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Phenotypic presentation of family members of ATTRv probands and subsequent disease penetrance ATTRv 感知者家族成员的表型表现及随后的疾病渗透性
Pub Date : 2024-09-07 DOI: 10.1101/2024.09.06.24313219
Luca Fazzini, Matteo Castrichini, Yan Li, Jose F de Melo, Marta Figueiral, Jenny J Cao, Eric Klee, Christian Cadeddu Dessalvi, Martha Grogan, Angela Dispenzieri, Naveen L. Pereira
BACKGROUND: Hereditary transthyretin amyloid cardiomyopathy (ATTRv-CM) is being increasingly diagnosed due to enhanced awareness and availability of newer therapeutics. Multiple TTR variants have been described worldwide, but with uncertain disease penetrance. The characteristics and outcomes of "previously undiagnosed" pathogenic-likely pathogenic (P/LP) TTR variant (genotype or G+; cardiac phenotype or P-) carriers are unknown which has important prognostic and therapeutic implications, especially for affected family members. This descriptive study aimed to delineate phenotype and cardiac penetrance in "previously undiagnosed" G+P- family members of ATTRv probands. METHODS: Demographic, electrocardiographic (ECG), genetic, and imaging (echocardiography, cardiac technetium-99m pyrophosphate (PYP) and magnetic resonance imaging) data were analyzed. The prediction effect of selected baseline characteristics for ATTRv-CM development was evaluated. Kaplan-Meier and Cox regression methods were used to describe risk and predictors of ATTRv-CM development in family members. RESULTS: There were 85 G+P- family members identified. Mean age was 48.5±11.7 years, 39% were male, 18% had a diagnosis of peripheral neuropathy, 15% with a history of carpal tunnel syndrome, and 4% had atrioventricular block at baseline. Of these, 55 patients had follow-up imaging studies. After a median 6.8-year follow-up, 22% developed ATTR-CM with a 10-year estimated risk of 29.5% (95% CI 7.9-46.0). Cardiac penetrance increased with increasing family member's age. Proband's diagnosis age (p=0.0096) and artificial intelligence (AI)-ECG prediction (p=0.0091) were promising baseline predictors of time to ATTRv-CM development.CONCLUSION: In previously undiagnosed G+P- ATTRv family members, the incidence of subsequent CM is high. Predictors for CM development such as proband's diagnosis age and AI-determined ECG probability of ATTR-CM require further investigation.
背景:由于人们对遗传性转甲状腺素淀粉样变性心肌病(ATTRv-CM)认识的提高和新疗法的出现,该病的诊断率越来越高。全球已发现多种 TTR 变体,但疾病的渗透性并不确定。先前未确诊的 "致病性-可能致病性(P/LP)TTR变体(基因型或G+;心脏表型或P-)携带者的特征和预后尚不清楚,这对预后和治疗有重要影响,尤其是对受影响的家庭成员。这项描述性研究的目的是描述 "先前未确诊 "的 ATTRv G+P- 家族成员的表型和心脏穿透性。方法:分析人口统计学、心电图(ECG)、遗传学和影像学(超声心动图、心脏锝-99m 焦磷酸(PYP)和磁共振成像)数据。评估了所选基线特征对 ATTRv-CM 发展的预测效果。采用 Kaplan-Meier 和 Cox 回归法描述家族成员发生 ATTRv-CM 的风险和预测因素。结果:共发现 85 名 G+P- 家族成员。平均年龄为(48.5±11.7)岁,39%为男性,18%诊断为周围神经病变,15%有腕管综合征病史,4%基线时有房室传导阻滞。其中,55 名患者接受了后续成像检查。中位随访 6.8 年后,22% 的患者发展为 ATTR-CM,10 年估计风险为 29.5%(95% CI 7.9-46.0)。心脏穿透性随着家庭成员年龄的增加而增加。Proband的诊断年龄(p=0.0096)和人工智能(AI)-ECG预测(p=0.0091)是ATTRv-CM发展时间的有希望的基线预测因子。结论:在既往未确诊的 G+P- ATTRv 家族成员中,后续 CM 的发生率很高。需要进一步研究 CM 发生的预测因素,如原告的诊断年龄和 AI 确定的 ATTR-CM 的心电图概率。
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引用次数: 0
Deep Learning based CT-scan Coronary Artery Segmentation and Calcium Scoring 基于深度学习的 CT 扫描冠状动脉分割和钙化评分
Pub Date : 2024-09-06 DOI: 10.1101/2024.09.06.24313174
Sai Koundinya Upadhyayula
Coronary artery disease (CAD), primarily driven by atherosclerosis, poses significant health risks, contributing to a rising mortality rate globally. This study introduces a deep learning framework designed for the automated segmentation of coronary arteries and quantification of coronary artery calcium (CAC) from CT scans, facilitating improved risk stratification in patients. Leveraging data from the National Lung Screening Trial, we developed a three-step model that includes heart localization, coronary calcium segmentation, and calcium scoring. Various configurations of the UNet architecture were employed, with the Extended UNet utilizing an autoencoder achieving the highest validation performance, reflected by an Intersection over Union (IoU) score of 0.78 and an F1 score of 0.83.The model's efficacy was validated against manually segmented masks, showcasing its potential for accurate risk assessment based on CAC scores. This automated approach significantly reduces the time and expertise required for traditional calcium scoring, enabling rapid and reliable assessments in clinical settings. Our findings indicate that the deep learning system can effectively classify patients into risk categories, underscoring its potential utility in enhancing the management of CAD and improving patient outcomes. This research highlights the feasibility of integrating advanced computational techniques into routine clinical practice, paving the way for more efficient cardiovascular risk stratification.
冠状动脉疾病(CAD)主要由动脉粥样硬化引起,对健康构成重大风险,导致全球死亡率上升。本研究介绍了一种深度学习框架,旨在自动分割冠状动脉并量化 CT 扫描结果中的冠状动脉钙(CAC),从而改善患者的风险分层。利用国家肺筛查试验的数据,我们开发了一个三步模型,包括心脏定位、冠状动脉钙化分割和钙化评分。我们采用了 UNet 架构的各种配置,其中利用自动编码器的扩展 UNet 获得了最高的验证性能,体现在交叉联合(IoU)得分为 0.78,F1 得分为 0.83。该模型的功效已通过人工分割掩膜的验证,展示了其基于 CAC 评分进行准确风险评估的潜力。这种自动化方法大大减少了传统钙质评分所需的时间和专业知识,从而在临床环境中实现了快速、可靠的评估。我们的研究结果表明,深度学习系统能有效地将患者划分为不同的风险类别,突出了它在加强 CAD 管理和改善患者预后方面的潜在作用。这项研究强调了将先进计算技术融入常规临床实践的可行性,为更有效的心血管风险分层铺平了道路。
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引用次数: 0
Enhancing Fetal Cardiac Ultrasound Diagnosis: A Multi-Task Hybrid Attention Model for Accurate Standard Plane Detection 增强胎儿心脏超声诊断:用于准确标准平面检测的多任务混合注意力模型
Pub Date : 2024-09-06 DOI: 10.1101/2024.09.05.24313076
Haodong Tian, Yuxi Liu, Frederick Au, Guannning Lin
Fetal heart health is a critical part of diagnosis and treatment, and one of the methods is fetal cardiac ultrasound. A key aspect of the process is the detection of standard ultrasound slices, which is essential for accurate diagnosis. The effectiveness of diagnosis relies heavily on the clinical experience and expertise of the ultrasound physician. To improve detection efficiency and minimize misdiagnosis, we developed a single-stage detection model for fetal cardiac ultrasound standard planes (FCUM) that uses multi-task learning and hybrid attention mechanisms to support the ultrasound physician’s diagnostic work.
胎儿心脏健康是诊断和治疗的关键部分,而胎儿心脏超声是其中的一种方法。该过程的一个关键环节是检测标准超声切片,这对准确诊断至关重要。诊断的有效性在很大程度上依赖于超声医生的临床经验和专业知识。为了提高检测效率并减少误诊,我们开发了一种胎儿心脏超声标准平面(FCUM)的单阶段检测模型,该模型采用多任务学习和混合注意力机制来支持超声波医生的诊断工作。
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引用次数: 0
Cardiac Cross-Reactivity of NaV Autoantibodies in Metastatic Breast Cancer: A Possible Trigger for Sudden Cardiac Death 转移性乳腺癌中 NaV 自身抗体的心脏交叉反应性:心脏性猝死的可能诱因
Pub Date : 2024-09-06 DOI: 10.1101/2024.09.06.24313111
Carlo Pappone, Adriana Tarantino, Dario Melgari, Marco Piccoli, Giuseppe Ciconte, Anthony Frosio, Emanuele Micaglio, Serena Calamaio, Chiara Vantellino, Federica Cirillo, Pasquale Creo, Valerio Castoldi, Rachele Prevostini, Alessandro De Toma, Antonio Boccellino, Gabriele Negro, Luigi Giannelli, Zarko Calovic, Letizia Leocani, Vincenzo Santinelli, Domenico De Toma, Ilaria Rivolta, Luigi Anastasia
Background and AimsPatients with metastatic breast cancer have an increased risk of sudden cardiac death (SCD) that cannot be fully explained by cardiotoxic treatments. Recent evidence shows that autoantibodies targeting the cardiac NaV1.5 sodium channel in Brugada syndrome (BrS) can trigger arrhythmias and elevate SCD risk. Similarly, autoantibodies against the neonatal NaV1.5 isoform have been found in metastatic breast cancer patients. Given the high homology between these NaV1.5 isoforms, we investigated whether these autoantibodies cross-react with the cardiac isoform, potentially contributing to SCD in this population. MethodsPlasma from twenty metastatic breast cancer patients was analyzed for anti-NaV1.5 autoantibodies using HEK293A cells expressing the NaV1.5 protein, followed by Western blotting. The effects of these autoantibodies on sodium current density were assessed in cellular models and wild-type mice, with electrocardiographic monitoring after plasma infusion. ResultsFifteen plasma samples from metastatic breast cancer patients tested positive for anti-NaV1.5 autoantibodies, significantly reducing sodium current density in vitro. Mice injected with these plasma samples developed severe arrhythmias and a Brugada syndrome-like ECG pattern. In contrast, plasma samples either without the autoantibodies or with IgG depletion showed no such effects, underscoring the role of IgG in sodium current reduction and confirming the pathogenicity of the autoantibodies. ConclusionsThis study demonstrates that anti-NaV1.5 autoantibodies in metastatic breast cancer patients can cross-react with the cardiac NaV1.5 isoform, potentially leading to fatal arrhythmias. These findings highlight a novel mechanism for the high SCD rate in this population and suggest that therapies involving sodium blockers should be used with caution to avoid exacerbating this risk. Reliable diagnostic tests and targeted therapies are urgently needed to mitigate SCD risk in affected patients.
背景和目的转移性乳腺癌患者发生心脏性猝死(SCD)的风险增加,而心脏毒性治疗无法完全解释这一现象。最近的证据显示,针对 Brugada 综合征(BrS)患者心脏 NaV1.5 钠通道的自身抗体可引发心律失常并增加 SCD 风险。同样,在转移性乳腺癌患者中也发现了针对新生儿 NaV1.5 同工型的自身抗体。鉴于这些 NaV1.5 同工型之间的高度同源性,我们研究了这些自身抗体是否会与心脏同工型发生交叉反应,从而可能导致这一人群中的 SCD。方法使用表达 NaV1.5 蛋白的 HEK293A 细胞对 20 名转移性乳腺癌患者的血浆进行抗 NaV1.5 自身抗体分析,然后进行 Western 印迹。在细胞模型和野生型小鼠中评估了这些自身抗体对钠电流密度的影响,并在输注血浆后进行了心电图监测。结果15份来自转移性乳腺癌患者的血浆样本检测出抗NaV1.5自身抗体阳性,显著降低了体外钠电流密度。注射了这些血浆样本的小鼠出现了严重的心律失常和类似布鲁格达综合征的心电图模式。与此相反,不含自身抗体或去除了 IgG 的血浆样本没有显示出这种效应,这突出了 IgG 在钠电流降低中的作用,并证实了自身抗体的致病性。结论这项研究表明,转移性乳腺癌患者体内的抗 NaV1.5 自身抗体可与心脏 NaV1.5 同工酶发生交叉反应,从而可能导致致命性心律失常。这些发现凸显了这一人群 SCD 高发的新机制,并建议应谨慎使用钠阻滞剂疗法,以避免加剧这一风险。目前迫切需要可靠的诊断测试和靶向疗法来降低受影响患者的 SCD 风险。
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引用次数: 0
Deep Learning Model and Multi Modal Late Fusion For Predicting Adverse Events Following Cardiothoracic Surgery in the ICU Using STS Data and Time Series Intraoperative Data 使用 STS 数据和时间序列术中数据预测重症监护室心胸外科手术后不良事件的深度学习模型和多模态晚期融合技术
Pub Date : 2024-09-05 DOI: 10.1101/2024.09.04.24312980
Rajashekar Korutla, Anne Hicks, Marko Milosevic, Dipti Kulkarni, Felistas Mazhude, Mehdi Mortazawy, Yashar Seyed Vahedein, Tyler Kelting, Jaime B Rabib, Qingchu Jin, Robert Kramer, Douglas Sawyer, Raimond L Winslow, Saeed Amal
Accurate prediction of post-operative adverse events following cardiothoracic surgery is crucial for timely interventions, potentially improving patient outcomes and reducing healthcare costs. By leveraging advanced deep learning techniques, this study highlights the transformative potential of incorporating intraoperative variables into predictive analytics models to enhance postoperative care for cardiothoracic surgery patients in the ICU. We developed deep learning predictive models for anticipating adverse events in patients following cardiothoracic surgery using a dataset from the Society of Thoracic Surgeons’ database (4) and intraoperative data. Our models perform late fusion by integrating static patient data and intra-operative time-series data, utilizing Fully Connected Neural Networks (FCNN) and long short-term memory (LSTM) networks, respectively. The hybrid model was validated through five-fold cross-validation, demonstrating robust performance with a mean AUC of 0.93, Sensitivity of 0.83 and Specificity of 0.89. This work represents a significant step forward in the proactive management of cardio thoracic surgery patients in the ICU by effectively predicting potential adverse events associated with mortality in the post operative period.
准确预测心胸手术后的不良事件对于及时干预、改善患者预后和降低医疗成本至关重要。通过利用先进的深度学习技术,本研究强调了将术中变量纳入预测分析模型的变革潜力,以加强重症监护室心胸手术患者的术后护理。我们利用胸外科医师学会数据库(4)中的数据集和术中数据开发了深度学习预测模型,用于预测心胸手术后患者的不良事件。我们的模型通过整合静态患者数据和术中时间序列数据,分别利用全连接神经网络(FCNN)和长短期记忆(LSTM)网络来实现后期融合。混合模型通过五倍交叉验证进行了验证,结果表明其性能稳定,平均 AUC 为 0.93,灵敏度为 0.83,特异度为 0.89。这项研究通过有效预测与术后死亡率相关的潜在不良事件,在主动管理重症监护室心胸手术患者方面迈出了重要一步。
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引用次数: 0
Enhancing Interventional Cardiology Training: A Porcine Heart-Based Coronary Intervention Simulator 加强介入心脏病学培训:基于猪心脏的冠状动脉介入模拟器
Pub Date : 2024-09-04 DOI: 10.1101/2024.09.02.24312944
Joerg Reifart, Paul Anthony Iaizzo
Introduction Access to simulators for interventional cardiology is currently limited. High acuity, low occurrence procedures (HALO), such as coronary perforation or iatrogenic dissection, are not trained in currently available simulators. We developed a cost-effective coronary intervention simulator designed to enhance the training of both novice and experienced interventionalists.
导言 目前,介入心脏病学使用模拟器的机会有限。目前可用的模拟器无法对冠状动脉穿孔或先天性夹层等高危、低发生率的手术(HALO)进行培训。我们开发了一种具有成本效益的冠状动脉介入模拟器,旨在加强对新手和经验丰富的介入医师的培训。
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引用次数: 0
Risks and long-term prognosis of new-onset heart failure after de novo permanent pacemaker implantation: nationwide cohort study 重新植入永久起搏器后新发心力衰竭的风险和长期预后:全国性队列研究
Pub Date : 2024-09-04 DOI: 10.1101/2024.09.03.24313045
Young Jun Park, Sungjoo Lee, Sungjun Hong, Kyunga Kim, Juwon Kim, Ju Youn Kim, Kyoung-Min Park, Young Keun On, Seung-Jung Park
Background Previous studies on pacemaker-associated heart failure (PaHF) have predominantly analyzed relatively small, single-center datasets, mainly focusing on incidence and predictors. However, the clinical implications of PaHF on mortality, particularly in relation to standard HF medications or upgrading to cardiac resynchronization therapy (CRT), has been underexplored.
背景 以往关于起搏器相关性心力衰竭(PaHF)的研究主要分析了相对较小的单中心数据集,主要侧重于发病率和预测因素。然而,PaHF 对死亡率的临床影响,尤其是与标准高血压药物治疗或升级为心脏再同步化治疗(CRT)相关的影响,尚未得到充分探讨。
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引用次数: 0
Antiplatelet Therapy Following Spontaneous Coronary Artery Dissection: Systemic Review 自发性冠状动脉夹层后的抗血小板疗法:系统回顾
Pub Date : 2024-09-04 DOI: 10.1101/2024.09.03.24312989
Huijun Edelyn Park, Leslie S. Cho, Natalia Fendrikova-Mahlay, Pulkit Chaudhury, Scott J. Cameron
Background Spontaneous coronary artery dissection (SCAD) is an understudied cause of acute coronary syndrome (ACS), particularly in women. Heart muscle damage may result from spontaneous dissection of coronary arteries. There is no clear consensus regarding the optimum antiplatelet medication regimen and treatment duration for SCAD despite current American Heart Association (AHA) consensus guidelines recommending 12-month regimen of dual antiplatelet therapy (DAPT) consisting of a P2Y12 inhibitor and aspirin for patients following myocardial infarction (MI). The objective of this study was to evaluate the safety and effectiveness of DAPT compared to using a single antiplatelet therapy (SAPT) as part of the medical armamentarium to treat SCAD.
背景 自发性冠状动脉夹层(SCAD)是急性冠状动脉综合征(ACS)的一个研究不足的病因,尤其是在女性中。自发性冠状动脉夹层可能导致心肌损伤。尽管目前美国心脏协会(AHA)的共识指南建议心肌梗死(MI)后的患者接受为期 12 个月的由 P2Y12 抑制剂和阿司匹林组成的双重抗血小板疗法(DAPT),但关于 SCAD 的最佳抗血小板药物治疗方案和治疗持续时间仍未达成明确共识。本研究的目的是评估 DAPT 与使用单一抗血小板疗法 (SAPT) 作为治疗 SCAD 的医疗手段相比的安全性和有效性。
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引用次数: 0
Should women have lower blood pressure targets than men? Sex differences in blood pressure and cardiovascular disease in the UK Biobank 女性的血压目标是否应低于男性?英国生物库中血压和心血管疾病的性别差异
Pub Date : 2024-09-04 DOI: 10.1101/2024.09.03.24313046
Rebecca K Kelly, Katie Harris, Cheryl Carcel, Paul Muntner, Mark Woodward
Background Recent studies show that the risk of cardiovascular disease (CVD) increases from a lower nadir of systolic blood pressure (SBP) in women than men, and increases thereafter at a greater rate. This has led to a suggestion that sex-based SBP thresholds are required. We aimed to investigate sex differences in the associations of SBP and incident atherosclerotic CVD in a large prospective cohort.
背景 最近的研究表明,与男性相比,女性患心血管疾病(CVD)的风险会从较低的收缩压(SBP)最低点开始增加,并且此后会以更高的速度增加。因此,有人认为需要制定基于性别的收缩压阈值。我们的目的是在一个大型前瞻性队列中调查收缩压与动脉粥样硬化性心血管疾病发病率之间的性别差异。
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引用次数: 0
Precision phenotyping from routine laboratory parameters for machine learning out-of-hospital survival prediction using 4D time-dependent SHAP plots in an all-comers prospective PCI registry 在全病例前瞻性PCI登记中,利用4D时间依赖性SHAP图从常规实验室参数中进行精准表型分析,从而进行机器学习的院外生存率预测
Pub Date : 2024-09-03 DOI: 10.1101/2024.08.31.24312888
Paul-Adrian Călburean, Anda-Cristina Scurtu, Paul Grebenisan, Ioana-Andreea Nistor, Victor Vacariu, Reka-Katalin Drincal, Ioana Paula Sulea, Tiberiu Oltean, László Hadadi
Introduction Out-of-hospital mortality in coronary artery disease (CAD) is particularly high and established adverse event prediction tools are yet to be available. Our study aimed to investigate whether precision phenotyping can be performed using routine laboratory parameters for the prediction of out-of-hospital survival in a CAD population treated by percutaneous coronary intervention (PCI).
导言:冠状动脉疾病(CAD)的院外死亡率特别高,而目前还没有成熟的不良事件预测工具。我们的研究旨在探讨能否利用常规实验室参数进行精确表型,以预测接受经皮冠状动脉介入治疗(PCI)的冠心病患者的院外生存率。
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引用次数: 0
期刊
medRxiv - Cardiovascular Medicine
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