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Clin Res Cardiol 2019 Mar 16. Epub 2019 Mar 16.

First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Background: Short QT syndrome (SQTS) is associated with sudden cardiac death and implantable cardioverter-defibrillator (ICD) implantation is recommended in this rare disease. However, only a few SQTS families have been reported in literature with limited follow-up data.

Objectives: In the recent study, we describe the outcome data of 57 SQTS patients receiving ICD implantation. Read More

Stem Cell Res 2019 Mar 6;36:101416. Epub 2019 Mar 6.

Coronary Care Unit and Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Department of Molecular Medicine, Unit of Cardiology, Università degli studi di Pavia, Pavia, Italy.; Department of Medicine, University of Cape Town, Cape Town, South Africa. Electronic address:

We generated human induced pluripotent stem cells (hiPSCs) from a symptomatic Long QT Syndrome (LQTS) type 1 patient, belonging to a South African (SA) founder population segregating the heterozygous mutation c.1022C > T p.A341V on the KCNQ1 gene. Read More

Turk J Med Sci 2019 Mar 14;49(2). Epub 2019 Mar 14.

Background/aim: The KCNQ1 gene has a significant role in long QT syndrome, Jervell and Lange-Nielsen syndrome, familial atrial fibrillation, and short QT syndrome. Analyzing such heterogeneous disorders, six novel short tandem repeat (STR) markers around the KCNQ1 gene were found and evaluated in a healthy population, and other statistical traits of the markers were detected.

Materials And Methods: Using Tandem Repeats Finder (TRF) and Sequence-Based Estimation of Repeat Variability (SERV) software, STR markers were detected with valid tetra- and pentanucleotide repeats. Read More

Med Clin (Barc) 2019 Mar 5. Epub 2019 Mar 5.

Servicio de Pediatría, Hospital Universitario Río Hortega, Valladolid, España.

J Am Med Inform Assoc 2019 Mar 8. Epub 2019 Mar 8.

University of Manchester, School of Computer Science, Manchester, UK.

Objective: The study sought to quantify a layperson's ability to detect drug-induced QT interval prolongation on an electrocardiogram (ECG) and determine whether the presentation of the trace affects such detection.

Materials And Methods: Thirty layperson participants took part in a psychophysical and eye-tracking experiment. Following training, participants completed 21 experimental trials, in which each trial consisted of 2 ECGs (a baseline and a comparison stimulus, both with a heart rate of 60 beats/min). Read More

Circ J 2019 Mar 6. Epub 2019 Mar 6.

Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center.

J R Coll Physicians Edinb 2019 Mar;49(1):26-30

Queen Elizabeth University Hospital, Glasgow, UK.

Diagnosis of inherited arrhythmia syndromes, including long-QT syndrome (LQTS), is challenging; however, early detection and initiation of therapies can reduce otherwise high rates of mortality. Two months following the birth of her first child a previously well 21-year-old female experienced four episodes of transient loss of consciousness (TLOC). The history was atypical for seizures but a video electroencephalogram (EEG) captured an episode with abnormal bifrontal epileptic discharge. Read More

Cureus 2018 Dec 18;10(12):e3751. Epub 2018 Dec 18.

Cardiology, Aga Khan University Hospital, Karachi, PAK.

Fainting is a common clinical presentation, with vagally mediated (neurocardiogenic) causes being the most common for syncope presentation to the emergency room, and for hospital admissions. Classic teaching is that upright posture is a prerequisite for vagally mediated syncope (VMS) and that syncope in the supine position has more sinister causes. We present five patients, three males and two females, with a mean age of 44. Read More

Indian Pacing Electrophysiol J 2019 Feb 25. Epub 2019 Feb 25.

Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA.

This article reviews important features for improving the diagnosis and management of fetal arrhythmias. The normal fetal heart rate ranges between 110 and 160 beats per minute. A fetal heart rate is considered abnormal if the heart rate is beyond the normal ranges or the rhythm is irregular. Read More

Mol Pharm 2019 Feb 26. Epub 2019 Feb 26.

The hERG potassium channel (IKr) encoded by human ether-a-go-go-related gene plays an important role in cardiac repolarization. Decreased IKr may lead to long QT syndrome, which subsequently causes torsade de pointes and sudden cardiac death. Previous studies have shown that statins inhibit IKr and are more potent in inhibiting hERG currents when combined with other drugs. Read More

Iran Biomed J 2019 Feb 24. Epub 2019 Feb 24.

Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Background: Long QT syndrome (LQTS) is characterized by the prolongation of QT interval, which results in syncope and sudden cardiac death in young people. KCNQ1 is the most common gene responsible for this syndrome.

Methods: Molecular investigation was performed by DNA Sanger sequencing in Iranian families with a history of syncope. Read More

Clin Ther 2019 Feb 18. Epub 2019 Feb 18.

Pfizer Inc, New York, NY, USA.

Purpose: In addition to biomarker status, treatment selection for metastatic breast cancer (mBC) includes individual patient and clinical characteristics such as tumor burden, timing of disease recurrence, and comorbidities. Women with mBC may take medications that can increase the risk of drug-induced toxicities, including prolongation of cardiac repolarization (prolongation of QT interval). Corrected QT (QTc) prolongation, a toxicity associated with many cancer treatments, can lead to potentially life-threatening ventricular arrhythmias. Read More

Int J Cardiol 2019 Jan 31. Epub 2019 Jan 31.

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, the Netherlands. Electronic address:

Background: Left-stellate ganglion stimulation (LSGS) can modify regional dispersion of ventricular refractoriness, promote triggered activity, and reduce the threshold for ventricular fibrillation (VF). Sympathetic hyperactivity precipitates torsades de pointes (TdP) and VF in susceptible patients with long-QT syndrome type 1 (LQT1). We investigated the electromechanical effects of LSGS in a canine model of drug-induced LQT1, gaining novel arrhythmogenic insights. Read More

Saudi Pharm J 2019 Feb 10;27(2):229-234. Epub 2018 Nov 10.

Department of Pharmacy, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.

Objectives: To evaluate the relationship between drug interactions and QT-interval prolongation in patients admitted to a general intensive care unit (ICU).

Methods: This study was approved by the Institutional Review Board and written informed consent was obtained from all patients. From May 2015 to July 2016, all patients over 18 years-old admitted to the ICU for more than 24 h and in whom the QT-interval on the ECG could be read were prospectively included in this observational, cross-sectional study. Read More

Heart Rhythm 2019 Feb 11. Epub 2019 Feb 11.

Division of Heart Rhythm Services, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota; Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota; Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by adrenergically induced ventricular tachycardia, syncope, and sudden cardiac arrest (SCA). In the absence of structural disease, exercise-provoked premature ventricular contractions in bigeminy or couplets and nonsustained ventricular tachycardia are highly predictive of CPVT.

Objective: The purpose of this study was to determine the number of missed or delayed CPVT diagnoses attributable to exercise testing oversights in a cohort of young SCA survivors. Read More

Circ Res 2019 Feb;124(4):459-461

Laboratory of Cardiovascular Genetics (P.J.S., L.S.), Milan, Italy.

JAMA Cardiol 2019 Feb 13. Epub 2019 Feb 13.

Clinical Cardiovascular Research Center, Division of Cardiology, University of Rochester Medical Center, Rochester, New York.

JAMA Cardiol 2019 Feb 13. Epub 2019 Feb 13.

Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Importance: Long QT syndrome (LQTS) is caused by several ion channel genes, yet risk of arrhythmic events is not determined solely by the responsible gene pathogenic variants. Female sex after adolescence is associated with a higher risk of arrhythmic events in individuals with congenital LQTS, but the association between sex and genotype-based risk of LQTS is still unclear.

Objective: To examine the association between sex and location of the LQTS-related pathogenic variant as it pertains to the risk of life-threatening arrhythmias. Read More

Eur Heart J 2019 Feb 6. Epub 2019 Feb 6.

Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin, Via Pier Lombardo 22, Milan, Italy.

Aims: Having shown that Lumacaftor rescued the hERG trafficking defect in the induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of two LQT2 patients, we tested whether the commercial association Lumacaftor + Ivacaftor (LUM + IVA) could shorten the QTc in the same two patients.

Methods And Results: After hospital admission and 1 day of baseline recordings, half dose LUM + IVA was administered on Day 1, followed by full dose (LUM 800 mg + IVA 500 mg) for 7 days. A continuous 12-lead Holter ECG allowed a large number of blind QTc measurements. Read More

Best Pract Res Clin Obstet Gynaecol 2019 Jan 9. Epub 2019 Jan 9.

Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK; Fetal Medicine Unit, St George's University Hospital, Blackshaw Road, London, SW17 0QT, UK; Molecular and Clinical Sciences Research Institute, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK. Electronic address:

Fetal dysrhythmias are common abnormalities, usually manifesting as irregular rhythms. Although most irregularities are benign and caused by isolated atrial ectopics, in a few cases, rhythm irregularity may indicate partial atrioventricular block, which has different etiological and prognostic implications. We provide a flowchart for the initial management of irregular rhythm to help select cases requiring urgent specialist referral. Read More

Physiol Rep 2019 Feb;7(3):e13957

Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, California.

Sudden cardiac death (SCD) is the leading global cause of mortality. SCD often arises from cardiac ischemia reperfusion (IR) injury, pathologic sequence variants within ion channel genes, or a combination of the two. Alternative approaches are needed to prevent or ameliorate ventricular arrhythmias linked to SCD. Read More

Ann Noninvasive Electrocardiol 2019 Feb 6:e12640. Epub 2019 Feb 6.

Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Background: The aim of study was to investigate effects of beta-blockade on microvolt T-wave alternans (TWA), a precursor of lethal arrhythmia, in patients with long QT syndrome (LQTS).

Methods: Eleven consecutive LQTS patients, types 1 (n = 6), 3 (n = 2), and "non-1, non-2, non-3" (n = 3) were enrolled. All patients underwent 24-hr continuous 12-lead ECG monitoring before and after initiation of beta-blockade therapy. Read More

Chronic Obstr Pulm Dis 2018 Sep 15;5(4):258-266. Epub 2018 Sep 15.

Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.

PIZZ alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive disease affecting approximately 100,000 individuals in the United States and one of the most common hereditary causes of liver disease. The most common form of the disease results from a single base pair mutation (Glu342Lys), known as the "Z" mutation, that encodes a mutant protein (Z alpha-1 antritypsin [AAT]) that is prone to misfolding and is retained in the endoplasmic reticulum (ER) rather than appropriately secreted. Some of the retained mutant protein attains an unusual aggregated or conformation. Read More

Am J Perinatol 2019 Feb 4. Epub 2019 Feb 4.

Division of Neonatology, Banner - University Medical Center Phoenix, Phoenix, Arizona.

Objective:  Long QT syndrome (LQTS) is a known cause of unexpected death, leading some to recommend routine neonatal electrocardiographic (ECG) screening. We used continuous electronic heart rate corrected QT interval (QTc) monitoring to screen for interval prolongation in a cohort of hospitalized neonates to identify those at a risk of having LQTS. We hypothesized that this screening method would yield an acceptable positive predictive value (PPV). Read More

Heart Rhythm 2019 Feb 2. Epub 2019 Feb 2.

Department of Pharmacology, Columbia University Medical Center, New York, New York. Electronic address:

Much has been written about arrhythmias in structurally normal hearts. In this review, we focus on rapid ventricular arrhythmias that occur in hearts having a pathogenic genetic variant that has been found in families in which arrhythmias occur. We discuss these mutations in terms of their effect on cardiac cell electrical function and initiation of arrhythmias. Read More

J Cardiovasc Electrophysiol 2019 Jan 30. Epub 2019 Jan 30.

Arrhythmia and EP Research Center, IRCCS Humanitas Research & University Hospital, Milan, Italy.

Oxf Med Case Reports 2019 Jan 24;2019(1):omy122. Epub 2019 Jan 24.

Department of Cardiovascular Medicine, First Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, China.

The risk factors of acquired long QT syndrome (aLQTS) are sometimes overlooked in clinics. Drugs, hypokalemia, age and female sex are well-known risk factors of QT prolongation-dependent torsade de pointes (TdP), which explains the high incidence of sudden cardiac death in LQT patients. Here, we report a case of an elderly female patient with lung cancer who was in poor condition, for whom amiodarone was mistakenly prescribed to rectify premature ventricular contractions. Read More

Circulation 2019 Jan 30. Epub 2019 Jan 30.

Cardiology Department, Sourasky Tel-Aviv Medical Center, Israel.

Background: Polymorphic ventricular tachycardia (VT) without QT prolongation is well described in patients without structural heart disease [mainly idiopathic ventricular fibrillation (VF) and Brugada syndrome] and in patients with acute ST-elevation myocardial infarction.

Methods: Retrospective study of patients with polymorphic VT related to coronary artery disease but without evidence of acute myocardial ischemia.

Results: We identified 43 patients who developed polymorphic VT within days of an otherwise uncomplicated myocardial infarction or coronary revascularization procedure. Read More

Clin Cancer Res 2019 Jan 28. Epub 2019 Jan 28.

Office of Oncology Drug Products, United States Food and Drug Administration.

The Food and Drug Administration approved ivosidenib (Tibsovo; Agios, Cambridge, MA), a small molecule inhibitor of isocitrate dehydrogenase (IDH)1 on July 20, 2018, for treatment of adults with relapsed or refractory acute myeloid leukemia (R/R AML) with susceptible IDH1 mutation as detected by an FDA-approved test. The efficacy of ivosidenib was established based on complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR+CRh, and conversion from transfusion-dependence (TD) to transfusion-independence (TI) in the single-arm Study AG120-C-001. With median follow-up 8. Read More

Res Vet Sci 2019 Jan 8;123:239-246. Epub 2019 Jan 8.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Background: The voltage-gated K-channel K11.1 has a central role in cardiac repolarization. Blockage of K11. Read More

Exp Ther Med 2019 Feb 30;17(2):1143-1148. Epub 2018 Nov 30.

Exercise Physiology and Sports Medicine Clinic, Center for Adolescent Medicine and UNESCO Chair on Adolescent Health Care, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, 11527 Athens, Greece.

Athletic pre-participation screening is essential for minimizing the risk for sudden cardiac death (SCD) in athletes participating in either competitive or leisure sporting activities. The primary causes of SCD in young athletes (<35 years of age) include hypertrophic cardiomyopathy, congenital anomalies of the coronary artery and arrhythmogenic right ventricular cardiomyopathy. Other abnormalities, such as malignant arrhythmia due to blunt trauma to the chest (commotio cordis), myocarditis, valvular disease, aortic rupture (in Marfan syndrome) and ion channelopathies (catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, long or short QT syndrome), also contribute to a lesser degree to SCD. Read More

Heart Rhythm 2019 Jan 21. Epub 2019 Jan 21.

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: We recently reported a quantitative relationship between the degree of functional perturbation reported in the literature for 356 variants in the cardiac sodium channel gene SCN5A and the penetrance of resulting arrhythmia phenotypes. In the course of that work, we identified multiple SCN5A variants, including R1193Q, that are common in populations but are reported in HEK cells to generate large late sodium current (I).

Objective: The purpose of this study was to compare the functional properties of R1193Q with those of the well-studied type 3 long QT syndrome mutation ΔKPQ. Read More

J Gen Physiol 2019 Feb 23;151(2):214-230. Epub 2019 Jan 23.

Department of Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan

Drug-induced block of the cardiac rapid delayed rectifying potassium current (), carried by the human ether-a-go-go-related gene (hERG) channel, is the most common cause of acquired long QT syndrome. Indeed, some, but not all, drugs that block hERG channels cause fatal cardiac arrhythmias. However, there is no clear method to distinguish between drugs that cause deadly arrhythmias and those that are clinically safe. Read More

Ann Noninvasive Electrocardiol 2019 Jan 23:e12624. Epub 2019 Jan 23.

Department of Congenital Heart Diseases, Institute of Cardiology, Warsaw, Poland.

We report on a 44-year-old woman with coincidence of two genetic disorders: Andersen-Tawil syndrome and Marfan syndrome. In both, life-threatening arrhythmias could occur. A 44-year-old woman presented acute ascending aortic dissection with aortic arch involvement and chronic thoracic descending and abdominal aortic dissection. Read More

Front Physiol 2018 7;9:1847. Epub 2019 Jan 7.

Columbia University Medical Center, New York, NY, United States.

The epidemics of obesity and diabetes mellitus are associated with an increased incidence of both atrial fibrillation (AF), the most common sustained arrhythmia in adults, and sudden cardiac death (SCD). Obesity and DM are known to have adverse effects on cardiac structure and function. The pathologic mechanisms are thought to involve cardiac tissue remodeling, metabolic dysregulation, inflammation, and oxidative stress. Read More

Mol Pharmacol 2019 Apr 21;95(4):386-397. Epub 2019 Jan 21.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada

The () encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (I). Drug-mediated or medical condition-mediated disruption of hERG function is the primary cause of acquired long-QT syndrome, which predisposes affected individuals to ventricular arrhythmias and sudden death. Fentanyl abuse poses a serious health concern, with abuse and death rates rising over recent years. Read More

Epilepsy Res 2019 02 14;150:66-69. Epub 2019 Jan 14.

Research Institute of the McGill University Health Center, 2155 Guy Street, Montreal, PQ, H3H 2L9, Canada; Department of Pediatrics, Division of Child Neurology, Montreal Children's Hospital, McGill University Health Centre, 1001 Boulevard Décarie, Montreal, PQ, H4A 3J1, Canada.

We aimed to describe families with genetic epilepsy with febrile seizures plus (GEFS+) in which individuals suffered sudden unexpected death. The Epilepsy Pharmacogenomics Research Database was reviewed for GEFS + families in which at least one individual had suffered sudden death, and two families were identified. In Family A, five males had febrile seizures and one girl had febrile seizures plus. Read More

Br J Pharmacol 2019 Jan 16. Epub 2019 Jan 16.

Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB Center for Brain & Disease Research, Leuven, Belgium.

Background And Purpose: The citrus flavanone hesperetin (HSP) has been proposed for the treatment of several human pathologies, but its cardiovascular actions remain largely unexplored. Here we evaluated HSP effects on cardiac electrical and contractile activities, on aortic contraction, on the wild type voltage-gated Na channel Na 1.5 and on a channel mutant (R1623Q) associated with lethal ventricular arrhythmias in the Long QT syndrome subtype 3 (LQT3). Read More

Circ Genom Precis Med 2019 Feb;12(2):e002419

Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology and Experimental Therapeutics, Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, and Division of Heart Rhythm Services, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (D.J.C., D.J.T., J.R.G., J.M.B., R.K.R., M.J.A.).

Background: Triadin knockout syndrome (TKOS) is a rare, inherited arrhythmia syndrome caused by recessive null mutations in TRDN-encoded cardiac triadin. Based previously on 5 triadin null patients, TKOS has been characterized by extensive T-wave inversions, transient QT prolongation, and severe disease expression of exercise-induced cardiac arrest in early childhood refractory to conventional therapy.

Methods: We have established the International Triadin Knockout Syndrome Registry to include patients who have genetically proven homozygous/compound heterozygous TRDN null mutations. Read More

Int J Cardiol 2019 Mar 27;279:105-111. Epub 2018 Dec 27.

Department of Pathophysiology, Oita University, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.

The most common cardiac feature of Kearns-Sayre syndrome (KSS) is atrioventricular block (AVB), and pacemaker implantations (PMIs) are recommended for KSS patients with advanced AVB. However, some KSS patients develop fatal arrhythmias such as polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) and die suddenly even after PMIs. We report a patient with KSS who developed PMVT, VF, and QT prolongation, and was treated with mexiletine and successfully managed with an implantable cardioverter defibrillator (ICD). Read More

Genet Med 2019 Jan 12. Epub 2019 Jan 12.

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università della Campania "Luigi Vanvitelli", Caserta, Italy.

Purpose: Beckwith-Wiedemann syndrome (BWS) is a developmental disorder caused by dysregulation of the imprinted gene cluster of chromosome 11p15.5 and often associated with loss of methylation (LOM) of the imprinting center 2 (IC2) located in KCNQ1 intron 10. To unravel the etiological mechanisms underlying these epimutations, we searched for genetic variants associated with IC2 LOM. Read More

Int J Mol Med 2019 Mar 2;43(3):1253-1262. Epub 2019 Jan 2.

Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Institute of Cardiovascular Channelopathy, Key Laboratory of Molecular Cardiology, Xi'an, Shaanxi 710061, P.R. China.

Congenital long QT syndrome (LQTS) is a cardiac channelopathy that often results in fatal arrhythmias. LQTS mutations not only lead to abnormal myocardial electrical activities but are associated with heart contraction abnormalities, cardiomyopathy and congenital heart defects. In vivo and in vitro studies have found that LQTS mutations are associated with cardiomyocyte apoptosis, cardiac developmental disorders and even embryonic mortality. Read More

Kardiologiia 2018 Dec 25;58(12):52-58. Epub 2018 Dec 25.

Clinical Institute of Pediatrics named after Academician Y. E. Veltishev; RNIMU after N.I. Pirogov.

Purpose: to assess specificities of course of the long-QT syndrome in children before and after implantation of cardioverter-defibrillator (ICD), and optimization of indications to ICD-therapy.

Materials And Methods: We included in this study 48 children with long-QT syndrome from 44 unrelated families (28 boys and 20 girls), who underwent ICD implantation at the mean age 11.8±3. Read More

Biochemistry 2019 Feb 30;58(7):965-973. Epub 2019 Jan 30.

Department of Chemistry and Biochemistry , Miami University , 651 East High Street , Oxford , Ohio 45056 , United States.

KCNQ1 (Kv7.1 or KvLQT1) is a potassium ion channel protein found in the heart, ear, and other tissues. In complex with the KCNE1 accessory protein, it plays a role during the repolarization phase of the cardiac action potential. Read More

Front Cardiovasc Med 2018 11;5:176. Epub 2018 Dec 11.

Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy.

In spite of the widespread role of calmodulin (CaM) in cellular signaling, CaM mutations lead specifically to cardiac manifestations, characterized by remarkable electrical instability and a high incidence of sudden death at young age. Penetrance of the mutations is surprisingly high, thus postulating a high degree of functional dominance. According to the clinical patterns, arrhythmogenesis in CaM mutations can be attributed, in the majority of cases, to either prolonged repolarization (as in long-QT syndrome, LQTS phenotype), or to instability of the intracellular Ca store (as in catecholamine-induced tachycardias, CPVT phenotype). Read More

Open Heart 2018 16;5(2):e000877. Epub 2018 Dec 16.

Department of Psychological Medicine, The University of Auckland, Auckland, New Zealand.

Objective: The cardiac inherited disease (CID) population has suboptimal adherence to long-term β-blocker therapy, which is known to be a risk for sudden cardiac death. This study aimed to identify the clinical and psychosocial variables associated with non-adherence in this population.

Methods: 130 individuals (aged 16-81 years, median: 54) from the New Zealand Cardiac Inherited Disease Registry taking β-blockers participated: 65 (50%) long QT syndrome, 42 (32%) hypertrophic cardiomyopathy and 23 (18%) other. Read More

J Cardiol 2018 Dec 24. Epub 2018 Dec 24.

Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan. Electronic address:

Background: KCNQ1-T587M is a C-terminal mutation correlated with severe phenotypes of long QT syndrome (LQTS). However, functional analysis of KCNQ1 channels with the T587M mutation showed a mild genotype in the form of haploinsufficiency in a heterologous expression system. This study sought to explore the molecular mechanism underlying the phenotype-genotype dissociation of LQTS patients carrying the KCNQ1-T587M mutation. Read More

J Physiol 2019 Mar 24;597(6):1531-1551. Epub 2019 Jan 24.

Department of Medicine, Division of Cardiovascular Medicine, University of Wisconsin-Madison, 1111, Highland Ave, Madison, WI, USA.

Key Points: Mutations in the caveolae scaffolding protein, caveolin-3 (Cav3), have been linked to the long QT type 9 inherited arrhythmia syndrome (LQT9) and the cause of underlying action potential duration prolongation is incompletely understood. In the present study, we show that LQT9 Cav3 mutations, F97C and S141R, cause mutation-specific gain of function effects on Ca 1.2-encoded L-type Ca channels responsible for I and also cause loss of function effects on heterologously expressed K 4. Read More

Circ J 2018 Dec 22. Epub 2018 Dec 22.

Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science.