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PCSK9 Inhibitors and Anthracyclines: The Future of Cardioprotection in Cardio-Oncology. PCSK9 抑制剂和蒽环类药物:肿瘤心脏病保护的未来。
Pub Date : 2024-09-01 Epub Date: 2024-09-03 DOI: 10.3390/hearts5030027
Matthew L Repp, Mark D Edwards, Christopher S Burch, Amith Rao, Ikeotunye Royal Chinyere

The field of cardio-oncology is an expanding frontier within cardiovascular medicine, and the need for evidence-based guidelines is apparent. One of the emerging focuses within cardio-oncology is the concomitant use of medications for cardioprotection in the setting of chemotherapy regimens that have known cardiovascular toxicity. While clinical trials focusing on cardioprotection during chemotherapy are sparse, an inaugural trial exploring the prophylactic potential of Sodium-Glucose Cotransporter-2 inhibitors (SGLT2is) for anthracycline (ANT)-induced cardiotoxicity has recently commenced. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, though less studied in this oncology demographic, have exhibited promise in preclinical studies for conferring cardiac protection during non-ischemic toxic insults. While primarily used to reduce low-density lipoprotein, PCSK9 inhibitors exhibit pleiotropic effects, including the attenuation of inflammation, reactive oxygen species, and endothelial dysfunction. In ANT-induced cardiotoxicity, these same processes are accelerated, resulting in premature termination of treatment, chronic cardiovascular sequelae, heart failure, and/or death. This review serves a dual purpose: firstly, to provide a concise overview of the mechanisms implicated in ANT-induced cardiotoxicity, and, finally, to summarize the existing preclinical data supporting the theoretical possibility of the cardioprotective effects of PCSK9 inhibition in ANT-induced cardiotoxicity.

心脏肿瘤学是心血管医学中一个不断扩展的前沿领域,因此显然需要以证据为基础的指南。心肿瘤学的一个新重点是在已知有心血管毒性的化疗方案中同时使用保护心脏的药物。虽然针对化疗期间心脏保护的临床试验并不多见,但一项探索钠-葡萄糖转运体-2抑制剂(SGLT2is)对蒽环类药物(ANT)诱导的心脏毒性的预防潜力的首期试验已于近期启动。Proprotein convertase subtilisin/kexin type 9 (PCSK9)抑制剂虽然在这一肿瘤治疗领域的研究较少,但在临床前研究中已显示出在非缺血性毒性损伤中保护心脏的前景。虽然 PCSK9 抑制剂主要用于降低低密度脂蛋白,但它也具有多生物效应,包括减轻炎症、活性氧和内皮功能障碍。在 ANT 诱导的心脏毒性中,这些过程同样会加速,导致治疗过早终止、慢性心血管后遗症、心力衰竭和/或死亡。本综述具有双重目的:首先,简要概述 ANT 诱导的心脏毒性的相关机制;最后,总结现有的临床前数据,支持 PCSK9 抑制在 ANT 诱导的心脏毒性中具有心脏保护作用的理论可能性。
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引用次数: 0
Deciphering the Intricate Molecular Bases of Atrial Fibrillation 解读心房颤动复杂的分子基础
Pub Date : 2023-11-10 DOI: 10.3390/hearts4040010
Diego Franco
Atrial fibrillation (AF) is the most prevalent electrophysiological disorder in humans [...]
心房颤动(AF)是人类最常见的电生理疾病[…]
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引用次数: 0
Deciphering the Involvement of the Epicardium in Cardiac Diseases 解读心外膜在心脏病中的作用
Pub Date : 2023-11-10 DOI: 10.3390/hearts4040011
Rita Carmona, Carmen López-Sánchez, Virginio García-Martinez, Virginio García-López, Ramón Muñoz-Chápuli, Estefanía Lozano-Velasco, Diego Franco
The epicardium is a very dynamic cardiac layer with pivotal contributions during cardiogenesis, acting in the postnatal period as an apparently dormant single-cell layer. In mammalian embryos, the epicardium, which originates form the proepicardium, translocates into the pericardial cavity and subsequently rests on the surface of the myocardium. Later, it gives rise to the epicardium-derived cells, which migrate into subepicardial space, invade the developing myocardium, promoting its growth, and contribute to different cell types. Anomalies in the process of epicardial development, the generation of epicardium-derived cells and their signaling mechanisms in different experimental models lead to defective cardiac development, reminiscent of human congenital heart diseases. Furthermore, recent studies have reported that epicardial derivates in adults, i.e., epicardial adipose tissue, are associated with electrophysiological cardiovascular anomalies. Herein, we provide a state-of-the-art review focusing on both congenital and adult heart diseases associated with epicardial development.
心外膜是一个非常活跃的心脏层,在心脏发生过程中起关键作用,在出生后时期作为一个明显休眠的单细胞层。在哺乳动物胚胎中,心外膜起源于前心外膜,移位到心包腔内,随后附着在心肌表面。随后产生心外膜源性细胞,这些细胞迁移到心外膜下空间,侵入正在发育的心肌,促进其生长,形成不同的细胞类型。心外膜发育过程中的异常、心外膜源性细胞的产生及其在不同实验模型中的信号传导机制导致心脏发育缺陷,令人联想起人类先天性心脏病。此外,最近的研究报道,成人心外膜衍生物,即心外膜脂肪组织,与电生理心血管异常有关。在此,我们提供了一项最新的综述,重点是先天性和成人心脏病与心外膜发育相关。
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引用次数: 0
Durable Continuous-Flow Mechanical Circulatory Support 耐用的连续流动机械循环支持
Pub Date : 2023-10-25 DOI: 10.3390/hearts4040009
John Pepper
The prevalence of heart failure in the UK is 1 in 35 people aged from 65 to 74 and 1 in 15 people aged from 75 to 84 [...]
在英国,65岁至74岁的人群中,35人中就有1人患心力衰竭,75岁至84岁的人群中,15人中就有1人患心力衰竭。
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引用次数: 0
Outcomes and Safety of Direct Oral Anticoagulants (DOACs) versus Vitamin K Antagonists (VKAs) amongst Patients with Valvular Heart Disease (VHD): A Systematic Review and Meta-Analysis 直接口服抗凝剂(DOACs)与维生素K拮抗剂(VKAs)在瓣膜性心脏病(VHD)患者中的疗效和安全性:一项系统综述和荟萃分析
Pub Date : 2023-09-07 DOI: 10.3390/hearts4030008
Ghanshyam Patel, Beshoy Iskandar, N. Chelikam, Siddhant Jain, Vandit Vyas, Tanvi Singla, Lavanya Dondapati, Ali Bombaywala, A. Peela, Milan Khealani, Sindhu Mukesh, Hariprasad Reddy Korsapati, A. R. Korsapati, H. Regassa, Nitesh Jain, Urvish Patel, V. S. Venkata
Background: Both valvular heart disease (VHD) and atrial fibrillation (AF) frequently coexist. AF is an important cause of arrhythmias with a definitive cardiovascular morbidity. The use of either vitamin K antagonists (VKAs/warfarin) or direct oral anticoagulants (DOACs) (also known as new oral anticoagulants (NOACs)) has been the mainstay for preventing stroke and systemic embolism in patients with VHD and/or AF, and this has been broadly discussed. However, there are limited studies on anticoagulation therapy for patients with valvular atrial fibrillation (VAF). The main aim of this meta-analysis was to evaluate the outcomes (stroke–vascular events and intracranial bleeding) following DOAC and VKA treatment amongst patients with VAF. Methods: We identified clinical trials and observational studies published in the last 10 years. A systematic review and a meta-analysis were performed to evaluate the outcomes of patients with valvular atrial fibrillation following DOAC vs. VKA treatment. Data evaluation was performed using Review Manager 5.4; the endpoints were stroke–vascular events and intracranial bleeding following DOAC and VKA treatment amongst VAF patients. Risk ratios (RR) were evaluated with 95% confidence intervals. Using random effects models, forest plots were obtained. Heterogeneity was assessed by using the I2 statistic. Results: Eight studies were included in this metanalysis, and a total of fifteen thousand two hundred and fifteen patients (DOAC (8732) and VKA (6483)) were pooled. We found a significant risk reduction in stroke–vascular events when using DOACs in comparison with using VKAs (pooled RR: 0.76; 95% CI: 0.64–0.90, p = 0.002). A total of 14862 patients (DOAC (8561) and VKA (6301)) were pooled from a total of six studies for intracranial bleeding. We found a significant risk reduction in terms of intracranial bleeding when using DOACs in comparison with using VKAs (pooled RR: 0.43; 95% CI: 0.24–0.77, p ≤ 0.05). Conclusions: When compared to VKAs, DOAC agents were found to have less risk of stroke–vascular events and intracranial bleeding. Further prospective studies are essential to establish the efficacy and safety of DOAC agents in patients with various subtypes of VAF.
背景:瓣膜性心脏病(VHD)和心房颤动(AF)经常并存。房颤是心律失常的一个重要原因,具有明确的心血管发病率。维生素K拮抗剂(VKAs/华法林)或直接口服抗凝剂(DOAC)(也称为新型口服抗凝剂)的使用一直是预防VHD和/或AF患者中风和系统性栓塞的主要方法,这一点已得到广泛讨论。然而,对瓣膜性心房颤动(VAF)患者的抗凝治疗研究有限。该荟萃分析的主要目的是评估VAF患者接受DOAC和VKA治疗后的结果(中风-血管事件和颅内出血)。方法:我们确定了过去10年中发表的临床试验和观察性研究。进行了一项系统综述和荟萃分析,以评估DOAC与VKA治疗后瓣膜性心房颤动患者的预后。使用Review Manager 5.4进行数据评估;终点是VAF患者接受DOAC和VKA治疗后的中风-血管事件和颅内出血。风险比(RR)采用95%置信区间进行评估。使用随机效应模型,获得了森林地块。通过使用I2统计来评估异质性。结果:本荟萃分析包括8项研究,共收集了15000名215名患者(DOAC(8732)和VKA(6483))。我们发现,与使用VKA相比,使用DOAC可显著降低中风-血管事件的风险(合并RR:0.76;95%CI:0.64–0.90,p=0.002)。共有14862名患者(DOAC(8561)和VKA(6301))来自六项颅内出血研究。我们发现,与使用VKAs相比,使用DOAC可显著降低颅内出血的风险(合并RR:0.43;95%CI:0.24-0.77,p≤0.05)。进一步的前瞻性研究对于确定DOAC药物对不同亚型VAF患者的疗效和安全性至关重要。
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引用次数: 0
Recent Advances in Peripheral Artery Disease 外周动脉疾病研究进展
Pub Date : 2023-08-18 DOI: 10.3390/hearts4030007
F. Biscetti
Despite its significant impact on patients’ lives and the healthcare system, peripheral arterial disease (PAD) has long been overshadowed by other cardiovascular diseases [...]
尽管外周动脉疾病对患者的生活和医疗系统产生了重大影响,但它长期以来一直被其他心血管疾病所掩盖[…]
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引用次数: 0
Monitoring Water Balance to Predict Hospitalization in Patients with Chronic Heart Failure: A Retrospective Study 监测水平衡预测慢性心力衰竭患者住院:一项回顾性研究
Pub Date : 2023-07-07 DOI: 10.3390/hearts4030006
Kenichi Hirose, Keita Otsuka, Shinichiro Shiozawa, Go Hirose, M. Shino, Takeo Hokari, Satoru Kohno, Kohzo Nakayama
Background: Patients with chronic heart failure often experience repeated acute exacerbations leading to high rates of rehospitalization. Therefore, the management of patients to prevent rehospitalization and retain their physical function is important. Brain natriuretic peptide (BNP) and N-terminal-pro BNP are used to estimate the conditions of patients with chronic heart failure, but some hospitals cannot measure these levels in real time. To overcome this, we used bioelectrical impedance analysis as an alternative. Methods and results: Between April 2017 and December 2019, we measured water balance in the outpatient department of Hirose Hospital in three groups: those who had been hospitalized for chronic heart failure (257 patients), those with chronic heart failure who had not been hospitalized (224 patients), and controls with other chronic diseases (275 patients). We found that water balance was significantly correlated to the history of hospitalization, and age was a confounding bias in this correlation, regardless of whether patients have been hospitalized with chronic heart failure. Moreover, patients who have high extracellular water content/total body water content ratios, even in a stable period, are at risk of becoming unstable and experiencing rehospitalization. Conclusion: Water balance monitoring could be a useful indicator to estimate patient condition in real time and predict improvement in chronic heart failure. This easy-to-use indicator may enable timely management of exacerbation of patient condition and reduce hospitalization events.
背景:慢性心力衰竭患者经常经历反复的急性加重,导致高比率的再次住院。因此,对患者进行管理以防止再次住院并保持其身体功能是很重要的。脑钠肽(BNP)和N-末端-pro BNP用于估计慢性心力衰竭患者的病情,但一些医院无法实时测量这些水平。为了克服这一点,我们使用了生物电阻抗分析作为替代方法。方法和结果:2017年4月至2019年12月,我们测量了三组广濑医院门诊部的水平衡:因慢性心力衰竭住院的患者(257名患者)、未住院的慢性心力衰竭患者(224名患者)和其他慢性病对照组(275名患者)。我们发现,水平衡与住院史显著相关,无论患者是否因慢性心力衰竭住院,年龄都是这种相关性中的一个混淆偏差。此外,细胞外含水量/全身含水量比率高的患者,即使在稳定期,也有变得不稳定和再次住院的风险。结论:水平衡监测可作为实时评估患者病情和预测慢性心力衰竭病情改善的有用指标。这种易于使用的指标可以及时管理患者病情恶化并减少住院事件。
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引用次数: 0
Hemodynamic Consequence of Interventional Cardiac Catheterization in the Early Postoperative Period after Congenital Heart Surgery 先心病手术后早期介入心导管插入术对血流动力学的影响
Pub Date : 2023-06-29 DOI: 10.3390/hearts4030005
D. Eason, A. Rossi, Khalifah Aldawsari, B. Patel, Habiba Farooq, D. Khan
While still considered a high-risk procedure, cardiac catheterization during the early postoperative period is being performed more frequently in the current era. Limited data are currently available concerning the acute hemodynamic consequences of these procedures. Therefore, the purpose of this study was to evaluate the safety/efficacy of cardiac catheterization performed within thirty days of congenital heart surgery. We completed a retrospective review of all catheterizations within 30 days of congenital heart surgery. Procedures were performed due to failure to progress or hemodynamic deterioration. There were 1873 congenital heart surgeries during the study period. One hundred and three (6.2%) patients with a median age of 124 days underwent catheterization. Sixty-three cases received interventions, and forty patients underwent diagnostic catheterization. Early cardiac catheterization did not show a significant immediate change in the hemodynamics or inotrope score. Survival for patients undergoing diagnostic Cath (81%) did not differ significantly from the intervention group (89%). Although cardiac catheterization was performed on patients at the highest risk for death in the postoperative period, catheter intervention did not increase the risk of death. Those patients undergoing catheter intervention did not seem to experience major adverse events but achieved mild improvement in tissue perfusion.
尽管仍然被认为是一种高风险的手术,但在当前时代,术后早期的心导管插入术正在更频繁地进行。目前关于这些手术的急性血液动力学后果的数据有限。因此,本研究的目的是评估先天性心脏手术后30天内进行心导管插入术的安全性/有效性。我们完成了对先天性心脏手术后30天内所有导管的回顾性审查。由于进展失败或血流动力学恶化而进行手术。在研究期间,共有1873例先天性心脏手术。103名(6.2%)中位年龄为124天的患者接受了导管插入术。63例接受了干预,40例患者接受了诊断性导管插入术。早期心导管插入术并未显示血液动力学或inotrope评分立即发生显著变化。接受诊断性Cath的患者的生存率(81%)与干预组(89%)没有显著差异。尽管心导管插入术是对术后死亡风险最高的患者进行的,但导管干预并没有增加死亡风险。接受导管介入治疗的患者似乎没有发生重大不良事件,但组织灌注略有改善。
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引用次数: 0
Premature Cardiovascular Misdiagnosis of Senior Endurance-Trained Athletes 高级耐力训练运动员心血管过早误诊
Pub Date : 2023-03-15 DOI: 10.3390/hearts4010004
J. Jackson
A mature Caucasian patient, an endurance-trained triathlete (age group), had a routine ECG. The patient was immediately referred to Emergency based on supposed ECG abnormalities indicating a heart attack. This diagnosis was quickly dismissed based on no symptoms, heart rate of 50 BPM, athletic status, excellent health, and no prior cardiovascular problems. The patient had a history of severe white coat hypertension and underwent a further stress test and echocardiogram. The stress test showed exaggerated systolic blood pressures (over 225 mmHg) and high in-clinic basal blood pressures (160/90 mmHg), and the patient was diagnosed as hypertensive with exercise blood pressure close to stroke territory. He was told to stop racing, reduce training, and was prescribed antihypertensive drugs (which he did not take). Subsequent at-home 24 h (values close to 120/80 mmHg) and stress blood pressure measurements reversed that decision when considered in combination with an excellent echocardiogram result. The literature clearly describes endurance-trained athletes with systolic pressures over 225 mmHg Hg as being conditioned with no pathological aspects. Endurance-trained athletes should be examined as special cases in the field of cardiovascular medicine as trained physiological responses often present as cardiac abnormalities, and misdiagnosis can inappropriately change the athlete’s life.
一个成熟的高加索病人,一个耐力训练的铁人三项运动员(年龄组),有一个常规的心电图。根据心电图异常提示心脏病发作,患者立即被转到急诊室。基于无症状、心率50 BPM、运动状态、良好的健康状况和既往无心血管问题,这一诊断很快被驳回。患者有严重的白大衣高血压病史,并进行了进一步的压力测试和超声心动图检查。压力测试显示收缩压过高(超过225 mmHg)和临床基础血压高(160/90 mmHg),患者被诊断为高血压,运动血压接近脑卒中范围。他被告知停止比赛,减少训练,并被开了抗高血压药物(他没有服用)。随后在家中24小时(数值接近120/80 mmHg)和压力血压测量与出色的超声心动图结果相结合时,逆转了这一决定。文献清楚地描述了收缩压超过225 mmHg Hg的耐力训练运动员没有任何病理方面的条件。耐力训练的运动员应作为心血管医学领域的特殊病例进行检查,因为训练后的生理反应通常表现为心脏异常,误诊可能会不适当地改变运动员的生活。
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引用次数: 0
Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Clinical and Laboratory Variables in Heart Failure Patients with Reduced Left Ventricular Ejection Fraction in a Latin American Hospital: A Retrospective Study 钠-葡萄糖协同转运蛋白2抑制剂对一家拉丁美洲医院左心室射血分数降低的心力衰竭患者临床和实验室变量的影响:一项回顾性研究
Pub Date : 2023-02-25 DOI: 10.3390/hearts4010003
M. Speranza-Sánchez, J. P. Díaz‐Madriz, Esteban Zavaleta‐Monestel, J. M. Chaverri-Fernández, Sebastián Arguedas‐Chacón, Marleny Blanco-Jara, Abigail Fallas-Mora, Luis Daniel Velásquez-Alfaro
Heart failure (HF) is a syndrome suffered by more than 26 million people worldwide. SGLT2 inhibitors are drugs that have been shown to positively affect the management of HF patients, regardless of their diabetes status. A retrospective observational study was conducted on heart failure patients with reduced ejection fraction (HFrEF) enrolled at the HF clinic, who were on SGLT2 inhibitors. For these patients, baseline and follow-up data were collected and analyzed over time. Changes over time were quantified and statistical analysis was conducted to validate whether the changes were significant. After the screening of all the HF program patients, 24 met the inclusion criteria, with an average age of 68 years. Through the study, it was possible to find a statistically significant difference in the values of NT-ProBNP before and after adding a SGLT2 inhibitor in 14 patients (p = 0.0214). In addition, there was an improvement in the NYHA functional scale of 71% and no significant change in renal function or other laboratory values. Based on the studied parameters and throughout the clinical changes during the follow-up period, it was possible to establish an improvement in HFrEF patients on SGLT2 inhibitors as part of their therapy.
心力衰竭(HF)是一种综合征,全世界有超过2600万人患有此病。SGLT2抑制剂是一种已被证明对HF患者管理有积极影响的药物,无论其糖尿病状态如何。一项回顾性观察性研究纳入了心衰门诊接受SGLT2抑制剂治疗的射血分数降低(HFrEF)心衰患者。对于这些患者,收集并分析了一段时间内的基线和随访数据。对随时间的变化进行量化,并进行统计分析以验证变化是否显著。经过对所有HF项目患者的筛选,24例符合纳入标准,平均年龄为68岁。通过本研究,发现14例患者在加入SGLT2抑制剂前后NT-ProBNP值有统计学差异(p = 0.0214)。此外,NYHA功能评分改善71%,肾功能及其他实验室指标无明显变化。根据研究参数和随访期间的临床变化,可以确定将SGLT2抑制剂作为HFrEF患者治疗的一部分有改善。
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引用次数: 0
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Hearts (Basel, Switzerland)
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