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Sample records for inherited arrhythmia clinic

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

    PubMed

    Shimizu, Wataru

    2008-12-01

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

  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.

  3. Inherited arrhythmias: The cardiac channelopathies

    PubMed Central

    Behere, Shashank P; Weindling, Steven N

    2015-01-01

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

  4. 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

  5. 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

  6. Rescue of mutated cardiac ion channels in inherited arrhythmia syndromes.

    PubMed

    Balijepalli, Sadguna Y; Anderson, Corey L; Lin, Eric C; January, Craig T

    2010-08-01

    Inherited arrhythmia syndromes comprise an increasingly complex group of diseases involving mutations in multiple genes encoding ion channels, ion channel accessory subunits and channel interacting proteins, and various regulatory elements. These mutations serve to disrupt normal electrophysiology in the heart, leading to increased arrhythmogenic risk and death. These diseases have added impact as they often affect young people, sometimes without warning. Although originally thought to alter ion channel function, it is now increasingly recognized that mutations may alter ion channel protein and messenger RNA processing, to reduce the number of channels reaching the surface membrane. For many of these mutations, it is also known that several interventions may restore protein processing of mutant channels to increase their surface membrane expression toward normal. In this article, we reviewed inherited arrhythmia syndromes, focusing on long QT syndrome type 2, and discuss the complex biology of ion channel trafficking and pharmacological rescue of disease-causing mutant channels. Pharmacological rescue of misprocessed mutant channel proteins, or their transcripts providing appropriate small molecule drugs can be developed, has the potential for novel clinical therapies in some patients with inherited arrhythmia syndromes.

  7. Molecular autopsy in victims of inherited arrhythmias.

    PubMed

    Semsarian, Christopher; Ingles, Jodie

    2016-10-01

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

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

    PubMed

    Mizusawa, Yuka

    2016-10-01

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

  9. 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.

  10. Arrhythmias

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Arrhythmias KidsHealth > For Teens > Arrhythmias Print A A A ... Treated? When to Call the Doctor What Are Arrhythmias? Arrhythmias are abnormal heartbeats usually caused by an ...

  11. 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.

  12. 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 ...

  13. Arrhythmias

    MedlinePlus Videos and Cool Tools

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

  14. Arrhythmia

    MedlinePlus

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

  15. Inherited Retinal Degenerative Clinical Trial Network

    DTIC Science & Technology

    2009-10-01

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

  16. Arrhythmia

    MedlinePlus

    ... are some of the types of arrhythmias?Atrial fibrillation: The heart beats too fast and irregularly. This ... or congenital heart failure).Ventricular tachycardia and ventricular fibrillation: The heart beats too fast and may not ...

  17. 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

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

    PubMed

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

    2016-05-15

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

  19. 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

  20. Ventricular arrhythmias. Clinical recognition and management.

    PubMed

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

    1984-05-01

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

  1. 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

  2. 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    1986-01-01

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

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

    PubMed

    Gillis, Anne M

    2017-02-07

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

  8. Inherited Retinal Degenerative Disease Clinical Trials Network

    DTIC Science & Technology

    2014-12-01

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

  9. Inherited Retinal Degenerative Disease Clinical Trial Network

    DTIC Science & Technology

    2012-10-01

    raster scans were performed with the Spectralis SD-OCT(Heidelberg Engineering) through 2,624 drusen in 14 eyes with clinically dry AMD who had been...NOTES 14 . ABSTRACT See next page 15. SUBJECT TERMS Retinal Degenerations; Clinical Trial Network; non-invasive imaging; treatment 16. SECURITY...THIS PAGE U UU 78 19b. TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 14 . ABSTRACT The

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

    PubMed Central

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

    2016-01-01

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

  11. Inherited Retinal Degenerative Disease Clinical Trial Network. Addendum

    DTIC Science & Technology

    2010-10-01

    DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14 . ABSTRACT 15. SUBJECT...ANSI Std. Z39.18 14 . Abstract (cont.) genotypes and phenotypes; and (iv) evaluations of the reliability and validity of different...preventive interventions for inherited orphan retinal degenerative diseases and dry age-related macular degeneration ( AMD ) through the conduct of clinical

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Sundararajan, Premkumar; Sangaralingam, Thangavelu

    2016-01-01

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

  14. Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations

    PubMed Central

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

    2015-01-01

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

  15. About Arrhythmia

    MedlinePlus

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More About Arrhythmia Updated:Oct 26,2016 The term "arrhythmia" refers ... damaged. View an animation of arrhythmia . Types of Arrhythmias Atrial Fibrillation = upper heart chambers contract irregularly Bradycardia = ...

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

    PubMed

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

    2016-10-25

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  18. 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

  19. Sudden Arrhythmia Death Syndromes (SADS) Foundation

    MedlinePlus

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

  20. 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.

  1. 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

  2. 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.

  3. [Supraventricular arrhythmia: electrocardiographic aspects].

    PubMed

    Bayés de Luna, Antoni

    2016-12-23

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

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

    PubMed

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

    2012-11-01

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

  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. 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.

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

    PubMed

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

    1994-11-01

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

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

    PubMed

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

    1992-12-01

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

  9. 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

  10. 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.

  11. 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.

  12. Chaos control of cardiac arrhythmias.

    PubMed

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

    1995-01-01

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

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

    PubMed

    Hersheson, Joshua; Haworth, Andrea; Houlden, Henry

    2012-09-01

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

  14. Treating Arrhythmias in Children

    MedlinePlus

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Treating Arrhythmias in Children Updated:Dec 21,2016 Many options ... card This content was last reviewed September 2016. Arrhythmia • Home • About Arrhythmia • Why Arrhythmia Matters • Understand Your ...

  15. Medications for Arrhythmia

    MedlinePlus

    ... Disease Venous Thromboembolism Aortic Aneurysm More Medications for Arrhythmia Updated:Dec 21,2016 When taken exactly as ... health. This content was last reviewed September 2016. Arrhythmia • Home • About Arrhythmia • Why Arrhythmia Matters • Understand Your ...

  16. Why Arrhythmia Matters

    MedlinePlus

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Why Arrhythmia Matters Updated:Dec 21,2016 When the heart's ... fibrillation. This content was last reviewed September 2016. Arrhythmia • Home • About Arrhythmia • Why Arrhythmia Matters • Understand Your ...

  17. Types of Arrhythmia

    MedlinePlus

    ... page from the NHLBI on Twitter. Types of Arrhythmia The four main types of arrhythmia are premature ( ... exercise, or too much caffeine or nicotine. Supraventricular Arrhythmias Supraventricular arrhythmias are tachycardias (fast heart rates) that ...

  18. Common Tests for Arrhythmia

    MedlinePlus

    ... Venous Thromboembolism Aortic Aneurysm More Common Tests for Arrhythmia Updated:Dec 21,2016 Several tests can help ... View an animation of arrhythmia . Common Tests for Arrhythmia Holter monitor (continuous ambulatory electrocardiographic monitor) Suspected arrhythmias ...

  19. Children and Arrhythmia

    MedlinePlus

    ... Disease Venous Thromboembolism Aortic Aneurysm More Children and Arrhythmia Updated:Dec 21,2016 If your child has ... options This content was last reviewed September 2016. Arrhythmia • Home • About Arrhythmia • Why Arrhythmia Matters • Understand Your ...

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

    PubMed

    Savige, Judy; Dagher, Hayat; Povey, Sue

    2014-07-01

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

  1. Inherited cardiomyopathies mimicking arrhythmogenic right ventricular cardiomyopathy.

    PubMed

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

    2010-01-01

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

  2. Intraoperative management of critical arrhythmia

    PubMed Central

    2017-01-01

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

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

    PubMed

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

    2013-03-01

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

  4. Common cardiac arrhythmias: recognition and treatment.

    PubMed

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

    1981-04-01

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

  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. 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

  7. 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

  8. 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

  9. Categories of Arrhythmias

    MedlinePlus

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

  10. How Are Arrhythmias Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Are Arrhythmias Diagnosed? Arrhythmias can be hard to diagnose, especially the types ... symptoms every once in a while. Doctors diagnose arrhythmias based on medical and family histories, a physical ...

  11. How Are Arrhythmias Treated?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Are Arrhythmias Treated? Common arrhythmia treatments include medicines, medical procedures, and surgery. Your doctor may recommend treatment if your arrhythmia causes serious symptoms, such as dizziness, chest pain, ...

  12. Devices for Arrhythmia

    MedlinePlus

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

  13. Arrhythmias (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Arrhythmias KidsHealth > For Parents > Arrhythmias Print A A A ... evaluated and treated by a doctor. What Causes Arrhythmias? A unique electrical conduction system in the heart ...

  14. Living with an Arrhythmia

    MedlinePlus

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

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

    PubMed

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

    2015-10-01

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

  16. 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.

  17. Spectrum of Fascicular Arrhythmias.

    PubMed

    Sung, Raphael; Scheinman, Melvin

    2016-09-01

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

  18. [Maternal cardiac arrhythmias in pregnancy].

    PubMed

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

    2000-12-23

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  1. Prevention and Treatment of Arrhythmia

    MedlinePlus

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

  2. Understand Your Risk for Arrhythmia

    MedlinePlus

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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Cardiac arrhythmias in paediatric practice.

    PubMed

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

    1989-01-01

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

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

    PubMed

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

    2011-06-01

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

  9. 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.

  10. Arrhythmias in peripartum cardiomyopathy.

    PubMed

    Honigberg, Michael C; Givertz, Michael M

    2015-06-01

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

  11. Increased Myofilament Ca2+-Sensitivity and Arrhythmia Susceptibility

    PubMed Central

    Huke, Sabine; Knollmann, Bjorn C.

    2010-01-01

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

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

    PubMed

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

    2014-12-01

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

  13. 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

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

    PubMed

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

    2017-01-20

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

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

    PubMed Central

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

    2017-01-01

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

  16. 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

  17. [Arrhythmia and sport].

    PubMed

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

    2005-12-01

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

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

    PubMed

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

    2015-01-01

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

  19. Systems Pharmacology of Arrhythmias

    PubMed Central

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

    2011-01-01

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

  20. 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.

  1. 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.

  2. 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

  3. 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.

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

    PubMed

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

    2008-04-01

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

  5. Autoantibodies and Cardiac Arrhythmias

    PubMed Central

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

    2013-01-01

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

  6. 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

  7. [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.

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

    PubMed Central

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

    2014-01-01

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

  9. [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.

  10. Types of Arrhythmia in Children

    MedlinePlus

    ... Disease Venous Thromboembolism Aortic Aneurysm More Types of Arrhythmia in Children Updated:Dec 21,2016 There are ... put in. Checklist for Parents of Children with Arrhythmias Learn CPR and emergency procedures Parents of all ...

  11. Arrhythmias in the setting of hematopoietic cell transplants.

    PubMed

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

    2015-09-01

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

  12. 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.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed

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

    2017-03-31

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

  16. [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.

  17. Therapy with conventional antiarrhythmic drugs for ventricular arrhythmias.

    PubMed

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

    1984-09-01

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

  18. 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.

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

    PubMed

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

    2015-05-01

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

  20. 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

  1. 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.

  2. 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.

  3. Who Is at Risk for Arrhythmia?

    MedlinePlus

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

  4. Arrhythmias in newborn thoroughbred foals.

    PubMed

    Yamamoto, K; Yasuda, J; Too, K

    1992-05-01

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

  5. Mitochondrial inheritance and disease.

    PubMed

    Fine, P E

    1978-09-23

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

  6. 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.

  7. 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).

  8. 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.

  9. 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.

  10. Maternal arrhythmia and perinatal outcomes

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-10-01

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

  12. Inherited ion channel diseases: a brief review.

    PubMed

    Lieve, Krystien V V; Wilde, Arthur A M

    2015-10-01

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

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

    PubMed

    Arujuna, Aruna; de Bono, Joseph

    2016-07-01

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

  14. Early afterdepolarizations and cardiac arrhythmias.

    PubMed

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

    2010-12-01

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

  15. 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…

  16. 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.

  17. Hepatitic inherited metabolic disorders.

    PubMed

    Arroyo, May; Crawford, James M

    2006-01-01

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

  18. 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

  19. Cardioverter-Defibrillator: A Treatment for Arrhythmia

    MedlinePlus

    ... life-threatening arrhythmias, including ventricular tachycardia and ventricular fibrillation.Ventricular tachycardia (say: "tack-ee-card-ee-ya") ... type of arrhythmia can be life threatening.Ventricular fibrillation is when the bottom chambers of your heart ( ...

  20. 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.

  1. Nonlinear-dynamical arrhythmia control in humans

    PubMed Central

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

    2001-01-01

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

  2. Nonlinear-dynamical arrhythmia control in humans.

    PubMed

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

    2001-05-08

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

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

    PubMed

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

    2014-09-01

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

  4. 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.

  5. Cardiac arrhythmias in Chagas' heart disease.

    PubMed

    Elizari, M V; Chiale, P A

    1993-10-01

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

  6. Cardiac arrhythmias in recently diagnosed hypertensive patients at first presentation: an electrocardiographic-based study.

    PubMed

    Ejim, E C; Ike, S O; Anisiuba, B C; Essien, I O; Onwubere, B J; Ikeh, V O

    2012-01-01

    Various forms of cardiac arrhythmias have been documented in hypertensive subjects, and hypertension is an important risk factor for the development of atrial and ventricular arrhythmias and sudden death. Electrocardiography at rest easily documents significant arrhythmias in patients, and this study was carried out to determine the types and frequency of arrhythmias in hypertensive subjects at first presentation in the Hypertension Clinics of the University of Nigeria Teaching Hospital (UNTH) Enugu, Nigeria. The study was hospitalbased and retrospective in nature. The resting 12lead ECG reports of 346 consecutive hypertensive subjects seen at the Hypertension clinics of the UNTH Enugu over a 14 month period were retrieved from the case files and studied. Other information obtained from the case files included the age and gender of the subjects. The mean age of the subjects was 57.3 years. Ninety-five of the subjects had arrhythmias representing 27% of the study population, out of which fifty-five were males (57.9%) and forty were females (42.1%). However 26.9% of all the male subjects had arrhythmias while 28.2% of all the females had arrhythmias. Multiple ventricular ectopics, sinus tachycardia, sinus bradycardia and atrial fibrillation were the most prevalent arrhythmias. This study showed that a significant proportion of hypertensive subjects present initially with significant rhythm disturbances.

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

    PubMed

    Imperato, Pascal James; Imperato, Gavin H

    2009-10-01

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

  8. 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.

  9. Evaluation and Management of Maternal Cardiac Arrhythmias.

    PubMed

    Metz, Torri D; Khanna, Amber

    2016-12-01

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

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

    PubMed

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

    2008-06-01

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

  11. 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.

  12. Mitochondrial inheritance in fungi.

    PubMed

    Basse, Christoph W

    2010-12-01

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

  13. Inherited disorders of desmosomes.

    PubMed

    McGrath, John A

    2005-11-01

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

  14. Cancer chemotherapy and cardiac arrhythmias: a review.

    PubMed

    Tamargo, Juan; Caballero, Ricardo; Delpón, Eva

    2015-02-01

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

  15. Catheter Ablation for Ventricular Arrhythmias

    PubMed Central

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

    2013-01-01

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

  16. Remote Arrhythmia Monitoring System Developed

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

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

  17. 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.

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

    PubMed

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

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

  19. Epigenetic inheritance: Uncontested?

    PubMed Central

    Zhu, Bing; Reinberg, Danny

    2011-01-01

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

  20. PGD for inherited cardiac diseases.

    PubMed

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

    2012-04-01

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

  1. 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.

  2. 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

  3. 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.

  4. 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.

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

    PubMed Central

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

    1979-01-01

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

  6. 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)

  7. Terlipressin-induced ventricular arrhythmia.

    PubMed

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

    2008-01-01

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

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

    PubMed Central

    Reid, D S

    1978-01-01

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

  9. Arrhythmias

    MedlinePlus

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

  10. Arrhythmias

    MedlinePlus

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

  11. Inherited abnormalities of skeletal development in sheep.

    PubMed

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

    2008-09-01

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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Evaluation of Cardiac Arrhythmia among Athletes

    PubMed Central

    Walker, James; Calkins, Hugh; Nazarian, Saman

    2010-01-01

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

  17. Children's Understanding of Inheritance.

    ERIC Educational Resources Information Center

    Clough, Elizabeth Engel; Wood-Robinson, Colin

    1985-01-01

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

  18. [Inherited aplastic anemias].

    PubMed

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

    2010-08-01

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

  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. 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.

  1. 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.

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

    PubMed

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

    2014-04-01

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

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

    PubMed

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

    2016-03-01

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

  4. Arrhythmias in the Heart Transplant Patient

    PubMed Central

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

    2014-01-01

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

  5. 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.

  6. 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

  7. Diagnosis and management of common fetal arrhythmias

    PubMed Central

    Weber, Roland; Stambach, Dominik; Jaeggi, Edgar

    2011-01-01

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

  8. The effects of dilazep on reperfusion arrhythmias.

    PubMed

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

    1985-01-01

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

  9. 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.

  10. 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

  11. Cardiac arrhythmias and sudden unexpected death in epilepsy (SUDEP).

    PubMed

    Velagapudi, Poonam; Turagam, Mohit; Laurence, Thomas; Kocheril, Abraham

    2012-03-01

    Sudden unexpected death in epilepsy (SUDEP) is a major clinical problem in epilepsy patients in the United States, especially those with chronic, uncontrolled epilepsy. Several pathophysiological events contributing to SUDEP include cardiac arrhythmias, respiratory dysfunction, and dysregulation of systemic or cerebral circulation. There is a significant body of literature suggesting the prominent role of cardiac arrhythmias in the pathogenesis of SUDEP. There is evidence to say that long-standing epilepsy can cause physiological and anatomical autonomic instability resulting in life-threatening arrhythmias. Tachyarrhythmias, bradyarrhythmias, and asystole are commonly seen during ictal, interictal, and postictal phase in epilepsy patients. It is unclear if these rhythm disturbances need attention as some of them may be just benign findings. Evidence regarding prolonged cardiovascular monitoring or the benefit of pacemaker/defibrillator implantation for primary or secondary prevention in epilepsy patients is limited. Awareness regarding pathophysiology, cardiac effects, and management options of SUDEP will become useful in guiding more individualized treatment in the near future. (PACE 2011; 1-8).

  12. 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.

  13. 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.

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

    PubMed Central

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

    2017-01-01

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

  15. Epigenetic transgenerational inheritance

    PubMed Central

    Skinner, Michael K.

    2017-01-01

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

  16. 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.

  17. Flecainide: Current status and perspectives in arrhythmia management

    PubMed Central

    Andrikopoulos, George K; Pastromas, Sokratis; Tzeis, Stylianos

    2015-01-01

    Flecainide acetate is a class IC antiarrhythmic agent and its clinical efficacy has been confirmed by the results of several clinical trials. Nowadays, flecainide is recommended as one of the first line therapies for pharmacological conversion as well as maintenance of sinus rhythm in patients with atrial fibrillation and/or supraventricular tachycardias. Based on the Cardiac Arrhythmia Suppression Trial study results, flecainide is not recommended in patients with structural heart disease due to high proarrhythmic risk. Recent data support the role of flecainide in preventing ventricular tachyarrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia associated both with ryanodine receptor and calsequestrin mutations. We herein review the current clinical data related to flecainide use in clinical practice and some concerns about its role in the management of patients with coronary artery disease. PMID:25717355

  18. Development of device therapy for ventricular arrhythmias.

    PubMed

    Holley, Loraine K

    2007-06-01

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

  19. Pathology of inherited rickets in Corriedale sheep.

    PubMed

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

    2009-01-01

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

  20. [Gene therapy for inherited retinal dystrophies].

    PubMed

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

    2009-01-01

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

  1. 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.

  2. Arrhythmias in viral myocarditis and pericarditis.

    PubMed

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

    2015-06-01

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

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

    PubMed

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

    2011-10-01

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

  4. Inheritance and testicular cancer.

    PubMed Central

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

    1995-01-01

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

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

    PubMed

    Gyawali, Rachana; Lin, Xiaorong

    2011-12-01

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

  6. 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.

  7. 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.

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

    PubMed

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

    2014-12-01

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

  9. 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.

  10. 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

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

    PubMed

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

    2017-03-23

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

  12. Ryanodine receptor-mediated arrhythmias and sudden cardiac death

    PubMed Central

    Blayney, Lynda M.; Lai, F. Anthony

    2009-01-01

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

  13. Fractals analysis of cardiac arrhythmias.

    PubMed

    Saeed, Mohammed

    2005-09-06

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

  14. 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

  15. 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.

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

    PubMed

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

    2017-03-24

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

  17. Mitochondrial inheritance in yeast.

    PubMed

    Westermann, Benedikt

    2014-07-01

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

  18. 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

  19. Novel approaches for diagnosing inherited platelet disorders.

    PubMed

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

    2017-01-20

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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Haemodynamic assessment of fetal heart arrhythmias.

    PubMed

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

    1984-07-01

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

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

    PubMed

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

    1977-09-15

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

  6. Progressive interatrial block and supraventricular arrhythmias.

    PubMed

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

    2015-07-01

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

  7. 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

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

    PubMed Central

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

    2012-01-01

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

  9. Malignant ventricular arrhythmias in chronic chagasic myocarditis.

    PubMed

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

    1982-03-01

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

  10. 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.

  11. Julia Bell and the Treasury of Human Inheritance.

    PubMed

    Harper, Peter S

    2005-04-01

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

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

    PubMed

    Lewis, R A; Sumner, A J

    1999-09-14

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

  13. 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.

  14. Mitochondrial inheritance in Aspergillus nidulans.

    PubMed

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

    1996-04-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Mavroudis, Constantine; Deal, Barbara J

    2016-07-01

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

  18. Prophylactic arrhythmia surgery in association with congenital heart disease

    PubMed Central

    Deal, Barbara J.

    2016-01-01

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

  19. 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.

  20. 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

  1. Internet resources cataloguing inherited disorders in dogs.

    PubMed

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

    2011-08-01

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

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

    PubMed

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

    2016-01-01

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

  3. 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.

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

    PubMed

    Stevenson, William G

    2013-12-01

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

  5. Arrhythmogenic right ventricular cardiomyopathy, clinical manifestations, and diagnosis.

    PubMed

    Haugaa, Kristina H; Haland, Trine F; Leren, Ida S; Saberniak, Jørg; Edvardsen, Thor

    2016-07-01

    This review aims to give an update on the pathogenesis, clinical manifestations, and diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Arrhythmogenic right ventricular cardiomyopathy is mainly an autosomal dominant inherited disease linked to mutations in genes encoding desmosomes or desmosome-related proteins. Classic symptoms include palpitations, cardiac syncope, and aborted cardiac arrest due to ventricular arrhythmias. Heart failure may develop in later stages. Diagnosis is based on the presence of major and minor criteria from the Task Force Criteria revised in 2010 (TFC 2010), which includes evaluation of findings from six different diagnostic categories. Based on this, patients are classified as having possible, borderline, or definite ARVC. Imaging is important in ARVC diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting structural and functional abnormalities, but importantly these findings may occur after electrical alterations and ventricular arrhythmias. Electrocardiograms (ECGs) and signal-averaged ECGs are analysed for depolarization and repolarization abnormalities, including T-wave inversions as the most common ECG alteration. Ventricular arrhythmias are common in ARVC and are considered a major diagnostic criterion if originating from the RV inferior wall or apex. Family history of ARVC and detection of an ARVC-related mutation are included in the TFC 2010 and emphasize the importance of family screening. Electrophysiological studies are not included in the diagnostic criteria, but may be important for differential diagnosis including RV outflow tract tachycardia. Further differential diagnoses include sarcoidosis, congenital abnormalities, myocarditis, pulmonary hypertension, dilated cardiomyopathy, and athletic cardiac adaptation, which may mimic ARVC.

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

    PubMed Central

    Levin, Mark D.; Lu, Min Min; Petrenko, Nataliya B.; Hawkins, Brian J.; Gupta, Tara H.; Lang, Deborah; Buckley, Peter T.; Jochems, Jeanine; Liu, Fang; Spurney, Christopher F.; Yuan, Li J.; Jacobson, Jason T.; Brown, Christopher B.; Huang, Li; Beermann, Friedrich; Margulies, Kenneth B.; Madesh, Muniswamy; Eberwine, James H.; Epstein, Jonathan A.; Patel, Vickas V.

    2009-01-01

    Atrial fibrillation is the most common clinical cardiac arrhythmia. It is often initiated by ectopic beats arising from the pulmonary veins and atrium, but the source and mechanism of these beats remains unclear. The melanin synthesis enzyme dopachrome tautomerase (DCT) is involved in intracellular calcium and reactive species regulation in melanocytes. Given that dysregulation of intracellular calcium and reactive species has been described in patients with atrial fibrillation, we investigated the role of DCT in this process. Here, we characterize a unique DCT-expressing cell population within murine and human hearts that populated the pulmonary veins, atria, and atrioventricular canal. Expression profiling demonstrated that this population expressed adrenergic and muscarinic receptors and displayed transcriptional profiles distinct from dermal melanocytes. Adult mice lacking DCT displayed normal cardiac development but an increased susceptibility to atrial arrhythmias. Cultured primary cardiac melanocyte-like cells were excitable, and those lacking DCT displayed prolonged repolarization with early afterdepolarizations. Furthermore, mice with mutations in the tyrosine kinase receptor Kit lacked cardiac melanocyte-like cells and did not develop atrial arrhythmias in the absence of DCT. These data suggest that dysfunction of melanocyte-like cells in the atrium and pulmonary veins may contribute to atrial arrhythmias. PMID:19855129

  7. 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

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

    PubMed Central

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

    2016-01-01

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

  9. 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.

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

    PubMed

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

    2004-12-01

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

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

    PubMed

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

    2015-05-01

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

  12. Cardiac Channelopathies and Sudden Death: Recent Clinical and Genetic Advances

    PubMed Central

    Fernández-Falgueras, Anna; Sarquella-Brugada, Georgia; Brugada, Josep; Brugada, Ramon; Campuzano, Oscar

    2017-01-01

    Sudden cardiac death poses a unique challenge to clinicians because it may be the only symptom of an inherited heart condition. Indeed, inherited heart diseases can cause sudden cardiac death in older and younger individuals. Two groups of familial diseases are responsible for sudden cardiac death: cardiomyopathies (mainly hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy) and channelopathies (mainly long QT syndrome, Brugada syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). This review focuses on cardiac channelopathies, which are characterized by lethal arrhythmias in the structurally normal heart, incomplete penetrance, and variable expressivity. Arrhythmias in these diseases result from pathogenic variants in genes encoding cardiac ion channels or associated proteins. Due to a lack of gross structural changes in the heart, channelopathies are often considered as potential causes of death in otherwise unexplained forensic autopsies. The asymptomatic nature of channelopathies is cause for concern in family members who may be carrying genetic risk factors, making the identification of these genetic factors of significant clinical importance. PMID:28146053

  13. 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.

  14. An interdisciplinary approach to personalized medicine: case studies from a cardiogenetics clinic.

    PubMed

    Erskine, Kathleen E; Griffith, Eleanor; Degroat, Nicole; Stolerman, Marina; Silverstein, Louise B; Hidayatallah, Nadia; Wasserman, David; Paljevic, Esma; Cohen, Lilian; Walsh, Christine A; McDonald, Thomas; Marion, Robert W; Dolan, Siobhan M

    2013-01-01

    In the genomic age, the challenges presented by various inherited conditions present a compelling argument for an interdisciplinary model of care. Cardiac arrhythmias with a genetic basis, such as long QT syndrome, require clinicians with expertise in many specialties to address the complex genetic, psychological, ethical and medical issues involved in treatment. The Montefiore-Einstein Center for CardioGenetics has been established to provide personalized, interdisciplinary care for families with a history of sudden cardiac death or an acute cardiac event. Four vignettes of patient care are presented to illustrate the unique capacity of an interdisciplinary model to address genetic, psychological, ethical and medical issues. Because interdisciplinary clinics facilitate collaboration among multiple specialties, they allow for individualized, comprehensive care to be delivered to families who experience complex inherited medical conditions. As the genetic basis of many complex conditions is discovered, the advantages of an interdisciplinary approach for delivering personalized medicine will become more evident.

  15. A review of maternally inherited diabetes and deafness.

    PubMed

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

    2014-01-01

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

  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.

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

    PubMed

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

    2016-10-01

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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Trends in Reporting Methadone-Associated Cardiac Arrhythmia, 1997–2011

    PubMed Central

    Kao, David; Bartelson, Becki Bucher; Khatri, Vaishali; Dart, Richard; Mehler, Philip S.; Katz, David; Krantz, Mori J.

    2013-01-01

    Background: Long-acting opioids are a leading cause of accidental death in the United States, and methadone is associated with greater mortality rates. Whether this increase is related to the proarrhythmic properties of methadone is unclear. Objective: To describe methadone-associated arrhythmia events reported in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Design: Description of national adverse event registry data before and after publication of a 2002 report describing an association between methadone and arrhythmia. Setting: FAERS, November 1997 and June 2011. Patients: Adults with QTc prolongation or torsade de pointes and ventricular arrhythmia or cardiac arrest. Measurements: FAERS reports before and after the 2002 report. Results: 1646 cases of ventricular arrhythmia or cardiac arrest and 379 cases of QTc prolongation or torsade de pointes were associated with methadone. Monthly reports of QTc prolongation or torsade de pointes increased from a mean of 0.3 (95% CI, 0.1 to 0.5) before the 2002 publication to a mean of 3.5 (CI, 2.5 to 4.8) after it. After 2000, methadone was the second-most common primary suspect in cases of QTc prolongation or torsade de pointes after dofetilide (a known proarrhythmic drug) and was associated with disproportionate reporting similar to that of antiarrhythmic agents known to promote torsade de pointes. Antiretroviral drugs for HIV were the most common coadministered drugs. Limitation: Reports to FAERs are voluntary and selective, and incidence rates cannot be determined from spontaneously reported data. Conclusion: Since 2002, reports to FAERS of methadone-associated arrhythmia have increased substantially and are disproportionately represented relative to other events with the drug. Coadministration of methadone with antiretrovirals in patients with HIV may pose particular risk. Primary Funding Source: Colorado Clinical and Translational Sciences Institute, National Institutes of Health, and

  3. 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

  4. Atrial Arrhythmias and Their Implications for Space Flight - Introduction

    NASA Technical Reports Server (NTRS)

    Polk, J. D.; Barr, Y. R.; Bauer, P.; Hamilton, D. R.; Kerstman, E.; Tarver, B.

    2010-01-01

    This panel will discuss the implications of atrial arrhythmias in astronauts from a variety of perspectives; including historical data, current practices, and future challenges for exploration class missions. The panelists will present case histories, outline the evolution of current NASA medical standards for atrial arrhythmias, discuss the use of predictive tools, and consider potential challenges for current and future missions.

  5. Psychophysiological factors in ventricular arrhythmias and sudden cardiac death.

    PubMed

    Hatton, D C; Gilden, E R; Edwards, M E; Cutler, J; Kron, J; McAnulty, J H

    1989-01-01

    Plasma catecholamine levels were measured preceding programmed electrophysiological studies of patients who had survived a ventricular tachyarrhythmia episode. Psychological assessments of desire for control, locus of control and behavior pattern were obtained. Psychophysiological variables were analysed with respect to the severity of arrhythmias induced by the electrophysiological procedure. Analysis of data from 17 subjects showed desire for control was significantly higher in those with induced sustained arrhythmias than in those in which nonsustained arrhythmias were induced. No relationship was found between behavior pattern and arrhythmia severity or plasma catecholamine levels. There was a significant interaction between desire for control and behavior pattern with respect to epinephrine level. The findings indicate that psychological factors such as desire for control may be associated with potentially lethal arrhythmias and implicated in sudden cardiac death.

  6. Altered Calcium Handling and Ventricular Arrhythmias in Acute Ischemia

    PubMed Central

    Baumeister, Peter; Quinn, T. Alexander

    2016-01-01

    Acute ischemia results in deadly cardiac arrhythmias that are a major contributor to sudden cardiac death (SCD). The electrophysiological changes involved have been extensively studied, yet the mechanisms of ventricular arrhythmias during acute ischemia remain unclear. What is known is that during acute ischemia both focal (ectopic excitation) and nonfocal (reentry) arrhythmias occur, due to an interaction of altered electrical, mechanical, and biochemical properties of the myocardium. There is particular interest in the role that alterations in intracellular calcium handling, which cause changes in intracellular calcium concentration and to the calcium transient, play in ischemia-induced arrhythmias. In this review, we briefly summarize the known contributors to ventricular arrhythmias during acute ischemia, followed by an in-depth examination of the potential contribution of altered intracellular calcium handling, which may include novel targets for antiarrhythmic therapy. PMID:28008297

  7. Molecular Mechanisms of Inherited Demyelinating Neuropathies

    PubMed Central

    SCHERER, STEVEN S.; WRABETZ, LAWRENCE

    2008-01-01

    The past 15 years have witnessed the identification of more than 25 genes responsible for inherited neuropathies in humans, many associated with primary alterations of the myelin sheath. A remarkable body of work in patients, as well as animal and cellular models, has defined the clinical and molecular genetics of these illnesses and shed light on how mutations in associated genes produce the heterogeneity of dysmyelinating and demyelinating phenotypes. Here, we review selected recent developments from work on the molecular mechanisms of these disorders and their implications for treatment strategies. PMID:18803325

  8. [Contribution to the inheritance of schizophrenic psychosis].

    PubMed

    Feyler, K P

    2000-05-01

    This case presentation involves a family study looking at the inheritance of schizophrenic psychosis. It refers to the increasing risk of disease in correlation to the closeness of the relationship. The study includes both affected parents, their three children and one grandchild, all of whom had multiple hospital admissions and received psychiatric treatment. The clinical features were typical of schizophrenia. The severity of illness increased within the later generation. This study indicates a high risk correlation in this family and is in keeping with other current field studies.

  9. Arrhythmias in athletes: evidence-based strategies and challenges for diagnosis, management, and sports eligibility.

    PubMed

    Fragakis, Nikolaos; Pagourelias, Efstathios D; Koskinas, Konstantinos C; Vassilikos, Vassilios

    2013-01-01

    Assessment and management of cardiac rhythm disorders in athletes is particularly challenging. An accurate diagnosis and optimal risk-stratification are often limited because of substantial phenotypic overlap between pathological entities and adaptive cardiovascular responses that normally occur in athletes. An accurate diagnosis, however, is particularly important in this population, as 2 competing risks need to be cautiously balanced: the risk of under-diagnosis of an arrhythmogenic substrate that may trigger life-threatening events versus the risk of over-diagnosis that may result in an athlete's improper disqualification. Accordingly, the management of arrhythmias in athletes may pose therapeutic dilemmas, and often differs substantially compared with the general population. In this review, we present the most frequently observed arrhythmias in athletes and briefly discuss their pathophysiologic substrate. We further propose diagnostic and therapeutic strategies based upon current guidelines, official recommendations, and emerging evidence from relevant clinical investigations. We focus particularly on disparities in current guidelines regarding the management of certain rhythm disorders, as these areas of uncertainty may reflect the challenging nature of these disorders and may indicate the need for individualized approaches in every-day clinical practice. A better understanding of the normal electrophysiological responses to chronic exercise, and of the pathophysiological basis and the true clinical significance of arrhythmias in athletes, may enhance decision-making, and may allow for management strategies which more prudently weigh the risk-to-benefit ratio of each approach.

  10. 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.

  11. Inherited Retinal Degenerative Clinical Trial Network. Addendum

    DTIC Science & Technology

    2013-10-01

    visual impairment usually ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other...linica l trial in the NEER network for autosomal dominant retinitis pigmentosa , and the ProgSTAR studies for Stargardt disease) . As new interventions b... retinitis pigmentosa continues at six sites- the CTEC site at University of Utah and five additional recruitment sites- the Retina Foundation of the

  12. Kin selection under blending inheritance.

    PubMed

    Gardner, Andy

    2011-09-07

    Why did Darwin fail to develop his insights on kin selection into a proper theory of social adaptation? One suggestion has been that his inadequate understanding of heredity kept the problem out of focus. Here, I determine whether it is possible to develop a quantitative theory of kin selection upon the assumption of blending inheritance. I find that, whilst Hamilton's rule of kin selection can be readily derived under the assumption of blending inheritance, this mechanism complicates the computation of relatedness coefficients, and can even cause them to fluctuate over generations. Nevertheless, I show that the ultimate criterion for selection to favour any social trait - i.e. a time-average of Hamilton's rule - remains the same as under particulate inheritance. By eliminating the gene from the theory of kin selection, I clarify the role that it plays in the theory of social adaptation.

  13. Back to Biology: New Insights on Inheritance in Myeloproliferative Disorders

    PubMed Central

    Braunstein, Evan M.

    2015-01-01

    The myeloproliferative disorders (MPDs) are a group of hematologic diseases with significant overlap in both clinical phenotype and genetic etiology. While most often caused by acquired somatic mutations in hematopoietic stem cells, the presence of familial clustering in MPD cases suggests that inheritance is an important factor in the etiology of this disease. Though far less common than sporadic disease, inherited MPDs can be clinically indistinguishable from sporadic disease. Recently, germline mutations in Janus kinase 2 (JAK2) and MPL, two genes frequently mutated in sporadic MPD, have been shown to cause inherited thrombocytosis. Study of the function of these mutant proteins has led to a new understanding of the biological mechanisms that produce myeloproliferative disease. In this review, we summarize the data regarding inherited mutations that cause or predispose to MPDs, with a focus on the biological effects of mutant proteins. We propose that defining inherited MPDs in this manner has the potential to simplify diagnosis in a group of disorders that can be difficult to differentiate clinically. PMID:25195195

  14. Effectiveness of amiodarone in resistant arrhythmias1

    PubMed Central

    Hollman, Arthur; Holt, Phyllis M

    1980-01-01

    Amiodarone is used in the treatment of previously drug-resistant supraventricular and ventricular arrhythmias. We report our experience with amiodarone in 8 patients. Five patients had paroxysmal atrial flutter, one had paroxysmal atrial fibrillation, one had supraventricular tachycardia, and one ventricular tachycardia. Considerable improvement, both objectively and subjectively, was observed in all patients. Side effects were as follows: all patients had corneal microdeposits, one developed left bundle branch block which resolved on stopping amiodarone, and one reported constipation and abdominal pains. Six patients have been treated for 10–28 months; 3 developed tolerance at 4–14 months after the introduction of amiodarone therapy, but symptoms improved with increased dosage. It is important to watch for the development of tolerance to this drug. PMID:7452643

  15. Genetics of inherited cardiomyopathy.

    PubMed

    Jacoby, Daniel; McKenna, William J

    2012-02-01

    During the past two decades, numerous disease-causing genes for different cardiomyopathies have been identified. These discoveries have led to better understanding of disease pathogenesis and initial steps in the application of mutation analysis in the evaluation of affected individuals and their family members. As knowledge of the genetic abnormalities, and insight into cellular and organ biology has grown, so has appreciation of the level of complexity of interaction between genotype and phenotype across disease states. What were initially thought to be one-to-one gene-disease correlates have turned out to display important relational plasticity dependent in large part on the genetic and environmental backgrounds into which the genes of interest express. The current state of knowledge with regard to genetics of cardiomyopathy represents a starting point to address the biology of disease, but is not yet developed sufficiently to supplant clinically based classification systems or, in most cases, to guide therapy to any significant extent. Future work will of necessity be directed towards elucidation of the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype-phenotype relationship with the ultimate goal of furthering our ability to identify, diagnose, risk stratify, and treat this group of disorders which cause heart failure and sudden death in the young.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    Myocardial fibrosis is an important risk factor for cardiac arrhythmias. Previous experimental and numerical studies have shown that the texture and spatial distribution of fibrosis may play an important role in arrhythmia onset. Here, we investigate how spatial heterogeneity of fibrosis affects arrhythmia onset using numerical methods. We generate various tissue textures that differ by the mean amount of fibrosis, the degree of heterogeneity and the characteristic size of heterogeneity. We study the onset of arrhythmias using a burst pacing protocol. We confirm that spatial heterogeneity of fibrosis increases the probability of arrhythmia induction. This effect is more pronounced with the increase of both the spatial size and the degree of heterogeneity. The induced arrhythmias have a regular structure with the period being mostly determined by the maximal local fibrosis level. We perform ablations of the induced fibrillatory patterns to classify their type. We show that in fibrotic tissue fibrillation is usually of the mother rotor type but becomes of the multiple wavelet type with increase in tissue size. Overall, we conclude that the most important factor determining the formation and dynamics of arrhythmia in heterogeneous fibrotic tissue is the value of maximal local fibrosis.

  17. 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.

  18. Efficient Fine Arrhythmia Detection Based on DCG P-T Features.

    PubMed

    Bie, Rongfang; Xu, Shuaijing; Zhang, Guangzhi; Zhang, Meng; Ma, Xianlin; Zhang, Xialin

    2016-07-01

    Due to the high mortality associated with heart disease, there is an urgent demand for advanced detection of abnormal heart beats. The use of dynamic electrocardiogram (DCG) provides a useful indicator of heart condition from long-term monitoring techniques commonly used in the clinic. However, accurately distinguishing sparse abnormal heart beats from large DCG data sets remains difficult. Herein, we propose an efficient fine solution based on 11 geometrical features of the DCG PQRST(P-T) waves and an improved hierarchical clustering method for arrhythmia detection. Data sets selected from MIT-BIH are used to validate the effectiveness of this approach. Experimental results show that the detection procedure of arrhythmia is fast and with accurate clustering.

  19. Transgenerational epigenetic inheritance in plants.

    PubMed

    Hauser, Marie-Theres; Aufsatz, Werner; Jonak, Claudia; Luschnig, Christian

    2011-08-01

    Interest in transgenerational epigenetic inheritance has intensified with the boosting of knowledge on epigenetic mechanisms regulating gene expression during development and in response to internal and external signals such as biotic and abiotic stresses. Starting with an historical background of scantily documented anecdotes and their consequences, we recapitulate the information gathered during the last 60 years on naturally occurring and induced epialleles and paramutations in plants. We present the major players of epigenetic regulation and their importance in controlling stress responses. The effect of diverse stressors on the epigenetic status and its transgenerational inheritance is summarized from a mechanistic viewpoint. The consequences of transgenerational epigenetic inheritance are presented, focusing on the knowledge about its stability, and in relation to genetically fixed mutations, recombination, and genomic rearrangement. We conclude with an outlook on the importance of transgenerational inheritance for adaptation to changing environments and for practical applications. This article is part of a Special Issue entitled "Epigenetic control of cellular and developmental processes in plants".

  20. Transgenerational epigenetic inheritance in plants☆

    PubMed Central

    Hauser, Marie-Theres; Aufsatz, Werner; Jonak, Claudia; Luschnig, Christian

    2015-01-01

    Interest in transgenerational epigenetic inheritance has intensified with the boosting of knowledge on epigenetic mechanisms regulating gene expression during development and in response to internal and external signals such as biotic and abiotic stresses. Starting with an historical background of scantily documented anecdotes and their consequences, we recapitulate the information gathered during the last 60 years on naturally occurring and induced epialleles and paramutations in plants. We present the major players of epigenetic regulation and their importance in controlling stress responses. The effect of diverse stressors on the epigenetic status and its transgenerational inheritance is summarized from a mechanistic viewpoint. The consequences of transgenerational epigenetic inheritance are presented, focusing on the knowledge about its stability, and in relation to genetically fixed mutations, recombination, and genomic rearrangement. We conclude with an outlook on the importance of transgenerational inheritance for adaptation to changing environments and for practical applications. This article is part of a Special Issue entitled “Epigenetic control of cellular and developmental processes in plants”. PMID:21515434

  1. A troubled beginning: evolving concepts of an old arrhythmia.

    PubMed

    Hanon, Sam; Shapiro, Michael; Schweitzer, Paul

    2005-07-01

    The development of the sphygmograph in the nineteenth century marked the beginning of graphic registration of the arterial and venous pulse. Mackenzie, among other investigators, used this technique to study cardiac rhythm. In the early 20th century, Einthoven developed the electrocardiogram, which replaced the less sophisticated arterial and venous registrations of cardiac events and allowed for more detailed arrhythmia analysis. Interestingly, the early study of cardiac arrhythmias was obscured by misinterpretation. Specifically, atrial fibrillation stands out as a rhythm that was extensively studied though misconstrued in its early history. What follows is an in-depth consideration of the original investigations and evolving theories of this important arrhythmia.

  2. Use of Intravenous Amiodarone in the Treatment of Nifekalant-Resistant Arrhythmia: A Review of 11 Consecutive Cases with Severe Heart Failure

    PubMed Central

    Nakagawa, Koji; Nakamura, Kazufumi; Kusano, Kengo Fukushima; Nagase, Satoshi; Tada, Takeshi; Murakami, Masato; Hata, Yoshiki; Morita, Hiroshi; Kohno, Kunihisa; Hina, Kazumasa; Ujihira, Tohru; Ohe, Tohru; Ito, Hiroshi

    2011-01-01

    Background: Both nifekalant hydrochloride (NIF), a selective IKr blocker, and intravenous amiodarone (AMD), a multi-channel (including IKr blocking) blocker, have been reported to be efficacious for refractory arrhythmias. However, the optimal use of those antiarrhythmic drugs for refractory arrhythmia with severe heart failure has not been established. Intravenous AMD might be effective for arrhythmias refractory to NIF in patients with severe heart failure. Here, we report that intravenous amiodarone was effective in the treatment of nifekalant-resistant in a group of arrhythmia patients with severe heart failure. Methods: Eleven severe heart failure patients who had received intravenous AMD for treatment of NIF-resistant arrhythmias were included in this study, and retrospective analysis was performed. Clinical efficacy (terminative and preventive effects on arrhythmia) of intravenous AMD was evaluated. Results: All cases were emergent cases and had depressed left ventricular ejection fraction (30 ± 13%). Clinical arrhythmias were ventricular fibrillation (VF) in four patients, ventricular tachycardia (VT) in six patients, and atrial fibrillation (AF) in one patient. NIF was administered to all patients by intravenous injection. After administration of NIF, VT/VF/AF was terminated in seven of the 10 patients, but a preventive effect was not obtained in any of the patients (NIF-resistance). Intravenous AMD (maintenance dose: 484 ± 166 mg/day) was effective both in termination (80%) and in prevention (80%) of VT/VF events in those patients. It was also effective in termination (80%) and prevention (60%) of AF events refractory to NIF. During continuous AMD administration, no significant adverse effects or proarrhythmic effects were observed in any of the patients. Five patients died within one month, but there was no arrhythmic deaths. Conclusions: Intravenous AMD was effective in NIF-resistant lethal arrhythmias and was relatively safe in emergent cases with

  3. Periodic Limb Movements during Sleep and Cardiac Arrhythmia in Older Men (MrOS Sleep)

    PubMed Central

    Koo, Brian B.; Mehra, Reena; Blackwell, Terri; Ancoli-Israel, Sonia; Stone, Katie L.; Redline, Susan

    2014-01-01

    Study Objectives: To determine if periodic limb movements during sleep (PLMS) are associated with nocturnal cardiac arrhythmia. Methods: 2,793 community-dwelling older men underwent polysomnography with measurement of limb movements and EKG. Logistic regression assessed association of periodic limb movement index and periodic limb movement arousal index with arrhythmia including atrial fibrillation and non-sustained ventricular tachycardia detected by polysomnography. Models were adjusted for age, race, cardiovascular risk factors, and clinic site. Secondary analyses were subset to men without calcium channel/β-adrenergic medication usage, and stratified by congestive heart failure or myocardial infarction history. Results: In the overall cohort, periodic limb movement index, and periodic limb movement arousal index were not associated with ventricular or atrial arrhythmia after considering potential confounders. In men not taking calcium channel/β-blocking medication, increased adjusted odds of non-sustained ventricular tachycardia were observed for periodic limb movement index (OR = 1.30 per SD increase; 95% CI 1.00, 1.68) and periodic limb movement arousal index (OR = 1.29 per SD increase; 95% CI 1.03, 1.62). In men with CHF or MI, there was a suggested association of atrial fibrillation with periodic limb movement index (OR = 1.29, 95% CI 0.96, 1.73 per SD increase; p = 0.09) or periodic limb movement arousal index (OR = 1.21, 95% CI 0.94, 1.57 per SD increase; p = 0.14), although results were not statistically significant. Conclusions: There is not an association between PLMS and cardiac arrhythmia in all older men but in subsets of men, particularly those with structural heart disease and not on calcium channel or β-adrenergic medication, cardiac arrhythmia does associate with PLMS. Citation: Koo BB; Mehra R; Blackwell T; Ancoli-Israel S; Stone KL; Redline S; for the Osteoporotic Fractures in Men (MrOS) Study Group. Periodic limb movements during sleep and

  4. 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

  5. Identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death

    PubMed Central

    Jagu, Benoît; Charpentier, Flavien; Toumaniantz, Gilles

    2013-01-01

    Researchers and clinicians have discovered several important concepts regarding the mechanisms responsible for increased risk of arrhythmias, heart failure, and sudden cardiac death. One major step in defining the molecular basis of normal and abnormal cardiac electrical behavior has been the identification of single mutations that greatly increase the risk for arrhythmias and sudden cardiac death by changing channel-gating characteristics. Indeed, mutations in several genes encoding ion channels, such as SCN5A, which encodes the major cardiac Na+ channel, have emerged as the basis for a variety of inherited cardiac arrhythmias such as long QT syndrome, Brugada syndrome, progressive cardiac conduction disorder, sinus node dysfunction, or sudden infant death syndrome. In addition, genes encoding ion channel accessory proteins, like anchoring or chaperone proteins, which modify the expression, the regulation of endocytosis, and the degradation of ion channel a-subunits have also been reported as susceptibility genes for arrhythmic syndromes. The regulation of ion channel protein expression also depends on a fine-tuned balance among different other mechanisms, such as gene transcription, RNA processing, post-transcriptional control of gene expression by miRNA, protein synthesis, assembly and post-translational modification and trafficking. The aim of this review is to inventory, through the description of few representative examples, the role of these different biogenic mechanisms in arrhythmogenesis, HF and SCD in order to help the researcher to identify all the processes that could lead to arrhythmias. Identification of novel targets for drug intervention should result from further understanding of these fundamental mechanisms. PMID:24065925

  6. Clinical management and prevention of sudden cardiac death.

    PubMed

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

    2015-06-05

    Despite the revolutionary advancements in the past 3 decades in the treatment of ventricular tachyarrhythmias with device-based therapy, sudden cardiac death (SCD) remains an enormous public health burden. Survivors of SCD are generally at high risk for recurrent events. The clinical management of such patients requires a multidisciplinary approach from postresuscitative care to a thorough cardiovascular investigation in an attempt to identify the underlying substrate, with potential to eliminate or modify the triggers through catheter ablation and ultimately an implantable cardioverter-defibrillator (ICD) for prompt treatment of recurrences in those at risk. Early recognition of low left ventricular ejection fraction as a strong predictor of death and association of ventricular arrhythmias with sudden death led to significant investigation with antiarrhythmic drugs. The lack of efficacy and the proarrhythmic effects of drugs catalyzed the development and investigation of the ICD through several major clinical trials that proved the efficacy of ICD as a bedrock tool to detect and promptly treat life-threatening arrhythmias. The ICD therapy is routinely used for primary prevention of SCD in patients with cardiomyopathy and high risk inherited arrhythmic conditions and secondary prevention in survivors of sudden cardiac arrest. This compendium will review the clinical management of those surviving SCD and discuss landmark studies of antiarrhythmic drugs, ICD, and cardiac resynchronization therapy in the primary and secondary prevention of SCD.

  7. 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…

  8. Elderly woman with cerebrovascular accident and refractory arrhythmias.

    PubMed

    Sethi, S K; Sarm, P S A

    2009-11-01

    Fatal bilateral cerebro-vascular accident with variable atrio-ventricular blocks, atrial fibrillation and refractory tachy-arrhythmias in a previously healthy 75-years-old hypertensive female is presented.

  9. 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.

  10. Primary Immune Deficiency Disease Genetics & Inheritance

    MedlinePlus

    ... twitter share with linkedin Primary Immune Deficiency Disease Genetics & Inheritance Primary Immune Deficiency Diseases (PIDDs) Primary Immune Deficiency Diseases (PIDDs) Types of PIDDs Genetics & Inheritance Talking to Your Doctor Featured Research Credit: ...

  11. [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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Benchmarking ventricular arrhythmias in the mouse--revisiting the 'Lambeth Conventions' 20 years on.

    PubMed

    Huggins, Catherine E; Bell, James R; Pepe, Salvatore; Delbridge, Lea M D

    2008-12-01

    The isolated Langendorff-mode perfused heart has become a valuable experimental model, used extensively to examine cardiac function, pathophysiology and pharmacology. For the clinical cardiologist an ECG is often a simple practicality, however in experimental circumstances, particularly with ex vivo murine hearts it is not always possible to obtain an ECG due to experimental recording constraints. However, the mechanical record of ventricular contractile function can be highly informative in relation to electrical state. It is difficult though to achieve consistency in these evaluations of arrhythmia as a validated common reference framework is lacking. In 1988, a group of investigators developed the 'Lambeth Conventions'--a standardised reference for the definition and classification of arrhythmias in animal experimental models of ischaemia, infarction and reperfusion in vivo. Now, two decades later it is timely to revisit the Lambeth Conventions, and to update the guidelines in the context of the marked increase in murine heart study in experimental cardiac pathophysiology. Here we describe an adjunct to the Lambeth Conventions for the reporting of ventricular arrhythmias post-ischaemia in ex vivo mouse hearts when ECG recordings are not employed. Of seven discrete and identifiable patterns of mechanical dysrhythmia observed in reperfusion, five could be classified using conventional ECG terminology: ventricular premature beat, bigeminy, trigeminy, ventricular tachycardia and ventricular fibrillation. Two additional rhythm variations detected from the pressure record are described (potentiated contraction and alternans).

  17. 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

  18. [Management of patients with arrhythmias undergoing thoracic surgery].

    PubMed

    Ishibashi, H; Okubo, K

    2012-07-01

    Recentry, surgical candidates have become older and have more surgical risk factors, perioperative patient management become more important than before. In the patients with significant arrhythmia observed in the preoperative period, examination of the baseline heart disease, i.e. myocardial ischemia or congestive heart failure, is mandatory and, if necessary, adequate treatment such as defibrillator, the implantation of a pacemaker, anticoagulation therapy, or other medical therapy should be performed. In the patients with atrial fibrillation, clinical prediction rules such as the congestive heart failure, hypertension, age>75, diabetes, previous stroke or transient ischemic attack (TIA) [CHADS 2] score have been developed to identify those patients at highest risk for thrombo-embolism and can be used when assessing the need for bridging anticoagulation by heparin prior to surgery. The electrical stimulus from electrocautery may inhibit demand pacemakers or may reprogram the pacemaker. An asynchronous or non-sensing pacemaker mode is recommended in patients who are pacemaker dependent and whose underlying rhythm is unreliable. The device has to be checked to ensure appropriate programming and sensing pacing thresholds after surgery. The implantable cardioverter defibrillator should be turned off during surgery and switched on in the recovery phase before discharge to the ward.

  19. Update on management of cardiac arrhythmias in acute coronary syndromes.

    PubMed

    Willich, T; Goette, A

    2015-04-01

    This review summarizes different types of arrhythmias in patients with acute coronary syndromes and provides an overview of the available therapeutic options for acute care and management of critical arrhythmias. The different therapeutic options are depending on the origin and type of arrhythmia. The main common dominant mechanisms are intramural re-entry in ischemia and triggered activity in reperfusion. The different forms of arrhythmia were explained in detail. Atrial arrhythmias are mainly atrial fibrillation; other forms are rare and usually self-limited. As therapeutic options antiarrhythmic drug therapy with beta-blockers or amiodarone and direct current cardioversion are suitable. Ventricular arrhythmias can be divided in premature ventricular complexes, accelerated idioventricular rhythm, non-sustained ventricular tachycardia, sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and electrical storm. As therapeutic options antiarrhythmic drug therapy, implantable cardioverter defibrillator therapy (ICD), radiofrequency catheter ablation (RFA) and stellate ganglion blockade are available. The treatment with antiarrhythmic drug is rather cautious recommended, with the exception of beta-blockers. An additional drug therapy with ranolazine may be considered. The advantage of ICD therapy for long-term primary or secondary prophylactic therapy has been well documented. ICD therapy is associated with significant reduction in mortality compared with antiarrhythmic drug therapy (mainly amiodarone), with the exception of beta-blockers. RFA and stellate ganglion blockade are rather intended as therapeutically options for incessant VT/VF or electrical storm.

  20. Epigenetic Inheritance across the Landscape

    PubMed Central

    Whipple, Amy V.; Holeski, Liza M.

    2016-01-01

    The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here, we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome–environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype. PMID:27826318

  1. 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.

  2. Inherited predisposition to multiple myeloma

    PubMed Central

    Koura, Divya T.

    2013-01-01

    Multiple myeloma (MM) is the second most common hematologic malignancy in the United States, after non-Hodgkin lymphoma. Family pedigree analyses of high-risk families, case-control studies and racial disparities in disease incidence all point to a potential inherited predisposition to MM. Genome-wide association studies (GWASs) have identified susceptibility loci in a number of cancers and such studies are currently underway in MM. To date, GWASs in MM have identified several potential regions of interest for further study on chromosomes 3p22, 7p15.3, 8q24 and 2p23.3. In addition, several targets of paraproteins (so called ‘paratargs’) in MM have been identified. Hyperphosphorylation of the paratarg protein, which is inherited in an autosomal dominant manner, appears a common mechanism underlying the antigenicity of these proteins. One particular protein, hyperphosphorylated paratarg-7 (pP-7) is a common target in persons with myeloma and has also been identified in affected members of several high-risk MM families. It appears that the frequency of pP-7 as an antigenic target may be particularly high in African American patients with MM, which could be part of the explanation for observed racial disparities in the incidence of MM. In this review we focus on available data in the area of inherited predisposition to MM, and highlight future research directions. PMID:23926460

  3. Gene therapy for inherited retinal degenerations.

    PubMed

    Dalkara, Deniz; Sahel, José-Alain

    2014-03-01

    Gene therapy is quickly becoming a reality applicable in the clinic for inherited retinal diseases. Progress over the past decade has moved proof-of-concept gene therapies from bench to bedside. The remarkable success in safety and efficacy, in the phase I/II clinical trials for the form of the severe childhood-onset blindness, Leber's Congenital Amaurosis (LCA) type II (due to mutations in the RPE65 gene) generated significant interest and opened up possibilities for a new era of retinal gene therapies. Success in these clinical trials was due to combining the favorable features of both the retina as a target organ and adeno-associated virus (AAV) as a vector. The retina offers several advantages for gene therapy approaches. It is an anatomically defined structure that is readily accessible for therapy and has some degree of immune privilege, making it suitable for application of viral vectors. AAV, on the other hand, is a non-pathogenic helper dependent virus that has little immunogenicity. This viral vector transduces quiescent cells efficiently and thanks to its small size diffuses well in the interneural matrix, making it suitable for applications in neural tissue. Building on this initial clinical success with LCA II, we have now many opportunities to extend this proof-of-concept to other retinal diseases. This article will discuss what are some of the most imminent targets for such therapies and what are the challenges that we face in moving these therapies to the clinic.

  4. 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

  5. Inherited secondary nephrogenic diabetes insipidus: concentrating on humans.

    PubMed

    Bockenhauer, D; Bichet, D G

    2013-04-15

    The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Mitochondrial inheritance in budding yeast.

    PubMed

    Boldogh, I R; Yang, H C; Pon, L A

    2001-06-01

    During the past decade significant advances were made toward understanding the mechanism of mitochondrial inheritance in the yeast Saccharomyces cerevisiae. A combination of genetics, cell-free assays and microscopy has led to the discovery of a great number of components. These fall into three major categories: cytoskeletal elements, mitochondrial membrane components and regulatory proteins. These proteins mediate activities, including movement of mitochondria from mother cells to buds, segregation of mitochondria and mitochondrial DNA, and equal distribution of the organelle between mother cells and buds during yeast cell division.

  12. 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.

  13. 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

  14. Macrolide Antibiotics and the Risk of Cardiac Arrhythmias

    PubMed Central

    Schuller, Joseph L.

    2014-01-01

    Randomized, controlled trials have demonstrated that chronic therapy with macrolide antibiotics reduces the morbidity of patients with cystic fibrosis, non–cystic fibrosis bronchiectasis, chronic obstructive pulmonary disease, and nontuberculous mycobacterial infections. Lower levels of evidence indicate that chronic macrolides are also effective in treating patients with panbronchiolitis, bronchiolitis obliterans, and rejection after lung transplant. Macrolides are known to cause torsade des pointes and other ventricular arrhythmias, and a recent observational study prompted the FDA to strengthen the Warnings and Precautions section of azithromycin drug labels. This summary describes the electrophysiological effects of macrolides, reviews literature indicating that the large majority of subjects experiencing cardiac arrhythmias from macrolides have coexisting risk factors and that the incidence of arrhythmias in absence of coexisting risk factors is very low, examines recently published studies describing the relative risk of arrhythmias from macrolides, and concludes that this risk has been overestimated and suggests an approach to patient evaluation that should reduce the relative risk and the incidence of arrhythmias to the point that chronic macrolides can be used safely in the majority of subjects for whom they are recommended. PMID:24707986

  15. Macrolide antibiotics and the risk of cardiac arrhythmias.

    PubMed

    Albert, Richard K; Schuller, Joseph L

    2014-05-15

    Randomized, controlled trials have demonstrated that chronic therapy with macrolide antibiotics reduces the morbidity of patients with cystic fibrosis, non-cystic fibrosis bronchiectasis, chronic obstructive pulmonary disease, and nontuberculous mycobacterial infections. Lower levels of evidence indicate that chronic macrolides are also effective in treating patients with panbronchiolitis, bronchiolitis obliterans, and rejection after lung transplant. Macrolides are known to cause torsade des pointes and other ventricular arrhythmias, and a recent observational study prompted the FDA to strengthen the Warnings and Precautions section of azithromycin drug labels. This summary describes the electrophysiological effects of macrolides, reviews literature indicating that the large majority of subjects experiencing cardiac arrhythmias from macrolides have coexisting risk factors and that the incidence of arrhythmias in absence of coexisting risk factors is very low, examines recently published studies describing the relative risk of arrhythmias from macrolides, and concludes that this risk has been overestimated and suggests an approach to patient evaluation that should reduce the relative risk and the incidence of arrhythmias to the point that chronic macrolides can be used safely in the majority of subjects for whom they are recommended.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. Digenic inheritance in medical genetics.

    PubMed

    Schäffer, Alejandro A

    2013-10-01

    Digenic inheritance (DI) is the simplest form of inheritance for genetically complex diseases. By contrast with the thousands of reports that mutations in single genes cause human diseases, there are only dozens of human disease phenotypes with evidence for DI in some pedigrees. The advent of high-throughput sequencing (HTS) has made it simpler to identify monogenic disease causes and could similarly simplify proving DI because one can simultaneously find mutations in two genes in the same sample. However, through 2012, I could find only one example of human DI in which HTS was used; in that example, HTS found only the second of the two genes. To explore the gap between expectation and reality, I tried to collect all examples of human DI with a narrow definition and characterise them according to the types of evidence collected, and whether there has been replication. Two strong trends are that knowledge of candidate genes and knowledge of protein-protein interactions (PPIs) have been helpful in most published examples of human DI. By contrast, the positional method of genetic linkage analysis, has been mostly unsuccessful in identifying genes underlying human DI. Based on the empirical data, I suggest that combining HTS with growing networks of established PPIs may expedite future discoveries of human DI and strengthen the evidence for them.

  1. 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.

  2. 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.

  3. Inherited Determinants of Ovarian Cancer Survival

    PubMed Central

    Goode, Ellen L.; Maurer, Matthew J.; Sellers, Thomas A.; Phelan, Catherine M.; Kalli, Kimberly R.; Fridley, Brooke L.; Vierkant, Robert A.; Armasu, Sebastian M.; White, Kristin L.; Keeney, Gary L.; Cliby, William A.; Rider, David N.; Kelemen, Linda E.; Jones, Monica B.; Peethambaram, Prema P.; Lancaster, Johnathan M.; Olson, Janet E.; Schildkraut, Joellen M.; Cunningham, Julie M.; Hartmann, Lynn C.

    2010-01-01

    Purpose Due to variation of outcome among cases, we sought to examine whether overall survival in ovarian cancer was associated with common inherited variants in 227 candidate genes from ovarian cancer-related pathways including angiogenesis, inflammation, detoxification, glycosylation, one-carbon transfer, apoptosis, cell cycle regulation, and cellular senescence. Experimental Design Blood samples were obtained from 325 women with invasive epithelial ovarian cancer diagnosed at the Mayo Clinic from 1999 to 2006. During a median follow-up of 3.8 years (range, 0.1 – 8.6 years), 157 deaths were observed. Germline DNA was analyzed at 1,416 single nucleotide polymorphisms (SNPs). For all patients, and for 203 with serous subtype, we assessed the overall significance of each gene and pathway, and estimated risk of death via hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for known prognostic factors. Results Variation within angiogenesis was most strongly associated with survival time overall (p=0.03) and among patients with serous cancer (p=0.05), particularly for EIF2B5 rs4912474 (all patients HR 0.69, 95% CI 0.54-0.89, p=0.004), VEGFC rs17697305 (serous subtype HR 2.29, 95% CI 1.34-3.92, p=0.003), and four SNPs in VHL. Variation within the inflammation pathway was borderline significant (all patients, p=0.09), and SNPs in CCR3, IL1B, IL18, CCL2, and ALOX5 which correlated with survival time are worthy of follow-up. Conclusion An extensive multiple-pathway assessment found evidence that inherited differences may play a role in outcome of ovarian cancer patients, particularly in genes within the angiogenesis and inflammation pathways. Our work supports efforts to target such mediators for therapeutic gain. PMID:20103664

  4. Cascade Classification with Adaptive Feature Extraction for Arrhythmia Detection.

    PubMed

    Park, Juyoung; Kang, Mingon; Gao, Jean; Kim, Younghoon; Kang, Kyungtae

    2017-01-01

    Detecting arrhythmia from ECG data is now feasible on mobile devices, but in this environment it is necessary to trade computational efficiency against accuracy. We propose an adaptive strategy for feature extraction that only considers normalized beat morphology features when running in a resource-constrained environment; but in a high-performance environment it takes account of a wider range of ECG features. This process is augmented by a cascaded random forest classifier. Experiments on data from the MIT-BIH Arrhythmia Database showed classification accuracies from 96.59% to 98.51%, which are comparable to state-of-the art methods.

  5. 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.

  6. Epileptic Patients are at Risk of Cardiac Arrhythmias: A Novel Approach using QT-nomogram, Tachogram, and Cardiac Restitution Plots

    PubMed Central

    Al-Nimer, Marwan S.; Al-Mahdawi, Sura A.; Abdullah, Namir M.; Al-Mahdawi, Akram

    2017-01-01

    Background: Sudden death is reported in patients who had a history of epilepsy and some authors believed that is due to cardiac arrhythmias. Objectives: This study aimed to predict that the epileptic patients are at risk of serious cardiac arrhythmias by QT-nomogram, tachogram (Lorenz), and cardiac restitution plots. Methods: A total number of 71 healthy subjects (Group I) and 64 newly diagnosed epileptic patients (Group II) were recruited from Al-Yarmouk and Baghdad Teaching hospitals in Baghdad from March 2015 to July 2015 and included in this study. The diagnosis of epilepsy achieved clinically, electroencephalograph record and radio-images including computerized tomography and magnetic image resonance. At the time of entry into the study, an electrocardiography (ECG) was done, and the determinants of each ECG record were calculated. The QT-nomogram, tachogram, and cardiac restitution plots were used to identify the patients at risk of cardiac arrhythmias. Results: Significant prolonged corrected QT corrected (QTc) and JT corrected intervals were observed in female compared with male at age ≥50 years while the TQ interval was significantly prolonged in males of Group II. Eight patients of Group II had a significant pathological prolonged QTc interval compared with undetectable finding in Group I. QT nomogram did not disclose significant findings while the plots of Lorenz and restitution steepness disclose that the patients of Group II were vulnerable to cardiac arrhythmias. Abnormal ECG findings were observed in the age extremities (≤18 years and ≥50 years) in Group II compared with Group I. Conclusion: Utilization of QT-nomogram, restitution steepness, and tachogram plots is useful tools for detection subclinical vulnerable epileptic patient with cardiac arrhythmias. PMID:28149075

  7. 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

  8. 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.

  9. 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...

  10. 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.

  11. Deep Dermatophytosis and Inherited CARD9 Deficiency

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2010-10-15

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

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

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

    PubMed

    Manolis, Antonis S; Manolis, Antonis A

    2016-07-01

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

  19. 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.

  20. 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)

  1. Severe Hypothermia Causing Ventricular Arrhythmia in Organophosphorus Poisoning.

    PubMed

    Munta, Kartik; Santosh, Paiullah; Surath, Manimala Rao

    2017-02-01

    Organophosphorus poisoning cases are routinely treated across all Intensive Care Units adjoining the rural areas where agriculture is the main source of income. We present a unique case of severe hypothermia seen in a case of organophosphorus poisoning, which led to electrocardiogram disturbances and life-threatening arrhythmias.

  2. Ventricular arrhythmia incidence in the rat is reduced by naloxone.

    PubMed

    Pugsley, M K; Hayes, E S; Wang, W Q; Walker, M J A

    2015-07-01

    This study characterized the antiarrhythmic effects of the opioid receptor antagonist naloxone in rats subject to electrically induced and ischemic arrhythmias. Naloxone (2, 8 and 32 μmol/kg/min) was examined on heart rate, blood pressure, and the electrocardiogram (EKG) as well as for effectiveness against arrhythmias produced by occlusion of the left anterior descending coronary artery or electrical stimulation of the left ventricle. Naloxone reduced blood pressure at the highest dose tested while heart rate was dose-dependently reduced. Naloxone dose-dependently prolonged the P-R and QRS intervals and increased the RSh amplitude indicative of effects on cardiac sodium (Na) channels. Naloxone prolonged the Q-T interval suggesting a delay in repolarization. Naloxone effects were comparable to the comparator quinidine. Naloxone (32 μmol/kg/min) reduced ventricular fibrillation (VF) incidence to 38% (from 100% in controls). This same dose significantly increased the threshold for induction of ventricular fibrillation (VFt), prolonged the effective refractory period (ERP) and reduced the maximal following frequency (MFF). The patterns of ECG changes, reduction in ischemic arrhythmia (VF) incidence and changes in electrically induced arrhythmia parameters at high doses of naloxone suggest that it directly blocks cardiac Na and potassium (K) ion channels.

  3. 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.

  4. Severe Hypothermia Causing Ventricular Arrhythmia in Organophosphorus Poisoning

    PubMed Central

    Munta, Kartik; Santosh, Paiullah; Surath, Manimala Rao

    2017-01-01

    Organophosphorus poisoning cases are routinely treated across all Intensive Care Units adjoining the rural areas where agriculture is the main source of income. We present a unique case of severe hypothermia seen in a case of organophosphorus poisoning, which led to electrocardiogram disturbances and life-threatening arrhythmias. PMID:28250607

  5. 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…

  6. 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.

  7. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Inherited lands. 213.13 Section 213.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.13 Inherited lands. Except...

  8. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Inherited lands. 213.13 Section 213.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.13 Inherited lands. Except...

  9. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Inherited lands. 213.13 Section 213.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.13 Inherited lands. Except...

  10. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Inherited lands. 213.13 Section 213.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.13 Inherited lands. Except...

  11. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  12. Mitochondrial movement and inheritance in budding yeast.

    PubMed

    Boldogh, Istvan R; Fehrenbacher, Kammy L; Yang, Hyeong-Cheol; Pon, Liza A

    2005-07-18

    Mitochondria are essential organelles that perform fundamental cellular functions including aerobic energy mobilization, fatty acid oxidation, amino acid metabolism, heme biosynthesis and apoptosis. Mitochondria cannot be synthesized de novo. Therefore, the inheritance of this organelle is an essential part of the cell cycle; that is, daughter cells that do not inherit mitochondria will not survive. The budding yeast, Saccharomyces cerevisiae, is a facultative aerobe that can tolerate mitochondrial mutations that would be lethal in other organisms. Therefore, yeast has been used extensively to study inheritance and segregation of mitochondria. As a result, much of what we know regarding mitochondrial inheritance has been uncovered using yeast as a model system. Here, we describe the latest developments in mitochondrial motility and inheritance.

  13. 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

  14. Association between Hypophosphatemia and Cardiac Arrhythmias in the Early Stage of Sepsis: Could Phosphorus Replacement Treatment Reduce the Incidence of Arrhythmias?

    PubMed

    Schwartz, Andrei; Brotfain, Evgeni; Koyfman, Leonid; Kutz, Ruslan; Gruenbaum, Shaun E; Klein, Moti; Zlotnik, Alexander

    2014-06-01

    It is well known that new-onset arrhythmias are common in septic patients. It is thought that hypophosphatemia in the early stages of sepsis may contribute to the development of new arrhythmias. In this study, we hypothesized that intravenous (IV) phosphorus replacement may reduce the incidence of arrhythmias in critically ill patients. 34 adult septic patients with hypophosphatemia admitted to the general intensive care unit were treated with IV phosphorus replacement per ICU protocol, and the incidence of new arrhythmias were compared with 16 patients from previously published data. IV phosphorus replacement was associated with a significantly reduced incidence of arrhythmias (38% vs. 63%, p=0.04). There were no differences in observed mortality between subgroups, which may be due to the small sample size. This study demonstrated that IV phosphorus replacement might be effective in reducing the incidence of new arrhythmias in septic patients.

  15. Inherited Thrombophilia in Pediatric Venous Thromboembolic Disease: Why and Who to Test

    PubMed Central

    van Ommen, C. Heleen; Nowak-Göttl, Ulrike

    2017-01-01

    Venous thromboembolic disease in childhood is a multifactorial disease. Risk factors include acquired clinical risk factors such as a central venous catheter and underlying disease and inherited thrombophilia. Inherited thrombophilia is defined as a genetically determined tendency to develop venous thromboembolism. In contrast to adults, acquired clinical risk factors play a larger role than inherited thrombophilia in the development of thrombotic disease in children. The contributing role of inherited thrombophilia is not clear in many pediatric thrombotic events, especially catheter-related thrombosis. Furthermore, identification of inherited thrombophilia will not often influence acute management of the thrombotic event as well as the duration of anticoagulation. In some patients, however, detection of inherited thrombophilia may lead to identification of other family members who can be counseled for their thrombotic risk. This article discusses the potential arguments for testing of inherited thrombophilia, including factor V Leiden mutation, prothrombin mutation, and deficiencies of antithrombin, protein C, or protein S and suggests some patient groups in childhood, which may be tested. PMID:28352625

  16. Inherited Thrombophilia in Pediatric Venous Thromboembolic Disease: Why and Who to Test.

    PubMed

    van Ommen, C Heleen; Nowak-Göttl, Ulrike

    2017-01-01

    Venous thromboembolic disease in childhood is a multifactorial disease. Risk factors include acquired clinical risk factors such as a central venous catheter and underlying disease and inherited thrombophilia. Inherited thrombophilia is defined as a genetically determined tendency to develop venous thromboembolism. In contrast to adults, acquired clinical risk factors play a larger role than inherited thrombophilia in the development of thrombotic disease in children. The contributing role of inherited thrombophilia is not clear in many pediatric thrombotic events, especially catheter-related thrombosis. Furthermore, identification of inherited thrombophilia will not often influence acute management of the thrombotic event as well as the duration of anticoagulation. In some patients, however, detection of inherited thrombophilia may lead to identification of other family members who can be counseled for their thrombotic risk. This article discusses the potential arguments for testing of inherited thrombophilia, including factor V Leiden mutation, prothrombin mutation, and deficiencies of antithrombin, protein C, or protein S and suggests some patient groups in childhood, which may be tested.

  17. 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.

  18. 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.

  19. 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.

  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. An Update on Laboratory Diagnosis of Liver Inherited Diseases

    PubMed Central

    Elce, Ausilia; Amato, Felice

    2013-01-01

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

  2. Linear and nonlinear quantification of respiratory sinus arrhythmia during propofol general anesthesia.

    PubMed

    Chen, Zhe; Purdon, Patrick L; Pierce, Eric T; Harrell, Grace; Walsh, John; Salazar, Andres F; Tavares, Casie L; Brown, Emery N; Barbieri, Riccardo

    2009-01-01

    Quantitative evaluation of respiratory sinus arrhythmia (RSA) may provide important information in clinical practice of anesthesia and postoperative care. In this paper, we apply a point process method to assess dynamic RSA during propofol general anesthesia. Specifically, an inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by a linear or bilinear bivariate regression on the previous R-R intervals and respiratory measures. The estimated second-order bilinear interaction allows us to evaluate the nonlinear component of the RSA. The instantaneous RSA gain and phase can be estimated with an adaptive point process filter. The algorithm's ability to track non-stationary dynamics is demonstrated using one clinical recording. Our proposed statistical indices provide a valuable quantitative assessment of instantaneous cardiorespiratory control and heart rate variability (HRV) during general anesthesia.

  3. Risk of ventricular arrhythmias associated with nonsedating antihistamine drugs

    PubMed Central

    José de Abajo, Francisco; Rodríguez, Luis Alberto García

    1999-01-01

    Aims To quantify and compare the incidence of ventricular arrhythmias associated with the use of five nonsedating antihistamines: acrivastine, astemizole, cetirizine, loratadine and terfenadine. The effects of age, sex, dose, duration of treatment, and the interaction with P450 inhibitor drugs were also examined. Methods We carried out a cohort study with a nested case-control analysis using the UK-based General Practice Research Database (GPRD). The study cohort included persons aged less than 80 years old who received their first prescription for any of the five study drugs between January 1, 1992 and September 30, 1996. We estimated relative risks and 95% confidence intervals of idiopathic ventricular arrhythmias with current use of antihistamines as compared with non use. Results The study cohort included 197 425 persons who received 513 012 prescriptions. Over the study period 18 valid cases of idiopathic ventricular arrhythmias were detected. Nine occurred during the current use of any antihistamine, resulting in a crude incidence of 1.9 per 10 000 person-years (95%CI: 1.0–3.6) and a relative risk of 4.2 (95%CI: 1.5–11.8) as compared with non use. Astemizole presented the highest relative risk (RR = 19.0; 95%CI: 4.8–76.0) of all study drugs, while terfenadine (RR = 2.1; 95%CI:0.5–8.5) was in the range of other nonsedating antihistamines. Older age was associated with a greater risk of ventricular arrhythmias (RR = 7.4; 95%CI: 2.6–21.4) and seemed to increase the effect of antihistamines (RR = 6.4; 95%CI: 1.7–24.8). The proportions of high dose terfenadine and the concomitant use with P450 inhibitors among current users of terfenadine were 2.7% and 3.4%, respectively over the study period with no single case of ventricular arrhythmias occurring in the presence of these two risk factors. Conclusions The use of nonsedating antihistamines increases the risk of ventricular arrhythmias by a factor of four in the general population. Yet, the absolute

  4. Prominent Optic Disc Featured in Inherited Retinopathy.

    PubMed

    Todorova, M G; Bojinova, R I; Valmaggia, C; Schorderet, D F

    2017-02-01

    Background We investigated the relationship between prominent optic disc (POD) and inherited retinal dystrophy (IRD). Patients and Methods A cross-sectional consecutive study was performed in 10 children and 11 adults of 7 non-related families. We performed clinical phenotyping, including a detailed examination, fundus autofluorescence, and colour fundus and OCT imaging. Genetic testing was subsequently performed for all family members presenting retinal pathology. Results In 4 members of a 3-generation family, hyperfluorescent deposits on the surface of POD were related to a p.(L224M) heterozygous mutation in BEST1. In the second family, one member presented deposits located on the surface on hyperaemic OD and a compound p.(R141H);(A195V) mutation in BEST1. In the third family, POD was observed in father and child with early onset cone-rod dystrophy and a novel autosomal recessive p.(W31*) homozygous mutation in ABCA4. In the fourth family, POD with "mulberry-like" deposits and attenuated vessels were observed in a 7-year old girl, with a mutation in USH1A, and with early onset rod-cone dystrophy, associated with hearing loss. In the fifth family, blurry OD with tortuous vessels was observed in 4 consanguineous female carriers and a hemizygous boy with a p.(R200H) mutation in the X-linked retinoschisis RS1. In the sixth family, a mother and her son were both affected with POD and attenuated peripapillary vessels, and presented with a p.(Y836C) heterozygous mutation in TOPORS, thus confirming autosomal dominant RP. In the seventh family, in 3 family members with POD, compound p.(L541P;A1038 V);(G1961E) mutations in ABCA4 confirmed the diagnosis of Stargardt disease. Conclusions A variety of OD findings are found in a genetically heterogeneous group of IRDs. In the presence of POD, an inherited progressive photoreceptor disease should be ruled out.

  5. [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.

  6. 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

  7. 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.

  8. [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»

  9. The role of genealogy and clinical family histories in documenting possible inheritance patterns for diabetes mellitus in the pre-insulin era: part 2. Genealogic evidence for type 2 diabetes mellitus in Josephine Imperato's paternal and maternal lineages.

    PubMed

    Imperato, Pascal James; Imperato, Gavin H

    2009-12-01

    Part 2 presents detailed genealogic information on Josephine Imperato's paternal and maternal lineages extending from four to seven generations into the nineteenth and eighteenth centuries. Among these lineages are some where early adult death over successive generations is perhaps indicative of type 2 diabetes mellitus (type 2 DM). These lineages, all in the town of San Prisco in Italy, include both paternal and maternal ones with the following surnames: Casaccia, Casertano, Cipriano, de Angelis, de Paulis, Peccerillo, Foniciello, di Monaco, Vaccarella, Valenziano, Ventriglia, and Zibella. Genealogic studies of eighteenth and nineteenth century vital records in this area of Italy cannot definitively establish type 2 diabetes mellitus as either an immediate or contributory cause of death. This is because causes of death were not recorded and because disease diagnostic capabilities were largely absent. Genealogic studies of those who lived in Italy in the eighteenth and nineteenth centuries can at best provide data on approximate age at time of death. Early adult death in this era was not uncommon. However, its presence over several successive generations in a lineage raises the possibility of inherited diseases prominent among which is type 2 DM.

  10. Image features of spectral correlation function for arrhythmia classification.

    PubMed

    Khalaf, Aya F; Owis, Mohammed I; Yassine, Inas A

    2015-01-01

    Recently, computerized arrhythmia classification tools have been intensively used to aid physicians to recognize different irregular heartbeats. In this paper, we introduce arrhythmia CAD system exploiting cyclostationary signal analysis through estimation of the spectral correlation function for 5 different beat types. Two experiments were performed. Raw spectral correlation data were used as features in the first experiment while the other experiment which dealt with the spectral correlation coefficients as image included extraction of wavelet and shape features followed by fisher score for dimensionality reduction. As for the classification task, Support Vector Machine (SVM) with linear kernel was used for both experiments. The experimental results showed that both proposed approaches are superior compared to several state of the art methods. This approach achieved sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 99.20%, 99.70%, 98.60%, 99.90% and 97.60% respectively.

  11. [Treatment of bradycardiac arrhythmias with depot-orciprenaline (author's transl)].

    PubMed

    So, C S; Volger, E

    1976-07-02

    24 patients with bradycardiac arrhythmias of various origin were treated with a new depot preparation of orciprenaline. The special galenical preparation guarantees effectiveness ofr 8-10 hours. In 21 patients (87%), therefore, one dragee morning and evening was sufficient to obtain a mean rise in frequency of 57%. The preparation had to be discontinued in 3 cases because of side effects such as increase in ventricular extrasystoles, anginal complaints and critical rise of blood pressure in hypertension. Because of its trouble-free administration in a depot form the preparation not only offers a practical advantage over the short-acting commercial preparations, but also shows a reliable efficacy. It can therefore be given under regular supervision in all forms of bradycardiac arrhythmias with stable ventricular frequency and satisfactory cardiac output.

  12. ECG Signal Analysis and Arrhythmia Detection using Wavelet Transform

    NASA Astrophysics Data System (ADS)

    Kaur, Inderbir; Rajni, Rajni; Marwaha, Anupma

    2016-12-01

    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.

  13. 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

  14. Developmental origins of epigenetic transgenerational inheritance.

    PubMed

    Hanson, Mark A; Skinner, Michael K

    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.

  15. 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

  16. Genetic Testing for Inherited Heart Disease

    MedlinePlus

    ... of the American Heart Association Cardiology Patient Page Genetic Testing for Inherited Heart Disease Allison L. Cirino , ... for developing the family’s heart condition. What Is Genetic Testing and What Can it Tell Me? Genetic ...

  17. 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.

  18. Inherited Disorders of Calcium and Phosphate Metabolism

    PubMed Central

    Gattineni, Jyothsna

    2014-01-01

    Purpose of Review Inherited disorders of calcium and phosphate homeostasis have variable presentation and can cause significant morbidity. Understanding the mode of inheritance and pathophysiology of these conditions will help in the diagnosis and early institution of therapy. Recent Findings Identification of genetic mutations in human subjects and animal models has advanced our understanding of many inherited disorders of calcium and phosphate regulation. Identification of mutations of CaSR also has improved our understanding of hypocalcemic and hypercalcemic conditions. Mutations of Fgf23, Klotho and phosphate transporter genes have been identified as causes for disorders of phosphate metabolism. Summary Calcium and phosphate homeostasis is tightly regulated in a narrow range due to their vital role in many biological processes. Inherited disorders of calcium and phosphate metabolism though uncommon can have severe morbidity. Genetic counseling of the affected families is an important part of the follow up of these patients. PMID:24553630

  19. 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.

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

    PubMed

    Colín Lizalde, Luis de Jesús

    2003-01-01

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

  1. Patterns of inheritance in familial ALS.

    PubMed

    Bradley, Marcus; Bradley, Lloyd; de Belleroche, Jackie; Orrell, Richard W

    2005-05-10

    We investigated 185 families with ALS for evidence of anticipation and mitochondrial inheritance. Although initial analysis demonstrated significant anticipation of age at death between generations in patients with familial ALS, further analysis demonstrated features of regression to the mean, suggesting that the perceived differences are the result of bias. In addition, there was no evidence of an effect of preferential maternal inheritance, which would have supported transmission of mitochondrial DNA mutations.

  2. Amiodarone for refractory cardiac arrhythmias: 10-year study.

    PubMed Central

    Leak, D; Eydt, J N

    1986-01-01

    Over a 10-year period 130 patients with drug-resistant cardiac arrhythmias associated mainly with coronary artery disease and its complications were treated with amiodarone. The drug controlled all the tachyarrhythmias associated with the Wolff-Parkinson-White syndrome, 95% of the ventricular arrhythmias, including recurrent ventricular tachycardia and fibrillation, and 92% of the supraventricular arrhythmias. The maximum duration of therapy was 111 months and the mean 34 months. Side effects occurred in 34% of the patients, and there was one withdrawal from therapy per 15.3 patient-years of treatment. The commonest cause of withdrawal was nausea, which was significantly related (p less than 0.01) to a drug interaction with digoxin and diuretics. Reversible neurologic complications occurred in eight patients (6%), and acute myositis was recognized for the first time. Pulmonary infiltration developed in four patients (3%), who were receiving 600 mg of amiodarone per day. The rates of side effects and of withdrawal from therapy differed significantly between the patients whose maintenance doses were 600 and 200 mg/d, at 59% v. 6% (p less than 0.01) and 32% v. 0% (p less than 0.05) respectively. Thus, amiodarone is a very effective antiarrhythmic that can be administered over long periods with acceptable rates of side effects and withdrawal provided the minimal effective dose is used; 400 mg/d or less is desirable. PMID:3948063

  3. 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

  4. A telemetry system for the study of spontaneous cardiac arrhythmias.

    PubMed

    Rollins, D L; Killingsworth, C R; Walcott, G P; Justice, R K; Ideker, R E; Smith, W M

    2000-07-01

    The characteristics of spontaneous cardiac arrhythmias leading to sudden cardiac death are largely unknown. To study arrhythmias in animal models, an eight-channel implantable radio telemetry system has been developed to record continuously cardiac electrograms over a period of weeks to months, with maintenance restricted to changing batteries. The inputs are connected in a unipolar manner. Each channel has a gain of fifty and is AC coupled, band limited to 0.07-260 Hz. The signals are digitized with 12 bits resolution at 1000 samples/s. The amplifiers, analog-to-digital converter, and control logic are packaged in an implantable unit. An umbilical cable is passed through the skin to an external backpack unit for power and data transmission. A custom serial interface card, a PC/104 form factor 25-MHz 80386-based single-board computer with a PCMCIA wireless local area network (WLAN) card, and battery power supply make up the backpack. Data are read into the parallel port of the computer, buffered, then transmitted over the WLAN to the laboratory network where it can be analyzed and archived. Approximately 12 h of 14,000 bytes/s data can be collected with each set of batteries. The system is suitable for continuous monitoring of animal models of spontaneous arrhythmias and sudden cardiac death.

  5. 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.

  6. 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

  7. Berberine alleviates ischemic arrhythmias via recovering depressed I(to) and I(Ca) currents in diabetic rats.

    PubMed

    Wang, Li-Hong; Li, Xue-Lian; Li, Qiang; Fu, Ying; Yu, Hai-Jing; Sun, Yu-Qian; Zhang, Li; Shan, Hong-Li

    2012-02-15

    The present study was designed to elucidate the potential mechanism underlying that berberine suppressed ischemic arrhythmias in a rat model of diabetes mellitus (DM). Streptozotocin (STZ)-induced diabetic rats were subjected to ischemia by the occlusion of left anterior descending (LAD) coronary artery. Berberine was orally administered for 7 days before ischemic injury in diabetic rats. Whole-cell patch-clamp was performed to measure the transient outward K⁺ current (I(to)) and L-type Ca²⁺ current (I(Ca)). Results showed that oral administration of berberine (100 mg/kg) attenuated ischemia-induced arrhythmias in diabetic rats. Berberine significantly shortened the prolonged QTc interval from 214 ± 6ms to 189 ± 5ms in ischemic diabetic rats, and also restored the diminished I(to) and I(Ca) current densities in the same animal model rats. In conclusion, the ability of berberine to protect diabetic rats against cardiac arrhythmias makes it possible to be a prospective therapeutic agent in clinical management of cardiac disease secondary to diabetes.

  8. 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

  9. Prevalence of arrhythmias during exercise stress testing in patients with congenital heart disease and severe right ventricular conduit dysfunction.

    PubMed

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

    2014-08-01

    The utility of cardiopulmonary exercise testing (CPET) to define the risks of arrhythmia and sudden death in postoperative patients with congenital heart disease (CHD) remains uncertain. As part of the US Melody valve trial, prospective standardized CPET, along with echocardiography, cardiac magnetic resonance imaging, and cardiac catheterization, were performed in 170 CHD patients with right ventricular outflow tract conduit dysfunction before Melody valve implantation. Ventricular premature complexes (VPC) occurred in 75 patients (44%) and were common during all phases of CPET (13% baseline, 24% exercise, and 23% recovery). Although no subjects had sustained arrhythmias, 2 had nonsustained ventricular tachycardia and 3 had nonsustained supraventricular tachycardia during recovery. There were no statistically significant differences between patients with or without VPCs in echocardiographic, cardiac magnetic resonance imaging, or catheterization measures of cardiac function. However, clinical parameters of age, New York Heart Association functional class ≥II, and ≥3 cardiac surgical procedures were correlated with VPCs. Persistent ventricular ectopy during all exercise stages was present in 11 patients (6.5%), including 3 of the 4 patients who died during follow-up. In conclusion, VPCs were common during CPET, although they were not correlated with various measures of hemodynamic impairment; conversely, increased age, functional class, and number of surgeries were correlated with an increased prevalence of VPCs. CPET appears to be of minimal risk for sustained arrhythmia provocation in CHD patients with right ventricular outflow tract conduits and various degrees of advanced subpulmonary ventricular dysfunction.

  10. Stability with Inheritance in the Conditional Strategy.

    PubMed

    Gross; Repka

    1998-06-21

    The conditional strategy is a theoretical framework that explains the existence within populations of individuals that express alternative behavioral, physical or life history tactics (phenotypes). An example is fighters and sneakers in many animal mating systems. In the conditional strategy the alternative tactics are chosen by individuals based on their state, for example large or small bodied. Since state is often heritable, due for example to additive genetic variance, the alternative tactics may also have inheritance. As the tactics do not have equal fitnesses, it is generally believed that any such inheritance would prevent the evolutionary stability of the conditional strategy. However, in previous work we introduced an Inheritance Theorem and were able to prove that a conditional strategy with tactic inheritances can have a unique equilibrium proportion of the tactics. We now prove a second property of our Inheritance Theorem, namely the stability of the equilibrium. This means that if the tactics are perturbed from their equilibrium proportions, they will return across generations to their equilibrium proportions. An example is provided in mites. We have therefore established an Inheritance Theorem which includes both the existence of an equilibrium and its stability for alternative tactics in a conditional strategy.Copyright 1998 Academic Press Limited

  11. 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.

  12. Vector platforms for gene therapy of inherited retinopathies.

    PubMed

    Trapani, Ivana; Puppo, Agostina; Auricchio, Alberto

    2014-11-01

    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.

  13. Inheritance of guttural pouch tympany in the arabian horse.

    PubMed

    Blazyczek, I; Hamann, H; Ohnesorge, B; Deegen, E; Distl, O

    2004-01-01

    The objective of the present study was to analyze the mode of inheritance of guttural pouch tympany (GPT) using pedigrees of Arabian horses. Complex segregation analyses were employed to test for the significance of nongenetic transmission and for monogenic, polygenic, and mixed monogenic-polygenic modes of inheritance. Horses affected by GPT comprised 27 Arabian purebred foals. Of these 27 animals, 22 were patients at the Clinic for Horses, School of Veterinary Medicine Hannover, Hannover, Germany, between 1994 and 2001 and 5 Arabian foals were from stud farms. Information on the pedigrees of these patients allowed us to classify the affected foals into four families with a total of 276 animals. The regressive logistic model analysis took into account the nonrandomness of the pedigrees through multiple single ascertainment correction. The complex segregation analysis showed that, among all other models employed, a polygenic and a mixed monogenic-polygenic model best explained the segregation of Arabian foals with GPT. Models including only nongenetic distributions and monogenic inheritance could be significantly rejected. This is the first report in which a genetic component could be shown to be responsible for GPT in horses.

  14. 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

  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. Catheter Ablation of Ventricular Arrhythmias Arising from the Left Ventricular Summit.

    PubMed

    Santangeli, Pasquale; Lin, David; Marchlinski, Francis E

    2016-03-01

    The left ventricular summit is a common site of origin of idiopathic ventricular arrhythmias. These arrhythmias are most commonly ablated within the coronary venous system or from other adjacent structures, such as the right ventricular and left ventricular outflow tract or coronary cusp region. When ablation from adjacent structures fails, a percutaneous epicardial approach can be considered, but is rarely successful in eliminating the arrhythmias due to proximity to major coronary vessels and/or epicardial fat.

  18. 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

  19. [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.

  20. Role of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone antagonists in the prevention of atrial and ventricular arrhythmias.

    PubMed

    Makkar, Kathy M; Sanoski, Cynthia A; Spinler, Sarah A

    2009-01-01

    Atrial arrhythmias, ventricular arrhythmias, and sudden cardiac death (SCD) are significant health problems and an economic burden to society. The renin-angiotensin-aldosterone system (RAAS) may play a key role in the occurrence of structural and electrical remodeling, potentially explaining the development of atrial and ventricular arrhythmias. Angiotensin II has been shown to regulate cardiac cell proliferation and to modulate cardiac myocyte ion channels. Results of post hoc analyses from prospective clinical trials appear to show that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are most effective in the prevention of new-onset atrial fibrillation in patients with heart failure. It is difficult to determine if these agents are useful in the prevention of new-onset atrial fibrillation after myocardial infarction, and available evidence suggests that the benefit of ACE inhibitors and ARBs for prevention of new-onset atrial fibrillation in patients with hypertension appears limited to those with left ventricular hypertrophy. Patients with structural changes in cardiac muscle, such as those with heart failure and left ventricular hypertrophy, appear to benefit the most from RAAS blockade, possibly due to the theory of reversal of cardiac remodeling. There is no evidence, to our knowledge, that either ACE inhibitors or ARBs facilitate direct electrical current cardioversion in patients with atrial fibrillation; however, it appears that RAAS blockade may be useful in the prevention of recurrent atrial fibrillation after direct electrical current cardioversion. Whether ACE inhibitors may prevent life-threatening ventricular arrhythmias or SCD is unclear. Aldosterone antagonists appear to be useful for the prevention of SCD in patients with left ventricular systolic dysfunction. Results from ongoing clinical trials are anticipated to provide further insight on the potential roles of RAAS inhibitors for the prevention of

  1. Inheritance in tetraploid yeast revisited: segregation patterns and statistical power under different inheritance models.

    PubMed

    Stift, M; Reeve, R; van Tienderen, P H

    2010-07-01

    In their recent article, Albertin et al. (2009) suggest an autotetraploid origin of 10 tetraploid strains of baker's yeast (Saccharomyces cerevisiae), supported by the frequent observation of double reduction meiospores. However, the presented inheritance results were puzzling and seemed to contradict the authors' interpretation that segregation ratios support a tetrasomic model of inheritance. Here, we provide an overview of the expected segregation ratios at the tetrad and meiospore level given scenarios of strict disomic and tetrasomic inheritance, for cases with and without recombination between locus and centromere. We also use a power analysis to derive adequate sample sizes to distinguish alternative models. Closer inspection of the Albertin et al. data reveals that strict disomy can be rejected in most cases. However, disomic inheritance with strong but imperfect preferential pairing could not be excluded with the sample sizes used. The possibility of tetrad analysis in tetraploid yeast offers a valuable opportunity to improve our understanding of meiosis and inheritance of tetraploids.

  2. Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia

    PubMed Central

    Weng, Ching-Hui; Chung, Fa-Po; Chen, Yao-Chang; Lin, Shien-Fong; Huang, Po-Hsun; Kuo, Terry B. J.; Hsu, Wei-Hsuan; Su, Wen-Cheng; Sung, Yen-Ling; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Yeh, Hung-I; Chen, Yi-Jen; Hong, Yi-Ren; Chen, Shih-Ann; Hu, Yu-Feng

    2016-01-01

    Observational studies have established a strong association between matrix metalloproteinase-9 (MMP-9) and ventricular arrhythmia. However, whether MMP-9 has a causal link to ventricular arrhythmia, as well as the underlying mechanism, remains unclear. Here, we investigated the mechanistic involvement of myocardial MMP-9 in the pathophysiology of ventricular arrhythmia. Increased levels of myocardial MMP-9 are linked to ventricular arrhythmia attacks after angiotensin II (Ang II) treatment. MMP-9-deficient mice were protected from ventricular arrhythmia. Increased expressions of protein kinase A (PKA) and ryanodine receptor phosphorylation at serine 2808 (pS2808) were correlated with inducible ventricular arrhythmia. MMP-9 deficiency consistently prevented PKA and pS2808 increases after Ang II treatment and reduced ventricular arrhythmia. Calcium dynamics were examined via confocal imaging in isolated murine cardiomyocytes. MMP-9 inhibition prevents calcium leakage from the sarcoplasmic reticulum and reduces arrhythmia-like irregular calcium transients via protein kinase A and ryanodine receptor phosphorylation. Human induced pluripotent stem cell-derived cardiomyocytes similarly show that MMP-9 inhibition prevents abnormal calcium leakage. Myocardial MMP-9 inhibition prevents ventricular arrhythmia through pleiotropic effects, including the modulation of calcium homeostasis and reduced calcium leakage. PMID:27966586

  3. 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.

  4. Early visual symptom patterns in inherited retinal dystrophies.

    PubMed

    Prokofyeva, Elena; Troeger, Eric; Wilke, Robert; Zrenner, Eberhart

    2011-01-01

    The present retrospective study compared initial visual symptom patterns in inherited retinal dystrophies (IRD) on the basis of records of 544 patients diagnosed with a wide variety of IRD at the Tuebingen University Eye Hospital from 2005 to 2008. Age at first onset of symptoms was noted, and the following clinical data were analyzed: visual acuity (VA), night vision disturbances, photophobia, onset of visual field defects, best corrected VA, and types of visual field defects. Median age at visual symptom onset was defined with 25th and 75th percentiles and compared in 15 IRD types. The main trends in VA changes in retinitis pigmentosa and cone-rod dystrophies were identified. This study was the first to combine disease history and clinical data analysis in such a wide variety of IRD. It showed that patterns of initial symptoms in IRD can provide extra clues for early differential diagnosis and inclusion of IRD patients in clinical trials.

  5. 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.

  6. 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.

  7. A Novel NaV1.5 Voltage Sensor Mutation Associated with Severe Atrial and Ventricular Arrhythmias

    PubMed Central

    Wang, Hong-Gang; Zhu, Wandi; Kanter, Ronald J.; Silva, Jonathan R.; Honeywell, Christina; Gow, Robert M.; Pitt, Geoffrey S.

    2016-01-01

    Background Inherited autosomal dominant mutations in cardiac sodium channels (NaV1.5) cause various arrhythmias, such as long QT syndrome and Brugada syndrome. Although dozens of mutations throughout the protein have been reported, there are few reported mutations within a voltage sensor S4 transmembrane segment and few that are homozygous. Here we report analysis of a novel lidocaine-sensitive recessive mutation, p.R1309H, in the NaV1.5 DIII/S4 voltage sensor in a patient with a complex arrhythmia syndrome. Methods and Results We expressed the wild type or mutant NaV1.5 heterologously for analysis with the patch-clamp and voltage clamp fluorometry (VCF) techniques. p.R1309H depolarized the voltage-dependence of activation, hyperpolarized the voltage-dependence of inactivation, and slowed recovery from inactivation, thereby reducing the channel availability at physiologic membrane potentials. Additionally, p.R1309H increased the “late” Na+ current. The location of the mutation in DIIIS4 prompted testing for a gating pore current. We observed an inward current at hyperpolarizing voltages that likely exacerbates the loss-of-function defects at resting membrane potentials. Lidocaine reduced the gating pore current. Conclusions The p.R1309H homozygous NaV1.5 mutation conferred both gain-of-function and loss-of-function effects on NaV1.5 channel activity. Reduction of a mutation-induced gating pore current by lidocaine suggested a therapeutic mechanism. PMID:26801742

  8. Subcutaneous Nerve Activity and Spontaneous Ventricular Arrhythmias in Ambulatory Dogs

    PubMed Central

    Doytchinova, Anisiia; Patel, Jheel; Zhou, Shengmei; Chen, Lan S.; Lin, Hongbo; Shen, Changyu; Everett, Thomas H; Lin, Shien-Fong; Chen, Peng-Sheng

    2014-01-01

    Background Stellate ganglion nerve activity (SGNA) is important in ventricular arrhythmogenesis. However, because thoracotomy is needed to access the stellate ganglion, it is difficult to use SGNA for risk stratification. Objective To test the hypothesis that subcutaneous nerve activity (SCNA) in canines can be used to estimate SGNA and predict ventricular arrhythmia. Methods We implanted radio transmitters to continuously monitor left stellate ganglion and subcutaneous electrical activities in 7 ambulatory dogs with myocardial infarction, complete heart block and nerve growth factor infusion to the left stellate ganglion. Results Spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) was documented in each dog. SCNA preceded a combined 61 episodes of VT and VF, 61 frequent bigeminy or couplets and 61 premature ventricular contractions within 15 s in 70%, 59% and 61% of arrhythmias, respectively. Similar incidence of 75%, 69% and 62% was noted for SGNA. Progressive increase in SCNA (48.9 (95% CI 39.3–58.5) vs. 61.8 (95% CI 45.9–77.6) vs. 75.1 (95% CI 57.5–92.7) mV-s) and SGNA (48.6 (95% CI 40.9–56.3) vs. 58.5 (95% CI 47.5–69.4) vs. 69.0 (95% CI 53.8–84.2) mV-s) integrated over 20 s intervals was demonstrated 60 s, 40 s and 20 s prior to VT/VF (p<0.05). The Pearson’s correlation coefficient for integrated SCNA and SGNA was 0.73±0.18 (p<0.0001 for all dogs, n=5). Both SCNA and SGNA exhibited circadian variation. Conclusions SCNA can be used as an estimate of SGNA to predict susceptibility to VT and VF in a canine model of ventricular arrhythmia and sudden cardiac death. PMID:25460171

  9. Role of CaMKII in cardiac arrhythmias

    PubMed Central

    Hund, Thomas J.; Mohler, Peter J.

    2014-01-01

    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

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

    PubMed

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

    2012-09-01

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

  11. Optogenetic Light Crafting Tools for the Control of Cardiac Arrhythmias.

    PubMed

    Richter, Claudia; Christoph, Jan; Lehnart, Stephan E; Luther, Stefan

    2016-01-01

    The control of spatiotemporal dynamics in biological systems is a fundamental problem in nonlinear sciences and has important applications in engineering and medicine. Optogenetic tools combined with advanced optical technologies provide unique opportunities to develop and validate novel approaches to control spatiotemporal complexity in neuronal and cardiac systems. Understanding of the mechanisms and instabilities underlying the onset, perpetuation, and control of cardiac arrhythmias will enable the development and translation of novel therapeutic approaches. Here we describe in detail the preparation and optical mapping of transgenic channelrhodopsin-2 (ChR2) mouse hearts, cardiac cell cultures, and the optical setup for photostimulation using digital light processing.

  12. Decreased respiratory sinus arrhythmia in individuals with deceptive intent.

    PubMed

    Aikins, Deane E; Martin, Daniel J; Morgan, C A

    2010-07-01

    In detecting deception, the Cognitive Load hypothesis states that lying requires more cognitive resources compared to truth telling. Further, increases in cognitive load are predicted to decrease respiratory sinus arrhythmia (RSA). We evaluated the impact of cognitive tasks and the intent to deceive on RSA in 40 male, native Arabic-speaking participants quasi-randomized into truthful (n=14) or deceptive (n=26) groups. Participants donned an ambulatory physiologic recording device and completed cognitive testing after receiving translated instructions about their role in an impending mock crime. The results show that a decrease in RSA recorded during the cognitive testing was greater in individuals who were about to commit a deceptive act.

  13. Arrhythmia ECG Noise Reduction by Ensemble Empirical Mode Decomposition

    PubMed Central

    Chang, Kang-Ming

    2010-01-01

    A novel noise filtering algorithm based on ensemble empirical mode decomposition (EEMD) is proposed to remove artifacts in electrocardiogram (ECG) traces. Three noise patterns with different power—50 Hz, EMG, and base line wander – were embedded into simulated and real ECG signals. Traditional IIR filter, Wiener filter, empirical mode decomposition (EMD) and EEMD were used to compare filtering performance. Mean square error between clean and filtered ECGs was used as filtering performance indexes. Results showed that high noise reduction is the major advantage of the EEMD based filter, especially on arrhythmia ECGs. PMID:22219702

  14. Cardiac arrhythmias produced by ultrasound and contrast agents

    NASA Astrophysics Data System (ADS)

    Rota, Claudio

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

  15. Anger, Emotion, and Arrhythmias: from Brain to Heart

    PubMed Central

    Taggart, Peter; Boyett, Mark R.; Logantha, Sunil Jit R. J.; Lambiase, Pier D.

    2011-01-01

    Strong emotion and mental stress are now recognized as playing a significant role in severe and fatal ventricular arrhythmias. The mechanisms, although incompletely understood, include central processing at the cortical and brain stem level, the autonomic nerves and the electrophysiology of the myocardium. Each of these is usually studied separately by investigators from different disciplines. However, many are regulatory processes which incorporate interactive feedforward and feedback mechanisms. In this review we consider the whole as an integrated interactive brain–heart system. PMID:22022314

  16. 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.

  17. New patterns of inheritance in mitochondrial disease.

    PubMed

    Schwartz, Marianne; Vissing, John

    2003-10-17

    With the identification of a patient with mutated mitochondrial DNA (mtDNA) of paternal origin, it has been unequivocally proven that not only does paternal mtDNA survive in the zygote, but it can also contribute substantially to the mtDNA pool of adult, human skeletal muscle. The questions are: how often does paternal mtDNA inheritance occur and what mechanisms are involved? In this paper, we will review current knowledge on the fate of sperm mitochondria after fertilization and discuss the impact paternal inheritance may have on our understanding of mitochondrial biology.

  18. Genetics beyond Mendel. Understanding nontraditional inheritance patterns.

    PubMed

    Wagstaff, J

    2000-09-01

    Many medical conditions that clearly have a strong genetic component are not transmitted in a straightforward dominant, recessive, or X-linked pattern. Recent progress in understanding other modes of inheritance, such as imprinting, trinucleotide repeat expansion, mitochondrial inheritance, and mosaicism, has allowed us to solve many of these hereditary puzzles. Such advances have led to improvements in diagnosis and genetic counseling for patients affected with these disorders and should be valuable in development of effective therapies for some of these disorders in the future.

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

    PubMed

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

    2015-04-01

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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Insulin tolerance test causes hypokalaemia and can provoke cardiac arrhythmias.

    PubMed

    Binder, Gerhard; Bosk, Axel; Gass, Matthias; Ranke, Michael B; Heidemann, Peter H

    2004-01-01

    We report the observation and analysis of a new adverse event during the insulin tolerance test (ITT) and propose additional safety procedures. An 8-year-old girl with growth hormone insufficiency had a cardiac arrest due to ventricular flutter when she was tested for growth hormone deficiency by the ITT. Severe hypokalaemia (K+ 2.6 mmol/l) was observed after resuscitation. Ergometry ECG revealed catecholaminergic polymorphic ventricular tachycardia, a hereditary arrhythmogenic disease. Consecutive measurements of serum potassium during ITT in 29 short children (21 boys) with growth failure revealed a mean decrease of serum potassium by 1.1 +/- 0.4 mmol/l with the nadir at 30 min after the insulin bolus. Hypokalaemia (serum potassium < 3.5 mmol/l) occurred in all but one child; severe hypokalaemia (serum potassium < 2.9 mmol/l) was measured in every third child. This observation indicates that acute hypokalaemia which is induced by insulin and catecholamine excess occurs frequently in ITT. The case shows that the combination of acute hypokalaemia and the adrenergic counterregulation in ITT is a strong trigger of cardiac arrhythmias, which can become life-threatening if the child has an arrhythmogenic disease. Therefore, we recommend ECG monitoring during ITT to enhance the detection of cardiac arrhythmias. In addition, in the case of a comatose child during ITT the determination of the glucose and potassium level as well as adequate treatment are necessary.

  5. 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.

  6. Postural effect on respiratory sinus arrhythmia with various respiratory frequencies.

    PubMed

    Kobayashi, H

    1996-03-01

    Heart rate variations during steady state respiration with various frequencies were studied on seven healthy male students at two different body positions. Respiration was controlled at four different frequencies (0.083, 0.100, 0.200, 0.250Hz), and the tidal volume was simultaneously controlled at 1500ml (0.083, 0.100Hz) or 1000ml (0.200, 0.250Hz). A tilting bed was used for changing body position, and the measurements were conducted at horizontal and vertical position. RSA (respiratory sinus arrhythmia) amplitude at 0.250Hz was significantly decreased at vertical position compared with horizontal position. At 0.200Hz the significant decrease could not be obtained although some tendency of decrease appeared. Contrary to these high frequencies, the amplitudes at low frequencies (0.083, 0.100Hz) were significantly increased (p < 0.01) during vertical position. This postural effect on the low frequency RSA could be regarded as a similar result on MWSA (Mayer wave relate sinus arrhythmia) which reflects sympathetic nervous activity. Furthermore, the ratio between the amplitude at 0.100Hz and that at 0.250Hz was significantly correlated with mean heart rate (n = 56, r = 0.73). From these results it was assumed that the RSA amplitude at low frequency associate a with not only parasympathetic nerves but also sympathetic nerves whereas the amplitude at high frequency was solely mediated by parasympathetic nerves.

  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.

  8. Arrhythmias, Sudden Cardiac Death and incapacitation of pilots

    PubMed Central

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

    2008-01-01

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

  9. Brugada Syndrome: Clinical, Genetic, Molecular, Cellular, and Ionic Aspects.

    PubMed

    Antzelevitch, Charles; Patocskai, Bence

    2016-01-01

    Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome first described as a new clinical entity in 1992. Electrocardiographically characterized by distinct coved type ST segment elevation in the right-precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young adults, and less frequently in infants and children. The electrocardiographic manifestations of BrS are often concealed and may be unmasked or aggravated by sodium channel blockers, a febrile state, vagotonic agents, as well as by tricyclic and tetracyclic antidepressants. An implantable cardioverter defibrillator is the most widely accepted approach to therapy. Pharmacologic therapy is designed to produce an inward shift in the balance of currents active during the early phases of the right ventricular action potential (AP) and can be used to abort electrical storms or as an adjunct or alternative to device therapy when use of an implantable cardioverter defibrillator is not possible. Isoproterenol, cilostazol, and milrinone boost calcium channel current and drugs like quinidine, bepridil, and the Chinese herb extract Wenxin Keli inhibit the transient outward current, acting to diminish the AP notch and thus to suppress the substrate and trigger for ventricular tachycardia or fibrillation. Radiofrequency ablation of the right ventricular outflow tract epicardium of patients with BrS has recently been shown to reduce arrhythmia vulnerability and the electrocardiographic manifestation of the disease, presumably by destroying the cells with more prominent AP notch. This review provides an overview of the clinical, genetic, molecular, and cellular aspects of BrS as well as the approach to therapy.

  10. Brugada Syndrome. Clinical, Genetic, Molecular, Cellular and Ionic Aspects

    PubMed Central

    Antzelevitch, Charles; Patocskai, Bence

    2015-01-01

    The Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome first described as a new clinical entity in 1992. Electrocardiographically characterized by distinct coved type ST segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young adults, and less frequently in infants and children. The ECG manifestations of the BrS are often concealed and may be unmasked or aggravated by sodium channel blockers, a febrile state, vagotonic agents, as well as by tricyclic and tetracyclic antidepressants. An implantable cardioverter defibrillator (ICD) is the most widely accepted approach to therapy. Pharmacological therapy is designed to produce an inward shift in the balance of currents active during the early phases of the right ventricular action potential and can be used to abort electrical storms or as an adjunct or alternative to device therapy when use of an ICD is not possible. Isoproterenol, cilostazol and milrinone boost calcium channel current and drugs like quinidine, bepridil and the Chinese herb extract Wenxin Keli inhibit the transient outward current, acting to diminish the action potential (AP) notch and thus to suppress the substrate and trigger for VT/VF. Radiofrequency ablation of the right ventricular outflow tract epicardium of BrS patients has recently been shown to reduce arrhythmia-vulnerability and the ECG-manifestation of the disease, presumably by destroying the cells with more prominent AP notch. This review provides an overview of the clinical, genetic, molecular and cellular aspects of the BrS as well as the approach to therapy. PMID:26671757

  11. A Simple Analysis of an Inherited Trait

    ERIC Educational Resources Information Center

    Aagaard, Stanley; Keller, Elhannan

    1977-01-01

    Described is a classroom activity for analyzing an inherited human trait, the ability to tast phenylthiocarbamide (PTC). Formulas for analyzing gene frequency are given for classroom and neighborhood samples. Additional tables include statistics on the ability to taste PTC and other easily sampled human traits. (MA)

  12. 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…

  13. 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

  14. 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…

  15. 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.

  16. 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…

  17. Inherited resistance to Corynebacterium kutscheri in mice.

    PubMed Central

    Hirst, R G; Wallace, M E

    1976-01-01

    An analysis of the factors responsible for inherited resistance to Corynebacterium kutscheri was undertaken. Various inbred mouse strains were examined; these included the Swiss Lynch and C57Bl/l mice, their F1 and F2 progeny, and the progeny of the F1 backcrossed to each parent strain. Two modes of inherited resistance are described. An examination suggested that resistance as measured by the mean lethal dose of C. kutscheri was under polygenic control and was inherited continuously. However, the efficiency with which C. kutscheri was eliminated by the mononuclear phagocyte cells of the liver over 3 days differed markedly among strains. A genetic analysis of this mononuclear phagocyte microbicidal efficiency (MPME) in Swiss Lynch and C57Bl/6 mice was undertaken. The trait, MPME, was present, but did not segregate, in the F1 progeny or in the progeny of the backcross to the resistant C57Bl/6 parent; this was clear evidence of dominance. Moreover, MPME segregated in a ratio of 1:1 in the progeny of the backcross to the sensitive Swiss Lynch parent and in a ratio of 3:1 in the F2 progeny. It was concluded that MPME was inherited discontinuously and was controlled by a single dominant autosomal gene (or closely linked group); the recessive allele was assigned the gene symbol ack. Linkage experiments showed there to be no association between the ack locus and any of the immune-response genes. PMID:971958

  18. The inheritance of acquired epigenetic variations.

    PubMed

    Jablonka, Eva; Lamb, Marion J

    2015-08-01

    There is evidence that the functional history of a gene in one generation can influence its expression in the next. In somatic cells, changes in gene activity are frequently associated with changes in the pattern of methylation of the cytosines in DNA; these methylation patterns are stably inherited. Recent work suggests that information about patterns of methylation and other epigenetic states can also be transmitted from parents to offspring. This evidence is the basis of a model for the inheritance of acquired epigenetic variations. According to the model, an environmental stimulus can induce heritable chromatin modifications which are very specific and predictable, and might result in an adaptive response to the stimulus. This type of response probably has most significance for adaptive evolution in organisms such as fungi and plants, which lack distinct segregation of the soma and germ line. However, in all organisms, the accumulation of specific and random chromatin modifications in the germ line may be important in speciation, because these modifications could lead to reproductive isolation between populations. Heritable chromatin variations may also alter the frequency and distribution of classical mutations and meiotic recombination. Therefore, inherited epigenetic changes in the structure of chromatin can influence neo-Darwinian evolution as well as cause a type of "Lamarckian" inheritance.

  19. The genetics of inherited macular dystrophies

    PubMed Central

    Michaelides, M; Hunt, D; Moore, A

    2003-01-01

    The aim of this paper is to review current knowledge relating to the monogenic macular dystrophies, with discussion of currently mapped genes, chromosomal loci and genotype-phenotype relationships. Inherited systemic disorders with a macular dystrophy component will not be discussed. PMID:12960208

  20. 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

  1. 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.

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

    PubMed

    Kalaji, I; Balasundaram, K; Umapathy, K

    2015-01-01

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

  3. 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...

  4. 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, ...

  5. Mice with cardiac overexpression of PPARγ have impaired repolarization and spontaneous fatal ventricular arrhythmias (Morrow, PPARγ overexpression induces fatal arrhythmias)

    PubMed Central

    Morrow, John P.; Katchman, Alexander; Son, Ni-Huiping; Trent, Chad M.; Khan, Raffay; Shiomi, Takayuki; Huang, Haiyan; Amin, Vaibhav; Lader, Joshua M.; Vasquez, Carolina; Morley, Gregory E.; D'Armiento, Jeanine; Homma, Shunichi; Goldberg, Ira J.; Marx, Steven O.

    2011-01-01

    Background Diabetes and obesity, which confer an increased risk of sudden cardiac death, are associated with cardiomyocyte lipid accumulation and altered cardiac electrical properties, manifested by prolongation of the QRS duration and QT interval. It is difficult to distinguish the contribution of cardiomyocyte lipid accumulation versus the contribution of global metabolic defects to the increased incidence of sudden death and electrical abnormalities. Methods and Results In order to study the effects of metabolic abnormalities on arrhythmias without the complex systemic effects of diabetes and obesity, we studied cardiac-specific transgenic mice expressing PPARγ1 via the cardiac α-myosin heavy-chain promoter. The PPARγ-transgenic mice develop abnormal accumulation of intracellular lipids and die as young adults, prior to a significant reduction in systolic function. Using implantable ECG telemeters, we found that these mice have prolongation of the QRS and QT intervals, and spontaneous ventricular arrhythmias, including polymorphic ventricular tachycardia and ventricular fibrillation. Isolated cardiomyocytes demonstrated prolonged action potential duration caused by reduced expression and function of the potassium channels responsible for repolarization. Short-term exposure to pioglitazone, a PPARγ agonist, had no effect on mortality or rhythm in WT mice, but further exacerbated the arrhythmic phenotype and increased the mortality in the PPARγ TG mice. Conclusions Our findings support an important link between PPARγ activation, cardiomyocyte lipid accumulation, ion channel remodeling and increased cardiac mortality. PMID:22124376

  6. 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

  7. The relationship of arrhythmias to walking activity during mobilization after myocardial infarction.

    PubMed Central

    Roland, J. M.; Banks, D. C.; Edwards, B.; Fentem, P. H.

    1986-01-01

    The extent to which everyday walking activity is responsible for ventricular arrhythmias in the first 6 weeks after suspected myocardial infarction has been studied by simultaneous 24-hour recordings of electrocardiogram and walking activity. Forty-eight recordings from 46 patients were identified which contained couplets, ventricular tachycardia or R-on-T extrasystoles. In 24 recordings (50%) all the arrhythmias occurred whilst the patient was at rest and in a further four recordings there were fewer arrhythmias during activity than would have been expected by chance. Nineteen recordings (40%) contained arrhythmias which may have been induced by activity but in only three of these was the relationship definite. Clear evidence of arrhythmias precipitated by walking was found in only a minority of patients mobilizing after suspected myocardial infarction. PMID:3714618

  8. A Novel Automatic Detection System for ECG Arrhythmias Using Maximum Margin Clustering with Immune Evolutionary Algorithm

    PubMed Central

    Zhu, Bohui; Ding, Yongsheng; Hao, Kuangrong

    2013-01-01

    This paper presents a novel maximum margin clustering method with immune evolution (IEMMC) for automatic diagnosis of electrocardiogram (ECG) arrhythmias. This diagnostic system consists of signal processing, feature extraction, and the IEMMC algorithm for clustering of ECG arrhythmias. First, raw ECG signal is processed by an adaptive ECG filter based on wavelet transforms, and waveform of the ECG signal is detected; then, features are extracted from ECG signal to cluster different types of arrhythmias by the IEMMC algorithm. Three types of performance evaluation indicators are used to assess the effect of the IEMMC method for ECG arrhythmias, such as sensitivity, specificity, and accuracy. Compared with K-means and iterSVR algorithms, the IEMMC algorithm reflects better performance not only in clustering result but also in terms of global search ability and convergence ability, which proves its effectiveness for the detection of ECG arrhythmias. PMID:23690875

  9. [Analysis of the heart sound with arrhythmia based on nonlinear chaos theory].

    PubMed

    Ding, Xiaorong; Guo, Xingming; Zhong, Lisha; Xiao, Shouzhong

    2012-10-01

    In this paper, a new method based on the nonlinear chaos theory was proposed to study the arrhythmia with the combination of the correlation dimension and largest Lyapunov exponent, through computing and analyzing these two parameters of 30 cases normal heart sound and 30 cases with arrhythmia. The results showed that the two parameters of the heart sounds with arrhythmia were higher than those with the normal, and there was significant difference between these two kinds of heart sounds. That is probably due to the irregularity of the arrhythmia which causes the decrease of predictability, and it's more complex than the normal heart sound. Therefore, the correlation dimension and the largest Lyapunov exponent can be used to analyze the arrhythmia and for its feature extraction.

  10. 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.

  11. 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.

  12. [On problems and thinking of methodology in the inheritance of the esteemed acupuncturists' experiences].

    PubMed

    Sun, Hai-Shu; Wang, Ke-Jian

    2011-01-01

    Based on the advantages and disadvantages of the esteemed acupuncturists' experiences, after analyzing the collection work on inheriting the esteemed acupuncturists' experiences, this paper proposes to apply the information technology to build a multimedia platform for the esteemed acupuncturists. Therefore, the precious clinical experiences of the esteemed acupuncturists are preserved. This paper states the potential future of the coming multimedia platform.

  13. Anatomical Consideration in Catheter Ablation of Idiopathic Ventricular Arrhythmias.

    PubMed

    Yamada, Takumi; Kay, G Neal

    2016-01-01

    Idiopathic ventricular arrhythmias (VAs) are ventricular tachycardias (VTs) or premature ventricular contractions (PVCs) with a mechanism that is not related to myocardial scar. The sites of successful catheter ablation of idiopathic VA origins have been progressively elucidated and include both the endocardium and, less commonly, the epicardium. Idiopathic VAs usually originate from specific anatomical structures such as the ventricular outflow tracts, aortic root, atrioventricular (AV) annuli, papillary muscles, Purkinje network and so on, and exhibit characteristic electrocardiograms based on their anatomical background. Catheter ablation of idiopathic VAs is usually safe and highly successful, but can sometimes be challenging because of the anatomical obstacles such as the coronary arteries, epicardial fat pads, intramural and epicardial origins, AV conduction system and so on. Therefore, understanding the relevant anatomy is important to achieve a safe and successful catheter ablation of idiopathic VAs. This review describes the anatomical consideration in the catheter ablation of idiopathic VAs.

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

    PubMed Central

    Brenes-Pereira, C

    1997-01-01

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

  15. Electrophysiological assessment of amiodarone in treatment of resistant supraventricular arrhythmias.

    PubMed Central

    Rowland, E; Krikler, D M

    1980-01-01

    Oral amiodarone has been used to treat 21 patients with various supraventricular arrhythmias; 13 had Wolff-Parkinson-White syndrome, which was complicated by atrial fibrillation and re-entry atrioventricular tachycardia in four, and re-entry tachycardia alone in the other nine. The remaining eight patients had paroxysmal atrial fibrillation or flutter without pre-excitation. All were refractory to conventional treatment and had undergone intracardiac electrophysiological study. Fifteen have been controlled with amiodarone, this treatment proving most effective in atrial fibrillation or flutter with or without pre-excitation. Amiodarone was successful in only four of the nine patients with re-entry atrioventricular tachycardia. In two patients who responded well the drug had to be discontinued because of side effects. Images PMID:7426165

  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. Coregulation of respiratory sinus arrhythmia in adult romantic partners.

    PubMed

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

    2014-06-01

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

  18. A Powerful Algorithm to aid Cardiac Arrhythmia Diagnosis.

    PubMed

    Bereksi-Reguig, F.; Hadj Slimane, Z. E.

    2000-01-01

    The Electrocardiogram (ECG), represents the electrical activity of the heart. It is characterised by a number of waves P, QRS, T which are correlated to the status of the heart activity. In this paper, the aim is to present a powerful algorithm to aid cardiac diagnosis. The approach used is based on a determinist method, that of the tree decision. However, the different waves of the ECG signal need to be identified and then measured following a signal to noise enhancement. Signal to noise enhancement is performed by a combiner linear adaptive filter whereas P, QRS, T wave identification and measurement are performed by a derivative approach. Results obtained on simulated and real ECG signals are shown to be highly, satisfactory in the aid of cardiac arrhythmia diagnosis, such as junctionnal escapes, blocks, etc.

  19. Anatomical Consideration in Catheter Ablation of Idiopathic Ventricular Arrhythmias

    PubMed Central

    Kay, G Neal

    2016-01-01

    Idiopathic ventricular arrhythmias (VAs) are ventricular tachycardias (VTs) or premature ventricular contractions (PVCs) with a mechanism that is not related to myocardial scar. The sites of successful catheter ablation of idiopathic VA origins have been progressively elucidated and include both the endocardium and, less commonly, the epicardium. Idiopathic VAs usually originate from specific anatomical structures such as the ventricular outflow tracts, aortic root, atrioventricular (AV) annuli, papillary muscles, Purkinje network and so on, and exhibit characteristic electrocardiograms based on their anatomical background. Catheter ablation of idiopathic VAs is usually safe and highly successful, but can sometimes be challenging because of the anatomical obstacles such as the coronary arteries, epicardial fat pads, intramural and epicardial origins, AV conduction system and so on. Therefore, understanding the relevant anatomy is important to achieve a safe and successful catheter ablation of idiopathic VAs. This review describes the anatomical consideration in the catheter ablation of idiopathic VAs. PMID:28116086

  20. Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

    PubMed Central

    Jungen, Christiane; Scherschel, Katharina; Eickholt, Christian; Kuklik, Pawel; Klatt, Niklas; Bork, Nadja; Salzbrunn, Tim; Alken, Fares; Angendohr, Stephan; Klene, Christiane; Mester, Janos; Klöcker, Nikolaj; Veldkamp, Marieke W.; Schumacher, Udo; Willems, Stephan; Nikolaev, Viacheslav O.; Meyer, Christian

    2017-01-01

    The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. Catheter ablation, a minimally invasive procedure deactivating abnormal firing cardiac tissue, is increasingly becoming the therapy of choice for atrial fibrillation. This is inevitably associated with the obliteration of cardiac cholinergic neurons. However, the impact on ventricular electrophysiology is unclear. Here we show that cardiac cholinergic neurons modulate ventricular electrophysiology. Mechanical disruption or pharmacological blockade of parasympathetic innervation shortens ventricular refractory periods, increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in murine hearts. Immunohistochemistry confirmed ventricular cholinergic innervation, revealing parasympathetic fibres running from the atria to the ventricles parallel to sympathetic fibres. In humans, catheter ablation of atrial fibrillation, which is accompanied by accidental parasympathetic and concomitant sympathetic denervation, raises the burden of premature ventricular complexes. In summary, our results demonstrate an influence of cardiac cholinergic neurons on the regulation of ventricular function and arrhythmogenesis. PMID:28128201

  1. 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

  2. Medical Problems in Obstetrics: Inherited Metabolic Disease.

    PubMed

    Murphy, Elaine

    2015-07-01

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

  3. [Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

    PubMed

    Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

    2017-02-10

    Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

  4. 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.

  5. A study of the possible relation of the cardiac arrhythmias occurrence to the polarity reversal of the solar magnetic field

    NASA Astrophysics Data System (ADS)

    Mavromichalaki, H.; Preka-Papadema, P.; Theodoropoulou, A.; Paouris, E.; Apostolou, Th.

    2017-01-01

    The biological human system is probably affected by the solar and geomagnetic disturbances as well as the cosmic ray variations. In this work, the relation between the solar activity and cosmic ray variations and the cardiac arrhythmias over the time period 1997-2009 covering the solar cycle 23, is studied. The used medical data set refers to 4741 patients with cardiac arrhythmias and 2548 of whom were diagnosed with atrial fibrillation, obtained from the 2nd Cardiological Clinic of the General Hospital of Nicaea, Piraeus, in Greece. The smoothing method on a 365-day basis and the Pearson r-coefficient were used in order to compare these records with the number of sunspots, flares, solar proton events, coronal mass ejections and cosmic ray intensity. Applying a moving correlation function to ±1500 days, it is suggested that a change of the correlation sign between the medical data and each one of the above parameters occurs during a time interval of about 2-3 years. This interval corresponds to the time span of the polarity reversal of the solar magnetic field of this solar cycle, which always takes place around the solar cycle maximum. After then a correlation analysis was carried out corresponding to the rise (1997-2001) and the decay (2002-2009) phases of the solar cycle 23. It is noticeable that the polarity reversal of the solar magnetic field coincides with the period where the sign of the correlation between the incidence of arrhythmias and the occurrence number of the solar eruptive events and the cosmic ray intensity, changes sign. The results are comparable with those obtained from the previous solar cycle 22 based on medical data from another country.

  6. CZ: Multimethods and Multiple Inheritance Without Diamonds

    DTIC Science & Technology

    2009-12-01

    Then, we would use the Scala solution for ensuring that C ’ s constructor is called only once. 15 To solve the multiple dispatch problem, if methods m(B...CZ:Multimethods andMultiple Inheritance Without Diamonds 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT...NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Carnegie Mellon University ,School of Computer

  7. 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.

  8. Inherited tertiary hypothyroidism in Sprague-Dawley rats.

    PubMed

    Stoica, George; Lungu, Gina; Xie, Xueyi; Abbott, Louise C; Stoica, Heidi M; Jaques, John T

    2007-05-07

    Thyroid hormones (THs) are important in the development and maturation of the central nervous system (CNS). The significant actions of THs during CNS development occur at the time when TH levels are lower than those in the mother and the hypothalamic-thyroid (HPT) axis is not fully functional. In the developing rat nervous system, primarily the cerebellum, the first three postnatal weeks represent a period of significant sensitivity to thyroid hormones. This study presents a spontaneous, inherited recessive hypothyroidism in Sprague-Dawley rats with devastating functional consequences to the development of the CNS. The clinical signs develop around 14 day's postnatal (dpn) and are characterized by ataxia, spasticity, weight loss and hypercholesterolemia. The afflicted rats died at 30 days due to severe neurological deficits. The deterioration affects the entire CNS and is characterized by progressive neuronal morphological and biochemical changes, demyelination and astrogliosis. The cerebellum, brain stem, neocortex, hippocampus and adrenal gland medulla appear to be most affected. Thyroid Stimulating Hormone (TSH), T3 and T4 levels were significantly lower in hypothyroid rats than control. Immunohistochemistry and RT-PCR demonstrated a reduction of Thyrotropin Releasing Hormone (TRH) in the hypothalamus of hypothyroid rats. The weight of both thyroid and pituitary glands were significantly less in hypothyroid rats than the corresponding normal littermate controls. Transmission electron microscopy demonstrates consistent postsynaptic dendritic, synaptic and spine alterative changes in the brain of hypothyroid rats. These data suggest that we discovered a tertiary form of inherited hypothyroidism involving the hypothalamus.

  9. Obstetric analgesia and anaesthesia in women with inherited bleeding disorders.

    PubMed

    Chi, Claudia; Lee, Christine A; England, Adrian; Hingorani, Jaishree; Paintsil, James; Kadir, Rezan A

    2009-06-01

    A retrospective review was carried out on the methods of obstetric analgesia/anesthesia used in 80 pregnancies amongst 63 women with inherited bleeding disorders (19 factor XI deficiency, 16 carriers of haemophilia, 15 von Willebrand disease, seven platelet function disorders, four factor VII deficiency, one factor VII and XI deficiency and one factor X deficiency). In 72 pregnancies, the woman was seen antenatally in a multidisciplinary clinic to discuss and plan pain relief options. Regional block was performed for 41 pregnancies. The mothers were known to have a bleeding disorder in 35 of these pregnancies. Prophylactic cover was given in 10 pregnancies prior to the insertion of regional block but not required in the remaining 25 pregnancies because the coagulation defects had spontaneously normalised at term. There were six reported adverse effects from regional block similar to that found in the general population: inadequate anesthesia/analgesia (2), bloody tap (2), hypotension and a possible dural puncture which was treated conservatively. There were no reports of long-term complications. The findings show that it is possible to offer women with inherited bleeding disorders the option of regional block provided their coagulation defects have normalised, either spontaneously during pregnancy or following adequate haemostatic cover.

  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 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

  12. 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.

  13. Mitochondrial inheritance in a mitochondrially mediated disease.

    PubMed

    Egger, J; Wilson, J

    1983-07-21

    Mendelian inheritance involves the transmission to successive generations of DNA contained in genes in the nucleus, but DNA is also contained in mitochondria, where it is believed to be responsible for the encoding of certain mitochondrial enzymes. Since nearly all mitochondrial DNA is maternally transmitted, one might expect a nonmendelian pattern of inheritance in mitochondrial cytopathy, a syndrome in which there are abnormalities in mitochondrial structure and deficiencies in a variety of mitochondrial enzymes. We studied the pedigrees of 6 affected families whose members we had examined personally and of 24 families described in the literature. In 27 families, exclusively maternal transmission occurred; in 3 there was also paternal transmission in one generation. Altogether, 51 mothers but only 3 fathers had transmitted the condition. These results are consistent with mitochondrial transmission of mitochondrial cytopathy; the inheritance and enzyme defects of mitochondrial cytopathy can be considered in the light of recent evidence that subunits of respiratory-enzyme complexes are encoded solely by mitochondrial DNA. The occasional paternal transmission may be explained if certain enzyme subunits that are encoded by nuclear DNA are affected.

  14. Arrhythmogenic inherited heart muscle diseases in children.

    PubMed

    Towbin, J A; Bowles, N E

    2001-01-01

    The left ventricle (LV) plays a central role in the maintenance of health of children and adults due to its role as the major pump of the heart. In cases of LV dysfunction, a significant percentage of affected individuals develop signs and symptoms of congestive heart failure, leading to the need for therapeutic intervention. Therapy for these patients include anticongestive medications and, in some, placement of devices such as aortic balloon pump or left ventricular assist device, or cardiac transplantation. In the majority of patients the origin is unknown, leading to the term idiopathic dilated cardiomyopathy. During the past decade, the basis of LV dysfunction has begun to unravel. In approximately 30% to 40% of cases, the disorder is inherited; autosomal dominant inheritance is most common (although X-linked, autosomal recessive and mitochondrial inheritance occurs). In the remaining patients, the disorder is presumed to be acquired, with inflammatory heart disease playing an important role. In the case of familial dilated cardiomyopathy, the genetic basis is beginning to unfold. To date, 2 genes for X-linked familial dilated cardiomyopathy (dystrophin, G4.5) have been identified and 4 genes for the autosomal dominant form (actin, desmin, lamin A/C, delta-sarcoglycan) have been described. In 1 form of inflammatory heart disease, coxsackievirus myocarditis, inflammatory mediators, and dystrophin cleavage play a role in the development of LV dysfunction. This review describes the molecular genetics of LV dysfunction and provide evidence for a "final common pathway" responsible for the phenotype.

  15. 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.

  16. Molecular findings from 537 individuals with inherited retinal disease

    PubMed Central

    Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; O'Sullivan, James; Williams, Simon G; Lamb, Janine A; Panda, Binay; Sergouniotis, Panagiotis I; Gillespie, Rachel L; Daiger, Stephen P; Hall, Georgina; Gale, Theodora; Lloyd, I Christopher; Bishop, Paul N; Ramsden, Simon C; Black, Graeme C M

    2016-01-01

    Background Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous set of disorders, for which diagnostic second-generation sequencing (next-generation sequencing, NGS) services have been developed worldwide. Methods We present the molecular findings of 537 individuals referred to a 105-gene diagnostic NGS test for IRDs. We assess the diagnostic yield, the spectrum of clinical referrals, the variant analysis burden and the genetic heterogeneity of IRD. We retrospectively analyse disease-causing variants, including an assessment of variant frequency in Exome Aggregation Consortium (ExAC). Results Individuals were referred from 10 clinically distinct classifications of IRD. Of the 4542 variants clinically analysed, we have reported 402 mutations as a cause or a potential cause of disease in 62 of the 105 genes surveyed. These variants account or likely account for the clinical diagnosis of IRD in 51% of the 537 referred individuals. 144 potentially disease-causing mutations were identified as novel at the time of clinical analysis, and we further demonstrate the segregation of known disease-causing variants among individuals with IRD. We show that clinically analysed variants indicated as rare in dbSNP and the Exome Variant Server remain rare in ExAC, and that genes discovered as a cause of IRD in the post-NGS era are rare causes of IRD in a population of clinically surveyed individuals. Conclusions Our findings illustrate the continued powerful utility of custom-gene panel diagnostic NGS tests for IRD in the clinic, but suggest clear future avenues for increasing diagnostic yields. PMID:27208204

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

    PubMed Central

    2012-01-01

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

  18. Iron does not cause arrhythmias in the guinea pig model of transfusional iron overload.

    PubMed

    Kaiser, Lana; Davis, John; Patterson, Jon; Boyd, Ryan F; Olivier, N Bari; Bohart, George; Schwartz, Kenneth A

    2007-08-01

    Cardiac events, including heart failure and arrhythmias, are the leading cause of death in patients with beta thalassemia. Although cardiac arrhythmias in humans are believed to result from iron overload, excluding confounding factors in the human population is difficult. The goal of the current study was to determine whether cardiac arrhythmias occurred in the guinea pig model of secondary iron overload. Electrocardiograms were recorded by using surgically implanted telemetry devices in guinea pigs loaded intraperitoneally with iron dextran (test animals) or dextran alone (controls). Loading occurred over approximately 6 wk. Electrocardiograms were recorded for 1 wk prior to loading, throughout loading, and for approximately 4 wk after loading was complete. Cardiac and liver iron concentrations were significantly increased in the iron-loaded animals compared with controls and were in the range of those reported for humans with thalassemia. Arrhythmias were rare in both iron-loaded and control guinea pigs. No life-threatening arrhythmias were detected in either group. These data suggest that iron alone may be insufficient to cause cardiac arrhythmias in the iron-loaded guinea pig model and that arrhythmias detected in human patients with iron overload may be the result of a complex interplay of factors.

  19. Feasibility and outcomes of ajmaline provocation testing for Brugada syndrome in children in a specialist paediatric inherited cardiovascular diseases centre

    PubMed Central

    McMillan, Merlin Ranald; Day, Thomas George; Bartsota, Margarita; Mead-Regan, Sarah; Bryant, Rory; Mangat, Jasveer; Abrams, Dominic; Lowe, Martin; Kaski, Juan Pablo

    2014-01-01

    Objectives Brugada syndrome (BrS) is an inherited arrhythmia syndrome that causes sudden cardiac death in the young. The class Ia antiarrhythmic ajmaline can be used to provoke the diagnostic ECG pattern. Its use has been established in adults, but little data exist on the ajmaline provocation test in children. This study aims to determine the safety and feasibility of ajmaline provocation testing in a large paediatric cohort in a specialist paediatric inherited cardiac diseases centre. Methods 98 consecutive ajmaline tests were performed in 95 children between September 2004 and July 2012 for family history of BrS (n=46 (48%)); family history of unexplained sudden cardiac death (n=39 (41%); symptoms with suspicious ECG abnormalities (n=9 (10%)). Three patients were retested with age, due to the possibility of age-related penetrance. ECG parameters were measured at baseline and during maximal ajmaline effect. Results The mean patient age was 12.55 years, 43% were female. Nineteen patients (20%) had a positive ajmaline test. There were no arrhythmias or adverse events during testing. Ajmaline provoked significant prolongation of the PR, QRS and QTc in all patients. Mean follow-up was 3.62 years with no adverse outcomes reported in any patients with BrS. There were no predictors of a positive ajmaline provocation test on multivariable analysis. One patient who tested negative at 12 years of age, subsequently tested positive at 15 years of age. Conclusions Ajmaline testing appears safe and feasible in children when performed in an appropriate setting by an experienced team. Test positivity may change with age in individuals, suggesting that the test should be repeated in the late teenage years or early adulthood. PMID:25332787

  20. Understanding of and attitudes to genetic testing for inherited retinal disease: a patient perspective

    PubMed Central

    Willis, T A; Potrata, B; Ahmed, M; Hewison, J; Gale, R; Downey, L; McKibbin, M

    2013-01-01

    Background/aims The views of people with inherited retinal disease are important to help develop health policy and plan services. This study aimed to record levels of understanding of and attitudes to genetic testing for inherited retinal disease, and views on the availability of testing. Methods Telephone questionnaires comprising quantitative and qualitative items were completed with adults with inherited retinal disease. Participants were recruited via postal invitation (response rate 48%), approach at clinic or newsletters of relevant charitable organisations. Results Questionnaires were completed with 200 participants. Responses indicated that participants’ perceived understanding of genetic testing for inherited retinal disease was variable. The majority (90%) considered testing to be good/very good and would be likely to undergo genetic testing (90%) if offered. Most supported the provision of diagnostic (97%) and predictive (92%) testing, but support was less strong for testing as part of reproductive planning. Most (87%) agreed with the statement that testing should be offered only after the individual has received genetic counselling from a professional. Subgroup analyses revealed differences associated with participant age, gender, education level and ethnicity (p<0.02). Participants reported a range of perceived benefits (eg, family planning, access to treatment) and risks (eg, impact upon family relationships, emotional consequences). Conclusions Adults with inherited retinal disease strongly support the provision of publicly funded genetic testing. Support was stronger for diagnostic and predictive testing than for testing as part of reproductive planning. PMID:23813418

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

    PubMed

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

    2016-08-01

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

  2. Novel PRRT2 mutations in paroxysmal dyskinesia patients with variant inheritance and phenotypes.

    PubMed

    Liu, X-R; Wu, M; He, N; Meng, H; Wen, L; Wang, J-L; Zhang, M-P; Li, W-B; Mao, X; Qin, J-M; Li, B-M; Tang, B; Deng, Y-H; Shi, Y-W; Su, T; Yi, Y-H; Tang, B-S; Liao, W-P

    2013-03-01

    Paroxysmal dyskinesias (PDs) are a group of episodic movement disorders with marked variability in clinical manifestation and potential association with epilepsy. PRRT2 has been identified as a causative gene for PDs, but the phenotypes and inheritance patterns of PRRT2 mutations need further clarification. In this study, 10 familial and 21 sporadic cases with PDs and PDs-related phenotypes were collected. Genomic DNA was screened for PRRT2 mutations by direct sequencing. Seven PRRT2 mutations were identified in nine (90.0%) familial cases and in six (28.6%) sporadic cases. Five mutations are novel: two missense mutations (c.647C>G/p.Pro216Arg and c.872C>T/p.Ala291Val) and three truncating mutations (c.117delA/p.Val41TyrfsX49, c.510dupT/p.Leu171SerfsX3 and c.579dupA/p.Glu194ArgfsX6). Autosomal dominant inheritance with incomplete penetrance was observed in most of the familial cases. In the sporadic cases, inheritance was heterogeneous including recessive inheritance with compound heterozygous mutations, inherited mutations with incomplete parental penetrance and de novo mutation. Variant phenotypes associated with PRRT2 mutations, found in 36.0% of the affected cases, included febrile convulsions, epilepsy, infantile non-convulsive seizures (INCS) and nocturnal convulsions (NC). All patients with INCS or NC, not reported previously, displayed abnormalities on electroencephalogram (EEG). No EEG abnormalities were recorded in patients with classical infantile convulsions and paroxysmal choreoathetosis (ICCA)/paroxysmal kinesigenic dyskinesia (PKD). Our study further confirms that PRRT2 mutations are the most common cause of familial PDs, displaying both dominant and recessive inheritance. Epilepsy may occasionally occur in ICCA/PKD patients with PRRT2 mutations. Variant phenotypes INCS or NC differ from classical ICCA/PKD clinically and electroencephalographically. They have some similarities with, but not identical to epilepsy, possibly represent an overlap between

  3. Mitochondrial inheritance is mediated by microtubules in mammalian cell division.

    PubMed

    Lawrence, Elizabeth; Mandato, Craig

    2013-11-01

    The mitochondrial network fragments and becomes uniformly dispersed within the cytoplasm when mammalian cells enter mitosis. Such morphology and distribution of mitochondria was previously thought to facilitate the stochastic inheritance of mitochondria by daughter cells. In contrast, we recently reported that mitochondria in dividing mammalian cells are inherited by an ordered mechanism of inheritance mediated by microtubules. We showed that mitochondria are progressively enriched at the cell equator and depleted at the poles throughout division. Furthermore, the mitochondrial distribution during division is dependent on microtubules, indicating an ordered inheritance strategy. The microtubule-mediated positioning of mitochondria in dividing mammalian cells may have functional consequences for cell division and/or mitochondrial inheritance.

  4. Patterns of mitochondrial inheritance in the myxogastrid Didymium iridis.

    PubMed

    Silliker, Margaret E; Liles, Jeffery L; Monroe, Jason A

    2002-01-01

    Seven strains of the Central American A1 mating series of Didymium iridis were crossed in all possible combinations. Individual plasmodia were isolated and grown to a stage where total DNA could be isolated for DNA-DNA hybridization with cloned mitochondrial DNA probes to determine the pattern of mitochondrial inheritance. Random, biased, and dominant patterns of uniparental mitochondrial inheritance were observed, as well as rare cases of biparental inheritance, depending on the particular parental strains mated. The diverse patterns suggest that the factors controlling mitochondrial inheritance in D. iridis are complex. Differences between trials of the same matings suggest that non-genetic factors may also influence mitochondrial inheritance.

  5. Intraoperative MRI electrical noise and monitor ECG filters affect arrhythmia detection and identification.

    PubMed

    Bailey, Melissa; Kirchen, Gwynne; Bonaventura, Bridget; Rosborough, Kelly; Abdel-Rasoul, Mahmoud; Dzwonczyk, Roger

    2012-06-01

    Most electrical equipment in the modern operating room (OR) radiates electrical noise (EN) that can interfere with patient monitors. We have described the EN that an intraoperative magnetic resonance imaging (iMRI) system emits and have shown that this high-energy EN diminishes the quality of the ECG waveform during iMRI scans in our neurosurgical OR. We have also shown that the ECG signal filters in our iMRI-compatible patient monitor reduce this interference but, in the process, disturb the true morphology of the displayed waveform. This simulation study evaluates how iMRI-generated EN affects the ability of the anesthetist to detect and identify ECG arrhythmias and whether the patient monitor's ECG signal filters can improve arrhythmia recognition. Using an ECG simulator, we generated Lead II and V5 ECG signal segments that contained either no arrhythmia or one of four common cardiac arrhythmias. We filtered the ECG segments with four filters available on our iMRI-compatible monitor (Veris MR, MEDRAD Inc., Indianola, PA USA). We then digitized the segments and mixed simulated iMRI EN into the resultant tracings. With institutional approval and written informed consent, board-certified anesthesiologists reviewed the tracings, determined if an arrhythmia was present and identified the arrhythmia. We conducted the study anonymously. We reported the data as percent correct arrhythmia detection and correct arrhythmia identification. Thirty-one anesthesiologists completed the study. Overall, the participants correctly detected 79.5% (95% CI: 77.2, 81.7%) of the arrhythmias and correctly identified 62.5% (95% CI: 59.8, 65.3%) of the arrhythmias, regardless of EN presence. Although the proportions among monitor noise filters studied were not significant, the manufacturer-designated MR5 Veris MR filter optimized arrhythmia detection and arrhythmia identification for our participants, regardless if EN was present in the ECG tracings. In the neurosurgical OR, the

  6. Double hazards of ischemia and reperfusion arrhythmias in a patient with variant angina pectoris.

    PubMed

    Xu, Mingzhu; Yang, Xiangjun

    2015-01-01

    Variant angina pectoris, also called Prinzmetal's angina, is a syndrome caused by vasospasms of the coronary arteries. It can lead to myocardial infarction, ventricular arrhythmias, atrioventricular block and even sudden cardiac death. We report the case of a 53 year-old male patient with recurrent episodes of chest pain and arrhythmias in the course of related variant angina pectoris. It is likely that the reperfusion following myocardial ischemia was responsible for the ventricular fibrillation while the ST-segment returned to the baseline. This case showed that potential lethal arrhythmias could arise due to variant angina pectoris. It also indicated that ventricular fibrillation could be self-terminated.

  7. Biparental chloroplast inheritance leads to rescue from cytonuclear incompatibility.

    PubMed

    Barnard-Kubow, Karen B; McCoy, Morgan A; Galloway, Laura F

    2017-02-01

    Although organelle inheritance is predominantly maternal across animals and plants, biparental chloroplast inheritance has arisen multiple times in the angiosperms. Biparental inheritance has the potential to impact the evolutionary dynamics of cytonuclear incompatibility, interactions between nuclear and organelle genomes that are proposed to be among the earliest types of genetic incompatibility to arise in speciation. We examine the interplay between biparental inheritance and cytonuclear incompatibility in Campanulastrum americanum, a plant species exhibiting both traits. We first determine patterns of chloroplast inheritance in genetically similar and divergent crosses, and then associate inheritance with hybrid survival across multiple generations. There is substantial biparental inheritance in C. americanum. The frequency of biparental inheritance is greater in divergent crosses and in the presence of cytonuclear incompatibility. Biparental inheritance helps to mitigate cytonuclear incompatibility, leading to increased fitness of F1 hybrids and recovery in the F2 generation. This study demonstrates the potential for biparental chloroplast inheritance to rescue cytonuclear compatibility, reducing cytonuclear incompatibility's contribution to reproductive isolation and potentially slowing speciation. The efficacy of rescue depended upon the strength of incompatibility, with a greater persistence of weak incompatibilities in later generations. These findings suggest that incompatible plastids may lead to selection for biparental inheritance.

  8. Neonatal manifestations of inherited bone marrow failure syndromes.

    PubMed

    Khincha, Payal P; Savage, Sharon A

    2016-02-01

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

  9. Frontonasal dysplasia: a family presenting autosomal dominant inheritance pattern.

    PubMed

    Koçak, H; Ceylaner, G

    2009-01-01

    Frontonasal dysplasia (FND, also called frontonasal dysostosis or median cleft face syndrome) includes a spectrum of abnormalities affecting the eyes, forehead and nose, and resulting from midfacial dysraphia. The clinical picture is highly variable, but major findings in FND include ocular hypertelorism, a broad nasal root, median cleft affecting nose or both the nose and upper lip, and widow's peak. It is usually a sporadic disorder, although a few familial cases have been reported. We report here a three-generation family with multiple affected members with frontonasal dysplasia. This observation suggests autosomal dominant inheritance. Furthermore, some of the features e.g. over-riding toes, nail changes, vertical crease on plantar region of the feet in the index patient were not reported up to now.

  10. Neonatal manifestations of inherited bone marrow failure syndromes

    PubMed Central

    Khincha, Payal P.; Savage, Sharon A.

    2015-01-01

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

  11. Transgenerational inheritance: Models and mechanisms of non-DNA sequence-based inheritance.

    PubMed

    Miska, Eric A; Ferguson-Smith, Anne C

    2016-10-07

    Heritability has traditionally been thought to be a characteristic feature of the genetic material of an organism-notably, its DNA. However, it is now clear that inheritance not based on DNA sequence exists in multiple organisms, with examples found in microbes, plants, and invertebrate and vertebrate animals. In mammals, the molecular mechanisms have been challenging to elucidate, in part due to difficulties in designing robust models and approaches. Here we review some of the evidence, concepts, and potential mechanisms of non-DNA sequence-based transgenerational inheritance. We highlight model systems and discuss whether phenotypes are replicated or reconstructed over successive generations, as well as whether mechanisms operate at transcriptional and/or posttranscriptional levels. Finally, we explore the short- and long-term implications of non-DNA sequence-based inheritance. Understanding the effects of non-DNA sequence-based mechanisms is key to a full appreciation of heritability in health and disease.

  12. An inherited LMNA gene mutation in atypical Progeria syndrome.

    PubMed

    Doubaj, Yassamine; De Sandre-Giovannoli, Annachiara; Vera, Esteves-Vieira; Navarro, Claire Laure; Elalaoui, Siham Chafai; Tajir, Mariam; Lévy, Nicolas; Sefiani, Abdelaziz

    2012-11-01

    Hutchinson-Gilford Progeria syndrome (HGPS) is a rare genetic disorder, characterized by several clinical features that begin in early childhood, recalling an accelerated aging process. The diagnosis of HGPS is based on the recognition of common clinical features and detection of the recurrent heterozygous c.1824C>T (p.Gly608Gly) mutation within exon 11 in the Lamin A/C encoding gene (LMNA). Besides "typical HGPS," several "atypical progeria" syndromes (APS) have been described, in a clinical spectrum ranging from mandibuloacral dysplasia to atypical Werner syndrome. These patients's clinical features include progeroid manifestations, such as short stature, prominent nose, premature graying of hair, partial alopecia, skin atrophy, lipodystrophy, skeletal anomalies, such as mandibular hypoplasia and acroosteolyses, and in some cases severe atherosclerosis with metabolic complications. APS are due in several cases to de novo heterozygous LMNA mutations other than the p.Gly608Gly, or due to homozygous BAFN1 mutations in Nestor-Guillermo Progeria syndrome (NGPS). We report here and discuss the observation of a non-consanguineous Moroccan patient presenting with atypical progeria. The molecular studies showed the heterozygous mutation c.412G>A (p.Glu138Lys) of the LMNA gene. This mutation, previously reported as a de novo mutation, was inherited from the apparently healthy father who showed a somatic cell mosaicism.

  13. Increased Local Sympathetic Nerve Activity During Pathogenesis of Ventricular Arrhythmias Originating from the Right Ventricular Outflow Tract

    PubMed Central

    Wang, Zefeng; Gao, Huikuan; Dong, Ruiqing; Zhao, Can; Yu, Tianyu; Yang, Lu; Peng, Hui; Wu, Yongquan

    2017-01-01

    Background The contribution of local sympathetic nerves to ventricular arrhythmia (VA) originating from the right ventricular outflow tract (RVOT) has not been elucidated. This study used a canine model to investigate the anatomical changes of the RVOT associated with VA, and the distribution of local sympathetic nerves. Material/Methods The RVOT-VA canine model (6 dogs) was induced with a circular catheter and high-frequency stimulation (100 Hz) in the middle of the pulmonary artery trunk. Six dogs who were not given stimulation served as the control group. The serum levels of neurotransmitters, the extent of myocardial extension, and the sympathetic nerve density of the RVOT were also analyzed. Results Ventricular arrhythmias, including premature ventricular contractions, were induced in the experimental group after high-frequency stimulation. Dogs from the RVOT-VA group showed enhanced myocardial extension and sympathetic nerve density in the septal wall as compared with those of the free wall of the RVOT. In the RVOT-VA dogs, serum norepinephrine and neuropeptide Y and the sympathetic nerve density were significantly higher compared with the control group. Conclusions Stimulation of the pulmonary artery could activate local sympathetic nerves and enhance myocardial extension, which may be the foundation of RVOT-VA. The RVOT voltage transitional zone positively correlated with myocardial extension, which may serve as an important target for the radiofrequency catheter ablation of RVOT-VA clinically. PMID:28248919

  14. Cell-cell junction remodeling in the heart: possible role in cardiac conduction system function and arrhythmias?

    PubMed

    Mezzano, Valeria; Sheikh, Farah

    2012-02-27

    Anchoring cell-cell junctions (desmosomes, fascia adherens) play crucial roles in maintaining mechanical integrity of cardiac muscle cells and tissue. Genetic mutations and/or loss of critical components in these macromolecular structures are increasingly being associated with arrhythmogenic cardiomyopathies; however, their specific roles have been primarily attributed to effects within the working (ventricular) cardiac muscle. Growing evidence also points to a key role for anchoring cell-cell junction components in cardiac muscle cells of the cardiac conduction system. This is not only evidenced by the molecular and ultra-structural presence of anchoring cell junctions in specific compartments/structures of the cardiac conduction system (sinoatrial node, atrioventricular node, His-Purkinje system), but also because conduction system-related arrhythmias can be found in humans and mouse models of cardiomyopathies harboring defects and/or mutations in key anchoring cell-cell junction proteins. These studies emphasize the clinical need to understand the molecular and cellular role(s) for anchoring cell-cell junctions in cardiac conduction system function and arrhythmias. This review will focus on (i) experimental findings that underline an important role for anchoring cell-cell junctions in the cardiac conduction system, (ii) insights regarding involvement of these structures in age-related cardiac remodeling of the conduction system, (iii) summarizing available genetic mouse models that can target cardiac conduction system structures and (iv) implications of these findings on future therapies for arrhythmogenic heart diseases.

  15. Fetal arrhythmias: the Saint-Justine hospital experience.

    PubMed

    Fouron, Jean-Claude

    2004-12-30

    We intend to review our experience with the investigation and management of foetal arrhythmia on the basis of superior vena cava/ascending aorta (SVC/AA) Doppler flow velocity recordings. Irregular rhythms n = 307. Premature atrial and ventricular contractions were easily identified and generally self-limited in time. Sustained bradycardia n = 19. Four had sinus bradycardia, six presented with blocked atrial bigeminism, three showed 2:1, and five had a complete atrio-ventricular (AV) block. Another foetus that presented with first-degree AV block developed a Luciani-Wenckebach phenomenon 1 week later. These different types of bradycardia were all identified on SVC/AA Doppler recordings. Tachyarrhythmia n = 30. Five types of tachyarrhythmia were observed: Type I: Short ventriculo-atrial (VA) tachycardia (VA < AV), n = 11. Ten foetuses of this group presented a distinctive Doppler flow velocity pattern characterised by 1:1 AV conduction and a tall atrial wave ('a' wave) superimposed on the aortic ejection wave. They were considered to have re-entrant tachycardia through a fast-conducting AV accessory pathway; all 10 responded to digoxin therapy. The eleventh foetus with short VA tachycardia had atrial ectopic tachycardia with AV node dysfunction; he was treated successfully with sotalol. Type II: Long VA tachycardia (VA > AV): n = 8. In seven cases, an 'a' wave of normal amplitude with normal AV time interval could be clearly identified in front of the aortic ejection wave: one foetus in this group was considered to be in sinus tachycardia based on the variability of its heart rate; in another, sudden onset of tachycardia triggered by extrasystoles led to the possibility of permanent junctional reciprocating tachycardia (PJRT). The five other foetuses had atrial ectopic tachycardia. The last foetus presented with AV and VA intervals of the same duration and a heart rate of 210 beats/min; he did not respond either to digoxin or to sotalol, and was found after birth to

  16. Diagnosis and management of inherited cardiomyopathies.

    PubMed

    Millar, Lynne; Sharma, Sanjay

    2014-10-01

    Inherited heart conditions are the most common cause of sudden cardiac death in those under the age of 35 and the leading cause of non-traumatic death in young athletes. Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease affecting 1 in 500 of the population. Some patients may exhibit severe left ventricular hypertrophy, others may show nothing more than an abnormal ECG. Left ventricular hypertrophy most commonly manifests in the second decade of life. Sudden death is rare and usually affects patients in the first three decades whereas older patients present with heart failure, atrial fibrillation and stroke. Arrhythmogenic right ventricular cardiomyopathy is a rare, autosomal dominant heart muscle disorder which affects between 1 in 1,000 and 1 in 5,000 of the population. Dilated cardiomyopathy (DCM) is characterised by a dilated left ventricle with impaired function that cannot be explained by ischaemic heart disease, hypertension or valvular heart disease. At least 25% of cases of DCM are familial. DCM may be associated with multisystem conditions such as muscular dystrophy. Chemotherapy and certain other drugs, alcohol abuse and myocarditis may also lead to a dilated and poorly contracting left ventricle. In many cases the first manifestation of an inherited cardiomyopathy can be a sudden cardiac arrest. Other presentations include chest pain or breathlessness during exertion, palpitations and syncope. In many of the cardiomyopathies, the diagnosis can be made with a standard ECG and echocardiogram. However if the diagnosis is not certain or the cardiologist wishes to look at the heart structure in greater detail, a cardiac MRI may be performed.

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

    PubMed Central

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

    2008-01-01

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

  18. Brainstem sources of cardiac vagal tone and respiratory sinus arrhythmia

    PubMed Central

    Farmer, David G.S.; Dutschmann, Mathias; Paton, Julian F.R.; Pickering, Anthony E.

    2016-01-01

    Key points Cardiac vagal tone is a strong predictor of health, although its central origins are unknown.Respiratory‐linked fluctuations in cardiac vagal tone give rise to respiratory sinus arryhthmia (RSA), with maximum tone in the post‐inspiratory phase of respiration.In the present study, we investigated whether respiratory modulation of cardiac vagal tone is intrinsically linked to post‐inspiratory respiratory control using the unanaesthetized working heart‐brainstem preparation of the rat.Abolition of post‐inspiration, achieved by inhibition of the pontine Kolliker‐Fuse nucleus, removed post‐inspiratory peaks in efferent cardiac vagal activity and suppressed RSA, whereas substantial cardiac vagal tone persisted. After transection of the caudal pons, part of the remaining tone was removed by inhibition of nucleus of the solitary tract.We conclude that cardiac vagal tone depends upon at least 3 sites of the pontomedullary brainstem and that a significant proportion arises independently of RSA. Abstract Cardiac vagal tone is a strong predictor of health, although its central origins are unknown. The rat working heart‐brainstem preparation shows strong cardiac vagal tone and pronounced respiratory sinus arrhythmia. In this preparation, recordings from the cut left cardiac vagal branch showed efferent activity that peaked in post‐inspiration, ∼0.5 s before the cyclic minimum in heart rate (HR). We hypothesized that respiratory modulation of cardiac vagal tone and HR is intrinsically linked to the generation of post‐inspiration. Neurons in the pontine Kölliker‐Fuse nucleus (KF) were inhibited with bilateral microinjections of isoguvacine (50–70 nl, 10 mm) to remove the post‐inspiratory phase of respiration. This also abolished the post‐inspiratory peak of cardiac vagal discharge (and cyclical HR modulation), although a substantial level of activity remained. In separate preparations with intact cardiac vagal branches but

  19. Endocardial fibroelastosis: possible X linked inheritance.

    PubMed Central

    Hodgson, S; Child, A; Dyson, M

    1987-01-01

    We report a pedigree in which six males died of cardiac failure within the first eight months of life. These males were related through healthy females, as with X linked recessive inheritance. There was no consanguinity. None of the affected boys had an anatomical cardiac abnormality. In two affected brothers, histological evidence for endomyocardial fibroelastosis was documented, and in one of these electron microscopy demonstrated abnormalities of the mitochondria as found in mitochondrial cytopathy. A review of published reports revealed five similar X linked pedigrees, and in two of these mitochondrial abnormalities were found. We suggest that these families may show an X linked recessive cardiomyopathy with mitochondrial abnormalities. Images PMID:3585935

  20. Transgenerational epigenetic inheritance: myths and mechanisms.

    PubMed

    Heard, Edith; Martienssen, Robert A

    2014-03-27

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