Abstract:
BACKGROUND:Although cardiomyopathy has emerged as a leading cause of death in Duchenne muscular dystrophy (DMD), limited studies and therapies have emerged for dystrophic heart failure. OBJECTIVES:The purpose of this study was to model DMD cardiomyopathy using DMD patient-specific human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and to identify physiological changes and future drug therapies. METHODS:To explore and define therapies for DMD cardiomyopathy, the authors used DMD patient-specific hiPSC-derived cardiomyocytes to examine the physiological response to adrenergic agonists and β-blocker treatment. The authors further examined these agents in vivo using wild-type and mdx mouse models. RESULTS:At baseline and following adrenergic stimulation, DMD hiPSC-derived cardiomyocytes had a significant increase in arrhythmic calcium traces compared to isogenic controls. Furthermore, these arrhythmias were significantly decreased with propranolol treatment. Using telemetry monitoring, the authors observed that mdx mice, which lack dystrophin, had an arrhythmic death when stimulated with isoproterenol; the lethal arrhythmias were rescued, in part, by propranolol pre-treatment. Using single-cell and bulk RNA sequencing (RNA-seq), the authors compared DMD and control hiPSC-derived cardiomyocytes, mdx mice, and control mice (in the presence or absence of propranolol and isoproterenol) and defined pathways that were perturbed under baseline conditions and pathways that were normalized after propranolol treatment in the mdx model. The authors also undertook transcriptome analysis of human DMD left ventricle samples and found that DMD hiPSC-derived cardiomyocytes have dysregulated pathways similar to the human DMD heart. The authors further determined that relatively few patients with DMD see a cardiovascular specialist or receive β-blocker therapy. CONCLUSIONS:The results highlight mechanisms and therapeutic interventions from human to animal and back to human in the dystrophic heart. These results may serve as a prelude for an adequately powered clinical study that examines the impact of β-blocker therapy in patients with dystrophinopathies.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Kamdar F,Das S,Gong W,Klaassen Kamdar A,Meyers TA,Shah P,Ervasti JM,Townsend D,Kamp TJ,Wu JC,Garry MG,Zhang J,Garry DJdoi
10.1016/j.jacc.2019.12.066subject
Has Abstractpub_date
2020-03-17 00:00:00pages
1159-1174issue
10eissn
0735-1097issn
1558-3597pii
S0735-1097(20)30254-0journal_volume
75pub_type
杂志文章abstract:OBJECTIVES:This study sought to describe the clinical correlates and heritability of the early repolarization pattern (ERP) in 2 large, population-based cohorts. BACKGROUND:There is growing recognition that ERP is associated with adverse outcomes. METHODS:Participants of the Framingham Heart Study (FHS) (N = 3,995) a...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2011.04.003
更新日期:2011-05-31 00:00:00
abstract::Two hundred ninety patients with acute myocardial infarction were treated according to random assignment with an intravenous infusion of either 80 mg of recombinant tissue plasminogen activator (rt-PA) over 3 h or 1.5 million units of streptokinase over 1 h. Patients received an intravenous bolus of heparin (5,000 U [...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0735-1097(88)90158-1
更新日期:1988-01-01 00:00:00
abstract::The complexity of the events that culminate in intimal proliferation after arterial injury and similarities between this response and benign neoplasia suggest that conventional medical therapies will continue to be unsuccessful in preventing recurrent stenosis after percutaneous coronary revascularization. By preventi...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/0735-1097(91)90948-9
更新日期:1991-05-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to investigate the effect of intracoronary administration of acetylcholine on large epicardial vessels 8 days after successful coronary angioplasty. BACKGROUND:Intracoronary infusion of acetylcholine causes vessel dilation in patients without angiographic evidence of coronary ather...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(93)90239-w
更新日期:1993-04-01 00:00:00
abstract:OBJECTIVES:The purposes of this study were to evaluate the atrial electrophysiology and autonomic nervous system in patients who had paroxysmal supraventricular tachycardia (PSVT) associated with paroxysmal atrial fibrillation (PAF). BACKGROUND:PAF frequently appeared in patients with PSVT. However, the critical deter...
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doi:10.1016/s0735-1097(98)00305-2
更新日期:1998-09-01 00:00:00
abstract:BACKGROUND:A high percentage of biventricular pacing is required for optimal outcome in patients treated with cardiac resynchronization therapy (CRT), but the influence of ectopic beats on the success of biventricular pacing has not been well established. OBJECTIVES:This study sought to determine if increased ectopic ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jacc.2014.06.1177
更新日期:2014-09-09 00:00:00
abstract::Inappropriate sinus tachycardia (IST) is a syndrome in which the sinus heart rate is inexplicably faster than expected and associated symptoms are present. The heart rate at rest, even in a supine position, can exceed 100 beats/min; minimal activity accelerates the rate rapidly and substantially. Patients with IST may...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.jacc.2012.07.074
更新日期:2013-02-26 00:00:00
abstract:OBJECTIVES:The aim of this study was to examine whether restrictive right ventricular (RV) physiology (the presence of antegrade pulmonary arterial flow in late diastole) occurred in patients with moderate to severe isolated pulmonary valvular stenosis (PVS) and to estimate its prevalence and relationship to RV functio...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2007.06.042
更新日期:2007-10-09 00:00:00
abstract:OBJECTIVES:This study was designed to compare the long-term clinical and angiographic effects of successful directional atherectomy and stent implantation and to examine whether restenosis is related to the mechanism of lumen improvement as well as the extent of lumen gain. BACKGROUND:Directional atherectomy and coron...
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pub_type: 杂志文章
doi:10.1016/0735-1097(96)00229-x
更新日期:1996-09-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jacc.2003.10.073
更新日期:2004-06-16 00:00:00
abstract::In 72 drug abusers surgically treated for acute infective endocarditis, 14 patients (19%) required surgical procedures on two valves. The predominant infecting organisms were Staphylococcus aureus and Pseudomonas aeruginosa (29%). In contrast to single valve infection, congestive heart failure was the most common oper...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(84)80393-9
更新日期:1984-10-01 00:00:00
abstract::The failure of exercise-induced ST segment depression to consistently predict prognosis in patients after myocardial infarction could be a result of population differences and the rest electrocardiogram (ECG). These hypotheses were tested by studying 198 veterans who survived a myocardial infarction, underwent a subma...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(89)90178-2
更新日期:1989-08-01 00:00:00
abstract:OBJECTIVES:To explain the discrepancy between the symptomatic status of patients and the hemodynamically calculated mitral valve area during long-term follow-up after mitral balloon valvulotomy, mitral valve orifice variability after dobutamine infusion was investigated in two groups of patients. BACKGROUND:A signific...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(93)90597-t
更新日期:1993-11-15 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/0735-1097(93)90562-f
更新日期:1993-11-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.jacc.2004.02.042
更新日期:2004-06-16 00:00:00
abstract::Antiarrhythmic drugs prolong the effective refractory period and depress conduction. To determine the exact role played by these two electrophysiologic effects in the termination of reentry, the effects of disopyramide, flecainide, propafenone and E-4031, a new class III drug, were examined in a canine model of atrial...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(91)90773-3
更新日期:1991-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.jacc.2016.11.065
更新日期:2017-02-21 00:00:00
abstract::Functional capacity is a robust predictor of clinical outcomes, and stress testing is used in current practice paradigms to guide referral to invasive coronary angiography. However, invasive coronary angiography is driven by ongoing symptoms, as well as risk of adverse outcomes. The limitations of current functional t...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.jacc.2015.04.060
更新日期:2015-06-30 00:00:00
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doi:10.1016/s0735-1097(98)00160-0
更新日期:1998-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s0735-1097(99)00506-9
更新日期:2000-01-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2007.01.085
更新日期:2007-05-22 00:00:00
abstract:OBJECTIVES:We evaluated the relationship between acute hemodynamic response (AHR) and reverse remodeling (RR) in cardiac resynchronization therapy (CRT). BACKGROUND:CRT reduces mortality and morbidity in heart failure patients; however, up to 30% of patients do not derive symptomatic benefit. Higher proportions do not...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2011.04.042
更新日期:2011-09-06 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2015.08.862
更新日期:2015-11-03 00:00:00
abstract:OBJECTIVES:The aim of this study was to compare the effectiveness of the implantable cardioverter defibrillator (ICD) and medical strategies for prevention of arrhythmic events and death. BACKGROUND:The ICD is a potential strategy to reduce mortality in patients at risk of sudden death. METHODS:The MEDLINE, EMBASE, a...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,meta分析
doi:10.1016/s0735-1097(03)00253-5
更新日期:2003-05-07 00:00:00
abstract:OBJECTIVES:The aim of this study was to investigate the effects of bariatric surgery on small artery function and the mechanisms underlying this. BACKGROUND:In lean healthy humans, perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arteries, but this is lost in obesity-associated con...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2013.04.027
更新日期:2013-07-09 00:00:00
abstract:OBJECTIVES:This meta-analysis was performed to determine the effects of various cholesterol-lowering treatments on the risk of stroke and its relationship with the extent of cholesterol lowering. BACKGROUND:Statins reduce the incidence of stroke, and it has been proposed that such effect is independent of cholesterol ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,meta分析
doi:10.1016/j.jacc.2009.07.062
更新日期:2010-01-19 00:00:00
abstract:OBJECTIVES:The purpose of this review is to assemble the widely dispersed information about cardiac alternans and to categorize the types and mechanisms of alternans, their clinical manifestations and possible therapeutic implications. BACKGROUND:The phenomena of mechanical and electrical alternans have been of contin...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/0735-1097(92)90122-4
更新日期:1992-08-01 00:00:00
abstract:OBJECTIVES:This study evaluated effects of protease-activated receptor-1 antagonist vorapaxar (Merck, Whitehouse Station, New Jersey) versus placebo among the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study patients with non-ST-segment elevation acute coronary syndrom...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2013.10.048
更新日期:2014-03-25 00:00:00
abstract::Myocardial thallium-201 scintigraphy is being increasingly employed as a method for assessing the efficacy of coronary reperfusion in acute myocardial infarction. New thallium uptake after intracoronary tracer administration after successful recanalization indicates that nutrient blood flow has been successfully resto...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(87)80062-1
更新日期:1987-03-01 00:00:00
abstract:OBJECTIVES:We tested the hypothesis that enalaprilat induces preconditioning (PC)-mimetic actions in patients with stable coronary artery disease. BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors increase the bioavailability of bradykinin, which induces cardiac PC. METHODS:Twenty-two patients undergoing coro...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2007.01.060
更新日期:2007-04-17 00:00:00