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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.

  2. 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

  3. 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

  4. 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

  5. Inherited arrhythmias: The cardiac channelopathies.

    PubMed

    Behere, Shashank P; Weindling, Steven N

    2015-01-01

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

  6. 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. Computers and clinical arrhythmias.

    PubMed

    Knoebel, S B; Lovelace, D E

    1983-02-01

    Cardiac arrhythmias are ubiquitous in normal and abnormal hearts. These disorders may be life-threatening or benign, symptomatic or unrecognized. Arrhythmias may be the precursor of sudden death, a cause or effect of cardiac failure, a clinical reflection of acute or chronic disorders, or a manifestation of extracardiac conditions. Progress is being made toward unraveling the diagnostic and therapeutic problems involved in arrhythmogenesis. Many of the advances would not be possible, however, without the availability of computer technology. To preserve the proper balance and purposeful progression of computer usage, engineers and physicians have been exhorted not to work independently in this field. Both should learn some of the other's trade. The two disciplines need to come together to solve important problems with computers in cardiology. The intent of this article was to acquaint the practicing cardiologist with some of the extant and envisioned computer applications and some of the problems with both. We conclude that computer-based database management systems are necessary for sorting out the clinical factors of relevance for arrhythmogenesis, but computer database management systems are beset with problems that will require sophisticated solutions. The technology for detecting arrhythmias on routine electrocardiograms is quite good but human over-reading is still required, and the rationale for computer application in this setting is questionable. Systems for qualitative, continuous monitoring and review of extended time ECG recordings are adequate with proper noise rejection algorithms and editing capabilities. The systems are limited presently for clinical application to the recognition of ectopic rhythms and significant pauses. Attention should now be turned to the clinical goals for detection and quantification of arrhythmias. We should be asking the following questions: How quantitative do systems need to be? Are computers required for the detection of

  9. 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

  10. 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.

  11. 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

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

    PubMed

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

    2016-01-01

    For the last 10 years, applying new sequencing technologies to thousands of whole exomes has revealed the high variability of the human genome. Extreme caution should thus be taken to avoid misinterpretation when associating rare genetic variants to disease susceptibility. The Brugada syndrome (BrS) is a rare inherited arrhythmia disease associated with high risk of sudden cardiac death in the young adult. Familial inheritance has long been described as Mendelian, with autosomal dominant mode of transmission and incomplete penetrance. However, all except 1 of the 23 genes previously associated with the disease have been identified through a candidate gene approach. To date, only rare coding variants in the SCN5A gene have been significantly associated with the syndrome. However, the genotype/phenotype studies conducted in families with SCN5A mutations illustrate the complex mode of inheritance of BrS. This genetic complexity has recently been confirmed by the identification of common polymorphic alleles strongly associated with disease risk. The implication of both rare and common variants in BrS susceptibility implies that one should first define a proper genetic model for BrS predisposition prior to applying molecular diagnosis. Although long remains the way to personalized medicine against BrS, the high phenotype variability encountered in familial forms of the disease may partly find an explanation into this specific genetic architecture. PMID:27200363

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-08-01

    Inherited cardiac arrhythmias such as long QT syndrome and Brugada syndrome, present clinical as well as ethical, legal, and social challenges. Many individuals who carry a deleterious mutation are largely asymptomatic and therefore may not be diagnosed until after the occurrence of a personal or family member's cardiac event. The familial nature of inherited genetic information raises numerous ethical, legal, and social issues regarding the sharing of genetic information, particularly when an individual found to carry a deleterious mutation refuses to disclose his or her results to at-risk family members who could benefit from life-saving treatments. This qualitative study sought to understand the experiences with genetic testing for individuals (n = 50) with a personal or family history of cardiac events or sudden death. Unstructured in-person focus groups or interviews were conducted for each participant in the study. The recordings of these interviews were transcribed verbatim and subsequently analyzed and coded. Participants' comments regarding sharing of genetic information centered around four main themes: (1) motivation to disclose; (2) extent of disclosure; (3) effect of disclosure on family dynamics; and (4) reasons for not sharing genetic information. The majority of individuals believed that affected individuals are obligated to disclose genetic information to family members. In the era of personalized medicine, the disclosure of genetic information provides individuals the opportunities to learn about the genetics, disease characteristics, and treatment options in order to reduce morbidity and mortality in themselves and their family members. Further research is necessary to identify and explore the barriers to sharing genetic information with at-risk family members. PMID:25400212

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

    PubMed Central

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

    2014-01-01

    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

  16. 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 ...

  17. 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 ...

  18. 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

  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. [Clinical significance of arrhythmia in patients with hypertension].

    PubMed

    Lazutin, V K; Nychkina, T N; Litvintsev, V P; Iakovlev, S V; Boĭko, S E

    1991-04-01

    Cardiac arrhythmias were studied in patients with essential hypertension in relation to their myocardial function. It was found that the arrhythmias occurring in the early period of the disease (borderline hypertension, Stage I hypertension) were primarily functional and affected the course of the disease and hemodynamics to a small degree. The life-threatening arrhythmias recorded in early hypertension were more commonly caused by mitral prolapse. The duration and severity of hypertension, development of left ventricular myocardial hypertrophy, myocardial fiber distension in relative heart failure play a decisive role in the development of cardiac arrhythmias in patients with Stage II hypertensive disease. It is essential to make comprehensive clinical and instrumental studies to clarify the genesis of the arrhythmic syndrome and to correctly choose the management policy in these patients.

  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. Manifestations and clinical impact of pediatric inherited thrombophilia.

    PubMed

    Klaassen, Irene L M; van Ommen, C Heleen; Middeldorp, Saskia

    2015-02-12

    The etiology of pediatric venous thromboembolic disease (VTE) is multifactorial, and in most children, 1 or more clinical risk factors are present. In addition, inherited thrombophilic disorders contribute to the development of pediatric VTE. In this review, the role of inherited thrombophilic disorders in the development of pediatric VTE, as well as the benefits and limitations of thrombophilia testing, will be discussed.

  5. Putting cocaine use and cocaine-associated cardiac arrhythmias into epidemiological and clinical perspective

    PubMed Central

    Wood, David M; Dargan, Paul I

    2010-01-01

    This is the first article in a series of three articles on cocaine-related cardiac arrhythmias, following on from the 2008 British Pharmacological Society Winter Meeting Clinical Section Symposium entitled ‘Cocaine induced cardiac arrhythmias – from ion channel to clinical treatment’. We will summarize the epidemiology of cocaine use across the world and in particular will focus on UK, Europe and US use prevalence data. We will discuss the acute cardiac and non-cardiac toxicity associated with cocaine and highlight the lack of data on the true UK prevalence of acute cocaine toxicity and on the incidence of cocaine-related cardiac arrhythmias. PMID:20573079

  6. 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.

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

    PubMed Central

    Trayanova, Natalia A.; Boyle, Patrick M.

    2014-01-01

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

  8. Clinical assessment of arrhythmias in tetralogy of Fallot.

    PubMed

    Le Gloan, Laurianne; Guerin, Patrice; Mercier, Lise-Andrée; Abbey, Sélim; Dore, Annie; Marcotte, François; Ibrahim, Reda; Poirier, Nancy C; Khairy, Paul

    2010-02-01

    As a major success story of an early surgical era, corrective surgery transformed the prognosis of patients born with tetralogy of Fallot. With lifelong care, healthy survival well into adulthood is now the norm, albeit somewhat blemished by long-term sequelae. Arrhythmias are an important source of morbidity and a leading cause of mortality. This succinct review provides a contemporary summary of the prevalence and types of arrhythmias encountered in tetralogy of Fallot, including conduction disorders, atrial and ventricular tachyarrhythmias, and sudden death. Current prognostic markers and existing diagnostic tools are discussed, and available therapeutic options are elaborated. PMID:20136605

  9. Clinical evaluation of a wireless ECG sensor system for arrhythmia diagnostic purposes.

    PubMed

    Fensli, Rune; Gundersen, Torstein; Snaprud, Tormod; Hejlesen, Ole

    2013-06-01

    In a clinical study, a novel wireless electrocardiogram (ECG) recorder has been evaluated with regard to its ability to perform arrhythmia diagnostics. As the ECG recorder will detect a "non-standard" ECG signal, it has been necessary to compare those signals to "standard" ECG recording signals in order to evaluate the arrhythmia detection ability of the new system. Simultaneous recording of ECG signals from both the new wireless ECG recorder and a conventional Holter recorder was compared by two independent cardiology specialists with regard to signal quality for performing arrhythmia diagnosis. In addition, calculated R-R intervals from the two systems were correlated. A total number of 16 patients participated in the study. It can be considered that recorded ECG signals obtained from the wireless ECG system had an acceptable quality for arrhythmia diagnosis. Some of the patients used the wireless sensor while doing physical sport activities, and the quality of the recorded ECG signals made it possible to perform arrhythmia diagnostics even under such conditions. Consequently, this makes possible improvements in correlating arrhythmias to physical activities.

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

    PubMed

    Nannucci, Serena; Donnini, Ida; Pantoni, Leonardo

    2014-12-15

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

  11. Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management.

    PubMed

    Fanoe, Søren; Kristensen, Diana; Fink-Jensen, Anders; Jensen, Henrik Kjærulf; Toft, Egon; Nielsen, Jimmi; Videbech, Poul; Pehrson, Steen; Bundgaard, Henning

    2014-05-21

    Several drugs used in the treatment of mental diseases are associated with an increased risk of sudden cardiac death (SCD). A general cause-relationship between the intake of these drugs and SCD is unattainable, but numerous case reports of drug-induced malignant arrhythmia and epidemiological studies, associating the use of specific drugs with SCD, strongly support the presence of an increased risk. Whereas the absolute risk of drug-induced life-threatening arrhythmia may be relatively low, even small increments in risk of SCD may have a major health impact considering that millions of patients are treated with psychotropics. In subgroups of pre-disposed patients, e.g. patients with cardiac diseases or other co-morbidities, the elderly or patients treated with other negatively interacting drugs, the absolute risk of drug-induced arrhythmia may be considerable. On the other hand, several of the major mental disorders are associated with a large risk of suicide if untreated. The observed risk of malignant arrhythmia associated with treatment with psychotropic drugs calls for clinical guidelines integrating the risk of the individual drug and other potentially interacting risk factors. In this review, data from various authorities on the risk of arrhythmia associated with psychotropic medications were weighted and categorized into three risk categories. Additionally, we suggest a clinically applicable algorithm to reduce the risk of malignant arrhythmia in patients to be treated with psychotropic medications. The algorithm integrates the risk categories of the individual drugs and pre-disposing risk factors and suggests a prudent follow-up for patients with an increased risk. We believe this clinically manageable guideline might improve safety in the many and rapidly increasing number of patients on psychotropic drugs.

  12. 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

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

    PubMed

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

    2014-10-16

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

  14. 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

  15. 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

  16. 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

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

    PubMed

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

    2008-01-01

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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. Diagnostic value of magnetocardiography in coronary artery disease and cardiac arrhythmias: a review of clinical data.

    PubMed

    Kwong, Joey S W; Leithäuser, Boris; Park, Jai-Wun; Yu, Cheuk-Man

    2013-09-01

    Despite the availability of several advanced non-invasive diagnostic tests such as echocardiography and magnetic resonance imaging, electrocardiography (ECG) remains as the most widely used diagnostic technique in clinical cardiology. ECG detects electrical potentials that are generated by cardiac electrical activity. In addition to electrical potentials, the same electrical activity of the heart also induces magnetic fields. These extremely weak cardiac magnetic signals are detected by a non-invasive, contactless technique called magnetocardiography (MCG), which has been evaluated in a number of clinical studies for its usefulness in diagnosing heart diseases. We reviewed the basic principles, history and clinical data on the diagnostic role of MCG in coronary artery disease and cardiac arrhythmias.

  3. 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

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

    PubMed

    Shen, Mark J; Zipes, Douglas P

    2014-03-14

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

  5. 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.

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

    PubMed

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

    2007-01-01

    Neuromyotonia is a disorder of peripheral nerve hyperexcitability characterized by myokymia, muscle cramps and stiffness, delayed muscle relaxation after contraction (pseudomyotonia), and hyperhidrosis, associated with well described spontaneous electromyographic features. It is usually an acquired disorder associated with autoantibodies against neuronal voltage-gated potassium channels. However, mutations of KCNA1, encoding the K(+) channel subunit hKv1.1, have been reported in rare families with neuromyotonia, and mutations in KCNQ2, encoding voltage-gated potassium M channel subunit, in families with benign neonatal seizures and myokymia. We report a three-generation family with inherited neuromyotonia without evidence of immunological involvement. Genetic study excluded mutations in KCNA1, KCNA2, KCNA6 and KCNQ2 genes. Our study does not completely exclude the involvement of other genes encoding ion channels subunits in the pathogenesis of this disorder. Further studies of familial cases will shed light on the molecular basis of inherited neuromyotonia. PMID:17140792

  7. 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

  8. Magnetocardiograms in clinical medicine: unique information on cardiac ischemia, arrhythmias, and fetal diagnosis.

    PubMed

    Yamada, Satsuki; Yamaguchi, Iwao

    2005-01-01

    Cardiac diseases are the leading cause of death in population. Diagnostic tests to detect cardiac dysfunction at an early stage of the disease are desirable. The major focus has been centered on tests evaluating the perfusion of the heart with imaging techniques or detecting alterations in electrical or mechanical function of the heart. The heart generates magnetic fields that can be detected by body surface mapping utilizing super conducting quantum interference device sensors giving magnetocardiograms (MCGs). The advantages of MCG over traditional electrocardiograms (ECGs) are increased sensitivity to small signals and lack of conductivity in body tissues, presentation of direct component signals and primary currents. This review will highlight the basic principles and recent advantages of MCGs, and the application of MCG in clinical diagnosis, especially in cases whose ECGs are non-diagnostic or not specific, such as detecting baseline shift in ischemic heart disease, noninvasive His potential recording, detection of arrhythmic mechanism defining reentrant circuits vs non reentrant mechanism, diagnosis of fetal arrhythmias and prolongation of QT interval. Areas of future basic and clinical research are also discussed. PMID:15704657

  9. Behavioral influences on cardiac arrhythmias.

    PubMed

    Lampert, Rachel

    2016-01-01

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

  10. Inherited Structural Heart Diseases With Potential Atrial Fibrillation Occurrence.

    PubMed

    Manuguerra, Roberta; Callegari, Sergio; Corradi, Domenico

    2016-02-01

    Inherited cardiac diseases inducing structural remodeling of the myocardium sometimes develop arrhythmias of various kinds. Among these rhythm disturbances, atrial fibrillation is well known to frequently worsen the prognosis of the primary disorder by increasing morbidity and mortality, especially because of a higher rate of heart failure. In this manuscript, we have reviewed the literature on the most important inherited structural cardiac diseases in whose clinical history atrial fibrillation may occur fairly often.

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

    PubMed

    Lee, Kristy; Garg, Seema

    2015-04-01

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

  12. Effect of prophylaxis of magnesium sulfate for reduction of postcardiac surgery arrhythmia: Randomized clinical trial

    PubMed Central

    Naghipour, Bahman; Faridaalaee, Gholamreza; Shadvar, Kamran; Bilehjani, Eissa; Khabaz, Ashkan Heyat; Fakhari, Solmaz

    2016-01-01

    Background: Arrhythmia is a common complication after heart surgery and is a major source of morbidity and mortality. Aims: This study aimed to study the effect of magnesium sulfate (MgSO4) for reduction of postcardiac surgery arrhythmia. Setting and Design: This study is performed in the cardiac operating room and Intensive Care Unit (ICU) of Shahid Madani Hospital of Tabriz (Iran) between January 1, 2014, and September 30, 2014. This study is a double-blind, randomized controlled trial. Materials and Methods: In Group 1 (group magnesium [Mg]), eighty patients received 30 mg/kg MgSO4 in 500 cc normal saline and in Group 2 (group control), eighty patients received 500 cc normal saline alone. Statistical Analysis: The occurrence of arrhythmia was compared between groups by Chi-square and Fisher's exact test. In addition, surgical time, length of ICU stay, and length of hospital stay were compared by independent t-test. P < 0.05 was considered as significant. Results: There was a significant difference in the incidence of arrhythmia between two groups (P = 0.037). The length of ICU stay was 3.4 ± 1.4 and 3.73 ± 1.77 days in group MgSO4 and control group, respectively, and there was no statistically significant difference between two groups (P = 0.2). Conclusion: Mg significantly decreases the incidence of all type of postcardiac surgery arrhythmia and hospital length of stay at patients undergo cardiac surgery. We offer prophylactic administration of Mg at patients undergo cardiac surgery. PMID:27716697

  13. Clinical approach to inherited metabolic disorders in neonates.

    PubMed

    Saudubray, J M; Narcy, C; Lyonnet, L; Bonnefont, J P; Poll The, B T; Munnich, A

    1990-01-01

    Most inborn errors of intermediary metabolism presenting in the neonatal period fall schematically into three clinical categories: (1) those which lead to a neurological distress 'intoxication type' with a symptom-free interval, vomiting, comas, hypertonia, abnormal movements and frequent humoral disturbances (organic acidaemias, congenital urea cycle defects); (2) those which lead to a neurological distress 'energy deficiency' type. Frequent symptoms in this group include hyperlactacidaemia, severe hypotonia, cardiomyopathy, failure to thrive and malformations (congenital lactic acidaemias, fatty acid oxidation defects, peroxysomal disorders); (3) those which present evidence of liver dysfunction and hepatomegaly (glycogenesis, neoglucogenesis defects, galactosaemia, fructosaemia, tyrosinaemia type I). According to these three major clinical presentations and according to the proper use of few screening tests (blood gases, glucose, ammonia, lactic acid, electrolytes, acetest), we propose a method of diagnosis which groups these children into five schematical syndromes: type I MSUD; type II organic acidaemias; type III; congenital lactic acidosis; type IVa, urea cycle defects; type IVb, non-ketotic hyperglycinaemia, sulfite oxidase deficiency, peroxisomal disorders; type V liver dysfunctions. Once the above classification has been made, sophisticated and specific investigations can be planned (amino acid chromatography, organic acid chromatography, enzymatic studies, etc).

  14. 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.

  15. 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

  16. Systems biology and cardiac arrhythmias

    PubMed Central

    Grace, Andrew A; Roden, Dan M

    2013-01-01

    During the past few years, the development of effective, empirical technologies for treatment of cardiac arrhythmias has exceeded the pace at which detailed knowledge of the underlying biology has accumulated. As a result, although some clinical arrhythmias can be cured with techniques such as catheter ablation, drug treatment and prediction of the risk of sudden death remain fairly primitive. The identification of key candidate genes for monogenic arrhythmia syndromes shows that to bring basic biology to the clinic is a powerful approach. Increasingly sophisticated experimental models and methods of measurement, including stem cell-based models of human cardiac arrhythmias, are being deployed to study how perturbations in several biologic pathways can result in an arrhythmia-prone heart. The biology of arrhythmia is largely quantifiable, which allows for systematic analysis that could transform treatment strategies that are often still empirical into management based on molecular evidence. PMID:23101717

  17. Systems biology and cardiac arrhythmias.

    PubMed

    Grace, Andrew A; Roden, Dan M

    2012-10-27

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

  18. [Inherited thrombophilia].

    PubMed

    Franchini, Massimo; Veneri, Dino

    2005-02-01

    Inherited thrombophilia can be defined as a genetically determined predisposition to develop thromboembolic complications. Inherited prothrombotic risk factors include antithrombin deficiency, protein C and protein S deficiencies, activated protein C resistance due to Leiden factor V mutation, inherited hyperhomocysteinemia, prothrombin G20210A variant, dysfibrinogenemia and elevated factor VIII levels. In this review we briefly analyze, from an epidemiologic, clinic and diagnostic point of view, the main inherited prothrombotic risk factors. Finally, we discuss the synergism between genetic and acquired prothrombotic risk factors in some conditions such as pregnancy and cardiovascular diseases.

  19. 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.

  20. [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

  1. [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.

  2. 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

  3. 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

  4. 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

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

    PubMed

    Kornacewicz-Jach, Zdzisława; Peregud-Pogorzelska, Małgorzata

    2014-01-01

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

  6. 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

  7. 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

  8. Gene therapy to treat cardiac arrhythmias.

    PubMed

    Bongianino, Rossana; Priori, Silvia G

    2015-09-01

    Gene therapy to treat electrical dysfunction of the heart is an appealing strategy because of the limited therapeutic options available to manage the most-severe cardiac arrhythmias, such as ventricular tachycardia, ventricular fibrillation, and asystole. However, cardiac genetic manipulation is challenging, given the complex mechanisms underlying arrhythmias. Nevertheless, the growing understanding of the molecular basis of these diseases, and the development of sophisticated vectors and delivery strategies, are providing researchers with adequate means to target specific genes and pathways involved in disorders of heart rhythm. Data from preclinical studies have demonstrated that gene therapy can be successfully used to modify the arrhythmogenic substrate and prevent life-threatening arrhythmias. Therefore, gene therapy might plausibly become a treatment option for patients with difficult-to-manage acquired arrhythmias and for those with inherited arrhythmias. In this Review, we summarize the preclinical studies into gene therapy for acquired and inherited arrhythmias of the atria or ventricles. We also provide an overview of the technical advances in the design of constructs and viral vectors to increase the efficiency and safety of gene therapy and to improve selective delivery to target organs.

  9. GENE THERAPIES FOR ARRHYTHMIAS IN HEART FAILURE

    PubMed Central

    Akar, Fadi G.; Hajjar, Roger J.

    2014-01-01

    In this article, we review recent advances in our understanding of arrhythmia mechanisms in the failing heart. We focus on changes in repolarization, conduction, and intracellular calcium cycling because of their importance to the vast majority of clinical arrhythmias in heart failure. We highlight recent efforts to combat arrhythmias using gene-based approaches that target ion channel, gap junction, and calcium cycling proteins. We further discuss the advantages and limitations associated with individual approaches. PMID:24566976

  10. Clinical significance of chemosensitivity in chronic heart failure: influence on neurohormonal derangement, Cheyne-Stokes respiration and arrhythmias.

    PubMed

    Giannoni, Alberto; Emdin, Michele; Poletti, Roberta; Bramanti, Francesca; Prontera, Concetta; Piepoli, Massimo; Passino, Claudio

    2008-04-01

    Increased chemosensitivity has been observed in HF (heart failure) and, in order to clarify its pathophysiological and clinical relevance, the aim of the present study was to investigate its impact on neurohormonal balance, breathing pattern, response to exercise and arrhythmic profile. A total of 60 patients with chronic HF [age, 66+/-1 years; LVEF (left ventricular ejection fraction), 31+/-1%; values are means+/-S.E.M.] underwent assessment of HVR (hypoxic ventilatory response) and HCVR (hypercapnic ventilatory response), neurohormonal evaluation, cardiopulmonary test, 24-h ECG monitoring, and assessment of CSR (Cheyne-Stokes respiration) by diurnal and nocturnal polygraphy. A total of 60% of patients had enhanced chemosensitivity. Those with enhanced chemosensitivity to both hypoxia and hypercapnia (i.e. HVR and HCVR), compared with those with normal chemosensitivity, had significantly (all P<0.01) higher noradrenaline (norepinephrine) and BNP (B-type natriuretic peptide) levels, higher prevalence of daytime and night-time CSR, worse NYHA (New York Heart Association) class and ventilatory efficiency [higher VE (minute ventilation)/VCO(2) (carbon dioxide output) slope], and a higher incidence of chronic atrial fibrillation and paroxysmal non-sustained ventricular tachycardia, but no difference in left ventricular volumes or LVEF. A direct correlation was found between HVR or HCVR and noradrenaline (R=0.40 and R=0.37 respectively; P<0.01), BNP (R=0.40, P<0.01), N-terminal pro-BNP (R=0.37 and R=0.41 respectively, P<0.01), apnoea/hypopnoea index (R=0.57 and R=0.59 respectively, P<0.001) and VE/VCO(2) slope (R=0.42 and R=0.50 respectively, P<0.001). Finally, by multivariate analysis, HCVR was shown to be an independent predictor of both daytime and night-time CSR. In conclusion, increased chemosensitivity to hypoxia and hypercapnia, particularly when combined, is associated with neurohormonal impairment, worse ventilatory efficiency, CSR and a higher incidence of

  11. 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

  12. 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

  13. 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.

  14. 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 ...

  15. 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 ...

  16. 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 ...

  17. 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 ...

  18. 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.

  19. [Cardiac arrhythmias: Diagnosis and management].

    PubMed

    Waldmann, V; Marijon, E

    2016-09-01

    Cardiac arrhythmias, with, on top of the list, atrial fibrillation, are frequent conditions and any physician might have to get involved at any stage of patient care (from diagnosis to treatment), without always having the opportunity to immediately refer to the cardiologist. The aim of this review is to present a summary of pathophysiology, clinical and electrocardiographic presentations, as well as diagnostic and therapeutic strategies for the main cardiac arrhythmias. Supra-ventricular tachycardias (atrial fibrillation and flutter, atrioventricular reciprocating tachycardias) and ventricular tachycardias will be consecutively presented and discussed.

  20. Ranolazine Therapy in Cardiac Arrhythmias.

    PubMed

    Pulford, Brian R; Kluger, Jeffrey

    2016-09-01

    Ranolazine is an antianginal medication originally granted approval by the U.S. Food and Drug Administration for therapeutic use in 2006. Since its introduction into the U.S. market, there have been multiple trials and clinical case reports that demonstrate ranolazine may be effective in the prevention and treatment of both atrial and ventricular arrhythmias, including postoperative atrial fibrillation following coronary artery bypass graft (CABG) surgery. More recently, the combination of dronedarone with ranolazine has demonstrated in initial studies to have a synergistic effect in the reduction of burden of atrial fibrillation. This article will review the basic pharmacology of ranolazine, the studies demonstrating use of ranolazine in atrial and ventricular arrhythmias, the limitations to the use of ranolazine as antiarrhythmic therapy, and explore the synergistic effect with other agents in the suppression of arrhythmias. PMID:27358212

  1. 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

  2. [An accelerated idioventricular rhythm and sports activity. Comments on a clinical case and a characterization of the arrhythmia].

    PubMed

    Riva, U R; Budriesi, N; Fancinelli, M; Labriola, E

    1994-08-01

    In the evaluation of an accelerated idioventricular rhythm (AIVR) case presented by an athlete, even though considered qualified for agonistic sport practice in compliance with the COCIS protocol, the authors made some considerations relative to such type of arrhythmia. AIVR are characterized by a wide oscillation of frequency (from 40 to 120 b/min) and are distinguished as active AIVR when the ventricular center exceeds the discharge frequency in a non depressed sinusal activity; and it's passive AIVR when an automatic ventricular center substitutes the physiological pacemaker in the presence of sinusal bradycardia. This leads to think that it could be two different phenomenons. The first is characterized by a low frequency and is determined by the activation of some automatic cells located under the His bundle, and the second arises with the extrasystolic modality. Moreover, AIVR manifest a parasystolic type of behaviour that complicates the diagnostic differentiation. Therefore it can be considered that the arrhythmia of ventricular genesis (AIVR, ventricular tachycardia, parasystole) represents the varied expression of the same electrogenic substratum with different discharge potentiality. Thus was formulated the proposal of unifying the ventricular rhythms in one group which includes: rhythm of ventricular escapement, AIVR, parasystole and ventricular tachycardia.

  3. Cardiac arrhythmias during or after epileptic seizures.

    PubMed

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

    2016-01-01

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

  4. Inherited thrombophilia: an update.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2005-01-01

    Inherited thrombophilia can be defined as a genetically determined predisposition to develop thromboembolic complications. Inherited prothrombotic risk factors include antithrombin deficiency, protein C and protein S deficiencies, activated protein C resistance due to factor V Leiden mutation, inherited hyperhomocysteinemia, prothrombin G20210A variant, dys- and hyperfibrinogenemia and elevated factor VIII levels. In this review we briefly analyze, from an epidemiologic, laboratory and clinical point of view, the main inherited prothrombotic risk factors. Finally, we discuss the synergism between genetic and acquired prothrombotic risk factors in some conditions such as pregnancy and cardiovascular diseases.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. Overview of fetal arrhythmias

    PubMed Central

    Srinivasan, Shardha; Strasburger, Janette

    2012-01-01

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

  10. 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

  11. 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

  12. 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.

  13. The acrocallosal syndrome in first cousins: widening of the spectrum of clinical features and further support for autosomal recessive inheritance.

    PubMed

    Schinzel, A

    1988-05-01

    First cousins, related through their mothers, showed a pattern of craniofacial, brain, and limb anomalies consistent with the acrocallosal syndrome. Both patients had a defect of the corpus callosum, macrocephaly with a protruding forehead and occiput, hypertelorism, non-horizontal palpebral fissures, a small nose, notched ear lobes, and postaxial polydactyly of the hands. The boy, in addition, had hypospadias, cryptorchidism, inguinal hernias, duplication with syndactyly of the phalanges of the big toe, and a bipartite right clavicle. The girl had an arachnoidal cyst, a calvarian defect, and digitalisation of the thumbs. Motor and mental development was retarded in both patients. This observation provides further evidence of probable autosomal recessive inheritance of the acrocallosal syndrome and widens the spectrum of clinical findings and the variability of features in this rare malformation syndrome. PMID:3385741

  14. 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

  15. 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 ...

  16. Effect of female sex on cardiac arrhythmias.

    PubMed

    Gowd, B M Pampana; Thompson, Paul D

    2012-01-01

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

  17. Inherited infantile dilated cardiomyopathy in dogs: genetic, clinical, biochemical, and morphologic findings.

    PubMed

    Alroy, J; Rush, J E; Freeman, L; Amarendhra Kumar, M S; Karuri, A; Chase, K; Sarkar, S

    2000-11-01

    Dilated cardiomyopathy, a lethal disease characterized by left ventricular dilation and systolic dysfunction, is relatively common in humans and other mammals. Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of unknown cause and can be a familial disorder. This report describes autosomal recessive IDCM in dogs. It occurs in Portuguese Water Dog (PWD) pups and is manifested by acute, vague clinical signs and sudden death. Affected pups have progressive reduction of fractional shortening that can be demonstrated by echocardiography prior to the development of clinical signs. Furthermore, these pups have low plasma taurine levels when consuming certain diets. Affected pups had dilation of the left ventricle and alterations in the sarcomere appearance, while immunohistochemical and biochemical studies demonstrate an increase in desmin, a cytoskeleton protein. The clinical and morphologic findings of IDCM in PWDs are distinct from those reported in adult IDCM. Finally, the clinical and echocardiographic manifestations were reversible in some pups following oral taurine supplementation for 2 months. These results suggest that IDCM in PWDs is correlated with low plasma taurine levels.

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

    PubMed

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

    2009-11-01

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

  19. [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

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

    PubMed

    Girmenia, E; Andrissi, L; Tambone, V

    2014-01-01

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

  1. 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

  2. [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

  3. 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

  4. [Arrhythmias from swallowing].

    PubMed

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

    1992-01-01

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

  5. 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

  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.

  7. Perinatal arrhythmias -- diagnosis and treatment.

    PubMed

    Moura, Cláudia; Vieira, António; Guimarães, Hercília; Areias, José Carlos

    2002-01-01

    We did a retrospective analysis of the clinical files of 26 neonates with arrhythmia born during the period between January 1994 and February 1999. Fourteen (53.8%) of the neonates were male and 16 (61.5%) had prenatal diagnosis. Four (15.3%) had associated congenital heart disease. Twenty-one (80.7%) had abnormal rhythm and five (19.2%) had cardiac conduction disorder. Digoxin was the therapy of first choice to restore normal rhythm, used in 66.6% of the patients, followed by adenosine (16.6%) and electrical cardioversion (16.6%). An epicardial pacemaker was used in two of the three neonates with complete atrioventricular (AV) block. One neonate died due to cerebral hemorrhage. All the neonates were discharged in a clinically stable condition and 16 (88.8%) of them were medicated with digoxin. In a follow-up period that varied from 0 to 71 months (mean of 30.8 months), two patients had an episode of supraventricular tachycardia (SVT) after treatment withdrawal. Perinatal arrhythmias, although uncommon, can be life-threatening, and hence we consider our experience with these situations worth presenting.

  8. Sleep-Disordered Breathing and Cardiac Arrhythmias.

    PubMed

    Bitter, Thomas; Fox, Henrik; Gaddam, SaiPrassad; Horstkotte, Dieter; Oldenburg, Olaf

    2015-07-01

    Over the past few years sleep-disordered breathing has been identified as an important factor in arrhythmogenesis and a potential target of therapy to prevent cardiac arrhythmias in selected patients. In this review we highlight the role of obstructive sleep apnea and Cheyne-Stokes respiration in the pathophysiology of arrhythmias, address their clinical effect in supraventricular and ventricular tachyarrhythmias, and in conduction disturbances, and address the role of current treatment options for sleep-disordered breathing in the primary and secondary prevention of arrhythmic events.

  9. [Psychosomatic aspects of cardiac arrhythmias].

    PubMed

    Siepmann, Martin; Kirch, Wilhelm

    2010-07-01

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

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

    PubMed

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

    2015-05-01

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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

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

    PubMed

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

    2016-04-01

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

  18. Arrhythmias in Adult Congenital Patients With Bodily Isomerism.

    PubMed

    Loomba, Rohit S; Aggarwal, Saurabh; Gupta, Navdeep; Buelow, Matthew; Alla, Venkata; Arora, Rohit R; Anderson, Robert H

    2016-02-01

    There are an increasing number of adults with congenital heart disease, some of whom have bodily isomerism. Bodily isomerism or heterotaxy is a unique clinical entity associated with congenital malformations of the heart which further increases the risk for future cardiovascular complications. We aimed to investigate the frequency of arrhythmias in adults with bodily isomerism. We utilized the 2012 iteration of the Nationwide Inpatient Sample to identify adult inpatient admissions associated with arrhythmias in patients with isomerism. Data regarding demographics, comorbidities, and various procedures were collected and compared between those with and without isomerism. A total of 6,907,109 admissions were analyzed with a total of 861 being associated isomerism. The frequency of arrhythmias was greater in those with isomerism (20.8 vs. 15.4 %). Those with isomerism were also more five times more likely to undergo invasive electrophysiology studies. Length and cost of hospitalization for patients with arrhythmias also tended to be greater in those with isomerism. Mortality did not differ between the two groups. Arrhythmias are more prevalent in those with isomerism, with a majority of arrhythmias in isomerism being atrial. Those with isomerism and arrhythmias also tended to have greater length and cost of hospitalization.

  19. Psychological aspects of cardiac arrhythmia.

    PubMed

    Lynch, J J; Paskewitz, D A; Gimbel, K S; Thomas, S A

    1977-05-01

    A review of data from a wide spectrum of research studies suggests that psychological-emotional factors can significantly influence and alter the incidence of cardiac arrhythmia. While the existing data are, in many cases, difficult to interpret because of theoretical and methodological problems, sufficient evidence does exist to warrant a concerted investigation into the total involvement of psychological factors in cardiac arrhythmia.

  20. 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.

  1. 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

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

    PubMed

    Giudicessi, John R; Ackerman, Michael J

    2012-01-31

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

  3. 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

  4. 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).

  5. 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

  6. 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

  7. Oral curcumin mitigates the clinical and neuropathologic phenotype of the Trembler-J mouse: a potential therapy for inherited neuropathy.

    PubMed

    Khajavi, Mehrdad; Shiga, Kensuke; Wiszniewski, Wojciech; He, Feng; Shaw, Chad A; Yan, Jiong; Wensel, Theodore G; Snipes, G Jackson; Lupski, James R

    2007-09-01

    Mutations in myelin genes cause inherited peripheral neuropathies that range in severity from adult-onset Charcot-Marie-Tooth disease type 1 to childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Many myelin gene mutants that cause severe disease, such as those in the myelin protein zero gene (MPZ) and the peripheral myelin protein 22 gene (PMP22), appear to make aberrant proteins that accumulate primarily within the endoplasmic reticulum (ER), resulting in Schwann cell death by apoptosis and, subsequently, peripheral neuropathy. We previously showed that curcumin supplementation could abrogate ER retention and aggregation-induced apoptosis associated with neuropathy-causing MPZ mutants. We now show reduced apoptosis after curcumin treatment of cells in tissue culture that express PMP22 mutants. Furthermore, we demonstrate that oral administration of curcumin partially mitigates the severe neuropathy phenotype of the Trembler-J mouse model in a dose-dependent manner. Administration of curcumin significantly decreases the percentage of apoptotic Schwann cells and results in increased number and size of myelinated axons in sciatic nerves, leading to improved motor performance. Our findings indicate that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and improves the neuropathologic phenotype in an animal model of human neuropathy, suggesting a potential therapeutic role in selected forms of inherited peripheral neuropathies. PMID:17701891

  8. 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.

  9. 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.

  10. Benign cardiac tumours, malignant arrhythmias

    PubMed Central

    Myers, Kimberley A; Wong, Kenny K; Tipple, Marion; Sanatani, Shubhayan

    2010-01-01

    Four cases of pediatric cardiac tumours (PCTs) associated with ventricular arrhythmias are reported. Sudden cardiac death attributable to the tumour occurred in two children. A third child received an implantable cardioverter defibrillator and the fourth had persistent ventricular arrhythmia despite medical therapy. Most PCTs are considered benign; however, the development of malignant arrhythmias may complicate the management of these tumours in some patients. The literature regarding the arrhythmogenic potential of PCTs and the use of implantable cardioverter defibrillators in these patients is reviewed. The series highlights the deficiency of prognostic information for this cohort. PMID:20151061

  11. Stochastic Aspects of Cardiac Arrhythmias

    NASA Astrophysics Data System (ADS)

    Lerma, Claudia; Krogh-Madsen, Trine; Guevara, Michael; Glass, Leon

    2007-07-01

    Abnormal cardiac rhythms (cardiac arrhythmias) often display complex changes over time that can have a random or haphazard appearance. Mathematically, these changes can on occasion be identified with bifurcations in difference or differential equation models of the arrhythmias. One source for the variability of these rhythms is the fluctuating environment. However, in the neighborhood of bifurcation points, the fluctuations induced by the stochastic opening and closing of individual ion channels in the cell membrane, which results in membrane noise, may lead to randomness in the observed dynamics. To illustrate this, we consider the effects of stochastic properties of ion channels on the resetting of pacemaker oscillations and on the generation of early afterdepolarizations. The comparison of the statistical properties of long records showing arrhythmias with the predictions from theoretical models should help in the identification of different mechanisms underlying cardiac arrhythmias.

  12. 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.

  13. Data analysis in cardiac arrhythmias.

    PubMed

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

    2015-01-01

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

  14. 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

  15. Inherited platelet disorders.

    PubMed

    Franchini, Massimo; Lippi, Giuseppe; Veneri, Dino; Targher, Giovanni; Zaffanello, Marco; Guidi, Gian Cesare

    2008-01-01

    Inherited platelet disorders are a rare, but probably underdiagnosed, cause of symptomatic bleeding. They are characterized by abnormalities of platelet number (inherited thrombocytopenias), function (inherited disorders of platelet function) or both. This review briefly discusses the inherited platelet disorders with respect to molecular defects, diagnostic evaluation and treatment strategies.

  16. 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

  17. 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.

  18. 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…

  19. 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

  20. Cardiac arrhythmias in hypertrophic cardiomyopathy.

    PubMed Central

    Bjarnason, I; Hardarson, T; Jonsson, S

    1982-01-01

    This study was designed to assess the prevalence of cardiac arrhythmias in a group of relatives of patients who had come to necropsy with hypertrophic cardiomyopathy. Another aim of the study was to assess the validity of an interventricular septal thickness of 1.3 cm or more, measured by echocardiography, as a diagnostic criterion of hypertrophic cardiomyopathy among relatives of cases proven at necropsy. Fifty close relatives of eight deceased patients were examined. By the above definition 22 relatives had hypertrophic cardiomyopathy and 28 did not. A comparison of the prevalence and types of cardiac arrhythmias, as shown by 24 hour ambulatory electrocardiographic monitoring, was made between the two groups and a third apparently healthy group of 40 people. The patients with hypertrophic cardiomyopathy showed a significant increase in supraventricular extrasystoles/24 hours, supraventricular arrhythmias, high grade ventricular arrhythmia, and the number of patients with more than 10 ventricular extrasystoles every 24 hours when compared with the other groups. There was no significant difference between normal relatives and controls. The prevalence and types of arrhythmia in these patients were similar to those found by other investigators using different diagnostic criteria. These results support the contention that these patients do indeed have hypertrophic cardiomyopathy and suggest that all close relatives of necropsy proven cases should be examined by echocardiography and subsequently by ambulatory electrocardiographic monitoring if the interventricular septal thickness is 1.3 more. PMID:7201843

  1. Almanac 2013: cardiac arrhythmias and pacing.

    PubMed

    Liew, Reginald

    2013-10-01

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

  2. Glutamine supplementation in a child with inherited GS deficiency improves the clinical status and partially corrects the peripheral and central amino acid imbalance.

    PubMed

    Häberle, Johannes; Shahbeck, Noora; Ibrahim, Khalid; Schmitt, Bernhard; Scheer, Ianina; O'Gorman, Ruth; Chaudhry, Farrukh A; Ben-Omran, Tawfeg

    2012-07-25

    Glutamine synthetase (GS) is ubiquitously expressed in mammalian organisms and is a key enzyme in nitrogen metabolism. It is the only known enzyme capable of synthesising glutamine, an amino acid with many critical roles in the human organism. A defect in GLUL, encoding for GS, leads to congenital systemic glutamine deficiency and has been described in three patients with epileptic encephalopathy. There is no established treatment for this condition.Here, we describe a therapeutic trial consisting of enteral and parenteral glutamine supplementation in a four year old patient with GS deficiency. The patient received increasing doses of glutamine up to 1020 mg/kg/day. The effect of this glutamine supplementation was monitored clinically, biochemically, and by studies of the electroencephalogram (EEG) as well as by brain magnetic resonance imaging and spectroscopy.Treatment was well tolerated and clinical monitoring showed improved alertness. Concentrations of plasma glutamine normalized while levels in cerebrospinal fluid increased but remained below the lower reference range. The EEG showed clear improvement and spectroscopy revealed increasing concentrations of glutamine and glutamate in brain tissue. Concomitantly, there was no worsening of pre-existing chronic hyperammonemia.In conclusion, supplementation of glutamine is a safe therapeutic option for inherited GS deficiency since it corrects the peripheral biochemical phenotype and partially also improves the central biochemical phenotype. There was some clinical improvement but the patient had a long standing severe encephalopathy. Earlier supplementation with glutamine might have prevented some of the neuronal damage.

  3. 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

  4. 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.

  5. Inherited factor XI deficiency: a concise review.

    PubMed

    Franchini, Massimo; Veneri, Dino; Lippi, Giuseppe

    2006-10-01

    Inherited factor XI (FXI) deficiency, also called Hemophilia C, is an uncommon autosomal recessive disorder, which is associated with a variable bleeding tendency that usually manifests after trauma or surgery. This concise report reviews current knowledge regarding the pathogenesis, genetics, diagnosis, clinical manifestations and management of this inherited bleeding disorder.

  6. KCNJ2 Mutation Causes an Adrenergic-Dependent Rectification Abnormality with Calcium Sensitivity and Ventricular Arrhythmia

    PubMed Central

    Kalscheur, Matthew M.; Vaidyanathan, Ravi; Orland, Kate M.; Abozeid, Sara; Fabry, Nicholas; Maginot, Kathleen R.; January, Craig T.; Makielski, Jonathan C.; Eckhardt, Lee L.

    2014-01-01

    Background KCNJ2 mutations are associated with a variety of inherited arrhythmia syndromes including CPVT3. Objective Detailed cellular and mechanistic characterization of the clinically recognized KCNJ2 mutation R67Q. Methods Kir2.1 current density was measured using the whole-cell voltage clamp technique from COS-1 cells transiently transfected with WT-Kir2.1 and/or R67Q-Kir2.1. Catecholamine activity was simulated with PKA stimulating cocktail exposure. Phosphorylation deficient mutants, S425N-Kir2.1 and S425N-Kir2.1/R67Q-S425N-Kir2.1, were used in a separate set of experiments. HA- or Myc-Tag-WT-Kir2.1 or HA-Tag-R67Q-Kir2.1 were used for confocal imaging. Results A 33 year old presented with a CPVT-like clinical phenotype and was found to have KCNJ2 missense mutation R67Q. Treatment with nadolol and flecainide resulted in complete suppression of arrhythmias and symptom resolution. Under baseline conditions, R67Q-Kir2.1 expressed alone did not produce IK1 while cells co-expressing WT-Kir2.1 and R67Q-Kir2.1 showed rectification index (RI) similar to WT-Kir2.1. After PKA stimulation, R67Q-Kir2.1/WT-Kir2.1 failed to increase peak outward current density; WT-Kir2.1 increased 46% (n=5) while R67Q-Kir2.1/WT-Kir2.1 decreased 6% (n=6), p=0.002. Rectification properties in R67Q-Kir2.1/WT-Kir2.1 demonstrated sensitivity to calcium with decreased RI in high-calcium pipette solution (RI 20.3 ± 4.1%) compared to low-calcium (RI 36.5 ± 5.7%) (p< 0.05). Immunostaining of WT-Kir2.1 and R67Q-Kir2.1 individually and together showed a normal membrane expression pattern and co-localization by Pearson’s correlation coefficient. Conclusion R67Q-Kir2.1 is associated with an adrenergic-dependent clinical and cellular phenotype with rectification abnormality enhanced by increased calcium. These findings are a significant advancement of our knowledge and understanding of phenotype-genotype relationship of arrhythmia syndromes related to KCNJ2 mutations. PMID:24561538

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

    PubMed

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

    2012-03-01

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

  8. 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.

  9. 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

  10. 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.

  11. [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

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

    PubMed

    Fu, Du-Guan

    2015-11-01

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

  13. Cancer chemotherapy and cardiac arrhythmias: a review.

    PubMed

    Tamargo, Juan; Caballero, Ricardo; Delpón, Eva

    2015-02-01

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

  14. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

    The paper describes a clinical case of a female patient with severe obstructive sleep apnea syndrome in the presence of congenital hemangioma of the face, soft palate, and tongue concurrent with paroxysmal atrial fibrillation and atrial flutter, paroxysmal supraventricular tachycardia, and sinoatrial block (maximally up to 3.9 sec). Continuous positive airway pressure therapy could reduce the number of paroxysms of atrial fibrillation and atrial flutter, supraventricular tachycardia and eliminate sinoatrial block. PMID:27636935

  17. Circadian arrhythmia dysregulates emotional behaviors in aged Siberian hamsters

    PubMed Central

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

    2014-01-01

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

  18. Circadian arrhythmia dysregulates emotional behaviors in aged Siberian hamsters.

    PubMed

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

    2014-03-15

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

  19. Cardiac arrhythmias misdiagnosed as epilepsy.

    PubMed Central

    Rutter, N; Southall, D P

    1985-01-01

    A mother and three children presenting with syncope induced by exercise and emotion were diagnosed as epileptic. They, and three symptom free children, showed frequent ventricular and supraventricular tachyarrhythmias on ambulatory electrocardiographic monitoring. Three died before the correct diagnosis of disordered sympathetic innervation of the heart was made, but episodes of syncope and cardiac arrhythmias in the survivors have been successfully treated by propranolol. Images Fig. 2 PMID:3970569

  20. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  2. Computerized arrhythmia monitoring systems: a review.

    PubMed

    Lipschultz, A

    1982-01-01

    The principles and different types of commercially available computerized ventricular arrhythmia detection algorithms are reviewed. Algorithms use either the feature extraction method or the cross correlation method. There are advantages and disadvantages to each method. The trend is to use some aspects of both methods. The American Hospital Association database may radically change the marketplace. Whether or not a system is successful in a clinical setting is dependent upon many factors including 1) whether the nurses believed that they were part of the decision process; 2) the human engineering for ease of everyday use; 3) the extent and type of in-service education; and 4) the number of false-positives and false-negatives called by the algorithm. PMID:10298704

  3. Transgenerational inheritance of metabolic disease.

    PubMed

    Stegemann, Rachel; Buchner, David A

    2015-07-01

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

  4. 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

  5. Inherited or acquired metabolic disorders.

    PubMed

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

    2016-01-01

    This chapter starts with a description of imaging of inherited metabolic disorders, followed by a discussion on imaging of acquired toxic-metabolic disorders of the adult brain. Neuroimaging is crucial for the diagnosis and management of a number of inherited metabolic disorders. Among these, inherited white-matter disorders commonly affect both the nervous system and endocrine organs. Magnetic resonance imaging (MRI) has enabled new classifications of these disorders that have greatly enhanced both our diagnostic ability and our understanding of these complex disorders. Beyond the classic leukodystrophies, we are increasingly recognizing new hereditary leukoencephalopathies such as the hypomyelinating disorders. Conventional imaging can be unrevealing in some metabolic disorders, but proton magnetic resonance spectroscopy (MRS) may be able to directly visualize the metabolic abnormality in certain disorders. Hence, neuroimaging can enhance our understanding of pathogenesis, even in the absence of a pathologic specimen. This review aims to present pathognomonic brain MRI lesion patterns, the diagnostic capacity of proton MRS, and information from clinical and laboratory testing that can aid diagnosis. We demonstrate that applying an advanced neuroimaging approach enhances current diagnostics and management. Additional information on inherited and metabolic disorders of the brain can be found in Chapter 63 in the second volume of this series. PMID:27432685

  6. Clinical profile and inheritance pattern of CYP21A2 gene mutations in patients with classical congenital adrenal hyperplasia from 10 families

    PubMed Central

    Yadav, Sarita; Birla, Shweta; Marumudi, Eunice; Sharma, Arundhati; Khadgawat, Rajesh; Khurana, M. L.; Ammini, A. C.

    2015-01-01

    Context: Congenital adrenal hyperplasia (CAH) is an autosomal recessive metabolic disorder caused by mutations in the CYP21A2 gene. Genetic diagnosis of 21-OH deficiency causing CAH is more complicated than any other monogenic disorder due to high variability of the locus. The disease has a wide spectrum of clinical variants making it difficult to establish a genotyp–phenotype correlation. Therefore, family studies are necessary to ascertain parental genotype and segregation of the mutant allele among the offspring. Aim: The present study aimed to identify CYP21A2 gene mutations and analyze the segregation pattern in CAH trios (patients and their parents). Materials and Methods: A total of ten families having at least one CAH child were recruited. Results: Out of 31 children from ten families, 15 were affected with CAH and 13 of/them (12 females and 1 male) were available for genetic testing. One family had all the children affected with CAH. Compound heterozygous mutations were identified in seven patients (53.8%) whereas p.P30L, In2 and Δ8 bp mutations were present in homozygous state in three (23.1%), two (15.3 %) and one (7.6%) patient respectively. Conclusions: In majority of the families, mutant alleles observed in the patients were inherited from the parents whereas three families showed sporadic mutations without any paternal or maternal origin. This indicated their novel occurrence due to misalignment of the parental genes and/or large deletion of the gene. Female preponderance was noted in the CAH families and also among the patients raising the possibility of survival advantage among females. PMID:26425475

  7. Family letters are an effective way to inform relatives about inherited cardiac disease.

    PubMed

    van der Roest, Wilma P; Pennings, José M; Bakker, Marian; van den Berg, Maarten P; van Tintelen, J Peter

    2009-03-01

    Increasing numbers of individuals are being referred to cardiogenetics outpatient clinics with potentially inherited arrhythmia (ARR) or cardiomyopathy (CM). To inform relatives at-risk, we ask index patients to distribute "family letters" containing information on the risks, possible genetic and other screenings, and preventive options. We assessed the responses to these letters in terms of referrals to a cardiologist and/or clinical geneticist. Fifty-six index patients were asked to distribute 249 family letters: 85 in the ARR group and 164 in the CM group. Within a mean follow-up period of 2 years (range 1-5 years) the number of relatives actually referred to the clinical geneticist and/or cardiologist was 57% (142 of 249). There was a significant difference (P < 0.01) between the ARR (80%) and CM groups (45.1%). To verify the results obtained from our files at the cardiogenetics department we sent a questionnaire to 52 index patients (response 50%). This showed that 23/26 (88%) index patients had distributed the letters to their relatives and that for 19/23 index patients one or more relatives had been screened. This is comparable with our files, which showed that 57% of relatives of index patients with a potentially inherited cardiac disease underwent screening, particularly in the ARR group. The actual response was underestimated because some relatives were investigated elsewhere or may still decide to be screened in the future. We conclude that distributing family letters is an effective way to inform and encourage relatives to undergo screening for high-risk inherited cardiac disease.

  8. Update on arrhythmias and cardiac pacing 2013.

    PubMed

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

    2014-04-01

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

  9. Update on arrhythmias and cardiac pacing 2013.

    PubMed

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

    2014-04-01

    This report discusses a selection of the most relevant articles on cardiac arrhythmias and pacing published in 2013. The first section discusses arrhythmias, classified as regular paroxysmal supraventricular tachyarrhythmias, atrial fibrillation, and ventricular arrhythmias, together with their treatment by means of an implantable cardioverter defibrillator. The next section reviews cardiac pacing, subdivided into resynchronization therapy, remote monitoring of implantable devices, and pacemakers. The final section discusses syncope. PMID:24774592

  10. 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)

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

    PubMed Central

    Patocskai, Bence; Antzelevitch, Charles

    2016-01-01

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

  12. 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 ...

  13. 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 ...

  14. 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.

  15. Perinatal Arrhythmias: Diagnosis and Management

    PubMed Central

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

    2012-01-01

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

  16. Iron sufficient to cause hepatic fibrosis and ascites does not cause cardiac arrhythmias in the gerbil.

    PubMed

    Kaiser, Lana; Davis, John M; Patterson, Jon; Johnson, Abby L; Bohart, George; Olivier, N Bari; Schwartz, Kenneth A

    2009-10-01

    Chronic iron overload associated with hereditary hemochromatosis or repeated red cell transfusions is known to cause cardiac failure. Cardiac arrhythmias have been incidentally noted in patients with iron overload, but they are often dismissed as being related to comorbid conditions. Studies with anesthetized iron-loaded gerbils using short recordings suggest a role for iron in the development of arrhythmias. Our goal was to characterize iron-induced arrhythmias in the chronically instrumented, untethered, telemetered gerbil. Electrocardiograms were recorded for 10 s every 30 min for approximately 6 months in iron-loaded (n=23) and control (n=8) gerbils. All gerbils in both groups showed evidence of frequent sinus arrhythmia. There was no difference in heart rate, electrocardiographic parameters, or number of arrhythmias per minute between groups. Gerbils rarely showed significant arrhythmias. Body weight and heart weight were not significantly different between groups, whereas liver weight increased with increasing iron dose in the treated group. Cardiac and hepatic iron concentrations were significantly increased in iron-loaded gerbils. Eight of 14 gerbils loaded to 6.2 g/kg body weight developed ascites. We conclude that an iron load sufficient to cause clinical liver disease does not cause cardiac arrhythmias in the gerbil model of iron overload.

  17. Update in cardiac arrhythmias and pacing.

    PubMed

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

    2015-03-01

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

  18. 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.

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

    PubMed

    Kohl, S; Biskup, S

    2013-03-01

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

  20. Incidence Of Supraventricular Arrhythmias During Autologous Peripheral Blood Stem Cell Transplantation

    PubMed Central

    Singla, Abhishek; Hogan, William J.; Ansell, Stephen M.; Buadi, Francis K.; Dingli, David; Dispenzieri, Angela; Gastineau, Dennis A.; Gertz, Morie A.; Hayman, Suzanne R.; Inwards, David J.; Johnston, Patrick B.; Lacy, Martha Q.; Litzow, Mark R.; Micallef, Ivana N.; Porrata, Luis F.; Kumar, Shaji K.

    2013-01-01

    Arrhythmias, especially supraventricular arrhythmias, often complicate the clinical course during autologous hematopoietic cell transplantation (AHCT). We undertook this study to determine the incidence and risk factors for cardiac arrhythmias during AHCT. The study included 983 patients who underwent AHCT between August 2006 and December 2010 at a single institution, and in whom all the relevant medical records were available for review. The median age was 58 years (range; 19–77); 61% were male. AHCT was done for plasma cell disorders in 58% patients and for lymphoma or leukemia in the remaining. Overall, 92 (9.4%) patients developed a supraventricular tachyarrhythmia at a median of 9 days post transplant (range; 0, 18) and with a median duration of <1 day (range; <1 to 17 days). Atrial fibrillation (AF) was the most common and seen in 71 (7%) patients, followed by atrial flutter and supraventricular tachycardia in 12 (1%) and 8 (1%) patients respectively. In multivariate analysis, age > 63 years, presence of premature supraventricular complexes or Atrio-ventricular conduction delay on pre-transplant ECG, and history of any prior arrhythmia increased the risk of arrhythmia. Development of arrhythmia resulted in longer outpatient follow up after AHCT, with the median follow-up for those developing an arrhythmia of 22 days compared with 19 days for the rest; P < 0.001. In conclusion, 9% of patients undergoing ASCT develop supraventricular arrhythmias post transplant and this risk is elevated among the older patients, those with a prior history of arrhythmias, and those with pre-transplant ECG abnormalities. PMID:23747600

  1. 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.

  2. 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.

  3. Mechanisms of ventricular arrhythmias: a perspective.

    PubMed

    Kléber, A G

    1991-01-01

    The most important ventricular arrhythmias, the ventricular tachycardias (VTs) and ventricular fibrillations (VFs), are thought to underlie the majority of cases of sudden cardiac death. In ischemic heart disease, they can be divided into several pathophysiological entities: (a) arrhythmias occurring during the acute reversible phase of ischemia, (b) arrhythmias taking place during reperfusion of acutely ischemic myocardium, (c) arrhythmias occurring 24-72 h after acute infarction, and (d) arrhythmias associated with chronic infarction. In all three settings, the mechanisms sustaining ventricular arrhythmias need to be distinguished from initiating mechanisms. With the exception of the 24-72-h stage, these arrhythmias are sustained by circus movement with reentry: the electrophysiological determinants of circus movements at a cellular level and, consequently, the appearance of the circulating wave fronts, differ according to the ischemic phase. In acute ischemia, multiple circulating waves, with somewhat large diameters, change their vortexes from beat to beat. In chronic infarction, the location of the stable circuits with elongated central zones of block are closely related to myocardial fiber architecture and probably to scar tissue. These differences indicate that (a) in acute ischemia, the conduction disturbances are mainly determined by the development of inexcitability at the level of cardiac membranes; and (b) in chronic infarction, the site of conduction block and the pivoting points of the wave fronts are determined by impairment of electrical cell-to-cell coupling. In contrast to the mechanisms sustaining VT and VF, the initiating mechanisms are less well defined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1723111

  4. 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.

  5. 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

  6. 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

  7. Inherited disorders of bilirubin clearance.

    PubMed

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

    2016-03-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin-Johnson syndrome), or (iv) 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

  8. Ventricular arrhythmias: state of the art.

    PubMed

    Schleifer, J William; Srivathsan, Komandoor

    2013-11-01

    The management of ventricular tachycardia and ventricular fibrillation in the cardiac intensive care unit can be complex. These arrhythmias have many triggers, including ischemia, sympathetic stimulation, and medication toxicities, as well as many different substrates, ranging from ischemic and nonischemic cardiomyopathies to rare genetic conditions such as Brugada syndrome and long QT syndrome. Different settings, such as congenital heart disease, postoperative ventricular arrhythmias, and ventricular assist devices, increase the complexity of management. This article reviews the variety of situations and cardiac conditions that give rise to ventricular arrhythmias, focusing on inpatient management strategies.

  9. [Diagnosis of inherited thrombocytopenia].

    PubMed

    Baccini, V; Alessi, M C

    2016-02-01

    Inherited thrombocytopenias are rare, heterogenous and probably under-diagnosed because often classified as autoimmune thrombocytopenia. About 20 genes were described responsible for these thrombocytopenias. Precise diagnosis is necessary because the prognosis is different and some of them can evolve into hemopathies. First of all, it is important to gather a body of evidence to orientate towards an inherited cause: presence of the thrombocytopenia since childhood and of other family cases is a strong argument. Secondly, it is difficult to target the genetic investigations that settle the precise diagnosis. Genetic variants responsible for inherited thrombocytopenias affect different stage during megakaryocytopoiesis and cause thrombocytopenias with distinct characteristics. Presence of extra-hematological features, platelets' size measurement and evaluation of bone marrow megakaryocyte morphology when it is possible allow a primary orientation. We propose a diagnostic approach considering extra-hematological features, mode of inheritance, morphology, molecular and functional platelets' studies and bone marrow megakaryocyte morphology in order to better target genetic study. Nevertheless, despite this approach, some inherited thrombocytopenias remain still unexplained and could benefit from new methods of new generation sequencing in the future. PMID:26617290

  10. hiPSC MODELING OF INHERITED CARDIOMYOPATHIES

    PubMed Central

    Jung, Gwanghyun; Bernstein, Daniel

    2014-01-01

    Opinion Statement Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a powerful new model system to study the basic mechanisms of inherited cardiomyopathies. hiPSC-CMs have been utilized to model several cardiovascular diseases, achieving the most success in the inherited arrhythmias, including long QT and Timothy syndromes (1,2) and arrhythmogenic right ventricular dysplasia (ARVD) (3). Recently, studies have applied hiPSC-CMs to the study of both dilated (DCM) (4) and hypertrophic (HCM) cardiomyopathies (5,6), providing new insights into basic mechanisms of disease. However, hiPSC-CMs do not recapitulate many of the structural and functional aspects of mature human cardiomyocytes, instead mirroring an immature, embryonic or fetal, phenotype. Thus, much work remains to better understand these differences as well as to develop methods to induce hiPSC-CMs into a fully mature phenotype. Despite these limitations, hiPSC-CMs represent the best current in vitro correlate of the human heart and an invaluable tool in the search for mechanisms underlying cardiomyopathy and for screening new pharmacologic therapies. PMID:24838688

  11. Organs as inheritable property?

    PubMed

    Voo, Teck Chuan; Holm, Soren

    2014-01-01

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

  12. 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

  13. Sudden Arrhythmia Death Syndromes (SADS) Foundation

    MedlinePlus

    ... SADS Foundation and John Hopkins Hospital Division of Cardiology are hosting a family support and educational meeting ... Baltimore/DC area families with cardiac arrhythmias. Sports Cardiology & Sudden Cardiac Arrest in the Young Conference 01/ ...

  14. 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

  15. Metabolic Stress, Reactive Oxygen Species, and Arrhythmia

    PubMed Central

    Jeong, Euy-Myoung; Liu, Man; Sturdy, Megan; Gao, Ge; Varghese, Susan T.; Sovari, Ali A.; Dudley, Samuel C.

    2011-01-01

    Cardiac arrhythmias can cause sudden cardiac death (SCD) and add to the current heart failure (HF) health crisis. Nevertheless, the pathological processes underlying arrhythmias are unclear. Arrhythmic conditions are associated with systemic and cardiac oxidative stress caused by reactive oxygen species (ROS). In excitable cardiac cells, ROS regulate both cellular metabolism and ion homeostasis. Increasing evidence suggests that elevated cellular ROS can cause alterations of the cardiac sodium channel (Nav1.5), abnormal Ca2+ handling, changes of mitochondrial function, and gap junction remodeling, leading to arrhythmogenesis. This review summarizes our knowledge of the mechanisms by which ROS may cause arrhythmias and discusses potential therapeutic strategies to prevent arrhythmias by targeting ROS and its consequences. PMID:21978629

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

    PubMed Central

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

    2015-01-01

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

  17. 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.

  18. 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.

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

    PubMed

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

    2013-01-01

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

  20. Arrhythmias and sudden cardiac death in elite athletes. American College of Cardiology, 16th Bethesda Conference.

    PubMed

    Garson, A

    1998-01-01

    With the recent high visibility deaths of Hank Gathers and Reggie Lewis, two nationally recognized elite basketball players due to cardiovascular disease and arrhythmias, our awareness of the most optimal ways to manage athletes with known arrhythmias has become heightened. In making medical decisions we physicians come to rely in large measure on data, in addition to clinical acumen and experience. Unfortunately, we are at a disadvantage with respect to athletes since previously published data on the natural history and outcome of such individuals with known arrhythmias are sparse. Furthermore, the tragedies of Lewis, Gathers, Pete Maravich and others are also poignant reminders that the denominator of this equation is not defined and that we do not really know precisely how many athletes experience important arrhythmias, nor their relation to sports activity. In the decade since the 16th Bethesda Conference, an American College of Cardiology sponsored consensus panel that developed standards and recommendations for the disqualification from competition of athletes with known cardiovascular disease, little new data have been developed to make objective decisions in these areas (including arrhythmias) much easier. Nevertheless, while such decision-making in athletes involves situations that are relatively rare, the consequences of misjudgement are substantial. Unfortunately, to complicate matters, even if the precise likelihood of sudden death for a given athlete with arrhythmias were known, many (if not most) professional and elite college athletes might still regard any risk as acceptable and withdrawal from formal competition as highly unacceptable from a financial and psychological standpoint. In this review, consideration will be given to the state of our medical knowledge in these areas. Many controversies persist with regard to arrhythmias, most notably for the athlete who has Wolff-Parkinson-White, mitral valve prolapse, myocarditis, or complex ventricular

  1. Epigenetic inheritance of centromeres.

    PubMed

    Henikoff, S; Furuyama, T

    2010-01-01

    Centromeres of higher eukaryotes are epigenetically maintained; however, the mechanism that underlies centromere inheritance is unknown. Centromere identity and inheritance require the assembly of nucleosomes containing the CenH3 histone variant in place of canonical H3. Work from our laboratory has led to the proposal that epigenetic inheritance of centromeres evolved as adaptations of CenH3 and other centromere proteins to resist drive of selfish centromeres during female meiosis. Our molecular studies have revealed that the Drosophila CenH3 nucleosome is equivalent to half of the canonical H3 nucleosome and induces positive supercoils, as opposed to the negative supercoils induced by an H3 nucleosome. CenH3 likewise induces positive supercoils in functional yeast centromeres in vivo. The right-handed wrapping of DNA around the histone core implied by positive supercoiling indicates that centromeric nucleosomes are unlikely to be octameric and that the exposed surfaces holding the nucleosome together would be available for kinetochore protein recruitment. The mutual incompatibility of nucleosomes with opposite topologies could explain how centromeres are efficiently maintained as unique loci on chromosomes. We propose that the opposite wrapping of DNA around a half-nucleosome core particle facilitates a mode of inheritance that does not depend on DNA sequence, DNA modification or protein conformation.

  2. 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

  3. 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

  4. Epigenetic inheritance in ciliates.

    PubMed

    Nowacki, Mariusz; Landweber, Laura F

    2009-12-01

    2009 marks not only the 200th anniversary of Darwin's birth but also publication of the first scientific evolutionary theory, Lamarck's Philosophie Zoologique. While Lamarck embraced the notion of the inheritance of acquired characters, he did not invent it (Burkhardt, 1984). New phenomena discovered recently offer molecular pathways for the transmission of several acquired characters. Ciliates have long provided model systems to study phenomena that bypass traditional modes of inheritance. RNA, normally thought of as a conduit in gene expression, displays a novel mode of action in ciliated protozoa. For example, maternal RNA templates provide both an organizing guide for DNA rearrangements in Oxytricha and a template that can transmit spontaneous mutations that may arise during somatic growth to the next generation, providing two such mechanisms of so-called Lamarckian inheritance. This suggests that the somatic ciliate genome is really an 'epigenome', formed through templates and signals arising from the previous generation. This review will discuss these new biological roles for RNA, including non-coding 'template' RNA molecules. The evolutionary consequences of viable mechanisms in ciliates to transmit acquired characters may create an additional store of heritable variation that contributes to the cosmopolitan success of this diverse lineage of microbial eukaryotes.

  5. 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

  6. Use of an implantable loop recorder in the investigation of arrhythmias in adult captive chimpanzees (Pan troglodytes).

    PubMed

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

    2011-02-01

    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

  7. 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

  8. Sarcolemmal KATP channel modulators and cardiac arrhythmias.

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2003-03-01

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

  10. A Case for Pharmacogenomics in Management of Cardiac Arrhythmias

    PubMed Central

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

    2012-01-01

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

  11. 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.

  12. [2 newborn infants with severe arrhythmia caused by hyperkalemia].

    PubMed

    Maclaine Pont, J; Hack, W W; Sobotka-Plojhar, M; Ekkelkamp, S

    1987-02-01

    Two newborn infants with ventricular arrhythmias secondary to hyperkalaemia are presented. One child also showed a decreased serum calcium concentration. There is scanty literature concerning the often life threatening cardiac arrhythmias due to hyperkalaemia in the newborn infants. Treatment of the cardiac arrhythmias require intravenous calcium gluconat and sodium bicarbonate infusion beside lowering the serum potassium level in the usual way.

  13. Pathophysiology and Management of Inherited Bone Marrow Failure Syndromes

    PubMed Central

    Shimamura, Akiko; Alter, Blanche P.

    2012-01-01

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

  14. 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

  15. 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.

  16. A vertical approach to cardiac arrhythmias.

    PubMed

    Vaughan Williams, E M

    1987-10-01

    Study of cardiac arrhythmia may be pursued vertically, as up the rungs of a ladder, from symptom to ECG, to EPS, to local lesion, to intracellular metabolism and to alterations of the latter and their effects on charge-transfer by ions across the cell membrane. Raised intracellular cAMP and calcium concentrations are responses to normal physiological controls, and highly abnormal ECGs occur in normal people under stress without progressing to life threatening arrhythmias, yet do so in susceptible individuals. Conversely, appropriate stimulation can precipitate ventricular fibrillation in normal myocardium. Selective stimulation of different types of adrenoceptor has differing electrophysiological effects. Beta 1-adrenoceptors increase contraction and calcium current, and shorten action potential duration (APD) by increasing potassium conductance. Beta 2-adrenoceptors do not increase calcium entry, but shorten APD by stimulating electrogenic Na/K pumping, alpha-adrenoceptors prolong contractions and lengthen APD. It is suggested that the tachycardia, extrasystoles and shortening of APD occurring in response to adrenergic stimuli and hypoxia, are accessory factors, not primary causes, in the development of arrhythmias, and constitute a danger when there is an appropriate anatomical substrate for re-entry. Serious arrhythmias are of multifactorial origin, of which "calcium overload" is but one, not proven to be a frequent one.

  17. Fetal cardiac arrhythmias: diagnosis and management.

    PubMed

    Feit, L R

    2001-05-01

    The diagnosis and management of fetal cardiac arrhythmias requires complex skills and knowledge, and has had a great impact on the care of infants with congenital heart disease and their families. Optimal benefits will be derived from a thoughtful team approach, with skillful internal communication, and especially when parental involvement is encouraged in the decision making process. PMID:11392955

  18. Sevoflurane-induced arrhythmia in healthy adult.

    PubMed

    Santos, João; Santos, Vera; Gago, Paula; Cortez-Dias, Nuno

    2016-11-01

    Inhalatory anesthetic agents are frequently used for anesthesia maintenance. Sevoflurane is considered one of the safest regarding its cardiac effects. We report a case of a cardiac arrhythmia induced by sevoflurane in an otherwise healthy adult and discuss sevoflurane's cardiac effects. PMID:27687440

  19. 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

  20. Fractals analysis of cardiac arrhythmias.

    PubMed

    Saeed, Mohammed

    2005-09-01

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

  1. 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

  2. Cardiac Arrhythmias and Abnormal Electrocardiograms After Acute Stroke.

    PubMed

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

    2016-01-01

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

  3. Inherited Colorectal Cancer Syndromes

    PubMed Central

    Kastrinos, Fay; Syngal, Sapna

    2011-01-01

    Colorectal cancer is the most common gastrointestinal malignancy and the second leading cause of cancer death in both men and women in the United States. Most colorectal cancer cases diagnosed annually are due to sporadic events but up to 5% are attributed to known monogenic disorders including Lynch syndrome, Familial Adenomatous Polyposis, MYH-associated polyposis, and the rare hamartomatous polyposis syndromes. These inherited colorectal cancer syndromes confer a markedly increased risk for the development of multiple cancers and predictive genetic testing is available to identify mutation carriers and at-risk family members. Through personalized strategies for diagnosis and management, a substantial reduction in morbidity and mortality has been appreciated among patients at highest risk for the development of colorectal cancer. PMID:22157284

  4. [Pertinence of animal and human models in the evaluation of ventricular anti-arrhythmia agents].

    PubMed

    Funck-Brentano, C; Le Heuzey, J Y

    1991-02-01

    The development of antiarrhythmic agents for the treatment of ventricular arrhythmias depends to a large extent on their effects in different animal and human models. The clinical relevance of the data so obtained is debatable. Firstly, in vitro animal models of arrhythmias are not very predictive of the multiple clinical forms of ventricular arrhythmias. Secondly, the intermediary criteria of evaluation of the effects of antiarrhythmic drugs in humans are generally not valid in terms of criteria of substitution for the evaluation of therapeutic effects. Nevertheless, cellular and hemodynamic studies of the electrophysiological properties of drugs are essential for correct clinical usage of antiarrhythmics. They help predict the principal clinical electrocardiographic changes and their modulation with respect to parameters such as ischemia or heart rate, their hemodynamic tolerance and certain undesirable, especially proarrhythmic, effects. However, the clinical pertinence of these studies remains limited for a number of reasons. In particular, most antiarrhythmic agents have multiple electrophysiological effects, the resultant of which is difficult to predict in the clinical situation. In addition, many of these drugs have active metabolites, the formation of which varies from person to person, which also reduces the clinical relevance of studies of the parent molecule alone. Clinical trials in appropriate patient populations should therefore be preferred to the multiplication of studies on experimental models of uncertain relevance.

  5. 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

  6. 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.

  7. 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

  8. Inherited disorders of blood coagulation.

    PubMed

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

    2012-08-01

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

  9. [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

  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. Robotic magnetic navigation for ablation of human arrhythmias

    PubMed Central

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

    2016-01-01

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

  12. Robotic magnetic navigation for ablation of human arrhythmias

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2002-09-01

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

  14. The inheritance of centromere identity.

    PubMed

    Niikura, Yohei; Kitagawa, Risa; Kitagawa, Katsumi

    2016-07-01

    CENP-A (Centromere protein A) is a histone H3 variant that epigenetically determines the centromere position, but the mechanism of its centromere inheritance is obscure. We propose that CENP-A ubiquitylation, which is inherited through dimerization between rounds of cell division, is a candidate for the epigenetic mark of centromere identity. PMID:27652331

  15. Cardiac arrhythmias the first month after acute traumatic spinal cord injury

    PubMed Central

    Bartholdy, Kim; Biering-Sørensen, Tor; Malmqvist, Lasse; Ballegaard, Martin; Krassioukov, Andrei; Hansen, Birgitte; Svendsen, Jesper Hastrup; Kruse, Anders; Welling, Karen-Lise; Biering-Sørensen, Fin

    2014-01-01

    Objective Cardiovascular complications including cardiac arrest and arrhythmias remain a clinical challenge in the management of acute traumatic spinal cord injury (SCI). Still, there is a lack of knowledge regarding the characteristics of arrhythmias in patients with acute traumatic SCI. The aim of this prospective observational study was to investigate the occurrence of cardiac arrhythmias and cardiac arrests in patients with acute traumatic SCI. Methods As early as possible after SCI 24-hour Holter monitoring was performed. Additional Holter recordings were performed 1, 2, 3, and 4 weeks after SCI. Furthermore, 12-lead electrocardiograms (ECGs) were obtained shortly after SCI and at 4 weeks. Results Thirty patients were included. Bradycardia (heart rate (HR) <50 b.p.m.) was present in 17–35% of the patients with cervical (C1–C8) SCI (n = 24) within the first 14 days. In the following 14 days, the occurrence was 22–32%. Bradycardia in the thoracic (Th1–Th12) SCI group (n = 6) was present in 17–33% during the observation period. The differences between the two groups were not statistically significant. The mean minimum HR was significantly lower in the cervical group compared with the thoracic group both on 12-lead ECGs obtained shortly after SCI (P = 0.030) and at 4 weeks (P = 0.041). Conclusion Many patients with cervical SCI experience arrhythmias such as bradycardia, sinus node arrest, supraventricular tachycardia, and more rarely cardiac arrest the first month after SCI. Apart from sinus node arrests and limited bradycardia, no arrhythmias were seen in patients with thoracic SCI. Standard 12-lead ECGs will often miss the high prevalence these arrhythmias have. PMID:24559419

  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. [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

  18. 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.

  19. Classification of arrhythmia using hybrid networks.

    PubMed

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

    2011-12-01

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

  20. Arrhythmias in patients with hypereosinophilia: a comparison of patients with and without Löffler's endomyocardial disease.

    PubMed Central

    Cohen, J.; Davies, J.; Goodwin, J. F.; Spry, C. J.

    1980-01-01

    About one third of patients with Löffler's endomyocardial disease have abnormal electrocardiograms and some develop arrhythmias and die suddenly. To assess the significance of these findings, continuous ambulatory ECG monitoring was performed for 48 hr on 6 patients with acute or chronic forms of Löffler's endomyocardial disease, and the types and frequencies of arrhythmias were compared with recordings from 6 other patients with equally high blood eosinophil counts who did not have clinically evident cardiac disease. It was hoped that this would show whether arrhythmias were related to high blood eosinophil counts, cardiac injury or other factors. Three of the patients with endomyocardial disease had multiple ventricular extrasystoles with episodes of ventricular arrhythmias and occasional supraventricular arrhythmias which had not been detected with conventional ECGs. These abnormalities did not occur in 2 of the patients with acute endomyocardial lesions who died, nor were they found in patients who did not have congestive cardiac failure or in the control patients. Rhythm disturbances appeared to be most closely related to the development of cardiac failure and they resolved after successful cardiac surgery. Multiple ventricular extrasystoles and arrhythmias occurring in these patients with Löffler's endomyocardial disease are probably due to metabolic changes in the heart associated with cardiac failure and mechanical changes related to valvular dysfunction rather than a direct effect of the eosinophils themselves on the heart. PMID:7267492

  1. 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.

  2. Inherited bleeding syndromes in Iraq.

    PubMed

    Al-Mondhiry, H A

    1977-06-30

    This paper presents data on the occurence and pattern of inherited bleeding syndromes (IBS) in Iraq, a hitherto unexplored problem. During the first fourteen months of a prospective on-going study at a major university center, 116 patients from 62 families were diagnosed as having IBS. All patients were referred because of moderate to severe bleeding diatheses. They included 62 haemophiliacs 32 patients with von Willebrand's disease (VWD), 9 with Christmas disease (CD), 6 with afibrinogenemia, 1 with prothrombin deficiency, and 6 were thought to have platelet dysfunction. 32 other bleeders (16 hemophiliacs, 14 VWD, and 2 CD) were also recognized among the pedigrees studied but were not available for full investigations. The clinical and laboratory features of the patients observed in Iraq do not seem to be significantly different from those of patients in Western Europe or North America. Although the absolute incidence and relative distribution of these disorders in the entire population cannot yet be determined, the rate of occurence per segment population is likely to be high, most likely due to the high rate of consanguinity and large number of births per family, phenomena still prevalent in this country.

  3. 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

  4. Management of inherited atherogenic dyslipidemias in children.

    PubMed

    Guardamagna, Ornella; Cagliero, Paola; Abello, Francesca

    2013-04-01

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

  5. Drug-associated arrhythmia in the military patient.

    PubMed

    Evans, Barry; Cox, A; Nicol, E; Patil Mead, M; Behr, E

    2015-09-01

    Members of the Armed Forces may be exposed to drugs, or combinations of drugs, with the potential to prolong the QRS or QT intervals. The effect of this is to increase the likelihood of developing dangerous ventricular tachyarrhythmias, including ventricular tachycardia, torsades de pointes or ventricular fibrillation. Common examples of the pharmacological agents associated include antibiotics, antiemetics and antimalarials. Genetic predisposition, electrolyte disturbance, anaesthesia and trauma may exacerbate the proarrhythmic effect of these medications. Screening of recruits does not detect all those with a genetic predisposition to drug-associated arrhythmias, so vigilance in preventing this iatrogenic disorder and recognising and appropriately managing it when present is important. This article explains the physiological basis of arrhythmogenesis, outlines the clinical features and provides guidance on investigation and management, with particular reference to military patients.

  6. Prophylactic arrhythmia surgery in association with congenital heart disease

    PubMed Central

    Deal, Barbara J.

    2016-01-01

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

  7. 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

  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. 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.

  10. Management of cocaine-induced cardiac arrhythmias due to cardiac ion channel dysfunction.

    PubMed

    Wood, David M; Dargan, Paul I; Hoffman, Robert S

    2009-01-01

    Cocaine use is common in many areas of the world, particularly the United States and Western Europe. Toxicity following the use of cocaine is associated with a wide range of clinical features. In this review, we will focus on the cocaine-associated cardiac arrhythmias and, in particular, some of the controversies in their etiology and management. Cocaine can produce arrhythmias either through the production of myocardial ischemia or as a direct result of ion channel alterations. Excessive catecholamines, combined with sodium and potassium channel blockades, give rise to a wide variety of supra-ventricular and ventricular rhythms. The animal and human evidence for ion channel dysfunction is reviewed, and the effects of catecholamines are followed from the cardiac action potential to the development of arrhythmias. Finally, theoretical constructs are combined with existing evidence to develop a rational treatment strategy for patients with cocaine-induced cardiac arrhythmias. In particular, we review the evidence concerning the controversies relating to the use of lidocaine in comparison with sodium bicarbonate, in terms of QRS prolongation secondary to sodium channel blockade.

  11. 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.

  12. 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

  13. 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

  14. 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

    Besides the consensus meeting in Amersfoort in 1988 and the Bethesda conference in 1994 recommendations are not available in the Netherlands for screening and evaluation of athletes with cardiac arrhythmias. Guidelines for competitive athletes with cardiac arrhythmias in the United States and Italy were published in 2000. In 1998 Estes et al. published the most important opinions on sudden cardiac death, screening and evaluation of athletes and arrhythmias. This study addresses the physiological and morphological consequences of athletic training, cardiac pathology and risk stratification for sudden cardiac death. Recommendations for competitive athletes with cardiovascular abnormalities, arrhythmias and proposals for specific protocols are given. ImagesFigure 1Figure 2 PMID:25696317

  15. 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

  16. 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

  17. 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.

  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. 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.

  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. Interdisciplinary psychosocial care for families with inherited cardiovascular diseases.

    PubMed

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

    2016-10-01

    Inherited cardiovascular diseases pose unique and complex psychosocial challenges for families, including coming to terms with life-long cardiac disease, risk of sudden death, grief related to the sudden death of a loved one, activity restrictions, and inheritance risk to other family members. Psychosocial factors impact not only mental health but also physical health and cooperation with clinical recommendations. We describe an interdisciplinary approach to the care of families with inherited cardiovascular disease, in which psychological care provided by specialized cardiac genetic counselors, nurses, and psychologists is embedded within the cardiovascular care team. We report illustrative cases and the supporting literature to demonstrate common scenarios, as well as practical guidance for clinicians working in the inherited cardiovascular disease setting. PMID:27256036

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

    PubMed

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

    2016-10-01

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

  3. Acute emotional stress and cardiac arrhythmias.

    PubMed

    Ziegelstein, Roy C

    2007-07-18

    Episodes of acute emotional stress can have significant adverse effects on the heart. Acute emotional stress can produce left ventricular contractile dysfunction, myocardial ischemia, or disturbances of cardiac rhythm. Although these abnormalities are often only transient, their consequences can be gravely damaging and sometimes fatal. Despite the many descriptions of catastrophic cardiovascular events in the setting of acute emotional stress, the anatomical substrate and physiological pathways by which emotional stress triggers cardiovascular events are only now being characterized, aided by the advent of functional neuroimaging. Recent evidence indicates that asymmetric brain activity is particularly important in making the heart more susceptible to ventricular arrhythmias. Lateralization of cerebral activity during emotional stress may stimulate the heart asymmetrically and produce areas of inhomogeneous repolarization that create electrical instability and facilitate the development of cardiac arrhythmias. Patients with ischemic heart disease who survive an episode of sudden cardiac death in the setting of acute emotional stress should receive a beta-blocker. Nonpharmacological approaches to manage emotional stress in patients with and without coronary artery disease, including social support, relaxation therapy, yoga, meditation, controlled slow breathing, and biofeedback, are also appropriate to consider and merit additional investigation in randomized trials.

  4. 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

  5. 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

  6. Dual-mode Continuous Arrhythmias Telemonitoring System

    NASA Astrophysics Data System (ADS)

    Amien, Magdi B. M.; Lin, Jiarui

    Coronary artery disease still remains the main cause of death. The existence of silent myocardial isocheim emphasized the need for All-day real-time monitoring. Therefore patient monitoring during normal activity has become increasingly important as a standard preventive craniological procedure for detection of cardiac Arrhythmias, transient ischemic episodes and silent myocardial ischemia. This paper deals the design and implementation of a Dual-mode, (700 m) Wireless Real-time Arrhythmias monitoring and Auto-warning System. The system consists of slave node, and master node with a PC-based Application user interface. The system operates at the license-free open frequency band 915 MHZ. The slave node is a DSP-based smart board carried by the patient; it acquires two channels of full-spectrum ECG, stores samples on a Flash memory capable of handling 1GBits of data, compress and transmits a digitally-processed cardiac heart signal each time with detected QRS synchronous pulses as transmission data packet. The master node is responsible for receiving, decompressing, and analyzing the transmitted data packets. The SRWF-501F915 integrated module realizes the data transmitting and receiving. The developed system can be configured as master-slave or Stand-Alone topology.

  7. Arrhythmias in patients with congenital heart disease.

    PubMed

    Walsh, Edward P

    2002-12-01

    Improved surgical outcome for patients with congenital heart disease (CHD) has created a rapidly expanding population of adolescents and young adult survivors. Cardiac arrhythmias are a common late sequelae of this form of heart disease. Effective treatment requires clear understanding of the underlying anatomic defect as well as the specific surgical interventions. Intraatrial reentrant tachycardia (IART) is the most common and difficult arrhythmia encountered in these patients. Traditional IART treatment with medication has been largely unsuccessful, but radiofrequency ablation has emerged in recent years as a promising option for many patients. The availability of three-dimensional mapping systems and irrigated-tip ablation catheters has improved acute success rates for IART to better than 90%. Postablation recurrence of IART still remains problematic for patients who have undergone the Fontan operation, in which case atrial maze surgery may be considered. Ventricular tachycardia (VT) is seen in a smaller number of CHD patients, most notably those with tetralogy of Fallot or aortic stenosis. The adoption of implantable defibrillator (ICD) therapy for these patients has improved outcome. Owing to their complex anatomy, the CHD population presents unique challenges during both catheterization and device implant. Multicenter study of this unique patient group is needed in order to develop more objective treatment guidelines.

  8. Heart-brain interactions in cardiac arrhythmia.

    PubMed

    Taggart, P; Critchley, H; Lambiase, P D

    2011-05-01

    This review examines current knowledge of the effects of higher brain centres and autonomic control loops on the heart with particular relevance to arrhythmogenesis. There is now substantial evidence that higher brain function (cortex), the brain stem and autonomic nerves affect cardiac electrophysiology and arrhythmia, and that these may function as an interactive system. The roles of mental stress and emotion in arrhythmogenesis and sudden cardiac death are no longer confined to the realms of anecdote. Advances in molecular cardiology have identified cardiac cellular ion channel mutations conferring vulnerability to arrhythmic death at the myocardial level. Indeed, specific channelopathies such as long QT syndrome and Brugada syndrome are selectively sensitive to either sympathetic or vagal stimulation. There is increasing evidence that afferent feedback from the heart to the higher centres may affect efferent input to the heart and modulate the cardiac electrophysiology. The new era of functional neuroimaging has identified the central neural circuitry in this brain-heart axis. Since precipitants of sudden fatal arrhythmia are frequently environmental and behavioural, central pathways translating stress into autonomic effects on the heart might be considered as therapeutic targets. These brain-heart interactions help explain the apparent randomness of sudden cardiac events and provide new insights into future novel therapies to prevent sudden death.

  9. 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

  10. Incidence of cardiac arrhythmias in asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

    PubMed

    Shizukuda, Yukitaka; Tripodi, Dorothy J; Zalos, Gloria; Bolan, Charles D; Yau, Yu-Ying; Leitman, Susan F; Waclawiw, Myron A; Rosing, Douglas R

    2012-03-15

    It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis." They completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The subjects with HH were classified as newly diagnosed (group A) and chronically treated (group B) subjects. All subjects with HH had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be greater in the combined HH groups than in the controls. Supraventricular ectopy was more frequently noted in group B compared to in the controls (ectopy rate per hour 11.1 ± 29.9 vs 1.5 ± 3.5, p < 0.05, using the Kruskal-Wallis test). No examples of heart block, other than first-degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in the group A subjects. No life-threatening arrhythmias were observed in our subjects with HH. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic subjects with HH. A larger clinical study is warranted to further clarify our observation.

  11. Incidence of cardiac arrhythmias in asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

    PubMed

    Shizukuda, Yukitaka; Tripodi, Dorothy J; Zalos, Gloria; Bolan, Charles D; Yau, Yu-Ying; Leitman, Susan F; Waclawiw, Myron A; Rosing, Douglas R

    2012-03-15

    It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis." They completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The subjects with HH were classified as newly diagnosed (group A) and chronically treated (group B) subjects. All subjects with HH had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be greater in the combined HH groups than in the controls. Supraventricular ectopy was more frequently noted in group B compared to in the controls (ectopy rate per hour 11.1 ± 29.9 vs 1.5 ± 3.5, p < 0.05, using the Kruskal-Wallis test). No examples of heart block, other than first-degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in the group A subjects. No life-threatening arrhythmias were observed in our subjects with HH. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic subjects with HH. A larger clinical study is warranted to further clarify our observation. PMID:22196777

  12. Irreversible Electroporation Near the Heart: Ventricular Arrhythmias Can Be Prevented With ECG Synchronization

    PubMed Central

    Deodhar, Ajita; Dickfeld, Timm; Single, Gordon W.; Hamilton, William C.; Thornton, Raymond H.; Sofocleous, Constantinos T.; Maybody, Majid; Gónen, Mithat; Rubinsky, Boris; Solomon, Stephen B.

    2013-01-01

    OBJECTIVE Irreversible electroporation is a nonthermal ablative tool that uses direct electrical pulses to create irreversible membrane pores and cell death. The ablation zone is surrounded by a zone of reversibly increased permeability; either zone can cause cardiac arrhythmias. Our purpose was to establish a safety profile for the use of irreversible electroporation close to the heart. MATERIALS and METHODS The effect of unsynchronized and synchronized (with the R wave on ECG) irreversible electroporation in swine lung and myocardium was studied in 11 pigs. Twelve lead ECG recordings were analyzed by an electrophysiologist for the presence of arrhythmia. Ventricular arrhythmias were categorized as major events. Minor events included all other dysrhythmias or ECG changes. Cardiac and lung tissue was submitted for histopathologic analysis. Electrical field modeling was performed to predict the distance from the applicators over which cells show electroporation-induced increased permeability. RESULTS At less than or equal to 1.7 cm from the heart, fatal (major) events occurred with all unsynchronized irreversible electroporation. No major and three minor events were seen with synchronized irreversible electroporation. At more than 1.7 cm from the heart, two minor events occurred with only unsynchronized irreversible electroporation. Electrical field modeling correlates well with the clinical results, revealing increased cell membrane permeability up to 1.7 cm away from the applicators. Complete lung ablation without intervening live cells was seen. No myocardial injury was seen. CONCLUSION Unsynchronized irreversible electroporation close to the heart can cause fatal ventricular arrhythmias. Synchronizing irreversible electroporation pulse delivery with absolute refractory period avoids significant cardiac arrhythmias. PMID:21343484

  13. 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.

  14. 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

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

    PubMed

    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.

  16. 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

  17. 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

  18. 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.

  19. Are specific allergen sensitivities inherited?

    PubMed

    Misiak, Rana Tawil; Wegienka, Ganesa; Zoratti, Edward

    2010-09-01

    A family history of an allergic condition is a well-accepted risk factor for the development of an allergic condition in an individual, particularly for allergic disorders such as asthma, eczema, and allergic rhinitis. However, the question of whether specific allergen sensitization is inherited requires a complicated answer, as environmental exposure plays an important role in the development of allergen-specific IgE. This article summarizes the findings of recent studies in the literature regarding what is known about the inheritance of specific allergens. Overall, properly collected and analyzed data appear to both support and refute the hypothesis that specific allergen sensitization is inherited, even when attempting to account for the complexities of varying study methodologies and the evaluation of diverse populations and communities. PMID:20574668

  20. Inherited peripheral neuropathy.

    PubMed

    Keller, M P; Chance, P F

    1999-01-01

    Hereditary disorders of the peripheral nerves constitute a group of frequently encountered neurological diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is genetically heterogeneous and characterized by demyelination with moderately to severely reduced nerve conduction velocities, absent muscle stretch reflexes and onion bulb formation. Genetic loci for CMT1 map to chromosome 17 (CMT1A), chromosome 1 (CMT1B), and another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1 B result from point mutations in the myelin protein zero (Po or MPZ) gene. The molecular defect in CMT1 C is unknown. Mutations in the early growth response 2 gene (EGR2) are also associated with demyelinating neuropathy. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q, and 11q. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is characterized by normal or mildly reduced nerve conduction velocity with decreased amplitude and axonal loss without hypertrophic features. One form of CMT2 maps to chromosome 1 p36 (CMT2A), another to chromosome 3p (CMT2B) and another to 7p (CMT2D). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy that may be associated with point mutations in either the PMP22 gene or the Po gene and shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced

  1. 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

  2. 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.

  3. [Pharmacotherapy of cardiac arrhythmias in women--what do we know, do we have a choice?].

    PubMed

    Klocek, Marek; Skrzek, Agnieszka; Czarnecka, Danuta

    2014-01-01

    The paper presents basic epidemiological, electrophysiological and therapeutical differences of cardiac arrhythmias depended on gender. Inadequate sinus tachycardia, orthostatic tachycardia syndrome and atrioventricular nodal reentrant tachycardia are more common in women as well as prolongation of QT interval and proarrhythmic phenomenon (especially torsade de pointes). Atrial fibrillation, although significantly less common in women, is more onerous, therapeutic aims are worse to achieve and outcomes are less favourable than in men. European guidelines do not recommend different pharmacological treatement of supraventricular and ventricular arrhythmias in relation to gender. Older antyarrhythmic drugs (beta-adrenolytics, amiodarone, sotalol) and as well as newer ones (dronedarone, ivabradine, vernakalant and ranolazine) seem to have the same influence on arrthythmias both in men and women, althouth their long-term safety may be different and depend on influence on QT interval. The paper presents the state of the art of antiarrhythmic drugs that might be prefered among woman in different clinical situations.

  4. Emerging concepts in the pharmacogenomics of arrhythmias: ion channel trafficking

    PubMed Central

    Harkcom, William T; Abbott, Geoffrey W

    2010-01-01

    Continuous, rhythmic beating of the heart requires exquisite control of expression, localization and function of cardiac ion channels – the foundations of the cardiac myocyte action potential. Disruption of any of these processes can alter the shape of the action potential, predisposing to cardiac arrhythmias. These arrhythmias can manifest in a variety of ways depending on both the channels involved and the type of disruption (i.e., gain or loss of function). As much as 1% of the population of developed countries is affected by cardiac arrhythmia each year, and a detailed understanding of the mechanism of each arrhythmia is crucial to developing and prescribing the proper therapies. Many of the antiarrhythmic drugs currently on the market were developed before the underlying cause of the arrhythmia was known, and as a result lack specificity, causing side effects. The majority of the available drugs target the conductance of cardiac ion channels, either by blocking or enhancing current through the channel. In recent years, however, it has become apparent that specific targeting of ion channel conductance may not be the most effective means for treatment. Here we review increasing evidence that suggests defects in ion channel trafficking play an important role in the etiology of arrhythmias, and small molecule approaches to correct trafficking defects will likely play an important role in the future of arrhythmia treatment. PMID:20670193

  5. In vitro arrhythmia generation by mild hypothermia: a pitchfork bifurcation type process.

    PubMed

    Xu, Binbin; Jacquir, Sabir; Laurent, Gabriel; Binczak, Stéphane; Pont, Oriol; Yahia, Hussein

    2015-03-01

    The neurological damage after cardiac arrest presents a huge challenge for hospital discharge. Therapeutic hypothermia (34 °C - 32 °C) has shown its benefits in reducing cerebral oxygen demand and improving neurological outcomes after cardiac arrest. However, it can have many adverse effects, among them cardiac arrhythmia generation which represents an important part (up to 34%, according different clinical studies). A monolayer cardiac culture is prepared with cardiomyocytes from a newborn rat, directly on a multi-electrode array, which allows the acquisition of the extracellular potential of the culture. The temperature range is 37 °C - 30 °C-37 °C, representing the cooling and rewarming process of therapeutic hypothermia. Experiments showed that at 35 °C, the acquired signals are characterized by period-doubling phenomenon, compared with signals at other temperatures. Spiral waves, commonly considered to be a sign of cardiac arrhythmia, are observed in the reconstructed activation map. With an approach from nonlinear dynamics, phase space reconstruction, it is shown that at 35 °C, the trajectories of these signals formed a spatial bifurcation, even trifurcation. Another transit point is found between 30 °C-33 °C, which agreed with other clinical studies that induced hypothermia after cardiac arrest should not fall below 32 °C. The process of therapeutic hypothermia after cardiac arrest can be represented by a pitchfork bifurcation type process, which could explain the different ratios of arrhythmia among the adverse effects after this therapy. This nonlinear dynamic suggests that a variable speed of cooling/rewarming, especially when passing 35 °C, would help to decrease the ratio of post-hypothermia arrhythmia and then improve the hospital output. PMID:25690526

  6. Cardiac Arrhythmia: In vivo screening in the zebrafish to overcome complexity in drug discovery

    PubMed Central

    MacRae, Calum A.

    2010-01-01

    Importance of the field Cardiac arrhythmias remain a major challenge for modern drug discovery. Clinical events are paroxysmal, often rare and may be asymptomatic until a highly morbid complication. Target selection is often based on limited information and though highly specific agents are identified in screening, the final efficacy is often compromised by unanticipated systemic responses, a narrow therapeutic index and substantial toxicities. Areas covered in this review Our understanding of complexity of arrhythmogenesis has grown dramatically over the last two decades, and the range of potential disease mechanisms now includes pathways previously thought only tangentially involved in arrhythmia. This review surveys the literature on arrhythmia mechanisms from 1965 to the present day, outlines the complex biology underlying potentially each and every rhythm disturbance, and highlights the problems for rational target identification. The rationale for in vivo screening is described and the utility of the zebrafish for this approach and for complementary work in functional genomics is discussed. Current limitations of the model in this setting and the need for careful validation in new disease areas are also described. What the reader will gain An overview of the complex mechanisms underlying most clinical arrhythmias, and insight into the limits of ion channel conductances as drug targets. An introduction to the zebrafish as a model organism, in particular for cardiovascular biology. Potential approaches to overcoming the hurdles to drug discovery in the face of complex biology including in vivo screening of zebrafish genetic disease models. Take home message In vivo screening in faithful disease models allows the effects of drugs on integrative physiology and disease biology to be captured during the screening process, in a manner agnostic to potential drug target or targets. This systematic strategy bypasses current gaps in our understanding of disease biology

  7. In vitro arrhythmia generation by mild hypothermia: a pitchfork bifurcation type process.

    PubMed

    Xu, Binbin; Jacquir, Sabir; Laurent, Gabriel; Binczak, Stéphane; Pont, Oriol; Yahia, Hussein

    2015-03-01

    The neurological damage after cardiac arrest presents a huge challenge for hospital discharge. Therapeutic hypothermia (34 °C - 32 °C) has shown its benefits in reducing cerebral oxygen demand and improving neurological outcomes after cardiac arrest. However, it can have many adverse effects, among them cardiac arrhythmia generation which represents an important part (up to 34%, according different clinical studies). A monolayer cardiac culture is prepared with cardiomyocytes from a newborn rat, directly on a multi-electrode array, which allows the acquisition of the extracellular potential of the culture. The temperature range is 37 °C - 30 °C-37 °C, representing the cooling and rewarming process of therapeutic hypothermia. Experiments showed that at 35 °C, the acquired signals are characterized by period-doubling phenomenon, compared with signals at other temperatures. Spiral waves, commonly considered to be a sign of cardiac arrhythmia, are observed in the reconstructed activation map. With an approach from nonlinear dynamics, phase space reconstruction, it is shown that at 35 °C, the trajectories of these signals formed a spatial bifurcation, even trifurcation. Another transit point is found between 30 °C-33 °C, which agreed with other clinical studies that induced hypothermia after cardiac arrest should not fall below 32 °C. The process of therapeutic hypothermia after cardiac arrest can be represented by a pitchfork bifurcation type process, which could explain the different ratios of arrhythmia among the adverse effects after this therapy. This nonlinear dynamic suggests that a variable speed of cooling/rewarming, especially when passing 35 °C, would help to decrease the ratio of post-hypothermia arrhythmia and then improve the hospital output.

  8. Arrhythmias in Adult Congenital Heart Disease: Diagnosis and Management.

    PubMed

    Kumar, Saurabh; Tedrow, Usha B; Triedman, John K

    2015-11-01

    Cardiac arrhythmias are a major source of morbidity and mortality in adults with CHD. A multidisciplinary approach in a center specializing in the care of ACHD is most likely to have the expertise needed provide this care. Knowledge of the underlying anatomy, mechanism of arrhythmia, and potential management strategies is critical, as well as access and expertise in the use of advanced imaging and ablative technologies. Future challenges in management include refining the underlying mechanism and putative ablation targets for catheter ablation of AF, an arrhythmia rapidly rising in prevalence in this population.

  9. 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…

  10. Arrhythmia Associated with Buprenorphine and Methadone Reported to the Food and Drug Administration

    PubMed Central

    Kao, David P; Haigney, Mark CP; Mehler, Philip S; Krantz, Mori J

    2015-01-01

    Aim To assess the relative frequency of reporting of adverse events involving ventricular arrhythmia, cardiac arrest, QTc prolongation, or torsade de pointes to the US Food and Drug Administration (FDA) between buprenorphine and methadone. Design Retrospective pharmacoepidemiologic study Setting Adverse drug events spontaneously reported to the FDA between 1969-June 2011 originating in 196 countries (71% events from the US). Cases Adverse event cases mentioning methadone (n=14,915) or buprenorphine (n=7,283) were evaluated against all other adverse event cases (n= 4,796,141). Measurements The primary outcome was the composite of ventricular arrhythmia or cardiac arrest. The secondary outcome was the composite of QTc prolongation or torsade de pointes. The proportional reporting ratio (PRR) was used to identify disproportionate reporting defined as a PRR>2, χ2 error>4, with ≥3 cases. Findings There were 132 (1.8%) ventricular arrhythmia/cardiac arrest and 19 (0.3%) QTc prolongation/torsade de pointes cases associated with buprenorphine compared with 1729 (11.6%) ventricular arrhythmia/cardiac arrest and 390 (2.6%) QTc prolongation/torsade de pointes cases involving methadone. PRRs associated with buprenorphine were not significant for ventricular arrhythmia/cardiac arrest (1.1 95% confidence interval (CI) 0.9–1.3, χ2=1.2) or QTc prolongation/torsade de pointes (1.0 95% CI 0.7–1.9, χ2=0.0006), but were for methadone (7.2 95% CI 6.9–7.5, χ2=9160; 10.6 95% CI 9.7–11.8, χ2=3305, respectively). Conclusion In spontaneously reported adverse events, methadone is associated with disproportionate reporting of cardiac arrhythmias, whereas buprenorphine is not. Although these findings probably reflect clinically relevant differences, a causal connection cannot be presumed and disproportionality analysis cannot quantify absolute risk per treatment episode. Population-based studies to definitively quantify differential incidence rates are warranted. PMID:26075588

  11. Hepatocyte transplantation for inherited metabolic diseases of the liver.

    PubMed

    Jorns, C; Ellis, E C; Nowak, G; Fischler, B; Nemeth, A; Strom, S C; Ericzon, B G

    2012-09-01

    Inherited metabolic diseases of the liver are characterized by deficiency of a hepatic enzyme or protein often resulting in life-threatening disease. The remaining liver function is usually normal. For most patients, treatment consists of supportive therapy, and the only curative option is liver transplantation. Hepatocyte transplantation is a promising therapy for patients with inherited metabolic liver diseases, which offers a less invasive and fully reversible approach. Procedure-related complications are rare. Here, we review the experience of hepatocyte transplantation for metabolic liver diseases and discuss the major obstacles that need to be overcome to establish hepatocyte transplantation as a reliable treatment option in the clinic.

  12. Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

    PubMed

    Yu-Wai-Man, Patrick

    2016-10-01

    Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation.

  13. Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

    PubMed Central

    Yu-Wai-Man, Patrick

    2016-01-01

    Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. PMID:27002113

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Digenic Inheritance in Cystinuria Mouse Model

    PubMed Central

    Espino, Meritxell; Font-Llitjós, Mariona; Vilches, Clara; Salido, Eduardo; Prat, Esther; López de Heredia, Miguel; Palacín, Manuel; Nunes, Virginia

    2015-01-01

    Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5-months) and late stage (8-months) of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/-) present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/-) and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients. PMID:26359869

  20. 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.

  1. Small-conductance Ca2+ -activated K+ channels and cardiac arrhythmias.

    PubMed

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

    2015-08-01

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

  2. Supraventricular Arrhythmias after Thoracotomy: Is There a Role for Autonomic Imbalance?

    PubMed Central

    Simeoforidou, Marina; Stamoulis, Konstantinos; Bareka, Metaxia

    2013-01-01

    Supraventricular arrhythmias are common rhythm disturbances following pulmonary surgery. The overall incidence varies between 3.2% and 30% in the literature, while atrial fibrillation is the most common form. These arrhythmias usually have an uneventful clinical course and revert to normal sinus rhythm, usually before patent's discharge from hospital. Their importance lies in the immediate hemodynamic consequences, the potential for systemic embolization and the consequent long-term need for prophylactic drug administration, and the increased cost of hospitalization. Their incidence is probably related to the magnitude of the performed operative procedure, occurring more frequently after pneumonectomy than after lobectomy. Investigators believe that surgical factors (irritation of the atria per se or on the ground of chronic inflammation of aged atria), direct injury to the anatomic structure of the autonomic nervous system in the thoracic cavity, and postthoracotomy pain may contribute independently or in association with each other to the development of these arrhythmias. This review discusses currently available information about the potential mechanisms and risk factors for these rhythm disturbances. The discussion is in particular focused on the role of postoperative pain and its relation to the autonomic imbalance, in an attempt to avoid or minimize discomfort with proper analgesia utilization. PMID:24235971

  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. Sleep Apnea and Nocturnal Cardiac Arrhythmia: A Populational Study

    PubMed Central

    Cintra, Fatima Dumas; Leite, Renata Pimentel; Storti, Luciana Julio; Bittencourt, Lia Azeredo; Poyares, Dalva; Castro, Laura de Siqueira; Tufik, Sergio; de Paola, Angelo

    2014-01-01

    Background The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. The authors hypothesized that nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea. Objective To analyze the relationship between obstructive sleep apnea and abnormal heart rhythm during sleep in a population sample. Methods Cross-sectional study with 1,101 volunteers, who form a representative sample of the city of São Paulo. The overnight polysomnography was performed using an EMBLA® S7000 digital system during the regular sleep schedule of the individual. The electrocardiogram channel was extracted, duplicated, and then analyzed using a Holter (Cardio Smart®) system. Results A total of 767 participants (461 men) with a mean age of 42.00 ± 0.53 years, were included in the analysis. At least one type of nocturnal cardiac rhythm disturbance (atrial/ventricular arrhythmia or beat) was observed in 62.7% of the sample. The occurrence of nocturnal cardiac arrhythmias was more frequent with increased disease severity. Rhythm disturbance was observed in 53.3% of the sample without breathing sleep disorders, whereas 92.3% of patients with severe obstructive sleep apnea showed cardiac arrhythmia. Isolated atrial and ventricular ectopy was more frequent in patients with moderate/severe obstructive sleep apnea when compared to controls (p < 0.001). After controlling for potential confounding factors, age, sex and apnea-hypopnea index were associated with nocturnal cardiac arrhythmia. Conclusion Nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea and the prevalence increases with disease severity. Age, sex, and the Apnea-hypopnea index were predictors of arrhythmia in this sample. PMID:25252161

  5. 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.

  6. 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

  7. [Ryanodine receptor, calcium leak and arrhythmias].

    PubMed

    Rueda, Angélica; de Alba-Aguayo, David R; Valdivia, Héctor H

    2014-01-01

    The participation of the ionic Ca(2+) release channel/ryanodine receptor in cardiac excitation-contraction coupling is well known since the late '80s, when various seminal papers communicated its purification for the first time and its identity with the "foot" structures located at the terminal cisternae of the sarcoplasmic reticulum. In addition to its main role as the Ca(2+) channel responsible for the transient Ca(2+) increase that activates the contractile machinery of the cardiomyocytes, the ryanodine receptor releases Ca(2+) during the relaxation phase of the cardiac cycle, giving rise to a diastolic Ca(2+) leak. In normal physiological conditions, diastolic Ca(2+) leak regulates the proper level of luminal Ca(2+), but in pathological conditions it participates in the generation of both, acquired and hereditary arrhythmias. Very recently, several groups have focused their efforts into the development of pharmacological tools to control the altered diastolic Ca(2+) leak via ryanodine receptors. In this review, we focus our interest on describing the participation of cardiac ryanodine receptor in the diastolic Ca(2+) leak under physiological or pathological conditions and also on the therapeutic approaches to control its undesired exacerbated activity during diastole.

  8. Alternans Arrhythmias: From Cell to Heart

    PubMed Central

    Weiss, James N.; Nivala, Michael; Garfinkel, Alan; Qu, Zhilin

    2010-01-01

    The goal of systems biology is to relate events at the molecular level to more integrated scales from organelle to cell, tissue and living organism. Here we review how normal and abnormal excitation-contraction (EC) coupling properties emerge from the protein scale, where behaviors are dominated by randomness, to the cell and tissue scales, where heart has to beat with reliable regularity for a life-time. Beginning with the fundamental unit of EC coupling, the couplon where L-type Ca channels in the sarcolemmal membrane adjoin ryanodine receptors in the sarcoplasmic reticulum membrane, we show how a network of couplons with three basic properties (random activation, refractoriness, and recruitment) produces the classical physiological properties of excitation-contraction (EC) coupling and, under pathophysiological conditions, leads to Ca alternans and Ca waves. Moving to the tissue scale, we discuss how cellular Ca alternans and Ca waves promote both reentrant and focal arrhythmias in the heart. Throughout, we emphasize the qualitatively novel properties which emerge at each new scale of integration. PMID:21212392

  9. Inherited disorders of hemostasis in dogs and cats.

    PubMed

    Barr, James W; McMichael, Maureen

    2012-05-01

    Inherited disorders of hemostasis encompass abnormalities in primary hemostasis, coagulation, and fibrinolysis resulting from genetic mutations. There is significant variation in the phenotype expressed ranging from life limiting to the absence of overt clinical signs. Von Willebrand disease is the most common primary hemostatic disorder in dogs, and hemophilia A is the most common coagulation factor disorder. The diagnosis of inherited bleeding disorders is made by functional and/or quantitative evaluation. Genetic testing has added to the knowledge base, allowing prevention through targeted breeding. Avoidance of trauma and injury is paramount in the prevention of bleeding in animals diagnosed with inherited hemostatic disorders. Current therapeutic options include platelet transfusions, broad replacement of coagulation factors (e.g., plasma), targeted factor replacement (e.g., cryoprecipitate), antifibrinolytic agents and specific factor replacement, and treatment of the symptoms (i.e., bleeding) with blood transfusions.

  10. 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

  11. Computer-assisted education system for arrhythmia (CAESAR).

    PubMed

    Fukushima, M; Inoue, M; Fukunami, M; Ishikawa, K; Inada, H; Abe, H

    1984-08-01

    A computer-assisted education system for arrhythmia (CAESAR) was developed for students to acquire the ability to logically diagnose complicated arrhythmias. This system has a logical simulator of cardiac rhythm using a mathematical model of the impulse formation and conduction system of the heart. A simulated arrhythmia (ECG pattern) is given on a graphic display unit with simulated series of the action potential of five pacemaker centers and the "ladder diagram" of impulse formation and conduction, which show the mechanism of that arrhythmia. For the purpose of the evaluation of this system, 13 medical students were given two types of tests concerning arrhythmias before and after 2-hr learning with this system. The scores they obtained after learning increased significantly from 73.3 +/- 11.9 to 93.2 +/- 3.0 (P less than 0.001) in one test and from 47.2 +/- 17.9 to 64.9 +/- 19.6 (P less than 0.001) in another one. These results proved that this CAI system is useful and effective for training ECG interpretation of arrhythmias.

  12. 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

  13. 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

  14. Molecular and clinical characterisation of three Spanish families with maternally inherited non‐syndromic hearing loss caused by the 1494C→T mutation in the mitochondrial 12S rRNA gene

    PubMed Central

    Rodríguez‐Ballesteros, M; Olarte, M; Aguirre, L A; Galán, F; Galán, R; Vallejo, L A; Navas, C; Villamar, M; Moreno‐Pelayo, M A; Moreno, F; del Castillo, I

    2006-01-01

    Mutations in the 12S rRNA gene of the mitochondrial genome are responsible for maternally inherited non‐syndromic hearing loss (NSHL), and for increased susceptibility to the ototoxicity of aminoglycoside antibiotics. Among these mutations, 1555A→G is the most prevalent in all populations tested so far. Recently, the 1494C→T mutation was reported in two large Chinese pedigrees with maternally inherited NSHL. In this study, sequencing of the 12S rRNA gene in a Spanish family with maternally inherited NSHL showed the presence of the 1494C→T mutation. An additional screening of 1339 unrelated Spanish patients with NSHL allowed the authors to find two other families with the mutation. Audiological data were obtained from 17 confirmed 1494C→T carriers, which showed that the hearing loss was sensorineural, bilateral and symmetrical, with a remarkable variability in age of onset and severity. Three carriers were asymptomatic. Three affected carriers had a history of treatment with aminoglycoside antibiotics. The mitochondrial genome of one affected person from each of these three families was entirely sequenced, and it was established that they belong to different mitochondrial haplogroups (H, U5b, U6a). The study results further support the pathogenic role of 1494C→T on hearing, and show that this mutation can be found in different Caucasian mitochondrial DNA backgrounds. PMID:17085680

  15. 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

  16. Inherited epidermolysis bullosa - the spectrum of complications.

    PubMed

    Murat-Sušić, Slobodna; Husar, Karmela; Skerlev, Mihael; Marinović, Branka; Babić, Irena

    2011-01-01

    Epidermolysis bullosa is a group of inherited diseases that are characterized by skin and mucosal fragility and blister formation. A wide variety of extracutaneous manifestations can develop as well as various complications of the disease such as severe anemia, growth retardation, esophageal stenosis, mutilating deformities of hands and feet, glomerulonephritis leading to chronic renal failure, and many others. One of the most important and often occurring complications is the development of cutaneous squamous cell carcinomas that grow and metastasize quickly. The objective of this paper is to give dermatologists a review of major complications encountered in patients with epidermolysis bullosa. Since these complications occur so often and can be considered to be part of the clinical picture, it is mandatory to develop a multidisciplinary well-educated team involved in follow-up and treatment of these patients. PMID:22185926

  17. QT interval dispersion: a non-invasive marker of susceptibility to arrhythmia in patients with sustained ventricular arrhythmias?

    PubMed Central

    Pye, M.; Quinn, A. C.; Cobbe, S. M.

    1994-01-01

    OBJECTIVE--To assess QT interval dispersion on the surface electrocardiogram in patients with sustained ventricular arrhythmias. DESIGN--A retrospective and prospective blinded controlled study of patients referred for investigation of ventricular arrhythmias at a tertiary cardiac centre. PATIENTS AND METHODS--89 consecutive patients with sustained ventricular arrhythmias due to chronic ischaemic heart disease, cardiomyopathy, or ventricular tachycardia (VT) in a normal heart. 32 patients did not meet the inclusion criteria; therefore 57 patients were compared with a control group of 40 patients with myocardial disease but no history of arrhythmias and 12 normal controls with no myocardial disease. Standard 12 lead electrocardiograms were enlarged, the QT intervals for each lead measured, and QT dispersion calculated. RESULTS--There was a significantly greater mean QT dispersion (77 ms) in patients with sustained ventricular arrhythmias compared with the control group (38 ms, p < 0.01). This held for all groups; after myocardial infarction VT (82 (22) ms v control 38 (10) ms; p < 0.01), dilated cardiomyopathy VT (76 (18) ms v control 40 (11) ms, p < 0.01), and normal heart VT (65 (7) ms v control 32 (8), p < 0.05). There was also a greater QT dispersion in patients with impaired left ventricular function and VT, with a correlation between left ventricular function and QT dispersion in patients with VT (r = 0.56, p < 0.01). CONCLUSION--QT interval dispersion may be a further non-invasive marker of susceptibility to ventricular arrhythmias. PMID:8043329

  18. Cardiac arrhythmias induced by chloral hydrate in rhesus monkeys.

    PubMed

    Han, Pengfei; Song, Haibo; Yang, Pingliang; Xie, Huiqi; Kang, Y James

    2011-06-01

    Chloral hydrate has been long used as a safe sedative and hypnotic drug in humans. However, reports on its cardiovascular adverse effects have been published from time to time. The present study was undertaken to use Rhesus monkeys as a model to define the dose regiment of chloral hydrate at which cardiac arrhythmias can be induced and the consequences of the cardiac events. Male Rhesus monkeys of 2-3 years old were intravenously infused with chloral hydrate starting at 50 mg/kg with an increasing increment of 25 mg/kg until the occurrence of cardiac arrhythmias. In addition, a traditional up-and-down dosing procedure was applied to define a single dose level at which cardiac arrhythmias can be induced. The data obtained showed that when the sequentially escaladed dose reached 125 mg/kg, cardiac arrhythmias occurred in all monkeys tested. The single effective dose to cause cardiac arrhythmias calculated from the crossover analysis was 143 ± 4 mg/kg. This value would be equivalent to 68.6 ± 1.9 mg/kg for children and 46.4 ± 1.3 mg/kg for adults in humans. Under either multiple or single dose condition, cardiac arrhythmias did not occur before 40 min after the onset of anesthesia induced by chloral hydrate. Cardiac arrhythmias were recovered without help at the end of the anesthesia in most cases, but also continued after the regain of consciousness in some cases. The cardiac arrhythmias were accompanied with compromised cardiac function including suppressed fractional shortening and ejection fraction. This study thus suggests that cautions need to be taken when chloral hydrate is used above certain levels and beyond a certain period of anesthesia, and cardiac arrhythmias induced by chloral hydrate need to be closely monitored because compromised cardiac function may occur simultaneously. In addition, patients with cardiac arrhythmias induced by chloral hydrate should be monitored even after they are recovered from the anesthesia.

  19. 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.

  20. Plate tectonics, damage and inheritance

    NASA Astrophysics Data System (ADS)

    Bercovici, David; Ricard, Yanick

    2014-04-01

    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.

  1. Plate tectonics, damage and inheritance

    NASA Astrophysics Data System (ADS)

    Bercovici, D. A.; Ricard, Y. R.

    2013-12-01

    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 4Ga, evident in geochemical analysis from ancient cratons, to global tectonics by 3-2.7Ga, suggests that plates and plate boundaries spread globally over a 1Gyr period. We hypothesize 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 plate boundaries and eventually fully formed tectonic plates driven by subduction alone. We demonstrate this process with an idealized model of pressure-driven flow (wherein a low pressure zone is equivalent to downwelling suction or slab pull) in a lithosphere that self-weakens according to a mylonitic-type polycrystalline grain-damage mechanism (Bercovici and Ricard, Phys. Earth Planet. Int. v.202-203, pp27-55, 2012). In the simplest case, for Earth-like conditions, four successive orthogonal rotations of the driving pressure field yield relic damage zones that are inherited to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even as flow is only driven by subduction. For Venus' hotter surface conditions, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which is compatible with observations. After plates are 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 and micro plates.

  2. 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

  3. 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.

  4. Prevention of Ventricular Arrhythmia and Calcium Dysregulation in a Catecholaminergic Polymorphic Ventricular Tachycardia Mouse Model Carrying Calsequestrin-2 Mutation

    PubMed Central

    Alcalai, Ronny; Wakimoto, Hiroko; Arad, Michael; Planer, David; Konno, Tetsuo; Wang, Libin; Seidman, Jon G.; Seidman, Christine E.; Berul, Charles I

    2010-01-01

    Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca2+ overload and increased Ca2+ leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. Method and results CPVT mouse models that lack CASQ2 were treated with Ca2+-channel inhibitors, β-adrenergic inhibitors, or Mg2+. Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca2+ transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca2+ channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca2+ content in mutant myocytes, diminished diastolic Ca2+ overload, increased systolic Ca2+ amplitude, and prevented Ca2+ oscillations in stressed mutant myocytes. Conclusions Ca2+ channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca2+ content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca2+ buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT. PMID:20807279

  5. Treatment of cardiac arrhythmias in a mouse model of Rett syndrome with Na+-channel-blocking antiepileptic drugs.

    PubMed

    Herrera, José A; Ward, Christopher S; Pitcher, Meagan R; Percy, Alan K; Skinner, Steven; Kaufmann, Walter E; Glaze, Daniel G; Wehrens, Xander H T; Neul, Jeffrey L

    2015-04-01

    One quarter of deaths associated with Rett syndrome (RTT), an X-linked neurodevelopmental disorder, are sudden and unexpected. RTT is associated with prolonged QTc interval (LQT), and LQT-associated cardiac arrhythmias are a potential cause of unexpected death. The standard of care for LQT in RTT is treatment with β-adrenergic antagonists; however, recent work indicates that acute treatment of mice with RTT with a β-antagonist, propranolol, does not prevent lethal arrhythmias. In contrast, acute treatment with the Na(+) channel blocker phenytoin prevented arrhythmias. Chronic dosing of propranolol may be required for efficacy; therefore, we tested the efficacy of chronic treatment with either propranolol or phenytoin on RTT mice. Phenytoin completely abolished arrhythmias, whereas propranolol showed no benefit. Surprisingly, phenytoin also normalized weight and activity, but worsened breathing patterns. To explore the role of Na(+) channel blockers on QT in people with RTT, we performed a retrospective analysis of QT status before and after Na(+) channel blocker antiepileptic therapies. Individuals with RTT and LQT significantly improved their QT interval status after being started on Na(+) channel blocker antiepileptic therapies. Thus, Na(+) channel blockers should be considered for the clinical management of LQT in individuals with RTT.

  6. Paternal inheritance of mitochondria in Chlamydomonas.

    PubMed

    Nakamura, Soichi

    2010-03-01

    To analyze mitochondrial DNA (mtDNA)inheritance, differences in mtDNA between Chlamydomonas reinhardtii and Chlamydomonas smithii, respiration deficiency and antibiotic resistance were used to distinguish mtDNA origins. The analyses indicated paternal inheritance. However, these experiments raised questions regarding whether paternal inheritance occurred normally.Mitochondrial nucleoids were observed in living zygotes from mating until 3 days after mating and then until progeny formation. However, selective disappearance of nucleoids was not observed. Subsequently, experimental serial backcrosses between the two strains demonstrated strict paternal inheritance. The fate of mt+ and mt- mtDNA was followed using the differences in mtDNA between the two strains. The slow elimination of mt+ mtDNA through zygote maturation in darkness was observed, and later the disappearance of mt+ mtDNA was observed at the beginning of meiosis. To explain the different fates of mtDNA, methylation status was investigated; however, no methylation was detected. Variously constructed diploid cells showed biparental inheritance. Thus, when the mating process occurs normally, paternal inheritance occurs. Mutations disrupting mtDNA inheritance have not yet been isolated. Mutations that disrupt maternal inheritance of chloroplast DNA (cpDNA) do not disrupt inheritance of mtDNA. The genes responsible for mtDNA inheritance are different from those of chloroplasts.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Mitochondrial DNA inheritance after SCNT.

    PubMed

    Hiendleder, Stefan

    2007-01-01

    Mitochondrial biogenesis and function is under dual genetic control and requires extensive interaction between biparentally inherited nuclear genes and maternally inherited mitochondrial genes. Standard SCNT procedures deprive an oocytes' mitochondrial DNA (mtDNA) of the corresponding maternal nuclear DNA and require it to interact with an entirely foreign nucleus that is again interacting with foreign somatic mitochondria. As a result, most SCNT embryos, -fetuses, and -offspring carry somatic cell mtDNA in addition to recipient oocyte mtDNA, a condition termed heteroplasmy. It is thus evident that somatic cell mtDNA can escape the selective mechanism that targets and eliminates intraspecific sperm mitochondria in the fertilized oocyte to maintain homoplasmy. However, the factors responsible for the large intra- and interindividual differences in heteroplasmy level remain elusive. Furthermore, heteroplasmy is probably confounded with mtDNA recombination. Considering the essential roles of mitochondria in cellular metabolism, cell signalling, and programmed cell death, future experiments will need to assess the true extent and impact of unorthodox mtDNA transmission on various aspects of SCNT success.

  13. Cardiac arrhythmia in refrigerator repairmen exposed to fluorocarbons.

    PubMed

    Edling, C; Ohlson, C G; Ljungkvist, G; Oliv, A; Söderholm, B

    1990-03-01

    A field study of 89 refrigerator repairmen was carried out to ascertain whether occupational exposure to fluorocarbons induces cardiac arrhythmia. The concentrations of fluorocarbons in the breathing zones and the heart activity were recorded simultaneously. Most cooling systems contained FC 12 or FC 22. The highest level recorded in one minute was 14,000 ppm and the highest time weighted level during eight hours was 280 ppm. Two types of arrhythmia were recorded, ectopic beats and sudden bradycardia. A within subject comparison design was applied and the main parameter was the difference in arrhythmia frequencies between exposed and unexposed periods. No appreciable differences between exposed and unexposed periods and no consistent dose effect relations were observed, although subjects in the medium exposure category showed a difference of borderline significance (Wilcoxon's test: p = 0.05, one tailed). The frequencies of arrhythmia when unexposed were somewhat higher than previously reported. Misclassification of the exposure and the possible confounding effect of physical workload and psychological strain may have obscured a causal relation and therefore a minor effect cannot be ruled out. The results do not support the notion that fluorocarbons induce cardiac arrhythmia in occupationally exposed refrigerator repairmen.

  14. Cardiac arrhythmia in refrigerator repairmen exposed to fluorocarbons.

    PubMed Central

    Edling, C; Ohlson, C G; Ljungkvist, G; Oliv, A; Söderholm, B

    1990-01-01

    A field study of 89 refrigerator repairmen was carried out to ascertain whether occupational exposure to fluorocarbons induces cardiac arrhythmia. The concentrations of fluorocarbons in the breathing zones and the heart activity were recorded simultaneously. Most cooling systems contained FC 12 or FC 22. The highest level recorded in one minute was 14,000 ppm and the highest time weighted level during eight hours was 280 ppm. Two types of arrhythmia were recorded, ectopic beats and sudden bradycardia. A within subject comparison design was applied and the main parameter was the difference in arrhythmia frequencies between exposed and unexposed periods. No appreciable differences between exposed and unexposed periods and no consistent dose effect relations were observed, although subjects in the medium exposure category showed a difference of borderline significance (Wilcoxon's test: p = 0.05, one tailed). The frequencies of arrhythmia when unexposed were somewhat higher than previously reported. Misclassification of the exposure and the possible confounding effect of physical workload and psychological strain may have obscured a causal relation and therefore a minor effect cannot be ruled out. The results do not support the notion that fluorocarbons induce cardiac arrhythmia in occupationally exposed refrigerator repairmen. PMID:2328227

  15. Epigenetic inheritance: a contributor to species differentiation?

    PubMed

    Boffelli, Dario; Martin, David I K

    2012-10-01

    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.

  16. 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

  17. Cardiac troponin T mutations promote life-threatening arrhythmias.

    PubMed

    Fiset, Céline; Giles, Wayne R

    2008-12-01

    Mutations in contractile proteins in heart muscle can cause anatomical changes that result in cardiac arrhythmias and sudden cardiac death. However, a conundrum has existed because mutations in one such contractile protein, a so-called Ca2+ sensor troponin T (TnT), can promote ventricular rhythm disturbances even in the absence of hypertrophy or fibrosis. Thus, these mutations must enhance abnormal electrophysiological events via alternative means. In this issue of the JCI, Baudenbacher et al. report a novel mechanism to explain this puzzle (see the related article beginning on page 3893). They show that a selected TnT mutation in the adult mouse heart can markedly increase the sensitivity of cardiac muscle myofilaments to Ca2+ and enhance the susceptibility to arrhythmia, even in the absence of anatomical deformities. As these same mutations can cause some forms of arrhythmias in humans, these findings are of both basic and translational significance. PMID:19033655

  18. Role of adipose tissue in the pathogenesis of cardiac arrhythmias.

    PubMed

    Samanta, Rahul; Pouliopoulos, Jim; Thiagalingam, Aravinda; Kovoor, Pramesh

    2016-01-01

    Epicardial adipose tissue is present in normal healthy individuals. It is a unique fat depot that, under physiologic conditions, plays a cardioprotective role. However, excess epicardial adipose tissue has been shown to be associated with prevalence and severity of atrial fibrillation. In arrhythmogenic right ventricular cardiomyopathy and myotonic dystrophy, fibrofatty infiltration of the myocardium is associated with ventricular arrhythmias. In the ovine model of ischemic cardiomyopathy, the presence of intramyocardial adipose or lipomatous metaplasia has been associated with increased propensity to ventricular tachycardia. These observations suggest a role of adipose tissue in the pathogenesis of cardiac arrhythmias. In this article, we review the role of cardiac adipose tissue in various cardiac arrhythmias and discuss the possible pathophysiologic mechanisms.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. Implantable Defibrillators for Secondary Prevention of Sudden Cardiac Death in Cardiac Surgery Patients With Perioperative Ventricular Arrhythmias

    PubMed Central

    Nageh, Maged F.; Kim, John J.; Chen, Lie‐Hong; Yao, Janis F.

    2014-01-01

    Background Randomized studies of implantable cardioverter defibrillators (ICD) have excluded sudden cardiac death survivors who had revascularization before or after an arrhythmic event. To evaluate the role of ICD and the effects of clinical variables including degree of revascularization, we studied cardiac surgery patients who had an ICD implanted for sustained perioperative ventricular arrhythmias. Methods and Results The electronic database for Southern California Kaiser Foundation hospitals was searched for patients who had cardiac surgery between 1999 and 2005 and an ICD implanted within 3 months of surgery. One hundred sixty‐four patients were identified; 93/164 had an ICD for sustained pre‐ or postoperative ventricular tachycardia or fibrillation requiring resuscitation. Records were reviewed for the following: presenting arrhythmia, ejection fraction, and degree of revascularization. The primary end point was total mortality (TM) and/or appropriate ICD therapy (ICD‐T), and secondary end points are TM and ICD‐T. During the mean follow up of 49 months, the primary endpoint of TM+ICD‐T and individual end points of TM and ICD‐T were observed in 52 (56%), 35 (38%), and 28 (30%) patients, respectively, with 55% of TM, and 23% of ICD‐T occurring within 2 years of implant. In multivariate risk analysis, none of the following was associated with any of the end points: incomplete revascularization, presenting ventricular arrhythmia, and timing of arrhythmias. Conclusion Our data supports the recent guidelines for ICD in this cohort of patients, as the presence of irreversible substrate and triggers of ventricular arrhythmias, cannot be reliably excluded even with complete revascularization. Further studies are needed to understand this complex group of patients. PMID:25146702

  4. Exome sequencing in undiagnosed inherited and sporadic ataxias

    PubMed Central

    Pyle, Angela; Smertenko, Tania; Bargiela, David; Griffin, Helen; Duff, Jennifer; Appleton, Marie; Douroudis, Konstantinos; Pfeffer, Gerald; Santibanez-Koref, Mauro; Eglon, Gail; Yu-Wai-Man, Patrick; Ramesh, Venkateswaran; Horvath, Rita

    2015-01-01

    Inherited ataxias are clinically and genetically heterogeneous, and a molecular diagnosis is not possible in most patients. Having excluded common sporadic, inherited and metabolic causes, we used an unbiased whole exome sequencing approach in 35 affected individuals, from 22 randomly selected families of white European descent. We defined the likely molecular diagnosis in 14 of 22 families (64%). This revealed de novo dominant mutations, validated disease genes previously described in isolated families, and broadened the clinical phenotype of known disease genes. The diagnostic yield was the same in both young and older-onset patients, including sporadic cases. We have demonstrated the impact of exome sequencing in a group of patients notoriously difficult to diagnose genetically. This has important implications for genetic counselling and diagnostic service provision. PMID:25497598

  5. Inheritance of goat coat colors.

    PubMed

    Adalsteinsson, S; Sponenberg, D P; Alexieva, S; Russel, A J

    1994-01-01

    Goat color inheritance was evaluated based on color description of 218 kids and their parents (10 sires, 178 dams) from mixed crosses between several goat populations in an experiment on cashmere fiber production. Altogether 10 color patterns were observed. They were postulated to be caused by 10 alleles at the Agouti locus, with the allele for white or tan color being the top dominant allele, and the nine others codominant. The bottom recessive allele, for nonagouti color, was the 11th allele at this locus. The postulated alleles are white or tan (A(wt)), black mask (A(blm)), bezoar (A(bz)), badgerface (A(b)), grey (A(g)), lightbelly (A(lb)), swiss markings (A(sm)), lateral stripes (A(ls)), mahogany (A(mh)), red cheek (A(rc)), and nonagouti (Aa). Two types of eumelanin pigment were observed, black and light brown, the latter being dominant. Recessive brown was not observed.

  6. Inheritance of epigenetic chromatin silencing

    PubMed Central

    David-Rus, Diana; Mukhopadhyay, Swagatam; Lebowitz, Joel L.; Sengupta, Anirvan M.

    2010-01-01

    Maintenance of alternative chromatin states through cell divisions pose some fundamental constraints on the dynamics of histone modifications. In this paper, we study the systems biology of epigenetic inheritance by defining and analyzing general classes of mathematical models. We discuss how the number of modification states involved plays an essential role in the stability of epigenetic states. In addition, DNA duplication and the consequent dilution of marked histones act as a large perturbation for a stable state of histone modifications. The requirement that this large perturbation falls into the basin of attraction of the original state sometimes leads to additional constraints on effective models. Two such models, inspired by two different biological systems, are compared in their fulfilling the requirements of multistability and of recovery after DNA duplication. We conclude that in the presence of multiple histone modifications that characterize alternative epigenetic stable states, these requirements are more easily fulfilled. PMID:19174167

  7. 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

  8. Cardiac arrhythmias and conduction defects in systemic sclerosis.

    PubMed

    Vacca, Alessandra; Meune, Christophe; Gordon, Jessica; Chung, Lorinda; Proudman, Susanna; Assassi, Shervin; Nikpour, Mandana; Rodriguez-Reyna, Tatiana S; Khanna, Dinesh; Lafyatis, Robert; Matucci-Cerinic, Marco; Distler, Oliver; Allanore, Yannick

    2014-07-01

    Signs and symptoms of arrhythmias or conduction defects are frequently reported in patients with SSc. These rhythm disorders may have several origins (i.e., related to primary heart involvement, pericardial disease, valvular regurgitation or pulmonary arterial hypertension) and may negatively affect the overall prognosis of these patients. It is therefore important to identify patients at high risk for cardiac arrhythmias with a complete cardiological evaluation and to identify the underlying heart disease, including SSc-related myocardial involvement. In addition, some therapeutic options in SSc patients may differ from those recommended in other populations.

  9. Update on inherited disorders of haemostasis and pregnancy.

    PubMed

    Lavee, Orly; Kidson-Gerber, Giselle

    2016-06-01

    Inherited bleeding disorders have the potential to cause bleeding complications during pregnancy, childbirth and the postpartum period as well as effect fetal outcomes. There is an evolving understanding of the need for specialised and individualised care for affected women during these times. The aim for each patient is to estimate the risk to mother, fetus and neonate; to implement measures to minimise these risks; and to anticipate complications and develop contingencies for these scenarios. This includes accurate diagnosis, preconceptual care, prenatal diagnostic options, antenatal care, delivery and postpartum care as well as care of an affected neonate. An understanding of the physiologic haemostatic changes associated with pregnancy as well as the scope of defects, inheritance and management of inherited bleeding disorders is paramount when caring for these women. Collaborative and prospective management in conjunction with haematology services underpins the approach advocated. This review draws on the available literature, and outlines the principles of care for women with inherited bleeding disorders before, during and after pregnancy, as well as their babies, based on both available data and collective clinical experience. PMID:27512496

  10. 78 FR 36787 - Rechanneling the Current Cardiac Risk Paradigm: Arrhythmia Risk Assessment During Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND 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...

  11. Acute cardiac arrhythmias following surgery for congenital heart disease: mechanisms, diagnostic tools, and management.

    PubMed

    Payne, Linda; Zeigler, Vicki L; Gillette, Paul C

    2011-06-01

    This article focuses on the management of those cardiac arrhythmias most commonly seen in the immediate postoperative period. They include ventricular tachycardia, ventricular fibrillation, atrial flutter, junctional ectopic tachycardia, bradycardia, and atrioventricular block. The mechanisms of cardiac arrhythmias are reviewed followed by a brief overview of the predominant acute arrhythmias, tools used for the diagnostic evaluation of these arrhythmias, management strategies, and, finally, nursing considerations.

  12. 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.

  13. 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…

  14. Pharmacological modulation of gap junction function with the novel compound rotigaptide: a promising new principle for prevention of arrhythmias.

    PubMed

    Kjølbye, Anne Louise; Haugan, Ketil; Hennan, James K; Petersen, Jørgen S

    2007-10-01

    Existing anti-arrhythmic therapy is hampered by lack of efficacy and unacceptable side effects. Thus, ventricular tachycardia and fibrillation remains the strongest predictor of in-hospital mortality in patients with myocardial infarction. In atrial fibrillation, rhythm control with conventional ion channel blockers provide no therapeutic benefit relative to rate control. Several lines of research indicate that impaired gap junctional cell-to-cell coupling between neighbouring cardiomyocytes is critical for the development of cardiac re-entry arrhythmias. Rotigaptide is the first drug that has been developed to prevent arrhythmias by re-establishing gap junctional intercellular communication. During conditions with acute cardiac ischaemia, rotigaptide effectively prevents induction of both ventricular and atrial tachyarrhythmia. Moreover, rotigaptide effectively prevents ischaemia reperfusion arrhythmias. At the cellular level, rotigaptide inhibits ischaemia-induced dephosphorylation of Ser297 and Ser368, which is considered important for the gating of connexin43 gap junction channels. No drug-related toxicity has been demonstrated at plasma concentrations 77,000 times above therapeutic concentrations. In rats and dogs, rotigaptide reduces infarct size following myocardial infarction. A series of phase I trials has been completed in which rotigaptide has been administered intravenously to ~200 healthy persons. No drug-related side effects have been demonstrated in healthy human beings. Clinical safety, tolerability and efficacy in patients with heart disease are being evaluated in ongoing clinical trials. Rotigaptide represents a pioneering pharmacological principle with a highly favourable preclinical and clinical safety profile, which makes this molecule a promising drug candidate for the prevention of cardiac arrhythmias.

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  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. 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.

  2. Transgenerational epigenetic inheritance in health and disease.

    PubMed

    Whitelaw, Nadia C; Whitelaw, Emma

    2008-06-01

    Over the past century, patterns of phenotypic inheritance have been observed that are not easily rationalised by Mendel's rules of inheritance. Now that we have begun to understand more about non-DNA based, or 'epigenetic', control of phenotype at the molecular level, the idea that the transgenerational inheritance of these epigenetic states could explain non-Mendelian patterns of inheritance has become attractive. There is a growing body of evidence that abnormal epigenetic states, termed epimutations, are associated with disease in humans. For example, in several cases of colorectal cancer, epimutations have been identified that silence the human mismatch repair genes, MLH1 and MSH2. But strong evidence that the abnormal epigenetic states are primary events that occur in the absence of genetic change and are inherited across generations is still absent.

  3. 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

  4. 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)

  5. Reduction in dynamin-2 is implicated in ischaemic cardiac arrhythmias.

    PubMed

    Shi, Dan; Xie, Duanyang; Zhang, Hong; Zhao, Hong; Huang, Jian; Li, Changming; Liu, Yi; Lv, Fei; The, Erlinda; Liu, Yuan; Yuan, Tianyou; Wang, Shiyi; Chen, Jinjin; Pan, Lei; Yu, Zuoren; Liang, Dandan; Zhu, Weidong; Zhang, Yuzhen; Li, Li; Peng, Luying; Li, Jun; Chen, Yi-Han

    2014-10-01

    Ischaemic cardiac arrhythmias cause a large proportion of sudden cardiac deaths worldwide. The ischaemic arrhythmogenesis is primarily because of the dysfunction and adverse remodelling of sarcolemma ion channels. However, the potential regulators of sarcolemma ion channel turnover and function in ischaemic cardiac arrhythmias remains unknown. Our previous studies indicate that dynamin-2 (DNM2), a cardiac membrane-remodelling GTPase, modulates ion channels membrane trafficking in the cardiomyocytes. Here, we have found that DNM2 plays an important role in acute ischaemic arrhythmias. In rat ventricular tissues and primary cardiomyocytes subjected to acute ischaemic stress, the DNM2 protein and transcription levels were markedly down-regulated. This DNM2 reduction was coupled with severe ventricular arrhythmias. Moreover, we identified that the down-regulation of DNM2 within cardiomyocytes increases the action potential amplitude and prolongs the re-polarization duration by depressing the retrograde trafficking of Nav1.5 and Kir2.1 channels. These effects are likely to account for the DNM2 defect-induced arrhythmogenic potentials. These results suggest that DNM2, with its multi-ion channel targeting properties, could be a promising target for novel antiarrhythmic therapies.

  6. 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

  7. 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.

  8. Supraventricular Arrhythmias in Patients With Pulmonary Arterial Hypertension.

    PubMed

    Cannillo, Margherita; Grosso Marra, Walter; Gili, Sebastiano; D'Ascenzo, Fabrizio; Morello, Mara; Mercante, Lorena; Mistretta, Elisa; Salera, Davide; Zema, Domenica; Bissolino, Arianna; Fusaro, Enrico; Marra, Sebastiano; Libertucci, Daniela; Gaita, Fiorenzo

    2015-12-15

    The onset of supraventricular arrhythmias (SVA) may be associated with clinical worsening in patients with pulmonary arterial hypertension (PAH). However, limited data have been reported, especially at long-term follow-up. Aim of this study was to investigate the incidence of SVA in our patients with PAH, the risk factors correlated to their onset and the prognostic impact. All consecutive patients with PAH without history of SVA were enrolled. Incidence of new SVA was investigated and also the risk factors for SVA. Primary end point of the study was the impact of SVA on a composite of all-cause mortality and re-hospitalization, whereas mortality was the secondary end point. Seventy-seven patients were enrolled. No significant differences in the clinical or instrumental baseline characteristics between the 2 study groups were reported. During a median follow-up of 35 months (interquartile range 21.5 to 53.5), 17 (22%) patients experienced SVA. Development of SVA was associated with worsening of prognostic parameters at the follow-up: increasing of World Health Organization (WHO) functional class (p = 0.005) and N-terminal-pro-brain natriuretic peptide (NT-proBNP) (p = 0.018) and reduction of 6-minute walking distance (p = 0.048), tricuspid annular plane systolic excursion (TAPSE) (p = 0.041), and diffusing capacity of the lung for carbon monoxide (p = 0.025). The primary end point occurred in 13 patients (76%) in the SVA group and in 22 patients (37%) in the group without SVA (p = 0.004), whereas 9 patients (53%) among those with SVA died during the follow-up compared with 8 (13%) among those without (p = 0.001). At multivariate analysis, development of SVA was independently associated with an increased risk to meet the both primary (hazard ratio 2.13; 95% confidence interval 1.07 to 4.34; p = 0.031) and secondary (hazard ratio 4.1; 95% confidence interval 1.6 to 10.6; p = 0.004) end points. In conclusion, during the 3-year follow-up period, 1/3 of patients with

  9. Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias

    PubMed Central

    Hoekstra, Maaike; Mummery, Christine L.; Wilde, Arthur A. M.; Bezzina, Connie R.; Verkerk, Arie O.

    2012-01-01

    Cardiac arrhythmias are a major cause of morbidity and mortality. In younger patients, the majority of sudden cardiac deaths have an underlying Mendelian genetic cause. Over the last 15 years, enormous progress has been made in identifying the distinct clinical phenotypes and in studying the basic cellular and genetic mechanisms associated with the primary Mendelian (monogenic) arrhythmia syndromes. Investigation of the electrophysiological consequences of an ion channel mutation is ideally done in the native cardiomyocyte (CM) environment. However, the majority of such studies so far have relied on heterologous expression systems in which single ion channel genes are expressed in non-cardiac cells. In some cases, transgenic mouse models have been generated, but these also have significant shortcomings, primarily related to species differences. The discovery that somatic cells can be reprogrammed to pluripotency as induced pluripotent stem cells (iPSC) has generated much interest since it presents an opportunity to generate patient- and disease-specific cell lines from which normal and diseased human CMs can be obtained These genetically diverse human model systems can be studied in vitro and used to decipher mechanisms of disease and identify strategies and reagents for new therapies. Here, we review the present state of the art with respect to cardiac disease models already generated using IPSC technology and which have been (partially) characterized. Human iPSC (hiPSC) models have been described for the cardiac arrhythmia syndromes, including LQT1, LQT2, LQT3-Brugada Syndrome, LQT8/Timothy syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). In most cases, the hiPSC-derived cardiomyoctes recapitulate the disease phenotype and have already provided opportunities for novel insight into cardiac pathophysiology. It is expected that the lines will be useful in the development of pharmacological agents for the management of these disorders. PMID

  10. Familial distal foregut atresia in a family with likely autosomal dominant inheritance pattern.

    PubMed

    Robinson, Ian; Gill, Harinder; Ng, Li Yen; Hayes, Roisin

    2012-11-01

    Familial occurrence of distal foregut atresia (DFA) (Type 1) is rare. Diagnosis is based upon the clinical symptomatology and confirmed by radiological studies, surgery and histology. A number of reports have described families in which several family members have been involved and suggested an autosomal recessive mode of inheritance. Little is known about the underlying genetic causes or indeed the likely pathogenic mechanism. We report a family in which there are five affected cases including three siblings where the DFA appears to be inherited in an autosomal dominant inheritance pattern with reduced penetrance.

  11. 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

  12. 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.

  13. 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

  14. The inheritance of fingerprint patterns.

    PubMed Central

    Slatis, H M; Katznelson, M B; Bonné-Tamir, B

    1976-01-01

    Analysis of the fingerprints of 571 members of the Habbanite isolate suggest inherited patterns and pattern sequences. A genetic theory has been developed; it assumes that the basic fingerprint pattern sequence is all ulnar loops and that a variety of genes cause deviations from this pattern sequence. Genes that have been proposed include: (1) a semidominant gene for whorls on the thumbs (one homozygote has whorls on both thumbs, the other has ulnar loops on both thumbs and the heterozygote usually has two ulnar loops or one ulnar loop and one whorl); (2) a semidominant gene for whorls on the ring fingers which acts like the gene for whorls on the thumbs; (3) a dominant gene for arches on the thumbs and often on other fingers; (4) one or more dominant genes for arches on the fingers; (5) a dominant gene for whorls on all fingers except for an ulnar loop on the middle finger; (6) a dominant gene for radial loops on the index fingers, frequently associated with an arch on the middle fingers; and (7) a recessive gene for radial loops on the ring and little fingers. These genes may act independently or may show epistasis. PMID:1266855

  15. Coalgebraic structure of genetic inheritance.

    PubMed

    Tian, Jianjun; Li, Bai-Lian

    2004-09-01

    Although in the broadly defined genetic algebra, multiplication suggests a forward direction of from parents to progeny, when looking from the reverse direction, it also suggests to us a new algebraic structure-coalge- braic structure, which we call genetic coalgebras. It is not the dual coalgebraic structure and can be used in the construction of phylogenetic trees. Math- ematically, to construct phylogenetic trees means we need to solve equations x([n]) = a, or x([n]) = b. It is generally impossible to solve these equations inalgebras. However, we can solve them in coalgebras in the sense of tracing back for their ancestors. A thorough exploration of coalgebraic structure in genetics is apparently necessary. Here, we develop a theoretical framework of the coalgebraic structure of genetics. From biological viewpoint, we defined various fundamental concepts and examined their elementary properties that contain genetic significance. Mathematically, by genetic coalgebra, we mean any coalgebra that occurs in genetics. They are generally noncoassociative and without counit; and in the case of non-sex-linked inheritance, they are cocommutative. Each coalgebra with genetic realization has a baric property. We have also discussed the methods to construct new genetic coalgebras, including cocommutative duplication, the tensor product, linear combinations and the skew linear map, which allow us to describe complex genetic traits. We also put forward certain theorems that state the relationship between gametic coalgebra and gametic algebra. By Brower's theorem in topology, we prove the existence of equilibrium state for the in-evolution operator. PMID:20369970

  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. [Inherited skin diseases - a review of selected genodermatoses].

    PubMed

    Wertheim-Tysarowska, Katarzyna; Gos, Monika; Niepokój, Katarzyna; Kowalewski, Cezary

    2012-01-01

    Inherited distubances in skin structure and its function are the main cause of diseases classified as genodermatoses. The following clinical entities are classified as genodermatoses: epidermolysis bullosa, keratotic disorders, disorders of skin color, ectodermal genodermatoses, genodermatoses associated with connective tissue, vascular genodermatoses and genodermatoses with skin manifestation and elevated cancer risk. One of the most clinically heterogenous group of genodermatoses, is epidermolysis bullosa. Four main subtypes were described: simplex, dystrophic, junctional and Kindler syndrome. These diseases are caused by mutations in the genes encoding proteins forming junctions between the dermis and epidermis (eg. COL7A1, COL17A1, KRT14, KRT5 or genes coding for 332 laminin). They are inherited in an autosomal recessive or dominant manner. The disease that is inherited as a dominant, sex dependent trait, is incontinenia pigmenti (Bloch-Sulzberger syndrome) characterized by the presence of extensive pigmentation changes already in the neonatal period. In patients with incontinenia pigmenti, mutations in the NEMO gene are found. The protein encoded by NEMO is involved in the negative regulation of activity of the NFκB transcription factor that is responsible for apoptosis and cell proliferation control. In the regulation of cell proliferation, the neurofibromin (NF1) - the suppressor of RAS/MAPK signaling pathway activity, is also involved. The mutations in the NF1 gene are identified in neurofibromatosis type I - a genodermatosis with higher risk of cancer development and tumor formation. Herein, a review of selected genodermatoses in the context of their molecular pathology is presented.

  18. 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

  19. 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

  20. 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.

  1. [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

  2. Law & psychiatry: Murder, inheritance, and mental illness.

    PubMed

    Gold, Azgad; Appelbaum, Paul S

    2011-07-01

    Should a murderer be allowed to inherit the victim's estate? The question dates from biblical times, but most jurisdictions today have statutes in place that bar inheritance by convicted murderers. However, a special problem arises when the killer has a severe mental illness and has been found not guilty by reason of insanity. Should such people, who have not been convicted of a crime, be permitted to collect their inheritance? Jurisdictions vary in their responses, with the rules reflecting a mix of practical and moral considerations influenced by different perspectives about what determines the behavior of persons with mental illness.

  3. [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.

  4. 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

  5. [Interatrial block as anatomical-electrical substrate for supraventricular arrhythmias: Bayés syndrome].

    PubMed

    Conde, Diego; Baranchuk, Adrián

    2014-01-01

    In this article we aimed to establish that interatrial block exists as an anatomical-electrical entity, which should be considered a true block. Interatrial block presents with different degrees as other blocks in the conduction system. It shows a correlation with the left atrium size, however, it can be seen in patients with normal atrial size too. Interatrial block is strongly associated with atrial arrhythmias and it could be considered a predictor of cardioembolic stroke. Interatrial block is an expression of atrial electrical remodeling and dysfunction. IAB can be transient and in certain clinical circumstances, may be reversible. The contribution of endocardial mapping has increased our knowledge of the anatomy and pathophysiology of interatrial block. Magnetocardiography could be a possible non-invasive procedure to further investigate this entity. The interatrial block classification should include first, second and third degree or alternatively, in order to simplify the terminology: partial or advanced. The P wave morphology should always be taking into consideration when diagnosing this condition. Finally, without the initial description of interatrial block made by Dr. Bayés de Luna, it would be impossible to understand interatrial block as an anatomical and electrical substrate for atrial arrhythmias. It is our opinion that this represents a major contribution to the knowledge of electrocardiography and electrophysiology, and makes commendable that this arrhythmic syndrome should be called «Bayés' syndrome»

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. Optical mapping system for visualizing arrhythmias in isolated mouse atria.

    PubMed

    Schmidt, Robyn; Nygren, Anders

    2006-01-01

    Optical mapping has become an important technique in the study of cardiac electrophysiology, especially in terms of investigating the mechanisms of cardiac arrhythmias. The increasing availability of transgenic mice as models for cardiovascular disease is driving the need for instrumentation suitable for the study of electrical activity in the mouse heart. In this paper we evaluate our optical mapping system's ability to clearly record induced arrhythmic activity in an isolated mouse atrial preparation. Preliminary results indicate that the signal quality is high enough that individual optically recorded action potentials can be discerned in many pixels, even without post-processing for noise removal. The optical mapping video is clear enough for general observations regarding the patterns of electrical propagation during arrhythmic behaviour. The induced arrhythmias appear to have a regular pattern of activity, and are likely best classified as atrial tachycardias.

  11. 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.

  12. 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.

  13. Arrhythmia as a cardiac manifestation in MELAS syndrome.

    PubMed

    Thomas, Tamara; Craigen, William J; Moore, Ryan; Czosek, Richard; Jefferies, John L

    2015-09-01

    A 44-year-old female with a diagnosis of mitochondrial myopathy, encephalopathy and stroke-like episodes (MELAS) syndrome had progressive left ventricular hypertrophy (LVH) on echocardiogram. A Holter monitor demonstrated episodes of non-sustained atrial tachycardia, a finding not been previously described in this population. This unique case of MELAS syndrome demonstrates the known associated cardiac manifestation of LVH and the new finding of atrial tachycardia which may represent the potential for subclinical arrhythmia in this population.

  14. 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

  15. 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.

  16. Computational approaches to understand cardiac electrophysiology and arrhythmias

    PubMed Central

    Roberts, Byron N.; Yang, Pei-Chi; Behrens, Steven B.; Moreno, Jonathan D.

    2012-01-01

    Cardiac rhythms arise from electrical activity generated by precisely timed opening and closing of ion channels in individual cardiac myocytes. These impulses spread throughout the cardiac muscle to manifest as electrical waves in the whole heart. Regularity of electrical waves is critically important since they signal the heart muscle to contract, driving the primary function of the heart to act as a pump and deliver blood to the brain and vital organs. When electrical activity goes awry during a cardiac arrhythmia, the pump does not function, the brain does not receive oxygenated blood, and death ensues. For more than 50 years, mathematically based models of cardiac electrical activity have been used to improve understanding of basic mechanisms of normal and abnormal cardiac electrical function. Computer-based modeling approaches to understand cardiac activity are uniquely helpful because they allow for distillation of complex emergent behaviors into the key contributing components underlying them. Here we review the latest advances and novel concepts in the field as they relate to understanding the complex interplay between electrical, mechanical, structural, and genetic mechanisms during arrhythmia development at the level of ion channels, cells, and tissues. We also discuss the latest computational approaches to guiding arrhythmia therapy. PMID:22886409

  17. Emergency therapy of maternal and fetal arrhythmias during pregnancy

    PubMed Central

    Trappe, Hans-Joachim

    2010-01-01

    Atrial premature beats are frequently diagnosed during pregnancy (PR); supraventricular tachycardia (SVT) (atrial tachycardia, AV-nodal reentrant tachycardia, circus movement tachycardia) is less frequently diagnosed. For acute therapy, electrical cardioversion with 50–100 J is indicated in all unstable patients (pts). In stable SVT, the initial therapy includes vagal maneuvers to terminate tachycardias. For short-term management, when vagal maneuvers fail, intravenous adenosine is the first choice drug and may safely terminate the arrhythmia. Ventricular premature beats are also frequently present during PR and benign in most of the pts; however, malignant ventricular tachyarrhythmias (sustained ventricular tachycardia [VT], ventricular flutter [VFlut] or ventricular fibrillation [VF]) may occur. Electrical cardioversion is necessary in all pts who are in hemodynamically unstable situation with life-threatening ventricular tachyarrhythmias. In hemodynamically stable pts, initial therapy with ajmaline, procainamide or lidocaine is indicated. In pts with syncopal VT, VF, VFlut or aborted sudden death, an implantable cardioverter-defibrillator is indicated. In pts with symptomatic bradycardia, a pacemaker can be implanted using echocardiography at any stage of PR. The treatment of the pregnant patient with cardiac arrhythmias requires important modifications of the standard practice of arrhythmia management. The goal of therapy is to protect the patient and fetus through delivery, after which chronic or definitive therapy can be administered. PMID:20606792

  18. 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

  19. Intramyocardial activation in early ventricular arrhythmias following coronary artery ligation.

    PubMed

    Kaplinsky, E; Ogawa, S; Kmetzo, J; Balke, C W; Dreifus, L S

    1980-01-01

    Subendocardial, subepicardial and intramyocardial activation in the ischemic zone was investigated in 20 anesthetized open chest dogs 0-30 minutes after the ligation of the left anterior descending coronary artery. Single and composite electrograms and lead 2 of the ECG were recorded. Coronary artery ligation produced marked delay, fragmentation, and reduction in amplitude in the electrical activity of the subepicardial and intramyocardial muscle layers. The activation remained synchronous in the subendocardial muscle layers. Extension of electrical activity in the ischemic subepicardium and intramyocardium beyond the T wave of the surface ECG preceded the onset of immediate ventricular arrhythmias (IVA) during the initial ten minute period after coronary artery ligation. However, a second surge of delayed ventricular arrhythmias (DVA), 10-30 minutes after ligation, was not associated with the appearance of diastolic electrical activity in any of the subepicardial or myocardial layers. It appears that subepicardial as well as intramyocardial reentry could play an important role in the genesis of the immediate ventricular arrhythmias (1-10 minutes after ligation). In contrast, no obvious reentrant activity as evidenced by delayed and fragmented electrical activity could be observed in the electrogram from any of the myocardial electrical activity could be observed in the electrogram from any of the myocardial layers with the appearance of delayed ventricular ectopic activity 10-30 minutes after ligation.

  20. Neuraxial Modulation for Refractory Ventricular Arrhythmias: Value of Thoracic Epidural Anesthesia and Surgical Left Cardiac Sympathetic Denervation

    PubMed Central

    Bourke, Tara; Vaseghi, Marmar; Michowitz, Yoav; Sankhla, Vineet; Shah, Mandar; Swapna, Nalla; Boyle, Noel G.; Mahajan, Aman; Narasimhan, Calambur; Lokhandwala, Yash; Shivkumar, Kalyanam

    2010-01-01

    Background Reducing sympathetic output to the heart from the neuraxis can protect against ventricular arrhythmias. The purpose of this study was to assess the value of thoracic epidural anesthesia (TEA) and left cardiac sympathetic denervation (LCSD) in the management of ventricular arrhythmias in patients with structural heart disease (SHD). Methods and Results Clinical data of 14 patients (age 25-75 years, 54.2±16.6 yrs,(mean±SD) 13 males) who underwent TEA, LCSD, or both, to control ventricular tachycardia (VT) refractory to medical therapy and catheter ablation were reviewed.12 patients were in VT storm and 2 patients experienced recurrent VT despite maximal medical therapy and catheter ablation procedures. Total number of therapies per patient prior to either procedure ranged from 5 to 202 (median of 24, 25th and 75th percentile of 5 and 56). Eight patients underwent TEA and 9 patients underwent LCSD (3 patients had both procedures). No major procedural complications occurred. After initiation of TEA, 6 patients had a large (≥80%) decrease in VT burden. Post LCSD, 3 patients had no further VT, 2 patients had recurrent VT which either resolved within 24 hours or responded to catheter ablation, and 4 patients continued to have recurrent VT. Nine out of 14 patients survived to hospital discharge (1 TEA alone, 3 TEA/LCSD combined, 4 LCSD alone), one of whom underwent an urgent cardiac transplantation (TEA alone). Conclusion Initiation of TEA and LCSD in patients with refractory VT was associated with a subsequent decrease in arrhythmia burden in 6 out of 8 (75%- CI 51% to 91%) and 5 out of 9 (56%- CI 34% to 75%) patients, respectively. These data suggest that TEA and LCSD may be effective additions to the management of refractory ventricular arrhythmias in SHD when other treatment modalities have failed and/or may serve as a bridge to more definitive therapy. PMID:20479150

  1. Advances in the treatment of inherited coagulation disorders.

    PubMed

    Escobar, M A

    2013-09-01

    Inherited coagulation disorders constitute a broad spectrum of coagulation factor deficiencies that include X-linked factor (F)VIII or FIX deficiency that causes haemophilia, and autosomal recessive disorders producing heterogeneous deficiencies in fibrinogen (FI), prothrombin (FII), FV, FVII, FX, FXI, FXIII and combined FV+FVIII. Significant advances in treatments for patients with congenital haemophilia A (FVIII deficiency) and B (FIX deficiency) over the last two decades have resulted from improvements in the production, availability and patient access to factor replacement products. Translation of advances in biotechnology, namely recombinant protein technology, targeted protein modifications to improve function and potentially reduce immunogenicity, and advanced formulations to optimize bioavailability and sustain activity offer promisingly new treatments for haemophilia as well as recessively inherited bleeding disorders in patients who otherwise have few therapeutic options. Though a theoretical risk remains for blood-borne viral infections with pooled plasma-derived products, this concern has diminished with breakthroughs in purification and viral inactivation methods. Development of inhibitory antibodies is still the most daunting problem for patients with inherited bleeding disorders, complicating treatment approaches to control and prevent bleeding, and posing risks for allergic and anaphylactic reactions in susceptible patients. The objectives of this review are to (i) highlight emerging advances in hemostatic therapies that are bioengineered to improve pharmacokinetic properties and bioavailability, sustain functional activity, and possibly eliminate immunogenicity of recombinant factor proteins; and (ii) present an overview of key clinical trials of novel factor products currently in the development pipeline.

  2. Inheritance of equine sarcoid disease in Franches-Montagnes horses.

    PubMed

    Christen, Garance; Gerber, Vinzenz; Dolf, Gaudenz; Burger, Dominique; Koch, Christoph

    2014-01-01

    The mode of inheritance for susceptibility to equine sarcoid disease (ES) remains unknown. The objectives of this study were to analyse a large sample of the Franches-Montagnes (FM) horse population and investigate the heritability and mode of inheritance for susceptibility to ES. Horses were clinically examined for the presence of sarcoid tumours. A standardized examination protocol and client questionnaire were used and a pedigree- and subsequent segregation-analysis for the ES trait performed. To investigate the mode of inheritance, five models were evaluated and compared in a hierarchical way. The analyses reveal that variation in susceptibility to ES is best explained by a model incorporating polygenic variation. The possible effect of a major gene, such as specific equine leukocyte antigen alleles, is unlikely, but cannot be ruled-out entirely. The heritability of the phenotype on the observation scale for the trait 'affected with ES' was estimated to be 8%. A corrected value for the heritability on a liability scale was estimated at 21% and it is therefore possible to estimate breeding values for ES. The arguments against the practical implementation of an estimated breeding value in a multifactorial condition like ES are discussed.

  3. 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

  4. Prediction of ventricular arrhythmia events in ischemic heart disease patients with implantable cardioverter-defibrillators.

    PubMed

    Feng, Tianjie; Zhang, Shu; Chen, Keping; Hua, Wei; Ren, Xiaoqing

    2015-10-01

    The aim of the study was to exam the prediction of ventricular arrhythmia events in ischemic heart disease patients with implantable cardioverter-defibrillators (ICD). A total of 123 consecutive patients confirmed ischemia heart disease with ICD were examined. After device implantation, the occurrence of appropriate ICD therapy was noted. Patients were divided into two groups according to the ventricular arrhythmia occurrence. Patients with ventricular arrhythmia occurrence had a significantly great incidence of atrial fibrillation history compare to the no-ventricular arrhythmia occurrence group (8 vs. 39%, P = 0.02). The level of high-sensitive C-reactive protein (hsCRP) baseline was also significantly higher in the ventricular arrhythmia group than in the no ventricular arrhythmia (3.78 ± 1.1 vs. 0.94 ± 0.7, P < 0.01). The taking of β blocker is not common in ventricular arrhythmia group patients than no ventricular arrhythmia group (5 vs. 29%, P = 0.03). By univariate comparison, male sex, the history of atrial fibrillation, and a high level of hsCRP were significant predictors for ventricular arrhythmia occurrence. By multivariate analysis, the atrial fibrillation burden, and had a high level of hsCRP were significant for incidence of ventricular arrhythmia occurrence in ischemic heart disease patients. β-block were more likely to be free from ventricular arrhythmia occurrence. The high level of hsCRP, and the atrial fibrillation burden were strong predictor of ventricular arrhythmia occurrence in secondary prevention ICD recipients with ischemic heart disease. Taking β-blockers was free from ventricular arrhythmia occurrence.

  5. Mechanoelectrical remodeling and arrhythmias during progression of hypertrophy

    PubMed Central

    Jin, Hongwei; Chemaly, Elie R.; Lee, Ahyoung; Kho, Changwon; Hadri, Lahouaria; Hajjar, Roger J.; Akar, Fadi G.

    2010-01-01

    Despite a clear association between left ventricular (LV) mechanical dysfunction in end-stage heart failure and the incidence of arrhythmias, the majority of sudden cardiac deaths occur at earlier stages of disease development. The mechanisms by which structural, mechanical, and molecular alterations predispose to arrhythmias at the tissue level before the onset of LV dysfunction remain unclear. In a rat model of pressure overload hypertrophy (PoH) produced by ascending aortic banding, we correlated mechanical and structural changes measured in vivo with key electrophysiological changes measured ex vivo in the same animals. We found that action potential prolongation, a hallmark of electrical remodeling at the tissue level, is highly correlated with changes in LV wall thickness but not mechanical function. In contrast, conduction delays are not predicted by either mechanical or structural changes during disease development. Moreover, disrupted Cx43 phosphorylation at intermediate (increased) and late (decreased) stages of PoH are associated with moderate and severe conduction delays, respectively. Interestingly, the level of interaction between Cx43 and the cytoskeletal protein ZO-1 is exclusively decreased at the late stage of PoH. Closely coupled action potentials consistent with afterdepolarization-mediated triggered beats were readily observed in 6 of 15 PoH hearts but never in controls. Similarly, PoH (8/15) but not control hearts exhibited sustained episodes of ventricular tachycardia after rapid stimulation. The initiation and early maintenance of arrhythmias in PoH were formed by rapid and highly uniform activation wavefronts emanating from sites distal to the former site of stimulation. In conclusion, repolarization but not conduction delays are predicted by structural remodeling in PoH. Cx43 phosphorylation is disrupted at intermediate (increased) and late (decreased) stages, which are associated with conduction delays. Dephosphorylation of Cx43 is

  6. Inherited metabolic diseases affecting the carrier.

    PubMed

    Endres, W

    1997-03-01

    The objective of this review is to draw attention to those inherited metabolic traits which are potentially harmful also for the carrier, and to outline preventive measures, at least for obligate heterozygotes, i.e. parents of homozygous children. Concerning carriers of food-dependent abnormalities, early vascular disease in homocystinuria, hyperammonaemic episodes in ornithine transcarbamylase deficiency, presenile cataracts in galactosaemia as well as galactokinase deficiency, spastic paraparesis in X-linked adrenoleukodystrophy, and HELLP syndrome in mothers of babies with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency have to be mentioned. In the group of food-independent disorders, clinical features in carriers may be paraesthesias and corneal dystrophy in Fabry disease, lens clouding in Lowe syndrome, lung and/or liver diseases in alpha 1-antitrypsin deficiency, and renal stones in cystinuria type II and III. Finally, two monogenic carrier states are known which in pregnant individuals could possibly afflict the developing fetus, i.e. heterozygosity for galactosaemia and for phenylketonuria. Elevated levels of galactose-1-phosphate have been found in red blood cells of infants heterozygous for galactosaemia born to heterozygous mothers. Aspartame in very high doses is reported to increase blood phenylalanine levels in heterozygotes for phenylketonuria, thus being a risk for the fetus of a heterozygous mother. For some of these carrier states preventive measures can be recommended, e.g. restriction of lactose in parents and heterozygous grandparents of children with galactosaemia and galactokinase deficiency as well as transiently in infants heterozygous for galactosaemia, dietary supplementation with monounsaturated fatty acids in symptomatic carriers for X-linked adrenoleukodystrophy, avoidance of smoking and alcohol in heterozygotes for alpha 1-antitrypsin deficiency, avoidance of episodes of dehydration in heterozygotes for cystinuria, and

  7. [Andersen-Tawil syndrome: a review of its clinical and genetic diagnosis with emphasis on cardiac manifestations].

    PubMed

    Márquez, Manlio F; Totomoch-Serra, Armando; Vargas-Alarcón, Gilberto; Cruz-Robles, David; Pellizzon, Oscar A; Cárdenas, Manuel

    2014-01-01

    The Andersen-Tawil syndrome is a cardiac ion channel disease that is inherited in an autosomal dominant way and is classified as type 7 of the congenital long QT syndromes. Affected gene is KCNJ2, which forms the inward rectifier potassium channel designated Kir2.1. This protein is involved in stabilizing the resting membrane potential and controls the duration of the action potential in skeletal muscle and heart. It also participates in the terminal repolarization phase of the action potential in ventricular myocytes and is a major component responsible for the correction in the potassium current during phase 3 of the action potential repolarization. Kir 2.1 channel has a predominant role in skeletal muscle, heart and brain. Alterations in this channel produce flaccid paralysis, arrhythmias, impaired skeletal development primarily in extremities and facial area. In this review we address the disease from the point of view of clinical and molecular diagnosis with emphasis on cardiac manifestations.

  8. 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

  9. Inherited ichthyoses/generalized Mendelian disorders of cornification

    PubMed Central

    Schmuth, Matthias; Martinz, Verena; Janecke, Andreas R; Fauth, Christine; Schossig, Anna; Zschocke, Johannes; Gruber, Robert

    2013-01-01

    Inherited ichthyoses, defined as the generalized form of Mendelian disorders of cornification, are characterized by visible scaling and/or hyperkeratosis of most or all of the skin. This etiologically and phenotypically heterogenous group of conditions is caused by mutations in various different genes important for keratinocyte differentiation and epidermal barrier function. Diagnosing a specific entity is a particular challenge for the nonspecialist presented with the common clinical scaling. For the clinician, this review outlines an algorithmic approach for utilizing diagnostic clues to narrow down the differential diagnosis and to guide further testing and treatment options. PMID:22739337

  10. 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

  11. 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

  12. Electrical heart disease: Genetic and molecular basis of cardiac arrhythmias in normal structural hearts.

    PubMed

    Farwell, David; Gollob, Michael H

    2007-08-01

    Purely electrical heart diseases, defined by the absence of any structural cardiac defects, are responsible for a large number of sudden, unexpected deaths in otherwise healthy, young individuals. These conditions include the long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia and the short QT syndrome. Collectively, these conditions have been referred to as channelopathies. Ion channels provide the molecular basis for cardiac electrical activity. These channels have specific ion selectivity and are responsible for the precise and timely regulation of the passage of charged ions across the cell membrane in myocytes, and the summation of their activity in cardiac muscle defines the surface electrocardiogram. Impairment in the flow of these ions in heart cells may mean the difference between a normal, prosperous life and the tragedy of a sudden, unexpected death due to ventricular arrhythmia. The present paper reviews the current clinical and molecular understanding of the electrical diseases of the heart associated with sudden cardiac death.

  13. 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

  14. Magnesium in the prevention of lethal arrhythmias in acute myocardial infarction.

    PubMed

    Abraham, A S; Rosenmann, D; Kramer, M; Balkin, J; Zion, M M; Farbstien, H; Eylath, U

    1987-04-01

    Seven of 48 patients (14.6%) with acute myocardial infarction who were given 2.4 g of magnesium sulfate as a single intravenous dose had potentially lethal arrhythmias during the first 24 hours after admission, whereas 16 (34.8%) of 46 patients receiving placebo had similar arrhythmias. In addition, 14 of these 16 patients in the placebo group had their first arrhythmia (in the intensive coronary-care unit) within two hours after the start of the study, whereas in the magnesium-treated group, there were no such arrhythmias until some four hours later. The higher the lymphocyte potassium concentration, the greater the reduction in the incidence of arrhythmias. Serum magnesium levels increased by 16.5% and lymphocyte magnesium concentrations by 72% in the magnesium treated group. Intravenous magnesium reduces the incidence of serious arrhythmias after acute myocardial infarction. PMID:3548627

  15. Interventional and surgical treatment of cardiac arrhythmias in adults with congenital heart disease.

    PubMed

    Koyak, Zeliha; de Groot, Joris R; Mulder, Barbara J M

    2010-12-01

    Arrhythmias are a major cause of morbidity, mortality and hospital admission in adults with congenital heart disease (CHD). The etiology of arrhythmias in this population is often multifactorial and includes electrical disturbances as part of the underlying defect, surgical intervention or hemodynamic abnormalities. Despite the numerous existing arrhythmia management tools including drug therapy, pacing and ablation, management of arrhythmias in adults with CHD remains difficult and challenging. Owing to improvement in mapping and ablation techniques, ablation and arrhythmia surgery are being performed more frequently in adults with CHD. However, there is little information on the long-term results of these treatment strategies. The purpose of this article is therefore to review the available data on nonpharmacological treatment of cardiac arrhythmias in adult patients with CHD and to give an overview of the available data on the early and late outcomes of these treatment strategies.

  16. 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.

  17. Environmental stress and epigenetic transgenerational inheritance.

    PubMed

    Skinner, Michael K

    2014-09-05

    Previous studies have shown a wide variety of environmental toxicants and abnormal nutrition can promote the epigenetic transgenerational inheritance of disease. More recently a number of studies have indicated environmental stress can also promote epigenetic alterations that are transmitted to subsequent generations to induce pathologies. A recent study by Yao and colleagues demonstrated gestational exposure to restraint stress and forced swimming promoted preterm birth risk and adverse newborn outcomes generationally. This ancestral stress promoted the epigenetic transgenerational inheritance of abnormalities in the great-grand offspring of the exposed gestating female. Several studies now support the role of environmental stress in promoting the epigenetic transgenerational inheritance of disease. Observations suggest ancestral environmental stress may be a component of disease etiology in the current population.

  18. Transgenerational epigenetic inheritance: an open discussion.

    PubMed

    Nagy, Corina; Turecki, Gustavo

    2015-08-01

    Much controversy surrounds the idea of transgenerational epigenetics. Recent papers argue that epigenetic marks acquired through experience are passed to offspring, but as in much of the field of epigenetics, there is lack of precision in the definitions and perhaps too much eagerness to translate animal research to humans. Here, we review operational definitions of transgenerational inheritance and the processes of epigenetic programing during early development. Subsequently, based on this background, we critically examine some recent findings of studies investigating transgenerational inheritance. Finally, we discuss possible mechanisms that may explain transgenerational inheritance, including transmission of an epigenetic blueprint, which may predispose offspring to specific epigenetic patterning. Taken together, we conclude that presently, the evidence suggesting that acquired epigenetic marks are passed to the subsequent generation remains limited.

  19. Transgenerational epigenetic inheritance: an open discussion.

    PubMed

    Nagy, Corina; Turecki, Gustavo

    2015-08-01

    Much controversy surrounds the idea of transgenerational epigenetics. Recent papers argue that epigenetic marks acquired through experience are passed to offspring, but as in much of the field of epigenetics, there is lack of precision in the definitions and perhaps too much eagerness to translate animal research to humans. Here, we review operational definitions of transgenerational inheritance and the processes of epigenetic programing during early development. Subsequently, based on this background, we critically examine some recent findings of studies investigating transgenerational inheritance. Finally, we discuss possible mechanisms that may explain transgenerational inheritance, including transmission of an epigenetic blueprint, which may predispose offspring to specific epigenetic patterning. Taken together, we conclude that presently, the evidence suggesting that acquired epigenetic marks are passed to the subsequent generation remains limited. PMID:26344807

  20. Maternal inheritance of mitochondria in Eucalyptus globulus.

    PubMed

    Vaillancourt, R E; Petty, A; McKinnon, G E

    2004-01-01

    It is important to verify mitochondrial inheritance in plant species in which mitochondrial DNA (mtDNA) will be used as a source of molecular markers. We used a polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) approach to amplify mitochondrial introns from subunits 1, 4, 5, and 7 of NADH dehydrogenase (nad) and cytochrome oxidase subunit II (cox2) in Eucalyptus globulus. PCR fragments were then either sequenced or cut with restriction enzymes to reveal polymorphism. Sequencing cox2 showed that eucalypts lack the intron between exons 1 and 2. One polymorphism was found in intron 2-3 of nad7 following restriction digests with HphI. Fifty-four F1 progeny from seven families with parents distinguishable in their mitochondrial nad7 were screened to show that mitochondria were maternally inherited in E. globulus. These results constitute the first report of mitochondrial inheritance in the family Myrtaceae.

  1. Relationship between heart rate and sinus arrhythmia in air traffic controllers at work.

    PubMed

    Lille, F; Burnod, Y; Borodulin, L

    1981-01-01

    Sinus arrhythmia and mean heart rate were calculated from continuous electrocardiogram recordings of ten air traffic controllers. The telemetric recordings were carried out during 1 day of work and the following day's night shift. The individual variations of sinus arrhythmia were very large. The different situations (rest, relaxed work, intense work, eating, movements within the control room) had no specific effect on sinus arrhythmia. For each subject and for each group it was the value of the mean heart rate and its temporal variations that had the greatest influence on variations of sinus arrhythmia.

  2. 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.

  3. Genetic modifiers and oligogenic inheritance.

    PubMed

    Kousi, Maria; Katsanis, Nicholas

    2015-06-01

    Despite remarkable progress in the identification of mutations that drive genetic disorders, progress in understanding the effect of genetic background on the penetrance and expressivity of causal alleles has been modest, in part because of the methodological challenges in identifying genetic modifiers. Nonetheless, the progressive discovery of modifier alleles has improved both our interpretative ability and our analytical tools to dissect such phenomena. In this review, we analyze the genetic properties and behaviors of modifiers as derived from studies in patient populations and model organisms and we highlight conceptual and technological tools used to overcome some of the challenges inherent in modifier mapping and cloning. Finally, we discuss how the identification of these modifiers has facilitated the elucidation of biological pathways and holds the potential to improve the clinical predictive value of primary causal mutations and to develop novel drug targets.

  4. Transgenerational epigenetic inheritance: how important is it?

    PubMed

    Grossniklaus, Ueli; Kelly, William G; Kelly, Bill; Ferguson-Smith, Anne C; Pembrey, Marcus; Lindquist, Susan

    2013-03-01

    Much attention has been given to the idea of transgenerational epigenetic inheritance, but fundamental questions remain regarding how much takes place and the impact that this might have on organisms. We asked five leading researchers in this area--working on a range of model organisms and in human disease--for their views on these topics. Their responses highlight the mixture of excitement and caution that surrounds transgenerational epigenetic inheritance and the wide gulf between species in terms of our knowledge of the mechanisms that may be involved.

  5. Mobile Telemonitoring for Arrhythmias in Outpatients in the Republic of Georgia: A Brief Report of a Pilot Study

    PubMed Central

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

    2012-01-01

    Abstract 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

  6. 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

  7. 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.

  8. 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

  9. [Emergency treatment of arrhythmias in neonates and infants].

    PubMed

    Weber, H; Wesselhoeft, H; Eigster, G

    1983-11-01

    Emergency treatment of cardiac arrhythmias was required in 41 newborn and infants aged two days to 9 months (mean 77 days) from July 1977 until September 1981. Heart defects were present in 27 (65.8%). Invasive electrophysiological studies were performed in all patients. The different types of arrhythmias were: bradyarrhythmias in 9 (21.9%): bradycardia to cardiac arrest (5), congenital complete AV-block (3), postoperative complete AV-block (1). Tachyarrhythmias in 32 patients (78.1%): reentry through accessory connections (21), congenital atrial flutter (6), ventricular flutter/fibrillation (3), and AV-nodal tachycardia (2). Overdrive atrial or ventricular stimulation with a consecutive series of 15-20 impulses of 5-10 Volts abolished arrhythmic attacks in 22 patients including 4 in whom prior digitalization had no effect. In two other patients overdrive pacing achieved sinus rhythm only after i.v. Propafenon. In 4 further patients 36.2 to 63.8 mg/m2 i.v. Propafenon and in 4 other patients DC synchronized cardioversion with 1 to 3 Wsec/kg restored a normal heart rate. The 3 patients with congenital complete heart block died, one despite permanent pacing. Oral Propafenon therapy with 300 mg/m2 die in three divided doses following emergency therapy of tachyarrhythmias was discontinued in patients without arrhythmias after 1 year on drug therapy. There was no relapse after a mean follow-up period of 1.9 years. Only patients with congestive heart failure due to cardiac defects needed additional digitalisation. Thus, in our experience antiarrhythmic drug therapy with Propafenon was more effective in this age group than digitalization. PMID:6664346

  10. Role of Cholinergic Innervation and RGS2 in Atrial Arrhythmia

    PubMed Central

    Jones, Douglas L.; Tuomi, Jari M.; Chidiac, Peter

    2012-01-01

    The heart receives sympathetic and parasympathetic efferent innervation as well as the ability to process information internally via an intrinsic cardiac autonomic nervous system (ICANS). For over a century, the role of the parasympathetics via vagal acetylcholine release was related to controlling primarily heart rate. Although in the late 1800s shown to play a role in atrial arrhythmia, the myocardium took precedence from the mid-1950s until in the last decade a resurgence of interest in the autonomics along with signaling cascades, regulators, and ion channels. Originally ignored as being benign and thus untreated, recent emphasis has focused on atrial arrhythmia as atrial fibrillation (AF) is the most common arrhythmia seen by the general practitioner. It is now recognized to have significant mortality and morbidity due to resultant stroke and heart failure. With the aging population, there will be an unprecedented increased burden on health care resources. Although it has been known for more than half a century that cholinergic stimulation can initiate AF, the classical concept focused on the M2 receptor and its signaling cascade including RGS4, as these had been shown to have predominant effects on nodal function (heart rate and conduction block) as well as contractility. However, recent evidence suggests that the M3 receptor may also playa role in initiation and perpetuation of AF and thus RGS2, a putative regulator of the M3 receptor, may be a target for therapeutic intervention. Mice lacking RGS2 (RGS2−/−), were found to have significantly altered electrophysiological atrial responses and were more susceptible to electrically induced AF. Vagally induced or programmed stimulation-induced AF could be blocked by the selective M3R antagonist, darifenacin. These results suggest a potential surgical target (ICANS) and pharmacological targets (M3R, RGS2) for the management of AF. PMID:22754542

  11. Mechanisms of Mechanically Induced Spontaneous Arrhythmias in Acute Regional Ischemia

    PubMed Central

    Jie, Xiao; Gurev, Viatcheslav; Trayanova, Natalia

    2010-01-01

    Rationale Although ventricular premature beats (VPBs) during acute regional ischemia have been linked to mechanical stretch of ischemic tissue, whether and how ischemia-induced mechanical dysfunction can induce VPBs and facilitate their degradation into reentrant arrhythmias has not been yet addressed. Objective This study used a novel multiscale electromechanical model of the rabbit ventricles to investigate the origin of and the substrate for spontaneous arrhythmias arising from ischemia-induced electrophysiological and mechanical changes. Methods and Results Two stages of ischemia were simulated. Dynamic mechanoelectrical feedback was modeled as spatially and temporally nonuniform membrane currents through mechanosensitive channels, the conductances of which depended on local strain rate. Our results reveal that both strains and strain rates were significantly larger in the central ischemic zone than in the border zone. However, in both ischemia stages, a VPB originated from the ischemic border in the left ventricular apical endocardium because of mechanically induced suprathreshold depolarizations. It then traveled fully intramurally until emerging from the ischemic border on the anterior epicardium. Reentry was formed only in the advanced ischemia stage as the result of a widened temporal excitable gap. Mechanically induced delayed afterdepolarization-like events contributed to the formation of reentry by further decreasing the already reduced-by-hyperkalemia local excitability, causing extended conduction block lines and slowed conduction in the ischemic region. Conclusions Mechanically induced membrane depolarizations in the ischemic region are the mechanism by which mechanical activity contributes to both the origin of and substrate for spontaneous arrhythmias under the conditions of acute regional ischemia. PMID:19893011

  12. Doubly uniparental inheritance: two mitochondrial genomes, one precious model for organelle DNA inheritance and evolution.

    PubMed

    Passamonti, Marco; Ghiselli, Fabrizio

    2009-02-01

    Eukaryotes have exploited several mechanisms for organelle uniparental inheritance, so this feature arose and evolved independently many times in their history. Metazoans' mitochondria commonly experience strict maternal inheritance; that is, they are only transmitted by females. However, the most noteworthy exception comes from some bivalve mollusks, in which two mitochondrial lineages (together with their genomes) are inherited: one through females (F) and the other through males (M). M and F genomes show up to 30% sequence divergence. This inheritance mechanism is known as doubly uniparental inheritance (DUI), because both sexes inherit uniparentally their mitochondria. Here, we review what we know about this unusual system, and we propose a model for evolution of DUI that might account for its origin as sex determination mechanism. Moreover, we propose DUI as a choice model to address many aspects that should be of interest to a wide range of biological subfields, such as mitochondrial inheritance, mtDNA evolution and recombination, genomic conflicts, evolution of sex, and developmental biology. Actually, as research proceeds, mitochondria appear to have acquired a central role in many fundamental processes of life, which are not only in their metabolic activity as cellular power plants, such as cell signaling, fertilization, development, differentiation, ageing, apoptosis, and sex determination. A function of mitochondria in the origin and maintenance of sex has been also proposed.

  13. 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

  14. 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.

  15. 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

  16. Esmolol activates endogenous neurokinin activity inhibiting infarction-induced arrhythmias in rats: novel mechanisms of anti-arrhythmia.

    PubMed

    Wang, Li-Li; Han, Yi; Guo, Zheng; Han, Shi-Qi; Liu, Tao

    2013-09-10

    Endogenous neurokinin and adrenergic mechanisms might co-participate in the pathology of acute myocardial infarction (MI). This study sought to investigate the role of endogenous neurokinin and its relationship with β1-adrenergic mechanism in the infarction induced arrhythmias. In 60min of MI in rats, the contents of substance P (SP), a native agonist of neurokinin 1 receptor (NK1-R), norepinephrine (NE), NK1-R and β1-adrenergic receptor in the myocardium at risk of ischemia were examined and the ventricular arrhythmias were analyzed. The effects of pretreatment with D-SP (152ng/kg), a specific antagonist of NK1-R, esmolol (10mg/kg), a specific blocker of β1-adrenergic receptor, and a combination of the two blockers were studied. The results showed that the overlaps of up-regulation of NE, SP and the increase of ventricular arrhythmias were observed. D-SP exacerbated the episodes and duration of VT & VF by 54% and 104%, respectively (all P<0.05). Esmolol inhibited the morbidity rate, the episodes and the duration of VT & VF by 66%, 92% and 95%, respectively. Surprisingly, esmolol significantly attenuated the arrhythmogenic effect of D-SP throughout the MI, beyond the time span of esmolol action, during which a significant up-regulation of the NK1-R (by 19%, P<0.05) was detected. In conclusion, the findings of this study may indicate an anti-arrhythmic effect of endogenous neurokinin mechanism, through the activation of which, via up-regulation of NK1 receptor, esmolol may exert its anti-arrhythmic action at the early time of acute myocardial infarction.

  17. Epigenetic inheritance of proteostasis and ageing

    PubMed Central

    Li, Cheryl; Casanueva, Olivia

    2016-01-01

    Abundant evidence shows that the genome is not as static as once thought and that gene expression can be reversibly modulated by the environment. In some cases, these changes can be transmitted to the next generation even if the environment has reverted. Such transgenerational epigenetic inheritance requires that information be stored in the germline in response to exogenous stressors. One of the most elusive questions in the field of epigenetic inheritance is the identity of such inherited factor(s). Answering this question would allow us to understand how the environment can shape human populations for multiple generations and may help to explain the rapid rise in obesity and neurodegenerative diseases in modern society. It will also provide clues on how we might be able to reprogramme the epigenome to prevent transmission of detrimental phenotypes and identify individuals who might be at increased risk of disease. In this article, we aim to review recent developments in this field, focusing on research conducted mostly in the nematode Caenorhabditis elegans and mice, that link environmental modulators with the transgenerational inheritance of phenotypes that affect protein-folding homoeostasis and ageing. PMID:27744335

  18. 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…

  19. 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.

  20. 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

  1. 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…

  2. 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…

  3. 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…

  4. 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

  5. [Recommendations for sports participation in patients with arrhythmia].

    PubMed

    Milliez, P; Haggui, A; Maltret, A; Leenhardt, A

    2006-11-01

    Nowadays, sports are a wonderful mean for social success, and the high-level athlete is the symbol of a perfect hygiene of life. Despite this, the occurrence of unexplained sudden death (SD) is not exceptional, especially during training and competition. In this context, it is important to intensify medical controls for these athletes, especially in a very early phase, in order to detect subjects at risk. In case of detection of a cardiac disease prone to cardiovascular or arrhythmic event, the practice of any high-level sportive activity or even any sustained sportive activity must be forbidden without hesitation, with the aim of protecting these subjects. Even though a total interdiction of sports practice can be a tough decision to be accepted, it should prevail on the dramatic consequences of sudden death. Physicians' responsibility issues in the screening and management of competition or leisure-time sportsmen are of high importance since in case of sudden death, the physician and the medical community liabilities can be considered. As a consequence, the medical community set up recommendations on the screening, treatment and even interdiction of sportive activity for athletes, which should also be applied to leisure-time sportsmen. In the first part of this article, the different causes (especially the arrhythmia-related) of sudden death occurring in sportsmen are reviewed. In the second part, the recommendations on practice of high-level sports in case of arrhythmia or genetic arrhythmic cardiac disease are summarized. PMID:17181039

  6. An ECG analysis interactive training system for understanding arrhythmias.

    PubMed

    Lessard, Yvon; Sinteff, Jean-Paul; Siregar, Pridi; Julen, Nathalie; Hannouche, Frédéric; Rio, Stéphane; Le Beux, Pierre

    2009-01-01

    The ECG remains a daily diagnostic tool for the detection of numerous cardiovascular diseases. Our goal was to use a computerized qualitative model (QM) of heart in order to build cases of simple arrhythmias dedicated to initial and more advanced medical teaching. The original QM is able to generate videograms of many cardiac disturbances. A Flash player is used to view ECG, synchronous Lewis diagram and chromatic 2D cardiac animation of a specific case. OAAT is a standardized 18 yes/no answers questionnaire which allows the learner to diagnose five main types of arrhythmias that can be compared with normal sinus rhythm (NSR) analysis. This new tool has been recently used by medical students during practical sessions. Based on medical reasoning learning on NSR video and upon trying to recognize an abnormal cardiac rhythm, all users can reach the 100% winning score since they can perform as many attempts as they like. We believe that unlimited case review with questionnaire answering, ECG and Lewis diagram replay and step-by-step visualization of the abnormal propagation of the cardiac impulse on the 2D heart videos are a highly efficient means to help students understand even complex arrhythmic mechanisms.

  7. 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

  8. 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.

  9. An ECG analysis interactive training system for understanding arrhythmias.

    PubMed

    Lessard, Yvon; Sinteff, Jean-Paul; Siregar, Pridi; Julen, Nathalie; Hannouche, Frédéric; Rio, Stéphane; Le Beux, Pierre

    2009-01-01

    The ECG remains a daily diagnostic tool for the detection of numerous cardiovascular diseases. Our goal was to use a computerized qualitative model (QM) of heart in order to build cases of simple arrhythmias dedicated to initial and more advanced medical teaching. The original QM is able to generate videograms of many cardiac disturbances. A Flash player is used to view ECG, synchronous Lewis diagram and chromatic 2D cardiac animation of a specific case. OAAT is a standardized 18 yes/no answers questionnaire which allows the learner to diagnose five main types of arrhythmias that can be compared with normal sinus rhythm (NSR) analysis. This new tool has been recently used by medical students during practical sessions. Based on medical reasoning learning on NSR video and upon trying to recognize an abnormal cardiac rhythm, all users can reach the 100% winning score since they can perform as many attempts as they like. We believe that unlimited case review with questionnaire answering, ECG and Lewis diagram replay and step-by-step visualization of the abnormal propagation of the cardiac impulse on the 2D heart videos are a highly efficient means to help students understand even complex arrhythmic mechanisms. PMID:19745450

  10. 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

  11. 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.

  12. Reentrant excitation as a cause of cardiac arrhythmias.

    PubMed

    Wit, A L; Cranefield, P F

    1978-07-01

    Mechanisms that cause reentry were defined in rings of tissue cut from jellyfish as early as 1906 by Mayer. The concepts were developed by Mines and Garrey during the next 10 years. Lewis then tried to demonstrate that reentry caused atrial flutter. Lewis, Garrey, and later Moe also proposed that atrial fibrillation was caused by reentry. Rosenblueth provided additional experimental evidence that reentry could cause atrial arrhythmias after crushing the intercaval bridge of atrial muscle. Recent studies by Allessie using microelectrodes have provided detailed evidence for reentry in atrial tissue. Mines in 1913 also proposed that reentry could occur in the AV node. Scherf then introduced the concept of functional longitudinal dissociation as a cause of return extrasystoles and this was later shown to happen in the node by Moe and his colleagues. Reentry can also occur between atria and ventricles utilizing accessory connecting pathways. Schmitt and Erlanger in 1913 were the first to do experiments which indicated that reentry can also occur in the ventricles. Subsequently it was shown that reentry can occur in Purkinje fiber bundles. Reentry in ventricular muscle may also cause some of the arrhythmias that occur after myocardial infarction.

  13. 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

  14. A semantic inheritance/inverse-inheritance mechanism for systematic bio-ontology construction.

    PubMed

    Kim, Ki-Heon; Yang, Jae-Dong; Choi, Jae-Hun; Yang, Kyung-Ah; Ha, Young-Guk

    2007-01-01

    In this paper, we propose a semantic inheritance/inverse-inheritance mechanism for systematic bio-ontology construction. This mechanism allows domain experts to easily manage sophisticated bio-ontologies in which biological knowledge is encoded; it automatically captures semantics inferred from the ontology structure being constructed or already constructed. Based on the captured semantics it suggests appropriate recommendation to the experts. While inheritance enables them to consistently determine the semantics of relationships between ontology concepts (or classes), inverse-inheritance allows them to incrementally refine the semantics by exploiting a huge amount of relationships between the instances of the concepts. To demonstrate the feasibility of the mechanism, we also implement an OWL(Web Ontology Language)-based graphical bio-ontology management system. In the system, the mechanism is seamlessly applied to the ontology by well defined graphic notations based on OWL. OWL is adopted to fully express the subtle semantics inherently buried in the bio-ontology.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. The inheritance of organelle genes and genomes: patterns and mechanisms.

    PubMed

    Xu, Jianping

    2005-12-01

    Unlike nuclear genes and genomes, the inheritance of organelle genes and genomes does not follow Mendel's laws. In this mini-review, I summarize recent research progress on the patterns and mechanisms of the inheritance of organelle genes and genomes. While most sexual eukaryotes show uniparental inheritance of organelle genes and genomes in some progeny at least part of the time, increasing evidence indicates that strictly uniparental inheritance is rare and that organelle inheritance patterns are very diverse and complex. In contrast with the predominance of uniparental inheritance in multicellular organisms, organelle genes in eukaryotic microorganisms, such as protists, algae, and fungi, typically show a greater diversity of inheritance patterns, with sex-determining loci playing significant roles. The diverse patterns of inheritance are matched by the rich variety of potential mechanisms. Indeed, many factors, both deterministic and stochastic, can influence observed patterns of organelle inheritance. Interestingly, in multicellular organisms, progeny from interspecific crosses seem to exhibit more frequent paternal leakage and biparental organelle genome inheritance than those from intraspecific crosses. The recent observation of a sex-determining gene in the basidiomycete yeast Cryptococcus neoformans, which controls mitochondrial DNA inheritance, has opened up potentially exciting research opportunities for identifying specific molecular genetic pathways that control organelle inheritance, as well as for testing evolutionary hypotheses regarding the prevalence of uniparental inheritance of organelle genes and genomes.

  20. 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, ...

  1. 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...

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. Ambulatory Cardiac Monitoring for Discharged Emergency Department Patients with Possible Cardiac Arrhythmias

    PubMed Central

    Schreiber, Donald; Sattar, Ayesha; Drigalla, Dorian; Higgins, Steven

    2014-01-01

    Introduction Many emergency department (ED) patients have symptoms that may be attributed to arrhythmias, necessitating outpatient ambulatory cardiac monitoring. Consensus is lacking on the optimal duration of monitoring. We describe the use of a novel device applied at ED discharge that provides continuous prolonged cardiac monitoring. Methods We enrolled discharged adult ED patients with symptoms of possible cardiac arrhythmia. A novel, single use continuous recording patch (Zio®Patch) was applied at ED discharge. Patients wore the device for up to 14 days or until they had symptoms to trigger an event. They then returned the device by mail for interpretation. Significant arrhythmias are defined as: ventricular tachycardia (VT) ≥4 beats, supraventricular tachycardia (SVT) ≥4 beats, atrial fibrillation, ≥3 second pause, 2nd degree Mobitz II, 3rd degree AV Block, or symptomatic bradycardia. Results There were 174 patients were enrolled and all mailed back their devices. The average age was 52.2 (± 21.0) years, and 55% were female. The most common indications for device placement were palpitations 44.8%, syncope 24.1% and dizziness 6.3%. Eighty-three patients (47.7%) had ≥1 arrhythmias and 17 (9.8%) were symptomatic at the time of their arrhythmia. Median time to first arrhythmia was 1.0 days (IQR 0.2–2.8) and median time to first symptomatic arrhythmia was 1.5 days (IQR 0.4–6.7). 93 (53.4%) of symptomatic patients did not have any arrhythmia during their triggered events. The overall diagnostic yield was 63.2% Conclusion The Zio®Patch cardiac monitoring device can efficiently characterize symptomatic patients without significant arrhythmia and has a higher diagnostic yield for arrhythmias than traditional 24–48 hour Holter monitoring. It allows for longer term monitoring up to 14 days. PMID:24672611

  8. 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- ...

  9. Sex- and Gender-Specific Research Priorities for the Emergency Management of Heart Failure and Acute Arrhythmia: Proceedings from the 2014 AEM Consensus Conference Cardiovascular Research Workgroup

    PubMed Central

    McGregor, Alyson J.; Peacock, Frank F.; Chang, Anna Marie; Safdar, Basmah; Diercks, Deborah

    2014-01-01

    The emergency department (ED) is the point of first contact for patients with acute heart failure and arrhythmias, with one million annual ED visits in the United States. Although the total numbers of men and women living with heart failure are similar, female patients are underrepresented in clinical studies, with current knowledge predominantly based on data from male patients. This has led to an under-appreciation of the sex-specific differences in clinical characteristics and pathophysiology-based management of heart failure. Similar disparities have been found in management of acute arrhythmias, especially atrial arrhythmias that lead to an increased risk of stroke in women. Additionally, peripartum and postpartum cardiomyopathy represent a diagnostic and treatment dilemma. This article is the result of a breakout session in the cardiovascular and resuscitation work group of the 2014 Academic Emergency Medicine consensus conference “Gender-Specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes.” A nominal group technique was used to identify and prioritize themes and research questions using electronic mail, monthly conference calls, in-person meetings, and web-based surveys between June 2013 and May 2014. Consensus was achieved through three rounds of nomination followed by the meeting on May 13, 2014, and resulted in seven priority themes that are essential to the common complex clinical syndrome of heart failure for both men and women, and include the areas of pathophysiology, presentation and symptomatology, diagnostic strategies using biomarkers, treatment, and mortality, with special consideration to arrhythmia management and pregnancy. PMID:25422074

  10. Genetics of neurocutaneous disorders: basic principles of inheritance as they apply to neurocutaneous syndromes.

    PubMed

    Dies, Kira A; Sahin, Mustafa

    2015-01-01

    Neurocutaneous disorders vary widely in clinical presentation as well as genetic cause and inheritance pattern. Recent advancements in genetic research have identified many of the causal genes for neurocutaneous disorders, allowing families to receive genetic testing and genetic counseling to better understand carrier risks, recurrence risks for future generations, and reproductive options such as prenatal testing and preimplantation diagnosis. Examples of specific neurocutaneous disorders are utilized to illustrate the various inheritance patterns seen in this heterogeneous group of disorders, including autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, de novo, and somatic and germline mosaicism.

  11. Guru - A tool for automatic restructuring of self inheritance hierarchies

    SciTech Connect

    Moore, I.

    1995-12-31

    This paper introduces Guru, a prototype tool for restructuring inheritance hierarchies in Self, while preserving the behavior of objects. Guru reverse engineers from existing inheritance hierarchies. Unlike previous work, Guru handles resends, redefined methods and the restructuring of only part of a system. Furthermore, Guru handles dynamic and cyclical inheritance, which are more specific to Self. Guru removes duplicated methods, and can create inheritance hierarchies with no overridden methods. The results of two non-trivial tests are presented and assessed.

  12. 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

  13. 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. PMID:27512458

  14. The guardians of inherited oncogenic vulnerabilities.

    PubMed

    Arnal, Audrey; Tissot, Tazzio; Ujvari, Beata; Nunney, Leonard; Solary, Eric; Laplane, Lucie; Bonhomme, François; Vittecoq, Marion; Tasiemski, Aurélie; Renaud, François; Pujol, Pascal; Roche, Benjamin; Thomas, Frédéric

    2016-01-01

    Similar to seemingly maladaptive genes in general, the persistence of inherited cancer-causing mutant alleles in populations remains a challenging question for evolutionary biologists. In addition to traditional explanations such as senescence or antagonistic pleiotropy, here we put forward a new hypothesis to explain the retention of oncogenic mutations. We propose that although natural defenses evolve to prevent neoplasm formation and progression thus increasing organismal fitness, they also conceal the effects of cancer-causing mutant alleles on fitness and concomitantly protect inherited ones from purging by purifying selection. We also argue for the importance of the ecological contexts experienced by individuals and/or species. These contexts determine the locally predominant fitness-reducing risks, and hence can aid the prediction of how natural selection will influence cancer outcomes. PMID:26519218

  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. 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.

  18. 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

  19. 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

  20. 25 CFR 91.9 - Inheritance of improvements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Inheritance of improvements. 91.9 Section 91.9 Indians..., 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...

  1. 25 CFR 91.9 - Inheritance of improvements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Inheritance of improvements. 91.9 Section 91.9 Indians..., 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, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Inheritance of improvements. 91.9 Section 91.9 Indians..., 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, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Inheritance of improvements. 91.9 Section 91.9 Indians..., 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, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Inheritance of improvements. 91.9 Section 91.9 Indians..., 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. Omega-3 Fatty Acids Do Not Protect Against Arrhythmias in Acute Nonreperfused Myocardial Infarction Despite Some Antiarrhythmic Effects.

    PubMed

    Mączewski, Michał; Duda, Monika; Marciszek, Mariusz; Kołodziejczyk, Joanna; Dobrzyń, Paweł; Dobrzyń, Agnieszka; Mackiewicz, Urszula

    2016-11-01

    Ventricular arrhythmias are an important cause of mortality in the acute myocardial infarction (MI). To elucidate the effect of the omega-3 polyunsaturated fatty acids (PUFAs) on ventricular arrhythmias in acute nonreperfused MI, rats were fed with normal or eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA)-enriched diet for 3 weeks. Subsequently the rats were subjected to either MI induction or sham operation. ECG was recorded for 6 h after the operation and episodes of ventricular tachycardia/fibrillation (VT/VF) were identified. Six hours after MI epicardial monophasic action potentials (MAPs) were recorded, cardiomyocyte Ca(2+) handling was assessed and expression of proteins involved in Ca(2+) turnover was studied separately in non-infarcted left ventricle wall and infarct borderzone. EPA and DHA had no effect on occurrence of post-MI ventricular arrhythmias or mortality. Nevertheless, DHA but not EPA prevented Ca(2+) overload in LV cardiomiocytes and improved rate of Ca(2+) transient decay, protecting PMCA and SERCA function. Moreover, both EPA and DHA prevented MI-induced hyperphosphorylation of ryanodine receptors (RyRs) as well as dispersion of action potential duration (APD) in the left ventricular wall. In conclusion, EPA and DHA have no antiarrhythmic effect in the non-reperfused myocardial infarction in the rat, although these omega-3 PUFAs and DHA in particular exhibit several potential antiarrhythmic effects at the subcellular and tissue level, that is, prevent MI-induced abnormalities in Ca(2+) handling and APD dispersion. In this context further studies are needed to see if these potential antiarrhythmic effects could be utilized in the clinical setting. J. Cell. Biochem. 117: 2570-2582, 2016. © 2016 Wiley Periodicals, Inc.

  6. 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.

  7. Inheritance law in an aging society.

    PubMed

    Hill, G J

    1995-01-01

    An exploratory analysis of states' inheritance law changes between 1961 and 1990 was conducted in order to discern major trends and their implications for older families. Results suggested that states were modifying their laws in ways similar to suggestions of the law community's Uniform Probate Code, with about one third of the states adopting the Code itself. Consequently, inheritance law has become less traditional and paternalistic and more like "facilitative law," that is, flexible, accommodating, and supportive of family autonomy and decisionmaking authority. These changes and new laws that simplify procedures, protect the dependent and vulnerable, treat marital property more like community property, recognize variant family forms, and enable extrafamilial bequests, may serve to minimize family disruption, conserve resources, and allow families to tailor property divisions and procedures to particular needs and wishes. An impact study is proposed for disclosing the actual effects on inheritance law reforms. Also, while trends observed in this study were fairly evident, states' adoption of new laws was uneven and selective, inviting continuing trend analyses and further research into the reasons for interstate variation.

  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. Phenotype as Agent for Epigenetic Inheritance

    PubMed Central

    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

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

    PubMed

    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.

  11. Phenotype as Agent for Epigenetic Inheritance.

    PubMed

    Torday, John S; Miller, William B

    2016-07-08

    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.

  12. [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.

  13. 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 .

  14. 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

  15. 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

  16. 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.

  17. [Analysis on prescription rules of treating senile dementia based on traditional Chinese medicine inheritance auxiliary systems].

    PubMed

    Zong, Xin; Ji, Xu-Ming; Wei, Feng-Qin; Shi, Zuo-Rong

    2014-02-01

    This is designed to analyze and summarize medication rules for treating senile dementia with Chinese medicine in CNKI according to the traditional Chinese medicine (TCM) inheritance auxiliary system. Collect documents in CNKI that account treating senile dementia with Chinese formula; filter and establish a formula database, and then to search for medication rules on the TCM inheritance auxiliary system. It is filtered that 104 formulas are used for treating senile dementia screening treat senile dementia, involving 147 kinds of Chinese medicine. Tonic medicine are most frequently used, followed by the medicine of activating blood circulation and resuscitating; medicine pair most used is Ligusticum chuanxiong Hort-Acorus tatarinowii, accounting for 27.9% of all formula. And then 8 core pairs and 4 new formulas are evolved. Analysis on formulas for treating senile dementia filtered form CNKI by TCM inheritance auxiliary system shows prescription is mainly tonifying, activating blood circulation and resuscitating, that reveals prescription rules, to provide a reference for clinical treatment.

  18. 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

  19. The effects of respiratory sinus arrhythmia on anger reactivity and persistence in major depression.

    PubMed

    Ellis, Alissa J; Shumake, Jason; Beevers, Christopher G

    2016-10-01

    The experience of anger during a depressive episode has recently been identified as a poor prognostic indicator of illness course. Given the clinical implications of anger in major depressive disorder (MDD), understanding the mechanisms involved in anger reactivity and persistence is critical for improved intervention. Biological processes involved in emotion regulation during stress, such as respiratory sinus arrhythmia (RSA), may play a role in maintaining negative moods. Clinically depressed (MDD; n = 49) and nondepressed (non-MDD; n = 50) individuals were challenged with a stressful computer task shown to increase anger, while RSA (high frequency range 0.15-0.4 Hz) was collected. RSA predicted future anger, but was unrelated to current anger. That is, across participants, low baseline RSA predicted anger reactivity during the task, and in depressed individuals, those with low RSA during the task had a greater likelihood of anger persistence during a recovery period. These results suggest that low RSA may be a psychophysiological process involved in anger regulation in depression. Low RSA may contribute to sustained illness course by diminishing the repair of angry moods. PMID:27401801

  20. Proton pump inhibitor use is not associated with cardiac arrhythmia in critically ill patients.

    PubMed

    Chen, Kenneth P; Lee, Joon; Mark, Roger G; Feng, Mengling; Celi, Leo A; Malley, Brian E; Danziger, John

    2015-07-01

    Hypomagnesemia can lead to cardiac arrythmias. Recently, observational data have 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 readings of a cardiac arrhythmia in more than 8000 patients. There were 25.4% PPI users, whereas 6% were taking a histamine 2 antagonist. In all, 14.0% had a cardiac arrhythmia. PPI use was associated with an unadjusted risk of arrhythmia of 1.15 (95% CI,1.00-1.32; P =.04) and an adjusted risk of arrhythmia of 0.91 (95% CI, 0.77-1.06; P =.22). Among diuretic users (n = 2476), 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.