Echocardiography-Guided Risk Stratification for Long QT Syndrome.

Published on Dec 15, 2020in Journal of the American College of Cardiology20.589
· DOI :10.1016/J.JACC.2020.10.024
Alan Sugrue12
Estimated H-index: 12
(Mayo Clinic),
Martin van Zyl4
Estimated H-index: 4
(Mayo Clinic)
+ 6 AuthorsMichael J. Ackerman144
Estimated H-index: 144
(Mayo Clinic)
Abstract Background The ability to identify those patients at the highest phenotypic risk for long QT syndrome (LQTS)–associated life-threatening cardiac events remains suboptimal. Objectives This study sought to validate the association between electromechanical window (EMW) negativity, as derived from echocardiography, and symptomatic versus asymptomatic status in patients with LQTS. Methods We analyzed a cohort of 651 patients with LQTS (age 26 ± 17 years; 60% females; 158 symptomatic; 51% LQTS type 1; 33% LQTS type 2; 11% LQTS type 3; 5% multiple mutations) and 50 healthy controls. EMW was calculated as the difference between the interval from QRS onset to aortic valve closure midline, as derived for continuous-wave Doppler, and the electrocardiogram-derived QT interval for the same beat. Results A negative EMW was found among nearly all patients with LQTS compared to controls, with more profound EMW negativity in patients with symptomatic LQTS compared to those with asymptomatic LQTS (−52 ± 38 ms vs. −18 ± 29 ms; p  Conclusions In this validation study, patients with a history of LQTS-associated life-threatening cardiac events had a more profoundly negative EMW. EMW outperformed heart rate–corrected QT interval as a predictor of symptomatic status. EMW is now a clinically validated risk factor. In December 2019, our institution’s echocardiography clinical practice committee approved use of EMW for patients with LQTS, making it a routinely reported echocardiographic finding.
#1Pyotr G. Platonov (URMC: University of Rochester Medical Center)H-Index: 32
#2Scott McNitt (URMC: University of Rochester Medical Center)H-Index: 69
Last. Wojciech Zareba (URMC: University of Rochester Medical Center)H-Index: 112
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Background: Long-QT (LQT) syndrome mutation carriers have higher risk of cardiac events than unaffected family members even in the absence of QTc prolongation. Changes in T-wave morphology may refl...
9 CitationsSource
#1Andrea Mazzanti (UNIPV: University of Pavia)H-Index: 20
#1Andrea Mazzanti (UNIPV: University of Pavia)H-Index: 18
Last. Silvia G. PrioriH-Index: 150
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Abstract Background Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1 , KCNH2 , and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs). Objectives This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS. Methods Data f...
60 CitationsSource
#1Ram K. Rohatgi (Mayo Clinic)H-Index: 8
#2Alan Sugrue (Mayo Clinic)H-Index: 12
Last. Michael J. AckermanH-Index: 144
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Abstract Background Long QT syndrome (LQTS) is a potentially lethal cardiac channelopathy with a 1% to 5% annual risk of LQTS-triggered syncope, aborted cardiac arrest, or sudden cardiac death. Objectives This study sought to evaluate LQTS outcomes from a single center in the contemporary era. Methods The authors conducted a retrospective study comprising the 606 patients with LQTS (LQT1 in 47%, LQT2 in 34%, and LQT3 in 9%) who were evaluated in Mayo Clinic’s Genetic Heart Rhythm Clinic from Jan...
39 CitationsSource
#1Andrew P. Landstrom (BCM: Baylor College of Medicine)H-Index: 23
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There has been a significant progress in our understanding of the molecular mechanisms by which calcium (Ca 2+ ) ions mediate various types of cardiac arrhythmias. A growing list of inherited gene defects can cause potentially lethal cardiac arrhythmia syndromes, including catecholaminergic polymorphic ventricular tachycardia, congenital long QT syndrome, and hypertrophic cardiomyopathy. In addition, acquired deficits of multiple Ca 2+ -handling proteins can contribute to the pathogenesis of arr...
171 CitationsSource
#1Andrew E. Schneider (Mayo Clinic)H-Index: 4
#2J. Martijn Bos (Mayo Clinic)H-Index: 32
Last. Michael J. Ackerman (Mayo Clinic)H-Index: 144
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Background Left cardiac sympathetic denervation (LCSD) exerts significant antifibrillatory effects in patients with long QT syndrome (LQTS). Recently, electromechanical window (EMW) has emerged as a novel torsadogenic marker in LQTS, superior to QT interval (QTc) in distinguishing symptomatic from asymptomatic patients. Objective To explore the hypothesis that LCSD improves EMW most favorably in patients with LQT1. Design From September 2006 to July 2015, 44 LQT1 and 25 LQT2 patients underwent L...
6 CitationsSource
#1Rémi PeyronnetH-Index: 17
#2Jeanne M. NerbonneH-Index: 76
Last. Peter KohlH-Index: 63
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Mechanical forces will have been omnipresent since the origin of life, and living organisms have evolved mechanisms to sense, interpret, and respond to mechanical stimuli. The cardiovascular system in general, and the heart in particular, is exposed to constantly changing mechanical signals, including stretch, compression, bending, and shear. The heart adjusts its performance to the mechanical environment, modifying electrical, mechanical, metabolic, and structural properties over a range of tim...
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#1Ehud Chorin (Tel Aviv Sourasky Medical Center)H-Index: 16
#2Ofer Havakuk (Tel Aviv Sourasky Medical Center)H-Index: 16
Last. Raphael Rosso (Tel Aviv Sourasky Medical Center)H-Index: 28
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Background Specific T-wave patterns on the resting electrocardiogram (ECG) aid in diagnosing long QT syndrome (LQTS) and identifying the specific genotype. However, provocation tests often are required to establish a diagnosis when the QT interval is borderline at rest. Objective The purpose of this study was to determine whether T-wave morphology changes provoked by standing aid in the diagnosis of LQTS and determination of the genotype. Methods The quick-standing test was performed by 100 LQTS...
24 CitationsSource
#1Rachel M.A. ter Bekke (Maastricht University Medical Centre)H-Index: 8
#2Kristina H. Haugaa (University of Oslo)H-Index: 45
Last. Paul G.A. Volders (Maastricht University Medical Centre)H-Index: 40
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Aim Prolonged and dispersed left-ventricular (LV) contraction is present in patients with long-QT syndrome (LQTS). Electrical and mechanical abnormalities appear most pronounced in symptomatic individuals. We focus on the ‘electromechanical window’ (EMW; duration of LV-mechanical systole minus QT interval) in patients with genotyped LQTS. Profound EMW negativity heralds torsades de pointes in animal models of drug-induced LQTS. Methods and results We included 244 LQTS patients from three centres...
38 CitationsSource
#1Rachel M.A. ter Bekke (Maastricht University Medical Centre)H-Index: 8
#2Paul G.A. Volders (Maastricht University Medical Centre)H-Index: 40
Abstract Since the first linkage of the long-QT syndrome to the Harvey ras -1 gene in 1991 ample research has been performed to decipher the molecular-biophysical basis of congenital repolarization defects and the electrophysiological mechanisms of torsades-de-pointes arrhythmias in this condition. Mechanistic knowledge is mostly derived from cellular experiments (cardiac myocytes, cultured cells), ventricular tissue (including arterially-perfused wedge) preparations and Langendorff-perfused hea...
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#1P-J Guns (Safety Pharmacology Society)H-Index: 3
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Abstract Introduction Assessment of the propensity of novel drugs to cause proarrhythmia is essential in the drug development process. It is increasingly recognized, however, that QT prolongation alone is an imperfect surrogate marker for Torsades de Pointes (TdP) arrhythmia prediction. In the present study we investigated the behavior of a novel surrogate marker for TdP, the electro-mechanical (E-M) window, prior to triggering of TdP episodes with sympathetic stimulation after administration of...
22 CitationsSource
Cited By3
#1Ioannis Mastoris (KU: University of Kansas)H-Index: 8
#2Andrew J. SauerH-Index: 12
#1John E. Madias (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 28
Each week, I record audio summaries for every paper in JACC, as well as an issue summary. Although this process is quite time-consuming, I have become familiar with every paper that we publish. Thus, I have personally selected the top 100 papers (both Original Investigations and Review Articles) from the distinct specialties each year. In addition to my personal choices, I have included papers that have been the most accessed or downloaded on our websites, as well as those selected by the JACC E...