Circulation最新文献

{"title":"Gene Therapy in Cardiovascular Disease: Recent Advances and Future Directions in Science: A Science Advisory From the American Heart Association.","authors":"Yuri Kim, Andrew P Landstrom, Svati H Shah, Joseph C Wu, Christine E Seidman","doi":"10.1161/CIR.0000000000001296","DOIUrl":"10.1161/CIR.0000000000001296","url":null,"abstract":"<p><p>Cardiovascular disease remains the foremost cause of morbidity and mortality globally, affecting millions of individuals. Recent discoveries illuminate the substantial role of genetics in cardiovascular disease pathogenesis, encompassing both monogenic and polygenic mechanisms and identifying tangible targets for gene therapies. Innovative strategies have emerged to rectify pathogenic variants that cause monogenic disorders such as hypertrophic, dilated, and arrhythmogenic cardiomyopathies and hypercholesterolemia. These include delivery of exogenous genes to supplement insufficient protein levels caused by pathogenic variants or genome editing to correct, delete, or modify mutant sequences to restore protein function. However, effective delivery of gene therapy to specified cells presents formidable challenges. Viral vectors, notably adeno-associated viruses and nonviral vectors such as lipid and engineered nanoparticles, offer distinct advantages and limitations. Additional risks and obstacles remain, including treatment durability, tissue-specific targeting, vector-associated adverse events, and off-target effects. Addressing these challenges is an ongoing imperative; several clinical gene therapy trials are underway, and many more first-in-human studies are anticipated. This science advisory reviews core concepts of gene therapy, key obstacles, patient risks, and ongoing research endeavors to enable clinicians to understand the complex landscape of this emerging therapy and its remarkable therapeutic potential to benefit cardiovascular disease.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e471-e480"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on Diagnosis and Management of Kawasaki Disease: A Scientific Statement From the American Heart Association.","authors":"Pei-Ni Jone, Adriana Tremoulet, Nadine Choueiter, Samuel R Dominguez, Ashraf S Harahsheh, Yoshihide Mitani, Meghan Zimmerman, Ming-Tai Lin, Kevin G Friedman","doi":"10.1161/CIR.0000000000001295","DOIUrl":"10.1161/CIR.0000000000001295","url":null,"abstract":"<p><p>Kawasaki disease (KD), an acute self-limited febrile illness that primarily affects children <5 years old, is the leading cause of acquired heart disease in developed countries, with the potential of leading to coronary artery dilation and coronary artery aneurysms in 25% of untreated patients. This update summarizes relevant clinical data published since the 2017 American Heart Association scientific statement on KD related to diagnosis, cardiac imaging in acute KD treatment, and long-term management. Criteria defining North American patients at high risk for developing coronary artery aneurysms who may benefit from more intensive initial treatment have been published. Advances in cardiovascular imaging have improved the ability to identify coronary artery stenosis in patients with KD, yet knowledge gaps remain regarding optimal frequency of serial imaging and the best imaging modality to identify those at risk for inducible myocardial ischemia. Recent data have advanced the understanding of safety and dosing for several anti-inflammatory therapies in KD. New anticoagulation medication, myocardial infarction management, transition of health care for patients with KD, and future directions in research are discussed.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e481-e500"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Smokeless Oral Nicotine Products on Cardiovascular Disease: Implications for Policy, Prevention, and Treatment: A Policy Statement From the American Heart Association.","authors":"Cheryl R Dennison Himmelfarb, Neal L Benowitz, Melissa D Blank, Aruni Bhatnagar, Paul J Chase, Esa M Davis, Jessica L Fetterman, Brittney Keller-Hamilton, Oluwabunmi Ogungbe, Robert L Page, Mary Rezk-Hanna, Rose Marie Robertson, Laurie P Whitsel","doi":"10.1161/CIR.0000000000001293","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001293","url":null,"abstract":"<p><p>Smokeless oral nicotine products are addictive, and their use has potential adverse effects on some but not all biomarkers of cardiovascular risk. The use of some types of these products, for instance, is associated with an increased mortality risk in those with ischemic heart or cerebrovascular disease. Similarly, smokeless tobacco has the potential to increase the risk of oral cancer, but the risks depend on the chemical composition of the product. The market of smokeless oral nicotine products has transformed since the last American Heart Association smokeless tobacco policy statement. Several varieties of tobacco-free oral nicotine products-including oral nicotine pouches; nontherapeutic nicotine gums, lozenges, and tablets; and nicotine gummies-have rapidly proliferated. The sales of oral nicotine pouches, in particular, have increased substantially; however, no data are available on their cardiovascular or health risks. In addition, synthetic (compared with tobacco-derived) nicotine has been used in some brands of oral nicotine products, but its cardiovascular and health effects have been inadequately studied. Robust public policy levers are identified to support ending addiction to all commercial tobacco products. Critical components and policy initiatives include clinicians emphasizing the prevention of tobacco product initiation and supporting cessation with established pharmacological and behavioral tobacco dependence treatment therapies as primary goals for achieving an end to commercial tobacco and nicotine addiction.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized Invitation to Systematic NT-proBNP and ECG Screening in 75-Year-Olds to Detect Atrial Fibrillation: STROKESTOP II.","authors":"Katrin Kemp Gudmundsdottir, Emma Svennberg, Leif Friberg, Tove Hygrell, Viveka Frykman, Faris Al-Khalili, Ziad Hijazi, Mårten Rosenqvist, Johan Engdahl","doi":"10.1161/CIRCULATIONAHA.124.071176","DOIUrl":"10.1161/CIRCULATIONAHA.124.071176","url":null,"abstract":"<p><strong>Background: </strong>Guidelines have suggested screening for atrial fibrillation to enable early treatment and avoid downstream negative clinical events. We aimed to determine whether atrial fibrillation screening potentially enhanced by NT-proBNP (N-terminal pro-B-type natriuretic peptide) would reduce stroke or systemic embolism incidence compared with a control group and to determine whether it was safe for those with low NT-proBNP concentrations to forfeit prolonged screening.</p><p><strong>Methods: </strong>In this randomized controlled trial, all 75- and 76-year-old individuals in Stockholm Region, Sweden, were randomized 1:1 to be invited to screening or serve as a control group. NT-proBNP concentrations were measured, and a single-lead ECG was registered only once if NT-proBNP <125 ng/L, whereas if NT-proBNP ≥125 ng/L, participants underwent prolonged screening, recording single-lead ECGs 4 times daily for 2 weeks. If atrial fibrillation was detected, treatment was initiated. Baseline and outcome data were collected from Swedish National Registries.</p><p><strong>Results: </strong>In total, 28 712 individuals were randomized. After exclusion of death and emigration, 13 905 remained in the intervention group, 13 884 in the control group. The participation rate in the intervention group was 49.2% (6843 of 13 905). Participants in the high NT-proBNP group (NT-proBNP≥125 ng/L) without previous atrial fibrillation constituted 60% of the total and underwent prolonged screening. New atrial fibrillation was detected in 2.4% (165 of 6843) in the intervention group. There was no difference in atrial fibrillation prevalence or oral anticoagulant treatment between the intervention and the control group after 5 years of follow-up. After a median of 5.1 years (interquartile range, 5.0-5.8), there was no difference in the primary outcome of stroke or systemic embolism between the intervention group and the control group (hazard ratio, 0.96 [95% CI, 0.86-1.06]). The low NT-proBNP group had significantly fewer strokes or systemic emboli than the control group (hazard ratio, 0.59 [95% CI, 0.46-0.74]; <i>P</i><0.001). In the high NT-proBNP group, the risk of stroke or systemic embolism was higher compared with the low NT-proBNP group (hazard ratio, 1.57 [95% CI, 1.22-2.02]; <i>P</i>=0.001).</p><p><strong>Conclusions: </strong>In this population-based screening trial for atrial fibrillation using NT-proBNP for screening enhancement, there was no difference in risk of stroke or systemic embolism for the intervention group compared with controls. Participation was moderate. The use of NT-proBNP for screening enhancement was safe in identifying low-risk participants.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT02743416.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1837-1846"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve <i>KCNH2</i>-LQTS Variant Classification and Cardiac Event Risk Stratification.","authors":"Matthew J O'Neill, Chai-Ann Ng, Takanori Aizawa, Luca Sala, Sahej Bains, Annika Winbo, Rizwan Ullah, Qianyi Shen, Chek-Ying Tan, Krystian Kozek, Loren R Vanags, Devyn W Mitchell, Alex Shen, Yuko Wada, Asami Kashiwa, Lia Crotti, Federica Dagradi, Giulia Musu, Carla Spazzolini, Raquel Neves, J Martijn Bos, John R Giudicessi, Xavier Bledsoe, Eric R Gamazon, Megan C Lancaster, Andrew M Glazer, Bjorn C Knollmann, Dan M Roden, Jochen Weile, Frederick Roth, Joe-Elie Salem, Nikki Earle, Rachael Stiles, Taylor Agee, Christopher N Johnson, Minoru Horie, Jonathan R Skinner, Michael J Ackerman, Peter J Schwartz, Seiko Ohno, Jamie I Vandenberg, Brett M Kroncke","doi":"10.1161/CIRCULATIONAHA.124.069828","DOIUrl":"10.1161/CIRCULATIONAHA.124.069828","url":null,"abstract":"<p><strong>Background: </strong>Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by <i>KCNH2</i>. Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance. Here we sought to test whether variant-specific information, primarily from high-throughput functional assays, could improve both classification and cardiac event risk stratification in a large, harmonized cohort of <i>KCNH2</i> missense variant heterozygotes.</p><p><strong>Methods: </strong>We quantified cell-surface trafficking of 18 796 variants in <i>KCNH2</i> using a multiplexed assay of variant effect (MAVE). We recorded <i>KCNH2</i> current density for 533 variants by automated patch clamping. We calibrated the strength of evidence of MAVE data according to ClinGen guidelines. We deeply phenotyped 1458 patients with <i>KCNH2</i> missense variants, including QTc, cardiac event history, and mortality. We correlated variant functional data and Bayesian long QT syndrome penetrance estimates with cohort phenotypes and assessed hazard ratios for cardiac events.</p><p><strong>Results: </strong>Variant MAVE trafficking scores and automated patch clamping peak tail currents were highly correlated (Spearman rank-order ρ=0.69; n=433). The MAVE data were found to provide up to pathogenic very strong evidence for severe loss-of-function variants. In the cohort, both functional assays and Bayesian long QT syndrome penetrance estimates were significantly predictive of cardiac events when independently modeled with patient sex and corrected QT interval (QTc); however, MAVE data became nonsignificant when peak tail current and penetrance estimates were also available. The area under the receiver operator characteristic curve for 20-year event outcomes based on patient-specific sex and QTc (area under the curve, 0.80 [0.76-0.83]) was improved with prospectively available penetrance scores conditioned on MAVE (area under the curve, 0.86 [0.83-0.89]) or attainable automated patch clamping peak tail current data (area under the curve, 0.84 [0.81-0.88]).</p><p><strong>Conclusions: </strong>High-throughput <i>KCNH2</i> variant MAVE data meaningfully contribute to variant classification at scale, whereas long QT syndrome penetrance estimates and automated patch clamping peak tail current measurements meaningfully contribute to risk stratification of cardiac events in patients with heterozygous <i>KCNH2</i> missense variants.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1869-1881"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catheter Ablation in Patients With End-Stage Heart Failure and Atrial Fibrillation: Two-Year Follow-Up of the CASTLE-HTx Trial.","authors":"Christian Sohns, Maximilian Moersdorf, Nassir F Marrouche, Leonard Bergau, Angelika Costard-Jaeckle, Harry J G M Crijns, Henrik Fox, Gerhard Hindricks, Nikolaos Dagres, Samuel Sossalla, Rene Schramm, Thomas Fink, Mustapha El Hamriti, Vanessa Sciacca, Maxim Didenko, Frank Konietschke, Volker Rudolph, Jan Gummert, Jan G P Tijssen, Philipp Sommer","doi":"10.1161/CIRCULATIONAHA.124.071517","DOIUrl":"10.1161/CIRCULATIONAHA.124.071517","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1904-1906"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlights From the <i>Circulation</i> Family of Journals.","authors":"","doi":"10.1161/CIRCULATIONAHA.124.072974","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072974","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 23","pages":"1898-1903"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pitfalls of Choosing a Study End Point Including Cardiovascular Death in Comparative Clinical Trials.","authors":"Stephanie Armbruster, Hicham Skali, Lee-Jen Wei","doi":"10.1161/CIRCULATIONAHA.124.070899","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070899","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 23","pages":"1823-1825"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-QT Trafficking Map.","authors":"Barry London","doi":"10.1161/CIRCULATIONAHA.124.072169","DOIUrl":"10.1161/CIRCULATIONAHA.124.072169","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 23","pages":"1882-1884"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vivo Cardiovascular Molecular Imaging: Contributions to Precision Medicine and Drug Development.","authors":"Jonathan R Lindner, Matteo Morello","doi":"10.1161/CIRCULATIONAHA.124.066522","DOIUrl":"10.1161/CIRCULATIONAHA.124.066522","url":null,"abstract":"<p><p>Conventional forms of noninvasive cardiovascular imaging that evaluate morphology, function, flow, and metabolism play a vital role in individual treatment decisions, often based on guidelines. Innovations in molecular imaging have enhanced our ability to spatially quantify the expression of a wider array of disease-related proteins, genes, or cell types, or the activity of specific pathogenic pathways. These techniques, which usually rely on design of targeted imaging probes, have already been used extensively in cancer medicine and have now become part of cardiovascular care in conditions such as amyloidosis and sarcoidosis. The recognition that common cardiovascular conditions are caused by a substantial diversity of pathobiologic pathways and the diversity of therapies available for use have rekindled interest in expanding the role of molecular imaging of tissue phenotype to improve precision in diagnosis and therapeutic decision-making. The intent of this article is to raise awareness and understanding of approaches to molecular or cellular imaging of phenotype with targeted probes, and their potential to promote the principles of precision medicine. Also addressed are the diverse roles of molecular imaging to improve precision and efficiency of new drug development at the stages of candidate identification, preclinical testing, and clinical trials.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 23","pages":"1885-1897"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}