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Sample records for inherited arrhythmia clinic

  1. Clinical and genetic diagnosis for inherited cardiac arrhythmias.

    PubMed

    Shimizu, Wataru

    2014-01-01

    Molecular genetic studies in the last 2 decades have revealed a link between several inherited cardiac arrhythmias and genes encoding for ion channels or other membrane components. Two recent international expert consensus statements endorsed by 3 continental electrophysiology societies have updated the clinical and genetic diagnoses and management in patients with inherited arrhythmia syndromes, including congenital long QT syndrome (LQTS) and Brugada syndrome. Thirteen genotypes have been identified in 50% to 80% of clinically affected patients with congenital LQTS. Therefore, genotype-phenotype correlations have been investigated, especially, in the 3 major genotypes--LQT1, LQT2 and LQT3 syndromes--enabling genotype-specific management and therapy. On the other hand, less than half of patients with Brugada syndrome can be genotyped, and mainly for the sodium channel gene, SCN5A. However, recent advances in molecular genetic testing include genome-wide association studies using gene arrays and targeted, whole-exome and whole-genome next-generation sequencing techniques. In this article, I will review the clinical and genetic diagnoses in congenital LQTS and Brugada syndrome.

  2. Clinical impact of genetic studies in lethal inherited cardiac arrhythmias.

    PubMed

    Shimizu, Wataru

    2008-12-01

    Over the past decade, molecular genetic studies have established a link between a number of inherited cardiac arrhythmias, including congenital long QT syndrome (LQTS) and Brugada syndrome (BrS), and mutations in genes encoding for ion channels or other membrane components. Twelve forms of LQTS have been identified in 50-70% of clinically affected patients. Genotype-phenotype correlations have been rigorously investigated in LQT1, LQT2 and LQT3 syndromes, which constitute more than 90% of genotyped LQTS patients, enabling stratification of risk and effective treatment of genotyped patients. Genotype-specific triggers for both the cardiac events and the clinical course have been reported, and genotype-specific therapy has been already introduced. More recently, mutation site-specific differences in the clinical phenotype have been reported in LQT1 and LQT2 patients, indicating the possibility of mutation site-specific management or treatment. In contrast, only one-third of BrS patients can be genotyped, and data on genotype-phenotype relationships in clinical studies are limited. A Haplotype B consisting of 6 individual DNA polymorphisms within the proximal promoter region of the SCN5A gene was recently identified only in Asians (frequency 22%). Individuals with Haplotype B show significantly longer duration of both PQ and QRS than those without Haplotype B, indicating that Haplotype B likely contributes to the higher incidence of BrS in Asian populations.

  3. Exercise and Inherited Arrhythmias.

    PubMed

    Cheung, Christopher C; Laksman, Zachary W M; Mellor, Gregory; Sanatani, Shubhayan; Krahn, Andrew D

    2016-04-01

    Sudden cardiac death (SCD) in an apparently healthy individual is a tragedy that prompts a series of investigations to identify the cause of death and to prevent SCD in potentially at-risk family members. Several inherited channelopathies and cardiomyopathies, including long QT syndrome (LQTS), catecholaminergic polymorphic ventricular cardiomyopathy (CPVT), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) are associated with exercise-related SCD. Exercise restriction has been a historical mainstay of therapy for these conditions. Syncope and cardiac arrest occur during exercise in LQTS and CPVT because of ventricular arrhythmias, which are managed with β-blockade and exercise restriction. Exercise may provoke hemodynamic or ischemic changes in HCM, leading to ventricular arrhythmias. ARVC is a disease of the desmosome, whose underlying disease process is accelerated by exercise. On this basis, expert consensus has erred on the side of caution, recommending rigorous exercise restriction for all inherited arrhythmias. With time, as familiarity with inherited arrhythmia conditions has increased and patients with milder forms of disease are diagnosed, practitioners have questioned the historical rigorous restrictions advocated for all. This change has been driven by the fact that these are often children and young adults who wish to lead active lives. Recent evidence suggests a lower risk of exercise-related arrhythmias in treated patients than was previously assumed, including those with previous symptoms managed with an implantable cardioverter-defibrillator. In this review, we emphasize shared decision making, monitored medical therapy, individual and team awareness of precautions and emergency response measures, and a more permissive approach to recreational and competitive exercise.

  4. TECRL, a new life-threatening inherited arrhythmia gene associated with overlapping clinical features of both LQTS and CPVT.

    PubMed

    Devalla, Harsha D; Gélinas, Roselle; Aburawi, Elhadi H; Beqqali, Abdelaziz; Goyette, Philippe; Freund, Christian; Chaix, Marie-A; Tadros, Rafik; Jiang, Hui; Le Béchec, Antony; Monshouwer-Kloots, Jantine J; Zwetsloot, Tom; Kosmidis, Georgios; Latour, Frédéric; Alikashani, Azadeh; Hoekstra, Maaike; Schlaepfer, Jurg; Mummery, Christine L; Stevenson, Brian; Kutalik, Zoltan; de Vries, Antoine Af; Rivard, Léna; Wilde, Arthur Am; Talajic, Mario; Verkerk, Arie O; Al-Gazali, Lihadh; Rioux, John D; Bhuiyan, Zahurul A; Passier, Robert

    2016-12-01

    , significantly reduced the triggered activity in these cells. In summary, we report that mutations in TECRL are associated with inherited arrhythmias characterized by clinical features of both LQTS and CPVT Patient-specific hiPSC-CMs recapitulated salient features of the clinical phenotype and provide a platform for drug screening evidenced by initial identification of flecainide as a potential therapeutic. These findings have implications for diagnosis and treatment of inherited cardiac arrhythmias. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  5. Inherited arrhythmias: The cardiac channelopathies.

    PubMed

    Behere, Shashank P; Weindling, Steven N

    2015-01-01

    Ion channels in the myocardial cellular membrane are responsible for allowing the cardiac action potential. Genetic abnormalities in these channels can predispose to life-threatening arrhythmias. We discuss the basic science of the cardiac action potential; outline the different clinical entities, including information regarding overlapping diagnoses, touching upon relevant genetics, new innovations in screening, diagnosis, risk stratification, and management. The special considerations of sudden unexplained death and sudden infant death syndrome are discussed. Scientists and clinicians continue to reconcile the rapidly growing body of knowledge regarding the molecular mechanisms and genetics while continuing to improve our understanding of the various clinical entities and their diagnosis and management in clinical setting. Two separate searches were run on the National Center for Biotechnology Information's website. The first using the term cardiac channelopathies was run on the PubMed database using filters for time (published in past 5 years) and age (birth-18 years), yielding 47 results. The second search using the medical subject headings (MeSH) database with the search terms "Long QT Syndrome" (MeSH) and "Short QT Syndrome" (MeSH) and "Brugada Syndrome" (MeSH) and "Catecholaminergic Polymorphic Ventricular Tachycardia" (MeSH), applying the same filters yielded 467 results. The abstracts of these articles were studied, and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles where further explored and read in full.

  6. Inherited arrhythmias: The cardiac channelopathies

    PubMed Central

    Behere, Shashank P; Weindling, Steven N

    2015-01-01

    Ion channels in the myocardial cellular membrane are responsible for allowing the cardiac action potential. Genetic abnormalities in these channels can predispose to life-threatening arrhythmias. We discuss the basic science of the cardiac action potential; outline the different clinical entities, including information regarding overlapping diagnoses, touching upon relevant genetics, new innovations in screening, diagnosis, risk stratification, and management. The special considerations of sudden unexplained death and sudden infant death syndrome are discussed. Scientists and clinicians continue to reconcile the rapidly growing body of knowledge regarding the molecular mechanisms and genetics while continuing to improve our understanding of the various clinical entities and their diagnosis and management in clinical setting. Two separate searches were run on the National Center for Biotechnology Information's website. The first using the term cardiac channelopathies was run on the PubMed database using filters for time (published in past 5 years) and age (birth-18 years), yielding 47 results. The second search using the medical subject headings (MeSH) database with the search terms “Long QT Syndrome” (MeSH) and “Short QT Syndrome” (MeSH) and “Brugada Syndrome” (MeSH) and “Catecholaminergic Polymorphic Ventricular Tachycardia” (MeSH), applying the same filters yielded 467 results. The abstracts of these articles were studied, and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles where further explored and read in full. PMID:26556967

  7. Channelopathies - Emerging Trends in The Management of Inherited Arrhythmias

    PubMed Central

    Chockalingam, Priya; Mizusawa, Yuka; Wilde, Arthur A.M.

    2016-01-01

    In spite of their relative rarity, inheritable arrhythmias have come to the forefront as a group of potentially fatal but preventable cause of sudden cardiac death in children and (young) adults. Comprehensive management of inherited arrhythmias includes diagnosing and treating the proband and identifying and protecting affected family members. This has been made possible by the vast advances in the field of molecular biology enabling better understanding of the genetic underpinnings of some of these disease groups, namely congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. The ensuing knowledge of the genotype-phenotype correlations enables us to risk-stratify, prognosticate and treat based on the genetic test results. The various diagnostic modalities currently available to us, including clinical tools and genetic technologies, have to be applied judiciously in order to promptly identify those affected and to spare the emotional burden of a potentially lethal disease in the unaffected individuals. The therapeutic armamentarium of inherited arrhythmias includes pharmacological agents, device therapies and surgical interventions. A treatment strategy keeping in mind the risk profile of the patients, the local availability of drugs and the expertise of the treating personnel is proving effective. While opportunities for research are numerous in this expanding field of medicine, there is also tremendous scope for incorporating the emerging trends in managing patients and families with inherited arrhythmias in the Indian subcontinent. PMID:25852242

  8. Genetics of inherited primary arrhythmia disorders

    PubMed Central

    Spears, Danna A; Gollob, Michael H

    2015-01-01

    A sudden unexplained death is felt to be due to a primary arrhythmic disorder when no structural heart disease is found on autopsy, and there is no preceding documentation of heart disease. In these cases, death is presumed to be secondary to a lethal and potentially heritable abnormality of cardiac ion channel function. These channelopathies include congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome. In certain cases, genetic testing may have an important role in supporting a diagnosis of a primary arrhythmia disorder, and can also provide prognostic information, but by far the greatest strength of genetic testing lies in the screening of family members, who may be at risk. The purpose of this review is to describe the basic genetic and molecular pathophysiology of the primary inherited arrhythmia disorders, and to outline a rational approach to genetic testing, management, and family screening. PMID:26425105

  9. Molecular autopsy in victims of inherited arrhythmias.

    PubMed

    Semsarian, Christopher; Ingles, Jodie

    2016-10-01

    Sudden cardiac death (SCD) is a rare but devastating complication of a number of underlying cardiovascular diseases. While coronary artery disease and acute myocardial infarction are the most common causes of SCD in older populations, inherited cardiac disorders comprise a substantial proportion of SCD cases aged less than 40 years. Inherited cardiac disorders include primary inherited arrhythmogenic disorders such as familial long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and inherited cardiomyopathies, most commonly hypertrophic cardiomyopathy (HCM). In up to 40% of young SCD victims (defined as 1-40 years old, excluding sudden unexplained death in infancy from 0 to 1 years, referred to as SIDS), no cause of death is identified at postmortem [so-called "autopsy negative" or "sudden arrhythmic death syndrome" (SADS)]. Management of families following a SCD includes the identification of the cause of death, based either on premorbid clinical details or the pathological findings at the postmortem. When no cause of death is identified, genetic testing of DNA extracted from postmortem tissue (the molecular autopsy) may identify a cause of death in up to 30% of SADS cases. Targeted clinical testing in a specialized multidisciplinary clinic in surviving family members combined with the results from genetic testing, provide the optimal setting for the identification of relatives who may be at risk of having the same inherited heart disease and are therefore also predisposed to an increased risk of SCD.

  10. Recent advances in genetic testing and counseling for inherited arrhythmias.

    PubMed

    Mizusawa, Yuka

    2016-10-01

    Inherited arrhythmias, such as cardiomyopathies and cardiac ion channelopathies, along with coronary heart disease (CHD) are three most common disorders that predispose adults to sudden cardiac death. In the last three decades, causal genes in inherited arrhythmias have been successfully identified. At the same time, it has become evident that the genetic architectures are more complex than previously known. Recent advancements in DNA sequencing technology (next generation sequencing) have enabled us to study such complex genetic traits. This article discusses indications for genetic testing of patients with inherited arrhythmias. Further, it describes the benefits and challenges that we face in the era of next generation sequencing. Finally, it briefly discusses genetic counseling, in which a multidisciplinary approach is required due to the increased complexity of the genetic information related to inherited arrhythmias.

  11. The Brugada Syndrome: A Rare Arrhythmia Disorder with Complex Inheritance.

    PubMed

    Gourraud, Jean-Baptiste; Barc, Julien; Thollet, Aurélie; Le Scouarnec, Solena; Le Marec, Hervé; Schott, Jean-Jacques; Redon, Richard; Probst, Vincent

    2016-01-01

    For the last 10 years, applying new sequencing technologies to thousands of whole exomes has revealed the high variability of the human genome. Extreme caution should thus be taken to avoid misinterpretation when associating rare genetic variants to disease susceptibility. The Brugada syndrome (BrS) is a rare inherited arrhythmia disease associated with high risk of sudden cardiac death in the young adult. Familial inheritance has long been described as Mendelian, with autosomal dominant mode of transmission and incomplete penetrance. However, all except 1 of the 23 genes previously associated with the disease have been identified through a candidate gene approach. To date, only rare coding variants in the SCN5A gene have been significantly associated with the syndrome. However, the genotype/phenotype studies conducted in families with SCN5A mutations illustrate the complex mode of inheritance of BrS. This genetic complexity has recently been confirmed by the identification of common polymorphic alleles strongly associated with disease risk. The implication of both rare and common variants in BrS susceptibility implies that one should first define a proper genetic model for BrS predisposition prior to applying molecular diagnosis. Although long remains the way to personalized medicine against BrS, the high phenotype variability encountered in familial forms of the disease may partly find an explanation into this specific genetic architecture.

  12. Wearable defibrillator in congenital structural heart disease and inherited arrhythmias.

    PubMed

    Rao, Mohan; Goldenberg, Ilan; Moss, Arthur J; Klein, Helmut; Huang, David T; Bianco, Nicole R; Szymkiewicz, Steven J; Zareba, Wojciech; Brenyo, Andrew; Buber, Jonathan; Barsheshet, Alon

    2011-12-01

    Patients with congenital structural heart disease (CSHD) and inherited arrhythmias (IAs) are at high risk of ventricular tachyarrhythmias and sudden cardiac death. The present study was designed to evaluate the short- and long-term outcomes of patients with CSHD and IA who received a wearable cardioverter-defibrillator (WCD) for the prevention of sudden cardiac death. The study population included 162 patients with CSHD (n = 43) and IA (n = 119) who were prospectively followed up in a nationwide registry from 2005 to 2010. The mortality rates were compared using Kaplan-Meier survival analysis. The mean age of the study patients was 38 ± 27 years. The patients with CSHD had a greater frequency of left ventricular dysfunction (ejection fraction <30%) than did the patients with IA (37% vs 5%, respectively; p = 0.002). The predominant indication for WCD was pending genetic testing in the IA group and transplant listing in the CSHD group. Compliance with the WCD was similar in the 2 groups (91%). WCD shocks successfully terminated 3 ventricular tachyarrhythmias in the patients with IA during a median follow-up of 29 days of therapy (corresponding to 23 appropriate WCD shocks per 100 patient-years). No arrhythmias occurred in the patients with CSHD during a median follow-up of 27 days. No patients died while actively wearing the WCD. At 1 year of follow-up, the survival rates were significantly lower among the patients with CSHD (87%) than among the patients with IA (97%, p = 0.02). In conclusion, our data suggest that the WCD can be safely used in high-risk adult patients with IA and CSHD. Patients with IA showed a greater rate of ventricular tachyarrhythmias during therapy but significantly lower long-term mortality rates. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Modeling Inherited Arrhythmia Disorders Using Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    PubMed

    Bezzerides, Vassilios J; Zhang, Donghui; Pu, William T

    2016-12-22

    Inherited arrhythmia disorders (IADs) are a group of potentially lethal diseases that remain diagnostic and management challenges. Although the genetic basis for many of these disorders is well known, the pathogenicity of individual mutations and the resulting clinical outcomes are difficult to predict. Treatment options remain imperfect, and optimizing therapy for individual patients can be difficult. Recent advances in the derivation of induced pluripotent stem cells (iPSCs) from patients and creation of genetically engineered human models using CRISPR/Cas9 has the potential to dramatically advance translational arrhythmia research. In this review, we discuss the current state of modeling IADs using human iPSC-derived cardiomyocytes. We also discuss current limitations and areas for further study.

  14. Disclosing Genetic Information to Family Members About Inherited Cardiac Arrhythmias: An Obligation or a Choice?

    PubMed

    Vavolizza, Rick D; Kalia, Isha; Erskine Aaron, Kathleen; Silverstein, Louise B; Barlevy, Dorit; Wasserman, David; Walsh, Christine; Marion, Robert W; Dolan, Siobhan M

    2015-08-01

    Inherited cardiac arrhythmias such as long QT syndrome and Brugada syndrome, present clinical as well as ethical, legal, and social challenges. Many individuals who carry a deleterious mutation are largely asymptomatic and therefore may not be diagnosed until after the occurrence of a personal or family member's cardiac event. The familial nature of inherited genetic information raises numerous ethical, legal, and social issues regarding the sharing of genetic information, particularly when an individual found to carry a deleterious mutation refuses to disclose his or her results to at-risk family members who could benefit from life-saving treatments. This qualitative study sought to understand the experiences with genetic testing for individuals (n = 50) with a personal or family history of cardiac events or sudden death. Unstructured in-person focus groups or interviews were conducted for each participant in the study. The recordings of these interviews were transcribed verbatim and subsequently analyzed and coded. Participants' comments regarding sharing of genetic information centered around four main themes: (1) motivation to disclose; (2) extent of disclosure; (3) effect of disclosure on family dynamics; and (4) reasons for not sharing genetic information. The majority of individuals believed that affected individuals are obligated to disclose genetic information to family members. In the era of personalized medicine, the disclosure of genetic information provides individuals the opportunities to learn about the genetics, disease characteristics, and treatment options in order to reduce morbidity and mortality in themselves and their family members. Further research is necessary to identify and explore the barriers to sharing genetic information with at-risk family members.

  15. Arrhythmia

    MedlinePlus

    An arrhythmia is a problem with the rate or rhythm of your heartbeat. It means that your heart beats ... is called bradycardia. The most common type of arrhythmia is atrial fibrillation, which causes an irregular and ...

  16. Arrhythmias

    MedlinePlus Videos and Cool Tools

    A change in the heart's normal electrical conduction system can result in an arrhythmia or irregular heartbeat. An arrhythmia can be an abnormally slow heartbeat, or an abnormally fast heartbeat. In ...

  17. Masked inherited primary arrhythmia syndromes in sudden cardiac death patients accompanied by coronary vasospasm

    PubMed Central

    Lee, Ki Hong; Park, Hyung Wook; Eun, Jeong Nam; Cho, Jeong Gwan; Yoon, Nam Sik; Kim, Mi Ran; Ku, Yo Han; Park, Hyukjin; Lee, Seung Hun; Kim, Jeong Han; Kim, Min Chul; Kim, Woo Jin; Kim, Hyun Kuk; Cho, Jae Yeong; Park, Keun-Ho; Sim, Doo Sun; Yoon, Hyun Ju; Kim, Kye Hun; Hong, Young Joon; Kim, Ju Han; Ahn, Youngkeun; Jeong, Myung Ho; Park, Jong Chun

    2017-01-01

    Background/Aims Coronary vasospasms are one of the important causes of sudden cardiac death (SCD). Provocation of coronary vasospasms can be useful, though some results may lead to false positives, with patients potentially experiencing recurrent SCD despite appropriate medical treatments. We hypothesized that it is not coronary vasospasms but inherited primary arrhythmia syndromes (IPAS) that underlie the development of SCD. Methods We analyzed 74 consecutive patients (3.8%) who survived out-of-hospital cardiac arrest among 1,986 patients who had angiographically proven coronary vasospasms. Electrical abnormalities were evaluated in serial follow-up electrocardiograms (ECGs) during and after the index event for a 3.9 years median follow-up. Major clinical events were defined as the composite of death and recurrent SCD events. Results Forty five patients (60.8%) displayed electrocardiographic abnormalities suggesting IPAS: Brugada type patterns in six (8.2%), arrhythmogenic right ventricular dysplasia patterns in three (4.1%), long QT syndrome pattern in one (2.2%), and early repolarization in 38 (51.4%). Patients having major clinical events showed more frequent Brugada type patterns, early repolarization, and more diffuse multivessel coronary vasospasms. Brugada type pattern ECGs (adjusted hazard ratio [HR], 4.22; 95% confidence interval [CI], 1.16 to 15.99; p = 0.034), and early repolarization (HR, 2.97; 95% CI, 1.09 to 8.10; p = 0.034) were ultimately associated with an increased risk of mortality. Conclusions Even though a number of aborted SCD survivors have coronary vasospasms, some also have IPAS, which has the potential to cause SCD. Therefore, meticulous evaluations and follow-ups for IPAS are required in those patients. PMID:28797161

  18. Masked inherited primary arrhythmia syndromes in sudden cardiac death patients accompanied by coronary vasospasm.

    PubMed

    Lee, Ki Hong; Park, Hyung Wook; Eun, Jeong Nam; Cho, Jeong Gwan; Yoon, Nam Sik; Kim, Mi Ran; Ku, Yo Han; Park, Hyukjin; Lee, Seung Hun; Kim, Jeong Han; Kim, Min Chul; Kim, Woo Jin; Kim, Hyun Kuk; Cho, Jae Yeong; Park, Keun-Ho; Sim, Doo Sun; Yoon, Hyun Ju; Kim, Kye Hun; Hong, Young Joon; Kim, Ju Han; Ahn, Youngkeun; Jeong, Myung Ho; Park, Jong Chun

    2017-09-01

    Coronary vasospasms are one of the important causes of sudden cardiac death (SCD). Provocation of coronary vasospasms can be useful, though some results may lead to false positives, with patients potentially experiencing recurrent SCD despite appropriate medical treatments. We hypothesized that it is not coronary vasospasms but inherited primary arrhythmia syndromes (IPAS) that underlie the development of SCD. We analyzed 74 consecutive patients (3.8%) who survived out-of-hospital cardiac arrest among 1,986 patients who had angiographically proven coronary vasospasms. Electrical abnormalities were evaluated in serial follow-up electrocardiograms (ECGs) during and after the index event for a 3.9 years median follow-up. Major clinical events were defined as the composite of death and recurrent SCD events. Forty five patients (60.8%) displayed electrocardiographic abnormalities suggesting IPAS: Brugada type patterns in six (8.2%), arrhythmogenic right ventricular dysplasia patterns in three (4.1%), long QT syndrome pattern in one (2.2%), and early repolarization in 38 (51.4%). Patients having major clinical events showed more frequent Brugada type patterns, early repolarization, and more diffuse multivessel coronary vasospasms. Brugada type pattern ECGs (adjusted hazard ratio [HR], 4.22; 95% confidence interval [CI], 1.16 to 15.99; p = 0.034), and early repolarization (HR, 2.97; 95% CI, 1.09 to 8.10; p = 0.034) were ultimately associated with an increased risk of mortality. Even though a number of aborted SCD survivors have coronary vasospasms, some also have IPAS, which has the potential to cause SCD. Therefore, meticulous evaluations and follow-ups for IPAS are required in those patients.

  19. Arrhythmia

    MedlinePlus

    ... from the NHLBI on Twitter. What Is an Arrhythmia? Español An arrhythmia (ah-RITH-me-ah) is a problem with ... rate or rhythm of the heartbeat. During an arrhythmia, the heart can beat too fast, too slow, ...

  20. Inherited Retinal Degenerative Clinical Trial Network

    DTIC Science & Technology

    2009-10-01

    ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited...AD_________________ AWARD NUMBER: W81XWH-07-1-0720 TITLE: Inherited Retinal Degenerative...Final 3. DATES COVERED 27 Sep 2007 – 29 Sep 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Inherited Retinal Degenerative Clinical Trial Network

  1. INHERITED NEUROPATHIES: CLINICAL OVERVIEW AND UPDATE

    PubMed Central

    KLEIN, CHRISTOPHER J.; DUAN, XIAOHUI; SHY, MICHAEL E.

    2014-01-01

    Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. PMID:23801417

  2. Inherited neuropathies: clinical overview and update.

    PubMed

    Klein, Christopher J; Duan, Xiaohui; Shy, Michael E

    2013-10-01

    Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. Copyright © 2013 Wiley Periodicals, Inc.

  3. Ventricular arrhythmias in Rhodesian Ridgebacks with a family history of sudden death and results of a pedigree analysis for potential inheritance patterns.

    PubMed

    Meurs, Kathryn M; Weidman, Jess A; Rosenthal, Steven L; Lahmers, Kevin K; Friedenberg, Steven G

    2016-05-15

    OBJECTIVE To evaluate a group of related Rhodesian Ridgebacks with a family history of sudden death for the presence of arrhythmia and to identify possible patterns of disease inheritance among these dogs. DESIGN Prospective case series and pedigree investigation. ANIMALS 25 Rhodesian Ridgebacks with shared bloodlines. PROCEDURES Pedigrees of 4 young dogs (1 female and 3 males; age, 7 to 12 months) that died suddenly were evaluated, and owners of closely related dogs were asked to participate in the study. Dogs were evaluated by 24-hour Holter monitoring, standard ECG, echocardiography, or some combination of these to assess cardiac status. Necropsy reports, if available, were reviewed. RESULTS 31 close relatives of the 4 deceased dogs were identified. Of 21 dogs available for examination, 8 (2 males and 6 females) had ventricular tachyarrhythmias (90 to 8,700 ventricular premature complexes [VPCs]/24 h). No dogs had clinical signs of cardiac disease reported. Echocardiographic or necropsy evaluation for 7 of 12 dogs deemed affected (ie, with frequent or complex VPCs or sudden death) did not identify structural lesions. Five of 6 screened parents of affected dogs had 0 to 5 VPCs/24 h (all singlets), consistent with a normal reading. Pedigree evaluation suggested an autosomal recessive pattern of inheritance, but autosomal dominant inheritance with incomplete penetrance could not be ruled out. CONCLUSIONS AND CLINICAL RELEVANCE Holter monitoring of Rhodesian Ridgebacks with a family history of an arrhythmia or sudden death is recommended for early diagnosis of disease. An autosomal recessive pattern of inheritance in the studied dogs was likely, and inbreeding should be strongly discouraged.

  4. Inherited epidermolysis bullosa: clinical and therapeutic aspects*

    PubMed Central

    Boeira, Vanessa Lys Simas Yamakawa; Souza, Erica Sales; Rocha, Bruno de Oliveira; Oliveira, Pedro Dantas; de Oliveira, Maria de Fátima Santos Paim; Rêgo, Vitória Regina Pedreira de Almeida; Follador, Ivonise

    2013-01-01

    Inherited epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders that present with skin and, in some cases, mucosal fragility, predisposing patients to the development of blisters and/or erosions after minimal trauma or friction. Children with a recurrent history of these kinds of lesions or neonates that present them in the absence of another reasonable explanation should be investigated. Diagnosis must be based on clinical and histopathological findings. To date, management of inherited EB basically consists in avoiding traumas that trigger lesions, as well as preventing infection and facilitating healing of the wounds with the systematic use of bandages. PMID:23739692

  5. Inherited Retinal Degenerative Disease Clinical Trial Network

    DTIC Science & Technology

    2012-10-01

    the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited retinal degenerative diseases is estimated at...for autosomal dominant retinitis pigmentosa ). As new interventions become available for clinical evaluation, the creation of such a network will...dominant retinitis pigmentosa at six sites- the CTEC site at University of Utah and five recruitment sites- the Retina Foundation of the Southwest

  6. Mitochondrial cardiomyopathy and related arrhythmias.

    PubMed

    Montaigne, David; Pentiah, Anju Duva

    2015-06-01

    Mitochondrial dysfunction has been shown to be involved in the pathophysiology of arrhythmia, not only in inherited cardiomyopathy due to specific mutations in the mitochondrial DNA but also in acquired cardiomyopathy such as ischemic or diabetic cardiomyopathy. This article briefly discusses the basics of mitochondrial physiology and details the mechanisms generating arrhythmias due to mitochondrial dysfunction. The clinical spectrum of inherited and acquired cardiomyopathies associated with mitochondrial dysfunction is discussed followed by general aspects of the management of mitochondrial cardiomyopathy and related arrhythmia. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Ventricular arrhythmias. Clinical recognition and management.

    PubMed

    Nestico, P F; DePace, N L; Morganroth, J

    1984-05-01

    The recognition that patients at high risk for sudden cardiac death can be identified raises our enthusiasm to eliminate some of these risk factors and thus our hope to prevent sudden cardiac death. Although this effect is yet to be shown in cooperative, well-controlled clinical trials, data exist to suggest that this result will be achieved. Thus, the use of antiarrhythmic agents in chronic ventricular ectopy, particularly in patients with left ventricular dysfunction, seems to be warranted, and new and more potent agents to be used for this end will be available in the future.

  8. Ventricular repolarization markers for predicting malignant arrhythmias in clinical practice

    PubMed Central

    Castro-Torres, Yaniel; Carmona-Puerta, Raimundo; Katholi, Richard E

    2015-01-01

    Malignant cardiac arrhythmias which result in sudden cardiac death may be present in individuals apparently healthy or be associated with other medical conditions. The way to predict their appearance represents a challenge for the medical community due to the tragic outcomes in most cases. In the last two decades some ventricular repolarization (VR) markers have been found to be useful to predict malignant cardiac arrhythmias in several clinical conditions. The corrected QT, QT dispersion, Tpeak-Tend, Tpeak-Tend dispersion and Tp-e/QT have been studied and implemented in clinical practice for this purpose. These markers are obtained from 12 lead surface electrocardiogram. In this review we discuss how these markers have demonstrated to be effective to predict malignant arrhythmias in medical conditions such as long and short QT syndromes, Brugada syndrome, early repolarization syndrome, acute myocardial ischemia, heart failure, hypertension, diabetes mellitus, obesity and highly trained athletes. Also the main pathophysiological mechanisms that explain the arrhythmogenic predisposition in these diseases and the basis for the VR markers are discussed. However, the same results have not been found in all conditions. Further studies are needed to reach a global consensus in order to incorporate these VR parameters in risk stratification of these patients. PMID:26301231

  9. Calcium Transients Closely Reflect Prolonged Action Potentials in iPSC Models of Inherited Cardiac Arrhythmia

    PubMed Central

    Spencer, C. Ian; Baba, Shiro; Nakamura, Kenta; Hua, Ethan A.; Sears, Marie A.F.; Fu, Chi-cheng; Zhang, Jianhua; Balijepalli, Sadguna; Tomoda, Kiichiro; Hayashi, Yohei; Lizarraga, Paweena; Wojciak, Julianne; Scheinman, Melvin M.; Aalto-Setälä, Katriina; Makielski, Jonathan C.; January, Craig T.; Healy, Kevin E.; Kamp, Timothy J.; Yamanaka, Shinya; Conklin, Bruce R.

    2014-01-01

    Summary Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site. PMID:25254341

  10. Multistep Ion Channel Remodeling and Lethal Arrhythmia Precede Heart Failure in a Mouse Model of Inherited Dilated Cardiomyopathy

    PubMed Central

    Suzuki, Takeshi; Shioya, Takao; Murayama, Takashi; Sugihara, Masami; Odagiri, Fuminori; Nakazato, Yuji; Nishizawa, Hiroto; Chugun, Akihito; Sakurai, Takashi; Daida, Hiroyuki; Morimoto, Sachio; Kurebayashi, Nagomi

    2012-01-01

    Background Patients with inherited dilated cardiomyopathy (DCM) frequently die with severe heart failure (HF) or die suddenly with arrhythmias, although these symptoms are not always observed at birth. It remains unclear how and when HF and arrhythmogenic changes develop in these DCM mutation carriers. In order to address this issue, properties of the myocardium and underlying gene expressions were studied using a knock-in mouse model of human inherited DCM caused by a deletion mutation ΔK210 in cardiac troponinT. Methodology/Principal Findings By 1 month, DCM mice had already enlarged hearts, but showed no symptoms of HF and a much lower mortality than at 2 months or later. At around 2 months, some would die suddenly with no clear symptoms of HF, whereas at 3 months, many of the survivors showed evident symptoms of HF. In isolated left ventricular myocardium (LV) from 2 month-mice, spontaneous activity frequently occurred and action potential duration (APD) was prolonged. Transient outward (Ito) and ultrarapid delayed rectifier K+ (IKur) currents were significantly reduced in DCM myocytes. Correspondingly, down-regulation of Kv4.2, Kv1.5 and KChIP2 was evident in mRNA and protein levels. In LVs at 3-months, more frequent spontaneous activity, greater prolongation of APD and further down-regulation in above K+ channels were observed. At 1 month, in contrast, infrequent spontaneous activity and down-regulation of Kv4.2, but not Kv1.5 or KChIP2, were observed. Conclusions/Significance Our results suggest that at least three steps of electrical remodeling occur in the hearts of DCM model mice, and that the combined down-regulation of Kv4.2, Kv1.5 and KChIP2 prior to the onset of HF may play an important role in the premature sudden death in this DCM model. DCM mice at 1 month or before, on the contrary, are associated with low risk of death in spite of inborn disorder and enlarged heart. PMID:22514734

  11. Advances in Modeling Ventricular Arrhythmias: from Mechanisms to the Clinic

    PubMed Central

    Trayanova, Natalia A.; Boyle, Patrick M.

    2014-01-01

    Modern cardiovascular research has increasingly recognized that heart models and simulation can help interpret an array of experimental data and dissect important mechanisms and interrelationships, with developments rooted in the iterative interaction between modeling and experimentation. This article reviews the progress made in simulating cardiac electrical behavior at the level of the organ and, specifically, in the development of models of ventricular arrhythmias and fibrillation, as well as their termination (defibrillation). The ability to construct multi-scale models of ventricular arrhythmias, representing integrative behavior from the molecule to the entire organ, has enabled mechanistic inquiry into the dynamics of ventricular arrhythmias in the diseased myocardium, in understanding drug-induced pro-arrhythmia, and in the development of new modalities for defibrillation, to name a few. In this article we also review the initial use of ventricular models of arrhythmia in personalized diagnosis, treatment planning, and prevention of sudden cardiac death. Implementing individualized cardiac simulations at the patient bedside is poised to become one of the most thrilling examples of computational science and engineering approaches in translational medicine. PMID:24375958

  12. Clinical outcome and circulatory effects of fetal cardiac arrhythmia.

    PubMed

    Lingman, G; Lundström, N R; Marsál, K

    1986-01-01

    By means of abdominal fetal ECG and non-invasive ultrasound blood flow studies 113 cases of fetal cardiac arrhythmia were classified according to the origin of arrhythmia. Pregnancy outcome was characterized by an increased frequency of fetal distress and heart malformation, and increased fetal and neonatal mortality. The following types of arrhythmia were identified: supraventricular extrasystoles (n = 84), paroxysmal tachycardia (n = 6), sinus bradycardia (n = 3), atrial flutter (n = 1), ventricular extrasystoles (n = 14), and atrioventricular block (n = 5). In 37 cases the combined Doppler and real-time ultrasound technique was used to measure fetal aortic blood flow as a means of studying the circulatory effects of the arrhythmia. Increased peak velocity, rising slope and acceleration were found in the first post-pausal beat after a supraventricular extrasystole or a missed beat; this supports the validity of Frank-Starling law for the fetal heart and suggests that a strong relationship exists between these variables and myocardial contractility. In two cases of intra-uterine heart failure, the effect of digoxin treatment in utero on the fetal aortic flow variables was studied, results indicating a positive inotropic effect of the drug on the fetal myocardium. The estimation of fetal aortic volume blood flow in cases of fetal cardiac arrhythmia is useful for early detection of fetal cardiac failure, and for monitoring the effects of intra-uterine treatment.

  13. Non-invasive cardiac mapping in clinical practice: Application to the ablation of cardiac arrhythmias.

    PubMed

    Dubois, Rémi; Shah, Ashok J; Hocini, Mélèze; Denis, Arnaud; Derval, Nicolas; Cochet, Hubert; Sacher, Frédéric; Bear, Laura; Duchateau, Josselin; Jais, Pierre; Haissaguerre, Michel

    2015-01-01

    Ten years ago, electrocardiographic imaging (ECGI) started to demonstrate its efficiency in clinical settings. The initial application to localize focal ventricular arrhythmias such as ventricular premature beats was probably the easiest to challenge and validates the concept. Our clinical experience in using this non-invasive mapping technique to identify the sources of electrical disorders and guide catheter ablation of atrial arrhythmias (premature atrial beat, atrial tachycardia, atrial fibrillation), ventricular arrhythmias (premature ventricular beats) and ventricular pre-excitation (Wolff-Parkinson-White syndrome) is described here.

  14. Sex differences in cardiac electrophysiology and clinical arrhythmias: epidemiology, therapeutics, and mechanisms.

    PubMed

    Tadros, Rafik; Ton, Anh-Tuan; Fiset, Céline; Nattel, Stanley

    2014-07-01

    Sex differences in cardiac electrophysiological properties and arrhythmias are evident in epidemiologic and investigative studies as well as in daily patient care. At the supraventricular level, women are at increased risk of sick sinus syndrome and atrioventricular (AV) node re-entrant tachycardia, whereas men manifest more AV block and accessory pathway-mediated arrhythmias. At the ventricular level, women are generally at higher risk of long QT-associated arrhythmias, whereas men are more likely to present with early repolarization, idiopathic ventricular fibrillation, and Brugada syndromes. Great advances have been made in unraveling the fundamental mechanisms underlying sex differences in ventricular arrhythmias, particularly those associated with abnormal repolarization. Conversely, the basis for male-predominant arrhythmia risk in structural heart disease and differences in supraventricular arrhythmia susceptibility are poorly understood. Beyond biological differences, arrhythmia occurrence and patient care decisions are also influenced by gender-related factors. This article reviews the current knowledge regarding the nature and underlying mechanisms of sex differences in basic cardiac electrophysiology and clinical arrhythmias. Copyright © 2014. Published by Elsevier Inc.

  15. Inherited Retinal Degenerative Disease Clinical Trials Network

    DTIC Science & Technology

    2014-12-01

    Network PRINCIPAL INVESTIGATOR: Patricia Zilliox., Ph.D. CONTRACTING ORGANIZATION: Foundation Fighting Blindness Clinical Research...fightblindness.org 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Foundation Fighting Blindness Clinical Research Institute

  16. Atrial Fibrillation and Ventricular Arrhythmias: Sex Differences in Electrophysiology, Epidemiology, Clinical Presentation, and Clinical Outcomes.

    PubMed

    Gillis, Anne M

    2017-02-07

    Sex-specific differences in the epidemiology, pathophysiology, clinical presentation, clinical treatment, and clinical outcomes of atrial fibrillation (AF), sustained ventricular arrhythmias, and sudden cardiac death are recognized. Sex hormones cause differences in cardiac electrophysiological parameters between men and women that may affect the risk for arrhythmias. The incidence and prevalence of AF is lower in women than in men. However, because women live longer and AF prevalence increases with age, the absolute number of women with AF exceeds that of men. Women with AF are more symptomatic, present with more atypical symptoms, and report worse quality of life in comparison with men. Female sex is an independent risk factor for death or stroke attributable to AF. Oral anticoagulation therapy for stroke prevention has similar efficacy for men and women, but older women treated with warfarin have a higher residual risk of stroke in comparison with men. Women with AF are less likely to receive rhythm control antiarrhythmic drug therapy, electric cardioversion, or catheter ablation in comparison with men. The incidence and prevalence of sustained ventricular arrhythmias and sudden cardiac death are lower in women than in men. Women receiving implantable cardioverter defibrillators for primary prevention of sudden cardiac death are less likely to experience sustained ventricular arrhythmias in comparison with men. In contrast, women receiving a cardiac resynchronization therapy implantable cardioverter defibrillator for the treatment of heart failure are more likely to benefit than men. Women are less likely to be referred for implantable cardioverter defibrillator therapy despite current guideline recommendations. Women are more likely to experience a significant complication related to implantable cardioverter defibrillator implantation in comparison with men. Whether sex differences in treatment decisions reflect patient preferences or treatment biases requires

  17. Familial epilepsy in Algeria: Clinical features and inheritance profiles.

    PubMed

    Chentouf, Amina; Dahdouh, Aïcha; Guipponi, Michel; Oubaiche, Mohand Laïd; Chaouch, Malika; Hamamy, Hanan; Antonarakis, Stylianos E

    2015-09-01

    To document the clinical characteristics and inheritance pattern of epilepsy in multigeneration Algerian families. Affected members from extended families with familial epilepsy were assessed at the University Hospital of Oran in Algeria. Available medical records, neurological examination, electroencephalography and imaging data were reviewed. The epilepsy type was classified according to the criteria of the International League Against Epilepsy and modes of inheritance were deduced from pedigree analysis. The study population included 40 probands; 23 male (57.5%) and 17 female subjects (42.5%). The mean age of seizure onset was 9.5 ± 6.1 years. According to seizure onset, 16 patients (40%) had focal seizures and 20 (50%) had generalized seizures. Seizure control was achieved for two patients (5%) for 10 years, while 28 (70%) were seizure-free for 3 months. Eleven patients (27.5%) had prior febrile seizures, 12 were diagnosed with psychiatric disorders and four families had syndromic epilepsy. The consanguinity rate among parents of affected was 50% with phenotypic concordance observed in 25 families (62.5%). Pedigree analysis suggested autosomal dominant (AD) inheritance with or without reduced penetrance in 18 families (45%), probable autosomal recessive (AR) inheritance in 14 families (35%), and an X-linked recessive inheritance in one family. This study reveals large Algerian families with multigenerational inheritance of epilepsy. Molecular testing such as exome sequencing would clarify the genetic basis of epilepsy in some of our families. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  18. Inherited leukoencephalopathies with clinical onset in middle and old age.

    PubMed

    Nannucci, Serena; Donnini, Ida; Pantoni, Leonardo

    2014-12-15

    The currently widespread use of neuroimaging has led neurologists to often face the problem of the differential diagnosis of white matter diseases. There are various forms of leukoencephalopathies (vascular, inflammatory and immunomediated, infectious, metabolic, neoplastic) and sometimes white matter lesions are expression of a genetic disease. While many inherited leukoencephalopathies fall in the child neurologist's interest, others may have a delayed or even a typical onset in the middle or old age. This field is rapidly growing and, in the last few years, many new inherited white matter diseases have been described and genetically defined. A non-delayed recognition of middle and old age inherited leukoencephalopathies appears important to avoid unnecessary tests and therapies in the patient and to possibly anticipate the diagnosis in relatives. The aim of this review is to provide a guide to direct the diagnostic process when facing a patient with a suspicion of an inherited form of leukoencephalopathy and with clinical onset in middle or old age. Based on a MEDLINE search from 1990 to 2013, we identified 24 middle and old age onset inherited leukoencephalopathies and reviewed in this relation the most recent findings focusing on their differential diagnosis. We provide summary tables to use as a check list of clinical and neuroimaging findings that are most commonly associated with these forms of leukoencephalopathies. When present, we reported specific characteristics of single diseases. Several genetic diseases may be suspected in patients with middle or old age and white matter abnormalities. In only few instances, pathognomonic clinical or associated neuroimaging features help identifying a specific disease. Therefore, a comprehensive knowledge of the characteristics of these inherited white matter diseases appears important to improve the diagnostic work-up, optimize the choice of genetic tests, increase the number of diagnosed patients, and stimulate

  19. Mechanisms and clinical significance of early recurrences of atrial arrhythmias after catheter ablation for atrial fibrillation

    PubMed Central

    Liang, Jackson J; Dixit, Sanjay; Santangeli, Pasquale

    2016-01-01

    Early recurrence of atrial arrhythmias (ERAA) after ablation is common and strongly predicts late recurrences and ablation failure. However, since arrhythmia may eventually resolve in up to half of patients with ERAA, guidelines do not recommend immediate reintervention for ERAA episodes occurring during a 3-mo post-ablation blanking period. Certain clinical demographic, electrophysiologic, procedural, and ERAA-related characteristics may predict a higher likelihood of long-term ablation failure. In this review, we aim to discuss potential mechanisms of ERAA, and to summarize the clinical significance, prognostic implications, and treatment options for ERAA. PMID:27957250

  20. Clinical profile and incidence of ventricular arrhythmia in patients undergoing defibrillator generator replacement in Spain.

    PubMed

    Fontenla, Adolfo; López Gil, María; Martínez Ferrer, José; Alzueta, Javier; Fernández Lozano, Ignacio; Viñolas, Xavier; Rodríguez, Aníbal; Fernández de la Concha, Joaquín; Anguera, Ignasi; Arribas, Fernando

    2014-12-01

    Implantable cardioverter-defibrillators reduce mortality in some patients with heart disease. Battery replacement is a frequent occurrence in clinical practice and is required in up to 30% of implants. The benefit/risk ratio of defibrillators varies over time and should be reevaluated at the time of replacement. The aim of this study was to determine the clinical characteristics and incidence of defibrillator therapies in patients who underwent generator replacement. This multicenter retrospective study involved patients from the UMBRELLA national registry who underwent replacement due to defibrillator battery depletion. The incidence of ventricular arrhythmias was determined via remote monitoring. Risk factors for sustained ventricular arrhythmia after replacement were analyzed. A total of 354 patients were included (mean age [standard deviation], 61.8 [14.5] years; men, 80%; secondary prevention, 42%; ventricular arrhythmias in the explanted generator, 62%). After a 25-month follow-up, 70 patients (20%) received appropriate therapies and 8 (2.3%) received inappropriate discharges. Male sex, structural heart disease, heart failure, and the absence of resynchronization were independent predictors of ventricular arrhythmia occurrence. One-fifth of patients had appropriate defibrillator therapies in the first 2 years after generator replacement. Determination of the factors associated with arrhythmia occurrence after replacement may be useful to optimize implantable cardioverter-defibrillator treatment. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  1. Effectiveness of Telemetry Guidelines in Predicting Clinically Significant Arrhythmias in Hospitalized Patients

    PubMed Central

    Dhillon, Sandeep K.; JosephTawil; Goldstein, Baruch; Eslava-Manchego, Dayana; Singh, Jagdeep; Hanon, Sam; Schweitzer, Paul; Bergmann, Steven R.

    2012-01-01

    Background Cardiac rhythm monitoring is widely applied on hospitalized patients. However, its value has not been evaluated systematically. Methods This study considered the utility of our institutional telemetry guidelines in predicting clinically significant arrhythmias. A retrospective analysis was performed of 562 patients admitted to the telemetry unit. A total of 1932 monitoring days were evaluated. Patients were divided into 2 groups based on telemetry guidelines: “telemetry indicated” and “telemetry not indicated”. Results Differences in arrhythmia event rates and pre-defined clinical significance were determined. One hundred and forty-four (34%) vs. 16 (11%) patients had at least one arrhythmic event in the “telemetry indicated” group compared with the “telemetry not indicated” group, respectively (P = 0.001). No patient in the “telemetry not indicated” group had a clinically significant arrhythmia. In contrast, of patients in the “telemetry indicated” group who had at least one arrhythmic event, 36% were considered clinically significant (P < 0.05). Conclusion In conclusion, this study validates and supports the use of our institutional telemetry guidelines to allocate this resource appropriately and predict clinically significant arrhythmias.

  2. Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations

    PubMed Central

    Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

    2015-01-01

    Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307–316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod–cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone–rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances. PMID:25324231

  3. Clinical characteristics and current therapies for inherited retinal degenerations.

    PubMed

    Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

    2014-10-16

    Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307-316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod-cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone-rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  4. Clinical Profile of Cardiac Arrhythmias in Children Attending the Out Patient Department of a Tertiary Paediatric Care Centre in Chennai.

    PubMed

    Premkumar, Sarala; Sundararajan, Premkumar; Sangaralingam, Thangavelu

    2016-12-01

    The presentation of symptoms of paediatric arrhythmias vary depending on the age and underlying heart disease. Physical examination of children with important arrhythmias may be entirely normal. Aim is to study the characteristics of cardiac arrhythmias in paediatric patients in a tertiary paediatric care centre in Chennai, India. The participants (n=60) were from birth to 12 years of age. Patients with sinus arrhythmias, sinus tachycardia and sinus bradycardia were excluded. Proportions of various parameters of interest like clinical features, age and sex distribution and underlying heart disease of children presenting with cardiac arrhythmias were arrived. Statistical analysis was performed using SPSS version 16.0. Ventricular ectopics were the most common type of arrhythmias observed in the present study followed by Sinus Node Dysfunction (SND). The most common type of SND was sino atrial arrest. Supra ventricular tachycardia was the most frequently sustained tachyarrhythmia in the present study. An increased association of WPW (Wolf Parkinson White Syndrome) with specific congenital cardiac defects was noted. Cardiac arrhythmias in children can present at anytime from fetal life to adolescence and their recognition requires high index of suspicion. While majority of children with arrhythmias have structurally normal heart, they are frequently encountered in children with underlying heart disease. Treatment of paediatric arrhythmias should be guided by the severity of the patient, the structure and function of the heart.

  5. Clinical Profile of Cardiac Arrhythmias in Children Attending the Out Patient Department of a Tertiary Paediatric Care Centre in Chennai

    PubMed Central

    Sundararajan, Premkumar; Sangaralingam, Thangavelu

    2016-01-01

    Introduction The presentation of symptoms of paediatric arrhythmias vary depending on the age and underlying heart disease. Physical examination of children with important arrhythmias may be entirely normal. Aim Aim is to study the characteristics of cardiac arrhythmias in paediatric patients in a tertiary paediatric care centre in Chennai, India. Materials and Methods The participants (n=60) were from birth to 12 years of age. Patients with sinus arrhythmias, sinus tachycardia and sinus bradycardia were excluded. Proportions of various parameters of interest like clinical features, age and sex distribution and underlying heart disease of children presenting with cardiac arrhythmias were arrived. Statistical analysis was performed using SPSS version 16.0. Results Ventricular ectopics were the most common type of arrhythmias observed in the present study followed by Sinus Node Dysfunction (SND). The most common type of SND was sino atrial arrest. Supra ventricular tachycardia was the most frequently sustained tachyarrhythmia in the present study. An increased association of WPW (Wolf Parkinson White Syndrome) with specific congenital cardiac defects was noted. Conclusion Cardiac arrhythmias in children can present at anytime from fetal life to adolescence and their recognition requires high index of suspicion. While majority of children with arrhythmias have structurally normal heart, they are frequently encountered in children with underlying heart disease. Treatment of paediatric arrhythmias should be guided by the severity of the patient, the structure and function of the heart. PMID:28208963

  6. [Clinical analysis of 19 cases of pregnant women with rapid arrhythmia in the treatment of radiofrequency catheter ablation].

    PubMed

    Chu, L; Zhang, J; Li, Y N; Long, D Y

    2016-10-25

    Objective: To investigate the risk of radiofrequency catheter ablation and maternal and infant in pregnant women with rapid arrhythmia during pregnancy. Methods: The clinical data of the 19 cases of pregnancy complicated with rapid arrhythmia were retrospectively analyzed and followed up, including the gestational week, the type of arrhythmia, the treatment, and the outcome of the mother and child in Beijing Anzhen Hospital of Capital Medical University from January 2002 to March 2016. Results: (1)Clinical characteristics: the ages of the 19 cases were(31±4)years old(ranged from 26 to 35 years old), the onset gestational ages were(21±4)weeks(ranged from 15 to 32 weeks).

  7. Private inherited microdeletion/microduplications: implications in clinical practice.

    PubMed

    Mencarelli, Maria Antonietta; Katzaki, Eleni; Papa, Filomena Tiziana; Sampieri, Katia; Caselli, Rossella; Uliana, Vera; Pollazzon, Marzia; Canitano, Roberto; Mostardini, Rosa; Grosso, Salvatore; Longo, Ilaria; Ariani, Francesca; Meloni, Ilaria; Hayek, Josef; Balestri, Paolo; Mari, Francesca; Renieri, Alessandra

    2008-01-01

    The introduction of array-CGH analysis is allowing the identification of novel genomic disorders. However, this new high-resolution technique is also opening novel diagnostic challenges when inherited private CNVs of unclear clinical significance are found. Oligo array-CGH analysis of 84 patients with mild to severe mental retardation associated with multiple congenital anomalies revealed 10 private CNVs inherited from a healthy parent. Three were deletions (7q31, 14q21.1, Xq25) and seven duplications (12p11.22, 12q21.31, 13q31.1, 17q12, Xp22.31, Xq28) ranging between 0.1 and 3.8Mb. Six rearrangements were not polymorphic. Four overlapped polymorphic regions to the extent of 10-61%. In one case the size was different between the proband and the healthy relative. Three small rearrangements were gene deserts. The remaining seven had a mean gene content of five (ranging from 1 to 18). None of the rearranged genes is known to be imprinted. Three disease-genes were found in three different cases: KAL1 in dupXp22.31, STS in another dupXp22.31 and TCF2 in dup17q12. The patient carrying the last duplication presents sex reversal, Peters' anomaly and renal cysts and the duplication is located 4Mb away from the HSD17B1 gene, coding a key enzyme of testosterone biosynthesis. Considering the overlap with polymorphic regions, size-identity within the family, gene content, kind of rearrangement and size of rearrangement we suggest that at least in five cases the relationship to the phenotype has not to be excluded. We recommend to maintain caution when asserting that chromosomal abnormalities inherited from a healthy parent are benign. A more complex mechanism may in fact be involved, such as a concurrent variation in the other allele or in another chromosome that influences the phenotype.

  8. Ventricular arrhythmias in congestive heart failure: clinical significance and management.

    PubMed Central

    Khoshnevis, G R; Massumi, A

    1999-01-01

    The benefit of defibrillator therapy has been well established for patients with LV dysfunction (ejection fraction less than 35%), coronary artery disease, NSVT, and inducible and nonsuppressible ventricular tachycardia. Implantable cardioverter-defibrillator therapy is also indicated for all CHF patients in NYHA functional classes I, II, and III who present with aborted sudden cardiac death, or ventricular fibrillation, or hemodynamically unstable ventricular tachycardia--and also in patients with syncope with no documented ventricular tachycardia but with inducible ventricular tachycardia at electrophysiology study. The ongoing MADIT II trial was designed to evaluate the benefit of prophylactic ICD implantation in these patients (ejection fraction less than 30%, coronary artery disease, and NSVT) without prior risk stratification by PES. The CABG Patch trial concluded that prophylactic placement of an ICD during coronary artery bypass grafting in patients with low ejection fraction and abnormal SAECG is not justifiable. Except for the indications described above, ICD implantation has not been proved to be beneficial as primary or secondary therapy. Until more data are available, patients should be encouraged to enroll in the ongoing clinical trials. PMID:10217470

  9. Sudden Arrhythmia Death Syndromes (SADS) Foundation

    MedlinePlus

    ... Family Seminar 04/29/17 Update on Inherited Arrhythmias: Recent Advancements in Therapies and Diagnosis--From 8: ... Legal Notice Privacy Policy COPYRIGHT ©2011-2016 Sudden Arrhythmia Death Syndromes Foundation 4527 South 2300 East, Suite ...

  10. Determining conduction patterns on a sparse electrode grid: Implications for the analysis of clinical arrhythmias

    NASA Astrophysics Data System (ADS)

    Vidmar, David; Narayan, Sanjiv M.; Krummen, David E.; Rappel, Wouter-Jan

    2016-11-01

    We present a general method of utilizing bioelectric recordings from a spatially sparse electrode grid to compute a dynamic vector field describing the underlying propagation of electrical activity. This vector field, termed the wave-front flow field, permits quantitative analysis of the magnitude of rotational activity (vorticity) and focal activity (divergence) at each spatial point. We apply this method to signals recorded during arrhythmias in human atria and ventricles using a multipolar contact catheter and show that the flow fields correlate with corresponding activation maps. Further, regions of elevated vorticity and divergence correspond to sites identified as clinically significant rotors and focal sources where therapeutic intervention can be effective. These flow fields can provide quantitative insights into the dynamics of normal and abnormal conduction in humans and could potentially be used to enhance therapies for cardiac arrhythmias.

  11. Mainstreaming genetics: a comparative review of clinical services for inherited cardiovascular conditions in the UK.

    PubMed

    Burton, Hilary; Alberg, C; Stewart, A

    2010-01-01

    Inherited cardiovascular conditions (ICCs) are a group of monogenic disorders caused by mutations in the components of the electrical and contractile system of the heart or its vasculature. ICCs include arrhythmias, cardiomyopathies, inherited arteriopathies such as Marfan syndrome, muscular dystrophies, and familial hypercholesterolaemia. Epidemiological data on ICCs are sparse but a survey of the available literature suggests that there are approximately 340,000 prevalent cases of these conditions in the UK (population 61 million). As a result of dramatic advances in understanding of the molecular pathology of ICCs, more than 50 ICCs have been recognised, and diagnostic genetic tests are increasingly available. As part of a needs assessment and review of provision of ICC services, a survey of all UK ICC services was undertaken focusing on both quantitative and qualitative aspects. Service provision was found to be highly inequitable, with typically a 10-20-fold variation in referral and genetic testing rates between different UK regions. Service levels per million population are much higher in London than in all but one of the regions. The review concluded that capacity of services is inadequate to meet current or future demand and many services lack the critical mass to provide the full range of services. Recommendations are made for the development of services appropriate for the future. Services should be led by cardiology but have close links with clinical genetics services, which should provide support with specialist genetics advice and cascade testing. Finally, the international relevance of this review is considered. Copyright 2010 S. Karger AG, Basel.

  12. Clinical Genetic Testing for the Cardiomyopathies and Arrhythmias: A Systematic Framework for Establishing Clinical Validity and Addressing Genotypic and Phenotypic Heterogeneity

    PubMed Central

    Garcia, John; Tahiliani, Jackie; Johnson, Nicole Marie; Aguilar, Sienna; Beltran, Daniel; Daly, Amy; Decker, Emily; Haverfield, Eden; Herrera, Blanca; Murillo, Laura; Nykamp, Keith; Topper, Scott

    2016-01-01

    Advances in DNA sequencing have made large, diagnostic gene panels affordable and efficient. Broad adoption of such panels has begun to deliver on the promises of personalized medicine, but has also brought new challenges such as the presence of unexpected results, or results of uncertain clinical significance. Genetic analysis of inherited cardiac conditions is particularly challenging due to the extensive genetic heterogeneity underlying cardiac phenotypes, and the overlapping, variable, and incompletely penetrant nature of their clinical presentations. The design of effective diagnostic tests and the effective use of the results depend on a clear understanding of the relationship between each gene and each considered condition. To address these issues, we developed simple, systematic approaches to three fundamental challenges: (1) evaluating the strength of the evidence suggesting that a particular condition is caused by pathogenic variants in a particular gene, (2) evaluating whether unusual genotype/phenotype observations represent a plausible expansion of clinical phenotype associated with a gene, and (3) establishing a molecular diagnostic strategy to capture overlapping clinical presentations. These approaches focus on the systematic evaluation of the pathogenicity of variants identified in clinically affected individuals, and the natural history of disease in those individuals. Here, we applied these approaches to the evaluation of more than 100 genes reported to be associated with inherited cardiomyopathies and arrhythmias including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia or cardiomyopathy, long QT syndrome, short QT syndrome, Brugada, and catecholaminergic polymorphic ventricular tachycardia, and to a set of related syndromes such as Noonan Syndrome and Fabry disease. These approaches provide a framework for delivering meaningful and accurate genetic test results to individuals with hereditary

  13. An update on insertable cardiac monitors: examining the latest clinical evidence and technology for arrhythmia management.

    PubMed

    Olsen, Flemming J; Biering-Sørensen, Tor; Krieger, Derk W

    2015-05-01

    Continuous cardiac rhythm monitoring has undergone compelling progress over the past decades. Cardiac monitoring has emerged from 12-lead electrocardiograms being performed at the discretion of the treating physician to in-hospital telemetry, Holter monitoring, prolonged external event monitoring and most recently toward insertable device monitoring for several years. Significant advantages and disadvantages pertaining to these monitoring options will be addressed in this review. Insertable cardiac monitors have several advantages over external monitoring techniques and may signify a clinical turning point in the field of arrhythmia management. However, their role in the detection of paroxysmal atrial fibrillation after cryptogenic strokes has yet to evolve. This will be the main focus of this review. Issues surrounding patient selection, clinical relevance and determination of cost-effectiveness for prolonged cardiac monitoring require further studies. Furthermore, insertable cardiac monitoring has not only the potential to augment diagnostic capabilities but also to improve the management of paroxysmal atrial fibrillation.

  14. [Acupuncture therapy for arrhythmia and other cardiac disorders: clinical and laboratory investigation].

    PubMed

    Kang, Xue-zhi; Xia, Ying

    2009-12-01

    Clinical studies have shown that acupuncture therapy is effective for certain cardiovascular diseases, especially cardiac arrhythmia resulting from neural dysfunction. The therapeutic efficacy varies depending on types of diseases, acupoints stimulated and acupuncture manipulation (or electroacupuncture parameters). The mechanistic research shows that acupuncture signal initiated at the acupoints is transferred to the brain through afferent nervous pathway and thus modulates the function of neurotransmitter systems. Then, the output signaling cascades relieve the cardiovascular dysfunction through efferent neural regulation. There are also several lines of evidence suggesting that the acupuncture effects involve complex mechanisms at multiple levels, including intracellular signal transduction, gene expression, endocrine secretion, humoral and dielectric regulation. Therefore, the acupuncture effects on cardiovascular disorders are dependent on an integrated mechanism mediated by multiple factors at central and peripheral levels. However, the detail of the mechanism is largely unclear yet. The potential problems in the literature are briefly discussed in this review.

  15. Role of the autonomic nervous system in modulating cardiac arrhythmias.

    PubMed

    Shen, Mark J; Zipes, Douglas P

    2014-03-14

    The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.

  16. [Supraventricular arrhythmia: electrocardiographic aspects].

    PubMed

    Bayés de Luna, Antoni

    2016-12-23

    Supraventricular arrhythmias are one of the main causes of medical consultation. They may also be the clinical presentation of various cardiovascular diseases and a marker of sudden death. The correct diagnosis of these arrhythmias could be a challenge. The purpose of this narrative review is to update succinctly on the topic.

  17. Inherited neuromyotonia: a clinical and genetic study of a family.

    PubMed

    Falace, Antonio; Striano, Pasquale; Manganelli, Fiore; Coppola, Antonietta; Striano, Salvatore; Minetti, Carlo; Zara, Federico

    2007-01-01

    Neuromyotonia is a disorder of peripheral nerve hyperexcitability characterized by myokymia, muscle cramps and stiffness, delayed muscle relaxation after contraction (pseudomyotonia), and hyperhidrosis, associated with well described spontaneous electromyographic features. It is usually an acquired disorder associated with autoantibodies against neuronal voltage-gated potassium channels. However, mutations of KCNA1, encoding the K(+) channel subunit hKv1.1, have been reported in rare families with neuromyotonia, and mutations in KCNQ2, encoding voltage-gated potassium M channel subunit, in families with benign neonatal seizures and myokymia. We report a three-generation family with inherited neuromyotonia without evidence of immunological involvement. Genetic study excluded mutations in KCNA1, KCNA2, KCNA6 and KCNQ2 genes. Our study does not completely exclude the involvement of other genes encoding ion channels subunits in the pathogenesis of this disorder. Further studies of familial cases will shed light on the molecular basis of inherited neuromyotonia.

  18. Interatrial block and atrial arrhythmias in centenarians: Prevalence, associations, and clinical implications.

    PubMed

    Martínez-Sellés, Manuel; Massó-van Roessel, Albert; Álvarez-García, Jesús; García de la Villa, Bernardo; Cruz-Jentoft, Alfonso J; Vidán, María Teresa; López Díaz, Javier; Felix Redondo, Francisco Javier; Durán Guerrero, Juan Manuel; Bayes-Genis, Antoni; Bayes de Luna, Antonio

    2016-03-01

    Data are lacking on the characteristics of atrial activity in centenarians, including interatrial block (IAB). The aim of this study was to describe the prevalence of IAB and auricular arrhythmias in subjects older than 100 years and to elucidate their clinical implications. We studied 80 centenarians (mean age 101.4 ± 1.5 years; 21 men) with follow-ups of 6-34 months. Of these 80 centenarians, 71 subjects (88.8%) underwent echocardiography. The control group comprised 269 septuagenarians. A total of 23 subjects (28.8%) had normal P wave, 16 (20%) had partial IAB, 21 (26%) had advanced IAB, and 20 (25.0%) had atrial fibrillation/flutter. The IAB groups exhibited premature atrial beats more frequently than did the normal P wave group (35.1% vs 17.4%; P < .001); also, other measurements in the IAB groups frequently fell between values observed in the normal P wave and the atrial fibrillation/flutter groups. These measurements included sex preponderance, mental status and dementia, perceived health status, significant mitral regurgitation, and mortality. The IAB group had a higher previous stroke rate (24.3%) than did other groups. Compared with septuagenarians, centenarians less frequently presented a normal P wave (28.8% vs 53.5%) and more frequently presented advanced IAB (26.3% vs 8.2%), atrial fibrillation/flutter (25.0% vs 10.0%), and premature atrial beats (28.3 vs 7.0%) (P < .01). Relatively few centenarians (<30%) had a normal P wave, and nearly half had IAB. Our data suggested that IAB, particularly advanced IAB, is a pre-atrial fibrillation condition associated with premature atrial beats. Atrial arrhythmias and IAB occurred more frequently in centenarians than in septuagenarians. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  19. Hypokalemic periodic paralysis, facial dysmorphism and ventricular arrhythmia (clinical triad of Andersen-Tawil syndrome).

    PubMed

    Thakkar, Mitesh; Biswas, T K; Desle, Hrishikesh B

    2012-11-01

    Andersen-Tawil Syndrome (ATS) is a rare potassium channel disorder, characterized by episodic weakness, ventricular arrhythmias and dysmorphic features (short stature, scoliosis, clinodactyly, hypertelorism, small or prominent low set ears, micrognathia and broad forehead). We report a case of hypokalemic periodic paralysis with dysmorphic facial features and ventricular arrhythmia resembling Andersen-Tawil syndrome.

  20. The role of the Arrhythmia Team, an integrated, multidisciplinary approach to treatment of patients with cardiac arrhythmias: results of the European Heart Rhythm Association survey.

    PubMed

    Fumagalli, Stefano; Chen, Jian; Dobreanu, Dan; Madrid, Antonio Hernandez; Tilz, Roland; Dagres, Nikolaos

    2016-04-01

    Management of patients with cardiac arrhythmias is increasingly complex because of continuous technological advance and multifaceted clinical conditions associated with ageing of the population, the presence of co-morbidities and the need for polypharmacy. The aim of this European Heart Rhythm Association Scientific Initiatives Committee survey was to provide an insight into the role of the Arrhythmia Team, an integrated, multidisciplinary approach to management of patients with cardiac arrhythmias. Forty-eight centres from 18 European countries replied to the Web-based questionnaire. The presence of an Arrhythmia Team was reported by 44% of the respondents, whereas 17% were not familiar with this term. Apart from the electrophysiologist, health professionals who should belong to such teams, according to the majority of the respondents, include a clinical cardiologist, a nurse, a cardiac surgeon, a heart failure specialist, a geneticist, and a geriatrician. Its main activity should be dedicated to the management of patients with complex clinical conditions or refractory or inherited forms of arrhythmias. When present, the Arrhythmia Team was considered helpful by 95% of respondents; the majority of centres (79%) agreed that it should be implemented. The Arrhythmia Team seems to be connected to important expectations in the management of cardiac arrhythmias. The efficacy of such an integrated and multidisciplinary approach should be encouraged and tested in clinical practice.

  1. Behavioral influences on cardiac arrhythmias

    PubMed Central

    Lampert, Rachel

    2015-01-01

    Stress can trigger both ventricular and atrial arrhythmias, as evidenced by epidemiological, clinical, and laboratory studies, through its impact on autonomic activity. Chronic stress also increases vulnerability to arrhythmias. Novel therapies aimed at decreasing the psychological and physiological response to stress may decrease arrhythmia frequency and improve quality of life. PMID:25983071

  2. Behavioral influences on cardiac arrhythmias.

    PubMed

    Lampert, Rachel

    2016-01-01

    Stress can trigger both ventricular and atrial arrhythmias, as evidenced by epidemiological, clinical, and laboratory studies, through its impact on autonomic activity. Chronic stress also increases vulnerability to arrhythmias. Novel therapies aimed at decreasing the psychological and physiological response to stress may decrease arrhythmia frequency and improve quality of life.

  3. Arrhythmias in mitral valve prolapse: relation to anterior mitral leaflet thickening, clinical variables, and color Doppler echocardiographic parameters.

    PubMed

    Zuppiroli, A; Mori, F; Favilli, S; Barchielli, A; Corti, G; Montereggi, A; Dolara, A

    1994-11-01

    Atrial and ventricular arrhythmias have been reported with variable incidence in symptomatic patients with mitral valve prolapse (MVP). The role of clinical and echocardiographic parameters as predictors for arrhythmias still needs to be clarified. One hundred nineteen consecutive patients (56 women and 63 men, mean age 40 +/- 17 years) with echocardiographically diagnosed MVP were examined. A complete echocardiographic study (M-mode, two-dimensional, and Doppler) and 24-hour electrocardiographic monitoring were performed in all patients. Complex atrial arrhythmias (CAAs) included atrial couplets, atrial tachycardia, and paroxysmal or sustained atrial flutter or fibrillation. Complex ventricular arrhythmias (CVAs) included multiform ventricular premature contractions (VPCs), VPC couplets, and runs of three or more sequential VPCs (salvos of ventricular tachycardia). The relation between complex arrhythmias and clinical parameters (age and gender) and echocardiographic parameters (left atrial and left ventricular dimensions, anterior mitral leaflet thickness [AMLT], and presence and severity of mitral regurgitation) was evaluated by multiple logistic regression analysis. CAA were present in 14% of patients and CVA in 30%. According to multiple logistic modeling, CAA correlated separately in the univariate analysis with age, presence of MR, and left ventricular and left atrial diameters; age was the only independent predictor (p < 0.001). CVA, in the univariate analysis, correlated with age, female gender, left ventricular end-diastolic diameter, and AMLT; only female gender and AMLT were independent predictors in the multivariate analysis (p < 0.01). The incidence of mitral regurgitation (59%) was higher than expected in a general population of MVP patients.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Enrollment in clinical trials: institutional factors affecting enrollment in the cardiac arrhythmia suppression trial (CAST).

    PubMed

    Shea, S; Bigger, J T; Campion, J; Fleiss, J L; Rolnitzky, L M; Schron, E; Gorkin, L; Handshaw, K; Kinney, M R; Branyon, M

    1992-12-01

    Recruitment and Enrollment Assessment in Clinical Trials (REACT), an NHLBI-sponsored substudy of the Cardiac Arrhythmia Suppression Trial (CAST), was conducted to assess factors associated with enrollment in clinical trials. We report on the relationships of institutional factors at CAST sites to patient enrollment. The proportion of CAST-eligible patients enrolling at each CAST site during the REACT study period was defined as the number of subjects enrolled divided by the sum of (1) the number enrolled plus (2) the number of eligibles who refused plus (3) the number of eligibles whose physicians refused to permit CAST personnel to attempt to enroll them. A questionnaire that included 78 questions regarding factors hypothesized to be associated with enrollment was completed between August 1988 and February 1990 by the nurse coordinators at all 112 CAST sites in the United States and Canada. Sixteen items were unanalyzable, and 37 of the remaining 62 were grouped into seven scales. The remaining items were analyzed individually. Enrollment proportions varied widely across the 112 CAST sites (mean 32.7% SD 22.6). Five variables or scales were included in the final multiple regression model (multiple R2 = .39). The most important of these was the proportion of eligible patients at a site cared for by medical staff other than private attending physicians (multiple R2 for this variable alone, .26). This proportion tended to be high in teaching hospitals. Other variables in this model that were associated with higher enrollment proportions included the number of days per week a nurse coordinator was present at the site, the number of nurse coordinator full-time equivalents at the site, fewer other clinical trials for which the nurse coordinator was responsible, and fewer perceived obstacles to enrollment. These findings indicate that enrollment was more successful at hospitals with higher proportions of eligible subjects cared for by fellows, housestaff, and service

  5. Macrolide and fluoroquinolone mediated cardiac arrhythmias: clinical considerations and comprehensive review.

    PubMed

    Cornett, Elyse; Novitch, Matthew B; Kaye, Alan D; Pann, Chris A; Bangalore, Harish Siddaiah; Allred, Gregory; Bral, Matthew; Jhita, Preya K; Kaye, Adam M

    2017-09-01

    While there is evidence for cardiac arrhythmias associated with macrolide and fluoroquinolone antibiotics, there is still debate among health care providers as to whether this risk of arrhythmia is overstated. A joint panel of the US Food and Drug Administration suggested that macrolide and fluoroquinolone labels need much stronger warnings regarding the possible serious adverse cardiac effects associated with these antibiotics, especially since they are so widely prescribed. And while health care providers may differ on the pertinence of the cardiac risks associated with antibiotic use, they can undoubtedly minimize the cardiac effects that are associated with these antibiotics by paying attention to the cardiac risk factors and drug history associated with the patient. Relevant studies for our review were identified from a PubMed search using keywords and combined word searches involving macrolides, fluoroquinolones, and cardiac arrhythmias. We attempted to include as many recent (>2015) articles as possible. We included case reports, randomized, controlled trials, observational studies, case-control studies, systematic reviews, and retrospective studies. Underlying cardiac issues can predispose patients to harmful cardiac side effects that can be exacerbated in the presence of antibiotics. The health care provider should rule out any risk factor associated with antibiotic-induced cardiac arrhythmia in the event that a patient does need a macrolide or fluoroquinolone antibiotic. Rigorous patient evaluation and a detailed patient history, including short and long term medication use, is the likely key to reducing any risk of cardiac arrhythmias associated with macrolides and fluoroquinolones. Clinicians should be cautious when prescribing macrolide and fluoroquinolone medications to patients with risk factors that may lead to antibiotic-induced cardiac arrhythmias, including a slow heart rate and those that are taking medications to treat arrhythmias.

  6. Caffeine and cardiac arrhythmias.

    PubMed

    Myers, M G

    1991-01-15

    To review the evidence supporting the belief that caffeine causes cardiac arrhythmias. Studies published since 1982 identified through computerized searches of MEDLINE, TOXLINE, and Chemical Abstracts and a review of bibliographies of relevant articles on the subject of caffeine and cardiac arrhythmias. All clinical studies examining caffeine as a cause of cardiac arrhythmias and a selection of basic science experiments to illustrate caffeine's effects in vitro. Study quality was assessed and all available clinical data pertaining to caffeine as a cause of arrhythmias were summarized. In one electrophysiologic study, caffeine was associated with an increased susceptibility to provoked cardiac arrhythmias. In five placebo-controlled trials, caffeine in doses up to 500 mg daily (equivalent to 5 to 6 cups of coffee) did not increase the frequency or severity of ventricular arrhythmias. One large epidemiologic study reported an increase in the frequency of ventricular extrasystoles in persons consuming 9 or more cups of coffee daily. Moderate ingestion of caffeine does not increase the frequency or severity of cardiac arrhythmias in normal persons, patients with ischemic heart disease, or those with pre-existing serious ventricular ectopy.

  7. Navigating the current landscape of clinical genetic testing for inherited retinal dystrophies.

    PubMed

    Lee, Kristy; Garg, Seema

    2015-04-01

    Inherited eye disorders are a significant cause of vision loss. Genetic testing can be particularly helpful for patients with inherited retinal dystrophies because of genetic heterogeneity and overlapping phenotypes. The need to identify a molecular diagnosis for retinal dystrophies is particularly important in the era of developing novel gene therapy-based treatments, such as the RPE65 gene-based clinical trials and others on the horizon, as well as recent advances in reproductive options. The introduction of massively parallel sequencing technologies has significantly advanced the identification of novel gene candidates and has expanded the landscape of genetic testing. In a relatively short time clinical medicine has progressed from limited testing options to a plethora of choices ranging from single-gene testing to whole-exome sequencing. This article outlines currently available genetic testing and factors to consider when selecting appropriate testing for patients with inherited retinal dystrophies.

  8. IK1-enhanced human-induced pluripotent stem cell-derived cardiomyocytes: an improved cardiomyocyte model to investigate inherited arrhythmia syndromes

    PubMed Central

    Vaidyanathan, Ravi; Markandeya, Yogananda S.; Kamp, Timothy J.; Makielski, Jonathan C.; January, Craig T.

    2016-01-01

    Currently available induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) do not ideally model cellular mechanisms of human arrhythmic disease due to lack of a mature action potential (AP) phenotype. In this study, we create and characterize iPS-CMs with an electrically mature AP induced by potassium inward rectifier (IK1) enhancement. The advantages of IK1-enhanced iPS-CMs include the absence of spontaneous beating, stable resting membrane potentials at approximately −80 mV and capability for electrical pacing. Compared with unenhanced, IK1-enhanced iPS-CMs calcium transient amplitudes were larger (P < 0.05) with a typical staircase pattern. IK1-enhanced iPS-CMs demonstrated a twofold increase in cell size and membrane capacitance and increased DNA synthesis compared with control iPS-CMs (P < 0.05). Furthermore, IK1-enhanced iPS-CMs expressing the F97C-CAV3 long QT9 mutation compared with wild-type CAV3 demonstrated an increase in AP duration and late sodium current. IK1-enhanced iPS-CMs represent a more mature cardiomyocyte model to study arrhythmia mechanisms. PMID:27059077

  9. IK1-enhanced human-induced pluripotent stem cell-derived cardiomyocytes: an improved cardiomyocyte model to investigate inherited arrhythmia syndromes.

    PubMed

    Vaidyanathan, Ravi; Markandeya, Yogananda S; Kamp, Timothy J; Makielski, Jonathan C; January, Craig T; Eckhardt, Lee L

    2016-06-01

    Currently available induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) do not ideally model cellular mechanisms of human arrhythmic disease due to lack of a mature action potential (AP) phenotype. In this study, we create and characterize iPS-CMs with an electrically mature AP induced by potassium inward rectifier (IK1) enhancement. The advantages of IK1-enhanced iPS-CMs include the absence of spontaneous beating, stable resting membrane potentials at approximately -80 mV and capability for electrical pacing. Compared with unenhanced, IK1-enhanced iPS-CMs calcium transient amplitudes were larger (P < 0.05) with a typical staircase pattern. IK1-enhanced iPS-CMs demonstrated a twofold increase in cell size and membrane capacitance and increased DNA synthesis compared with control iPS-CMs (P < 0.05). Furthermore, IK1-enhanced iPS-CMs expressing the F97C-CAV3 long QT9 mutation compared with wild-type CAV3 demonstrated an increase in AP duration and late sodium current. IK1-enhanced iPS-CMs represent a more mature cardiomyocyte model to study arrhythmia mechanisms. Copyright © 2016 the American Physiological Society.

  10. About Arrhythmia

    MedlinePlus

    ... early heart beat Tachycardia = very fast heart rate Ventricular Fibrillation = disorganized contraction of the lower chambers of the ... Atrial Fibrillation Bradycardia Conduction Disorders Premature Contractions Tachycardia Ventricular Fibrillation Other Rhythm Disorders Types of Arrhythmia in Children • ...

  11. The inherited ataxias: genetic heterogeneity, mutation databases, and future directions in research and clinical diagnostics.

    PubMed

    Hersheson, Joshua; Haworth, Andrea; Houlden, Henry

    2012-09-01

    The inherited cerebellar ataxias are a diverse group of clinically and genetically heterogeneous neurodegenerative disorders. Inheritance patterns of these disorders can be complex with autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance demonstrated by one or more ataxic syndromes. The broad range of mutation types found in inherited ataxia contributes to the complex genetic etiology of these disorders. The majority of inherited ataxias are caused by repeat expansions; however, conventional mutations are important causes of the rarer dominant and recessive ataxias. Advances in sequencing technology have allowed for much broader testing of these rare ataxia genes. This is relevant to the aims of the Human Variome Project, which aims to collate and store gene variation data through mutation databases. Variant data is currently located in a range of public and commercial resources. Few locus-specific databases have been created to catalogue variation in the dominant ataxia genes although there are several databases for some recessive genes. Developing these resources will facilitate a better understanding of the complex genotype-phenotype relationships in these disorders and assist interpretation of gene variants as testing for rarer ataxia genes becomes commonplace.

  12. Assessment of inherited colour vision defects in clinical practice.

    PubMed

    Cole, Barry L

    2007-05-01

    Colour vision deficiency (CVD) has a high prevalence and is often a handicap in everyday life. Those who have CVD will be better able to adapt and make more informed career choices, if they know about their deficiency. The fact that from 20 to 30 per cent of adults with abnormal colour vision do not know they have CVD suggests that colour vision is not tested as often as it should be. This may be because of practitioner uncertainty about which tests to use, how to interpret them and the advice that should be given to patients on the basis of the results. The purpose of this paper is to recommend tests for primary care assessment of colour vision and provide guidance on the advice that can be given to patients with CVD. The literature on colour vision tests and the relationship between the results of the tests and performance at practical colour tasks was reviewed. The colour vision tests that are most suitable for primary care clinical practice are the Ishihara test, the Richmond HRR 4th edition 2002 test, the Medmont C-100 test and the Farnsworth D15 test. These tests are quick to administer, give clear results and are easy to interpret. Tables are provided summarising how these tests should be interpreted, the advice that can be given to CVD patients on basis of the test results, and the occupations in which CVD is a handicap. Optometrists should test the colour vision of all new patients with the Ishihara and Richmond HRR (2002) tests. Those shown to have CVD should be assessed with the Medmont C-100 test and the Farnsworth D15 test and given appropriate advice based on the test results.

  13. Systems biology and cardiac arrhythmias.

    PubMed

    Grace, Andrew A; Roden, Dan M

    2012-10-27

    During the past few years, the development of effective, empirical technologies for treatment of cardiac arrhythmias has exceeded the pace at which detailed knowledge of the underlying biology has accumulated. As a result, although some clinical arrhythmias can be cured with techniques such as catheter ablation, drug treatment and prediction of the risk of sudden death remain fairly primitive. The identification of key candidate genes for monogenic arrhythmia syndromes shows that to bring basic biology to the clinic is a powerful approach. Increasingly sophisticated experimental models and methods of measurement, including stem cell-based models of human cardiac arrhythmias, are being deployed to study how perturbations in several biologic pathways can result in an arrhythmia-prone heart. The biology of arrhythmia is largely quantifiable, which allows for systematic analysis that could transform treatment strategies that are often still empirical into management based on molecular evidence.

  14. A comparison of heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major.

    PubMed

    Amoozgar, Hamid; Zeighami, Samaneh; Haghpanah, Sezaneh; Karimi, Mehran

    2017-01-01

    The goal of this study was to compare heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major. In this cross-sectional study, 60 patients with beta thalassemia major and 60 patients with beta thalassemia intermedia who had clinically no symptoms of arrhythmia and clinically normal heart function were evaluated using 24-hour ambulatory electrocardiogram monitoring and echocardiography. For data analysis SPSS ver.20 software was used. A P-value of less than 0.05 was considered statistically significant. The mean age of the beta thalassemia intermedia patients was 24.18 ± 7.9 years and the mean age in beta thalassemia major was 24.38 ± 7.7 years (P>0.05). Premature atrial contractions (PACs) were observed in 14 (23.3%) patients with beta thalassemia intermedia and in 22 (36.6%) beta thalassemia major patients. Premature ventricular contractions (PVCs) were detected in 8 (13.3%) patients in the beta thalassemia intermediate group and 16 (26.6) patients in the beta thalassemia major group, respectively. The left ventricular diastolic dimension, end-diastolic volume, and stroke volume were significantly higher in beta thalassemia intermedia group (P<0.05). Pulmonary acceleration time as an indicator of pulmonary pressure was lower in beta thalassemia intermedia group. Both atrial and ventricular arrhythmias were more common in the beta thalassemia major group. Higher end-diastolic volume and stroke volume were detected in the beta thalassemia intermedia group. Pulmonary acceleration time was lower in the beta thalassemia intermedia group, which can be an indicator of higher pulmonary pressure.

  15. Recurrences of symptoms after AV node re-entrant tachycardia ablation: a clinical arrhythmia risk score to assess putative underlying cause.

    PubMed

    Brembilla-Perrot, Béatrice; Sellal, Jean-Marc; Olivier, Arnaud; Manenti, Vladimir; Beurrier, Daniel; de Chillou, Christian; Villemin, Thibaut; Girerd, Nicolas

    2015-01-20

    To identify clinical factors associated with the probability for each arrhythmic mechanism causing recurring symptoms after atrioventricular nodal re-entrant tachycardia (AVNRT) ablation. Slow pathway radiofrequency ablation is used to treat AVNRT. After ablation, recurrence of symptoms due to AVNRT or other arrhythmias can occur. We studied 835 patients successfully treated with AVNRT ablation. Variables associated with each specific arrhythmia underlying symptom recurrence were studied by logistic regression. During a mean follow-up of 2.2 ± 2 years, 136 (16%) patients had a recurrence of symptoms. Following invasive and non-invasive studies, symptoms were mostly attributed to sinus tachycardia, recurrence of AVNRT and atrial arrhythmias (respectively 4.7%, 5.2% and 6.1%). Older age and history of atrial fibrillation were associated with a markedly increased risk of symptom recurrence due to atrial arrhythmias (OR=15.58, 7.09-35.22, p<0.001) whereas younger age was associated with a higher risk of sinus tachycardia. A simple 3-item clinical score based on age categories and atrial fibrillation history efficiently predicted atrial arrhythmia (C-Index=0.82, 0.75-0.89) and sinus tachycardia (C-Index=0.83, 0.75-0.90). 8.3% of patients with scores=0 had atrial arrhythmias whereas 100% of patients with scores ≥4 had atrial arrhythmias. While recurrence of symptoms after successful AVNRT ablation is relatively frequent (16%), true AVNRT recurrence accounts for only 1/3 of these recurrences. A simple clinical score based on age and history of atrial fibrillation enables efficient risk stratification for symptom recurrence attributable to atrial arrhythmias and inappropriate sinus tachycardia. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Chaos control of cardiac arrhythmias.

    PubMed

    Garfinkel, A; Weiss, J N; Ditto, W L; Spano, M L

    1995-01-01

    Chaos theory has shown that many disordered and erratic phenomena are in fact deterministic, and can be understood causally and controlled. The prospect that cardiac arrhythmias might be instances of deterministic chaos is therefore intriguing. We used a recently developed method of chaos control to stabilize a ouabain-induced arrhythmia in rabbit ventricular tissue in vitro. Extension of these results to clinically significant arrhythmias such as fibrillation will require overcoming the additional obstacles of spatiotemporal complexity.

  17. Effect of caffeine on ventricular arrhythmia: a systematic review and meta-analysis of experimental and clinical studies.

    PubMed

    Zuchinali, Priccila; Ribeiro, Paula A B; Pimentel, Maurício; da Rosa, Priscila R; Zimerman, Leandro I; Rohde, Luis E

    2016-02-01

    The relationship between caffeine consumption and the occurrence of arrhythmias remains controversial. Despite this lack of scientific evidence, counselling to reduce caffeine consumption is still widely advised in clinical practice. We conducted a systematical review and meta-analysis of interventional studies of the caffeine effects on ventricular arrhythmias. The search was performed on Pubmed, Embase, and Cochrane database, and terms related to coffee, caffeine, and cardiac arrhythmias were used. Methodological quality was assessed based on The Cochrane Collaboration recommendations and the ARRIVE guidelines. There were 2016 citations retrieved on the initial research. After full-text assessment, seven human and two animal studies were included in the meta-analysis. In animal studies, the main outcome reported was the ventricular fibrillation threshold. We observed a significant mean difference of -2.15 mA (95% CI -3.43 to -0.87; I(2) 0.0%, P for heterogeneity = 0.37). The main outcome evaluated in human studies was the rate of ventricular premature beats (VPBs). The overall relative risk for occurrence of VPBs in 24 h attributed to caffeine exposure was 1.00 (95% CI 0.94-1.06; I(2) 13.5%, P for heterogeneity = 0.32). Sensitivity analysis for caffeine dose, different designs, and subject profile was performed and no major differences were observed. Our meta-analysis demonstrates that data from human interventional studies do not show a significant effect of caffeine consumption on the occurrence of VBPs. The effects observed in animal studies are most probably the result of very high caffeine doses that are not regularly consumed in a daily basis by humans. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  18. Mutation databases for inherited renal disease: are they complete, accurate, clinically relevant, and freely available?

    PubMed

    Savige, Judy; Dagher, Hayat; Povey, Sue

    2014-07-01

    This study examined whether gene-specific DNA variant databases for inherited diseases of the kidney fulfilled the Human Variome Project recommendations of being complete, accurate, clinically relevant and freely available. A recent review identified 60 inherited renal diseases caused by mutations in 132 genes. The disease name, MIM number, gene name, together with "mutation" or "database," were used to identify web-based databases. Fifty-nine diseases (98%) due to mutations in 128 genes had a variant database. Altogether there were 349 databases (a median of 3 per gene, range 0-6), but no gene had two databases with the same number of variants, and 165 (50%) databases included fewer than 10 variants. About half the databases (180, 54%) had been updated in the previous year. Few (77, 23%) were curated by "experts" but these included nine of the 11 with the most variants. Even fewer databases (41, 12%) included clinical features apart from the name of the associated disease. Most (223, 67%) could be accessed without charge, including those for 50 genes (40%) with the maximum number of variants. Future efforts should focus on encouraging experts to collaborate on a single database for each gene affected in inherited renal disease, including both unpublished variants, and clinical phenotypes. © 2014 WILEY PERIODICALS, INC.

  19. Inherited cardiomyopathies mimicking arrhythmogenic right ventricular cardiomyopathy.

    PubMed

    Roberts, Jason D; Veinot, John P; Rutberg, Julie; Gollob, Michael H

    2010-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents an inherited cardiomyopathy that manifests clinically with malignant ventricular arrhythmias, sudden cardiac death, and less commonly heart failure. The condition is characterized by replacement of the myocardium, primarily of the right ventricle, with fibrofatty tissue. Extensive fibrofatty replacement of the myocardium has been previously thought to be pathognomonic of ARVC; however, this report details two other forms of inherited cardiomyopathy, namely hypertrophic cardiomyopathy (HCM) and the PRKAG2 cardiac syndrome, that were found to have significant fibrofatty myocardial replacement at pathologic examination. This report represents the first documentation of inherited cardiomyopathies mimicking ARVC and highlights the concept that other cardiac conditions can be associated with fibrofatty replacement of the myocardium. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Inherited cardiomyopathies: molecular genetics and clinical genetic testing in the postgenomic era.

    PubMed

    Teekakirikul, Polakit; Kelly, Melissa A; Rehm, Heidi L; Lakdawala, Neal K; Funke, Birgit H

    2013-03-01

    Inherited cardiomyopathies include hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular noncompaction, and restrictive cardiomyopathy. These diseases have a substantial genetic component and predispose to sudden cardiac death, which provides a high incentive to identify and sequence disease genes in affected individuals to identify pathogenic variants. Clinical genetic testing, which is now widely available, can be a powerful tool for identifying presymptomatic individuals. However, locus and allelic heterogeneity are the rule, as are clinical variability and reduced penetrance of disease in carriers of pathogenic variants. These factors, combined with genetic and phenotypic overlap between different cardiomyopathies, have made clinical genetic testing a lengthy and costly process. Next-generation sequencing technologies have removed many limitations such that comprehensive testing is now feasible, shortening diagnostic odysseys for clinically complex cases. Remaining challenges include the incomplete understanding of the spectrum of benign and pathogenic variants in the cardiomyopathy genes, which is a source of inconclusive results. This review provides an overview of inherited cardiomyopathies with a focus on their genetic etiology and diagnostic testing in the postgenomic era. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  1. Inherited Neuropathies

    PubMed Central

    Li, Jun

    2013-01-01

    With a prevalence of 1 in 2500 people, inherited peripheral nerve diseases, collectively called Charcot-Marie-Tooth disease (CMT), are among the most common inherited neurologic disorders. Patients with CMT typically present with chronic muscle weakness and atrophy in limbs, sensory loss in the feet and hands, and foot deformities. Clinical similarities between patients often require genetic testing to achieve a precise diagnosis. In this article, the author reviews the clinical and pathologic features of CMT, and demonstrates how electrodiagnostic and genetic tools are used to assist in the diagnosis and symptomatic management of the diseases. Several cases are presented to illustrate the diagnostic processes. PMID:23117945

  2. Intraoperative management of critical arrhythmia

    PubMed Central

    2017-01-01

    The incidence of intraoperative arrhythmia is extremely high, and some arrhythmias require clinical attention. Therefore, it is essential for the anesthesiologist to evaluate risk factors for arrhythmia and understand their etiology, electrophysiology, diagnosis, and treatment. Anesthetic agents reportedly affect normal cardiac electrical activity. In the normal cardiac cycle, the sinoatrial node initiates cardiac electrical activity through intrinsic autonomous pacemaker activity. Sequential atrial and ventricular contractions result in an effective cardiac pumping mechanism. Arrhythmia occurs due to various causes, and the cardiac pumping mechanism may be affected. A severe case may result in hemodynamic instability. In this situation, the anesthesiologist should eliminate the possible causes of arrhythmia and manage the condition, creating hemodynamic stability under proper electrocardiographic monitoring. PMID:28367281

  3. Clinical significance of second degree Wenckebach type sinoatrial block identified during Holter monitoring in patients with symptoms suggestive of arrhythmia.

    PubMed

    Kramarz, Elżbieta; Makowski, Karol

    2015-01-01

    To determine the clinical significance of the sinoatrial block II° of the Wenckebach type (block W) identified during Holter monitoring. The study included 300 patients (mean age 54 ± 17 years; 130 women) with symptoms suggestive of arrhythmia who underwent Holter monitoring. Block W was identified by a dedicated computer program and subsequently confirmed by a cardiologist. Block W was diagnosed in 88 patients (29%). It occurred only during sleep in 37 (12%) patients and during both daytime activity and sleep in 51 (17%) patients. Block W only during sleep happened predominately in young patients aged between 20 and 30 years, whereas episodes that occurred during both daytime and sleep were found mainly in patients between 60 and 70 years of age. Prospective observation time averaged 41 ± 11 months, and the time to the diagnosis of sinus node disease was 26 ± 10 months. Cox multivariate analyses showed that block W during both daytime and sleep is an independent predictor for the future diagnosis of sinus node disease [hazard ratio-13.6 (5.2-35.5); P < 0.0001]. Age-specific analyses confined this effect to the patients ≥50 years of age. The results also suggest that in patients ≥50 years of age block W during both daytime and sleep may be related to a significant improvement in survival [hazard ratio-0.03 (0.007-0.16); P < 0.0001]. Block W during daytime activity in patients with symptoms suggestive of arrhythmia indicates an increased likelihood of the future diagnosis of sinus node disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  4. The genomics of inherited bone marrow failure: from mechanism to the clinic.

    PubMed

    Wegman-Ostrosky, Talia; Savage, Sharon A

    2017-05-01

    The inherited bone marrow failure syndromes (IBMFS) typically present with significant cytopenias in at least one haematopoietic cell lineage that may progress to pancytopenia, and are associated with increased risk of cancer. Although the clinical features of the IBMFS are often diagnostic, variable disease penetrance and expressivity may result in diagnostic dilemmas. The discovery of the genetic aetiology of the IBMFS has been greatly facilitated by next-generation sequencing methods. This has advanced understanding of the underlying biology of the IBMFS and been essential in improving clinical management and genetic counselling for affected patients. Herein we review the clinical features, underlying biology, and new genomic discoveries in the IBMFS, including Fanconi anaemia, dyskeratosis congenita, Diamond Blackfan anaemia, Shwachman Diamond syndrome and some disorders of the myeloid and megakaryocytic lineages. 2017. This article is a U.S. Government work and is in the public domain in the USA.

  5. Inherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile.

    PubMed

    McDonnell, Aoibhinn; Schulman, Betsy; Ali, Zahid; Dib-Hajj, Sulayman D; Brock, Fiona; Cobain, Sonia; Mainka, Tina; Vollert, Jan; Tarabar, Sanela; Waxman, Stephen G

    2016-04-01

    Inherited erythromelalgia, the first human pain syndrome linked to voltage-gated sodium channels, is widely regarded as a genetic model of human pain. Because inherited erythromelalgia was linked to gain-of-function changes of sodium channel Na(v)1.7 only a decade ago, the literature has mainly consisted of reports of genetic and/or clinical characterization of individual patients. This paper describes the pattern of pain, natural history, somatosensory profile, psychosocial status and olfactory testing of 13 subjects with primary inherited erythromelalgia with mutations of SCN9A, the gene encoding Na(v)1.7. Subjects were clinically profiled using questionnaires, quantitative sensory testing and olfaction testing during the in-clinic phase of the study. In addition, a detailed pain phenotype for each subject was obtained over a 3-month period at home using diaries, enabling subjects to self-report pain attacks, potential triggers, duration and severity of pain. All subjects reported pain and heat in the extremities (usually feet and/or hands), with pain attacks triggered by heat or exercise and relieved mainly by non-pharmacological manoeuvres such as cooling. A large proportion of pain attacks (355/1099; 32%) did not involve a specific trigger. There was considerable variability in the number, duration and severity of pain attacks between subjects, even those carrying the same mutation within a family, and within individuals over the 12-13 week observation period. Most subjects (11/13) had pain between attacks. For these subjects, mean pain severity between pain attacks was usually lower than that during an attack. Olfaction testing using the Sniffin'T test did not demonstrate hyperosmia. One subject had evidence of orthostatic hypotension. Overall, there was a statistically significant correlation between total Hospital Anxiety and Depression Scale scores (P= 0.005) and pain between attacks and for Hospital Anxiety and Depression Scale Depression scores and pain

  6. [Maternal arrhythmias during pregnancy. Practical review].

    PubMed

    Kornacewicz-Jach, Zdzisława; Peregud-Pogorzelska, Małgorzata

    2014-01-01

    Pregnancy is accompanied by a variety of cardiovascular changes in normal women, and these changes can increased incidence of maternal cardiac arrhythmias. Supraventricular and ventricular arrhythmias reguiring treatment are rarely seen during pregnancy in healthy women. Structural cardiac defects or residual defects after repair may contribute to the occurrence of clinically relevant arrhythmias. Arrhythmias during pregnancy include a wide spectrum. The most common are simple ventricular and atrial ectopy, sinusal tachycardia and supraventricular tachycardia. The foetus may suffer both haemodynamic alternations and adverse effects of the treatment (teratogenic risk, foetal growth and development). The management of arrhythmias in pregnant women is similar to that taken in patients who are not pregnant.

  7. Common cardiac arrhythmias: recognition and treatment.

    PubMed

    Talmers, F N; Kinhal, V; Sabharwal, S; Weissler, A M

    1981-04-01

    Cardiac arrhythmias are commonly seen in the everyday practice of medicine by the physician. Although certain arrhythmias may be suspected clinically, precise diagnosis is made by electrocardiographic recording of the abnormal rhythm. Once the arrhythmia has been recorded, the next steps are proper electrocardiographic diagnosis and selection of proper treatment. The specific mode of therapy and the speed with which it is delivered will depend not only on the type of arrhythmia, but also on the hemodynamic consequences of the rhythm abnormality on the patient's cardiovascular system. The purpose of this paper is to discuss the electrocardiographic criteria of common cardiac arrhythmias as well as current concepts regarding therapy.

  8. Fetal cardiac arrhythmia detection and in utero therapy

    PubMed Central

    Strasburger, Janette F.; Wakai, Ronald T.

    2010-01-01

    The human fetal heart develops arrhythmias and conduction disturbances in response to ischemia, inflammation, electrolyte disturbances, altered load states, structural defects, inherited genetic conditions, and many other causes. Yet sinus rhythm is present without altered rate or rhythm in some of the most serious electrophysiological diseases, which makes detection of diseases of the fetal conduction system challenging in the absence of magnetocardiographic or electrocardiographic recording techniques. Life-threatening changes in QRS or QT intervals can be completely unrecognized if heart rate is the only feature to be altered. For many fetal arrhythmias, echocardiography alone can assess important clinical parameters for diagnosis. Appropriate treatment of the fetus requires awareness of arrhythmia characteristics, mechanisms, and potential associations. Criteria to define fetal bradycardia specific to gestational age are now available and may allow detection of ion channelopathies, which are associated with fetal and neonatal bradycardia. Ectopic beats, once thought to be entirely benign, are now recognized to have important pathologic associations. Fetal tachyarrhythmias can now be defined precisely for mechanism-specific therapy and for subsequent monitoring of response. This article reviews the current and future diagnostic techniques and pharmacologic treatments for fetal arrhythmia. PMID:20418904

  9. Categories of Arrhythmias

    MedlinePlus

    ... previous page En español Aneurysms and Dissections Angina Arrhythmia Bundle Branch Block Cardiomyopathy Carotid Artery Disease Chronic ... Cardiac Arrest Valve Disease Vulnerable Plaque Categories of Arrhythmias Arrhythmias are generally divided into two categories: ventricular ...

  10. Devices for Arrhythmia

    MedlinePlus

    ... Disease Venous Thromboembolism Aortic Aneurysm More Devices for Arrhythmia Updated:Dec 21,2016 In a medical emergency, ... This content was last reviewed September 2016. Printable Arrhythmia Information Sheets What is Arrhythmia? What is Atrial ...

  11. [Rational management of arrhythmias].

    PubMed

    González-Hermosillo, J A; Colín, L; Iturralde, P; Romero, L

    1990-01-01

    Despite the development of better diagnostic techniques and new modes of therapy, management of cardiac arrhythmias is still difficult. The lack of standardization in the indications of each technique has increased the risk of overtreatment and unnecessary cost. This paper describes the minimal requirements necessary for the different techniques and the appropriate information that should be collected from each. A well taken clinical history and a 12-lead EKG give very important information for the decision on when and how to treat.

  12. Diagnostics of Inherited Bleeding Disorders of Secondary Hemostasis: An Easy Guide for Routine Clinical Laboratories.

    PubMed

    Lippi, Giuseppe; Franchini, Massimo; Favaloro, Emmanuel J

    2016-07-01

    The investigation of inherited bleeding disorders of secondary hemostasis remains a challenge for most clinical laboratories, especially those that lack experience or specialized personnel. Bleeding can be essentially caused by a variety of acquired or congenital conditions, which impair either primary or secondary hemostasis. Since a universally agreed approach for the diagnostics of hemorrhagic disorders is still unavailable, this article aims to provide an easy guidance for routine clinical laboratories. This pragmatic approach to identifying and diagnosing inherited bleeding disorders of secondary hemostasis entails a multifaceted strategy, based on a collection of personal and family history, the results of first-line tests, which can then be followed by second- or third-line analyses to definitely establish the specific nature and the severity of the bleeding phenotype. Briefly, the presence of profound hemorrhages rather than mucocutaneous bleeding is suggestive of a disorder of secondary hemostasis. Although a positive family history is frequently reported in patients with congenital conditions, the lack of clinically meaningful symptoms in patient's relatives is not absolutely indicative of an acquired disorder. The next step encompasses the assessment of first-line coagulation tests (i.e., prothrombin time, activated partial thromboplastin time, and fibrinogen) if family history is not suggestive of a specific factor deficiency. The emergence of abnormal data of these assays and the variable combination of their results is then helpful to guide the performance of second-line tests, in particular specific factor assays, which will then provide a reasonable basis for a preliminary diagnosis. Third-line tests (namely, immunological assays of clotting factors and molecular biology) are then supportive for a final diagnosis and for identifying the nature of the factor deficiency (i.e., quantitative or functional). Thieme Medical Publishers 333 Seventh Avenue

  13. [Analysis of clinical phenotype and mode of inheritance in retinitis pigmentosa patients with consanguineous marriage].

    PubMed

    Rong, Wei-ning; Sheng, Xun-lun; Liu, Ya-ni

    2012-10-01

    To analyse the mode of inheritance and clinical characteristics of retinitis pigmentosa (RP) patients with consanguineous marriage. RP patients were recruited for this study in Ningxia Eye Hospital from September 2009 to July 2011. All patients received complete ophthalmic examination. The mode of inheritance were determined based on family history and marriage history. Clinical features were characterized by complete ophthalmic examinations including visual acuity, macular OCT, visual field and electroretinogram (ERG). A total of 143 individuals with RP (33 families) were recruited. Based on analysis of family history and marriage history, 20 RP families (23 patients) had consanguineous marriage history accounted for 60.6% RP families (16.1% RP patients). There were 4 patients (from 4 families) diagnosed as Usher syndrome. In 20 RP families with consanguineous marriage history, 7 families (35.0%) were Hui ethnicity and 13 families (65%) were Han ethnicity. The marriages of 15 families were between first cousins and 3 families were between second cousins, only 2 families were between half cousins matrimony. Of 23 RP patients, 12 were males and 11 were females. The average age of onset was 11.4 ± 6.8 years and the average age of recruitment was (32.0 ± 13.5) years. The best-corrected visual acuity was less than 0.6 in 78.2% patients. According to the features of the fundus, 13 patients were classical retinitis pigmentosa and 10 patients were retinitis pigmentosa sine pigmento. Visual field examination showed that all patients had varying degrees of peripheral visual field defect. Retinal neuroepithelial layer of macular and peripheral retina became thinner and retinal photoreceptors were disappeared. The average thickness of macular fovea was (186.1 ± 78.7) µm on right eyes and (187.4 ± 76.3) µm on left eyes. The incidence of RP with consanguineous marriages was high in Ningxia Region. The mode of inheritance of RP patients with consanguinity is autosomal

  14. A prospective 5-year study of the frequency of arrhythmias during serial exercise testing and clinical follow-up after Melody valve implant.

    PubMed

    Priromprintr, Bryant; Silka, Michael J; Rhodes, Jonathan; Batra, Anjan S

    2016-11-01

    Although percutaneous Melody valve implant has become an accepted alternative to surgical pulmonary valve replacement in patients with congenital heart disease, the benefit regarding frequency and severity of arrhythmias remains undefined. The purpose of this study was to evaluate the impact of Melody valve implant on the type and frequency of arrhythmias during cardiopulmonary exercise testing (CPET) and subsequent clinical outcome. As part of the phase I Melody valve clinical trial, 136 patients with congenital heart disease underwent prospective serial evaluation including CPET before implant, 6 months after implant, and annually thereafter for 5 years. Arrhythmias were defined as premature ventricular complexes (PVCs) and supraventricular or ventricular tachycardia (VT). Before Melody implant, PVCs occurred in 55 patients (40%) and nonsustained ventricular tachycardia (NSVT) in 1 patient during CPET. Median age at valve implantation was 19.0 years (range 7-53 years). During median follow-up of 4.9 years (range 0.8-7.3 years), there was no significant change in the proportion of patients with PVCs during CPET at any follow-up interval (40%-45%). However, postimplant, NSVT occurred in 18 patients, including 8 during CPET. Diagnoses in the patients with NSVT were tetralogy of Fallot (11), transposition (2), and post-Ross procedure (5). Improved hemodynamic status was not associated with resolution or prevention of arrhythmias. Despite improvement in hemodynamics, Melody valve implant was not associated with resolution or prevention of arrhythmias during CPET. PVCs or VT may be related to pathologic hypertrophy, fibrosis, dilation, or possible mechanical effects of the Melody device. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  15. The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease.

    PubMed

    Hendriksz, Christian J; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Klünemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Then Bergh, Florian; Topçu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A

    2017-05-01

    Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups ("clinical niches") have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Several clinical niches have been identified that harbor patients at increased risk of NP-C.

  16. Heterogeneity of Ventricular Sympathetic Nervous Activity is Associated with Clinically Relevant Ventricular Arrhythmia in Postoperative Patients with Tetralogy of Fallot.

    PubMed

    Ono, Shin; Ohuchi, Hideo; Miyazaki, Aya; Abe, Tadaaki; Kiso, Keisuke; Yamada, Osamu

    2015-10-01

    This study aimed to clarify whether there is an association between ventricular sympathetic nervous activity (SNA) and clinically relevant ventricular arrhythmia (a run of ≥ 3 consecutive ventricular beats, RVA) in postoperative patients with tetralogy of Fallot (TOF). We performed a retrospective study in a national referral center of pediatric cardiology in Japan. Twenty-four postoperative TOF patients (13 males, median age 17 years) undergoing myocardial (123)I metaiodobenzylguanidine (MIBG) scintigraphy were included. We measured the heart-to-mediastinum ratio (HMR) and washout ratio (WR) from planar MIBG myocardial scintigraphy. Tomographic images and polar maps were generated with 20 segments. The standard deviation of percentage uptake of 20 segments (SD-uptake) as an index of heterogeneous MIBG uptake to the ventricular myocardium was calculated. We compared these MIBG-derived variables with the patients' clinical profiles, including ECG findings and hemodynamics. Eight of 24 patients had RVA (RVA group), and the other 16 did not have RVA (non-RVA group). There were no significant differences in the HMR (1.9 ± 0.5 vs. 2.2 ± 0.4) and WR (50 ± 5 vs. 42 ± 10) between the two groups. SD-uptake was significantly higher in the RVA group than in the non-RVA group (15 ± 3 vs. 12 ± 3, p = 0.03). QT dispersion (ms) was also higher in the RVA group than in the non-RVA group (53 ± 23 vs. 44 ± 18, p = 0.04). Multivariate logistic regression showed that SD-uptake and QT dispersion were independent predictors in the RVA group (p = 0.02, p = 0.03). In addition to greater QT dispersion, heterogeneous SNA is associated with RVA in TOF patients postoperatively.

  17. Spectrum of Fascicular Arrhythmias.

    PubMed

    Sung, Raphael; Scheinman, Melvin

    2016-09-01

    Fascicular arrhythmias encompass a wide spectrum of ventricular arrhythmias that depend on the specialized conduction system of the right and left ventricles. These arrhythmias include premature ventricular complexes, monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, and ventricular fibrillation. These arrhythmias may be organized by mechanism, including intrafascicular reentry, interfascicular reentry, and focal. Mapping and ablation of the fascicular system can result in high cure rates of debilitating and potentially life-threatening arrhythmias. When approaching these arrhythmias, careful consideration of the structure of the His Purkinje system as well as their electrophysiologic properties may help guide even the most complex of arrhythmias.

  18. [Maternal cardiac arrhythmias in pregnancy].

    PubMed

    Facchini, M; Bauersfeld, U; Fasnacht, M; Candinas, R

    2000-12-23

    During pregnancy an increased incidence of maternal cardiac arrhythmias is observed. These include a wide spectrum, from clinically irrelevant isolated premature beats to debilitating supraventricular and ventricular tachycardias. In principle, management of arrhythmias during pregnancy is similar to that in non-pregnant patients. However, special consideration should be given to foetal age and potential teratogenic and haemodynamic adverse drug effects on the foetus. Therapeutic strategy should be guided by interdisciplinary consulting (i.e. cardiology, obstetrics, neonatology). Diagnostic evaluation must rule out underlying cardiovascular, pulmonary, endocrine or metabolic diseases. Additionally, precipitating factors such as excessive caffeine and/or alcohol ingestion and cigarette smoking should be avoided. For benign arrhythmias a conservative approach is appropriate. Antiarrhythmic drug selection depends on the specific arrhythmia being treated and the cardiac condition of the mother and the foetus. Some antiarrhythmic agents, such as propranolol, metoprolol, digoxin and quinidine, have been extensively tested during pregnancy and have proven to be safe; they should therefore, whenever possible, be used as firstline. For supraventricular tachycardia, intravenous adenosine may be used to terminate the arrhythmia if vagal manoeuvres fail. In emergency situations cardioversion may be performed with relative safety. Implantable cardioverter defibrillators as a preventive measure for life-threatening arrhythmias in pregnant patients do not seem to increase the risk of major complications.

  19. Induced pluripotent stem cells in the inherited cardiomyopathies: From disease mechanisms to novel therapies.

    PubMed

    Ross, Samantha Barratt; Fraser, Stuart T; Semsarian, Christopher

    2016-11-01

    Inherited cardiomyopathies lead to diverse clinical outcomes including heart failure, arrhythmias, and sudden death. Mutations in over 100 genes have been implicated in the pathogenesis of genetic heart diseases, including the main inherited cardiomyopathies, such as hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathies. Understanding how these gene mutations lead to clinical disease and the various secondary genetic and environmental factors, which may modify the clinical phenotype, are key areas of research ultimately influencing diagnosis and management of patients. The emergence of patient-derived induced pluripotent stem cells (iPSCs), which can be differentiated into functional cardiomyocytes (CMs) in vitro, may provide an exciting new approach to understand disease mechanisms underpinning inherited heart diseases. This review will focus specifically on the key role of iPSC-based studies in the inherited cardiomyopathies, both in their potential utility as well as the significant challenges they present. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Inherited genetic markers for thrombophilia in northeastern Iran (a clinical-based report)

    PubMed Central

    Keify, Fatemeh; Azimi-Nezhad, Mohsen; Zhiyan-abed, Narges; Nasseri, Mojila; Abbaszadegan, Mohammad Reza

    2014-01-01

    Background: Thrombophilia is a main predisposition to thrombosis due to a procoagulant state. Several point mutations play key roles in blood-clotting disorders, which are grouped under the term thrombophilia. These thrombophilic mutations are methylenetetrahydrofolate reductase (MTHFR, C677T, and A1298C), factor V Leiden (G1691A), prothrombin gene mutation (factor II, G20210A), and plasminogen activator inhibitor (PAI). In the present study, we assessed the prevalence of the above thrombophilia markers in patients with recurrent pregnancy loss or first and second trimester abortions, infertility, and failed in vitro fertilization (IVF). Methods: This study was conducted among 457 cases those were referred to detect the inherited genetic markers for thrombophilia. Markers for MTHFR, Factor II, and Factor V were assessed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and PAI was assessed by Amplification Refractory Mutation System (ARMS-PCR). Results: Two hundred sixty cases (56.89%) were diagnosed as having at least one thrombophilia marker, whereas 197 cases (43.11%) had no thrombophilia markers and were normal. Conclusion: According to the current study, the pattern of abnormal genetic markers for thrombophilia in northeastern Iran demonstrates the importance of genetic evaluations in patients who show clinical abnormalities with recurrent spontaneous abortion (RSA) or other serious obstetric complications. PMID:26989725

  1. The clinical implications of molecular monitoring and analyses of inherited retinal diseases.

    PubMed

    Chacón-Camacho, Oscar F; García-Montaño, Leopoldo A; Zenteno, Juan C

    2017-11-01

    Retinal dystrophies (RDs) are the most common cause of inherited blindness and one of the most genetically heterogeneous human diseases. RDs arise from mutations in genes involved in development and function of photoreceptors or other retinal cells. Identification of the genetic defect causing RD allows accurate diagnosis, prognosis, and counseling in affected patients. Molecular diagnosis is a tremendous challenge in RDs due to their locus and phenotypic heterogeneity. As conventional DNA sequencing approaches are impractical in such situation, Next Generation Sequencing (NGS)-based protocols are needed to identify RD-causing mutations. This is being accomplished by sequencing RD gene panels or by whole exome or whole genome sequencing approaches. Areas covered: This review discusses the current strategies for molecular diagnosis in RDs including their advantages and limitations, as well as their utility in diagnosis of non-syndromic versus syndromic RDs. Results of ongoing gene therapy protocols in RDs are also presented. Expert commentary: Molecular diagnosis in RD improves the medical management of patients. Importantly, demand for molecular screening for RDs is greatly expanding not only as a result of increasing development and availability of NGS technologies, but also of the growing number of gene-based clinical trials offering a potential treatment to patients.

  2. Clinical, cytogenetic, environmental and inheritance findings in Mexican neonates with VACTERL association.

    PubMed

    Salinas-Torres, Victor M; Pérez-García, Nicolás; Pérez-García, Guillermo

    2015-01-01

    In this series the authors evaluate clinical, cytogenetic, environmental and inheritance characteristics of neonates with VACTERL association. Twenty-six patients were diagnosed with VACTERL association and had a normal somatometric profile. Fifty-eight percent cases were males. The frequency of each component was: vertebral defects (V), 77 %; anal atresia (A), 62 %; tracheo-esophageal fistula/esophageal atresia (TEF/EA), 58 %; renal anomalies (R), 58 %; limb abnormalities (L), 50 %, and cardiac malformations (C), 42 %. The most frequent combination was VAR (n = 3). Sixteen patients had non-VACTERL anomalies such as bilateral cryptorchidism (n = 4). Two probands (8 %) had first or second-degree relatives with two components. Five patients (19 %) had environmental factors that interacted with occurrence of VACTERL association. All patients had a normal karyotype. This study contributes to a better characterization of VACTERL phenotype in neonatal period. In spite of predominant sporadic occurrence, underlying genetic susceptibility and environmental influences point to a complex interplay between genes and environmental factors in VACTERL association.

  3. Why Arrhythmia Matters

    MedlinePlus

    ... cardiac arrest Arrhythmias can cause stroke ( View an animation of arrhythmia ) Stroke is a cerebrovascular disease that ... and Live Our Interactive Cardiovascular Library has detailed animations and illustrations to help you learn about conditions, ...

  4. Cardiac arrhythmias in pregnancy.

    PubMed

    Knotts, Robert J; Garan, Hasan

    2014-08-01

    As more women with repaired congenital heart disease survive to their reproductive years and many other women are delaying pregnancy until later in life, a rising concern is the risk of cardiac arrhythmias during pregnancy. Naturally occurring cardiovascular changes during pregnancy increase the likelihood that a recurrence of a previously experienced cardiac arrhythmia or a de novo arrhythmia will occur. Arrhythmias should be thoroughly investigated to determine if there is a reversible etiology, and risks/benefits of treatment options should be fully explored. We discuss the approach to working up and treating various arrhythmias during pregnancy with attention to fetal and maternal risks as well as treatment of fetal arrhythmias. Acute management in stable patients includes close monitoring and intravenous pharmacologic therapy, while DC cardioversion should be used to terminate arrhythmias in hemodynamically unstable patients. Long-term management may require continued oral antiarrhythmic therapy, with particular attention to fetal safety, to prevent complications associated with arrhythmias.

  5. Prevention and Treatment of Arrhythmia

    MedlinePlus

    ... Venous Thromboembolism Aortic Aneurysm More Prevention & Treatment of Arrhythmia Updated:Dec 21,2016 Do you need treatment? ... Trials . This content was last reviewed September 2016. Arrhythmia • Home • About Arrhythmia • Why Arrhythmia Matters • Understand Your ...

  6. Understand Your Risk for Arrhythmia

    MedlinePlus

    ... Thromboembolism Aortic Aneurysm More Understand Your Risk for Arrhythmia Updated:Dec 21,2016 Expected changes in heart ... spirits.) This content was last reviewed September 2016. Arrhythmia • Home • About Arrhythmia • Why Arrhythmia Matters • Understand Your ...

  7. Can inherited thrombophilia modulate the clinical phenotype of patients with antiphospholipid syndrome?

    PubMed

    Berman, Horacio; Ugarte-Gil, Manuel F; Espinosa, Gerard; Tàssies, Dolors; Monteagudo, Joan; Reverter, Joan Carles; Cervera, Ricard

    2013-01-01

    The current case-control study was aimed to determine the prevalence and the clinical significance of inherited thrombophilia - factor V Leiden and G20210A prothrombin polymorphisms - in patients with antiphospholipid syndrome (APS). 100 patients with APS (77 with primary APS and 23 with systemic lupus erythematosus [SLE]-APS), and 100 patients with first lower extremity deep venous thrombosis (DVT), and 200 healthy individuals as a control groups were analysed. Patients and control group were tested for factor V Leiden and prothrombin G20210A gene polymorphism. Factor V Leiden variant was found in 1% of APS patients, in 3% of healthy individuals (p=0.49), and 16% of patients with first DVT (p<0.0005). Prothrombin gene polymorphism was found in 6% of APS patients and in 2.5% of healthy subjects (p=0.21), and 13% of patients with DVT (p=0.14). In primary APS patients, factor V Leiden was present in 1.3% (1/77) and prothrombin gene polymorphism in 6.5% (5/77). No patient with SLE-APS had factor V Leiden and prothrombin gene variant was present in only one patient (4.3%). Patients with prothrombin polymorphism had higher prevalence of venous thrombosis, with no statistical significance (80% vs. 47.9%, p=0.35). There were no differences in the prevalence of recurrent thrombosis before or after APS diagnosis in patients with or without prothrombin gene polymorphism. Factor V Leiden and G20210A prothrombin variant seem to play no role in either the development of APS or in the type of involved vessel, with no increased risk of re-thrombosis during follow-up.

  8. Ranolazine Therapy in Cardiac Arrhythmias.

    PubMed

    Pulford, Brian R; Kluger, Jeffrey

    2016-09-01

    Ranolazine is an antianginal medication originally granted approval by the U.S. Food and Drug Administration for therapeutic use in 2006. Since its introduction into the U.S. market, there have been multiple trials and clinical case reports that demonstrate ranolazine may be effective in the prevention and treatment of both atrial and ventricular arrhythmias, including postoperative atrial fibrillation following coronary artery bypass graft (CABG) surgery. More recently, the combination of dronedarone with ranolazine has demonstrated in initial studies to have a synergistic effect in the reduction of burden of atrial fibrillation. This article will review the basic pharmacology of ranolazine, the studies demonstrating use of ranolazine in atrial and ventricular arrhythmias, the limitations to the use of ranolazine as antiarrhythmic therapy, and explore the synergistic effect with other agents in the suppression of arrhythmias.

  9. Almanac 2013: cardiac arrhythmias and pacing--an editorial overview of selected research that has driven recent advances in clinical cardiology.

    PubMed

    Liew, Reginald

    2014-04-01

    Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection, risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF. Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms, many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management.This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing.

  10. Analyses of Genetic and Clinical Parameters for Screening Patients With Inherited Thrombocytopenia with Small or Normal-Sized Platelets.

    PubMed

    Ouchi-Uchiyama, Meri; Sasahara, Yoji; Kikuchi, Atsuo; Goi, Kumiko; Nakane, Takaya; Ikeno, Mitsuru; Noguchi, Yasushi; Uike, Naokuni; Miyajima, Yuji; Matsubara, Kousaku; Koh, Katsuyoshi; Sugita, Kanji; Imaizumi, Masue; Kure, Shigeo

    2015-12-01

    Childhood thrombocytopenias include immune thrombocytopenic purpura (ITP) and inherited thrombocytopenia; the former is caused by autoantibodies to platelets, whereas the latter can be distinguished by platelet size and underlying genetic mutations. Due to limited methods for the definite diagnosis of ITP, genetic and clinical parameters are required for diagnosing inherited thrombocytopenias with small or normal-sized platelets. In total, 32 Japanese patients with thrombocytopenia with small or normal-sized platelets from 29 families were enrolled. All the patients were under 20 years of age, with family histories of early-onset thrombocytopenia and/or poor response to conventional therapies for ITP. Genotypes and clinical parameters were retrospectively evaluated according to the disease type. Twelve cases of inherited thrombocytopenia were observed. We identified chromosomal deletions within the WASP gene in two patients with Wiskott-Aldrich syndrome; a missense mutation in a patient with X-linked thrombocytopenia; and mutations in the RUNX1 gene of five patients with familial platelet disorder with propensity to acute myelogenous leukemia, and in the ANKRD26 gene of four patients with autosomal dominant thrombocytopenia-2. All 12 carried germline mutations, three of which were de novo. Furthermore, we observed significantly elevated serum thrombopoietin (TPO) levels and dysplasia of megakaryocytes in patients carrying the RUNX1 and ANKRD26 mutations. Genetic analyses and detection of TPO levels and dysmegakaryopoiesis were clinically useful for screening patients with inherited thrombocytopenias, irrespective of the family history. We hypothesize that the WASP, RUNX1, and ANKRD26 genes are important for normal TPO signaling and the network underlying thrombopoiesis. © 2015 Wiley Periodicals, Inc.

  11. Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial.

    PubMed

    Zuchinali, Priccila; Souza, Gabriela C; Pimentel, Maurício; Chemello, Diego; Zimerman, André; Giaretta, Vanessa; Salamoni, Joyce; Fracasso, Bianca; Zimerman, Leandro I; Rohde, Luis E

    2016-12-01

    The presumed proarrhythmic action of caffeine is controversial. Few studies have assessed the effect of high doses of caffeine in patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias. To compare the effect of high-dose caffeine or placebo on the frequency of supraventricular and ventricular arrhythmias, both at rest and during a symptom-limited exercise test. Double-blinded randomized clinical trial with a crossover design conducted at the heart failure and cardiac transplant clinic of a tertiary-care university hospital. The trial included patients with chronic heart failure with moderate-to-severe systolic dysfunction (left ventricular ejection fraction <45%) and New York Heart Association functional class I to III between March 5, 2013, and October 2, 2015. Caffeine (100 mg) or lactose capsules, in addition to 5 doses of 100 mL decaffeinated coffee at 1-hour intervals, for a total of 500 mg of caffeine or placebo during a 5-hour protocol. After a 1-week washout period, the protocol was repeated. Number and percentage of ventricular and supraventricular premature beats assessed by continuous electrocardiographic monitoring. We enrolled 51 patients (37 [74%] male; mean [SD] age, 60.6 [10.9] years) with predominantly moderate-to-severe left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 29% [7%]); 31 [61%] had an implantable cardioverter-defibrillator device. No significant differences between the caffeine and placebo groups were observed in the number of ventricular (185 vs 239 beats, respectively; P = .47) and supraventricular premature beats (6 vs 6 beats, respectively; P = .44), as well as in couplets, bigeminal cycles, or nonsustained tachycardia during continuous electrocardiographic monitoring. Exercise test-derived variables, such as ventricular and supraventricular premature beats, duration of exercise, estimated peak oxygen consumption, and heart rate

  12. Systematic review of pregnancy in women with inherited cardiomyopathies.

    PubMed

    Krul, Sébastien P J; van der Smagt, Jasper J; van den Berg, Maarten P; Sollie, Krystyna M; Pieper, Petronella G; van Spaendonck-Zwarts, Karin Y

    2011-06-01

    Pregnancy exposes women with inherited cardiomyopathies to increased risk for heart failure and arrhythmias. In this paper, we review the clinical course and management of pregnant women with the following inherited cardiomyopathies: hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular non-compaction cardiomyopathy, and restrictive cardiomyopathy. We also discuss peripartum cardiomyopathy. Pregnancy is generally well tolerated in asymptomatic patients with inherited cardiomyopathies. However, worsening of the clinical condition can occur during pregnancy, despite intensive medical treatment. If prior cardiac events, poor functional class (New York Heart Association class III or IV), or advanced left ventricular systolic dysfunction are present, the risk of maternal cardiac complications during pregnancy are markedly increased. The postpartum condition is generally no worse than the antepartum condition, but no long-term follow-up studies have been reported. Preconception evaluation and counselling are important aspects of managing women with inherited cardiomyopathies. Genetic counselling and DNA testing should be offered to all women following the diagnosis of an inherited cardiomyopathy.

  13. Use of Whole Exome Sequencing for the Identification of Ito-Based Arrhythmia Mechanism and Therapy

    PubMed Central

    Sturm, Amy C; Kline, Crystal F; Glynn, Patric; Johnson, Benjamin L; Curran, Jerry; Kilic, Ahmet; Higgins, Robert S D; Binkley, Philip F; Janssen, Paul M L; Weiss, Raul; Raman, Subha V; Fowler, Steven J; Priori, Silvia G; Hund, Thomas J; Carnes, Cynthia A; Mohler, Peter J

    2015-01-01

    Background Identified genetic variants are insufficient to explain all cases of inherited arrhythmia. We tested whether the integration of whole exome sequencing with well-established clinical, translational, and basic science platforms could provide rapid and novel insight into human arrhythmia pathophysiology and disease treatment. Methods and Results We report a proband with recurrent ventricular fibrillation, resistant to standard therapeutic interventions. Using whole-exome sequencing, we identified a variant in a previously unidentified exon of the dipeptidyl aminopeptidase-like protein-6 (DPP6) gene. This variant is the first identified coding mutation in DPP6 and augments cardiac repolarizing current (Ito) causing pathological changes in Ito and action potential morphology. We designed a therapeutic regimen incorporating dalfampridine to target Ito. Dalfampridine, approved for multiple sclerosis, normalized the ECG and reduced arrhythmia burden in the proband by >90-fold. This was combined with cilostazol to accelerate the heart rate to minimize the reverse-rate dependence of augmented Ito. Conclusions We describe a novel arrhythmia mechanism and therapeutic approach to ameliorate the disease. Specifically, we identify the first coding variant of DPP6 in human ventricular fibrillation. These findings illustrate the power of genetic approaches for the elucidation and treatment of disease when carefully integrated with clinical and basic/translational research teams. PMID:26015324

  14. Cardiac arrhythmias in paediatric practice.

    PubMed

    Chan, K Y; Loke, K Y; Yip, W C; Tay, J S

    1989-01-01

    Clinical data of patients with cardiac arrhythmias managed between May 1986 and March 1988 were reviewed to determine their mode of presentation and clinical course. Of the 5,768 admissions, 62 (1.07%) patients had arrhythmias. During the same period, 21 patients were managed as outpatients with 13 being new referrals. Thirty-eight patients had undergone corrective cardiac procedures, 8 others had congenital heart lesions, 3 were associated with acquired cardiac pathology and the remaining had isolated arrhythmias. The cardiac arrhythmias were: right bundle branch block 36, premature atrial and ventricular contractions 15, supraventricular tachycardia (SVT) 15, atrioventricular (AV) block 7, sinus bradycardia 3, atrial fibrillation 2, ventricular tachycardia and fibrillation 2, Wolff-Parkinson-White syndrome without SVT 2, bradytachyarrhythmia 1. There were 3 patients with foetal SVT, one persisting till day 1. High grade AV block occurred in 2 patients post-surgically and needed pacing. Only 2 others were symptomatic. Other than the 38 patients who underwent corrective procedures (2 had balloon valvuloplasty for pulmonary stenosis), 8 others had structural heart disease. There was 1 sudden death and 5 died from their primary heart disease.

  15. [Late potentials and ventricular arrhythmia].

    PubMed

    Adamec, R; Zimmermann, M

    1986-04-01

    When electrodes are placed at the surface of the thorax, high-amplification electrocardiography (HA-ECG) combined with signal summation as a function of time provides a non-invasive method for detecting electric potentials occurring after the QRS complex of the clinical electrocardiogram. These potentials are called late, and can probably be likened to the "divided" or "fragmented" potentials recorded directly on the heart or in its ventricles near zones of ischemia, infarction or aneurysm. The prevalence of late potentials of ventricular activation (LPVA) and their association with the occurrence of ventricular arrhythmias seems well established, notably in the presence of ventricular aneurysm and anamnesis of severe ventricular arrhythmia. Some studies have shown that detection of LPVAs is of value in identifying heart patients at risk of ventricular arrhythmia or sudden death. Heart disease aside, the presence of LPVAs has been demonstrated in arrhythmogenic right ventricular dysplasia and reported in Fallot's tetralogy after complete correction. A standardization of recordings and a more precise definition of LPVAs are necessary before HA-ECG can become a routine clinical method. Further, the possibility of "beat by beat" recordings with "spatial" summation will allow detection of LPVAs which vary with time and in nature and hence provide a better understanding of the genesis of ventricular arrhythmias.

  16. Arrhythmias in peripartum cardiomyopathy.

    PubMed

    Honigberg, Michael C; Givertz, Michael M

    2015-06-01

    Peripartum cardiomyopathy (PPCM) is a complication of late pregnancy and the early postpartum period characterized by dilated cardiomyopathy and heart failure with reduced ejection fraction. Approximately half of women fail to recover left ventricular function. Standard management of heart failure is indicated, with some exceptions for women who are predelivery or breastfeeding. Atrial and ventricular arrhythmias are reported in PPCM, but the frequency of arrhythmias in this condition is not well characterized. Management of PPCM-associated arrhythmias may include antiarrhythmic drugs, catheter ablation, and wearable or implantable cardioverter-defibrillators. Further research is needed on the prevalence, natural history, and optimal management of arrhythmias in PPCM.

  17. Cardiac arrhythmias during or after epileptic seizures.

    PubMed

    van der Lende, Marije; Surges, Rainer; Sander, Josemir W; Thijs, Roland D

    2016-01-01

    Seizure-related cardiac arrhythmias are frequently reported and have been implicated as potential pathomechanisms of Sudden Unexpected Death in Epilepsy (SUDEP). We attempted to identify clinical profiles associated with various (post)ictal cardiac arrhythmias. We conducted a systematic search from the first date available to July 2013 on the combination of two terms: 'cardiac arrhythmias' and 'epilepsy'. The databases searched were PubMed, Embase (OVID version), Web of Science and COCHRANE Library. We attempted to identify all case reports and case series. We identified seven distinct patterns of (post)ictal cardiac arrhythmias: ictal asystole (103 cases), postictal asystole (13 cases), ictal bradycardia (25 cases), ictal atrioventricular (AV)-conduction block (11 cases), postictal AV-conduction block (2 cases), (post)ictal atrial flutter/atrial fibrillation (14 cases) and postictal ventricular fibrillation (3 cases). Ictal asystole had a mean prevalence of 0.318% (95% CI 0.316% to 0.320%) in people with refractory epilepsy who underwent video-EEG monitoring. Ictal asystole, bradycardia and AV-conduction block were self-limiting in all but one of the cases and seen during focal dyscognitive seizures. Seizure onset was mostly temporal (91%) without consistent lateralisation. Postictal arrhythmias were mostly found following convulsive seizures and often associated with (near) SUDEP. The contrasting clinical profiles of ictal and postictal arrhythmias suggest different pathomechanisms. Postictal rather than ictal arrhythmias seem of greater importance to the pathophysiology of SUDEP.

  18. Increased Myofilament Ca2+-Sensitivity and Arrhythmia Susceptibility

    PubMed Central

    Huke, Sabine; Knollmann, Bjorn C.

    2010-01-01

    Increased myofilament Ca2+ sensitivity, a common attribute of inherited and acquired cardiomyopathies, is often associated with cardiac arrhythmias. Accumulating evidence supports that increased myofilament Ca2+ sensitivity is an independent risk factor for arrhythmias, but the underlying molecular mechanism remains unclear. This review focuses on potential mechanisms how myofilament Ca2+ sensitivity may affect cardiac excitation and leads to the generation of arrhythmias. We discuss in detail the downstream effects of increased myofilament Ca2+ sensitivity, i.e. altered Ca2+ buffering/handling, impaired energy metabolism and increased mechanical stretch, and how they may contribute to the proarrhythmic effect. PMID:20097204

  19. Rationale, objectives, and design of the EUTrigTreat clinical study: a prospective observational study for arrhythmia risk stratification and assessment of interrelationships among repolarization markers and genotype

    PubMed Central

    Seegers, Joachim; Vos, Marc A.; Flevari, Panagiota; Willems, Rik; Sohns, Christian; Vollmann, Dirk; Lüthje, Lars; Kremastinos, Dimitrios T.; Floré, Vincent; Meine, Mathias; Tuinenburg, Anton; Myles, Rachel C.; Simon, Dirk; Brockmöller, Jürgen; Friede, Tim; Hasenfuß, Gerd; Lehnart, Stephan E.; Zabel, Markus

    2012-01-01

    Aims The EUTrigTreat clinical study has been designed as a prospective multicentre observational study and aims to (i) risk stratify patients with an implantable cardioverter defibrillator (ICD) for mortality and shock risk using multiple novel and established risk markers, (ii) explore a link between repolarization biomarkers and genetics of ion (Ca2+, Na+, K+) metabolism, (iii) compare the results of invasive and non-invasive electrophysiological (EP) testing, (iv) assess changes of non-invasive risk stratification tests over time, and (v) associate arrythmogenomic risk through 19 candidate genes. Methods and results Patients with clinical ICD indication are eligible for the trial. Upon inclusion, patients will undergo non-invasive risk stratification, including beat-to-beat variability of repolarization (BVR), T-wave alternans, T-wave morphology variables, ambient arrhythmias from Holter, heart rate variability, and heart rate turbulence. Non-invasive or invasive programmed electrical stimulation will assess inducibility of ventricular arrhythmias, with the latter including recordings of monophasic action potentials and assessment of restitution properties. Established candidate genes are screened for variants. The primary endpoint is all-cause mortality, while one of the secondary endpoints is ICD shock risk. A mean follow-up of 3.3 years is anticipated. Non-invasive testing will be repeated annually during follow-up. It has been calculated that 700 patients are required to identify risk predictors of the primary endpoint, with a possible increase to 1000 patients based on interim risk analysis. Conclusion The EUTrigTreat clinical study aims to overcome current shortcomings in sudden cardiac death risk stratification and to answer several related research questions. The initial patient recruitment is expected to be completed in July 2012, and follow-up is expected to end in September 2014. Clinicaltrials.gov identifier: NCT01209494. PMID:22117037

  20. Panel-based testing for inherited colorectal cancer: a descriptive study of clinical testing performed by a US laboratory.

    PubMed

    Cragun, D; Radford, C; Dolinsky, J S; Caldwell, M; Chao, E; Pal, T

    2014-12-01

    Next-generation sequencing enables testing for multiple genes simultaneously ('panel-based testing') as opposed to sequential testing for one inherited condition at a time ('syndrome-based testing'). This study presents results from patients who underwent hereditary colorectal cancer (CRC) panel-based testing ('ColoNext(™) '). De-identified data from a clinical testing laboratory were used to calculate (1) frequencies for patient demographic, clinical, and family history variables and (2) rates of pathogenic mutations and variants of uncertain significance (VUS). The proportion of individuals with a pathogenic mutation who met national syndrome-based testing criteria was also determined. Of 586 patients, a pathogenic mutation was identified in 10.4%, while 20.1% had at least one VUS. After removing eight patients with CHEK2 mutations and 11 MUTYH heterozygotes, the percentage of patients with 'actionable' mutations that would clearly alter cancer screening recommendations per national guidelines decreased to 7.2%. Of 42 patients with an 'actionable' result, 30 (71%) clearly met established syndrome-based testing guidelines. This descriptive study is among the first to report on a large clinical series of patients undergoing panel-based testing for inherited CRC. Results are discussed in the context of benefits and concerns that have been raised about panel-based testing implementation.

  1. Methadone overdose and cardiac arrhythmia potential: findings from a review of the evidence for an American Pain Society and College on Problems of Drug Dependence clinical practice guideline.

    PubMed

    Chou, Roger; Weimer, Melissa B; Dana, Tracy

    2014-04-01

    The number of deaths associated with methadone use increased dramatically in parallel with marked increases in its use, particularly for treatment of chronic pain. To develop a clinical guideline on methadone prescribing to reduce potential harms, the American Pain Society commissioned a review of various aspects related to methadone safety. This article summarizes evidence related to unintentional overdose due to methadone and harms related to cardiac arrhythmia potential. We searched Ovid MEDLINE, the Cochrane Library, and PsycINFO databases through January 2014 for studies assessing harms associated with methadone use; we judged 70 studies to be relevant and to meet inclusion criteria. The majority of studies on overdose and cardiac arrhythmia risk are observational and provide weak evidence on which to base clinical guidelines. In patients prescribed methadone for treatment of opioid dependence, data suggest that mortality benefits related to reduction in illicit drug use outweigh harms. Despite epidemiologic data showing marked increases in the numbers of methadone-related deaths that have been primarily attributed to increased use of methadone for chronic pain, evidence on methadone and mortality risk in this population has been somewhat contradictory. There is some evidence that recent initiation of methadone, psychiatric admissions, and concomitant use of benzodiazepines are associated with a higher risk for overdose. Evidence on cardiac risks is primarily limited to case reports of torsades de pointes, primarily in patients on high doses of methadone, and to studies showing an association between methadone use and prolongation of QTc intervals. Research is needed to understand the effectiveness of dosing methods, electrocardiogram monitoring, and other risk mitigation strategies in patients prescribed methadone. This systematic review synthesizes the evidence related to methadone use and risk for overdose and cardiac arrhythmia. Findings regarding the

  2. Overview of fetal arrhythmias

    PubMed Central

    Srinivasan, Shardha; Strasburger, Janette

    2012-01-01

    Purpose of review Though fetal arrhythmias account for a small proportion of referrals to a fetal cardiologist, they may be associated with significant morbidity and mortality. The present review outlines the current literature with regard to the diagnosis and, in brief, some management strategies in fetal arrhythmias. Recent findings Advances in echocardiography have resulted in significant improvements in our ability to elucidate the mechanism of arrhythmia at the bedside. At the same time, fetal magnetocardiography is broadening our understanding of mechanisms of arrhythmia especially as it pertains to ventricular arrhythmias and congenital heart block. It provides a unique window to study electrical properties of the fetal heart, unlike what has been available to date. Recent reports of bedside use of fetal ECG make it a promising new technology. The underlying mechanisms resulting in immune-mediated complete heart block in a small subset of ‘at-risk’ fetuses is under investigation. Summary There have been great strides in noninvasive diagnosis of fetal arrhythmias. However, we still need to improve our knowledge of the electromechanical properties of the fetal heart as well as the mechanisms of arrhythmia to further improve outcomes. Multiinstitutional collaborative studies are needed to help answer some of the questions regarding patient, drug selection and management algorithms. PMID:18781114

  3. Prediction of very late arrhythmia recurrence after radiofrequency catheter ablation of atrial fibrillation: The MB-LATER clinical score.

    PubMed

    Mujović, Nebojša; Marinković, Milan; Marković, Nebojša; Shantsila, Alena; Lip, Gregory Y H; Potpara, Tatjana S

    2017-01-20

    Reliable prediction of very late recurrence of atrial fibrillation (VLRAF) occuring >12 months after catheter ablation (CA) in apparently "cured" patients could optimize long-term follow-up and modify decision-making regarding the discontinuation of oral anticoagulant therapy. In a single-centre cohort of consecutive patients post radiofrequency AFCA, we retrospectively derived a novel score for VLRAF prediction. Of 133 consecutive post AFCA patients (mean age 56.9 ± 11.8 years, 63.9% male, 69.2% with paroxysmal AF) who were arrhythmia-free at 12 months (excluding 3-month "blanking period"), 20 patients expirienced a VLRAF during a 29.1 ± 10.1-month follow-up, with a 3-year cumulative VLRAF rate of 31.1%. The MB-LATER score (Male, Bundle brunch block, Left atrium ≥47 mm, Type of AF [paroxysmal, persistent or long-standing persistent], and ER-AF = early recurrent AF), had better predictive ability for VLRAF (AUC 0.782) than the APPLE, ALARMc, BASE-AF2, CHADS2, CHA2DS2VASc or HATCH score (AUC 0.716, 0.671, 0.648, 0.552, 0.519 and 0.583, respectively), resulted in an improved net reclassification index (NRI) of 48.6-95.1% and better identified patients with subsequent VLRAF using decision-curve analysis (DCA). The MB-LATER score provides a readily available VLRAF risk assessment, and performs better than other scores. Validation of the MB-LATER score in other cohorts is underway.

  4. Prediction of very late arrhythmia recurrence after radiofrequency catheter ablation of atrial fibrillation: The MB-LATER clinical score

    PubMed Central

    Mujović, Nebojša; Marinković, Milan; Marković, Nebojša; Shantsila, Alena; Lip, Gregory Y. H.; Potpara, Tatjana S.

    2017-01-01

    Reliable prediction of very late recurrence of atrial fibrillation (VLRAF) occuring >12 months after catheter ablation (CA) in apparently “cured” patients could optimize long-term follow-up and modify decision-making regarding the discontinuation of oral anticoagulant therapy. In a single-centre cohort of consecutive patients post radiofrequency AFCA, we retrospectively derived a novel score for VLRAF prediction. Of 133 consecutive post AFCA patients (mean age 56.9 ± 11.8 years, 63.9% male, 69.2% with paroxysmal AF) who were arrhythmia-free at 12 months (excluding 3-month “blanking period”), 20 patients expirienced a VLRAF during a 29.1 ± 10.1-month follow-up, with a 3-year cumulative VLRAF rate of 31.1%. The MB-LATER score (Male, Bundle brunch block, Left atrium ≥47 mm, Type of AF [paroxysmal, persistent or long-standing persistent], and ER-AF = early recurrent AF), had better predictive ability for VLRAF (AUC 0.782) than the APPLE, ALARMc, BASE-AF2, CHADS2, CHA2DS2VASc or HATCH score (AUC 0.716, 0.671, 0.648, 0.552, 0.519 and 0.583, respectively), resulted in an improved net reclassification index (NRI) of 48.6–95.1% and better identified patients with subsequent VLRAF using decision-curve analysis (DCA). The MB-LATER score provides a readily available VLRAF risk assessment, and performs better than other scores. Validation of the MB-LATER score in other cohorts is underway. PMID:28106147

  5. INHERITED CARDIOMYOPATHIES

    PubMed Central

    Towbin, Jeffrey A.

    2015-01-01

    Cardiomyopathies, diseases of the heart muscle, are major causes of morbidity and mortality. A significant percentage of patients with cardiomyopathies have genetic-based, inheritable disease and, over the past two decades the genetic causes of these disorders have been increasingly discovered. The genes causing these disorders when they are mutated appear to encode proteins that frame a “final common pathway” for that specific disorder but the specifics of the phenotype, including age of onset, severity, and outcome is variable for reasons not yet understood. The “final common pathways” for the classified forms of cardiomyopathy include the sarcomere in the primarily diastolic dysfunction disorders hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM), the linkage of the sarcomere and sarcolemma in the systolic dysfunction disorder dilated cardiomyopathy (DCM), and the desmosome in arrhythmogenic cardiomyopathy (AVC). Left ventricular noncompaction cardiomyopathy (LVNC) is an overlap disorder and appears that any of these “final common pathways” can be involved depending on the specific form of LVNC. The genetics and mechanisms responsible for these clinical phenotypes will be described. PMID:25186923

  6. Cardiac arrhythmias during or after epileptic seizures

    PubMed Central

    van der Lende, Marije; Surges, Rainer; Sander, Josemir W; Thijs, Roland D

    2016-01-01

    Seizure-related cardiac arrhythmias are frequently reported and have been implicated as potential pathomechanisms of Sudden Unexpected Death in Epilepsy (SUDEP). We attempted to identify clinical profiles associated with various (post)ictal cardiac arrhythmias. We conducted a systematic search from the first date available to July 2013 on the combination of two terms: ‘cardiac arrhythmias’ and ‘epilepsy’. The databases searched were PubMed, Embase (OVID version), Web of Science and COCHRANE Library. We attempted to identify all case reports and case series. We identified seven distinct patterns of (post)ictal cardiac arrhythmias: ictal asystole (103 cases), postictal asystole (13 cases), ictal bradycardia (25 cases), ictal atrioventricular (AV)-conduction block (11 cases), postictal AV-conduction block (2 cases), (post)ictal atrial flutter/atrial fibrillation (14 cases) and postictal ventricular fibrillation (3 cases). Ictal asystole had a mean prevalence of 0.318% (95% CI 0.316% to 0.320%) in people with refractory epilepsy who underwent video-EEG monitoring. Ictal asystole, bradycardia and AV-conduction block were self-limiting in all but one of the cases and seen during focal dyscognitive seizures. Seizure onset was mostly temporal (91%) without consistent lateralisation. Postictal arrhythmias were mostly found following convulsive seizures and often associated with (near) SUDEP. The contrasting clinical profiles of ictal and postictal arrhythmias suggest different pathomechanisms. Postictal rather than ictal arrhythmias seem of greater importance to the pathophysiology of SUDEP. PMID:26038597

  7. Inherited Pain

    PubMed Central

    Eberhardt, Mirjam; Nakajima, Julika; Klinger, Alexandra B.; Neacsu, Cristian; Hühne, Kathrin; O'Reilly, Andrias O.; Kist, Andreas M.; Lampe, Anne K.; Fischer, Kerstin; Gibson, Jane; Nau, Carla; Winterpacht, Andreas; Lampert, Angelika

    2014-01-01

    Inherited erythromelalgia (IEM) causes debilitating episodic neuropathic pain characterized by burning in the extremities. Inherited “paroxysmal extreme pain disorder” (PEPD) differs in its clinical picture and affects proximal body areas like the rectal, ocular, or jaw regions. Both pain syndromes have been linked to mutations in the voltage-gated sodium channel Nav1.7. Electrophysiological characterization shows that IEM-causing mutations generally enhance activation, whereas mutations leading to PEPD alter fast inactivation. Previously, an A1632E mutation of a patient with overlapping symptoms of IEM and PEPD was reported (Estacion, M., Dib-Hajj, S. D., Benke, P. J., Te Morsche, R. H., Eastman, E. M., Macala, L. J., Drenth, J. P., and Waxman, S. G. (2008) NaV1.7 Gain-of-function mutations as a continuum. A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. J. Neurosci. 28, 11079–11088), displaying a shift of both activation and fast inactivation. Here, we characterize a new mutation of Nav1.7, A1632T, found in a patient suffering from IEM. Although transfection of A1632T in sensory neurons resulted in hyperexcitability and spontaneous firing of dorsal root ganglia (DRG) neurons, whole-cell patch clamp of transfected HEK cells revealed that Nav1.7 activation was unaltered by the A1632T mutation but that steady-state fast inactivation was shifted to more depolarized potentials. This is a characteristic normally attributed to PEPD-causing mutations. In contrast to the IEM/PEPD crossover mutation A1632E, A1632T failed to slow current decay (i.e. open-state inactivation) and did not increase resurgent currents, which have been suggested to contribute to high-frequency firing in physiological and pathological conditions. Reduced fast inactivation without increased resurgent currents induces symptoms of IEM, not PEPD, in the new Nav1.7 mutation, A1632T

  8. The clinical spectrum of inherited diseases involved in the synthesis and remodeling of complex lipids. A tentative overview.

    PubMed

    Garcia-Cazorla, Àngels; Mochel, Fanny; Lamari, Foudil; Saudubray, Jean-Marie

    2015-01-01

    Over one hundred diseases related to inherited defects of complex lipids synthesis and remodeling are now reported. Most of them were described within the last 5 years. New descriptions and phenotypes are expanding rapidly. While the associated clinical phenotype is currently difficult to outline, with only a few patients identified, it appears that all organs and systems may be affected. The main clinical presentations can be divided into (1) Diseases affecting the central and peripheral nervous system. Complex lipid synthesis disorders produce prominent motor manifestations due to upper and/or lower motoneuron degeneration. Motor signs are often complex, associated with other neurological and extra-neurological signs. Three neurological phenotypes, spastic paraparesis, neurodegeneration with brain iron accumulation and peripheral neuropathies, deserve special attention. Many apparently well clinically defined syndromes are not distinct entities, but rather clusters on a continuous spectrum, like for the PNPLA6-associated diseases, extending from Boucher-Neuhauser syndrome via Gordon Holmes syndrome to spastic ataxia and pure hereditary spastic paraplegia; (2) Muscular/cardiac presentations; (3) Skin symptoms mostly represented by syndromic (neurocutaneous) and non syndromic ichthyosis; (4) Retinal dystrophies with syndromic and non syndromic retinitis pigmentosa, Leber congenital amaurosis, cone rod dystrophy, Stargardt disease; (5) Congenital bone dysplasia and segmental overgrowth disorders with congenital lipomatosis; (6) Liver presentations characterized mainly by transient neonatal cholestatic jaundice and non alcoholic liver steatosis with hypertriglyceridemia; and (7) Renal and immune presentations. Lipidomics and molecular functional studies could help to elucidate the mechanism(s) of dominant versus recessive inheritance observed for the same gene in a growing number of these disorders.

  9. OPA1-related disorders: Diversity of clinical expression, modes of inheritance and pathophysiology.

    PubMed

    Chao de la Barca, Juan Manuel; Prunier-Mirebeau, Delphine; Amati-Bonneau, Patrizia; Ferré, Marc; Sarzi, Emmanuelle; Bris, Céline; Leruez, Stéphanie; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Gueguen, Naïg; Verny, Christophe; Hamel, Christian; Miléa, Dan; Procaccio, Vincent; Bonneau, Dominique; Lenaers, Guy; Reynier, Pascal

    2016-06-01

    Mutations in the Optic Atrophy 1 gene (OPA1) were first identified in 2000 as the main cause of Dominant Optic Atrophy, a disease specifically affecting the retinal ganglion cells and the optic nerve. Since then, an increasing number of symptoms involving the central, peripheral and autonomous nervous systems, with considerable variations of age of onset and severity, have been reported in OPA1 patients. This variety of phenotypes is attributed to differences in the effects of OPA1 mutations, to the mode of inheritance, which may be mono- or bi-allelic, and eventually to somatic mitochondrial DNA mutations. The diversity of the pathophysiological mechanisms involved in OPA1-related disorders is linked to the crucial role played by OPA1 in the maintenance of mitochondrial structure, genome and function. The neurological expression of these disorders highlights the importance of mitochondrial dynamics in neuronal processes such as dendritogenesis, axonal transport, and neuronal survival. Thus, OPA1-related disorders may serve as a paradigm in the wider context of neurodegenerative syndromes, particularly for the development of novel therapeutic strategies against these diseases.

  10. Types of Arrhythmia

    MedlinePlus

    ... other, more serious arrhythmias, such as v-fib. Ventricular Fibrillation V-fib occurs if disorganized electrical signals make ... because of another condition. The animation below shows ventricular fibrillation. Click the "start" button to play the animation. ...

  11. [Arrhythmia and sport].

    PubMed

    Saoudi, N; Yaici, K; Zarkane, N; Darmon, J P; Rinaldi, J P; Brunner, P; Ricard, P; Mourou, M Y

    2005-12-01

    Sports arrhythmia has gained wide attention with the mediatization of the death of famous sports stars. Sport strongly modifies the structure of the heart with the development of left ventricular hypertrophy which may be difficult to differentiate from that due to doping. Intense training modifies also the resting electrocardiogram with appearance of signs of left ventricular hypertrophy whereas resting sinus bradycardia and atrioventricular conduction disturbances usually reverts upon exertion. Accordingly, arrhythmia may develop ranging from extrasystoles to atrial fibrillation and even sudden death. Recent data suggest that if benign arrhythmia may be the result of the sole intense training and are reversible, malignant ventricular arrhythmia and sudden death mostly occur in unknown structural heart disease. Hypertrophic cardiomyopathy is amongst the most frequent post mortem diagnosis in this situation. Doping is now present in many sports and further threatens the athlete in the safe practice of sport.

  12. Common Tests for Arrhythmia

    MedlinePlus

    ... more about Cardiac Event Recorders . Treadmill testing (Exercise Stress Test or Stress Test) This is an option that provokes arrhythmias and ... rhythm are monitored. Learn more about the exercise stress test . Tilt-Table Test A tilt test may be ...

  13. Management of perioperative arrhythmias.

    PubMed

    Feeley, T W

    1997-04-01

    Electrocardiography was the first application of electronic monitoring to anesthesia care. The detection of arrhythmias remains the most important use of this technology today. Several predisposing factors tend to emerge when perioperative arrhythmias are evaluated. These are the anesthetic given, the site of surgery, abnormalities of blood gases or electrolytes, tracheal intubation, reflexes such as vagal slowing and the oculocardiac reflex, stimulation of the central nervous system, the presence of preexisting heart disease, and the use of intracardiac devices. In the evaluation of cardiac arrhythmias, several facts need to be determined. The most important is to determine if there is an underlying complication of anesthesia and surgery that may explain the arrhythmia. In addition, it is vital to evaluate the heart rate, the regularity, the number of P waves per QRS, and the configuration of the QRS. The anesthesiologist needs to determine whether the rhythm is dangerous to the patient and whether it requires treatment. Prompt evaluation and management of perioperative arrhythmias reduce anesthetic morbidity and mortality. This article reviews the causes and pharmacological treatment of major abnormalities of atrial and ventricular cardiac arrhythmias occurring in the perioperative period.

  14. Systems Pharmacology of Arrhythmias

    PubMed Central

    Berger, Seth I.; Ma’ayan, Avi; Iyengar, Ravi

    2011-01-01

    Long-QT syndrome (LQTS) is a congenital or drug-induced change in electrical activity of the heart that can lead to fatal arrhythmias. Mutations in 12 genes encoding ion channels and associated proteins are linked with congenital LQTS. With a computational systems biology approach, we found that gene products involved in LQTS formed a distinct functional neighborhood within the human interactome. Other diseases form similarly selective neighborhoods, and comparison of the LQTS neighborhood with other disease-centered neighborhoods suggested a molecular basis for associations between seemingly unrelated diseases that have increased risk of cardiac complications. By combining the LQTS neighborhood with published genome-wide association study data, we identified previously unknown single-nucleotide polymorphisms likely to affect the QT interval. We found that targets of U.S. Food and Drug Administration (FDA)–approved drugs that cause LQTS as an adverse event were enriched in the LQTS neighborhood. With the LQTS neighborhood as a classifier, we predicted drugs likely to have risks for QT effects and we validated these predictions with the FDA’s Adverse Events Reporting System, illustrating how network analysis can enhance the detection of adverse drug effects associated with drugs in clinical use. Thus, the identification of disease-selective neighborhoods within the human interactome can be useful for predicting new gene variants involved in disease, explaining the complexity underlying adverse drug side effects, and predicting adverse event susceptibility for new drugs. PMID:20407125

  15. Relationship Between Foveal Cone Structure and Clinical Measures of Visual Function in Patients With Inherited Retinal Degenerations

    PubMed Central

    Ratnam, Kavitha; Carroll, Joseph; Porco, Travis C.; Duncan, Jacque L.; Roorda, Austin

    2013-01-01

    Purpose. To study the relationship between cone spacing and density and clinical measures of visual function near the fovea. Methods. High-resolution images of the photoreceptor mosaic were obtained with adaptive optics scanning laser ophthalmoscopy from 26 patients with inherited retinal degenerations. Cone spacing measures were made close to or at the foveal center (mean [SD] eccentricity, 0.02 [0.03] degree; maximum eccentricity, 0.13 degree) and were converted to Z-scores, fraction of cones, and percentage-of-cones-below-average compared with normal values for each location (based on 37 age-similar visually normal eyes). Z-scores and percentage of cones below average were compared with best-corrected visual acuity (VA) and foveal sensitivity. Results. Visual acuity was significantly correlated with cone spacing (Spearman rank correlation ρ = −0.60, P = 0.003) and was preserved (≥80 letters), despite cone density measures that were 52% below normal. Foveal sensitivity showed significant correlation with cone spacing (ρ = −0.47, P = 0.017) and remained normal (≥35 decibels), despite density measures that were approximately 52% to 62% below normal. Conclusions. Cone density was reduced by up to 62% below normal at or near the fovea in eyes with VA and sensitivity that remained within normal limits. Despite a significant correlation with foveal cone spacing, VA and sensitivity are insensitive indicators of the integrity of the foveal cone mosaic. Direct, objective measures of cone structure may be more sensitive indicators of disease severity than VA or foveal sensitivity in eyes with inherited retinal degenerations. (ClinicalTrials.gov number, NCT00254605.) PMID:23908179

  16. Effect of female sex on cardiac arrhythmias.

    PubMed

    Gowd, B M Pampana; Thompson, Paul D

    2012-01-01

    We performed a systematic literature review to examine the effect of female sex on cardiac electrophysiology and arrhythmias. Women have faster resting heart rates yet longer QTc intervals. Women also have shorter PR and QRS intervals; these are presumed to be due to the small heart size of women and hormonal effects on ion channels. Women are two times more likely to experience atrioventricular nodal re-entry tachycardia than men. In contrast to atrioventricular nodal re-entry tachycardia, accessory-pathway-mediated atrial arrhythmias are less common in women, and women have more concealed and fewer manifest accessory pathways. Supraventricular tachycardia in women varies with the menstrual cycle and is more frequent in the luteal phase and inversely correlated with estrogen levels. Atrial fibrillation (AF) is less prevalent in women, but the absolute number of women with AF is higher because AF prevalence increases with age and women live longer. Also, complications of AF are greater in women. Women are generally less prone to ventricular arrhythmias, but they comprise a higher percentage of symptomatic subjects with congenital long QT syndrome and are more often affected by drugs that prolong the QT. Women are less prone to arrhythmias during pregnancy although they commonly complain of palpitations, which are sometimes related to the increase in heart rate during pregnancy. Clinicians should explore the relationship of arrhythmias to the menstrual cycle in female patients and should know that the menstrual cycle may affect the induction of arrhythmias during electrophysiological testing. Clinicians should also be aware that the arrhythmia and the result of clinical trials examining arrhythmia treatment may have different implications in women than in men.

  17. [Imaging studies in arrhythmias].

    PubMed

    Nowalany-Kozielska, Ewa

    2014-01-01

    Imaging studies play a very important role in the diagnosis of cardiac arrhythmias. They are able to answer many questions relating to the diagnosis and treatment of patients. Not all types of arrhythmias require you to perform imaging studies. Diagnosis require above all: ventricular tachycardia and supraventricular tachycardia, ventricular extrasystoles requiring treatment, atrialfibrillation, individuals who are at genetically diseases leading to severe arrhythmia, patients before ablation procedures and cardioversion, arrhythmias in athletes and people performing specific professions (eg pilots). The primary non-invasive imaging technique for the diagnosis of arrhythmias is the ECHO, also safe in pregnant women. Other imaging studies should be performed in case of inability to obtain sufficient diagnostic information in ECHO, because of the cost, availability and worse side effects (class of recommendation IIaB by AHA/ACC/ESC). Among these studies is the study of magnetic resonance imaging "gold standard" for assessing the anatomy and function of the heart, allows the assessment of myocardial structure and can significantly supplement the information obtained in the study of ECHO, is also safe in pregnant women.

  18. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation.

    PubMed

    Murphy, R; Turnbull, D M; Walker, M; Hattersley, A T

    2008-04-01

    Maternally inherited diabetes and deafness (MIDD) affects up to 1% of patients with diabetes but is often unrecognized by physicians. It is important to make an accurate genetic diagnosis, as there are implications for clinical investigation, diagnosis, management and genetic counselling. This review summarizes the range of clinical phenotypes associated with MIDD; outlines the advances in genetic diagnosis and pathogenesis of MIDD; summarizes the published prevalence data and provides guidance on the clinical management of these patients and their families.

  19. Pharmacotherapy of cardiac arrhythmias--basic science for clinicians.

    PubMed

    Shu, Juan; Zhou, Jun; Patel, Chinmay; Yan, Gan-Xin

    2009-11-01

    Cardiac arrhythmias occur in approximately 5.3% of the population and contribute substantially to morbidity and mortality. Pharmacological therapy still remains the major approach in management of patients with nearly every form of cardiac arrhythmia. Effective and safe management of cardiac arrhythmias with antiarrhythmic drugs requires understanding of basic mechanisms for various cardiac arrhythmias, clinical diagnosis of an arrhythmia and identification of underlying cardiac diseases, pharmacokinetics, and antiarrhythmic properties of each individual antiarrhythmic drug. Most cardiac arrhythmias occur via one of the two mechanisms: abnormal impulse formation and reentry or both. Antiarrhythmic drugs primarily work via influencing cardiac automaticity or triggered activity or by their effects on effective refractoriness of cardiac cells. Proarrhythmic effects of antiarrhythmic drugs are also briefly discussed in this review article.

  20. [On the clinical applications of logotherapy: a review of Victor Emil Frankl inheritance].

    PubMed

    Girmenia, E; Andrissi, L; Tambone, V

    2014-01-01

    The Viktor E. Frankl's thought has found wide application in many areas of the Clinic, not limited to the neuropsychiatric area. If the franklian work is known worldwide for being a theory and a practice within neurotic disorders, we must not forget how logotherapy has been put at the disposal of the sufferer in its broadest sense. Especially in the context of care and care of the chronically and evolutionary ill (cancer, heart disease, degenerative diseases, etc.), the thought and practice logotherapy have made and continue to make a valuable contribution. In this review we will cover in more detail the application of logotherapy in clinical-care, pausing to examine the international literature.

  1. Mitochondria and Arrhythmias

    PubMed Central

    Yang, Kai-Chien; Bonini, Marcelo G.; Dudley, Samuel C.

    2014-01-01

    Mitochondria are essential to providing ATP thereby satisfying the energy demand of the incessant electrical activity and contractile action of cardiac muscle. Emerging evidence indicates that mitochondrial dysfunction can adversely impact cardiac electrical functioning by impairing the intracellular ion homeostasis and membrane excitability through reduced ATP production and excessive reactive oxidative species (ROS) generation, resulting in increased propensity to cardiac arrhythmias. In this review, the molecular mechanisms linking mitochondrial dysfunction to cardiac arrhythmias are discussed with an emphasis on the impact of increased mitochondrial ROS on the cardiac ion channels and transporters that are critical to maintaining normal electromechanical functioning of the cardiomyocytes. The potential of using mitochondria-targeted antioxidants as a novel anti-arrhythmia therapy is highlighted. PMID:24713422

  2. Autoantibodies and Cardiac Arrhythmias

    PubMed Central

    Lee, Hon-Chi; Huang, Kristin T. L.; Wang, Xiao-Li; Shen, Win-Kuang

    2013-01-01

    Autoimmune diseases are associated with significant morbidity and mortality, afflicting about 5% of the population of the United States. They encompass a wide range of disorders that affect all organs of the human body and have a predilection for women. In the past, autoimmune pathogenesis was not thought to be a major mechanism for cardiovascular disorders, and potential relationships remain understudied. However, accumulating evidence suggests that a number of vascular and cardiac conditions are autoimmune-mediated. Recent studies indicate that autoantibodies play an important role in the development of cardiac arrhythmias, including atrial fibrillation, modulation of autonomic influences on heart rate and rhythm, conduction system abnormalities, and ventricular arrhythmias. This manuscript will review the current evidence for the role of autoantibodies in the development of cardiac arrhythmias. PMID:21740882

  3. Clinical Features of Candidiasis in Patients With Inherited Interleukin 12 Receptor β1 Deficiency

    PubMed Central

    Ouederni, Monia; Sanal, Ozden; Ikincioğullari, Aydan; Tezcan, Ilhan; Dogu, Figen; Sologuren, Ithaisa; Pedraza-Sánchez, Sigifredo; Keser, Melike; Tanir, Gonul; Nieuwhof, Chris; Colino, Elena; Kumararatne, Dinakantha; Levy, Jacov; Kutukculer, Necil; Aytekin, Caner; Herrera-Ramos, Estefanía; Bhatti, Micah; Karaca, Neslihan; Barbouche, Ridha; Broides, Arnon; Goudouris, Ekaterini; Franco, José Luis; Parvaneh, Nima; Reisli, Ismail; Strickler, Alexis; Shcherbina, Anna; Somer, Ayper; Segal, Anthony; Angel-Moreno, Alfonso; Lezana-Fernandez, José Luis; Bejaoui, Mohamed; Bobadilla-Del Valle, Miriam; Kachboura, Salem; Sentongo, Timothy; Ben-Mustapha, Imen; Bustamante, Jacinta; Picard, Capucine; Puel, Anne; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent; Rodríguez-Gallego, Carlos

    2014-01-01

    Background. Interleukin 12Rβ1 (IL-12Rβ1)–deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12–dependent interferon γ production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23–dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rβ1 deficiency. Results. Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin. Conclusions. Patients who are deficient in IL-12Rβ1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients. PMID:24186907

  4. An easy-to-use, operator-independent, clinical model to predict the left vs. right ventricular outflow tract origin of ventricular arrhythmias.

    PubMed

    Penela, Diego; De Riva, Marta; Herczku, Csaba; Catto, Valentina; Pala, Salvatore; Fernández-Armenta, Juan; Acosta, Juan; Cipolletta, Laura; Andreu, David; Borras, Roger; Rios, Jose; Mont, Lluis; Brugada, Josep; Carbucicchio, Corrado; Zeppenfeld, Katja; Berruezo, Antonio

    2015-07-01

    To identify clinical characteristics able to predict a left ventricular outflow tract (LVOT) origin in outflow tract ventricular arrhythmias (OTVAs). We included 117 consecutive patients (training sample) with successful radiofrequency ablation of OTVA in one centre. A predictive model for LVOT origin was obtained using clinical data. The model was prospectively validated in a second population (testing sample) of 143 patients from two additional centres. In training sample, mean age was 54 ± 17 years, 72 patients (61%) were male, and 63 (54%) had cardiovascular risk factors. Sixty (51%) patients had LVOT origin. Independent predictors for LVOT origin were the presence of hypertension [odds ratio (OR) 2.17, confidence interval (CI) 0.91-6.20, P = 0.09], male gender (OR 4.83, 95% CI 1.89-12.33, P < 0.001), and age >50 years (OR 4.46, 95% CI 1.57-12.7, P = 0.005). A simple score was constructed with these three variables to predict LVOT origin (mean predicted probability of 15% for score 0, 26% for score 1, 60% for score 2, and 87% for score 3, P < 0.001) and reached 80% sensitivity and 75% specificity. The score was validated in the testing sample and was not inferior to previously described electrocardiogram algorithms. Patients currently referred for OTVA ablation are older, more frequently men, and with a higher probability for LVOT origin than previously described. A LVOT origin is associated with the presence of hypertension, male gender, and older age, and can be anticipated by using a simple clinical score. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  5. [Arrhythmias from swallowing].

    PubMed

    Palazzuoli, V; Mondillo, S; Faglia, S; D'Aprile, N; De Luca, G; Kristodhullu, A; Corba, E

    1992-01-01

    We describe the case of a 51-year old, non cardiopathic patient, with recurrent attacks of supraventricular tachycardia induced by swallowing. In the existing literature we found several descriptions of hypokinetic arrhythmias, easily explained by a mechanism of vagal inhibition. The cases of predominantly hyperkinetic arrhythmias, however, are much less common. In these patients the origin of the disease seems to be due to sympathetic oesophageal fibers and superior and medium cardiac nerves. In the present case, as in the others reported in the literature, the drug of choice seems to be Amiodarone which appears to be the most effective in preventing tachyarrhythmias caused by swallowing.

  6. Types of Arrhythmia in Children

    MedlinePlus

    ... block .) Disease or an injury to the electrical conduction system during heart surgery can also cause it. ... Arrhythmia • Home • About Arrhythmia Introduction Atrial Fibrillation Bradycardia Conduction Disorders Premature Contractions Tachycardia Ventricular Fibrillation Other Rhythm ...

  7. [Arrhythmia and sleep apnea syndrome].

    PubMed

    Marrakchi, S; Kammoun, I; Kachboura, S

    2015-10-01

    Arrhythmia is a major cause of morbidity and mortality in Europe and in the United States. The aim of this review article was to assess the results of the prospective studies that evaluated the risk of arrhythmia in patients with sleep apnea syndrome and discuss the management of this arrhythmia. Reports published with the following search terms were searched: sleep apnea syndrome, atrial flutter, supraventricular arrhythmia, ventricular arrhythmia, ventricular tachycardia, ventricular fibrillation, torsade de pointe, atrial fibrillation and sudden death. The investigation was restricted to reports published in English and French. The outcome of this analysis suggests that patients with untreated overt sleep apnea syndrome are at increased risk of arrhythmia. The timely recognition and effective treatment of sleep apnea syndrome in patients with arrhythmia are mandatory because the prognosis of arrhythmia may be improved with the appropriate treatment of sleep apnea syndrome. Copyright © 2015. Published by Elsevier Masson SAS.

  8. Clinical and Psychological Characteristics of Initial Cohort of the Dominantly Inherited Alzheimer Network (DIAN)

    PubMed Central

    Storandt, Martha; Balota, David A.; Aschenbrenner, Andrew J.; Morris, John C.

    2013-01-01

    Objective To describe clinical, cognitive, and personality characteristics at baseline assessment of 249 participants 19 to 60 years of age in a multinational longitudinal study (DIAN) of autosomal dominant Alzheimer disease (ADAD). Method Participants (74% cognitively normal) were from ADAD families with mutations in one of three genes (APP, PSEN1, or PSEN2). Mixed model analyses including family as a random variable and controlling for years from expected time of symptomatic onset of ADAD based on parental age at onset compared three groups (cognitively normal mutation noncarriers, cognitively normal mutation carriers, very mildly impaired mutation carriers). Results Global cognitive deficits similar to those observed in late-life sporadic Alzheimer disease (AD) existed in very mild ADAD compared with cognitively normal carriers and noncarriers on all but two measures (Digit Span Backward, Letter Fluency for FAS) of episodic memory, semantic memory, working memory, attention, and speeded visuospatial abilities. Demented individuals were less extraverted, open, and conscientious than cognitively normal participants on the International Personality Item Pool. Differences in the relation between three measures (Logical Memory, Digit Symbol, attention switching) and time to expected age at symptomatic onset indicate that cognitive deficits on some measures can be detected in mutation carriers prior to symptomatic AD and hence should be useful markers in subsequent longitudinal follow-up. Conclusions Overall cognitive and personality deficits in very mild ADAD are similar to those seen in sporadic AD. Cognitive deficits also occur in asymptomatic mutation carriers who are closer to the expected time of dementia onset. PMID:24219606

  9. Clinical and psychological characteristics of the initial cohort of the Dominantly Inherited Alzheimer Network (DIAN).

    PubMed

    Storandt, Martha; Balota, David A; Aschenbrenner, Andrew J; Morris, John C

    2014-01-01

    The purpose was to describe clinical, cognitive, and personality characteristics at baseline assessment of 249 participants, 19 to 60 years of age, in a multinational longitudinal study of autosomal dominant Alzheimer's disease (ADAD). Participants (74% cognitively normal) were from ADAD families with mutations in 1 of 3 genes (APP, PSEN1, or PSEN2). Mixed model analyses, including family as a random variable and controlling for years from expected time of symptomatic onset of ADAD based on parental age at onset, compared 3 groups (cognitively normal mutation noncarriers, cognitively normal mutation carriers, very mildly impaired mutation carriers). Global cognitive deficits similar to those observed in late-life sporadic Alzheimer's disease (AD) existed in very mild ADAD compared with cognitively normal carriers and noncarriers on all but 2 measures (Digit Span Backward, Letter Fluency for FAS) of episodic memory, semantic memory, working memory, attention, and speeded visuospatial abilities. Demented individuals were less extraverted, open, and conscientious than cognitively normal participants on the International Personality Item Pool. Differences in the relation between 3 measures (Logical Memory, Digit Symbol, attention switching) and time to expected age at symptomatic onset indicate that cognitive deficits on some measures can be detected in mutation carriers prior to symptomatic AD, and hence should be useful markers in subsequent longitudinal follow-up. Overall cognitive and personality deficits in very mild ADAD are similar to those seen in sporadic AD. Cognitive deficits also occur in asymptomatic mutation carriers who are closer to the expected time of dementia onset.

  10. Clinical effects of phosphodiesterase 3A mutations in inherited hypertension with brachydactyly.

    PubMed

    Toka, Okan; Tank, Jens; Schächterle, Carolin; Aydin, Atakan; Maass, Philipp G; Elitok, Saban; Bartels-Klein, Eireen; Hollfinger, Irene; Lindschau, Carsten; Mai, Knut; Boschmann, Michael; Rahn, Gabriele; Movsesian, Matthew A; Müller, Thomas; Doescher, Andrea; Gnoth, Simone; Mühl, Astrid; Toka, Hakan R; Wefeld-Neuenfeld, Yvette; Utz, Wolfgang; Töpper, Agnieszka; Jordan, Jens; Schulz-Menger, Jeanette; Klussmann, Enno; Bähring, Sylvia; Luft, Friedrich C

    2015-10-01

    Autosomal-dominant hypertension with brachydactyly is a salt-independent Mendelian syndrome caused by activating mutations in the gene encoding phosphodiesterase 3A. These mutations increase the protein kinase A-mediated phosphorylation of phosphodiesterase 3A resulting in enhanced cAMP-hydrolytic affinity and accelerated cell proliferation. The phosphorylated vasodilator-stimulated phosphoprotein is diminished, and parathyroid hormone-related peptide is dysregulated, potentially accounting for all phenotypic features. Untreated patients die prematurely of stroke; however, hypertension-induced target-organ damage is otherwise hardly apparent. We conducted clinical studies of vascular function, cardiac functional imaging, platelet function in affected and nonaffected persons, and cell-based assays. Large-vessel and cardiac functions indeed seem to be preserved. The platelet studies showed normal platelet function. Cell-based studies demonstrated that available phosphodiesterase 3A inhibitors suppress the mutant isoforms. However, increasing cGMP to indirectly inhibit the enzyme seemed to have particular use. Our results shed more light on phosphodiesterase 3A activation and could be relevant to the treatment of severe hypertension in the general population. © 2015 American Heart Association, Inc.

  11. How Are Arrhythmias Treated?

    MedlinePlus

    ... treated. Some people who are at risk for ventricular fibrillation are treated with a device called an implantable cardioverter defibrillator (ICD). Like a pacemaker, an ICD is a small ... senses a dangerous ventricular arrhythmia, it sends an electric shock to the ...

  12. Cardiac mitochondria and arrhythmias

    PubMed Central

    Brown, David A.; O'Rourke, Brian

    2010-01-01

    Despite a high prevalence of sudden cardiac death throughout the world, the mechanisms that lead to ventricular arrhythmias are not fully understood. Over the last 20 years, a growing body of evidence indicates that cardiac mitochondria are involved in the genesis of arrhythmia. In this review, we have attempted to describe the role that mitochondria play in altering the heart's electrical function by introducing heterogeneity into the cardiac action potential. Specifically, we have focused on how the energetic status of the mitochondrial network can alter sarcolemmal potassium fluxes through ATP-sensitive potassium channels, creating a ‘metabolic sink’ for depolarizing wave-fronts and introducing conditions that favour catastrophic arrhythmia. Mechanisms by which mitochondria depolarize under conditions of oxidative stress are characterized, and the contributions of several mitochondrial ion channels to mitochondrial depolarization are presented. The inner membrane anion channel in particular opens upstream of other inner membrane channels during metabolic stress, and may be an effective target to prevent the metabolic oscillations that create action potential lability. Finally, we discuss therapeutic strategies that prevent arrhythmias by preserving mitochondrial membrane potential in the face of oxidative stress, supporting the notion that treatments aimed at cardiac mitochondria have significant potential in attenuating electrical dysfunction in the heart. PMID:20621924

  13. Arrhythmias in the setting of hematopoietic cell transplants.

    PubMed

    Tonorezos, E S; Stillwell, E E; Calloway, J J; Glew, T; Wessler, J D; Rebolledo, B J; Pham, A; Steingart, R M; Lazarus, H; Gale, R P; Jakubowski, A A; Schaffer, W L

    2015-09-01

    Prior studies report that 9-27% of persons receiving a hematopoietic cell transplant develop arrhythmias, but the effect on outcomes is largely unknown. We reviewed data from 1177 consecutive patients ⩾40 years old receiving a hematopoietic cell transplant at one center during 1999-2009. Transplant indication was predominately leukemia, lymphoma and multiple myeloma. Overall, 104 patients were found to have clinically significant arrhythmia: 43 before and 61 after transplant. Post-transplant arrhythmias were most frequently atrial fibrillation (N=30), atrial flutter (N=7) and supraventricular tachycardia (N=11). Subjects with an arrhythmia post transplant were more likely to have longer median hospital stays (32 days vs 23, P=<0.001), a greater probability of an intensive care unit admission (52% vs 7%; P<0.001), greater probability of in-hospital deaths (28% vs 3%, P<0.001), and greater probability of death within 1 year of transplant (41% vs 15%; P<0.001) compared with patients without arrhythmia at any time. In a multivariate model including age at transplant, diagnosis, history of pretransplant arrhythmia, and transplant-related variables, post-transplant arrhythmia was associated with a greater risk for death within a year of transplant (odds ratio 3.5, 95% confidence interval: 2.1, 5.9; P<0.001). Our data suggest that arrhythmias after transplants are associated with significant morbidity and mortality. A prospective study of arrhythmia in the transplant setting is warranted.

  14. Propranolol prevents life-threatening arrhythmias in LQT3 transgenic mice: Implications for the clinical management of LQT3 patients☆

    PubMed Central

    Calvillo, Laura; Spazzolini, Carla; Vullo, Eleonora; Insolia, Roberto; Crotti, Lia; Schwartz, Peter J.

    2014-01-01

    Background The efficacy of beta-blockers for treatment of patients with long QT syndrome type 3 (LQT3) has been repeatedly questioned, and it has been suggested that they might be detrimental for this genetic subgroup of patients with long QT syndrome (LQTS). The disquieting consequence has been that cardiologists confronted with LQT3 patients often do not even attempt pharmacologic therapy and implant cardioverter-defibrillators as first-choice treatment. However, the most recent clinical data indicate high efficacy of beta-blocker therapy in LQT3 patients. Objective The purpose of this study was to test the antiarrhythmic efficacy of beta-blockers in an established experimental model for LQT3. Methods After phenotypic validation of 65 ∆KPQ-SCN5A knock-in transgenic (TG) mice compared to 32 wild-type (WT) mice, we tested the effect of the arrhythmogenic cholinergic muscarinic agonist carbachol in 19 WT and 39 TG anesthetized mice, with and without pretreatment with propranolol given intraperitoneally. Results At the same heart rates, TG mice had a markedly longer QT interval than WT mice. Whereas carbachol had minor arrhythmic effects in the WT mice, it produced ventricular tachycardia (VT) and ventricular fibrillation (VF) in 55% of 20 TG mice. By contrast, in none of 19 TG mice pretreated with propranolol did VT/VF occur after carbachol injection. Conclusion These experimental data indicate that, contrary to previous reports, beta-blockade effectively prevents VT/VF in a validated LQT3 model. Together with the most recent clinical data, these findings indicate that there is no reason for not initiating protective therapy with beta-blockers in LQT3 patients. PMID:24135497

  15. Late onset of clinically apparent central vein stenosis due to previous central venous catheter in a patient with inherited thrombophilia.

    PubMed

    Eleftheriadis, Theodoros; Liakopoulos, Vassilios; Antoniadi, Georgia; Pissas, Georgios; Leivaditis, Konstantinos; Stefanidis, Ioannis

    2014-04-01

    We describe a case of a patient with a functional kidney transplant who was admitted to our department with clinically evident central vein stenosis (CVS) 7 years after the removal of a central venous catheter (CVC) from the right internal jugular vein. The catheter was used as a hemodialysis access for a 2-month period. In the interval before his last admission, the patient suffered two episodes of deep vein thrombosis. Investigation revealed heterozygosity for factor V Leiden, the most common inherited thrombophilia encountered in 5% of Caucasians, and anticoagulation treatment was started. Magnetic resonance angiography showed stenosis just after the convergence of the right subclavian vein with the internal jugular vein to the innominate vein. Transluminal angioplasty restored venous patency and right upper arm edema resolved. Coexistence of CVS, accompanied by hemodynamic changes and endothelial dysfunction, with thrombophilia fulfill all the elements of the Virchow's triad. Therefore, the patient was at great risk for central vein thrombosis, from which he was possibly protected by the early administration of anticoagulant treatment. This case indicates that CVS can be asymptomatic for several years after CVC removal and also raises the question if thrombophilia workup and investigation for CVS may be beneficial in every patient with CVC placement in order to avoid any harmful outcomes.

  16. Cisapride and ventricular arrhythmia

    PubMed Central

    Hennessy, Sean; Leonard, Charles E; Newcomb, Craig; Kimmel, Stephen E; Bilker, Warren B

    2008-01-01

    AIMS We aimed to examine the association between cisapride and ventricular arrhythmia, and examine the relationship to dose and CYP3A4 inhibitors. METHODS A nested case–control study was conducted in Medicaid beneficiaries exposed to cisapride, metoclopramide or a proton pump inhibitor (PPI) from 1999 to 2000. Cases were hospitalized with a principal International Classification of Diseases-9 code indicating sudden cardiac death or ventricular arrhythmia. Controls had at least as much event-free person time following the study prescription as its matched case. RESULTS A total of 145 cases and 7250 controls were identified. The unadjusted rate ratio for cisapride vs. PPIs was 1.49 (95% confidence interval 0.96, 2.25). The adjusted odds ratio (OR) for cisapride vs. PPIs was 2.10 (1.34, 3.28). Excluding persons in managed care, the adjusted OR for cisapride was 2.92 (1.55, 5.49). In the initial prescription period, the adjusted OR for cisapride vs. PPIs was 7.85 (1.95, 31.60). Non-arrhythmogenic CYP3A4 inhibitors were not associated with an increased risk in users of cisapride or PPI inhibitors. The OR for potentially arrhythmogenic CYP3A4 inhibitors was 3.79 (1.76, 8.15) in cisapride users and 3.47 (2.06, 5.83) in PPI users. CONCLUSIONS Cisapride was associated with a doubling to tripling of the risk of hospitalization for ventricular arrhythmia, and a nearly eightfold risk in the initial prescription period. Although use of potentially arrhythmogenic CYP3A4 inhibitors was associated with an increased risk, this appears to be due to a direct effect of the drugs themselves rather than an interaction with cisapride. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Case reports have linked cisapride to ventricular arrhythmia and sudden cardiac death. However, two prior epidemiological studies have failed to show an association between cisapride and serious arrhythmia. WHAT THIS STUDY ADDS Overall, cisapride was associated with a doubling to tripling of the risk of

  17. The role of the autonomic nervous system in arrhythmias and sudden cardiac death.

    PubMed

    Franciosi, Sonia; Perry, Frances K G; Roston, Thomas M; Armstrong, Kathryn R; Claydon, Victoria E; Sanatani, Shubhayan

    2017-03-31

    The autonomic nervous system (ANS) is complex and plays an important role in cardiac arrhythmia pathogenesis. A deeper understanding of the anatomy and development of the ANS has shed light on its involvement in cardiac arrhythmias. Alterations in levels of Sema-3a and NGF, both growth factors involved in innervation patterning during development of the ANS, leads to cardiac arrhythmias. Dysregulation of the ANS, including polymorphisms in genes involved in ANS development, have been implicated in sudden infant death syndrome. Disruptions in the sympathetic and/or parasympathetic systems of the ANS can lead to cardiac arrhythmias and can vary depending on the type of arrhythmia. Simultaneous stimulation of both the sympathetic and parasympathetic systems is thought to lead to atrial fibrillation whereas increased sympathetic stimulation is thought to lead to ventricular fibrillation or ventricular tachycardia. In inherited arrhythmia syndromes, such as Long QT and Catecholaminergic Polymorphic Ventricular Tachycardia, sympathetic system stimulation is thought to lead to ventricular tachycardia, subsequent arrhythmias, and in severe cases, cardiac death. On the other hand, arrhythmic events in Brugada Syndrome have been associated with periods of high parasympathetic tone. Increasing evidence suggests that modulation of the ANS as a therapeutic strategy in the treatment of cardiac arrhythmias is safe and effective. Further studies investigating the involvement of the ANS in arrhythmia pathogenesis and its modulation for the treatment of cardiac arrhythmias is warranted.

  18. [Psychosomatic aspects of cardiac arrhythmias].

    PubMed

    Siepmann, Martin; Kirch, Wilhelm

    2010-07-01

    Emotional stress facilitates the occurrence of cardiac arrhythmias including sudden cardiac death. The prevalence of anxiety and depression is increased in cardiac patients as compared to the normal population. The risk of cardiovascular mortality is enhanced in patients suffering from depression. Comorbid anxiety disorders worsen the course of cardiac arrhythmias. Disturbance of neurocardiac regulation with predominance of the sympathetic tone is hypothesized to be causative for this. The emotional reaction to cardiac arrhythmias is differing to a large extent between individuals. Emotional stress may result from coping with treatment of cardiac arrhythmias. Emotional stress and cardiac arrhythmias may influence each other in the sense of a vicious circle. Somatoform cardiac arrhythmias are predominantly of psychogenic origin. Instrumental measures and frequent contacts between physicians and patients may facilitate disease chronification. The present review is dealing with the multifaceted relationships between cardiac arrhythmias and emotional stress. The underlying mechanisms and corresponding treatment modalities are discussed.

  19. Electromechanical wave imaging for arrhythmias

    NASA Astrophysics Data System (ADS)

    Provost, Jean; Thanh-Hieu Nguyen, Vu; Legrand, Diégo; Okrasinski, Stan; Costet, Alexandre; Gambhir, Alok; Garan, Hasan; Konofagou, Elisa E.

    2011-11-01

    Electromechanical wave imaging (EWI) is a novel ultrasound-based imaging modality for mapping of the electromechanical wave (EW), i.e. the transient deformations occurring in immediate response to the electrical activation. The correlation between the EW and the electrical activation has been established in prior studies. However, the methods used previously to map the EW required the reconstruction of images over multiple cardiac cycles, precluding the application of EWI for non-periodic arrhythmias such as fibrillation. In this study, new imaging sequences are developed and applied based on flash- and wide-beam emissions to image the entire heart at very high frame rates (2000 fps) during free breathing in a single heartbeat. The methods are first validated by imaging the heart of an open-chest canine while simultaneously mapping the electrical activation using a 64-electrode basket catheter. Feasibility is then assessed by imaging the atria and ventricles of closed-chest, conscious canines during sinus rhythm and during right-ventricular pacing following atrio-ventricular dissociation, i.e., during a non-periodic rhythm. The EW was validated against electrode measurements in the open-chest case, and followed the expected electrical propagation pattern in the closed-chest setting. These results indicate that EWI can be used for the characterization of non-periodic arrhythmias in conditions similar to the clinical setting, in a single heartbeat, and during free breathing.

  20. Magnetocardiography in the diagnosis of fetal arrhythmia.

    PubMed

    van Leeuwen, P; Hailer, B; Bader, W; Geissler, J; Trowitzsch, E; Grönemeyer, D H

    1999-11-01

    To examine the possible use of magnetocardiography in the diagnosis of fetal arrhythmias. Investigation of routinely examined pregnant women, as well as women referred because of arrhythmias or other reasons. Sixty-three women between the 13th and 42nd week of pregnancy. Recording of 189 fetal magnetocardiograms, of which 173 traces (92%) demonstrated sufficient fetal signal strength to permit evaluation. After digital subtraction of the maternal artefact, all fetal complexes were identified and the recording was examined for arrhythmic events. Short bradycardic episodes, not associated with any pathological condition, were found in 26% of all recordings, usually in mid-pregnancy. In 12 cases, isolated extrasystoles of no clinical importance could be identified. There were nine traces which revealed multiple arrhythmias including ventricular and supraventricular ectopic beats, bigeminy and trigeminy, sino-atrial block and atrio-ventricular conduction disturbances. Furthermore, two cases with tachycardia were found. Magnetocardiography offers a simple noninvasive method for examination of the fetal cardiac electrophysiological signal. It may thus be useful in the identification and classification of clinically relevant arrhythmia and aid in decisions concerning treatment.

  1. Neuroanatomical correlates of severe cardiac arrhythmias in acute ischemic stroke.

    PubMed

    Seifert, Frank; Kallmünzer, Bernd; Gutjahr, Isabell; Breuer, Lorenz; Winder, Klemens; Kaschka, Iris; Kloska, Stephan; Doerfler, Arnd; Hilz, Max-Josef; Schwab, Stefan; Köhrmann, Martin

    2015-05-01

    Neurocardiological interactions can cause severe cardiac arrhythmias in patients with acute ischemic stroke. The relationship between the lesion location in the brain and the occurrence of cardiac arrhythmias is still discussed controversially. The aim of the present study was to correlate the lesion location with the occurrence of cardiac arrhythmias in patients with acute ischemic stroke. Cardiac arrhythmias were systematically assessed in patients with acute ischemic stroke during the first 72 h after admission to a monitored stroke unit. Voxel-based lesion-symptom mapping (VLSM) was used to correlate the lesion location with the occurrence of clinically relevant severe arrhythmias. Overall 150 patients, 56 with right-hemispheric and 94 patients with a left-hemispheric lesion, were eligible to be included in the VLSM study. Severe cardiac arrhythmias were present in 49 of these 150 patients (32.7%). We found a significant association (FDR correction, q < 0.05) between lesions in the right insular, right frontal and right parietal cortex as well as the right amygdala, basal ganglia and thalamus and the occurrence of cardiac arrhythmias. Because left- and right-hemispheric lesions were analyzed separately, the significant findings rely on the 56 patients with right-hemispheric lesions. The data indicate that these areas are involved in central autonomic processing and that right-hemispheric lesions located to these areas are associated with an elevated risk for severe cardiac arrhythmias.

  2. Therapy with conventional antiarrhythmic drugs for ventricular arrhythmias.

    PubMed

    Nestico, P F; DePace, N L; Morganroth, J

    1984-09-01

    Conventional antiarrhythmic drugs are an important tool for the clinical cardiologist for the treatment of ventricular arrhythmias. Knowledge of the different properties of these drugs will help decrease the incidence of adverse effects and increase the frequency of successful therapy.

  3. Perspective: A Dynamics-Based Classification of Ventricular Arrhythmias

    PubMed Central

    Weiss, James N.; Garfinkel, Alan; Karagueuzian, Hrayr S.; Nguyen, Thao P.; Olcese, Riccardo; Chen, Peng-Sheng; Qu, Zhilin

    2015-01-01

    Despite key advances in the clinical management of life-threatening ventricular arrhythmias, culminating with the development of implantable cardioverter-defibrillators and catheter ablation techniques, pharmacologic/biologic therapeutics have lagged behind. The fundamental issue is that biological targets are molecular factors. Diseases, however, represent emergent properties at the scale of the organism that result from dynamic interactions between multiple constantly changing molecular factors. For a pharmacologic/biologic therapy to be effective, it must target the dynamic processes that underlie the disease. Here we propose a classification of ventricular arrhythmias that is based on our current understanding of the dynamics occurring at the subcellular, cellular, tissue and organism scales, which cause arrhythmias by simultaneously generating arrhythmia triggers and exacerbating tissue vulnerability. The goal is to create a framework that systematically links these key dynamic factors together with fixed factors (structural and electrophysiological heterogeneity) synergistically promoting electrical dispersion and increased arrhythmia risk to molecular factors that can serve as biological targets. We classify ventricular arrhythmias into three primary dynamic categories related generally to unstable Ca cycling, reduced repolarization, and excess repolarization, respectively. The clinical syndromes, arrhythmia mechanisms, dynamic factors and what is known about their molecular counterparts are discussed. Based on this framework, we propose a computational-experimental strategy for exploring the links between molecular factors, fixed factors and dynamic factors that underlie life-threatening ventricular arrhythmias. The ultimate objective is to facilitate drug development by creating an in silico platform to evaluate and predict comprehensively how molecular interventions affect not only a single targeted arrhythmia, but all primary arrhythmia dynamics

  4. Perspective: a dynamics-based classification of ventricular arrhythmias.

    PubMed

    Weiss, James N; Garfinkel, Alan; Karagueuzian, Hrayr S; Nguyen, Thao P; Olcese, Riccardo; Chen, Peng-Sheng; Qu, Zhilin

    2015-05-01

    Despite key advances in the clinical management of life-threatening ventricular arrhythmias, culminating with the development of implantable cardioverter-defibrillators and catheter ablation techniques, pharmacologic/biologic therapeutics have lagged behind. The fundamental issue is that biological targets are molecular factors. Diseases, however, represent emergent properties at the scale of the organism that result from dynamic interactions between multiple constantly changing molecular factors. For a pharmacologic/biologic therapy to be effective, it must target the dynamic processes that underlie the disease. Here we propose a classification of ventricular arrhythmias that is based on our current understanding of the dynamics occurring at the subcellular, cellular, tissue and organism scales, which cause arrhythmias by simultaneously generating arrhythmia triggers and exacerbating tissue vulnerability. The goal is to create a framework that systematically links these key dynamic factors together with fixed factors (structural and electrophysiological heterogeneity) synergistically promoting electrical dispersion and increased arrhythmia risk to molecular factors that can serve as biological targets. We classify ventricular arrhythmias into three primary dynamic categories related generally to unstable Ca cycling, reduced repolarization, and excess repolarization, respectively. The clinical syndromes, arrhythmia mechanisms, dynamic factors and what is known about their molecular counterparts are discussed. Based on this framework, we propose a computational-experimental strategy for exploring the links between molecular factors, fixed factors and dynamic factors that underlie life-threatening ventricular arrhythmias. The ultimate objective is to facilitate drug development by creating an in silico platform to evaluate and predict comprehensively how molecular interventions affect not only a single targeted arrhythmia, but all primary arrhythmia dynamics

  5. Mechanisms of cardiac arrhythmias

    PubMed Central

    Tse, Gary

    2015-01-01

    Blood circulation is the result of the beating of the heart, which provides the mechanical force to pump oxygenated blood to, and deoxygenated blood away from, the peripheral tissues. This depends critically on the preceding electrical activation. Disruptions in the orderly pattern of this propagating cardiac excitation wave can lead to arrhythmias. Understanding of the mechanisms underlying their generation and maintenance requires knowledge of the ionic contributions to the cardiac action potential, which is discussed in the first part of this review. A brief outline of the different classification systems for arrhythmogenesis is then provided, followed by a detailed discussion for each mechanism in turn, highlighting recent advances in this area. PMID:27092186

  6. Clinical spectrum in homozygotes and compound heterozygotes inheriting cystic fibrosis mutation 3849+10kbC>T: Significance for geneticists

    SciTech Connect

    Gilbert, F.; Li, Zhen; Arzimanoglou, I.

    1995-09-25

    We describe patients inheriting cystic fibrosis (CF) mutation 3849+10kbC>T as homozygotes or compound heterozygotes. Three unrelated homozygotes for this mutation were all pancreatic-sufficient and sweat test-negative or inconclusive. Among the compound heterozygotes, both pancreatic sufficiency and insufficiency, as well as positive and negative/inconclusive sweat test results are reported, expanding the range of clinical expression associated with inheritance of this mutation. 3849+10kbC>T is one of several CF mutations that can result in atypical or variant forms of CF. For geneticists, the diagnosis of variant CF has implications for recurrence risk and prognosis counseling of the families of affected individuals, and possibly for CF carrier screening in the general population. 19 refs., 1 tab.

  7. Inherited 1q21.1q21.2 duplication and 16p11.2 deletion: a two-hit case with more severe clinical manifestations.

    PubMed

    Brisset, Sophie; Capri, Yline; Briand-Suleau, Audrey; Tosca, Lucie; Gras, Domitille; Fauret-Amsellem, Anne-Laure; Pineau, Dominique; Saada, Julien; Ortonne, Valérie; Verloes, Alain; Goossens, Michel; Tachdjian, Gérard; Métay, Corinne

    2015-09-01

    We report paternally inherited duplication of 1q12q21.2 of 5.8 Mb associated with maternally inherited deletion of 16p11.2 of 545 Kb, this latter first identified in a fetus exhibiting an absent nasal bone detected during pregnancy. During the neonatal period, the young boy presented developmental delay, epilepsy, congenital anomalies and overweight. The clinical features of the proband with two rearrangements were more severe than in either of the parents carrying only one or the other mutation. Thus our data support a two-hit model in which the concomitant presence of these two copy-number variations exacerbates the neurodevelopmental phenotype. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Mitochondrial inheritance and disease.

    PubMed

    Fine, P E

    1978-09-23

    Spontaneously occurring variants of the D.N.A. content of mitochondria may be responsible for human disease. Among the prime candidates for such a mitochondrial aetiology are certain drug-induced blood dyscrasias, particularly that due to chloramphenicol. Because mitochondria are generally inherited from the female parent, such disorders should be clustered among matroclinally related individuals. The clinical manifestations of such diseases are a function of the manner in which mitochondria are allocated to somatic cells and tissues during development.

  9. Cardiac arrhythmias during exercise testing in healthy men.

    NASA Technical Reports Server (NTRS)

    Beard, E. F.; Owen, C. A.

    1973-01-01

    Clinically healthy male executives who participate in a long-term physical conditioning program have demonstrated cardiac arrhythmia during and after periodic ergometric testing at submaximal and maximal levels. In 1,385 tests on 248 subjects, it was found that 34% of subjects demonstrated an arrhythmia at some time and 13% of subjects developed arrhythmia on more than one test. Premature systoles of ventricular origin were most common, but premature systoles of atrial origin, premature systoles of junctional origin, paroxysmal atrial tachycardia, atrioventricular block, wandering pacemaker, and pre-excitation were also seen. Careful post-test monitoring and pulse rate regulated training sessions are suggested for such programs.

  10. Cardiac arrhythmias during exercise testing in healthy men.

    NASA Technical Reports Server (NTRS)

    Beard, E. F.; Owen, C. A.

    1973-01-01

    Clinically healthy male executives who participate in a long-term physical conditioning program have demonstrated cardiac arrhythmia during and after periodic ergometric testing at submaximal and maximal levels. In 1,385 tests on 248 subjects, it was found that 34% of subjects demonstrated an arrhythmia at some time and 13% of subjects developed arrhythmia on more than one test. Premature systoles of ventricular origin were most common, but premature systoles of atrial origin, premature systoles of junctional origin, paroxysmal atrial tachycardia, atrioventricular block, wandering pacemaker, and pre-excitation were also seen. Careful post-test monitoring and pulse rate regulated training sessions are suggested for such programs.

  11. Who Is at Risk for Arrhythmia?

    MedlinePlus

    ... on Twitter. Who Is at Risk for an Arrhythmia? Arrhythmias are very common in older adults. Atrial fibrillation (a common type of arrhythmia that can cause problems) affects millions of people, ...

  12. Arrhythmias in newborn thoroughbred foals.

    PubMed

    Yamamoto, K; Yasuda, J; Too, K

    1992-05-01

    Foetal electrocardiograms (ECG) were obtained from 39 of 50 Thoroughbred foaling mares close to delivery. The 50 newborn foals were studied electrocardiographically during their adaptive period, immediately after birth. In 48 foals there were paroxysmal arrhythmias or mixed arrhythmias. The most common arrhythmias were sinus arrhythmias including wandering pacemaker (32/50) and atrial premature contraction (30/50). The others observed were atrial fibrillation (15/50), ventricular premature contraction (10/50), partial atrioventricular block (7/50), ventricular tachycardia (4/50), atrial tachycardia (3/50) and idioventricular rhythm (1/50). The duration of the arrhythmias was approximately 5 min, and in all cases the arrhythmia disappeared within 15 min of birth. From foetal ECG recordings, no indication of the likelihood of neonatal arrhythmias was detected. With the exception of 2 cases, all foals have continued to grow and develop normally. These arrhythmias are considered normal physiological processes in newborn Thoroughbred foals during the adaptive period to extra-uterine life. High vagal tone and hypoxaemia at birth are probably the main contributing factors.

  13. The correlation between CRB1 variants and the clinical severity of Brazilian patients with different inherited retinal dystrophy phenotypes.

    PubMed

    Motta, Fabiana Louise; Salles, Mariana Vallim; Costa, Karita Antunes; Filippelli-Silva, Rafael; Martin, Renan Paulo; Sallum, Juliana Maria Ferraz

    2017-08-17

    Inherited retinal dystrophies are characterized by progressive retina degeneration and mutations in at least 250 genes have been associated as disease-causing. CRB1 is one of many genes analyzed in molecular diagnosis for inherited retinal dystrophy. Crumbs homolog-1 protein encoded by CRB1 is important for cell-to-cell contact, polarization of epithelial cells and the morphogenesis of photoreceptors. Pathogenic variants in CRB1 lead to a huge variety of phenotypes ranging from milder forms of inherited retinal dystrophy, such as retinitis pigmentosa to more severe phenotypes such as Leber congenital amaurosis. In this study, seven novel likely-pathogenic variants were identified: four missense variants (p.Leu479Pro, p.Ala921Pro, p.Cys948Arg and p.Asp1031Asn), two frameshift deletions (c.2536_2542del7 and c.3460_3461delTG) and one frameshift indel variant (c.276_294delinsTGAACACTGTAC). Furthermore, two patients with cone-rod dystrophy due to mutations in CRB1 were reported, supporting previous data, in which mutations in CRB1 can also cause cone-rod dystrophy. Finally, our data suggested there was a direct relation between phenotype severity and the mutation effect on protein functionality in 15 Brazilian CRB1 patients.

  14. Inherit Space

    NASA Technical Reports Server (NTRS)

    Giarratano, Joseph C.; Jenks, K. C.

    1997-01-01

    The objective of the proposed research was to begin development of a unique educational tool targeted at educating and inspiring young people 12-16 years old about NASA and the Space Program. Since these young people are the future engineers, scientists and space pioneers, the nurturing of their enthusiasm and interest is of critical importance to the Nation. This summer the basic infrastructure of the tool was developed in the context of an educational game paradigm. The game paradigm has achieved remarkable success in maintaining the interest of young people in a self-paced, student-directed learning environment. This type of environment encourages student exploration and curiosity which are exactly the traits that future space pioneers need to develop to prepare for the unexpected. The Inherit Space Educational Tool is an open-ended learning environment consisting of a finite-state machine classic adventure game paradigm. As the young person explores this world, different obstacles must be overcome. Rewards will be offered such as using the flight simulator to fly around and explore Titan. This simulator was modeled on conventional Earth flight simulators but has been considerably enhanced to add texture mapping of Titan's atmosphere utilizing the latest information from the NASA Galileo Space Probe. Additional scenery was added to provide color VGA graphics of a futuristic research station on Titan as well as an interesting story to keep the youngster's attention. This summer the game infrastructure has been developed as well as the Titan Flight Simulator. A number of other enhancements are planned.

  15. Role of Genetic Testing in Inherited Cardiovascular Disease: A Review.

    PubMed

    Cirino, Allison L; Harris, Stephanie; Lakdawala, Neal K; Michels, Michelle; Olivotto, Iacopo; Day, Sharlene M; Abrams, Dominic J; Charron, Philippe; Caleshu, Colleen; Semsarian, Christopher; Ingles, Jodie; Rakowski, Harry; Judge, Daniel P; Ho, Carolyn Y

    2017-08-09

    Genetic testing is a valuable tool for managing inherited cardiovascular disease in patients and families, including hypertrophic, dilated, and arrhythmogenic cardiomyopathies and inherited arrhythmias. By identifying the molecular etiology of disease, genetic testing can improve diagnostic accuracy and refine family management. However, unique features associated with genetic testing affect the interpretation and application of results and differentiate it from traditional laboratory-based diagnostics. Clinicians and patients must have accurate and realistic expectations about the yield of genetic testing and its role in management. Familiarity with the rationale, implications, benefits, and limitations of genetic testing is essential to achieve the best possible outcomes. Successfully incorporating genetic testing into clinical practice requires (1) recognizing when inherited cardiovascular disease may be present, (2) identifying appropriate individuals in the family for testing, (3) selecting the appropriate genetic test, (4) understanding the complexities of result interpretation, and (5) effectively communicating the results and implications to the patient and family. Obtaining a detailed family history is critical to identify families who will benefit from genetic testing, determine the best strategy, and interpret results. Instead of focusing on an individual patient, genetic testing requires consideration of the family as a unit. Consolidation of care in centers with a high level of expertise is recommended. Clinicians without expertise in genetic testing will benefit from establishing referral or consultative networks with experienced clinicans in specialized multidisciplinary clinics. Genetic testing provides a foundation for transitioning to more precise and individualized management. By distinguishing phenotypic subgroups, identifying disease mechanisms, and focusing family care, gene-based diagnosis can improve management. Successful integration of

  16. Developing and assessing the utility of a You-Tube based clinical genetics video channel for families affected by inherited tumours.

    PubMed

    Jones, G E; Singletary, J H; Cashmore, A; Jain, V; Abhulimhen, J; Chauhan, J; Musson, H V; Barwell, J G

    2016-04-01

    We have designed and implemented the first worldwide You Tube channel with 22 videos covering common questions asked in familial cancer susceptibility clinics. We discuss the use of the videos including demographics of registered You Tube users, and what lessons have been learnt about how the general public uses medical information online. The most popular video on inheritance patterns has been watched on average 84 times per month. The mostly highly viewed videos include inheritance patterns, breast cancer screening and hereditary non-polyposis colorectal cancer. Registered viewers were more commonly male and the average age of the registered user was 45-54 years; similar to that seen in Genetics Clinics suggesting that age may not be a major barrier to access to this type of information for patients. The videos have been viewed in more than 140 countries confirming that there is clearly an audience for this type of information. Patient feedback questionnaires indicate that these videos provide a useful aide memoir for the clinic appointment, and most people would recommend them to others. In summary, You Tube videos are easy and cost effective to make. They have the ability to disseminate genetics education to a worldwide audience and may be a useful adjunct to clinical appointments.

  17. Lipedema: an inherited condition.

    PubMed

    Child, Anne H; Gordon, Kristiana D; Sharpe, Pip; Brice, Glen; Ostergaard, Pia; Jeffery, Steve; Mortimer, Peter S

    2010-04-01

    Lipedema is a condition characterized by swelling and enlargement of the lower limbs due to abnormal deposition of subcutaneous fat. Lipedema is an under-recognized condition, often misdiagnosed as lymphedema or dismissed as simple obesity. We present a series of pedigrees and propose that lipedema is a genetic condition with either X-linked dominant inheritance or more likely, autosomal dominant inheritance with sex limitation. Lipedema appears to be a condition almost exclusively affecting females, presumably estrogen-requiring as it usually manifests at puberty. Lipedema is an entity distinct from obesity, but may be wrongly diagnosed as primary obesity, due to clinical overlap. The phenotype suggests a condition distinct from obesity and associated with pain, tenderness, and easy bruising in affected areas. (c) 2010 Wiley-Liss, Inc.

  18. Potassium-channel mutations and cardiac arrhythmias--diagnosis and therapy.

    PubMed

    Giudicessi, John R; Ackerman, Michael J

    2012-01-31

    The coordinated generation and propagation of action potentials within cardiomyocytes creates the intrinsic electrical stimuli that are responsible for maintaining the electromechanical pump function of the human heart. The synchronous opening and closing of cardiac Na(+), Ca(2+), and K(+) channels corresponds with the activation and inactivation of inward depolarizing (Na(+) and Ca(2+)) and outward repolarizing (K(+)) currents that underlie the various phases of the cardiac action potential (resting, depolarization, plateau, and repolarization). Inherited mutations in pore-forming α subunits and accessory β subunits of cardiac K(+) channels can perturb the atrial and ventricular action potential and cause various cardiac arrhythmia syndromes, including long QT syndrome, short QT syndrome, Brugada syndrome, and familial atrial fibrillation. In this Review, we summarize the current understanding of the molecular and cellular mechanisms that underlie K(+)-channel-mediated arrhythmia syndromes. We also describe translational advances that have led to the emerging role of genetic testing and genotype-specific therapy in the diagnosis and clinical management of individuals who harbor pathogenic mutations in genes that encode α or β subunits of cardiac K(+) channels.

  19. Impact of Inherited Prothrombotic Disorders on the Long-Term Clinical Outcome of Percutaneous Transluminal Angioplasty in Patients with Diabetes

    PubMed Central

    Dubský, Michal; Jirkovská, Alexandra; Pagáčová, Libuše; Bém, Robert; Němcová, Andrea; Fejfarová, Vladimíra; Wosková, Veronika; Jude, Edward B.

    2015-01-01

    The aim of our study was to analyse inherited thrombotic disorders that influence the long-term outcome of PTA. Methods. Diabetic patients with peripheral arterial disease (PAD) treated by PTA in our centre between 2008 and 2011 were included in the study. Patients were divided into unsuccessful PTA group (75 patients), successful PTA group (58 patients), and control group (65 patients, with diabetes but no PAD). Diagnosis of inherited thrombotic disorders included mutation in factor V (Leiden), factor II (prothrombin), and mutation in genes for methylenetetrahydrofolate reductase—MTHFR (C677T and A1298C). Results. The genotypic frequency of Leiden allele G1691A was significantly associated with a risk of unsuccessful PTA in comparison with successful PTA group and control group (OR 8.8 (1.1–70.6), p = 0.041, and OR 9.8 (1.2–79.2), p = 0.032, resp.). However, we only observed a trend for the association of the prothrombin allele G20210A and risk of PTA failure. The frequencies of alleles of MTHFR 677 or 1298 did not differ significantly among the groups. Conclusion. Our study showed higher frequency of heterozygous form of Leiden mutation in diabetic patients with unsuccessful outcome of PTA in comparison with patients with successful PTA and diabetic patients without PAD. PMID:26247037

  20. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)

    PubMed Central

    Tristani-Firouzi, Martin; Jensen, Judy L.; Donaldson, Matthew R.; Sansone, Valeria; Meola, Giovanni; Hahn, Angelika; Bendahhou, Said; Kwiecinski, Hubert; Fidzianska, Anna; Plaster, Nikki; Fu, Ying-Hui; Ptacek, Louis J.; Tawil, Rabi

    2002-01-01

    Andersen syndrome (AS) is a rare, inherited disorder characterized by periodic paralysis, long QT (LQT) with ventricular arrhythmias, and skeletal developmental abnormalities. We recently established that AS is caused by mutations in KCNJ2, which encodes the inward rectifier K+ channel Kir2.1. In this report, we characterized the functional consequences of three novel and seven previously described KCNJ2 mutations using a two-microelectrode voltage-clamp technique and correlated the findings with the clinical phenotype. All mutations resulted in loss of function and dominant-negative suppression of Kir2.1 channel function. In mutation carriers, the frequency of periodic paralysis was 64% and dysmorphic features 78%. LQT was the primary cardiac manifestation, present in 71% of KCNJ2 mutation carriers, with ventricular arrhythmias present in 64%. While arrhythmias were common, none of our subjects suffered sudden cardiac death. To gain insight into the mechanism of arrhythmia susceptibility, we simulated the effect of reduced Kir2.1 using a ventricular myocyte model. A reduction in Kir2.1 prolonged the terminal phase of the cardiac action potential, and in the setting of reduced extracellular K+, induced Na+/Ca2+ exchanger–dependent delayed afterdepolarizations and spontaneous arrhythmias. These findings suggest that the substrate for arrhythmia susceptibility in AS is distinct from the other forms of inherited LQT syndrome. PMID:12163457

  1. Maternal arrhythmia and perinatal outcomes

    PubMed Central

    Henry, Dana; Gonzalez, Juan M; Harris, Ian, S.; Sparks, Teresa; Killion, Molly; Thiet, Mari-Paule; Bianco, Katherine

    2016-01-01

    Objective To determine if arrhythmia in the setting of maternal cardiac disease (MCD) affects perinatal outcomes. Study Design This is a retrospective cohort study of pregnant women with MCD who delivered from 2008 to 2013. Perinatal outcomes among women with an arrhythmia were compared to those without. Result Among 143 women; 36 (25%) had an arrhythmia. Those with an arrhythmia were more likely to have a spontaneous vaginal delivery (64% vs. 43%, p < 0.05) and required fewer operative vaginal births (8% vs. 27%, p=0.02). Pregnancies were more likely to be complicated by IUGR (17% vs. 5%, p < 0.05) although there were no differences in the rate of small for gestational age. The risk of IUGR remained increased after controlling for confounding (aOR 6.98, 95% CI 1.59–30.79, p=0.01). Two cases of placental abruption were identified among mothers with arrhythmia while none were identified in the controls (p < 0.05) Conclusion Patients with arrhythmias were more likely to have a spontaneous vaginal delivery. Our data suggests that these pregnancies were an increased risk for IUGR. PMID:27309629

  2. Data analysis in cardiac arrhythmias.

    PubMed

    Rodrigo, Miguel; Pedrón-Torecilla, Jorge; Hernández, Ismael; Liberos, Alejandro; Climent, Andreu M; Guillem, María S

    2015-01-01

    Cardiac arrhythmias are an increasingly present in developed countries and represent a major health and economic burden. The occurrence of cardiac arrhythmias is closely linked to the electrical function of the heart. Consequently, the analysis of the electrical signal generated by the heart tissue, either recorded invasively or noninvasively, provides valuable information for the study of cardiac arrhythmias. In this chapter, novel cardiac signal analysis techniques that allow the study and diagnosis of cardiac arrhythmias are described, with emphasis on cardiac mapping which allows for spatiotemporal analysis of cardiac signals.Cardiac mapping can serve as a diagnostic tool by recording cardiac signals either in close contact to the heart tissue or noninvasively from the body surface, and allows the identification of cardiac sites responsible of the development or maintenance of arrhythmias. Cardiac mapping can also be used for research in cardiac arrhythmias in order to understand their mechanisms. For this purpose, both synthetic signals generated by computer simulations and animal experimental models allow for more controlled physiological conditions and complete access to the organ.

  3. Arrhythmia discrimination using a smart phone.

    PubMed

    Chong, Jo Woon; Esa, Nada; McManus, David D; Chon, Ki H

    2015-05-01

    We hypothesize that our smartphone-based arrhythmia discrimination algorithm with data acquisition approach reliably differentiates between normal sinus rhythm (NSR), atrial fibrillation (AF), premature ventricular contractions (PVCs) and premature atrial contraction (PACs) in a diverse group of patients having these common arrhythmias. We combine root mean square of successive RR differences and Shannon entropy with Poincare plot (or turning point ratio method) and pulse rise and fall times to increase the sensitivity of AF discrimination and add new capabilities of PVC and PAC identification. To investigate the capability of the smartphone-based algorithm for arrhythmia discrimination, 99 subjects, including 88 study participants with AF at baseline and in NSR after electrical cardioversion, as well as seven participants with PACs and four with PVCs were recruited. Using a smartphone, we collected 2-min pulsatile time series from each recruited subject. This clinical application results show that the proposed method detects NSR with specificity of 0.9886, and discriminates PVCs and PACs from AF with sensitivities of 0.9684 and 0.9783, respectively.

  4. Cardiac arrhythmias in stroke unit patients. Evaluation of the cardiac monitoring data.

    PubMed

    Fernández-Menéndez, S; García-Santiago, R; Vega-Primo, A; González Nafría, N; Lara-Lezama, L B; Redondo-Robles, L; Montes-Montes, M; Riveira-Rodríguez, M C; Tejada-García, J

    2016-06-01

    Cardiac arrhythmias are frequent in acute stroke. Stroke units are widely equipped with cardiac monitoring systems. Pre-existing heart diseases and heart-brain interactions may be implicated in causing cardiac arrhythmias in acute stroke. This article analyses cardiac arrhythmias detected in patients hospitalised in a stroke unit. Prospective observational study of consecutive patients admitted to a stroke unit with cardiac monitoring. We collected clinical data from patients and the characteristics of their cardiac arrhythmias over a 1-year period (2013). Time of arrhythmia onset, associated predisposing factors, and the therapeutic decisions made after detection of arrhythmia were examined. All patients underwent continuous cardiac monitoring during no less than 48hours. Of a total of 332 patients admitted, significant cardiac arrhythmias occurred in 98 patients (29.5%) during their stay in the stroke unit. Tachyarrhythmia (ventricular tachyarrhythmias, supraventricular tachyarrhythmias, complex ventricular ectopy) was present in 90 patients (27.1%); bradyarrhythmia was present in 13 patients (3.91%). Arrhythmias were independently associated with larger size of brain lesion and older age. In 10% of the patient total, therapeutic actions were taken after detection of significant cardiac arrhythmias. Most events occurred within the first 48hours after stroke unit admission. Systematic cardiac monitoring in patients with acute stroke is useful for detecting clinically relevant cardiac arrhythmias. Incidence of arrhythmia is higher in the first 48hours after stroke unit admission. Age and lesion size were predicted appearance of arrhythmias. Detection of cardiac arrhythmias in a stroke unit has important implications for treatment. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  5. A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias.

    PubMed

    Roy, Noémi B A; Wilson, Edward A; Henderson, Shirley; Wray, Katherine; Babbs, Christian; Okoli, Steven; Atoyebi, Wale; Mixon, Avery; Cahill, Mary R; Carey, Peter; Cullis, Jonathan; Curtin, Julie; Dreau, Helene; Ferguson, David J P; Gibson, Brenda; Hall, Georgina; Mason, Joanne; Morgan, Mary; Proven, Melanie; Qureshi, Amrana; Sanchez Garcia, Joaquin; Sirachainan, Nongnuch; Teo, Juliana; Tedgård, Ulf; Higgs, Doug; Roberts, David; Roberts, Irene; Schuh, Anna

    2016-10-01

    Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical-grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. To achieve a clinically-reliable diagnostic test and minimize false-negative results we developed an open-source tool (CoverMi) to accurately determine base-coverage and the 'discoverability' of known mutations for every sample. We validated our 33-gene panel using Sanger sequencing and microarray. Our panel demonstrated 100% specificity and 99·7% sensitivity. We then analysed 57 clinical samples: molecular diagnoses were made in 22/57 (38·6%), corresponding to 32 mutations of which 16 were new. In all cases, accurate molecular diagnosis had a positive impact on clinical management. Using a validated NGS-based platform for routine molecular diagnosis of previously undiagnosed congenital anaemias is feasible in a clinical diagnostic setting, improves precise diagnosis and enhances management and counselling of the patient and their family.

  6. Inherited ion channel diseases: a brief review.

    PubMed

    Lieve, Krystien V V; Wilde, Arthur A M

    2015-10-01

    Ion channelopathies are diseases caused by dysfunctional ion channels that may lead to sudden death. These diseases can be either acquired or inherited. The main phenotypes observed in patients carrying these heritable arrhythmia syndromes are congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome. In the recent years, tremendous progress has been made in the recognition, mechanisms, and treatment of these diseases. The goal of this review is to provide an overview of the main phenotypes, genetic underpinnings, risk stratification, and treatment options for these so-called cardiac ion channelopathies.

  7. Hepatitic inherited metabolic disorders.

    PubMed

    Arroyo, May; Crawford, James M

    2006-01-01

    Primary metabolic disorders are a disparate group of diseases that may or may not be accompanied by hepatic manifestations. Those with liver involvement may show a range of histopathologic changes. Proper histologic diagnosis requires correlation with clinical and laboratory data, including evaluation for mutations either via serum protein electrophoresis or through formal genetic analysis. This article is a review of the three most common inherited metabolic disorders which may present with a hepatitic pattern. In alpha1-antitrypsin disorder, there is a broad range of clinical presentations, age at presentation, and histological features ranging from "neonatal hepatitis" to a chronic progressive hepatitis in later childhood and adulthood. Hence, this disorder must be in the differential diagnosis of liver disease of the very young, and in older children and adults, with or without coexistent overt pulmonary symptoms. In Wilson disease, presentation tends to be in older childhood or the adult, with a progressive chronic hepatitis. Cystic fibrosis may feature a characteristic obstructive biliary syndrome, coexisting with the many extrahepatic manifestations of this debilitating disease. Lastly, the progressive familial intrahepatic cholestasis (PFIC) syndromes are given as examples of inherited metabolic conditions in which relentlessly progressive cholestatic liver disease eventuates over years in end-stage cholestatic liver disease with cirrhosis. Distinguishing features include absence of elevated serum gamma-glutamyl transpeptidase (GGT) in PFIC-1 and PFIC-2, and elevated GGT in PFIC-3. However, molecular studies are required for a confident diagnosis of the rare PFIC syndromes.

  8. A preliminary study of inherited thrombophilic risk factors in different clinical manifestations of venous thromboembolism in central Iran

    PubMed Central

    Karimi, Ali; Abolhasani, Marziyeh; Hashemzadeh-Chaleshtori, Morteza; Pourgheysari, Batoul

    2015-01-01

    Background & objectives: Inherited thrombophilia is known to be an important risk factor for developing venous thromboembolism. Whether such abnormalities may impact the development of deep vein thrombosis (DVT) and pulmonary embolism (PE) differently is not well defined. This preliminary study was undertaken to compare thrombophilic polymorphism in patients with DVT and PE. Methods: A total of 35 DVT, 23 DVT/PE, and 37 PE patients admitted to the Hajar Hospital, Shahrekord, Iran, between October 2009 and February 2011 were included in the study and 306 healthy volunteers matched by age and sex from the same geographical area with no history of venous or arterial diseases were included as control group. Factor V Leiden (FV 1691G/A, rs6025), prothrombin (FII 20210G/A), methylene tetrahydrofulate reductase (MTHFR 677C/T, rs1801133), and PLA2 polymorphisms of platelet glycoprotein IIb/IIIa (GpIIIa 1565T/C, rs5918) were investigated by polymerase chain reaction-restriction fragment length polymorphism. Results: The number of patients with the investigated polymorphisms and homozygous carriers was significantly different among the groups (P<0.05). No significant difference was observed in the presence of FV 1691G/A and FII 20210G/A between any of the patients groups and the control group. GpIIIa 1565T/C and homozygous MTHFR 677C/T polymorphisms were higher in DVT patients compared with the control group (OR=6.65, 95% CI=3.09-14.30 and OR=4.08, 95% CI=1.35-12.38, respectively). Interpretation & conclusions: As none of the investigated polymorphisms were associated with PE, other thrombophilia polymorphisms may have a role in the pathogenesis of PE in these patients and should be investigated. Because of different prognostic risk factors among different types of patients, the treatment approach could be different. PMID:26261166

  9. Development and Initial Psychometric Evaluation of the Patient Perspective of Arrhythmia Questionnaire

    PubMed Central

    Wood, Kathryn A.; Stewart, Anita L.; Drew, Barbara J.; Scheinman, Melvin M.; Froëlicher, Erika S.

    2010-01-01

    There are no disease-specific questionnaires to measure patient sensitive outcomes in arrhythmia patients. We report the development and preliminary psychometric testing of the Patient Perception of Arrhythmia Questionnaire (PPAQ). The PPAQ was developed using formative research, exploratory factor analysis, expert review, pilot study, and regression. The PPAQ measures frequency and duration of episodes, symptoms, impact on daily activities, and restricted activity days. After preliminary content validation, the responsiveness of the PPAQ was tested in 103 arrhythmia patients. The measures showed good sensitivity and reliability. Preliminary construct validation was supported by significant differences (p<.001) among groups of arrhythmia patients consistent with clinical patterns. Preliminary evidence from patients with supraventricular arrhythmias suggests that the questionnaire has acceptable psychometrics and could be useful in future studies of arrhythmia patients. PMID:19701927

  10. Clinical Management of a Child with Prader-Willi Syndrome from Maternal Uniparental Disomy (UPD) Genetic Inheritance

    ERIC Educational Resources Information Center

    Bellon-Harn, Monica L.

    2005-01-01

    Prader-Willi Syndrome (PWS) is reported in 1 in 10,000-15,000 individuals. Unfortunately, many cases are missed due to clinicians' lack of familiarity with the syndrome as well as clinical and laboratory diagnostic criteria. Although common clinical characteristics are reported, variety exists in the nature and severity of dysfunction associated…

  11. Clinical Management of a Child with Prader-Willi Syndrome from Maternal Uniparental Disomy (UPD) Genetic Inheritance

    ERIC Educational Resources Information Center

    Bellon-Harn, Monica L.

    2005-01-01

    Prader-Willi Syndrome (PWS) is reported in 1 in 10,000-15,000 individuals. Unfortunately, many cases are missed due to clinicians' lack of familiarity with the syndrome as well as clinical and laboratory diagnostic criteria. Although common clinical characteristics are reported, variety exists in the nature and severity of dysfunction associated…

  12. Early afterdepolarizations and cardiac arrhythmias.

    PubMed

    Weiss, James N; Garfinkel, Alan; Karagueuzian, Hrayr S; Chen, Peng-Sheng; Qu, Zhilin

    2010-12-01

    Early afterdepolarizations (EADs) are an important cause of lethal ventricular arrhythmias in long QT syndromes and heart failure, but the mechanisms by which EADs at the cellular scale cause arrhythmias such as polymorphic ventricular tachycardia (PVT) and torsades de pointes (TdP) at the tissue scale are not well understood. Here we summarize recent progress in this area, discussing (1) the ionic basis of EADs, (2) evidence that deterministic chaos underlies the irregular behavior of EADs, (3) mechanisms by which chaotic EADs synchronize in large numbers of coupled cells in tissue to overcome source-sink mismatches, (4) how this synchronization process allows EADs to initiate triggers and generate mixed focal reentrant ventricular arrhythmias underlying PVT and TdP, and (5) therapeutic implications.

  13. High-frequency power within the QRS complex in ischemic cardiomyopathy patients with ventricular arrhythmias: Insights from a clinical study and computer simulation of cardiac fibrous tissue.

    PubMed

    Tsutsumi, Takeshi; Okamoto, Yoshiwo; Takano, Nami; Wakatsuki, Daisuke; Tomaru, Takanobu; Nakajima, Toshiaki

    2017-08-01

    The distribution of frequency power (DFP) within the QRS complex (QRS) is unclear. This study aimed to investigate the DFP within the QRS in ischemic cardiomyopathy (ICM) with lethal ventricular arrhythmias (L-VA). A computer simulation was performed to explore the mechanism of abnormal frequency power. The study included 31 ICM patients with and without L-VA (n = 10 and 21, respectively). We applied the continuous wavelet transform to measure the time-frequency power within the QRS. Integrated time-frequency power (ITFP) was measured within the frequency range of 5-300 Hz. The simulation model consisted of two-dimensional myocardial tissues intermingled with fibroblasts. We examined the relation between frequency power calculated from the simulated QRS and the fibroblast-to-myocyte ratio (r) of the model. The frequency powers significantly increased from 180 to 300 Hz and from 5 to 15 Hz, and also decreased from 45 to 80 Hz in patients with ICM and L-VA compared with the normal individuals. They increased from 110 Hz to 250 Hz in ICM alone. In the simulation, the high-frequency power increased when the ratio (r) were 2.0-2.5. Functional reentry was initiated if the ratio (r) increased to 2.0. Abnormal higher-frequency power (180-300 Hz) may provide arrhythmogenic signals in ICM with L-VA that may be associated with the fibrous tissue proliferation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Almanac 2013: cardiac arrhythmias and pacing.

    PubMed

    Liew, Reginald

    2013-10-01

    Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection, risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF. Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms, many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management. This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing.

  15. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death.

    PubMed

    Mohler, Peter J; Schott, Jean-Jacques; Gramolini, Anthony O; Dilly, Keith W; Guatimosim, Silvia; duBell, William H; Song, Long-Sheng; Haurogné, Karine; Kyndt, Florence; Ali, Mervat E; Rogers, Terry B; Lederer, W J; Escande, Denis; Le Marec, Herve; Bennett, Vann

    2003-02-06

    Mutations in ion channels involved in the generation and termination of action potentials constitute a family of molecular defects that underlie fatal cardiac arrhythmias in inherited long-QT syndrome. We report here that a loss-of-function (E1425G) mutation in ankyrin-B (also known as ankyrin 2), a member of a family of versatile membrane adapters, causes dominantly inherited type 4 long-QT cardiac arrhythmia in humans. Mice heterozygous for a null mutation in ankyrin-B are haploinsufficient and display arrhythmia similar to humans. Mutation of ankyrin-B results in disruption in the cellular organization of the sodium pump, the sodium/calcium exchanger, and inositol-1,4,5-trisphosphate receptors (all ankyrin-B-binding proteins), which reduces the targeting of these proteins to the transverse tubules as well as reducing overall protein level. Ankyrin-B mutation also leads to altered Ca2+ signalling in adult cardiomyocytes that results in extrasystoles, and provides a rationale for the arrhythmia. Thus, we identify a new mechanism for cardiac arrhythmia due to abnormal coordination of multiple functionally related ion channels and transporters.

  16. Maximizing the Effectiveness of Ablation for Arrhythmias in the Congenital Heart Patients.

    PubMed

    Arujuna, Aruna; de Bono, Joseph

    2016-07-01

    Arrhythmias are common in adults with congenital heart disease and account for a large proportion of hospitalizations. The complex anatomical heterogeneity, often in the presence of a delicate hemodynamic system, presents a significant electrophysiological challenge. This review outlines current clinical practice and advances in maximizing the effectiveness of ablation for arrhythmias in congenital heart patients.

  17. Inherited Xq13.2-q21.31 duplication in a boy with recurrent seizures and pubertal gynecomastia: Clinical, chromosomal and aCGH characterization.

    PubMed

    Linhares, Natália D; Valadares, Eugênia R; da Costa, Silvia S; Arantes, Rodrigo R; de Oliveira, Luiz Roberto; Rosenberg, Carla; Vianna-Morgante, Angela M; Svartman, Marta

    2016-09-01

    We report on a 16-year-old boy with a maternally inherited ~ 18.3 Mb Xq13.2-q21.31 duplication delimited by aCGH. As previously described in patients with similar duplications, his clinical features included intellectual disability, developmental delay, speech delay, generalized hypotonia, infantile feeding difficulties, self-injurious behavior, short stature and endocrine problems. As additional findings, he presented recurrent seizures and pubertal gynecomastia. His mother was phenotypically normal and had completely skewed inactivation of the duplicated X chromosome, as most female carriers of such duplications. Five previously reported patients with partial Xq duplications presented duplication breakpoints similar to those of our patient. One of them, a fetus with multiple congenital abnormalities, had the same cytogenetic duplication breakpoint. Three of the reported patients shared many features with our proband but the other had some clinical features of the Prader-Willi syndrome. It was suggested that ATRX overexpression could be involved in the major clinical features of patients with partial Xq duplications. We propose that this gene could also be involved with the obesity of the patient with the Prader-Willi-like phenotype. Additionally, we suggest that the PCDH11X gene could be a candidate for our patient's recurrent seizures. In males, the Xq13-q21 duplication should be considered in the differential diagnosis of Prader-Willi syndrome, as previously suggested, and neuromuscular diseases, particularly mitochondriopathies.

  18. Mitochondrial inheritance in fungi.

    PubMed

    Basse, Christoph W

    2010-12-01

    Faithful inheritance of mitochondria is essential for growth and development. Uniparental inheritance of mitochondria is a common phenomenon in sexual eukaryotes and has been reported for numerous fungal species. Uniparental inheritance is a genetically regulated process, aimed to gain a homoplasmic state within cells, and this is often associated with selective elimination of one parental mitochondria population. This review will focus on recent developments in our understanding of common and specified regulatory circuits of selective mitochondrial inheritance during sexual development. It further refers to the influence of mitochondrial fusion on generation of recombinant mitochondrial DNA molecules. The latter aspect appears rather exciting in the context of intron homing and could bring a new twist to the debate on the significance of uniparental inheritance. The emergence of genome-wide studies offers new perspectives to address potential relationships between uniparental inheritance, vegetative inheritance and last but not least cellular scavenging systems to dispose of disintegrated organelles.

  19. Inherited disorders of desmosomes.

    PubMed

    McGrath, John A

    2005-11-01

    Desmosomes are highly organized intercellular junctions that provide mechanical integrity to tissues by anchoring intermediate filaments to sites of strong adhesion. These cell-cell adhesion junctions are found in skin, heart, lymph nodes and meninges. Over the last 8 years, several naturally occurring human gene mutations in structural components of desmosomes have been reported. These comprise autosomal dominant or recessive mutations in plakophilin 1, plakophilin 2, desmoplakin, plakoglobin, desmoglein 1, desmoglein 4 and corneodesmosin. These discoveries have often highlighted novel or unusual phenotypes, including abnormal skin fragility and differentiation, and developmental anomalies of various ectodermal appendages, especially hair. Some desmosomal gene mutations may also result in cardiac disease, notably cardiomyopathy. This article describes the spectrum of clinical features that may be found in the inherited disorders of desmosomes and highlights the key functions of several of the desmosomal proteins in tissue adhesion and cell biology.

  20. Inherited mitochondrial optic neuropathies

    PubMed Central

    Yu-Wai-Man, P; Griffiths, P G; Hudson, G; Chinnery, P F

    2009-01-01

    Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited. PMID:19001017

  1. Nonlinear-dynamical arrhythmia control in humans

    PubMed Central

    Christini, David J.; Stein, Kenneth M.; Markowitz, Steven M.; Mittal, Suneet; Slotwiner, David J.; Scheiner, Marc A.; Iwai, Sei; Lerman, Bruce B.

    2001-01-01

    Nonlinear-dynamical control techniques, also known as chaos control, have been used with great success to control a wide range of physical systems. Such techniques have been used to control the behavior of in vitro excitable biological tissue, suggesting their potential for clinical utility. However, the feasibility of using such techniques to control physiological processes has not been demonstrated in humans. Here we show that nonlinear-dynamical control can modulate human cardiac electrophysiological dynamics by rapidly stabilizing an unstable target rhythm. Specifically, in 52/54 control attempts in five patients, we successfully terminated pacing-induced period-2 atrioventricular-nodal conduction alternans by stabilizing the underlying unstable steady-state conduction. This proof-of-concept demonstration shows that nonlinear-dynamical control techniques are clinically feasible and provides a foundation for developing such techniques for more complex forms of clinical arrhythmia. PMID:11320216

  2. Nonlinear-dynamical arrhythmia control in humans.

    PubMed

    Christini, D J; Stein, K M; Markowitz, S M; Mittal, S; Slotwiner, D J; Scheiner, M A; Iwai, S; Lerman, B B

    2001-05-08

    Nonlinear-dynamical control techniques, also known as chaos control, have been used with great success to control a wide range of physical systems. Such techniques have been used to control the behavior of in vitro excitable biological tissue, suggesting their potential for clinical utility. However, the feasibility of using such techniques to control physiological processes has not been demonstrated in humans. Here we show that nonlinear-dynamical control can modulate human cardiac electrophysiological dynamics by rapidly stabilizing an unstable target rhythm. Specifically, in 52/54 control attempts in five patients, we successfully terminated pacing-induced period-2 atrioventricular-nodal conduction alternans by stabilizing the underlying unstable steady-state conduction. This proof-of-concept demonstration shows that nonlinear-dynamical control techniques are clinically feasible and provides a foundation for developing such techniques for more complex forms of clinical arrhythmia.

  3. Cardiac arrhythmias in hypokalemic periodic paralysis: Hypokalemia as only cause?

    PubMed

    Stunnenberg, Bas C; Deinum, Jaap; Links, Thera P; Wilde, Arthur A; Franssen, Hessel; Drost, Gea

    2014-09-01

    It is unknown how often cardiac arrhythmias occur in hypokalemic periodic paralysis (HypoPP) and if they are caused by hypokalemia alone or other factors. This systematic review shows that cardiac arrhythmias were reported in 27 HypoPP patients. Cases were confirmed genetically (13 with an R528H mutation in CACNA1S, 1 an R669H mutation in SCN4A) or had a convincing clinical diagnosis of HypoPP (13 genetically undetermined) if reported prior to the availability of genetic testing. Arrhythmias occurred during severe hypokalemia (11 patients), between attacks at normokalemia (4 patients), were treatment-dependent (2 patients), or unspecified (10 patients). Nine patients died from arrhythmia. Convincing evidence for a pro-arrhythmogenic factor other than hypokalemia is still lacking. The role of cardiac expression of defective skeletal muscle channels in the heart of HypoPP patients remains unclear. Clinicians should be aware of and prevent treatment-induced cardiac arrhythmia in HypoPP.

  4. Cardiac arrhythmias in Chagas' heart disease.

    PubMed

    Elizari, M V; Chiale, P A

    1993-10-01

    Chagas' disease is a chronic parasitosis affecting most Latin American countries. Its most important clinical manifestation is a late developing chronic myocarditis and, much less frequently, an early acute myocarditis. Chagasic myocardial damage is microfocal and disseminated throughout the heart. In most cases, the coexistence of areas of myocytic degeneration, inflammatory infiltration, and fibrosis suggests a permanent evolving process. Commonly, chronic chagasic myocarditis resembles a dilated cardiomyopathy, with characteristic ECG abnormalities (atrial and ventricular extrasystoles, intraventricular and/or AV conduction disturbances, and primary ST-T wave changes). Since myocardial damage is scattered throughout the heart, the ECG abnormalities (arrhythmias, conduction disturbances, and repolarization changes) are also representative of the widespread cardiac involvement. Thus, sick sinus syndrome, atrial extrasystoles, intraatrial conduction disturbances, and atrial fibrillation or flutter are common findings in different stages of the disease. At the ventricular level, both conduction disturbances and arrhythmias are conspicuous expressions of the myocardial damage. Right bundle branch block alone or in combination with left anterior hemiblock are the most common conduction defects. Further compromise of the conduction system can lead to different degrees of AV block. Chagas' disease is the main cause of bundle branch block and AV block in endemic areas. In advanced cases of Chagas' heart disease, ventricular premature contractions are extremely frequent, multiform, and repetitive (couplets and runs of ventricular tachycardia), and show R on T phenomenon. These arrhythmias are usually aggravated by increased sympathetic tone, implying an enhanced risk of cardiac sudden death among chagasic patients, which is sometimes the first manifestation of the illness. Chronic chagasic myocarditis is the leading cause of cardiovascular death, mostly as a consequence

  5. A review of the clinical presentation, natural history and inheritance of variegate porphyria: its implausibility as the source of the 'Royal Malady'.

    PubMed

    Hift, Richard J; Peters, Timothy J; Meissner, Peter N

    2012-03-01

    It has been suggested that King George III of Great Britain suffered from the haem biosynthetic disorder, variegate porphyria. This diagnosis is pervasive throughout the scientific and popular literature, and is often referred to as the 'Royal Malady.' The authors believe it inappropriate to view the case for porphyria purely in terms of symptoms, as has generally been the case in his presumptive acute porphyria diagnosis. Accordingly, this review provides a current description of the natural history and clinical presentation of the porphyrias, against which we measure the case for porphyria in George III and his relatives. The authors have critically assessed the prevalence of porphyria in a population, the expected patterns and frequency of inheritance, its penetrance and its expected natural history in affected individuals, and conclude that neither George nor his relatives had porphyria, based on four principal reasons. First, the rarity of the disease mandates a very low prior probability, and therefore implies a vanishingly low positive predictive value for any diagnostic indicator of low specificity, such as a historical reading of the symptoms. Second, penetrance of this autosomal dominant disorder is approximately 40%, and one may expect to have identified characteristic clinical features of porphyria in a large number of descendants without difficulty. Third, the symptoms of both George III and his relatives are highly atypical for porphyria and are more appropriately explained by other much commoner conditions. Finally, the natural history of the illnesses reported in this family is as atypical for variegate porphyria as are their symptoms.

  6. Clinical delineation of Giuffrè-Tsukahara syndrome: another case with microcephaly and radio-ulnar synostosis with apparent X-linked semi-dominant inheritance.

    PubMed

    Gaspar, Harald; Albermann, Kurt; Baumer, Alessandra; Schinzel, Albert

    2008-06-01

    Two families and three sporadic cases have been described so far with the combination of radio-ulnar synostosis and microcephaly as main features. Some authors have discussed whether the first family reported by Giuffrè et al. [1994] and the second family described by Tsukahara et al. [1995] had the same syndrome. Although there is phenotypic variability among the described cases (especially with respect to facial dysmorphisms and mental retardation), the clinical patterns do not seem to be clearly distinguishable from each other. We describe another family with apparent X-linked semi-dominant inheritance with milder features in the female patient due to skewed X-inactivation. From a clinical synopsis, we consider the Giuffrè-Tsukahara syndrome as one genetic entity, which is characterized by the association of microcephaly and radio-ulnar synostosis, mental retardation in male patients and variable minor features. Patients with the Giuffrè-Tsukahara syndrome do not present with a characteristic pattern of facial features.

  7. The role of genealogy and clinical family histories in documenting possible inheritance patterns for diabetes mellitus in the pre-insulin era: part 1. The clinical case of Josephine Imperato.

    PubMed

    Imperato, Pascal James; Imperato, Gavin H

    2009-10-01

    Establishing the role of heredity in type 2 diabetes mellitus (type 2 DM) is challenging. While type 2 DM frequently displays a pattern of familial aggregation, many other risk factors are responsible for the clinical expression of the disease. This paper reviews a number of the early twentieth-century studies of inheritance patterns for type 2 DM and presents in detail the history of Josephine Foniciello Imperato (Maria Giuseppa Foniciello) who died from the disease in New York City at the age of 52 years on 14 November 1921, ten months before commercial insulin became available.

  8. Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease.

    PubMed

    Goudis, Christos A; Konstantinidis, Athanasios K; Ntalas, Ioannis V; Korantzopoulos, Panagiotis

    2015-11-15

    Chronic obstructive pulmonary disease (COPD) is independently associated with an increased burden of cardiovascular disease. Besides coronary artery disease (CAD) and congestive heart failure (CHF), specific electrocardiographic (ECG) abnormalities and cardiac arrhythmias seem to have a significant impact on cardiovascular prognosis of COPD patients. Disturbances of heart rhythm include premature atrial contractions (PACs), premature ventricular contractions (PVCs), atrial fibrillation (AF), atrial flutter (AFL), multifocal atrial tachycardia (MAT), and ventricular tachycardia (VT). Of note, the identification of ECG abnormalities and the evaluation of the arrhythmic risk may have significant implications in the management and outcome of patients with COPD. This article provides a concise overview of the available data regarding ECG abnormalities and arrhythmias in these patients, including an elaborated description of the underlying arrhythmogenic mechanisms. The clinical impact and prognostic significance of ECG abnormalities and arrhythmias in COPD as well as the appropriate antiarrhythmic therapy and interventions in this setting are also discussed.

  9. Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds.

    PubMed

    Prando, Carolina; Samarina, Arina; Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Cobat, Aurelie; Picard, Capucine; AlSum, Zobaida; Al-Jumaah, Suliman; Al-Hajjar, Sami; Frayha, Husn; Alangari, Abdullah; Al-Mousa, Hamoud; Mobaireek, Khalid F; Ben-Mustapha, Imen; Adimi, Parisa; Feinberg, Jacqueline; de Suremain, Maylis; Jannière, Lucile; Filipe-Santos, Orchidée; Mansouri, Nahal; Stephan, Jean-Louis; Nallusamy, Revathy; Kumararatne, Dinakantha S; Bloorsaz, Mohamad Reza; Ben-Ali, Meriem; Elloumi-Zghal, Houda; Chemli, Jalel; Bouguila, Jihene; Bejaoui, Mohamed; Alaki, Emadia; AlFawaz, Tariq S; Al Idrissi, Eman; ElGhazali, Gehad; Pollard, Andrew J; Murugasu, Belinda; Wah Lee, Bee; Halwani, Rabih; Al-Zahrani, Mohammed; Al Shehri, Mohammed A; Al-Zahrani, Mofareh; Bin-Hussain, Ibrahim; Mahdaviani, Seyed Alireza; Parvaneh, Nima; Abel, Laurent; Mansouri, Davood; Barbouche, Ridha; Al-Muhsen, Saleh; Casanova, Jean-Laurent

    2013-03-01

    Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation. Four of these 9 variants are recurrent, affecting 25 of the 30 reported kindreds, due to founder effects in specific countries. All patients are homozygous and display complete IL-12p40 deficiency. As a result, the patients lack detectable IL-12p70 and IL-12p40 and have low levels of interferon gamma (IFN-γ). The clinical features are characterized by childhood onset of bacille Calmette-Guérin (attenuated Mycobacterium bovis strain) (BCG) and Salmonella infections, with recurrences of salmonellosis (36.4%) more common than recurrences of mycobacterial disease (25%). BCG vaccination led to BCG disease in 40 of the 41 patients vaccinated (97.5%). Multiple mycobacterial infections were rare, observed in only 3 patients, whereas the association of salmonellosis and mycobacteriosis was observed in 9 patients. A few other infections were diagnosed, including chronic mucocutaneous candidiasis (n = 3), nocardiosis (n = 2), and klebsiellosis (n = 1). IL-12p40 deficiency has a high but incomplete clinical penetrance, with 33.3% of genetically affected relatives of index cases showing no symptoms. However, the prognosis is poor, with mortality rates of up to 28.6%. Overall, the clinical phenotype of IL-12p40 deficiency closely resembles that of interleukin 12 receptor β1 (IL-12Rβ1) deficiency. In conclusion, IL-12p40 deficiency is more common than initially thought and should be considered worldwide in patients with MSMD

  10. Cardiac Arrhythmias: Diagnosis, Symptoms, and Treatments.

    PubMed

    Fu, Du-Guan

    2015-11-01

    The cardiac arrhythmia is characterized by irregular rhythm of heartbeat which could be either too slow (<60 beats/min) or too fast (>100 beats/min) and can happen at any age. The use of pacemaker and defibrillators devices has been suggested for heart arrhythmias patients. The antiarrhythmic medications have been reported for the treatment of cardiac arrhythmias or irregular heartbeats. The diagnosis, symptoms, and treatments of cardiac arrhythmias as well as the radiofrequency ablation, tachycardia, Brugada syndrome, arterial fibrillation, and recent research on the genetics of cardiac arrhythmias have been described here.

  11. Evaluation and Management of Maternal Cardiac Arrhythmias.

    PubMed

    Metz, Torri D; Khanna, Amber

    2016-12-01

    Pregnant women often complain of palpitations. The differential diagnosis for new-onset palpitations in pregnancy ranges from benign conditions to life-threatening arrhythmias. Maternal arrhythmias can occur in isolation or in the setting of underlying structural heart disease. Optimal management of maternal cardiac arrhythmias includes identification of the specific arrhythmia, diagnosis of comorbid conditions, and appropriate intervention. In general, management of maternal cardiac arrhythmias is similar to that of the general population. Special consideration must be given as to the effects of medications and procedures on both the mother and fetus to optimize outcomes. The importance of multidisciplinary care with cardiology, obstetrics, and anesthesia is emphasized.

  12. Epigenetic inheritance: Uncontested?

    PubMed Central

    Zhu, Bing; Reinberg, Danny

    2011-01-01

    “Epigenetics” is currently defined as “the inheritance of variation (-genetics) above and beyond (epi-) changes in the DNA sequence”. Despite the fact that histones are believed to carry important epigenetic information, little is known about the molecular mechanisms of the inheritance of histone-based epigenetic information, including histone modifications and histone variants. Here we review recent progress and discuss potential models for the mitotic inheritance of histone modifications-based epigenetic information. PMID:21321606

  13. PGD for inherited cardiac diseases.

    PubMed

    Kuliev, Anver; Pomerantseva, Ekaterina; Polling, Dana; Verlinsky, Oleg; Rechitsky, Svetlana

    2012-04-01

    Preimplantation genetic diagnosis (PGD) has been applied for more than 200 different inherited conditions, with expanding application to common disorders with genetic predisposition. One of the recent indications for PGD has been inherited cardiac disease, for which no preclinical diagnosis and preventive management may exist and which may lead to premature or sudden death. This paper presents the first, as far as is known, cumulative experience of PGD for inherited cardiac diseases, including familial hypertrophic and dilated cardiomyopathy, cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy. A total of 18 PGD cycles were performed, resulting in transfer in 15 of them, which yielded nine unaffected pregnancies and the births of seven disease- or disease predisposition-free children. The data open the prospect of PGD for inherited cardiac diseases, allowing couples carrying cardiac disease predisposing genes to reproduce without much fear of having offspring with these genes, which are at risk for premature or sudden death. Preimplantation genetic diagnosis (PGD) is currently an established clinical procedure in assisted reproduction and genetic practices. Its application has been expanding beyond traditional indications of prenatal diagnosis and currently includes common disorders with genetic predisposition, such as inherited forms of cancer. This applies also to the diseases with no current prospect of treatment, which may manifest despite presymptomatic diagnosis and follow up, when PGD may provide the only relief for the at-risk couples to reproduce. One of the recent indications for PGD has been inherited cardiac disease, for which no preclinical diagnosis and preventive management may exist and which may lead to premature or sudden death. We present here our first cumulative experience of PGD for inherited cardiac diseases, including familial hypertrophic and dilated cardiomyopathy, cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy. A

  14. Cancer chemotherapy and cardiac arrhythmias: a review.

    PubMed

    Tamargo, Juan; Caballero, Ricardo; Delpón, Eva

    2015-02-01

    Cardiovascular toxicity is a potential complication of cancer chemotherapy (CC) that increases the morbidity and mortality of cancer patients. Cardiac arrhythmias have been reported as an adverse effect of many chemotherapeutic drugs, including novel targeted therapies. The relationship between chemotherapy and arrhythmias has not been well-established and the proarrhythmogenic mechanisms remain uncertain as they can be the result of a direct electrophysiological effect or of changes in cardiac structure and function, including myocardial ischaemia and heart failure, which create an arrhythmogenic substrate. In this review we summarise available evidence of proarrhythmia induced by CC, discuss the possible mechanisms involved in this adverse effect and emphasise the importance of cardiac monitoring for the early diagnosis, intervention and surveillance of those patients more susceptible to develop proarrhythmia in an attempt to reduce the morbidity and mortality. Oncologists should be fully aware of proarrhythmia and the close collaboration between cardiologists and oncologists would result in a better cardiovascular assessment, risk stratification, cardiac monitoring and treatment during CC and during the follow-up. The final objective is to understand the mechanisms of proarrhythmia and evaluate its real incidence and clinical relevance so as to select the safest and most effective treatment for cancer patients.

  15. Catheter Ablation for Ventricular Arrhythmias

    PubMed Central

    Nof, Eyal; Stevenson, William G; John, Roy M

    2013-01-01

    Catheter ablation has emerged as an important and effective treatment option for many recurrent ventricular arrhythmias. The approach to ablation and the risks and outcomes are largely determined by the nature of the severity and type of underlying heart disease. In patients with structural heart disease, catheter ablation can effectively reduce ventricular tachycardia (VT) episodes and implantable cardioverter defibrillator (ICD) shocks. For VT and symptomatic premature ventricular beats that occur in the absence of structural heart disease, catheter ablation is often effective as the sole therapy. Advances in catheter technology, imaging and mapping techniques have improved success rates for ablation. This review discusses current approaches to mapping and ablation for ventricular arrhythmias. PMID:26835040

  16. Remote Arrhythmia Monitoring System Developed

    NASA Technical Reports Server (NTRS)

    York, David W.; Mackin, Michael A.; Liszka, Kathy J.; Lichter, Michael J.

    2004-01-01

    Telemedicine is taking a step forward with the efforts of team members from the NASA Glenn Research Center, the MetroHealth campus of Case Western University, and the University of Akron. The Arrhythmia Monitoring System is a completed, working test bed developed at Glenn that collects real-time electrocardiogram (ECG) signals from a mobile or homebound patient, combines these signals with global positioning system (GPS) location data, and transmits them to a remote station for display and monitoring. Approximately 300,000 Americans die every year from sudden heart attacks, which are arrhythmia cases. However, not all patients identified at risk for arrhythmias can be monitored continuously because of technological and economical limitations. Such patients, who are at moderate risk of arrhythmias, would benefit from technology that would permit long-term continuous monitoring of electrical cardiac rhythms outside the hospital environment. Embedded Web Technology developed at Glenn to remotely command and collect data from embedded systems using Web technology is the catalyst for this new telemetry system (ref. 1). In the end-to-end system architecture, ECG signals are collected from a patient using an event recorder and are transmitted to a handheld personal digital assistant (PDA) using Bluetooth, a short-range wireless technology. The PDA concurrently tracks the patient's location via a connection to a GPS receiver. A long distance link is established via a standard Internet connection over a 2.5-generation Global System for Mobile Communications/General Packet Radio Service (GSM/GPRS)1 cellular, wireless infrastructure. Then, the digital signal is transmitted to a call center for monitoring by medical professionals.

  17. Transgenerational inheritance of metabolic disease.

    PubMed

    Stegemann, Rachel; Buchner, David A

    2015-07-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from Caenorhabditis elegans to Mus musculus to Sus scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment.

  18. Transgenerational Inheritance of Metabolic Disease

    PubMed Central

    Stegemann, Rachel; Buchner, David A.

    2015-01-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from C. elegans to M. musculus to S. scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment. PMID:25937492

  19. Inherited or acquired metabolic disorders.

    PubMed

    Eichler, Florian; Ratai, Eva; Carroll, Jason J; Masdeu, Joseph C

    2016-01-01

    This chapter starts with a description of imaging of inherited metabolic disorders, followed by a discussion on imaging of acquired toxic-metabolic disorders of the adult brain. Neuroimaging is crucial for the diagnosis and management of a number of inherited metabolic disorders. Among these, inherited white-matter disorders commonly affect both the nervous system and endocrine organs. Magnetic resonance imaging (MRI) has enabled new classifications of these disorders that have greatly enhanced both our diagnostic ability and our understanding of these complex disorders. Beyond the classic leukodystrophies, we are increasingly recognizing new hereditary leukoencephalopathies such as the hypomyelinating disorders. Conventional imaging can be unrevealing in some metabolic disorders, but proton magnetic resonance spectroscopy (MRS) may be able to directly visualize the metabolic abnormality in certain disorders. Hence, neuroimaging can enhance our understanding of pathogenesis, even in the absence of a pathologic specimen. This review aims to present pathognomonic brain MRI lesion patterns, the diagnostic capacity of proton MRS, and information from clinical and laboratory testing that can aid diagnosis. We demonstrate that applying an advanced neuroimaging approach enhances current diagnostics and management. Additional information on inherited and metabolic disorders of the brain can be found in Chapter 63 in the second volume of this series.

  20. Circadian arrhythmia dysregulates emotional behaviors in aged Siberian hamsters

    PubMed Central

    Prendergast, Brian J.; Onishi, Kenneth G.; Patel, Priyesh N.; Stevenson, Tyler J.

    2014-01-01

    Emotional behaviors are influenced by the circadian timing system. Circadian disruptions are associated with depressive-like symptoms in clinical and preclinical populations. Circadian rhythm robustness declines markedly with aging and may contribute to susceptibility to emotional dysregulation in aged individuals. The present experiments used a model of chronic circadian arrhythmia generated noninvasively, via a series of circadian-disruptive light treatments, to investigate interactions between circadian desynchrony and aging on depressive- and anxiety-like behaviors, and on limbic neuroinflammatory gene expression that has been linked with emotionality. We also examined whether a social manipulation (group housing) would attenuate effects of arrhythmia on emotionality. In aged (14-18 months of age) male Siberian hamsters, circadian arrhythmia increased behavioral despair and decreased social motivation, but decreased exploratory anxiety. These effects were not evident in younger (5-9 months of age) hamsters. Social housing (3-5 hamsters/cage) abolished the effects of circadian arrhythmia on emotionality. Circadian arrhythmia alone was without effect on hippocampal or cortical interleukin-1β (IL-1β) and indoleamine 2,3-dioxygenase (Ido) mRNA expression in aged hamsters, but social housing decreased hippocampal IL-1β and Ido mRNAs. The data demonstrate that circadian disruption can negatively impact affective state, and that this effect is pronounced in older individuals. Although clear associations between circadian arrhythmia and constitutive limbic proinflammatory activity were not evident, the present data suggest that social housing markedly inhibits constitutive hippocampal IL-1β and Ido activity, which may contribute to the ameliorating effects of social housing on a number of emotional behaviors. PMID:24333374

  1. Calcium and voltage imaging in arrhythmia models by high-speed microscopy

    NASA Astrophysics Data System (ADS)

    de Mauro, C.; Cecchetti, C. A.; Alfieri, D.; Borile, G.; Urbani, A.; Mongillo, M.; Pavone, F. S.

    2014-03-01

    Alterations in intracellular cardiomyocyte calcium handling have a key role in initiating and sustaining arrhythmias. Arrhythmogenic calcium leak from sarcoplasmic reticulum (SR) can be attributed to all means by which calcium exits the SR store in an abnormal fashion. Abnormal SR calcium exit maymanifest as intracellular Ca2+ sparks and/or Ca2+ waves. Ca2+ signaling in arrhythmogenesis has been mainly studied in isolated cardiomyocytes and given that the extracellular matrix influences both Ca2+ and membrane potential dynamics in the intact heart and underlies environmentally mediated changes, understanding how Ca2+ and voltage are regulated in the intact heart will represent a tremendous advancement in the understanding of arrhythmogenic mechanisms. Using novel high-speed multiphoton microscopy techinques, such as multispot and random access, we investigated animal models with inherited and acquired arrhythmias to assess the role of Ca2+ and voltage signals as arrhythmia triggers in cell and subcellular components of the intact heart and correlate these with electrophysiology.

  2. Vagal modulation of cardiac ventricular arrhythmia.

    PubMed

    Ng, G André

    2014-02-01

    What is the topic of this review? This article addresses the relationship between vagus nerve activity and malignant ventricular arrhythmias. It focuses on the clinical association of an impaired vagal tone in cardiac disease states with high mortality from sudden cardiac death and the potential underlying mechanisms. What advances does it highlight? The article summarizes the mounting evidence that vagal innervation in the cardiac ventricle plays a key direct role in the prevention of the initiation of ventricular fibrillation. Data are presented on the role that nitric oxide plays in mediating the effects of vagal protection against ventricular fibrillation, supporting the notion that a separate non-muscarinic, nitrergic population of vagal neurons is responsible for this protection. Sudden cardiac death remains a significant unresolved clinical problem, with many of the deaths being due to malignant ventricular arrhythmias. Markers of abnormal autonomic function have been shown to be strong prognostic predictors, highlighting the important relationship between reduced vagal tone and malignant ventricular arrhythmias, such as ventricular fibrillation, in cardiac patients. Exploring the mechanisms underlying the autonomic modulation of ventricular fibrillation, my group has shown that vagus nerve stimulation protects against ventricular fibrillation in the innervated isolated heart preparation. We have provided direct evidence that nitric oxide is released in the ventricle with cervical vagus nerve stimulation and NO mediates the antifibrillatory actions of vagus nerve stimulation in the ventricle. Classical physiology teaches that vagal postganglionic nerves modulate the heart via acetylcholine acting at muscarinic receptors and, dogmatically, that there is little vagal effect in the ventricle, as innervation was believed to be sparse. Mounting evidence from many species now supports the presence of a rich vagal innervation in the ventricle. Data from my group

  3. HeartSearcher: finds patients with similar arrhythmias based on heartbeat classification.

    PubMed

    Park, Juyoung; Kang, Kyungtae

    2015-12-01

    Long-term electrocardiogram data can be acquired by linking a Holter monitor to a mobile phone. However, most systems of this variety are simply designed to detect arrhythmia through heartbeat classification, and do not provide any additional support for clinical decisions. HeartSearcher identifies patients with similar arrhythmias from heartbeat classifications, by summarising each patient's typical heartbeat pattern in the form of a regular expression, and then ranking patients according to the similarities of their patterns. Results obtained using electrocardiogram data from the MIT-BIH arrhythmia database show that this abstraction reduces the volume of heartbeat classifications by 98% on average, offering great potential to support clinical decisions.

  4. Ventricular arrhythmia during ajmaline challenge for the Brugada syndrome.

    PubMed

    Dobbels, Bieke; De Cleen, Dieter; Ector, Joris

    2016-10-01

    The Brugada syndrome is a genetic disease characterized by an abnormal electrocardiogram (ECG) and an elevated risk of sudden cardiac death. Sodium channel blockers (SCBs), such as ajmaline, are used to unmask the characteristic type 1 Brugada electrocardiographic pattern. We review the literature on the incidence of ventricular arrhythmia (VA) during SCB challenge. We evaluate the clinical and electrocardiographic characteristics of these patients as well as their prognosis. All articles published from January 2000 until August 2015, in which the incidence and predictors of VAs during SCB challenge were reported, are reviewed. The occurrence of VA during SCB challenge ranges from 0 to 17.8%. The weighted average for induction of any VA during sodium blocking challenge is 2.4%; for non-sustained ventricular tachycardia (VT), it is 0.34% and for sustained VT 0.59%. No fatal cases were reported. Predictors may be young age, conduction disturbance at baseline ECG, and mutations in the SCN5A gene. All other clinical and electrocardiographic characteristics failed to be consistent predictors. Life-threatening arrhythmias during SCB challenge are not an exceptional event. Therefore, provocation testing must necessarily be performed in an appropriate environment in which advanced life support facilities are present. Patients who have a higher risk for induced arrhythmias might be those who display a conduction disturbance at baseline ECG or have certain SCN5A mutations or are of a younger age. However, survivors of these induced arrhythmias do not seem to suffer from a worse prognosis.

  5. [A clinical case of hemangioma of the face and tongue concurrent with severe obstructive sleep apnea syndrome complicated by cardiac arrhythmias and conduction disturbances].

    PubMed

    Konovalova, K I; Elfimova, E M; Butorova, E A; Aksenova, A V; Galitsin, P V; Bulkina, O S; Litvin, A Yu; Chazova, I E

    The paper describes a clinical case of a female patient with severe obstructive sleep apnea syndrome in the presence of congenital hemangioma of the face, soft palate, and tongue concurrent with paroxysmal atrial fibrillation and atrial flutter, paroxysmal supraventricular tachycardia, and sinoatrial block (maximally up to 3.9 sec). Continuous positive airway pressure therapy could reduce the number of paroxysms of atrial fibrillation and atrial flutter, supraventricular tachycardia and eliminate sinoatrial block.

  6. Remote monitoring of patients with biventricular defibrillators through the CareLink system improves clinical management of arrhythmias and heart failure episodes.

    PubMed

    Santini, Massimo; Ricci, Renato P; Lunati, Maurizio; Landolina, Maurizio; Perego, Giovanni B; Marzegalli, Maurizio; Schirru, Milena; Belvito, Chiara; Brambilla, Roberto; Guenzati, Giuseppe; Gilardi, Serena; Valsecchi, Sergio

    2009-01-01

    The aim of the present study is to evaluate if remote monitoring with the CareLink Network may improve clinical management of tachyarrhythmias and heart failure episodes in patients treated with biventricular defibrillators (CRT-D). Patients implanted with CRT-D for more than 6 months received the CareLink monitor and were trained to perform device interrogation. At-home transmissions were scheduled at 2 weeks, 1 and 2 months after training, with a final in-office visit after 3 months. Sixty-seven patients performed 264 data transmissions. Twenty-three unscheduled data transmissions were requested by the centers after patient contact. Ventricular tachyarrhythmias were reported in nine patients during 16 data reviews. Thirteen data reviews (81%) were performed remotely via CareLink transmissions (nine scheduled and four unscheduled), in seven patients. Of these events, in two cases (15%) in-hospital visits were requested, while in 11 (85%) no action was needed and no additional in-clinic visits were scheduled. During the study period, in 20/28 (71%) intra-thoracic impedance alerts, the patients remotely transmitted their device data. After remote data review, in ten cases drug therapy was adjusted by phone and in four cases no action was needed and the patient reassured. In six episodes an in-hospital extra visit was scheduled. On the whole, in 14 cases (70%), the patient could be managed remotely avoiding a visit to the hospital. Our study showed that remote follow-up is an efficient method to manage tachyarrhythmias and heart failure episodes in CRT-D patients. Early reaction to clinical events may improve overall patient care.

  7. An 8086-based Holter arrhythmia monitor.

    PubMed

    Tandon, S N; Rahman, S M; Sahambi, J S; Goel, S; Talwar, K K

    1992-01-01

    Holter monitoring is a technique which involves the use of a specialized recorder to record and analyze the ECG of an ambulatory subject for a duration up to 24 h. It is used for persons who have generally normal ECG, but who experience heart disorders under some particular stress conditions. This paper describes the design of an 8086-based Holter monitor using state-of-the-art technology. The old concept of analog signal processing and cassette recording has been replaced by digital signal processing and solid state memories. The main features of the new monitor, as compared with conventional ones, is its intelligence to detect and record arrhythmias which are of clinical importance. Emphasis was placed on miniaturization and minimization of the power consumption while designing the monitor.

  8. Update on arrhythmias and cardiac pacing 2013.

    PubMed

    Almendral, Jesús; Pombo, Marta; Martínez-Alday, Jesús; González-Rebollo, José M; Rodríguez-Font, Enrique; Martínez-Ferrer, José; Castellanos, Eduardo; García-Fernández, F Javier; Ruiz-Mateas, Francisco

    2014-04-01

    This report discusses a selection of the most relevant articles on cardiac arrhythmias and pacing published in 2013. The first section discusses arrhythmias, classified as regular paroxysmal supraventricular tachyarrhythmias, atrial fibrillation, and ventricular arrhythmias, together with their treatment by means of an implantable cardioverter defibrillator. The next section reviews cardiac pacing, subdivided into resynchronization therapy, remote monitoring of implantable devices, and pacemakers. The final section discusses syncope.

  9. Inherited abnormalities of skeletal development in sheep.

    PubMed

    Thompson, K G; Piripi, S A; Dittmer, K E

    2008-09-01

    Inherited diseases of the skeleton are reported less often in sheep than in most other domestic animal species but are likely to occur more frequently than the veterinary literature would suggest. Although most are lethal or semi-lethal, the gene frequency for some of these diseases has reached surprisingly high levels in defined populations, presumably due either to the founder effect or the presence of a selective advantage of heterozygous individuals. This article reviews the clinical characteristics, pathology, mode of inheritance and molecular basis of skeletal diseases known to have a genetic aetiology in sheep. Inherited skeletal diseases of sheep are potential models for studying the treatment of similar diseases in humans.

  10. Inherited epidermolysis bullosa

    PubMed Central

    2010-01-01

    Inherited epidermolysis bullosa (EB) encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Each EB subtype is known to arise from mutations within the genes encoding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis. EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis. Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct whenever possible the extracutaneous complications. Prognosis varies considerably and is based on both EB subtype and the overall health of the patient. PMID:20507631

  11. Inherited mitochondrial neuropathies.

    PubMed

    Finsterer, Josef

    2011-05-15

    Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations. MIDs in which polyneuropathy is an inconstant feature among others is the MELAS syndrome, MERRF syndrome, LHON, Mendelian PEO, KSS, Leigh syndrome, MNGIE, SANDO; MIRAS, MEMSA, AHS, MDS (hepato-cerebral form), IOSCA, and ADOA syndrome. In the majority of the cases polyneuropathy presents in a multiplex neuropathy distribution. Nerve conduction studies may reveal either axonal or demyelinated or mixed types of neuropathies. If a hereditary neuropathy is due to mitochondrial dysfunction, the management of these patients is at variance from non-mitochondrial hereditary neuropathies. Patients with mitochondrial hereditary neuropathy need to be carefully investigated for clinical or subclinical involvement of other organs or systems. Supportive treatment with co-factors, antioxidants, alternative energy sources, or lactate lowering agents can be tried. Involvement of other organs may require specific treatment. Mitochondrial neuropathies should be included in the differential diagnosis of hereditary neuropathies. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Carbon monoxide and lethal arrhythmias

    SciTech Connect

    Farber, J.P.; Schwartz, P.J.; Vanoli, E.; Stramba-Badiale, M.; De Ferrari, G.M. )

    1990-12-01

    The effect of acute exposure to carbon monoxide on ventricular arrhythmias was studied in a previously described chronically maintained animal model of sudden cardiac death. In 60 percent of dogs with a healed anterior myocardial infarction, the combination of mild exercise and acute myocardial ischemia induces ventricular fibrillation. The events in this model are highly reproducible, thus allowing study by internal control analysis. Dogs that develop ventricular fibrillation during the test of exercise and acute myocardial ischemia are considered at high risk for sudden death and are defined as 'susceptible'; dogs that survive the test without a fatal arrhythmia are considered at low risk for sudden death and are defined as 'resistant.' In the current study, the effects of carboxyhemoglobin levels ranging from 5 to 15 percent were tested in resistant and susceptible dogs. A trend toward higher heart rates was observed at all levels of carboxyhemoglobin, although significant differences were observed only with 15 percent carboxyhemoglobin. This trend was observed at rest and during exercise in both resistant and susceptible dogs. In resistant animals, in which acute myocardial ischemia is typically associated with bradycardia even under the control condition, this reflex response occurred earlier and was augmented after exposure to carbon monoxide. This effect may depend on the increased hypoxic challenge caused by carbon monoxide, and thus on an augmentation of the neural reflex activation or a sensitization of the sinus node to acetylcholine induced by hypoxia. In both resistant and susceptible dogs, carbon monoxide exposure induced a worsening of ventricular arrhythmias in a minority of cases. This worsening was not reproducible in subsequent trials. These data indicate that acute exposure to carbon monoxide is seldom arrhythmogenic in dogs that have survived myocardial infarction. (Abstract Truncated)

  13. Remote Navigation for Complex Arrhythmia

    PubMed Central

    Suman-Horduna, Irina; Babu-Narayan, Sonya V; Ernst, Sabine

    2013-01-01

    Magnetic navigation has been established as an alternative to conventional, manual catheter navigation for invasive electrophysiology interventions about a decade ago. Besides the obvious advantage of radiation protection for the operator who is positioned remotely from the patient, there are additional benefits of steering the tip of a very floppy catheter. This manuscript reviews the published evidence from simple arrhythmias in patients with normal cardiac anatomy to the most complex congenital heart disease. This progress was made possible by the introduction of improved catheters and most importantly irrigated-tip electrodes. PMID:26835041

  14. Terlipressin-induced ventricular arrhythmia.

    PubMed

    Urge, Ján; Sincl, Frantisek; Procházka, Vlastimil; Urbánek, Karel

    2008-01-01

    During intravenous treatment with terlipressin for recurrent gastrointestinal (GI) bleeding, a 50-year-old male with no history of heart disease developed a newly prolonged QT interval and torsade de pointes. Risk factors present for acquired long QT syndrome were mineral dysbalance and a history of alcohol abuse with hepatic impairment. The patient was brought back to a normal sinus rhythm after a single 300-J counter-shock. Terlipressin was discontinued, and the patient's QTc interval subsequently returned to baseline. During 6 weeks of monitoring, arrhythmia did not recur.

  15. Arrhythmias

    MedlinePlus

    ... the doctor. Pacemakers. A pacemaker is a small battery-operated device implanted into the body (near the ... to speed up the heartbeat. Defibrillators. A small battery-operated implantable cardioverter defibrillator (ICD) is surgically placed ...

  16. Arrhythmia

    MedlinePlus

    ... heart is to wear a machine called a Holter monitor. It records your heart’s rhythms for 24 ... Heart Disease, EKG, fatigue, heart disease, Heart Failure, Holter monitoring, shortness of breath Family Health, Kids and ...

  17. Arrhythmias

    MedlinePlus

    ... monitors the heartbeat for about 15–20 minutes. Holter monitor. This is an ECG/EKG done over ... lot of sweating). There are two kinds of Holter monitoring — continuous recording , which means the ECG/EKG ...

  18. Arrhythmias

    MedlinePlus

    Abnormal heart rhythms; Bradycardia; Tachycardia; Fibrillation ... the more common abnormal heart rhythms are: Atrial fibrillation or flutter Atrioventricular nodal reentry tachycardia (AVNRT) Heart ...

  19. Amiodarone in the treatment of refractory supraventricular and ventricular arrhythmias

    PubMed Central

    Wheeler, P. J.; Ingram, D. V.; Puritz, R.; Chamberlain, D. A.

    1979-01-01

    Amiodarone is an antiarrhythmic agent unrelated to other drugs in current use. It has been little used in Britain, and no formal clinical trials have been possible because the drug has not been licensed by the Committee on Safety of Medicines. Nevertheless it has unique properties which can be valuable in the treatment of a wide spectrum of arrhythmias, particularly supraventricular tachycardias. Amiodarone has a slow onset of action and is cumulative. A sustained action is therefore achieved without the need for frequent maintenance dosage. Fifty patients have been treated with amiodarone in maintenance doses ranging from 200 mg on alternate days to 200 mg twice daily either alone, or in combination with conventional therapy. All were resistant to conventional therapy alone or could not be treated with usual agents because of unwanted drug effects. Of 27 patients with supraventricular arrhythmias, 18 were completely controlled and the other 9 were markedly improved. Six of 8 patients with recurrent life-threatening ventricular arrhythmias were well controlled symptomatically. Results were predictably less satisfactory in 15 high risk post-infarction patients with malignant arrhythmias and severe myocardial damage, but 6 were probably improved as a result of amiodarone. All patients on maintenance therapy for 3 months or more developed corneal microdeposits. None has any visual symptoms or other ocular defect, and treatment has not been curtailed as a result of this well recognized effect which is believed to be reversible and benign. Amiodarone can control patients with otherwise refractory arrhythmias including some which are life-threatening. Formal clinical trials are needed to define accurately its future role in the prevention and treatment of serious rhythm disorders of the heart. PMID:432163

  20. Clinical significance of rapid ventricular tachycardia (> 270 beats per minute) provoked at programmed stimulation in patients without confirmed rapid ventricular arrhythmias.

    PubMed Central

    Brembilla-Perrot, B; Terrier de la Chaise, A; Briançon, S; Takoordial, M; Suty-Selton, C; Thiel, B; Brua, J L

    1993-01-01

    Rapid uniform ventricular tachycardia (VT) (> 270 beats/min) or ventricular flutter induced during electrophysiological studies is thought not to be clinically significant in patients without cardiac arrest or documented rapid VT. The purpose of the study was to follow up 73 patients with inducible ventricular flutter but without confirmed rapid spontaneous VT. A long follow up (mean 3.5 years) identified two groups of patients. The first group had an excellent outcome and was characterised by a normal 24 hour Holter monitoring. In the second group, however, the risk of cardiac mortality was high (35%) and spontaneous VT was < 270 beats/min (26%) and was characterised by couplets or salvos of extrasystoles on Holter monitoring. In this group the history of syncope and decreased left ejection fraction increased the risk of mortality and VT. The presence of late potentials increased the risk of spontaneous VT. Electrophysiologically guided antiarrhythmic therapy reduced the risk of VT. Ventricular flutter was a non-specific finding in patients with normal Holter monitoring. In contrast, in patients with salvos of extrasystoles, ventricular flutter was associated with a high risk of cardiac mortality and VT. PMID:8457388

  1. Children's Understanding of Inheritance.

    ERIC Educational Resources Information Center

    Clough, Elizabeth Engel; Wood-Robinson, Colin

    1985-01-01

    Investigated common belief patterns secondary school students (N=84) have about inheritance, noting the most prevalent misconceptions about genetics which occur at different age levels. Implications based on findings and suggestions for teaching lower secondary courses are included. (ML)

  2. Importance of the atrial channel for ventricular arrhythmia therapy in the dual chamber implantable cardioverter defibrillator.

    PubMed

    Dijkman, B; Wellens, H J

    2000-12-01

    Performance of dual chamber implantable cardioverter defibrillator (ICD) systems has been judged based on functioning of the ventricular tachycardia:supraventricular tachycardia (VT:SVT) discrimination criteria and DDD pacing. The purpose of this study was to evaluate the use of dual chamber diagnostics to improve the electrical and antiarrhythmic therapy of ventricular arrhythmias. Information about atrial and ventricular rhythm in relation to ventricular arrhythmia occurrence and therapy was evaluated in 724 spontaneous arrhythmia episodes detected and treated by three types of dual chamber ICDs in 41 patients with structural heart disease. Device programming was based on clinically documented and induced ventricular arrhythmias. In ambulatory patients, sinus tachycardia preceded ventricular arrhythmias more often than in the hospital during exercise testing. The incidence of these VTs could be reduced by increasing the dose of a beta-blocking agent in only two patients. In five patients in whom sinus tachycardia developed after onset of hemodynamic stable VT, propranolol was more effective than Class III antiarrhythmics combined with another beta-blocking agent with regard to the incidence of VT and pace termination. In all but three cases, atrial arrhythmias were present for a longer time before the onset of ventricular arrhythmias. During atrial arrhythmias, fast ventricular rates before the onset of ventricular rate were observed more often than RR irregularities and short-long RR sequences. Dual chamber diagnostics allowed proper interpretation of detection and therapy outcome in patients with different types of ventricular arrhythmia. The advantages of the dual chamber ICD system go further than avoiding the shortcomings of the single chamber system. Information from the atrial chamber allows better device programming and individualization of drug therapy for ventricular arrhythmia.

  3. Patient characteristics associated with false arrhythmia alarms in intensive care.

    PubMed

    Harris, Patricia R; Zègre-Hemsey, Jessica K; Schindler, Daniel; Bai, Yong; Pelter, Michele M; Hu, Xiao

    2017-01-01

    A high rate of false arrhythmia alarms in the intensive care unit (ICU) leads to alarm fatigue, the condition of desensitization and potentially inappropriate silencing of alarms due to frequent invalid and nonactionable alarms, often referred to as false alarms. The aim of this study was to identify patient characteristics, such as gender, age, body mass index, and diagnosis associated with frequent false arrhythmia alarms in the ICU. This descriptive, observational study prospectively enrolled patients who were consecutively admitted to one of five adult ICUs (77 beds) at an urban medical center over a period of 31 days in 2013. All monitor alarms and continuous waveforms were stored on a secure server. Nurse scientists with expertise in cardiac monitoring used a standardized protocol to annotate six clinically important types of arrhythmia alarms (asystole, pause, ventricular fibrillation, ventricular tachycardia, accelerated ventricular rhythm, and ventricular bradycardia) as true or false. Total monitoring time for each patient was measured, and the number of false alarms per hour was calculated for these six alarm types. Medical records were examined to acquire data on patient characteristics. A total of 461 unique patients (mean age =60±17 years) were enrolled, generating a total of 2,558,760 alarms, including all levels of arrhythmia, parameter, and technical alarms. There were 48,404 hours of patient monitoring time, and an average overall alarm rate of 52 alarms/hour. Investigators annotated 12,671 arrhythmia alarms; 11,345 (89.5%) were determined to be false. Two hundred and fifty patients (54%) generated at least one of the six annotated alarm types. Two patients generated 6,940 arrhythmia alarms (55%). The number of false alarms per monitored hour for patients' annotated arrhythmia alarms ranged from 0.0 to 7.7, and the duration of these false alarms per hour ranged from 0.0 to 158.8 seconds. Patient characteristics were compared in relation to 1) the

  4. Patient characteristics associated with false arrhythmia alarms in intensive care

    PubMed Central

    Harris, Patricia R; Zègre-Hemsey, Jessica K; Schindler, Daniel; Bai, Yong; Pelter, Michele M; Hu, Xiao

    2017-01-01

    Introduction A high rate of false arrhythmia alarms in the intensive care unit (ICU) leads to alarm fatigue, the condition of desensitization and potentially inappropriate silencing of alarms due to frequent invalid and nonactionable alarms, often referred to as false alarms. Objective The aim of this study was to identify patient characteristics, such as gender, age, body mass index, and diagnosis associated with frequent false arrhythmia alarms in the ICU. Methods This descriptive, observational study prospectively enrolled patients who were consecutively admitted to one of five adult ICUs (77 beds) at an urban medical center over a period of 31 days in 2013. All monitor alarms and continuous waveforms were stored on a secure server. Nurse scientists with expertise in cardiac monitoring used a standardized protocol to annotate six clinically important types of arrhythmia alarms (asystole, pause, ventricular fibrillation, ventricular tachycardia, accelerated ventricular rhythm, and ventricular bradycardia) as true or false. Total monitoring time for each patient was measured, and the number of false alarms per hour was calculated for these six alarm types. Medical records were examined to acquire data on patient characteristics. Results A total of 461 unique patients (mean age =60±17 years) were enrolled, generating a total of 2,558,760 alarms, including all levels of arrhythmia, parameter, and technical alarms. There were 48,404 hours of patient monitoring time, and an average overall alarm rate of 52 alarms/hour. Investigators annotated 12,671 arrhythmia alarms; 11,345 (89.5%) were determined to be false. Two hundred and fifty patients (54%) generated at least one of the six annotated alarm types. Two patients generated 6,940 arrhythmia alarms (55%). The number of false alarms per monitored hour for patients’ annotated arrhythmia alarms ranged from 0.0 to 7.7, and the duration of these false alarms per hour ranged from 0.0 to 158.8 seconds. Patient

  5. [Inherited aplastic anemias].

    PubMed

    Esteves, A C; Freitas, O; Almeida, T; Rosado, L

    2010-08-01

    The inherited aplastic anaemias are a heterogeneous group of disorders characterized by bone marrow failure, frequent association with one or more somatic anomalies and increased risk of cancer. They are rare disorders, usually diagnosed at paediatric age, and have significant premature mortality. The authors report 11 cases of inherited aplastic anaemias, 8 of Fanconi's anaemia and 3 of Dyskeratosis congenita. These cases were diagnosed in the last 14 years in the Dona Estefânia Hospital.

  6. Perinatal Arrhythmias: Diagnosis and Management

    PubMed Central

    Strasburger, Janette F.; Cheulkar, Bageshree; Wichman, Heather J.

    2012-01-01

    The final common pathway to death in all of us is an arrhythmia, yet we still know far too little about the contribution of conduction abnormalities and arrhythmias to the compromised states of the human fetus. At no other time in the human life cycle is the human being at more risk of unexplained and unexpected death than during the prenatal period. The risk of sudden death from 20 to 40 weeks gestation is 6 to 12 deaths/1000 fetuses/year. This is equal to, and in some ethnic groups HIGHER, than the risk of death in the adult population with known coronary artery disease over the same time frame (6 to 12 deaths/1000 patients/year). Because only a small percentage of the United States population is pregnant each year, because fetal demise is not often acknowledged through public displays such as funerals, and finally because fetal death is culturally accepted to a much greater extent than it should be, this critically important area of women’s healthcare has not had the technological advances that have been seen in adult cardiac intensive care and other areas of medicine. Fetal cardiac deaths may be preventable and the diseases that lead to these deaths are often treatable, especially if the sophistication of our modern ICU’s could somehow be translated to the prenatal monitoring arena. PMID:18063110

  7. The electrocardiogram in the assessment of the effect of drugs on cardiac arrhythmias.

    PubMed Central

    Reid, D S

    1978-01-01

    The search for the ideal antiarrhythmic drug continues since none of the available agents offers optimum antiarrhythmic therapy. The continuing search coupled with the interest in the mechanisms of cardiac arrhythmias has led to the development of new techniques for the study of arrhythmias and antiarrhythmic drugs. In this article it is proposed to discuss the electrocardiographic methods used in the assessment of antiarrhythmic drugs. Firstly, to discuss the electrocardiogram in the assessment of the clinical electrophysiological properties of a drug and secondly, the electrocardiogram in the assessment of the value of the drug in the management of cardiac arrhythmias in man. PMID:365208

  8. Novel Therapeutic Strategies for the Management of Ventricular Arrhythmias Associated with the Brugada Syndrome

    PubMed Central

    Patocskai, Bence; Antzelevitch, Charles

    2016-01-01

    Introduction Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome characterized by prominent J waves appearing as distinct coved type ST segment elevation in the right precordial leads of the ECG. It is associated with a high risk for sudden cardiac death. Areas Covered We discuss 1) ECG manifestations of BrS which can be unmasked or aggravated by sodium channel blockers, febrile states, vagotonic agents, as well as tricyclic and tetracyclic antidepressants; 2) Genetic basis of BrS; 3) Ionic and cellular mechanisms underlying BrS; 4) Therapy involving devices including an implantable cardioverter defibrillator (ICD); 5) Therapy involving radiofrequency ablation; and 6) Therapy involving pharmacological therapy which is aimed at producing an inward shift in the balance of the currents active during phase 1 of the right ventricular action potential either by boosting calcium channel current (isoproterenol, cilostazol and milrinone) or by inhibition of transient outward current Ito (quinidine, bepridil and the Chinese herb extract Wenxin Keli). Expert Opinion This review provides an overview of the clinical and molecular aspects of BrS with a focus on approaches to therapy. Available data suggest that agents capable of inhibiting the transient outward current Ito can exert an ameliorative effect regardless of the underlying cause. PMID:27559494

  9. Evaluation of Cardiac Arrhythmia among Athletes

    PubMed Central

    Walker, James; Calkins, Hugh; Nazarian, Saman

    2010-01-01

    Due to the growing awareness of exercise related arrhythmias and improved sensitivity of diagnostic modalities, physicians are increasingly faced with choices that may have life changing impact for the athlete. This article surveys recent research and expert opinion addressing benign and pathogenic cardiac changes underlying arrhythmias in athletes. PMID:20870195

  10. Update in cardiac arrhythmias and pacing.

    PubMed

    García-Bolao, Ignacio; Ruiz-Mateas, Francisco; Bazan, Victor; Berruezo, Antonio; Alcalde, Oscar; Leal del Ojo, Juan; Acosta, Juan; Martínez Sellés, Manuel; Mosquera, Ignacio

    2015-03-01

    This article discusses the main advances in cardiac arrhythmias and pacing published between 2013 and 2014. Special attention is given to the interventional treatment of atrial fibrillation and ventricular arrhythmias, and on advances in cardiac pacing and implantable cardioverter defibrillators, with particular reference to the elderly patient.

  11. Atrial Arrhythmia Summit: Post Summit Report

    NASA Technical Reports Server (NTRS)

    Barr, Yael

    2010-01-01

    The Atrial Arrhythmia Summit brought together nationally and internationally recognized experts in cardiology, electrophysiology, exercise physiology, and space medicine in an effort to elucidate the mechanisms, risk factors, and management of atrial arrhythmias in the unique occupational cohort of the U.S. astronaut corps.

  12. [Genetic diagnostic testing in inherited retinal dystrophies].

    PubMed

    Kohl, S; Biskup, S

    2013-03-01

    Inherited retinal dystrophies are clinically and genetically highly heterogeneous. They can be divided according to the clinical phenotype and course of the disease, as well as the underlying mode of inheritance. Isolated retinal dystrophies (i.e., retinitis pigmentosa, Leber's congenital amaurosis, cone and cone-rod dystrophy, macular dystrophy, achromatopsia, congenital stationary nightblindness) and syndromal forms (i.e., Usher syndrome, Bardet-Biedl syndrome) can be differentiated. To date almost 180 genes and thousands of distinct mutations have been identified that are responsible for the different forms of these blinding illnesses. Until recently, there was no adequate diagnostic genetic testing available. With the development of the next generation sequencing technologies, a comprehensive genetic screening analysis for all known genes for inherited retinal dystrophies has been established at reasonable costs and in appropriate turn-around times. Depending on the primary clinical diagnosis and the presumed mode of inheritance, different diagnostic panels can be chosen for genetic testing. Statistics show that in 55-80 % of the cases the genetic defect of the inherited retinal dystrophy can be identified with this approach, depending on the initial clinical diagnosis. The aim of any genetic diagnostics is to define the genetic cause of a given illness within the affected patient and family and thereby i) confirm the clinical diagnosis, ii) provide targeted genetic testing in family members, iii) enable therapeutic intervention, iv) give a prognosis on disease course and progression and v) in the long run provide the basis for novel therapeutic approaches and personalised medicine.

  13. Radio-frequency ablation of arrhythmias following congenital heart surgery.

    PubMed

    Kalarus, Zbigniew; Kowalski, Oskar; Lenarczyk, Radosław; Pruszkowska-Skrzep, Patrycja; Pluta, Sławomir; Zeifert, Bozena; Chodór, Beata; Białkowski, Jacek; Skalski, Janusz; Zembala, Marian

    2006-12-01

    Cardiac arrhythmias as a late complication following congenital heart surgery are encountered more and more frequently in clinical practice. The use of new electrophysiological methods of visualisation and mapping improves the efficacy of radio-frequency (RF) ablation of these arrhythmias. To assess patterns of atrial arrhythmias following congenital heart surgery and to examine the efficacy of RF ablation using the electro-anatomical CARTO system. Electrophysiological diagnostic study and RF ablation were performed in 24 consecutive patients (mean age 36+/-18 years) who had atrial arrhythmias following congenital heart surgery. The mechanism of arrhythmia (ectopic or reentrant) and strategy of RF ablation procedure were based on the results of the right atrial map performed during index arrhythmia. The patients were divided into five groups according to the type of congenital heart surgery. The ASD group consisted of 17 patients who had undergone in the past surgery due to atrial septal defect, four patients had a history of surgery due to ventricular septal defect (VSD group), and one patient each had undergone surgery due to corrected transposition of the great arteries (ccTGA), tetralogy of Fallot (TF) or dual-outflow right ventricle (DORV). During diagnostic electrophysiological study typical atrial flutter (AFL) was diagnosed in nine patients from the ASD group, atypical AFL in three ASD patients, and ectopic atrial tachycardia (EAT) in six ASD patients. In one patient EAT was induced after ablation of typical AFL. Of the VSD patients, three had atypical AFL, and one had typical AFL. The patient following surgery for ccTGA had atypical AFL and EAT, whereas in the two remaining patients (DORV and TF) atypical AFL was demonstrated. The efficacy of the first session of RF ablation was 83% and no complications were observed. The efficacy of RF ablation of typical AFL was 90%, atypical AFL 78%, and EAT 86% (NS). During the long-term follow-up (24+/-17 months

  14. A multiscale computational modelling approach predicts mechanisms of female sex risk in the setting of arousal‐induced arrhythmias

    PubMed Central

    Yang, Pei‐Chi; Perissinotti, Laura L.; López‐Redondo, Fernando; Wang, Yibo; DeMarco, Kevin R.; Jeng, Mao‐Tsuen; Vorobyov, Igor; Kurokawa, Junko

    2017-01-01

    Key points This study represents a first step toward predicting mechanisms of sex‐based arrhythmias that may lead to important developments in risk stratification and may inform future drug design and screening.We undertook simulations to reveal the conditions (i.e. pacing, drugs, sympathetic stimulation) required for triggering and sustaining reentrant arrhythmias.Using the recently solved cryo‐EM structure for the Eag‐family channel as a template, we revealed potential interactions of oestrogen with the pore loop hERG mutation (G604S).Molecular models suggest that oestrogen and dofetilide blockade can concur simultaneously in the hERG channel pore. Abstract Female sex is a risk factor for inherited and acquired long‐QT associated torsade de pointes (TdP) arrhythmias, and sympathetic discharge is a major factor in triggering TdP in female long‐QT syndrome patients. We used a combined experimental and computational approach to predict ‘the perfect storm’ of hormone concentration, I Kr block and sympathetic stimulation that induces arrhythmia in females with inherited and acquired long‐QT. More specifically, we developed mathematical models of acquired and inherited long‐QT syndrome in male and female ventricular human myocytes by combining effects of a hormone and a hERG blocker, dofetilide, or hERG mutations. These ‘male’ and ‘female’ model myocytes and tissues then were used to predict how various sex‐based differences underlie arrhythmia risk in the setting of acute sympathetic nervous system discharge. The model predicted increased risk for arrhythmia in females when acute sympathetic nervous system discharge was applied in the settings of both inherited and acquired long‐QT syndrome. Females were predicted to have protection from arrhythmia induction when progesterone is high. Males were protected by the presence of testosterone. Structural modelling points towards two plausible and distinct mechanisms of oestrogen action

  15. Inherited peripheral neuropathies.

    PubMed

    Shy, Michael E

    2011-04-01

    Mutations in genes expressed in Schwann cells and the axons they ensheathe cause the hereditary motor and sensory neuropathies, also known as Charcot-Marie-Tooth disease (CMT). More than 40 different genes have been shown to cause inherited neuropathies; chromosomal localizations of many other distinct inherited neuropathies have been mapped, and new genetic causes for inherited neuropathies continue to be discovered. How to keep track of all of these disorders, when to pursue genetic testing, and what tests to order for specific patients are difficult challenges for any neurologist. This review addresses these issues and provides illustrative cases to help in dealing with them. CMT serves as a living system to identify molecules necessary for normal peripheral nervous system (PNS) function. Understanding how these various molecules interact will provide a better understanding of the pathogenesis of peripheral neuropathies in general as well as other neurodegenerative disorders involving the PNS.

  16. Organs as inheritable property?

    PubMed

    Voo, Teck Chuan; Holm, Soren

    2014-01-01

    It has been argued that organs should be treated as individual tradable property like other material possessions and assets, on the basis that this would promote individual freedom and increase efficiency in addressing the shortage of organs for transplantation. If organs are to be treated as property, should they be inheritable? This paper seeks to contribute to the idea of organs as inheritable property by providing a defence of a default of the family of a dead person as inheritors of transplantable organs. In the course of discussion, various succession rules for organs and their justifications will be suggested. We then consider two objections to organs as inheritable property. Our intention here is to provoke further thought on whether ownership of one's body parts should be assimilated to property ownership.

  17. Inherited peripheral neuropathies.

    PubMed

    Saporta, Mario A; Shy, Michael E

    2013-05-01

    Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurologic or multisystem syndrome. Because of the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. This article reviews the biology of the inherited peripheral neuropathies, delineates major phenotypic features of the CMT subtypes, and suggest strategies for focusing genetic testing. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Inherited Peripheral Neuropathies

    PubMed Central

    Saporta, Mario A.; Shy, Michael E.

    2013-01-01

    SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725

  19. Intermittent short ECG recording is more effective than 24-hour Holter ECG in detection of arrhythmias.

    PubMed

    Hendrikx, Tijn; Rosenqvist, Mårten; Wester, Per; Sandström, Herbert; Hörnsten, Rolf

    2014-04-01

    Many patients report symptoms of palpitations or dizziness/presyncope. These patients are often referred for 24-hour Holter ECG, although the sensitivity for detecting relevant arrhythmias is comparatively low. Intermittent short ECG recording over a longer time period might be a convenient and more sensitive alternative. The objective of this study is to compare the efficacy of 24-hour Holter ECG with intermittent short ECG recording over four weeks to detect relevant arrhythmias in patients with palpitations or dizziness/presyncope. prospective, observational, cross-sectional study. Clinical Physiology, University Hospital. 108 consecutive patients referred for ambiguous palpitations or dizziness/presyncope. All individuals underwent a 24-hour Holter ECG and additionally registered 30-second handheld ECG (Zenicor EKG® thumb) recordings at home, twice daily and when having cardiac symptoms, during 28 days. Significant arrhythmias: atrial fibrillation (AF), paroxysmal supraventricular tachycardia (PSVT), atrioventricular (AV) block II-III, sinus arrest (SA), wide complex tachycardia (WCT). 95 patients, 42 men and 53 women with a mean age of 54.1 years, completed registrations. Analysis of Holter registrations showed atrial fibrillation (AF) in two patients and atrioventricular (AV) block II in one patient (= 3.2% relevant arrhythmias [95% CI 1.1-8.9]). Intermittent handheld ECG detected nine patients with AF, three with paroxysmal supraventricular tachycardia (PSVT) and one with AV-block-II (= 13.7% relevant arrhythmias [95% CI 8.2-22.0]). There was a significant difference between the two methods in favour of intermittent ECG with regard to the ability to detect relevant arrhythmias (P = 0.0094). With Holter ECG, no symptoms were registered during any of the detected arrhythmias. With intermittent ECG, symptoms were registered during half of the arrhythmia episodes. Intermittent short ECG recording during four weeks is more effective in detecting AF and PSVT in

  20. A case series of neonatal arrhythmias.

    PubMed

    Isik, Dilek Ulubas; Celik, Istemi Han; Kavurt, Sumru; Aydemir, Ozge; Kibar, Ayse Esin; Bas, Ahmet Yagmur; Demirel, Nihal

    2016-01-01

    Neonatal arrhythmias (NAs) are defined as abnormal heart rates in the neonatal period. They may occur as a result of various cardiovascular, systemic and metabolic problems. A retrospective chart review was performed on newborns who were diagnosed with NA during hospitalization in a neonatal intensive care unit (NICU), or who were admitted to the NICU because of an arrhythmia diagnosis in two NICUs in Turkey from May 2011 to June 2013. Seventeen neonates with arrhythmias were identified. The incidence of NA was 0.4% and 0.3% in the two NICUs, and was 0.37% in the study population as a whole. Mean gestational age was 37 (29-40) weeks. Nine of the infants (53%) were diagnosed with fetal arrhythmia (FA) during the last week of gestation. The distribution of NA types was as follows: six (35%) supraventricular tachycardia (SVT), six (35%) premature atrial contractions (PACs), two (11%) premature ventricular contractions (PVCs), two (11%) multiple arrhythmias such as SVT + PAC and AV block + PVC, and one (5%) AV block. Wolff-Parkinson-White syndrome was present in one patient. An association of NA with congenital heart malformations was identified in five cases. Cardiac arrhythmias are important causes of infant morbidity, and an occasional cause of infant mortality if undiagnosed and untreated. It is important for the physician to be aware of the etiology, development and natural history of arrhythmias in the fetal and neonatal period.

  1. Arrhythmias After Tetralogy of Fallot Repair

    PubMed Central

    Folino, Antonio Franco; Daliento, Luciano

    2005-01-01

    Tetralogy of Fallot is the most common cyanotic congenital heart disease, with a good outcome after total surgical correction. In spite of a low perioperative mortality and a good quality of life, late sudden death remains a significant clinical problem, mainly related to episodes of sustained ventricular tachycardia and ventricular fibrillation. Fibro-fatty substitution around infundibular resection, intraventricular septal scar, and patchy myocardial fibrosis, may provide anatomical substrates of abnormal depolarization and repolarization causing reentrant ventricular arrhythmias. Several non-invasive indices based on classical examination such as ECG, signal-averaging ECG, and echocardiography have been proposed to identify patients at high risk of sudden death, with hopeful results. In the last years other more sophisticated invasive and non-invasive tools, such as heart rate variability, electroanatomic mapping and cardiac magnetic resonance added a relevant contribution to risk stratification. Even if each method per se is affected by some limitations, a comprehensive multifactorial clinical and investigative examination can provide an accurate risk evaluation for every patient. PMID:16943881

  2. Recent molecular insights from mutated IKS channels in cardiac arrhythmia.

    PubMed

    Dvir, Meidan; Peretz, Asher; Haitin, Yoni; Attali, Bernard

    2014-04-01

    Co-assembly of KCNQ1 with KCNE1 generates the IKS potassium current that is vital for the proper repolarization of the cardiac action potential. Mutations in either KCNQ1 or KCNE1 genes lead to life-threatening cardiac arrhythmias causing long QT syndrome, short QT syndrome, sinus bradycardia and atrial fibrillation. Findings emerging from recent studies are beginning to provide a picture of how gain-of-function and loss-of-function mutations are associated with pleiotropic cardiac phenotypes in the clinics. In this review, we discuss recent molecular insights obtained from mutations altering different structural modules of the channel complex that are essential for proper IKS function. We present the possible molecular mechanisms underlying mutations impairing the voltage sensing functions, as well as those altering the channel regulation by phosphatidylinositol-4,5-bisphosphate, calmodulin and protein kinase A. We also discuss the significance of diseased IKS channels for adequate pharmacological targeting of cardiac arrhythmias.

  3. Prevalence of perioperative arrhythmias in 50 young, healthy dogs

    PubMed Central

    Duerr, Felix M.; Carr, Anthony P.; Duke, Tanya; Shmon, Cindy L.; Monnet, Eric

    2007-01-01

    The objective of this study was to assess the type and frequency of cardiac dysrhythmias occurring after routine ovariohysterectomy or orchidectomy in young, healthy dogs by using 2 anesthetic protocols (group I: propofol and isoflurane; group II: thiopental and halothane). Fifty dogs under 2 years of age, judged to be clinically normal by physical examination and standard electrocardiography, were evaluated by using 24-hour ambulatory electrocardiography. The most common dysrhythmias in the postoperative period were 2nd degree atrioventricular block (44%), ventricular premature complexes (44%), and atrial premature complexes (32%). For study purposes, more than 100 ventricular or atrial premature complexes per 24 hours, or any occurrence of R-on-T phenomenon, ventricular or atrial tachycardia were classified as clinically significant arrhythmias. Significant arrhythmias were observed in 9 dogs in the postoperative period, 5 of which were in group I and 4 in group II. All of these dogs were under 1 year of age. The R-on-T phenomenon occurred in 4 dogs in group II and 1 dog in group I. Results from this study show that significant arrhythmias, including R-on-T phenomenon, can occur in the perioperative period in young, healthy dogs undergoing routine surgeries with both protocols used. PMID:17334031

  4. Recognition and management of arrhythmias in adult congenital heart disease.

    PubMed

    McLeod, Christopher J; Warnes, Carole

    2016-01-01

    Adults with congenital heart disease now outnumber children with these syndromes in developed countries. This has seen a surge in the care required for these patients, and the development of an entirely new realm of cardiology. Arrhythmia is one of the most common causes of morbidity and mortality in this group, and this review highlights current approaches to recognition and management. Atrial arrhythmias are especially common in this group of patients, while pacemaker or implantable cardioverter defibrillator implantation and cardiac ablation are also frequently necessary. The presentation and management of these entities present salient differences for the clinician--for both acute and chronic care--and more recently a national societal consensus statement has attempted to encapsulate the best approach. Without any level of evidence A, all recommendations are based on data derived from nonrandomized studies or only expert/consensus opinion. This review is aimed at providing current opinion on optimum clinical care in this arena in lieu of this publication and the more novel corroborative clinical studies. Recognition and appropriate management of arrhythmia in adults with congenital heart disease frequently differ from those patients with a normal heart or acquired heart disease. Early diagnosis and proper treatment are essential in this complex patient category.

  5. Induced pluripotent stem cell-derived cardiomyocytes: boutique science or valuable arrhythmia model?

    PubMed

    Knollmann, Björn C

    2013-03-15

    This article reviews the strengths and limitations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as models of cardiac arrhythmias. Specifically, the article attempts to answer the following questions: Which clinical arrhythmias can be modeled by iPSC-CM? How well can iPSC-CM model adult ventricular myocytes? What are the strengths and limitations of published iPSC-CM arrhythmia models? What new mechanistic insight has been gained? What is the evidence that would support using iPSC-CM to personalize antiarrhythmic drug therapy? The review also discusses the pros and cons of using the iPSC-CM technology for modeling specific genetic arrhythmia disorders, such as long QT syndrome, Brugada Syndrome, or Catecholaminergic Polymorphic Ventricular Tachycardia.

  6. The electrical heart: 25 years of discovery in cardiac electrophysiology, arrhythmias and sudden death.

    PubMed

    Saffitz, Jeffrey E; Corradi, Domenico

    2016-01-01

    This review summarizes progress in the fields of cardiac electrophysiology, arrhythmias and sudden death made in the 25-year interval between 1992 and 2016 during which time Cardiovascular Pathology has been published. Organized along clinical lines, it considers the major heart rhythm disorders underlying atrial, atrioventricular and ventricular arrhythmias, and sudden cardiac death. There is a strong focus on the remarkable advances in understanding the genetic basis for cardiac rhythm disturbances and elucidating fundamental mechanisms of abnormal conduction and impulse formation. During this 25-year period, our understanding of how altered tissue structure (classical pathology) contributes to arrhythmias and sudden death has undergone continuous refinement as new insights have been gained about arrhythmia mechanisms and the dynamic interplay between anatomic substrates and triggers of the major heart rhythm disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Dipyridamole-thallium tests are predictive of severe cardiac arrhythmias in patients with left ventricular hypertrophy

    SciTech Connect

    Saragoca, M.A.; Canziani, M.E.; Gil, M.A.; Castiglioni, M.L.; Cassiolato, J.L.; Barbieri, A.; Lima, V.C.; Draibe, S.A.; Martinez, E.E. )

    1991-01-01

    In a population of patients with chronic renal failure (CRF) and a high prevalence of left ventricular hypertrophy (LVH) undergoing chronic hemodialysis, the authors investigated the association between the results of dipyridamole-thallium tests (DTTs) and the occurrence of ventricular arrhythmias. They observed a positive significant association between positive DTTs and the occurrence of severe forms of ventricular arrhythmias. A significant association was also observed between the presence of severe LVH and the occurrence of severe ventricular arrhythmias. However, no association was found between the presence of LVH and the positivity of the DTT. As most of their patients with positive DTTs had unimpaired coronary circulations, they conclude that positive DTTs, although falsely indicative of impaired myocardial blood supply, does have an important clinical relevance, indicating increased risk of morbidity (and, possibly, mortality) due to ventricular arrhythmias in a population of CRF patients submitted to chronic renal function replacement program.

  8. [Myocardial ischemia and ventricular arrhythmia].

    PubMed

    Vester, E G

    1998-01-01

    A relation between myocardial ischemia and induction of ventricular arrhythmias can be demonstrated in patients with coronary heart disease--in contrast to patients with primary non ischemic cardiac diseases--using a combined metabolic-electrophysiological investigation protocol consisting of programmed atrial and ventricular stimulation with simultaneous measurement of the arterio/coronary venous difference for lactate, pyruvate, free fatty acids and amino acids. There are significant metabolic distinctions between both ischemic and non ischemic heart disease under pacing stress conditions as well as at rest. Areas of "hibernating myocardium" resp. "mismatch" zones in the myocardium showing reduced or abolished perfusion and preserved metabolism during scintographic SPECT/PET studies, may be found more often in patients with ventricular tachycardias (VT) or ventricular fibrillation (VF) in the chronic post myocardial infarction state than in patients without VT/VF. The proof of such zones may be considered a possible risk factor for arrhythmic events and sudden cardiac death after myocardial infarction. Hereby the concept of an interaction between acute and chronic ischemia triggering the onset of polymorphic VT or VF gaines increasing acceptance. In contrast, monomorphic reentrant VT are usually generated in the border zone of scarred areas where islands of vital fibers are surrounded by fibrotic tissue. These arrhythmogenic origin regions are characterized by a "match" pattern presenting a comparably severe reduction of perfusion and metabolism. Under those circumstances a control resp. suppression of the VT focus can only be provided by interventional techniques like catheter ablation, antitachycardiac surgery or implantation of a cardioverter/defibrillator beyond antiarrhythmic drug therapy. An antiischemic causal treatment (bypass surgery or angioplasty) represents for maximal 40% of patients with ischemically induced ventricular arrhythmias an adequate and

  9. Arrhythmias Following Comprehensive Stage II Surgical Palliation in Single Ventricle Patients.

    PubMed

    Wilhelm, Carolyn M; Paulus, Diane; Cua, Clifford L; Kertesz, Naomi J; Cheatham, John P; Galantowicz, Mark; Fernandez, Richard P

    2016-03-01

    Post-operative arrhythmias are common in pediatric patients following cardiac surgery. Following hybrid palliation in single ventricle patients, a comprehensive stage II palliation is performed. The incidence of arrhythmias in patients following comprehensive stage II palliation is unknown. The purpose of this study is to determine the incidence of arrhythmias following comprehensive stage II palliation. A single-center retrospective chart review was performed on all single ventricle patients undergoing a comprehensive stage II palliation from January 2010 to May 2014. Pre-operative, operative, and post-operative data were collected. A clinically significant arrhythmia was defined as an arrhythmia which led to cardiopulmonary resuscitation or required treatment with either pacing or antiarrhythmic medication. Statistical analysis was performed with Wilcoxon rank-sum test and Fisher's exact test with p < 0.05 significant. Forty-eight single ventricle patients were reviewed (32 hypoplastic left heart syndrome, 16 other single ventricle variants). Age at surgery was 185 ± 56 days. Cardiopulmonary bypass time was 259 ± 45 min. Average vasoactive-inotropic score was 5.97 ± 7.58. Six patients (12.5 %) had clinically significant arrhythmias: four sinus bradycardia, one 2:1 atrioventricular block, and one slow junctional rhythm. No tachyarrhythmias were documented for this patient population. Presence of arrhythmia was associated with elevated lactate (p = 0.04) and cardiac arrest (p = 0.002). Following comprehensive stage II palliation, single ventricle patients are at low risk for development of tachyarrhythmias. The most frequent arrhythmia seen in these patients was sinus bradycardia associated with respiratory compromise.

  10. Arrhythmias in the Heart Transplant Patient

    PubMed Central

    Hamon, David; Taleski, Jane; Vaseghi, Marmar; Shivkumar, Kalyanam

    2014-01-01

    Orthotopic heart transplantation (OHT) is currently the most effective long-term therapy for patients with end-stage cardiac disease, even as left ventricular devices show markedly improved outcomes. As surgical techniques and immunosuppressive regimens have been refined, short-term mortality caused by sepsis has decreased, while morbidity caused by repeated rejection episodes and vasculopathy has increased, and is often manifested by arrhythmias. These chronic transplant complications require early and aggressive multidisciplinary treatment. Understanding the relationship between arrhythmias and these complications in the acute and chronic stages following OHT is critical in improving patient prognosis, as arrhythmias may be the earliest or sole presentation. Finally, decentralised/ denervated hearts represent a unique opportunity to investigate the underlying mechanisms of arrhythmias. PMID:26835083

  11. Microwave Treatment for Cardiac Arrhythmias

    NASA Technical Reports Server (NTRS)

    Arndt, G. Dickey (Inventor); Carl, James R. (Inventor); Raffoul, George W. (Inventor); Pacifico, Antonio (Inventor)

    1999-01-01

    Method and apparatus are provided for propagating microwave energy into heart tissues to produce a desired temperature profile therein at tissue depths sufficient for thermally ablating arrhythmogenic cardiac tissue to treat ventricular tachycardia and other arrhythmias while preventing excessive heating of surrounding tissues, organs, and blood. A wide bandwidth double-disk antenna is effective for this purpose over a bandwidth of about six gigahertz. A computer simulation provides initial screening capabilities for an antenna such as antenna, frequency, power level, and power application duration. The simulation also allows optimization of techniques for specific patients or conditions. In operation, microwave energy between about 1 Gigahertz and 12 Gigahertz is applied to monopole microwave radiator having a surface wave limiter. A test setup provides physical testing of microwave radiators to determine the temperature profile created in actual heart tissue or ersatz heart tissue. Saline solution pumped over the heart tissue with a peristaltic pump simulates blood flow. Optical temperature sensors disposed at various tissue depths within the heart tissue detect the temperature profile without creating any electromagnetic interference. The method may be used to produce a desired temperature profile in other body tissues reachable by catheter such as tumors and the like.

  12. The effects of dilazep on reperfusion arrhythmias.

    PubMed

    Sugiyama, S; Kondo, T; Ajioka, M; Hattori, M; Nagai, S; Ozawa, T

    1985-01-01

    The effects of 3,3'-(perhydro-1,4-diazepine-1,4-diyl) (propyl-3,4,5-trimethoxybenzoate (dilazep, Comelian) on reperfusion arrhythmias were investigated. 49 adult mongrel dogs were divided into 2 groups; the control group (n = 38) and the dilazep group (n = 11). 15 min after premedication with physiological saline or dilazep (2 mg/kg), the left anterior descending coronary artery was occluded for 15 min and then reperfused for 5 min. 12 dogs (32%) of the control developed "reperfusion arrhythmias" (arrhythmias cases) but 26 did not (non-arrhythmias cases). None of the 11 dogs pretreated with dilazep developed arrhythmias (dilazep group). Immediately after 5 min of reperfusion, plasma membrane and microsomes were prepared from the normal and reperfused myocardium. In the arrhythmias cases of the control group, an increase in free fatty acids and a decrease in phospholipids of plasma membrane obtained from the reperfused myocardium were observed. The endogenous phospholipase activity in the heart microsomes obtained from reperfused myocardium increased significantly compared with that from the normal myocardium. In the non-arrhythmias cases of the control group and in the dilazep group, there was no significant difference in the contents of free fatty acids and phospholipids in plasma membrane between normal and reperfused area. Phospholipase activity in the microsomes prepared from the reperfused myocardium did not change significantly compared with that in the microsomes from normal area in these groups. These results suggest that the activation of phospholipases associated with coronary reperfusion is closely related to the development of reperfusion arrhythmias.

  13. Diagnosis and management of common fetal arrhythmias

    PubMed Central

    Weber, Roland; Stambach, Dominik; Jaeggi, Edgar

    2011-01-01

    Fetal arrhythmias are detected in at least 2% of unselected pregnancies during routine obstetrical scans. Most common are transient, brief episodes of a slow or fast heart rate or of an irregular heart rhythm. Less common are prolonged or persistent abnormalities such as supraventricular tachycardia and complete heart block which may lead to low cardiac output, fetal hydrops and demise. The objectives of this review are to update the reader on the diagnosis and management of the more common arrhythmias. PMID:23960639

  14. β1-Adrenoceptor blocker aggravated ventricular arrhythmia.

    PubMed

    Wang, Yan; Patel, Dimpi; Wang, Dao Wu; Yan, Jiang Tao; Hsia, Henry H; Liu, Hao; Zhao, Chun Xia; Zuo, Hou Juan; Wang, Dao Wen

    2013-11-01

    To assess the impact of β1 -adrenoceptor blockers (β1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety. From January 2010 to July 2012, six patients were identified who had idiopathic ventricular arrhythmias that apparently decreased (by greater than 90%) with preprocedural anxiety. The number of ectopic ventricular beats per hour (VPH) was calculated from Holter or telemetry monitoring to assess the ectopic burden. The mean VPH of 24 hours from Holter before admission (VPH-m) was used as baseline (100%) for normalization. β1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias. Among 97 consecutive patients with idiopathic ventricular arrhythmias, six had reduction in normalized VPHs in the hour before the scheduled procedure time from (104.6 ± 4.6%) to (2.8 ± 1.6%) possibly due to preprocedural anxiety (P < 0.05), then increased to (97.9 ± 9.7%) during β1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated β1 -blocker quickly counteracted the inhibitory effect of isoprenaline, and VPHs increased to (120.9 ± 2.4%) from (1.6 ± 1.0%; P < 0.05). Isoprenaline and β1 -blocker showed similar effects on the arrhythmias in catheter lab. In some patients with structurally normal heart and ventricular arrhythmias there is a marked reduction of arrhythmias associated with preprocedural anxiety. These patients exhibit a reproducible sequence of β1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

  15. Small Conductance Ca2+-Activated K+ Channels and Cardiac Arrhythmias

    PubMed Central

    Zhang, Xiao-Dong; Lieu, Deborah K.; Chiamvimonvat, Nipavan

    2015-01-01

    Small conductance Ca2+-activated K+ (SK, KCa2) channels are unique in that they are gated solely by changes in intracellular Ca2+ and hence, function to integrate intracellular Ca2+ and membrane potentials on a beat-to-beat basis. Recent studies have provided evidence for the existence and functional significance of SK channels in the heart. Indeed, our knowledge of cardiac SK channels has been greatly expanded over the past decade. Interests in cardiac SK channels are further driven by recent studies suggesting the critical roles of SK channels in human atrial fibrillation, SK channel as a possible novel therapeutic target in atrial arrhythmias and up-regulation of SK channels in heart failure (HF) in animal models and human HF. However, there remain critical gaps in our knowledge. Specifically, blockade of SK channels in cardiac arrhythmias has been shown to be both anti-arrhythmic and proarrhythmic. This contemporary review will provide an overview of the literature on the role of cardiac SK channels in cardiac arrhythmias and to serve as a discussion platform for the current clinical perspectives. At the translational level, development of SK channel blockers as a new therapeutic target in the treatment of atrial fibrillation and the possible pro-arrhythmic effects merit further considerations and investigations. PMID:25956967

  16. Epigenetic transgenerational inheritance

    PubMed Central

    Skinner, Michael K.

    2017-01-01

    Endocrine disruptors are critical environmental exposures that influence health and can promote epigenetic transgenerational inheritance of disease and abnormal physiology. Advances in 2015 included analyses of the effects of endocrine disruptors on human disease, further examples of endocrine disruptors promoting transgenerational behavioural effects, insights into effects of endocrine disruptors on epigenetic programming of primordial germ cells and the finding that endocrine disruptors can transgenerationally promote genetic mutations. PMID:26585656

  17. Inherited hepatocellular carcinoma.

    PubMed

    Villanueva, Augusto; Newell, Pippa; Hoshida, Yujin

    2010-10-01

    Inherited liver disorders that cause chronic inflammation, fibrosis, and cirrhosis can lead to the development of liver cancer. Because of the rarity and diversity of some of these syndromes, the relative risk of developing HCC in these patients and the age at which tumours typically arise cannot be accurately estimated. Among patients with hereditary hemachromatosis (HH), the annual incidence of HCC is 4% once cirrhosis has been established. Fibrosis and portal hypertension associated with HH can be partially reversed with therapeutic phlebotomy, but it is unclear whether this treatment alters the incidence of HCC in these patients. Importantly, it seems likely that coincidence of these genetic disorders with known HCC risk factors such as alcoholism and viral hepatitis would amplify their oncogenic potential. For this reason, patients with known genetic disorders of the liver should be repeatedly counselled to avoid environmental and toxic injury to the liver. Treatment of HCC in patients with inherited liver disease mirrors that of HCC associated with other etiologies. Unfortunately, there are case series which suggest these patients with inherited liver disease and HCC tend to present at more advanced stages and are therefore not eligible for curative therapies, causing overall decreased survival relative to patients with HCC of viral or other etiologies. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans

    NASA Technical Reports Server (NTRS)

    Taylor, J. A.; Myers, C. W.; Halliwill, J. R.; Seidel, H.; Eckberg, D. L.

    2001-01-01

    Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.

  19. Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans

    NASA Technical Reports Server (NTRS)

    Taylor, J. A.; Myers, C. W.; Halliwill, J. R.; Seidel, H.; Eckberg, D. L.

    2001-01-01

    Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.

  20. Severity of nocturnal cardiac arrhythmias correlates with intensity of sleep apnea in men.

    PubMed

    Szaboova, E; Holoubek, D; Tomori, Z; Szabo, P; Donic, V; Stancak, B

    2013-01-01

    Various cardiac arrhythmias frequently occur in patients with sleep apnea, but complex analysis of the relationship between their severity and the probable arrhythmogenic risk factors is conflicting. The question is what cardiovascular risk factors and how strongly they are associated with the severity of cardiac arrhythmias in sleep apnea. Adult males (33 with and 16 without sleep apnea), matched for cardiovascular co-morbidity were studied by polysomnography with simultaneous ECG monitoring. Arrhythmia severity was evaluated for each subject by a special 7-degree scoring system. Laboratory, clinical, echocardiographic, carotid ultrasonographic, ambulatory blood pressure, and baroreflex sensitivity values were also assessed. Moderate sleep apnea patients had benign, but more exaggerated cardiac arrhythmias than control subjects (2.53 ± 2.49 vs. 1.13 ± 1.64 degrees of cumulative severity, p < 0.05). We confirmed strong correlations between the arrhythmia severity and known arrhythmogenic risk factors (left ventricular ejection fraction and dimensions, right ventricular diameter, baroreflex sensitivity, carotid intima-media thickness, age, previous myocardial infarction, and also apnea-hypopnea index). In multivariate modelling only the apnea-hypopnea index indicating the sleep apnea intensity remained highly significantly correlated with the cumulative arrhythmia severity (beta = 0.548, p < 0.005). In conclusion, sleep apnea modifying cardiovascular risk factors and structures or functions provoked various nocturnal arrhythmias. The proposed scoring system allowed a complex analysis of the contribution of various triggers to arrhythmogenesis and confirmed the apnea-hypopnea index as an independent risk for nocturnal cardiac arrhythmia severity in sleep apnea.

  1. Electrical storm: A clinical and electrophysiological overview

    PubMed Central

    Conti, Sergio; Pala, Salvatore; Biagioli, Viviana; Del Giorno, Giuseppe; Zucchetti, Martina; Russo, Eleonora; Marino, Vittoria; Dello Russo, Antonio; Casella, Michela; Pizzamiglio, Francesca; Catto, Valentina; Tondo, Claudio; Carbucicchio, Corrado

    2015-01-01

    Electrical storm (ES) is a clinical condition characterized by three or more ventricular arrhythmia episodes leading to appropriate implantable cardioverter-defibrillator (ICD) therapies in a 24 h period. Mostly, arrhythmias responsible of ES are multiple morphologies of monomorphic ventricular tachycardia (VT), but polymorphic VT and ventricular fibrillation can also result in ES. Clinical presentation is very dramatic in most cases, strictly related to the cardiac disease that may worsen electrical and hemodynamic decompensation. Therefore ES management is challenging in the majority of cases and a high mortality is the rule both in the acute and in the long-term phases. Different underlying cardiomyopathies provide significant clues into the mechanism of ES, which can arise in the setting of structural arrhythmogenic cardiomyopathies or rarely in patients with inherited arrhythmic syndrome, impacting on pharmacological treatment, on ICD programming, and on the opportunity to apply strategies of catheter ablation. This latter has become a pivotal form of treatment due to its high efficacy in modifying the arrhythmogenic substrate and in achieving rhythm stability, aiming at reducing recurrences of ventricular arrhythmia and at improving overall survival. In this review, the most relevant epidemiological and clinical aspects of ES, with regard to the acute and long-term follow-up implications, were evaluated, focusing on these novel therapeutic strategies of treatment. PMID:26413232

  2. Electrical storm: A clinical and electrophysiological overview.

    PubMed

    Conti, Sergio; Pala, Salvatore; Biagioli, Viviana; Del Giorno, Giuseppe; Zucchetti, Martina; Russo, Eleonora; Marino, Vittoria; Dello Russo, Antonio; Casella, Michela; Pizzamiglio, Francesca; Catto, Valentina; Tondo, Claudio; Carbucicchio, Corrado

    2015-09-26

    Electrical storm (ES) is a clinical condition characterized by three or more ventricular arrhythmia episodes leading to appropriate implantable cardioverter-defibrillator (ICD) therapies in a 24 h period. Mostly, arrhythmias responsible of ES are multiple morphologies of monomorphic ventricular tachycardia (VT), but polymorphic VT and ventricular fibrillation can also result in ES. Clinical presentation is very dramatic in most cases, strictly related to the cardiac disease that may worsen electrical and hemodynamic decompensation. Therefore ES management is challenging in the majority of cases and a high mortality is the rule both in the acute and in the long-term phases. Different underlying cardiomyopathies provide significant clues into the mechanism of ES, which can arise in the setting of structural arrhythmogenic cardiomyopathies or rarely in patients with inherited arrhythmic syndrome, impacting on pharmacological treatment, on ICD programming, and on the opportunity to apply strategies of catheter ablation. This latter has become a pivotal form of treatment due to its high efficacy in modifying the arrhythmogenic substrate and in achieving rhythm stability, aiming at reducing recurrences of ventricular arrhythmia and at improving overall survival. In this review, the most relevant epidemiological and clinical aspects of ES, with regard to the acute and long-term follow-up implications, were evaluated, focusing on these novel therapeutic strategies of treatment.

  3. Pathology of inherited rickets in Corriedale sheep.

    PubMed

    Dittmer, K E; Thompson, K G; Blair, H T

    2009-01-01

    A skeletal disease with features of rickets and simple autosomal recessive inheritance has been discovered in Corriedale sheep in New Zealand. The clinical signs resemble rickets in other species and include decreased growth rate, thoracic lordosis and angular limb deformities. Gross lesions include segmental thickening of physes, growth arrest lines, collapse of subchondral bone of the humeral head, thickened cortices and enthesophytes around distal limb joints. Microscopically, there is persistence of hypertrophic chondrocytes at sites of endochondral ossification, inappropriate and excessive osteoclastic resorption, microfractures and wide, unmineralized osteoid seams lining trabeculae and filling secondary osteons. This study confirms that this skeletal disease of Corriedale sheep is a newly discovered form of inherited rickets and suggests that the genetic defect may be different from inherited forms of rickets described to date in man and animals.

  4. [Gene therapy for inherited retinal dystrophies].

    PubMed

    Côco, Monique; Han, Sang Won; Sallum, Juliana Maria Ferraz

    2009-01-01

    The inherited retinal dystrophies comprise a large number of disorders characterized by a slow and progressive retinal degeneration. They are the result of mutations in genes that express in either the photoreceptor cells or the retinal pigment epithelium. The mode of inheritance can be autosomal dominant, autosomal recessive, X linked recessive, digenic or mitochondrial DNA inherited. At the moment, there is no treatment for these conditions and the patients can expect a progressive loss of vision. Accurate genetic counseling and support for rehabilitation are indicated. Research into the molecular and genetic basis of disease is continually expanding and improving the prospects for rational treatments. In this way, gene therapy, defined as the introduction of exogenous genetic material into human cells for therapeutic purposes, may ultimately offer the greatest treatment for the inherited retinal dystrophies. The eye is an attractive target for gene therapy because of its accessibility, immune privilege and translucent media. A number of retinal diseases affecting the eye have known gene defects. Besides, there is a well characterized animal model for many of these conditions. Proposals for clinical trials of gene therapy for inherited retinal degenerations owing to defects in the gene RPE65, have recently received ethical approval and the obtained preliminary results brought large prospects in the improvement on patient's quality of life.

  5. The evolutionary and clinical implications of the uneven distribution of the frequency of the inherited haemoglobin variants over short geographical distances.

    PubMed

    Premawardhena, Anuja; Allen, Angela; Piel, Fred; Fisher, Chris; Perera, Laxman; Rodrigo, Rexan; Goonathilaka, Gayan; Ramees, Lebbe; Peto, Tim; Olivieri, Nancy; Weatherall, David

    2017-02-01

    Studies of the frequency of heterozygous carriers for common inherited diseases of haemoglobin in over 7500 adolescent children in 25 districts in Sri Lanka have disclosed a highly significant variation over very short geographical distances. A further analysis of these findings, including their relationship to the past frequency and distribution of malaria, climatic variation, altitude, ethnic origin and consanguinity rates, have provided evidence regarding the evolutionary basis for the variable distribution of these conditions over short distances. It is likely that the complex interplay between malaria and the environment, together with related ethnic and social issues, exists in many countries across the tropical belt. Hence, these observations emphasise the importance of micromapping heterozygote distributions in high-frequency countries in order to define their true burden and the facilities required for the prevention and management of the homozygous and compound heterozygous disorders that result from their interaction. © 2016 John Wiley & Sons Ltd.

  6. Atrial Arrhythmias and Scintigraphic “D-shape” Sign in Pulmonary Artery Hypertension

    PubMed Central

    Ferrando-Castagnetto, Federico; Ricca-Mallada, Roberto; Selios, Valentina; Ferrando, Rodolfo

    2017-01-01

    Pulmonary hypertension significantly changes biventricular anatomy and physiology, frequently evolving to clinical deterioration and right ventricular failure. The case of a woman developing atrial arrhythmias complicating dipyridamole stress in concomitance with scintigraphic “D-shaped” left ventricle is briefly reported. Although rare, our finding may suggest that nonselective vasodilators should be used with caution in this clinical setting. PMID:28217026

  7. Inheritance and testicular cancer.

    PubMed Central

    Nicholson, P. W.; Harland, S. J.

    1995-01-01

    Statistical analysis of published data on the age of onset of germ cell tumours of the testis and of the prevalence of bilateral disease in familial and general cases suggest the following: 1. Patients with bilateral disease carry the same genetic predisposition as familial cases. 2. Males with the hereditary predisposition develop none, unilateral or bilateral tumours in the proportions 55%, 38% and 7% respectively. 3. One-third of all testis cancer patients are genetically predisposed to the disease. 4. The 2.2% risk to brothers of cases as reported elsewhere can be accounted for by the homozygous (recessive) inheritance of a single predisposing gene. PMID:7841065

  8. Development of device therapy for ventricular arrhythmias.

    PubMed

    Holley, Loraine K

    2007-06-01

    The past 25 years have seen the implantable cardioverter defibrillator emerge as the treatment of choice for ventricular arrhythmias with reduction in size but increased therapeutic options. Understanding the complex mechanisms of ventricular arrhythmias and defibrillation in normal and diseased hearts has been the focus of many research teams including that of John Uther at the Westmead Hospital Department of Cardiology. Marked improvements in capacitor and battery technologies, arrhythmia discrimination, pacing algorithms, shock waveforms and monitoring capabilities enable wider use and patient acceptance. Emergence of cardiac resynchronisation therapy and the implantable defibrillator for treatment of chronic heart failure is not only giving quality of life and extended survival for heart failure patients but has also cast new light on the evolution of heart failure.

  9. Inherited mitochondrial disorders.

    PubMed

    Finsterer, Josef

    2012-01-01

    Though inherited mitochondrial disorders (MIDs) are most well known for their syndromic forms, for which widely known acronyms (MELAS, MERRF, NARP, LHON etc.) have been coined, the vast majority of inherited MIDs presents in a non-syndromic form. Since MIDs are most frequently multisystem disorders already at onset or during the disease course, a MID should be suspected if there is a combination of neurological and non-neurological abnormalities. Neurological abnormalities occurring as a part of a MID include stroke-like episodes, epilepsy, migraine-like headache, movement disorders, cerebellar ataxia, visual impairment, encephalopathy, cognitive impairment, dementia, psychosis, hypopituitarism, aneurysms, or peripheral nervous system disease, such as myopathy, neuropathy, or neuronopathy. Non-neurological manifestations concern the ears, the endocrine organs, the heart, the gastrointestinal tract, the kidneys, the bone marrow, and the skin. Whenever there is an unexplained combination of neurological and non-neurological disease in a patient or kindred, a MID should be suspected and appropriate diagnostic measures initiated. Genetic testing should be guided by the phenotype, the biopsy findings, and the biochemical results.

  10. Sarcolemmal KATP channel modulators and cardiac arrhythmias.

    PubMed

    Baczkó, I; Husti, Z; Lang, V; Leprán, I; Light, P E

    2011-01-01

    Cardiac atrial and ventricular arrhythmias are major causes of mortality and morbidity. Ischemic heart disease is the most common cause underlying 1) the development of ventricular fibrillation that results in sudden cardiac death and 2) atrial fibrillation that can lead to heart failure and stroke. Current pharmacological agents for the treatment of ventricular and atrial arrhythmias exhibit limited effectiveness and many of these agents can cause serious adverse effects - including the provocation of lethal ventricular arrhythmias. Sarcolemmal ATP-sensitive potassium channels (sarcK(ATP)) couple cellular metabolism to membrane excitability in a wide range of tissues. In the heart, sarcK(ATP) are activated during metabolic stress including myocardial ischemia, and both the opening of sarcK(ATP) and mitochondrial K(ATP) channels protect the ischemic myocardium via distinct mechanisms. Myocardial ischemia leads to a series of events that promote the generation of arrhythmia substrate eventually resulting in the development of life-threatening arrhythmias. In this review, the possible mechanisms of the anti- and proarrhythmic effects of sarcK(ATP) modulation as well as the influence of pharmacological K(ATP) modulators are discussed. It is concluded that in spite of the significant advances made in this field, the possible cardiovascular therapeutic utility of current sarcK(ATP) channel modulators is still hampered by the lack of chamber-specific selectivity. However, recent insights into the chamber-specific differences in the molecular composition of sarcKATP in addition to already existing cardioselective sarcK(ATP) channel modulators with sarcK(ATP) isoform selectivity holds the promise for the future development of pharmacological strategies specific for a variety of atrial and ventricular arrhythmias.

  11. Mechanisms of Uniparental Mitochondrial DNA Inheritance in Cryptococcus neoformans.

    PubMed

    Gyawali, Rachana; Lin, Xiaorong

    2011-12-01

    In contrast to the nuclear genome, the mitochondrial genome does not follow Mendelian laws of inheritance. The nuclear genome of meiotic progeny comes from the recombination of both parental genomes, whereas the meiotic progeny could inherit mitochondria from one, the other, or both parents. In fact, one fascinating phenomenon is that mitochondrial DNA in the majority of eukaryotes is inherited from only one particular parent. Typically, such unidirectional and uniparental inheritance of mitochondrial DNA can be explained by the size of the gametes involved in mating, with the larger gamete contributing towards mitochondrial DNA inheritance. However, in the human fungal pathogen Cryptococcus neoformans, bisexual mating involves the fusion of two isogamous cells of mating type (MAT) a and MATα, yet the mitochondrial DNA is inherited predominantly from the MATa parent. Although the exact mechanism underlying such uniparental mitochondrial inheritance in this fungus is still unclear, various hypotheses have been proposed. Elucidating the mechanism of mitochondrial inheritance in this clinically important and genetically amenable eukaryotic microbe will yield insights into general mechanisms that are likely conserved in higher eukaryotes. In this review, we highlight studies on Cryptococcus mitochondrial inheritance and point out some important questions that need to be addressed in the future.

  12. Arrhythmias in viral myocarditis and pericarditis.

    PubMed

    Baksi, A John; Kanaganayagam, G Sunthar; Prasad, Sanjay K

    2015-06-01

    Acute viral myocarditis and acute pericarditis are self-limiting conditions that run a benign course and that may not involve symptoms that lead to medical assessment. However, ventricular arrhythmia is frequent in viral myocarditis. Myocarditis is thought to account for a large proportion of sudden cardiac deaths in young people without prior structural heart disease. Identification of acute myocarditis either with or without pericarditis is therefore important. However, therapeutic interventions are limited and nonspecific. Identifying those at greatest risk of a life-threatening arrhythmia is critical to reducing the mortality. This review summarizes current understanding of this challenging area in which many questions remain.

  13. Arrhythmia Management in the Elderly-Implanted Cardioverter Defibrillators and Prevention of Sudden Death.

    PubMed

    Manian, Usha; Gula, Lorne J

    2016-09-01

    We present an overview of arrhythmia management in elderly patients as it pertains to implantable cardioverter defibrillator (ICD) therapy and prevention of sudden death. Treatment of arrhythmia in elderly patients is fraught with challenges pertaining to goals of care and patient frailty. With an ever increasing amount of technology available, realistic expectations of therapy need to balance quality and quantity of life. The ICD is an important treatment option for selected patients at risk of ventricular arrhythmia and sudden cardiac death. However, the incidence of sudden death as a percentage of all-cause mortality decreases with age. Studies have reported that 20% of elderly patients might die within 1 year of an episode of life-threatening ventricular arrhythmia, but most because of nonarrhythmic causes. This illustrates the 'sudden cardiac death paradox,' with a great proportion of death in elderly patients, even those at risk for ventricular arrhythmias, attributable to medical conditions that cannot be addressed by an ICD. We discuss current practices in ICD therapy in elderly patients, existing evidence from registries and clinical trials, approaches to risk stratification, and important ethical considerations. Although the decision on whether ICD insertion is appropriate in the elderly population remains an area of uncertainty from an evidence-based and ethical perspective, we offer insight on potential clinical and research strategies for this growing population.

  14. The inheritance of groin hernia: a systematic review.

    PubMed

    Burcharth, J; Pommergaard, H C; Rosenberg, J

    2013-04-01

    Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias. A literature search in the MEDLINE and Embase databases was performed with the following search terms: genetics, heredity, multifactorial inheritance, inheritance patterns, sibling relations, family relations, and abdominal hernia. Only English human clinical or register-based studies describing the inheritance of groin hernias, family history of groin hernias, or familial accumulation of groin hernias were included. Eleven studies evaluating 37,166 persons were included. The overall findings were that a family history of inguinal hernia was a significant risk factor for the development of a primary hernia. A family history of inguinal hernia showed a tendency toward increased hernia recurrence rate and significantly earlier recurrence. The included studies did not agree on the possible inheritance patterns differing between polygenic inheritance, autosomal dominant inheritance, and multifactorial inheritance. Furthermore, the studies did not agree on the degree of penetrance. The literature on the inheritance of groin hernias indicates that groin hernia is most likely an inherited disease; however, neither the extent of familial accumulation nor a clear inheritance pattern has yet been found. In order to establish whether groin hernias are accumulated in certain families and to what extent, large register studies based on hernia repair data or clinical examinations are needed. Groin hernia repair (inguinal and femoral hernia) is among the most commonly performed gastrointestinal surgical procedures [1]. Emergency groin hernia surgery is associated with increased mortality, increased patient-related morbidity, and increased hospital stay compared with elective groin hernia procedures [2, 3

  15. Ablation of Macro-Re-Entrant Atrial Arrhythmia Late after Surgical Aortic Valve Replacement.

    PubMed

    Orczykowski, Michał; Derejko, Paweł; Urbanek, Piotr; Bodalski, Robert; Kodziszewska, Katarzyna; Sierpiński, Radosław; Baranowski, Rafał; Bilińska, Maria; Szumowski, Łukasz

    2016-09-01

    -re-entrant clinical arrhythmia in all subjects. Atrial fibrillation was frequently observed among those patients during follow up.

  16. [Effect of anti-arrhythmia drugs on mouse arrhythmia induced by Bufonis Venenum].

    PubMed

    Lu, Wen-juan; Zhou, Jing; Ma, Hong-yue; Lü, Gao-hong; You, Fen-qiang; Ding, An-wei; Duan, Jin-ao

    2011-10-01

    This study is to investigate the effects of phenytoin sodium, lidocaine (sodium channel blockers), propranolol (beta-adrenergic receptor antagonist), amiodarone (drugs prolonging the action potential duration) and verapamil (calcium channel blockers) on arrhythmia of mice induced by Bufonis Venenum (Chansu) and isolated mouse hearts lethal dose of Chansu. Arrhythmia of mice were induced by Chansu and then electrocardiograms (ECGs) were recorded. The changes of P-R interval, QRS complex, Q-T interval, T wave amplitude, heart rate (HR) were observed. Moreover, arrhythmia rate, survival rate and arrhythmia score were counted. Isolated mouse hearts were prefused, and the lethal dose of Chansu was recorded. Compared with control group, after pretreatment with phenytoin sodium, broadening of QRS complex and HR were inhibited, and the incidence of ventricular arrhythmia was reduced dramatically, while survival rate was improved; the isolated mouse hearts lethal dose of Chansu was increased significantly. After pretreatment with lidocaine, the prolongation of P-R interval and broadening of QRS complex were inhibited, and the incidences of ventricular arrhythmia were reduced dramatically, while survival rate was improved; the isolated mouse hearts lethal dose of Chansu was increased significantly. After pretreatment with propranolol, prolongation of P-R interval, broadening of QRS complex, prolongation of Q-T interval and HR were inhibited, and the incidences of both supraventricular and ventricular arrhythmias were reduced dramatically, while survival rate was improved. After pretreatment with amiodarone, HR was inhibited, the incidences of ventricular tachycardia were reduced dramatically. Lastly, after pretreatment with verapamil, the prolongation of P-R interval and Q-T interval were inhibited and the incidences of both supraventricular and ventricular arrhythmias were reduced dramatically; the isolated mouse hearts lethal dose of Chansu was reduced significantly. In in

  17. Clinical features of diabetes mellitus with the mitochondrial DNA 3243 (A-G) mutation in Japanese: maternal inheritance and mitochondria-related complications.

    PubMed

    Suzuki, Susumu; Oka, Yoshitomo; Kadowaki, Takashi; Kanatsuka, Azuma; Kuzuya, Takeshi; Kobayashi, Masashi; Sanke, Tokio; Seino, Yutaka; Nanjo, Kishio

    2003-03-01

    Diabetes mellitus with the mitochondrial DNA 3243(A-G) mutation is reported to represent 0.5-2.8% of the general diabetic population. Since the characterization of diabetes with the mutation is still incomplete, we undertook a nation-wide case-finding study of genetically defined patients using questionnaires in Japan. One hundred and thirteen Japanese diabetic patients with the mutation were registered and analyzed. The patients had a high prevalence of maternal inheritance of diabetes and deafness, short and thin stature, and showed an early middle-aged onset of diabetes and deafness. Eighty-six percent of the patients required insulin therapy due to the progressive insulin secretory defect. Glucose intolerance of the mothers was associated with an early middle-aged onset of diabetes, reduction in the insulin secretory capacity, early requirement of insulin therapy, and increases in the daily insulin dose. The heteroplasmic concentrations of the 3243 mutation in leukocytes were low and declined with aging. The patients had advanced microvascular complications, and mitochondria-related complications such as cardiomyopathy, cardiac conductance disorders, neuromuscular symptoms, neuropsychiatric disturbance, and macular pattern dystrophy. Thus, this study has revealed that: (1) diabetes mellitus with the 3243 mutation is a subtype of diabetes mellitus with mitochondria-related complications; and (2) insulin secretory ability is more severely impaired in the patients whose mothers were glucose intolerance.

  18. Dominantly-inherited lop ears.

    PubMed

    Leung, Alexander K C; Kong, Albert Y F; Robson, W Lane M; McLeod, D Ross

    2007-10-01

    We describe a four-generation Chinese family that included five members who had an isolated bilateral lop ear anomaly. The presentation suggested a dominant mode of inheritance. The absence of male-to-male transmission does not exclude an X-linked dominant mode of inheritance. Since the phenotypic anomaly of the male proband was no more severe than the affected female members, an autosomal dominant mode of inheritance is most likely. 2007 Wiley-Liss, Inc

  19. Arrhythmia and Sudden Death in Hemodialysis Patients: Protocol and Baseline Characteristics of the Monitoring in Dialysis Study.

    PubMed

    Charytan, David M; Foley, Robert; McCullough, Peter A; Rogers, John D; Zimetbaum, Peter; Herzog, Charles A; Tumlin, James A

    2016-04-07

    Dialysis patients have high rates of cardiovascular morbidity and mortality, but data on arrhythmia burden, arrhythmia type, arrhythmia triggers, and the identity of terminal arrhythmias have historically been limited by an inability to monitor heart rhythm for prolonged periods. To investigate arrhythmia and its association with sudden death in dialysis-dependent ESRD, describe the potential for implantable devices to advance study of dialysis physiology, review the ethical implications of using implantable devices in clinical studies, and report on the protocol and baseline results of the Monitoring in Dialysis Study (MiD). In this multicenter, interventional-observational, prospective cohort study, we placed implantable loop recorders in patients undergoing long-term hemodialysis. The proportion of patients experiencing clinically significant arrhythmias was the primary endpoint. For 6 months, we captured detailed data on the primary endpoint, symptomatic arrhythmias, other electrocardiographic variables, dialysis prescription, electrolytes, dialysis-related variables, and vital signs. We collected additional electrocardiographic data for up to 1 year. Overall, 66 patients underwent implantation in sites in the United States and India. Diabetes was present in 63.6% of patients, 12.1% were age ≥70 years, 69.7% were men, and 53.0% were black. Primary and secondary endpoint data are expected in 2016. Cardiac arrhythmia is an important contributor to cardiovascular morbidity and mortality in dialysis patients, but available technology has previously limited the ability to estimate its true burden and triggers and to define terminal rhythms in sudden death. Use of implantable technology in observational studies raises complex issues but may greatly expand understanding of dialysis physiology. The use of implantable loop recorders in MiD is among the first examples of such a trial, and the results are expected to provide novel insights into the nature of arrhythmia

  20. Arrhythmia and Sudden Death in Hemodialysis Patients: Protocol and Baseline Characteristics of the Monitoring in Dialysis Study

    PubMed Central

    Foley, Robert; McCullough, Peter A.; Rogers, John D.; Zimetbaum, Peter; Herzog, Charles A.; Tumlin, James A.

    2016-01-01

    Background Dialysis patients have high rates of cardiovascular morbidity and mortality, but data on arrhythmia burden, arrhythmia type, arrhythmia triggers, and the identity of terminal arrhythmias have historically been limited by an inability to monitor heart rhythm for prolonged periods. Objectives To investigate arrhythmia and its association with sudden death in dialysis-dependent ESRD, describe the potential for implantable devices to advance study of dialysis physiology, review the ethical implications of using implantable devices in clinical studies, and report on the protocol and baseline results of the Monitoring in Dialysis Study (MiD). Design, setting, participants, & measurements In this multicenter, interventional-observational, prospective cohort study, we placed implantable loop recorders in patients undergoing long-term hemodialysis. The proportion of patients experiencing clinically significant arrhythmias was the primary endpoint. For 6 months, we captured detailed data on the primary endpoint, symptomatic arrhythmias, other electrocardiographic variables, dialysis prescription, electrolytes, dialysis-related variables, and vital signs. We collected additional electrocardiographic data for up to 1 year. Results Overall, 66 patients underwent implantation in sites in the United States and India. Diabetes was present in 63.6% of patients, 12.1% were age ≥70 years, 69.7% were men, and 53.0% were black. Primary and secondary endpoint data are expected in 2016. Conclusions Cardiac arrhythmia is an important contributor to cardiovascular morbidity and mortality in dialysis patients, but available technology has previously limited the ability to estimate its true burden and triggers and to define terminal rhythms in sudden death. Use of implantable technology in observational studies raises complex issues but may greatly expand understanding of dialysis physiology. The use of implantable loop recorders in MiD is among the first examples of such a

  1. Mitochondrial inheritance in yeast.

    PubMed

    Westermann, Benedikt

    2014-07-01

    Mitochondria are the site of oxidative phosphorylation, play a key role in cellular energy metabolism, and are critical for cell survival and proliferation. The propagation of mitochondria during cell division depends on replication and partitioning of mitochondrial DNA, cytoskeleton-dependent mitochondrial transport, intracellular positioning of the organelle, and activities coordinating these processes. Budding yeast Saccharomyces cerevisiae has proven to be a valuable model organism to study the mechanisms that drive segregation of the mitochondrial genome and determine mitochondrial partitioning and behavior in an asymmetrically dividing cell. Here, I review past and recent advances that identified key components and cellular pathways contributing to mitochondrial inheritance in yeast. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference. Guest Editors: Manuela Pereira and Miguel Teixeira.

  2. Pathophysiology and Management of Inherited Bone Marrow Failure Syndromes

    PubMed Central

    Shimamura, Akiko; Alter, Blanche P.

    2012-01-01

    The inherited marrow failure syndromes are a diverse set of genetic disorders characterized by hematopoietic aplasia and cancer predisposition. The clinical phenotypes are highly variable and much broader than previously recognized. The medical management of the inherited marrow failure syndromes differs from that of acquired aplastic anemia or malignancies arising in the general population. Diagnostic workup, molecular pathogenesis, and clinical treatment are reviewed. PMID:20417588

  3. Arrhythmias: Opening Pandora's Box -- incidental genetic findings.

    PubMed

    Behr, Elijah R; Krahn, Andrew D

    2016-04-01

    A major goal of precision medicine is to improve disease prevention and therapy by using big data provided by genomic technology and electronic health records. In a new study, assessment of a patient population without a history of cardiac disease revealed that genetic variants putatively associated with a risk of sudden death were not linked with arrhythmia phenotypes.

  4. [Arrhythmias in adults with congenital heart disease].

    PubMed

    Townsend, Santiago Nava

    2007-01-01

    Patients with surgical correction of congenital cardiopathies have a high incidence of macro-reentrant arrhythmias. In previous reports the incidence of atrial fibrillation or flutter is around 20% preoperatively and increases to 10% more after surgery. In Mustard and Senning procedures the incidence could be as high as 30%. The physiopathology of these arrhythmias is due to conduction block and heterogeneity of refractory periods due to scaring and fibrosis left by the surgical procedure. Radiofrequency ablation is a good treatment option in this patients, but with conventional approaches the percentage of success is lower and with higher recurrence. In our institution out of 39 patients with macro-reentrant atrial tachycardia, acute success was 77% in patients with isthmus dependent flutter and 44% if the Isthmus was not part of the circuit. Recurrence in both groups was 42%. New mappings systems like Localisa, CARTO an NavX, are useful to localize areas of scar and block, that produce multiple conduction channels that can participate in reentrant arrhythmias. Radiofrequency ablation of these channels is up to day the ideal approach for these patients. Arrhythmias in patients with congenital cardiopathies are frequent and complicate the evolutions of these patients. Radiofrequency ablation is the treatment of choice in centers with experience. The use of non fluoroscopic electroanatomic mapping systems is of great help in this setting.

  5. Ryanodine receptor-mediated arrhythmias and sudden cardiac death

    PubMed Central

    Blayney, Lynda M.; Lai, F. Anthony

    2009-01-01

    The cardiac ryanodine receptor-Ca2+ release channel (RyR2) is an essential sarcoplasmic reticulum (SR) transmembrane protein that plays a central role in excitation–contraction coupling (ECC) in cardiomyocytes. Aberrant spontaneous, diastolic Ca2+ leak from the SR due to dysfunctional RyR2 contributes to the formation of delayed after-depolarisations, which are thought to underlie the fatal arrhythmia that occurs in both heart failure (HF) and in catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT is an inherited disorder associated with mutations in either the RyR2 or a SR luminal protein, calsequestrin. RyR2 shows normal function at rest in CPVT but the RyR2 dysfunction is unmasked by physical exercise or emotional stress, suggesting abnormal RyR2 activation as an underlying mechanism. Several potential mechanisms have been advanced to explain the dysfunctional RyR2 observed in HF and CPVT, including enhanced RyR2 phosphorylation status, altered RyR2 regulation at luminal/cytoplasmic sites and perturbed RyR2 intra/inter-molecular interactions. This review considers RyR2 dysfunction in the context of the structural and functional modulation of the channel, and potential therapeutic strategies to stabilise RyR2 function in cardiac pathology. PMID:19345240

  6. Fractals analysis of cardiac arrhythmias.

    PubMed

    Saeed, Mohammed

    2005-09-06

    Heart rhythms are generated by complex self-regulating systems governed by the laws of chaos. Consequently, heart rhythms have fractal organization, characterized by self-similar dynamics with long-range order operating over multiple time scales. This allows for the self-organization and adaptability of heart rhythms under stress. Breakdown of this fractal organization into excessive order or uncorrelated randomness leads to a less-adaptable system, characteristic of aging and disease. With the tools of nonlinear dynamics, this fractal breakdown can be quantified with potential applications to diagnostic and prognostic clinical assessment. In this paper, I review the methodologies for fractal analysis of cardiac rhythms and the current literature on their applications in the clinical context. A brief overview of the basic mathematics of fractals is also included. Furthermore, I illustrate the usefulness of these powerful tools to clinical medicine by describing a novel noninvasive technique to monitor drug therapy in atrial fibrillation.

  7. Inhibition of serum and glucocorticoid regulated kinase-1 as novel therapy for cardiac arrhythmia disorders.

    PubMed

    Bezzerides, Vassilios J; Zhang, Aifeng; Xiao, Ling; Simonson, Bridget; Khedkar, Santosh A; Baba, Shiro; Ottaviano, Filomena; Lynch, Stacey; Hessler, Katherine; Rigby, Alan C; Milan, David; Das, Saumya; Rosenzweig, Anthony

    2017-03-23

    Alterations in sodium flux (INa) play an important role in the pathogenesis of cardiac arrhythmias and may also contribute to the development of cardiomyopathies. We have recently demonstrated a critical role for the regulation of the voltage-gated sodium channel NaV1.5 in the heart by the serum and glucocorticoid regulated kinase-1 (SGK1). Activation of SGK1 in the heart causes a marked increase in both the peak and late sodium currents leading to prolongation of the action potential duration and an increased propensity to arrhythmia. Here we show that SGK1 directly regulates NaV1.5 channel function, and genetic inhibition of SGK1 in a zebrafish model of inherited long QT syndrome rescues the long QT phenotype. Using computer-aided drug discovery coupled with in vitro kinase assays, we identified a novel class of SGK1 inhibitors. Our lead SGK1 inhibitor (5377051) selectively inhibits SGK1 in cultured cardiomyocytes, and inhibits phosphorylation of an SGK1-specific target as well as proliferation in the prostate cancer cell line, LNCaP. Finally, 5377051 can reverse SGK1's effects on NaV1.5 and shorten the action potential duration in induced pluripotent stem cell (iPSC)-derived cardiomyocytes from a patient with a gain-of-function mutation in Nav 1.5 (Long QT3 syndrome). Our data suggests that SGK1 inhibitors warrant further investigation in the treatment of cardiac arrhythmias.

  8. The developmental basis of adult arrhythmia: atrial fibrillation as a paradigm

    PubMed Central

    Kapur, Sunil; MacRae, Calum A.

    2013-01-01

    Normal cardiac rhythm is one of the most fundamental physiologic phenomena, emerging early in the establishment of the vertebrate body plan. The developmental pathways underlying the patterning and maintenance of stable cardiac electrophysiology must be extremely robust, but are only now beginning to be unraveled. The step-wise emergence of automaticity, AV delay and sequential conduction are each tightly regulated and perturbations of these patterning events is now known to play an integral role in pediatric and adult cardiac arrhythmias. Electrophysiologic patterning within individual cardiac chambers is subject to exquisite control and is influenced by early physiology superimposed on the underlying gene networks that regulate cardiogenesis. As additional cell populations migrate to the developing heart these too bring further complexity to the organ, as it adapts to the dynamic requirements of a growing organism. A comprehensive understanding of the developmental basis of normal rhythm will inform not only the mechanisms of inherited arrhythmias, but also the differential regional propensities of the adult heart to acquired arrhythmias. In this review we use atrial fibrillation as a generalizable example where the various factors are perhaps best understood. PMID:24062689

  9. Inherited platelet disorders and oral health.

    PubMed

    Valera, Marie-Cécile; Kemoun, Philippe; Cousty, Sarah; Sie, Pierre; Payrastre, Bernard

    2013-02-01

    Platelets play a key role in thrombosis and hemostasis. Accumulation of platelets at the site of vascular injury is the first step in the formation of hemostatic plugs, which play a pivotal role in preventing blood loss after injury. Platelet adhesion at sites of injury results in spreading, secretion, recruitment of additional platelets, and formation of platelet aggregates. Inherited platelet disorders are rare causes of bleeding syndromes, ranging from mild bruising to severe hemorrhage. The defects can reflect deficiency or dysfunction of platelet surface glycoproteins, granule contents, cytoskeletal proteins, platelet pro-coagulant function, and signaling pathways. For instance, Bernard-Soulier syndrome and Glanzmann thrombasthenia are attributed to deficiencies of glycoprotein Ib/IX/V and GPIIb/IIIa, respectively, and are rare but severe platelet disorders. Inherited defects that impair platelet secretion and/or signal transduction are among the most common forms of mild platelet disorders and include gray platelet syndrome, Hermansky-Pudlak syndrome, and Chediak-Higashi syndrome. When necessary, desmopressin, antifibrinolytic agents, and transfusion of platelets remain the most common treatment of inherited platelet disorders. Alternative therapies such as recombinant activated factor VII are also available for a limited number of situations. In this review, we will discuss the management of patients with inherited platelet disorders in various clinical situations related to dental cares, including surgical intervention. © 2012 John Wiley & Sons A/S.

  10. A Case for Pharmacogenomics in Management of Cardiac Arrhythmias

    PubMed Central

    Kandoi, Gaurav; Nanda, Anjali; Scaria, Vinod; Sivasubbu, Sridhar

    2012-01-01

    Disorders of the cardiac rhythm are quite prevalent in clinical practice. Though the variability in drug response between individuals has been extensively studied, this information has not been widely used in clinical practice. Rapid advances in the field of pharmacogenomics have provided us with crucial insights on inter-individual genetic variability and its impact on drug metabolism and action. Technologies for faster and cheaper genetic testing and even personal genome sequencing would enable clinicians to optimize prescription based on the genetic makeup of the individual, which would open up new avenues in the area of personalized medicine. We have systematically looked at literature evidence on pharmacogenomics markers for anti-arrhythmic agents from the OpenPGx consortium collection and reason the applicability of genetics in the management of arrhythmia. We also discuss potential issues that need to be resolved before personalized pharmacogenomics becomes a reality in regular clinical practice. PMID:22557843

  11. Novel approaches for diagnosing inherited platelet disorders.

    PubMed

    Bastida Bermejo, José María; Hernández-Rivas, Jesús María; González-Porras, José Ramón

    2017-01-20

    Inherited platelet disorders diagnosis is based on the clinical history and bleeding assessment tools. The laboratory functional assays as well as the molecular test to identify the pathogenic genetic variant are essential to confirm the accurate diagnosis of these disorders. Nowadays, the main challenges to developing a new diagnostic system are involved in reducing the samples' volume, and faster and more helpful analysis. Moreover, there are no widely available and standardised global tests. High throughput genetic testing such as next-generation sequencing has revolutionised DNA sequencing technologies as it allows the simultaneous and faster investigation of multiple genes at a manageable cost. This technology has improved the molecular characterisation of inherited platelet disorders and has been implemented in the research studies and the clinical routine practice. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  12. Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias

    NASA Technical Reports Server (NTRS)

    Estes, N. A. 3rd; Michaud, G.; Zipes, D. P.; El-Sherif, N.; Venditti, F. J.; Rosenbaum, D. S.; Albrecht, P.; Wang, P. J.; Cohen, R. J.

    1997-01-01

    This investigation was performed to evaluate the feasibility of detecting repolarization alternans with the heart rate elevated with a bicycle exercise protocol. Sensitive spectral signal-processing techniques are able to detect beat-to-beat alternation of the amplitude of the T wave, which is not visible on standard electrocardiogram. Previous animal and human investigations using atrial or ventricular pacing have demonstrated that T-wave alternans is a marker of vulnerability to ventricular arrhythmias. Using a spectral analysis technique incorporating noise reduction signal-processing software, we evaluated electrical alternans at rest and with the heart rate elevated during a bicycle exercise protocol. In this study we defined optimal criteria for electrical alternans to separate patients from those without inducible arrhythmias. Alternans and signal-averaged electrocardiographic results were compared with the results of vulnerability to ventricular arrhythmias as defined by induction of sustained ventricular tachycardia or fibrillation at electrophysiologic evaluation. In 27 patients alternans recorded at rest and with exercise had a sensitivity of 89%, specificity of 75%, and overall clinical accuracy of 80% (p <0.003). In this patient population the signal-averaged electrocardiogram was not a significant predictor of arrhythmia vulnerability. This is the first study to report that repolarization alternans can be detected with heart rate elevated with a bicycle exercise protocol. Alternans measured using this technique is an accurate predictor of arrhythmia inducibility.

  13. RyR2 QQ2958 Genotype and Risk of Malignant Ventricular Arrhythmias.

    PubMed

    Galati, Francesca; Galati, Antonio; Massari, Serafina

    2016-01-01

    Ventricular arrhythmias are one of the most common causes of death in developed countries. The use of implantable cardiac defibrillators is the most effective treatment to prevent sudden cardiac death. To date, the ejection fraction is the only approved clinical variable used to determine suitability for defibrillator placement in subjects with heart failure. The purpose of this study was to assess whether genetic polymorphisms found in the ryanodine receptor type 2 (Q2958R) and histidine-rich calcium-binding protein (S96A) might serve as markers for arrhythmias. Genotyping was performed in 235 patients treated with defibrillator for primary and secondary prevention of arrhythmias. No significant association was found between the S96A polymorphism and arrhythmia onset, whereas the QQ2958 genotype in the ryanodine receptor gene was correlated with an increased risk of life-threatening arrhythmias. Concurrent stressor conditions, such as hypertension, seem to increase this effect. Our findings might help to better identify patients who could benefit from defibrillator implantation.

  14. RyR2 QQ2958 Genotype and Risk of Malignant Ventricular Arrhythmias

    PubMed Central

    Galati, Francesca; Galati, Antonio; Massari, Serafina

    2016-01-01

    Ventricular arrhythmias are one of the most common causes of death in developed countries. The use of implantable cardiac defibrillators is the most effective treatment to prevent sudden cardiac death. To date, the ejection fraction is the only approved clinical variable used to determine suitability for defibrillator placement in subjects with heart failure. The purpose of this study was to assess whether genetic polymorphisms found in the ryanodine receptor type 2 (Q2958R) and histidine-rich calcium-binding protein (S96A) might serve as markers for arrhythmias. Genotyping was performed in 235 patients treated with defibrillator for primary and secondary prevention of arrhythmias. No significant association was found between the S96A polymorphism and arrhythmia onset, whereas the QQ2958 genotype in the ryanodine receptor gene was correlated with an increased risk of life-threatening arrhythmias. Concurrent stressor conditions, such as hypertension, seem to increase this effect. Our findings might help to better identify patients who could benefit from defibrillator implantation. PMID:26904356

  15. Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias

    NASA Technical Reports Server (NTRS)

    Estes, N. A. 3rd; Michaud, G.; Zipes, D. P.; El-Sherif, N.; Venditti, F. J.; Rosenbaum, D. S.; Albrecht, P.; Wang, P. J.; Cohen, R. J.

    1997-01-01

    This investigation was performed to evaluate the feasibility of detecting repolarization alternans with the heart rate elevated with a bicycle exercise protocol. Sensitive spectral signal-processing techniques are able to detect beat-to-beat alternation of the amplitude of the T wave, which is not visible on standard electrocardiogram. Previous animal and human investigations using atrial or ventricular pacing have demonstrated that T-wave alternans is a marker of vulnerability to ventricular arrhythmias. Using a spectral analysis technique incorporating noise reduction signal-processing software, we evaluated electrical alternans at rest and with the heart rate elevated during a bicycle exercise protocol. In this study we defined optimal criteria for electrical alternans to separate patients from those without inducible arrhythmias. Alternans and signal-averaged electrocardiographic results were compared with the results of vulnerability to ventricular arrhythmias as defined by induction of sustained ventricular tachycardia or fibrillation at electrophysiologic evaluation. In 27 patients alternans recorded at rest and with exercise had a sensitivity of 89%, specificity of 75%, and overall clinical accuracy of 80% (p <0.003). In this patient population the signal-averaged electrocardiogram was not a significant predictor of arrhythmia vulnerability. This is the first study to report that repolarization alternans can be detected with heart rate elevated with a bicycle exercise protocol. Alternans measured using this technique is an accurate predictor of arrhythmia inducibility.

  16. Inherited disorders of blood coagulation.

    PubMed

    Lippi, Giuseppe; Franchini, Massimo; Montagnana, Martina; Favaloro, Emmanuel J

    2012-08-01

    Hemostasis is traditionally defined as a physiological response to blood vessel injury and bleeding, which entails a co-ordinated process involving the blood vessel, platelets, and blood clotting proteins (i.e. coagulation factors). Hemostasis can be divided into primary and secondary components. The former rapidly initiates after endothelial damage and is characterized by vascular contraction, platelet adhesion, and formation of a soft aggregate plug. The latter is initiated following the release of tissue factor and involves a complex sequence of events known as the blood coagulation cascade, encompassing serial steps where each coagulation factor activates another in a chain reaction that culminates in the conversion of fibrinogen to fibrin. Patients carrying abnormalities of the coagulation cascade (i.e. deficiencies of coagulation factors) have an increased bleeding tendency, where the clinical severity is mostly dependent upon the type and the plasma level of the factor affected. These disorders also impose a heavy medical and economic burden on individual patients and society in general. The aim of this article is to provide a general overview on the pathophysiology, clinics, diagnostics, and therapy of inherited disorders of coagulation factors.

  17. Dog Models for Blinding Inherited Retinal Dystrophies

    PubMed Central

    Komáromy, András M.

    2015-01-01

    Abstract Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials. PMID:25671556

  18. Dog models for blinding inherited retinal dystrophies.

    PubMed

    Petersen-Jones, Simon M; Komáromy, András M

    2015-03-01

    Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials.

  19. Ubiquitous health monitoring and real-time cardiac arrhythmias detection: a case study.

    PubMed

    Li, Jian; Zhou, Haiying; Zuo, Decheng; Hou, Kun-Mean; De Vaulx, Christophe

    2014-01-01

    As the symptoms and signs of heart diseases that cause sudden cardiac death, cardiac arrhythmia has attracted great attention. Due to limitations in time and space, traditional approaches to cardiac arrhythmias detection fail to provide a real-time continuous monitoring and testing service applicable in different environmental conditions. Integrated with the latest technologies in ECG (electrocardiograph) analysis and medical care, the pervasive computing technology makes possible the ubiquitous cardiac care services, and thus brings about new technical challenges, especially in the formation of cardiac care architecture and realization of the real-time automatic ECG detection algorithm dedicated to care devices. In this paper, a ubiquitous cardiac care prototype system is presented with its architecture framework well elaborated. This prototype system has been tested and evaluated in all the clinical-/home-/outdoor-care modes with a satisfactory performance in providing real-time continuous cardiac arrhythmias monitoring service unlimitedly adaptable in time and space.

  20. Right Ventricular Outflow Tract Arrhythmias: Benign Or Early Stage Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia?

    PubMed

    Lin Md, Tina; Conti Md, Sergio; Cipolletta Md, Laura; Marino Md, Vittoria; Zucchetti Md, Martina; Russo Md, Eleonora; Pizzamiglio Md, Francesca; Al-Mohani Md, Ghaliah; Pala Be, Salvatore; Catto Be PhD, Valentina; Di Biase Md PhD, Luigi; Natale Md, Andrea; Tondo Md PhD Fesc, Claudio; Carbucicchio Md, Corrado

    2014-12-01

    Ventricular arrhythmias (VAs) arising from the right ventricular outflow tract (RVOT) are a common and heterogeneous entity. Idiopathic right ventricular arrhythmias (IdioVAs) are generally benign, with excellent ablation outcomes and long-term arrhythmia-free survival, and must be distinguished from other conditions associated with VAs arising from the right ventricle: the differential diagnosis with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is therefore crucial because VAs are one of the most important causes of sudden cardiac death (SCD) in young individuals even with early stage of the disease. Radiofrequency catheter ablation (RFCA) is a current option for the treatment of VAs but important differences must be considered in terms of indication, purposes and procedural strategies in the treatment of the two conditions. In this review, we comprehensively discuss clinical and electrophysiological features, diagnostic and therapeutic techniques in a compared analysis of these two entities.

  1. Brief history of arrhythmia in the WPW syndrome - the contribution of George Ralph Mines.

    PubMed

    Boukens, Bas J; Janse, Michiel J

    2013-09-01

    George Ralph Mines studied the basic principles of reentry and published his data in The Journal of Physiology in 1913. Exactly 100 years later we discuss his first electrophysiological experiments and how his results lead to the insight that was the basis for the treatment of the clinical arrhythmias seen in Wolff-Parkinson-White syndrome.

  2. Cardiac Arrhythmias and Abnormal Electrocardiograms After Acute Stroke.

    PubMed

    Ruthirago, Doungporn; Julayanont, Parunyou; Tantrachoti, Pakpoom; Kim, Jongyeol; Nugent, Kenneth

    2016-01-01

    Cardiac arrhythmias and electrocardiogram (ECG) abnormalities occur frequently but are often underrecognized after strokes. Acute ischemic and hemorrhagic strokes in some particular area of brain can disrupt central autonomic control of the heart, precipitating cardiac arrhythmias, ECG abnormalities, myocardial injury and sometimes sudden death. Identification of high-risk patients after acute stroke is important to arrange appropriate cardiac monitoring and effective management of arrhythmias, and to prevent cardiac morbidity and mortality. More studies are needed to better clarify pathogenesis, localization of areas associated with arrhythmias and practical management of arrhythmias and abnormal ECGs after acute stroke.

  3. Mechanistic and therapeutic perspectives for cardiac arrhythmias: beyond ion channels.

    PubMed

    Wu, Yufei; Li, Jun; Xu, Liang; Lin, Li; Chen, Yi-Han

    2017-03-24

    Cardiac arrhythmias are among the most common causes of death in the world. Foundational studies established the critical role of ion channel disorders in arrhythmias, yet defects in ion channels themselves, such as mutations, may not account for all arrhythmias. Despite the progress made in recent decades, the antiarrhythmic drugs currently available have limited effectiveness, and the majority of these drugs can have proarrhythmic effects. This review describes novel knowledge on cellular mechanisms that cause cardiac arrhythmias, focuses on the dysfunction of subcellular organelles and intracellular logistics, and discusses potential strategies and challenges for developing novel, safe and effective treatments for arrhythmias.

  4. Asymptomatic Intradialytic Supraventricular Arrhythmias and Adverse Outcomes in Patients on Hemodialysis.

    PubMed

    Verde, Eduardo; Pérez de Prado, Armando; López-Gómez, Juan M; Quiroga, Borja; Goicoechea, Marian; García-Prieto, Ana; Torres, Esther; Reque, Javier; Luño, José

    2016-12-07

    Supraventricular arrhythmias are associated with high morbidity and mortality. Nevertheless, this condition has received little attention in patients on hemodialysis. The objective of this study was to analyze the incidence of intradialysis supraventricular arrhythmia and its long-term prognostic value. We designed an observational and prospective study in a cohort of patients on hemodialysis with a 10-year follow-up period. All patients were recruited for study participation and were not recruited for clinical indications. The study population comprised 77 patients (42 men and 35 women; mean age =58±15 years old) with sinus rhythm monitored using a Holter electrocardiogram over six consecutive hemodialysis sessions at recruitment. Hypertension was present in 68.8% of patients, and diabetes was present in 29.9% of patients. Supraventricular arrhythmias were recorded in 38 patients (49.3%); all of these were short, asymptomatic, and self-limiting. Age (hazard ratio, 1.04 per year; 95% confidence interval, 1.00 to 1.08) and right atrial enlargement (hazard ratio, 4.29; 95% confidence interval, 1.30 to 14.09) were associated with supraventricular arrhythmia in the multivariate analysis. During a median follow-up of 40 months, 57 patients died, and cardiovascular disease was the main cause of death (52.6%). The variables associated with all-cause mortality in the Cox model were age (hazard ratio, 1.04 per year; 95% confidence interval, 1.00 to 1.08), C-reactive protein (hazard ratio, 1.04 per 1 mg/L; 95% confidence interval, 1.00 to 1.08), and supraventricular arrhythmia (hazard ratio, 3.21; 95% confidence interval, 1.29 to 7.96). Patients with supraventricular arrhythmia also had a higher risk of nonfatal cardiovascular events (hazard ratio, 4.32; 95% confidence interval, 2.11 to 8.83) and symptomatic atrial fibrillation during follow-up (hazard ratio, 17.19; 95% confidence interval, 2.03 to 145.15). The incidence of intradialysis supraventricular arrhythmia was high

  5. Robotic magnetic navigation for ablation of human arrhythmias

    PubMed Central

    Da Costa, Antoine; Guichard, Jean Baptiste; Roméyer-Bouchard, Cécile; Gerbay, Antoine; Isaaz, Karl

    2016-01-01

    Radiofrequency treatment represents the first choice of treatment for arrhythmias, in particular complex arrhythmias and especially atrial fibrillation, due to the greater benefit/risk ratio compared to antiarrhythmic drugs. However, complex arrhythmias such as atrial fibrillation require long procedures with additional risks such as X-ray exposure or serious complications such as tamponade. Given this context, the treatment of arrhythmias using robotic magnetic navigation entails a technique well suited to complex arrhythmias on account of its efficacy, reliability, significant reduction in X-ray exposure for both patient and operator, as well as a very low risk of perforation. As ongoing developments will likely improve results and procedure times, this technology will become one of the most modern technologies for treating arrhythmias. Based on the literature, this review summarizes the advantages and limitations of robotic magnetic navigation for ablation of human arrhythmias. PMID:27698569

  6. Enhanced self-termination of re-entrant arrhythmias as a pharmacological strategy for antiarrhythmic action

    NASA Astrophysics Data System (ADS)

    Aslanidi, O. V.; Bailey, A.; Biktashev, V. N.; Clayton, R. H.; Holden, A. V.

    2002-09-01

    Ventricular tachycardia and fibrillation are potentially lethal cardiac arrhythmias generated by high frequency, irregular spatio-temporal electrical activity. Re-entrant propagation has been demonstrated as a mechanism generating these arrhythmias in computational and in vitro animal models of these arrhythmias. Re-entry can be idealised in homogenous isotropic virtual cardiac tissues as spiral and scroll wave solutions of reaction-diffusion equations. A spiral wave in a bounded medium can be terminated if its core reaches a boundary. Ventricular tachyarrhythmias in patients are sometimes observed to spontaneously self-terminate. One possible mechanism for self-termination of a spiral wave is meander of its core to an inexcitable boundary. We have previously proposed the hypothesis that the spatial extent of meander of a re-entrant wave in the heart can be directly related to its probability of self-termination, and so inversely related to its lethality. Meander in two-dimensional virtual ventricular tissues based on the Oxsoft family of cell models, with membrane excitation parameters simulating the inherited long Q-T syndromes has been shown to be consistent with this hypothesis: the largest meander is seen in the syndrome with the lowest probability of death per arrhythmic episode. Here we extend our previous results to virtual tissues based on the Luo-Rudy family of models. Consistent with our hypothesis, for both families of models, whose different ionic mechanisms produce different patterns of meander, the LQT virtual tissue with the larger meander simulates the syndrome with the lower probability of death per episode. Further, we search the parameter space of the repolarizing currents to find their conductance parameter values that give increased meander of spiral waves. These parameters may provide targets for antiarrhythmic drugs designed to act by increasing the likelihood of self-termination of re-entrant arrhythmias.

  7. Drug-induced fatal arrhythmias: Acquired long QT and Brugada syndromes.

    PubMed

    Turker, Isik; Ai, Tomohiko; Itoh, Hideki; Horie, Minoru

    2017-08-01

    Since the early 1990s, the concept of primary "inherited" arrhythmia syndromes or ion channelopathies has evolved rapidly as a result of revolutionary progresses made in molecular genetics. Alterations in genes coding for membrane proteins such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP) have been shown to cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, progressive cardiac conduction disease, etc. Among these, long QT and Brugada syndromes are the most extensively studied, and drugs cause a phenocopy of these two diseases. To date, more than 10 different genes have been reported to be responsible for each syndrome. More recently, it was recognized that long QT syndrome can be latent, even in the presence of an unequivocally pathogenic mutation (silent mutation carrier). Co-existence of other pathological conditions in these silent mutation carriers may trigger a malignant form of ventricular arrhythmia, the so called torsade de pointes (TdP) that is most commonly brought about by drugs. In analogy to the drug-induced long QT syndrome, Brugada type 1 ECG can also be induced or unmasked by a wide variety of drugs and pathological conditions; so physicians may encounter patients with a latent form of Brugada syndrome. Of particular note, Brugada syndrome is frequently associated with atrial fibrillation whose therapeutic agents such as Vaughan Williams class IC drugs can unmask the dormant and asymptomatic Brugada syndrome. This review describes two types of drug-induced arrhythmias: the long QT and Brugada syndromes. Copyright © 2017. Published by Elsevier Inc.

  8. Mitochondrial inheritance in Aspergillus nidulans.

    PubMed

    Coenen, A; Croft, J H; Slakhorst, M; Debets, F; Hoekstra, R

    1996-04-01

    Mitochondrial chloramphenicol and oligomycin resistance mutations were used to investigate mitochondrial inheritance in A. nidulans. Mitochondrial RFLPs could not be used to distinguish between paternal and maternal mitochondria because none were detected in the 54 isolates investigated. Several thousand ascospores from each of 111 hybrid cleistothecia from 21 different crosses between 7 heterokaryon incompatible isolates were tested for biparental inheritance. All mitochondrial inheritance was strictly uniparental. Not one instance of paternal inheritance of mitochondria was observed. The implications of our results for the theory that uniparental inheritance evolved to avoid cytoplasmic conflict are discussed. Possible explanations for the maintenance of strict uniparental inheritance of mitochondria in an inbreeding homothallic organism are suggested. The chloramphenicol resistance marker was inherited preferentially to the oligomycin resistance marker probably due to the inhibited energy production of mitochondria with the oligomycin resistance mutation. The maternal parent was determined for 93 hybrid cleistothecia from 17 crosses between 7 different strains. Contrary to previous reports A. nidulans strains functioned as both maternal and paternal parent in most crosses.

  9. Diagnosis and Treatment of Fetal Arrhythmia

    PubMed Central

    Wacker-Gussmann, Annette; Strasburger, Janette F.; Cuneo, Bettina F.; Wakai, Ronald T.

    2014-01-01

    Detection and careful stratification of fetal heart rate (FHR) is extremely important in all pregnancies. The most lethal cardiac rhythm disturbances occur during apparently normal pregnancies where FHR and rhythmare regular and within normal or low-normal ranges. These hidden depolarization and repolarization abnormalities, associated with genetic ion channelopathies cannot be detected by echocardiography, and may be responsible for up to 10% of unexplained fetal demise, prompting a need for newer and better fetal diagnostic techniques. Other manifest fetal arrhythmias such as premature beats, tachycardia, and bradycardia are commonly recognized. Heart rhythm diagnosis in obstetrical practice is usually made by M-mode and pulsed Doppler fetal echocardiography, but not all fetal cardiac time intervals are captured by echocardiographic methods. This article reviews different types of fetal arrhythmias, their presentation and treatment strategies, and gives an overview of the present and future diagnostic techniques. PMID:24858320

  10. Progressive interatrial block and supraventricular arrhythmias.

    PubMed

    Enriquez, Andres; Conde, Diego; Redfearn, Damian P; Baranchuk, Adrian

    2015-07-01

    Interatrial conduction disorders are frequent in patients with structural heart diseases, including hypertension, coronary disease, and hypertrophic cardiomyopathy, and they are strongly associated with atrial tachyarrhythmias, especially atrial fibrillation and flutter. Conduction delays lead to dispersion of refractory periods and participate in initiating and maintaining reentry circuits, facilitating atrial arrhythmias. In this case, the changing pattern over time is a manifestation of progressive atrial remodeling and conduction delay. The terminal negative component of the P wave in the inferior leads suggests block of the electrical impulse in the Bachman bundle zone, with retrograde activation of the left atria via muscular connections at the coronary sinus. This has been reproduced in experimental models and confirmed by endocardial mapping. Physicians should be aware of the association between advanced interatrial block and development of atrial arrhythmias as its recognition could prompt early and aggressive antiarrhythmic treatment.

  11. Haemodynamic assessment of fetal heart arrhythmias.

    PubMed

    Lingman, G; Dahlström, J A; Eik-Nes, S H; Marsál, K; Ohlin, P; Ohrlander, S

    1984-07-01

    The effects of fetal heart arrhythmias were examined serially in two pregnancies by three non-invasive methods: fetal ECG, fetal phonocardiography and ultrasonic measurement of fetal blood flow. In a case of supraventricular arrhythmia, there was evidence suggesting that the stroke volume varied with ventricular filling according to the Frank-Starling law. In a case of total atrioventricular block the mean blood flow in the fetal descending aorta and in the umbilical vein was within the normal range. Blood flow velocity in the inferior vena cava of the fetus reflected atrial contractions. In the phonocardiogram, a phenomenon similar to 'bruit de canon' was found. Both pregnancies had good outcomes and subsequent development of the infants was normal except for the persisting dysrhythmias. The two cases exemplify how fetal heart function can be assessed in utero.

  12. [Compromized myocardial perfusion in arrhythmias (author's transl)].

    PubMed

    Simon, H; Neumann, G; Felix, R; Hedde, H; Schaede, A; Thurn, P; Winkler, C

    1977-09-15

    In 7 patients with arrhythmias of various origin the myocardial scintigram displayed either a diffuse or circumscript defect of the perfusion. The coronary arteriogram was normal in all patients. The localized defect of the perfusion in 2 patients was in the region of the upper part of the interventricular septum. Both had a left bundle brunch block. A correlation between the perfusion defect and the electrophysiological abnormality seems probable. The perfusion defect in one of the patients is most probably caused by a previous myocarditis followed by fibrous changes. In the other 6 patients the cause for the perfusion defect is not obvious. A history of myocarditis is missing. The presence of "small vessel disease" in those patients has however to be considered. Our results point to the relation between an abnormality of the microcirculation and arrhythmias in younger patients.

  13. Julia Bell and the Treasury of Human Inheritance.

    PubMed

    Harper, Peter S

    2005-04-01

    The Treasury of Human Inheritance represents the most extensive, and one of the earliest series of documentations and analyses of human genetic disorders. Published between 1909 and 1958, from The Galton Laboratory, London, most of the numerous sections were written by Julia Bell, who represents a key figure in the development of human and medical genetics. Her combination of mathematical training, genetic knowledge and clinical expertise yielded numerous important insights into human inheritance first appearing in the Treasury; it remains a valuable scientific as well as an historical record of the genetics of a range of important inherited disorders.

  14. Electrophysiologic features of inherited demyelinating neuropathies: a reappraisal.

    PubMed

    Lewis, R A; Sumner, A J

    1999-09-14

    The observation that inherited demyelinating neuropathies tend to have uniform conduction slowing and acquired disorders (CIDP and variants) have nonuniform or multifocal slowing was made before the identification of genetic defects of specific myelin constituents that cause the different forms of Charcot-Marie-Tooth and other inherited disorders involving peripheral nerve myelin. It is becoming clear that the electrophysiologic aspects of these disorders are more complex than previously realized. We review the current information available on the electrophysiologic features of the inherited demyelinating neuropathies in hopes of clarifying the clinical electrodiagnostic features of these disorders as well as to shed light on the physiologic consequences of the different genetic mutations.

  15. Treatable inherited rare movement disorders.

    PubMed

    Jinnah, H A; Albanese, Alberto; Bhatia, Kailash P; Cardoso, Francisco; Da Prat, Gustavo; de Koning, Tom J; Espay, Alberto J; Fung, Victor; Garcia-Ruiz, Pedro J; Gershanik, Oscar; Jankovic, Joseph; Kaji, Ryuji; Kotschet, Katya; Marras, Connie; Miyasaki, Janis M; Morgante, Francesca; Munchau, Alexander; Pal, Pramod Kumar; Rodriguez Oroz, Maria C; Rodríguez-Violante, Mayela; Schöls, Ludger; Stamelou, Maria; Tijssen, Marina; Uribe Roca, Claudia; de la Cerda, Andres; Gatto, Emilia M

    2017-09-01

    There are many rare movement disorders, and new ones are described every year. Because they are not well recognized, they often go undiagnosed for long periods of time. However, early diagnosis is becoming increasingly important. Rapid advances in our understanding of the biological mechanisms responsible for many rare disorders have enabled the development of specific treatments for some of them. Well-known historical examples include Wilson disease and dopa-responsive dystonia, for which specific and highly effective treatments have life-altering effects. In recent years, similarly specific and effective treatments have been developed for more than 30 rare inherited movement disorders. These treatments include specific medications, dietary changes, avoidance or management of certain triggers, enzyme replacement therapy, and others. This list of treatable rare movement disorders is likely to grow during the next few years because a number of additional promising treatments are actively being developed or evaluated in clinical trials. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  16. Classification of arrhythmia using hybrid networks.

    PubMed

    Haseena, Hassan H; Joseph, Paul K; Mathew, Abraham T

    2011-12-01

    Reliable detection of arrhythmias based on digital processing of Electrocardiogram (ECG) signals is vital in providing suitable and timely treatment to a cardiac patient. Due to corruption of ECG signals with multiple frequency noise and presence of multiple arrhythmic events in a cardiac rhythm, computerized interpretation of abnormal ECG rhythms is a challenging task. This paper focuses a Fuzzy C- Mean (FCM) clustered Probabilistic Neural Network (PNN) and Multi Layered Feed Forward Network (MLFFN) for the discrimination of eight types of ECG beats. Parameters such as fourth order Auto Regressive (AR) coefficients along with Spectral Entropy (SE) are extracted from each ECG beat and feature reduction has been carried out using FCM clustering. The cluster centers form the input of neural network classifiers. The extensive analysis of Massachusetts Institute of Technology- Beth Israel Hospital (MIT-BIH) arrhythmia database shows that FCM clustered PNNs is superior in cardiac arrhythmia classification than FCM clustered MLFFN with an overall accuracy of 99.05%, 97.14%, respectively.

  17. Malignant ventricular arrhythmias in chronic chagasic myocarditis.

    PubMed

    Chiale, P A; Halpern, M S; Nau, G J; Przybylski, J; Tambussi, A M; Lázzari, J O; Elizari, M V; Rosenbaum, M B

    1982-03-01

    We studied 28 cases of chronic chagasic myocarditis (CCM) with frequent ventricular arrhythmias. Two-hundred and three conventional ECGs recorded during 3 months showed ventricular extrasystoles (VE) ranging between 0.2 and 6 per ten beats in 100%; multiform VE in 97.04%; couplets in 79.31%; ventricular tachycardia (VT) in 42.85%; and R on T in 21.67%. A 24-hour continuous recording showed that VE ranged between 3780 and 61733 (mean 16618 +/- 2627); multiform VE and couplets were present in 100% of patients, and VT was present in 78.5%. In 16 patients (group I) the frequency of VE was persistently high, without diurnal variation; 11 patients showed sustained reduction during sleeping hours and only one showed an increase during night sleep (group II). Even in group II, VE never disappeared for periods longer than 10 minutes. In five patients, four 24-hour recordings were obtained at weekly intervals, and in five other patients a second 24-hour recording was performed 10 to 24 months later. The remarkable frequency, persistence and low variability of ventricular arrhythmias in CCM suggest that such arrhythmias can be used as a most stable, reliable, but highly demanding model for testing the efficacy of antiarrhythmic drugs.

  18. Remote continuous cardiac arrhythmias detection and monitoring.

    PubMed

    Zhou, Haiying; Hou, Kun Mean; Ponsonnaille, Jean; Gineste, Laurent; Coudon, Julien; de Sousa, Gil; de Vaulx, Christophe; Li, Jian-Jin; Chainais, Pierre; Aufrère, Romuald; Amamra, Abdelaziz; Chanet, Jean-Pierre

    2004-01-01

    The current techniques used to diagnose cardiac arrhythmias such as Holter, Rtest and telemetry systems are partially efficient because they are limited either in time or in space. In this paper, a platform dedicated to the real-time remote continuous cardiac arrhythmias detection and monitoring is proposed. Such a platform allows to improve the accuracy and the efficiency of the diagnostic of ventricular tachycardia among the high-risk patients and enables the implantation of ICD to prevent sudden death. The new method allows the patient to lead a normal life while being remotely monitored in real-time by an ambulatory wireless ECG sensor. When a cardiac arrhythmia is detected a message including a sequence of ECG signals and the patient's images (indoors only) is sent to a remote surveillance server. According to the gravity of the symptom, the cardiologist can intervene in real time or later. The system has been evaluated on some ten patients with regard to heartbeat and cardiac rhythm disturbance. The real-time results are similar to those offered by HP telemetry systems.

  19. Internet resources cataloguing inherited disorders in dogs.

    PubMed

    Nicholas, Frank W; Crook, Alice; Sargan, David R

    2011-08-01

    Up-to-date annotated catalogues of known inherited disorders in dogs are freely available on the Internet, providing vital information to existing and prospective dog owners, dog breeders, veterinarians, geneticists and others interested in the occurrence and control of inherited disorders. These resources are the Canine Inherited Disorders Database (CIDD), Inherited Diseases in Dogs (IDID) and Online Mendelian Inheritance in Animals (OMIA) the latter associated with Listing of Inherited Disorders in Animals (LIDA). The history and features of these resources are summarised.

  20. Management of inherited atherogenic dyslipidemias in children.

    PubMed

    Guardamagna, Ornella; Cagliero, Paola; Abello, Francesca

    2013-04-01

    In order to prevent cardiovascular disease, the treatment of inherited dyslipidemias in childhood represents an emerging topic capturing scientists' consideration. A body of findings emerged in the last decade for diagnosis and therapy, and results were recently summarized to introduce new guidelines by the American Academy of Pediatrics and National Institute for Health and Clinical Excellence. It is well known and generally shared the need to detect affected children precociously, when the family history address to genetic dyslipidemia and when familial premature cardiovascular disease occurs. A spectrum of disorders involving lipoproteins could be recognized by specific biochemical and genetic markers. A defined diagnosis represents the starting point to establish a correct treatment and follow-up program. This review represents a literature synthesis of the main cornerstones and criticisms concerning the screening program and management of atherogenic inherited dyslipidemias in children and adolescents.

  1. Inherited cardiovascular conditions: the challenges of genomic medicine.

    PubMed

    Burton, H; Alberg, C; Hall, A; Sagoo, G S; Stewart, A

    2010-03-01

    The report Heart to Heart published in 2009 by the Foundation for Genomics and Population Health provided an account of new health services needs arising from greater scientific and clinical understanding of inherited cardiovascular conditions. Informed by advice from an expert working group, the report makes recommendations for the development of specialised inherited cardiovascular conditions services within the UK. The report will also be of relevance internationally, wherever cardiologists and geneticists aim to provide care for these patients and their families.

  2. Is the diagnostic function of pacemakers a reliable source of information about ventricular arrhythmias?

    PubMed

    Kumor, Magdalena; Baranowski, Rafał; Koźluk, Edward; Walczak, Franciszek

    2010-01-01

    The aim of this study was to evaluate the reliability of pacemaker diagnostic function in diagnosing ventricular arrhythmias. We compared the occurrence of ventricular ectopic beats in 51 simultaneous 24-hour electrocardiogram (ECG) recordings and pacemaker event counters printouts. The diagnostic function of a pacemaker allowed also for a qualitative assessment in 38 patients. In these cases, the occurrence of complex forms of ventricular arrhythmias was cross-checked for accelerated ventricular rhythms together with ventricular tachycardia, and triplets and couplets. The detection of at least one type of complex ventricular form of arrhythmia, diagnosed by both methods, was considered as an agreement between the methods. The results of ventricular ectopic beat counts differed significantly between the methods. In three (6%) patients, the results were consistent; in 20 (39%) the pacemaker underestimated results; in 28 (55%) they were overestimated. When more liberal criteria of agreement were applied, clinically significant differences were observed in 24 (47%) patients; in seven (29%) patients the count made by the pacemaker was lowered; and in 17 (71%) it was overestimated. Ventricular tachycardias were recorded in 24-hour ECG in eight patients. In three, they were identified by the pacemaker diagnostic function. In five, the pacemaker did not recognize tachycardia (because of its frequency being below 120/min). In nine, tachycardia was recognized falsely. The sensitivity in ventricular tachycardia diagnosis by pacemaker diagnostic function was 38%, specificity - 70%, the value of a positive result - 25%, negative - 81%. The evaluation of ventricular arrhythmias by pacemaker cannot serve as the only reliable diagnostic method of arrhythmias. The presence of a large number of sequences that may correspond to ventricular arrhythmia or failure to sense, should result in verification via 24-hour ECG monitoring.

  3. Carbon Monoxide Induces Cardiac Arrhythmia via Induction of the Late Na+ Current

    PubMed Central

    Dallas, Mark L.; Yang, Zhaokang; Boyle, John P.; Boycott, Hannah E.; Scragg, Jason L.; Milligan, Carol J.; Elies, Jacobo; Duke, Adrian; Thireau, Jérôme; Reboul, Cyril; Richard, Sylvain; Bernus, Olivier; Steele, Derek S.

    2012-01-01

    Rationale: Clinical reports describe life-threatening cardiac arrhythmias after environmental exposure to carbon monoxide (CO) or accidental CO poisoning. Numerous case studies describe disruption of repolarization and prolongation of the QT interval, yet the mechanisms underlying CO-induced arrhythmias are unknown. Objectives: To understand the cellular basis of CO-induced arrhythmias and to indentify an effective therapeutic approach. Methods: Patch-clamp electrophysiology and confocal Ca2+ and nitric oxide (NO) imaging in isolated ventricular myocytes was performed together with protein S-nitrosylation to investigate the effects of CO at the cellular and molecular levels, whereas telemetry was used to investigate effects of CO on electrocardiogram recordings in vivo. Measurements and Main Results: CO increased the sustained (late) component of the inward Na+ current, resulting in prolongation of the action potential and the associated intracellular Ca2+ transient. In more than 50% of myocytes these changes progressed to early after-depolarization–like arrhythmias. CO elevated NO levels in myocytes and caused S-nitrosylation of the Na+ channel, Nav1.5. All proarrhythmic effects of CO were abolished by the NO synthase inhibitor l-NAME, and reversed by ranolazine, an inhibitor of the late Na+ current. Ranolazine also corrected QT variability and arrhythmias induced by CO in vivo, as monitored by telemetry. Conclusions: Our data indicate that the proarrhythmic effects of CO arise from activation of NO synthase, leading to NO-mediated nitrosylation of NaV1.5 and to induction of the late Na+ current. We also show that the antianginal drug ranolazine can abolish CO-induced early after-depolarizations, highlighting a novel approach to the treatment of CO-induced arrhythmias. PMID:22822026

  4. Autosomal Recessive Inheritance

    MedlinePlus

    ... visual function, preservation of sight, and the special health problems and requirements of the blind.” News & Events Events Calendar NEI Press Releases News from NEI Grantees Spokesperson bios Statistics and ... Frequently asked questions Clinical Studies Publications Catalog ...

  5. [Clinical and genetic findings in patients with biotinidase deficiency detected through newborn screening or selective screening for hearing loss or inherited metabolic disease].

    PubMed

    Couce, María Luz; Pérez-Cerdá, Celia; García Silva, María Teresa; García Cazorla, Angels; Martín-Hernández, Elena; Castiñeiras, Daisy; Pineda, Merçè; Navarrete, Rosa; Campistol, Jaume; Fraga, José María; Pérez, Belén; Ugarte, Magdalena

    2011-10-22

    To evaluate clinical, biochemical and genetic findings of two series of patients with biotinidase deficiency. Fifteen cases detected through newborn screening and six through selective screening for hearing loss or metabolic disease. No patient detected by neonatal screening had symptoms and only one case with partial biotinidase activity developed myoclonic seizures that resolved with biotin. More common mutations found among this group were p.D444H and the double mutation [p.D444H;p.A171T]. However, neurological and hearing manifestations predominated among the six symptomatic cases and mutations p.L32fs, p.G34fs, p.T401I, p.D444H, p.T532M and the novel one p.L466fs were identified. Patients with profound biotinidase deficiency and/or clinical signs were treated with pharmacological doses of biotin (10-30mg daily). Biotinidase deficiency must be included in the newborn screening programmes in order to begin early treatment even in partial forms. Different mutations found in both series of patients suggest that routine genetic procedure of the BTD gene by direct sequencing might be useful to assign patients to the partial or profound form of the disease. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  6. Central Sympathetic Inhibition: a Neglected Approach for Treatment of Cardiac Arrhythmias?

    PubMed

    Cagnoni, Francesca; Destro, Maurizio; Bontempelli, Erika; Locatelli, Giovanni; Hering, Dagmara; Schlaich, Markus P

    2016-02-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Overactivation of the sympathetic nervous system (SNS) plays an important role in the pathogenesis of comorbidities related to AF such as hypertension, congestive heart failure, obesity, insulin resistance, and obstructive sleep apnea. Methods that reduce sympathetic drive, such as centrally acting sympatho-inhibitory agents, have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. Moxonidine acts centrally to reduce activity of the SNS, and clinical trials indicate that this is associated with a decreased AF burden in hypertensive patients with paroxysmal AF and reduced post-ablation recurrence of AF in patients with hypertension who underwent pulmonary vein isolation (PVI). Furthermore, device-based approaches to reduce sympathetic drive, such as renal denervation, have yielded promising results in the prevention and treatment of cardiac arrhythmias. In light of these recent findings, targeting elevated sympathetic drive with either pharmacological or device-based approaches has become a focus of clinical research. Here, we review the data currently available to explore the potential utility of sympatho-inhibitory therapies in the prevention and treatment of cardiac arrhythmias.

  7. Non-Invasive Assessment of Susceptibility to Ventricular Arrhythmias During Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Cohen, Richard J.

    1999-01-01

    cardiac susceptibility to ventricular arrhythmias in subjects exposed to simulated space flight in the Human Studies Core protocol being conducted by the Cardiovascular Alterations Team, which involves sixteen days .of bed rest. In particular, we are applying a powerful new non-invasive technology, developed in Professor Cohen's laboratory at MIT for the quantitative assessment of the risk of life-threatening ventricular arrhythmias. This technology involves the measurement of microvolt levels of T wave alternans (TWA) during exercise stress, and was recently granted approval by the Food and Drug Administration to be used for the clinical evaluation of patients suspected to be at risk of ventricular arrhythmias. In addition, we are obtaining 24 hour Holter monitoring (to detect non-sustained ventricular tachycardia and to assess heart rate variability). We are also conducting protocols to obtain these same measures on a monthly basis for up to four months in subjects in the Bone Demineralization/calcium Metaboloism Team's long term bed rest study.

  8. Non-Invasive Assessment of Susceptibility to Ventricular Arrhythmias During Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Cohen, Richard J.

    1999-01-01

    cardiac susceptibility to ventricular arrhythmias in subjects exposed to simulated space flight in the Human Studies Core protocol being conducted by the Cardiovascular Alterations Team, which involves sixteen days .of bed rest. In particular, we are applying a powerful new non-invasive technology, developed in Professor Cohen's laboratory at MIT for the quantitative assessment of the risk of life-threatening ventricular arrhythmias. This technology involves the measurement of microvolt levels of T wave alternans (TWA) during exercise stress, and was recently granted approval by the Food and Drug Administration to be used for the clinical evaluation of patients suspected to be at risk of ventricular arrhythmias. In addition, we are obtaining 24 hour Holter monitoring (to detect non-sustained ventricular tachycardia and to assess heart rate variability). We are also conducting protocols to obtain these same measures on a monthly basis for up to four months in subjects in the Bone Demineralization/calcium Metaboloism Team's long term bed rest study.

  9. Prophylactic arrhythmia surgery in association with congenital heart disease.

    PubMed

    Mavroudis, Constantine; Deal, Barbara J

    2016-07-01

    Certain congenital heart anomalies make patients more susceptible to arrhythmia development throughout their lives. This poses the question whether prophylactic arrhythmia surgery should be incorporated into reparative open heart procedures for congenital heart disease. There is currently no consensus on what constitutes a standard prophylactic procedure, owing to the questions that remain regarding lesions to be performed; energy sources to use; proximity of energy source or incisions to coronary arteries, sinoatrial node, atrioventricular node; circumstances for right atrial, left atrial, or biatrial appendectomy; and whether to perform a right, left, or biatrial maze procedure. These considerations are important because prophylactic arrhythmia procedures are performed without knowing if the patient will actually develop an arrhythmia in his or her lifetime. By reviewing and summarizing the literature, congenital heart disease patients who are at risk for developing atrial arrhythmias can be identified and lesion sets can be suggested in an effort to standardize experimental protocols for prophylactic arrhythmia surgery.

  10. Prophylactic arrhythmia surgery in association with congenital heart disease

    PubMed Central

    Deal, Barbara J.

    2016-01-01

    Certain congenital heart anomalies make patients more susceptible to arrhythmia development throughout their lives. This poses the question whether prophylactic arrhythmia surgery should be incorporated into reparative open heart procedures for congenital heart disease. There is currently no consensus on what constitutes a standard prophylactic procedure, owing to the questions that remain regarding lesions to be performed; energy sources to use; proximity of energy source or incisions to coronary arteries, sinoatrial node, atrioventricular node; circumstances for right atrial, left atrial, or biatrial appendectomy; and whether to perform a right, left, or biatrial maze procedure. These considerations are important because prophylactic arrhythmia procedures are performed without knowing if the patient will actually develop an arrhythmia in his or her lifetime. By reviewing and summarizing the literature, congenital heart disease patients who are at risk for developing atrial arrhythmias can be identified and lesion sets can be suggested in an effort to standardize experimental protocols for prophylactic arrhythmia surgery. PMID:27709096

  11. Oxidative stress, fibrosis, and early afterdepolarization-mediated cardiac arrhythmias

    PubMed Central

    Karagueuzian, Hrayr S.; Nguyen, Thao P.; Qu, Zhilin; Weiss, James N.

    2013-01-01

    Animal and clinical studies have demonstrated that oxidative stress, a common pathophysiological factor in cardiac disease, reduces repolarization reserve by enhancing the L-type calcium current, the late Na, and the Na-Ca exchanger, promoting early afterdepolarizations (EADs) that can initiate ventricular tachycardia and ventricular fibrillation (VT/VF) in structurally remodeled hearts. Increased ventricular fibrosis plays a key facilitatory role in allowing oxidative-stress induced EADs to manifest as triggered activity and VT/VF, since normal non-fibrotic hearts are resistant to arrhythmias when challenged with similar or higher levels of oxidative stress. The findings imply that antifibrotic therapy, in addition to therapies designed to suppress EAD formation at the cellular level, may be synergistic in reducing the risk of sudden cardiac death. PMID:23423152

  12. Oxidative stress, fibrosis, and early afterdepolarization-mediated cardiac arrhythmias.

    PubMed

    Karagueuzian, Hrayr S; Nguyen, Thao P; Qu, Zhilin; Weiss, James N

    2013-01-01

    Animal and clinical studies have demonstrated that oxidative stress, a common pathophysiological factor in cardiac disease, reduces repolarization reserve by enhancing the L-type calcium current, the late Na, and the Na-Ca exchanger, promoting early afterdepolarizations (EADs) that can initiate ventricular tachycardia and ventricular fibrillation (VT/VF) in structurally remodeled hearts. Increased ventricular fibrosis plays a key facilitatory role in allowing oxidative-stress induced EADs to manifest as triggered activity and VT/VF, since normal non-fibrotic hearts are resistant to arrhythmias when challenged with similar or higher levels of oxidative stress. The findings imply that antifibrotic therapy, in addition to therapies designed to suppress EAD formation at the cellular level, may be synergistic in reducing the risk of sudden cardiac death.

  13. Propofol and arrhythmias: two sides of the coin

    PubMed Central

    Liu, Qiang; Kong, Ai-ling; Chen, Rong; Qian, Cheng; Liu, Shao-wen; Sun, Bao-gui; Wang, Le-xin; Song, Long-sheng; Hong, Jiang

    2011-01-01

    The hypnotic agent propofol is effective for the induction and maintenance of anesthesia. However, recent studies have shown that propofol administration is related to arrhythmias. Propofol displays both pro- and anti-arrhythmic effects in a concentration-dependent manner. Data indicate that propofol can convert supraventricular tachycardia and ventricular tachycardia and may inhibit the conduction system of the heart. The mechanism of the cardiac effects remains poorly defined and may involve ion channels, the autonomic nervous system and cardiac gap junctions. Specifically, sodium, calcium and potassium currents in cardiac cells are suppressed by clinically relevant concentrations of propofol. Propofol shortens the action potential duration (APD) but lessens the ischemia-induced decrease in the APD. Furthermore, propofol suppresses both sympathetic and parasympathetic tone and preserves gap junctions during ischemia. All of these effects cumulatively contribute to the antiarrhythmic and proarrhythmic properties of propofol. PMID:21642950

  14. Factor XI replacement for inherited factor XI deficiency in routine clinical practice: results of the HEMOLEVEN prospective 3-year postmarketing study.

    PubMed

    Bauduer, F; de Raucourt, E; Boyer-Neumann, C; Trossaert, M; Beurrier, P; Faradji, A; Peynet, J; Borg, J-Y; Chamouni, P; Chatelanaz, C; Henriet, C; Bridey, F; Goudemand, J

    2015-07-01

    Factor XI (FXI)-deficient patients may develop excessive bleeding after trauma or surgery. Replacement therapy should be considered in high-risk situations, especially when FXI levels are below 20 IU dL(-1) . HEMOLEVEN is a human plasma-derived factor XI concentrate available in France since 1992, but there are few data regarding its use by physicians. This prospective study assessed the use, efficacy and safety of HEMOLEVEN in common clinical practice. HEMOLEVEN was evaluated in FXI-deficient patients in 13 French centres in a 3-year postmarketing study. Forty-four patients (30 females, 14 males) received 67 treatments. The median age was 37 years (8 months-91 years). Basal FXI levels were <1 to 51 IU dL(-1) (median: 5.5); 29 patients were severely FXI-deficient (<20 IU dL(-1) ). FXI was administered prophylactically before 43 surgical procedures, 10 invasive procedures, 8 vaginal deliveries, or as curative treatment for six bleeds. The efficacy was assessed as excellent/good in 63, moderate in two and undetermined in two treatments. Seven patients experienced seven adverse effects, including two rated as serious: one sudden massive pulmonary embolism with fatal outcome and one case of inhibitor to FXI. HEMOLEVEN is effective for bleeding prevention in FXI deficiency. However, considering the benefit/risk ratio observed in relation to dosage in this study; firstly, it should be used sparingly due to its potential prothrombotic effect; secondly, new prescription procedures should be defined to adapt the dosage, especially in patients with intrinsic and/or acquired risk factors for thrombosis. © 2015 John Wiley & Sons Ltd.

  15. Antisense Oligonucleotide Therapy for Inherited Retinal Dystrophies.

    PubMed

    Gerard, Xavier; Garanto, Alejandro; Rozet, Jean-Michel; Collin, Rob W J

    2016-01-01

    Inherited retinal dystrophies (IRDs) are an extremely heterogeneous group of genetic diseases for which currently no effective treatment strategies exist. Over the last decade, significant progress has been made utilizing gene augmentation therapy for a few genetic subtypes of IRD, although several technical challenges so far prevent a broad clinical application of this approach for other forms of IRD. Many of the mutations leading to these retinal diseases affect pre-mRNA splicing of the mutated genes . Antisense oligonucleotide (AON)-mediated splice modulation appears to be a powerful approach to correct the consequences of such mutations at the pre-mRNA level , as demonstrated by promising results in clinical trials for several inherited disorders like Duchenne muscular dystrophy, hypercholesterolemia and various types of cancer. In this mini-review, we summarize ongoing pre-clinical research on AON-based therapy for a few genetic subtypes of IRD , speculate on other potential therapeutic targets, and discuss the opportunities and challenges that lie ahead to translate splice modulation therapy for retinal disorders to the clinic.

  16. Novel Calmodulin (CALM2) Mutations Associated with Congenital Arrhythmia Susceptibility

    PubMed Central

    Makita, Naomasa; Yagihara, Nobue; Crotti, Lia; Johnson, Christopher N.; Beckmann, Britt-Maria; Roh, Michelle S.; Shigemizu, Daichi; Lichtner, Peter; Ishikawa, Taisuke; Aiba, Takeshi; Homfray, Tessa; Behr, Elijah R.; Klug, Didier; Denjoy, Isabelle; Mastantuono, Elisa; Theisen, Daniel; Tsunoda, Tatsuhiko; Satake, Wataru; Toda, Tatsushi; Nakagawa, Hidewaki; Tsuji, Yukiomi; Tsuchiya, Takeshi; Yamamoto, Hirokazu; Miyamoto, Yoshihiro; Endo, Naoto; Kimura, Akinori; Ozaki, Kouichi; Motomura, Hideki; Suda, Kenji; Tanaka, Toshihiro; Schwartz, Peter J.; Meitinger, Thomas; Kääb, Stefan; Guicheney, Pascale; Shimizu, Wataru; Bhuiyan, Zahurul A.; Watanabe, Hiroshi; Chazin, Walter J.; George, Alfred L.

    2014-01-01

    Background Genetic predisposition to life-threatening cardiac arrhythmias such as in congenital long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) represent treatable causes of sudden cardiac death in young adults and children. Recently, mutations in calmodulin (CALM1, CALM2) have been associated with severe forms of LQTS and CPVT, with life-threatening arrhythmias occurring very early in life. Additional mutation-positive cases are needed to discern genotype-phenotype correlations associated with calmodulin mutations. Methods and Results We employed conventional and next-generation sequencing approaches including exome analysis in genotype-negative LQTS probands. We identified five novel de novo missense mutations in CALM2 in three subjects with LQTS (p.N98S, p.N98I, p.D134H) and two subjects with clinical features of both LQTS and CPVT (p.D132E, p.Q136P). Age of onset of major symptoms (syncope or cardiac arrest) ranged from 1–9 years. Three of five probands had cardiac arrest and one of these subjects did not survive. Although all probands had LQTS, two subjects also exhibited electrocardiographic features consistent with CPVT. The clinical severity among subjects in this series was generally less than that originally reported for CALM1 and CALM2 associated with recurrent cardiac arrest during infancy. Four of five probands responded to β-blocker therapy whereas one subject with mutation p.Q136P died suddenly during exertion despite this treatment. Mutations affect conserved residues located within calcium binding loops III (p.N98S, p.N98I) or IV (p.D132E, p.D134H, p.Q136P) and caused reduced calcium binding affinity. Conclusions CALM2 mutations can be associated with LQTS and with overlapping features of LQTS and CPVT. PMID:24917665

  17. Interdisciplinary psychosocial care for families with inherited cardiovascular diseases.

    PubMed

    Caleshu, Colleen; Kasparian, Nadine A; Edwards, Katharine S; Yeates, Laura; Semsarian, Christopher; Perez, Marco; Ashley, Euan; Turner, Christian J; Knowles, Joshua W; Ingles, Jodie

    2016-10-01

    Inherited cardiovascular diseases pose unique and complex psychosocial challenges for families, including coming to terms with life-long cardiac disease, risk of sudden death, grief related to the sudden death of a loved one, activity restrictions, and inheritance risk to other family members. Psychosocial factors impact not only mental health but also physical health and cooperation with clinical recommendations. We describe an interdisciplinary approach to the care of families with inherited cardiovascular disease, in which psychological care provided by specialized cardiac genetic counselors, nurses, and psychologists is embedded within the cardiovascular care team. We report illustrative cases and the supporting literature to demonstrate common scenarios, as well as practical guidance for clinicians working in the inherited cardiovascular disease setting.

  18. Current treatment of ventricular arrhythmias: state of the art.

    PubMed

    Stevenson, William G

    2013-12-01

    Ventricular arrhythmias may be benign, requiring only evaluation for associated risks and then reassurance, or associated with a risk of sudden death or significant morbidity. Therapies for these arrhythmias have evolved considerably over the past 20 years. For some, a definitive, curative therapy is available in the form of catheter ablation. Others are best managed with an implantable cardioverter-defibrillator that provides effective arrhythmia termination and protection from sudden death, with antiarrhythmic drugs or ablation to control recurrent arrhythmias. Although progress has been substantial, many challenges remain.

  19. Basic Cardiac Electrophysiology and Common Drug-induced Arrhythmias.

    PubMed

    Lee, Aimee; Pickham, David

    2016-09-01

    Drugs can be a double-edged sword, providing the benefit of symptom alleviation and disease modification but potentially causing harm from adverse cardiac arrhythmic events. Proarrhythmia is the ability of a drug to cause an arrhythmia, the number one reason for drugs to be withdrawn from the patient. Drug-induced arrhythmias are defined as the production of de novo arrhythmias or aggravation of existing arrhythmias, as a result of previous or concomitant pharmacologic treatment. This review summarizes normal cardiac cell and tissue functioning and provides an overview of drugs that effect cardiac repolarization and the adverse effects of commonly administered antiarrhythmics.

  20. Classification of cardiac arrhythmias using competitive networks.

    PubMed

    Leite, Cicilia R M; Martin, Daniel L; Sizilio, Glaucia R A; Dos Santos, Keylly E A; de Araujo, Bruno G; Valentim, Ricardo A M; Neto, Adriao D D; de Melo, Jorge D; Guerreiro, Ana M G

    2010-01-01

    Information generated by sensors that collect a patient's vital signals are continuous and unlimited data sequences. Traditionally, this information requires special equipment and programs to monitor them. These programs process and react to the continuous entry of data from different origins. Thus, the purpose of this study is to analyze the data produced by these biomedical devices, in this case the electrocardiogram (ECG). Processing uses a neural classifier, Kohonen competitive neural networks, detecting if the ECG shows any cardiac arrhythmia. In fact, it is possible to classify an ECG signal and thereby detect if it is exhibiting or not any alteration, according to normality.

  1. [An arrhythmia ECG analog signal generator using standard MIT-BIH arrhythmia database].

    PubMed

    Wang, Ying; Zhang, Yong; Fang, Zu-xiang

    2005-07-01

    Microchip MSP430F149 is used to control DAC to attain an amplification-controllable analog output of data of MIT-BIH Arrhythmia Database which is useful in testing medical machines. Data are written into Smart Media (SM) Card with Fat Format to make convenient the replacement of database.

  2. Arrhythmias in Patients with Cardiac Implantable Electrical Devices after Implantation of a Left Ventricular Assist Device.

    PubMed

    Rosenbaum, Andrew N; Kremers, Walter K; Duval, Sue; Sakaguchi, Scott; John, Ranjit; Eckman, Peter M

    2016-01-01

    Utilization of continuous-flow left ventricular assist devices (CF-LVADs) for advanced heart failure is increasing, and the role of cardiac implantable electrical devices (CIED) is unclear. Prior studies of the incidence of arrhythmias and shocks are frequently limited by ascertainment. One hundred and seventy-eight patients were examined with a previous CIED who were implanted with a CF-LVAD. Medical history, medications, and CIED data from device interrogations were gathered. A cardiac surgery control group (n = 38) was obtained to control for surgical factors. Several clinically significant events increased after LVAD implantation: treated-zone ventricular arrhythmias (VA; p < 0.01), monitored-zone VA (p < 0.01), antitachycardia pacing (ATP)-terminated episodes (p < 0.01), and shocks (p = 0.01), although administered shocks later decreased (p < 0.01). Presence of a preimplant VA was associated with postoperative VA (odds ratio [OR]: 4.31; confidence interval [CI]: 1.5-12.3, p < 0.01). Relative to cardiac surgery, LVAD patients experienced more perioperative events (i.e., monitored VAs and shocks, p < 0.01 and p = 0.04). Neither implantable cardioverter defibrillator (ICD) shocks before implant nor early or late postimplant arrhythmias or shocks predicted survival (p = 0.07, p = 0.55, and p = 0.55). Our experience demonstrates time-dependent effects on clinically significant arrhythmias after LVAD implantation, including evidence that early LVAD-related arrhythmias may be caused by the unique arrhythmogenic effects of VAD implant.

  3. Arrhythmia care co-ordinators: Their impact on anxiety and depression, readmissions and health service costs.

    PubMed

    Ismail, Hanif; Coulton, Simon

    2016-08-01

    In 2005, the UK Department of Health recommended that a new role, the arrhythmia care coordinator (ACC), be created to guide patients through the diagnosis and treatment for arrhythmia. The belief was that this would improve the efficiency of care and improve their quality of life. The British Heart Foundation provided funding for 32 such posts, all of which were filled by arrhythmia specialist nurses, and commissioned an evaluation of the new service to assess its impact on patients. This paper focuses on the impact of the ACCs on their patients' levels of anxiety and depression, hospital readmissions and costs to the National Health Service (NHS). From 2008 to 2010, using questionnaires, we conducted a longitudinal audit of the psychological status of the patients referred to the ACCs; we also assessed the ACCs' impact on readmissions and cost benefits to the NHS using UK Hospital Episode Statistics. We found high levels of anxiety and depression amongst patients. Nearly one-third were at the 'borderline' or 'clinically anxious' and 18% were at the 'borderline' or 'clinically depressed' level at their first assessment with small changes at follow-up. In arrhythmia specialist nurse sites, readmission rates were reduced by half. After deducting the cost of the ACCs and their support, the estimated annual saving was £29,357 per ACC. This evaluation has shown that the NHS saves £29,357 per year over and above the costs of employing a British Heart Foundation ACC and that all arrhythmia centres should be encouraged to employ an appropriate number of such specialists. © The European Society of Cardiology 2015.

  4. A review of maternally inherited diabetes and deafness.

    PubMed

    Li, Hui-Zhen; Li, Rui-Yu; Li, Meng

    2014-01-01

    Maternally inherited diabetes and deafness (MIDD), a mitochondrial disease first described in 1992, results from the mitochondrial DNA mutation and affects up to 1% of the patients with diabetes. This review discusses the biomedical mechanisms of MIDD patients; summarizes the recent improvement of clinical and genetic diagnosis of MIDD; outlines the advances of the clinical management of these patients and their families.

  5. Experimental therapy of genetic arrhythmias: disease-specific pharmacology.

    PubMed

    Priori, S G; Napolitano, C; Cerrone, M

    2006-01-01

    The integration between molecular biology and clinical practice requires the achievement of fundamental steps to link basic science to diagnosis and management of patients. In the last decade, the study of genetic bases of human diseases has achieved several milestones, and it is now possible to apply the knowledge that stems from the identification of the genetic substrate of diseases to clinical practice. The first step along the process of linking molecular biology to clinical medicine is the identification of the genetic bases of inherited diseases. After this important goal is achieved, it becomes possible to extend research to understand the functional impairments of mutant protein(s) and to link them to clinical manifestations (genotype-phenotype correlation). In genetically heterogeneous diseases, it may be possible to identify locus-specific risk stratification and management algorithms. Finally, the most ambitious step in the study of genetic disease is to discover a novel pharmacological therapy targeted at correcting the inborn defect (locus-specific therapy) or even to "cure" the DNA abnormality by replacing the defective gene with gene therapy. At present, this curative goal has been successful only for very few diseases. In the field of inherited arrhythmogenic diseases, several genes have been discovered, and genetics is now emerging as a source of information contributing not only to a better diagnosis but also to risk stratification and management of patients. The functional characterization of mutant proteins has opened new perspectives about the possibility of performing gene-specific or mutation-specific therapy. In this chapter, we will briefly summarize the genetic bases of inherited arrhythmogenic conditions and we will point out how the information derived from molecular genetics has influenced the "optimal use of traditional therapies" and has paved the way to the development of gene-specific therapy.

  6. Characterization of fetal arrhythmias by means of fetal magnetocardiography in three cases of difficult ultrasonographic imaging.

    PubMed

    Comani, Silvia; Liberati, Marco; Mantini, Dante; Gabriele, Elisabetta; Brisinda, Donatella; Di Luzio, Silvano; Fenici, Riccardo; Romani, Gian Luca

    2004-12-01

    Characterization of ultrasound detected fetal arrhythmias is generally performed by means of M-mode and pulsed Doppler echocardiography (fECHO), sonographic techniques that allow only indirect and approximate reconstruction of the true electrophysiological events that occur in the fetal heart. Several studies demonstrated the ability of fetal magnetocardiography (fMCG) to identify fetal arrhythmias. We report on three women, studied after the 32nd gestational week, who were referred for fMCG because of unsatisfying fetal cardiac visualization with fECHO due to maternal obesity, fetus in constant dorsal position hiding the fetal heart, intrauterine growth retardation, and oligohydramnios. Minor pericardial effusion was present in the third patient and digoxin therapy was given. FMCG were recorded with a 77-channel MCG system working in a shielded room. Independent Component Analysis (FastICA algorithm) was used to reconstruct fetal signals. The good quality of the retrieved fetal signals allowed real-time detection of arrhythmias and their classification as supraventricular extrasystoles (SVE), with/without aberrant ventricular conduction and/or atrioventricular block. The time course of the fetal cardiac rhythm was reconstructed for the entire recording duration; hence, fetal heart rate variability could be studied in time and frequency. Since isolated extrasystoles may progress to more hazardous supraventricular tachycardias, the noninvasive antenatal characterization of, even transient, fetal arrhythmias and their monitoring during pregnancy can be of great clinical impact.

  7. Simulation of Cardiac Arrhythmias Using a 2D Heterogeneous Whole Heart Model.

    PubMed

    Balakrishnan, Minimol; Chakravarthy, V Srinivasa; Guhathakurta, Soma

    2015-01-01

    Simulation studies of cardiac arrhythmias at the whole heart level with electrocardiogram (ECG) gives an understanding of how the underlying cell and tissue level changes manifest as rhythm disturbances in the ECG. We present a 2D whole heart model (WHM2D) which can accommodate variations at the cellular level and can generate the ECG waveform. It is shown that, by varying cellular-level parameters like the gap junction conductance (GJC), excitability, action potential duration (APD) and frequency of oscillations of the auto-rhythmic cell in WHM2D a large variety of cardiac arrhythmias can be generated including sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinus pause, junctional rhythm, Wolf Parkinson White syndrome and all types of AV conduction blocks. WHM2D includes key components of the electrical conduction system of the heart like the SA (Sino atrial) node cells, fast conducting intranodal pathways, slow conducting atriovenctricular (AV) node, bundle of His cells, Purkinje network, atrial, and ventricular myocardial cells. SA nodal cells, AV nodal cells, bundle of His cells, and Purkinje cells are represented by the Fitzhugh-Nagumo (FN) model which is a reduced model of the Hodgkin-Huxley neuron model. The atrial and ventricular myocardial cells are modeled by the Aliev-Panfilov (AP) two-variable model proposed for cardiac excitation. WHM2D can prove to be a valuable clinical tool for understanding cardiac arrhythmias.

  8. Simulation of Cardiac Arrhythmias Using a 2D Heterogeneous Whole Heart Model

    PubMed Central

    Balakrishnan, Minimol; Chakravarthy, V. Srinivasa; Guhathakurta, Soma

    2015-01-01

    Simulation studies of cardiac arrhythmias at the whole heart level with electrocardiogram (ECG) gives an understanding of how the underlying cell and tissue level changes manifest as rhythm disturbances in the ECG. We present a 2D whole heart model (WHM2D) which can accommodate variations at the cellular level and can generate the ECG waveform. It is shown that, by varying cellular-level parameters like the gap junction conductance (GJC), excitability, action potential duration (APD) and frequency of oscillations of the auto-rhythmic cell in WHM2D a large variety of cardiac arrhythmias can be generated including sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinus pause, junctional rhythm, Wolf Parkinson White syndrome and all types of AV conduction blocks. WHM2D includes key components of the electrical conduction system of the heart like the SA (Sino atrial) node cells, fast conducting intranodal pathways, slow conducting atriovenctricular (AV) node, bundle of His cells, Purkinje network, atrial, and ventricular myocardial cells. SA nodal cells, AV nodal cells, bundle of His cells, and Purkinje cells are represented by the Fitzhugh-Nagumo (FN) model which is a reduced model of the Hodgkin-Huxley neuron model. The atrial and ventricular myocardial cells are modeled by the Aliev-Panfilov (AP) two-variable model proposed for cardiac excitation. WHM2D can prove to be a valuable clinical tool for understanding cardiac arrhythmias. PMID:26733873

  9. Weather and triggering of ventricular arrhythmias in patients with implantable cardioverter-defibrillators

    PubMed Central

    Nguyen, Jennifer L.; Laden, Francine; Link, Mark S.; Schwartz, Joel; Luttmann-Gibson, Heike; Dockery, Douglas W.

    2015-01-01

    Outdoor ambient weather has been hypothesized to be responsible for the seasonal distribution of cardiac arrhythmias. Because people spend most of their time indoors, we hypothesized that weather-related arrhythmia risk would be better estimated using an indoor measure or an outdoor measure that correlates well with indoor conditions, such as absolute humidity. The clinical records of 203 patients in eastern Massachusetts, USA, with an implantable cardioverter-defibrillator were abstracted for arrhythmias between 1995 and 2002. We used case-crossover methods to examine the association between weather and ventricular arrhythmia (VA). Among 84 patients who experienced 787 VAs, lower estimated indoor temperature (odds ratio (OR) = 1.16, 95% confidence interval (CI) 1.05–1.27 for a 1 °C decrease in the 24-h average) and lower absolute humidity (OR = 1.06, 95% CI 1.03–1.08 for a 0.5 g/m3 decrease in the 96-h average) were associated with increased risk. Lower outdoor temperature increased risk only in warmer months, likely attributable to the poor correlation between outdoor and indoor temperature during cooler months. These results suggest that lower temperature and drier air are associated with increased risk of VA onset among implantable cardioverter-defibrillator patients. PMID:24169878

  10. Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations

    PubMed Central

    Boyle, Patrick M.; Vogt, Christoph C.; Karathanos, Thomas V.; Arevalo, Hermenegild J.; Fleischmann, Bernd K.; Trayanova, Natalia A.

    2016-01-01

    Ventricular arrhythmias are among the most severe complications of heart disease and can result in sudden cardiac death. Patients at risk currently receive implantable defibrillators that deliver electrical shocks to terminate arrhythmias on demand. However, strong electrical shocks can damage the heart and cause severe pain. Therefore, we have tested optogenetic defibrillation using expression of the light-sensitive channel channelrhodopsin-2 (ChR2) in cardiac tissue. Epicardial illumination effectively terminated ventricular arrhythmias in hearts from transgenic mice and from WT mice after adeno-associated virus–based gene transfer of ChR2. We also explored optogenetic defibrillation for human hearts, taking advantage of a recently developed, clinically validated in silico approach for simulating infarct-related ventricular tachycardia (VT). Our analysis revealed that illumination with red light effectively terminates VT in diseased, ChR2-expressing human hearts. Mechanistically, we determined that the observed VT termination is due to ChR2-mediated transmural depolarization of the myocardium, which causes a block of voltage-dependent Na+ channels throughout the myocardial wall and interrupts wavefront propagation into illuminated tissue. Thus, our results demonstrate that optogenetic defibrillation is highly effective in the mouse heart and could potentially be translated into humans to achieve nondamaging and pain-free termination of ventricular arrhythmia. PMID:27617859

  11. Cardiorenal axis and arrhythmias: Will renal sympathetic denervation provide additive value to the therapeutic arsenal?

    PubMed

    van Brussel, Peter M; Lieve, Krystien V V; de Winter, Robbert J; Wilde, Arthur A M

    2015-05-01

    Disruption of sympathetic tone may result in the occurrence or maintenance of cardiac arrhythmias. Multiple arrhythmic therapies that intervene by influencing cardiac sympathetic tone are common in clinical practice. These vary from pharmaceutical (β-blockers, angiotensin-converting enzyme inhibitors, and calcium antagonists) to percutaneous/surgical (cardiac sympathetic denervation) interventions. In some patients, however, these therapies have insufficient prophylactic and therapeutic capabilities. A safe and effective additional therapy wherein sympathetic drive is further attenuated would be expedient. Recently, renal sympathetic denervation (RSD) has been subject of research for various sympathetic nervous system-related diseases. By its presumed afferent and efferent sympatholytic effects, RSD might indirectly attenuate sympathetic outflow via the brain to the heart but might also reduce systemic catecholamine excretion and might therefore reduce catecholamine-sensitive arrhythmias. RSD is subject of research for various sympathetically driven arrhythmias, both supraventricular and ventricular. In this review, we give an overview of the rationale behind RSD as potential therapy in mediating arrhythmias that are triggered by a disrupted sympathetic nervous system and discuss the presently available results from animal and human studies.

  12. Melanocyte-like cells in the heart and pulmonary veins contribute to atrial arrhythmia triggers

    PubMed Central

    Levin, Mark D.; Lu, Min Min; Petrenko, Nataliya B.; Hawkins, Brian J.; Gupta, Tara H.; Lang, Deborah; Buckley, Peter T.; Jochems, Jeanine; Liu, Fang; Spurney, Christopher F.; Yuan, Li J.; Jacobson, Jason T.; Brown, Christopher B.; Huang, Li; Beermann, Friedrich; Margulies, Kenneth B.; Madesh, Muniswamy; Eberwine, James H.; Epstein, Jonathan A.; Patel, Vickas V.

    2009-01-01

    Atrial fibrillation is the most common clinical cardiac arrhythmia. It is often initiated by ectopic beats arising from the pulmonary veins and atrium, but the source and mechanism of these beats remains unclear. The melanin synthesis enzyme dopachrome tautomerase (DCT) is involved in intracellular calcium and reactive species regulation in melanocytes. Given that dysregulation of intracellular calcium and reactive species has been described in patients with atrial fibrillation, we investigated the role of DCT in this process. Here, we characterize a unique DCT-expressing cell population within murine and human hearts that populated the pulmonary veins, atria, and atrioventricular canal. Expression profiling demonstrated that this population expressed adrenergic and muscarinic receptors and displayed transcriptional profiles distinct from dermal melanocytes. Adult mice lacking DCT displayed normal cardiac development but an increased susceptibility to atrial arrhythmias. Cultured primary cardiac melanocyte-like cells were excitable, and those lacking DCT displayed prolonged repolarization with early afterdepolarizations. Furthermore, mice with mutations in the tyrosine kinase receptor Kit lacked cardiac melanocyte-like cells and did not develop atrial arrhythmias in the absence of DCT. These data suggest that dysfunction of melanocyte-like cells in the atrium and pulmonary veins may contribute to atrial arrhythmias. PMID:19855129

  13. Kin selection under blending inheritance.

    PubMed

    Gardner, Andy

    2011-09-07

    Why did Darwin fail to develop his insights on kin selection into a proper theory of social adaptation? One suggestion has been that his inadequate understanding of heredity kept the problem out of focus. Here, I determine whether it is possible to develop a quantitative theory of kin selection upon the assumption of blending inheritance. I find that, whilst Hamilton's rule of kin selection can be readily derived under the assumption of blending inheritance, this mechanism complicates the computation of relatedness coefficients, and can even cause them to fluctuate over generations. Nevertheless, I show that the ultimate criterion for selection to favour any social trait - i.e. a time-average of Hamilton's rule - remains the same as under particulate inheritance. By eliminating the gene from the theory of kin selection, I clarify the role that it plays in the theory of social adaptation.

  14. Imitation as an inheritance system

    PubMed Central

    Shea, Nicholas

    2009-01-01

    What is the evolutionary significance of the various mechanisms of imitation, emulation and social learning found in humans and other animals? This paper presents an advance in the theoretical resources for addressing that question, in the light of which standard approaches from the cultural evolution literature should be refocused. The central question is whether humans have an imitation-based inheritance system—a mechanism that has the evolutionary function of transmitting behavioural phenotypes reliably down the generations. To have the evolutionary power of an inheritance system, an imitiation-based mechanism must meet a range of demanding requirements. The paper goes on to review the evidence for and against the hypothesis that there is indeed an imitation-based inheritance system in humans. PMID:19620113

  15. Molecular Mechanisms of Inherited Demyelinating Neuropathies

    PubMed Central

    SCHERER, STEVEN S.; WRABETZ, LAWRENCE

    2008-01-01

    The past 15 years have witnessed the identification of more than 25 genes responsible for inherited neuropathies in humans, many associated with primary alterations of the myelin sheath. A remarkable body of work in patients, as well as animal and cellular models, has defined the clinical and molecular genetics of these illnesses and shed light on how mutations in associated genes produce the heterogeneity of dysmyelinating and demyelinating phenotypes. Here, we review selected recent developments from work on the molecular mechanisms of these disorders and their implications for treatment strategies. PMID:18803325

  16. [Contribution to the inheritance of schizophrenic psychosis].

    PubMed

    Feyler, K P

    2000-05-01

    This case presentation involves a family study looking at the inheritance of schizophrenic psychosis. It refers to the increasing risk of disease in correlation to the closeness of the relationship. The study includes both affected parents, their three children and one grandchild, all of whom had multiple hospital admissions and received psychiatric treatment. The clinical features were typical of schizophrenia. The severity of illness increased within the later generation. This study indicates a high risk correlation in this family and is in keeping with other current field studies.

  17. Clinical Severity of PGK1 Deficiency Due To a Novel p.E120K Substitution Is Exacerbated by Co-inheritance of a Subclinical Translocation t(3;14)(q26.33;q12), Disrupting NUBPL Gene.

    PubMed

    David, Dezső; Almeida, Lígia S; Maggi, Maristella; Araújo, Carlos; Imreh, Stefan; Valentini, Giovanna; Fekete, György; Haltrich, Irén

    2015-01-01

    Carriers of cytogenetically similar, apparently balanced familial chromosome translocations not always exhibit the putative translocation-associated disease phenotype. Additional genetic defects, such as genomic imbalance at breakpoint regions or elsewhere in the genome, have been reported as the most plausible explanation.By means of comprehensive molecular and functional analyses, additional to careful dissection of the t(3;14)(q26.33;q12) breakpoints, we unveil a novel X-linked PGK1 mutation and examine the contribution of these to the extremely severe clinical phenotype characterized by hemolytic anemia and neuromyopathy.The 3q26.33 breakpoint is 40 kb from the 5' region of tetratricopeptide repeat domain 14 gene (TTC14), whereas the 14q12 breakpoint is within IVS6 of nucleotide-binding protein-like gene (NUBPL) that encodes a mitochondrial complex I assembly factor. Disruption of NUBPL in translocation carriers leads to a decrease in the corresponding mRNA accompanied by a decrease in protein level. Exclusion of pathogenic genomic imbalance and reassessment of familial clinical history indicate the existence of an additional causal genetic defect. Consequently, by WES a novel mutation, c.358G>A, p.E120K, in the X-linked phosphoglycerate kinase 1 (PGK1) was identified that segregates with the phenotype. Specific activity, kinetic properties, and thermal stability of this enzyme variant were severely affected. The novel PGK1 mutation is the primary genetic alteration underlying the reported phenotype as the translocation per se only results in a subclinical phenotype. Nevertheless, its co-inheritance presumably exacerbates PGK1-deficient phenotype, most likely due to a synergistic interaction of the affected genes both involved in cell energy supply.

  18. Fetal Arrhythmias Associated with Cardiac Rhabdomyomas

    PubMed Central

    Wacker-Gussmann, Annette; Strasburger, Janette F; Cuneo, Bettina; Wiggins, Delonia; Gotteiner, Nina; Wakai, Ronald T

    2014-01-01

    Background Primary heart tumors in fetuses are rare and mainly represent rhabdomyomas. The tumors have a variable expression and can be associated with arrhythmias, including both wide and narrow QRS tachycardia. Although multiple Doppler techniques exist to assess fetal heart rhythm, it can be difficult to record precise electrophysiological pathologies in fetal life. Objective Investigations defining precise electrophysiological diagnosis were performed using fetal magnetocardiography (fMCG). Methods In addition to routine fetal echocardiography, fMCG was used to investigate electrophysiologic rhythm patterns in a series of 10 fetuses with cardiac rhabdomyomas. Results The mean gestational age of the fetuses was 28.6 weeks (SD ± 4.7 weeks). The multiple rhabdomyomas were mainly located in the right and left ventricles as well as around the AV groove. Arrhythmias or conduction abnormalities were diagnosed in all 10 patients, although only six of them were referred due to that indication. Remarkably, 80% (8/10) had associated Wolff-Parkinson-White pre-excitation. In addition, we found prominent p waves in four fetuses. Conclusion In fetuses with rhabdomyomas, a disease where rhythm pathology is common, precise electrophysiological diagnosis can now be made by fMCG. fMCG is complimentary to echocardiography for rhythm assessment, and can detect conduction abnormalities that are not possible to diagnose prenatally with M-mode or pulsed Doppler ultrasound. Risk factor assessment using fMCG can support pregnancy management and post-natal treatment and follow-up. PMID:24333285

  19. Heart-brain interactions in cardiac arrhythmia.

    PubMed

    Taggart, P; Critchley, H; Lambiase, P D

    2011-05-01

    This review examines current knowledge of the effects of higher brain centres and autonomic control loops on the heart with particular relevance to arrhythmogenesis. There is now substantial evidence that higher brain function (cortex), the brain stem and autonomic nerves affect cardiac electrophysiology and arrhythmia, and that these may function as an interactive system. The roles of mental stress and emotion in arrhythmogenesis and sudden cardiac death are no longer confined to the realms of anecdote. Advances in molecular cardiology have identified cardiac cellular ion channel mutations conferring vulnerability to arrhythmic death at the myocardial level. Indeed, specific channelopathies such as long QT syndrome and Brugada syndrome are selectively sensitive to either sympathetic or vagal stimulation. There is increasing evidence that afferent feedback from the heart to the higher centres may affect efferent input to the heart and modulate the cardiac electrophysiology. The new era of functional neuroimaging has identified the central neural circuitry in this brain-heart axis. Since precipitants of sudden fatal arrhythmia are frequently environmental and behavioural, central pathways translating stress into autonomic effects on the heart might be considered as therapeutic targets. These brain-heart interactions help explain the apparent randomness of sudden cardiac events and provide new insights into future novel therapies to prevent sudden death.

  20. Acute emotional stress and cardiac arrhythmias.

    PubMed

    Ziegelstein, Roy C

    2007-07-18

    Episodes of acute emotional stress can have significant adverse effects on the heart. Acute emotional stress can produce left ventricular contractile dysfunction, myocardial ischemia, or disturbances of cardiac rhythm. Although these abnormalities are often only transient, their consequences can be gravely damaging and sometimes fatal. Despite the many descriptions of catastrophic cardiovascular events in the setting of acute emotional stress, the anatomical substrate and physiological pathways by which emotional stress triggers cardiovascular events are only now being characterized, aided by the advent of functional neuroimaging. Recent evidence indicates that asymmetric brain activity is particularly important in making the heart more susceptible to ventricular arrhythmias. Lateralization of cerebral activity during emotional stress may stimulate the heart asymmetrically and produce areas of inhomogeneous repolarization that create electrical instability and facilitate the development of cardiac arrhythmias. Patients with ischemic heart disease who survive an episode of sudden cardiac death in the setting of acute emotional stress should receive a beta-blocker. Nonpharmacological approaches to manage emotional stress in patients with and without coronary artery disease, including social support, relaxation therapy, yoga, meditation, controlled slow breathing, and biofeedback, are also appropriate to consider and merit additional investigation in randomized trials.

  1. Arrhythmogenic right ventricular cardiomyopathy, clinical manifestations, and diagnosis.

    PubMed

    Haugaa, Kristina H; Haland, Trine F; Leren, Ida S; Saberniak, Jørg; Edvardsen, Thor

    2016-07-01

    This review aims to give an update on the pathogenesis, clinical manifestations, and diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Arrhythmogenic right ventricular cardiomyopathy is mainly an autosomal dominant inherited disease linked to mutations in genes encoding desmosomes or desmosome-related proteins. Classic symptoms include palpitations, cardiac syncope, and aborted cardiac arrest due to ventricular arrhythmias. Heart failure may develop in later stages. Diagnosis is based on the presence of major and minor criteria from the Task Force Criteria revised in 2010 (TFC 2010), which includes evaluation of findings from six different diagnostic categories. Based on this, patients are classified as having possible, borderline, or definite ARVC. Imaging is important in ARVC diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting structural and functional abnormalities, but importantly these findings may occur after electrical alterations and ventricular arrhythmias. Electrocardiograms (ECGs) and signal-averaged ECGs are analysed for depolarization and repolarization abnormalities, including T-wave inversions as the most common ECG alteration. Ventricular arrhythmias are common in ARVC and are considered a major diagnostic criterion if originating from the RV inferior wall or apex. Family history of ARVC and detection of an ARVC-related mutation are included in the TFC 2010 and emphasize the importance of family screening. Electrophysiological studies are not included in the diagnostic criteria, but may be important for differential diagnosis including RV outflow tract tachycardia. Further differential diagnoses include sarcoidosis, congenital abnormalities, myocarditis, pulmonary hypertension, dilated cardiomyopathy, and athletic cardiac adaptation, which may mimic ARVC.

  2. Catheter ablation of organized atrial arrhythmias in orthotopic heart transplantation.

    PubMed

    Mouhoub, Yamina; Laredo, Mikael; Varnous, Shaida; Leprince, Pascal; Waintraub, Xavier; Gandjbakhch, Estelle; Hébert, Jean-Louis; Frank, Robert; Maupain, Carole; Pavie, Alain; Hidden-Lucet, Françoise; Duthoit, Guillaume

    2017-07-21

    Organized atrial arrhythmias (OAAs) are common after orthotopic heart transplantation (OHT). Some controversies remain about their clinical presentation, relationship with atrial anastomosis and electrophysiologic features. The objectives of this retrospective study were to determine the mechanisms of OAAs after OHT and describe the outcomes of radiofrequency catheter ablation (RFCA). Thirty consecutive transplanted patients (mean age 48 ± 17 years, 86.6% male) underwent 3-dimensional electroanatomic mapping and RFCA of their OAA from 2004 to 2012 at our center. Twenty-two patients had biatrial anastomosis and 8 had bicaval anastomosis. Macro-reentry was the arrhythmia mechanism for 96% of patients. The electrophysiologic diagnoses were: cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) in 93% of patients (n = 28); perimitral AFL in 3% (n = 1); and focal atrial tachycardia (FAT) in 3% (n = 1). In 5 patients with biatrial anastomosis, a right FAT was inducible. Primary RFCA success was obtained in 93% of patients. Mean follow-up time was 39 ± 26.8 months. Electrical repermeation between recipient and donor atria, present in 20% of patients (n = 6), did not account for any of the OAAs observed. Survival without OAA relapse at 12, 24 and 60 months was 93%, 89% and 79%, respectively. CTI-dependent AFL accounted for most instances of OAA after OHT, regardless of anastomosis type. Time from transplantation to OAA was shorter with bicaval than with biatrial anastomosis. RFCA was safe and provided good long-term results. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Inherited Retinal Degenerative Clinical Trial Network. Addendum

    DTIC Science & Technology

    2013-10-01

    visual impairment usually ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other...linica l trial in the NEER network for autosomal dominant retinitis pigmentosa , and the ProgSTAR studies for Stargardt disease) . As new interventions b... retinitis pigmentosa continues at six sites- the CTEC site at University of Utah and five additional recruitment sites- the Retina Foundation of the

  4. Atrial Arrhythmias and Their Implications for Space Flight - Introduction

    NASA Technical Reports Server (NTRS)

    Polk, J. D.; Barr, Y. R.; Bauer, P.; Hamilton, D. R.; Kerstman, E.; Tarver, B.

    2010-01-01

    This panel will discuss the implications of atrial arrhythmias in astronauts from a variety of perspectives; including historical data, current practices, and future challenges for exploration class missions. The panelists will present case histories, outline the evolution of current NASA medical standards for atrial arrhythmias, discuss the use of predictive tools, and consider potential challenges for current and future missions.

  5. Research and development of the device for diagnostics of arrhythmia

    NASA Astrophysics Data System (ADS)

    Lezhnina, I. A.; Boyakhchyan, A. A.; Overchuk, K. V.; Uvarov, A. A.

    2017-08-01

    The article describes the results of the research for sensors optimal arrangement during one limb ECG detection. The found placement provides the registration of the enough quality signal sufficient for the diagnosis of arrhythmia, the QRS complex is clearly recognized. Authors also show the test results of the device developed for the diagnosis of arrhythmia and sudden cardiac death.

  6. Genetics of inherited cardiomyopathy.

    PubMed

    Jacoby, Daniel; McKenna, William J

    2012-02-01

    During the past two decades, numerous disease-causing genes for different cardiomyopathies have been identified. These discoveries have led to better understanding of disease pathogenesis and initial steps in the application of mutation analysis in the evaluation of affected individuals and their family members. As knowledge of the genetic abnormalities, and insight into cellular and organ biology has grown, so has appreciation of the level of complexity of interaction between genotype and phenotype across disease states. What were initially thought to be one-to-one gene-disease correlates have turned out to display important relational plasticity dependent in large part on the genetic and environmental backgrounds into which the genes of interest express. The current state of knowledge with regard to genetics of cardiomyopathy represents a starting point to address the biology of disease, but is not yet developed sufficiently to supplant clinically based classification systems or, in most cases, to guide therapy to any significant extent. Future work will of necessity be directed towards elucidation of the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype-phenotype relationship with the ultimate goal of furthering our ability to identify, diagnose, risk stratify, and treat this group of disorders which cause heart failure and sudden death in the young.

  7. Genetics of inherited cardiomyopathy

    PubMed Central

    Jacoby, Daniel; McKenna, William J.

    2012-01-01

    During the past two decades, numerous disease-causing genes for different cardiomyopathies have been identified. These discoveries have led to better understanding of disease pathogenesis and initial steps in the application of mutation analysis in the evaluation of affected individuals and their family members. As knowledge of the genetic abnormalities, and insight into cellular and organ biology has grown, so has appreciation of the level of complexity of interaction between genotype and phenotype across disease states. What were initially thought to be one-to-one gene-disease correlates have turned out to display important relational plasticity dependent in large part on the genetic and environmental backgrounds into which the genes of interest express. The current state of knowledge with regard to genetics of cardiomyopathy represents a starting point to address the biology of disease, but is not yet developed sufficiently to supplant clinically based classification systems or, in most cases, to guide therapy to any significant extent. Future work will of necessity be directed towards elucidation of the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype–phenotype relationship with the ultimate goal of furthering our ability to identify, diagnose, risk stratify, and treat this group of disorders which cause heart failure and sudden death in the young. PMID:21810862

  8. Back to Biology: New Insights on Inheritance in Myeloproliferative Disorders

    PubMed Central

    Braunstein, Evan M.

    2015-01-01

    The myeloproliferative disorders (MPDs) are a group of hematologic diseases with significant overlap in both clinical phenotype and genetic etiology. While most often caused by acquired somatic mutations in hematopoietic stem cells, the presence of familial clustering in MPD cases suggests that inheritance is an important factor in the etiology of this disease. Though far less common than sporadic disease, inherited MPDs can be clinically indistinguishable from sporadic disease. Recently, germline mutations in Janus kinase 2 (JAK2) and MPL, two genes frequently mutated in sporadic MPD, have been shown to cause inherited thrombocytosis. Study of the function of these mutant proteins has led to a new understanding of the biological mechanisms that produce myeloproliferative disease. In this review, we summarize the data regarding inherited mutations that cause or predispose to MPDs, with a focus on the biological effects of mutant proteins. We propose that defining inherited MPDs in this manner has the potential to simplify diagnosis in a group of disorders that can be difficult to differentiate clinically. PMID:25195195

  9. Transgenerational epigenetic inheritance in plants.

    PubMed

    Hauser, Marie-Theres; Aufsatz, Werner; Jonak, Claudia; Luschnig, Christian

    2011-08-01

    Interest in transgenerational epigenetic inheritance has intensified with the boosting of knowledge on epigenetic mechanisms regulating gene expression during development and in response to internal and external signals such as biotic and abiotic stresses. Starting with an historical background of scantily documented anecdotes and their consequences, we recapitulate the information gathered during the last 60 years on naturally occurring and induced epialleles and paramutations in plants. We present the major players of epigenetic regulation and their importance in controlling stress responses. The effect of diverse stressors on the epigenetic status and its transgenerational inheritance is summarized from a mechanistic viewpoint. The consequences of transgenerational epigenetic inheritance are presented, focusing on the knowledge about its stability, and in relation to genetically fixed mutations, recombination, and genomic rearrangement. We conclude with an outlook on the importance of transgenerational inheritance for adaptation to changing environments and for practical applications. This article is part of a Special Issue entitled "Epigenetic control of cellular and developmental processes in plants".

  10. Transgenerational epigenetic inheritance in plants☆

    PubMed Central

    Hauser, Marie-Theres; Aufsatz, Werner; Jonak, Claudia; Luschnig, Christian

    2015-01-01

    Interest in transgenerational epigenetic inheritance has intensified with the boosting of knowledge on epigenetic mechanisms regulating gene expression during development and in response to internal and external signals such as biotic and abiotic stresses. Starting with an historical background of scantily documented anecdotes and their consequences, we recapitulate the information gathered during the last 60 years on naturally occurring and induced epialleles and paramutations in plants. We present the major players of epigenetic regulation and their importance in controlling stress responses. The effect of diverse stressors on the epigenetic status and its transgenerational inheritance is summarized from a mechanistic viewpoint. The consequences of transgenerational epigenetic inheritance are presented, focusing on the knowledge about its stability, and in relation to genetically fixed mutations, recombination, and genomic rearrangement. We conclude with an outlook on the importance of transgenerational inheritance for adaptation to changing environments and for practical applications. This article is part of a Special Issue entitled “Epigenetic control of cellular and developmental processes in plants”. PMID:21515434

  11. How computer simulations of the human heart can improve anti‐arrhythmia therapy

    PubMed Central

    Chang, Kelly C.

    2016-01-01

    Abstract Over the last decade, the state‐of‐the‐art in cardiac computational modelling has progressed rapidly. The electrophysiological function of the heart can now be simulated with a high degree of detail and accuracy, opening the doors for simulation‐guided approaches to anti‐arrhythmic drug development and patient‐specific therapeutic interventions. In this review, we outline the basic methodology for cardiac modelling, which has been developed and validated over decades of research. In addition, we present several recent examples of how computational models of the human heart have been used to address current clinical problems in cardiac electrophysiology. We will explore the use of simulations to improve anti‐arrhythmic pacing and defibrillation interventions; to predict optimal sites for clinical ablation procedures; and to aid in the understanding and selection of arrhythmia risk markers. Together, these studies illustrate how the tremendous advances in cardiac modelling are poised to revolutionize medical treatment and prevention of arrhythmia. PMID:26621489

  12. Protective effects of Hawthorn (Crataegus oxyacantha) extract against digoxin-induced arrhythmias in rats.

    PubMed

    Alp, Hayrullah; Soner, Burak Cem; Baysal, Tamer; Şahin, Ayşe Saide

    2015-01-01

    Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study is to evaluate the antiarrhythmic effect of Crataegus oxyacantha extract on digoxin-induced arrhythmias in anesthetized Wistar rats. Control and experimental groups were evaluated for arrhythmias induced by digoxin. Fifteen rats (7 as controls and 8 as the experimental group) were included in the study. The dry fruits of 100 mg Crataegus oxyacantha were extracted by percolation method. Digoxin, at a dose of 40 µg/kg/min, was infused to form the arrhythmias in all rats. Simultaneously, the extract was infused into the experimental group, while 0.9% NaCl was infused into control group. Electrocardiographic QRS prolongation and arterial blood pressure changes were analyzed. The experimental group lived longer (62.13±2.20 min) than the controls (p=0.002). On the other hand, the time to beginning of QRS prolongation did not differ between the two groups (p=0.812). Bradycardia was significant in the control group (288.01±10.54 beat/min and p=0.01). The maximum QRS duration was observed in the control group during the digoxin and 0.9% NaCl infusion period (53.29±3.99 ms and p=0.001). Also, the durations of atrial and ventricular arrhythmias were shorter in the experimental group. However, arterial blood pressure dipping was significant in the experimental group (23.67±10.89 mm Hg and p<0.001). Crataegus oxyacantha alcoholic extract produced an antiarrhythmic effect that was induced by digoxin in Wistar rats. However, in the clinical use of this extract, the hypotensive effect should be considered. Also, the alcoholic extract of Crataegus oxyacantha may be an alternative treatment medication for arrhythmias induced by digoxin toxicity in humans.

  13. Protective effects of Hawthorn (Crataegus oxyacantha) extract against digoxin-induced arrhythmias in rats

    PubMed Central

    Alp, Hayrullah; Soner, Burak Cem; Baysal, Tamer; Şahin, Ayşe Saide

    2016-01-01

    Objective: Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study is to evaluate the antiarrhythmic effect of Crataegus oxyacantha extract on digoxin-induced arrhythmias in anesthetized Wistar rats. Methods: Control and experimental groups were evaluated for arrhythmias induced by digoxin. Fifteen rats (7 as controls and 8 as the experimental group) were included in the study. The dry fruits of 100 mg Crataegus oxyacantha were extracted by percolation method. Digoxin, at a dose of 40 μg/kg/min, was infused to form the arrhythmias in all rats. Simultaneously, the extract was infused into the experimental group, while 0.9% NaCl was infused into control group. Electrocardiographic QRS prolongation and arterial blood pressure changes were analyzed. Results: The experimental group lived longer (62.13±2.20 min) than the controls (p=0.002). On the other hand, the time to beginning of QRS prolongation did not differ between the two groups (p=0.812). Bradycardia was significant in the control group (288.01±10.54 beat/min and p=0.01). The maximum QRS duration was observed in the control group during the digoxin and 0.9% NaCl infusion period (53.29±3.99 ms and p=0.001). Also, the durations of atrial and ventricular arrhythmias were shorter in the experimental group. However, arterial blood pressure dipping was significant in the experimental group (23.67±10.89 mm Hg and p<0.001). Conclusion: Crataegus oxyacantha alcoholic extract produced an antiarrhythmic effect that was induced by digoxin in Wistar rats. However, in the clinical use of this extract, the hypotensive effect should be considered. Also, the alcoholic extract of Crataegus oxyacantha may be an alternative treatment medication for arrhythmias induced by digoxin toxicity in humans. PMID:25880053

  14. Incidence of cardiac arrhythmias in asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

    PubMed

    Shizukuda, Yukitaka; Tripodi, Dorothy J; Zalos, Gloria; Bolan, Charles D; Yau, Yu-Ying; Leitman, Susan F; Waclawiw, Myron A; Rosing, Douglas R

    2012-03-15

    It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis." They completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The subjects with HH were classified as newly diagnosed (group A) and chronically treated (group B) subjects. All subjects with HH had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be greater in the combined HH groups than in the controls. Supraventricular ectopy was more frequently noted in group B compared to in the controls (ectopy rate per hour 11.1 ± 29.9 vs 1.5 ± 3.5, p < 0.05, using the Kruskal-Wallis test). No examples of heart block, other than first-degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in the group A subjects. No life-threatening arrhythmias were observed in our subjects with HH. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic subjects with HH. A larger clinical study is warranted to further clarify our observation.

  15. Trends in Reporting Methadone-Associated Cardiac Arrhythmia, 1997–2011

    PubMed Central

    Kao, David; Bartelson, Becki Bucher; Khatri, Vaishali; Dart, Richard; Mehler, Philip S.; Katz, David; Krantz, Mori J.

    2013-01-01

    Background: Long-acting opioids are a leading cause of accidental death in the United States, and methadone is associated with greater mortality rates. Whether this increase is related to the proarrhythmic properties of methadone is unclear. Objective: To describe methadone-associated arrhythmia events reported in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Design: Description of national adverse event registry data before and after publication of a 2002 report describing an association between methadone and arrhythmia. Setting: FAERS, November 1997 and June 2011. Patients: Adults with QTc prolongation or torsade de pointes and ventricular arrhythmia or cardiac arrest. Measurements: FAERS reports before and after the 2002 report. Results: 1646 cases of ventricular arrhythmia or cardiac arrest and 379 cases of QTc prolongation or torsade de pointes were associated with methadone. Monthly reports of QTc prolongation or torsade de pointes increased from a mean of 0.3 (95% CI, 0.1 to 0.5) before the 2002 publication to a mean of 3.5 (CI, 2.5 to 4.8) after it. After 2000, methadone was the second-most common primary suspect in cases of QTc prolongation or torsade de pointes after dofetilide (a known proarrhythmic drug) and was associated with disproportionate reporting similar to that of antiarrhythmic agents known to promote torsade de pointes. Antiretroviral drugs for HIV were the most common coadministered drugs. Limitation: Reports to FAERs are voluntary and selective, and incidence rates cannot be determined from spontaneously reported data. Conclusion: Since 2002, reports to FAERS of methadone-associated arrhythmia have increased substantially and are disproportionately represented relative to other events with the drug. Coadministration of methadone with antiretrovirals in patients with HIV may pose particular risk. Primary Funding Source: Colorado Clinical and Translational Sciences Institute, National Institutes of Health, and

  16. [Identification of patients at risk of malignant arrhythmia in the 1st year after myocardial infarction].

    PubMed

    Araya-Gómez, V; González-Hermosillo, J A; Casanova Garcés, J M; Colín, L; Kershenovich, S; Iturralde, P

    1994-01-01

    Two hundred twenty two consecutive patients with acute myocardial infarction were followed for one year. We evaluated the usefulness of late potentials, the spectral analysis, heart rate variability, infarct-related coronary artery, ejection fraction, arrhythmias during Holter monitoring and other clinical variables as risk markers for developing of ventricular arrhythmias and/or sudden death. Twenty four patients (10.8%) had late arrhythmic events: sudden death in 7, sustained ventricular tachycardia in 15 and unexplained syncope in 2. Late potentials had high sensitivity (94%) and negative predictive value (99%), followed by an occluded related-infarct coronary artery (75% sensitivity and 96% negative predictive value). Complex ventricular arrhythmias during Holter monitoring was the test with the highest specificity (92%). A combination of late potentials plus an occluded infarct-related coronary artery or late potentials plus ejection fraction showed 100% sensitivity with 100% negative predictive value. Of the 16 studied variables, 5 had independent and significative value as a predictor of arrhythmic events, these are, according to the relative risk: late potentials (20.2), ejection fraction less than 40% (12.1), complex arrhythmias during Holter monitoring (7.5), the presence of an occluded infarct-related coronary artery (6.4) and anterior myocardial infarction localization (4.5). We consider, that with a combination of simple methods of assessment, we can select a subgroup of survivors of an acute myocardial infarction at high risk of developing ventricular arrhythmias and sudden death, which also identifies patients with low risk for these complications.

  17. Irreversible Electroporation Near the Heart: Ventricular Arrhythmias Can Be Prevented With ECG Synchronization

    PubMed Central

    Deodhar, Ajita; Dickfeld, Timm; Single, Gordon W.; Hamilton, William C.; Thornton, Raymond H.; Sofocleous, Constantinos T.; Maybody, Majid; Gónen, Mithat; Rubinsky, Boris; Solomon, Stephen B.

    2013-01-01

    OBJECTIVE Irreversible electroporation is a nonthermal ablative tool that uses direct electrical pulses to create irreversible membrane pores and cell death. The ablation zone is surrounded by a zone of reversibly increased permeability; either zone can cause cardiac arrhythmias. Our purpose was to establish a safety profile for the use of irreversible electroporation close to the heart. MATERIALS and METHODS The effect of unsynchronized and synchronized (with the R wave on ECG) irreversible electroporation in swine lung and myocardium was studied in 11 pigs. Twelve lead ECG recordings were analyzed by an electrophysiologist for the presence of arrhythmia. Ventricular arrhythmias were categorized as major events. Minor events included all other dysrhythmias or ECG changes. Cardiac and lung tissue was submitted for histopathologic analysis. Electrical field modeling was performed to predict the distance from the applicators over which cells show electroporation-induced increased permeability. RESULTS At less than or equal to 1.7 cm from the heart, fatal (major) events occurred with all unsynchronized irreversible electroporation. No major and three minor events were seen with synchronized irreversible electroporation. At more than 1.7 cm from the heart, two minor events occurred with only unsynchronized irreversible electroporation. Electrical field modeling correlates well with the clinical results, revealing increased cell membrane permeability up to 1.7 cm away from the applicators. Complete lung ablation without intervening live cells was seen. No myocardial injury was seen. CONCLUSION Unsynchronized irreversible electroporation close to the heart can cause fatal ventricular arrhythmias. Synchronizing irreversible electroporation pulse delivery with absolute refractory period avoids significant cardiac arrhythmias. PMID:21343484

  18. Cardiac Channelopathies and Sudden Death: Recent Clinical and Genetic Advances

    PubMed Central

    Fernández-Falgueras, Anna; Sarquella-Brugada, Georgia; Brugada, Josep; Brugada, Ramon; Campuzano, Oscar

    2017-01-01

    Sudden cardiac death poses a unique challenge to clinicians because it may be the only symptom of an inherited heart condition. Indeed, inherited heart diseases can cause sudden cardiac death in older and younger individuals. Two groups of familial diseases are responsible for sudden cardiac death: cardiomyopathies (mainly hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy) and channelopathies (mainly long QT syndrome, Brugada syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). This review focuses on cardiac channelopathies, which are characterized by lethal arrhythmias in the structurally normal heart, incomplete penetrance, and variable expressivity. Arrhythmias in these diseases result from pathogenic variants in genes encoding cardiac ion channels or associated proteins. Due to a lack of gross structural changes in the heart, channelopathies are often considered as potential causes of death in otherwise unexplained forensic autopsies. The asymptomatic nature of channelopathies is cause for concern in family members who may be carrying genetic risk factors, making the identification of these genetic factors of significant clinical importance. PMID:28146053

  19. Altered Calcium Handling and Ventricular Arrhythmias in Acute Ischemia

    PubMed Central

    Baumeister, Peter; Quinn, T. Alexander

    2016-01-01

    Acute ischemia results in deadly cardiac arrhythmias that are a major contributor to sudden cardiac death (SCD). The electrophysiological changes involved have been extensively studied, yet the mechanisms of ventricular arrhythmias during acute ischemia remain unclear. What is known is that during acute ischemia both focal (ectopic excitation) and nonfocal (reentry) arrhythmias occur, due to an interaction of altered electrical, mechanical, and biochemical properties of the myocardium. There is particular interest in the role that alterations in intracellular calcium handling, which cause changes in intracellular calcium concentration and to the calcium transient, play in ischemia-induced arrhythmias. In this review, we briefly summarize the known contributors to ventricular arrhythmias during acute ischemia, followed by an in-depth examination of the potential contribution of altered intracellular calcium handling, which may include novel targets for antiarrhythmic therapy. PMID:28008297

  20. An interdisciplinary approach to personalized medicine: case studies from a cardiogenetics clinic.

    PubMed

    Erskine, Kathleen E; Griffith, Eleanor; Degroat, Nicole; Stolerman, Marina; Silverstein, Louise B; Hidayatallah, Nadia; Wasserman, David; Paljevic, Esma; Cohen, Lilian; Walsh, Christine A; McDonald, Thomas; Marion, Robert W; Dolan, Siobhan M

    2013-01-01

    In the genomic age, the challenges presented by various inherited conditions present a compelling argument for an interdisciplinary model of care. Cardiac arrhythmias with a genetic basis, such as long QT syndrome, require clinicians with expertise in many specialties to address the complex genetic, psychological, ethical and medical issues involved in treatment. The Montefiore-Einstein Center for CardioGenetics has been established to provide personalized, interdisciplinary care for families with a history of sudden cardiac death or an acute cardiac event. Four vignettes of patient care are presented to illustrate the unique capacity of an interdisciplinary model to address genetic, psychological, ethical and medical issues. Because interdisciplinary clinics facilitate collaboration among multiple specialties, they allow for individualized, comprehensive care to be delivered to families who experience complex inherited medical conditions. As the genetic basis of many complex conditions is discovered, the advantages of an interdisciplinary approach for delivering personalized medicine will become more evident.

  1. [Magnetocardiographic diagnosis for myocardial ischemia and arrhythmias].

    PubMed

    Watanabe, Shigeyuki; Yamaguchi, Iwao

    2006-05-01

    Magnetocardiography (MCG) is a non-invasive and non-contact mapping technique to analyze cardiac electromagnetic activities. The SQUID (superconducting quantum interference device) system has made it possible to detect very weak cardiac magnetic signals noninvasively. In electrocardiography (ECG), the conductivity of electric current varies according to body composition, while in MCG, conductivity of magnetic field is constant regardless of body composition. Moreover, as the magnetic field detected in MCG originates not from the cardiac 'volume current' as in ECG, but from the cardiac 'primary current', the cardiac electromagnetic information of the MCG is minimally distorted. Furthermore, ECG is a record of a potential difference, so it gives only a relative value, while magnetic field strength is an absolute value. Therefore, MCG is expected to be more sensitive to minute electromagnetic abnormalities of heart disease than ECG. In this article, we discuss the usefulness of MCG in diagnosing ischemic heart diseases and arrhythmias.

  2. Effectiveness of amiodarone in resistant arrhythmias1

    PubMed Central

    Hollman, Arthur; Holt, Phyllis M

    1980-01-01

    Amiodarone is used in the treatment of previously drug-resistant supraventricular and ventricular arrhythmias. We report our experience with amiodarone in 8 patients. Five patients had paroxysmal atrial flutter, one had paroxysmal atrial fibrillation, one had supraventricular tachycardia, and one ventricular tachycardia. Considerable improvement, both objectively and subjectively, was observed in all patients. Side effects were as follows: all patients had corneal microdeposits, one developed left bundle branch block which resolved on stopping amiodarone, and one reported constipation and abdominal pains. Six patients have been treated for 10–28 months; 3 developed tolerance at 4–14 months after the introduction of amiodarone therapy, but symptoms improved with increased dosage. It is important to watch for the development of tolerance to this drug. PMID:7452643

  3. Ivabradine Reduces Digitalis-induced Ventricular Arrhythmias.

    PubMed

    Frommeyer, Gerrit; Weller, Jan; Ellermann, Christian; Bögeholz, Nils; Leitz, Patrick; Dechering, Dirk G; Kochhäuser, Simon; Wasmer, Kristina; Eckardt, Lars

    2017-06-19

    The I(f) channel inhibitor ivabradine is recommended for treatment of heart failure but also affects potassium currents and thereby prolongs ventricular repolarization. The aim of this study was to examine the electrophysiological effects of ivabradine on digitalis-induced ventricular arrhythmias. Thirteen rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, the digitalis glycoside ouabain was infused (0.2 μM). Monophasic action potentials and ECG showed a significant abbreviation of QT interval (-34 ms, p < 0.05) and action potential duration (APD90 ; -27 ms, p < 0.05). The shortening of ventricular repolarization was accompanied by a reduction in effective refractory period (ERP; -27 ms, p < 0.05). Thereafter, hearts were additionally treated with ivabradine (5 μM). Of note, this did not exert significant effects on QT interval (-4 ms, p = ns) or APD90 (-15 ms, p = ns) but resulted in an increase in ERP (+17 ms, p < 0.05). This led to a significant increase in post-repolarization refractoriness (PRR, +32 ms, p < 0.01) as compared with sole ouabain treatment. Under baseline conditions, ventricular fibrillation (VF) was inducible by a standardized pacing protocol including programmed stimulation and burst stimulation in four of 13 hearts (31%; 15 episodes). After application of 0.2 μM ouabain, eight of 13 hearts were inducible (62%, 49 episodes). Additional infusion of 5 μM ivabradine led to a significant suppression of VF. Only four episodes could be induced in two of 13 hearts (15%). In this study, ivabradine reduced digitalis-induced ventricular arrhythmias. Ivabradine did not affect ventricular repolarization in the presence of digitalis treatment but demonstrated potent anti-arrhythmic properties based on an increase in both ERP and PRR. The study further characterizes the beneficial electrophysiological profile of ivabradine. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  4. General anxiety, depression, and physical health in relation to symptoms of heart-focused anxiety- a cross sectional study among patients living with the risk of serious arrhythmias and sudden cardiac death.

    PubMed

    Hamang, Anniken; Eide, Geir E; Rokne, Berit; Nordin, Karin; Øyen, Nina

    2011-11-14

    To investigate the role of three distinct symptoms of heart-focused anxiety (cardio-protective avoidance, heart-focused attention, and fear about heart sensations) in relation to general anxiety, depression and physical health in patients referred to specialized cardio-genetics outpatient clinics in Norway for genetic investigation and counseling. Participants were 126 patients (mean age 45 years, 53.5% women). All patients were at higher risk than the average person for serious arrhythmias and sudden cardiac death (SCD) because of a personal or a family history of an inherited cardiac disorder (familial long QT syndrome or hypertrophic cardiomyopathy). Patients filled in, Hospital Anxiety and Depression Scale, Short-Form 36 Health Survey, and Cardiac Anxiety Questionnaire, two weeks before the scheduled counseling session. The patients experienced higher levels of general anxiety than expected in the general population (mean difference 1.1 (p < 0.01)). Hierarchical regression analyses showed that avoidance and fear was independently related to general anxiety, depression, and physical health beyond relevant demographic covariates (age, gender, having children) and clinical variables (clinical diagnosis, and a recent SCD in the family). In addition to heart-focused anxiety, having a clinical diagnosis was of importance for physical health, whereas a recent SCD in the family was independently related to general anxiety and depression, regardless of disease status. Avoidance and fear may be potentially modifiable symptoms. Because these distinct symptoms may have important roles in determining general anxiety, depression and physical health in at-risk individuals of inherited cardiac disorders, the present findings may have implications for the further development of genetic counseling for this patient group.

  5. General anxiety, depression, and physical health in relation to symptoms of heart-focused anxiety- a cross sectional study among patients living with the risk of serious arrhythmias and sudden cardiac death

    PubMed Central

    2011-01-01

    Objective To investigate the role of three distinct symptoms of heart-focused anxiety (cardio-protective avoidance, heart-focused attention, and fear about heart sensations) in relation to general anxiety, depression and physical health in patients referred to specialized cardio-genetics outpatient clinics in Norway for genetic investigation and counseling. Methods Participants were 126 patients (mean age 45 years, 53.5% women). All patients were at higher risk than the average person for serious arrhythmias and sudden cardiac death (SCD) because of a personal or a family history of an inherited cardiac disorder (familial long QT syndrome or hypertrophic cardiomyopathy). Patients filled in, Hospital Anxiety and Depression Scale, Short-Form 36 Health Survey, and Cardiac Anxiety Questionnaire, two weeks before the scheduled counseling session. Results The patients experienced higher levels of general anxiety than expected in the general population (mean difference 1.1 (p < 0.01)). Hierarchical regression analyses showed that avoidance and fear was independently related to general anxiety, depression, and physical health beyond relevant demographic covariates (age, gender, having children) and clinical variables (clinical diagnosis, and a recent SCD in the family). In addition to heart-focused anxiety, having a clinical diagnosis was of importance for physical health, whereas a recent SCD in the family was independently related to general anxiety and depression, regardless of disease status. Conclusion Avoidance and fear may be potentially modifiable symptoms. Because these distinct symptoms may have important roles in determining general anxiety, depression and physical health in at-risk individuals of inherited cardiac disorders, the present findings may have implications for the further development of genetic counseling for this patient group. PMID:22081957

  6. Arrhythmias in athletes: evidence-based strategies and challenges for diagnosis, management, and sports eligibility.

    PubMed

    Fragakis, Nikolaos; Pagourelias, Efstathios D; Koskinas, Konstantinos C; Vassilikos, Vassilios

    2013-01-01

    Assessment and management of cardiac rhythm disorders in athletes is particularly challenging. An accurate diagnosis and optimal risk-stratification are often limited because of substantial phenotypic overlap between pathological entities and adaptive cardiovascular responses that normally occur in athletes. An accurate diagnosis, however, is particularly important in this population, as 2 competing risks need to be cautiously balanced: the risk of under-diagnosis of an arrhythmogenic substrate that may trigger life-threatening events versus the risk of over-diagnosis that may result in an athlete's improper disqualification. Accordingly, the management of arrhythmias in athletes may pose therapeutic dilemmas, and often differs substantially compared with the general population. In this review, we present the most frequently observed arrhythmias in athletes and briefly discuss their pathophysiologic substrate. We further propose diagnostic and therapeutic strategies based upon current guidelines, official recommendations, and emerging evidence from relevant clinical investigations. We focus particularly on disparities in current guidelines regarding the management of certain rhythm disorders, as these areas of uncertainty may reflect the challenging nature of these disorders and may indicate the need for individualized approaches in every-day clinical practice. A better understanding of the normal electrophysiological responses to chronic exercise, and of the pathophysiological basis and the true clinical significance of arrhythmias in athletes, may enhance decision-making, and may allow for management strategies which more prudently weigh the risk-to-benefit ratio of each approach.

  7. Epigenetic inheritance in rice plants.

    PubMed

    Akimoto, Keiko; Katakami, Hatsue; Kim, Hyun-Jung; Ogawa, Emiko; Sano, Cecile M; Wada, Yuko; Sano, Hiroshi

    2007-08-01

    Epigenetics is defined as mechanisms that regulate gene expression without base sequence alteration. One molecular basis is considered to be DNA cytosine methylation, which reversibly modifies DNA or chromatin structures. Although its correlation with epigenetic inheritance over generations has been circumstantially shown, evidence at the gene level has been limited. The present study aims to find genes whose methylation status directly correlates with inheritance of phenotypic changes. DNA methylation in vivo was artificially reduced by treating rice (Oryza sativa ssp. japonica) seeds with 5-azadeoxycytidine, and the progeny were cultivated in the field for > 10 years. Genomic regions with changed methylation status were screened by the methylation-sensitive amplified polymorphysm (MSAP) method, and cytosine methylation was directly scanned by the bisulfite mapping method. Pathogen infection with Xanthomonas oryzae pv. oryzae, race PR2 was performed by the scissors-dip method on mature leaf blades. The majority of seedlings were lethal, but some survived to maturity. One line designated as Line-2 showed a clear marker phenotype of dwarfism, which was stably inherited by the progeny over nine generations. MSAP screening identified six fragments, among which two were further characterized by DNA blot hybridization and direct methylation mapping. One clone encoding a retrotransposon gag-pol polyprotein showed a complete erasure of 5-methylcytosines in Line-2, but neither translocation nor expression of this region was detectable. The other clone encoded an Xa21-like protein, Xa21G. In wild-type plants, all cytosines were methylated within the promoter region, whereas in Line-2, corresponding methylation was completely erased throughout generations. Expression of Xa21G was not detectable in wild type but was constitutive in Line-2. When infected with X. oryzae pv. oryzae, against which Xa21 confers resistance in a gene-for-gene manner, the progeny of Line-2 were

  8. Genetic Counselling for Maternally Inherited Mitochondrial Disorders.

    PubMed

    Poulton, Joanna; Finsterer, Josef; Yu-Wai-Man, Patrick

    2017-08-01

    The aim of this review was to provide an evidence-based approach to frequently asked questions relating to the risk of transmitting a maternally inherited mitochondrial disorder (MID). We do not address disorders linked with disturbed mitochondrial DNA (mtDNA) maintenance, causing mtDNA depletion or multiple mtDNA deletions, as these are autosomally inherited. The review addresses questions regarding prognosis, recurrence risks and the strategies available to prevent disease transmission. The clinical and genetic complexity of maternally inherited MIDs represent a major challenge for patients, their relatives and health professionals. Since many of the genetic and pathophysiological aspects of MIDs remain unknown, counselling of affected patients and at-risk family members remains difficult. MtDNA mutations are maternally transmitted or, more rarely, they are sporadic, occurring de novo (~25%). Females carrying homoplasmic mtDNA mutations will transmit the mutant species to all of their offspring, who may or may not exhibit a similar phenotype depending on modifying, secondary factors. Females carrying heteroplasmic mtDNA mutations will transmit a variable amount of mutant mtDNA to their offspring, which can result in considerable phenotypic heterogeneity among siblings. The majority of mtDNA rearrangements, such as single large-scale deletions, are sporadic, but there is a small risk of recurrence (~4%) among the offspring of affected women. The range and suitability of reproductive choices for prospective mothers is a complex area of mitochondrial medicine that needs to be managed by experienced healthcare professionals as part of a multidisciplinary team. Genetic counselling is facilitated by the identification of the underlying causative genetic defect. To provide more precise genetic counselling, further research is needed to clarify the secondary factors that account for the variable penetrance and the often marked differential expressivity of pathogenic mt

  9. Genetic testing for inherited cardiac disease.

    PubMed

    Wilde, Arthur A M; Behr, Elijah R

    2013-10-01

    Over the past 2 decades, investigators in the field of cardiac genetics have evolved a complex understanding of the pathophysiological basis of inherited cardiac diseases, which predispose individuals to sudden cardiac death. In this Review, we describe the current status of gene discovery and the associations between phenotype and genotype in the cardiac channelopathies and cardiomyopathies. The various indications for genetic testing and its utility in the clinic are assessed in relation to diagnosis, cascade testing, guiding management, and prognosis. Some common problems exist across all phenotypes: the variable penetrance and expressivity of genetic disease, and the difficulty of assessing the functional and clinical effects of novel mutations. These issues will be of particular importance as the next-generation sequencing technologies are used by genetics laboratories to provide results from large panels of genes. The accurate interpretation of these results will be the main challenge for the future.

  10. Inherited renal tubular defects with hypokalemia.

    PubMed

    Muthukrishnan, J; Modi, K D; Kumar, P Jagdish; Jha, Ratan

    2009-03-01

    Bartter's and Gitelman's syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hypercalciuria and was diagnosed as having Bartter's syndrome. The second patient is a lady who had recurrent tetany as the only manifestation of Gitelman's syndrome, which is an unusual presentation. Potassium replacement with supplementation of other deficient ions led to satisfactory clinical and biochemical response.

  11. Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism

    NASA Astrophysics Data System (ADS)

    Kazbanov, Ivan V.; Ten Tusscher, Kirsten H. W. J.; Panfilov, Alexander V.

    2016-02-01

    Myocardial fibrosis is an important risk factor for cardiac arrhythmias. Previous experimental and numerical studies have shown that the texture and spatial distribution of fibrosis may play an important role in arrhythmia onset. Here, we investigate how spatial heterogeneity of fibrosis affects arrhythmia onset using numerical methods. We generate various tissue textures that differ by the mean amount of fibrosis, the degree of heterogeneity and the characteristic size of heterogeneity. We study the onset of arrhythmias using a burst pacing protocol. We confirm that spatial heterogeneity of fibrosis increases the probability of arrhythmia induction. This effect is more pronounced with the increase of both the spatial size and the degree of heterogeneity. The induced arrhythmias have a regular structure with the period being mostly determined by the maximal local fibrosis level. We perform ablations of the induced fibrillatory patterns to classify their type. We show that in fibrotic tissue fibrillation is usually of the mother rotor type but becomes of the multiple wavelet type with increase in tissue size. Overall, we conclude that the most important factor determining the formation and dynamics of arrhythmia in heterogeneous fibrotic tissue is the value of maximal local fibrosis.

  12. Management of supraventricular arrhythmias in adults with congenital heart disease.

    PubMed

    Wasmer, Kristina; Eckardt, Lars

    2016-10-15

    Supraventricular arrhythmias are a frequent complication in adults with congenital heart disease (ACHD). The prevalence increases with time since surgery, complexity of the underlying defect, type of repair and older age at surgery. Arrhythmias are the most frequent reason for hospital admission and along with heart failure the leading cause of death. The arrhythmia-associated increase in morbidity and mortality makes their management a key task in patients with ACHD. Intra-atrial re-entry is the most frequent arrhythmia mechanism. Less common arrhythmia mechanisms are supraventricular tachycardias in the presence of an accessory pathway, atrioventricular nodal re-entrant tachycardia or focal tachycardias. Patient management includes stroke prevention, acute termination and prevention of arrhythmia recurrence. Acute treatment depends on patients' symptoms. In cases of haemodynamic instability, immediate cardioversion is warranted. For stable patients, acute treatment includes rate control and termination by antiarrhythmic drugs or electrical cardioversion. Following a symptomatic arrhythmia, catheter ablation or treatment with antiarrhythmic drugs is recommended to prevent recurrences. Advances in mapping and ablation technology are now associated with high success rates of catheter ablation. In patients with a complex substrate recurrence rates of 50% remain high. However, in the presence of side effects and complications associated with long-term antiarrhythmic drug therapy, redo procedures are encouraged by current guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. The limited utility of electrocardiography variables used to predict arrhythmia in psychotropic drug overdose

    PubMed Central

    Buckley, Nicholas A; Chevalier, Stephan; Leditschke, I Anne; O'Connell, Dianne L; Leitch, James; Pond, Susan M

    2003-01-01

    Objective The aim of the present study was to examine the relationship between serious arrhythmias in patients with psychotropic drug overdose and electrocardiography (ECG) findings that have been suggested previously to predict this complication. Methods Thirty-nine patients with serious arrhythmias (ventricular tachycardia, supraventricular tachycardia or cardiac arrest) after tricyclic antidepressant overdose or thioridazine overdose were compared with 117 controls with clinically significant overdose matched to each case for the drug ingested. These patients with psychotropic drug overdose had presented for treatment to the Department of Clinical Toxicology, Newcastle and to the Princess Alexandra Hospital, Brisbane. The heart rate, the QRS width, the QTc and QT intervals, the QT dispersion, and the R wave and R/S ratios in aVR on the initial ECGs were compared in cases and controls. Results The cases had taken dothiepin (16 patients), doxepin (six patients), thioridazine (five patients), amitriptyline (five patients), nortriptyline (three patients), imipramine (one patient) and a combination of dothiepin and thioridazine (three patients). In 20 of the 39 patients with arrhythmias, the arrhythmia had been a presumed ventricular tachycardia. Of the other 19 patients, 15 patients had a supraventricular tachycardia, two patients had cardiac arrests (one asystole, one without ECG monitoring) and two patients had insufficient data recorded to make classification of the arrhythmias possible. The QRS was ≥ 100 ms in 82% of cases but also in 76% of controls. QRS ≥ 160 ms had a sensitivity of only 13% and occurred in 2% of controls. QRS > 120 ms, QTc > 500 and the R/S ratio in aVR appeared to have a stronger association with the occurrence of arrhythmia: QRS > 120 ms (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.46–8.68), QTc > 500 (OR, 3.07; 95% CI, 1.33–7.07), and R/S ratio in aVR > 0.7 (OR, 16; 95% CI, 3.47–74). Excluding thioridazine overdoses

  14. Epigenetic Inheritance across the Landscape

    PubMed Central

    Whipple, Amy V.; Holeski, Liza M.

    2016-01-01

    The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here, we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome–environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype. PMID:27826318

  15. Multivalvular Replacement and Ventricular Arrhythmias in a Female Child With Congenital Polyvalvular Disease.

    PubMed

    Goot, Benjamin H; Jaggers, James; Anagnost, Miran Rhee; Collins, Kathryn K

    2014-07-01

    We report the clinical course of a female child with a normal karyotype and chromosomal microarray who presented as an infant with clinical findings consistent with congenital polyvalvular disease (CPVD). This clinical entity describes patients with multiple congenitally dysplastic valves, often showing nodular or cystic malformation in at least two cardiac valves. This patient then developed medically refractory multifocal ventricular arrhythmia and required radiofrequency ablation at seven months of age. She had good tachycardia control but became symptomatic with right heart failure related to progressive tricuspid, pulmonary, and mitral valve dysfunction necessitating multivalvular replacement at 21 months of age. © The Author(s) 2013.

  16. Utilizing inheritance in requirements engineering

    NASA Technical Reports Server (NTRS)

    Kaindl, Hermann

    1994-01-01

    The scope of this paper is the utilization of inheritance for requirements specification, i.e., the tasks of analyzing and modeling the domain, as well as forming and defining requirements. Our approach and the tool supporting it are named RETH (Requirements Engineering Through Hypertext). Actually, RETH uses a combination of various technologies, including object-oriented approaches and artificial intelligence (in particular frames). We do not attempt to exclude or replace formal representations, but try to complement and provide means for gradually developing them. Among others, RETH has been applied in the CERN (Conseil Europeen pour la Rechereche Nucleaire) Cortex project. While it would be impossible to explain this project in detail here, it should be sufficient to know that it deals with a generic distributed control system. Since this project is not finished yet, it is difficult to state its size precisely. In order to give an idea, its final goal is to substitute the many existing similar control systems at CERN by this generic approach. Currently, RETH is also tested using real-world requirements for the Pastel Mission Planning System at ESOC in Darmstadt. First, we outline how hypertext is integrated into a frame system in our approach. Moreover, the usefulness of inheritance is demonstrated as performed by the tool RETH. We then summarize our experiences of utilizing inheritance in the Cortex project. Lastly, RETH will be related to existing work.

  17. Inherited predisposition to multiple myeloma

    PubMed Central

    Koura, Divya T.

    2013-01-01

    Multiple myeloma (MM) is the second most common hematologic malignancy in the United States, after non-Hodgkin lymphoma. Family pedigree analyses of high-risk families, case-control studies and racial disparities in disease incidence all point to a potential inherited predisposition to MM. Genome-wide association studies (GWASs) have identified susceptibility loci in a number of cancers and such studies are currently underway in MM. To date, GWASs in MM have identified several potential regions of interest for further study on chromosomes 3p22, 7p15.3, 8q24 and 2p23.3. In addition, several targets of paraproteins (so called ‘paratargs’) in MM have been identified. Hyperphosphorylation of the paratarg protein, which is inherited in an autosomal dominant manner, appears a common mechanism underlying the antigenicity of these proteins. One particular protein, hyperphosphorylated paratarg-7 (pP-7) is a common target in persons with myeloma and has also been identified in affected members of several high-risk MM families. It appears that the frequency of pP-7 as an antigenic target may be particularly high in African American patients with MM, which could be part of the explanation for observed racial disparities in the incidence of MM. In this review we focus on available data in the area of inherited predisposition to MM, and highlight future research directions. PMID:23926460

  18. A troubled beginning: evolving concepts of an old arrhythmia.

    PubMed

    Hanon, Sam; Shapiro, Michael; Schweitzer, Paul

    2005-07-01

    The development of the sphygmograph in the nineteenth century marked the beginning of graphic registration of the arterial and venous pulse. Mackenzie, among other investigators, used this technique to study cardiac rhythm. In the early 20th century, Einthoven developed the electrocardiogram, which replaced the less sophisticated arterial and venous registrations of cardiac events and allowed for more detailed arrhythmia analysis. Interestingly, the early study of cardiac arrhythmias was obscured by misinterpretation. Specifically, atrial fibrillation stands out as a rhythm that was extensively studied though misconstrued in its early history. What follows is an in-depth consideration of the original investigations and evolving theories of this important arrhythmia.

  19. PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    CENTERWALL, WILLARD R.; CENTERWALL, SIEGRIED A.

    ADDRESSED TO PUBLIC HEALTH WORKERS AND PHYSICIANS IN GENERAL PRACTICE, THE PAMPHLET INTRODUCES METHODS OF DETECTING AND MANAGING PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION. INFORMATION, UPDATED FROM THE 1961 EDITION, IS INCLUDED ON THE INCIDENCE AND GENETICS, BIOCHEMISTRY, AND CLINICAL COURSE OF THE…

  20. PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    CENTERWALL, WILLARD R.; CENTERWALL, SIEGRIED A.

    ADDRESSED TO PUBLIC HEALTH WORKERS AND PHYSICIANS IN GENERAL PRACTICE, THE PAMPHLET INTRODUCES METHODS OF DETECTING AND MANAGING PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION. INFORMATION, UPDATED FROM THE 1961 EDITION, IS INCLUDED ON THE INCIDENCE AND GENETICS, BIOCHEMISTRY, AND CLINICAL COURSE OF THE…

  1. Electrocardiographic Presentation, Cardiac Arrhythmias, and Their Management in β-Thalassemia Major Patients.

    PubMed

    Russo, Vincenzo; Rago, Anna; Papa, Andrea Antonio; Nigro, Gerardo

    2016-07-01

    Beta-thalassemia major (β-TM) is a genetic hemoglobin disorder characterized by an absent synthesis of globin chains that are essential for hemoglobin formation, causing chronic hemolytic anemia. Clinical management of thalassemia major consists in regular long-life red blood cell transfusions and iron chelation therapy to remove iron introduced in excess with transfusions. Iron deposition in combination with inflammatory and immunogenic factors is involved in the pathophysiology of cardiac dysfunction in these patients. Heart failure and arrhythmias, caused by myocardial siderosis, are the most important life-limiting complications of iron overload in beta-thalassemia patients. Cardiac complications are responsible for 71% of global death in the beta-thalassemia major patients. The aim of this review was to describe the most frequent electrocardiographic abnormalities and arrhythmias observed in β-TM patients, analyzing their prognostic impact and current treatment strategies.

  2. Efficient Fine Arrhythmia Detection Based on DCG P-T Features.

    PubMed

    Bie, Rongfang; Xu, Shuaijing; Zhang, Guangzhi; Zhang, Meng; Ma, Xianlin; Zhang, Xialin

    2016-07-01

    Due to the high mortality associated with heart disease, there is an urgent demand for advanced detection of abnormal heart beats. The use of dynamic electrocardiogram (DCG) provides a useful indicator of heart condition from long-term monitoring techniques commonly used in the clinic. However, accurately distinguishing sparse abnormal heart beats from large DCG data sets remains difficult. Herein, we propose an efficient fine solution based on 11 geometrical features of the DCG PQRST(P-T) waves and an improved hierarchical clustering method for arrhythmia detection. Data sets selected from MIT-BIH are used to validate the effectiveness of this approach. Experimental results show that the detection procedure of arrhythmia is fast and with accurate clustering.

  3. Computational model of erratic arrhythmias in a cardiac cell network: the role of gap junctions.

    PubMed

    Casaleggio, Aldo; Hines, Michael L; Migliore, Michele

    2014-01-01

    Cardiac morbidity and mortality increases with the population age. To investigate the underlying pathological mechanisms, and suggest new ways to reduce clinical risks, computational approaches complementing experimental and clinical investigations are becoming more and more important. Here we explore the possible processes leading to the occasional onset and termination of the (usually) non-fatal arrhythmias widely observed in the heart. Using a computational model of a two-dimensional network of cardiac cells, we tested the hypothesis that an ischemia alters the properties of the gap junctions inside the ischemic area. In particular, in agreement with experimental findings, we assumed that an ischemic episode can alter the gap junctions of the affected cells by reducing their average conductance. We extended these changes to include random fluctuations with time, and modifications in the gap junction rectifying conductive properties of cells along the edges of the ischemic area. The results demonstrate how these alterations can qualitatively give an account of all the main types of non-fatal arrhythmia observed experimentally, and suggest how premature beats can be eliminated in three different ways: a) with a relatively small surgical procedure, b) with a pharmacological reduction of the rectifying conductive properties of the gap-junctions, and c) by pharmacologically decreasing the gap junction conductance. In conclusion, our model strongly supports the hypothesis that non-fatal arrhythmias can develop from post-ischemic alteration of the electrical connectivity in a relatively small area of the cardiac cell network, and suggests experimentally testable predictions on their possible treatments.

  4. Genetic testing in heritable cardiac arrhythmia syndromes: differentiating pathogenic mutations from background genetic noise.

    PubMed

    Giudicessi, John R; Ackerman, Michael J

    2013-01-01

    In this review, we summarize the basic principles governing rare variant interpretation in the heritable cardiac arrhythmia syndromes, focusing on recent advances that have led to disease-specific approaches to the interpretation of positive genetic testing results. Elucidation of the genetic substrates underlying heritable cardiac arrhythmia syndromes has unearthed new arrhythmogenic mechanisms and given rise to a number of clinically meaningful genotype-phenotype correlations. As such, genetic testing for these disorders now carries important diagnostic, prognostic, and therapeutic implications. Recent large-scale systematic studies designed to explore the background genetic 'noise' rate associated with these genetic tests have provided important insights and enhanced how positive genetic testing results are interpreted for these potentially lethal, yet highly treatable, cardiovascular disorders. Clinically available genetic tests for heritable cardiac arrhythmia syndromes allow the identification of potentially at-risk family members and contribute to the risk-stratification and selection of therapeutic interventions in affected individuals. The systematic evaluation of the 'signal-to-noise' ratio associated with these genetic tests has proven critical and essential to assessing the probability that a given variant represents a rare pathogenic mutation or an equally rare, yet innocuous, genetic bystander.

  5. Atypical inheritance: new horizons for neurology.

    PubMed

    Wilson, G N

    1994-11-01

    Rediscovery of Mendel's laws produced an enthusiastic new discipline at the turn of this century. The eugenics movement had many disciples in the United States, and it should be noted that the term "final solution" was first used by the National Association of Charities and Corrections in the 1920s. American advocates of eugenics accomplished mass sterilization of retarded individuals and the prohibition of Jewish immigration from Germany during World War II. It is interesting that the close of this century has produced a similar revolution in genetics. These newer genetic mechanisms expose the major fallacy of eugenics: traits may be genetic without showing obvious familial transmission. Sanctions against reproduction or immigration thus will have little effect on the gene pool. The clinical implications of atypical inheritance are enormous. Almost every medical disorder must be reinvestigated for evidence of subtle chromosome changes, for worsening in progressive generations, and for influence of parental origin. The classical Mendelian model taught that extreme and rare phenotypes shed light on more frequent ones, hence the definition of genes responsible for hypercholesterolemia, for Alzheimer disease, and for amyotrophic lateral sclerosis. Atypical inheritance mechanisms further enhance this approach, bringing all of neurology under the light of genetic technology. The lure for the practitioner, then, is not the hyperbole of molecular biology; it is the need for a seasoned hand so emphasized by Huntington's disease and the duty to protect the next century from disasters of the current one.

  6. Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

    PubMed Central

    Yu-Wai-Man, Patrick

    2016-01-01

    Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. PMID:27002113

  7. In vitro arrhythmia generation by mild hypothermia: a pitchfork bifurcation type process.

    PubMed

    Xu, Binbin; Jacquir, Sabir; Laurent, Gabriel; Binczak, Stéphane; Pont, Oriol; Yahia, Hussein

    2015-03-01

    The neurological damage after cardiac arrest presents a huge challenge for hospital discharge. Therapeutic hypothermia (34 °C - 32 °C) has shown its benefits in reducing cerebral oxygen demand and improving neurological outcomes after cardiac arrest. However, it can have many adverse effects, among them cardiac arrhythmia generation which represents an important part (up to 34%, according different clinical studies). A monolayer cardiac culture is prepared with cardiomyocytes from a newborn rat, directly on a multi-electrode array, which allows the acquisition of the extracellular potential of the culture. The temperature range is 37 °C - 30 °C-37 °C, representing the cooling and rewarming process of therapeutic hypothermia. Experiments showed that at 35 °C, the acquired signals are characterized by period-doubling phenomenon, compared with signals at other temperatures. Spiral waves, commonly considered to be a sign of cardiac arrhythmia, are observed in the reconstructed activation map. With an approach from nonlinear dynamics, phase space reconstruction, it is shown that at 35 °C, the trajectories of these signals formed a spatial bifurcation, even trifurcation. Another transit point is found between 30 °C-33 °C, which agreed with other clinical studies that induced hypothermia after cardiac arrest should not fall below 32 °C. The process of therapeutic hypothermia after cardiac arrest can be represented by a pitchfork bifurcation type process, which could explain the different ratios of arrhythmia among the adverse effects after this therapy. This nonlinear dynamic suggests that a variable speed of cooling/rewarming, especially when passing 35 °C, would help to decrease the ratio of post-hypothermia arrhythmia and then improve the hospital output.

  8. Identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death

    PubMed Central

    Jagu, Benoît; Charpentier, Flavien; Toumaniantz, Gilles

    2013-01-01

    Researchers and clinicians have discovered several important concepts regarding the mechanisms responsible for increased risk of arrhythmias, heart failure, and sudden cardiac death. One major step in defining the molecular basis of normal and abnormal cardiac electrical behavior has been the identification of single mutations that greatly increase the risk for arrhythmias and sudden cardiac death by changing channel-gating characteristics. Indeed, mutations in several genes encoding ion channels, such as SCN5A, which encodes the major cardiac Na+ channel, have emerged as the basis for a variety of inherited cardiac arrhythmias such as long QT syndrome, Brugada syndrome, progressive cardiac conduction disorder, sinus node dysfunction, or sudden infant death syndrome. In addition, genes encoding ion channel accessory proteins, like anchoring or chaperone proteins, which modify the expression, the regulation of endocytosis, and the degradation of ion channel a-subunits have also been reported as susceptibility genes for arrhythmic syndromes. The regulation of ion channel protein expression also depends on a fine-tuned balance among different other mechanisms, such as gene transcription, RNA processing, post-transcriptional control of gene expression by miRNA, protein synthesis, assembly and post-translational modification and trafficking. The aim of this review is to inventory, through the description of few representative examples, the role of these different biogenic mechanisms in arrhythmogenesis, HF and SCD in order to help the researcher to identify all the processes that could lead to arrhythmias. Identification of novel targets for drug intervention should result from further understanding of these fundamental mechanisms. PMID:24065925

  9. Inherited secondary nephrogenic diabetes insipidus: concentrating on humans.

    PubMed

    Bockenhauer, D; Bichet, D G

    2013-04-15

    The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.

  10. Inherited disorders of hemostasis in dogs and cats.

    PubMed

    Barr, James W; McMichael, Maureen

    2012-05-01

    Inherited disorders of hemostasis encompass abnormalities in primary hemostasis, coagulation, and fibrinolysis resulting from genetic mutations. There is significant variation in the phenotype expressed ranging from life limiting to the absence of overt clinical signs. Von Willebrand disease is the most common primary hemostatic disorder in dogs, and hemophilia A is the most common coagulation factor disorder. The diagnosis of inherited bleeding disorders is made by functional and/or quantitative evaluation. Genetic testing has added to the knowledge base, allowing prevention through targeted breeding. Avoidance of trauma and injury is paramount in the prevention of bleeding in animals diagnosed with inherited hemostatic disorders. Current therapeutic options include platelet transfusions, broad replacement of coagulation factors (e.g., plasma), targeted factor replacement (e.g., cryoprecipitate), antifibrinolytic agents and specific factor replacement, and treatment of the symptoms (i.e., bleeding) with blood transfusions.

  11. Periodic Limb Movements during Sleep and Cardiac Arrhythmia in Older Men (MrOS Sleep)

    PubMed Central

    Koo, Brian B.; Mehra, Reena; Blackwell, Terri; Ancoli-Israel, Sonia; Stone, Katie L.; Redline, Susan

    2014-01-01

    Study Objectives: To determine if periodic limb movements during sleep (PLMS) are associated with nocturnal cardiac arrhythmia. Methods: 2,793 community-dwelling older men underwent polysomnography with measurement of limb movements and EKG. Logistic regression assessed association of periodic limb movement index and periodic limb movement arousal index with arrhythmia including atrial fibrillation and non-sustained ventricular tachycardia detected by polysomnography. Models were adjusted for age, race, cardiovascular risk factors, and clinic site. Secondary analyses were subset to men without calcium channel/β-adrenergic medication usage, and stratified by congestive heart failure or myocardial infarction history. Results: In the overall cohort, periodic limb movement index, and periodic limb movement arousal index were not associated with ventricular or atrial arrhythmia after considering potential confounders. In men not taking calcium channel/β-blocking medication, increased adjusted odds of non-sustained ventricular tachycardia were observed for periodic limb movement index (OR = 1.30 per SD increase; 95% CI 1.00, 1.68) and periodic limb movement arousal index (OR = 1.29 per SD increase; 95% CI 1.03, 1.62). In men with CHF or MI, there was a suggested association of atrial fibrillation with periodic limb movement index (OR = 1.29, 95% CI 0.96, 1.73 per SD increase; p = 0.09) or periodic limb movement arousal index (OR = 1.21, 95% CI 0.94, 1.57 per SD increase; p = 0.14), although results were not statistically significant. Conclusions: There is not an association between PLMS and cardiac arrhythmia in all older men but in subsets of men, particularly those with structural heart disease and not on calcium channel or β-adrenergic medication, cardiac arrhythmia does associate with PLMS. Citation: Koo BB; Mehra R; Blackwell T; Ancoli-Israel S; Stone KL; Redline S; for the Osteoporotic Fractures in Men (MrOS) Study Group. Periodic limb movements during sleep and

  12. Arrhythmia Associated with Buprenorphine and Methadone Reported to the Food and Drug Administration

    PubMed Central

    Kao, David P; Haigney, Mark CP; Mehler, Philip S; Krantz, Mori J

    2015-01-01

    Aim To assess the relative frequency of reporting of adverse events involving ventricular arrhythmia, cardiac arrest, QTc prolongation, or torsade de pointes to the US Food and Drug Administration (FDA) between buprenorphine and methadone. Design Retrospective pharmacoepidemiologic study Setting Adverse drug events spontaneously reported to the FDA between 1969-June 2011 originating in 196 countries (71% events from the US). Cases Adverse event cases mentioning methadone (n=14,915) or buprenorphine (n=7,283) were evaluated against all other adverse event cases (n= 4,796,141). Measurements The primary outcome was the composite of ventricular arrhythmia or cardiac arrest. The secondary outcome was the composite of QTc prolongation or torsade de pointes. The proportional reporting ratio (PRR) was used to identify disproportionate reporting defined as a PRR>2, χ2 error>4, with ≥3 cases. Findings There were 132 (1.8%) ventricular arrhythmia/cardiac arrest and 19 (0.3%) QTc prolongation/torsade de pointes cases associated with buprenorphine compared with 1729 (11.6%) ventricular arrhythmia/cardiac arrest and 390 (2.6%) QTc prolongation/torsade de pointes cases involving methadone. PRRs associated with buprenorphine were not significant for ventricular arrhythmia/cardiac arrest (1.1 95% confidence interval (CI) 0.9–1.3, χ2=1.2) or QTc prolongation/torsade de pointes (1.0 95% CI 0.7–1.9, χ2=0.0006), but were for methadone (7.2 95% CI 6.9–7.5, χ2=9160; 10.6 95% CI 9.7–11.8, χ2=3305, respectively). Conclusion In spontaneously reported adverse events, methadone is associated with disproportionate reporting of cardiac arrhythmias, whereas buprenorphine is not. Although these findings probably reflect clinically relevant differences, a causal connection cannot be presumed and disproportionality analysis cannot quantify absolute risk per treatment episode. Population-based studies to definitively quantify differential incidence rates are warranted. PMID:26075588

  13. Use of Intravenous Amiodarone in the Treatment of Nifekalant-Resistant Arrhythmia: A Review of 11 Consecutive Cases with Severe Heart Failure

    PubMed Central

    Nakagawa, Koji; Nakamura, Kazufumi; Kusano, Kengo Fukushima; Nagase, Satoshi; Tada, Takeshi; Murakami, Masato; Hata, Yoshiki; Morita, Hiroshi; Kohno, Kunihisa; Hina, Kazumasa; Ujihira, Tohru; Ohe, Tohru; Ito, Hiroshi

    2011-01-01

    Background: Both nifekalant hydrochloride (NIF), a selective IKr blocker, and intravenous amiodarone (AMD), a multi-channel (including IKr blocking) blocker, have been reported to be efficacious for refractory arrhythmias. However, the optimal use of those antiarrhythmic drugs for refractory arrhythmia with severe heart failure has not been established. Intravenous AMD might be effective for arrhythmias refractory to NIF in patients with severe heart failure. Here, we report that intravenous amiodarone was effective in the treatment of nifekalant-resistant in a group of arrhythmia patients with severe heart failure. Methods: Eleven severe heart failure patients who had received intravenous AMD for treatment of NIF-resistant arrhythmias were included in this study, and retrospective analysis was performed. Clinical efficacy (terminative and preventive effects on arrhythmia) of intravenous AMD was evaluated. Results: All cases were emergent cases and had depressed left ventricular ejection fraction (30 ± 13%). Clinical arrhythmias were ventricular fibrillation (VF) in four patients, ventricular tachycardia (VT) in six patients, and atrial fibrillation (AF) in one patient. NIF was administered to all patients by intravenous injection. After administration of NIF, VT/VF/AF was terminated in seven of the 10 patients, but a preventive effect was not obtained in any of the patients (NIF-resistance). Intravenous AMD (maintenance dose: 484 ± 166 mg/day) was effective both in termination (80%) and in prevention (80%) of VT/VF events in those patients. It was also effective in termination (80%) and prevention (60%) of AF events refractory to NIF. During continuous AMD administration, no significant adverse effects or proarrhythmic effects were observed in any of the patients. Five patients died within one month, but there was no arrhythmic deaths. Conclusions: Intravenous AMD was effective in NIF-resistant lethal arrhythmias and was relatively safe in emergent cases with

  14. Gene therapy for inherited retinal degenerations.

    PubMed

    Dalkara, Deniz; Sahel, José-Alain

    2014-03-01

    Gene therapy is quickly becoming a reality applicable in the clinic for inherited retinal diseases. Progress over the past decade has moved proof-of-concept gene therapies from bench to bedside. The remarkable success in safety and efficacy, in the phase I/II clinical trials for the form of the severe childhood-onset blindness, Leber's Congenital Amaurosis (LCA) type II (due to mutations in the RPE65 gene) generated significant interest and opened up possibilities for a new era of retinal gene therapies. Success in these clinical trials was due to combining the favorable features of both the retina as a target organ and adeno-associated virus (AAV) as a vector. The retina offers several advantages for gene therapy approaches. It is an anatomically defined structure that is readily accessible for therapy and has some degree of immune privilege, making it suitable for application of viral vectors. AAV, on the other hand, is a non-pathogenic helper dependent virus that has little immunogenicity. This viral vector transduces quiescent cells efficiently and thanks to its small size diffuses well in the interneural matrix, making it suitable for applications in neural tissue. Building on this initial clinical success with LCA II, we have now many opportunities to extend this proof-of-concept to other retinal diseases. This article will discuss what are some of the most imminent targets for such therapies and what are the challenges that we face in moving these therapies to the clinic.

  15. Atrial Arrhythmias in Astronauts. Summary of a NASA Summit

    NASA Technical Reports Server (NTRS)

    Barr, Yael; Watkins, Sharmila; Polk, J. D.

    2011-01-01

    This slide presentation reviews the findings of a panel of heart experts brought together to study if atrial arrhythmias more prevalent in astronauts, and potential risk factors that may predispose astronauts to atrial arrhythmias. The objective of the panel was to solicit expert opinion on screening, diagnosis, and treatment options, identify gaps in knowledge, and propose relevant research initiatives. While Atrial Arrhythmias occur in approximately the same percents in astronauts as in the general population, they seem to occur at younger ages in astronauts. Several reasons for this predisposition were given: gender, hypertension, endurance training, and triggering events. Potential Space Flight-Related Risk factors that may play a role in precipitating lone atrial fibrillation were reviewed. There appears to be no evidence that any variable of the space flight environment increases the likelihood of developing atrial arrhythmias during space flight.

  16. Ablation of Arrhythmias in Patients with Adult Congenital Heart Disease

    PubMed Central

    Lobo, Rodrigo Gallardo; Griffith, Michael

    2014-01-01

    Arrhythmias in adults with congenital heart disease, most commonly related to previous surgical procedures, are a frequent comorbidity in this growing population thanks to the improved outcome of surgical techniques. Re-entrant circuits around areas of scarring and natural barriers, combined with abnormal haemodynamics and the underlying anatomy, are the most common cause for these arrhythmias. They are often poorly tolerated and medical treatment is frequently inadequate. In recent years, catheter ablation has emerged as a successful therapeutic option. New advanced techniques such as the use of modern three-dimensional (3D) navigation systems have contributed to better understanding of the arrhythmia mechanisms and higher success rates of the ablation procedures. In this article we briefly summarise the characteristics of the most common arrhythmias in this patient population and some key aspects in their treatment by catheter ablation. PMID:26835063

  17. Accurate arrhythmia classification using auto-associative neural network.

    PubMed

    Chakroborty, Sandipan

    2013-01-01

    Currently about one in eighteen of the American population suffer from cardiac Arrhythmias that lead to Coronary Heart Diseases and this rate is steadily increasing. An early monitoring and diagnosis of Arrhythmia based on Electrocardiogram signals can help in reducing mortality. This paper primarily focuses on the application of Auto Associative Neural Network as a new classification approach, which does not require feature extraction task. The weights of a trained Neural Network are stored as class representative models that results in high compression gain with respect to the size of training data. The evaluation of the proposed technique is tested on segmented ECG beats of four different classes of Arrhythmia excluding normal pattern. These beats have been extracted from the MIT/BIH Arrhythmia database and compared against the state-of-the art template matching technique such as Dynamic Time Warping. The proposed technique yields an average accuracy of more than 97% and a relative compression gain of above 90%.

  18. Elderly woman with cerebrovascular accident and refractory arrhythmias.

    PubMed

    Sethi, S K; Sarm, P S A

    2009-11-01

    Fatal bilateral cerebro-vascular accident with variable atrio-ventricular blocks, atrial fibrillation and refractory tachy-arrhythmias in a previously healthy 75-years-old hypertensive female is presented.

  19. [Ryanodine receptor, calcium leak and arrhythmias].

    PubMed

    Rueda, Angélica; de Alba-Aguayo, David R; Valdivia, Héctor H

    2014-01-01

    The participation of the ionic Ca(2+) release channel/ryanodine receptor in cardiac excitation-contraction coupling is well known since the late '80s, when various seminal papers communicated its purification for the first time and its identity with the "foot" structures located at the terminal cisternae of the sarcoplasmic reticulum. In addition to its main role as the Ca(2+) channel responsible for the transient Ca(2+) increase that activates the contractile machinery of the cardiomyocytes, the ryanodine receptor releases Ca(2+) during the relaxation phase of the cardiac cycle, giving rise to a diastolic Ca(2+) leak. In normal physiological conditions, diastolic Ca(2+) leak regulates the proper level of luminal Ca(2+), but in pathological conditions it participates in the generation of both, acquired and hereditary arrhythmias. Very recently, several groups have focused their efforts into the development of pharmacological tools to control the altered diastolic Ca(2+) leak via ryanodine receptors. In this review, we focus our interest on describing the participation of cardiac ryanodine receptor in the diastolic Ca(2+) leak under physiological or pathological conditions and also on the therapeutic approaches to control its undesired exacerbated activity during diastole. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  20. Ethanol for the treatment of cardiac arrhythmias

    PubMed Central

    Schurmann, Paul; Peñalver, Jorge; Valderrábano, Miguel

    2015-01-01

    Introduction Ethanol infusion was an early mode of ablative treatment for cardiac arrhythmias. Its initial descriptions involved coronary intra-arterial delivery, targeting arrhythmogenic substrates in drug-refractory ventricular tachycardia or the atrioventricular node. Largely superseded by radiofrequency ablation (RFA) and other contact-based technologies as a routine ablation strategy, intracoronary arterial ethanol infusion remains as an alternative option in the treatment of ventricular tachycardia when conventional ablation fails. Arrhythmic foci that are deep-seated in the myocardium may not be amenable to catheter ablation from either the endocardium or the epicardium by RFA, but they can be targeted by an ethanol infusion. Recent findings Recently, we have explored ethanol injection through cardiac venous systems, in order to avoid the risks of complications and limitations of coronary arterial instrumentation. Vein of Marshall ethanol infusion is being studied as an adjunctive procedure in ablation of atrial fibrillation, and coronary venous ethanol infusion for ventricular tachycardia. Conclusion Ethanol ablation remains useful as a bail-out technique for refractory cases to RFA, or as an adjunctive therapy that may improve the efficacy of catheter ablation procedures. PMID:26049378

  1. Models of Stretch-Activated Ventricular Arrhythmias

    PubMed Central

    Trayanova, Natalia A.; Constantino, Jason; Gurev, Viatcheslav

    2010-01-01

    One of the most important components of mechano-electric coupling is stretch-activated channels, sarcolemmel channels that open upon mechanical stimuli. Uncovering the mechanisms by which stretch-activated channels contribute to ventricular arrhythmogenesis under a variety of pathological conditions is hampered by the lack of experimental methodologies that can record the three-dimensional electromechanical activity simultaneously at high spatiotemporal resolution. Computer modeling provides such an opportunity. This goal of this review is to illustrate the utility of sophisticated, physiologically realistic, whole heart computer simulations in determining the role of mechano-electric coupling in ventricular arrhythmogeneisis. We first present the various ways by which stretch-activated channels have been modeled and demonstrate how these channels affect cardiac electrophysiological properties. Next, we employ an electrophysiological model of the rabbit ventricles to understand how so-called commotio cordis, the mechanical impact to the pre-cordial region of the heart, can initiate ventricular tachycardia via the recruitment of stretch-activated channels. Using the same model, we also provide mechanistic insight to the termination of arrhythmias by precordial thump under normal and globally-ischemic conditions. Lastly, we employ a novel anatomically-realistic dynamic 3D coupled electromechanical model of the rabbit ventricles to gain insight into the role of electromechanical dysfunction in arrhythmogenesis during acute regional ischemia. PMID:20638670

  2. Alternans Arrhythmias: From Cell to Heart

    PubMed Central

    Weiss, James N.; Nivala, Michael; Garfinkel, Alan; Qu, Zhilin

    2010-01-01

    The goal of systems biology is to relate events at the molecular level to more integrated scales from organelle to cell, tissue and living organism. Here we review how normal and abnormal excitation-contraction (EC) coupling properties emerge from the protein scale, where behaviors are dominated by randomness, to the cell and tissue scales, where heart has to beat with reliable regularity for a life-time. Beginning with the fundamental unit of EC coupling, the couplon where L-type Ca channels in the sarcolemmal membrane adjoin ryanodine receptors in the sarcoplasmic reticulum membrane, we show how a network of couplons with three basic properties (random activation, refractoriness, and recruitment) produces the classical physiological properties of excitation-contraction (EC) coupling and, under pathophysiological conditions, leads to Ca alternans and Ca waves. Moving to the tissue scale, we discuss how cellular Ca alternans and Ca waves promote both reentrant and focal arrhythmias in the heart. Throughout, we emphasize the qualitatively novel properties which emerge at each new scale of integration. PMID:21212392

  3. Endocardial electrogram characteristics of epicardial ventricular arrhythmias.

    PubMed

    Tzou, Wendy S; Nguyen, Duy T; Aleong, Ryan G; Varosy, Paul D; Katz, David F; Heath, Russell R; Schuller, Joseph L; Lowery, Christopher M; Lewkowiez, Laurent; Sauer, William H

    2013-06-01

    While most ventricular arrhythmias (VA) can be ablated successfully using an endocardial (endo) approach, epicardial (epi) mapping and ablation is sometimes required. There may be suggestive clues on the surface electrocardiogram; however, identification of an epi origin of VA with certainty remains problematic. All patients referred for ablation of ventricular tachycardia or frequent ventricular ectopy from June 2007 to July 2011 were evaluated. Patients with completed endo and epi electroanatomical activation maps of an epi VA were included (n = 10). Bipolar electrograms (EGMs) in the area of earliest endo activation were analyzed and compared to the area of early epi activation. An EGM component was characterized as far field if it was monophasic and there was inability to capture. We identified 3 characteristics from endo mapping that consistently indicated need for epi ablation: (1) Diffusely early activation (>2 cm(2) region of sites with equally earliest activation within 10 milliseconds). (2) Sequence of a far-field EGM followed by a near-field EGM in the region of earliest endo activation. (3) Inability to capture the far-field component of the earliest EGM (stim-QRS < egm-QRS time) or reproduce morphological features of the VA complex with stimulation at the earliest endo site of activation. The presence of a diffusely early area of activation and inability to capture a far-field endo EGM indicates that epi ablation may be needed to eliminate a VA. © 2013 Wiley Periodicals, Inc.

  4. Plate tectonics, damage and inheritance.

    PubMed

    Bercovici, David; Ricard, Yanick

    2014-04-24

    The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The reason for this time lag is unknown but fundamental to understanding the origin of plate tectonics. Here we suggest that when sufficient lithospheric damage (which promotes shear localization and long-lived weak zones) combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of weak plate boundaries and eventually to fully formed tectonic plates driven by subduction alone. We simulate this process using a grain evolution and damage mechanism with a composite rheology (which is compatible with field and laboratory observations of polycrystalline rocks), coupled to an idealized model of pressure-driven lithospheric flow in which a low-pressure zone is equivalent to the suction of convective downwellings. In the simplest case, for Earth-like conditions, a few successive rotations of the driving pressure field yield relic damaged weak zones that are inherited by the lithospheric flow to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even though flow is driven only by subduction. But for hotter surface conditions, such as those on Venus, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which corresponds to observations. After plates have developed, continued changes in driving forces, combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor plates.

  5. Update on management of cardiac arrhythmias in acute coronary syndromes.

    PubMed

    Willich, T; Goette, A

    2015-04-01

    This review summarizes different types of arrhythmias in patients with acute coronary syndromes and provides an overview of the available therapeutic options for acute care and management of critical arrhythmias. The different therapeutic options are depending on the origin and type of arrhythmia. The main common dominant mechanisms are intramural re-entry in ischemia and triggered activity in reperfusion. The different forms of arrhythmia were explained in detail. Atrial arrhythmias are mainly atrial fibrillation; other forms are rare and usually self-limited. As therapeutic options antiarrhythmic drug therapy with beta-blockers or amiodarone and direct current cardioversion are suitable. Ventricular arrhythmias can be divided in premature ventricular complexes, accelerated idioventricular rhythm, non-sustained ventricular tachycardia, sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and electrical storm. As therapeutic options antiarrhythmic drug therapy, implantable cardioverter defibrillator therapy (ICD), radiofrequency catheter ablation (RFA) and stellate ganglion blockade are available. The treatment with antiarrhythmic drug is rather cautious recommended, with the exception of beta-blockers. An additional drug therapy with ranolazine may be considered. The advantage of ICD therapy for long-term primary or secondary prophylactic therapy has been well documented. ICD therapy is associated with significant reduction in mortality compared with antiarrhythmic drug therapy (mainly amiodarone), with the exception of beta-blockers. RFA and stellate ganglion blockade are rather intended as therapeutically options for incessant VT/VF or electrical storm.

  6. Molecular therapies for inherited epidermolysis bullosa.

    PubMed

    Has, Cristina

    2016-08-01

    Inherited epidermolysis bullosa (EB) comprises rare genetic disorders characterized by formation of blisters and erosions of skin and mucous membranes after minor mechanical trauma. The molecular basis and the pathomechanisms of the main EB types have been largely deciphered in the past decades. The burden of the disease is high and quality of life strongly affected. The treatment is still symptomatic aiming to support wound healing and resolve complications. Numerous experimental therapeutic approaches for EB have been explored in the last years, most of them dedicated to dystrophic EB. Although gene and cell therapies have been already applied in patients, molecular therapies including gene editing and repurposing of small molecules are currently very attractive. Recent data on the effect of small molecules, like aminoglycosides and angiotensin receptor blockers in preclinical models for dystrophic EB are encouraging. The efficacy in patients remains to be proven in clinical trials. Therapeutic efficacy, as well as unexpected outcomes must be carefully monitored.

  7. Therapeutic strategies for the inherited neuropathies.

    PubMed

    Shy, Michael E

    2006-01-01

    More than 30 genetic causes have been identified for the inherited neuropathies collectively referred to as Charcot-Marie-Tooth (CMT) disease. Previous therapies for CMT were limited to traditional approaches such as rehabilitation medicine, ambulation aids, and pain management. Identification of the genes causing CMT has led to improved genetic counseling and assistance in family planning. Identification of these genes is beginning to delineate common molecular pathways in multiple forms of CMT that can be exploited in future molecular therapies. Scientifically based clinical trials for CMT are currently being implemented. Techniques of gene therapy are advancing to the point that they may become feasible options for patients with CMT and other neurodegenerative diseases.

  8. Mitochondrial inheritance in budding yeast.

    PubMed

    Boldogh, I R; Yang, H C; Pon, L A

    2001-06-01

    During the past decade significant advances were made toward understanding the mechanism of mitochondrial inheritance in the yeast Saccharomyces cerevisiae. A combination of genetics, cell-free assays and microscopy has led to the discovery of a great number of components. These fall into three major categories: cytoskeletal elements, mitochondrial membrane components and regulatory proteins. These proteins mediate activities, including movement of mitochondria from mother cells to buds, segregation of mitochondria and mitochondrial DNA, and equal distribution of the organelle between mother cells and buds during yeast cell division.

  9. Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data.

    PubMed

    Sessler, Nelson E; Walker, Ekaterina; Chickballapur, Harsha; Kacholakalayil, James; Coplan, Paul M

    2017-01-01

    Positive-controlled clinical studies have shown a dose dependent effect of buprenorphine transdermal system on QTc interval prolongation. This study provides assessment of the buprenorphine transdermal system and cardiac arrhythmia using US FDA and WHO postmarketing reporting databases. Disproportionality analysis of spontaneously reported adverse events to assess whether the reporting rate of cardiac arrhythmia events was disproportionately elevated relative to expected rates of reporting in both FDA and WHO databases. Cardiac arrhythmia events were identified using the standardized Medical Dictionary for Regulatory Activities query for torsade de pointes and/or QT prolongation (TdP/QTP). The threshold for a signal of disproportionate adverse event reporting was defined as the lower 90% confidence limit ≥ 2 of the Empiric Bayes geometric mean in FDA database and as the lower 95% confidence limit of the Informational Component >0 in WHO database. There were 124 (<1%) and 77 (2%) cardiac arrhythmia event cases associated with buprenorphine transdermal as compared to 3206 (12%) and 2913 (14%) involving methadone in the FDA and WHO databases, respectively. In the FDA database methadone was associated with a signal of disproportionate reporting for TdP/QTP (EB05 3.26); however, buprenorphine transdermal was not (EB05 0.33). In the WHO database methadone was associated with a signal of disproportionate reporting for TdP/QTP (IC025 2.66); however, buprenorphine transdermal was not (IC025 -0.88). Similar trends were observed in sensitivity analyses by age, gender, and specific terms related to ventricular arrhythmia. The signal identified in the transdermal buprenorphine thorough QTc study, which led to a dose limitation in its US label, does not translate into a signal of increased risk for cardiac arrhythmia in real world use, as assessed by this method of analyzing post-market surveillance data.

  10. Fluoroless Catheter Ablation of Cardiac Arrhythmias: A 5-Year Experience.

    PubMed

    Razminia, Mansour; Willoughby, Michael Cameron; Demo, Hany; Keshmiri, Hesam; Wang, Theodore; D'Silva, Oliver J; Zheutlin, Terry A; Jibawi, Hakeem; Okhumale, Paul; Kehoe, Richard F

    2017-04-01

    Catheter ablations have been traditionally performed with the use of fluoroscopic guidance, which exposes the patient and staff to the inherent risks of radiation. We have developed techniques to eliminate the use of fluoroscopy during cardiac ablations and have been performing completely fluoroless catheter ablations on our patients for over 5 years. We present a retrospective analysis of the safety, efficacy, and feasibility data from 500 consecutive patients who underwent nonfluoroscopic catheter ablation, targeting a total of 639 arrhythmias, including atrioventricular reciprocating tachycardia (AVRT), atrioventricular nodal reentrant tachycardia (AVNRT), atrial tachycardia (AT), atrial fibrillation (AF), premature ventricular contractions (PVCs), and ventricular tachycardia (VT). We perform fluoroless ablations using intracardiac electrograms, electroanatomic mapping, and for most cases intracardiac echocardiography. Our experience includes exclusively endocardial cardiac ablations. The mean follow-up was 20.5 months. Recurrence rate for AVRT was 6.5%, for AVNRT 2.5%, for macro-reentrant AT 6.4%, for focal AT 5.4%, for AF 22.6%, for PVC 6.7%, and for VT 21.4%. Major complications occurred in five patients (1.0%); minor complications occurred in three patients (0.6%). No deaths occurred. Fluoroscopy was used in one instance, for 0.3 minutes, to confirm venous access. Completely fluoroless catheter ablations may be routinely performed for all endocardial ablations without compromising safety, efficacy, or procedural duration. © 2017 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals, Inc.

  11. [Management of patients with arrhythmias undergoing thoracic surgery].

    PubMed

    Ishibashi, H; Okubo, K

    2012-07-01

    Recentry, surgical candidates have become older and have more surgical risk factors, perioperative patient management become more important than before. In the patients with significant arrhythmia observed in the preoperative period, examination of the baseline heart disease, i.e. myocardial ischemia or congestive heart failure, is mandatory and, if necessary, adequate treatment such as defibrillator, the implantation of a pacemaker, anticoagulation therapy, or other medical therapy should be performed. In the patients with atrial fibrillation, clinical prediction rules such as the congestive heart failure, hypertension, age>75, diabetes, previous stroke or transient ischemic attack (TIA) [CHADS 2] score have been developed to identify those patients at highest risk for thrombo-embolism and can be used when assessing the need for bridging anticoagulation by heparin prior to surgery. The electrical stimulus from electrocautery may inhibit demand pacemakers or may reprogram the pacemaker. An asynchronous or non-sensing pacemaker mode is recommended in patients who are pacemaker dependent and whose underlying rhythm is unreliable. The device has to be checked to ensure appropriate programming and sensing pacing thresholds after surgery. The implantable cardioverter defibrillator should be turned off during surgery and switched on in the recovery phase before discharge to the ward.

  12. Development and validation of a new Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) with focus on symptom burden

    PubMed Central

    2012-01-01

    Background Arrhythmias can appear with a variety of symptoms, all from vague to pronounced and handicapping symptoms. Therefore, patient-reported outcomes (PROs) concerning symptom burden are important to assess and take into consideration in the care and treatment of patients with arrhythmias. The main purpose was to develop and validate a disease-specific questionnaire evaluating symptom burden in patients with different forms of arrhythmias. Methods A literature review was conducted and arrhythmia patients were interviewed. Identified symptoms were evaluated by an expert panel consisting of cardiologists and nurses working daily with arrhythmia patients. SF-36 and Symptoms Checklist (SCL) were used in the validation of the new questionnaire Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA). Homogeneity was evaluated with Spearman´s correlations and Cronbach´s alpha coefficient (α) was used to evaluate internal consistency. Construct validity was evaluated using item-total correlations and convergent and discriminant validity. For this, Spearman´s correlations were calculated between the ASTA symptom scale, SCL and SF-36. Concurrent validity was validated by Spearman´s correlations between the ASTA symptom scale and SCL. Results The correlations between the different items in the ASTA symptom scale showed generally sufficient homogeneity. Cronbach´s coefficient was found to be satisfactory (α = 0.80; lower bound 95 % CI for α = 0.76). Construct validity was supported by item-total correlations where all items in the symptom scale were sufficiently correlated (≥0.3). Convergent and discriminant validity was supported by the higher correlations to the arrhythmia-specific SCL compared to the generic SF-36. Concurrent validity was evaluated and there were sufficiently, but not extremely strong correlations found between the ASTA symptom scale and SCL. Conclusions The nine items of the ASTA symptom scale were found to have good

  13. Carbon monoxide and lethal arrhythmias. Research report, Jul 85-Jan 89

    SciTech Connect

    Farber, J.P.; Schwartz, P.J.; Vanoli, E.; Stramba-Badiale, M.

    1990-01-01

    The effect of acute exposure to carbon monoxide on ventricular arrhythmias was studied in dogs with a healed anterior myocardial infarction. The combination of mild exercise and acute myocardial ischemia induces ventricular fibrillation in 60 percent of the animals. Dogs that develop ventricular fibrillation are considered at high risk for sudden death and are defined as susceptible; dogs that survive the test without fatal arrhythmia are considered at low risk and are defined as 'resistant.' The effects of carboxyhemoglobin levels ranging from 5 to 15 percent were tested in resistant and susceptible dogs. A trend toward higher heart rates was observed at rest and during exercise in both resistant and susceptible dogs at all levels of carboxyhemoglobin, although significant differences were observed only with 15 percent carboxyhemoglobin. In resistant animals, in which acute myocardial ischemia is typically associated with bradycardia even under the control condition, the reflex response occurred earlier and was augmented after exposure to carbon monoxide. In both resistant and susceptible dogs, carbon monoxide exposure induced a worsening of ventricular arrhythmias in a minority of cases. The worsening was not reproducible in subsequent trials. These data indicate that acute exposure to carbon monoxide is seldom arrhythmogenic in dogs that have survived myocardial infarction. Nevertheless, the observation that carbon monoxide exposure increases heart rate at rest and during moderate exercise may have clinical implications relevant to patients with coronary artery disease.

  14. A feasibility study of arrhythmia risk prediction in patients with myocardial infarction and preserved ejection fraction.

    PubMed

    Deng, Dongdong; Arevalo, Hermenegild J; Prakosa, Adityo; Callans, David J; Trayanova, Natalia A

    2016-12-01

    To predict arrhythmia susceptibility in myocardial infarction (MI) patients with left ventricular ejection fraction (LVEF)  >35% using a personalized virtual heart simulation approach. A total of four contrast enhanced magnetic resonance imaging (MRI) datasets of patient hearts with MI and average LVEF of 44.0 ± 2.6% were used in this study. Because of the preserved LVEF, the patients were not indicated for implantable cardioverter defibrillator (ICD) insertion. One patient had spontaneous ventricular tachycardia (VT) prior to the MRI scan; the others had no arrhythmic events. Simulations of arrhythmia susceptibility were blind to clinical outcome. Models were constructed from patient MRI images segmented to identify myocardium, grey zone, and scar based on pixel intensity. Grey zone was modelled as having altered electrophysiology. Programmed electrical stimulation (PES) was performed to assess VT inducibility from 19 bi-ventricular sites in each heart model. Simulations successfully predicted arrhythmia risk in all four patients. For the patient with arrhythmic event, in-silico PES resulted in VT induction. Simulations correctly predicted that VT was non-inducible for the three patients with no recorded VT events. Results demonstrate that the personalized virtual heart simulation approach may provide a novel risk stratification modality to non-invasively and effectively identify patients with LVEF  >35% who could benefit from ICD implantation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

  15. Small-conductance Ca2+ -activated K+ channels and cardiac arrhythmias.

    PubMed

    Zhang, Xiao-Dong; Lieu, Deborah K; Chiamvimonvat, Nipavan

    2015-08-01

    Small-conductance Ca2+ -activated K+ (SK, KCa2) channels are unique in that they are gated solely by changes in intracellular Ca2+ and, hence, function to integrate intracellular Ca2+ and membrane potentials on a beat-to-beat basis. Recent studies have provided evidence for the existence and functional significance of SK channels in the heart. Indeed, our knowledge of cardiac SK channels has been greatly expanded over the past decade. Interests in cardiac SK channels are further driven by recent studies suggesting the critical roles of SK channels in human atrial fibrillation, the SK channel as a possible novel therapeutic target in atrial arrhythmias, and upregulation of SK channels in heart failure in animal models and in human heart failure. However, there remain critical gaps in our knowledge. Specifically, blockade of SK channels in cardiac arrhythmias has been shown to be both antiarrhythmic and proarrhythmic. This contemporary review provides an overview of the literature on the role of cardiac SK channels in cardiac arrhythmias and serves as a discussion platform for the current clinical perspectives. At the translational level, development of SK channel blockers as a new therapeutic strategy in the treatment of atrial fibrillation and the possible proarrhythmic effects merit further considerations and investigations.

  16. Benchmarking ventricular arrhythmias in the mouse--revisiting the 'Lambeth Conventions' 20 years on.

    PubMed

    Huggins, Catherine E; Bell, James R; Pepe, Salvatore; Delbridge, Lea M D

    2008-12-01

    The isolated Langendorff-mode perfused heart has become a valuable experimental model, used extensively to examine cardiac function, pathophysiology and pharmacology. For the clinical cardiologist an ECG is often a simple practicality, however in experimental circumstances, particularly with ex vivo murine hearts it is not always possible to obtain an ECG due to experimental recording constraints. However, the mechanical record of ventricular contractile function can be highly informative in relation to electrical state. It is difficult though to achieve consistency in these evaluations of arrhythmia as a validated common reference framework is lacking. In 1988, a group of investigators developed the 'Lambeth Conventions'--a standardised reference for the definition and classification of arrhythmias in animal experimental models of ischaemia, infarction and reperfusion in vivo. Now, two decades later it is timely to revisit the Lambeth Conventions, and to update the guidelines in the context of the marked increase in murine heart study in experimental cardiac pathophysiology. Here we describe an adjunct to the Lambeth Conventions for the reporting of ventricular arrhythmias post-ischaemia in ex vivo mouse hearts when ECG recordings are not employed. Of seven discrete and identifiable patterns of mechanical dysrhythmia observed in reperfusion, five could be classified using conventional ECG terminology: ventricular premature beat, bigeminy, trigeminy, ventricular tachycardia and ventricular fibrillation. Two additional rhythm variations detected from the pressure record are described (potentiated contraction and alternans).

  17. Supraventricular Arrhythmias after Thoracotomy: Is There a Role for Autonomic Imbalance?

    PubMed Central

    Simeoforidou, Marina; Stamoulis, Konstantinos; Bareka, Metaxia

    2013-01-01

    Supraventricular arrhythmias are common rhythm disturbances following pulmonary surgery. The overall incidence varies between 3.2% and 30% in the literature, while atrial fibrillation is the most common form. These arrhythmias usually have an uneventful clinical course and revert to normal sinus rhythm, usually before patent's discharge from hospital. Their importance lies in the immediate hemodynamic consequences, the potential for systemic embolization and the consequent long-term need for prophylactic drug administration, and the increased cost of hospitalization. Their incidence is probably related to the magnitude of the performed operative procedure, occurring more frequently after pneumonectomy than after lobectomy. Investigators believe that surgical factors (irritation of the atria per se or on the ground of chronic inflammation of aged atria), direct injury to the anatomic structure of the autonomic nervous system in the thoracic cavity, and postthoracotomy pain may contribute independently or in association with each other to the development of these arrhythmias. This review discusses currently available information about the potential mechanisms and risk factors for these rhythm disturbances. The discussion is in particular focused on the role of postoperative pain and its relation to the autonomic imbalance, in an attempt to avoid or minimize discomfort with proper analgesia utilization. PMID:24235971

  18. The Role of Biologically Active Ingredients from Natural Drug Treatments for Arrhythmias in Different Mechanisms

    PubMed Central

    Li, Jie; Hu, Dan; Song, Xiaoli; Han, Tao

    2017-01-01

    Arrhythmia is a disease that is caused by abnormal electrical activity in the heart rate or rhythm. It is the major cause of cardiovascular morbidity and mortality. Although several antiarrhythmic drugs have been used in clinic for decades, their application is often limited by their adverse effects. As a result, natural drugs, which have fewer side effects, are now being used to treat arrhythmias. We searched for all articles on the role of biologically active ingredients from natural drug treatments for arrhythmias in different mechanisms in PubMed. This study reviews 19 natural drug therapies, with 18 active ingredient therapies, such as alkaloids, flavonoids, saponins, quinones, and terpenes, and two kinds of traditional Chinese medicine compound (Wenxin-Keli and Shensongyangxin), all of which have been studied and reported as having antiarrhythmic effects. The primary focus is the proposed antiarrhythmic mechanism of each natural drug agent. Conclusion. We stress persistent vigilance on the part of the provider in discussing the use of natural drug agents to provide a solid theoretical foundation for further research on antiarrhythmia drugs. PMID:28497050

  19. A differential diagnosis of inherited endocrine tumors and their tumor counterparts

    PubMed Central

    Toledo, Sergio P. A.; Lourenço, Delmar M.; Toledo, Rodrigo A.

    2013-01-01

    Inherited endocrine tumors have been increasingly recognized in clinical practice, although some difficulties still exist in differentiating these conditions from their sporadic endocrine tumor counterparts. Here, we list the 12 main topics that could add helpful information and clues for performing an early differential diagnosis to distinguish between these conditions. The early diagnosis of patients with inherited endocrine tumors may be performed either clinically or by mutation analysis in at-risk individuals. Early detection usually has a large impact in tumor management, allowing preventive clinical or surgical therapy in most cases. Advice for the clinical and surgical management of inherited endocrine tumors is also discussed. In addition, recent clinical and genetic advances for 17 different forms of inherited endocrine tumors are briefly reviewed. PMID:23917672

  20. Paternal inheritance of mitochondria in Chlamydomonas.

    PubMed

    Nakamura, Soichi

    2010-03-01

    To analyze mitochondrial DNA (mtDNA)inheritance, differences in mtDNA between Chlamydomonas reinhardtii and Chlamydomonas smithii, respiration deficiency and antibiotic resistance were used to distinguish mtDNA origins. The analyses indicated paternal inheritance. However, these experiments raised questions regarding whether paternal inheritance occurred normally.Mitochondrial nucleoids were observed in living zygotes from mating until 3 days after mating and then until progeny formation. However, selective disappearance of nucleoids was not observed. Subsequently, experimental serial backcrosses between the two strains demonstrated strict paternal inheritance. The fate of mt+ and mt- mtDNA was followed using the differences in mtDNA between the two strains. The slow elimination of mt+ mtDNA through zygote maturation in darkness was observed, and later the disappearance of mt+ mtDNA was observed at the beginning of meiosis. To explain the different fates of mtDNA, methylation status was investigated; however, no methylation was detected. Variously constructed diploid cells showed biparental inheritance. Thus, when the mating process occurs normally, paternal inheritance occurs. Mutations disrupting mtDNA inheritance have not yet been isolated. Mutations that disrupt maternal inheritance of chloroplast DNA (cpDNA) do not disrupt inheritance of mtDNA. The genes responsible for mtDNA inheritance are different from those of chloroplasts.

  1. Atypical mitochondrial inheritance patterns in eukaryotes.

    PubMed

    Breton, Sophie; Stewart, Donald T

    2015-10-01

    Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

  2. Risk assessment of ventricular arrhythmia using new parameters based on high resolution body surface potential mapping.

    PubMed

    Fereniec, Malgorzata; Stix, Gunter; Kania, Michal; Mroczka, Tomasz; Janusek, Dariusz; Maniewski, Roman

    2011-02-25

    The effective screening of myocardial infarction (MI) patients threatened by ventricular tachycardia (VT) is an important issue in clinical practice, especially in the process of implantable cardioverter-defibrillator (ICD) therapy recommendation. This study proposes new parameters describing depolarization and repolarization inhomogeneity in high resolution body surface potential maps (HR BSPM) to identify MI patients threatened by VT. High resolution ECGs were recorded from 64 surface leads. Time-averaged HR BSPMs were used. Several parameters for arrhythmia risk assessment were calculated in 2 groups of MI patients: those with and without documented VT. Additionally, a control group of healthy subjects was studied. To assess the risk of VT, the following parameters were proposed: correlation coefficient between STT and QRST integral maps (STT_QRST_CORR), departure index of absolute value of STT integral map (STT_DI), and departure index of absolute value of T-wave shape index (TSI_DI). These new parameters were compared to known parameters: QRS width, QT interval, QT dispersion, Tpeak-Tend interval, total cosines between QRS complex and T wave, and non-dipolar content of QRST integral maps. STT_DI, TSI_DI, STT_QRST_CORR, QRS width, and QT interval parameters were statistically significant (p ≤ 0.05) in arrhythmia risk assessment. The highest sensitivity was found for the STT_DI parameter (0.77) and the highest specificity for TSI_DI (0.79). Arrhythmia risk is demonstrated by both abnormal spatial distribution of the repolarization phase and changed relationship between depolarization and repolarization phases, as well as their prolongation. The proposed new parameters might be applied for risk stratification of cardiac arrhythmia.

  3. Risk assessment of ventricular arrhythmia using new parameters based on high resolution body surface potential mapping

    PubMed Central

    Fereniec, Malgorzata; Stix, Gunter; Kania, Michal; Mroczka, Tomasz; Janusek, Dariusz; Maniewski, Roman

    2011-01-01

    Summary Background The effective screening of myocardial infarction (MI) patients threatened by ventricular tachycardia (VT) is an important issue in clinical practice, especially in the process of implantable cardioverter-defibrillator (ICD) therapy recommendation. This study proposes new parameters describing depolarization and repolarization inhomogeneity in high resolution body surface potential maps (HR BSPM) to identify MI patients threatened by VT. Material/Methods High resolution ECGs were recorded from 64 surface leads. Time-averaged HR BSPMs were used. Several parameters for arrhythmia risk assessment were calculated in 2 groups of MI patients: those with and without documented VT. Additionally, a control group of healthy subjects was studied. To assess the risk of VT, the following parameters were proposed: correlation coefficient between STT and QRST integral maps (STT_QRST_CORR), departure index of absolute value of STT integral map (STT_DI), and departure index of absolute value of T-wave shape index (TSI_DI). These new parameters were compared to known parameters: QRS width, QT interval, QT dispersion, Tpeak-Tend interval, total cosines between QRS complex and T wave, and non-dipolar content of QRST integral maps. Results STT_DI, TSI_DI, STT_QRST_CORR, QRS width, and QT interval parameters were statistically significant (p≤0.05) in arrhythmia risk assessment. The highest sensitivity was found for the STT_DI parameter (0.77) and the highest specificity for TSI_DI (0.79). Conclusions Arrhythmia risk is demonstrated by both abnormal spatial distribution of the repolarization phase and changed relationship between depolarization and repolarization phases, as well as their prolongation. The proposed new parameters might be applied for risk stratification of cardiac arrhythmia. PMID:21358612

  4. Depression and Risk of Sudden Cardiac Death and Arrhythmias: A Meta-Analysis.

    PubMed

    Shi, Shaobo; Liu, Tao; Liang, Jinjun; Hu, Dan; Yang, Bo

    Depression is an independent risk factor for cardiac events and mortality in individuals with or without cardiovascular disease (CVD), although the underlying mechanisms involved in sudden cardiac death (SCD) and arrhythmias remain unclear. This meta-analysis aimed to assess the relationship between depression and risk of SCD and arrhythmias. We systematically searched MEDLINE, Elsevier, and PsycINFO databases for articles (January 1990 to June 2015) describing the correlation of depression ("depressive symptoms," "depression," or "depressive disorder") with SCD or arrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF], or atrial fibrillation [AF]). Data were meta-analyzed with random-effects models. A total of 17 studies met the inclusion criteria: 4 of SCD (n = 83,659), 8 of VT/VF (n = 4,048), and 5 of AF (n = 31,247). The total sample consisted of 8,533 individuals with and 110,421 individuals without previous CVD. Depression was associated with increased risk of SCD (hazard risk [HR], 1.62; 95% confidence interval [CI], 1.37-1.92; p < .001), VT/VF (HR, 1.47; 95% CI, 1.23-1.76; p < .001) and AF recurrence (HR, 1.88; 95% CI, 1.54-2.30; p < .001). There was no significant association, however, between depression and risk of new-onset AF (HR, 0.96; 95% CI, 0.87-1.04; p = .311). Depression (clinical depression and depressive symptoms) is associated with increased risk of SCD, VT/VF, and AF recurrence. These findings suggest that arrhythmias play an important role in the association between depression and increased mortality in individuals with or without CVD. Systematic evaluation and treatment of depression may contribute to the prevention of lethal cardiac events in the general population and in high-risk individuals with CVD.

  5. Performance of an automatic arrhythmia classification algorithm: comparison to the ALTITUDE electrophysiologist panel adjudications.

    PubMed

    Mahajan, Deepa; Dong, Yanting; Saxon, Leslie A; Cha, Yong-Mei; Gilliam, Francis Roosevelt; Asirvatham, Samuel J; Cesario, David A; Jones, Paul W; Seth, Milan; Powell, Brian D

    2014-07-01

    Adjudication of thousands of implantable cardioverter defibrillator (ICD)-treated arrhythmia episodes is labor intensive and, as a result, is most often left undone. The objective of this study was to evaluate an automatic classification algorithm for adjudication of ICD-treated arrhythmia episodes. The algorithm uses a machine learning algorithm and was developed using 776 arrhythmia episodes. The algorithm was validated on 131 dual-chamber ICD shock episodes from 127 patients adjudicated by seven electrophysiologists (EPs). Episodes were classified by panel consensus as ventricular tachycardia/ventricular fibrillation (VT/VF) or non-VT/VF, with the resulting classifications used as the reference. Subsequently, each episode electrogram (EGM) data was randomly assigned to three EPs without the atrial lead information, and to three EPs with the atrial lead information. Those episodes were also classified by the automatic algorithm with and without atrial information. Agreement with the reference was compared between the three EPs consensus group and the algorithm. The overall agreement with the reference was similar between three-EP consensus and the algorithm for both with atrial EGM (94% vs 95%, P = 0.87) and without atrial EGM (90% vs 91%, P = 0.91). The odds of accurate adjudication, after adjusting for covariates, did not significantly differ between the algorithm and EP consensus (odds ratio 1.02, 95% confidence interval: 0.97-1.06). This algorithm performs at a level comparable to an EP panel in the adjudication of arrhythmia episodes treated by both dual- and single-chamber ICDs. This type of algorithm has the potential for automated analysis of clinical ICD episodes, and adjudication of EGMs for research studies and quality analyses. ©2014 Wiley Periodicals, Inc.

  6. Ventricular arrhythmias originating from the aortomitral continuity: an uncommon variant of left ventricular outflow tract tachycardia.

    PubMed

    Chen, Jian; Hoff, Per Ivar; Rossvoll, Ole; De Bortoli, Alessandro; Solheim, Eivind; Sun, Lizhi; Schuster, Peter; Larsen, Terje; Ohm, Ole-Jørgen

    2012-03-01

    Ventricular arrhythmias arising from the fibrous rings have been demonstrated, but knowledge about the aortomitral continuity (AMC) as a source of the arrhytmias is still limited. The objective is to describe the characteristics of ventricular arrhythmias originating from the AMC in patients without structural heart disease. Ten patients with ventricular tachycardia (VT) and/or premature ventricular contractions, who had been successfully treated by catheter ablation at the AMC beneath the aortic valve, were enrolled. Clinical data and electrocardiographic characteristics were analysed. Three of the 10 patients had previously registered episodes of supraventricular tachycardia and had undergone catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT). In four patients with anterior AMC location, early R/S wave transition was found in the precordial leads, with equal R and S amplitudes in V2, rS in V1, and R in V3. In six patients whose VT arose from the middle part of the AMC, we demonstrated a special ('rebound') transition pattern, with which equal R and S amplitudes occurred in V2, and high R waves in V1 and V3. In the anterior AMC location, the S/R ratios in leads V1 and V2 were >1 and statistically significantly higher than those located in the middle (V1: 1.59 vs. 0.23, P< 0.001; V2: 1.52 vs. 0.41, P< 0.01). We report a series of ventricular arrhythmias arising from the AMC with different R/S wave transition patterns in the precordial leads on the electrocardiogram. There may be a relationship between ventricular arrhythmias from AMC and AVNRT.

  7. Digenic inheritance in medical genetics.

    PubMed

    Schäffer, Alejandro A

    2013-10-01

    Digenic inheritance (DI) is the simplest form of inheritance for genetically complex diseases. By contrast with the thousands of reports that mutations in single genes cause human diseases, there are only dozens of human disease phenotypes with evidence for DI in some pedigrees. The advent of high-throughput sequencing (HTS) has made it simpler to identify monogenic disease causes and could similarly simplify proving DI because one can simultaneously find mutations in two genes in the same sample. However, through 2012, I could find only one example of human DI in which HTS was used; in that example, HTS found only the second of the two genes. To explore the gap between expectation and reality, I tried to collect all examples of human DI with a narrow definition and characterise them according to the types of evidence collected, and whether there has been replication. Two strong trends are that knowledge of candidate genes and knowledge of protein-protein interactions (PPIs) have been helpful in most published examples of human DI. By contrast, the positional method of genetic linkage analysis, has been mostly unsuccessful in identifying genes underlying human DI. Based on the empirical data, I suggest that combining HTS with growing networks of established PPIs may expedite future discoveries of human DI and strengthen the evidence for them.

  8. Cardiac arrhythmias induced by chloral hydrate in rhesus monkeys.

    PubMed

    Han, Pengfei; Song, Haibo; Yang, Pingliang; Xie, Huiqi; Kang, Y James

    2011-06-01

    Chloral hydrate has been long used as a safe sedative and hypnotic drug in humans. However, reports on its cardiovascular adverse effects have been published from time to time. The present study was undertaken to use Rhesus monkeys as a model to define the dose regiment of chloral hydrate at which cardiac arrhythmias can be induced and the consequences of the cardiac events. Male Rhesus monkeys of 2-3 years old were intravenously infused with chloral hydrate starting at 50 mg/kg with an increasing increment of 25 mg/kg until the occurrence of cardiac arrhythmias. In addition, a traditional up-and-down dosing procedure was applied to define a single dose level at which cardiac arrhythmias can be induced. The data obtained showed that when the sequentially escaladed dose reached 125 mg/kg, cardiac arrhythmias occurred in all monkeys tested. The single effective dose to cause cardiac arrhythmias calculated from the crossover analysis was 143 ± 4 mg/kg. This value would be equivalent to 68.6 ± 1.9 mg/kg for children and 46.4 ± 1.3 mg/kg for adults in humans. Under either multiple or single dose condition, cardiac arrhythmias did not occur before 40 min after the onset of anesthesia induced by chloral hydrate. Cardiac arrhythmias were recovered without help at the end of the anesthesia in most cases, but also continued after the regain of consciousness in some cases. The cardiac arrhythmias were accompanied with compromised cardiac function including suppressed fractional shortening and ejection fraction. This study thus suggests that cautions need to be taken when chloral hydrate is used above certain levels and beyond a certain period of anesthesia, and cardiac arrhythmias induced by chloral hydrate need to be closely monitored because compromised cardiac function may occur simultaneously. In addition, patients with cardiac arrhythmias induced by chloral hydrate should be monitored even after they are recovered from the anesthesia.

  9. Clinical management and prevention of sudden cardiac death.

    PubMed

    Yousuf, Omair; Chrispin, Jonathan; Tomaselli, Gordon F; Berger, Ronald D

    2015-06-05

    Despite the revolutionary advancements in the past 3 decades in the treatment of ventricular tachyarrhythmias with device-based therapy, sudden cardiac death (SCD) remains an enormous public health burden. Survivors of SCD are generally at high risk for recurrent events. The clinical management of such patients requires a multidisciplinary approach from postresuscitative care to a thorough cardiovascular investigation in an attempt to identify the underlying substrate, with potential to eliminate or modify the triggers through catheter ablation and ultimately an implantable cardioverter-defibrillator (ICD) for prompt treatment of recurrences in those at risk. Early recognition of low left ventricular ejection fraction as a strong predictor of death and association of ventricular arrhythmias with sudden death led to significant investigation with antiarrhythmic drugs. The lack of efficacy and the proarrhythmic effects of drugs catalyzed the development and investigation of the ICD through several major clinical trials that proved the efficacy of ICD as a bedrock tool to detect and promptly treat life-threatening arrhythmias. The ICD therapy is routinely used for primary prevention of SCD in patients with cardiomyopathy and high risk inherited arrhythmic conditions and secondary prevention in survivors of sudden cardiac arrest. This compendium will review the clinical management of those surviving SCD and discuss landmark studies of antiarrhythmic drugs, ICD, and cardiac resynchronization therapy in the primary and secondary prevention of SCD.

  10. Percutaneous epicardial ablation in ventricular arrhythmias.

    PubMed

    Galvão Santos, Pedro; Cavaco, Diogo; Adragão, Pedro; Scanavacca, Mauricio; Reis Santos, Katya; Belo Morgado, Francisco; Carmo, Pedro; Costa, Francisco; Bernardo, Ricardo; Nunes, Manuela; Abecasis, Miguel; Neves, José; Mendes, Miguel

    2014-05-01

    Reentrant circuits of ventricular tachycardia may involve not only the endocardium but also the epicardium. Epicardial ablation can be useful in these situations. The aim of this study was to assess efficacy, safety and complications in a series of consecutive patients who underwent ablation of ventricular tachycardia with epicardial mapping. The study included all patients undergoing ventricular tachycardia ablation with epicardial mapping from 2004 to 2012. Of a total of 95 ablations, an epicardial approach was attempted in nine patients, eight male, mean age 58±12 years. Endocardial mapping was performed in all patients previously or simultaneously. The etiology of the arrhythmia was non-ischemic in eight patients and ischemic in one. We compared the number of events in the six months prior to the epicardial procedure and six months after. Percutaneous epicardial access was achieved in eight patients. In one case it was not possible due to the presence of adhesions. In none of the patients was the procedure repeated and there were no major complications during hospitalization. In a mean follow-up of 3.5±1.2 years, one patient suffered stroke; there were no other medium-to-long-term complications and the number of ventricular tachycardia episodes was reduced in all patients after ablation. Epicardial radiofrequency ablation of ventricular tachycardia was effective in reducing morbidity in eight patients, with a low risk of complications in the short and medium-to-long term. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  11. [Magnetic navigation for ablation of cardiac arrhythmias].

    PubMed

    Chen, Jian; Hoff, Per Ivar; Solheim, Eivind; Schuster, Peter; Off, Morten Kristian; Ohm, Ole-Jørgen

    2010-08-12

    The first use of magnetic navigation for radiofrequency ablation of supraventricular tachycardias, was published in 2004. Subsequently, the method has been used for treatment of most types of tachyarrhythmias. This paper provides an overview of the method, with special emphasis on usefulness of a new remote-controlled magnetic navigation system. The paper is based on our own scientific experience and literature identified through a non-systematic search in PubMed. The magnetic navigation system consists of two external electromagnets (to be placed on opposite sides of the patient), which guide an ablation catheter (with a small magnet at the tip of the catheter) to the target area in the heart. The accuracy of this procedure is higher than that with manual navigation. Personnel can be quickly trained to use remote magnetic navigation, but the procedure itself is time-consuming, particularly for patients with atrial fibrillation. The major advantage is a considerably lower radiation burden to both patient and operator, in some studies more than 50 %, and a corresponding reduction in physical strain on the operator. The incidence of procedure-related complications seems to be lower than that observed with use of manually operated ablation catheters. Work is ongoing to improve magnetic ablation catheters and methods that can simplify mapping procedures and improve efficacy of arrhythmia ablation. The basic cost for installing a complete magnetic navigation laboratory may be three times that of a conventional electrophysiological laboratory. The new magnetic navigation system has proved to be applicable during ablation for a variety of tachyarrhythmias, but is still under development.

  12. Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants.

    PubMed

    Boehnert, M T; Lovejoy, F H

    1985-08-22

    There is a need for a rapid predictor of potential clinical severity to guide therapy in patients with an acute overdose of tricyclic antidepressant drugs. We performed a prospective study of 49 such patients to observe the associations among serum drug levels, maximal limb-lead QRS duration, and the incidence of seizures and ventricular arrhythmias. Patients were divided into two groups on the basis of maximal limb-lead QRS duration. Group A (13 patients) had a duration of less than 0.10 second, and Group B (36 patients) had a QRS duration of 0.10 second or longer. No seizures or ventricular arrhythmias occurred in Group A. In Group B there was a 34 per cent incidence of seizures and a 14 per cent incidence of ventricular arrhythmias. All patients survived. Serum drug levels failed to predict the risk of seizures or ventricular arrhythmias accurately. Seizures occurred at any QRS duration of 0.10 second or longer (P less than 0.05), but ventricular arrhythmias were seen only with a QRS duration of 0.16 second or longer (P less than 0.0005). We conclude that determination of the maximal limb-lead QRS duration predicts the risk of seizures and ventricular arrhythmias in acute overdose with tricyclic antidepressants. Serum drug levels are not of predictive value.

  13. The role of EP-guided therapy in ventricular arrhythmias: beta-blockers, sotalol, and ICD's.

    PubMed

    Capucci, A; Aschieri, D; Villani, G Q

    2000-01-01

    Arrhythmic death can be reduced by antiarrhythmic drugs to a range of 24%. Electrophysiologic study by testing noninducibility of ventricular arrhythmia represents the classic method for evaluating the effectiveness of drug therapy. Several clinical studies have shown thaat sotalol suppresses VT induction and prevents arrhythmias recurrences at long term follow-up in 23% to 67% of patients. The efficacy of sotalol EP guided therapy in preventing VT/VF is not necessarily related to prevention of sudden death. In the ESVEM study the superiority of d,l-sotalol to other antiarrhythmic drugs was confirmed. The response to programmed ventricular stimulation was found to be strongly predictive for arrhythmia free state while the failure of sotalol therapy to suppress VT at the EP study was associated with an high recurrence rate (40%). However, EP study failes to predict freedom from sudden death. The beta-blocking activity of racemic sotalol may account for some of the observed survival benefit.Beta-blockers therapy reduces mortality in patients after myocardial infarction primarily by a reduction of sudden death. A reduction of death, worsening heart failure and life threatening ventricular arrhythmias was shown in a recent study on carvedilol. In the prospective study of Steinbeck the EP guided-therapy did not improve the overall outcome when compared to metoprolol. Suppression of inducible arrhythmias by antiarrhythmic drugs was associated with a better outcome. The effectiveness of defibrillator therapy in reducing overall mortality, has been uncertain since great clinical trials have been concluded. MADIT, AVID and CASH trials confirmed the superiority of ICD therapy over antiarrhythmic drugs therapy: ICD should be considered the first choice therapy in post-cardiac arrest patients. The ongoing BEST Trial will give us further responses about the interaction between EP study and metoprolol effect compared to ICD in patients post myocardial infarction also focusing on

  14. Ventricular arrhythmias originating from papillary muscles in the right ventricle.

    PubMed

    Crawford, Thomas; Mueller, Giesela; Good, Eric; Jongnarangsin, Krit; Chugh, Aman; Pelosi, Frank; Ebinger, Matthew; Oral, Hakan; Morady, Fred; Bogun, Frank

    2010-06-01

    Premature ventricular complexes (PVCs) and ventricular tachycardia (VT) with origin in the left ventricular papillary muscle have recently been described. There are no prior studies describing the characteristics of the ventricular arrhythmias (VAs) arising from the right ventricular papillary muscles (RV PAPs). Among 169 consecutive patients who underwent a catheter ablation of a VA, eight patients with RV PAPs were identified (seven men, mean PVC burden 17.0% +/- 20%). A control group consisted of 10 consecutive patients with arrhythmias originating from the right ventricle (10 women, mean PVC burden 13.9% +/- 12.8%). All patients underwent cardiac magnetic resonance imaging (MRI). Intracardiac echocardiography was used to identify the site of origin of the RV PAP arrhythmias. The site of origin of a total of 15 distinct PAP arrhythmias was mapped to the following papillary muscles: posterior (n = 3), anterior (n = 4), or septal (n = 8). Postablation echocardiograms did not reveal new tricuspid regurgitation. During a mean follow-up of 8 +/- 9 months, there were no adverse outcomes. The PVC burden was reduced from 17% +/- 20% preablation to 0.6% +/- 0.8% postablation in the RV PAP group and from 13.9% +/- 12.8% to 0.3% +/- 0.4% in the control group. The QRS complex was broader in the RV PAP group compared with in the control group (163 +/- 21 ms vs. 141 +/- 22 ms; P = .02). RV PAP arrhythmias originating from the posterior or anterior RV PAPs more often had a superior axis with late R-wave transition (>V4) compared with septal RV RAP arrhythmias, which more often had an inferior axis with an earlier R-wave transition in the precordial leads (arrhythmias. Copyright (c) 2010 Heart Rhythm Society. All rights reserved.

  15. Pilot evaluation of an integrated monitor-adhesive patch for long-term cardiac arrhythmia detection in India.

    PubMed

    Shrivastav, Maneesh; Padte, Sanjay; Arora, Vanita; Biffi, Mauro

    2014-01-01

    Electrocardiographic monitoring represents one of the most reliable and time-tested methods for reducing ambiguity in cardiac arrhythmia diagnosis. In India, the resting ECG is generally the first tool of choice for in-clinic diagnosis. The external loop recorder (ELR) is another useful tool that compounds the advantages of traditional tools by coupling ambulatory monitoring with a long-term window. Thus, the objective was to test the use of a 7-day ELR for arrhythmia diagnosis in India for a broad range of presenting symptoms. In this study set in the Indian healthcare environment, an auto-triggered, wireless patch-type ELR was used with 125 patients (62.5 ± 16.7 years, 76 males) presenting a broad range of symptoms. Eighty percent of the symptoms were related to syncope, presyncope or palpitations. Patients were administered an ELR for 7-28 days depending on the physician's prescription. Prespecified significant arrhythmias included sinus pause >2 s, symptomatic bradycardia <40 b.p.m., second-degree (and higher) AV block, complete heart block, ventricular fibrillation, sustained/nonsustained ventricular tachycardia (>3 beats), atrial fibrillation (chronic or paroxysmal), atrial flutter and supraventricular tachycardia (SVT) >130 b.p.m. Diagnostic yield was 38% when a stringent tabulation methodology considering only clinically significant arrhythmia was used. When first-degree AV block, premature atrial and ventricular beats, couplets (both atrial and ventricular in origin), bigeminy or trigeminy, or sudden changes in rate (noted as sinus arrhythmia) were included in the calculation, diagnostic yield was 80%. Patient compliance was 98%; patients wore the patch for the entire prescribed monitoring period without disruption. Seventy percent of the reported symptoms corresponded with an arrhythmia. Use of the ELR led to therapy change in 24% of patients: 15 patients went on to receive an implantable cardioverter defibrillator or pacemaker, 4 received ablation

  16. Detection and Prevention of Cardiac Arrhythmias During Space Flight

    NASA Technical Reports Server (NTRS)

    Pillai, Dilip; Rosenbaum, David S.; Liszka, Kathy J.; York, David W.; Mackin, Michael A.; Lichter, Michael J.

    2004-01-01

    There have been reports suggesting that long-duration space flight might lead to an increased risk of potentially serious heart rhythm disturbances. If space flight does, in fact, significantly decrease cardiac electrical stability, the effects could be catastrophic, potentially leading to sudden cardiac death. It will be important to determine the mechanisms underlying this phenomenon in order to prepare for long-term manned lunar and interplanetary missions and to develop appropriate countermeasures. Our hypothesis is that prolonged exposure to microgravity will alter T wave alternans measurements, decrease heart rate variance, increase QT dispersion, decrease heart rate recovery and alter QT restitution curve. A recently published study has shown that long duration spaceflights prolong cardiac conduction and repolarization. They concluded that long duration flight is associated with QT interval prolongation and may increase arrhythmia susceptibility. We propose using computer technology as a noninvasive clinical tool to detect and study clinically significant TWA during standard exercise testing using electrode systems specifically adapted for the purpose of obtaining and measuring TWA. A population of approximately 15 healthy men and 5 healthy women subjects, representative of the astronaut cohort will be asked to voluntarily participate in this study. Their blood pressure and ECG/TWA will be measured pre-flight and in-flight. Prior to flight, subjects will be asked to participate in an orientation session. Still photos will be taken of the skin where the conductive gel is used for the multi-segment sensors. Photos will be recorded preflight, immediately postflight, and several times during the proceeding week until it has been determined that any skin reaction has disappeared or that no rash is present and will not appear.

  17. Inherited Determinants of Ovarian Cancer Survival

    PubMed Central

    Goode, Ellen L.; Maurer, Matthew J.; Sellers, Thomas A.; Phelan, Catherine M.; Kalli, Kimberly R.; Fridley, Brooke L.; Vierkant, Robert A.; Armasu, Sebastian M.; White, Kristin L.; Keeney, Gary L.; Cliby, William A.; Rider, David N.; Kelemen, Linda E.; Jones, Monica B.; Peethambaram, Prema P.; Lancaster, Johnathan M.; Olson, Janet E.; Schildkraut, Joellen M.; Cunningham, Julie M.; Hartmann, Lynn C.

    2010-01-01

    Purpose Due to variation of outcome among cases, we sought to examine whether overall survival in ovarian cancer was associated with common inherited variants in 227 candidate genes from ovarian cancer-related pathways including angiogenesis, inflammation, detoxification, glycosylation, one-carbon transfer, apoptosis, cell cycle regulation, and cellular senescence. Experimental Design Blood samples were obtained from 325 women with invasive epithelial ovarian cancer diagnosed at the Mayo Clinic from 1999 to 2006. During a median follow-up of 3.8 years (range, 0.1 – 8.6 years), 157 deaths were observed. Germline DNA was analyzed at 1,416 single nucleotide polymorphisms (SNPs). For all patients, and for 203 with serous subtype, we assessed the overall significance of each gene and pathway, and estimated risk of death via hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for known prognostic factors. Results Variation within angiogenesis was most strongly associated with survival time overall (p=0.03) and among patients with serous cancer (p=0.05), particularly for EIF2B5 rs4912474 (all patients HR 0.69, 95% CI 0.54-0.89, p=0.004), VEGFC rs17697305 (serous subtype HR 2.29, 95% CI 1.34-3.92, p=0.003), and four SNPs in VHL. Variation within the inflammation pathway was borderline significant (all patients, p=0.09), and SNPs in CCR3, IL1B, IL18, CCL2, and ALOX5 which correlated with survival time are worthy of follow-up. Conclusion An extensive multiple-pathway assessment found evidence that inherited differences may play a role in outcome of ovarian cancer patients, particularly in genes within the angiogenesis and inflammation pathways. Our work supports efforts to target such mediators for therapeutic gain. PMID:20103664

  18. Calcium Ions in Inherited Cardiomyopathies.

    PubMed

    Deftereos, Spyridon; Papoutsidakis, Nikolaos; Giannopoulos, Georgios; Angelidis, Christos; Raisakis, Konstantinos; Bouras, Georgios; Davlouros, Periklis; Panagopoulou, Vasiliki; Goudevenos, John; Cleman, Michael W; Lekakis, John

    2016-01-01

    Inherited cardiomyopathies are a known cause of heart failure, although the pathways and mechanisms leading from mutation to the heart failure phenotype have not been elucidated. There is strong evidence that this transition is mediated, at least in part, by abnormal intracellular Ca(2+) handling, a key ion in ventricular excitation, contraction and relaxation. Studies in human myocytes, animal models and in vitro reconstituted contractile protein complexes have shown consistent correlations between Ca(2+) sensitivity and cardiomyopathy phenotype, irrespective of the causal mutation. In this review we present the available data about the connection between mutations linked to familial hypertrophic (HCM), dilated (DCM) and restrictive (RCM) cardiomyopathy, right ventricular arrhythmogenic cardiomyopathy/dysplasia (ARVC/D) as well as left ventricular non-compaction and the increase or decrease in Ca(2+) sensitivity, together with the results of attempts to reverse the manifestation of heart failure by manipulating Ca(2+) homeostasis.

  19. POPDC1S201F causes muscular dystrophy and arrhythmia by affecting protein trafficking

    PubMed Central

    Schindler, Roland F.R.; Scotton, Chiara; Zhang, Jianguo; Passarelli, Chiara; Ortiz-Bonnin, Beatriz; Simrick, Subreena; Schwerte, Thorsten; Poon, Kar-Lai; Fang, Mingyan; Rinné, Susanne; Froese, Alexander; Nikolaev, Viacheslav O.; Grunert, Christiane; Müller, Thomas; Tasca, Giorgio; Sarathchandra, Padmini; Drago, Fabrizio; Dallapiccola, Bruno; Rapezzi, Claudio; Arbustini, Eloisa; Di Raimo, Francesca Romana; Neri, Marcella; Selvatici, Rita; Gualandi, Francesca; Fattori, Fabiana; Pietrangelo, Antonello; Li, Wenyan; Jiang, Hui; Xu, Xun; Bertini, Enrico; Decher, Niels; Wang, Jun; Brand, Thomas; Ferlini, Alessandra

    2015-01-01

    The Popeye domain–containing 1 (POPDC1) gene encodes a plasma membrane–localized cAMP-binding protein that is abundantly expressed in striated muscle. In animal models, POPDC1 is an essential regulator of structure and function of cardiac and skeletal muscle; however, POPDC1 mutations have not been associated with human cardiac and muscular diseases. Here, we have described a homozygous missense variant (c.602C>T, p.S201F) in POPDC1, identified by whole-exome sequencing, in a family of 4 with cardiac arrhythmia and limb-girdle muscular dystrophy (LGMD). This allele was absent in known databases and segregated with the pathological phenotype in this family. We did not find the allele in a further screen of 104 patients with a similar phenotype, suggesting this mutation to be family specific. Compared with WT protein, POPDC1S201F displayed a 50% reduction in cAMP affinity, and in skeletal muscle from patients, both POPDC1S201F and WT POPDC2 displayed impaired membrane trafficking. Forced expression of POPDC1S201F in a murine cardiac muscle cell line (HL-1) increased hyperpolarization and upstroke velocity of the action potential. In zebrafish, expression of the homologous mutation (popdc1S191F) caused heart and skeletal muscle phenotypes that resembled those observed in patients. Our study therefore identifies POPDC1 as a disease gene causing a very rare autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous group of inherited rare diseases. PMID:26642364

  20. POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking.

    PubMed

    Schindler, Roland F R; Scotton, Chiara; Zhang, Jianguo; Passarelli, Chiara; Ortiz-Bonnin, Beatriz; Simrick, Subreena; Schwerte, Thorsten; Poon, Kar-Lai; Fang, Mingyan; Rinné, Susanne; Froese, Alexander; Nikolaev, Viacheslav O; Grunert, Christiane; Müller, Thomas; Tasca, Giorgio; Sarathchandra, Padmini; Drago, Fabrizio; Dallapiccola, Bruno; Rapezzi, Claudio; Arbustini, Eloisa; Di Raimo, Francesca Romana; Neri, Marcella; Selvatici, Rita; Gualandi, Francesca; Fattori, Fabiana; Pietrangelo, Antonello; Li, Wenyan; Jiang, Hui; Xu, Xun; Bertini, Enrico; Decher, Niels; Wang, Jun; Brand, Thomas; Ferlini, Alessandra

    2016-01-01

    The Popeye domain-containing 1 (POPDC1) gene encodes a plasma membrane-localized cAMP-binding protein that is abundantly expressed in striated muscle. In animal models, POPDC1 is an essential regulator of structure and function of cardiac and skeletal muscle; however, POPDC1 mutations have not been associated with human cardiac and muscular diseases. Here, we have described a homozygous missense variant (c.602C>T, p.S201F) in POPDC1, identified by whole-exome sequencing, in a family of 4 with cardiac arrhythmia and limb-girdle muscular dystrophy (LGMD). This allele was absent in known databases and segregated with the pathological phenotype in this family. We did not find the allele in a further screen of 104 patients with a similar phenotype, suggesting this mutation to be family specific. Compared with WT protein, POPDC1(S201F) displayed a 50% reduction in cAMP affinity, and in skeletal muscle from patients, both POPDC1(S201F) and WT POPDC2 displayed impaired membrane trafficking. Forced expression of POPDC1(S201F) in a murine cardiac muscle cell line (HL-1) increased hyperpolarization and upstroke velocity of the action potential. In zebrafish, expression of the homologous mutation (popdc1(S191F)) caused heart and skeletal muscle phenotypes that resembled those observed in patients. Our study therefore identifies POPDC1 as a disease gene causing a very rare autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous group of inherited rare diseases.

  1. Inherited predisposition to myeloproliferative neoplasms

    PubMed Central

    Jones, Amy V.

    2013-01-01

    Myeloproliferative neoplasms (MPNs) are haematological disorders characterized by an overproduction of mature myeloid cells with a tendency to transform to acute myeloid leukaemia. Clonal proliferation of myeloid progenitor cells is driven by somatically acquired mutations, most notably JAK2 V617F, but there are important features relating to pathogenesis and phenotypic diversity that cannot be explained by acquired mutations alone. In this review we consider what is currently known about the role that inherited factors play in the development and biology of both sporadic and familial forms of MPN. Although most MPN cases appear to be sporadic, familial predisposition has been recognized for many years in a subset of cases and epidemiological studies have indicated the presence of common susceptibility alleles. Currently the JAK2 46/1 haplotype (also referred to as ‘GGCC’) is the strongest known predisposition factor for sporadic MPNs carrying a JAK2 V617F mutation, explaining a large proportion of the heritability of this disorder. Less is known about what genetic variants predispose to MPNs that lack JAK2 V617F, but there have been recent reports of interesting associations in biologically plausible candidates, and more loci are set to emerge with the application of systematic genome-wide association methodologies. Several highly penetrant predisposition variants that affect erythropoietin signalling, thrombopoietin signalling or oxygen sensing have been characterized in families with nonclonal hereditary erythrocytosis or thrombocytosis, but much less is known about familial predisposition to true clonal MPN. The heterogeneous pattern of inheritance and presumed genetic heterogeneity in these families makes analysis difficult, but whole exome or genome sequencing should provide novel insights into these elusive disorders. PMID:23926457

  2. Personalized Monitoring and Advance Warning System for Cardiac Arrhythmias.

    PubMed

    Kiranyaz, Serkan; Ince, Turker; Gabbouj, Moncef

    2017-08-24

    Each year more than 7 million people die from cardiac arrhythmias. Yet no robust solution exists today to detect such heart anomalies right at the moment they occur. The purpose of this study was to design a personalized health monitoring system that can detect early occurrences of arrhythmias from an individual's electrocardiogram (ECG) signal. We first modelled the common causes of arrhythmias in the signal domain as a degradation of normal ECG beats to abnormal beats. Using the degradation models, we performed abnormal beat synthesis which created potential abnormal beats from the average normal beat of the individual. Finally, a Convolutional Neural Network (CNN) was trained using real normal and synthesized abnormal beats. As a personalized classifier, the trained CNN can monitor ECG beats in real time for arrhythmia detection. Over 34 patients' ECG records with a total of 63,341 ECG beats from the MIT-BIH arrhythmia benchmark database, we have shown that the probability of detecting one or more abnormal ECG beats among the first three occurrences is higher than 99.4% with a very low false-alarm rate.

  3. Macrolide Antibiotics and the Risk of Cardiac Arrhythmias

    PubMed Central

    Schuller, Joseph L.

    2014-01-01

    Randomized, controlled trials have demonstrated that chronic therapy with macrolide antibiotics reduces the morbidity of patients with cystic fibrosis, non–cystic fibrosis bronchiectasis, chronic obstructive pulmonary disease, and nontuberculous mycobacterial infections. Lower levels of evidence indicate that chronic macrolides are also effective in treating patients with panbronchiolitis, bronchiolitis obliterans, and rejection after lung transplant. Macrolides are known to cause torsade des pointes and other ventricular arrhythmias, and a recent observational study prompted the FDA to strengthen the Warnings and Precautions section of azithromycin drug labels. This summary describes the electrophysiological effects of macrolides, reviews literature indicating that the large majority of subjects experiencing cardiac arrhythmias from macrolides have coexisting risk factors and that the incidence of arrhythmias in absence of coexisting risk factors is very low, examines recently published studies describing the relative risk of arrhythmias from macrolides, and concludes that this risk has been overestimated and suggests an approach to patient evaluation that should reduce the relative risk and the incidence of arrhythmias to the point that chronic macrolides can be used safely in the majority of subjects for whom they are recommended. PMID:24707986

  4. Primer in Genetics and Genomics, Article 4-Inheritance Patterns.

    PubMed

    Aiello, Lisa B; Chiatti, Beth Desaretz

    2017-07-01

    Since the completion of the Human Genome Project, much has been uncovered about inheritance of various illnesses and disorders. There are two main types of inheritance: Mendelian and non-Mendelian. Mendelian inheritance includes autosomal dominant, autosomal recessive, X-linked, and Y-linked inheritance. Non-Mendelian inheritance includes mitochondrial and multifactorial inheritance. Nurses must understand the types of inheritance in order to identify red flags that may indicate the possibility of a hereditary disorder in a patient or family.

  5. Treatment of cardiac arrhythmias in a mouse model of Rett syndrome with Na+-channel-blocking antiepileptic drugs.

    PubMed

    Herrera, José A; Ward, Christopher S; Pitcher, Meagan R; Percy, Alan K; Skinner, Steven; Kaufmann, Walter E; Glaze, Daniel G; Wehrens, Xander H T; Neul, Jeffrey L

    2015-04-01

    One quarter of deaths associated with Rett syndrome (RTT), an X-linked neurodevelopmental disorder, are sudden and unexpected. RTT is associated with prolonged QTc interval (LQT), and LQT-associated cardiac arrhythmias are a potential cause of unexpected death. The standard of care for LQT in RTT is treatment with β-adrenergic antagonists; however, recent work indicates that acute treatment of mice with RTT with a β-antagonist, propranolol, does not prevent lethal arrhythmias. In contrast, acute treatment with the Na(+) channel blocker phenytoin prevented arrhythmias. Chronic dosing of propranolol may be required for efficacy; therefore, we tested the efficacy of chronic treatment with either propranolol or phenytoin on RTT mice. Phenytoin completely abolished arrhythmias, whereas propranolol showed no benefit. Surprisingly, phenytoin also normalized weight and activity, but worsened breathing patterns. To explore the role of Na(+) channel blockers on QT in people with RTT, we performed a retrospective analysis of QT status before and after Na(+) channel blocker antiepileptic therapies. Individuals with RTT and LQT significantly improved their QT interval status after being started on Na(+) channel blocker antiepileptic therapies. Thus, Na(+) channel blockers should be considered for the clinical management of LQT in individuals with RTT.

  6. Role of adipose tissue in the pathogenesis of cardiac arrhythmias.

    PubMed

    Samanta, Rahul; Pouliopoulos, Jim; Thiagalingam, Aravinda; Kovoor, Pramesh

    2016-01-01

    Epicardial adipose tissue is present in normal healthy individuals. It is a unique fat depot that, under physiologic conditions, plays a cardioprotective role. However, excess epicardial adipose tissue has been shown to be associated with prevalence and severity of atrial fibrillation. In arrhythmogenic right ventricular cardiomyopathy and myotonic dystrophy, fibrofatty infiltration of the myocardium is associated with ventricular arrhythmias. In the ovine model of ischemic cardiomyopathy, the presence of intramyocardial adipose or lipomatous metaplasia has been associated with increased propensity to ventricular tachycardia. These observations suggest a role of adipose tissue in the pathogenesis of cardiac arrhythmias. In this article, we review the role of cardiac adipose tissue in various cardiac arrhythmias and discuss the possible pathophysiologic mechanisms.

  7. Convulsive Syncope Induced by Ventricular Arrhythmia Masquerading as Epileptic Seizures: Case Report and Literature Review

    PubMed Central

    Sabu, John; Regeti, Kalyani; Mallappallil, Mary; Kassotis, John; Islam, Hamidul; Zafar, Shoaib; Khan, Rafay; Ibrahim, Hiyam; Kanta, Romana; Sen, Shuvendu; Yousif, Abdalla; Nai, Qiang

    2016-01-01

    It is important but difficult to distinguish convulsive syncope from epileptic seizure in many patients. We report a case of a man who presented to emergency department after several witnessed seizure-like episodes. He had a previous medical history of systolic heart failure and automated implantable converter defibrillator (AICD) in situ. The differential diagnoses raised were epileptic seizures and convulsive syncope secondary to cardiac arrhythmia. Subsequent AICD interrogation revealed ventricular tachycardia and fibrillation (v-tach/fib). Since convulsive syncope and epileptic seizure share many similar clinical features, early diagnosis is critical for choosing the appropriate management and preventing sudden cardiac death in patients with presumed epileptic seizure. PMID:27429683

  8. Non-Linear Dynamics of Cardiac Alternans: Subcellular to Tissue-Level Mechanisms of Arrhythmia

    PubMed Central

    Gaeta, Stephen A.; Christini, David J.

    2012-01-01

    Cardiac repolarization alternans is a rhythm disturbance of the heart in which rapid stimulation elicits a beat-to-beat alternation in the duration of action potentials and magnitude of intracellular calcium transients in individual cardiac myocytes. Although this phenomenon has been identified as a potential precursor to dangerous reentrant arrhythmias and sudden cardiac death, significant uncertainty remains regarding its mechanism and no clinically practical means of halting its occurrence or progression currently exists. Cardiac alternans has well-characterized tissue, cellular, and subcellular manifestations, the mechanisms and interplay of which are an active area of research. PMID:22783195

  9. Legal Portion in Russian Inheritance Law

    ERIC Educational Resources Information Center

    Inshina, Roza; Murzalimova, Lyudmila

    2013-01-01

    In this paper the authors describe the right to inherit as one of the basic human rights guaranteed by the Constitution of the Russian Federation. The state has set rules according to which after a person's death, his or her property is inherited by other persons. The Russian civil legislation establishes the institution of legal portions that is…

  10. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Cancer.gov

    The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.