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Sample records for inherited arrhythmia clinic

  1. 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. PMID:26927864

  2. 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. PMID:26556967

  3. 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

  4. Inherited Arrhythmias - Where do we Stand?

    PubMed

    Katritsis, Demosthenes G; Gersh, Bernard J; Camm, A John

    2014-08-01

    This review discusses inherited arrhythmias and conduction disturbances due to genetic disorders. Known channel mutations that are responsible for these conditions are presented, the indications and value of genetic testing are discussed, and a glossary of terms related to the discipline of genetic cardiology has been compiled. PMID:26835071

  5. Channelopathies - emerging trends in the management of inherited arrhythmias.

    PubMed

    Chockalingam, Priya; Mizusawa, Yuka; Wilde, Arthur Am

    2015-01-01

    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

  6. 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

  7. 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

  8. Unveiling specific triggers and precipitating factors for fatal cardiac events in inherited arrhythmia syndromes.

    PubMed

    Nakajima, Tadashi; Kaneko, Yoshiaki; Kurabayashi, Masahiko

    2015-01-01

    Patients with inherited arrhythmia syndromes, such as long QT syndrome, Brugada syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, and their latent forms, are at risk for fatal arrhythmias. These diseases are typically associated with genetic mutations that perturb cardiac ionic currents. The analysis of cardiac events by genotype-phenotype correlation studies has revealed that fatal arrhythmias in some genotypes are triggered by physical or emotional stress, and those in the others are more likely to occur during sleep or at rest. Thus, the risk stratification and management of affected patients differ strikingly according to the genetic variant of the inherited arrhythmia syndrome. Risk stratification may be further refined by considering the precipitating factors, such as drugs, bradycardia, electrolyte disturbances, fever, and cardiac memory. Moreover, an increasing number of studies imply that the susceptibility of fatal arrhythmias in patients with acute coronary syndrome or takotsubo cardiomyopathy is at least partly ascribed to the genetic variants causing inherited arrhythmia syndromes. In this article, we review the recent advances in the understanding of the molecular genetics and genotype-phenotype correlations in inherited arrhythmia syndromes and consider the triggers and precipitating factors for fatal arrhythmias in these disorders. Further studies to explore the triggers and precipitating factors specific to the genotypes and diseases are needed for better clinical management. PMID:25925977

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

    PubMed Central

    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. PMID:27200363

  10. Family and population strategies for screening and counselling of inherited cardiac arrhythmias.

    PubMed

    van Langen, I M; Hofman, N; Tan, H L; Wilde, A A M

    2004-01-01

    Family screening in inherited cardiac arrhythmias has been performed in The Netherlands since 1996, when diagnostic DNA testing in long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM) became technically possible. In multidisciplinary outpatient academic clinics, an adjusted protocol for genetic counselling, originally derived from predictive testing in Huntington's disease, is being used. 1110 individuals, including 842 relatives of index patients, were informed about their risks, and most were tested molecularly and/or clinically for carriership of the disease present in their family. Of 345 relatives who were referred for cardiologic follow-up, 189 are being treated, because of an increased risk of life-threatening arrhythmias. Evaluation of the psychological and social consequences of family screening for inherited arrhythmias can be performed by using the adapted criteria of Wilson and Jüngner, i.e., from a point of view of public health. Preliminary results of psychological research show that parents of children at risk for LQTS show high levels of distress. Many other aspects have to be evaluated yet, making final conclusions about the feasibility of family screening difficult, particularly in HCM. Clinical guidelines are urgently needed. Population screening by molecular testing, for instance in athletic preparticipation screening, will become possible in the future and has its own prerequisites for success. PMID:15176433

  11. Diagnosis and management of patients with inherited arrhythmia syndromes in Europe: results of the European Heart Rhythm Association Survey.

    PubMed

    Hocini, Mélèze; Pison, Laurent; Proclemer, Alessandro; Larsen, Torben Bjerregaard; Madrid, Antonio; Blomström-Lundqvist, Carina

    2014-04-01

    Inherited arrhythmia disorders associated with structurally normal heart (i.e. long and short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, early repolarization syndrome, idiopathic ventricular fibrillation) cause 10% of 1.1 million sudden deaths in Europe and the USA. The purpose of this European Heart Rhythm Association (EHRA) electrophysiology wire survey was to assess the European clinical practice adopted for the diagnosis and management of these disorders. The survey was based on an electronic questionnaire sent out to the EHRA Research Network centres. Responses were received from 50 centres in 23 countries. The results of the survey show that inherited arrhythmia syndromes have a relatively low burden and are diagnosed and managed in accordance with the current guidelines. However, more than 50% of centres do not participate in any existing registry underlining the need for establishing a pan-European registry of these disorders. PMID:24711616

  12. 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. PMID:25400212

  13. Arrhythmias

    MedlinePlus

    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 ...

  14. 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 ...

  15. 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, ...

  16. 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

  17. Inherited arrhythmia syndromes leading to sudden cardiac death in the young: A global update and an Indian perspective

    PubMed Central

    Chockalingam, Priya; Wilde, Arthur A.

    2014-01-01

    Inherited primary arrhythmias, namely congenital long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia, account for a significant proportion of sudden cardiac deaths in young and apparently healthy individuals. Genetic testing plays an integral role in the diagnosis, risk-stratification and treatment of probands and family members. It is increasingly obvious that collaborative efforts are required to understand and manage these relatively rare but potentially lethal diseases. This article aims to update readers on the recent developments in our knowledge of inherited arrhythmias and to lay the foundation for a national synergistic effort to characterize them in the Indian population. PMID:24568830

  18. Arrhythmia

    MedlinePlus

    ... beats too quickly, too slowly, or with an irregular pattern. When the heart beats faster than normal, ... of arrhythmia is atrial fibrillation, which causes an irregular and fast heart beat. Many factors can affect ...

  19. [Arrhythmias].

    PubMed

    Misaki, Takuro; Fukahara, Kazuaki

    2004-07-01

    The success of the radiofrequency catheter ablation procedure for most types of supraventricular and ventricular tachycardia largely eliminated the role of surgical therapy of arrhythmias. However, there remains a subset of arrhythmia patients in whom urgent surgical treatments are required. In this review we mention recent developments of the urgent surgical treatment for arrhythmias. In cases with complete atrioventricular (AV) block and ventricular fibrillation which associated with sudden death, temporary cardiac pacing and cardiac defibrillation using direct current (DC) cardioversion must be immediately induced and followed by implantation of permanent cardiac pacemaker or implantable cardioverter defibrillator (ICD), if necessary. In addition to usual cardiac pacing therapy, novel pacing therapy has been developed recently for the patients with symptomatic heart failure. Cardiac resynchronization therapy (CRT) using biventricular pacing is an emerging therapy for improvement of cardiac function in patients with heart failure in association with intraventricular conduction delay. To prevent the sudden death in patients with heart failure, biventricular pacing combined with ICD are also implanted and its efficacy are reported. With the exception of the pacing therapy, curative surgical treatments are limited in drug-refractory atrial fibrillation and ventricular fibrillation/tachycardia after myocardial infarction requiring Dor's type operation. In any case surgical treatment must be performed promptly and suitably with lower invasive methods. PMID:15362552

  20. 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. PMID:27135669

  1. 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

  2. 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

  3. 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

  4. 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. PMID:26403066

  5. Clinical management of arrhythmias in elderly patients: results of the European Heart Rhythm Association survey.

    PubMed

    Chen, Jian; Hocini, Mélèze; Larsen, Torben Bjerregaard; Proclemer, Alessandro; Sciaraffia, Elena; Blomström-Lundqvist, Carina

    2015-02-01

    The purpose of this survey was to assess clinical practice in management of cardiac arrhythmias in elderly patients (age ≥75 years) in the European countries. The data are based on an electronic questionnaire sent to the European Heart Rhythm Association Research Network members. Responses were received from 50 centres in 20 countries. The results of the survey have shown that management of cardiac arrhythmias is generally in accordance with the guidelines and consensus recommendations on management of cardiac arrhythmias, although there are some areas of variation, especially on age limit and exclusion of elderly patients for anticoagulation, ablation, and device therapy. PMID:25634939

  6. Clinical observations of supraventricular arrhythmias in patients with brugada syndrome

    PubMed Central

    Liu, Bing; Guo, Chengjun; Fang, Dongping; Guo, Jinping

    2015-01-01

    Objective: To study various types of supraventricular arrhythmias in patients with Brugada Syndrome. Methods: Forty six patients with ECG of spontaneous type Brugada and with ventricular and/or supraventricular tachyarrhythmia, without structural heart diseases which were excluded by echocardiography, underwent 24 h-Holter recording, electrophysiological study and/or radiofrequency ablation. Results: There were thirty-nine male and seven female (mean age 37.44 years) among total forty-six patients. Twenty one patients had family histories of tachycardia, twentythree patients experienced episodes of syncope, and three patients were resuscitated from cardiac arrest. One patient had ventricular fibrillation and third degree atrioventricular block, eleven patients had polymorphic ventricular tachycardia and five patients had monomorphic ventricular tachycardia. Fourteen patients had atrial tachyarrhythmia, paroxysmal supraventricular tachycardia was found in five patients including four Wolf-Parkinson-White syndrome, two patients hadventricular tachycardia and third degree atrioventricular block, one of them had atrial fibrillation, two patients had both supraventricular tachycardia and ventricular tachycardia, three patients had both atrial tachyarrhythmia and supraventricular tachycardia, two third degree atrioventricular block patients had atrial flutter, one patienthad both atrial tachyrhythmia and ventricular tachycardia. Radiofrequency blation was performed in thirty-nine patients and succeed in thirty-two, four patients were implanted with pacemakers, and four patients had implantable cardioverter defibrillators. Conclusion: In addition to ventricular tachycardia and ventricular fibrillation, patients with Brugada syndrome exhibit various supraventricular tachyarrhythmia and third degree atrioventricular block. In patients with Brugada syndrome, the dysfunction of the cardiac ion channel, which related to mutation of cardiac sodium channelgene, is not limited in

  7. Clinical neurogenetics: behavioral management of inherited neurodegenerative disease.

    PubMed

    Wexler, Eric

    2013-11-01

    Psychiatric symptoms often manifest years before overt neurologic signs in patients with inherited neurodegenerative disease. The most frequently cited example of this phenomenon is the early onset of personality changes in "presymptomatic" Huntington patients. In some cases the changes in mood and cognition are even more debilitating than their neurologic symptoms. The goal of this article is to provide the neurologist with a concise primer that can be applied in a busy clinic or private practice. PMID:24176427

  8. Iatrogenic QT Abnormalities and Fatal Arrhythmias: Mechanisms and Clinical Significance

    PubMed Central

    Cubeddu, Luigi X

    2009-01-01

    Severe and occasionally fatal arrhythmias, commonly presenting as Torsade de Pointes [TdP] have been reported with Class III-antiarrhythmics, but also with non-antiarrhythmic drugs. Most cases result from an action on K+ channels encoded by the HERG gene responsible for the IKr repolarizing current, leading to a long QT and repolarization abnormalities. The hydrophobic central cavity of the HERG-K+ channels, allows a large number of structurally unrelated drugs to bind and cause direct channel inhibition. Some examples are dofetilide, quinidine, sotalol, erythromycin, grepafloxacin, cisapride, dolasetron, thioridazine, haloperidol, droperidol and pimozide. Other drugs achieve channel inhibition indirectly by impairing channel traffic from the endoplasmic reticulum to the cell membrane, decreasing channel membrane density (pentamidine, geldalamicin, arsenic trioxide, digoxin, and probucol). Whereas, ketoconazole, fluoxetine and norfluoxetine induce both direct channel inhibition and impaired channel trafficking. Congenital long QT syndrome, subclinical ion-channel mutations, subjects and relatives of subjects with previous history of drug-induced long QT or TdP, dual drug effects on cardiac repolarization [long QT plus increased QT dispersion], increased transmural dispersion of repolarization and T wave abnormalities, use of high doses, metabolism inhibitors and/or combinations of QT prolonging drugs, hypokalemia, structural cardiac disease, sympathomimetics, bradycardia, women and older age, have been shown to increase the risk for developing drug-induced TdP. Because most of these reactions are preventable, careful evaluation of risk factors and increased knowledge of drugs use associated with repolarization abnormalities is strongly recommended. Future genetic testing and development of practical and simple provocation tests are in route to prevent iatrogenic TdP. PMID:20676275

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

    PubMed

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

    2015-02-01

    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

  10. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials

    PubMed Central

    2013-01-01

    The Dominantly Inherited Alzheimer Network (DIAN) is an international registry of individuals at risk for developing autosomal dominant Alzheimer’s disease (AD). Its primary aims are to investigate the temporal ordering of AD pathophysiological changes that occur in asymptomatic mutation carriers and to identify those markers that herald the transition from cognitive normality to symptomatic AD. DIAN participants undergo longitudinal evaluations, including clinical and cognitive assessments and measurements of molecular and imaging AD biomarkers. This review details the unique attributes of DIAN as a model AD biomarker study and how it provides the infrastructure for innovative research projects, including clinical trials. The recent design and launch of the first anti-amyloid-beta secondary prevention trial in AD, led by the related DIAN Trials Unit, also are discussed. PMID:24131566

  11. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials.

    PubMed

    Moulder, Krista L; Snider, B Joy; Mills, Susan L; Buckles, Virginia D; Santacruz, Anna M; Bateman, Randall J; Morris, John C

    2013-01-01

    The Dominantly Inherited Alzheimer Network (DIAN) is an international registry of individuals at risk for developing autosomal dominant Alzheimer's disease (AD). Its primary aims are to investigate the temporal ordering of AD pathophysiological changes that occur in asymptomatic mutation carriers and to identify those markers that herald the transition from cognitive normality to symptomatic AD. DIAN participants undergo longitudinal evaluations, including clinical and cognitive assessments and measurements of molecular and imaging AD biomarkers. This review details the unique attributes of DIAN as a model AD biomarker study and how it provides the infrastructure for innovative research projects, including clinical trials. The recent design and launch of the first anti-amyloid-beta secondary prevention trial in AD, led by the related DIAN Trials Unit, also are discussed. PMID:24131566

  12. 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

  13. Next Generation Sequencing for the Diagnosis of Cardiac Arrhythmia Syndromes

    PubMed Central

    Lubitz, Steven A.; Ellinor, Patrick T.

    2015-01-01

    Inherited arrhythmia syndromes are collectively associated with substantial morbidity, yet our understanding of the genetic architecture of these conditions remains limited. Recent technological advances in DNA sequencing have led to the commercialization of genetic testing now widely available in clinical practice. In particular, next generation sequencing allows the large-scale and rapid assessment of entire genomes. Although next generation sequencing represents a major technological advance, it has introduced numerous challenges with respect to the interpretation of genetic variation, and has opened a veritable floodgate of biological data of unknown clinical significance to practitioners. In this review, we discuss current genetic testing indications for inherited arrhythmia syndromes, broadly outline characteristics of next generation sequencing techniques, and highlight challenges associated with such testing. We further summarize future directions that will be necessary to address to enable the widespread adoption of next generation sequencing in the routine management of patients with inherited arrhythmia syndromes. PMID:25625719

  14. 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

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

    PubMed

    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

  16. Ranolazine in Cardiac Arrhythmia.

    PubMed

    Saad, Marwan; Mahmoud, Ahmed; Elgendy, Islam Y; Richard Conti, C

    2016-03-01

    Ranolazine utilization in the management of refractory angina has been established by multiple randomized clinical studies. However, there is growing evidence showing an evolving role in the field of cardiac arrhythmias. Multiple experimental and clinical studies have evaluated the role of ranolazine in prevention and management of atrial fibrillation, with ongoing studies on its role in ventricular arrhythmias. In this review, we will discuss the pharmacological, experimental, and clinical evidence behind ranolazine use in the management of various cardiac arrhythmias. PMID:26459200

  17. [Reperfusion arrhythmias].

    PubMed

    Jurkovicová, O; Cagán, S

    1998-01-01

    recanalization of infarction-related coronary artery. However, they are also a sign of reperfusion injury and a finding which may limit the favourable effect of reperfusion. In account of that, there is a very intensive search for pharmacologic interventions which could protect or attenuate the reperfusion injury and thereby also the genesis of reperfusion arrthythmias. Although promising results were obtained with many substances antagonizing the effects of mediators of reperfusion injury, there is no definite recommendation for their use under clinical conditions. However, the results from the latest clinical trials with ACE inhibitors are very promising. These trials render relative conclusive evidence, that ACE inhibitors could have a protective effect against reperfusion arrhythmias. (Ref. 89, Tab. 1.) PMID:9919746

  18. Mechanisms and Clinical Management of Ventricular Arrhythmias following Blunt Chest Trauma

    PubMed Central

    Wolbrom, Daniel H.; Rahman, Aleef; Tschabrunn, Cory M.

    2016-01-01

    Nonpenetrating, blunt chest trauma is a serious medical condition with varied clinical presentations and implications. This can be the result of a dense projectile during competitive and recreational sports but may also include other etiologies such as motor vehicle accidents or traumatic falls. In this setting, the manifestation of ventricular arrhythmias has been observed both acutely and chronically. This is based on two entirely separate mechanisms and etiologies requiring different treatments. Ventricular fibrillation can occur immediately after chest wall injury (commotio cordis) and requires rapid defibrillation. Monomorphic ventricular tachycardia can develop in the chronic stage due to underlying structural heart disease long after blunt chest injury. The associated arrhythmogenic tissue may be complex and provides the necessary substrate to form a reentrant VT circuit. Ventricular tachycardia in the absence of overt structural heart disease appears to be focal in nature with rapid termination during ablation. Regardless of the VT mechanism, patients with recurrent episodes, despite antiarrhythmic medication in the chronic stage following blunt chest injury, are likely to require ablation to achieve VT control. This review article will describe the mechanisms, pathophysiology, and treatment of ventricular arrhythmias that occur in both the acute and chronic stages following blunt chest trauma. PMID:26981308

  19. Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy.

    PubMed

    Weidemann, Frank; Maier, Sebastian K G; Störk, Stefan; Brunner, Thomas; Liu, Dan; Hu, Kai; Seydelmann, Nora; Schneider, Andreas; Becher, Jan; Canan-Kühl, Sima; Blaschke, Daniela; Bijnens, Bart; Ertl, Georg; Wanner, Christoph; Nordbeck, Peter

    2016-07-15

    Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holter electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holter ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 ± 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses ≥3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter-defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holter ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with

  20. Arrhythmias Seen in Baseline 24-Hour Holter ECG Recordings in Healthy Normal Volunteers During Phase 1 Clinical Trials.

    PubMed

    Hingorani, Pooja; Karnad, Dilip R; Rohekar, Prashant; Kerkar, Vaibhav; Lokhandwala, Yash Y; Kothari, Snehal

    2016-07-01

    Regulatory agencies encourage sponsors to submit 24-hour ambulatory ECG data for assessing cardiac safety of new drugs, and some arrhythmias, hitherto considered rare, have been observed in some early-phase studies. Interpretation of these observations is difficult given the dearth of published data on the prevalence of cardiac arrhythmias seen during 24-hour continuous ECG monitoring in healthy volunteers (HV) from clinical trials. We analyzed drug-free ambulatory ECG recordings from 1273 HV (1000 males, 273 females; age 18-65 years) from 22 phase 1 studies that were analyzed in a core ECG laboratory; all subjects had normal screening ECGs. Supraventricular arrhythmias such as supraventricular premature complexes were observed in 60.8% of healthy volunteers, supraventricular tachycardia in 2.2%, and atrial fibrillation in 0.1%. Ventricular arrhythmias included premature ventricular complexes (PVCs) in 43.4%, >200 PVCs per 24 hours in 3.3%, multifocal PVCs in 5.3%, nonsustained ventricular tachycardia in 0.7%, and accelerated idioventricular rhythm in 0.3%. Bradyarrhythmias included sinus pause >3 seconds in 0.3%, and second-degree AV block in 2.4%. Complete heart block and torsades de pointes were not seen in any subject. Based on the observed incidence, we estimated the maximum number of healthy subjects in whom these arrhythmias may be seen as a matter of chance in studies with smaller sample sizes if the study drug has no arrhythmogenic effect. Our results and these estimates could help interpret whether cardiac arrhythmias observed in early-phase studies are due to chance or possibly are a drug effect. PMID:26626443

  1. 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. PMID:27174994

  2. Next-generation sequencing for the diagnosis of cardiac arrhythmia syndromes.

    PubMed

    Lubitz, Steven A; Ellinor, Patrick T

    2015-05-01

    Inherited arrhythmia syndromes are collectively associated with substantial morbidity, yet our understanding of the genetic architecture of these conditions remains limited. Recent technological advances in DNA sequencing have led to the commercialization of genetic testing now widely available in clinical practice. In particular, next-generation sequencing allows the large-scale and rapid assessment of entire genomes. Although next-generation sequencing represents a major technological advance, it has introduced numerous challenges with respect to the interpretation of genetic variation and has opened a veritable floodgate of biological data of unknown clinical significance to practitioners. In this review, we discuss current genetic testing indications for inherited arrhythmia syndromes, broadly outline characteristics of next-generation sequencing techniques, and highlight challenges associated with such testing. We further summarize future directions that will be necessary to address to enable the widespread adoption of next-generation sequencing in the routine management of patients with inherited arrhythmia syndromes. PMID:25625719

  3. Experience inheritance from famous specialists based on real-world clinical research paradigm of traditional Chinese medicine.

    PubMed

    Song, Guanli; Wang, Yinghui; Zhang, Runshun; Liu, Baoyan; Zhou, Xuezhong; Zhou, Xiaji; Zhang, Hong; Guo, Yufeng; Xue, Yanxing; Xu, Lili

    2014-09-01

    The current modes of experience inheritance from famous specialists in traditional Chinese medicine (TCM) include master and disciple, literature review, clinical-epidemiology-based clinical research observation, and analysis and data mining via computer and database technologies. Each mode has its advantages and disadvantages. However, a scientific and instructive experience inheritance mode has not been developed. The advent of the big data era as well as the formation and practice accumulation of the TCM clinical research paradigm in the real world have provided new perspectives, techniques, and methods for inheriting experience from famous TCM specialists. Through continuous exploration and practice, the research group proposes the innovation research mode based on the real-world TCM clinical research paradigm, which involves the inheritance and innovation of the existing modes. This mode is formulated in line with its own development regularity of TCM and is expected to become the main mode of experience inheritance in the clinical field. PMID:25159993

  4. Marine omega-3 highly unsaturated fatty acids: From mechanisms to clinical implications in heart failure and arrhythmias.

    PubMed

    Glück, Tobias; Alter, Peter

    2016-07-01

    Therapeutic implications of marine omega-3 highly unsaturated fatty acids (HUFA) in cardiovascular disease are still discussed controversially. Several clinical trials report divergent findings and thus leave ambiguity on the meaning of oral omega-3 therapy. Potential prognostic indications of HUFA treatment have been predominantly studied in coronary artery disease, sudden cardiac death, ventricular arrhythmias, atrial fibrillation and heart failure of various origin. It is suspected that increased ventricular wall stress is crucially involved in the prognosis of heart failure. Increased wall stress and an unfavorable myocardial remodeling is associated with an increased risk of arrhythmias by stretch-activated membrane ion channels. Integration of HUFA into the microenvironment of cardiomyocyte ion channels lead to allosteric changes and increase the electrical stability. Increased ventricular wall stress appears to be involved in the local myocardial as well as in the hepatic fatty acid metabolism, i.e. a cardio-hepatic syndrome. Influences of an altered endogenous HUFA metabolism and an inverse shift of the fatty acid profile was underrated in the past. A better understanding of these interacting endogenous mechanisms appears to be required for interpreting the findings of recent experimental and clinical studies. The present article critically reviews major studies on basic pathophysiological mechanisms and treatment effects in clinical trials. PMID:27080538

  5. [Arrhythmias in athlets (author's transl)].

    PubMed

    Degenhardt, H; Jungmann, H

    1978-10-20

    380 athletes in optimal performance were examinated within 10 years between 2 and 13 times (average: 4 times): ECG were taken at rest, during breathing tests and under maximal physical load by ergometry. 88 (23.2%) of them showed arrhythmias, 32 in the same examination different forms of premature beats. All kinds of arrhythmias were seen except atrial flatter, total av-block and paroxysmal tachycardias. Breathing tests provoked most of arrhythmias followed by the recovery after maximal physical load. Follow-up studies and clinical examinations proved that in 86 sportsmen these arrhythmias were not a symptom of heart disease. Only in 2 athletes heart injury could not be excluded. But in nearly 50% extracardial inflammations, like tonsillitis, bronchitis etc., were found. It is discussed that bradycardia and vagotonia of the highly trained sportsmen cause the arrhythmias. This vagotonia is intensified by breathing tests. But arrhythmias found in athletes should cause an examination for other chronical sicknesses. PMID:703672

  6. Arrhythmias in pulmonary arterial hypertension.

    PubMed

    Rajdev, Archana; Garan, Hasan; Biviano, Angelo

    2012-01-01

    Cardiac arrhythmias are important contributors to morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Such patients manifest a substrate resulting from altered autonomics, repolarization abnormalities, and ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter are associated with worsened outcomes, and maintenance of sinus rhythm is a goal. Sudden death is a relatively common issue, though the contribution of malignant ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients. Congenital heart disease patients with PAH benefit from catheter ablation of medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker therapy for primary prevention against sudden death in PAH patients are lacking. PMID:23009914

  7. Arrhythmias in Pulmonary Arterial Hypertension

    PubMed Central

    Rajdev, Archana; Garan, Hasan; Biviano, Angelo

    2013-01-01

    Cardiac arrhythmias are important contributors to morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Such patients manifest a substrate resulting from altered autonomics, repolarization abnormalities, and ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter are associated with worsened outcomes, and maintenance of sinus rhythm is a goal. Sudden death is a relatively common issue, though the contribution of malignant ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients. Congenital heart disease patients with PAH benefit from catheter ablation of medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker therapy for primary prevention against sudden death in PAH patients are lacking. PMID:23009914

  8. [New diagnostic tools for arrhythmias].

    PubMed

    Teres, C; Burri, H

    2015-05-27

    Cardiac arrhythmias are common conditions that often manifest themselves intermittently, thus complicating their diagnosis, particularly in the ambulatory setting. Recently, technological advances have facilitated public access to health applications and devices. This article reviews the available technologies and analyses their usefulness for the diagnosis of arrhythmias in the context of everyday clinical practice. PMID:26182638

  9. Chronic granulomatous disease with unusual clinical manifestation, outcome, and pattern of inheritance in an Iranian family.

    PubMed

    Tafti, Saeed F; Tabarsi, Payam; Mansouri, Nahal; Mirsaeidi, Mehdi; Motazedi Ghajar, Mohamad A; Karimi, Shirin; Najar, Hossain M; Mansouri, Davood

    2006-05-01

    CGD is a rare phagocytic disorder manifesting as recurrent, severe bacterial and fungal infections. We describe an Iranian family with eight children, of whom six, five males and one female were diagnosed with CGD resulting in diffuse pulmonary sterile granulomatous lesions. Three died despite multiple courses of antibiotic and antituberculosis medications while three are alive, to date they are asymptomatic but with imaging and pathologic findings of pulmonary granulomatosis, treated with steroids. The parents are healthy. Our report describes the clinical manifestations and outcome in this family. The inheritance pattern suggests an autosomal recessive pattern with high penetrance. PMID:16783468

  10. Hemodynamics in fetal arrhythmia.

    PubMed

    Sonesson, Sven-Erik; Acharya, Ganesh

    2016-06-01

    Fetal arrhythmias are among the few conditions that can be managed in utero. However, accurate diagnosis is essential for appropriate management. Ultrasound-based imaging methods can be used to study fetal heart structure and function noninvasively and help to understand fetal cardiovascular pathophysiology, and they remain the mainstay of evaluating fetuses with arrhythmias in clinical settings. Hemodynamic evaluation using Doppler echocardiography allows the elucidation of the electrophysiological mechanism and helps to make an accurate diagnosis. It can also be used as a tool to understand fetal cardiac pathophysiology, for assessing fetal condition and monitoring the effect of antiarrhythmic treatment. This narrative review describes Doppler techniques that are useful for evaluating fetal cardiac rhythms to refine diagnosis and provides an overview of hemodynamic changes observed in different types of fetal arrhythmia. PMID:26660845

  11. History of arrhythmias.

    PubMed

    Janse, M J; Rosen, M R

    2006-01-01

    the late 1970s, and optical mapping in the 1980s, simultaneous registrations could be made from many sites. The analysis of atrial and ventricular fibrillation then became much more precise. The old question whether an arrhythmia is due to a focal or a re-entrant mechanism could be answered, and for atrial fibrillation, for instance, the answer is that both mechanisms may be operative. The road from understanding the mechanism of an arrhythmia to its successful therapy has been long: the studies of Mines in 1913 and 1914, microelectrode studies in animal preparations in the 1960s and 1970s, experimental and clinical demonstrations of initiation and termination of tachycardias by premature stimuli in the 1960s and 1970s, successful surgery in the 1980s, the development of external and implantable defibrillators in the 1960s and 1980s, and finally catheter ablation at the end of the previous century, with success rates that approach 99% for supraventricular tachycardias. PMID:16610339

  12. 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

  13. 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

  14. 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

  15. Inherited retinal disorders in South Africa and the clinical impact of evolving technologies.

    PubMed

    Roberts, L; Goliath, R; Rebello, G; Bardien, S; September, A V; Bartmann, L; Loubser, F; Greenberg, L J; Ramesar, R S

    2016-01-01

    Retinal degenerative disorders (RDDs) encompass a group of inherited diseases characterised by vision loss. The genetic and clinical complexity poses a challenge in unravelling the molecular genetic aetiology of this group of disorders. Furthermore, the population diversity in South Africa (SA) presents researchers with a particularly complicated task. Rapid advances in the development of cutting-edge technological platforms over the past two decades, however, have assisted in overcoming some of the challenges. The RDD research team has utilised these escalating technologies, which has facilitated a corresponding increase in molecular diagnoses. A biorepository has been established and comprises ~3 200 patient DNA samples archived with many forms of RDD (including retinitis pigmentosa, macular dystrophies, Stargardt disease, Leber congenital amaurosis, Usher syndrome and Bardet Biedl syndrome). A comprehensive review is presented of the SA journey spanning 25 years, into elucidating the molecular genetic basis of various forms of RDD in SA. PMID:27245521

  16. [Retracted] Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin 2 centronuclear myopathy.

    PubMed

    Liu, Xinhong; Wu, Huamin; Gong, Jian; Wang, Tao; Yan, Chuanzhu

    2016-07-01

    We wish to retract our article entitled 'Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin 2 centronuclear myopathy' published in Molecular Medicine Reports 13: 4273-4278, 2016. The article was submitted by the first author, Xinhong Liu, without the prior knowledge of the corresponding author, Chuanzhu Yan, or the other authors included on the paper. Furthermore, the details of the paper were not discussed by the authors prior to the submission, and all are in agreement that the paper contains data therein (and interpretations thereof) which are either inaccurate or inappropriate. All the authors agree to this retraction, and we apologize for the inconvenience caused in this regard.[the original article was published in the Molecular Medicine Reports 13: 4273-4278, 2016; DOI: 10.3892/mmr.2016.5047]. PMID:27176730

  17. Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin 2 centronuclear myopathy.

    PubMed

    Liu, Xinhong; Wu, Huamin; Gong, Jian; Wang, Tao; Yan, Chuanzhu

    2016-05-01

    The aim of the present study was to report on a family with pathologically and genetically diagnosed autosomal dominant inherited centronuclear myopathy (CNM). In addition, this study aimed to investigate the clinical, pathological and molecular genetic characteristics of the disease. This pedigree was traced back three generations, four patients underwent neurological examination, two patients underwent muscle biopsy, and eight family members were subjected to dynamin 2 (DNM2) gene mutation analysis. DNM2 mutations were detected in seven family members, of which four patients exhibited DNM2 mutation‑specific clinical and pathological features. Lower extremity weakness was the predominant symptom of these patients, however, proximal and distal lower extremity involvement was inconsistent. All patients exhibited marked systematic muscle atrophy and various degrees of facial muscle involvement. The patients presented the typical pathological changes of CNM, and their muscle tissues were heavily replaced by adipose tissue, with clustered distribution of muscle fibers as another notable feature. DNM2‑CNM patients of this pedigree exhibited heterogeneous clinical and pathological features, providing a basis for further molecular genetic analysis. PMID:27035234

  18. Living with an Arrhythmia

    MedlinePlus

    ... from the NHLBI on Twitter. Living With an Arrhythmia Many arrhythmias are harmless. It's common to have an occasional ... heartbeat or mild palpitations . People who have harmless arrhythmias can live healthy lives. They usually don't ...

  19. Correlating perceived arrhythmia symptoms and QoL in the elderly with Heart Failure in an urban clinic: A prospective, single center study

    PubMed Central

    Hickey, Kathleen T.; Reiffel, James; Sciacca, Robert R.; Whang, William; Biviano, Angelo; Baumeister, Maurita; Castillo, Carmen; Talathothi, Jyothi; Garan, Hasan

    2013-01-01

    Aim To determine the relationship between quality of life (QoL) and perceived self reported symptoms in an elderly, ambulatory, urban population living with heart failure (HF). Background While arrhythmias in the elderly with HF are well documented, the association between perceived arrhythmia symptoms and QoL is not well defined. Design Prospective, cross sectional single center study. Methods A single-center, prospective study was conducted with HF patients recruited from an urban outpatient cardiology clinic in the United States. Fifty-seven patients completed a baseline QoL survey with 42 of these completing the 6-month follow-up survey. QoL was evaluated with the SF-36v2™ and frequency of symptoms with the Atrial Fibrillation Severity Scale. Subjects wore an auto triggered cardiac loop monitor (LifeStar AF Express®) for 2-weeks to document arrhythmias. Data analysis utilized Spearman’s rank correlation and logistic regression. Results Baseline and 6-month QoL measures did not correlate with recorded arrhythmias. However, perceptions of diminished general health correlated significantly with symptoms of exercise intolerance, lightheadedness/dizziness, palpitations, and chest pain/pressure. By multivariable logistic regression, more severe perceived arrhythmic, symptoms of exercise intolerance, and lightheadedness/dizziness were independently associated with diminished QoL. Conclusion QoL was significantly worse in patients with perceptions of severe arrhythmic episodes and in those whose symptoms of dizziness and exercise intolerance. Relevance to clinical practice The findings of this study indicate that symptomatic HF patients suffer from poor QoL and that interventions are needed to improve QoL and decrease symptom severity. Nurses who care for HF patients play an essential role in symptom evaluation and management and could significantly improve overall QoL in these patients by carefully evaluating symptomatology and testing interventions and

  20. 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. PMID:27521090

  1. Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancer.

    PubMed

    Knutson, Keith L; Maurer, Matthew J; Preston, Claudia C; Moysich, Kirsten B; Goergen, Krista; Hawthorne, Kieran M; Cunningham, Julie M; Odunsi, Kunle; Hartmann, Lynn C; Kalli, Kimberly R; Oberg, Ann L; Goode, Ellen L

    2015-12-01

    The immune system constitutes one of the host factors modifying outcomes in ovarian cancer. Regulatory T cells (Tregs) are believed to be a major factor in preventing the immune response from destroying ovarian cancers. Understanding mechanisms that regulate Tregs in the tumor microenvironment could lead to the identification of novel targets aimed at reducing their influence. In this study, we used immunofluorescence-based microscopy to enumerate Tregs, total CD4 T cells, and CD8(+) cytotoxic T cells in fresh frozen tumors from over 400 patients with ovarian cancer (>80 % high-grade serous). We sought to determine whether Tregs were associated with survival and genetic variation in 79 genes known to influence Treg induction, trafficking, or function. We used Cox regression, accounting for known prognostic factors, to estimate hazard ratios (HRs) associated with T cell counts and ratios. We found that the ratios of CD8 T cells and total CD4 T cells to Tregs were associated with improved overall survival (CD8/Treg HR 0.84, p = 0.0089; CD4/Treg HR 0.88, p = 0.046) and with genetic variation in IL-10 (p = 0.0073 and 0.01, respectively). In multivariate analyses, the associations between the ratios and overall survival remained similar (IL-10 and clinical covariate-adjusted CD8/Treg HR 0.85, p = 0.031; CD4/Treg HR 0.87, p = 0.093), suggesting that this association was not driven by variation in IL-10. Thus, integration of novel tumor phenotyping measures with extensive clinical and genetic information suggests that the ratio of T cells to Tregs may be prognostic of outcome in ovarian cancer, regardless of inherited genotype in genes related to Tregs. PMID:26298430

  2. [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. PMID:2091549

  3. 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. PMID:24783482

  4. Oculodentodigital dysplasia: study of ophthalmological and clinical manifestations in three boys with probably autosomal recessive inheritance.

    PubMed

    Frasson, Maria; Calixto, Nassim; Cronemberger, Sebastião; de Aguiar, Regina Amélia Lopes Pessoa; Leão, Letícia Lima; de Aguiar, Marcos José Burle

    2004-09-01

    Oculodentodigital dysplasia (ODDD) is a rare inherited disorder affecting the development of the face, eyes, teeth, and limbs. The majority of cases of ODDD are inherited as an autosomal dominant condition. There are few reports of probable autosomal recessive transmission. Affected patients exhibit a distinctive physiognomy with a narrow nose, hypoplastic alae nasi, and anteverted nostrils, bilateral microphthalmos, and microcornea. Sometimes iris anomalies and secondary glaucoma are present. There are malformations of the distal extremities such as syndactyly. In addition, there are defects in the dental enamel with hypoplasia and yellow discoloration of the teeth. Less common features include hypotrichosis, intracranial calcifications, and conductive deafness secondary to recurrent otitis media. We describe three brothers with ODDD. Their parents are first cousins and present no features of ODDD. These data are in favor of autosomal recessive inheritance and suggest genetic heterogeneity for this entity. PMID:15512999

  5. Prevention and Treatment of Arrhythmia

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Prevention & Treatment of Arrhythmia Updated:Sep 2,2016 Do ... Risk for Arrhythmia • Symptoms, Diagnosis & Monitoring of Arrhythmia • Prevention & Treatment of Arrhythmia Introduction Medications Ablation Devices for ...

  6. Children and Arrhythmia

    MedlinePlus

    ... and is at risk for sudden arrhythmias including sudden death. Learn about special considerations for cardiac arrest in ... and is at risk for sudden arrhythmias including sudden death. Learn about special considerations for cardiac arrest in ...

  7. Treating Arrhythmias in Children

    MedlinePlus

    ... and is at risk for sudden arrhythmias including sudden death. Learn about special considerations for cardiac arrest in ... and is at risk for sudden arrhythmias including sudden death. Learn about special considerations for cardiac arrest in ...

  8. How Are Arrhythmias Treated?

    MedlinePlus

    ... Some arrhythmias are treated with a jolt of electricity to the heart. This type of treatment is ... senses a dangerous ventricular arrhythmia, it sends an electric shock to the heart to restore a normal ...

  9. 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. PMID:25037518

  10. 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

  11. A clinical perspective on ethical arguments around prenatal diagnosis and preimplantation genetic diagnosis for later onset inherited cancer predispositions.

    PubMed

    Clancy, Tara

    2010-03-01

    Prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) for later onset and/or reduced penetrance inherited cancer predispositions, e.g. familial adenomatous polyposis, hereditary non-polyposis colorectal cancer/Lynch syndrome and hereditary breast and ovarian cancer, raise a number of ethical issues. Some of these are the same as for conditions which present early in childhood, are fully penetrant and for which no/limited treatment options are possible; others relate to whether reduced penetrance and/or the availability of treatment mean that these are not serious (enough) conditions to warrant tests prior to/during pregnancy or to justify termination of pregnancy. However, attempts to reach a consensus on what counts as a serious (enough) condition in the context of PND and PGD have been unsuccessful. Such a definition may anyway be unhelpful if it cannot also take into account, for example, the woman's/couple's awareness and experience of the condition and the impact of the condition on affected individuals and their families. Individuals affected by, or at high risk of, later onset and/or reduced penetrance inherited cancer predispositions are generally supportive of access to PND and PGD for their own conditions, even if they would not consider using it themselves. Professionals working in clinical cancer genetics need to be prepared to discuss PND and PGD with this group of patients. PMID:19644768

  12. Anger and ventricular arrhythmias

    PubMed Central

    Lampert, Rachel

    2011-01-01

    Purpose of review Although anecdotal evidence has long suggested links between emotion and ventricular arrhythmia, more recent studies have prospectively demonstrated the arrhythmogenic effects of anger, as well as mechanisms underlying these effects. Recent findings Epidemiological studies reveal that psychological stress increases sudden death, as well as arrhythmias, in patients with implantable cardioverter-defibrillators, in populations during emotionally devastating disasters such as earthquake or war. Diary-based studies confirm that anger and other negative emotions can trigger potentially lethal ventricular arrhythmias. Anger alters electrophysiological properties of the myocardium, including T-wave alternans, a measure of heterogeneity of repolarization, suggesting one mechanistic link between emotion and arrhythmia. Pilot studies of behavioral interventions have shown promise in decreasing arrhythmias in patients with implantable cardioverter-defibrillators. Summary Anger and other strong emotions can trigger polymorphic, potentially life-threatening ventricular arrhythmias in vulnerable patients. Through autonomic changes including increased sympathetic activity and vagal withdrawal, anger leads to increases in heterogeneity of repolarization as measured by T-wave alternans, known to be associated with arrhythmogenesis, as well as increasing inducibility of arrhythmia. Further delineation of mechanisms linking anger and arrhythmia, and of approaches to decrease the detrimental effects of anger and other negative emotions on arrhythmogenesis, are important areas of future investigation. PMID:19864944

  13. 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. PMID:26311407

  14. Preimplantation genetic diagnosis for inherited breast cancer: first clinical application and live birth in Spain.

    PubMed

    Ramón Y Cajal, Teresa; Polo, Ana; Martínez, Olga; Giménez, Carles; Arjona, César; Llort, Gemma; Bassas, Lluís; Viscasillas, Pere; Calaf, Joaquin

    2012-06-01

    Carriers of a mutation in BRCA1/2 genes confront a high lifetime risk of breast and ovarian cancer and fifty percent probability of passing the mutation to their offspring. Current options for risk management influence childbearing decisions. The indications for preimplantation genetic diagnosis (PGD) have now been expanded to include predisposition for single-gene, late-onset cancer but few cases have been reported to date despite the favorable opinion among professionals and carriers. A 28-year-old BRCA1 mutation carrier (5273G>A in exon 19) with a strong maternal history of breast cancer and 2 years of infertility decided to pursue PGD to have a healthy descendent after an accurate assessment of her reproductive options. The procedure was approved by the national regulation authority and a PGD cycle was initiated. Four out of 6 embryos harbored the mutation. The two unaffected embryos were implanted in the uterus. A singleton pregnancy was achieved and a male baby was delivered at term. Consented umbilical cord blood testing confirmed the accuracy of the technique. Individualized PGD for inherited breast predisposition is feasible in the context of a multidisciplinary team. PMID:22179695

  15. Noninvasive diagnostic mapping of supraventricular arrhythmias (Wolf-Parkinson-White syndrome and atrial arrhythmias).

    PubMed

    Cakulev, Ivan; Sahadevan, Jayakumar; Waldo, Albert L

    2015-03-01

    The 12-lead electrocardiogram has limited value in precisely identifying the origin of focal or critical component of reentrant arrhythmias during supraventricular arrhythmias, as well as precisely locating accessory atrioventricular conduction pathways. Because of these limitations, efforts have been made to reconstruct epicardial activation sequences from body surface measurements obtained noninvasively. The last decade has registered significant progress in obtaining clinically useful data from the attempts to noninvasively map the epicardial electrical activity. This article summarizes the recent advances made in this area, specifically addressing the clinical outcomes of such efforts relating to atrial arrhythmias and Wolf-Parkinson-White syndrome. PMID:25784024

  16. 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

  17. Arrhythmias presenting in neonatal lupus.

    PubMed

    Brucato, A; Previtali, E; Ramoni, V; Ghidoni, S

    2010-09-01

    Perfusion of human foetal heart with anti-Ro/SSA antibodies induces transient heart block. Anti-Ro/SSA antibodies may cross-react with T- and L-type calcium channels, and anti-p200 antibodies may cause calcium to accumulate in rat heart cells. These actions may explain a direct electrophysiological effect of these antibodies. Congenital complete heart block is the more severe manifestation of so-called "Neonatal Lupus". In clinical practice, it is important to distinguish in utero complete versus incomplete atrioventricular (AV) block, as complete AV block to date is irreversible, while incomplete AV block has been shown to be potentially reversible after fluorinated steroid therapy. Another issue is the definition of congenital AV block, as cardiologists have considered congenital blocks detected months or years after birth. We propose as congenital blocks detected in utero or within the neonatal period (0-27 days after birth). The possible detection of first degree AV block in utero, with different techniques, might be a promising tool to assess the effects of these antibodies. Other arrhythmias have been described in NL or have been linked to anti-Ro/SSA antibodies: first degree AV block, in utero and after birth, second degree (i.e. incomplete block), sinus bradycardia and QT prolongation, both in infants and in adults, ventricular arrhythmias (in adults). Overall, these arrhythmias have not a clinical relevance, but are important for research purposes. PMID:20696016

  18. 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

  19. Inherited renal cystic diseases.

    PubMed

    Kim, Bohyun; King, Bernard F; Vrtiska, Terri J; Irazabal, Maria V; Torres, Vicente E; Harris, Peter C

    2016-06-01

    A number of inherited renal diseases present with renal cysts and often lead to end-stage renal disease. With recent advances in genetics, increasing number of genes and mutations have been associated with cystic renal diseases. Although genetic testing can provide a definite diagnosis, it is often reserved for equivocal cases or for ongoing investigational research. Therefore, imaging findings are essential in the routine diagnosis, follow-up, and detection of complications in patients with inherited cystic renal diseases. In this article, the most recent classification, genetic analysis, clinical presentations, and imaging findings of inherited cystic renal diseases will be discussed. PMID:27167233

  20. 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

  1. Understand Your Risk for Arrhythmia

    MedlinePlus

    ... Tools & Resources Stroke More Understand Your Risk for Arrhythmia Updated:Apr 6,2016 Expected changes in heart ... content was last reviewed on 10/23/2014. Arrhythmia • Home • About Arrhythmia • Why Arrhythmia Matters • Understand Your ...

  2. [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. PMID:25203351

  3. Devices for Arrhythmia

    MedlinePlus

    ... the heart an electric shock (as with a defibrillator ). For people with recurrent arrhythmias, medical devices such as a pacemaker and implantable cardioverter defibrillator (ICD) can help by continuously monitoring the heart's ...

  4. 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

  5. Giant axonal neuropathy: a rare inherited neuropathy with simple clinical clues

    PubMed Central

    Kamate, Mahesh; Ramakrishna, Shashikala; Kambali, Shweta; Mahadevan, Anita

    2014-01-01

    Giant axonal neuropathy (GAN) is a rare hereditary neurodegenerative disorder characterised by accumulation of excess neurofilaments in the axons of peripheral and central nervous systems, which hampers signal transmission. It usually manifests in infancy and early childhood and is slowly progressive. Those affected with GAN have characteristic curly kinky hair, everted feet and a crouched gait, which suggest the diagnosis in most cases. We describe twin children who presented with difficulty in walking and an abnormal gait since they began walking; clinical clues such as hair changes led us to the final diagnosis. PMID:25216920

  6. 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. PMID:26283042

  7. Short QT Syndrome in Current Clinical Practice.

    PubMed

    Khera, Sahil; Jacobson, Jason T

    2016-01-01

    Short QT syndrome is a rare inherited autosomal dominant cardiac channelopathy associated with malignant ventricular and atrial arrhythmias. A shortened corrected QT interval is a marker for risk of malignant arrhythmias, which are secondary to increased transmural dispersion of repolarization. The underlying gain of function mutations in the potassium channels are most common but genetic testing remains low yield. This review discusses the cellular mechanisms, genetic involvement, clinical presentation, and current recommended management of patients with short QT syndrome relevant to current clinical practice. PMID:26440650

  8. Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in 25 Cavalier King Charles spaniel dogs. Part I: clinical signs, histopathology, and inheritance.

    PubMed

    Hartley, Claudia; Donaldson, David; Smith, Ken C; Henley, William; Lewis, Tom W; Blott, Sarah; Mellersh, Cathryn; Barnett, Keith C

    2012-09-01

    The clinical presentation and progression (over 9 months to 13 years) of congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in the Cavalier King Charles spaniel dog are described for six new cases and six previously described cases. Cases presented with a congenitally abnormal (rough/curly) coat and signs of KCS from eyelid opening. Persistent scale along the dorsal spine and flanks with a harsh frizzy and alopecic coat was evident in the first few months of life. Ventral abdominal skin was hyperpigmented and hyperkeratinized in adulthood. Footpads were hyperkeratinized from young adulthood with nail growth abnormalities and intermittent sloughing. Long-term follow-up of cases (13/25) is described. Immunomodulatory/lacrimostimulant treatment had no statistically significant effect on Schirmer tear test results, although subjectively, this treatment reduced progression of the keratitis. Histopathological analysis of samples (skin/footpads/lacrimal glands/salivary glands) for three new cases was consistent with an ichthyosiform dermatosis, with no pathology of the salivary or lacrimal glands identified histologically. Pedigree analysis suggests the syndrome is inherited by an autosomal recessive mode. PMID:22212237

  9. Noninvasive mapping of ventricular arrhythmias.

    PubMed

    Shah, Ashok J; Lim, Han S; Yamashita, Seigo; Zellerhoff, Stephan; Berte, Benjamin; Mahida, Saagar; Hooks, Darren; Aljefairi, Nora; Derval, Nicolas; Denis, Arnaud; Sacher, Frédéric; Jais, Pierre; Dubois, Rémi; Hocini, Meleze; Haissaguerre, Michel

    2015-03-01

    Several decades of research has led to the development of a 252-lead electrocardiogram-based three-dimensional imaging modality to refine noninvasive diagnosis and improve the management of heart rhythm disorders. This article reviews the clinical potential of this noninvasive mapping technique in identifying the sources of electrical disorders and guiding the catheter ablation of ventricular arrhythmias (premature ventricular beats and ventricular tachycardia). The article also briefly refers to the noninvasive electrical imaging of the arrhythmogenic ventricular substrate based on the electrophysiologic characteristics of postinfarction ventricular myocardium. PMID:25784026

  10. 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

  11. [Alcohol and arrhythmias].

    PubMed

    Pfeiffer, D; Jurisch, D; Neef, M; Hagendorff, A

    2016-09-01

    The effects of alcohol on induction of arrhythmias is dose-dependent, independent of preexisting cardiovascular diseases or heart failure and can affect otherwise healthy subjects. While the probability of atrial fibrillation increases with the alcohol dosage, events of sudden cardiac death are less frequent with low and moderate consumption but occur more often in heavy drinkers with alcoholic cardiomyopathy. Men are first affected at higher dosages of alcohol but women can suffer from arrhythmias at lower dosages. Thromboembolisms and ischemic stroke can occur less often at lower dosages of alcohol; however, hemorrhagic stroke and subarachnoid hemorrhage are increased with higher alcohol dosages. Recognizable protective mechanisms of alcohol with respect to cardiovascular diseases only occur with lower amounts of alcohol of less than 10 g per day. Underlying mechanisms explain these controversial effects. Specific therapeutic options for alcohol-related arrhythmias apart from abstinence from alcohol consumption are not known. PMID:27582366

  12. The Utility of Ambulatory Electrocardiographic Monitoring for Detecting Silent Arrhythmias and Clarifying Symptom Mechanism in an Urban Elderly Population with Heart Failure and Hypertension: Clinical Implications.

    PubMed

    Hickey, Kathleen T; Reiffel, James; Sciacca, Robert R; Whang, William; Biviano, Angelo; Baumeister, Maurita; Castillo, Carmen; Talathothi, Jyothi; Garan, Hasan

    2010-01-01

    BACKGROUND: Atrial and ventriclar tachyarrhythmias, as well as bradyarrhythmias, in the elderly with heart failure (HF) and/or hypertension (HTN) have been well documented. However, the frequency of these arrhythmias, whether silent or symptomatic, and their association with subsequent cardiac events has not been well defined in patients 65 years or older with HF and other cardiovascular risk factors. OBJECTIVE: To assess the value of 2 weeks of remote, transtelephonic cardiac monitoring for detecting arrhythmias in an elderly, urban population living with HF. METHODS: Fifty-four patients with a history of systolic HF and/or HTN were consented and enrolled. All wore an auto triggered cardiac loop monitor for 2 weeks that captures EKG data and both silent and symptomatic arrhythmias were recorded. RESULTS: Mean age was 73 ± 6 years with 59% of subjects were females, 74% Hispanic, 22% black, and 4% white/other. All patients had HF and 94% had HTN. From the cardiac monitoring, 72% demonstrated ectopic atrial and ventricular activity, and 1 paroxysmal episode of atrial fibrillation was documented. In addition, 3 subjects had significant non-sustained ventricular tachycardia, and 4 individuals had severe bradycardia recorded on cardiac monitoring. These 7 individuals underwent placement of an implantable cardioverter defibrillator (ICD) or pacemaker based on the documented arrhythmias which may have otherwise gone undetected. CONCLUSION: A substantial proportion of patients exhibited cardiac arrhythmias. Future morbidity was prevented because of the detection of arrhythmias on monitoring that led to specific therapies such as pacemaker or ICD implantation which otherwise may not have been implemented. PMID:20798788

  13. The Utility of Ambulatory Electrocardiographic Monitoring for Detecting Silent Arrhythmias and Clarifying Symptom Mechanism in an Urban Elderly Population with Heart Failure and Hypertension: Clinical Implications

    PubMed Central

    Hickey, Kathleen T.; Reiffel, James; Sciacca, Robert R.; Whang, William; Biviano, Angelo; Baumeister, Maurita; Castillo, Carmen; Talathothi, Jyothi; Garan, Hasan

    2010-01-01

    Background Atrial and ventriclar tachyarrhythmias, as well as bradyarrhythmias, in the elderly with heart failure (HF) and/or hypertension (HTN) have been well documented. However, the frequency of these arrhythmias, whether silent or symptomatic, and their association with subsequent cardiac events has not been well defined in patients 65 years or older with HF and other cardiovascular risk factors. Objective To assess the value of 2 weeks of remote, transtelephonic cardiac monitoring for detecting arrhythmias in an elderly, urban population living with HF. Methods Fifty-four patients with a history of systolic HF and/or HTN were consented and enrolled. All wore an auto triggered cardiac loop monitor for 2 weeks that captures EKG data and both silent and symptomatic arrhythmias were recorded. Results Mean age was 73 ± 6 years with 59% of subjects were females, 74% Hispanic, 22% black, and 4% white/other. All patients had HF and 94% had HTN. From the cardiac monitoring, 72% demonstrated ectopic atrial and ventricular activity, and 1 paroxysmal episode of atrial fibrillation was documented. In addition, 3 subjects had significant non-sustained ventricular tachycardia, and 4 individuals had severe bradycardia recorded on cardiac monitoring. These 7 individuals underwent placement of an implantable cardioverter defibrillator (ICD) or pacemaker based on the documented arrhythmias which may have otherwise gone undetected. Conclusion A substantial proportion of patients exhibited cardiac arrhythmias. Future morbidity was prevented because of the detection of arrhythmias on monitoring that led to specific therapies such as pacemaker or ICD implantation which otherwise may not have been implemented. PMID:20798788

  14. Fetal and Neonatal Arrhythmias.

    PubMed

    Jaeggi, Edgar; Öhman, Annika

    2016-03-01

    Cardiac arrhythmias are an important aspect of fetal and neonatal medicine. Premature complexes of atrial or ventricular origin are the main cause of an irregular heart rhythm. The finding is typically unrelated to an identifiable cause and no treatment is required. Tachyarrhythmia most commonly relates to supraventricular reentrant tachycardia, atrial flutter, and sinus tachycardia. Several antiarrhythmic agents are available for the perinatal treatment of tachyarrhythmias. Enduring bradycardia may result from sinus node dysfunction, complete heart block and nonconducted atrial bigeminy as the main arrhythmia mechanisms. The management and outcome of bradycardia depend on the underlying mechanism. PMID:26876124

  15. Inherited interstitial lung disease.

    PubMed

    Garcia, Christine Kim; Raghu, Ganesh

    2004-09-01

    This article focuses on recent advances in the identification of genes and genetic polymorphisms that have been implicated in the development of human interstitial lung diseases. It focuses on the inherited mendelian diseases in which pulmonary fibrosis is part of the clinical phenotype and the genetics of familial idiopathic pulmonary fibrosis and other rare inherited interstitial lung diseases. The article also reviews the association studies that have been published to date regarding the genetics of sporadic idiopathic pulmonary fibrosis. The reader is directed to recent reviews on human genetic predisposition of sarcoidosis, environmental-related, drug-related, connective tissue related pulmonary fibrosis, and genetic predisposition of fibrosis in animal models. PMID:15331184

  16. 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.

  17. Electromechanical Wave Imaging for Arrhythmias

    PubMed Central

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

    2015-01-01

    Electromechanical Wave Imaging (EWI) is a novel ultrasound-based imaging modality for the 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 previous studies. However, the methods used previously to map the EW required the reconstruction of images over multiple cardiac cycle, precluding the application of EWI for non-periodic arrhythmia such as fibrillation. In this study, we develop new imaging sequences based on flash and wide-beam emissions to image the entire heart at very high frame rate (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 atrioventricular dissociation, i.e., 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 arrhythmia in conditions close to the clinical setting, in a single heartbeat, and during free-breathing. PMID:22024555

  18. Electromechanical wave imaging for arrhythmias.

    PubMed

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

    2011-11-21

    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. PMID:22024555

  19. 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. PMID:26162704

  20. 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.

  1. 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

  2. [Arrhythmias during pregnancy].

    PubMed

    Trappe, H-J

    2008-09-01

    Cardiovascular emergencies are rare during pregnancy with an incidence of 0,2-4,0%. Emergencies include arrhythmias, acute coronary syndrome, peripartum cardiomyopathy and hypertensive disorders. Electrical DC-cardioversion with 50-100 Joules is indicated in the acute treatment of arrhythmias in all patients in an unstable hemodynamic state. If 100 J fails higher energies (up to 360 J) will be necessary. In stable supraventricular tachycardia intravenous adenosine is the first choice drug and may safely terminate the arrhythmia. Ventricular premature beats are frequently present during pregnancy and benign in most patients. However, life-threatening ventricular tachyarrhythmias (sustained ventricular tachycardia [VT], ventricular flutter [VFlt], ventricular fibrillation [VF]) were observed less frequently. Electrical DC-cardioversion is necessary in all pregnant women who are in a hemodynamically unstable state and have a life-threatening ventricular tachyarrhythmias. In hemodynamically stable pregnant women the initial therapy with ajmaline, procainamide or lidocaine is indicated. Implantation of a cardioverter-defibrillator is indicated in patients with syncope caused by VT, VF, VFlt or aborted sudden death. PMID:18767007

  3. Clinical and genetic study of a family with a paternally inherited 15q11-q13 duplication.

    PubMed

    Marini, Carla; Cecconi, Antonella; Contini, Elisa; Pantaleo, Marilena; Metitieri, Tiziana; Guarducci, Silvia; Giglio, Sabrina; Guerrini, Renzo; Genuardi, Maurizio

    2013-06-01

    Interstitial chromosome 15q11-q13 duplications are associated with developmental delay, behavioral problems and additional manifestations, including epilepsy. In most affected individuals the duplicated chromosome is maternally derived, whereas paternal inheritance is more often associated with a normal phenotype. Seizures have not been described in patients with paternal dup 15q11-q13. We describe a family with five individuals in three generations with a paternally-inherited 15q11-q13 duplication, four of whom exhibited abnormal phenotypic characteristics, including seizures. The 18-year-old female proband presented with moderate intellectual disability, obesity, and epilepsy. Her brother manifested learning disability and behavioral problems. They both inherited the 15q11-q13 dup from their father who had a normal phenotype. Their paternal uncle and grandfather also had the duplication and were reported to have had seizures. Array-CGH and MLPA analyses showed that the duplication included the TUBGCP5, CYFIP1, MKRN3, MAGEL2, NDN, SNRPN, UBE3A, ATP10A, GABRB3, GABRA5, GABRG3, and OCA2 genes. This report provides evidence for intrafamilial phenotypic variability of paternal dup 15q11-q13, ranging from normal to intellectual disability and seizures, and potentially expanding the phenotype of paternal 15q11-q13 interstitial duplications. PMID:23633446

  4. Mechanisms of Ventricular Arrhythmias: From Molecular Fluctuations to Electrical Turbulence

    PubMed Central

    Qu, Zhilin; Weiss, James N.

    2015-01-01

    Ventricular arrhythmias have complex causes and mechanisms. Despite extensive investigation involving many clinical, experimental, and computational studies, effective biological therapeutics are still very limited. In this article, we review our current understanding of the mechanisms of ventricular arrhythmias by summarizing the state of knowledge spanning from the molecular scale to electrical wave behavior at the tissue and organ scales and how the complex nonlinear interactions integrate into the dynamics of arrhythmias in the heart. We discuss the challenges that we face in synthesizing these dynamics to develop safe and effective novel therapeutic approaches. PMID:25340965

  5. Mechanisms of ventricular arrhythmias: from molecular fluctuations to electrical turbulence.

    PubMed

    Qu, Zhilin; Weiss, James N

    2015-01-01

    Ventricular arrhythmias have complex causes and mechanisms. Despite extensive investigation involving many clinical, experimental, and computational studies, effective biological therapeutics are still very limited. In this article, we review our current understanding of the mechanisms of ventricular arrhythmias by summarizing the state of knowledge spanning from the molecular scale to electrical wave behavior at the tissue and organ scales and how the complex nonlinear interactions integrate into the dynamics of arrhythmias in the heart. We discuss the challenges that we face in synthesizing these dynamics to develop safe and effective novel therapeutic approaches. PMID:25340965

  6. 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.

  7. Arrhythmias in the athlete.

    PubMed

    Bisbal, F; Mont, L

    2012-06-01

    Regular exercise provides substantial health benefits, mostly by reducing cardiovascular risk factors. However, it may also trigger acute cardiac events and cause sudden cardiac death in individuals with a pre-existing condition. In an otherwise healthy population, intense regular exercise may lead to morphological and electrical cardiac adaptations commonly referred as "athlete's heart." Recent data suggest that this may itself produce structural changes of atrial and ventricular myocardium with enlargement and fibrosis, creating the substrate for development of arrhythmias in apparently healthy athletes. The state of the art in this controversial issue is reviewed. PMID:22782729

  8. 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

  9. The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer: A Report of the Association for Molecular Pathology.

    PubMed

    Joseph, Loren; Cankovic, Milena; Caughron, Samuel; Chandra, Pranil; Emmadi, Rajyasree; Hagenkord, Jill; Hallam, Stephanie; Jewell, Kay E; Klein, Roger D; Pratt, Victoria M; Rothberg, Paul G; Temple-Smolkin, Robyn L; Lyon, Elaine

    2016-09-01

    Clinical utility describes the benefits of each laboratory test for that patient. Many stakeholders have adopted narrow definitions for the clinical utility of molecular testing as applied to targeted pharmacotherapy in oncology, regardless of the population tested or the purpose of the testing. This definition does not address all of the important applications of molecular diagnostic testing. Definitions consistent with a patient-centered approach emphasize and recognize that a clinical test result's utility depends on the context in which it is used and are particularly relevant to molecular diagnostic testing because of the nature of the information they provide. Debates surrounding levels and types of evidence needed to properly evaluate the clinical value of molecular diagnostics are increasingly important because the growing body of knowledge, stemming from the increase of genomic medicine, provides many new opportunities for molecular testing to improve health care. We address the challenges in defining the clinical utility of molecular diagnostics for inherited diseases or cancer and provide assessment recommendations. Starting with a modified analytic validity, clinical validity, clinical utility, and ethical, legal, and social implications model for addressing clinical utility of molecular diagnostics with a variety of testing purposes, we recommend promotion of patient-centered definitions of clinical utility that appropriately recognize the valuable contribution of molecular diagnostic testing to improve patient care. PMID:27542512

  10. An update on risk factors for drug-induced arrhythmias.

    PubMed

    Vlachos, Konstantinos; Georgopoulos, Stamatis; Efremidis, Michael; Sideris, Antonios; Letsas, Konstantinos P

    2016-01-01

    A variety of drugs, either anti-arrhythmics or non-antiarrhythmics, have been associated with drug-induced arrhythmias. Drug-induced arrhythmias are usually observed in the presence of long QT interval or Brugada electrocardiographic pattern. Clinical risk factors, such as female gender, structural heart disease, metabolic and electrolyte abnormalities, bradycardia and conduction disease, increased drug bioavailability, and silent channelopathies act as ''effect amplifiers'' which can make an otherwise relatively safe drug dangerous with regard to risk for polymorphic ventricular tachycardia in the setting of QT interval prolongation. A drug-induced type 1 electrocardiographic pattern of Brugada syndrome is considered highly proarrhythmic. Specific electrocardiographic markers including the corrected QT interval, QRS duration, Tpeak-Tend/QT ratio, and others may predict the risk of arrhythmias in both situations. The present review highlights on the current clinical and electrocardiographic risk factors for prediction of drug-induced arrhythmias. PMID:26460585

  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. 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

  13. HERG1 Channel Agonists and Cardiac Arrhythmia

    PubMed Central

    Sanguinetti, Michael

    2014-01-01

    Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key determinant of normal repolarization of cardiac action potentials. Loss of function mutations in hERG1 channels cause inherited long QT syndrome and increased risk of cardiac arrhythmia and sudden death. Many common medications that block hERG1 channels as an unintended side effect also increase arrhythmic risk. Routine preclinical screening for hERG1 block led to the discovery of agonists that shorten action potential duration and QT interval. Agonists have the potential to be used as pharmacotherapy for long QT syndrome, but can also be proarrhythmic. Recent studies have elucidated multiple mechanisms of action for these compounds and the structural basis for their binding to the pore domain of the hERG1 channel. PMID:24721650

  14. HERG1 channel agonists and cardiac arrhythmia.

    PubMed

    Sanguinetti, Michael C

    2014-04-01

    Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key determinant of normal repolarization of cardiac action potentials. Loss of function mutations in hERG1 channels cause inherited long QT syndrome and increased risk of cardiac arrhythmia and sudden death. Many common medications that block hERG1 channels as an unintended side effect also increase arrhythmic risk. Routine preclinical screening for hERG1 block led to the discovery of agonists that shorten action potential duration and QT interval. Agonists have the potential to be used as pharmacotherapy for long QT syndrome, but can also be proarrhythmic. Recent studies have elucidated multiple mechanisms of action for these compounds and the structural basis for their binding to the pore domain of the hERG1 channel. PMID:24721650

  15. Arrhythmia in Stem Cell Transplantation

    PubMed Central

    Almeida, Shone O.; Skelton, Rhys J.; Adigopula, Sasikanth; Ardehali, Reza

    2015-01-01

    Synopsis Stem cell regenerative therapies hold promise for treating diseases across the spectrum of medicine. Recent clinical trials have confirmed the safety of stem cell delivery to the heart with promising but variable results. While significant progress has been made in the preclinical stages, the clinical application of cardiac cell therapy is limited by technical challenges, including inability to isolate a pure population of cardiac-specific progenitors capable of robust engraftment and regeneration, lack of appropriate pre-clinical animal models, uncertainty about the best mode of delivery, paucity of adequate imaging modalities, and lack of knowledge about the fate of transplanted cells. The inability of transplanted cells to structurally and functionally integrate into the host myocardium may pose arrhythmogenic risk to patients. This is in part dependent on the type of cell transplanted, where the expression of gap junctions such as connexin-43 is essential not only for electromechanical integration, but has also been found to be protective against electrical instability post-transplant. Additionally, certain methods of cell delivery, such as intramyocardial injection, carry a higher rate of arrhythmias. Other potential contributors to the arrhythmogenicity of cell transplantation include re-entrant pathways due to heterogeneity in conduction velocities between graft and host as well as graft automaticity. In this paper, we discuss the arrhythmogenic potential of cell delivery to the heart. PMID:26002399

  16. Caveolae, Ion Channels and Cardiac Arrhythmias

    PubMed Central

    Balijepalli, Ravi C.; Kamp, Timothy J.

    2009-01-01

    Caveolae are specialized membrane microdomains enriched in cholesterol and sphingolipids which are present in multiple cell types including cardiomyocytes. Along with the essential scaffolding protein caveolin-3, a number of different ion channels and transporters have been localized to caveolae in the heart including L-type Ca2+ channels (Cav1.2), Na+ channels (Nav1.5), pacemaker channels (HCN4), Na+/Ca2+ exchnager (NCX1) and others. Closely associated with these channels are specific macromolecular signaling complexes that provide highly localized regulation of the channels. Mutations in the caveolin-3 gene (CAV3) have been linked with the congenital long QT syndrome (LQT9), and mutations in caveolar-localized ion channels may contribute to other inherited arrhythmias. Changes in the caveolar microdomain in acquired heart disease may also lead to dysregulation and dysfunction of ion channels, altering the risk of arrhythmias in conditions such as heart failure. This review highlights the existing evidence identifying and characterizing ion channels localized to caveolae in cardiomyocytes and their role in arrhythmogenesis. PMID:19351512

  17. A clinical variant in SCN1A inherited from a mosaic father cosegregates with a novel variant to cause Dravet syndrome in a consanguineous family.

    PubMed

    Tuncer, Feyza N; Gormez, Zeliha; Calik, Mustafa; Altiokka Uzun, Gunes; Sagiroglu, Mahmut S; Yuceturk, Betul; Yuksel, Bayram; Baykan, Betul; Bebek, Nerses; Iscan, Akin; Ugur Iseri, Sibel A; Ozbek, Ugur

    2015-07-01

    A consanguineous family from Turkey having two children with intellectual disability exhibiting myoclonic, febrile and other generalized seizures was recruited to identify the genetic origin of these phenotypes. A combined approach of SNP genotyping and exome sequencing was employed both to screen genes associated with Dravet syndrome and to detect homozygous variants. Analysis of exome data was extended further to identify compound heterozygosity. Herein, we report identification of two paternally inherited genetic variants in SCN1A (rs121917918; p.R101Q and p.I1576T), one of which was previously implicated in Dravet syndrome. Interestingly, the previously reported clinical variant (rs121917918; p.R101Q) displayed mosaicism in the blood and saliva of the father. The study supported the genetic diagnosis of affected children as Dravet syndrome possibly due to the combined effect of one clinically associated (rs121917918; p.R101Q) and one novel (p.I1576T) variants in SCN1A gene. This finding is important given that heterozygous variants may be overlooked in standard exome scans of consanguineous families. Thus, we are presenting an interesting example, where the inheritance of the condition may be misinterpreted as recessive and identical by descent due to consanguinity and mosaicism in one of the parents. PMID:25986186

  18. 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.

  19. Mechanisms of Arrhythmias and Conduction Disorders in Older Adults

    PubMed Central

    Mirza, Mahek; Strunets, Anton; Shen, Win-Kuang; Jahangir, Arshad

    2012-01-01

    Synopsis Aging is associated with an increased prevalence of cardiac arrhythmias, which contribute to higher morbidity and mortality in the elderly. The frequency of cardiac arrhythmias, particularly atrial fibrillation and ventricular tachyarrhythmia, is projected to increase as the population ages, greatly impacting health care resource utilization. Several clinical factors associated with the risk of arrhythmias have been identified in the population, yet the molecular bases for the increased predisposition to arrhythmogenesis in the elderly are not fully understood. Therefore, only limited therapeutic strategies directed at pathophysiological processes that enhance cardiac vulnerability to arrhythmias are available. This is further compounded by the paucity of outcome studies providing evidence on which optimal management guidelines can be formulated for the very elderly. This review highlights the epidemiology of cardiac dysrhythmias, changes incardiac structure and function associated with aging, and the basis for arrhythmogenesis in the elderly, the understanding of which is critical to formulate preventive strategies. PMID:23101571

  20. Cardiac arrhythmias in space. Role of vagotonia.

    PubMed

    Leguay, G; Seigneuric, A

    1981-07-01

    Rhythm disorders observed in space have always been minor but they are not unfrequent. They include: ventricular or supra-ventricular extrasystoles, nodal arrhythmias, auriculo-ventricular conduction disorders. There are several etiopathogenetic hypotheses: a strict selection must permit its elimination of an underlying heart disease; the potassium deficiency is often advanced but its role is not certain; the role of catecholamines is also discussed; the role of hypervagotony is extensively analysed as great clinical and electro-cardiographic evidence speaks for it. It can induce disorders which are more serious than those observed so far, particularly fibrillation or intermittent atrial flutter; weightlessness itself could partly condition the vagotonic state; and the effects of fluid shifts are also discussed from this point of view. The possible therapies for various atrial, nodal, ventricular disorders are reviewed, with greater detail for vagal atrial arrhythmias. PMID:11542963

  1. Non-invasive Mapping of Cardiac Arrhythmias.

    PubMed

    Shah, Ashok; Hocini, Meleze; Haissaguerre, Michel; Jaïs, Pierre

    2015-08-01

    Since more than 100 years, 12-lead electrocardiography (ECG) is the standard-of-care tool, which involves measuring electrical potentials from limited sites on the body surface to diagnose cardiac disorder, its possible mechanism, and the likely site of origin. Several decades of research has led to the development of a 252-lead ECG and computed tomography (CT) scan-based three-dimensional electro-imaging modality to non-invasively map abnormal cardiac rhythms including fibrillation. These maps provide guidance towards ablative therapy and thereby help advance the management of complex heart rhythm disorders. Here, we describe the clinical experience obtained using non-invasive technique in mapping the electrical disorder and guide the 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). PMID:26072438

  2. Cardiovascular profiles of scleroderma patients with arrhythmias and conduction disorders.

    PubMed

    Muresan, L; Petcu, A; Pamfil, C; Muresan, C; Rinzis, M; Mada, R O; Gusetu, G N; Pop, D; Zdrenghea, D; Rednic, S

    2016-01-01

    Introduction Arrhythmias and conduction disorders are common among patients with scleroderma. Their early identification is important, since scleroderma patients with arrhythmias have a higher mortality risk compared with scleroderma patients without arrhythmias. The aim of this study was to characterize the cardiovascular profiles of scleroderma patients with different types of arrhythmias and conduction disorders. Methods One hundred and ten consecutive patients with a diagnosis of systemic sclerosis according to the ACR criteria were included in the study. Patients underwent a 12-lead ECG and a 24-hour Holter ECG monitoring for arrhythmias and conduction disorders identification. Blood sample testing, echocardiography, spirometry, chest X-ray and, when considered appropriate, high resolution chest CT were also performed. A subgroup of 21 patients underwent NT-pro BNP level measurements. Patients' clinical and para-clinical characteristics were compared according to the presence or absence of arrhythmias and conduction disorders. Results The prevalence of arrhythmia and conduction disturbances was 60.9%. Patients with such disorders were older (54.4 ± 13.3 vs. 49.7 ± 10.1 years, p=0.05), had a higher prevalence of pulmonary hypertension (p=0.008), valve disease (p < 0.001), especially mitral and tricuspid regurgitation, chamber enlargement on echocardiography (left atrial and right ventricular, p = 0.012 and 0.005, respectively) as well as higher NT-pro BNP levels: 265.5 ± 399.7 vs. 163 ± 264.3 pg/ml, p=0.04. Conclusion Arrhythmias and conduction disorders are common in patients with scleroderma. Patients with such disorders are older, have a higher prevalence of pulmonary hypertension, more severe mitral and tricuspid regurgitation, left atrial and right ventricular dilation on echocardiography. PMID:27115105

  3. Inherited platelet disorders.

    PubMed

    Sandrock-Lang, Kirstin; Wentzell, Rüdiger; Santoso, Sentot; Zieger, Barbara

    2016-08-01

    Inherited platelet disorders may be the cause of bleeding symptoms of varying severity as platelets fail to fulfil their haemostatic role after vessel injury. Platelet disorders may be difficult to diagnose (and are likely to be misdiagnosed) and raise problems in therapy and management. This review explores the clinical and molecular genetic phenotype of several inherited disorders. Inherited platelet disorders can be classified according to their platelet defects: receptor defects (adhesion or aggregation), secretion disorder, and cytoskeleton defects. The best characterized platelet receptor defects are Glanzmann thrombasthenia (integrin αIIbβ3 defect) and Bernard-Soulier syndrome (defect of GPIb/IX/V). Detailed case reports of patients suffering from Glanzmann thrombasthenia (GT) or Bernard-Soulier syndrome (BSS) showing the bleeding diathesis as well as investigation of platelet aggregation/agglutination and platelet receptor expression will complement this review. In addition, Hermansky-Pudlak syndrome (HPS) as an important defect of δ-granule secretion is extensively described together with a case report of a patient suffering from HPS type 1. PMID:25707719

  4. The genetic basis of inherited anomalies of the teeth. Part 1: clinical and molecular aspects of non-syndromic dental disorders.

    PubMed

    Bailleul-Forestier, Isabelle; Molla, Muriel; Verloes, Alain; Berdal, Ariane

    2008-01-01

    The genetic control of dental development represents a complex series of events, which can very schematically be divided in two pathways: specification of type, size and position of each dental organ, and specific processes for the formation of enamel and dentin. Several genes linked with early tooth positioning and development, belong to signalling pathways and have morphogenesis regulatory functions in morphogenesis of other organs where they are associated with the signalling pathways. Their mutations often show pleïotropic effects beyond dental morphogenesis resulting in syndromic developmental disorders. Some genes affecting early tooth development (MSX1, AXIN2) are associated with tooth agenesis and systemic features (cleft palate, colorectal cancer). By contrast, genes involved in enamel (AMELX, ENAM, MMP20, and KLK4) and dentin (DSPP) structures are highly specific for tooth. Mutations in these genes have been identified as causes of amelogenesis imperfecta, dentinogenesis imperfecta, dentin dysplasias and anomalies of teeth number (hypo-, oligo and anodontia), which only partially overlap with the classical phenotypic classifications of dental disorders. This review of genetic basis of inherited anomalies describes, in this first paper, the molecular bases and clinical features of inherited non-syndromic teeth disorders. And in a second part, the review focus on genetic syndromes with dental involvement. PMID:18499550

  5. 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…

  6. 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. PMID:25838530

  7. 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

  8. 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. PMID:27617217

  9. Brain-heart interactions. The neurocardiology of arrhythmia and sudden cardiac death.

    PubMed Central

    Davis, A M; Natelson, B H

    1993-01-01

    Neuroanatomic connections between the brain and the heart provide links that allow cardiac arrhythmias to occur in response to brain activation. Recognition and analysis of such links in the pathogenesis of malignant cardiac arrhythmia are emphasized in this review. Neurocardiac links have been shown to produce arrhythmia both experimentally and clinically; specific examples, including stroke, epilepsy, and environmental stress are presented. We hypothesize that the individual with a diseased heart has a greater likelihood of experiencing cardiac arrhythmia and sudden cardiac death when the neurocardiac axis is activated. Reviewing possible mechanisms of brain-related arrhythmias, we suggest that the nervous system directs the events leading to cardiac damage by raising catecholamine levels and potentially inducing arrhythmia. PMID:8219819

  10. Exercising arrhythmias and sudden cardiac death in horses: Review of the literature and comparative aspects.

    PubMed

    Navas de Solis, C

    2016-07-01

    Arrhythmias are common in equine athletes during and immediately after exercise. Many of these rhythm variations are not clinically relevant. In horses, a link between different exercising arrhythmias and poor performance or between exercising arrhythmias and sudden cardiac death (SCD) is strongly suspected but not fully understood or proven. SCD during races or competitions is rare, but has catastrophic consequences for the safety of the human partner and public perceptions of welfare during equestrian sports. This review summarises current knowledge of equine exercise arrhythmias and their implications in SCD and compares existing principles and recommendations for equine subjects with those for human athletes. PMID:27156002

  11. Defining a new paradigm for human arrhythmia syndromes: Phenotypic manifestations of gene mutations in ion channel- and transporter-associated proteins

    PubMed Central

    Ackerman, Michael J.; Mohler, Peter J.

    2010-01-01

    Over the past fifteen years, gene mutations in cardiac ion channels have been linked with a host of potentially fatal human arrhythmias including long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. More recently, a new paradigm for human arrhythmia has emerged based on gene mutations that affect the activity of cardiac ion channel- and transporter- associated proteins. As part of the Circulation Research thematic series on Inherited Arrhythmias, this review will focus on the emerging field of human arrhythmias due to dysfunction in cytosolic gene products (including ankyrins, yotiao, syntrophin, and caveolin-3) that regulate the activities of key membrane ion channels and transporters. PMID:20724725

  12. Arrhythmogenic right-ventricular cardiomyopathy: molecular genetics into clinical practice in the era of next generation sequencing.

    PubMed

    Poloni, Giulia; De Bortoli, Marzia; Calore, Martina; Rampazzo, Alessandra; Lorenzon, Alessandra

    2016-06-01

    Sudden death, ventricular arrhythmia and heart failure are common features in arrhythmogenic right-ventricular cardiomyopathy (ARVC), an inheritable heart muscle disease, characterized by clinical and genetic heterogeneity. So far, 13 disease genes have been identified, responsible for around 60% of all ARVC cases. In this review, we summarize the main clinical and pathological aspects of ARVC, focusing on the importance of the genetic testing and the application of the new sequencing techniques referred to next generation sequencing technology. PMID:26990921

  13. Arrhythmia risk in liver cirrhosis

    PubMed Central

    Mozos, Ioana

    2015-01-01

    Interactions between the functioning of the heart and the liver have been described, with heart diseases affecting the liver, liver diseases affecting the heart, and conditions that simultaneously affect both. The heart is one of the most adversely affected organs in patients with liver cirrhosis. For example, arrhythmias and electrocardiographic changes are observed in patients with liver cirrhosis. The risk for arrhythmia is influenced by factors such as cirrhotic cardiomyopathy, cardiac ion channel remodeling, electrolyte imbalances, impaired autonomic function, hepatorenal syndrome, metabolic abnormalities, advanced age, inflammatory syndrome, stressful events, impaired drug metabolism and comorbidities. Close monitoring of cirrhotic patients is needed for arrhythmias, particularly when QT interval-prolonging drugs are given, or if electrolyte imbalances or hepatorenal syndrome appear. Arrhythmia risk may persist after liver transplantation due to possible QT interval prolongation, persistence of the parasympathetic impairment, post-transplant reperfusion and chronic immunosuppression, as well as consideration of the fact that the transplant itself is a stressful event for the cardiovascular system. The aims of the present article were to provide a review of the most important data regarding the epidemiology, pathophysiology, and biomarkers of arrhythmia risk in patients with liver cirrhosis, to elucidate the association with long-term outcome, and to propose future research directions. PMID:25866603

  14. 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. PMID:27289368

  15. EFFECTS OF 4% AND 5% CARBOXYHEMOGLOBIN ON ARRHYTHMIA PRODUCTION IN PATIENTS WITH CORONARY ARTERY DISEASE

    EPA Science Inventory

    Sudden death frequently occurs from coronary artery disease. t almost always results from cardiac arrhythmias and is often the first and only clinically recognizable manifestation of the disease process (1). ecause of the relations among cardiac arrhythmias, sudden death, and cor...

  16. Arrhythmias in the muscular dystrophies.

    PubMed

    Rajdev, Archana; Groh, William J

    2015-06-01

    In patients with muscular dystrophies, cardiac involvement leading to cardiomyopathy and arrhythmias occurs with variable prevalence, mirroring the phenotypic variability seen among and within the various hereditary myopathies. Knowledge of the incidence of arrhythmias and predictors of sudden death in the various hereditary myopathies can help guide screening and appropriate management of these patients, thereby improving survival. The noncardiac manifestations can lead to delayed recognition of symptoms, affect the decision to implant a prophylactic device, and once a decision is made to proceed with device implant, increase peri-procedural respiratory and anesthesia-related complications. PMID:26002394

  17. [Inherited bone marrow failure syndromes].

    PubMed

    Okuno, Yusuke

    2016-02-01

    Inherited bone marrow failure syndromes comprise a series of disorders caused by various gene mutations. Genetic tests were formerly difficult to perform because of the large size and number of causative genes. However, recent advances in next-generation sequencing has enabled simultaneous testing of all causative genes to be performed at an acceptable cost. We collaboratively conducted a series of whole-exome sequencing studies of patients with inherited bone marrow failure syndromes and discovered RPS27/RPL27 and FANCT as causative genes of Diamond-Blackfan anemia and Fanconi anemia, respectively. Furthermore, we established a target gene sequencing system to cover 189 genes associated with pediatric blood diseases to assist genetic diagnoses in clinical practice. In this review, discovery of new causative genes and possible roles of next-generation sequencing in the genetic diagnosis of inherited bone marrow failure syndromes are discussed. PMID:26935625

  18. Sudden Arrhythmia Death Syndromes (SADS) Foundation

    MedlinePlus

    ... all proceeds benefiting the SADS Foundation (Sudden Arrhythmia Death Syndrome). Each year 4,000 young Americans die ... Investigator Awardees 5/19/2016 The Sudden Arrhythmia Death Syndromes (SADS) Foundation announces the winners for the ...

  19. Arrhythmia - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Arrhythmia URL of this page: https://medlineplus.gov/languages/arrhythmia.html Other topics A-Z A B ...

  20. Arrhythmia - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Arrhythmia URL of this page: https://www.nlm.nih.gov/medlineplus/languages/arrhythmia.html Other topics A-Z A B ...

  1. Inherited renal carcinomas.

    PubMed

    Kawashima, Akira; Young, Scott W; Takahashi, Naoki; King, Bernard F; Atwell, Thomas D

    2016-06-01

    Hereditary forms of kidney carcinoma account for 5-8% of all malignant kidney neoplasms. The renal tumors are often multiple and bilateral and occur at an earlier age. Each of the hereditary kidney carcinoma syndromes is associated with specific gene mutations as well as a specific histologic type of kidney carcinoma. The presence of associated extrarenal manifestations may suggest a hereditary kidney cancer syndrome. Radiology is most commonly used to screen and manage patients with hereditary kidney cancer syndromes. This manuscript reviews the clinical and imaging findings of well-defined inherited kidney cancer syndromes including von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, hereditary papillary renal carcinoma syndrome, hereditary leiomyomatosis and RCC syndrome, tuberous sclerosis complex, and Lynch syndrome. PMID:27108134

  2. 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. PMID:25088161

  3. Arrhythmias in Complex Congenital Heart Disease

    PubMed Central

    Hayward, Robert M.; Tseng, Zian H.

    2014-01-01

    Late after surgical repair of complex congenital heart disease, atrial arrhythmias are a major cause of morbidity, and ventricular arrhythmias and sudden cardiac death are a major cause of mortality. The six cases in this article highlight common challenges in the management of arrhythmias in the adult congenital heart disease population. PMID:25197326

  4. 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. PMID:26218181

  5. Laboratory Markers of Ventricular Arrhythmia Risk in Renal Failure

    PubMed Central

    2014-01-01

    Sudden cardiac death continues to be a major public health problem. Ventricular arrhythmia is a main cause of sudden cardiac death. The present review addresses the links between renal function tests, several laboratory markers, and ventricular arrhythmia risk in patients with renal disease, undergoing or not hemodialysis or renal transplant, focusing on recent clinical studies. Therapy of hypokalemia, hypocalcemia, and hypomagnesemia should be an emergency and performed simultaneously under electrocardiographic monitoring in patients with renal failure. Serum phosphates and iron, PTH level, renal function, hemoglobin and hematocrit, pH, inflammatory markers, proteinuria and microalbuminuria, and osmolarity should be monitored, besides standard 12-lead ECG, in order to prevent ventricular arrhythmia and sudden cardiac death. PMID:24982887

  6. Method for classifying cardiac arrhythmias using photoplethysmography.

    PubMed

    Polania, Luisa F; Mestha, Lalit K; Huang, David T; Couderc, Jean-Philippe

    2015-08-01

    Advances in mobile computing and miniature devices have contributed to the accelerated development of wearable technologies for clinical applications. The new trend of wearable technologies has fostered a growth of interest for sensors that can be easily integrated into wearable devices. In particular, photoplethysmography (PPG) is especially suitable for wearable sensing, as it is low-cost, noninvasive, and does not require wet electrodes like the electrocardiogram. Photoplethysmograph signals contain rich information about the blood pulsating variation which is strongly related to the electrical activities of the heart. Therefore, in this paper we hypothesize that the ambulatory PPG monitoring could be employed for arrhythmia detection and classification. This paper presents a method for classifying ventricular premature contraction (VPC) and ventricular tachycardia (VT) from normal sinus rhythm (NSR) and supraventricular premature contraction (SVPC) recorded in patients going through ablation therapy for arrhythmia. Although occasional VPCs are benign, the increase in the frequency of VPC events may lead to VT, which in turn,could evolve into ventricular fibrillation and sudden cardiac death. Therefore the accurate measurement of VPC frequency and early detection of VT events becomes essential for patients with cardiac disease. PMID:26737799

  7. 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. PMID:26577165

  8. Clinical aspects of an autosomal dominantly inherited hearing impairment linked to the DFNA60 locus on chromosome 2q23.1-2q23.3.

    PubMed

    van Beelen, E; Schraders, M; Huygen, P L M; Oostrik, J; Plantinga, R F; van Drunen, W; Collin, R W J; Kooper, D P; Pennings, R J E; Cremers, C W R J; Kremer, H; Kunst, H P M

    2013-06-01

    A total of 64 loci for autosomal dominant non-syndromic hearing impairment have been described, and the causative genes have been identified for 24 of these. The present study reports on the clinical characteristics of an autosomal dominantly inherited hearing impairment that is linked to a region within the DFNA60 locus located on chromosome 2 in q22.1-24.1. A pedigree spanning four generations was established with 13 affected individuals. Linkage analysis demonstrated that the locus extended over a 2.96 Mb region flanked by markers D2S2335 and D2S2275. The audiograms mainly showed a distinctive U-shaped configuration. Deterioration of hearing started at a wide age range, from 12 to 40 years. Cross-sectional analysis showed rapid progression of hearing impairment from mild to severe, between the ages of 40 and 60 years, a phenomenon that is also observed in DFNA9 patients. The results of the individual longitudinal analyses were generally in line with those obtained by the cross-sectional analysis. Speech recognition scores related to the level of hearing impairment (PTA1,2,4 kHz) appeared to be fairly similar to those of presbyacusis patients. It is speculated that hearing impairment starting in mid-life, as shown by DFNA60 patients, could play a role in the development of presbyacusis. Furthermore, speech recognition did not deteriorate appreciably before the sixth decade of life. We conclude that DFNA60 should be considered in hearing impaired patients who undergo a rapid progression in middle age and are negative for DFNA9. Furthermore, cochlear implantation resulted in good rehabilitation in two DFNA60 patients. PMID:23538131

  9. Arrhythmias in the Muscular Dystrophies

    PubMed Central

    Rajdev, Archana; Groh, William J.

    2015-01-01

    Synopsis In patients with muscular dystrophies, cardiac involvement leading to cardiomyopathy and arrhythmias occur with variable prevalence mirroring the phenotypic variability seen among and within the various hereditary myopathies. These patients are at risk for development for bradyarrhythmias and tachyarrhythmias including sudden cardiac death. Knowledge of the incidence of arrhythmias and predictors of sudden death in the various hereditary myopathies can help guide screening and appropriate management of these patients, thereby improving survival. The non-cardiac manifestations can lead to delayed recognition of symptoms (limited mobility and respiratory weakness masking cardiac manifestations), affect decision to implant prophylactic device (quantity vs. quality of life) and once a decision is made to proceed with device implant, increase peri-procedural respiratory and anesthesia-related complications. PMID:26002394

  10. 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

  11. 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.

  12. 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.

  13. Electrical injury causing ventricular arrhythmias.

    PubMed Central

    Jensen, P J; Thomsen, P E; Bagger, J P; Nørgaard, A; Baandrup, U

    1987-01-01

    Dangerous or long lasting ventricular arrhythmias developed in three patients who had sustained an electrical injury in which current passed through the thorax. In all three cases there was a delay of 8-12 hours between the injury and the onset of symptoms. The ventricular arrhythmias were severe and long lasting. In two of the three patients, ventricular tachycardia or ventricular fibrillation or both occurred and in one patient ventricular parasystole developed. No enzymatic evidence of myocardial necrosis was found but the results of an endomyocardial biopsy carried out in two of the three patients showed focal myocardial fibrosis and increased numbers of Na, K-pumps. The two patients with ventricular tachycardia became symptom free after appropriate antiarrhythmic treatment and in the third patient ventricular parasystole disappeared spontaneously within two years. Patients sustaining electrical injury in which current passes through the thorax should be monitored electrocardiographically for at least 24 hours, and patients with unexpected arrhythmias should be questioned about previous electrical injury. Images Fig 2 PMID:3566986

  14. 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. PMID:21402391

  15. Circadian rhythms in cardiac arrhythmias and opportunities for their chronotherapy.

    PubMed

    Portaluppi, Francesco; Hermida, Ramón C

    2007-08-31

    It is now well established that nearly all functions of the body, including those that influence the pharmacokinetics and pharmacodynamics of medications, exhibit significant 24-hour variation. The electrical properties of the heart as well as cardiac arrhythmias also vary as circadian rhythms, even though the suboptimal methods initially used for their investigation slowed their identification and thorough characterization. The application of continuous Holter monitoring of the electrical properties of the heart has revealed 24-hour variation in the occurrence of ventricular premature beats with the peak in events, in diurnally active persons, between 6 a.m. and noon. After the introduction of implantable cardioverter-defibrillators, ventricular tachycardia or fibrillation were also found to peak in the same period of the day. Even defibrillator energy requirements show circadian variation, thus supporting the need for a temporal awareness in the therapeutic approach to arrhythmias. Imbalanced autonomic tone, circulating levels of catecholamines, increased heart rate and blood pressure, all established determinants of cardiac arrhythmias, show circadian variations and underlie the genesis of the circadian pattern of cardiac arrhythmias. Arrhythmogenesis appears to be suppressed during nighttime sleep, and this can influence the evaluation of the efficacy of antiarrhythmic medications in relation to their administration time. Unfortunately, very few studies have been undertaken to assess the proper timing (chronotherapy) of antiarrhythmic medications as means to maximize efficacy and possibly reduce side effects. Further research in this field is warranted and could bring new insight and clinical advantage. PMID:17659808

  16. [Inherited amino acid transport disorders].

    PubMed

    Igarashi, Y; Tada, K

    1992-07-01

    Disorders due to inherited amino acids transport defect are reviewed. The disorders were categorized into three types of transport defects, namely, brush-border membrane of epithelial cells of small intestine and kidney tubules (Hartnup disease, blue diaper syndrome, cystinuria, iminoglycinuria and lysine malabsorption syndrome), basolateral membrane (lysinuric protein intolerance) and membrane of intracellular organelles (cystinosis and hyperornitinemia-hyperammonemia-homocitrullinuria syndrome). Pathogenesis, clinical feature, laboratory findings, diagnosis, genetics and treatment of these disorders are described, briefly. There is not much data for the transport systems themselves, so that further investigation in molecular and gene levels for transport systems is necessary to clarify the characteristics of the transport and heterogeneity of phenotypes in inherited amino acids transport disorders. PMID:1404888

  17. Maternal cardiac arrhythmias during pregnancy and lactation

    PubMed Central

    Cordina, Rachael; McGuire, Mark A

    2010-01-01

    Arrhythmias occurring during pregnancy can cause significant symptoms and even death in mother and fetus. The management of these arrhythmias is complicated by the need to avoid harm to the fetus and neonate. It is useful to classify patients with arrhythmias into those with and without structural heart disease. Those with a primary electrical problem, but an otherwise normal heart, often tolerate rapid heart rates without compromise whereas patients with problems such as rheumatic heart disease, congenital heart disease or cardiomyopathy may quickly decompensate during an arrhythmia.

  18. 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

  19. 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)

  20. 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.

  1. Arrhythmias

    MedlinePlus

    ... travels through the heart along a set electrical pathway. Different nerve messages signal your heart to beat ... slowed. Electrical signals travel in new or different pathways through the heart. Some common causes of abnormal ...

  2. Arrhythmias

    MedlinePlus

    ... done to look at heart function: Coronary angiography ECG (electrocardiogram) Echocardiogram A special test, called an electrophysiology ... through the middle Heart, front view Atrioventricular block, ECG tracing Normal heart rhythm Bradycardia Ventricular tachycardia Conduction ...

  3. Arrhythmia

    MedlinePlus

    ... chambers. The walls of the heart squeeze together (contract) to push blood through the chambers. The contractions ... heart beats too slowly. Cardiac defibrillation (very brief electric shock) can be used to stop an abnormal ...

  4. Arrhythmias

    MedlinePlus

    ... a heart function test, like an electrocardiogram (ECG/EKG) . continue What's a Normal Heart Rate? Heart rate ... suspected, the doctor will probably recommend an ECG/EKG to measure the heart's electrical activity. There's nothing ...

  5. Sinus Node and Atrial Arrhythmias.

    PubMed

    John, Roy M; Kumar, Saurabh

    2016-05-10

    Although sinus node dysfunction (SND) and atrial arrhythmias frequently coexist and interact, the putative mechanism linking the 2 remain unclear. Although SND is accompanied by atrial myocardial structural changes in the right atrium, atrial fibrillation (AF) is a disease of variable interactions between left atrial triggers and substrate most commonly of left atrial origin. Significant advances have been made in our understanding of the genetic and pathophysiologic mechanism underlying the development and progression of SND and AF. Although some patients manifest SND as a result of electric remodeling induced by periods of AF, others develop progressive atrial structural remodeling that gives rise to both conditions together. The treatment strategy will thus vary according to the predominant disease phenotype. Although catheter ablation will benefit patients with predominantly AF and secondary SND, cardiac pacing may be the mainstay of therapy for patients with predominant fibrotic atrial cardiomyopathy. This contemporary review summarizes current knowledge on sinus node pathophysiology with the broader goal of yielding insights into the complex relationship between sinus node disease and atrial arrhythmias. PMID:27166347

  6. [Electrophysiologic study in arrhythmia surgery].

    PubMed

    Nitta, Takashi

    2007-07-01

    The traditional paradigm in surgery for cardiac arrhythmias has been the electrophysiological assessment of the arrhythmia followed by the determination of a specific lesion set for the ablation or a definitive procedure based on the results of the analysis in each patient. The maze procedure was developed as a definitive procedure for atrial fibrillation (AF) and was not guided by electrophysiologic findings in individual patients. The rationale behind the maze procedure is to create a line of conduction block to prevent the propagation of repetitive activations from the pulmonary veins toward the left atrium and to block the reentrant activations occurring on the atrial wall. The cut-and-sew technique is the most reliable method to accomplish conduction block. However, it extends the cardiac arrest and cardiopulmonary times and increases the risk of bleeding. During the past decade, a number of ablation devices have been developed and tested in animals and humans for their ability to create complete conduction block. The use of ablation devices enables less invasive AF surgery. However, the non-transmural or non-contiguous necrosis caused by an incomplete ablation can permit conduction across the ablation line and impair the efficacy of the surgery. Intraoperative verification of conduction block is mandatory to assure the transmurality and contiguity of the lesions created by the ablation devices. PMID:17763669

  7. Exercise-induced ventricular arrhythmias in congestive heart failure and role of ACE inhibitors.

    PubMed

    Hasija, P K; Karloopia, S D; Shahi, B N; Chauhan, S S

    1998-02-01

    Ventricular arrhythmias are considered to be related to left ventricular (LV) dysfunction. ACE inhibitors though improve LV function their beneficial role on exercise-induced ventricular arrhythmias is not established. To study the effects of ACE inhibitors on exercise capacity vis-a-vis their role on exercise-induced ventricular arrhythmias, 25 patients of congestive heart failure (CHF) of various etiologies in NYHA Class II and III were subjected to a prospective randomised controlled trial. The control group comprising of 12 patients received conventional treatment (digitalis and diuretics) and the test group was given enalapril/captopril in addition as tolerated. They were followed up for 3 months. Exercise testing on treadmill and monitoring of clinical and biochemical parameters were done at the beginning and end of study in all cases. Ventricular arrhythmias observed during exercise and post-exercise for 10 minutes was analysed using Lown's grading for frequency and severity of ventricular arrhythmia. The mean exercise duration showed significant improvement on ACE inhibitor as compared to the control group (p < 0.05) however there was no significant change in the grades of arrhythmia. Serum electrolytes and other bio-chemical parameter were within normal range. It is concluded that effect of ACE inhibitor on improving functional capacity in CHF is independent of it's any effect on exercise-induced ventricular arrhythmias. PMID:11273109

  8. Inherited disorders of GABA metabolism

    PubMed Central

    Pearl, Phillip L; Hartka, Thomas R; Cabalza, Jessica L; Taylor, Jacob; Gibson, Michael K

    2013-01-01

    The inherited disorders of γ-amino butyric acid (GABA) metabolism require an increased index of clinical suspicion. The known genetic disorders are GABA-transaminase deficiency, succinic semialdehyde dehydrogenase (SSADH) deficiency and homocarnosinosis. A recent link has also been made between impaired GABA synthesis and nonsyndromic cleft lip, with or without cleft palate. SSADH deficiency is the most commonly occurring of the inherited disorders of neurotransmitters. The disorder has a nonspecific phenotype with myriad neurological and psychiatric manifestations, and usually has a nonprogressive temporal course. Diagnosis is made by the detection of γ-hydroxybutyrate excretion on urine organic acid testing. The most consistent magnetic resonance imaging abnormality is an increased signal in the globus pallidus. Magnetic resonance spectroscopy has demonstrated the first example of increased endogenous GABA in human brain parenchyma in this disorder. GABA-transaminase deficiency and homocarnosinosis appear to be very rare, but require cerebrospinal fluid for detection, thus allowing for the possibility that these entities, as in the other inherited neurotransmitter disorders, are under-recognized. PMID:23842532

  9. 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.

  10. Inherited Disorders of Bilirubin Clearance

    PubMed Central

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2016-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

  11. 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

  12. 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.

  13. 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. PMID:23569106

  14. [Treatment of arrhythmia in atrial fibrillation].

    PubMed

    Daubert, Jean-Claude; Pavin, Dominique

    2013-02-01

    The initial therapy after onset of atrial fibrillation (AF) should always include adequate antithrombotic treatment and control of the ventricular rate. Depending on the patient's course, this strategy may prove insufficient and may then be supplemented by rhythm control using drugs or interventions. Clinical frustration came by clinical trials that have demonstrated that the strategy of maintaining sinus rhythm has no demonstrable value when compared with the "laissez-faire" approach of leaving AF to a permanent form and controlling ventricular rate. These disappointing findings can be considered as paradoxical when considering the severe complications associated with AF in epidemiological studies. New anti-arrhythmic approaches might offer added value but this is still a matter of debate. Non-pharmacological interventions to prevent AF recurrences or to limit its expression have been substantially developed in the past decade. Ablation techniques, usually done percutaneously using a catheter, have proved successful n the treatment of AF, particularly by reducing the symptomatic burden associated with the arrhythmia, to such an extent that a 'cure' may be achieved in some patients with paroxysmal AF. PMID:23513784

  15. Biomarkers in electrophysiology: role in arrhythmias and resynchronization therapy

    PubMed Central

    Bose, Abhishek; Truong, Quynh A.

    2015-01-01

    Circulating biomarkers related to inflammation, neurohormones, myocardial stress, and necrosis have been associated with commonly encountered arrhythmic disorders such as atrial fibrillation (AF) and more malignant processes including ventricular arrhythmias (VA) and sudden cardiac death (SCD). Both direct and indirect biomarkers implicated in the heart failure cascade have potential prognostic value in patients undergoing cardiac resynchronization therapy (CRT). This review will focus on the role of biomarkers in AF, history of SCD, and CRT with an emphasis to improve clinical risk assessment for arrhythmias and patient selection for device therapy. Notably, information obtained from biomarkers may supplement traditional diagnostic and imaging techniques, thus providing an additional benefit in the management of patients. PMID:25715916

  16. Lysophosphatidylcholine (LPC) metabolism and cardiac arrhythmias

    SciTech Connect

    Giffin, D.M.; Man, R.Y.K.; Arthur, G.; Choy, P.C.

    1986-05-01

    The effect of LPC in the production of cardiac arrhythmias in isolated mammalian hearts has been well-documented. Cardiac arrhythmias are initiated by the accumulation of the lysolipid in the cardiac membrane. When isolated rat hearts were perfused in 10 ..mu..M LPC for 10 min, severe arrhythmias were observed in all experiments. In isolated guinea pig hearts that were perfused under identical conditions, the development of severe arrhythmias was never observed, and mild arrhythmias were produced in less than 50% of the hearts used. When the hearts of both species were perfused with (/sup 14/C-palmitate)-LPC, the labellings found in the microsomal fractions (expressed in mg protein) were similar. However, a higher amount of labelled LPC (2-fold) was found in rat heart microsomes, whereas a higher amount of labelled fatty acid was located in the guinea pig heart microsomes. Determination of lysophospholipase activities in these microsomal fractions revealed that the specific activity of the enzyme was much higher in the guinea pig heart than the rat heart. The authors conclude that the differential effect of LPC-induced arrhythmias between the rat and guinea pig heart may be a direct result of the lysophospholipase activities in these hearts. The ability to catabolize LPC more rapidly in the guinea pig heart may decrease the accumulation of LPC in the membrane, and hence, reduce the production of arrhythmias.

  17. 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

  18. The year in review of clinical cardiac electrophysiology.

    PubMed

    Marcus, Gregory M; Keung, Edmund; Scheinman, Melvin M

    2013-02-19

    This past year saw multiple important advances in the field clinical cardiac electrophysiology. Seminal articles describing new anticoagulant drugs for stroke prevention in atrial fibrillation were published. New results that raise questions regarding the safety of dronedarone and several new promising techniques in AF ablation were described. Important articles that refine our understanding of the risk of sudden death among Wolff-Parkinson-White patients were published. In the basic and translational sciences, the application of gene therapy to the study and potential treatment of arrhythmias was described, whereas genetic determinants important to the optimal treatment of inherited arrhythmia syndromes were further elucidated. Issues relevant to cardiac rhythm device therapy included investigations into the St. Jude Riata lead, new applications of device monitoring, predicting response to cardiac resynchronization therapy, and the use of pacemakers for vasovagal syncope. PMID:23312706

  19. Cardiac Arrhythmias In Congenital Heart Diseases

    PubMed Central

    Khairy, Paul; Balaji, Seshadri

    2009-01-01

    Arrhythmias figure prominently among the complications encountered in the varied and diverse population of patients with congenital heart disease, and are the leading cause of morbidity and mortality. The incidence generally increases as the patient ages, with multifactorial predisposing features that may include congenitally malformed or displaced conduction systems, altered hemodynamics, mechanical or hypoxic stress, and residual or postoperative sequelae. The safe and effective management of arrhythmias in congenital heart disease requires a thorough appreciation for conduction system variants, arrhythmia mechanisms, underlying anatomy, and associated physiology. We, therefore, begin this review by presenting the scope of the problem, outlining therapeutic options, and summarizing congenital heart disease-related conduction system anomalies associated with disorders of the sinus node and AV conduction system. Arrhythmias encountered in common forms of congenital heart disease are subsequently discussed. In so doing, we touch upon issues related to risk stratification for sudden death, implantable cardiac devices, catheter ablation, and adjuvant surgical therapy. PMID:19898654

  20. 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.

  1. Cibenzoline versus flecainide in the prevention of paroxysmal atrial arrhythmias: a double-blind randomized study.

    PubMed

    Babuty, D; D'Hautefeuille, B; Scheck, F; Mycinsky, C; Pruvost, P; Peraudeau, P

    1995-05-01

    In a randomized, double-blind, parallel clinical trial, the authors tested and compared flecainide and cibenzoline, a new antiarrhythmic drug, on atrial arrhythmias. Sixty-eight patients (36 men, 32 women, mean age 62.5 +/- 1.6 years) with documented symptomatic paroxysmal atrial arrhythmias (fibrillation in 56, flutter in 12) were recruited and received either cibenzoline 260 mg/day (n = 33) or flecainide 200 mg/day (n = 35). Patients were assessed with physical examination, resting ECG, 24-hour ambulatory ECG recording, two-dimensional echocardiography, and standard biologic titrations before the inclusion day, and 3 months and 6 months after the randomization day. Sixteen patients were withdrawn (7 were lost to follow-up, 7 had side effects, 2 had another medical event). Seventeen patients had documented recurrence of atrial arrhythmia (9 in the cibenzoline group, 8 in the flecainide group) during the study. The efficacy of cibenzoline and flecainide for preventing recurrence of atrial arrhythmias was not significantly different (62.5% versus 71.4%). Eleven patients complained of one or more side effects (cibenzoline, n = 6; flecainide, n = 5), justifying leaving the trial in 6 cases (cibenzoline, n = 3; flecainide, n = 3). Two ventricular proarrhythmic effects were observed. No atrial proarrhythmic effects were reported. The efficacy of cibenzoline and flecainide for preventing atrial arrhythmia is good and similar during a follow-up period of 6 months. In view of these results, cibenzoline may be administered first to prevent atrial arrhythmia. PMID:7657846

  2. Shensong Yangxin capsules prevent ischemic arrhythmias by prolonging action potentials and alleviating Ca2+ overload.

    PubMed

    Zhao, Yixiu; Gao, Feng; Zhang, Yong; Wang, Hongtao; Zhu, Jiuxin; Chang, Liping; Du, Zhimin; Zhang, Yan

    2016-06-01

    Shensong Yangxin capsules (SSYX) are an effective traditional Chinese medicine that has been used to treat coronary heart disease clinically. The present study aimed to establish whether SSYX prevent ischemic arrhythmias in rats, and to explore the underlying mechanisms. Male rats were pretreated with distilled water, SSYX and amiodarone for one week. Acute myocardial ischemia (AMI) was performed to induce ischemic arrhythmias. The incidence and severity of ischemic arrhythmias were evaluated. The action potential, transient outward K+ current (Ito) and inward rectifier K+ current (IK1) of rat cardiomyocytes were measured using the patch‑clamp technique. The intracellular Ca2+ concentration of the cardiomyocytes was measured using a laser scanning confocal microscope. The results revealed that SSYX lowered the incidence of arrhythmia markedly during AMI. Furthermore, SSYX delayed the appearance, and reduced the severity, of ischemic arrhythmias compared with the control. In addition, SSYX markedly decreased the ratio of the myocardial infarction region to the whole heart. In an in vitro study, SSYX prolonged the action potential duration of rat cardiomyocytes, and inhibited Ito and IK1 markedly. Additionally, SSYX inhibited Ca2+ elevation induced by KCl in cardiomyocytes. These results suggested that SSYX prevents ischemic arrhythmia, and the underlying mechanism responsible for this process may include prolonging the action potential and alleviating Ca2+ overload. PMID:27122298

  3. 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.

  4. [Cardiac arrhythmias in targeted connexin deficient mice: significance for the arrhythmia field].

    PubMed

    Hagendorff, A; Plum, A

    2000-12-01

    Intercellular communication can be mediated by gap junction channels. One channel is composed of two hexameric hemichannels which consist of six polypeptide subunits called connexines (Cx). Three different connexines were documented in the cardiac myocytes: Cx40, Cx43 and Cx45. The labeling by number represents the rounded, molecular mass of the amino acid sequences given in kD. Identical connexons form homotypic channels different connexons can form heterotypic channels. Each channel type has specific properties regarding permeability and electrical conductance. Beside a typical age-dependent alignment of gap junction channels on the surface of the cardiac myocytes, regional distribution of the different connexins is different at distinct parts of the mouse heart. The ventricular working myocardium is characterized by Cx43, whereas Cx40 and Cx45 were not found in this region. In the atria as well as in the conduction system, Cx40 is the most frequently expressed. Cx45 appears to form a border zone between conductive and the surrounding working myocardium. In line with the localization and the conduction properties of distinct homotypic gap junction channels, the Cx43 deficient mouse is suitable for analysis of ventricular arrhythmias and the Cx40 deficient mouse primarily for studies of atrial arrhythmias. Increased ventricular conduction velocity and increased ventricular vulnerability were observed in the presence of a decreased number and density of Cx43 gap junction channels. This observation, however, is controversially discussed. Cx40 deficiency induces an impairment of the sinuatrial, intraatrial and atrioventricular conduction properties and is associated with an increased atrial vulnerability. Transgenic mouse models and new mapping techniques for detection of the electrical wavefront propagation provide new insights into the mechanisms of arrhythmogenesis. Geneticists, clinicians and basic researchers need to collaborate in order to explore the clinical

  5. [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. PMID:19820803

  6. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models.

    PubMed

    Arevalo, Hermenegild J; Vadakkumpadan, Fijoy; Guallar, Eliseo; Jebb, Alexander; Malamas, Peter; Wu, Katherine C; Trayanova, Natalia A

    2016-01-01

    Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients' clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations. PMID:27164184

  7. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models

    PubMed Central

    Arevalo, Hermenegild J.; Vadakkumpadan, Fijoy; Guallar, Eliseo; Jebb, Alexander; Malamas, Peter; Wu, Katherine C.; Trayanova, Natalia A.

    2016-01-01

    Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients' clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations. PMID:27164184

  8. 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. PMID:27568872

  9. Use of an Implantable Loop Recorder in the Investigation of Arrhythmias in Adult Captive Chimpanzees (Pan troglodytes)

    PubMed Central

    Lammey, Michael L; Jackson, Raven; Ely, John J; Lee, D Rick; Sleeper, Meg M

    2011-01-01

    Cardiovascular disease in general, and cardiac arrhythmias specifically, is common in great apes. However, the clinical significance of arrhythmias detected on short-duration electrocardiograms is often unclear. Here we describe the use of an implantable loop recorder to evaluate cardiac rhythms in 4 unanesthetized adult chimpanzees (Pan troglodytes), 1 with a history of possible syncope and 3 with the diagnosis of multiform ventricular ectopy (ventricular premature complexes) and cardiomyopathy. The clinical significance of ventricular ectopy was defined further by using the implantable loop recorder. Arrhythmia was ruled out as a cause of collapse in the chimpanzee that presented with possible syncope because the implantable loop recorder demonstrated normal sinus rhythm during a so-called syncopal event. This description is the first report of the use of an implantable loop recorder to diagnose cardiac arrhythmias in an unanesthetized great ape species. PMID:21819684

  10. The involvement of TRPC3 channels in sinoatrial arrhythmias

    PubMed Central

    Ju, Yue-Kun; Lee, Bon Hyang; Trajanovska, Sofie; Hao, Gouliang; Allen, David G.; Lei, Ming; Cannell, Mark B.

    2015-01-01

    Atrial fibrillation (AF) is a significant contributor to cardiovascular morbidity and mortality. The currently available treatments are limited and AF continues to be a major clinical challenge. Clinical studies have shown that AF is frequently associated with dysfunction in the sino-atrial node (SAN). The association between AF and SAN dysfunction is probably related to the communication between the SAN and the surrounding atrial cells that form the SAN-atrial pacemaker complex and/or pathological processes that affect both the SAN and atrial simultaneously. Recent evidence suggests that Ca2+ entry through TRPC3 (Transient Receptor Potential Canonical-3) channels may underlie several pathophysiological conditions -including cardiac arrhythmias. However, it is still not known if atrial and sinoatrial node cells are also involved. In this article we will first briefly review TRPC3 and IP3R signaling that relate to store/receptor-operated Ca2+ entry (SOCE/ROCE) mechanisms and cardiac arrhythmias. We will then present some of our recent research progress in this field. Our experiments results suggest that pacing-induced AF in angiotensin II (Ang II) treated mice are significantly reduced in mice lacking the TRPC3 gene (TRPC3−/− mice) compared to wild type controls. We also show that pacemaker cells express TRPC3 and several other molecular components related to SOCE/ROCE signaling, including STIM1 and IP3R. Activation of G-protein coupled receptors (GPCRs) signaling that is able to modulate SOCE/ROCE and Ang II induced Ca2+ homeostasis changes in sinoatrial complex being linked to TRPC3. The results provide new evidence that TRPC3 may play a role in sinoatrial and atrial arrhythmias that are caused by GPCRs activation. PMID:25859221

  11. Inheritance of Cytosine Methylation.

    PubMed

    Tillo, Desiree; Mukherjee, Sanjit; Vinson, Charles

    2016-11-01

    There are numerous examples of parental transgenerational inheritance that is epigenetic. The informational molecules include RNA, chromatin modifications, and cytosine methylation. With advances in DNA sequencing technologies, the molecular and epigenetic mechanisms mediating these effects are now starting to be uncovered. This mini-review will highlight some of the examples of epigenetic inheritance, the establishment of cytosine methylation in sperm, and recent genomic studies linking sperm cytosine methylation to epigenetic effects on offspring. A recent paper examining changes in diet and sperm cytosine methylation from pools of eight animals each, found differences between a normal diet, a high fat diet, and a low protein diet. However, epivariation between individuals within a group was greater than the differences between groups obscuring any potential methylation changes linked to diet. Learning more about epivariation may help unravel the mechanisms that regulate cytosine methylation. In addition, other experimental and genetic systems may also produce more dramatic changes in the sperm methylome, making it easier to unravel potential transgenerational phenomena. J. Cell. Physiol. 231: 2346-2352, 2016. © 2016 Wiley Periodicals, Inc. PMID:26910768

  12. 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. PMID:22399423

  13. Gene therapies for inherited skin disorders.

    PubMed

    Abdul-Wahab, Alya; Qasim, Waseem; McGrath, John A

    2014-06-01

    Skin is an amenable organ for gene replacement and gene editing therapeutics. Its accessibility makes it well-suited for direct topical gene delivery, grafting of genetically corrected cells, and monitoring of possible adverse events. Monogenic recessive disorders with a clinically severe or life-threatening phenotype provide the best candidate diseases for the introduction of a single normal copy of the gene into the target cell, usually keratinocytes. Preclinical studies have shown impressive results in terms of gene correction using both in vivo and ex vivo approaches. The clinical application of gene replacement or genomic editing as potential therapies for inherited skin disorders, however, has been held back by the inadequacy of delivery vectors and concerns from regulatory agencies regarding safety; thus translation to clinical trials has been slow. Over the past 15 years, cell culture and animal models have shown efficient gene correction techniques as preludes to treat inherited skin disorders such as junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, xeroderma pigmentosum, lamellar ichthyosis and Netherton syndrome, but so far only one patient has been treated in a clinical trial. This article reviews the current status of gene therapies for patients with inherited skin diseases and explores future perspectives. PMID:25085667

  14. 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

  15. 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. PMID:23858007

  16. 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.

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

    PubMed

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

    1997-11-15

    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. PMID:9388105

  18. 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. PMID:24211993

  19. 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. PMID:26935036

  20. Cardiac arrhythmias associated with spinal cord injury

    PubMed Central

    Hector, Sven Magnus; Biering-Sørensen, Tor; Krassioukov, Andrei; Biering-Sørensen, Fin

    2013-01-01

    Context/Objectives To review the current literature to reveal the incidence of cardiac arrhythmias and its relation to spinal cord injury (SCI). Methods Data source: MEDLINE database, 304 hits, and 32 articles were found to be relevant. The relevant articles all met the inclusion criteria: (1) contained original data (2) on cardiac arrhythmias (3) in humans with (4) traumatic SCI. Results In the acute phase of SCI (1–14 days after injury) more cranial as well as more severe injuries seemed to increase the incidence of bradycardia. Articles not covering the first 14 days after injury, thus describing the chronic phase of SCI, showed that individuals with SCI did not have a higher incidence of cardiac arrhythmias compared with able-bodied controls. Furthermore, their heart rate did not differ significantly. Penile vibro-stimulation was the procedure investigated most likely to cause bradycardia, which in turn was associated with episodes of autonomic dysreflexia. The incidence of bradycardia was found to be 17–77% for individuals with cervical SCI. For individuals with thoracolumbar SCI, the incidence was 0–13%. Conclusion Bradycardia was commonly seen in the acute stage after SCI as well as during procedures such as penile vibro-stimulation and tracheal suction. These episodes of bradycardia were seen more often in individuals with cervical injuries. Longitudinal studies with continuous electrocardiogram recordings are needed to uncover the true relation between cardiac arrhythmias and SCI. PMID:24090076

  1. [Inherited thrombopathia in Simmental cattle].

    PubMed

    Aebi, M; Wiedemar, N; Drögemüller, C; Zanolari, R

    2016-02-01

    During the years 2012 to 2014, a total of 5 affected Simmental cattle showing persistent bleeding after minor or unknown trauma, were presented at the Clinic for Ruminants or at the Institute for Genetics of the Vetsuisse-Faculty, University of Berne. The homozygous mutation RASGRP2, initially reported in 2007, was present in all these cases and all available parents were heterozygous carriers thus confirming the recessive mode of inheritance. Three affected animals died as a result of persistent bleeding. One animal was stabilized at the Clinic for Ruminants and was slaughtered one month later. Another case showing persistent bleeding and several hematomas was euthanized after genotyping. A frequency of 10% carriers for the associated mutation was detected in a sample of 145 Simmental sires which were used 2013 for artificial insemination in Switzerland. These bulls are designated as TP carriers and should not be used uncontrolled. Breeding organizations in Switzerland make use of the gene test to select bulls which do not carry the mutation. PMID:27145685

  2. Inherited cardiomyopathies--Novel therapies.

    PubMed

    Leviner, Dror B; Hochhauser, Edith; Arad, Michael

    2015-11-01

    Cardiomyopathies arising due to a single gene defect represent various pathways that evoke adverse remodeling and cardiac dysfunction. While the gene therapy approach is slowly evolving and has not yet reached clinical "prime time" and gene correction approaches are applicable at the bench but not at the bedside, major advances are being made with molecular and drug therapies. This review summarizes the contemporary drugs introduced or being tested to help manage these unique disorders bearing a major impact on the quality of life and survival of the affected individuals. The restoration of the RNA reading frame facilitates the expression of partly functional protein to salvage or alleviate the disease phenotype. Chaperones are used to prevent the degradation of abnormal but still functional proteins, while other molecules are given for pathogen silencing, to prevent aggregation or to enhance clearance of protein deposits. The absence of protein may be managed by viral gene delivery or protein therapy. Enzyme replacement therapy is already a clinical reality for a series of metabolic diseases. The progress in molecular biology, based on the knowledge of the gene defect, helps generate small molecules and pharmaceuticals targeting the key events occurring in the malfunctioning element of the sick organ. Cumulatively, these tools augment the existing armamentarium of phenotype oriented symptomatic and evidence-based therapies for patients with inherited cardiomyopathies. PMID:26297672

  3. 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. PMID:25671556

  4. 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

  5. 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

  6. Controversies in Cardiovascular Research: Induced pluripotent stem cell-derived cardiomyocytes – boutique science or valuable arrhythmia model?

    PubMed Central

    Knollmann, Björn C

    2013-01-01

    As part of the series on Controversies in Cardiovascular Research, the 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 anti-arrhythmic 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. PMID:23569106

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

    PubMed Central

    2014-01-01

    Background 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. Methods Design: prospective, observational, cross-sectional study. Setting: Clinical Physiology, University Hospital. Patients: 108 consecutive patients referred for ambiguous palpitations or dizziness/presyncope. Interventions: 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. Main outcome measures: Significant arrhythmias: atrial fibrillation (AF), paroxysmal supraventricular tachycardia (PSVT), atrioventricular (AV) block II–III, sinus arrest (SA), wide complex tachycardia (WCT). Results 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

  8. Family-based associations in measures of psychological distress and quality of life in a cardiac screening clinic for inheritable cardiac diseases: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Family-based cardiac screening programmes for persons at risk for genetic cardiac diseases are now recommended. However, the psychological wellbeing and health related quality of life (QoL) of such screened patients is poorly understood, especially in younger patients. We sought to examine wellbeing and QoL in a representative group of adults aged 16 and over in a dedicated family cardiac screening clinic. Methods Prospective survey of consecutive consenting patients attending a cardiac screening clinic, over a 12 month period. Data were collected using two health measurement tools: the Short Form 12 (version 2) and the Hospital Anxiety and Depression Scale (HADS), along with baseline demographic and screening visit-related data. The HADS and SF-12v.2 outcomes were compared by age group. Associations with a higher HADS score were examined using logistic regression, with multi-level modelling used to account for the family-based structure of the data. Results There was a study response rate of 86.6%, with n=334 patients providing valid HADS data (valid response rate 79.5%), and data on n=316 retained for analysis. One-fifth of patients were aged under 25 (n=61). Younger patients were less likely than older to describe significant depression on their HADS scale (p<0.0001), although there were overall no difference between the prevalence of a significant HADS score between the younger and older age groups (18.0% vs 20.0%, p=0.73). Significant positive associates of a higher HADS score were having lower educational attainment, being single or separated, and being closely related to the family proband. Between-family variance in anxiety and depression scores was greater than within-family variance. Conclusions High levels of anxiety were seen amongst patients attending a family-based cardiac screening clinic.Younger patients also had high rates of clinically significant anxiety. Higher levels of anxiety and depression tends to run in families, and this has

  9. 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. PMID:26802767

  10. Recommendations and cardiological evaluation of athletes with arrhythmias

    PubMed Central

    Hoogsteen, J.; Bennekers, J.H.; van der Wall, E.E.; van Hemel, N.M.; Wilde, A.A.M.; Crijns, H.J.G.M.; Gorgels, A.P.M.; Smeets, J.L.R.M.; Hauer, R.N.W.; Jordaens, J.L.M.; Schalij, M.J.

    2004-01-01

    Confronted with a competitive or recreational athlete, the physician has to discriminate between benign, paraphysiological and pathological arrhythmias. Benign arrhythmias do not represent a risk for SCD, nor do they induce haemodynamic consequences during athletic activities. These arrhythmias are not markers for heart disease. Paraphysiological arrhythmias are related to athletic performance. Long periods of endurance training induce changes in rhythm, conduction and repolarisation. These changes are fully reversible and disappear when the sport is terminated. Pathological arrhythmias have haemodynamic consequences and express disease, such as sick sinus syndrome, cardiomyopathy or inverse consequences of physical training. Arrhythmias can be classified as bradyarrhythmias and tachyarrhythmias. Conduction disorders can be seen in fast as well as in slow arrhythmias. ImagesFigure 2 PMID:25696329

  11. Introduction: Mapping and control of complex cardiac arrhythmias.

    PubMed

    Christini, David J.; Glass, Leon

    2002-09-01

    This paper serves as an introduction to the Focus Issue on mapping and control of complex cardiac arrhythmias. We first introduce basic concepts of cardiac electrophysiology and describe the main clinical methods being used to treat arrhythmia. We then provide a brief summary of the main themes contained in the articles in this Focus Issue. In recent years there have been important advances in the ability to map the spread of excitation in intact hearts and in laboratory settings. This work has been combined with simulations that use increasingly realistic geometry and physiology. Waves of excitation and contraction in the heart do not always propagate with constant velocity but are often subject to instabilities that may lead to fluctuations in velocity and cycle time. Such instabilities are often treated best in the context of simple one- or two-dimensional geometries. An understanding of the mechanisms of propagation and wave stability is leading to the implementation of different stimulation protocols in an effort to modify or eliminate abnormal rhythms. (c) 2002 American Institute of Physics. PMID:12779601

  12. Hematopoietic transcription factor mutations and inherited platelet dysfunction

    PubMed Central

    Songdej, Natthapol

    2015-01-01

    The molecular and genetic mechanisms in most patients with inherited platelet dysfunction are unknown. There is increasing evidence that mutations in hematopoietic transcription factors are major players in the pathogenesis of defective megakaryopoiesis and platelet dysfunction in patients with inherited platelet disorders. These hematopoietic transcription factors include RUNX1, FLI1, GATA-1, and GFI1B. Mutations involving these transcription factors affect diverse aspects of platelet production and function at the genetic and molecular levels, culminating in clinical manifestations of thrombocytopenia and platelet dysfunction. This review focuses on these hematopoietic transcription factors in the pathobiology of inherited platelet dysfunction. PMID:26097739

  13. Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk.

    PubMed Central

    Zimmerman, P. A.; Buckler-White, A.; Alkhatib, G.; Spalding, T.; Kubofcik, J.; Combadiere, C.; Weissman, D.; Cohen, O.; Rubbert, A.; Lam, G.; Vaccarezza, M.; Kennedy, P. E.; Kumaraswami, V.; Giorgi, J. V.; Detels, R.; Hunter, J.; Chopek, M.; Berger, E. A.; Fauci, A. S.; Nutman, T. B.; Murphy, P. M.

    1997-01-01

    BACKGROUND: CC chemokine receptor 5 (CCR5) is a cell entry cofactor for macrophage-tropic isolates of human immunodeficiency virus-1 (HIV-1). Recently, an inactive CCR5 allele (designated here as CCR5-2) was identified that confers resistance to HIV-1 infection in homozygotes and slows the rate of progression to AIDS in heterozygotes. The reports conflict on the effect of heterozygous CCR5-2 on HIV-1 susceptibility, and race and risk levels have not yet been fully analyzed. Here we report our independent identification of CCR5-2 and test its effects on HIV-1 pathogenesis in individuals with contrasting clinical outcomes, defined race, and quantified risk. MATERIALS AND METHODS: Mutant CCR5 alleles were sought by directed heteroduplex analysis of genomic DNA from random blood donors. Genotypic frequencies were then determined in (1) random blood donors from North America, Asia, and Africa; (2) HIV-1+ individuals; and (3) highly exposed-seronegative homosexuals with quantified risk. RESULTS: CCR5-2 was the only mutant allele found. It was common in Caucasians, less common in other North American racial groups, and not detected in West Africans or Tamil Indians. Homozygous CCR5-2 frequencies differed reciprocally in highly exposed-seronegative (4.5%, n = 111) and HIV-1-seropositive (0%, n = 614) Caucasians relative to Caucasian random blood donors (0.8%, n = 387). This difference was highly significant (p < 0.0001). By contrast, heterozygous CCR5-2 frequencies did not differ significantly in the same three groups (21.6, 22.6, and 21.7%, respectively). A 55% increase in the frequency of heterozygous CCR5-2 was observed in both of two cohorts of Caucasian homosexual male, long-term nonprogressors compared with other HIV-1+ Caucasian homosexuals (p = 0.006) and compared with Caucasian random blood donors. Moreover, Kaplan-Meier estimates indicated that CCR5-2 heterozygous seroconvertors had a 52.6% lower risk of developing AIDS than homozygous wild-type seroconvertors

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25817556

  15. 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. PMID:25201217

  16. 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

  17. 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. PMID:26781253

  18. [Managing acute supraventricular arrhythmia in pregnancy].

    PubMed

    Manzo-Silberman, Stéphane

    2015-01-01

    Palpitations: frequent reason for referral to a cardiologist. Arrythmia: rare, mostly benign. Premature extra-beats and sustained tachy-arrhythmias: more frequent or revealed during pregnancy. Hemodynamic changes in expectant women favor an environment conducive to arrhythmogenesis. AF and flutter: very rare unless structural heart disease or hyperthyroidism. Drugs: careful monitoring of the patient and dose adjustments. Cardioversion: only in case of severe symptoms or hemodynamically unstable. PMID:26277779

  19. Catheter Ablation of Arrhythmia During Pregnancy.

    PubMed

    Driver, Kevin; Chisholm, Christian A; Darby, Andrew E; Malhotra, Rohit; Dimarco, John P; Ferguson, John D

    2015-06-01

    Cardiac arrhythmia as a complication of pregnancy can be problematic to maternal health and fetal life and development. Catheter ablation of tachyarrhythmias during pregnancy has been successfully performed in selected patients with limited experience. Techniques to limit maternal and fetal radiation exposure, including intracardiac echo and electroanatomic mapping systems, are particularly important in this setting. Specific accommodations are necessary in the care of the gravid patient during catheter ablation. PMID:25828853

  20. 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. PMID:26498164

  1. 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. PMID:25814383

  2. 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.

  3. Defects in Cytoskeletal Signaling Pathways, Arrhythmia, and Sudden Cardiac Death

    PubMed Central

    Smith, Sakima; Curran, Jerry; Hund, Thomas J.; Mohler, Peter J.

    2012-01-01

    Ankyrin polypeptides are cellular adapter proteins that tether integral membrane proteins to the cytoskeleton in a host of human organs. Initially identified as integral components of the cytoskeleton in erythrocytes, a recent explosion in ankyrin research has demonstrated that these proteins play prominent roles in cytoskeletal signaling pathways and membrane protein trafficking/regulation in a variety of excitable and non-excitable cells including heart and brain. Importantly, ankyrin research has translated from bench to bedside with the discovery of human gene variants associated with ventricular arrhythmias that alter ankyrin–based pathways. Ankyrin polypeptides have also been found to play an instrumental role in various forms of sinus node disease and atrial fibrillation (AF). Mouse models of ankyrin-deficiency have played fundamental roles in the translation of ankyrin-based research to new clinical understanding of human sinus node disease, AF, and ventricular tachycardia. PMID:22586405

  4. Update: Arrhythmias (V). Paroxysmal supraventricular tachycardias and preexcitation syndromes.

    PubMed

    Almendral, Jesús; Castellanos, Eduardo; Ortiz, Mercedes

    2012-05-01

    Paroxysmal supraventricular tachycardias are fast and usually regular rhythms that require some structure above the bifurcation of the His bundle to be continued. The 3 most common types are atrial tachycardias, atrioventricular nodal reentrant tachycardias, and tachycardias mediated by an accessory pathway. The last two varieties are discussed in the present manuscript. Their prognosis is benign regarding life expectancy but typically they are symptomatic and chronically recurrent, producing a certain disability. They usually occur in people without structural heart disease. Pharmacologic therapy is possible, but given the high efficacy of catheter ablation, these procedures are frequently chosen. Ventricular preexcitation is due to the presence of an accessory pathway, usually atrioventricular. The clinical course can be asymptomatic, generating a characteristic electrocardiographic pattern, produce paroxysmal supraventricular tachycardias, or facilitate other types of arrhythmias. Very rarely, they can cause sudden cardiac death. The treatment of choice for symptomatic patients is catheter ablation of the accessory pathway. The therapeutic attitude towards asymptomatic preexcitation remains controversial. PMID:22459483

  5. 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. PMID:26427454

  6. 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

  7. Arrhythmias following spinal anesthesia for cesarean delivery - Is Wenckebach common?

    PubMed Central

    Kalra, Seema; Hayaran, Nitin

    2011-01-01

    Arrhythmias in pregnancy are common and may cause concern for the well-being of both mother and fetus. Generally, no previous history of heart disease is elicited and majority of the arrhythmias are benign. Bradycardia is commonly seen following subarachnoid block for cesarean section. However, the incidence of subsequent heart block is low. This case report highlights the occurrence of perioperative arrhythmias following sympathetic blockade in pregnant patients and their early detection by vigilant monitoring. PMID:22096293

  8. Anger-induced T-wave alternans predicts future ventricular arrhythmias in patients with implantable cardioverter-defibrillators

    PubMed Central

    Lampert, Rachel; Shusterman, Vladimir; Burg, Matthew; McPherson, Craig; Batsford, William; Goldberg, Anna; Soufer, Robert

    2014-01-01

    Objective To determine whether T-wave alternans (TWA) induced by anger in a laboratory setting predicts future ventricular arrhythmias (VT/VF) in patients with implantable cardioverter-defibrillators (ICDs). Background Anger can precipitate spontaneous VT/VF, and induce TWA. Whether anger-induced TWA predicts future arrhythmias is unknown. Methods Sixty-two patients with ICDs underwent ambulatory ECG during a mental stress protocol, three months post-implant. TWA was analyzed using time-domain methods. After ≥ 1 year follow-up, ICD stored data was reviewed to determine incidence of ICD-terminated VT/VF. Results Patients with ICD-terminated arrhythmias during follow-up (N=10) had higher TWA induced by anger, 13.2uV (iqr 9.3-16), compared to 9.3uV (7.5-11.5) (p<0.01). Patients in the highest quartile of anger-induced TWA (>11.9uV, N=15) were more likely to experience arrhythmias by one year than those in the lower quartiles, (33% versus 4%), and during extended follow-up (40% versus 9%, p<0.01 for both.) In multivariable regression controlling for ejection fraction, prior clinical arrhythmia, and wide QRS, anger-induced TWA remained a significant predictor of arrhythmia, with likelihood in the top quartile 10.8 times that of other patients (CI 1.6-113, p<0.05.) Conclusion Anger-induced TWA predicts future ventricular arrhythmias in patients with ICDs, suggesting that emotion-induced repolarization instability may be one mechanism linking stress and sudden death. Whether there is a clinical role for anger-induced TWA testing requires further study. PMID:19245968

  9. KCNE genetics and pharmacogenomics in cardiac arrhythmias: much ado about nothing?

    PubMed Central

    Abbott, Geoffrey W.

    2014-01-01

    Voltage-gated ion channels respond to changes in membrane potential with conformational shifts that either facilitate or stem the movement of charged ions across the cell membrane. This controlled movement of ions is particularly important for the action potentials of excitable cells such as cardiac myocytes, and therefore essential for timely beating of the heart. Inherited mutations in ion channel genes and in the genes encoding proteins that regulate them can cause lethal cardiac arrhythmias either by direct channel disruption or by altering interactions with therapeutic drugs, the best-understood example of both these scenarios being Long QT Syndrome (LQTS). Unsurprisingly, mutations in the genes encoding ion channel pore-forming α subunits underlie the large majority (~90%) of identified cases of inherited LQTS. Given that inherited LQTS is comparatively rare in itself (~0.04% of the US population), is pursuing study of the remaining known and unknown LQTS-associated genes subject to the law of diminishing returns? Here, with a particular focus on the KCNE family of single transmembrane domain K+ channel ancillary subunits, the significance to cardiac pharmacogenetics of ion channel regulatory subunits is discussed. PMID:23272793

  10. 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

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

    PubMed

    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/m(3) 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

  12. 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. PMID:26733873

  13. Arrhythmia-induced cardiomyopathies: the riddle of the chicken and the egg still unanswered?

    PubMed

    Simantirakis, Emmanuel N; Koutalas, Emmanuel P; Vardas, Panos E

    2012-04-01

    The hypothesis testing of inappropriate fast, irregular, or asynchronous myocardial contraction provoking cardiomyopathy has been the primary focus of numerous research efforts, especially during the last few decades. Rapid ventricular rates resulting from supraventricular arrhythmias and atrial fibrillation (AF), irregularity of heart rhythm-basic element of AF-and asynchrony, as a consequence of right ventricular pacing, bundle branch block, or frequent premature ventricular complexes, have been established as primary causes of arrhythmia-induced cardiomyopathy. The main pathophysiological pathways involved have been clarified, including neurohumoral activation, energy stores depletion, and abnormalities in stress and strain. Unfortunately, from a clinical point of view, patients usually seek medical advice only when symptoms develop, while the causative arrhythmia may be present for months or years, resulting in myocardial remodelling, diastolic, and systolic dysfunction. In some cases, making a definite diagnosis may become a strenuous exercise for the treating physician, as the arrhythmia may not be present and, additionally, therapy must be applied for the diagnosis to be confirmed retrospectively. The diagnostic process is also hardened due to the fact that strict diagnosing criteria are still a matter of discrepancy. Therapy options include pharmaceutical agents trials, catheter-based therapies and, in the context of chronic ventricular pacing, resynchronization. For the majority of patients, partial or complete recovery is expected, although they have to be followed up thoroughly due to the risk of recurrence. Large, randomized controlled trials are more than necessary to optimize patients' stratification and therapeutic strategy choices. PMID:22084300

  14. 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

  15. [Correlation between QT interval, ventricular arrhythmias and left ventricular function in chronic alcoholics].

    PubMed

    Pomini, G; Gribaldo, R; Bellavere, F; Lupia, M; Sale, F; Rugna, A; Costa, L; Molfese, G

    1986-04-01

    Prolonged QT interval and arrhythmias have been reported to occur in chronic alcoholics. To investigate the role of chronic alcohol consumption in the onset of arrhythmias and the development of the preclinical left ventricular dysfunction, in a group of 12 asymptomatic chronic alcoholics with no clinical evidence of heart disease, with histologically proven hepatic damage, after a week of abstinence from alcohol, the following investigations were performed: measurements of the corrected QT interval (QTc), 24-hours Holter monitoring, systolic time intervals, M-mode echocardiograms. The results were compared to those of 10 normal subjects. Our data suggested no difference in QTc interval between chronic alcoholics and normal persons. The distribution of arrhythmias was not statistically different in the two groups, particularly frequent and complicated arrhythmias occurred in only one subject in each group. Preejection period corrected for heart rate (PEPI) was significantly longer in alcoholics (132 +/- 16 vs 119 +/- 11, p less than 0.05). All echocardiographic parameters examined were not significantly different in the two groups. On the basis of our results, our impression is that the arrhythmogenic role of alcohol, not under acute ingestion, is relatively unimportant and further studies are needed to become a definitive conclusion about subclinical alcoholic cardiomyopathy. PMID:3743931

  16. 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. PMID:27484663

  17. 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

  18. 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. PMID:21096338

  19. Arrhythmia analysis with an expert system.

    PubMed

    Redman, T C; Hahn, A W

    1989-01-01

    We have developed a rule based expert system which was designed to diagnose electrocardiographic arrhythmias in several species. The program, called ECG-X, is written in OPS5 and runs under MS-DOS 2.1 and higher on an IBM-PC or AT type machine. The program uses the paper speed, the species, the temporal relationships between the P waves and the QRS complexes as well as basic information about the P and QRS morphology, and provides the user with a rhythm diagnosis consistent with rules provided by contemporary cardiac electrophysiologic knowledge. PMID:2742969

  20. Drug Resistant Fetal Arrhythmia in Obstetric Cholestasis

    PubMed Central

    Altug, Nahide; Kirbas, Ayse; Daglar, Korkut; Biberoglu, Ebru; Uygur, Dilek; Danisman, Nuri

    2015-01-01

    Obstetric cholestasis (OC) is a pregnancy specific liver disease characterized by increased levels of bile acid (BA) and pruritus. Raised maternal BA levels could be associated with intrauterine death, fetal distress, and preterm labor and also alter the rate and rhythm of cardiomyocyte contraction and may cause fetal arrhythmic events. We report a case of drug resistant fetal supraventricular tachycardia and concomitant OC. Conclusion. If there are maternal OC and concomitant fetal arrhythmia, possibility of the resistance to antiarrhythmic treatment should be kept in mind. PMID:25821617

  1. Difficulties with Ablation for Arrhythmias in Children

    PubMed Central

    Asirvatham, Samuel J

    2008-01-01

    Radiofrequency ablation procedures in children present unique challenges for the electrophysiologist. At times, obtaining vascular access to reach the heart is a problem. If this first step is accomplished, the small size of the child's heart, arrhythmias relatively unique to the pediatric population, and the presence of congenital heart disease add to the complexity. In this manuscript, a review of commonly encountered problems and suggested solutions based on practice are presented. Precise mapping of the arrhythmogenic substrate, techniques to access excluded portions of the atrium from prior surgery, and the basis for electrophysiology maneuvers important in pediatric ablation are highlighted. PMID:18478062

  2. Respiratory sinus arrhythmia in Chagas disease.

    PubMed

    Neves, Victor Ribeiro; Peltola, Mirja; Huikuri, Heikki; Rocha, Manoel Otávio da Costa; Ribeiro, Antonio Luiz

    2014-10-01

    We applied the respiratory sinus arrhythmia (RSA) quantification algorithm to 24-hour ECG recordings of Chagas disease (ChD) patients with (G1, n=148) and without left ventricular dysfunction (LVD) (G2, n=33), and in control subjects (G0, n=28). Both ChD groups displayed a reduced RSA index; G1=299 (144-812); G2=335 (162-667), p=0.011, which was correlated with vagal indexes of heart rate variability analysis. RSA index is a marker of vagal modulation in ChD patients. PMID:25130950

  3. Inherited thrombophilia and reproductive disorders

    PubMed Central

    Liatsikos, Spyros A.; Tsikouras, Panagiotis; Manav, Bachar; Csorba, Roland; von Tempelhoff, Georg Friedrich; Galazios, Georgios

    2016-01-01

    Apart from its established role in the pathogenesis of venous thromboembolism (VTE), inherited thrombophilia has been proposed as a possible cause of pregnancy loss and vascular gestational complications. There is a lot of controversy in the literature on the relationship between inherited prothrombotic defects and these obstetric complications. This is a review of the literature on inherited thrombophilia and reproductive disorders. Factor V Leiden, prothrombin G20210A mutation, and protein S deficiency seem to be associated with late and recurrent early pregnancy loss, while their impact on other pregnancy complications is conflicting. No definite association has been established between protein C and antithrombin deficiency and adverse pregnancy outcome, primarily due to their low prevalence. Screening is suggested only for women with early recurrent loss or late pregnancy loss. Anticoagulant treatment during pregnancy should be considered for women with complications who were tested positive for thrombophilia. PMID:27026779

  4. Inherited thrombophilia and reproductive disorders.

    PubMed

    Liatsikos, Spyros A; Tsikouras, Panagiotis; Manav, Bachar; Csorba, Roland; von Tempelhoff, Georg Friedrich; Galazios, Georgios

    2016-01-01

    Apart from its established role in the pathogenesis of venous thromboembolism (VTE), inherited thrombophilia has been proposed as a possible cause of pregnancy loss and vascular gestational complications. There is a lot of controversy in the literature on the relationship between inherited prothrombotic defects and these obstetric complications. This is a review of the literature on inherited thrombophilia and reproductive disorders. Factor V Leiden, prothrombin G20210A mutation, and protein S deficiency seem to be associated with late and recurrent early pregnancy loss, while their impact on other pregnancy complications is conflicting. No definite association has been established between protein C and antithrombin deficiency and adverse pregnancy outcome, primarily due to their low prevalence. Screening is suggested only for women with early recurrent loss or late pregnancy loss. Anticoagulant treatment during pregnancy should be considered for women with complications who were tested positive for thrombophilia. PMID:27026779

  5. Nongenetic inheritance and transgenerational epigenetics.

    PubMed

    Szyf, Moshe

    2015-02-01

    The idea that inherited genotypes define phenotypes has been paramount in modern biology. The question remains, however, whether stable phenotypes could be also inherited from parents independently of the genetic sequence per se. Recent data suggest that parental experiences can be transmitted behaviorally, through in utero exposure of the developing fetus to the maternal environment, or through either the male or female germline. The challenge is to delineate a plausible mechanism. In the past decade it has been proposed that epigenetic mechanisms are involved in multigenerational transmission of phenotypes and transgenerational inheritance. The prospect that ancestral experiences are written in our epigenome has immense implications for our understanding of human behavior, health, and disease. PMID:25601643

  6. Outcomes after nonemergent electrical cardioversion for atrial arrhythmias.

    PubMed

    Steinberg, Benjamin Adam; Schulte, Phillip Joel; Hofmann, Paul; Ersbøll, Mads; Alexander, John Hunter; Broderick-Forsgren, Kathleen; Anstrom, Kevin Joseph; Granger, Christopher Bull; Piccini, Jonathan Paul; Velazquez, Eric Jose; Shah, Bimal Ramesh

    2015-05-15

    Electrical cardioversion (ECV) is recommended for rhythm control in patients with atrial arrhythmia; yet, ECV use and outcomes in contemporary practice are unknown. We reviewed all nonemergent ECVs for atrial arrhythmias at a tertiary care center (2010 to 2013), stratifying patients by transesophageal echocardiography (TEE) use before ECV and comparing demographics, history, vitals, and laboratory studies. Outcomes included postprocedural success and complications and repeat cardioversion, rehospitalization, and death within 30 days. Overall, 1,017 patients underwent ECV, 760 (75%) for atrial fibrillation and 240 (24%) for atrial flutter; 633 underwent TEE before ECV and 384 did not. TEE recipients were more likely to be inpatients (74% vs 44%, p <0.001), have higher mean CHADS2 scores (2.6 vs 2.4, p = 0.03), and lower mean international normalized ratios (1.2 vs 2.1, p <0.001). Overall, 89 patients (8.8%) did not achieve sinus rhythm and 14 experienced procedural complications (1.4%). Within 30 days, 80 patients (7.9%) underwent repeat ECV, 113 (11%) were rehospitalized, and 14 (1.4%) died. Although ECV success was more common in patients who underwent TEE before ECV (77% vs 68%, p = 0.01), there were no differences in 30-day death or rehospitalization rates (11.1% vs 13.0%, p = 0.37). In multivariate analyses, higher pre-ECV heart rate was associated with increased rehospitalization or death (adjusted hazard ratio 1.15/10 beats/min, 95% confidence interval 1.07 to 1.24, p <0.001), whereas TEE use was associated with lower rates (adjusted hazard ratio 0.58, 95% confidence interval 0.39 to 0.86, p = 0.007). In conclusion, failures, complications, and rehospitalization after nonemergent ECV are common and associated more with patient condition than procedural characteristics. TEE use was associated with better clinical outcomes. PMID:25784514

  7. Outcomes Following Non-Emergent Electrical Cardioversion for Atrial Arrhythmias

    PubMed Central

    Steinberg, Benjamin Adam; Schulte, Phillip; Hofmann, Paul; Ersbøll, Mads; Alexander, John Hunter; Broderick-Forsgren, Kathleen; Anstrom, Kevin Joseph; Granger, Christopher Bull; Piccini, Jonathan Paul; Velazquez, Eric Jose; Shah, Bimal Ramesh

    2015-01-01

    Electrical cardioversion (ECV) is recommended for rhythm control in atrial arrhythmia patients, yet ECV use and outcomes in contemporary practice are unknown. We reviewed all non-emergent ECVs for atrial arrhythmias at a tertiary care center (2010–2013), stratifying patients by transesophageal echocardiography (TEE) use pre-ECV and comparing demographics, history, vitals, and laboratory studies. Outcomes included post-procedure success and complications, and repeat cardioversion, rehospitalization, and death within 30 days. Overall, 1017 patients underwent ECV; 760 (75%) for atrial fibrillation and 240 (24%) for atrial flutter; 633 underwent TEE pre-ECV and 384 did not. TEE recipients were more likely to be inpatients (74% vs. 44%, p<0.001), have higher mean CHADS2 scores (2.6 vs. 2.4, p=0.03), and lower mean international normalized ratios (1.2 vs. 2.1, p<0.001). Overall, 89 (8.8%) did not achieve sinus rhythm and 14 experienced procedural complications (1.4%). Within 30 days, 80 (7.9%) underwent repeat ECV, 113 (11%) were rehospitalized, and 14 (1.4%) died. Although ECV success was more common in patients who underwent TEE pre-ECV (77% vs. 68%, p=0.01), there were no differences in 30-day death or rehospitalization rates (11.1% vs. 13.0%, p=0.37). In multivariable analyses, higher pre-ECV heart rate was associated with increased rehospitalization or death (adjusted HR 1.15/10 bpm, 95% CI 1.07–1.24, p<0.001), while TEE use was associated with lower rates (adjusted HR 0.58, 95% CI 0.39–0.86, p=0.007). In conclusion, failures, complications, and rehospitalization following non-emergent ECV are common, and associated more with patient condition than procedural characteristics. TEE use was associated with better clinical outcomes. PMID:25784514

  8. Inherited desmosomal disorders.

    PubMed

    Samuelov, Liat; Sprecher, Eli

    2015-06-01

    Desmosomes serve as intercellular junctions in various tissues including the skin and the heart where they play a crucial role in cell-cell adhesion, signalling and differentiation. The desmosomes connect the cell surface to the keratin cytoskeleton and are composed of a transmembranal part consisting mainly of desmosomal cadherins, armadillo proteins and desmoplakin, which form the intracytoplasmic desmosomal plaque. Desmosomal genodermatoses are caused by mutations in genes encoding the various desmosomal components. They are characterized by skin, hair and cardiac manifestations occurring in diverse combinations. Their classification into a separate and distinct clinical group not only recognizes their common pathogenesis and facilitates their diagnosis but might also in the future form the basis for the design of novel and targeted therapies for these occasionally life-threatening diseases. PMID:25487406

  9. 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

  10. Loperamide Induced Life Threatening Ventricular Arrhythmia

    PubMed Central

    Bodar, Vijaykumar; Singh, Sharanjit; Frumkin, William; Mangla, Aditya; Doshi, Kaushik

    2016-01-01

    Loperamide is over-the-counter antidiarrheal agent acting on peripherally located μ opioid receptors. It is gaining popularity among drug abusers as opioid substitute. We report a case of a 46-year-old male that was presented after cardiac arrest. After ruling out ischemia, cardiomyopathy, pulmonary embolism, central nervous system pathology, sepsis, and other drug toxicity, we found out that patient was using around 100 mg of Loperamide to control his chronic diarrhea presumably because of irritable bowel syndrome for last five years and consumed up to 200 mg of Loperamide daily for last two days before the cardiac arrest. We hypothesize that the patient's QTc prolongation and subsequent cardiac arrest are due to Loperamide toxicity. Patient experienced gradual resolution of tachyarrhythmia and gradual decrease in QTc interval during hospitalization which supports the evidence of causal relationship between Loperamide overdose and potentially fatal arrhythmias. It also provided the clue that patient may have congenital long QT syndrome which was unmasked by Loperamide causing ventricular arrhythmias. This case adds one more pearl in the literature to support that Loperamide overdose related cardiac toxicity does exist and it raises concerns over Loperamide abuse in the community. PMID:27547470

  11. Loperamide Induced Life Threatening Ventricular Arrhythmia.

    PubMed

    Upadhyay, Ankit; Bodar, Vijaykumar; Malekzadegan, Mohammad; Singh, Sharanjit; Frumkin, William; Mangla, Aditya; Doshi, Kaushik

    2016-01-01

    Loperamide is over-the-counter antidiarrheal agent acting on peripherally located μ opioid receptors. It is gaining popularity among drug abusers as opioid substitute. We report a case of a 46-year-old male that was presented after cardiac arrest. After ruling out ischemia, cardiomyopathy, pulmonary embolism, central nervous system pathology, sepsis, and other drug toxicity, we found out that patient was using around 100 mg of Loperamide to control his chronic diarrhea presumably because of irritable bowel syndrome for last five years and consumed up to 200 mg of Loperamide daily for last two days before the cardiac arrest. We hypothesize that the patient's QTc prolongation and subsequent cardiac arrest are due to Loperamide toxicity. Patient experienced gradual resolution of tachyarrhythmia and gradual decrease in QTc interval during hospitalization which supports the evidence of causal relationship between Loperamide overdose and potentially fatal arrhythmias. It also provided the clue that patient may have congenital long QT syndrome which was unmasked by Loperamide causing ventricular arrhythmias. This case adds one more pearl in the literature to support that Loperamide overdose related cardiac toxicity does exist and it raises concerns over Loperamide abuse in the community. PMID:27547470

  12. Severe arrhythmia induced by orally disintegrating aripiprazole tablets (Bosiqing(®)): a case report.

    PubMed

    Shao, Qing; Quan, Wei; Jia, Xiaoni; Chen, Jianbo; Ma, Shanbo; Zhang, Xiaohong

    2015-01-01

    Psychotropic medications have been known to cause cardiac conduction disturbances. Not much is known about the cardiovascular side effects of newer atypical antipsychotics such as aripiprazole. A case of a 13-year-old girl with schizophrenia is presented. An analysis of the presented patient's clinical history indicates the need for a detailed analysis of the severe arrhythmia induced by aripiprazole. This presented case report contains valuable guidelines that can be of assistance in the treatment of patients with aripiprazole. PMID:26677328

  13. [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. PMID:8074586

  14. Basic mechanisms of monogenic inheritance.

    PubMed

    Ziegler, A

    1999-01-01

    To revive the appreciation of the importance of genetic studies for the understanding of neurologic diseases inherited in a monogenic fashion. After a description of the basic patterns of monogenic inheritance, the importance of linkage studies for the mapping of a disease gene is mentioned. Furthermore, the term linkage disequilibrium is introduced. Finally, several procedures used in current linkage analyses are briefly mentioned, with the aim of identifying the disease gene. The importance of genetic studies of disease families with many members, preferably from isolated surroundings to favor homogeneity, is stressed. However, such analyses can be performed only as a consequence of a close cooperation between clinicians and research scientists. PMID:10446743

  15. 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.

  16. Risk Prediction of One-Year Mortality in Patients with Cardiac Arrhythmias Using Random Survival Forest

    PubMed Central

    Miao, Fen; Cai, Yun-Peng; Zhang, Yu-Xiao; Li, Ye; Zhang, Yuan-Ting

    2015-01-01

    Existing models for predicting mortality based on traditional Cox proportional hazard approach (CPH) often have low prediction accuracy. This paper aims to develop a clinical risk model with good accuracy for predicting 1-year mortality in cardiac arrhythmias patients using random survival forest (RSF), a robust approach for survival analysis. 10,488 cardiac arrhythmias patients available in the public MIMIC II clinical database were investigated, with 3,452 deaths occurring within 1-year followups. Forty risk factors including demographics and clinical and laboratory information and antiarrhythmic agents were analyzed as potential predictors of all-cause mortality. RSF was adopted to build a comprehensive survival model and a simplified risk model composed of 14 top risk factors. The built comprehensive model achieved a prediction accuracy of 0.81 measured by c-statistic with 10-fold cross validation. The simplified risk model also achieved a good accuracy of 0.799. Both results outperformed traditional CPH (which achieved a c-statistic of 0.733 for the comprehensive model and 0.718 for the simplified model). Moreover, various factors are observed to have nonlinear impact on cardiac arrhythmias prognosis. As a result, RSF based model which took nonlinearity into account significantly outperformed traditional Cox proportional hazard model and has great potential to be a more effective approach for survival analysis. PMID:26379761

  17. 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

  18. Clinical management and prevention of sudden cardiac death.

    PubMed

    Yousuf, Omair; Chrispin, Jonathan; Tomaselli, Gordon F; Berger, Ronald D

    2015-06-01

    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. PMID:26044254

  19. Therapies for inherited skin fragility disorders.

    PubMed

    Has, Cristina; Kiritsi, Dimitra

    2015-05-01

    Inherited skin fragility comprises disorders characterized by mechanical induced blistering and erosions within the skin and mucosal membranes as a consequence of mutations in genes encoding proteins involved in intra-epidermal or dermal-epidermal adhesion. As the molecular pathology is largely known, it is a prototype group of disorders for which numerous experimental treatments have been developed. However, it became clear that single therapeutic strategies will not be able to address all molecular and clinical aspects. Significant progress has been achieved in gene, cell and protein therapies. Although the way towards clinical application seems obvious, major challenges must be addressed before these therapies become largely accessible. Until curative treatments will become available, alternative strategies which aim at increasing protein stability, amending apoptosis, inflammation and scarring may alleviate skin fragility and prevent or delay the onset of complications. PMID:25916580

  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. PMID:27324981

  2. [Verification of therapeutic levels of procainamide and N-acetyl- procainamide in ventricular arrhythmia].

    PubMed

    Sinkiewicz, W; Marzec, A; Jankowski, A; Hoffmann, A; Makuch, K; Romański, B

    Therapeutical efficacy was clinically evaluated in 21 patients with ventricular cardiac arrhythmias. The drug was given orally with preceded intramuscular dose. Therapeutic effect was verified by the measurements of procainamide and N-acetylprocainamide concentrations in blood serum to determine the minimal effective concentration of the drug required to obtain satisfactory antiarrhythmic effect. Procainamide proved effective in cardiac arrhythmias in 14 patients (66.7%) with statistical significance in the acute myocardial infarctions; blood serum procainamide plus N-acetylprocainamide levels being were below the therapeutical range. The poor correlation of the dose of the drug and respective procainamide, N-acetylprocainamide concentrations in blood was observed. Relationship of the therapeutical effects blood serum level of the drug should be estimated basing of the assays of both procainamide and N-acetylprocainamide . PMID:1703654

  3. Treatment of patients with cocaine-induced arrhythmias: bringing the bench to the bedside.

    PubMed

    Hoffman, Robert S

    2010-05-01

    Widespread use of cocaine and its attendant toxicity has produced a wealth of benchwork studies and small animal investigations that evaluated the effects of cocaine on the cardiovascular system. Despite this wealth of knowledge, very little is known about the frequency or types of arrhythmias in patients with significant cocaine toxicity. The likely aetiologies; catecholamine excess, sodium channel blockade, potassium channel blockade, calcium channel effects, or ischaemia may act alone or in concert to produce a vast array of clinical findings that are modulated by hyperthermia, acidosis, hypoxia and electrolyte abnormalities. The initial paper in the series by Wood & Dargan providing the epidemiological framework of cocaine use and abuse is followed by a detailed review of the electrophysiological effects of cocaine by O'Leary & Hancox. This review is designed to complement the previous papers and focuses on the diagnosis and treatment of patients with cocaine-associated arrhythmias. PMID:20573080

  4. Epigenetic Inheritance in Rice Plants

    PubMed Central

    Akimoto, Keiko; Katakami, Hatsue; Kim, Hyun-Jung; Ogawa, Emiko; Sano, Cecile M.; Wada, Yuko; Sano, Hiroshi

    2007-01-01

    Background and Aims 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. Methods 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. Key Results 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

  5. Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism

    PubMed Central

    Kazbanov, Ivan V.; ten Tusscher, Kirsten H. W. J.; Panfilov, Alexander V.

    2016-01-01

    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. PMID:26861111

  6. Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism.

    PubMed

    Kazbanov, Ivan V; ten Tusscher, Kirsten H W J; Panfilov, Alexander V

    2016-01-01

    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. PMID:26861111

  7. Inherited bone marrow failure syndromes in adolescents and young adults.

    PubMed

    Wilson, David B; Link, Daniel C; Mason, Philip J; Bessler, Monica

    2014-09-01

    The inherited bone marrow failure syndromes are a diverse group of genetic diseases associated with inadequate production of one or more blood cell lineages. Examples include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, thrombocytopenia absent radii syndrome, severe congenital neutropenia, and Shwachman-Diamond syndrome. The management of these disorders was once the exclusive domain of pediatric subspecialists, but increasingly physicians who care for adults are being called upon to diagnose or treat these conditions. Through a series of patient vignettes, we highlight the clinical manifestations of inherited bone marrow failure syndromes in adolescents and young adults. The diagnostic and therapeutic challenges posed by these diseases are discussed. PMID:24888387

  8. Inherited bone marrow failure syndromes in adolescents and young adults

    PubMed Central

    Wilson, David B.; Link, Daniel C.; Mason, Philip J.; Bessler, Monica

    2015-01-01

    The inherited bone marrow failure syndromes are a diverse group of genetic diseases associated with inadequate production of one or more blood cell lineages. Examples include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, thrombocytopenia absent radii syndrome, severe congenital neutropenia, and Shwachman-Diamond syndrome. The management of these disorders was once the exclusive domain of pediatric subspecialists, but increasingly physicians who care for adults are being called upon to diagnose or treat these conditions. Through a series of patient vignettes, we highlight the clinical manifestations of inherited bone marrow failure syndromes in adolescents and young adults. The diagnostic and therapeutic challenges posed by these diseases are discussed. PMID:24888387

  9. Symmetry inheritance of scalar fields

    NASA Astrophysics Data System (ADS)

    Smolić, Ivica

    2015-07-01

    Matter fields do not necessarily have to share the symmetries with the spacetime they live in. When this happens, we speak of the symmetry inheritance of fields. In this paper we classify the obstructions of symmetry inheritance by the scalar fields, both real and complex, and look more closely at the special cases of stationary and axially symmetric spacetimes. Since the symmetry noninheritance is present in the scalar fields of boson stars and may enable the existence of the black hole scalar hair, our results narrow the possible classes of such solutions. Finally, we define and analyse the symmetry noninheritance contributions to the Komar mass and angular momentum of the black hole scalar hair.

  10. Neuromuscular imaging in inherited muscle diseases

    PubMed Central

    Kley, Rudolf A.; Fischer, Dirk

    2010-01-01

    Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies. PMID:20422195

  11. An integrated circuit for wireless ambulatory arrhythmia monitoring systems.

    PubMed

    Kim, Hyejung; Yazicioglu, Refet Firat; Torfs, Tom; Merken, Patrick; Van Hoof, Chris; Yoo, Hoi-Jun

    2009-01-01

    An ECG signal processor (ESP) is proposed for the low energy wireless ambulatory arrhythmia monitoring system. The ECG processor mainly performs filtering, compression, classification and encryption. The data compression flow consisting of skeleton and modified Huffman coding is the essential function to reduce the transmission energy consumption and the memory capacity, which are the most energy consuming part. The classification flow performs the arrhythmia analysis to alert the abnormality. The proposed ESP IC is implemented in 0.18-microm CMOS process and integrated into the wireless arrhythmia monitoring sensor platform. By integration of the ESP, the total system energy reduction is evaluated by 95.6%. PMID:19963908

  12. 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.

  13. 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

  14. Cellular and Molecular Mechanisms of Arrhythmia by Oxidative Stress

    PubMed Central

    Sovari, Ali A.

    2016-01-01

    Current therapies for arrhythmia using ion channel blockade, catheter ablation, or an implantable cardioverter defibrillator have limitations, and it is important to search for new antiarrhythmic therapeutic targets. Both atrial fibrillation and heart failure, a condition with increased arrhythmic risk, are associated with excess amount of reactive oxygen species (ROS). There are several possible ways for ROS to induce arrhythmia. ROS can cause focal activity and reentry. ROS alter multiple cardiac ionic currents. ROS promote cardiac fibrosis and impair gap junction function, resulting in reduced myocyte coupling and facilitation of reentry. In order to design effective antioxidant drugs for treatment of arrhythmia, it is essential to explore the molecular mechanisms by which ROS exert these arrhythmic effects. Activation of Ca2+/CaM-dependent kinase II, c-Src tyrosine kinase, protein kinase C, and abnormal splicing of cardiac sodium channels are among the recently discovered molecular mechanisms of ROS-induced arrhythmia. PMID:26981310

  15. Radiofrequency catheter ablation in pediatric patients with supraventricular arrhythmias.

    PubMed

    Rhodes, L A; Lobban, J H; Schmidt, S B

    1995-01-01

    Radiofrequency (RF) ablation of foci leading to abnormal cardiac rhythms is rapidly becoming the procedure of choice in the management of arrhythmias in adults. This report reviews our initial experience with RF ablation in the pediatric population. PMID:8533398

  16. 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.

  17. Arrhythmia diagnosis and management throughout life in congenital heart disease.

    PubMed

    Clark, Bradley C; Berul, Charles I

    2016-03-01

    Arrhythmias, covering bradycardia and tachycardia, occur in association with congenital heart disease (CHD) and as a consequence of surgical repair. Symptomatic bradycardia can occur due to sinus node dysfunction or atrioventricular block secondary to either unrepaired CHD or surgical repair in the area of the conduction system. Tachyarrhythmias are common in repaired CHD due to scar formation, chamber distension or increased chamber pressure, all potentially leading to abnormal automaticity and heterogeneous conduction properties as a substrate for re-entry. Atrial arrhythmias occur more frequently, but ventricular tachyarrhythmias may be associated with an increased risk of sudden cardiac death, notably in patients with repaired tetralogy of Fallot or aortic stenosis. Defibrillator implantation provides life-saving electrical therapy for hemodynamically unstable arrhythmias. Ablation procedures with 3D electroanatomic mapping technology offer a viable alternative to pharmacologic or device therapy. Advances in electrophysiology have allowed for successful management of arrhythmias in patients with congenital heart disease. PMID:26642231

  18. Cardiac Arrhythmia Management: Why Women Are Different from Men

    MedlinePlus

    ... led to incorrect diagnoses including anxiety neurosis and panic attacks. However, since serotonin reuptake inhibitors can be effective ... Cardiac Arrhythmia Management in Women | Heart Disease Facts | Panic Attack or Heart Attack | Three Women from New Jersey | ...

  19. Reducing False Alarm Rates for Critical Arrhythmias Using the Arterial Blood Pressure Waveform

    PubMed Central

    Aboukhalil, Anton; Nielsen, Larry; Saeed, Mohammed; Mark, Roger G.; Clifford, Gari D.

    2008-01-01

    ). True alarm (TA) reduction rates were all 0%, except for ventricular tachycardia alarms (9.4%). Conclusions The FA suppression algorithm reduced the incidence of false critical ECG arrhythmia alarms from 42.7% to 17.2%, where simultaneous ECG and ABP data were available. The present algorithm demonstrated the potential of data fusion to reduce false ECG arrhythmia alarms in a clinical setting, but the non-zero TA reduction rate for ventricular tachycardia indicates the need for further refinement of the suppression strategy. To avoid suppressing any true alarms, the algorithm could be implemented for all alarms except ventricular tachycardia. Under these conditions the FA rate would be reduced from 42.7% to 22.7%. This implementation of the algorithm should be considered for prospective clinical evaluation. The public availability of a real-world ICU database of multiparameter physiologic waveforms, together with their associated annotated alarms is a new and valuable research resource for algorithm developers. PMID:18440873

  20. 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. PMID:27149615

  1. Ranolazine reduces remodeling of the right ventricle and provoked arrhythmias in rats with pulmonary hypertension.

    PubMed

    Liles, John T; Hoyer, Kirsten; Oliver, Jason; Chi, Liguo; Dhalla, Arvinder K; Belardinelli, Luiz

    2015-06-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that often results in right ventricular (RV) failure and death. During disease progression, structural and electrical remodeling of the right ventricle impairs pump function, creates proarrhythmic substrates, and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in patients with PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an antianginal, anti-ischemic drug that has cardioprotective effects in experimental and clinical settings of left-sided heart dysfunction. RAN also has antiarrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. We therefore hypothesized that RAN could reduce the maladaptive structural and electrical remodeling of the right ventricle and could prevent triggered ventricular arrhythmias in the monocrotaline rat model of PAH. Indeed, in both in vivo and ex vivo experimental settings, chronic RAN treatment reduced electrical heterogeneity (right ventricular-left ventricular action potential duration dispersion), shortened heart-rate corrected QT intervals in the right ventricle, and normalized RV dysfunction. Chronic RAN treatment also dose-dependently reduced ventricular hypertrophy, reduced circulating levels of B-type natriuretic peptide, and decreased the expression of fibrotic markers. In addition, the acute administration of RAN prevented isoproterenol-induced ventricular tachycardia/ventricular fibrillation and subsequent cardiovascular death in rats with established PAH. These results support the notion that RAN can improve the electrical and functional properties of the right ventricle, highlighting its potential benefits in the setting of RV impairment. PMID:25770134

  2. 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.

  3. Arrhythmias in two patients with left ventricular bypass transplants.

    PubMed Central

    Kennelly, B M; Corte, P; Losman, J; Barnard, C N

    1976-01-01

    Two patients who underwent left ventricular bypass transplants are described. Both patients sustained postoperative rhythm disturbances of their own hearts during sinus rhythm of the donor hearts. Illustrative examples of atrial flutter, ventricular flutter, ventricular fibrillation, blocked atrial extrasystoles, and double ventricular parasystole in the recipient hearts are presented. The patients tolerated all these arrhythmias well during uninterrupted sinus rhythm in the donor heart. The problems in interpretation of arrhythmias in the presence of two hearts are discussed. Images PMID:788729

  4. 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

  5. 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

  6. 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. PMID:25612305

  7. 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. PMID:24717430

  8. 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

  9. Synchronous Systolic Subcellular Ca2+-Elevations Underlie Ventricular Arrhythmia in Drug-Induced Long QT Type 2

    PubMed Central

    Kim, Jong J.; Němec, Jan; Li, Qiao; Salama, Guy

    2015-01-01

    Background Repolarization-delay is a common clinical problem which can promote ventricular arrhythmias. In myocytes, abnormal sarcoplasmic reticulum Ca2+-release is proposed as the mechanism that causes early afterdepolarizations, the cellular equivalent of ectopic-activity in drug-induced long QT syndrome. A crucial missing link is how such a stochastic process can overcome the source-sink mismatch to depolarize sufficient ventricular tissue to initiate arrhythmias. Methods and Results Optical maps of action potentials (APs) and Ca2+-transients (CaT) from Langendorff rabbit hearts were measured at low (150×150 μm2/pixel) and high (1.5×1.5 μm2/pixel) resolution before and during arrhythmias. Drug-induced long QT type 2, elicited with dofetilide inhibition, produced spontaneous Ca2+-elevations during diastole and systole, before the onset of arrhythmias. Diastolic Ca2+− waves appeared randomly, propagated within individual myocytes, were out-of-phase with adjacent myocytes and often died-out. Systolic secondary Ca2+− elevations were synchronous within individual myocytes, appeared 188±30ms after the AP-upstroke, occurred during high cytosolic-Ca2+ (40–60% of peak-CaT), appeared first in small islands (0.5×0.5 mm2) that enlarged and spread throughout the epicardium. Synchronous systolic Ca2+-elevations preceded voltage-depolarizations (9.2±5ms, n=5) and produced pronounced Spatial Heterogeneities of CaT-durations and AP-durations. Early afterdepolarizations originating from sites with the steepest gradients of membrane-potential propagated and initiated arrhythmias. Interestingly, more complex subcellular Ca2+-dynamics (multiple chaotic Ca2+-waves) occurred during arrhythmias. K201, a ryanodine receptor stabilizer, eliminated Ca2+-elevations and arrhythmias. Conclusions The results indicate that systolic and diastolic Ca2+-elevations emanate from sarcoplasmic reticulum Ca2+-release and systolic Ca2+-elevations are synchronous because of high cytosolic

  10. 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

  11. 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

  12. 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. PMID:26501689

  13. Digenic inheritance in medical genetics

    PubMed Central

    Schäffer, Alejandro A

    2013-01-01

    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. PMID:23785127

  14. 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.

  15. Epigenetic Inheritance: A Contributor to Species Differentiation?

    PubMed Central

    Boffelli, Dario

    2012-01-01

    Multiple epigenetic states can be associated with the same genome, and transmitted through the germline for generations, to create the phenomenon of epigenetic inheritance. This form of inheritance is mediated by complex and highly diverse components of the chromosome that associate with DNA, control its transcription, and are inherited alongside it. But, how extensive, and how stable, is the information carried in the germline by the epigenome? Several known examples of epigenetic inheritance demonstrate that it has the ability to create selectable traits, and thus to mediate Darwinian evolution. Here we discuss the possibility that epigenetic inheritance is responsible for some stable characteristics of species, focusing on a recent comparison of the human and chimpanzee methylomes which reveals that somatic methylation states are related to methylation states in the germline. Interpretation of this finding highlights the potential significance of germline epigenetic states, as well as the challenge of investigating a form of inheritance with complex and unfamiliar rules. PMID:22966965

  16. 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. PMID:25713300

  17. 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. PMID:26642364

  18. 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

  19. Convulsive Syncope Induced by Ventricular Arrhythmia Masquerading as Epileptic Seizures: Case Report and Literature Review.

    PubMed

    Sabu, John; Regeti, Kalyani; Mallappallil, Mary; Kassotis, John; Islam, Hamidul; Zafar, Shoaib; Khan, Rafay; Ibrahim, Hiyam; Kanta, Romana; Sen, Shuvendu; Yousif, Abdalla; Nai, Qiang

    2016-08-01

    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

  20. 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

  1. 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

  2. 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. PMID:26411603

  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. Deep Dermatophytosis and Inherited CARD9 Deficiency

    PubMed Central

    Vincent, Quentin B.; Liu, Luyan; Cypowyj, Sophie; Prando, Carolina; Migaud, Mélanie; Taibi, Lynda; Ammar-Khodja, Aomar; Stambouli, Omar Boudghene; Guellil, Boumediene; Jacobs, Frederique; Goffard, Jean-Christophe; Schepers, Kinda; del Marmol, Véronique; Boussofara, Lobna; Denguezli, Mohamed; Larif, Molka; Bachelez, Hervé; Michel, Laurence; Lefranc, Gérard; Hay, Rod; Jouvion, Gregory; Chretien, Fabrice; Fraitag, Sylvie; Bougnoux, Marie-Elisabeth; Boudia, Merad

    2014-01-01

    BACKGROUND Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. METHODS We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain–containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. RESULTS Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. CONCLUSIONS All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.) PMID:24131138

  5. How are arrhythmias detected by implanted cardiac devices managed in Europe? Results of the European Heart Rhythm Association Survey.

    PubMed

    Todd, Derick; Hernandez-Madrid, Antonio; Proclemer, Alessandro; Bongiorni, Maria Grazia; Estner, Heidi; Blomström-Lundqvist, Carina

    2015-09-01

    The management of arrhythmias detected by implantable cardiac devices can be challenging. There are no formal international guidelines to inform decision-making. The purpose of this European Heart Rhythm Association (EHRA) survey was to assess the management of various clinical scenarios among members of the EHRA electrophysiology research network. There were 49 responses to the questionnaire. The survey responses were mainly (81%) from medium-high volume device implanting centres, performing more than 200 total device implants per year. Clinical scenarios were described focusing on four key areas: the implantation of pacemakers for bradyarrhythmia detected on an implantable loop recorder (ILR), the management of patients with ventricular arrhythmia detected by an ILR or pacemaker, the management of atrial fibrillation in patients with pacemakers and cardiac resynchronization therapy devices and the management of ventricular tachycardia in patients with implantable cardioverter-defibrillators. PMID:26443791

  6. Psychological Distress and Arrhythmia: Risk Prediction and Potential Modifiers

    PubMed Central

    Peacock, James; Whang, William

    2014-01-01

    The connection between the heart and the brain has long been anecdotally recognized but systematically studied only relatively recently. Cardiac arrhythmias, especially sudden cardiac death, remain a major public health concern and there is mounting evidence that psychological distress plays a critical role as both a predictor of high-risk cardiac substrate and as an inciting trigger. The transient, unpredictable nature of emotions and cardiac arrhythmias have made their study challenging, but evolving technologies in monitoring and imaging along with larger epidemiological data sets have encouraged more sophisticated studies examining this relationship. Here we review the research on psychological distress including anger, depression and anxiety on cardiac arrhythmias, insights into proposed mechanisms, and potential avenues for future research. PMID:23621968

  7. Exploiting periodicity to extract the atrial activity in atrial arrhythmias

    NASA Astrophysics Data System (ADS)

    Llinares, Raul; Igual, Jorge

    2011-12-01

    Atrial fibrillation disorders are one of the main arrhythmias of the elderly. The atrial and ventricular activities are decoupled during an atrial fibrillation episode, and very rapid and irregular waves replace the usual atrial P-wave in a normal sinus rhythm electrocardiogram (ECG). The estimation of these wavelets is a must for clinical analysis. We propose a new approach to this problem focused on the quasiperiodicity of these wavelets. Atrial activity is characterized by a main atrial rhythm in the interval 3-12 Hz. It enables us to establish the problem as the separation of the original sources from the instantaneous linear combination of them recorded in the ECG or the extraction of only the atrial component exploiting the quasiperiodic feature of the atrial signal. This methodology implies the previous estimation of such main atrial period. We present two algorithms that separate and extract the atrial rhythm starting from a prior estimation of the main atrial frequency. The first one is an algebraic method based on the maximization of a cost function that measures the periodicity. The other one is an adaptive algorithm that exploits the decorrelation of the atrial and other signals diagonalizing the correlation matrices at multiple lags of the period of atrial activity. The algorithms are applied successfully to synthetic and real data. In simulated ECGs, the average correlation index obtained was 0.811 and 0.847, respectively. In real ECGs, the accuracy of the results was validated using spectral and temporal parameters. The average peak frequency and spectral concentration obtained were 5.550 and 5.554 Hz and 56.3 and 54.4%, respectively, and the kurtosis was 0.266 and 0.695. For validation purposes, we compared the proposed algorithms with established methods, obtaining better results for simulated and real registers.

  8. Controlled Exposures to Air Pollutants and Risk of Cardiac Arrhythmia

    PubMed Central

    Watts, Simon J.; Hunter, Amanda J.; Shah, Anoop S.V.; Bosson, Jenny A.; Unosson, Jon; Barath, Stefan; Lundbäck, Magnus; Cassee, Flemming R.; Donaldson, Ken; Sandström, Thomas; Blomberg, Anders; Newby, David E.; Mills, Nicholas L.

    2014-01-01

    Background: Epidemiological studies have reported associations between air pollution exposure and increases in cardiovascular morbidity and mortality. Exposure to air pollutants can influence cardiac autonomic tone and reduce heart rate variability, and may increase the risk of cardiac arrhythmias, particularly in susceptible patient groups. Objectives: We investigated the incidence of cardiac arrhythmias during and after controlled exposure to air pollutants in healthy volunteers and patients with coronary heart disease. Methods: We analyzed data from 13 double-blind randomized crossover studies including 282 participants (140 healthy volunteers and 142 patients with stable coronary heart disease) from whom continuous electrocardiograms were available. The incidence of cardiac arrhythmias was recorded for each exposure and study population. Results: There were no increases in any cardiac arrhythmia during or after exposure to dilute diesel exhaust, wood smoke, ozone, concentrated ambient particles, engineered carbon nanoparticles, or high ambient levels of air pollution in either healthy volunteers or patients with coronary heart disease. Conclusions: Acute controlled exposure to air pollutants did not increase the short-term risk of arrhythmia in participants. Research employing these techniques remains crucial in identifying the important pathophysiological pathways involved in the adverse effects of air pollution, and is vital to inform environmental and public health policy decisions. Citation: Langrish JP, Watts SJ, Hunter AJ, Shah AS, Bosson JA, Unosson J, Barath S, Lundbäck M, Cassee FR, Donaldson K, Sandström T, Blomberg A, Newby DE, Mills NL. 2014. Controlled exposures to air pollutants and risk of cardiac arrhythmia. Environ Health Perspect 122:747–753; http://dx.doi.org/10.1289/ehp.1307337 PMID:24667535

  9. Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes

    PubMed Central

    Zorzi, Alessandro; Perazzolo Marra, Martina; Rigato, Ilaria; De Lazzari, Manuel; Susana, Angela; Niero, Alice; Pilichou, Kalliopi; Migliore, Federico; Rizzo, Stefania; Giorgi, Benedetta; De Conti, Giorgio; Sarto, Patrizio; Serratosa, Luis; Patrizi, Giampiero; De Maria, Elia; Pelliccia, Antonio; Basso, Cristina; Schiavon, Maurizio; Bauce, Barbara; Iliceto, Sabino; Thiene, Gaetano

    2016-01-01

    Background— The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain to be elucidated. Methods and Results— We compared 35 athletes (80% men, age: 14–48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls. Conclusions— Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography. PMID:27390211

  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.

  11. 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…

  12. 76 FR 75825 - Streamlining Inherited Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ...The Bureau of Consumer Financial Protection (the Bureau) is requesting specific suggestions from the public for streamlining regulations it recently inherited from other Federal agencies. This document asks the public to identify provisions of the inherited regulations that the Bureau should make the highest priority for updating, modifying, or eliminating because they are outdated, unduly......

  13. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Inherited lands. 213.13 Section 213.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.13 Inherited lands. Except...

  14. Inheritance of grain proteins in wheat.

    PubMed

    Kraljević-Balalić, M; Stajner, D; Gašić, O

    1982-06-01

    Diallel crosses between five divergent vulgare wheat cultivars were made in order to evaluate the mode of inheritance and combining ability of grain proteins. Significant differences in grain protein content were found between cultivars and their hybrids. It was established that the inheritance of seed protein in the F1 generation included both additive and non-additive gene action. PMID:24270758

  15. Innovation in the diagnosis and treatment of cardiac arrhythmias.

    PubMed

    Friedman, Paul A; Eldar, Michal; Ovsyshcher, I Eli

    2012-08-01

    The 11th International Dead Sea Symposium on Cardiac Arrhythmias and Device Therapy - the 20th Anniversary of the meeting - was held in Jerusalem, Israel on the 26-29 February 2012. The global meeting was conducted with the goal of providing a venue for a multidisciplinary approach to exchange knowledge in all areas related to arrhythmia care. In addition to presentations of original research and keynote lectures, special educational sessions were offered that included hands-on anatomy training and interesting case presentations. A series of innovations sessions included presentations by start-up companies and inventors, leveraging the venue's entrepreneurial environment. PMID:23030286

  16. Paternity and inheritance of wealth

    NASA Astrophysics Data System (ADS)

    Hartung, John

    1981-06-01

    One of the oldest conjectures in anthropology is that men transfer wealth to their sister's son when the biological paternity of their `own' children is in doubt1-12. Because maternity is certain, a man is necessarily related to his sister's son and his brother (see Fig. 1). It is argued here that relatedness to male heirs can be assured by passing wealth to sister's sons or down a line of brothers, whether the prevailing kinship system reckons those brothers matrilineally or patrilineally. It is also argued that when several transfers of wealth are considered, a man's likelihood of being cuckolded need not be unrealistically high13 for his successive matrilineal heirs to be more related to him than his successive patrilineal heirs (see Fig. 2). Cross-cultural data on sister's son/brother inheritance14 and frequency of extramarital sex for females15 support the hypothesis that men tend to transmit wealth to their sister's son and/or brother when the probability that their putative children are their genetic children is relatively low.

  17. Leading the Team You Inherit.

    PubMed

    Watkins, Michael D

    2016-06-01

    Most leaders don't have the luxury of building their teams from scratch. Instead they're put in charge of an existing group, and they need guidance on the best way to take over and improve performance. Watkins, an expert on transitions, suggests a three-step approach: Assess. Act quickly to size up the personnel you've inherited, systematically gathering data from one-on-one chats, team meetings, and other sources. Reflect, too, on the business challenges you face, the kinds of people you want in various roles, and the degree to which they need to collaborate. Reshape. Adjust the makeup of the team by moving people to new positions, shifting their responsibilities, or replacing them. Make sure that everyone is aligned on goals and how to achieve them--you may need to change the team's stated direction. Consider also making changes in the way the team operates (reducing the frequency of meetings, for example, or creating new subteams). Then establish ground rules and processes to sustain desired behaviors, and revisit those periodically. Accelerate team development. Set your people up for some early wins. Initial successes will boost everyone's confidence and reinforce the value of your new operating model, thus paving the way for ongoing growth. PMID:27491196

  18. An extended family suddenly confronted with a life-threatening hereditary arrhythmia

    PubMed Central

    Hendriks, K.S.W.H.; van Langen, I.M.; van Tintelen, J.P.; Grosfeld, F.J.M.; Wilde, A.A.M.; ten Kroode, H.F.J.

    2005-01-01

    Objective This exploratory study serves to illustrate the psychological impact on an extended family in the process of genetic counselling and testing for a potentially life-threatening arrhythmia, the long-QT syndrome (LQTS). Method All members of the third generation and their partners (n=11) were interviewed, the mutation carriers with partners twice. In addition they completed measures for anxiety and depression three times in 18 months. Results During the interviews these family members emphasised the damaged solidarity when the family is divided into carriers and noncarriers of a mutation in a LQTS predisposing gene. This demonstrates one way in which a family can react to the reality of being at risk of a potentially severe disease. Rewriting family history and mourning early death seem other ways to deal with this. The distress scores, especially of the women, were moderate to clinically high, not because of their own chance of having an arrhythmia but more due to their children's risk. Conclusion Mothers need educational even more than emotional support, because the lifestyle of their carrier children is in need of radical change. The setting of a combined outpatient cardiogenetic clinic with a medical and psychosocial staff meets such needs efficiently. PMID:25696515

  19. Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model mice

    PubMed Central

    Heier, Christopher R.; Satta, Rosalba; Lutz, Cathleen; DiDonato, Christine J.

    2010-01-01

    Proximal spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Traditionally, SMA has been described as a motor neuron disease; however, there is a growing body of evidence that arrhythmia and/or cardiomyopathy may present in SMA patients at an increased frequency. Here, we ask whether SMA model mice possess such phenotypes. We find SMA mice suffer from severe bradyarrhythmia characterized by progressive heart block and impaired ventricular depolarization. Echocardiography further confirms functional cardiac deficits in SMA mice. Additional investigations show evidence of both sympathetic innervation defects and dilated cardiomyopathy at late stages of disease. Based upon these data, we propose a model in which decreased sympathetic innervation causes autonomic imbalance. Such imbalance would be characterized by a relative increase in the level of vagal tone controlling heart rate, which is consistent with bradyarrhythmia and progressive heart block. Finally, treatment with the histone deacetylase inhibitor trichostatin A, a drug known to benefit phenotypes of SMA model mice, produces prolonged maturation of the SMA heartbeat and an increase in cardiac size. Treated mice maintain measures of motor function throughout extended survival though they ultimately reach death endpoints in association with a progression of bradyarrhythmia. These data represent the novel identification of cardiac arrhythmia as an early and progressive feature of murine SMA while providing several new, quantitative indices of mouse health. Together with clinical cases that report similar symptoms, this reveals a new area of investigation that will be important to address as we move SMA therapeutics towards clinical success. PMID:20693262

  20. Chronic Arrhythmias in the Setting of Heterotaxy: Differences between Right and Left Isomerism.

    PubMed

    Loomba, Rohit S; Willes, Richard J; Kovach, Joshua R; Anderson, Robert H

    2016-01-01

    So-called heterotaxy affects lateralization of the thoracic and abdominal organs. Congenital malformations may be present in one of several organ systems. Cardiac involvement includes both structural and conduction abnormalities. Data regarding arrhythmias in heterotaxy come from case reports and small case series. We pooled available data to further characterize arrhythmias in heterotaxy. A systematic review of the literature for manuscripts describing arrhythmias in heterotaxy patients was conducted. Databases including PubMed, EMBASE, and Ovid were searched. Studies describing arrhythmias in patients with heterotaxy were included if they were in English and presented characteristics of the arrhythmias. Arrhythmia characteristics were abstracted and are presented as pooled data. Freedom from arrhythmia by age was then analyzed using Kaplan-Meier analysis. A total of 19 studies with 121 patients were included in the pooled analysis. Those with right isomerism were found to be more likely to have atrial flutter, atrial tachycardia, junctional tachycardia, and ventricular tachycardia. Those with left isomerism were more likely to have atrioventricular block, intraventricular conduction delay, sick sinus syndrome, and atrioventricular nodal reentry tachycardia. Median age of onset for all arrhythmias was 4 years with no difference by specific arrhythmia or isomerism. Those with right and left isomerism are at risk for different arrhythmias but are likely to develop arrhythmias at the same age. Those with left isomerism are more likely to require pacemaker placement due to atrioventricular block. Understanding these differences allows for focused surveillance of development of these arrhythmias. PMID:26219620

  1. 21 CFR 870.1025 - Arrhythmia detector and alarm (including ST-segment measurement and alarm).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Arrhythmia detector and alarm (including ST... Diagnostic Devices § 870.1025 Arrhythmia detector and alarm (including ST-segment measurement and alarm). (a) Identification. The arrhythmia detector and alarm device monitors an electrocardiogram and is designed to...

  2. 21 CFR 870.1025 - Arrhythmia detector and alarm (including ST-segment measurement and alarm).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Arrhythmia detector and alarm (including ST... Diagnostic Devices § 870.1025 Arrhythmia detector and alarm (including ST-segment measurement and alarm). (a) Identification. The arrhythmia detector and alarm device monitors an electrocardiogram and is designed to...

  3. 21 CFR 870.1025 - Arrhythmia detector and alarm (including ST-segment measurement and alarm).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Arrhythmia detector and alarm (including ST... Diagnostic Devices § 870.1025 Arrhythmia detector and alarm (including ST-segment measurement and alarm). (a) Identification. The arrhythmia detector and alarm device monitors an electrocardiogram and is designed to...

  4. 21 CFR 870.1025 - Arrhythmia detector and alarm (including ST-segment measurement and alarm).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Arrhythmia detector and alarm (including ST... Diagnostic Devices § 870.1025 Arrhythmia detector and alarm (including ST-segment measurement and alarm). (a) Identification. The arrhythmia detector and alarm device monitors an electrocardiogram and is designed to...

  5. 21 CFR 870.1025 - Arrhythmia detector and alarm (including ST-segment measurement and alarm).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Arrhythmia detector and alarm (including ST... Diagnostic Devices § 870.1025 Arrhythmia detector and alarm (including ST-segment measurement and alarm). (a) Identification. The arrhythmia detector and alarm device monitors an electrocardiogram and is designed to...

  6. [Arrhythmias in pregnancy. How and when to treat?].

    PubMed

    Flores, Jorge R Gómez; Márquez, Manlio F

    2007-01-01

    Cardiac arrhythmias can develop during pregnancy. The risk of arrhythmias is relatively higher during labor and delivery. Potential factors that can promote arrhythmias in pregnancy or during labor and delivery, include the direct cardiac electrophysiological effects of hormones, changes in autonomic tone, hemodynamic perturbations, hypokalemia, and underlying heart disease. In this review, the basis for treatment of supraventricular and ventricular tachycardias are described. No drug therapy is usually needed for the management of supraventricular or ventricular premature beats, but potential stimulants, such as smoking, caffeine, and alcohol should be eliminated. In paroxysmal supraventricular tachycardia, vagal stimulation maneuvers should be attempted first. In pregnant women with atrial fibrillation, the goal of treatment is conversion to sinus rhythm by electrical cardioversion. Rate control can be achieved by a cardioselective beta-adrenergic blocker drug and/ or digoxin. Ventricular arrhythmias may occur in the pregnant women, specially when cardiomyopathy, congenital heart disease, valvular heart disease, or mitral valve prolapse exists. Electrical cardioversion or treatment with sotalol may be used (amiodarone is not safe for the fetus). Finally, in women with congenital long QT syndrome, beta-blocker therapy must be continued during pregnancy and postpartum period. PMID:17972373

  7. Diagnosis, treatment and follow up of neonatal arrhythmias

    PubMed Central

    Binnetoğlu, Fatih Köksal; Babaoğlu, Kadir; Altun, Gürkan; Türker, Gülcan

    2014-01-01

    Summary Objective This study aimed to evaluate the aetiology, spectrum, course and outcomes of neonates with arrhythmias observed in a tertiary neonatal intensive care unit from 2007 to 2012. Methods Neonates with rhythm problems were included. The results of electrocardiography (ECG), Holter ECG, echocardiography and biochemical analysis were evaluated. The long-term results of follow up were reviewed. Results Forty-five patients were male (68%) and 21 (32%) were female. Fifty-five patients (83.3%) were term, 11 (16.6%) were preterm, and 34% were diagnosed in the prenatal period. Twenty cases (30.3%) had congenital heart disease. Twenty-three patients (34.8%) were diagnosed during the foetal period. The most common arrhythmias were supraventricular ectopic beats and supraventricular tachycardia (SVT) at 39.3 and 22.7%, respectively. SVT recurred in five patients after the neonatal period. Conclusion Supraventricular ectopic beats and SVT were the most common arrhythmias during the neonatal period. Although the prognosis of arrhythmias in the neonatal period is relatively good, regular monitoring is required. PMID:24844549

  8. Infant Visual Sustained Attention and Respiratory Sinus Arrhythmia.

    ERIC Educational Resources Information Center

    Richards, John E.

    1987-01-01

    Tested the model which posits that heart-rate deceleration and respiratory sinus arrhythmia are indices of infant attention. Infants studied cross-sectionally at 14, 20, and 26 weeks of age were presented with complex patterns on a TV screen which were accompanied by an "interrupting stumulus". (Author/BN)

  9. Electrocardiographic abnormalities and cardiac arrhythmias in structural brain lesions.

    PubMed

    Katsanos, Aristeidis H; Korantzopoulos, Panagiotis; Tsivgoulis, Georgios; Kyritsis, Athanassios P; Kosmidou, Maria; Giannopoulos, Sotirios

    2013-07-31

    Cardiac arrhythmias and electrocardiographic abnormalities are frequently observed after acute cerebrovascular events. The precise mechanism that leads to the development of these arrhythmias is still uncertain, though increasing evidence suggests that it is mainly due to autonomic nervous system dysregulation. In massive brain lesions sympathetic predominance and parasympathetic withdrawal during the first 72 h are associated with the occurrence of severe secondary complications in the first week. Right insular cortex lesions are also related with sympathetic overactivation and with a higher incidence of electrocardiographic abnormalities, mostly QT prolongation, in patients with ischemic stroke. Additionally, female sex and hypokalemia are independent risk factors for severe prolongation of the QT interval which subsequently results in malignant arrhythmias and poor outcome. The prognostic value of repolarization changes commonly seen after aneurysmal subarachnoid hemorrhage, such as ST segment, T wave, and U wave abnormalities, still remains controversial. In patients with traumatic brain injury both intracranial hypertension and cerebral hypoperfusion correlate with low heart rate variability and increased mortality. Given that there are no firm guidelines for the prevention or treatment of the arrhythmias that appear after cerebral incidents this review aims to highlight important issues on this topic. Selected patients with the aforementioned risk factors could benefit from electrocardiographic monitoring, reassessment of the medications that prolong QTc interval, and administration of antiadrenergic agents. Further research is required in order to validate these assumptions and to establish specific therapeutic strategies. PMID:22809542

  10. The Wedensky test predicts malignant ventricular arrhythmias after myocardial infarction

    PubMed Central

    2013-01-01

    Objectives. Better tools are needed for detection of future malignant ventricular arrhythmias post myocardial infarct (MI). Wedensky Modulation (WM) is a new semi-invasive method: A short low-amplitude electrical impulse is applied synchronized to the QRS between a precordial and dorsal thoracic patch, and changes in the following QRS-T are registered. Design. A total of 357 (MI) ICD patients underwent WM testing. QRS-T wavelet analysis provided WM Indexes for the QRS complex (WMI-R) and T wave (WMI-T). Outcome was the time to first occurrence of appropriate device therapy for ventricular arrhythmia. Patients were followed at 6-month intervals for 2 years. Results. No arrhythmia was induced by the testing. Two-year appropriate arrhythmia treatment occurred in 35% (WMI-R positive) versus 25% (WMI-R negative, p = 0.014), and. 45% versus 26% (p = 0.001) for WMI-T positive versus negative. Two-year event rates of WMI-R or WMI-T positive versus WMI-R and WMI-T negative were 36% versus 22% (p = 0.004). In Cox proportional hazard model, the combination of WMI-R and WMI-T was the only statistically significant event predictor (p = 0.003). Conclusion. Potentially life-threatening ventricular arrhythmic events could be predicted by the WM test. In combination with other risk factors WMI may be useful in these patients. PMID:24050376

  11. Potentially fatal arrhythmias in two cases of adult Kawasaki disease.

    PubMed

    Watanabe, Hirofumi; Kato, Masataka; Ayusawa, Mamoru

    2016-03-01

    Fatal arrhythmias in asymptomatic Kawasaki disease patients with normal left ventricular function have rarely been reported. In this study, we report the cases of two adult patients with largely unpredictable sudden cardiac arrest, despite almost-normal left ventricular function even after the diagnosis of presumed Kawasaki disease, as well as consider the mechanisms involved with reference to the literature. PMID:26424562

  12. An Update on Laboratory Diagnosis of Liver Inherited Diseases

    PubMed Central

    Elce, Ausilia; Amato, Felice

    2013-01-01

    Liver inherited diseases are a group of genetically determined clinical entities that appear with an early chronic liver involvement. They include Wilson's disease (hepatolenticular degeneration), hereditary hemochromatosis, and alpha-1-antitrypsin deficiency. In addition, cystic fibrosis, although it is not specifically a liver disease, may cause a severe liver involvement in a significant percentage of cases. For all these pathologies, the disease gene is known, and molecular analysis may contribute to the unequivocal diagnosis. This approach could avoid the patient invasive procedures and limit complications associated with a delay in diagnosis. We review liver inherited diseases on the basis of the genetic defect, focusing on the contribution of molecular analysis in the multistep diagnostic workup. PMID:24222913

  13. Using whole exome sequencing to identify inherited causes of autism

    PubMed Central

    Yu, T.W.; Chahrour, M.H.; Coulter, M.E.; Jiralerspong, S.; Okamura-Ikeda, K.; Ataman, B.; Schmitz-Abe, K.; Harmin, D.A.; Adli, M.; Malik, A.N.; D’Gama, A.M.; Lim, E.T.; Sanders, S.J.; Mochida, G.H.; Partlow, J.N.; Sunu, C.M.; Felie, J.M.; Rodriguez, J.; Nasir, R.H.; Ware, J.; Joseph, R.M.; Hill, R.S.; Kwan, B.Y.; Al-Saffar, M.; Mukaddes, N.M.; Hashmi, A.; Balkhy, S.; Gascon, G.G.; Hisama, F.M.; LeClair, E.; Poduri, A.; Oner, O.; Al-Saad, S.; Al-Awadi, S.A.; Bastaki, L.; Ben-Omran, T.; Teebi, A.; Al-Gazali, L.; Eapen, V.; Stevens, C.R.; Rappaport, L.; Gabriel, S.B.; Markianos, K.; State, M.W.; Greenberg, M.E.; Taniguchi, H.; Braverman, N.E.; Morrow, E.M.; Walsh, C.A.

    2013-01-01

    Summary Despite significant heritability of autism spectrum disorders (ASDs), their extreme genetic heterogeneity has proven challenging for gene discovery. Studies of primarily simplex families have implicated de novo copy number changes and point mutations, but are not optimally designed to identify inherited risk alleles. We apply whole exome sequencing (WES) to ASD families enriched for inherited causes due to consanguinity and find familial ASD associated with biallelic mutations in disease genes (AMT, PEX7, SYNE1, VPS13B, PAH, POMGNT1), some implicated for the first time in ASD. At least some of these genes show biallelic mutations in nonconsanguineous families as well. These mutations are often only partially disabling or present atypically, with patients lacking diagnostic features of the Mendelian disorders with which these genes are classically associated. Our study shows the utility of WES for identifying specific genetic conditions not clinically suspected and the importance of partial loss of gene function in ASDs. PMID:23352163

  14. Association of Bartonella spp bacteremia with Chagas cardiomyopathy, endocarditis and arrhythmias in patients from South America.

    PubMed

    Corrêa, F G; Pontes, C L S; Verzola, R M M; Mateos, J C P; Velho, P E N F; Schijman, A G; Selistre-de-Araujo, H S

    2012-07-01

    Infection with Bartonella spp may cause cardiac arrhythmias, myocarditis and endocarditis in humans. The aim of the present study was to evaluate a possible association between Bartonella spp bacteremia and endocarditis, arrhythmia and Chagas cardiomyopathy in patients from Brazil and Argentina. We screened for the presence of bacterial 16S rRNA in human blood by PCR using oligonucleotides to amplify a 185-bp bacterial DNA fragment. Blood samples were taken from four groups of subjects in Brazil and Argentina: i) control patients without clinical disease, ii) patients with negative blood-culture endocarditis, iii) patients with arrhythmias, and iv) patients with chronic Chagas cardiomyopathy. PCR products were analyzed on 1.5% agarose gel to visualize the 185-bp fragment and then sequenced to confirm the identity of DNA. Sixty of 148 patients (40.5%) with cardiac disease and 1 of 56 subjects (1.8%) from the control group presented positive PCR amplification for Bartonella spp, suggesting a positive association of the bacteria with these diseases. Separate analysis of the four groups showed that the risk of a Brazilian patient with endocarditis being infected with Bartonella was 22 times higher than in the controls. In arrhythmic patients, the prevalence of infection was 45 times higher when compared to the same controls and 40 times higher for patients with Chagas cardiomyopathy. To the best of our knowledge this is the first report of the association between Bartonella spp bacteremia and Chagas disease. The present data may be useful for epidemiological and prevention studies in Brazil and Argentina. PMID:22584639

  15. Inheritance of seed color in Capsicum.

    PubMed

    Zewdie, Y; Bosland, P W

    2003-01-01

    The mode of seed color inheritance in Capsicum was studied via an interspecific hybridization between C. pubescens Ruiz and Pav. (black seed color) and C. eximium Hunz. (yellow seed color). Black seed color was dominant over yellow seed color. The F(2) segregation pattern showed continuous variation. The generation means analysis indicated the presence of a significant effect of additive [d], dominance [h], and additive x additive [i] interaction for seed color inheritance. The estimate for a minimum number of effective factors (genes) involved in seed color inheritance was approximately 3. PMID:12920108

  16. [INHERITANCE OF EPIDERMIS PIGMENTATION IN SUNFLOWER ACHENES].

    PubMed

    Gorohivets, N A; Vedmedeva, E V

    2016-01-01

    Inheritance of epidermis pigmentation in the pericarp of sunflower seeds was studied. Inheritance of pigmentation was confirmed by three alleles Ew (epidermis devoid of pigmentation), Estr (epidermal pigmentation in strips), Edg (solid pigmentation). Dominance of the lack of epidermis pigmentation over striped epidermis and striped epidermis over solid pigmentation was established. It was shown that the striped epidermis pigmentation and the presence of testa layer are controlled by two genes, expression of which is independent from each other. Yellowish hypodermis was discovered in the sample I2K2218, which is inherited monogenically dominantly. PMID:27281924

  17. Arrhythmias and Electrocardiographic Changes in Systolic Heart Failure

    PubMed Central

    Devkota, Ashok; Bakhit, Ahmed; Dufresne, Alix; Oo, Aung Naing; Parajuli, Premraj; Manhas, Saveena

    2016-01-01

    Background: Heart failure is a common condition that that leads to hospitalization. It is associated with various atrial and ventricular arrhythmias. Aim: The aim of this study is to find common arrhythmias and electrocardiographic changes in hospitalized patients who have systolic heart failure. Materials and Methods: This is a retrospective study of medical records, and electrocardiograms (EKGs) of 157 patients admitted to our hospital who had systolic heart failure with ejection fraction (EF) <50% on echocardiogram. Based on EF, the patients were divided into two groups; one with EF ≤ 35% and the other with EF > 35%. Twelve-lead EKG of these patients was studied to identify common arrhythmia and demographic variables; laboratory results were compared to identify the differences. Results: A total of 157 patients with systolic heart failure, 63.7% had an EF ≤ 35%. Hypertension 82.8%, diabetes 49%, coronary artery disease 40.8%, chronic obstructive pulmonary disease or bronchial asthma 22.3%, and stroke 12.1% were common associated co-morbidities. On analysis of EKG, 28.6% had tachycardia, 21.9% had prolonged PR > 200 ms, 16.3% had wide QRS > 120 ms, 70.7% had prolonged corrected QT (QTc), and 42.2% had left axis deviation. The most common arrhythmias were sinus tachycardia and atrial fibrillation/flutter which were found in 14.6% and 13.4%, respectively. The left ventricular hypertrophy was a common abnormality found in 22.4% followed by ventricular premature contractions 18.4%, atrial premature contractions 9.5%, and left bundle branch block 6.1%. Patients with severe systolic heart failure had prolonged QRS (P = 0.02) and prolonged QTc (P = 0.01) as compared to the other group. Conclusions: Sinus tachycardia and atrial fibrillation/flutter were common arrhythmias in patients with systolic heart failure. Patients with severe systolic heart failure had statistically significant prolongation of the QRS duration and QTc interval. PMID:27213140

  18. Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat.

    PubMed Central

    Curtis, M. J.; MacLeod, B. A.; Walker, M. J.

    1984-01-01

    The actions of intravenous verapamil against arrhythmias induced by occlusion of a coronary artery were investigated in conscious rats. Verapamil (2-20 mg kg-1, i.v. given pre-occlusion) dose-dependently reduced arrhythmias in rats with either large or small occluded zones at an ED50 of 6 mg kg-1. This dose was effective when given immediately post-occlusion. Severe arrhythmias, as opposed to PVC, were preferentially reduced. In conscious, and pentobarbitone-anaesthetized rats, verapamil (6 mg kg-1) had different effects on electrically-induced arrhythmias, and the ECG, from an equi-effective anti-arrhythmic dose of quinidine (20 mg kg-1, i.v.). Quinidine decreased following frequency, but increased threshold current and pulse width, whereas verapamil did not. Both drugs increased P-R interval, but only quinidine increased QRS and Q-T intervals. Thirty minutes post-occlusion, the verapamil content of tissue and blood was determined after a 6 mg kg-1 dose given pre- or post-occlusion. Measurable levels of verapamil were found in both normal and ischaemic myocardium. Plasma and plasma water concentrations were 3.6 +/- 0.8 mumol l-1 and 0.6 +/- 0.1 mumol l-1 (mean +/- s.e. mean), respectively following post-occlusion administration vs. 2.7 +/- 1.2 and 0.24 +/- 0.04 for pre-occlusion administration. Plasma water concentrations were close to IC50 values for inhibition of contractility in rat atria and ventricles. Similar concentrations depressed slow action potentials induced in rat ventricles by raised K+ We suggest that the ability of verapamil to prevent severe ventricular arrhythmias following myocardial ischaemia in the conscious rat is largely due to the calcium antagonist effects of the drug. PMID:6487902

  19. Atrial Arrhythmias in Astronauts - Summary of a NASA Summit

    NASA Technical Reports Server (NTRS)

    Barr, Yael R.; Watkins, Sharmila D.; Polk, J. D.

    2010-01-01

    Background and Problem Definition: To evaluate NASA s current standards and practices related to atrial arrhythmias in astronauts, Space Medicine s Advanced Projects Section at the Johnson Space Center was tasked with organizing a summit to discuss the approach to atrial arrhythmias in the astronaut cohort. Since 1959, 11 cases of atrial fibrillation, atrial flutter, or supraventricular tachycardia have been recorded among active corps crewmembers. Most of the cases were paroxysmal, although a few were sustained. While most of the affected crewmembers were asymptomatic, those slated for long-duration space flight underwent radiofrequency ablation treatment to prevent further episodes of the arrhythmia. The summit was convened to solicit expert opinion on screening, diagnosis, and treatment options, to identify gaps in knowledge, and to propose relevant research initiatives. Summit Meeting Objectives: The Atrial Arrhythmia Summit brought together a panel of six cardiologists, including nationally and internationally renowned leaders in cardiac electrophysiology, exercise physiology, and space flight cardiovascular physiology. The primary objectives of the summit discussions were to evaluate cases of atrial arrhythmia in the astronaut population, to understand the factors that may predispose an individual to this condition, to understand NASA s current capabilities for screening, diagnosis, and treatment, to discuss the risks associated with treatment of crewmembers assigned to long-duration missions or extravehicular activities, and to discuss recommendations for prevention or management of future cases. Summary of Recommendations: The summit panel s recommendations were grouped into seven categories: Epidemiology, Screening, Standards and Selection, Treatment of Atrial Fibrillation Manifesting Preflight, Atrial Fibrillation during Flight, Prevention of Atrial Fibrillation, and Future Research

  20. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

    PubMed Central

    Bayzigitov, Daniel R.; Medvedev, Sergey P.; Dementyeva, Elena V.; Bayramova, Sevda A.; Pokushalov, Evgeny A.; Karaskov, Alexander M.; Zakian, Suren M.

    2016-01-01

    Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes. PMID:27110425

  1. Center for Inherited Disease Research (CIDR)

    Cancer.gov

    The Center for Inherited Disease Research (CIDR) Program at The Johns Hopkins University provides high-quality next generation sequencing and genotyping services to investigators working to discover genes that contribute to common diseases.

  2. Developmental origins of epigenetic transgenerational inheritance

    PubMed Central

    Hanson, Mark A.; Skinner, Michael K.

    2016-01-01

    Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective. PMID:27390622

  3. Left Ventricular Dilatation Increases the Risk of Ventricular Arrhythmias in Patients With Reduced Systolic Function

    PubMed Central

    Aleong, Ryan G; Mulvahill, Matthew J; Halder, Indrani; Carlson, Nichole E; Singh, Madhurmeet; Bloom, Heather L; Dudley, Samuel C; Ellinor, Patrick T; Shalaby, Alaa; Weiss, Raul; Gutmann, Rebecca; Sauer, William H; Narayanan, Kumar; Chugh, Sumeet S; Saba, Samir; London, Barry

    2015-01-01

    ejection fraction to predict ventricular arrhythmias. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02045043. PMID:26231842

  4. Outcomes among athletes with arrhythmias and electrocardiographic abnormalities: implications for ECG interpretation.

    PubMed

    McClaskey, David; Lee, Daniel; Buch, Eric

    2013-10-01

    Electrocardiographic (ECG) aberrations and arrhythmias occur frequently among athletes due to normal variants, subclinical cardiac disease or structural and electrical remodeling in response to training. It is unclear whether these changes are associated with adverse clinical outcomes over time among otherwise asymptomatic, healthy athletes. Consensus guidelines have been developed to guide the clinician regarding further management of these arrhythmias. The purpose of this review is to summarize prospective data regarding cardiovascular outcomes related to ECG changes among athletes and compare these findings with current guidelines. A review of the literature was conducted using the PubMed database (1966--present). Outcomes of interest included documented cardiac symptoms or events, such as episodes of cardiac or cerebral hypoperfusion, sudden death or prophylactic procedural interventions. Studies were included for analysis if they involved (1) athletes with documented, baseline arrhythmias and/or abnormal ECG variations; (2) a study design with longitudinal follow-up (designated as >1 month, to exclude short-term Holter studies); and (3) outcomes that include documented cardiac symptoms or events. A total of 33 studies met the above criteria, encompassing over 4,200 athletes, with follow-up ranging from 2 months to 14.6 years. There were few adverse outcomes among cases of sinus bradycardia >30 bpm, sinus pauses <3 s, first-degree atrioventricular (AV) block, second-degree type I AV block and incomplete right bundle branch block. Results among these studies are concordant with guidelines that recommend work-up in the setting of cardiac symptoms, history or physical examination indicative of cardiac disease, severe sinus bradycardia or AV block that does not resolve with exercise or hyperventilation. Outcomes among prospective studies also support guidelines that recommend further evaluation for repolarization abnormalities and supraventricular tachycardias

  5. Respiratory involvement in inherited primary muscle conditions

    PubMed Central

    Shahrizaila, N; Kinnear, W J M; Wills, A J

    2006-01-01

    Patients with inherited muscle disorders can develop respiratory muscle weakness leading to ventilatory failure. Predicting the extent of respiratory involvement in the different types of inherited muscle disorders is important, as it allows clinicians to impart prognostic information and offers an opportunity for early interventional management strategies. The approach to respiratory assessment in patients with muscle disorders, the current knowledge of respiratory impairment in different muscle disorders and advice on the management of respiratory complications are summarised. PMID:16980655

  6. The pathology and treatment of cardiac arrhythmias: focus on atrial fibrillation

    PubMed Central

    Schmidt, Constanze; Kisselbach, Jana; Schweizer, Patrick A; Katus, Hugo A; Thomas, Dierk

    2011-01-01

    Atrial fibrillation (AF) is the most frequently encountered sustained cardiac arrhythmia in clinical practice and a major cause of morbidity and mortality. Effective treatment of AF still remains an unmet medical need. Treatment of AF is based on drug therapy and ablative strategies. Antiarrhythmic drug therapy is limited by a relatively high recurrence rate and proarrhythmic side effects. Catheter ablation suppresses paroxysmal AF in the majority of patients without structural heart disease but is more difficult to achieve in patients with persistent AF or with concomitant cardiac disease. Stroke is a potentially devastating complication of AF, requiring anticoagulation that harbors the risk of bleeding. In search of novel treatment modalities, targeted pharmacological treatment and gene therapy offer the potential for greater selectivity than conventional small-molecule or interventional approaches. This paper summarizes the current understanding of molecular mechanisms underlying AF. Established drug therapy and interventional treatment of AF is reviewed, and emerging clinical and experimental therapeutic approaches are highlighted. PMID:21490945

  7. Nonlinear dynamics, chaos and complex cardiac arrhythmias

    NASA Technical Reports Server (NTRS)

    Glass, L.; Courtemanche, M.; Shrier, A.; Goldberger, A. L.

    1987-01-01

    Periodic stimulation of a nonlinear cardiac oscillator in vitro gives rise to complex dynamics that is well described by one-dimensional finite difference equations. As stimulation parameters are varied, a large number of different phase-locked and chaotic rhythms is observed. Similar rhythms can be observed in the intact human heart when there is interaction between two pacemaker sites. Simplified models are analyzed, which show some correspondence to clinical observations.

  8. The implantable defibrillator and antiarrhythmic drugs--competitive and complementary treatment for severe ventricular arrhythmia.

    PubMed

    Dorian, P; Newman, D

    1993-11-01

    Most patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) are at high risk of recurrence. Implanted defibrillators (ICDs) are highly effective in sensing and converting VT or VF to a perfusing rhythm. "Conventional" antiarrhythmic agents, which primarily block cardiac sodium channels, are relatively ineffective in preventing arrhythmia recurrence; amiodarone and sotalol appear to be effective in reducing recurrence and mortality rates, although the extent of benefit is not well understood. Despite the apparent advantage of ICDs, they have short- and long-term complications, are costly, and their benefit in prolonging the quantity or quality of life remains unproven. Randomized clinical trials which compare the effect of ICDs with that of antiarrhythmic drugs on mortality, cost, and quality of life will be necessary to understand how patients with malignant arrhythmias ought to be treated. If an ICD is implanted, adjunctive therapies need to be considered to treat the underlying heart disease and to derive optimum benefit from the device. Drugs may have beneficial or adverse interactions with devices, and the full understanding of these interactions requires further study. PMID:8269662

  9. Hemodynamic effects of encainide in patients with ventricular arrhythmia and poor ventricular function

    SciTech Connect

    Sami, M.H.; Derbekyan, V.A.; Lisbona, R.

    1983-09-01

    Gated cardiac scanning was used to evaluate the hemodynamic effects of encainide in 19 patients (1 woman) with complex ventricular arrhythmia and depressed left ventricular (LV) function (ejection fraction less than 45%). Patients were 36 to 80 years old (average 61). All were candidates for long-term encainide therapy after having failed with currently available antiarrhythmics. Sixty-three percent had congestive heart failure before they received encainide. All were evaluated in the hospital before encainide therapy by a gated cardiac scan performed at least 3 days after discontinuing all antiarrhythmic drugs. Patients received oral encainide in doses of 75 to 200 mg. Gated cardiac scans were repeated 1 to 2 weeks later when an 80% reduction in frequency of premature ventricular complexes was observed on a 24-hour Holter recording. No patient had worsening of congestive heart failure during encainide therapy. Encainide did not significantly affect ejection fraction, which averaged 22 +/- 10% before and 25 +/- 14% (SD) after encainide (difference not significant (NS)). Other hemodynamic variables, including heart rate, blood pressure, stroke volume and end-diastolic volume, remained unchanged during encainide therapy. Digoxin blood levels in 10 patients averaged 1.04 +/- 0.43 before and 1.22 +/- 0.47 mg/ml (NS) during encainide therapy. Thus, encainide given orally in clinically effective doses does not appear to have significant hemodynamic effects in patients with ventricular arrhythmia and depressed LV function.

  10. Repetitive nonreentrant ventriculoatrial synchrony: An underrecognized cause of pacemaker-related arrhythmia.

    PubMed

    Sharma, Parikshit S; Kaszala, Karoly; Tan, Alex Y; Koneru, Jayanthi N; Shepard, Richard; Ellenbogen, Kenneth A; Huizar, Jose F

    2016-08-01

    Similar to endless loop tachycardia (ELT), repetitive nonreentrant ventriculoatrial synchrony (RNRVAS) is a ventriculoatrial (VA) synchrony pacemaker-mediated arrhythmia. RNRVAS was first described in 1990 and can only occur in the presence of retrograde VA conduction and dual-chamber or cardiac resynchronization devices with tracking (P-synchronous ventricular pacing such as DDD, DDDR) or nontracking pacing modes that allow AV-sequential pacing (DDI, DDIR). RNRVAS is promoted by (1) high lower rate limit or any feature that allows rapid pacing, (2) long AV intervals, or (3) long postventricular atrial refractory period (PVARP). In contrast to ELT, RNRVAS is a less well-recognized form of pacemaker-mediated arrhythmia; thus, unlike ELT, there are no specific device algorithms to prevent, recognize, and terminate RNRVAS. However, RNRVAS has been recently shown to occur frequently. We present a series of cases, some of which were found fortuitously. Owing to its clinical implications, we propose that algorithms should be developed to prevent, identify, and terminate RNRVAS. PMID:27050909

  11. Inherited disorders of brain neurotransmitters: pathogenesis and diagnostic approach.

    PubMed

    Szymańska, Krystyna; Kuśmierska, Katarzyna; Demkow, Urszula

    2015-01-01

    Neurotransmitters (NTs) play a central role in the efficient communication between neurons necessary for normal functioning of the nervous system. NTs can be divided into two groups: small molecule NTs and larger neuropeptide NTs. Inherited disorders of NTs result from a primary disturbance of NTs metabolism or transport. This group of disorders requires sophisticated diagnostic procedures. In this review we discuss disturbances in the metabolism of tetrahydrobiopterin, biogenic amines, γ-aminobutyric acid, foliate, pyridoxine-dependent enzymes, and also the glycine-dependent encephalopathy. We point to pathologic alterations of proteins involved in synaptic neurotransmission that may cause neurological and psychiatric symptoms. We postulate that synaptic receptors and transporter proteins for neurotransmitters should be investigated in unresolved cases. Patients with inherited neurotransmitters disorders present various clinical presentations such as mental retardation, refractory seizures, pyramidal and extrapyramidal syndromes, impaired locomotor patterns, and progressive encephalopathy. Every patient with suspected inherited neurotransmitter disorder should undergo a structured interview and a careful examination including neurological, biochemical, and imaging. PMID:25310959

  12. Vector platforms for gene therapy of inherited retinopathies

    PubMed Central

    Trapani, Ivana; Puppo, Agostina; Auricchio, Alberto

    2014-01-01

    Inherited retinopathies (IR) are common untreatable blinding conditions. Most of them are inherited as monogenic disorders, due to mutations in genes expressed in retinal photoreceptors (PR) and in retinal pigment epithelium (RPE). The retina’s compatibility with gene transfer has made transduction of different retinal cell layers in small and large animal models via viral and non-viral vectors possible. The ongoing identification of novel viruses as well as modifications of existing ones based either on rational design or directed evolution have generated vector variants with improved transduction properties. Dozens of promising proofs of concept have been obtained in IR animal models with both viral and non-viral vectors, and some of them have been relayed to clinical trials. To date, recombinant vectors based on the adeno-associated virus (AAV) represent the most promising tool for retinal gene therapy, given their ability to efficiently deliver therapeutic genes to both PR and RPE and their excellent safety and efficacy profiles in humans. However, AAVs’ limited cargo capacity has prevented application of the viral vector to treatments requiring transfer of genes with a coding sequence larger than 5 kb. Vectors with larger capacity, i.e. nanoparticles, adenoviral and lentiviral vectors are being exploited for gene transfer to the retina in animal models and, more recently, in humans. This review focuses on the available platforms for retinal gene therapy to fight inherited blindness, highlights their main strengths and examines the efforts to overcome some of their limitations. PMID:25124745

  13. Alternating Wenckebach periods and allied arrhythmias.

    PubMed

    Castellanos, A; Interian, A; Cox, M M; Myerburg, R J

    1993-12-01

    Alternating Wenckebach periods (AWPs) are episodes of 2:1 block during which the PR, AH, or AV intervals of the conducted beats gradually increase until a greater degree of block ensues. Most episodes occur at the AV node, but some have also been reported in other structures. AWPs are usually attributed to multilevel block due to transverse (horizontal) dissociation. This assumption was initially based on a method in which the solutions to difficult electrocardiographic rhythms were arrived at by analysis and deduction based on the knowledge existing at that particular time. Subsequently, it was reinforced by information extrapolated from intracardiac recordings performed in patients with documented multilevel block in separate anatomical structures (atria, AV node, and His bundle), as well as from microelectrode studies and computer simulations. Although AWPs are frequently observed in clinical tracings, those occurring at the AV node are best categorized during incremental atrial stimulation because then they occupy a specific point in the wide spectrum of tachycardia dependent AV nodal conduction disturbances. In fact, the A:H ratios occurring in the episodes where the degree of block increases can be represented by "universal" mathematical formulas. However, in the clinical setting, drugs affecting the electrophysiology of the node can alter the pacing induced symmetry by producing additional differential effects on the various levels. The latter still requires further elucidation. PMID:7508606

  14. Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

    NASA Technical Reports Server (NTRS)

    Armoundas, A. A.; Rosenbaum, D. S.; Ruskin, J. N.; Garan, H.; Cohen, R. J.

    1998-01-01

    OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular

  15. Development of a remote handheld cardiac arrhythmia monitor.

    PubMed

    Singh, Swaroop S; Hsiao, Henry S

    2006-01-01

    In this paper we present the design and development of a real-time remote handheld cardiac arrhythmic monitoring system (RCAM). A client-server model based on Internet protocols was used. ECG data was transmitted from the remote handheld client to a centralized server, where the QRS and premature ventricular contraction detection algorithms were implemented and graded depending on the number and pattern of PVCs present. The QRS sensitivity and specificity on ECG records from Physionet archives in absence of arrhythmia was 100% and 99.62%, while in presence of arrhythmia was 99.34% and 99.31%. The average 'negative time' measured on ventricular tachyarrhythmia records was 92 seconds. The RCAM can provide remote detection of cardiac abnormalities and give specific diagnosis and recommendations of actions to be taken immediately. The limitation due to the inability of the PDA to perform complex computations was overcome by the use of the remote server. PMID:17947043

  16. ECG Signal Analysis and Arrhythmia Detection using Wavelet Transform

    NASA Astrophysics Data System (ADS)

    Kaur, Inderbir; Rajni, Rajni; Marwaha, Anupma

    2016-06-01

    Electrocardiogram (ECG) is used to record the electrical activity of the heart. The ECG signal being non-stationary in nature, makes the analysis and interpretation of the signal very difficult. Hence accurate analysis of ECG signal with a powerful tool like discrete wavelet transform (DWT) becomes imperative. In this paper, ECG signal is denoised to remove the artifacts and analyzed using Wavelet Transform to detect the QRS complex and arrhythmia. This work is implemented in MATLAB software for MIT/BIH Arrhythmia database and yields the sensitivity of 99.85 %, positive predictivity of 99.92 % and detection error rate of 0.221 % with wavelet transform. It is also inferred that DWT outperforms principle component analysis technique in detection of ECG signal.

  17. Multiple cardiac arrhythmia recognition using adaptive wavelet network.

    PubMed

    Lin, Chia-Hung; Chen, Pei-Jarn; Chen, Yung-Fu; Lee, You-Yun; Chen, Tainsong

    2005-01-01

    This paper proposes a method for electrocardiogram (ECG) heartbeat pattern recognition using adaptive wavelet network (AWN). The ECG beat recognition can be divided into a sequence of stages, starting from feature extraction and conversion of QRS complexes, and then identifying cardiac arrhythmias based on the detected features. The discrimination method of ECG beats is a two-subnetwork architecture, consisting of a wavelet layer and a probabilistic neural network (PNN). Morlet wavelets are used to extract the features from each heartbeat, and then PNN is used to analyze the meaningful features and perform discrimination tasks. The AWN is suitable for application in a dynamic environment, with add-in and delete-off features using automatic target adjustment and parameter tuning. The experimental results obtained by testing the data of the MIT-BIH arrhythmia database demonstrate the efficiency of the proposed method. PMID:17281539

  18. Classification enhancible grey relational analysis for cardiac arrhythmias discrimination.

    PubMed

    Lin, Chia-Hung

    2006-04-01

    This paper proposes a method for electrocardiogram (ECG) heartbeat recognition using classification enhancible grey relational analysis (GRA). The ECG beat recognition can be divided into a sequence of stages, starting with feature extraction and then according to characteristics to identify the cardiac arrhythmias including the supraventricular ectopic beat, bundle branch ectopic beat, and ventricular ectopic beat. Gaussian wavelets are used to enhance the features from each heartbeat, and GRA performs the recognition tasks. With the MIT-BIH arrhythmia database, the experimental results demonstrate the efficiency of the proposed non-invasive method. Compared with artificial neural network, the test results also show high accuracy, good adaptability, and faster processing time for the detection of heartbeat signals. PMID:16937172

  19. Cryotherapy of cardiac arrhythmia: From basic science to the bedside.

    PubMed

    Avitall, Boaz; Kalinski, Arthur

    2015-10-01

    This review focuses on the basic science of cellular destruction by tissue freezing and application of transvenous cryocatheter technology to treat cardiac arrhythmia. Ideally, foci for arrhythmias are selectively ablated, arrhythmogenic tissues are destroyed, and reentry circuits are bisected in order to silence adverse electrical activity, with the goal of restoring normal sinus rhythm. The mechanism of ablation using cryotherapy results in distinct lesion qualities advantageous to radiofrequency (Khairy P, Chauvet M, Lehman J, et al. Lower incidence of thrombus formation with cryoenergy versus radiofrequency catheter ablation. Circulation 2003;107:2045-2050). This review is devoted to the mechanism of cryoablation, postablation histopathological changes, and how this information should be used by the clinicians to improve safety and maximize ablation success. PMID:26031374

  20. Efficient identification of inherited chromosomally integrated human herpesvirus 6 using specimen pooling☆

    PubMed Central

    Hill, Joshua A.; HallSedlak, Ruth; Magaret, Amalia; Huang, Meei-Li; Zerr, Danielle M.; Jerome, Keith R.; Boeckh, Michael

    2016-01-01

    Background Human herpesvirus 6 (HHV-6) has a unique ability to integrate into chromosomal telomeres. Vertical transmission via germ cell integration results in offspring with inherited chromosomally integrated (ci)HHV-6 in all nucleated cells, affecting ~1% of the population. Objectives Inherited ciHHV-6 may be a direct or indirect mediator of human disease, but efficient identification of affected individuals is a fundamental roadblock to larger studies exploring the clinical importance of this condition. Study design A group testing strategy was designed to efficiently identify individuals with inherited ciHHV-6. DNA was extracted from 2496 cellular samples from hematopoietic cell transplant (HCT) donor–recipient pairs. Pools of 12 samples were screened for HHV-6 DNA with quantitative (q)PCR. Individual samples from high positive pools were tested with qPCR, and high positive individual samples were tested for inherited ciHHV-6 using droplet digital (dd)PCR to determine HHV-6 DNA copies/cellular genome. Results Thirty-one pools had high positive HHV-6 DNA detection with >103 HHV-6 DNA copies/μg. Each pool had one sample with >104 copies/μg HHV-6 DNA. Inherited ciHHV-6 was confirmed by ddPCR in every high positive sample (>103 HHV-6 DNA copies/μg), yielding a prevalence of 1.5% in HCT recipients and 0.96% in donors. We performed 580 qPCR tests to screen 2496 samples for inherited ciHHV-6, a 77% reduction in testing. Conclusions Inherited ciHHV-6 can be efficiently identified by specimen pooling coupled with modern molecular techniques. This algorithm can be used to facilitate cost-effective identification of patients with inherited ciHHV-6, thereby removing a major hurdle for large-scale study of its clinical impact. PMID:26921738

  1. [Hypertrophic cardiomyopathy. Arrhythmia in hypertrophic cardiomyopathy].

    PubMed

    Colín Lizalde, Luis de Jesús

    2003-01-01

    Hypertrophic cardiomyopathy is a relatively common genetic disorder with heterogeneity in mutations, forms of presentation, prognosis and treatment strategies. Hypertrophic cardiomyopathy is recognized as the most common cause of sudden cardiac death that occurs in young people, including athletes. The clinical diagnosis is complemented with the ecocardiographic study, in which an abnormal myocardial hypertrophy of the septum can be observed in the absence of a cardiac or systemic disease (arterial systemic hypertension, aortic stenosis). The annual sudden mortality rate is 1% and, in selected populations, it ranges between 3 and 6%. The therapeutic strategies depend on the different subsets of patients according to the morbidity and mortality, sudden cardiac death, obstructive symptoms, heart failure or atrial fibrillation and stroke. High risk patients for sudden death may effectively be treated with the automatic implantable cardioverter-defibrillator. PMID:12966640

  2. REM sleep-related brady-arrhythmia syndrome.

    PubMed

    Janssens, Wim; Willems, Rik; Pevernagie, Dirk; Buyse, Bertien

    2007-09-01

    Rapid eye movement (REM) sleep-related brady-arrhythmia syndrome is a cardiac rhythm disorder characterised by asystoles lasting several seconds during REM sleep in otherwise healthy individuals. In contrast to arrhythmias associated with obstructive sleep apnea, REM sleep-related sinus arrests and atrioventricular (AV) blocks are not associated with episodes of apnea or hypopnea. In literature, only few cases have been published, suggesting that the prevalence of this nighttime rhythm disorder is very rare. In this paper, we report two new cases of REM sleep-related sinus arrests and one case of REM sleep-related total AV block. To explore the underlying mechanism, an analysis of heart rate variability was performed. In a matched control population, we observed a significant lower low-to-high frequency (LF/HF) ratio in slow wave sleep as compared to REM sleep (2.04 +/- 1.2 vs 4.55 +/- 1.82, respectively [Mann-Whitney U test p < 0.01]), demonstrating a global increase in sympathetic activity during REM. When using the same technique in two of three patients with REM-related arrhythmias, the shift to an increased LF/HF ratio from slow wave sleep to REM sleep tended to be lower. This may reflect an increased vagal activity (HF component) during REM sleep in these subjects. We, therefore, hypothesise that, in our patients with REM sleep-related arrhythmias, the overall dominance of sympathetic activity during REM is present but to a lesser extent and temporarily switches into vagal dominance when the bursts of REMs occur. As it was still unclear whether these REM sleep-related asystoles needed to be paced, we compared our treatment and these of previously reported cases with the current American College of Cardiology/American Heart Association guidelines for implantation of cardiac pacemakers. PMID:17375344

  3. Feature-based MRI data fusion for cardiac arrhythmia studies.

    PubMed

    Magtibay, Karl; Beheshti, Mohammadali; Foomany, Farbod Hosseyndoust; Massé, Stéphane; Lai, Patrick F H; Zamiri, Nima; Asta, John; Nanthakumar, Kumaraswamy; Jaffray, David; Krishnan, Sridhar; Umapathy, Karthikeyan

    2016-05-01

    Current practices in studying cardiac arrhythmias primarily use electrical or optical surface recordings of a heart, spatially limited transmural recordings, and mathematical models. However, given that such arrhythmias occur on a 3D myocardial tissue, information obtained from such practices lack in dimension, completeness, and are sometimes prone to oversimplification. The combination of complementary Magnetic-Resonance Imaging (MRI)-based techniques such as Current Density Imaging (CDI) and Diffusion Tensor Imaging (DTI) could provide more depth to current practices in assessing the cardiac arrhythmia dynamics in entire cross sections of myocardium. In this work, we present an approach utilizing feature-based data fusion methods to demonstrate that complimentary information obtained from electrical current distribution and structural properties within a heart could be quantified and enhanced. Twelve (12) pairs of CDI and DTI image data sets were gathered from porcine hearts perfused through a Langendorff setup. Images were fused together using feature-based data fusion techniques such as Joint Independent Component Analysis (jICA), Canonical Correlation Analysis (CCA), and their combination (CCA+jICA). The results suggest that the complimentary information of cardiac states from CDI and DTI are enhanced and are better classified with the use of data fusion methods. For each data set, an increase in mean correlations of fused images were observed with 38% increase from CCA+jICA compared to the original images while mean mutual information of the fused images from jICA and CCA+jICA increased by approximately three-fold. We conclude that MRI-based techniques present potential viable tools in furthering studies for cardiac arrhythmias especially Ventricular Fibrillation. PMID:26970857

  4. Exercise and Arrhythmias: A Double-Edged Sword.

    PubMed

    Manolis, Antonis S; Manolis, Antonis A

    2016-07-01

    Ample evidence indicates that moderate regular exercise is beneficial for both normal individuals and patients with cardiovascular (CV) disease. However, intense and strenuous exercise in individuals with evident or occult underlying CV abnormalities may have adverse effects with provocation and exacerbation of arrhythmias that may lead to life-threatening situations. Both of these aspects of exercise-induced effects are herein reviewed. PMID:27120033

  5. Treatment of depression in an adolescent with cardiomyopathy and arrhythmia.

    PubMed

    Tanidir, Canan; Tanidir, Ibrahim C; Tuzcu, Volkan

    2015-10-01

    Patients with cardiomyopathy have a higher incidence of mood and anxiety disorders, resulting in greater probability for hospitalisation and increased risk for arrhythmia and death. We report a case of a 16-year-old boy with Danon disease, Wolff-Parkinson-White syndrome, and hypertrophic cardiomyopathy, who later developed depression and significant weight loss. The patient was successfully treated for his anxiety and depression with mirtazapine without any adverse cardiac effects. PMID:25400066

  6. The EINTHOVEN system: toward an improved cardiac arrhythmia monitor.

    PubMed Central

    Widman, L. E.

    1991-01-01

    Contemporary cardiac arrhythmia monitors, used commonly in intensive care settings, are highly sensitive to artifact, resulting in high false alarm rates, inability to detect P waves reliably, and crude rhythm interpretation. We report on two new approaches that address these problems: a noise preprocessor that characterizes the type and degree of artifact in an ECG, and a model-based rhythm interpretation algorithm. PMID:1807639

  7. Endogenous chemical mediators of ventricular arrhythmias in ischaemic heart disease.

    PubMed

    Curtis, M J; Pugsley, M K; Walker, M J

    1993-05-01

    The causes of ventricular arrhythmias in the acute setting of coronary artery disease (myocardial ischaemia and reperfusion) may be approached using two paradigms. One, the electrophysiological paradigm (disturbance of ionic homeostasis, electrogenesis, and conduction) has not been addressed in detail here. Instead, we have focused on the concept of a chemical paradigm of arrhythmogenesis. Many endogenous chemical substances (derived from the myocardium, nerves, blood plasma, platelets, leucocytes, and endothelium) accumulate in the ischaemic tissue or are produced during reperfusion and many of these have been suggested to modulate ventricular arrhythmias. Some substances may be arrhythmogenic and others may be antiarrhythmic. Together they determine whether or not arrhythmias occur. Potentially arrhythmogenic substances include potassium, catecholamines, cAMP, histamine, 5-HT, lysophosphatidylcholine, palmitylcarnitine, platelet activating factor, prostaglandins, leukotrienes, thromboxane A2, angiotensin II, endothelin, opioids, protons, calcium, and free radicals. We have considered each of these, with the objective of evaluating which are important in arrhythmogenesis in acute ischaemia and reperfusion. Two alternative models of arrhythmogenesis are possible in the context of the chemical paradigm: a series model (where one substance or its effects determines the arrhythmogenicity of another) and a parallel model (where numerous substances operate independently to cause ventricular arrhythmias). It is not yet clear which model is most appropriate; a combination of the two is possible, so a working prototype has been constructed which accommodates both. A set of criteria (hitherto lacking) for establishing whether a substance is sufficient and necessary for arrhythmogenesis is proposed. Some generalisations are given on approaches to establishment of these criteria for putative arrhythmogenic substances. Finally, we have considered how arrhythmogenic drug

  8. Carbon monoxide exposure of subjects with documented cardiac arrhythmias

    SciTech Connect

    Chaitman, B.R.; Dahms, T.E.; Byers, S.; Carroll, L.W.; Younis, L.T.; Wiens, R.D. )

    1992-09-01

    The impact of low-level carbon monoxide exposure on ventricular arrhythmia frequency in patients with ischemic heart disease has not been thoroughly studied. The issue is of concern because of the potential proarrhythmic effect of carbon monoxide in patients with ischemic heart disease. We studied 30 subjects with well-documented coronary artery disease who had an average of at least 30 ventricular ectopic beats per hour over a 20-hour monitoring interval. By using appropriate inclusion and exclusion criteria, subjects were selected and enrolled in a randomized double-blind study to determine the effects of carbon monoxide exposure on ventricular arrhythmia frequency at rest, during exercise, and during ambulatory activities. The carbon monoxide exposure was designed to result in 3% or 5% carboxyhemoglobin levels, as measured by gas chromatography. The carbon monoxide exposure protocol produced target levels in 60 minutes, and the levels were maintained for an additional 90 minutes to provide adequate time to assess the impact of carbon monoxide on the frequency of ventricular ectopic beats. The data on total and repetitive ventricular arrhythmias were analyzed for seven specific time intervals: (1) two hours before carbon monoxide exposure; (2) during the two-hour carbon monoxide or air exposure; (3) during a two-hour rest period; (4) during an exercise period; (5) during an exercise recovery period; (6) six hours after carbon monoxide or air exposure; and (7) approximately 10 hours after exposure, or the remaining recording interval on the Holter monitor. There was no increase in ventricular arrhythmia frequency after carbon monoxide exposure, regardless of the level of carboxyhemoglobin or the type of activity.

  9. Cardioprotective activity of alcoholic extract of Tinospora cordifolia (Willd.) Miers in calcium chloride-induced cardiac arrhythmia in rats

    PubMed Central

    Sharma, Ashish Kumar; Kishore, Kunal; Sharma, Divya; Srinivasan, B.P; Agarwal, Shyam Sunder; Sharma, Ashok; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh

    2011-01-01

    The present study investigated the antiarrhythmic activity of alcoholic extract of Tinospora cordifolia (T. cordifolia) in CaCl2 induced arrhythmia. CaCl2 (25 mg/kg) was administered by intravenous infusion (iv) to produce arrhythmia in rats. The animals were then treated with T. cordifolia extract (150, 250, and 450 mg/kg) and verapamil (5 mg/kg,iv). Lead II electrocardiogram was monitored. Plasma calcium, sodium and potassium levels were measured. In CaCl2 induced arrhythmia, heart rate was decreased by 41.10%, T. cordifolia at 150, 300, and 450 mg/kg decreased the heart rate by 26.30%, 29.16%, and 38.29%, respectively, and verapamil reduced the heart rate by 9.70% compared to the normal group. The PQRST waves were normalized and atrial and ventricular fibrillation was controlled in rats treated with verapamil and T. cordifolia. CaCl2 increased calcium and sodium levels and decreased potassium levels in blood. T. cordifolia dose-dependently decreased calcium and sodium levels and increased potassium levels. Hence, T. cordifolia can be used in antiarrhythmic clinical settings and beneficial in atrial and ventricular fibrillation and flutter and may be indicated in ventricular tachyarrhythmia. PMID:23554702

  10. Statistical Versus Individual Forecasting Of Life-Threatening Cardiac Arrhythmias

    NASA Astrophysics Data System (ADS)

    Wessel, Niels; Meyerfeldt, Udo; Ziehmann, Christine; Schirdewan, Alexander; Kurths, Jürgen

    2002-07-01

    Ventricular tachycardia or fibrillation (VT) as fatal cardiac arrhythmias are the main factors triggering sudden cardiac death. The objective of this investigation is to find early signs of sustained VT in patients with an implanted cardioverter-defibrillator (ICD). These devices are able to safeguard patients by returning their hearts to a normal rhythm via strong defibrillatory shocks; additionally, they are able to store at least 1000 beat-to-beat intervals immediately before the onset of a life-threatening arrhythmia. We study these 1000 beat-to-beat intervals of 63 chronic heart failure ICD patients before the onset of a life-threatening arrhythmia and at a control time, i.e. without VT event. To characterize these rather short data sets, we calculate heart rate variability (HRV) parameters from time and frequency domain, from symbolic dynamics as well as the finite-time growth rates. We find that no linear parameter shows significant differences in HRV between the VT and the control time series. However, the nonlinear parameters detected a significant increase in short phases with low variability before the onset of VT (p<0.05, for time series with less than 10% ectopy). Finally, we are investigating whether these results may lead to individual predictions of VT.

  11. Ventricular arrhythmias and the His-Purkinje system.

    PubMed

    Haissaguerre, Michel; Vigmond, Edward; Stuyvers, Bruno; Hocini, Meleze; Bernus, Olivier

    2016-03-01

    Ventricular arrhythmias are a major cause of sudden death, which accounts for approximately half of cardiac mortality. The His-Purkinje system is composed of specialized cells responsible for the synchronous activation of the ventricles. However, experimental studies show that the Purkinje system can be arrhythmogenic during electrolyte imbalance, after exposure to various drugs, and in myocardial ischaemia, during which Purkinje cells can survive in anaerobic conditions. Purkinje cells can generate both automatic and triggered focal rhythms, and their network configuration can accommodate re-entrant circuits. In humans, a variety of monomorphic ventricular tachycardias can be sustained within the architecture of the Purkinje branches. Furthermore, discrete Purkinje sources can serve as critical triggers of ventricular fibrillation in a wide spectrum of patients with structural heart disease or with an apparently normal heart. In drug-resistant cases of monomorphic and polymorphic Purkinje-related ventricular tachycardias, catheter ablation is a very effective treatment. The specific transcriptional signatures and functional properties of Purkinje cells, including their intracellular calcium dynamics, underlie their extreme arrhythmogenicity. However, the identification of vulnerable individuals remains challenging, and the molecular mechanisms of Purkinje-related arrhythmias have to be characterized further to enable the development of interventions to prevent lethal cardiac arrhythmias. PMID:26727298

  12. Pattern of arrhythmias among Nigerians with congestive heart failure

    PubMed Central

    Ajayi, Olufemi E; Abiodun, Olugbenga O; Akintomide, Anthony O; Adebayo, Rasaaq A; Ogunyemi, Suraj A; Balogun, Michael O; Bamikole, Olaniyi J; Ajibare, Adeola O; Ajayi, Adesuyi A

    2015-01-01

    Background In patients with heart failure, death is often sudden due to life-threatening arrhythmias. This work was carried out to evaluate the pattern of arrhythmias in Nigerians with heart failure. Materials and methods Thirty subjects with congestive heart failure (CHF), 30 subjects with hypertensive heart disease, and 15 normal subjects with no obvious features of heart disease were evaluated with resting and 24-hour electrocardiographic monitoring and transthoracic echocardiography. Data were analyzed with one-way analysis of variance with post hoc Duncan’s analysis, Fisher’s exact test, and linear regression analysis using SPSS version 16. Results CHF subjects had more instances of supraventricular tachycardia (P=0.005), ventricular extrasystoles (P<0.001), bigeminy (P<0.001), trigeminy (P<0.001), couplets (P<0.001), triplets (P<0.001), and nonsustained ventricular tachycardia (VT) (P=0.003) than the other two control groups. They also showed a significantly longer VT duration (4.6±5.6 seconds) compared with the other groups (P<0.001). Linear regression analysis showed a significant direct relationship between VT and the maximum number of ventricular extrasystoles per hour (P=0.001). Conclusion Cardiac arrhythmias are common in subjects with CHF and are more frequent when compared with patients with hypertensive heart disease and normal subjects. PMID:25870514

  13. Cardiac arrhythmia classification using multi-modal signal analysis.

    PubMed

    Kalidas, V; Tamil, L S

    2016-08-01

    In this paper, as a contribution to the Physionet/Computing in Cardiology 2015 Challenge, we present individual algorithms to accurately classify five different life threatening arrhythmias with the goal of suppressing false alarm generation in intensive care units. Information obtained by analysing electrocardiogram, photoplethysmogram and arterial blood pressure signals was utilized to develop the classification models. Prior to classification, the signals were subject to a signal pre-processing stage for quality analysis. Classification was performed using a combination of support vector machine based machine learning approach and logical analysis techniques. The predicted result for a certain arrhythmia classification model was verified by logical analysis to aid in reduction of false alarms. Separate feature vectors were formed for predicting the presence or absence of each arrhythmia, using both spectral and time-domain information. The training and test data were obtained from the Physionet/CinC Challenge 2015 database. Classification algorithms were written for two different categories of data, namely real-time and retrospective, whose data lengths were 10 s and an additional 30 s, respectively. For the real-time test dataset, sensitivity of 94% and specificity of 82% were obtained. Similarly, for the retrospective test dataset, sensitivity of 94% and specificity of 86% were obtained. PMID:27454417

  14. Nandrolone Plus Moderate Exercise Increases the Susceptibility to Lethal Arrhythmias

    PubMed Central

    Ghorbani Baravati, Hamideh; Joukar, Siyavash; Fathpour, Hossein; Kordestani, Zeinab

    2015-01-01

    Background: Until now, no experimental study has directly assessed the arrhythmogenesis of chronic consumption of anabolic androgenic steroids along with moderate-intensity endurance exercise. Objectives: We evaluated the influence of integration of anabolic androgenic steroids along with moderate-intensity endurance exercise on susceptibility to lethal ventricular arrhythmias in rat. Materials and Methods: The animal groups were as follows: control group (CTL); exercise group (EX) which were under 6 weeks of treadmill exercise; nandrolone group (Nan) which received 5 mg/kg of nandrolone decanoate twice a week; vehicle group (Arach) which received Arachis oil (solvent of nandrolone); trained vehicle group (Arach + Ex); and trained nandrolone group (Nan + Ex). One day after ending of the intervention period, arrhythmia was inducted by intravenous infusion of aconitine and ventricular arrhythmias were recorded. Then malondialdehyde (MDA) and glutathione peroxidase (GPX) of heart tissue were measured. Results: Nandrolone, exercise, and their combination were associated with heart hypertrophy. Exercise could prevent the incremental effect of nandrolone on MDA/GPX ratio. Chronic administration of nandrolone with moderate-intensity endurance exercise had no significant effect on blood pressure, heart rate, and basal electrocardiographic parameters. Combination of nandrolone and exercise significantly increased the incidence of ventricular fibrillation (VF) and reduced the VF latency (P < 0.05). Conclusions: The findings suggest that chronic coadministration of nandrolone with moderate-intensity endurance exercise facilitates the VF occurrence in rat. Complementary studies are needed to elucidate the involved mechanisms of this abnormality. PMID:26396972

  15. Detection of Shockable Ventricular Arrhythmia using Variational Mode Decomposition.

    PubMed

    Tripathy, R K; Sharma, L N; Dandapat, S

    2016-04-01

    Ventricular tachycardia (VT) and ventricular fibrillation (VF) are shockable ventricular cardiac ailments. Detection of VT/VF is one of the important step in both automated external defibrillator (AED) and implantable cardioverter defibrillator (ICD) therapy. In this paper, we propose a new method for detection and classification of shockable ventricular arrhythmia (VT/VF) and non-shockable ventricular arrhythmia (normal sinus rhythm, ventricular bigeminy, ventricular ectopic beats, and ventricular escape rhythm) episodes from Electrocardiogram (ECG) signal. The variational mode decomposition (VMD) is used to decompose the ECG signal into number of modes or sub-signals. The energy, the renyi entropy and the permutation entropy of first three modes are evaluated and these values are used as diagnostic features. The mutual information based feature scoring is employed to select optimal set of diagnostic features. The performance of the diagnostic features is evaluated using random forest (RF) classifier. Experimental results reveal that, the feature subset derived from mutual information based scoring and the RF classifier produces accuracy, sensitivity and specificity values of 97.23 %, 96.54 %, and 97.97 %, respectively. The proposed method is compared with some of the existing techniques for detection of shockable ventricular arrhythmia episodes from ECG. PMID:26798076

  16. Life-threatening arrhythmia verification in ICU patients using the joint cardiovascular dynamical model and a Bayesian filter.

    PubMed

    Sayadi, Omid; Shamsollahi, Mohammad B

    2011-10-01

    In this paper, a novel nonlinear joint dynamical model is presented, which is based on a set of coupled ordinary differential equations of motion and a Gaussian mixture model representation of pulsatile cardiovascular (CV) signals. In the proposed framework, the joint interdependences of CV signals are incorporated by assuming a unique angular frequency that controls the limit cycle of the heart rate. Moreover, the time consequence of CV signals is controlled by the same phase parameter that results in the space dimensionality reduction. These joint equations together with linear assignments to observation are further used in the Kalman filter structure for estimation and tracking. Moreover, we propose a measure of signal fidelity by monitoring the covariance matrix of the innovation signals throughout the filtering procedure. Five categories of life-threatening arrhythmias were verified by simultaneously tracking the signal fidelity and the polar representation of the CV signal estimations. We analyzed data from Physiobank multiparameter databases (MIMIC I and II). Performance evaluation results demonstrated that the sensitivity of the detection ranges over 93.50% and 100.00%. In particular, the addition of more CV signals improved the positive predictivity of the proposed method to 99.27% for the total arrhythmic types. The method was also used for false arrhythmia suppression issued by ICU monitors, with an overall false suppression rate reduced from 42.3% to 9.9%. In addition, false critical ECG arrhythmia alarm rates were found to be, on average, 42.3%, with individual rates varying between 16.7% and 86.5%. The results illustrate that the method can contribute to, and enhance the performance of clinical life-threatening arrhythmia detection. PMID:21324772

  17. Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

    PubMed Central

    Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; Azbaoui, Safaa El; Agader, Aomar; Hassani, Amal; Hafidi, Naima El; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent

    2015-01-01

    Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555

  18. [Mapping and ablation of malignant ventricular arrhythmias].

    PubMed

    Hocini, M; Jais, P; Sacher, F; Reuter, S; Clémenty, J; Haïssaguerre, M

    2005-12-01

    Endocavitary investigations showed that the ventricular extrasystoles originated in the common ventricular myocardium (pulmonary infundibulum) in only 9 cases whereas the majority arose from the Parkinje system either on the anterior wall of the right ventricle or in septal region of the left ventricle. The extrasystoles arising from the Parkinje system and pulmonary infundibulum differed in their duration and polymorphism (128 +/- 18 ms vs 145 +/- 13 ms, p = 0.05; 3.3 +/- 2.7 morphologies vs 1.1 +/- 0.4, p < 0.001, respectively). During the extrasystoles, the local Pukinje potential preceded the ventricular activation by variable intervals, some of which were very long, up to 150 ms. Seven applications of radiofrequency were delivered on average per patient on the most distal part of the Purkinje system leading to ablation of the specific activation. The clinical results were spectacular: 88% of patients had no further episodes of ventricular fibrillation as demonstrated by analysis of the defibrillator with an average follow-up period of more than 34 months. PMID:16433241

  19. Computer-assisted instruction of arrhythmia for MS-windows.

    PubMed

    Takeuchi, A; Nara, Y; Ikeda, N; Miyahara, H; Mitobe, H

    1995-01-01

    1. INTRODUCTION. Training in the diagnosis of arrhythmias is an important part of the curriculum for medical students, postgraduates, and paramedical staff. Although several CAI for arrhythmia have been developed [1-3], we could not get CAI software for arrhythmia for the MS-Windows environment. In this report, we present a newly-developed computer-assisted reference system for arrhythmia that functions in the Windows environment. 2. DESCRIPTION OF THE SYSTEM. The system consists of a program and two data files. An MS-Windows program (ECG9405.EXE, 180kB) was compiled using Borland's C++ v.3.1. A binary file (ECPAT.BAS 33kB) includes data of normal and abnormal wave segments of ECG: P wave, PQ interval segment, and QRs complex with/without T wave. A mother file (ECG9405.sys, 57kB) includes 85 data sets to generate ECG waveforms of arrhythmia. Each data set contains a sequence of wave form numbers, the text for questions and answers, and the commands strings. There are five major commands: 1) to create a new window as "wave window"; 2) to make electrocardiogram data; 3) to plot the data on the window; 4) to create a "dialog box" for questions and explanations; and 5) to check the answers. he program gets a data set from the data according to the user's choice. The program then interprets the data set and executes the commands. The wave segment data are plotted in a "wave window" at every 10 milliseconds; this is controlled by the MS-Windows' timer. The timer interval can be changed by selecting the speed button. The ECG waveforms are displayed on a window just like an ordinary ECG monitor with beat sound. Many windows can be created by the user and many ECG waves simultaneously plotted on CRT. 3. USAGE OF THE SYSTEM. The "main window" has a menu that has three items corresponding to the training course: BASIC, TRY, and TEST. Thirty-five types of arrythmias are listed in the "list box" of the windows in BASIC course e.g., sinus arrhythmia, atrial flutter, atrial

  20. Cardiac Resynchronization Therapy Defibrillator Treatment in a Child with Heart Failure and Ventricular Arrhythmia

    PubMed Central

    Kim, Hak Ju; Cho, Sungkyu; Kim, Woong-Han

    2016-01-01

    Cardiac resynchronization therapy (CRT) is a new treatment for refractory heart failure. However, most patients with heart failure treated with CRT are adults, middle-aged or older with idiopathic or ischemic dilated cardiomyopathy. We treated a 12-year-old boy, who was transferred after cardiac arrest, with dilated cardiomyopathy, left bundle-branch block, and ventricular tachycardia. We performed cardiac resynchronization therapy with a defibrillator (CRT-D). After CRT-D, left ventricular ejection fraction improved from 22% to 44% assessed by echocardiogram 1 year postoperatively. On electrocardiogram, QRS duration was shortened from 206 to 144 ms. The patient’s clinical symptoms also improved. For pediatric patients with refractory heart failure and ventricular arrhythmia, CRT-D could be indicated as an effective therapeutic option. PMID:27525239

  1. Cardiac Resynchronization Therapy Defibrillator Treatment in a Child with Heart Failure and Ventricular Arrhythmia.

    PubMed

    Kim, Hak Ju; Cho, Sungkyu; Kim, Woong-Han

    2016-08-01

    Cardiac resynchronization therapy (CRT) is a new treatment for refractory heart failure. However, most patients with heart failure treated with CRT are adults, middle-aged or older with idiopathic or ischemic dilated cardiomyopathy. We treated a 12-year-old boy, who was transferred after cardiac arrest, with dilated cardiomyopathy, left bundle-branch block, and ventricular tachycardia. We performed cardiac resynchronization therapy with a defibrillator (CRT-D). After CRT-D, left ventricular ejection fraction improved from 22% to 44% assessed by echocardiogram 1 year postoperatively. On electrocardiogram, QRS duration was shortened from 206 to 144 ms. The patient's clinical symptoms also improved. For pediatric patients with refractory heart failure and ventricular arrhythmia, CRT-D could be indicated as an effective therapeutic option. PMID:27525239

  2. Chromatin insulators: regulatory mechanisms and epigenetic inheritance

    PubMed Central

    Bushey, Ashley M.; Dorman, Elizabeth R.; Corces, Victor G.

    2008-01-01

    Enhancer-blocking insulators are DNA elements that disrupt the communication between a regulatory sequence, such as an enhancer or a silencer, and a promoter. Insulators participate in both transcriptional regulation and global nuclear organization, two features of chromatin that are thought to be maintained from one generation to the next through epigenetic mechanisms. Furthermore, there are many regulatory mechanisms in place that enhance or hinder insulator activity. These modes of regulation could be used to establish cell-type specific insulator activity that is epigenetically inherited along a cell and/or organismal lineage. This review will discuss the evidence for epigenetic inheritance and regulation of insulator function. PMID:18851828

  3. [Application of qualitative interviews in inheritance research of famous old traditional Chinese medicine doctors: ideas and experience].

    PubMed

    Luo, Jing; Fu, Chang-geng; Xu, Hao

    2015-04-01

    The inheritance of famous old traditional Chinese medicine (TCM) doctors plays an essential role in the fields of TCM research. Qualitative interviews allow for subjectivity and individuality within clinical experience as well as academic ideas of doctors, making it a potential appropriate research method for inheritance of famous old TCM doctors. We summarized current situations of inheritance research on famous old TCM doctors, and then discussed the feasibility of applying qualitative interviews in inheritance of famous old TCM doctors. By combining our experience in research on inheritance of famous old TCM doctors, we gave some advice on study design, interview implementation, data transcription and analyses , and report writing, providing a reference for further relevant research. PMID:26043577

  4. Cytogenomic Delineation and Clinical Follow-up of Two Siblings with an 8.5 Mb 6q24.2-q25.2 Deletion Inherited From a Paternal Insertion†

    PubMed Central

    Meloni, Vera Ayres; Guilherme, Roberta Santos; Oliveira, Mariana Moyses; Migliavacca, Michele; Takeno, Sylvia Satomi; Sobreira, Nara Lygia Macena; Soares, Maria de Fatima Faria; de Mello, Claudia Berlim; Melaragno, Maria Isabel

    2014-01-01

    The chromosomal segment 6q24-q25 comprises a contiguous gene microdeletion syndrome characterized by intrauterine growth retardation, growth delay, intellectual disability, cardiac anomalies, and a dysmorphic facial phenotype. We describe here a 10-year follow-up with detailed clinical, neuropsychological, and cytomolecular data of two siblings, male and female, who presented with developmental delay, microcephaly, short stature, characteristic facial dysmorphisms, multiple organ anomalies, and intellectual disability. Microarray analysis showed an 8.5 Mb 6q24.2-q25.2 interstitial deletion. Fluorescence in situ hybridization analyses confirmed the deletions and identified an insertion of 6q into 8q13 in their father, resulting in a high recurrence risk. This is the first report in sibs with distinct neuropsychological involvement, one of them with stenosis of the descending branch of the aorta. PMID:24898331

  5. Neurology of inherited glycosylation disorders

    PubMed Central

    Freeze, HH; Eklund, E A; Ng, BG; Patterson, M C

    2013-01-01

    Congenital disorders of glycosylation comprise most of the nearly 70 genetic disorders known to be caused by impaired synthesis of glycoconjugates. The effects are expressed in most organ systems, and most involve the nervous system. Typical manifestations include structural abnormalities, (eg, rapidly progressive cerebellar atrophy), myopathies (including congenital muscular dystrophies and limb-girdle dystrophies), strokes and stroke-like episodes, epileptic seizures, developmental delay, and demyelinating neuropathy. Patients can have neurological symptoms associated with coagulopathies, immune dysfunction with or without infections, and cardiac, renal, or hepatic failure, which are common features of glycosylation disorders. The diagnosis of congenital disorders of glycosylation should be considered for any patient with multisystem disease and in those with more specific phenotypic features. Measurement of concentrations of selected glycoconjugates can be used to screen for many of these disorders, and molecular diagnosis is becoming more widely available in clinical practice. Disease-modifying treatments are available for only a few disorders, but all affected individuals benefit from early diagnosis and aggressive management. PMID:22516080

  6. Device-Based Autonomic Modulation in Arrhythmia Patients: the Role of Vagal Nerve Stimulation

    PubMed Central

    Huang, William A.; Shivkumar, Kalyanam; Vaseghi, Marmar

    2015-01-01

    Opinion statement Vagal nerve stimulation (VNS) has shown promise as an adjunctive therapy for management of cardiac arrhythmias by targeting the cardiac parasympathetic nervous system. VNS has been evaluated in the setting of ischemia-driven ventricular arrhythmias and atrial arrhythmias, as well as a treatment option for heart failure. As better understanding of the complexities of the cardiac autonomic nervous system is obtained, vagal nerve stimulation will likely become a powerful tool in the current cardiovascular therapeutic armamentarium. PMID:25894588

  7. Surveillance of fetal arrhythmias in the outpatient setting: current limitations and call for action.

    PubMed

    Freire, Grace

    2015-12-01

    Surveillance of fetal arrhythmias in the outpatient setting remains limited by lack of monitoring modalities. Despite technological advances made in the field of obstetrics, existing devices are not currently suitable to monitor fetal arrhythmias. In this report, the author describes the current and developing fetal heart rate monitoring technologies including the recent introduction of hand-held Doppler monitors for outpatient surveillance of fetal arrhythmias. PMID:26675609

  8. Inherited platelet disorders: toward DNA-based diagnosis

    PubMed Central

    Lentaigne, Claire; Freson, Kathleen; Laffan, Michael A.; Turro, Ernest

    2016-01-01

    Variations in platelet number, volume, and function are largely genetically controlled, and many loci associated with platelet traits have been identified by genome-wide association studies (GWASs).1 The genome also contains a large number of rare variants, of which a tiny fraction underlies the inherited diseases of humans. Research over the last 3 decades has led to the discovery of 51 genes harboring variants responsible for inherited platelet disorders (IPDs). However, the majority of patients with an IPD still do not receive a molecular diagnosis. Alongside the scientific interest, molecular or genetic diagnosis is important for patients. There is increasing recognition that a number of IPDs are associated with severe pathologies, including an increased risk of malignancy, and a definitive diagnosis can inform prognosis and care. In this review, we give an overview of these disorders grouped according to their effect on platelet biology and their clinical characteristics. We also discuss the challenge of identifying candidate genes and causal variants therein, how IPDs have been historically diagnosed, and how this is changing with the introduction of high-throughput sequencing. Finally, we describe how integration of large genomic, epigenomic, and phenotypic datasets, including whole genome sequencing data, GWASs, epigenomic profiling, protein–protein interaction networks, and standardized clinical phenotype coding, will drive the discovery of novel mechanisms of disease in the near future to improve patient diagnosis and management. PMID:27095789

  9. Inherited platelet disorders: toward DNA-based diagnosis.

    PubMed

    Lentaigne, Claire; Freson, Kathleen; Laffan, Michael A; Turro, Ernest; Ouwehand, Willem H

    2016-06-01

    Variations in platelet number, volume, and function are largely genetically controlled, and many loci associated with platelet traits have been identified by genome-wide association studies (GWASs).(1) The genome also contains a large number of rare variants, of which a tiny fraction underlies the inherited diseases of humans. Research over the last 3 decades has led to the discovery of 51 genes harboring variants responsible for inherited platelet disorders (IPDs). However, the majority of patients with an IPD still do not receive a molecular diagnosis. Alongside the scientific interest, molecular or genetic diagnosis is important for patients. There is increasing recognition that a number of IPDs are associated with severe pathologies, including an increased risk of malignancy, and a definitive diagnosis can inform prognosis and care. In this review, we give an overview of these disorders grouped according to their effect on platelet biology and their clinical characteristics. We also discuss the challenge of identifying candidate genes and causal variants therein, how IPDs have been historically diagnosed, and how this is changing with the introduction of high-throughput sequencing. Finally, we describe how integration of large genomic, epigenomic, and phenotypic datasets, including whole genome sequencing data, GWASs, epigenomic profiling, protein-protein interaction networks, and standardized clinical phenotype coding, will drive the discovery of novel mechanisms of disease in the near future to improve patient diagnosis and management. PMID:27095789

  10. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... prevent loss or waste, leases on undivided inherited lands will not be approved until the heirship... necessary to lease the lands to prevent loss or waste, the Area Director will report the facts to the Commissioner of Indian Affairs and ask for instructions. Minor heirs can lease or joint adult heirs in...

  11. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... prevent loss or waste, leases on undivided inherited lands will not be approved until the heirship... necessary to lease the lands to prevent loss or waste, the Area Director will report the facts to the Commissioner of Indian Affairs and ask for instructions. Minor heirs can lease or joint adult heirs in...

  12. Difficulties in Learning Inheritance and Polymorphism

    ERIC Educational Resources Information Center

    Liberman, Neomi; Beeri, Catriel; Kolikant, Yifat Ben-David

    2011-01-01

    This article reports on difficulties related to the concepts of inheritance and polymorphism, expressed by a group of 22 in-service CS teachers with an experience with the procedural paradigm, as they coped with a course on OOP. Our findings are based on the analysis of tests, questionnaires that the teachers completed in the course, as well as on…

  13. Inherited Oral Cancer: A Rare Reality.

    PubMed

    Sarode, Gargi S; Sarode, Sachin C; Patil, Shankargouda

    2015-01-01

    Majority of oral cancers (around 90-95%) found today are caused by various environmental factors. These generally include the chemical and physical carcinogens, like tobacco, diet, microorganisms, radiations, etc. The remaining 5% of the cases are caused by inherited mutated genes carrying the defect. PMID:27018035

  14. Epigenetic Inheritance of Disease and Disease Risk

    PubMed Central

    Bohacek, Johannes; Mansuy, Isabelle M

    2013-01-01

    Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations. This review examines the challenging possibility that epigenetic changes induced by environmental factors can contribute to some of the inheritance of disease and disease risk. This concept has immense implications for the understanding of biological functions and disease etiology, and provides potential novel strategies for diagnosis and treatment. Examples of epigenetic inheritance relevant to human disease, such as the detrimental effects of traumatic stress or drug/toxic exposure on brain functions, are reviewed. Different possible routes of transmission of epigenetic information involving the germline or germline-independent transfer are discussed, and different mechanisms for the maintenance and transmission of epigenetic information like chromatin remodeling and small noncoding RNAs are considered. Future research directions and remaining major challenges in this field are also outlined. Finally, the adaptive value of epigenetic inheritance, and the cost and benefit of allowing acquired epigenetic marks to persist across generations is critically evaluated. PMID:22781843

  15. Prenatal diagnosis of inherited metabolic diseases.

    PubMed Central

    Diukman, R; Goldberg, J D

    1993-01-01

    Advances in the prenatal diagnosis of inherited metabolic disease have provided new reproductive options to at-risk couples. These advances have occurred in both sampling techniques and methods of analysis. In this review we present an overview of the currently available prenatal diagnostic approaches for the diagnosis of metabolic disease in a fetus. Images PMID:8236980

  16. Phylogenetics Exercise Using Inherited Human Traits

    ERIC Educational Resources Information Center

    Tuimala, Jarno

    2006-01-01

    A bioinformatics laboratory exercise based on inherited human morphological traits is presented. It teaches how morphological characters can be used to study the evolutionary history of humans using parsimony. The exercise can easily be used in a pen-and-paper laboratory, but if computers are available, a more versatile analysis can be carried…

  17. Understanding Genetics and Inheritance in Rural Schools

    ERIC Educational Resources Information Center

    Kibuka-Sebitosi, Esther

    2007-01-01

    Conducted in urban and rural schools in two provinces of South Africa, the present study reports biology learners' understanding of concepts about genetics and inheritance. Participants were Grade 11 and 12 learners, aged 15-16 years. The tools included a written questionnaire, interviews, pre- and post-paper and pencil tests and focus group…

  18. Fractional populations in sex-linked inheritance

    NASA Astrophysics Data System (ADS)

    Pyo Lee, Seung; Chung, Myung-Hoon; Koo Kim, Chul; Nahm, Kyun

    2001-03-01

    We study the fractional populations in chromosome inherited diseases. The governing equations for the fractional populations are found and solved in the presence of mutation and selection. The physical fixed points obtained are used to discuss the cases of color blindness and hemophilia.

  19. Ethnogenetics: Interpreting Ideas about Diabetes and Inheritance.

    ERIC Educational Resources Information Center

    Weiner, Diane

    1999-01-01

    Interviews with American Indian tribal members in California and Arizona and their physicians revealed different beliefs about the causes and inheritance of diabetes. These differences in understanding are examined in terms of differences between physician and client communication practices and between professional medical education and lay health…

  20. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM)

    EPA Science Inventory

    Welcome to OMIM(TM), Online Mendelian Inheritance in Man. This database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor McKusick and his colleagues at Johns Hopkins and elsewhere, and developed for the World Wide Web by NCBI, the National Cent...

  1. Left ventricular function in patients with ventricular arrhythmias and aortic valve disease

    SciTech Connect

    Santinga, J.T.; Kirsh, M.M.; Brady, T.J.; Thrall, J.; Pitt, B.

    1983-02-01

    Forty patients having aortic valve replacement were evaluated preoperatively for ventricular arrhythmia and left ventricular ejection fraction. Arrhythmias were classified as complex or simple using the Lown criteria on the 24-hour ambulatory electrocardiogram; ejection fractions were determined by radionuclide gated blood pool analysis and contrast angiography. The ejection fractions determined by radionuclide angiography were 59.1 +/- 13.1% for 26 patients with simple or no ventricular arrhythmias, and 43.9 +/- 20.3% for 14 patients with complex ventricular arrhythmias (p less than 0.01). Ejection fractions determined by angiography, available for 31 patients, were also lower in patients with complex ventricular arrhythmias (61.1 +/- 16.3% versus 51.4 +/- 13.4%; p less than 0.05). Seven of 9 patients showing conduction abnormalities on the electrocardiogram had complex ventricular arrhythmias. Eight of 20 patients with aortic stenosis had complex ventricular arrhythmias, while 2 of 13 patients with aortic insufficiency had such arrhythmias. It is concluded that decreased left ventricular ejection fraction, intraventricular conduction abnormalities, and aortic stenosis are associated with an increased frequency of complex ventricular arrhythmias in patients with aortic valve disease.

  2. Mobile telemonitoring for arrhythmias in outpatients in the Republic of Georgia: a brief report of a pilot study.

    PubMed

    Kirtava, Zviad; Gegenava, Thea; Gegenava, Maka; Matoshvili, Zviad; Kasradze, Sofia; Kasradze, Pavle

    2012-09-01

    As the very first trial of mobile telemedicine in the Republic of Georgia, in June-December 2010 we investigated 35 outpatients with different types of arrhythmia (male/female ratio=16/19; 12-80 years old), among them 5 patients with concomitant epilepsy. The control group comprised 7 clinically healthy sportsmen (soccer players, all men; 15-17 years old), during a 30-min velo ergometer stress test. A three-lead electrocardiogram (ECG) loop recorder (Vitaphone BT 3300; Vitasystems GmbH, Mannheim, Germany) was used in automatic mode, using special LRMA software (MDT, Lázně Bohdaneč, Czech Republic) and a Nokia (Espoo, Finland) model 6730 Symbian phone. Automatically recorded arrhythmia events were transmitted from the loop recorder by Bluetooth(®) (Bluetooth SIG, Inc., Kirkland, WA) to a phone and then by 3G (through our partner mobile operator, MagtiCom Ltd. [Tbilsi, Georgia]) to the Vitasystems server in Germany and were available to Georgian physicians via e-mail/Internet. Arrhythmias were recorded/monitored during 7-68 h of observation. The number of automatically recorded ECG events varied between 3 and 170 per observation, or 0.4-10.7 hourly. Cases of sinus brady- and tachyarrhythmia, sinus node weakness syndrome, atrial fibrillation, supraventricular tachycardia, supraventricular premature complexes, and ventricular premature complexes were correctly recognized by automatic recognition software and recorded. In 3 patients and 1 sportsman previously unspecified (despite multiple investigations), arrhythmias were recorded: paroxysmal tachycardia (n=1), sinus node weakness syndrome (n=1), and ventricular premature complexes (n=2). In 3 cases (all women) light insomnia and nervousness were reported. In 2 patients with neurosis (both elderly men, 1 with epilepsy) we had to stop investigation prematurely because of anxiety/agitation. Mobile telecardiology represents feasible methodology to monitor arrhythmias in outpatients in Georgia, promoting earlier

  3. Role of CaMKII in cardiac arrhythmias.

    PubMed

    Hund, Thomas J; Mohler, Peter J

    2015-07-01

    Protein phosphorylation is a central mechanism in vertebrates for the regulation of signaling. With regard to the cardiovascular system, phosphorylation of myocyte targets is critical for the regulation of excitation contraction coupling, metabolism, intracellular calcium regulation, mitochondrial activity, transcriptional regulation, and cytoskeletal dynamics. In fact, pathways that tune protein kinase signaling have been a mainstay for cardiovascular therapies for the past 60 years. The calcium/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine kinase with numerous roles in human physiology. Dysfunction in CaMKII-based signaling has been linked with a host of cardiovascular phenotypes including heart failure and arrhythmia, and CaMKII levels are elevated in human and animal disease models of heart disease. While nearly a decade has been invested in targeting CaMKII for the treatment of heart failure and arrhythmia phenotypes, to date, approaches to target the molecule for antiarrhythmic benefit have been unsuccessful for reasons that are still not entirely clear, although (1) lack of compound specificity and (2) the multitude of downstream targets are likely contributing factors. This review will provide an update on current pathways regulated by CaMKII with the goal of illustrating potential upstream regulatory mechanisms and downstream targets that may be modulated for the prevention of cardiac electrical defects. While the review will cover multiple aspects of CaMKII dysfunction in cardiovascular disease, we have given special attention to the potential of CaMKII-associated late Na(+) current as a novel therapeutic target for cardiac arrhythmia. PMID:25577293

  4. Quinine-induced arrhythmia in a patient with severe malaria.

    PubMed

    Gunawan, Carta A; Harijanto, Paul N; Nugroho, Agung

    2007-01-01

    It was reported that there was a case of severe malaria patient with jaundice who presented with arrhythmia (premature ventricular contraction) while getting quinine infusion was reported. A man, 25 years old, was admitted to hospital with high fever, chill, vomiting, jaundice. The patient was fully conscious, blood pressure 120/80 mmHg, pulse rate 100 x/minute, regular. On admission, laboratory examination showed Plasmodium falciparum (++++), total bilirubin 8.25 mg/dL, conjugated bilirubin 4.36 mg/dL, unconjugated bilirubin 3.89 mg/dL, potassium 3.52 meq/L Patient was diagnosed as severe malaria with jaundice and got quinine infusion in dextrose 5% 500 mg/8 hour. On the second day the patient had vomitus, diarrhea, tinnitus, loss of hearing. After 30 hours of quinine infusion the patient felt palpitation and electrocardiography (ECG) recording showed premature ventricular contraction (PVC) > 5 x/minute, trigemini, constant type--sinoatrial block, positive U wave. He was treated with lidocaine 50 mg intravenously followed by infusion 1500 mg in dextrose 5%/24 hour and potassium aspartate tablet. Quinine infusion was discontinued and changed with sulfate quinine tablets. Three hours later the patient felt better, the frequency of PVC reduced to 4 - 5 x/minute and on the third day ECG was normal, potassium level was 3.34 meq/L. He was discharged on 7th day in good condition. Quinine, like quinidine, is a chincona alkaloid that has anti-arrhythmic property, although it also pro-arrhythmic that can cause various arrhythmias, including severe arrhythmia such as multiple PVC. Administration of parenteral quinine must be done carefully and with good observation because of its pro-arrhythmic effect, especially in older patients who have heart diseases or patients with electrolyte disorder (hypokalemia) which frequently occurs due to vomiting and or diarrhea in malaria cases. PMID:17297207

  5. Cardiac arrhythmias produced by ultrasound and contrast agents

    NASA Astrophysics Data System (ADS)

    Rota, Claudio

    Ultrasound is used widely in medicine for both diagnostic and therapeutic applications. Ultrasound contrast agents are suspensions of gas-filled microbubbles used to enhance diagnostic imaging. Microbubble contrast agents can increase the likelihood of bioeffects of ultrasound associated with acoustic cavitation. Under certain exposure conditions, the interaction of ultrasound with cardiac tissues can produce cardiac arrhythmias. The general objective of this thesis was to develop a greater understanding of ultrasound-induced premature cardiac beats. The hypothesis guiding this work was that acoustic cavitation is the physical mechanism for the production of arrhythmias with ultrasound. This hypothesis was tested through a series of experiments with mice in vivo and theoretical investigations. Results of this research supported the acoustic cavitation hypothesis. The acoustic pressure threshold for premature beats was significantly lower with microbubble contrast agents present in the blood than without. With microbubbles, the threshold for premature beats was below the current output limits of diagnostic devices. The threshold was not significantly dependent upon contrast agent type and was not influenced by contrast agent dose over three orders of magnitude. Furthermore, the dependence of the threshold on acoustic frequency was consistent with the frequency dependence of acoustic cavitation. Experimentally determined thresholds for premature beats in vivo were in excellent agreement with theoretically estimated thresholds for inertial cavitation. A passive cavitation detector (PCD) was used to measure the acoustic emissions produced by cavitating microbubbles in vivo. A direct correlation between the amplitude of the PCD and the percentage of ultrasound pulses producing a premature beat was consistent with cavitation as a mechanism for this bioeffect. Although this thesis focused on the mechanistic understanding of ultrasound-induced arrhythmias, more persistent

  6. Utility of noninvasive, mobile, continuous outpatient rhythm monitoring to diagnose seizure-related arrhythmias.

    PubMed

    Driver, Kevin; Gilliam, Frank; Dizon, Jose; Whang, William; Ehlert, Frederick; Hickey, Kathleen; Garan, Hasan; Biviano, Angelo B

    2009-07-01

    The identification of patients with a diagnosis of seizure disorder who are also at risk for clinically significant bradycardia and/or tachycardia may require long-term cardiac rhythm monitoring. Noninvasive, continuous, outpatient cardiac rhythm monitoring may be useful for such clinical scenarios. The study group consisted of two male patients with a history of seizure disorder involving loss of consciousness. Clinical data and results of electrocardiography, echocardiography, electroencephalography, and continuous, mobile, outpatient cardiac rhythm monitoring are described. In the first patient, while cardiac bradyarrhythmias were secondary to seizures, sinus arrest most likely complicated the episodes by leading to more prolonged states of unconsciousness. In the second patient, permanent pacemaker implantation for AV block averted all clinical events previously attributed to seizures. Despite the different causal relationships between seizures and bradyarrhythmias in these two patients, mobile, cardiac outpatient telemetry was successful in diagnosing the contribution of cardiac dysrhythmia, leading to permanent pacemaker implantation. A diagnostic strategy that incorporates mobile, noninvasive, continuous, outpatient cardiac rhythm monitoring can effectively be utilized to diagnose significant seizure-related arrhythmias. PMID:19572879

  7. The pioneering work of George Mines on cardiac arrhythmias: groundbreaking ideas that remain influential in contemporary cardiac electrophysiology.

    PubMed

    Aguilar, Martin; Nattel, Stanley

    2016-05-01

    George Mines was a pioneering physiologist who, despite an extremely short period of professional activity and only primitive experimental methodology, succeeded in formulating concepts that continue to be of great influence today. Here, we review some of his most important discoveries and their impact on contemporary concepts and clinical practice. Mines' greatest contribution was his conceptualization and characterization of circus movement reentry. His observations and ideas about the basis for cardiac reentrant activity underlie how we understand and manage a wide range of important clinical rhythm disturbances today. The notions he introduced regarding the influence of premature extrastimuli on reentry (termination, resetting and entrainment) are central to contemporary assessment of arrhythmia mechanisms in clinical electrophysiology laboratories and modern device therapy of cardiac tachyarrhythmias. Refinements of his model of reentry have led to sophisticated biophysical theories of the mechanisms underlying cardiac fibrillation. His seminal observations on the influence of electrolyte derangements and autonomic tone on the heart are relevant to our understanding of the physiology and pharmacology of arrhythmias caused by cardiac pathology. In this era of advanced technology, it is important to appreciate that ideas of lasting impact come from great minds and do not necessarily require great tools. PMID:26607760

  8. High-throughput cardiac safety evaluation and multi-parameter arrhythmia profiling of cardiomyocytes using microelectrode arrays.

    PubMed

    Gilchrist, Kristin H; Lewis, Gregory F; Gay, Elaine A; Sellgren, Katelyn L; Grego, Sonia

    2015-10-15

    Microelectrode arrays (MEAs) recording extracellular field potentials of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) provide a rich data set for functional assessment of drug response. The aim of this work is the development of a method for a systematic analysis of arrhythmia using MEAs, with emphasis on the development of six parameters accounting for different types of cardiomyocyte signal irregularities. We describe a software approach to carry out such analysis automatically including generation of a heat map that enables quick visualization of arrhythmic liability of compounds. We also implemented signal processing techniques for reliable extraction of the repolarization peak for field potential duration (FPD) measurement even from recordings with low signal to noise ratios. We measured hiPS-CM's on a 48 well MEA system with 5minute recordings at multiple time points (0.5, 1, 2 and 4h) after drug exposure. We evaluated concentration responses for seven compounds with a combination of hERG, QT and clinical proarrhythmia properties: Verapamil, Ranolazine, Flecainide, Amiodarone, Ouabain, Cisapride, and Terfenadine. The predictive utility of MEA parameters as surrogates of these clinical effects were examined. The beat rate and FPD results exhibited good correlations with previous MEA studies in stem cell derived cardiomyocytes and clinical data. The six-parameter arrhythmia assessment exhibited excellent predictive agreement with the known arrhythmogenic potential of the tested compounds, and holds promise as a new method to predict arrhythmic liability. PMID:26232523

  9. Ataxias with autosomal, X-chromosomal or maternal inheritance.

    PubMed

    Finsterer, Josef

    2009-07-01

    Heredoataxias are a group of genetic disorders with a cerebellar syndrome as the leading clinical manifestation. The current classification distinguishes heredoataxias according to the trait of inheritance into autosomal dominant, autosomal recessive, X-linked, and maternally inherited heredoataxias. The autosomal dominant heredoataxias are separated into spinocerebellar ataxias (SCA1-8, 10-15, 17-23, 25-30, and dentato-rubro-pallido-luysian atrophy), episodic ataxias (EA1-7), and autosomal dominant mitochondrial heredoataxias (Leigh syndrome, MIRAS, ADOAD, and AD-CPEO). The autosomal recessive ataxias are separated into Friedreich ataxia, ataxia due to vitamin E deficiency, ataxia due to Abeta-lipoproteinemia, Refsum disease, late-onset Tay-Sachs disease, cerebrotendineous xanthomatosis, spinocerebellar ataxia with axonal neuropathy, ataxia telangiectasia, ataxia telangiectasia-like disorder, ataxia with oculomotor apraxia 1 and 2, spastic ataxia of Charlevoix-Saguenay, Cayman ataxia, Marinesco-Sjögren syndrome, and autosomal recessive mitochondrial ataxias (AR-CPEO, SANDO, SCAE, AHS, IOSCA, MEMSA, LBSL CoQ-deficiency, PDC-deficiency). Only two of the heredoataxias, fragile X/tremor/ataxia syndrome, and XLSA/A are transmitted via an X-linked trait. Maternally inherited heredoataxias are due to point mutations in genes encoding for tRNAs, rRNAs, respiratory chain subunits or single large scale deletions/duplications of the mitochondrial DNA and include MELAS, MERRF, KSS, PS, MILS, NARP, and non-syndromic mitochondrial disorders. Treatment of heredoataxias is symptomatic and supportive and may have a beneficial effect in single patients. **Please see page 424 for abbreviation list. PMID:19650351

  10. Inherited and noninherited risk factors in rheumatoid arthritis.

    PubMed

    Weyand, C M; Goronzy, J J

    1995-05-01

    Rheumatoid arthritis (RA) is likely the result of a concerted action of several inherited and noninherited factors. Although there is a high suspicion that environmental factors are important, proof is missing. Most information has been collected on genetic risk factors. The inheritance pattern for RA is complex, and there is good evidence that HLA as well as non-HLA genes are involved. Almost all racial-ethnic groups share the association of RA with the HLA-DRB1-encoded sequence motif QKRAA or QRRAA. However, the completeness of the association varies significantly in different ethnic cohorts, as can be expected in a multigene model. The sequence motif translates into a pocket in the antigen-binding site of the HLA-DR molecule. The "rheumatoid pocket" accommodates peptide side chains and has distinct binding characteristics. Epidemiologic evidence points toward a role for non-HLA genes. Candidate genes, such as transporter in antigen processing (TAP) genes are currently explored. Major advances in defining and understanding the contribution of inherited and noninherited factors in RA may come from abandoning the concept of RA as a single entity and accepting a heterogeneity model for RA. Distributions of HLA-DR genes indicate that several subsets of RA patients exist. Seronegative (prognostically good) and seropositive (prognostically worse) patients can be distinguished by the arginine versus lysine substitution at position 71 of the HLA-DRB1 gene. A different dimension of disease, rheumatoid organ disease, appears to be reached in patients with two HLA-DRB1*0401 alleles. Identification of distinct RA subsets may allow us to stratify patients into categories that differ with respect to etiology, disease course, clinical pattern, and treatment response. PMID:7612412

  11. Factor XII mutations, estrogen-dependent inherited angioedema, and related conditions.

    PubMed

    Binkley, Karen E

    2010-01-01

    The clinical, biochemical and genetic features of the conditions known as estrogen-dependent inherited angioedema, estrogen-associated angioedema, hereditary angioedema with normal C-1 inhibitor, type III angioedema, or factor XII angioedema are reviewed. Discussion emphasizes pathogenesis, diagnosis, and management. PMID:20667119

  12. Elusive inheritance: Transgenerational effects and epigenetic inheritance in human environmental disease

    PubMed Central

    Martos, Suzanne N.; Tang, Wan-yee; Wang, Zhibin

    2016-01-01

    Epigenetic mechanisms involving DNA methylation, histone modification, histone variants and nucleosome positioning, and noncoding RNAs regulate cell-, tissue-, and developmental stage-specific gene expression by influencing chromatin structure and modulating interactions between proteins and DNA. Epigenetic marks are mitotically inherited in somatic cells and may be altered in response to internal and external stimuli. The idea that environment-induced epigenetic changes in mammals could be inherited through the germline, independent of genetic mechanisms, has stimulated much debate. Many experimental models have been designed to interrogate the possibility of transgenerational epigenetic inheritance and provide insight into how environmental exposures influence phenotypes over multiple generations in the absence of any apparent genetic mutation. Unexpected molecular evidence has forced us to reevaluate not only our understanding of the plasticity and heritability of epigenetic factors, but of the stability of the genome as well. Recent reviews have described the difference between transgenerational and intergenerational effects; the two major epigenetic reprogramming events in the mammalian lifecycle; these two events making transgenerational epigenetic inheritance of environment-induced perturbations rare, if at all possible, in mammals; and mechanisms of transgenerational epigenetic inheritance in non-mammalian eukaryotic organisms. This paper briefly introduces these topics and mainly focuses on (1) transgenerational phenotypes and epigenetic effects in mammals, (2) environment-induced intergenerational epigenetic effects, and (3) the inherent difficulties in establishing a role for epigenetic inheritance in human environmental disease. PMID:25792089

  13. Elusive inheritance: Transgenerational effects and epigenetic inheritance in human environmental disease.

    PubMed

    Martos, Suzanne N; Tang, Wan-Yee; Wang, Zhibin

    2015-07-01

    Epigenetic mechanisms involving DNA methylation, histone modification, histone variants and nucleosome positioning, and noncoding RNAs regulate cell-, tissue-, and developmental stage-specific gene expression by influencing chromatin structure and modulating interactions between proteins and DNA. Epigenetic marks are mitotically inherited in somatic cells and may be altered in response to internal and external stimuli. The idea that environment-induced epigenetic changes in mammals could be inherited through the germline, independent of genetic mechanisms, has stimulated much debate. Many experimental models have been designed to interrogate the possibility of transgenerational epigenetic inheritance and provide insight into how environmental exposures influence phenotypes over multiple generations in the absence of any apparent genetic mutation. Unexpected molecular evidence has forced us to reevaluate not only our understanding of the plasticity and heritability of epigenetic factors, but of the stability of the genome as well. Recent reviews have described the difference between transgenerational and intergenerational effects; the two major epigenetic reprogramming events in the mammalian lifecycle; these two events making transgenerational epigenetic inheritance of environment-induced perturbations rare, if at all possible, in mammals; and mechanisms of transgenerational epigenetic inheritance in non-mammalian eukaryotic organisms. This paper briefly introduces these topics and mainly focuses on (1) transgenerational phenotypes and epigenetic effects in mammals, (2) environment-induced intergenerational epigenetic effects, and (3) the inherent difficulties in establishing a role for epigenetic inheritance in human environmental disease. PMID:25792089

  14. 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. Electrical alternans affecting the ST segment and T-wave have been demonstrated to be common among patients at increased risk for ventricular arrhythmias. Subtle electrical alternans on the ECG may serve as a noninvasive marker of vulnerability to ventricular arrhythmias. We are studying indices of electrical instability in the heart for long term space missions by non-invasively measuring microvolt level T-wave alternans in a reduced gravity environment. In this investigation we are using volunteer subjects on the KC-135 aircraft as an initial study of the effect of electrical adaptation of the heart to microgravity. T-wave alternans will be analyzed for heart rate variability and QT restitution curve plotting will be compared for statistical significance.

  15. Klotho protein lowered in senile patients with brady sinus arrhythmia

    PubMed Central

    Wang, Ying; Yang, Wei; Zheng, Ernv; Zhang, Wei; Su, Xianming

    2015-01-01

    Objective: To explore the correlationship between brady sinus arrhythmia and the levels of serum klotho protein in aged. Methods: 104 patients over 75 years old with brady sinus arrhythmia (experiment group) were enrolled, including 34 cases of sinus arrest, 43 cases of sinus bradycardia and 25 cases of atrioventricular block. 109 patients over 75 years old without brady sinus arrhymia were chosen as control group. All subjects were monitored by Holter. The levels of serum klotho protein were detected and compared among three groups. The correlation between the frequency of sinus arrest and the levels of serum klotho protein was analyzed simultaneously. Results: The levels of serum klotho protein in experiment group were lower than that in control group (P<0.01); the sinus arrest frequency was negatively correlated with the levels of serum klotho protien. The levels of serum klotho protein in patients with sinus arrest were lower than that with sinus bradycardia and atrioventricularblock (P<0.05). But there was no significant difference between sinus bradycardia group and atrioventricular block group. Conclusion: The levels of serum klotho protein may reflect the function of sinoatrial node and could be used as an index to estimate the function of sinoatrial node. PMID:26550342

  16. BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias.

    PubMed

    Stambolija, Vasilije; Stambolija, Tamara Perleta; Holjevac, Jadranka Katancic; Murselovic, Tamara; Radonic, Jelena; Duzel, Viktor; Duplancic, Bozidar; Uzun, Sandra; Zivanovic-Posilovic, Gordana; Kolenc, Danijela; Drmic, Domagoj; Romic, Zeljko; Seiwerth, Sven; Sikiric, Predrag

    2016-06-15

    After the demonstration of its life-saving effect in severe hyperkalemia and the recovery of skeletal muscle after injury, pentadecapeptide BPC 157 has been shown to attenuate the local paralytic effect induced by succinylcholine, in addition to systemic muscle disability (and consequent muscle damage). Hyperkalemia, arrhythmias and a rise in serum enzyme values, were counteracted in rats. Assessments were made at 3 and 30min and 1, 3, 5, and 7 days after succinylcholine administration (1.0mg/kg into the right anterior tibial muscle). BPC 157 (10µg/kg, 10ng/kg) (given intraperitoneally 30min before or immediately after succinylcholine or per-orally in drinking water through 24h until succinylcholine administration) mitigated both local and systemic disturbances. BPC 157 completely eliminated hyperkalemia and arrhythmias, markedly attenuated or erradicated behavioral agitation, muscle twitches, motionless resting and completely eliminated post-succinylcholine hyperalgesia. BPC 157 immediately eliminated leg contractures and counteracted both edema and the decrease in muscle fibers in the diaphragm and injected/non-injected anterior tibial muscles. Therefore, the depolarizing neuromuscular blocker effects of succinylcholine were successfully antagonized. PMID:27060013

  17. Review of complementary and alternative medical treatment of arrhythmias.

    PubMed

    Brenyo, Andrew; Aktas, Mehmet K

    2014-03-01

    Complementary and alternative medical (CAM) therapies are commonly used by patients for the treatment of medical conditions spanning the full spectrum of severity and chronicity. The use of alternative remedies, both herbal and others, for conditions lacking effective medical treatment, is on the increase. Included within this categorization, arrhythmic disease-absent effective catheter-based therapy or with medical therapy limited by the toxicities of contemporary antiarrhythmic agents is frequently managed by patients with CAM therapies without their practitioner's knowledge and in the face of potential herb-drug toxicities. This study reviews 9 CAM therapies: 7 individual herbal therapies along with acupuncture and yoga that have been studied and reported as having an antiarrhythmic effect. The primary focuses are the proposed antiarrhythmic mechanism of each CAM agent along with interactions between the CAM therapies and commonly prescribed medical therapy for arrhythmia patients. We stress persistent vigilance on the part of the provider in discussing the use of herbal or other CAM agents within the arrhythmia population. PMID:24528618

  18. Evaluation and management of arrhythmia in the athletic patient.

    PubMed

    Lampert, Rachel

    2012-01-01

    Athletes may present with palpitations, syncope, or arrest resulting in the diagnosis of arrhythmia, or screening may result in diagnosis of conditions with predisposition to arrhythmia. This chapter focuses on 3 common arrhythmic conditions in athletes-atrial fibrillation, premature ventricular contractions (PVCs), and the athlete with an implanted device. (1) Atrial fibrillation: most studies show that atrial fibrillation is more common in competitive athletes, particularly those participating in long-term endurance sports. Postulated mechanisms include morphologic changes such as atrial dilatation, autonomic changes such as increased vagal tone, or inflammatory changes due to sports participation. Treatment options include long-term antiarrhythmic agents, "pill in the pocket" medications, or radiofrequency ablation, a highly successful procedure in athletes. (2) Premature ventricular contractions: data conflict on whether the incidence of PVCs is increased in highly trained individuals. Very frequent PVCs in athletes, however, can be a manifestation of underlying heart disease, and athletes presenting with PVCs should undergo evaluation. In the absence of underlying heart disease, PVCs do not carry a poor prognosis, and US guidelines do not recommend restriction from sports. (3) Implanted devices: the safety of sports for the athlete with an implanted device is unknown, and current guidelines recommend against participation in vigorous competitive sports, based on postulated risks including failure to defibrillate and risk of injury. Many athletes with defibrillators and pacemakers do participate in sports. Ongoing research will better delineate the risks of sports for the athlete with an implanted device. PMID:22386293

  19. Arrhythmias, Sudden Cardiac Death and incapacitation of pilots

    PubMed Central

    Mantziari, L; Styliadis, C; Kourtidou-Papadeli, C; Styliadis, I

    2008-01-01

    Inflight medical emergencies occur at a rate of 20 to 100 per million passengers, with a death rate of 0.1 to 1 per million. Cardiac, neurologic, and respiratory complaints comprise the more serious emergencies, as defined by aircraft diversion or use of ground-based medical assistance. In this paper, we review changes seen in the resting electrocardiogram in normal individuals exposed to high altitude, alongside important implications for patients with heart diseases in high altitude exposures and the possible effects of high altitude to permanent cardiac pacemakers. Arrhythmias in pilots and public safety are revisited together with the guidelines of the Joint Aviation Requirements (JAR) in Europe. The situation of Military flights is also discussed. Physicians ought to become knowledgeable about the specific medical job standards for their patients when asked to render opinions regarding fitness to fly. A database must be established to obtain prospective data that defines the risk of accidents in patients who are or were being treated for arrhythmias. Current guidelines could then be updated and revised as appropriate. PMID:19050752

  20. Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

    PubMed Central

    Armoundas, A; Rosenbaum, D; Ruskin, J; Garan, H; Cohen, R

    1998-01-01

    Objective—To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias.
Design—Analysis of new data from a previously published prospective investigation.
Setting—Electrophysiology laboratory of a major referral hospital.
Patients and interventions—43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0.
Main outcome measures—Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival.
Results—The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. 
Conclusions—T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk

  1. 25 CFR 91.9 - Inheritance of improvements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., OSAGE RESERVATION, OKLAHOMA § 91.9 Inheritance of improvements. (a) Upon the death of the owner of... of the county courts, State of Oklahoma, and shall be subject to inheritance or bequest in...

  2. 25 CFR 91.9 - Inheritance of improvements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., OSAGE RESERVATION, OKLAHOMA § 91.9 Inheritance of improvements. (a) Upon the death of the owner of... of the county courts, State of Oklahoma, and shall be subject to inheritance or bequest in...

  3. 25 CFR 91.9 - Inheritance of improvements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., OSAGE RESERVATION, OKLAHOMA § 91.9 Inheritance of improvements. (a) Upon the death of the owner of... of the county courts, State of Oklahoma, and shall be subject to inheritance or bequest in...

  4. 25 CFR 91.9 - Inheritance of improvements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., OSAGE RESERVATION, OKLAHOMA § 91.9 Inheritance of improvements. (a) Upon the death of the owner of... of the county courts, State of Oklahoma, and shall be subject to inheritance or bequest in...

  5. 25 CFR 91.9 - Inheritance of improvements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., OSAGE RESERVATION, OKLAHOMA § 91.9 Inheritance of improvements. (a) Upon the death of the owner of... of the county courts, State of Oklahoma, and shall be subject to inheritance or bequest in...

  6. Genetics Home Reference: inherited thyroxine-binding globulin deficiency

    MedlinePlus

    ... Although inherited thyroxine-binding globulin deficiency does not cause any health problems, it can be mistaken for more serious thyroid disorders (such as hypothyroidism). Therefore, it is important to diagnose inherited thyroxine- ...

  7. Nature and Nurture in Arrhythmogenic Right Ventricular Cardiomyopathy - A Clinical Perspective.

    PubMed

    James, Cynthia A

    2015-12-01

    Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterised by frequent ventricular arrhythmias and slowly progressive predominant RV dysfunction. Up to two-thirds of ARVD/C patients have mutations in genes encoding the cardiac desmosome. Mutations in other genes are increasingly recognised. Inheritance of ARVD/C is generally autosomal dominant with reduced age-related penetrance and significant variable expressivity. While the full explanation for this phenotypic heterogeneity remains unclear, there is increasing evidence that exercise plays a major role in disease penetrance and arrhythmic risk. The disproportionate representation of athletes among ARVD/C patients has long been noted. Recently, the association of exercise with earlier onset and more severe arrhythmic and structural disease has been documented. This article reviews current evidence regarding the association of genotype, exercise and clinical outcomes and discusses the emerging paradigm in which genetic predisposition and environmental factors (exercise) interact around a threshold for phenotypic expression of ARVD/C. PMID:26835118

  8. Nature and Nurture in Arrhythmogenic Right Ventricular Cardiomyopathy – A Clinical Perspective

    PubMed Central

    James, Cynthia A

    2015-01-01

    Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterised by frequent ventricular arrhythmias and slowly progressive predominant RV dysfunction. Up to two-thirds of ARVD/C patients have mutations in genes encoding the cardiac desmosome. Mutations in other genes are increasingly recognised. Inheritance of ARVD/C is generally autosomal dominant with reduced age-related penetrance and significant variable expressivity. While the full explanation for this phenotypic heterogeneity remains unclear, there is increasing evidence that exercise plays a major role in disease penetrance and arrhythmic risk. The disproportionate representation of athletes among ARVD/C patients has long been noted. Recently, the association of exercise with earlier onset and more severe arrhythmic and structural disease has been documented. This article reviews current evidence regarding the association of genotype, exercise and clinical outcomes and discusses the emerging paradigm in which genetic predisposition and environmental factors (exercise) interact around a threshold for phenotypic expression of ARVD/C. PMID:26835118

  9. Preimplantation genetic diagnosis for inherited neurological disorders.

    PubMed

    Tur-Kaspa, Ilan; Jeelani, Roohi; Doraiswamy, P Murali

    2014-07-01

    Preimplantation genetic diagnosis (PGD) is an option for couples at risk of having offspring with an inherited debilitating or fatal neurological disorder who wish to conceive a healthy child. PGD has been carried out for conditions with various modes of inheritance, including spinal muscular atrophy, Huntington disease, fragile X syndrome, and chromosomal or mitochondrial disorders, and for susceptibility genes for cancers with nervous system involvement. Most couples at risk of transmitting a genetic mutation would opt for PGD over prenatal testing and possible termination of a pregnancy. The aim of this Perspectives article is to assist neurologists in counselling and treating patients who wish to explore the option of PGD to enable conception of an unaffected child. PGD can be accomplished for most disorders in which the genetic basis is known, and we argue that it is time for clinicians and neurological societies to consider the evidence and to formulate guidelines for the responsible integration of PGD into modern preventative neurology. PMID:24866878

  10. Pregnancy in women with inherited metabolic disease

    PubMed Central

    2015-01-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Whilst, in general, outcomes for women and their children are good, there are issues that need to be considered. Due to the rarity of many conditions, there is limited specific guidance available on best management. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in other disorders of intoxication or energy metabolism significantly reduced. Newer therapies, such as enzyme replacement therapy, appear to be safe in pregnancy, but specific advice should be sought. Multidisciplinary management, and close liaison between obstetricians and other specialists is required for women in whom there is cardiac, renal, respiratory, joint or other organ involvement.

  11. Evolutionary inheritance of elemental stoichiometry in phytoplankton

    PubMed Central

    Quigg, Antonietta; Irwin, Andrew J.; Finkel, Zoe V.

    2011-01-01

    The elemental composition of phytoplankton is a fusion of the evolutionary history of the host and plastid, resulting in differences in genetic constraints and selection pressures associated with environmental conditions. The evolutionary inheritance hypothesis predicts similarities in elemental composition within related taxonomic lineages of phytoplankton. To test this hypothesis, we measured the elemental composition (C, N, P, S, K, Mg, Ca, Sr, Fe, Mn, Zn, Cu, Co, Cd and Mo) of 14 phytoplankton species and combined these with published data from 15 more species from both marine and freshwater environments grown under nutrient-replete conditions. The largest differences in the elemental profiles of the species distinguish between the prokaryotic Cyanophyta and primary endosymbiotic events that resulted in the green and red plastid lineages. Smaller differences in trace element stoichiometry within the red and green plastid lineages are consistent with changes in trace elemental stoichiometry owing to the processes associated with secondary endosymbioses and inheritance by descent with modification. PMID:20826483

  12. Medical Problems in Obstetrics: Inherited Metabolic Disease.

    PubMed

    Murphy, Elaine

    2015-07-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Although, in general, outcomes for women and their children are good, there are a number of issues that need to be considered. Currently, limited specific guidance on the management of these conditions in pregnancy is available. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in disorders of energy metabolism or intoxication significantly reduced. Multidisciplinary management, and close liaison between obstetricians and other specialists, is required for those women in whom there is cardiac, renal, respiratory, joint or other organ involvement. PMID:26088792

  13. Inheritance is where physiology meets evolution

    PubMed Central

    Danchin, Étienne; Pocheville, Arnaud

    2014-01-01

    Physiology and evolutionary biology have developed as two separated disciplines, a separation that mirrored the hypothesis that the physiological and evolutionary processes could be decoupled. We argue that non-genetic inheritance shatters the frontier between physiology and evolution, and leads to the coupling of physiological and evolutionary processes to a point where there exists a continuum between accommodation by phenotypic plasticity and adaptation by natural selection. This approach is also profoundly affecting the definition of the concept of phenotypic plasticity, which should now be envisaged as a multi-scale concept. We further suggest that inclusive inheritance provides a quantitative way to help bridging infra-individual (i.e. physiology) with supra-individual (i.e. evolution) approaches, in a way that should help building the long sough inclusive evolutionary synthesis. PMID:24882815

  14. X-linked Inheritance in Females with Chronic Granulomatous Disease

    PubMed Central

    Mills, Elaine L.; Rholl, Kenneth S.; Quie, Paul G.

    1980-01-01

    Chronic granulomatous disease in males is familial and its transmission is is usually clearly x-linked. The mode of inheritance in females with the syndrome is unknown and the carrier state difficult to identify. Defective polymorphonuclear leukocyte bactericidal activity in this disease is associated with an absence of the respiratory burst generated in stimulated phagocytes and may be detected by the chemiluminescence assay. Polymorphonuclear leukocytes from three of four females with chronic granulomatous disease had extremely low chemiluminescence production, their asymptomatic mothers had intermediate values, and their fathers were normal. Polymorphonuclear neutrophils of two affected males in these kinships generated no chemiluminescence, whereas two of seven female relatives had intermediate values, and all nonaffected males had normal values. In the three families in which leukocytes were studied by nitroblue tetrazolium reduction, two populations of neutrophils were demonstrated for the female patients and/or their mothers. The wide phenotypic variability for clinical disease, evidence of two leukocyte populations in the patients or their mothers, and low but detectable leukocyte chemiluminescence in the affected females is consistent with the Lyon hypothesis of x-chromosome inactivation in these families. The findings suggest an x-linked inheritance in these females with chronic granulomatous disease. Images PMID:7400319

  15. Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity.

    PubMed

    Torres, Juan Manuel; Martinez-Barricarte, Rubén; García-Gómez, Sonia; Mazariegos, Marina S; Itan, Yuval; Boisson, Bertrand; Rholvarez, Rita; Jiménez-Reinoso, Anaïs; del Pino, Lucia; Rodríguez-Pena, Rebeca; Ferreira, Antonio; Hernández-Jiménez, Enrique; Toledano, Victor; Cubillos-Zapata, Carolina; Díaz-Almirón, Mariana; López-Collazo, Eduardo; Unzueta-Roch, José L; Sánchez-Ramón, Silvia; Regueiro, Jose R; López-Granados, Eduardo; Casanova, Jean-Laurent; Pérez de Diego, Rebeca

    2014-12-01

    Heterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain-containing (CARD) family adaptors play a role in NF-κB activation and have been shown to be involved in both the innate and the adaptive arms of immunity in murine models. Moreover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and clinical phenotypes. Here, we characterized a case of autosomal-recessive, complete BCL10 deficiency in a child with a broad immunodeficiency, including defects of both hematopoietic and nonhematopoietic immunity. The patient died at 3 years of age and was homozygous for a loss-of-expression, loss-of-function BCL10 mutation. The effect of BCL10 deficiency was dependent on the signaling pathway, and, for some pathways, the cell type affected. Despite the noted similarities to BCL10 deficiency in mice, including a deficient adaptive immune response, human BCL10 deficiency in this patient resulted in a number of specific features within cell populations. Treatment of the patient's myeloid cells with a variety of pathogen-associated molecular pattern molecules (PAMPs) elicited a normal response; however, NF-κB-mediated fibroblast functions were dramatically impaired. The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects. PMID:25365219

  16. Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity

    PubMed Central

    Torres, Juan Manuel; Martinez-Barricarte, Rubén; García-Gómez, Sonia; Mazariegos, Marina S.; Itan, Yuval; Boisson, Bertrand; ρlvarez, Rita; Jiménez-Reinoso, Anaïs; del Pino, Lucia; Rodríguez-Pena, Rebeca; Ferreira, Antonio; Hernández-Jiménez, Enrique; Toledano, Victor; Cubillos-Zapata, Carolina; Díaz-Almirón, Mariana; López-Collazo, Eduardo; Unzueta-Roch, José L.; Sánchez-Ramón, Silvia; Regueiro, Jose R.; López-Granados, Eduardo; Casanova, Jean-Laurent; Pérez de Diego, Rebeca

    2014-01-01

    Heterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain–containing (CARD) family adaptors play a role in NF-κB activation and have been shown to be involved in both the innate and the adaptive arms of immunity in murine models. Moreover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and clinical phenotypes. Here, we characterized a case of autosomal-recessive, complete BCL10 deficiency in a child with a broad immunodeficiency, including defects of both hematopoietic and nonhematopoietic immunity. The patient died at 3 years of age and was homozygous for a loss-of-expression, loss-of-function BCL10 mutation. The effect of BCL10 deficiency was dependent on the signaling pathway, and, for some pathways, the cell type affected. Despite the noted similarities to BCL10 deficiency in mice, including a deficient adaptive immune response, human BCL10 deficiency in this patient resulted in a number of specific features within cell populations. Treatment of the patient’s myeloid cells with a variety of pathogen-associated molecular pattern molecules (PAMPs) elicited a normal response; however, NF-κB–mediated fibroblast functions were dramatically impaired. The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects. PMID:25365219

  17. 78 FR 36787 - Rechanneling the Current Cardiac Risk Paradigm: Arrhythmia Risk Assessment During Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... HUMAN SERVICES Food and Drug Administration Rechanneling the Current Cardiac Risk Paradigm: Arrhythmia... the Current Cardiac Risk Paradigm: Arrhythmia Risk Assessment During Drug Development Without the... the current guidelines, and the importance of a uniform assay schema. Date and Time: The...

  18. Cardiac arrhythmias associated with a liquid protein diet for the treatment of obesity

    SciTech Connect

    Lantigua, R.A.; Amatruda, J.M.; Biddle, T.L.; Forbes, G.B.; Lockwood, D.H.

    1980-09-25

    Our data demonstrate that a liquid protein diet is frequently associated with potentially life-threatening arrhythmias that are not detected on routine electrocardiography. Several studies of metabolic balance failed to reveal a cause for these arrhythmias. We recommended that the use of liquid protein diets should be terminated pending further investigation of the causes and prevention of the cardiac toxicity.

  19. Effect of beta-blockers on arrhythmias during six weeks after suspected myocardial infarction.

    PubMed

    Roland, J M; Wilcox, R G; Banks, D C; Edwards, B; Fentem, P H; Hampton, J R

    1979-09-01

    Twenty-four-hour electrocardiographic tape-recording was used to investigate the incidence of arrhythmias in patients with suspected myocardial infarction who were receiving either propranolol, atenolol, or placebo. Recordings begun within 24 hours after admission to a coronary care unit showed that 76% of patients eventually found to have had a myocardial infarction had ventricular arrhythmias of a type generally regarded as serious, whereas of patients in whom myocardial infarction was not substantiated, only 24% had such arrhythmias. At one and six weeks after admission the incidence of arrhythmias ranged from 25% to 33% irrespective of diagnosis. Of patients monitored at both one and six weeks, however, only 5% had arrhythmias on each occasion. Patients treated with propranolol and atenolol showed a similar incidence of arrhythmias to those taking placebo. There was no difference in the incidence or type of arrhythmias recorded between patients who died and those who were still alive at six weeks.These results confirm that "serious" ventricular arrythmias occur in most patients during the acute phase of myocardial infarction and suggest that they do not constitute an independent risk factor. Beta-blockers showed little evidence of useful antiarrhythmic action in the dosage used, but increasing the dosage in suspected myocardial infarction is not practicable because of the risk of hypotension. The findings raise grave doubts about the value of studying arrhythmias to assess drugs intended to reduce mortality from myocardial infarction. PMID:387170

  20. Arrhythmia triggers in heart failure: the smoking gun of [Ca2+]i dysregulation.

    PubMed

    Aistrup, Gary L; Balke, C William; Wasserstrom, J Andrew

    2011-11-01

    Among the most serious problems associated with heart failure is the increased likelihood of life-threatening arrhythmias. Both triggered and reentrant arrhythmias in heart failure may arise as a result of aberrant intracellular Ca cycling. This article presents some new ideas, based on recent studies, about how altered Ca cycling in heart failure might serve as the cellular basis for arrhythmogenesis. PMID:21699870

  1. Discriminative sparse coding of ECG during ventricular arrhythmias using LC-K-SVD approach.

    PubMed

    Kalaji, I; Balasundaram, K; Umapathy, K

    2015-01-01

    Ventricular tachycardia (VT) and ventricular fibrillation (VF) are two major types of ventricular arrhythmias that results due to abnormalities in the electrical activation in the ventricles of the heart. VF is the lethal of the two arrhythmias, which may lead to sudden cardiac death. The treatment options for the two arrhythmias are different. Therefore, detection and characterization of the two arrhythmias is critical to choose appropriate therapy options. Due to the time-varying nature of the signal content during cardiac arrhythmias, modeling and extracting information from them using time and frequency localized functions would be ideal. To this effect, in this work, we perform discriminative sparse coding of the ECG during ventricular arrhythmia with hybrid time-frequency dictionaries using the recently introduced Label consistent K-SVD (LC-K-SVD) approach. Using 944 segments of ventricular arrhythmias extracted from 23 patients in the Malignant Ventricular Ectopy and Creighton University Tachy-Arrhythmia databases, an overall classification accuracy of 71.55% was attained with a hybrid dictionary of Gabor and symlet4 atoms. In comparison, for the same database and non-trained dictionary (i.e the original dictionary) the classification accuracy was found to be 62.71%. In addition, the modeling error using the trained dictionary from LC-K-SVD approach was found to be significantly lower to the one using the non-trained dictionary. PMID:26737466

  2. Investigation of mechanisms and non-pharmacological therapy of cardiac arrhythmias

    NASA Astrophysics Data System (ADS)

    Vago, Hajnalka

    Learning of mechanisms of arrhythmias may contribute substantially to the development of effective pharmacological and non-pharmacological therapeutic methods. Clinical relevance of endothelin-1 (ET-1), a strong vasoconstrictor and arrhythmogenic endogenous substrate, is not clarified yet. In our experimental studies, performed in the in situ canine heart, electrophysiological effects and the role in the pathomechanism of malignant ventricular tachyarrhythmias of endogenous and exogenous ET-1 was investigated. It has been proven in the in vivo ischaemia-reperfusion canine heart model, that during reperfusion ET-1 and big-ET levels increase in the coronary sinus, however there was no correlation between endothelin levels and electrophysiological changes. ET A-receptor antagonist darusentan does not prevent electrophysiological changes and development of ventricular tachyarrhythmias during ischaemia and reperfusion. On the contrary, during ischaemia endogenous ET-1 tends to show balancing effect. It has been proven that administration of high dose intracoronary ET-1 bolus has dual, ischaemic and direct, electrophysiological effect. It has been shown for the first time, that ET-1 causes monophasic action potential (MAP) and T-wave alternant. Our clinical study leads to the conclusion that previous atrial fibrillation, absence of preoperative beta-blocker treatment and combined heart surgery are strong predictors of atrial fibrillation following open heart surgery. The basis of new nonpharmacological therapies is the learning of pathomechanisms of arrhythmias and in some cases heart failure, which is an arrhythmogenic substrate. In our experimental study reliable MAP measurements, suitable for investigation of arrhythmogenesis, were performed for the first time using fractally coated ablation catheters during spontaneous rate and during stimulations. It has been proven that radiofrequency ablation affects significantly MAP parameters. In Hungary, we were the first to

  3. Problem of technological inheritance in machine engineering

    NASA Astrophysics Data System (ADS)

    Blumenstein, Valery; Rakhimyanov, Kharis; Heifetz, Mikhail; Kleptzov, Alexander

    2016-01-01

    This article demonstrates the importance of the research study with regard to the technological inheritance of the properties, which characterize the surface layer, at different stages of a part's life cycle. It looks back at the major achievements and gives the findings relating to the technological inheritance of the parameters of the surface layer strength and quality as well as to how they affect the performance properties of machine parts. It demonstrates that high rates of machine engineering development, occurrence of new materials and more complicated machine operation environment require a shorter period for design-to-manufacture facility by reducing experiments and increasing design work. That, in its turn, generates the necessity in more complex but also more accurate models of metal behavior under stressing. It is especially critical for strengthening treatment. Among them are the models developed within the mechanics of technological inheritance. It is assumed that at the stages of a part's life cycle deformation accumulates on a continuous basis and the plasticity reserve of the metal, which the surface layer is made of, depletes. The research study of technological inheritance and the discovery of physical patterns of the evolution and degradation of the structures in a thin surface layer, which occur during machining and operational stressing of parts made from existing and unique including nanopatterned metals, is a crucial scientific challenge. This leads to the acquisition of new knowledge in the plasticity of state-of-the-art metals in the conditions of complex non monotonous stressing and to the development of efficient integrated and combined methods of technological impact.

  4. Mouse models of Inherited Cancer Syndromes

    PubMed Central

    Jahid, Sohail; Lipkin, Steven

    2010-01-01

    Animal models of cancer have been instrumental in understanding the progression and therapy for hereditary cancer syndromes. The ability to alter the genome of individual mouse cell types in both constitutive and inducible approaches has led to many novel insights into their human disease counterparts. In this review, conventional, conditional and inducible knockout mouse models of inherited human cancer syndromes are presented and insights from the study of these models are highlighted. PMID:21075289

  5. 26 CFR 1.102-1 - Gifts and inheritances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Gifts and inheritances. 1.102-1 Section 1.102-1...) INCOME TAXES (CONTINUED) Items Specifically Excluded from Gross Income § 1.102-1 Gifts and inheritances... inheritances. The income from any property received as a gift, or under a will or statute of descent...

  6. 26 CFR 1.102-1 - Gifts and inheritances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Gifts and inheritances. 1.102-1 Section 1.102-1...) INCOME TAXES (CONTINUED) Items Specifically Excluded from Gross Income § 1.102-1 Gifts and inheritances... inheritances. The income from any property received as a gift, or under a will or statute of descent...

  7. Paternal inheritance in mealybugs (Hemiptera: Coccoidea: Pseudococcidae)

    NASA Astrophysics Data System (ADS)

    Kol-Maimon, Hofit; Mendel, Zvi; Franco, José Carlos; Ghanim, Murad

    2014-10-01

    Mealybugs have a haplodiploid reproduction system, with paternal genome elimination (PGE); the males are diploid soon after fertilization, but during embryogenesis, the male paternal set of chromosomes becomes heterochromatic (HC) and therefore inactive. Previous studies have suggested that paternal genes can be passed on from mealybug males to their sons, but not necessarily by any son, to the next generation. We employed crosses between two mealybug species— Planococcus ficus (Signoret) and Planococcus citri (Risso)—and between two populations of P. ficus, which differ in their mode of pheromone attraction, in order to demonstrate paternal inheritance from males to F2 through F1 male hybrids. Two traits were monitored through three generations: mode of male pheromone attraction (pherotype) and sequences of the internal transcribed spacer 2 (ITS2) gene segment (genotype). Our results demonstrate that paternal inheritance in mealybugs can occur from males to their F2 offspring, through F1 males (paternal line). F2 backcrossed hybrid males expressed paternal pherotypes and ITS2 genotypes although their mother originated through a maternal population. Further results revealed other, hitherto unknown, aspects of inheritance in mealybugs, such as that hybridization between the two species caused absence of paternal traits in F2 hybrid females produced by F1 hybrid females. Furthermore, hybridization between the two species raised the question of whether unattracted males have any role in the interactions between P. ficus and P. citri.

  8. Phenotype as Agent for Epigenetic Inheritance.

    PubMed

    Torday, John S; Miller, William B

    2016-01-01

    The conventional understanding of phenotype is as a derivative of descent with modification through Darwinian random mutation and natural selection. Recent research has revealed Lamarckian inheritance as a major transgenerational mechanism for environmental action on genomes whose extent is determined, in significant part, by germ line cells during meiosis and subsequent stages of embryological development. In consequence, the role of phenotype can productively be reconsidered. The possibility that phenotype is directed towards the effective acquisition of epigenetic marks in consistent reciprocation with the environment during the life cycle of an organism is explored. It is proposed that phenotype is an active agent in niche construction for the active acquisition of epigenetic marks as a dominant evolutionary mechanism rather than a consequence of Darwinian selection towards reproductive success. The reproductive phase of the life cycle can then be appraised as a robust framework in which epigenetic inheritance is entrained to affect growth and development in continued reciprocal responsiveness to environmental stresses. Furthermore, as first principles of physiology determine the limits of epigenetic inheritance, a coherent justification can thereby be provided for the obligate return of all multicellular eukaryotes to the unicellular state. PMID:27399791

  9. Aconitine "challenge" test reveals a single whole-body exposure to diesel exhaust increases cardiac arrhythmia risk in hypertensive rats

    EPA Science Inventory

    Epidemiological studies demonstrate a significant association between cardiac electrical dysfunction, arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electri...

  10. Aconitine Challenge Test Reveals a Single Exposure to Air Pollution Causes Increased Cardiac Arrhythmia Risk in Hypertensive Rats - Abstract

    EPA Science Inventory

    Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...

  11. Alkaptonuria: A Case of Familial Inheritance from Hangarki Village in Dharwad District of Karnataka.

    PubMed

    Trivedi, Dhiraj J; Naik, Prashanth

    2016-07-01

    Alkaptonuria is a genetic disorder, unknown to the general public and ignored by general physicians due to lack of awareness of its high prevalence. Increasing incidences of familial inheritance are recorded. A 41 years 8 months male with the swollen knee, chronic mechanical pain, restricted limping walk and tingling sensation in the limb. Also, has a complaint of the stiffness of back in the morning, which gets relieved by movement. Mild hyper pigmentation of pinna and sclera of eye. X-ray report reveals osteoarthritis of the knee and thoracic kyphosis. After considering clinical finding, report of radiological investigation and Biochemical test results, patient was diagnosed as a case of Alkaptonuria. Screening of entire family revealed a typical case of familial inheritance. Hidden familial inheritance can be disclosed by mass screening of families and medical awareness. PMID:27382210

  12. Guiametabolica.org: empowerment through internet tools in inherited metabolic diseases

    PubMed Central

    2012-01-01

    Web-based interventions are effective on the patient empowerment. Guiametabolica.org constitutes an interface for people involved in inherited metabolic diseases, trying to facilitate access to information and contact with professionals and other patients, offering a platform to develop support groups. Guiametabolica.org is widely considered for Spanish-speaking patients and caregivers with inherited metabolic diseases. Preliminary evaluations show changes in their habits, decrease in their senses of isolation and improvement regarding self-efficacy. Specific inherited metabolic diseases websites, especially participative websites, should be considered as a complement to more traditional clinical approaches. Their contribution lies in patient’s general well-being, without interfering with traditional care. PMID:22909005

  13. Real-time arrhythmia detection with supplementary ECG quality and pulse wave monitoring for the reduction of false alarms in ICUs.

    PubMed

    Krasteva, Vessela; Jekova, Irena; Leber, Remo; Schmid, Ramun; Abächerli, Roger

    2016-08-01

    False intensive care unit (ICU) alarms induce stress in both patients and clinical staff and decrease the quality of care, thus significantly increasing both the hospital recovery time and rehospitalization rates. In the PhysioNet/CinC Challenge 2015 for reducing false arrhythmia alarms in ICU bedside monitor data, this paper validates the application of a real-time arrhythmia detection library (ADLib, Schiller AG) for the robust detection of five types of life-threatening arrhythmia alarms. The strength of the application is to give immediate feedback on the arrhythmia event within a scan interval of 3 s-7.5 s, and to increase the noise immunity of electrocardiogram (ECG) arrhythmia analysis by fusing its decision with supplementary ECG quality interpretation and real-time pulse wave monitoring (quality and hemodynamics) using arterial blood pressure or photoplethysmographic signals. We achieved the third-ranked real-time score (79.41) in the challenge (Event 1), however, the rank was not officially recognized due to the 'closed-source' entry. This study shows the optimization of the alarm decision module, using tunable parameters such as the scan interval, lead quality threshold, and pulse wave features, with a follow-up improvement of the real-time score (80.07). The performance (true positive rate, true negative rate) is reported in the blinded challenge test set for different arrhythmias: asystole (83%, 96%), extreme bradycardia (100%, 90%), extreme tachycardia (98%, 80%), ventricular tachycardia (84%, 82%), and ventricular fibrillation (78%, 84%). Another part of this study considers the validation of ADLib with four reference ECG databases (AHA, EDB, SVDB, MIT-BIH) according to the international recommendations for performance reports in ECG monitors (ANSI/AAMI EC57). The sensitivity (Se) and positive predictivity (+P) are: QRS detector QRS (Se, +P)  >  99.7%, ventricular ectopic beat (VEB) classifier VEB (Se, +P)  =  95%, and ventricular

  14. [Diagnosis and management of inherited bone marrow failure syndrome].

    PubMed

    Yabe, Miharu; Yabe, Hiromasa

    2015-10-01

    The inherited bone marrow failure syndromes (IBMFS) are rare disorders in which there is usually some form of bone marrow failure and typical changes in physical appearance, associated with a family history of the same disorder. Patients with IBMFS have a very high risk of developing myelodysplastic syndrome, acute myeloid leukemia, and solid tumors. The latest technology applied to the molecular pathogenesis of these disorders has led to identification of specific genetic mutations and now facilitates determining the appropriate diagnosis and management of afflicted patients. In this section, we describe physical and laboratory findings and management of the major IBMFS: Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, and Diamond Blackfan anemia. We also discuss their possible implications in the clinical features of Japanese patients. PMID:26458429

  15. Neonatal manifestations of inherited bone marrow failure syndromes.

    PubMed

    Khincha, Payal P; Savage, Sharon A

    2016-02-01

    The inherited bone marrow failure syndromes (IBMFS) are a rare yet clinically important cause of neonatal hematological and non-hematological manifestations. Many of these syndromes, such as Fanconi anemia, dyskeratosis congenita and Diamond-Blackfan anemia, confer risks of multiple medical complications later in life, including an increased risk of cancer. Some IBMFS may present with cytopenias in the neonatal period whereas others may present only with congenital physical abnormalities and progress to pancytopenia later in life. A thorough family history and detailed physical examination are integral to the work-up of any neonate in whom there is a high index of suspicion for an IBMFS. Correct detection and diagnosis of these disorders is important for appropriate long-term medical surveillance and counseling not only for the patient but also for appropriate genetic counselling of their families regarding recurrence risks in future children and generations. PMID:26724991

  16. Stable isotopes in the diagnosis and treatment of inherited hyperammonemia

    PubMed Central

    Mew, Nicholas Ah; Yudkoff, Marc; Tuchman, Mendel

    2014-01-01

    Stable isotopes have greatly contributed to our understanding of nitrogen metabolism and the urea cycle. The measurement of urea flux via isotopic methods has traditionally been utilized to determine total body protein synthesis in subjects with an intact urea cycle. However, isotopic studies of nitrogen metabolism are also a useful adjunct to conventional clinical investigations in the diagnosis and management of the inherited hyperammonemias. Such studies offer a safe non-invasive method of measuring the reduction of in vivo hepatic ureagenesis, and thus may provide a more accurate measure of phenotypic severity in affected patients. In addition, isotopic methods are ideally suited to evaluate the efficacy of novel therapies to augment urea production. PMID:24634704

  17. New bipolar leads for the study of atrial arrhythmias.

    PubMed Central

    Brenes-Pereira, C

    1997-01-01

    The electrocardiography study of atrial arrhythmias has been hindered by the frequent occurrence of a "hidden". P wave in standard lead recordings. We present a modified method of surface electrocardiography that proved helpful in our prospective study of 26 consecutive patients in whom traditional surface recordings did not show the atrial mechanism. We recorded leads I, II, and III in their customary positions, except that we repositioned a pertinent limb electrode at a precordial site, in order to identify a P wave. The 4 alternative sites that we found most helpful were at the high and low parasternal positions, both to the right and to the left of the sternum. Confirmatory examples are submitted. PMID:9205986

  18. Coregulation of respiratory sinus arrhythmia in adult romantic partners.

    PubMed

    Helm, Jonathan L; Sbarra, David A; Ferrer, Emilio

    2014-06-01

    Questions surrounding physiological interdependence in romantic relationships are gaining increased attention in the research literature. One specific form of interdependence, coregulation, can be defined as the bidirectional linkage of oscillating signals within optimal bounds. Conceptual and theoretical work suggests that physiological coregulation should be instantiated in romantic couples. Although these ideas are appealing, the central tenets of most coregulatory models await empirical evaluation. In the current study, we evaluate the covariation of respiratory sinus arrhythmia (RSA) in 32 romantic couples during a series of laboratory tasks using a cross-lagged panel model. During the tasks, men's and women's RSA were associated with their partners' previous RSA responses, and this pattern was stronger for those couples with higher relationship satisfaction. The findings are discussed in terms of their implications for attachment theory, as well as the association between relationships and health. PMID:24708502

  19. Developmental trajectories of respiratory sinus arrhythmia: associations with social responsiveness.

    PubMed

    Patriquin, Michelle A; Lorenzi, Jill; Scarpa, Angela; Bell, Martha Ann

    2014-04-01

    The present longitudinal study examined relations between respiratory sinus arrhythmia (RSA) development and social responsiveness characteristics associated with autism spectrum disorders. Group-based developmental trajectory modeling was used to characterize RSA development patterns in 106 typically developing children across 5, 10, 24, 36, and 48 months of age. A two-group model fit of RSA development was found: a "typically" and "atypically" developing group. The typical group gradually increased in RSA across 5-48 months of age. The atypical group, however, increased in RSA from 5 to 24 months and demonstrated a plateau or "delay" in RSA development from 24 to 48 months. The atypical RSA development group also demonstrated more difficulties in parent-reported social responsiveness at 48 months. The results support current literature that identifies RSA as a marker of social functioning level. PMID:23341170

  20. Developmental trajectories of respiratory sinus arrhythmia: Associations with social responsiveness

    PubMed Central

    Patriquin, Michelle A.; Lorenzi, Jill; Scarpa, Angela; Bell, Martha Ann

    2012-01-01

    The present longitudinal study examined relations between respiratory sinus arrhythmia (RSA) development and social responsiveness characteristics associated with autism spectrum disorders. Group-based developmental trajectory modeling was used to characterize RSA development patterns in 106 typically developing children across 5, 10, 24, 36, and 48 months of age. A two-group model fit of RSA development was found: a “typically” and “atypically” developing group. The typical group gradually increased in RSA across 5–48 months of age. The atypical group, however, increased in RSA from 5–24 months and demonstrated a plateau or “delay” in RSA development from 24–48 months. The atypical RSA development group also demonstrated more difficulties in parent-reported social responsiveness at 48 months. The results support current literature that identifies RSA as a marker of social functioning level. PMID:23341170

  1. Synthetic opioids and arrhythmia risk: a new paradigm?

    PubMed

    Schuller, Joseph L; Krantz, Mori J

    2012-09-01

    The most commonly prescribed class of medications in the United States for chronic severe pain is opioid analgesics. Due to their low cost and widespread availability, the synthetic opioids are popular choices among clinicians and patients. However, there is an increasingly recognized risk of QT prolongation with several drugs in this class, and recently propoxyphene (Darvon) was withdrawn from the market by the Food and Drug Administration (FDA) due to, in part, the risk of QT prolongation and ventricular arrhythmias Updated Epidemiological Review of Propoxyphene Safety. [FDA Alert]. Rockville, MD: U.S. Food and Drug Administration; 2010. Available from: http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM234383.pdf on 5 May 2012 . PMID:22770657

  2. Ultra-High-Definition Mapping of Atrial Arrhythmias.

    PubMed

    Bun, Sok-Sithikun; Latcu, Decebal Gabriel; Delassi, Tahar; Jamili, Mohammed El; Amoura, Alaa Al; Saoudi, Nadir

    2016-02-25

    The advantages of ultra-high-definition (UHD) mapping are presented in the context of different atrial arrhythmias, whether focal or macroreentrant. Not only are these sophisticated systems time-saving, but they also allow accurate identification of the substrate (scar quantification), as well as a more precise characterization of the critical isthmuses or focal sources of the atrial circuits. UHD mapping may become a standard approach for their curative treatment. This new technology allows automatic acquisition and accurate annotation of the electrograms, without the need for manual correction. Owing to better resolution, critical isthmuses and low-voltage regions of interest may now be successfully targeted without the need for entrainment maneuvers. Finally, the system also allows rapid assessment of the completeness of the lesions once delivered. (Circ J 2016; 80: 579-586). PMID:26853721

  3. Spectral analysis of sinus arrhythmia - A measure of mental effort

    NASA Technical Reports Server (NTRS)

    Vicente, Kim J.; Craig Thornton, D.; Moray, Neville

    1987-01-01

    The validity of the spectral analysis of sinus arrhythmia as a measure of mental effort was investigated using a computer simulation of a hovercraft piloted along a river as the experimental task. Strong correlation was observed between the subjective effort-ratings and the heart-rate variability (HRV) power spectrum between 0.06 and 0.14 Hz. Significant correlations were observed not only between subjects but, more importantly, within subjects as well, indicating that the spectral analysis of HRV is an accurate measure of the amount of effort being invested by a subject. Results also indicate that the intensity of effort invested by subjects cannot be inferred from the objective ratings of task difficulty or from performance.

  4. Respiratory sinus arrhythmia and cognitive functioning in children.

    PubMed

    Staton, Lori; El-Sheikh, Mona; Buckhalt, Joseph A

    2009-04-01

    We examined associations between children's cognitive performance and both basal respiratory sinus arrhythmia (RSA) and RSA regulation to a reaction time task. Cognitive performance was examined in the lab via standardized tests of cognitive functioning (Woodcock-Johnson III) and a reaction time task. Results suggest that a higher level of basal RSA is predictive of better performance on WJ III scales examining fluid intelligence (e.g., working memory, cognitive efficiency). RSA reactivity was not significantly related to cognitive performance. Results build on and extend the literature by demonstrating that, in typically developing elementary school age children, RSA is related to well-standardized measures of cognitive performance even after controlling for potential confounds. PMID:19107730

  5. [Research progress of quantitative analysis for respiratory sinus arrhythmia].

    PubMed

    Sun, Congcong; Zhang, Zhengbo; Wang, Buqing; Liu, Hongyun; Ang, Qing; Wang, Weidong

    2011-12-01

    Respiratory sinus arrhythmia (RSA) is known as fluctuations of heart rate associated with breathing. It has been increasingly used as a noninvasive index of cardiac vagal tone in psychophysiological research recently. Its analysis is often influenced or distorted by respiratory parameters, posture and action, etc. This paper reviews five methods of quantification, including the root mean square of successive differences (RMSSD), peak valley RSA (pvRSA), cosinor fitting, spectral analysis, and joint timing-frequency analysis (JTFA). Paced breathing, analysis of covariance, residua method and msRSA per liter tidal volume are adjustment strategies of measurement and analysis of RSA in this article as well. At last, some prospects of solutions of the problems of RSA research are given. PMID:22295719

  6. Arrhythmia causes lipid accumulation and reduced glucose uptake.

    PubMed

    Lenski, Matthias; Schleider, Gregor; Kohlhaas, Michael; Adrian, Lucas; Adam, Oliver; Tian, Qinghai; Kaestner, Lars; Lipp, Peter; Lehrke, Michael; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

    2015-01-01

    Atrial fibrillation (AF) is characterized by irregular contractions of atrial cardiomyocytes and increased energy demand. The aim of this study was to characterize the influence of arrhythmia on glucose and fatty acid (FA) metabolism in cardiomyocytes, mice and human left atrial myocardium. Compared to regular pacing, irregular (pseudo-random variation at the same number of contractions/min) pacing of neonatal rat cardiomyocytes induced shorter action potential durations and effective refractory periods and increased diastolic [Ca(2+)]c. This was associated with the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and AMP-activated protein kinase (AMPK). Membrane expression of fatty acid translocase (FAT/CD36) and (14)C-palmitic acid uptake were augmented while membrane expression of glucose transporter subtype 4 (GLUT-4) as well as (3)H-glucose uptake were reduced. Inhibition of AMPK and CaMKII prevented these arrhythmia-induced metabolic changes. Similar alterations of FA metabolism were observed in a transgenic mouse model (RacET) for spontaneous AF. Consistent with these findings samples of left atrial myocardium of patients with AF compared to matched samples of patients with sinus rhythm showed up-regulation of CaMKII and AMPK and increased membrane expression of FAT/CD36, resulting in lipid accumulation. These changes of FA metabolism were accompanied by decreased membrane expression of GLUT-4, increased glycogen content and increased expression of the pro-apoptotic protein bax. Irregular pacing of cardiomyocytes increases diastolic [Ca(2+)]c and activation of CaMKII and AMPK resulting in lipid accumulation, reduced glucose uptake and increased glycogen synthesis. These metabolic changes are accompanied by an activation of pro-apoptotic signalling pathways. PMID:26018791

  7. Role of ATP-sensitive K+ channels in cardiac arrhythmias.

    PubMed

    Nakaya, Haruaki

    2014-05-01

    The sarcolemmal adenosine triphosphate (ATP)-sensitive K(+) (sarcKATP) channel in the heart is a hetero-octamer comprising the pore-forming subunit Kir6.2 and the regulatory subunit sulfonylurea receptor SUR2A. By functional analysis of genetically engineered mice lacking sarcKATP channels, the pathophysiological roles of the K(+) channel in the heart have been extensively evaluated. Although mitochondrial KATP (mitoKATP) channel is proposed to be an important effector for the protection of ischemic myocardium and the inhibition of ischemia/reperfusion-induced ventricular arrhythmias, the molecular identity of mitoKATP channel has not been established. Although selective sarcKATP-channel blockers can prevent ischemia/reperfusion-induced ventricular arrhythmias by inhibiting the action potential shortening in the acute phase, the drugs may aggravate the ischemic damages due to intracellular Ca(2+) overload. The sarcKATP channel is also mandatory for optimal adaptation to hemodynamic stress such as sympathetic activation. Dysfunction of mutated sarcKATP channels in atrial cells may lead to electrical instability and atrial fibrillation. Recently, it has been proposed that the gain-of-function mutation of cardiac Kir6.1 channel can be a pathogenic substrate for J wave syndromes, a cause of idiopathic ventricular fibrillation as early repolarization syndrome or Brugada syndrome, whereas loss of function of the channel mutations can underlie sudden infant death syndrome. However, precise role of Kir6.1 channels in cardiac cells remains to be defined and further study may be needed to clarify the role of Kir6.1 channel in the heart. PMID:24367007

  8. Prevention of reoxygenation-induced arrhythmias in guinea pig papillary muscles.

    PubMed

    Hayashi, H; Terada, H; Katoh, H; McDonald, T F

    1996-06-01

    Effects of various agents on reoxygenation-induced arrhythmias, action potentials, and tension of guinea pig papillary muscles were recorded to investigate the site of action. Triggered activities due to delayed afterdepolarizations (DADs) and aftercontractions were elicited on reoxygenation after 60-min substrate-free hypoxia. Low extracellular Ca2+ (0.1 mM) abolished arrhythmias, and high Ca2+ (4.9 mM) increased the amplitudes of DADs and aftercontractions. D-600 at the high concentration (20 microM) decreased the incidence of arrhythmias (p < 0.05 vs. no drug) and decreased the recovery of developed tension after reoxygenation (p < 0.001). Ryanodine (1 microM) abolished aftercontractions and arrhythmias but did not affect the recovery of developed tension. Tetrodotoxin (TTX 3 microM) and nicorandil (100 microM) decreased the incidence of arrhythmias (p < 0.05), but did not affect the recovery of developed tension or the amplitudes of aftercontractions. TTX caused only a slight decrease in Ca2+ transients in a fluo-3-loaded guinea pig ventricular myocyte. The Ca2+ entry through the Ca2+ channels apparently synchronized Ca2+ release from the sarcoplasmic reticulum, and D-600 at the high concentration apparently decreased the incidence of arrhythmias. TTX and nicorandil decreased arrhythmias, probably by decreasing the Na+ current or by increasing the ATP-sensitive K+ current, respectively. PMID:8761848

  9. Proton Pump Inhibitor Use Is not Associated with Cardiac Arrhythmia in Critically Ill Patients

    PubMed Central

    Chen, Kenneth P.; Lee, Joon; Mark, Roger G.; Feng, Mornin; Celi, Leo A.; Danziger, John

    2016-01-01

    Hypomagnesemia can lead to cardiac arrhythmias. Recently, observational data has linked chronic proton pump inhibitor (PPI) exposure to hypomagnesemia. Whether PPI exposure increases the risk for arrhythmias has not been well studied. Using a large, single center inception cohort of critically ill patients, we examined whether PPI exposure was associated with admission electrocardiogram (ECG) readings of a cardiac arrhythmia in over 8000 patients. There were 24.5% PPI users while 6% were taking a histamine 2 antagonist. 14.3% had a cardiac arrhythmia. PPI use was associated with a 1.18 (95% CI=1.02–1.36, p=0.02) unadjusted and 0.96 (95% CI=0.83–1.12, p=0.62) adjusted risk of arrhythmia. Amongst diuretic users (n=2468), PPI use was similarly not associated with an increased risk of cardiac arrhythmia. In summary, in a large cohort of critically ill patients, PPI exposure is not associated with an increased risk of cardiac arrhythmia. PMID:25655574

  10. Transgenerational Epigenetic Inheritance: myths and mechanisms

    PubMed Central

    Heard, Edith; Martienssen, Robert A.

    2014-01-01

    Since the human genome was sequenced, the term “epigenetics” is increasingly being associated with the hope that we are more than just the sum of our genes. Might what we eat, the air we breathe, or even the emotions we feel, influence not only our genes but those of descendents? The environment can certainly influence gene expression, and can lead to disease, but trans-generational consequences are another matter. While the inheritance of epigenetic characters can certainly occur - particularly in plants – how much is due to the environment and the extent to which it happens in humans, remains unclear. PMID:24679529

  11. The inherited bone marrow failure syndromes.

    PubMed

    Chirnomas, S Deborah; Kupfer, Gary M

    2013-12-01

    Molecular pathogenesis may be elucidated for inherited bone marrow failure syndromes (IBMFS). The study and presentation of the details of their molecular biology and biochemistry is warranted for appropriate diagnosis and management of afflicted patients and to identify the physiology of the normal hematopoiesis and mechanisms of carcinogenesis. Several themes have emerged within each subsection of IBMFS, including the ribosomopathies, which include ribosome assembly and ribosomal RNA processing. The Fanconi anemia pathway has become interdigitated with the familial breast cancer syndromes. In this article, the diseases that account for most IBMFS diagnoses are analyzed. PMID:24237972

  12. Extending the SSCLI to Support Dynamic Inheritance

    NASA Astrophysics Data System (ADS)

    Redondo, Jose Manuel; Ortin, Francisco; Perez-Schofield, J. Baltasar Garcia

    This paper presents a step forward on a research trend focused on increasing runtime adaptability of commercial JIT-based virtual machines, describing how to include dynamic inheritance into this kind of platforms. A considerable amount of research aimed at improving runtime performance of virtual machines has converted them into the ideal support for developing different types of software products. Current virtual machines do not only provide benefits such as application interoperability, distribution and code portability, but they also offer a competitive runtime performance.

  13. A common SCN5A polymorphism attenuates a severe cardiac phenotype caused by a nonsense SCN5A mutation in a Chinese family with an inherited cardiac conduction defect

    PubMed Central

    Niu, Dau‐Ming; Hwang, Betau; Hwang, Han‐Wei; Wang, Nana H; Wu, Jer‐Yuarn; Lee, Pi‐Chang; Chien, Jen‐Chung; Shieh, Ru‐Chi

    2006-01-01

    The SCN5A mutations have been associated with a variety of arrhythmic disorders, including type 3 long QT syndrome (LQT3), Brugada syndrome and inherited cardiac conduction defects. The relationship between genotype and phenotype in SCN5A mutations is complex. Some SCN5A mutations may cause death or severe manifestations in some people and may not cause any symptoms or arrhythmias in others. The causes of these unpredictable clinical manifestations remain incompletely understood. The molecular basis of a four‐generation family with cardiac conduction abnormalities was studied and whether variants in the SCN5A gene could account for the cardiac phenotypic variability observed in this family was determined. A novel mutation (W1421X) of SCN5A was identified in a four‐generation family with cardiac conduction abnormalities and several cases of sudden death. Most family members who carry this W1421X mutation have developed major clinical manifestations or electrocardiographic abnormalities, both of which became more prominent as the patients grew older. However, the 73‐year‐old grandfather, who carried both the W1421X and R1193Q mutations, had thus far remained healthy and presented with only subtle electrocardiographic abnormalities, whereas most of his offspring, who carried a single mutation (W1421X), had died early or had major disease manifestations. This observation suggests that the R1193Q mutation has a complementary role in alleviating the deleterious effects conferred by W1421X in the function of the SCN5A gene. This report provides a good model to explain the mechanism of penetrance of genetic disorders. PMID:16707561

  14. Global Carrier Rates of Rare Inherited Disorders Using Population Exome Sequences

    PubMed Central

    Fujikura, Kohei

    2016-01-01

    Exome sequencing has revealed the causative mutations behind numerous rare, inherited disorders, but it is challenging to find reliable epidemiological values for rare disorders. Here, I provide a genetic epidemiology method to identify the causative mutations behind rare, inherited disorders using two population exome sequences (1000 Genomes and NHLBI). I created global maps of carrier rate distribution for 18 recessive disorders in 16 diverse ethnic populations. Out of a total of 161 mutations associated with 18 recessive disorders, I detected 24 mutations in either or both exome studies. The genetic mapping revealed strong international spatial heterogeneities in the carrier patterns of the inherited disorders. I next validated this methodology by statistically evaluating the carrier rate of one well-understood disorder, sickle cell anemia (SCA). The population exome-based epidemiology of SCA [African (allele frequency (AF) = 0.0454, N = 2447), Asian (AF = 0, N = 286), European (AF = 0.000214, N = 4677), and Hispanic (AF = 0.0111, N = 362)] was not significantly different from that obtained from a clinical prevalence survey. A pair-wise proportion test revealed no significant differences between the two exome projects in terms of AF (46/48 cases; P > 0.05). I conclude that population exome-based carrier rates can form the foundation for a prospectively maintained database of use to clinical geneticists. Similar modeling methods can be applied to many inherited disorders. PMID:27219052

  15. Global Carrier Rates of Rare Inherited Disorders Using Population Exome Sequences.

    PubMed

    Fujikura, Kohei

    2016-01-01

    Exome sequencing has revealed the causative mutations behind numerous rare, inherited disorders, but it is challenging to find reliable epidemiological values for rare disorders. Here, I provide a genetic epidemiology method to identify the causative mutations behind rare, inherited disorders using two population exome sequences (1000 Genomes and NHLBI). I created global maps of carrier rate distribution for 18 recessive disorders in 16 diverse ethnic populations. Out of a total of 161 mutations associated with 18 recessive disorders, I detected 24 mutations in either or both exome studies. The genetic mapping revealed strong international spatial heterogeneities in the carrier patterns of the inherited disorders. I next validated this methodology by statistically evaluating the carrier rate of one well-understood disorder, sickle cell anemia (SCA). The population exome-based epidemiology of SCA [African (allele frequency (AF) = 0.0454, N = 2447), Asian (AF = 0, N = 286), European (AF = 0.000214, N = 4677), and Hispanic (AF = 0.0111, N = 362)] was not significantly different from that obtained from a clinical prevalence survey. A pair-wise proportion test revealed no significant differences between the two exome projects in terms of AF (46/48 cases; P > 0.05). I conclude that population exome-based carrier rates can form the foundation for a prospectively maintained database of use to clinical geneticists. Similar modeling methods can be applied to many inherited disorders. PMID:27219052

  16. Proposition of novel classification approach and features for improved real-time arrhythmia monitoring.

    PubMed

    Kim, Yoon Jae; Heo, Jeong; Park, Kwang Suk; Kim, Sungwan

    2016-08-01

    Arrhythmia refers to a group of conditions in which the heartbeat is irregular, fast, or slow due to abnormal electrical activity in the heart. Some types of arrhythmia such as ventricular fibrillation may result in cardiac arrest or death. Thus, arrhythmia detection becomes an important issue, and various studies have been conducted. Additionally, an arrhythmia detection algorithm for portable devices such as mobile phones has recently been developed because of increasing interest in e-health care. This paper proposes a novel classification approach and features, which are validated for improved real-time arrhythmia monitoring. The classification approach that was employed for arrhythmia detection is based on the concept of ensemble learning and the Taguchi method and has the advantage of being accurate and computationally efficient. The electrocardiography (ECG) data for arrhythmia detection was obtained from the MIT-BIH Arrhythmia Database (n=48). A novel feature, namely the heart rate variability calculated from 5s segments of ECG, which was not considered previously, was used. The novel classification approach and feature demonstrated arrhythmia detection accuracy of 89.13%. When the same data was classified using the conventional support vector machine (SVM), the obtained accuracy was 91.69%, 88.14%, and 88.74% for Gaussian, linear, and polynomial kernels, respectively. In terms of computation time, the proposed classifier was 5821.7 times faster than conventional SVM. In conclusion, the proposed classifier and feature showed performance comparable to those of previous studies, while the computational complexity and update interval were highly reduced. PMID:27318329

  17. Ventricular Arrhythmias in Apparently Normal Hearts: Who Needs an Implantable Cardiac Defibrillator?

    PubMed

    Tan, Alex Y; Ellenbogen, Kenneth

    2016-09-01

    Idiopathic ventricular tachycardia is often considered a benign form of ventricular arrhythmia in patients without apparent structural heart disease. However, a subset of patients may develop malignant ventricular arrhythmias and present with syncope and sudden cardiac arrest. Survivors of cardiac arrest are candidates for implantable cardiac defibrillators (ICDs). The indications for ICDs in patients with less than a full-blown cardiac arrest presentation but with electrocardiographically high-risk ectopy features remain uncertain. This article addresses some of the uncertainties and pitfalls in ICD risk stratification in this patient group and explores potential mechanisms for malignant conversion of benign premature ventricular complexes to sustained arrhythmia. PMID:27521094

  18. Spectrum of Ventricular Arrhythmias Arising from Papillary Muscle in the Structurally Normal Heart.

    PubMed

    Naksuk, Niyada; Kapa, Suraj; Asirvatham, Samuel J

    2016-09-01

    Papillary muscle is an endocavitary structure that can give rise to ventricular arrhythmias in a structurally normal heart. Its manifestation is generally benign. The papillary muscle's complex anatomy and the presence of intermixed Purkinje fibers can create a substrate for idiopathic ventricular fibrillation. Although differentiating ventricular arrhythmias originating from the papillary muscle and the fascicles is challenging and not always possible, the distinction may be helpful for planning ablation. The propensity for difficulty with ablation of papillary arrhythmias results in a variable success rate. Improvement in techniques to stabilize the catheter, use of imaging, and methods of energy delivery are required to improve ablation outcomes. PMID:27521089

  19. Ultrasound of Inherited vs. Acquired Demyelinating Polyneuropathies

    PubMed Central

    Zaidman, Craig M.; Harms, Matthew B.; Pestronk, Alan

    2013-01-01

    Introduction We compared features of nerve enlargement in inherited and acquired demyelinating neuropathies using ultrasound. Methods We measured median and ulnar nerve cross-sectional areas in proximal and distal regions in 128 children and adults with inherited (Charcot-Marie Tooth-1 (CMT-1) (n=35)) and acquired (Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (n=55), Guillaine-Barre Syndrome (GBS) (n=21) and Multifocal Motor Neuropathy (MMN) (n=17)) demyelinating neuropathies. We classified nerve enlargement by degree and number of regions affected. We defined patterns of nerve enlargement as: none- no enlargement; mild-nerves enlarged but never more than twice normal; regional- nerves normal at at least one region and enlarged more than twice normal at atleast one region; diffuse- nerves enlarged at all four regions with atleast one region more than twice normal size. Results Nerve enlargement was commonly diffuse (89%) and generally more than twice normal size in CMT-1, but not (p<0.001) in acquired disorders which mostly had either no, mild or regional nerve enlargement (CIDP (64%), GBS (95%), and MMN (100%)). In CIDP, subjects treated within three months of disease onset had less nerve enlargement than those treated later. Discussion Ultrasound identified patterns of diffuse nerve enlargement can be used to screen patients suspected of having CMT-1. Normal, mildly, or regionally enlarged nerves in demyelinating polyneuropathy suggests an acquired etiology. Early treatment in CIDP may impede nerve enlargement. PMID:24101129

  20. Information accumulation system by inheritance and diffusion

    NASA Astrophysics Data System (ADS)

    Shin, J. K.

    2009-09-01

    This paper suggests a new model, called as the IAS (Information Accumulation System), for the description of the dynamic process that people use to accumulate their information (knowledge or opinion) for specific issues. Using the concept of information, both the internal and the external mechanism of the opinion dynamics are treated on a unified frame. The information is quantified as a real number with fixed bounds. New concepts, such as inheritance and differential absorption, are incorporated in IAS in addition to the conventional diffusive interaction between people. Thus, the dynamics of the IAS are governed by following three factors: inheritance rate, diffusivity and absorption rate. The original set of equations was solved with an agent based modeling technique. In addition, the individual equations for each of the agents were assembled and transformed into a set of equations for the ensemble averages, which are greatly reduced in number and can be solved analytically. The example simulations showed interesting results such as the critical behavior with respect to diffusivity, the information polarization out of zero-sum news and the dependence of the solutions on the initial conditions alone. The results were speculated in relation to today’s modern society where the diffusivity of information has been greatly increased through the internet and mobile phones.

  1. Oxidative stress in inherited mitochondrial diseases.

    PubMed

    Hayashi, Genki; Cortopassi, Gino

    2015-11-01

    Mitochondria are a source of reactive oxygen species (ROS). Mitochondrial diseases are the result of inherited defects in mitochondrially expressed genes. One potential pathomechanism for mitochondrial disease is oxidative stress. Oxidative stress can occur as the result of increased ROS production or decreased ROS protection. The role of oxidative stress in the five most common inherited mitochondrial diseases, Friedreich ataxia, LHON, MELAS, MERRF, and Leigh syndrome (LS), is discussed. Published reports of oxidative stress involvement in the pathomechanisms of these five mitochondrial diseases are reviewed. The strongest evidence for an oxidative stress pathomechanism among the five diseases was for Friedreich ataxia. In addition, a meta-analysis was carried out to provide an unbiased evaluation of the role of oxidative stress in the five diseases, by searching for "oxidative stress" citation count frequency for each disease. Of the five most common mitochondrial diseases, the strongest support for oxidative stress is for Friedreich ataxia (6.42%), followed by LHON (2.45%), MELAS (2.18%), MERRF (1.71%), and LS (1.03%). The increased frequency of oxidative stress citations was significant relative to the mean of the total pool of five diseases (p<0.01) and the mean of the four non-Friedreich diseases (p<0.0001). Thus there is support for oxidative stress in all five most common mitochondrial diseases, but the strongest, significant support is for Friedreich ataxia. PMID:26073122

  2. Human handedness: an inherited evolutionary trait.

    PubMed

    Forrester, Gillian S; Quaresmini, Caterina; Leavens, David A; Mareschal, Denis; Thomas, Michael S C

    2013-01-15

    Our objective was to demonstrate that human population-level, right-handedness, is not species specific, precipitated from language areas in the brain, but rather is context specific and inherited from a behavior common to both humans and great apes. In general, previous methods of assessing human handedness have neglected to consider the context of action, or employ methods suitable for direct comparison across species. We employed a bottom-up, context-sensitive method to quantitatively assess manual actions in right-handed, typically developing children during naturalistic behavior. By classifying the target to which participants directed a manual action, as animate (social partner, self) or inanimate (non-living functional objects), we found that children demonstrated a significant right-hand bias for manual actions directed toward inanimate targets, but not for manual actions directed toward animate targets. This pattern was revealed at both the group and individual levels. We used a focal video sampling, corpus data-mining approach to allow for direct comparisons with captive gorillas (Forrester et al. Animal Cognition 2011;14(6):903-7) and chimpanzees (Forrester et al. Animal Cognition, in press). Comparisons of handedness patters support the view that population-level, human handedness, and its origin in cerebral lateralization is not a new or human-unique characteristic. These data are consistent with the theory that human right-handedness is a trait developed through tool use that was inherited from an ancestor common to both humans and great apes. PMID:23022751

  3. Inherited cardiomyopathies caused by troponin mutations

    PubMed Central

    Lu, Qun-Wei; Wu, Xiao-Yan; Morimoto, Sachio

    2013-01-01

    Genetic investigations of cardiomyopathy in the recent two decades have revealed a large number of mutations in the genes encoding sarcomeric proteins as a cause of inherited hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive cardiomyopathy (RCM). Most functional analyses of the effects of mutations on cardiac muscle contraction have revealed significant changes in the Ca2+-regulatory mechanism, in which cardiac troponin (cTn) plays important structural and functional roles as a key regulatory protein. Over a hundred mutations have been identified in all three subunits of cTn, i.e., cardiac troponins T, I, and C. Recent studies on cTn mutations have provided plenty of evidence that HCM- and RCM-linked mutations increase cardiac myofilament Ca2+ sensitivity, while DCM-linked mutations decrease it. This review focuses on the functional consequences of mutations found in cTn in terms of cardiac myofilament Ca2+ sensitivity, ATPase activity, force generation, and cardiac troponin I phosphorylation, to understand potential molecular and cellular pathogenic mechanisms of the three types of inherited cardiomyopathy. PMID:23610579

  4. Analyticity of strictly static and strictly stationary, inheriting and non-inheriting Einstein-Maxwell solutions

    NASA Astrophysics Data System (ADS)

    Tod, Paul

    2007-07-01

    Following the technique of Müller zum Hagen (Proc. Camb. Phil. Soc. 67: 415-421, 1970) we show that strictly static and strictly stationary solutions of the Einstein-Maxwell equations are analytic in harmonic coordinates. This holds whether or not the Maxwell field inherits the symmetry.

  5. Brugada syndrome in the paediatric population: a comprehensive approach to clinical manifestations, diagnosis, and management.

    PubMed

    Gonzalez Corcia, M Cecilia; de Asmundis, Carlo; Chierchia, Gian-Battista; Brugada, Pedro

    2016-08-01

    Brugada syndrome is an inherited arrhythmogenic disorder, characterised by coved-type ST-segment elevation in the right precordial leads, and is associated with increased risk of sudden death. It is genetically and clinically heterogeneous, presenting typically in the fourth or fifth decade of life. The prevalence of Brugada syndrome in the paediatric population is low compared with the adult population. Interestingly, over the last several years, there has been growing evidence in the literature of onset of the disease during childhood. Most of the paediatric cases reported in the literature consist of asymptomatic Brugada syndrome; however, some patients manifest the disease at different regions of the cardiac conduction system at a young age. Early expression of the disease can be affected by multiple factors, including genetic substrate, hormonal changes, and still unknown environmental exposures. The initial manifestation of Brugada syndrome in children can include sinus node dysfunction and atrial arrhythmias. Brugada syndrome can also manifest as ventricular arrhythmias leading to sudden death at an early age. In symptomatic children, performance of the ajmaline test by an experienced team can be safely used as a diagnostic tool to unmask latent Brugada syndrome. Defining indications for an implantable cardioverter defibrillator in children with the diagnosis of Brugada syndrome remains challenging. Given the rarity of the syndrome in children, most paediatric cardiologists will only rarely see a young patient with Brugada syndrome and there is still no universal consensus regarding the optimal management approach. Care should be individualised according to the specific clinical presentation, taking into account the family history, genetic data, and the family's specific preferences. PMID:27151277

  6. Effect of fish oil on arrhythmias and mortality: systematic review

    PubMed Central

    León, Hernando; Shibata, Marcelo C; Sivakumaran, Soori; Dorgan, Marlene; Chatterley, Trish

    2008-01-01

    Objective To synthesise the literature on the effects of fish oil—docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)—on mortality and arrhythmias and to explore dose response and formulation effects. Design Systematic review and meta-analysis. Data sources Medline, Embase, the Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, Allied and Complementary Medicine, Academic OneFile, ProQuest Dissertations and Theses, Evidence-Based Complementary Medicine, and LILACS. Studies reviewed Randomised controlled trials of fish oil as dietary supplements in humans. Data extraction The primary outcomes of interest were the arrhythmic end points of appropriate implantable cardiac defibrillator intervention and sudden cardiac death. The secondary outcomes were all cause mortality and death from cardiac causes. Subgroup analyses included the effect of formulations of EPA and DHA on death from cardiac causes and effects of fish oil in patients with coronary artery disease or myocardial infarction. Data synthesis 12 studies totalling 32 779 patients met the inclusion criteria. A neutral effect was reported in three studies (n=1148) for appropriate implantable cardiac defibrillator intervention (odds ratio 0.90, 95% confidence interval 0.55 to 1.46) and in six studies (n=31 111) for sudden cardiac death (0.81, 0.52 to 1.25). 11 studies (n=32 439 and n=32 519) provided data on the effects of fish oil on all cause mortality (0.92, 0.82 to 1.03) and a reduction in deaths from cardiac causes (0.80, 0.69 to 0.92). The dose-response relation for DHA and EPA on reduction in deaths from cardiac causes was not significant. Conclusions Fish oil supplementation was associated with a significant reduction in deaths from cardiac causes but had no effect on arrhythmias or all cause mortality. Evidence to recommend an optimal formulation of EPA or DHA to reduce these outcomes is insufficient. Fish oils are a heterogeneous product, and the optimal formulations

  7. Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction.

    PubMed

    Li, Chang-Yi; Li, Yi-Gang

    2015-01-01

    Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control. PMID:26793403

  8. Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction

    PubMed Central

    Li, Chang-Yi; Li, Yi-Gang

    2015-01-01

    Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control. PMID:26793403

  9. Study of features based on nonlinear dynamical modeling in ECG arrhythmia detection and classification.

    PubMed

    Owis, Mohamed I; Abou-Zied, Ahmed H; Youssef, Abou-Bakr M; Kadah, Yasser M

    2002-07-01

    We present a study of the nonlinear dynamics of electrocardiogram (ECG) signals for arrhythmia characterization. The correlation dimension and largest Lyapunov exponent are used to model the chaotic nature of five different classes of ECG signals. The model parameters are evaluated for a large number of real ECG signals within each class and the results are reported. The presented algorithms allow automatic calculation of the features. The statistical analysis of the calculated features indicates that they differ significantly between normal heart rhythm and the different arrhythmia types and, hence, can be rather useful in ECG arrhythmia detection. On the other hand, the results indicate that the discrimination between different arrhythmia types is difficult using such features. The results of this work are supported by statistical analysis that provides a clear outline for the potential uses and limitations of these features. PMID:12083309

  10. Getting your signals straight. Comparing radio-frequency ablation and cryoablation for treating cardiac arrhythmias.

    PubMed

    2010-08-01

    Radio-frequency ablation has proven to be an effective method for treating cardiac arrhythmias. However, a newer treatment method called cryoablation is becoming increasingly popular. In this article, we discuss the advantages and disadvantages of each. PMID:21305902

  11. Extracellular photosensitization reaction progress and effect on myocardial cell necrosis for arrhythmia treatment application

    NASA Astrophysics Data System (ADS)

    Ogawa, Emiyu; Takahashi, Mei; Ito, Arisa; Arai, Tsunenori

    2013-06-01

    We investigated detailed extracellular photosensitization reaction effect on rat myocardial cells and the photosensitization reaction progress in a well to study a new application of photodynamic therapy for arrhythmia therapy.

  12. Mechanisms of Non-Genetic Inheritance and Psychiatric Disorders

    PubMed Central

    Toth, Miklos

    2015-01-01

    Inheritance is typically associated with the Mendelian transmission of information from parents to offspring by alleles (DNA sequence). However, empirical data clearly suggest that traits can be acquired from ancestors by mechanisms that do not involve genetic alleles, referred to as non-genetic inheritance. Information that is non-genetically transmitted across generations includes parental experience and exposure to certain environments, but also parental mutations and polymorphisms, because they can change the parental ‘intrinsic' environment. Non-genetic inheritance is not limited to the first generation of the progeny, but can involve the grandchildren and even further generations. Non-genetic inheritance has been observed for multiple traits including overall development, cardiovascular risk and metabolic symptoms, but this review will focus on the inheritance of behavioral abnormalities pertinent to psychiatric disorders. Multigenerational non-genetic inheritance is often interpreted as the transmission of epigenetic marks, such as DNA methylation and chromatin modifications, via the gametes (transgenerational epigenetic inheritance). However, information can be carried across generations by a large number of bioactive substances, including hormones, cytokines, and even microorganisms, without the involvement of the gametes. We reason that this broader definition of non-genetic inheritance is more appropriate, especially in the context of psychiatric disorders, because of the well-recognized role of parental and early life environmental factors in later life psychopathology. Here we discuss the various forms of non-genetic inheritance in humans and animals, as well as rodent models of psychiatric conditions to illustrate possible mechanisms. PMID:24889369

  13. Identification of chromosome inheritance modifiers in Drosophila melanogaster.

    PubMed Central

    Dobie, K W; Kennedy, C D; Velasco, V M; McGrath, T L; Weko, J; Patterson, R W; Karpen, G H

    2001-01-01

    Faithful chromosome inheritance is a fundamental biological activity and errors contribute to birth defects and cancer progression. We have performed a P-element screen in Drosophila melanogaster with the aim of identifying novel candidate genes involved in inheritance. We used a "sensitized" minichromosome substrate (J21A) to screen approximately 3,000 new P-element lines for dominant effects on chromosome inheritance and recovered 78 Sensitized chromosome inheritance modifiers (Scim). Of these, 69 decreased minichromosome inheritance while 9 increased minichromosome inheritance. Fourteen mutations are lethal or semilethal when homozygous and all exhibit dramatic mitotic defects. Inverse PCR combined with genomic analyses identified P insertions within or close to genes with previously described inheritance functions, including wings apart-like (wapl), centrosomin (cnn), and pavarotti (pav). Further, lethal insertions in replication factor complex 4 (rfc4) and GTPase-activating protein 1 (Gap1) exhibit specific mitotic chromosome defects, discovering previously unknown roles for these proteins in chromosome inheritance. The majority of the lines represent mutations in previously uncharacterized loci, many of which have human homologs, and we anticipate that this collection will provide a rich source of mutations in new genes required for chromosome inheritance in metazoans. PMID:11290718

  14. Identification and Characterization of a Compound That Protects Cardiac Tissue from Human Ether-à-go-go-related Gene (hERG)-related Drug-induced Arrhythmias*

    PubMed Central

    Potet, Franck; Lorinc, Amanda N.; Chaigne, Sebastien; Hopkins, Corey R.; Venkataraman, Raghav; Stepanovic, Svetlana Z.; Lewis, L. Michelle; Days, Emily; Sidorov, Veniamin Y.; Engers, Darren W.; Zou, Beiyan; Afshartous, David; George, Alfred L.; Campbell, Courtney M.; Balser, Jeffrey R.; Li, Min; Baudenbacher, Franz J.; Lindsley, Craig W.; Weaver, C. David; Kupershmidt, Sabina

    2012-01-01

    The human Ether-à-go-go-related gene (hERG)-encoded K+ current, IKr is essential for cardiac repolarization but is also a source of cardiotoxicity because unintended hERG inhibition by diverse pharmaceuticals can cause arrhythmias and sudden cardiac death. We hypothesized that a small molecule that diminishes IKr block by a known hERG antagonist would constitute a first step toward preventing hERG-related arrhythmias and facilitating drug discovery. Using a high-throughput assay, we screened a library of compounds for agents that increase the IC70 of dofetilide, a well characterized hERG blocker. One compound, VU0405601, with the desired activity was further characterized. In isolated, Langendorff-perfused rabbit hearts, optical mapping revealed that dofetilide-induced arrhythmias were reduced after pretreatment with VU0405601. Patch clamp analysis in stable hERG-HEK cells showed effects on current amplitude, inactivation, and deactivation. VU0405601 increased the IC50 of dofetilide from 38.7 to 76.3 nm. VU0405601 mitigates the effects of hERG blockers from the extracellular aspect primarily by reducing inactivation, whereas most clinically relevant hERG inhibitors act at an inner pore site. Structure-activity relationships surrounding VU0405601 identified a 3-pyridiyl and a naphthyridine ring system as key structural components important for preventing hERG inhibition by multiple inhibitors. These findings indicate that small molecules can be designed to reduce the sensitivity of hERG to inhibitors. PMID:23033485

  15. Transient myocardial ischaemia after acute myocardial infarction does not induce ventricular arrhythmias.

    PubMed Central

    Currie, P; Saltissi, S

    1993-01-01

    OBJECTIVE--To see whether transient myocardial ischaemia on ambulatory monitoring after myocardial infarction is associated with ventricular arrhythmias. DESIGN--A prospective study. SETTING--The coronary care unit, general medical wards, and cardiorespiratory department of a major teaching hospital. PATIENTS--203 consecutive patients without specific exclusion criteria admitted with acute myocardial infarction. INTERVENTIONS--24 hour ambulatory electrocardiographic monitoring for ventricular arrhythmias and ST depression both early (mean 6.3 days after infarction, n = 201) and late (mean 38 days, n = 177). MAIN OUTCOME MEASURES--Episodes of myocardial ischaemia were identified during ambulatory monitoring by transient ST depression of > or = 1.0 mm lasting for > or = 30 s. Ventricular arrhythmias were single extrasystoles, couplets, or ventricular tachycardia. RESULTS--All ventricular arrhythmias were significantly more frequent in late than early monitoring. The arrhythmias included couplets (in 83/174 (48%) v 49/200 (25%) of patients, p = 0.0000028) and ventricular tachycardia (29/174 (17%) v 15/199 (8%), p = 0.0064). Patients with ST depression (29 early; 56 late), compared with those without ischaemia, did not experience a significant increase in single extrasystoles, couplets (31% v 23% early; 47% v 48% late), or ventricular tachycardia (3% v 8% early; 18% v 16% late). Even patients with frequent (> or = 3 episodes), and deep (> or = 1.5 mm) or prolonged (> or = 20 min) ST depression had no increase in arrhythmias. CONCLUSIONS--Ventricular arrhythmias after myocardial infarction are not associated with transient myocardial ischaemia during daily activities. This study does not support the belief that to abolish silent ischaemia would reduce the incidence of sudden death due to uncontrollable ventricular arrhythmias after myocardial infarction. PMID:8489860

  16. Inhibition of Rac1 reduces store overload-induced calcium release and protects against ventricular arrhythmia.

    PubMed

    Zhang, Lili; Lu, Xiangru; Gui, Le; Wu, Yan; Sims, Stephen M; Wang, Guoping; Feng, Qingping

    2016-08-01

    Rac1 is a small GTPase and plays key roles in multiple cellular processes including the production of reactive oxygen species (ROS). However, whether Rac1 activation during myocardial ischaemia and reperfusion (I/R) contributes to arrhythmogenesis is not fully understood. We aimed to study the effects of Rac1 inhibition on store overload-induced Ca(2+) release (SOICR) and ventricular arrhythmia during myocardial I/R. Adult Rac1(f/f) and cardiac-specific Rac1 knockdown (Rac1(ckd) ) mice were subjected to myocardial I/R and their electrocardiograms (ECGs) were monitored for ventricular arrhythmia. Myocardial Rac1 activity was increased and ventricular arrhythmia was induced during I/R in Rac1(f/f) mice. Remarkably, I/R-induced ventricular arrhythmia was significantly decreased in Rac1(ckd) compared to Rac1(f/f) mice. Furthermore, treatment with Rac1 inhibitor NSC23766 decreased I/R-induced ventricular arrhythmia. Ca(2+) imaging analysis showed that in response to a 6 mM external Ca(2+) concentration challenge, SOICR was induced with characteristic spontaneous intracellular Ca(2+) waves in Rac1(f/f) cardiomyocytes. Notably, SOICR was diminished by pharmacological and genetic inhibition of Rac1 in adult cardiomyocytes. Moreover, I/R-induced ROS production and ryanodine receptor 2 (RyR2) oxidation were significantly inhibited in the myocardium of Rac1(ckd) mice. We conclude that Rac1 activation induces ventricular arrhythmia during myocardial I/R. Inhibition of Rac1 suppresses SOICR and protects against ventricular arrhythmia. Blockade of Rac1 activation may represent a new paradigm for the treatment of cardiac arrhythmia in ischaemic heart disease. PMID:27222313

  17. Plan of Action for Inherited Cardiovascular Diseases: Synthesis of Recommendations and Action Algorithms.

    PubMed

    Barriales-Villa, Roberto; Gimeno-Blanes, Juan Ramón; Zorio-Grima, Esther; Ripoll-Vera, Tomás; Evangelista-Masip, Artur; Moya-Mitjans, Angel; Serratosa-Fernández, Luis; Albert-Brotons, Dimpna C; García-Pinilla, José Manuel; García-Pavía, Pablo

    2016-03-01

    The term inherited cardiovascular disease encompasses a group of cardiovascular diseases (cardiomyopathies, channelopathies, certain aortic diseases, and other syndromes) with a number of common characteristics: they have a genetic basis, a familial presentation, a heterogeneous clinical course, and, finally, can all be associated with sudden cardiac death. The present document summarizes some important concepts related to recent advances in sequencing techniques and understanding of the genetic bases of these diseases. We propose diagnostic algorithms and clinical practice recommendations and discuss controversial aspects of current clinical interest. We highlight the role of multidisciplinary referral units in the diagnosis and treatment of these conditions. PMID:26856793

  18. Conjunction of Endocardial and Coronary Venous System Mapping to Ablate Ventricular Arrhythmias

    PubMed Central

    Wo, Hung-Ta; Yeh, Jih-Kai; Chang, Po-Cheng; Wen, Ming-Shien; Wang, Chun-Chieh; Chou, Chung-Chuan; Yeh, San-Jou

    2016-01-01

    Background Ablation of idiopathic ventricular arrhythmias (VAs) with epicardial or intramural origins is technically challenging. Herein, we have described the successful ablation of left VAs via the coronary venous system (CVS) in conjunction with endocardial map guided by three-dimensional electroanatomical map in six patients. Methods Out of a total consecutive 84 patients with symptomatic idiopathic VAs, radiofrequency ablation via the CVS was performed on six patients (7%). Furthermore, we reviewed patient records and electrophysiologic studies with respect to clinical characteristics. Results Activation map was conducted in 5 patients, and the earliest activation sites were identified within the CVS. The preceding times to the onset of QRS complex were longer than those at the earliest endocardial sites (36.2 ± 5.6 ms vs. 14.2 ± 6.4 ms, p = 0.02, n = 5). Spiky fractionated long-duration potentials were recorded at the successful ablation sites in all 5 patients. The other patient received pacemapping only because of few spontaneous VAs during the procedure, and the best pacemap spot was found within the CVS. Irrigated catheters were required in 4 out of 6 patients because VAs were temporarily suppressed with regular ones. Conclusions Idiopathic VAs can be ablated via the CVS in conjunction with endocardial mapping. Additionally, spiky fractionated long-duration potential can function as a clue to identify the good ablation site.

  19. Study of atrial arrhythmias in a computer model based on magnetic resonance images of human atria

    NASA Astrophysics Data System (ADS)

    Virag, N.; Jacquemet, V.; Henriquez, C. S.; Zozor, S.; Blanc, O.; Vesin, J.-M.; Pruvot, E.; Kappenberger, L.

    2002-09-01

    The maintenance of multiple wavelets appears to be a consistent feature of atrial fibrillation (AF). In this paper, we investigate possible mechanisms of initiation and perpetuation of multiple wavelets in a computer model of AF. We developed a simplified model of human atria that uses an ionic-based membrane model and whose geometry is derived from a segmented magnetic resonance imaging data set. The three-dimensional surface has a realistic size and includes obstacles corresponding to the location of major vessels and valves, but it does not take into account anisotropy. The main advantage of this approach is its ability to simulate long duration arrhythmias (up to 40 s). Clinically relevant initiation protocols, such as single-site burst pacing, were used. The dynamics of simulated AF were investigated in models with different action potential durations and restitution properties, controlled by the conductance of the slow inward current in a modified Luo-Rudy model. The simulation studies show that (1) single-site burst pacing protocol can be used to induce wave breaks even in tissue with uniform membrane properties, (2) the restitution-based wave breaks in an atrial model with realistic size and conduction velocities are transient, and (3) a significant reduction in action potential duration (even with apparently flat restitution) increases the duration of AF.

  20. Study of atrial arrhythmias in a computer model based on magnetic resonance images of human atria.

    PubMed

    Virag, N.; Jacquemet, V.; Henriquez, C. S.; Zozor, S.; Blanc, O.; Vesin, J.-M.; Pruvot, E.; Kappenberger, L.

    2002-09-01

    The maintenance of multiple wavelets appears to be a consistent feature of atrial fibrillation (AF). In this paper, we investigate possible mechanisms of initiation and perpetuation of multiple wavelets in a computer model of AF. We developed a simplified model of human atria that uses an ionic-based membrane model and whose geometry is derived from a segmented magnetic resonance imaging data set. The three-dimensional surface has a realistic size and includes obstacles corresponding to the location of major vessels and valves, but it does not take into account anisotropy. The main advantage of this approach is its ability to simulate long duration arrhythmias (up to 40 s). Clinically relevant initiation protocols, such as single-site burst pacing, were used. The dynamics of simulated AF were investigated in models with different action potential durations and restitution properties, controlled by the conductance of the slow inward current in a modified Luo-Rudy model. The simulation studies show that (1) single-site burst pacing protocol can be used to induce wave breaks even in tissue with uniform membrane properties, (2) the restitution-based wave breaks in an atrial model with realistic size and conduction velocities are transient, and (3) a significant reduction in action potential duration (even with apparently flat restitution) increases the duration of AF. (c) 2002 American Institute of Physics. PMID:12779604