scholarly journals Beneficial electrophysiologic effects of sacubitril in different arrhythmia syndromes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Frommeyer ◽  
D Dimanski ◽  
C Ellermann ◽  
J Wolfes ◽  
L Eckardt
Keyword(s):  
Long Qt Syndrome ◽  
Cardiac Electrophysiology ◽  
Torsade De Pointes ◽  
Additional Treatment ◽  
Long Qt ◽  
Beneficial Effects ◽  
Dispersion Of Repolarization ◽  
Qt Syndrome ◽  
The Impact ◽  
Antiarrhythmic Effects

Abstract Background Previous studies report conflicting data regarding anti- or proarrhythmic effects of sacubitril. The aim of the presents study was to assess the impact of sacubitril in different arrhythmia models. Methods and results In 12 isolated rabbit hearts, sacubitril was infused in rising concentrations (3, 5, 10μM) after obtaining baseline data. In 12 further hearts, erythromycin was administered to simulate long QT syndrome-2 (LQT2). Other 12 hearts were perfused with veratridine to mimic long QT syndrome-3 (LQT3). Both LQT groups were treated with sacubitril (5μM). Ventricular vulnerability was assessed by a pacing protocol. AV-blocked bradycardic hearts were perfused with a hypokalemic solution to trigger torsade de pointes (TdP). In further 13 hearts, AF was induced by a combination of acetylcholine and isoproterenol (ACH/ISO) and sacubitril (5μM) was added afterwards. With sacubitril, action potential duration (APD) was abbreviated whereas spatial dispersion of repolarization (SDR) remained stable. In both LQT groups, APD and SDR were increased. Infusion of sacubitril reduced APD and SDR in the LQT2-group (APD: −21 ms, p<0.05; SDR: −8 ms, p=ns) and did not alter APD but reduced SDR in the LQT3-group (APD: +2 ms, p=ns; SDR: −9 ms, p<0.05). Ventricular vulnerability was not altered by sacubitril. No TdP were observed with sacubitril treatment or under baseline conditions in any group. Erythromycin provoked 43 episodes of TdP (p<0.05). Additional treatment with sacubitril significantly suppressed TdP (3 episodes, p<0.05). With veratridine, 16 episodes of TdP (p=0.07) occurred. Further treatment with sacubitril did not reduce TdP (10 episodes, p=ns) significantly. Infusion of ACH/ISO led to an increased inducibility of atrial fibrillation (31 vs. 7 episodes). Additional infusion of sacubitril increased atrial ERP (+21ms, p<0.05) and reduced inducibility of AF (9 episodes). Conclusion Sacubitril abbreviated APD and was not proarrhythmic. SDR is a major pathomechanism of TdP and was reduced by sacubitril in both LQT groups. Thereby, sacubitril exhibits antiarrhythmic effects in LQT2 and may be beneficial in LQT3. Furthermore, sacubitril suppressed AF by prolonging aERP. Our results indicate beneficial effects of sacubitril on cardiac electrophysiology. Funding Acknowledgement Type of funding source: None

Long QT syndrome masquerading as epilepsy

2018 ◽  
Vol 19 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Clare M Galtrey ◽  
Viva Levee ◽  
Jan Arevalo ◽  
Damian Wren
Keyword(s):  
Early Diagnosis ◽  
Long Qt Syndrome ◽  
Refractory Epilepsy ◽  
Near Miss ◽  
Long Qt ◽  
Her Family ◽  
Fatal Arrhythmia ◽  
Qt Syndrome ◽  
The Impact ◽  
Treatable Condition

The diagnosis of epilepsy is incorrect in up to 20% of cases so should be revisited if attacks are not responding to treatment. We present a case of long QT syndrome that remained undiagnosed in the epilepsy clinic for 15 years until a near-fatal arrhythmia revealed the diagnosis and allowed effective treatment of her attacks. We hope this near miss raises awareness of long QT syndrome as a potentially fatal, rare but treatable condition that neurologists must consider in people with a label of refractory epilepsy. We provide practical pointers to increase the chance of early diagnosis and explore the impact of a late diagnosis for the patient and her family.

Pro- and antiarrhythmic effects of fast cardiac pacing in a canine model of acquired long QT syndrome

2004 ◽  
Vol 369 (4) ◽  
pp. 447-454 ◽  
Author(s):  
Alexander Bauer ◽  
J. Kevin Donahue ◽  
Frederik Voss ◽  
Ruediger Becker ◽  
Patricia Kraft ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Cardiac Pacing ◽  
Canine Model ◽  
Long Qt ◽  
Acquired Long Qt Syndrome ◽  
Qt Syndrome ◽  
Antiarrhythmic Effects

Antiarrhythmic Effects of Ranolazine in a Guinea Pig in Vitro Model of Long-QT Syndrome

2004 ◽  
Vol 310 (2) ◽  
pp. 599-605 ◽  
Author(s):  
Lin Wu ◽  
John C. Shryock ◽  
Yejia Song ◽  
Yuan Li ◽  
Charles Antzelevitch ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Long Qt Syndrome ◽  
In Vitro Model ◽  
Long Qt ◽  
Qt Syndrome ◽  
Vitro Model ◽  
Antiarrhythmic Effects

Acquired long QT syndrome and torsade de pointes

2018 ◽  
Vol 41 (4) ◽  
pp. 414-421 ◽  
Author(s):  
Nabil El-Sherif ◽  
Gioia Turitto ◽  
Mohamed Boutjdir
Keyword(s):  
Long Qt Syndrome ◽  
Torsade De Pointes ◽  
Long Qt ◽  
Acquired Long Qt Syndrome ◽  
Qt Syndrome

scholarly journals Complex and Novel Arrhythmias Precede Stillbirth in Fetuses With De Novo Long QT Syndrome

2020 ◽  
Vol 13 (5) ◽  
Author(s):  
Sarah Strand ◽  
Janette F. Strasburger ◽  
Bettina F. Cuneo ◽  
Ronald T. Wakai
Keyword(s):  
Atrioventricular Block ◽  
Long Qt Syndrome ◽  
De Novo ◽  
Perinatal Death ◽  
Torsade De Pointes ◽  
Fetal Loss ◽  
Long Qt ◽  
Premature Ventricular Contractions ◽  
Fetal Magnetocardiography ◽  
Qt Syndrome

Background: Long QT syndrome (LQTS) is a leading cause of sudden cardiac death in early life and has been implicated in ≈10% of sudden infant deaths and unexplained stillbirths. The purpose of our study was to use fetal magnetocardiography to characterize the electrophysiology and rhythm phenotypes of fetuses with de novo and inherited LQTS variants and identify risk factors for sudden death before birth. Methods: We reviewed the fetal magnetocardiography database from the University of Wisconsin Biomagnetism Laboratory for fetuses with confirmed LQTS. We assessed waveform intervals, heart rate, and rhythm, including the signature LQTS rhythms: functional 2° atrioventricular block, T-wave alternans, and torsade de pointes (TdP). Results: Thirty-nine fetuses had pathogenic variants in LQTS genes: 27 carried the family variant, 11 had de novo variants, and 1 was indeterminate. De novo variants, especially de novo SCN5A variants, were strongly associated with a severe rhythm phenotype and perinatal death: 9 (82%) showed signature LQTS rhythms, 6 (55%) showed TdP, 5 (45%) were stillborn, and 1 (9%) died in infancy. Those that died exhibited novel fetal rhythms, including atrioventricular block with 3:1 conduction ratio, QRS alternans in 2:1 atrioventricular block, long-cycle length TdP, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with TdP and perinatal death. Fetuses with familial variants showed a lower incidence of signature LQTS rhythm (6/27=22%), including TdP (3/27=11%). All were live born. Conclusions: The malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth. Their ability to manifest rhythms not known to be associated with LQTS increases the difficulty of echocardiographic diagnosis and decreases the likelihood that a resultant fetal loss is attributed to LQTS. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT03047161.

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