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https://www.readbyqxmd.com/read/28335032/allele-specific-ablation-rescues-electrophysiological-abnormalities-in-a-human-ips-cell-model-of-long-qt-syndrome-with-a-calm2-mutation
#1
Yuta Yamamoto, Takeru Makiyama, Takeshi Harita, Kenichi Sasaki, Yimin Wuriyanghai, Mamoru Hayano, Suguru Nishiuchi, Hirohiko Kohjitani, Sayako Hirose, Jiarong Chen, Fumika Yokoi, Taisuke Ishikawa, Seiko Ohno, Kazuhisa Chonabayashi, Hideki Motomura, Yoshinori Yoshida, Minoru Horie, Naomasa Makita, Takeshi Kimura
Background: Calmodulin is a ubiquitous Ca 2+ sensor molecule encoded by three distinct calmodulin genes, CALM1-3 . Recently, mutations in CALM1-3 have been reported to be associated with severe early-onset long-QT syndrome (LQTS). However, the underlying mechanism through which heterozygous calmodulin mutations lead to severe LQTS remains unknown, particularly in human cardiomyocytes. Objectives: We aimed to establish an LQTS disease model associated with a CALM2 mutation (LQT15) using human induced pluripotent stem cells (hiPSCs) and to assess mutant allele-specific ablation by genome editing for the treatment of LQT15...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28326207/dasatinib-and-prednisolone-induction-therapy-for-a-case-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-with-dilated-cardiomyopathy-accompanied-by-life-threatening-ventricular-tachycardia
#2
Mitsutaka Nishimoto, Hirohisa Nakamae, Kana Matsumoto, Kunihiko Morita, Yuki Koga, Dai Momose, Masayuki Hino
A 56-year-old man being treated for dilated cardiomyopathy presented with epigastralgia. He was diagnosed with ventricular tachycardia and Philadelphia chromosome-positive acute lymphoblastic leukemia. After treating incessant ventricular tachycardia, we commenced induction therapy for leukemia with dasatinib and prednisolone to minimize toxicity towards cardiomyocytes and the cardiac conduction system. Although dasatinib was temporarily withheld because of a recurrence of ventricular tachycardia, we rechallenged dasatinib while using bisoprolol and amiodarone and achieved a complete hematological response three weeks later...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28323171/acquired-long-qt-syndrome-in-hospitalized-patients
#3
Haixu Yu, Li Zhang, Jinqiu Liu, Ying Liu, Peter R Kowey, Yanli Zhang, Yue Chen, Yushan Wei, Lianjun Gao, Huihua Li, Jie Du, Yunlong Xia
BACKGROUND: Acquired long QT syndrome (ALQTS) has long been overlooked in clinical practice. Recent studies reported that severe ALQTS (QTc ≥500 ms) in hospitalized patients is associated with increased all-cause mortality. OBJECTIVE: We aimed to determine the role of ALQTS in the clinical outcomes of hospitalized patients. METHODS: Electronic medical records were reviewed to identify severe ALQTS in hospitalized patients in a single study center from 9-1-2013 to 2-28-2014...
March 16, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28323007/intrathecal-application-of-the-microglial-inhibitor-minocycline-attenuates-sympathoexcitatory-and-proarrhythmogenic-changes-in-rats-with-chronic-temporal-lobe-epilepsy
#4
Amol M Bhandare, Komal Kapoor, Kim L Powell, Emma Braine, Pablo Casillas-Espinosa, Terence J O'Brien, Melissa M J Farnham, Paul M Pilowsky
The incidence of sudden unexpected death in epilepsy (SUDEP) is highest in people with chronic and drug resistant epilepsy. Chronic spontaneous recurrent seizures cause cardiorespiratory autonomic dysfunctions. Pituitary adenylate cyclase-activating polypeptide (PACAP) is neuroprotective, whereas microglia produce both pro- and anti- inflammatory effects in the CNS. During acute seizures in rats, PACAP and microglia produce sympathoprotective effect at the intermediolateral cell column (IML), whereas their action on the presympathetic rostral ventrolateral medulla (RVLM) neurons mediates proarrhythmogenic changes...
March 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28316985/prolonged-p-wave-and-qt-dispersion-in-children-with-inflammatory-bowel-disease-in-remission
#5
Helen Aghdasi Bornaun, Nuh Yılmaz, Günsel Kutluk, Reyhan Dedeoğlu, Kazım Öztarhan, Gonca Keskindemirci, Aras Tulunoğlu, Fatih Şap
Objectives. Ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory bowel diseases (IBD) with unclear underlying aetiologies. Severe cardiac arrhythmias have been emphasised in a few studies on adult IBD patients. This study aimed to investigate the alteration of the P-wave and QT interval dispersion parameters to assess the risk of atrial conduction and ventricular repolarisation abnormalities in pediatric IBD patients. Patients and Methods. Thirty-six IBD patients in remission (UC: 20, CD: 16) aged 3-18 years and 36 age- and sex-matched control patients were enrolled in the study...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28316956/sudden-infant-death-syndrome-due-to-long-qt-syndrome-a-brief-review-of-the-genetic-substrate-and-prevalence
#6
REVIEW
Nikolaos S Ioakeimidis, Theodora Papamitsou, Soultana Meditskou, Zafiroula Iakovidou-Kritsi
The pathophysiological mechanisms which lead to sudden infant death syndrome (SIDS) are not completely understood. Cardiac channelopathies are a well-established causative factor with long QT syndrome (LQTS) being the most frequent one, accounting for approximately 12% of SIDS cases. The genetic substrate of the above arrhythmogenic syndrome has been thoroughly described but only specific gene mutations or polymorphisms have been identified as SIDS causative. The review will focus on the prevalence of LQTS-induced SIDS or near-SIDS cases and the mutations held responsible...
December 2017: Journal of Biological Research
https://www.readbyqxmd.com/read/28316033/cardiovascular-complications-of-targeted-therapies-for-chronic-myeloid-leukemia
#7
REVIEW
Rongras Damrongwatanasuk, Michael G Fradley
The development of tyrosine kinase inhibitors (TKIs) dramatically changed the treatment landscape for many different cancers including chronic myeloid leukemia (CML). With the introduction of imatinib, the first TKI developed and approved to effectively treat CML, patient survival has increased dramatically and, in some cases, this fatal cancer can be managed as a chronic disease. Since the approval of imatinib in 2002, four additional TKIs have been developed to treat this disease including the second-generation TKIs nilotinib, dasatinib, and bosutinib and the third-generation TKI ponatinib...
April 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28315637/trpm4-non-selective-cation-channel-variants-in-long-qt-syndrome
#8
Thomas Hof, Hui Liu, Laurent Sallé, Jean-Jacques Schott, Corinne Ducreux, Gilles Millat, Philippe Chevalier, Vincent Probst, Romain Guinamard, Patrice Bouvagnet
BACKGROUND: Long QT syndrome (LQTS) is an inherited arrhythmic disorder characterized by prolongation of the QT interval, a risk of syncope, and sudden death. There are already a number of causal genes in LQTS, but not all LQTS patients have an identified mutation, which suggests LQTS unknown genes. METHODS: A cohort of 178 LQTS patients, with no mutations in the 3 major LQTS genes (KCNQ1, KCNH2, and SCN5A), was screened for mutations in the transient potential melastatin 4 gene (TRPM4)...
March 18, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28315570/tp-e-interval-and-tp-e-qtc-ratio-as-novel-surrogate-markers-for-prediction-of-ventricular-arrhythmic-events-in-hypertrophic-cardiomyopathy
#9
Mehmet Kadri Akboğa, Kevser Gülcihan Balcı, Samet Yılmaz, Selahattin Aydın, Çağrı Yayla, Ahmet Göktuğ Ertem, Sefa Ünal, Mustafa Mücahit Balcı, Yücel Balbay, Dursun Aras, Serkan Topaloğlu
OBJECTIVE: Hypertrophic cardiomyopathy (HCM) as a common genetic heart disease characterized by ventricular hypertrophy and myocardial fibrosis is significantly associated with a higher risk of fatal ventricular arrhythmic events (VAEs). We aimed to assess the interval between the peak and the end of the electrocardiographic T wave (Tp-e) and Tp-e/corrected QT (QTc) ratio as candidate markers of ventricular arrhythmias in patients with HCM. METHODS: In this single-center, prospective study, a total of 66 patients with HCM and 88 controls were enrolled...
March 9, 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28299825/fingolimod-gilenya-%C3%A2-in-multiple-sclerosis-bradycardia-atrioventricular-blocks-and-mild-effect-on-the-qtc-interval-something-to-do-with-the-l-type-calcium-channel
#10
Sylvie Pilote, Chantale Simard, Benoit Drolet
Cardiac arrhythmias and ECG abnormalities including bradycardia, prolongation of the QT interval and atrioventricular (AV) conduction blocks have been extensively observed with fingolimod, the first marketed oral drug for treating the relapsing-remitting form of multiple sclerosis. The present study was aiming to further elucidate the effects of fingolimod on cardiac electrophysiology at three different levels; 1) in vitro, 2) ex vivo and 3) in vivo. 1) Patch-clamp experiments in whole cell configuration were performed on Cav 1...
March 16, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28297125/a-new-formula-for-estimating-the-true-qt-interval-in-left-bundle-branch-block
#11
Binhao Wang, L I Zhang, Peixin Cong, Huimin Chu, Ying Liu, Jinqiu Liu, William Surkis, Yunlong Xia
INTRODUCTION: QT prolongation is an independent risk factor for cardiac mortality. Left bundle branch block (LBBB) is more common in patients as they age. Widening of the QRS in LBBB causes false QT prolongation and thus makes true QT assessment difficult. We aimed to develop a simple formula to achieve a good estimate of the QT interval in the presence of LBBB. METHODS AND RESULTS: To determine the effect of QRS duration on the QT interval, QRS and QT were measured in sinus rhythm (SR) and during right ventricular apical pacing in 62 patients (age 55 ± 11 years, 60% male) undergoing electrophysiology studies...
March 15, 2017: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/28292795/primary-care-management-of-opioid-use-disorders-abstinence-methadone-or-buprenorphine-naloxone
#12
REVIEW
Anita Srivastava, Meldon Kahan, Maya Nader
OBJECTIVE: To advise physicians on which treatment options to recommend for specific patient populations: abstinence-based treatment, buprenorphine-naloxone maintenance, or methadone maintenance. SOURCES OF INFORMATION: PubMed was searched and literature was reviewed on the effectiveness, safety, and side effect profiles of abstinence-based treatment, buprenorphine-naloxone treatment, and methadone treatment. Both observational and interventional studies were included...
March 2017: Canadian Family Physician Médecin de Famille Canadien
https://www.readbyqxmd.com/read/28290796/-sudden-cardiac-death-in-patients-with-chronic-obstructive-pulmonary-disease
#13
N A Karoli, A P Rebrov
The article contains review of data on the problem of sudden cardiac death (SCD) in patients with chronic obstructive pulmonary disease (COPD). Large studies have shown that risk of cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD) is 2-3 times greater than in general population. The incidence of COPD and ischemic heart disease (IHD) progressively rises with age. Combination of these diseases is often observed in clinical practice among patients older than 40 years. According to the population study published in 2015 COPD has been associated with elevated risk of SCD especially in patients with frequent exacerbations within 5 years after diagnosis...
February 2017: Kardiologiia
https://www.readbyqxmd.com/read/28284166/the-effect-of-targeted-temperature-management-on-qt-and-corrected-qt-intervals-in-patients-with-cardiac-arrest
#14
Zachary Rosol, David F Miranda, Yader Sandoval, Bradley A Bart, Stephen W Smith, Steven R Goldsmith
BACKGROUND: Targeted Temperature Management (TTM) improves outcomes after cardiac arrest but may affect the QT and QTc intervals which could increase the chance of subsequent arrhythmia. We report here the effects of TTM on both computer-derived and manually calculated QT and QTc as well as the relationship of the length of the QTc and serious arrhythmia in a retrospective single-center experience. METHODS: 193 patients undergoing TTM for cardiac arrest were studied...
February 22, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28275963/adverse-drug-event-causality-analysis-adeca-a-process-for-evaluating-evidence-and-assigning-drugs-to-risk-categories-for-sudden-death
#15
Raymond L Woosley, Klaus Romero, Craig W Heise, Tyler Gallo, Jared Tate, Raymond David Woosley, Sophie Ward
Growing evidence indicates that many drugs have the ability to cause a potentially lethal cardiac arrhythmia, torsades de pointes (TdP). This necessitates the development of a compilation of drugs that have this potential toxicity. Such a list is helpful in identifying the etiology of TdP in patients taking multiple drugs and assists decision making by those caring for patients at high risk of TdP. The Arizona Center for Education and Research on Therapeutics (AZCERT) has developed a process to standardize the identification of drugs and place them in risk categories for their clinical ability to cause TdP and QT prolongation...
March 8, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28274542/hypokalemia-in-women-and-methadone-therapy-are-the-strongest-non-cardiologic-factors-associated-with-qt-prolongation-in-an-emergency-department-setting
#16
Keith A Marill, Emily S Miller
BACKGROUND: Our primary objective was to determine the adjusted quantitative associations of clinical predictors with QT prolongation, a defining cause of Torsades de Pointes (TdP). METHODS: A retrospective cohort study was performed on consecutive emergency department patients identified by ECG acquisition date, and heart rate corrected QT (QTc) and QRS durations. QTc was modeled as a function of clinical predictors with multiple linear regression. RESULTS: 1010 patients were included...
February 10, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28273109/recent-heart-rate-history-affects-qt-interval-duration-in-atrial-fibrillation
#17
Fady S Riad, Eathar Razak, Samir Saba, Alaa Shalaby, Jan Nemec
QT interval prolongation is associated with a risk of polymorphic ventricular tachycardia. QT interval shortens with increasing heart rate and correction for this effect is necessary for meaningful QT interval assessment. We aim to improve current methods of correcting the QT interval during atrial fibrillation (AF). Digitized Holter recordings were analyzed from patients with AF. Models of QT interval dependence on RR intervals were tested by sorting the beats into 20 bins based on corrected RR interval and assessing ST-T variability within the bins...
2017: PloS One
https://www.readbyqxmd.com/read/28271153/low-iron-stores-in-otherwise-healthy-children-affect-electrocardiographic-markers-of-important-cardiac-events
#18
Cem Karadeniz, Rahmi Özdemir, Mustafa Demirol, Nagehan Katipoğlu, Yılmaz Yozgat, Timur Meşe, Nurettin Ünal
Both an excess of iron and iron deficiency (ID) may lead to significant cardiac problems. Parameters that represent ventricular repolarization heterogeneity, like QT dispersion (QTd), corrected QT dispersion (QTcd), the interval between the peak and the end of the T wave (Tp-e), and Tp-e dispersion, have not been evaluated in otherwise healthy children with low iron levels before. Here we assessed the effects of low iron storage on P wave dispersion (PWd), QTd, Tp-e intervals, and Tp-e dispersion in otherwise healthy children...
March 7, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28264985/kcnq1-p-l353l-affects-splicing-and-modifies-the-phenotype-in-a-founder-population-with-long-qt-syndrome-type-1
#19
Jamie D Kapplinger, Anders Erickson, Sirisha Asuri, David J Tester, Sarah McIntosh, Charles R Kerr, Julie Morrison, Anthony Tang, Shubhayan Sanatani, Laura Arbour, Michael J Ackerman
BACKGROUND: Variable expressivity and incomplete penetrance between individuals with identical long QT syndrome (LQTS) causative mutations largely remain unexplained. Founder populations provide a unique opportunity to explore modifying genetic effects. We examined the role of a novel synonymous KCNQ1 p.L353L variant on the splicing of exon 8 and on heart rate corrected QT interval (QTc) in a population known to have a pathogenic LQTS type 1 (LQTS1) causative mutation, p.V205M, in KCNQ1-encoded Kv7...
March 6, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28249770/long-qt-syndrome-and-left-ventricular-noncompaction-in-4-family-members-across-2-generations-with-kcnq1-mutation
#20
Mira Kharbanda, Amanda Hunter, Stephen Tennant, David Moore, Stephanie Curtis, Jules C Hancox, Victoria Murday
The association of long QT syndrome and left ventricular noncompaction is uncommon, with only a handful of previous reports, and only one reported case in association with a mutation in KCNQ1. Here we present genetic and phenotypic data for 4 family members across 2 generations who all have evidence of prolonged QT interval and left ventricular noncompaction in association with a pathogenic mutation in KCNQ1, and discuss the potential mechanisms of this association. In conclusion, we suggest that it may be helpful to consider looking for mutations in KCNQ1 in similar patients...
February 27, 2017: European Journal of Medical Genetics
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