spinner JA, Hope KD, ... Cabrera AG, Price JF</i><br /><b>Background</b><br />Despite growing cardiogenic shock (CS) research in adults, the epidemiology, clinical features, and outcomes of children with CS are lacking.<br /><b>Objectives</b><br />This study sought to describe the epidemiology, clinical presentation, hospital course, risk factors, and outcomes of CS among children hospitalized for acute decompensated heart failure (ADHF).<br /><b>Methods</b><br />We examined consecutive ADHF hospitalizations (<21 years of age) from a large single-center retrospective cohort. Patients with CS at presentation were analyzed and risk factors for CS and for the primary outcome of in-hospital mortality were identified. A modified Society for Cardiovascular Angiography and Interventions shock classification was created and patients were staged accordingly.<br /><b>Results</b><br />A total of 803 hospitalizations for ADHF were identified in 591 unique patients (median age 7.6 years). CS occurred in 207 (26%) hospitalizations. ADHF hospitalizations with CS were characterized by worse systolic function (P = 0.040), higher B-type natriuretic peptide concentration (P = 0.032), and more frequent early severe renal (P = 0.023) and liver (P < 0.001) injury than those without CS. Children presenting in CS received mechanical ventilation (87% vs 26%) and mechanical circulatory support (45% vs 16%) more frequently (both P < 0.001). Analyzing only the most recent ADHF hospitalization, children with CS were at increased risk of in-hospital mortality compared with children without CS (28% vs 11%; OR: 1.91; 95% CI: 1.05-3.45; P = 0.033). Each higher CS stage was associated with greater inpatient mortality (OR: 2.40-8.90; all P < 0.001).<br /><b>Conclusions</b><br />CS occurs in 26% of pediatric hospitalizations for ADHF and is independently associated with hospital mortality. A modified Society for Cardiovascular Angiography and Interventions classification for CS severity showed robust association with increasing mortality.<br /><br />Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 06 Feb 2024; 83:595-608</small></div>
Puri K, Jentzer JC, Spinner JA, Hope KD, ... Cabrera AG, Price JF
J Am Coll Cardiol: 06 Feb 2024; 83:595-608 | PMID: 38296404
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<div><h4>Exposome in ischaemic heart disease: beyond traditional risk factors.</h4><i>Montone RA, Camilli M, Calvieri C, Magnani G, ... Crea F, Niccoli G</i><br /><AbstractText>Ischaemic heart disease represents the leading cause of morbidity and mortality, typically induced by the detrimental effects of risk factors on the cardiovascular system. Although preventive interventions tackling conventional risk factors have helped to reduce the incidence of ischaemic heart disease, it remains a major cause of death worldwide. Thus, attention is now shifting to non-traditional risk factors in the built, natural, and social environments that collectively contribute substantially to the disease burden and perpetuate residual risk. Of importance, these complex factors interact non-linearly and in unpredictable ways to often enhance the detrimental effects attributable to a single or collection of these factors. For this reason, a new paradigm called the \'exposome\' has recently been introduced by epidemiologists in order to define the totality of exposure to these new risk factors. The purpose of this review is to outline how these emerging risk factors may interact and contribute to the occurrence of ischaemic heart disease, with a particular attention on the impact of long-term exposure to different environmental pollutants, socioeconomic and psychological factors, along with infectious diseases such as influenza and COVID-19. Moreover, potential mitigation strategies for both individuals and communities will be discussed.</AbstractText><br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Feb 2024; 45:419-438</small></div>
Montone RA, Camilli M, Calvieri C, Magnani G, ... Crea F, Niccoli G
Eur Heart J: 07 Feb 2024; 45:419-438 | PMID: 38238478
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<div><h4>Merging machine learning and patient preference: a novel tool for risk prediction of percutaneous coronary interventions.</h4><i>Hamilton DE, Albright J, Seth M, Painter I, ... Sukul D, Gurm HS</i><br /><b>Background:</b><br/>and aims</b><br />Predicting personalized risk for adverse events following percutaneous coronary intervention (PCI) remains critical in weighing treatment options, employing risk mitigation strategies, and enhancing shared decision-making. This study aimed to employ machine learning models using pre-procedural variables to accurately predict common post-PCI complications.<br /><b>Methods</b><br />A group of 66 adults underwent a semiquantitative survey assessing a preferred list of outcomes and model display. The machine learning cohort included 107 793 patients undergoing PCI procedures performed at 48 hospitals in Michigan between 1 April 2018 and 31 December 2021 in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) registry separated into training and validation cohorts. External validation was conducted in the Cardiac Care Outcomes Assessment Program database of 56 583 procedures in 33 hospitals in Washington.<br /><b>Results</b><br />Overall rate of in-hospital mortality was 1.85% (n = 1999), acute kidney injury 2.51% (n = 2519), new-onset dialysis 0.44% (n = 462), stroke 0.41% (n = 447), major bleeding 0.89% (n = 942), and transfusion 2.41% (n = 2592). The model demonstrated robust discrimination and calibration for mortality {area under the receiver-operating characteristic curve [AUC]: 0.930 [95% confidence interval (CI) 0.920-0.940]}, acute kidney injury [AUC: 0.893 (95% CI 0.883-0.903)], dialysis [AUC: 0.951 (95% CI 0.939-0.964)], stroke [AUC: 0.751 (95%CI 0.714-0.787)], transfusion [AUC: 0.917 (95% CI 0.907-0.925)], and major bleeding [AUC: 0.887 (95% CI 0.870-0.905)]. Similar discrimination was noted in the external validation population. Survey subjects preferred a comprehensive list of individually reported post-procedure outcomes.<br /><b>Conclusions</b><br />Using common pre-procedural risk factors, the BMC2 machine learning models accurately predict post-PCI outcomes. Utilizing patient feedback, the BMC2 models employ a patient-centred tool to clearly display risks to patients and providers (https://shiny.bmc2.org/pci-prediction/). Enhanced risk prediction prior to PCI could help inform treatment selection and shared decision-making discussions.<br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 21 Feb 2024; 45:601-609</small></div>
Hamilton DE, Albright J, Seth M, Painter I, ... Sukul D, Gurm HS
Eur Heart J: 21 Feb 2024; 45:601-609 | PMID: 38233027
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<div><h4>Clonal haematopoiesis of indeterminate potential and atrial fibrillation: an east Asian cohort study.</h4><i>Ahn HJ, An HY, Ryu G, Lim J, ... Koh Y, Choi EK</i><br /><b>Background:</b><br/>and aims</b><br />Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF.<br /><b>Methods</b><br />Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort.<br /><b>Results</b><br />The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E\', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death).<br /><b>Conclusions</b><br />CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.<br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 07 Mar 2024; 45:778-790</small></div>
Ahn HJ, An HY, Ryu G, Lim J, ... Koh Y, Choi EK
Eur Heart J: 07 Mar 2024; 45:778-790 | PMID: 38231881
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<div><h4>Aspirin-free antiplatelet strategies after percutaneous coronary interventions.</h4><i>Capranzano P, Moliterno D, Capodanno D</i><br /><AbstractText>Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 receptor inhibitor is the standard antithrombotic treatment after percutaneous coronary interventions (PCI). Several trials have challenged guideline-recommended DAPT after PCI by testing the relative clinical effect of an aspirin-free antiplatelet approach-consisting of P2Y12 inhibitor monotherapy after a short course (mostly 1-3 months) of DAPT-among patients undergoing PCI without a concomitant indication for oral anticoagulation (OAC). Overall, these studies have shown P2Y12 inhibitor monotherapy after short DAPT to be associated with a significant reduction in the risk of bleeding without an increase in thrombotic or ischaemic events compared with continued DAPT. Moreover, the effects of the P2Y12 inhibitor monotherapy without prior DAPT or following a very short course of DAPT after PCI are being investigated in emerging studies, of which one has recently reported unfavourable efficacy results associated with the aspirin-free approach compared with conventional DAPT. Finally, P2Y12 inhibitor alone has been compared with aspirin alone as chronic therapy after DAPT discontinuation, thus challenging the historical role of aspirin as a standard of care for secondary prevention following PCI. A thorough understanding of study designs, populations, treatments, results, and limitations of trials testing P2Y12 inhibitor monotherapy vs. DAPT or vs. aspirin is required to consider adopting this treatment in clinical practice. This review addresses the use of aspirin-free antiplatelet strategies among patients undergoing PCI without a concomitant indication for OAC, providing an overview of clinical evidence, guideline indications, practical implications, ongoing issues, and future perspectives.</AbstractText><br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 21 Feb 2024; 45:572-585</small></div>
Capranzano P, Moliterno D, Capodanno D
Eur Heart J: 21 Feb 2024; 45:572-585 | PMID: 38240716
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<div><h4>Atrial electro-functional predictors of incident atrial fibrillation in cardiac amyloidosis.</h4><i>Sinigiani G, De Michieli L, Porcari A, Zocchi C, ... Cappelli F, Cipriani A</i><br /><b>Background</b><br />Atrial fibrillation (AF) is common in patients with cardiac amyloidosis (CA) and is a significant risk factor for heart failure hospitalization and thromboembolic events.<br /><b>Objective</b><br />to investigate the atrial electro-functional predictors of incident AF in CA.<br /><b>Methods</b><br />A multicenter, observational study performed in 4 CA referral centers including sinus rhythm patients with light-chain (AL) and transthyretin (ATTR) CA undergoing electrocardiogram (ECG) and cardiac magnetic resonance (CMR). The primary endpoint was new-onset AF occurrence.<br /><b>Results</b><br />Overall, 96 patients (AL-CA: n=40; ATTR-CA n=56) were enrolled. During an 18-month median follow-up (Q1-Q3:7-29), 30 patients (29%) had incident AF. Compared with those without, patients with AF were older (79 vs 73 years, p=0.001) and more frequently with ATTR (73% vs 27%, p<0.001), ECG inter-atrial block (IAB), either partial (47% vs 21%, p=0.011) or advanced (17% vs 3%,p=0.017), and lower left atrium ejection fraction (LAEF) (29% vs 41%, p=0.004). Age (HR=1.059; 95%CI 1.002-1.118,p=0.042), any type of IAB (HR=2.211; 95%CI 1.03-4.75, p=0.041) and LAEF (HR=0.967; 95%CI 0.936-0.998, p=0.044) emerged as independent predictors of incident AF. Patients exhibiting any type of IAB, LAEF<40%, and aged>78 years showed a cumulative incidence for AF of 40% at 12 months. This risk was significantly higher than that carried by one (8.5%) or none (7.6%) of these three risk factors.<br /><b>Conclusions</b><br />In patients with CA, older age, IAB on 12-lead ECG and reduced LAEF on CMR are significant and independent predictors of incident AF. A closer screening for AF is advisable in CA patients carrying these features.<br /><br />Copyright © 2024. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 01 Feb 2024; epub ahead of print</small></div>
Sinigiani G, De Michieli L, Porcari A, Zocchi C, ... Cappelli F, Cipriani A
Heart Rhythm: 01 Feb 2024; epub ahead of print | PMID: 38309449
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<div><h4>Ablation of epicardial ventricular focus through coronary sinus using pulsed-field ablation. A case report.</h4><i>Mestrovic IP, Breskovic T, Markovic M, Kurtic E, Mestrovic T, Anic A</i><br /><b>Introduction</b><br />With the entry of pulsed-field ablation (PFA) into electrophysiology, new possibilities for ablation of different substrates such as epicardial foci of premature ventricular contractions (PVCs) from coronary venous system (CVS) have been opened.<br /><b>Methods</b><br />This article focuses on a case of a 27-year-old patient with frequent monomorphic PVCs of epicardial origin, treated by radiofrequency ablation, followed by PFA.<br /><b>Results</b><br />After unsuccessful focus ablation through CVS with RFA, successful ablations from the same region with PFA were achieved.<br /><b>Conclusion</b><br />This is the first described case of successful ablation of epicardial PVCs using PFA, which we hope will help in defining indications for this novel technology and enhance quality of treatment for patients with different arrhythmias.<br /><br />© 2024 Wiley Periodicals LLC.<br /><br /><small>J Cardiovasc Electrophysiol: 31 Jan 2024; epub ahead of print</small></div>
Mestrovic IP, Breskovic T, Markovic M, Kurtic E, Mestrovic T, Anic A
J Cardiovasc Electrophysiol: 31 Jan 2024; epub ahead of print | PMID: 38297424
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<div><h4>Risk Prediction in Male Adolescents With Congenital Long QT Syndrome: Implications for Sex-Specific Risk Stratification in Potassium Channel-Mediated Long QT Syndrome.</h4><i>Bjelic M, Goldenberg I, Younis A, Chen AY, ... Ackerman MJ, Goldenberg I</i><br /><b>Background</b><br />Sex-specific risk management may improve outcomes in congenital long QT syndrome (LQTS). We recently developed a prediction score for cardiac events (CEs) and life-threatening events (LTEs) in postadolescent women with LQTS. In the present study, we aimed to develop personalized risk estimates for the burden of CEs and LTEs in male adolescents with potassium channel-mediated LQTS.<br /><b>Methods and results</b><br />The prognostic model was derived from the LQTS Registry headquartered in Rochester, NY, comprising 611 LQT1 or LQT2 male adolescents from age 10 through 20 years, using the following variables: genotype/mutation location, QTc-specific thresholds, history of syncope, and β-blocker therapy. Anderson-Gill modeling was performed for the end point of CE burden (total number of syncope, aborted cardiac arrest, and appropriate defibrillator shocks). The applicability of the CE prediction model was tested for the end point of the first LTE (excluding syncope and adding sudden cardiac death) using Cox modeling. A total of 270 CEs occurred during follow-up. The genotype-phenotype risk prediction model identified low-, intermediate-, and high-risk groups, comprising 74%, 14%, and 12% of the study population, respectively. Compared with the low-risk group, high-risk male subjects experienced a pronounced 5.2-fold increased risk of recurrent CEs (<i>P</i><0.001), whereas intermediate-risk patients had a 2.1-fold (<i>P</i>=0.004) increased risk . At age 20 years, the low-, intermediate-, and high-risk adolescent male patients had on average 0.3, 0.6, and 1.4 CEs per person, respectively. Corresponding 10-year adjusted probabilities for a first LTE were 2%, 6%, and 8%.<br /><b>Conclusions</b><br />Personalized genotype-phenotype risk estimates can be used to guide sex-specific management in male adolescents with potassium channel-mediated LQTS.<br /><br /><br /><br /><small>J Am Heart Assoc: 06 Feb 2024; 13:e028902</small></div>
Bjelic M, Goldenberg I, Younis A, Chen AY, ... Ackerman MJ, Goldenberg I
J Am Heart Assoc: 06 Feb 2024; 13:e028902 | PMID: 38240206
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<div><h4>Atrial Fibrillation Detection and Ischemic Stroke Recurrence in Cryptogenic Stroke: A Retrospective, Multicenter, Observational Study.</h4><i>Todo K, Okazaki S, Doijiri R, Yamazaki H, ... Mochizuki H, CRYPTON‐ICM Registry Investigators</i><br /><b>Background</b><br />Atrial fibrillation (AF) is known to be a strong risk factor for stroke. However, the risk of stroke recurrence in patients with cryptogenic stroke with AF detected after stroke by an insertable cardiac monitor (ICM) is not well known. We sought to evaluate the risk of ischemic stroke recurrence in patients with cryptogenic stroke with and without ICM-detected AF.<br /><b>Methods and results</b><br />We retrospectively reviewed patients with cryptogenic stroke who underwent ICM implantation at 8 stroke centers in Japan. Cox regression models were developed using landmark analysis and time-dependent analysis. We set the target sample size at 300 patients based on our estimate of the annualized incidence of ischemic stroke recurrence to be 3% in patients without AF detection and 9% in patients with AF detection. Of the 370 patients, 121 were found to have AF, and 110 received anticoagulation therapy after AF detection. The incidence of ischemic stroke recurrence was 4.0% in 249 patients without AF detection and 5.8% in 121 patients with AF detection (<i>P</i>=0.45). In a landmark analysis, the risk of ischemic stroke recurrence was not higher in patients with AF detected ≤90 days than in those without (hazard ratio, 1.47 [95% CI, 0.41-5.28]). In a time-dependent analysis, the risk of ischemic stroke recurrence did not increase after AF detection (hazard ratio, 1.77 [95% CI, 0.70-4.47]).<br /><b>Conclusions</b><br />The risk of ischemic stroke recurrence in patients with cryptogenic stroke with ICM-detected AF, 90% of whom were subsequently anticoagulated, was not higher than in those without ICM-detected AF.<br /><br /><br /><br /><small>J Am Heart Assoc: 06 Feb 2024; 13:e031508</small></div>
Todo K, Okazaki S, Doijiri R, Yamazaki H, ... Mochizuki H, CRYPTON‐ICM Registry Investigators
J Am Heart Assoc: 06 Feb 2024; 13:e031508 | PMID: 38240210
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<div><h4>Outcomes of Valve-in-Valve Transcatheter Aortic Valve Replacement.</h4><i>Ahmad D, Yousef S, Kliner D, Brown JA, ... Thoma FW, Sultan I</i><br /><AbstractText>Structural valve degeneration is increasingly seen given the higher rates of bioprosthetic heart valve use for surgical and transcatheter aortic valve replacement (TAVR). Valve-in-valve TAVR (VIV-TAVR) is an attractive alternate for patients who are otherwise at high risk for reoperative surgery. We compared patients who underwent VIV-TAVR and native valve TAVR through a retrospective analysis of our institutional transcatheter valve therapy (TVT) database from 2013 to 2022. Patients who underwent either a native valve TAVR or VIV-TAVR were included. VIV-TAVR was defined as TAVR in patients who underwent a previous surgical aortic valve replacement. Kaplan-Meier survival analysis was used to obtain survival estimates. A Cox proportional hazards regression model was used for the multivariable analysis of mortality. A total of 3,532 patients underwent TAVR, of whom 198 (5.6%) underwent VIV-TAVR. Patients in the VIV-TAVR cohort were younger than patients who underwent native valve TAVR (79.5 vs 84 years, p <0.001), with comparable number of women and a higher Society of Thoracic Surgeons risk score (6.28 vs 4.46, p <0.001). The VIV-TAVR cohort had a higher incidence of major vascular complications (2.5% vs 0.8%, p = 0.008) but lower incidence of permanent pacemaker placement (2.5% vs 8.1%, p = 0.004). The incidence of stroke was comparable between the groups (VIV-TAVR 2.5% vs native TAVR 2.4%, p = 0.911). The 30-day readmission rates (VIV-TAVR 7.1% vs native TAVR 9%, p = 0.348), as well as in-hospital (VIV-TAVR 2% vs native TAVR 1.4%, p = 0.46), and overall (VIV-TAVR 26.3% vs native TAVR 30.8%, p = 0.18) mortality at a follow-up of 1.8 years (0.83 to 3.5) were comparable between the groups. The survival estimates were also comparable between the groups (log-rank p = 0.27). On multivariable Cox regression analysis, VIV-TAVR was associated with decreased hazards of death (hazard ratio 0.68 [0.5 to 0.9], p = 0.02). In conclusion, VIV-TAVR is a feasible and safe strategy for high-risk patients with bioprosthetic valve failure. There may be potentially higher short-term morbidity with VIV-TAVR, with no overt impact on survival.</AbstractText><br /><br />Copyright © 2024 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 15 Mar 2024; 215:1-7</small></div>
Ahmad D, Yousef S, Kliner D, Brown JA, ... Thoma FW, Sultan I
Am J Cardiol: 15 Mar 2024; 215:1-7 | PMID: 38232811
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<div><h4>Clinical Impact of In-Stent Calcification in Coronary Arteries: Optical Coherence Tomography Study.</h4><i>Jinnouchi H, Sakakura K, Taniguchi Y, Yamamoto K, ... Seguchi M, Fujita H</i><br /><AbstractText>In-stent restenosis with neoatherosclerosis has been known as the predictor of target lesion revascularization (TLR) after percutaneous coronary intervention. However, the impact of in-stent calcification (ISC) alone on clinical outcomes remains unknown since neoatherosclerosis by optical coherence tomography includes in-stent lipid and calcification. We aimed to assess the effect of ISC on clinical outcomes and clinical differences among different types of ISC. We included 126 lesions that underwent optical coherence tomography-guided percutaneous coronary intervention and divided those into the ISC group (n = 38) and the non-ISC group (n = 88) according to the presence of ISC. The cumulative incidence of clinically driven TLR (CD-TLR) was compared between the ISC and non-ISC groups. The impact of in-stent calcified nodule and nodular calcification on CD-TLR was evaluated using the Cox hazard model. The incidence of CD-TLR was significantly higher in the ISC group than in the non-ISC group (p = 0.004). In the multivariate Cox hazard model, ISC was significantly associated with CD-TLR (hazard ratio [HR] 3.58, 95% confidence interval [CI] 1.33 to 9.65, p = 0.01). In-stent calcified nodule/nodular calcification and in-stent nodular calcification alone were also the factors significantly associated with CD-TLR (HR 3.34, 95%CI 1.15 to 9.65, p = 0.03 and HR 5.21, 95%CI 1.82 to 14.91, p = 0.002, respectively). ISC without in-stent calcified nodule/nodular calcification, which was defined as in-stent smooth calcification, was not associated with CD-TLR. In conclusion, ISC was associated with a higher rate of CD-TLR. The types of calcifications that led to a high rate of CD-TLR were in-stent calcified nodule/nodular calcification and in-stent nodular calcification alone but not in-stent smooth calcification. In-stent calcified nodule and nodular calcification should be paid more attention.</AbstractText><br /><br />Copyright © 2024 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 01 Mar 2024; 214:115-124</small></div>
Jinnouchi H, Sakakura K, Taniguchi Y, Yamamoto K, ... Seguchi M, Fujita H
Am J Cardiol: 01 Mar 2024; 214:115-124 | PMID: 38232806
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<div><h4>Impella Versus Intra-Aortic Balloon Pump in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: An Observational Study.</h4><i>Yeo I, Axman R, Lu DY, Feldman DN, ... Wong SC, Kim LK</i><br /><b>Background</b><br />Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for patients with cardiogenic shock. Although Impella or intra-aortic balloon pump (IABP) is frequently used for left ventricular unloading (LVU) during VA-ECMO treatment, there are limited data on comparative outcomes. We compared outcomes of Impella and IABP for LVU during VA-ECMO.<br /><b>Methods and results</b><br />Using the Nationwide Readmissions Database between 2016 and 2020, we analyzed outcomes in 3 groups of patients with cardiogenic shock requiring VA-ECMO based on LVU strategies: extracorporeal membrane oxygenation (ECMO) only, ECMO with IABP, and ECMO with Impella. Of 15 980 patients on VA-ECMO, IABP and Impella were used in 19.4% and 16.4%, respectively. The proportion of patients receiving Impella significantly increased from 2016 to 2020 (6.5% versus 25.8%; <i>P</i>-trend<0.001). In-hospital mortality was higher with ECMO with Impella (54.8%) compared with ECMO only (50.4%) and ECMO with IABP (48.4%). After adjustment, ECMO with IABP versus ECMO only was associated with lower in-hospital mortality (adjusted odds ratio [aOR], 0.83; <i>P</i>=0.02). ECMO with Impella versus ECMO only had similar in-hospital mortality (aOR, 1.09; <i>P</i>=0.695) but was associated with more bleeding (aOR, 1.21; <i>P</i>=0.007) and more acute kidney injury requiring hemodialysis (aOR, 1.42; <i>P</i><0.001). ECMO with Impella versus ECMO with IABP was associated with greater risk of acute kidney injury requiring hemodialysis (aOR, 1.49; <i>P</i>=0.002), higher in-hospital mortality (aOR, 1.32; <i>P</i>=0.001), and higher 40-day mortality (hazard ratio, 1.25; <i>P</i><0.001).<br /><b>Conclusions</b><br />In patients with cardiogenic shock on VA-ECMO, LVU with Impella, particularly with 2.5/CP, was not associated with improved survival at 40 days but was associated with increased adverse events compared with IABP. More data are needed to assess Impella platform-specific comparative outcomes of LVU.<br /><br /><br /><br /><small>J Am Heart Assoc: 06 Feb 2024; 13:e032607</small></div>
Yeo I, Axman R, Lu DY, Feldman DN, ... Wong SC, Kim LK
J Am Heart Assoc: 06 Feb 2024; 13:e032607 | PMID: 38240236
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<div><h4>Epidemiology, Pathophysiology, and Imaging of Atherosclerotic Intracranial Disease.</h4><i>Chen LH, Spagnolo-Allende A, Yang D, Qiao Y, Gutierrez J</i><br /><AbstractText>Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide. Among people with stroke, those of East Asia descent and non-White populations in the United States have a higher burden of ICAD-related stroke compared with Whites of European descent. Disparities in the prevalence of asymptomatic ICAD are less marked than with symptomatic ICAD. In addition to stroke, ICAD increases the risk of dementia and cognitive decline, magnifying ICAD societal burden. The risk of stroke recurrence among patients with ICAD-related stroke is the highest among those with confirmed stroke and stenosis ≥70%. In fact, the 1-year recurrent stroke rate of >20% among those with stenosis >70% is one of the highest rates among common causes of stroke. The mechanisms by which ICAD causes stroke include plaque rupture with in situ thrombosis and occlusion or artery-to-artery embolization, hemodynamic injury, and branch occlusive disease. The risk of stroke recurrence varies by the presumed underlying mechanism of stroke, but whether techniques such as quantitative magnetic resonance angiography, computed tomographic angiography, magnetic resonance perfusion, or transcranial Doppler can help with risk stratification beyond the degree of stenosis is less clear. The diagnosis of ICAD is heavily reliant on lumen-based studies, such as computed tomographic angiography, magnetic resonance angiography, or digital subtraction angiography, but newer technologies, such as high-resolution vessel wall magnetic resonance imaging, can help distinguish ICAD from stenosing arteriopathies.</AbstractText><br /><br /><br /><br /><small>Stroke: 01 Feb 2024; 55:311-323</small></div>
Chen LH, Spagnolo-Allende A, Yang D, Qiao Y, Gutierrez J
Stroke: 01 Feb 2024; 55:311-323 | PMID: 38252756
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<div><h4>Connectivity-guided intermittent theta burst versus repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled trial.</h4><i>Morriss R, Briley PM, Webster L, Abdelghani M, ... Walters Y, Auer DP</i><br /><AbstractText>Disruption in reciprocal connectivity between the right anterior insula and the left dorsolateral prefrontal cortex is associated with depression and may be a target for neuromodulation. In a five-center, parallel, double-blind, randomized controlled trial we personalized resting-state functional magnetic resonance imaging neuronavigated connectivity-guided intermittent theta burst stimulation (cgiTBS) at a site based on effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. We tested its efficacy in reducing the primary outcome depression symptoms measured by the GRID Hamilton Depression Rating Scale 17-item over 8, 16 and 26 weeks, compared with structural magnetic resonance imaging (MRI) neuronavigated repetitive transcranial magnetic stimulation (rTMS) delivered at the standard stimulation site (F3) in patients with \'treatment-resistant depression\'. Participants were randomly assigned to 20 sessions over 4-6 weeks of either cgiTBS (n = 128) or rTMS (n = 127) with resting-state functional MRI at baseline and 16 weeks. Persistent decreases in depressive symptoms were seen over 26 weeks, with no differences between arms on the primary outcome GRID Hamilton Depression Rating Scale 17-item score (intention-to-treat adjusted mean, -0.31, 95% confidence interval (CI) -1.87, 1.24, P = 0.689). Two serious adverse events were possibly related to TMS (mania and psychosis). MRI-neuronavigated cgiTBS and rTMS were equally effective in patients with treatment-resistant depression over 26 weeks (trial registration no. ISRCTN19674644).</AbstractText><br /><br />© 2024. The Author(s).<br /><br /><small>Nat Med: 01 Feb 2024; 30:403-413</small></div>
Morriss R, Briley PM, Webster L, Abdelghani M, ... Walters Y, Auer DP
Nat Med: 01 Feb 2024; 30:403-413 | PMID: 38228914
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<div><h4>Prediction of preeclampsia from retinal fundus images via deep learning in singleton pregnancies: a prospective cohort study.</h4><i>Zhou T, Gu S, Shao F, Li P, ... Gao P, Hua X</i><br /><b>Introduction</b><br />Early prediction of preeclampsia (PE) is of universal importance in controlling the disease process. Our study aimed to assess the feasibility of using retinal fundus images to predict preeclampsia via deep learning in singleton pregnancies.<br /><b>Methods</b><br />This prospective cohort study was conducted at Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Eligible participants included singleton pregnancies who presented for prenatal visits before 14 weeks of gestation from September 1, 2020, to February 1, 2022. Retinal fundus images were obtained using a nonmydriatic digital retinal camera during their initial prenatal visit upon admission before 20 weeks of gestation. In addition, we generated fundus scores, which indicated the predictive value of hypertension, using a hypertension detection model. To evaluate the predictive value of the retinal fundus image-based deep learning algorithm for preeclampsia, we conducted stratified analyses and measured the area under the curve (AUC), sensitivity, and specificity. We then conducted sensitivity analyses for validation.<br /><b>Results</b><br />Our study analyzed a total of 1138 women, 92 pregnancies developed into hypertension disorders of pregnancy (HDP), including 26 cases of gestational hypertension and 66 cases of preeclampsia. The adjusted odds ratio (aOR) of the fundus scores was 2.582 (95% CI, 1.883-3.616; P  < 0.001). Otherwise, in the categories of prepregnancy BMI less than 28.0 and at least 28.0, the aORs were 3.073 (95%CI, 2.265-4.244; P  < 0.001) and 5.866 (95% CI, 3.292-11.531; P  < 0.001). In the categories of maternal age less than 35.0 and at least 35.0, the aORs were 2.845 (95% CI, 1.854-4.463; P  < 0.001) and 2.884 (95% CI, 1.794-4.942; P  < 0.001). The AUC of the fundus score combined with risk factors was 0.883 (sensitivity, 0.722; specificity, 0.934; 95% CI, 0.834-0.932) for predicting preeclampsia.<br /><b>Conclusion</b><br />Our study demonstrates that the use of deep learning algorithm-based retinal fundus images offers promising predictive value for the early detection of preeclampsia.<br /><br />Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.<br /><br /><small>J Hypertens: 01 Apr 2024; 42:701-710</small></div>
Zhou T, Gu S, Shao F, Li P, ... Gao P, Hua X
J Hypertens: 01 Apr 2024; 42:701-710 | PMID: 38230614
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<div><h4>Spatial lipidomics of coronary atherosclerotic plaque development in a familial hypercholesterolemia swine model.</h4><i>Slijkhuis N, Razzi F, Korteland SA, Heijs B, ... van Beusekom HMM, van Soest G</i><br /><AbstractText>Coronary atherosclerosis is caused by plaque build-up, with lipids playing a pivotal role in its progression. However, lipid composition and distribution within coronary atherosclerosis remain unknown. This study aims to characterize lipids and investigate differences in lipid composition across disease stages to aid in the understanding of disease progression. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize lipid distributions in coronary artery sections (n = 17) from hypercholesterolemic swine. We performed histology on consecutive sections to classify the artery segments and to investigate colocalization between lipids and histological regions of interest in advanced plaque, including necrotic core and inflammatory cells. Segments were classified as healthy (n = 6), mild (n = 6), and advanced disease (n = 5) artery segments. Multivariate data analysis was employed to find differences in lipid composition between the segment types, and the lipids\' spatial distribution was investigated using non-negative matrix factorization (NMF). Through this process, MALDI-MSI detected 473 lipid-related features. NMF clustering described three components in positive ionization mode: triacylglycerides (TAG), phosphatidylcholines (PC), and cholesterol species. In negative ionization mode, two components were identified: one driven by phosphatidylinositol(PI)(38:4), and one driven by ceramide-phosphoethanolamine(36:1). Multivariate data analysis showed the association between advanced disease and specific lipid signatures like PC(O-40:5) and cholesterylester(CE)(18:2). Ether-linked phospholipids and LysoPC species were found to colocalize with necrotic core, and mostly CE, ceramide, and PI species colocalized with inflammatory cells. This study, therefore, uncovers distinct lipid signatures correlated with plaque development and their colocalization with necrotic core and inflammatory cells, enhancing our understanding of coronary atherosclerosis progression.</AbstractText><br /><br />Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Lipid Res: 01 Feb 2024; 65:100504</small></div>
Slijkhuis N, Razzi F, Korteland SA, Heijs B, ... van Beusekom HMM, van Soest G
J Lipid Res: 01 Feb 2024; 65:100504 | PMID: 38246237
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<div><h4>Carotid Intima-Media Thickness and Improved Stroke Risk Assessment in Hypertensive Black Adults.</h4><i>Abe TA, Olanipekun T, Yan F, Effoe V, ... Benjamin EJ, Echols M</i><br /><b>Background</b><br />We aim to determine the added value of carotid intima-media thickness (cIMT) in stroke risk assessment for hypertensive Black adults.<br /><b>Methods</b><br />We examined 1,647 participants with hypertension without a history of cardiovascular (CV) disease, from the Jackson Heart Study. Cox regression analysis estimated hazard ratios (HRs) for incident stroke per standard deviation increase in cIMT and quartiles while adjusting for baseline variables. We then evaluated the predictive capacity of cIMT when added to the pool cohort equations (PCEs).<br /><b>Results</b><br />The mean age at baseline was 57 ± 10 years. Each standard deviation increase in cIMT (0.17 mm) was associated with approximately 30% higher risk of stroke (HR 1.27, 95% confidence interval: 1.08-1.49). Notably, cIMT proved valuable in identifying residual stroke risk among participants with well-controlled blood pressure, showing up to a 56% increase in the odds of stroke for each 0.17 mm increase in cIMT among those with systolic blood pressure <120 mm Hg. Additionally, the addition of cIMT to the PCE resulted in the reclassification of 58% of low to borderline risk participants with stroke to a higher-risk category and 28% without stroke to a lower-risk category, leading to a significant net reclassification improvement of 0.22 (0.10-0.30).<br /><b>Conclusions</b><br />In this community-based cohort of middle-aged Black adults with hypertension and no history of CV disease at baseline, cIMT is significantly associated with incident stroke and enhances stroke risk stratification.<br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Am J Hypertens: 15 Mar 2024; 37:290-297</small></div>
Abe TA, Olanipekun T, Yan F, Effoe V, ... Benjamin EJ, Echols M
Am J Hypertens: 15 Mar 2024; 37:290-297 | PMID: 38236147
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<div><h4>Combined Free-running 4D anatomical and flow MRI with native contrast using Synchronization of Neighboring Acquisitions by Physiological Signals (SyNAPS).</h4><i>Falcão MBL, Mackowiak ALC, Rossi GMC, Prša M, ... Stuber M, Roy CW</i><br /><b>Background</b><br />4D flow MRI often relies on the injection of gadolinium- or iron-oxide-based contrast agents to improve vessel delineation. In this work, a novel technique is developed to acquire and reconstruct 4D flow data with excellent dynamic visualization of blood vessels but without the need for contrast injection. Synchronization of Neighboring Acquisitions by Physiological Signals (SyNAPS) uses Pilot Tone (PT) navigation to retrospectively synchronize the reconstruction of two free-running 3D radial acquisitions, to create co-registered anatomy and flow images.<br /><b>Methods</b><br />Thirteen volunteers and two Marfan Syndrome patients were scanned without contrast agent using one free-running fast interrupted steady-state (FISS) sequence and one free-running phase-contrast MRI (PC-MRI) sequence. PT signals spanning the two sequences were recorded for retrospective respiratory motion correction and cardiac binning. The magnitude and phase images reconstructed, respectively, from FISS and PC-MRI, were synchronized to create SyNAPS 4D flow datasets. Conventional 2D flow data were acquired for reference in ascending (AAo) and descending aorta (DAo). The blood-to-myocardium contrast ratio, dynamic vessel area, net volume, and peak flow were used to compare SyNAPS 4D flow with Native 4D flow (without FISS information) and 2D flow. A score of 0-4 was given to each dataset by two blinded experts regarding the feasibility of performing vessel delineation.<br /><b>Results</b><br />Blood-to-myocardium contrast ratio for SyNAPS 4D flow magnitude images (1.5±0.3) was significantly higher than for Native 4D flow (0.7±0.1, p<0.01), and was comparable to 2D flow (2.3±0.9, p=0.02). Image quality scores of SyNAPS 4D flow from the experts (MP: 1.9±0.3, ET: 2.5±0.5) were overall significantly higher than the scores from Native 4D flow (MP: 1.6±0.6, p=0.03, ET: 0.8±0.4, p<0.01) but still significantly lower than the scores from the reference 2D flow datasets (MP: 2.8±0.4, p<0.01, ET: 3.5±0.7, p<0.01). The Pearson correlation coefficient between the dynamic vessel area measured on SyNAPS 4D flow and that from 2D flow was 0.69±0.24 for the AAo and 0.83±0.10 for the DAo, whereas the Pearson correlation between Native 4D flow and 2D flow measurements was 0.12±0.48 for the AAo and 0.08±0.39 for the DAo. Linear correlations between SyNAPS 4D flow and 2D flow measurements of net volume (r<sup>2</sup>=0.83) and peak flow (r<sup>2</sup>=0.87) were larger than the correlations between Native 4D flow and 2D flow measurements of net volume (r<sup>2</sup>=0.79) and peak flow (r<sup>2</sup>=0.76).<br /><b>Discussion and conclusion</b><br />The feasibility and utility of SyNAPS was demonstrated for joint whole-heart anatomical and flow MRI without requiring ECG gating, respiratory navigators, or contrast agents. Using SyNAPS a high-contrast anatomical imaging sequence can be used to improve 4D flow measurements that often suffer from poor delineation of vessel boundaries in the absence of contrast agents.<br /><br />Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Cardiovasc Magn Reson: 01 Feb 2024:101006; epub ahead of print</small></div>
Falcão MBL, Mackowiak ALC, Rossi GMC, Prša M, ... Stuber M, Roy CW
J Cardiovasc Magn Reson: 01 Feb 2024:101006; epub ahead of print | PMID: 38309581
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<div><h4>Clinical prediction tool to identify children at risk of pulmonary embolism.</h4><i>Tiratrakoonseree T, Charoenpichitnun S, Natesirinilkul R, Songthawee N, ... Vaewpanich J, Sirachainan N</i><br /><b>Introduction</b><br />The diagnosis of pediatric pulmonary embolism (PE) is often delayed due to non-specific symptoms, and clinical prediction tools designed for adults are unsuitable for children. This study aimed to create a PE predictive model and to evaluate the reported tools in the Thai pediatric population.<br /><b>Materials and methods</b><br />A multi-center retrospective study from 4 university hospitals included children ≤18 years of age undergoing computed tomography pulmonary angiogram from 2000 to 2020 with the suspicion of PE. Patients\' clinical presentations and risk factors of venous thromboembolism (VTE) were compared between the PE-positive and PE-negative groups. Significant risk factors from univariate and multivariate logistic regression were included to create a clinical prediction tool. The performance of the model was demonstrated by sensitivity, specificity, area under the curve (AUC), Hosmer Lemeshow test, ratio of observed and expected outcomes and bootstrapping.<br /><b>Results</b><br />Of the 104 patients included, 43 (41.3 %) were grouped as PE-positive and 61 (58.7 %) as PE-negative. Five parameters, including congenital heart disease/pulmonary surgery, known thrombophilia, previous VTE, nephrotic syndrome and chest pain showed significant differences between the two groups. Score ≥ 2 yielded a 74.4 % sensitivity and a 75.4 % specificity with an AUC of the model of 0.809. The model performance and validation results were within satisfactory ranges.<br /><b>Conclusion</b><br />The study created a clinical prediction tool indicating the likelihood of PE among Thai children. A score ≥2 was suggestive of PE.<br /><br />Copyright © 2024 Faculty of Medicine Ramathibodi Hospital, Mahidol University. Published by Elsevier Ltd.. All rights reserved.<br /><br /><small>Thromb Res: 01 Feb 2024; 234:151-157</small></div>
Tiratrakoonseree T, Charoenpichitnun S, Natesirinilkul R, Songthawee N, ... Vaewpanich J, Sirachainan N
Thromb Res: 01 Feb 2024; 234:151-157 | PMID: 38241765
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<div><h4>Pregnancy-An Ideal Period to Identify Women at Risk for Chronic Hypertension.</h4><i>Charakida M, Wright A, Magee LA, Syngelaki A, ... Wright D, Nicolaides KH</i><br /><b>Background</b><br />Cardiovascular disease is the leading cause of mortality in women. Pregnancy is an ideal period to implement cardiovascular prevention strategies as women seek medical help. We aimed to develop a predictive model to identify women at increased risk for chronic hypertension (CH) based on information collected in the index pregnancy.<br /><b>Methods</b><br />Cohort of 26 511 women seen in 2 consecutive pregnancies. Included were women without CH, with information on maternal characteristics and blood pressure at 11 to 13 weeks\' gestation, and the development of preeclampsia or gestational hypertension (GH) in the index pregnancy. Logistic regression models were fitted for the prediction of the development of future CH by the 20th week of the subsequent pregnancy. The performance of screening and risk calibration of the model were assessed.<br /><b>Results</b><br />In this study 1560 (5.9%) women developed preeclampsia or GH (index pregnancy), and 215 (0.8%) developed future CH, with a median of 3.0 years later. Predictors of development of future CH were maternal age, weight, and blood pressure; Black and South Asian ethnicity; family history of preeclampsia; parity; and development of preeclampsia or GH. Preeclampsia or GH detected 52.1% (45.2%-58.9%) of future CH. At a screen-positive rate of 10%, a model including maternal characteristics, early pregnancy blood pressure, and development of preeclampsia or GH detected 73.5% (67.1-79.3) of future CH.<br /><b>Conclusions</b><br />Early pregnancy maternal characteristics, blood pressure, and development of preeclampsia or GH identify three-fourths of women at risk for future CH. Our results offer an important preventative strategy for identifying women at increased risk of future CH, which is applicable worldwide.<br /><br /><br /><br /><small>Hypertension: 01 Feb 2024; 81:311-318</small></div>
Charakida M, Wright A, Magee LA, Syngelaki A, ... Wright D, Nicolaides KH
Hypertension: 01 Feb 2024; 81:311-318 | PMID: 38232144
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<div><h4>Higher Cholesterol Absorption Marker at Baseline Predicts Fewer Cardiovascular Events in Elderly Patients Receiving Hypercholesterolemia Treatment: The KEEP Study.</h4><i>Kuwabara M, Sasaki J, Ouchi Y, Oikawa S, ... Saikawa T, Arai H</i><br /><b>Background</b><br />Higher cholesterol absorption has been reported to be related to a higher incidence of cardiovascular events (CVEs). The KEEP (Kyushu Elderly Ezetimibe Phytosterol) study, a substudy of the EWTOPIA 75 (Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older) study, investigated the relationships of cholesterol absorption and synthesis markers with CVEs in older old individuals with hypercholesterolemia, particularly in relation to ezetimibe treatment.<br /><b>Methods and results</b><br />Eligible patients were those aged ≥75 years who had low-density lipoprotein cholesterol ≥140 mg/dL, no history of coronary artery disease, and no recent use of lipid-lowering drugs. Participants were randomly assigned into a diet-only or diet-plus-ezetimibe group. Baseline and 24-week follow-up blood samples were analyzed for cholesterol absorption (eg, campesterol) and synthesis markers (eg, lathosterol). Of 1287 patients, 1061 patients with baseline measurement were analyzed. Over a median follow-up of 4.0 years, 64 CVEs occurred. Higher campesterol levels at baseline were significantly associated with a lower risk of CVEs. After adjustment for sex, age, and treatment, the hazard ratios for the lowest to highest quartile categories of baseline campesterol were 1.00 (reference), 0.59 (95% CI, 0.30-1.17), 0.44 (95% CI, 0.21-0.94), and 0.44 (95% CI, 0.21-0.93), respectively (trend <i>P</i>=0.01). This association persisted after further adjustment for hypertension, diabetes, and other cardiovascular risk factors. Neither interactions with ezetimibe treatment nor mediating effects of the changes in cholesterol absorption markers were observed.<br /><b>Conclusions</b><br />The KEEP study indicated that higher campesterol levels without lipid-lowering drugs were associated with a lower incidence of CVEs in older old individuals with hypercholesterolemia who were subsequently treated with diet or ezetimibe.<br /><b>Registration</b><br />URL: https://www.umin.ac.jp; unique identifier: UMIN000017769.<br /><br /><br /><br /><small>J Am Heart Assoc: 06 Feb 2024; 13:e031865</small></div>
Kuwabara M, Sasaki J, Ouchi Y, Oikawa S, ... Saikawa T, Arai H
J Am Heart Assoc: 06 Feb 2024; 13:e031865 | PMID: 38240241
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<div><h4>CRISPR-Cas9 In Vivo Gene Editing of for Hereditary Angioedema.</h4><i>Longhurst HJ, Lindsay K, Petersen RS, Fijen LM, ... Lebwohl D, Cohn DM</i><br /><b>Background</b><br />Hereditary angioedema is a rare genetic disease that leads to severe and unpredictable swelling attacks. NTLA-2002 is an in vivo gene-editing therapy based on clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9. NTLA-2002 targets the gene encoding kallikrein B1 (<i>KLKB1</i>), with the goal of lifelong control of angioedema attacks after a single dose.<br /><b>Methods</b><br />In this phase 1 dose-escalation portion of a combined phase 1-2 trial of NTLA-2002 in adults with hereditary angioedema, we administered NTLA-2002 at a single dose of 25 mg, 50 mg, or 75 mg. The primary end points were the safety and side-effect profile of NTLA-2002 therapy. Secondary and exploratory end points included pharmacokinetics, pharmacodynamics, and clinical efficacy determined on the basis of investigator-confirmed angioedema attacks.<br /><b>Results</b><br />Three patients received 25 mg of NTLA-2002, four received 50 mg, and three received 75 mg. At all dose levels, the most common adverse events were infusion-related reactions and fatigue. No dose-limiting toxic effects, serious adverse events, grade 3 or higher adverse events, or clinically important laboratory findings were observed after the administration of NTLA-2002. Dose-dependent reductions in the total plasma kallikrein protein level were observed between baseline and the latest assessment, with a mean percentage change of -67% in the 25-mg group, -84% in the 50-mg group, and -95% in the 75-mg group. The mean percentage change in the number of angioedema attacks per month between baseline and weeks 1 through 16 (primary observation period) was -91% in the 25-mg group, -97% in the 50-mg group, and -80% in the 75-mg group. Among all the patients, the mean percentage change in the number of angioedema attacks per month from baseline through the latest assessment was -95%.<br /><b>Conclusions</b><br />In this small study, a single dose of NTLA-2002 led to robust, dose-dependent, and durable reductions in total plasma kallikrein levels, and no severe adverse events were observed. In exploratory analyses, reductions in the number of angioedema attacks per month were observed at all dose levels. (Funded by Intellia Therapeutics; ClinicalTrials.gov number, NCT05120830.).<br /><br />Copyright © 2024 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 01 Feb 2024; 390:432-441</small></div>
Longhurst HJ, Lindsay K, Petersen RS, Fijen LM, ... Lebwohl D, Cohn DM
N Engl J Med: 01 Feb 2024; 390:432-441 | PMID: 38294975
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<div><h4>The Born in Guangzhou Cohort Study enables generational genetic discoveries.</h4><i>Huang S, Liu S, Huang M, He JR, ... Xia H, Qiu X</i><br /><AbstractText>Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health<sup>1</sup>. Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study<sup>2</sup> (BIGCS), which encompasses the sequencing and analysis of 4,053 Chinese individuals, primarily composed of trios or mother-infant duos residing in South China. Our analysis reveals novel genetic variants, a high-quality reference panel, and fine-scale local genetic structure within BIGCS. Notably, we identify previously unreported East Asian-specific genetic associations with maternal total bile acid, gestational weight gain and infant cord blood traits. Additionally, we observe prevalent age-specific genetic effects on lipid levels in mothers and infants. In an exploratory intergenerational Mendelian randomization analysis, we estimate the maternal putatively causal and fetal genetic effects of seven adult phenotypes on seven fetal growth-related measurements. These findings illuminate the genetic links between maternal and early-life traits in an East Asian population and lay the groundwork for future research into the intricate interplay of genetics, intrauterine exposures and early-life experiences in shaping long-term health.</AbstractText><br /><br />© 2024. The Author(s), under exclusive licence to Springer Nature Limited.<br /><br /><small>Nature: 31 Jan 2024; epub ahead of print</small></div>
Huang S, Liu S, Huang M, He JR, ... Xia H, Qiu X
Nature: 31 Jan 2024; epub ahead of print | PMID: 38297123
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Abstract
<div><h4>7-Dehydrocholesterol dictates ferroptosis sensitivity.</h4><i>Li Y, Ran Q, Duan Q, Jin J, ... Jiang X, Wang P</i><br /><AbstractText>Ferroptosis, a form of regulated cell death that is driven by iron-dependent phospholipid peroxidation, has been implicated in multiple diseases, including cancer<sup>1-3</sup>, degenerative disorders<sup>4</sup> and organ ischaemia-reperfusion injury (IRI)<sup>5,6</sup>. Here, using genome-wide CRISPR-Cas9 screening, we identified that the enzymes involved in distal cholesterol biosynthesis have pivotal yet opposing roles in regulating ferroptosis through dictating the level of 7-dehydrocholesterol (7-DHC)-an intermediate metabolite of distal cholesterol biosynthesis that is synthesized by sterol C5-desaturase (SC5D) and metabolized by 7-DHC reductase (DHCR7) for cholesterol synthesis. We found that the pathway components, including MSMO1, CYP51A1, EBP and SC5D, function as potential suppressors of ferroptosis, whereas DHCR7 functions as a pro-ferroptotic gene. Mechanistically, 7-DHC dictates ferroptosis surveillance by using the conjugated diene to exert its anti-phospholipid autoxidation function and shields plasma and mitochondria membranes from phospholipid autoxidation. Importantly, blocking the biosynthesis of endogenous 7-DHC by pharmacological targeting of EBP induces ferroptosis and inhibits tumour growth, whereas increasing the 7-DHC level by inhibiting DHCR7 effectively promotes cancer metastasis and attenuates the progression of kidney IRI, supporting a critical function of this axis in vivo. In conclusion, our data reveal a role of 7-DHC as a natural anti-ferroptotic metabolite and suggest that pharmacological manipulation of 7-DHC levels is a promising therapeutic strategy for cancer and IRI.</AbstractText><br /><br />© 2024. The Author(s), under exclusive licence to Springer Nature Limited.<br /><br /><small>Nature: 31 Jan 2024; epub ahead of print</small></div>
Li Y, Ran Q, Duan Q, Jin J, ... Jiang X, Wang P
Nature: 31 Jan 2024; epub ahead of print | PMID: 38297130
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Abstract
<div><h4>7-Dehydrocholesterol is an endogenous suppressor of ferroptosis.</h4><i>Freitas FP, Alborzinia H, Dos Santos AF, Nepachalovich P, ... Conrad M, Friedmann Angeli JP</i><br /><AbstractText>Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation<sup>1,2</sup>. Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation<sup>3</sup>, we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells. Because of its far superior reactivity towards peroxyl radicals, 7-DHC effectively shields (phospho)lipids from autoxidation and subsequent fragmentation. We provide validation in neuroblastoma and Burkitt\'s lymphoma xenografts where we demonstrate that the accumulation of 7-DHC is capable of inducing a shift towards a ferroptosis-resistant state in these tumours ultimately resulting in a more aggressive phenotype. Conclusively, our findings provide compelling evidence of a yet-unrecognized antiferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis.</AbstractText><br /><br />© 2024. The Author(s), under exclusive licence to Springer Nature Limited.<br /><br /><small>Nature: 31 Jan 2024; epub ahead of print</small></div>
Freitas FP, Alborzinia H, Dos Santos AF, Nepachalovich P, ... Conrad M, Friedmann Angeli JP
Nature: 31 Jan 2024; epub ahead of print | PMID: 38297129
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Abstract
<div><h4>Single-photon superradiance in individual caesium lead halide quantum dots.</h4><i>Zhu C, Boehme SC, Feld LG, Moskalenko A, ... Kovalenko MV, Rainò G</i><br /><AbstractText>The brightness of an emitter is ultimately described by Fermi\'s golden rule, with a radiative rate proportional to its oscillator strength times the local density of photonic states. As the oscillator strength is an intrinsic material property, the quest for ever brighter emission has relied on the local density of photonic states engineering, using dielectric or plasmonic resonators<sup>1,2</sup>. By contrast, a much less explored avenue is to boost the oscillator strength, and hence the emission rate, using a collective behaviour termed superradiance. Recently, it was proposed<sup>3</sup> that the latter can be realized using the giant oscillator-strength transitions of a weakly confined exciton in a quantum well when its coherent motion extends over many unit cells. Here we demonstrate single-photon superradiance in perovskite quantum dots with a sub-100 picosecond radiative decay time, almost as short as the reported exciton coherence time<sup>4</sup>. The characteristic dependence of radiative rates on the size, composition and temperature of the quantum dot suggests the formation of giant transition dipoles, as confirmed by effective-mass calculations. The results aid in the development of ultrabright, coherent quantum light sources and attest that quantum effects, for example, single-photon emission, persist in nanoparticles ten times larger than the exciton Bohr radius.</AbstractText><br /><br />© 2024. The Author(s).<br /><br /><small>Nature: 31 Jan 2024; epub ahead of print</small></div>
Zhu C, Boehme SC, Feld LG, Moskalenko A, ... Kovalenko MV, Rainò G
Nature: 31 Jan 2024; epub ahead of print | PMID: 38297126
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Abstract
<div><h4>Stereodivergent 1,3-difunctionalization of alkenes by charge relocation.</h4><i>Brutiu BR, Iannelli G, Riomet M, Kaiser D, Maulide N</i><br /><AbstractText>Alkenes are indispensable feedstocks in chemistry. Functionalization at both carbons of the alkene-1,2-difunctionalization-is part of chemistry curricula worldwide<sup>1</sup>. Although difunctionalization at distal positions has been reported<sup>2-4</sup>, it typically relies on designer substrates featuring directing groups and/or stabilizing features, all of which determine the ultimate site of bond formation<sup>5-7</sup>. Here we introduce a method for the direct 1,3-difunctionalization of alkenes, based on a concept termed \'charge relocation\', which enables stereodivergent access to 1,3-difunctionalized products of either syn- or anti-configuration from unactivated alkenes, without the need for directing groups or stabilizing features. The usefulness of the approach is demonstrated in the synthesis of the pulmonary toxin 4-ipomeanol and its derivatives.</AbstractText><br /><br />© 2024. The Author(s).<br /><br /><small>Nature: 01 Feb 2024; 626:92-97</small></div>
Brutiu BR, Iannelli G, Riomet M, Kaiser D, Maulide N
Nature: 01 Feb 2024; 626:92-97 | PMID: 38297174
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Abstract
<div><h4>Establishing reaction networks in the 16-electron sulfur reduction reaction.</h4><i>Liu R, Wei Z, Peng L, Zhang L, ... Sautet P, Duan X</i><br /><AbstractText>The sulfur reduction reaction (SRR) plays a central role in high-capacity lithium sulfur (Li-S) batteries. The SRR involves an intricate, 16-electron conversion process featuring multiple lithium polysulfide intermediates and reaction branches<sup>1-3</sup>. Establishing the complex reaction network is essential for rational tailoring of the SRR for improved Li-S batteries, but represents a daunting challenge<sup>4-6</sup>. Herein we systematically investigate the electrocatalytic SRR to decipher its network using the nitrogen, sulfur, dual-doped holey graphene framework as a model electrode to understand the role of electrocatalysts in acceleration of conversion kinetics. Combining cyclic voltammetry, in situ Raman spectroscopy and density functional theory calculations, we identify and directly profile the key intermediates (S<sub>8</sub>, Li<sub>2</sub>S<sub>8</sub>, Li<sub>2</sub>S<sub>6</sub>, Li<sub>2</sub>S<sub>4</sub> and Li<sub>2</sub>S) at varying potentials and elucidate their conversion pathways. Li<sub>2</sub>S<sub>4</sub> and Li<sub>2</sub>S<sub>6</sub> were predominantly observed, in which Li<sub>2</sub>S<sub>4</sub> represents the key electrochemical intermediate dictating the overall SRR kinetics. Li<sub>2</sub>S<sub>6</sub>, generated (consumed) through a comproportionation (disproportionation) reaction, does not directly participate in electrochemical reactions but significantly contributes to the polysulfide shuttling process. We found that the nitrogen, sulfur dual-doped holey graphene framework catalyst could help accelerate polysulfide conversion kinetics, leading to faster depletion of soluble lithium polysulfides at higher potential and hence mitigating the polysulfide shuttling effect and boosting output potential. These results highlight the electrocatalytic approach as a promising strategy for tackling the fundamental challenges regarding Li-S batteries.</AbstractText><br /><br />© 2024. The Author(s), under exclusive licence to Springer Nature Limited.<br /><br /><small>Nature: 01 Feb 2024; 626:98-104</small></div>
Liu R, Wei Z, Peng L, Zhang L, ... Sautet P, Duan X
Nature: 01 Feb 2024; 626:98-104 | PMID: 38297176
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Abstract
<div><h4>Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol.</h4><i>Zhang Y, Dron JS, Bellows BK, Khera AV, ... de Ferranti SD, Moran AE</i><br /><b>Importance</b><br />Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified.<br /><b>Objective</b><br />To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults.<br /><b>Design, setting, and participants</b><br />A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023.<br /><b>Exposures</b><br />LDL-C, cumulative past LDL-C, FH variant status.<br /><b>Main outcomes and measures</b><br />Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults.<br /><b>Results</b><br />Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.<br /><br /><br /><br /><small>JAMA Cardiol: 31 Jan 2024; epub ahead of print</small></div>
Zhang Y, Dron JS, Bellows BK, Khera AV, ... de Ferranti SD, Moran AE
JAMA Cardiol: 31 Jan 2024; epub ahead of print | PMID: 38294787
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