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https://www.readbyqxmd.com/read/29791480/complex-interactions-in-a-novel-scn5a-compound-mutation-associated-with-long-qt-and-brugada-syndrome-implications-for-na-channel-blocking-pharmacotherapy-for-de-novo-conduction-disease
#1
Jie Liu, Jason D Bayer, Roozbeh Aschar-Sobbi, Marianne Wauchop, Danna Spears, Michael Gollob, Edward J Vigmond, Robert Tsushima, Peter H Backx, Vijay S Chauhan
BACKGROUND: The SCN5A mutation, P1332L, is linked to a malignant form of congenital long QT syndrome, type 3 (LQT3), and affected patients are highly responsive to the Na+ channel blocking drug, mexiletine. In contrast, A647D is an atypical SCN5A mutation causing Brugada syndrome. An asymptomatic male with both P1332L and A647D presented with varying P wave/QRS aberrancy and mild QTc prolongation which did not shorten measurably with mexiletine. OBJECTIVE: We characterized the biophysical properties of P1332L, A647D and wild-type (WT) Na+ channels as well as their combinations in order to understand our proband's phenotype and to guide mexilitine therapy...
2018: PloS One
https://www.readbyqxmd.com/read/29759533/12-lead-electrocardiogram-to-localize-region-of-abnormal-electroanatomic-substrate-in-arrhythmogenic-right-ventricular-cardiomyopathy
#2
Cory M Tschabrunn, Haris M Haqqani, Pasquale Santangeli, Erica S Zado, Francis E Marchlinski
OBJECTIVES: The purpose of this study was to evaluate the relationship between electrocardiogram (ECG) QRS fragmentation (fQRS) and right ventricular (RV) endocardial (ENDO) and epicardial (EPI) electroanatomic substrate abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND: fQRS is frequently observed in patients with ARVC and reflects delayed conduction due to RV fibrosis. METHODS: A total of 30 consecutive patients met the task force criteria for ARVC (19 men, mean age 41...
July 2017: JACC. Clinical Electrophysiology
https://www.readbyqxmd.com/read/29748195/does-high-intensity-endurance-training-increase-the-risk-of-atrial-fibrillation-a-longitudinal-study-of-left-atrial-structure-and-function
#3
Mildred A Opondo, Norman Aiad, Matthew A Cain, Satyam Sarma, Erin Howden, Douglas A Stoller, Jason Ng, Pieter van Rijckevorsel, Michinari Hieda, Takashi Tarumi, M Dean Palmer, Benjamin D Levine
BACKGROUND: Exercise mitigates many cardiovascular risk factors associated with atrial fibrillation. Endurance training has been associated with atrial structural changes which can increase the risk for atrial fibrillation. The dose of exercise training required for these changes is uncertain. We sought to evaluate the impact of exercise on left atrial (LA) mechanical and electrical function in healthy, sedentary, middle-aged adults. METHODS: Sixty-one adults (52±5 years) were randomized to either 10 months of high-intensity exercise training or yoga...
May 2018: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29728952/myocardial-perfusion-reserve-and-global-longitudinal-strain-as-potential-markers-of-coronary-allograft-vasculopathy-in-late-stage-orthotopic-heart-transplantation
#4
Akhil Narang, John E Blair, Mita B Patel, Victor Mor-Avi, Savitri E Fedson, Nir Uriel, Roberto M Lang, Amit R Patel
Coronary allograft vasculopathy (CAV) is a major cause of mortality in late-stage orthotopic heart transplantation (OHT) patients. Recent evidence has shown that myocardial perfusion reserve (MPR) derived from vasodilator cardiovascular magnetic resonance imaging (vCMR) and global longitudinal strain (GLS) from transthoracic echocardiography (TTE) are useful to detect CAV. However, previous studies have not comprehensively addressed whether these parameters are confounded by allograft rejection, myocardial scar/fibrosis, or allograft dysfunction...
May 4, 2018: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/29716709/management-of-electrical-storm-of-unstable-ventricular-tachycardia-in-post-myocardial-infarction-patients-a-single-centre-experience
#5
B Hygriv Rao, Mohammed Sadiq Azam, Geetesh Manik
OBJECTIVE: This is a case series of consecutive patients with past myocardial infarction presenting with Electrical Storm (ES) of unstable ventricular tachycardia (VT) treated by a protocol directed algorithm. METHODS: Management protocol involved treatment of reversible causes, ventilatory & hemodynamic support, administration of antiarrhythmic drugs (AAD) & maximally tolerated doses of beta-blockers, stellate ganglionectomy and Radiofrequency ablation (RFA) guided by Electro Anatomic Mapping (EAM)...
March 2018: Indian Heart Journal
https://www.readbyqxmd.com/read/29683198/two-dimensional-speckle-tracking-echocardiographic-evaluation-of-the-longitudinal-deformation-of-the-left-ventricular-myocardium-in-patients-with-severe-coronary-artery-tortuosity
#6
Mohsen Khosravani-Rudpishi, Niloofar Akhavan-Khaleghi, Ali Hosseinsabet
PURPOSE: Coronary artery tortuosity (CAT) is an anatomical condition in which epicardial coronary arteries have abnormal curves or spiral courses. Although correlated with higher rates of positive stress test, its effects on the myocardial function remain to be clearly defined. METHODS: We included in this cross-sectional study and evaluated with 2D speckle-tracking echocardiography 40 consecutive patients admitted to our hospital for selective coronary angiography which showed severe CAT without significant epicardial coronary artery stenosis, and 40 consecutive subjects matched for age, hypertension, and diabetes in whom selective coronary angiography showed neither CAT nor significant epicardial coronary artery stenosis...
April 23, 2018: Journal of Clinical Ultrasound: JCU
https://www.readbyqxmd.com/read/29672845/drug-induced-proarrhythmia-and-torsade-de-pointes-a-primer-for-students-and-practitioners-of-medicine-and-pharmacy
#7
REVIEW
J Rick Turner, Ignacio Rodriguez, Emily Mantovani, Gary Gintant, Peter R Kowey, Ralph J Klotzbaugh, Krishna Prasad, Philip T Sager, Norman Stockbridge, Colette Strnadova
Multiple marketing withdrawals due to proarrhythmic concerns occurred in the United States, Canada, and the United Kingdom in the late 1980s to early 2000s. This primer reviews the clinical implications of a drug's identified proarrhythmic liability, the issues associated with these safety-related withdrawals, and the actions taken by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and by regulatory agencies in terms of changing drug development practices and introducing new nonclinical and clinical tests to asses proarrhythmic liability...
April 19, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29644942/postnatal-undernutrition-in-mice-causes-cardiac-arrhythmogenesis-which-is-exacerbated-when-pharmacologically-stressed
#8
J R Visker, D P Ferguson
Growth restriction caused by postnatal undernutrition increases risk for cardiovascular disease in adulthood with the potential to induce arrhythmogenesis. Thus, the purpose was to determine if undernutrition during development produced arrhythmias at rest and when stressed with dobutamine in adulthood. Mouse dams were fed (CON: 20% protein), or low-protein (LP: 8%) diet before mating. A cross-fostering model was used where pups nursed by dams fed LP diet in early [EUN; postnatal day (PN) 1-10], late (LUN; PN11-21) and whole (PUN; 1-21) phases of postnatal life...
April 12, 2018: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/29604289/effect-of-spironolactone-on-myocardial-fibrosis-and-other-clinical-variables-in-patients-with-hypertrophic-cardiomyopathy-a-prospective-randomized-trial
#9
Martin S Maron, Raymond H Chan, Navin Kapur, Iris J Jaffe, Adam P McGraw, Raj Kerur, Barry J Maron, James E Udelson
BACKGROUND: Myocardial fibrosis has proved to be an important marker and determinant in the pathogenesis of hypertrophic cardiomyopathy . In particular, scar formation, if substantial, can promote ventricular tachyarrhythmias or progressive heart failure in the absence ofleft ventricular outflow obstruction. Therefore, an intervention to mitigate myocardial fibrosis would be potentially advantageous to hypertrophic cardiomyopathy patients. METHODS: Eligible hypertrophic cardiomyopathy patients were randomized 1:1 in a prospective double-blind fashion to spironolactone 50 mg or placebo to be taken over a 12-month period...
March 28, 2018: American Journal of Medicine
https://www.readbyqxmd.com/read/29593564/dynamic-action-potential-restitution-contributes-to-mechanical-restitution-in-right-ventricular-myocytes-from-pulmonary-hypertensive-rats
#10
Matthew E L Hardy, Eleftheria Pervolaraki, Olivier Bernus, Ed White
We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29582428/selective-late-sodium-current-inhibitor-gs-458967-suppresses-torsades-de-pointes-by-mostly-affecting-perpetuation-but-not-initiation-of-the-arrhythmia
#11
Alexandre Bossu, Marien J C Houtman, Veronique M F Meijborg, Rosanne Varkevisser, Henriette D M Beekman, Albert Dunnink, Jacques M T de Bakker, Nevena Mollova, Sridharan Rajamani, Luiz Belardinelli, Marcel A G van der Heyden, Marc A Vos
BACKGROUND AND PURPOSE: Enhanced late sodium current (late INa ) in heart failure and long QT syndrome type 3 is proarrhythmic. GS-458967 (GS967) is a selective and potent late INa inhibitor. This study aimed to evaluate the antiarrhythmic effect of late INa inhibition by GS967 in the chronic atrioventricular block (CAVB) dog model sensitive to Torsade de Pointes arrhythmias (TdP) and to elucidate its electrophysiological mode of action in vivo and in vitro. METHODS - RESULTS: GS967 (IC50 for late INa ~ 200 nM) markedly shortened action potential duration of canine ventricular cardiomyocytes and repolarization parameters in vivo in sinus rhythm (SR, n=10) dogs, in a concentration-dependent manner...
March 27, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29581187/rbm4-modulates-radial-migration-via-alternative-splicing-of-dab1-during-cortex-development
#12
Dhananjaya D, Kuan-Yang Hung, Woan-Yuh Tarn
The RNA-binding motif 4 (RBM4) protein participates in cell differentiation via its role in regulating the expression of or tissue-specific or developmentally regulated mRNA splice isoforms. RBM4 is expressed in embryonic brain during development; it is initially enriched in the ventricular zone/subventricular zone and subsequently distributed throughout the cortical cortex. Rbm4a knockout brain exhibited delayed migration of late-born neurons. Using in utero electroporation, we confirmed that knockdown of RBM4 impaired cortical neuronal migration...
March 26, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29579779/late-sodium-current-inhibitors-to-treat-exercise-induced-obstruction-in-hypertrophic-cardiomyopathy-an-in-vitro-study-in-human-myocardium
#13
Cecilia Ferrantini, Josè Manuel Pioner, Luca Mazzoni, Francesca Gentile, Benedetta Tosi, Alessandra Rossi, Luiz Belardinelli, Chiara Tesi, Chiara Palandri, Rosanna Matucci, Elisabetta Cerbai, Iacopo Olivotto, Corrado Poggesi, Alessandro Mugelli, Raffaele Coppini
BACKGROUND AND PURPOSE: In 30-40% of hypertrophic cardiomyopathy (HCM) patients, symptomatic left-ventricular (LV) outflow gradients develop only during exercise due to catecholamine-induced LV-hypercontractility (inducible obstruction). Negative-inotropic pharmacological options are limited to β-blockers or disopyramide, with scarce efficacy and tolerability. We assessed the potential use of late Na+ -current (INaL )-inhibitors to treat inducible obstruction in HCM. EXPERIMENTAL APPROACH: The electrophysiological and mechanical responses to β-adrenergic stimulation were studied in human myocardium from HCM versus control patients...
March 26, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29576422/late-characterisation-of-cardiac-effects-following-anthracycline-and-trastuzumab-treatment-in-breast-cancer-patients
#14
Ashlee Kimball, Sanjana Patil, Bogda Koczwara, Karthigesh Sree Raman, Rebecca Perry, Suchi Grover, Joseph Selvanayagam
BACKGROUND: Anthracycline (A) and trastuzumab (T) chemotherapy have well-recognized cardiac toxicity, potentially leading to significant morbidity and mortality. Our previous work in 46 prospectively enrolled breast cancer patients showed early left ventricular (LV) and right ventricular (RV) function decline at 1 and 3 months, but only persistent RV dysfunction at 12 months which correlated with myocardial oedema observed early (1 and 3 months) after administration of chemotherapy regimes...
March 8, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29572643/novel-mapping-strategies-for-ventricular-tachycardia-ablation
#15
REVIEW
Zaid Aziz, Roderick Tung
Despite advances in antiarrhythmic and device therapy, ventricular tachycardia (VT) continues to be a major cause of increased morbidity and mortality. During scar-mediated monomorphic ventricular tachycardia ablation, the search for critical isthmus sites continues to be the primary goal during successful ablative procedures. However, given the overwhelming hemodynamic instability of most ventricular arrhythmias (> 70%), VT ablation is increasingly performed during sinus rhythm. This technique requires either a greater reliance on isthmus surrogates, or more extensive ablation techniques and is a more probabilistic approach to substrate modification...
March 23, 2018: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29550324/native-t1-and-extracellular-volume-in-transthyretin-amyloidosis
#16
Ana Martinez-Naharro, Tushar Kotecha, Karl Norrington, Michele Boldrini, Tamer Rezk, Candida Quarta, Thomas A Treibel, Carol J Whelan, Daniel S Knight, Peter Kellman, Frederick L Ruberg, Julian D Gillmore, James C Moon, Philip N Hawkins, Marianna Fontana
OBJECTIVES: This study evaluated the prognostic potential of native myocardial T1 in cardiac transthyretin amyloidosis (ATTR) and compared native T1 with extracellular volume (ECV) in terms of diagnostic accuracy and prognosis. BACKGROUND: ATTR is an increasingly recognized cause of heart failure that has an overlapping clinical phenotype with hypertrophic cardiomyopathy (HCM). Native T1 mapping by cardiac magnetic resonance (CMR) is useful for diagnosis in cardiac amyloidosis but its prognostic potential has never been assessed...
March 12, 2018: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/29545480/ion-channel-dysfunctions-in-dilated-cardiomyopathy-in-limb-girdle-muscular-dystrophy
#17
Ibrahim El-Battrawy, Zhihan Zhao, Huan Lan, Xin Li, Gökhan Yücel, Siegfried Lang, Katherine Sattler, Jan-Dierk Schünemann, Wolfram-Hubertus Zimmermann, Lukas Cyganek, Jochen Utikal, Thomas Wieland, Karen Bieback, Ralf Bauer, Antonius Ratte, Regina Pribe-Wolferts, Kleopatra Rapti, Daniel Nowak, Janina Wittig, Dierk Thomas, Patrick Most, Hugo A Katus, Ursula Ravens, Constanze Schmidt, Martin Borggrefe, Xiao-Bo Zhou, Oliver J Müller, Ibrahim Akin
BACKGROUND: Limb-Girdle muscular dystrophies (LGMD) are a heritable group of genetically determined disorders with a primary involvement of the pelvic or shoulder girdle musculature with partially cardiac manifestation, such as dilated cardiomyopathy (DCM) and life-threatening tachyarrhythmia. We report here that human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes from a patient with LGMD2I and DCM associated with recurrent ventricular tachycardia displayed ion channel dysfunction and abnormality of calcium homeostasis...
March 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29543365/late-potentials-abolition-reduces-ventricular-tachycardia-recurrence-after-ablation-especially-in-higher-risk-patients-with-a-chronic-total-occlusion-in-an-infarct-related-artery
#18
Andrea Di Marco, Teresa Oloriz Sanjuan, Gabriele Paglino, Francesca Baratto, Pasquale Vergara, Caterina Bisceglia, Nicola Trevisi, Simone Sala, Alessandra Marzi, Simone Gulletta, Manuela Cireddu, Ignasi Anguera, Paolo Della Bella
INTRODUCTION: Late potentials (LP) abolition is recognized as an effective strategy for substrate ablation of ventricular tachycardia (VT). The presence of a chronic total occlusion in a coronary artery responsible for a previous myocardial infarction (infarct related artery CTO, IRA-CTO) is emerging as a predictor of ventricular arrhythmias and VT recurrence after ablation. We sought to analyze the effects of LP abolition, focusing on the high-risk subgroup of patients with IRA-CTO. METHODS AND RESULTS: This was a single-center, observational study that screened all patients with prior myocardial infarction and clinical VT, referred for VT ablation at San Raffaele Hospital between 2010 and June 2013...
March 15, 2018: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/29541612/echocardiographic-assessment-of-right-ventricular-systolic-function
#19
REVIEW
Victor Chien-Chia Wu, Masaaki Takeuchi
Assessment of right chamber function has become increasingly popular and important in recent decades, complementing the evaluation of left chamber functional parameters. The late adoption and integration of right ventricular (RV) function into a complete evaluation of cardiac function could be due in part to the difficulty in visualization of the whole right ventricle, inconsistency in the analysis of RV parameters, and poor understanding of the impact of RV function on prognosis. From M-mode to 2-dimensional (2D) measurements of RV size and function, there have been arrays of parameters that provide important information of the right ventricle...
February 2018: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/29540431/device-complications-with-addition-of-defibrillation-to-cardiac-resynchronisation-therapy-for-primary-prevention
#20
Sérgio Barra, Rui Providência, Serge Boveda, Rudolf Duehmke, Kumar Narayanan, Anthony W Chow, Olivier Piot, Didier Klug, Pascal Defaye, Daniel Gras, Jean-Claude Deharo, Paul Milliez, Antoine Da Costa, Pierre Mondoly, Jorge Gonzalez-Panizo, Christophe Leclercq, Patrick Heck, Munmohan Virdee, Nicolas Sadoul, Jean-Yves Le Heuzey, Eloi Marijon
OBJECTIVE: In patients indicated for cardiac resynchronisation therapy (CRT), the choice between a CRT-pacemaker (CRT-P) versus defibrillator (CRT-D) remains controversial and indications in this setting have not been well delineated. Apart from inappropriate therapies, which are inherent to the presence of a defibrillator, whether adding defibrillator to CRT in the primary prevention setting impacts risk of other acute and late device-related complications has not been well studied and may bear relevance for device selection...
March 14, 2018: Heart: Official Journal of the British Cardiac Society
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