[Inherited thrombocytopenias].

PubMed

Leverger, G; Petit, A; Fasola, S; Landman-Parker, J; Favier, R

2010-08-01

Secondary causes of thrombocytopenia as immunologic thrombopenia purpura, or ITP, are far more common than inherited causes, which even as a group, are rare. Nevertheless, diagnosis is important and progress made in uncovering the molecular basis of these disorders has contributed greatly to our knowledge of these diseases. Inherited thrombocytopenias are a heterogeneous group of disorders. Different criteria have been suggested to classify the forms, such as the inheritance mechanism and the platelet volume as well as the associated platelet dysfunctions or clinical abnormality. This paper describes the clinical and biological data, and current knowledge of the molecular findings of inherited thrombocytopenia, allowing a diagnostic approach to these diseases. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

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

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

PubMed Central

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

2002-01-01

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

The Renin-Angiotensin-Aldosterone System (RAAS) and Cardiac Arrhythmias

PubMed Central

Iravanian, Shahriar; Dudley, Samuel C.

2008-01-01

The role of the renin-angiotensin-aldosterone system (RAAS) in many cardiovascular disorders, including hypertension, cardiac hypertrophy, and atherosclerosis is well established, whereas its relationship with cardiac arrhythmias is a new area of investigation. Atrial fibrillation and malignant ventricular tachyarrhythmias, especially in the setting of cardiac hypertrophy or failure, appear to be examples of RAAS-related arrhythmias, since treatment with RAAS modulators, including angiotensin converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid receptor blockers, reduces the incidence of these arrhythmias. RAAS has a multitude of electrophysiological effects and can potentially cause arrhythmia through a variety of mechanisms. We review new experimental results that suggest RAAS has pro-arrhythmic effects on membrane and sarcoplasmic reticulum ion channels and that increased oxidative stress is likely contributing to the increased arrhythmic incidence. A summary of ongoing clinical trials that will address the clinical usefulness of RAAS modulators for prevention or treatment of arrhythmias is presented. PMID:18456194

The renin-angiotensin-aldosterone system (RAAS) and cardiac arrhythmias.

PubMed

Iravanian, Shahriar; Dudley, Samuel C

2008-06-01

The role of the renin-angiotensin-aldosterone system (RAAS) in many cardiovascular disorders, including hypertension, cardiac hypertrophy, and atherosclerosis, is well established, whereas its relationship with cardiac arrhythmias is a new area of investigation. Atrial fibrillation and malignant ventricular tachyarrhythmias, especially in the setting of cardiac hypertrophy or failure, seem to be examples of RAAS-related arrhythmias because treatment with RAAS modulators, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor blockers, reduces the incidence of these arrhythmias. RAAS has a multitude of electrophysiological effects and can potentially cause arrhythmia through a variety of mechanisms. We review new experimental results that suggest that RAAS has proarrhythmic effects on membrane and sarcoplasmic reticulum ion channels and that increased oxidative stress is likely contributing to the increased arrhythmic incidence. A summary of ongoing clinical trials that will address the clinical usefulness of RAAS modulators for prevention or treatment of arrhythmias is presented.

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

Arrhythmia

MedlinePlus

... cardiologists who specialize in arrhythmias. Medical and Family Histories To diagnose an arrhythmia, your doctor may ask ... your doctor will use a procedure called cardiac catheterization (KATH-e-ter-ih-ZA-shun). A thin, ...

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

Clinical management of a child with Prader-Willi Syndrome from maternal uniparental disomy (UPD) genetic inheritance.

PubMed

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 with PWS. Case studies can provide information to understand relationships between phenotypic characteristics and genetic inheritance, which can in turn lead to effective clinical management. The purpose of this case study was to describe the characteristics of a child with PWS due to maternal uniparental disomy inheritance pattern and to describe clinical management and treatment outcomes. The reader will obtain information about: (1) the genetic inheritance patterns and clinical characteristics of Prader-Willi Syndrome, (2) genotypic/phenotypic relationships specific to Prader-Willi Syndrome, and (3) clinical implications, management, and outcomes in a case description of a child with PWS due to maternal uniparental disomy inheritance pattern.

Frailty syndrome: an emerging clinical problem in the everyday management of clinical arrhythmias. The results of the European Heart Rhythm Association survey.

PubMed

Fumagalli, Stefano; Potpara, Tatjana S; Bjerregaard Larsen, Torben; Haugaa, Kristina H; Dobreanu, Dan; Proclemer, Alessandro; Dagres, Nikolaos

2017-11-01

The age of patients presenting with complex arrhythmias is increasing. Frailty is a multifaceted syndrome characterized by an increased vulnerability to stressors and a decreased ability to maintain homeostasis. The prevalence of frailty is associated with age. The aims of this European Heart Rhythm Association (EHRA) EP Wire survey were to evaluate the proportion of patients with frailty and its influence on the clinical management of arrhythmias. A total of 41 centres-members of the EHRA Electrophysiology Research Network-in 14 European countries completed the web-based questionnaire in June 2017. Patients over 70 years represented 53% of the total treated population, with the proportion of frail elderly individuals reaching approximately 10%; 91.7% of the responding centres reported treating frail subjects in the previous year. The respondents usually recognized frailty based on the presence of problems of mobility, nutrition, and cognition and inappropriate loss of body weight and muscle mass. Renal failure, dementia, disability, atrial fibrillation, heart failure, falls, and cancer were reported to characterize the elderly frail individuals. Atrial fibrillation was considered the prevalent arrhythmia associated with frailty by 72% of the responding centres, and for stroke prevention, non-vitamin K antagonist oral anticoagulants were preferred. None of the respondents considered withholding the prevention of thrombo-embolic events in subjects with a history of falls. All participants have agreed that cardiac resynchronization therapy exerts positive effects including improvement in cardiac, physical, and cognitive performance and quality of life. The majority of respondents preferred an Arrhythmia Team to manage this special population of elderly patients, and many would like having a simple tool to quickly assess the presence of frailty to guide their decisions, particularly on the use of complex cardiac implantable electrical devices (CIEDs). In conclusion

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.

Clinical characteristics and current therapies for inherited retinal degenerations.

PubMed

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

2014-10-16

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

Inherited Retinal Degenerative Disease Clinical Trial Network. Addendum

DTIC Science & Technology

2010-10-01

by retinitis pigmentosa (RP) and other forms of rare inherited retinal degenerative diseases is estimated at approximately 200,000 individuals. RP... Retinitis Pigmentosa ). NNRI is awaiting final protocol review and HRPO approval for NNRI and the three enrolling clinical sites- the CTEC site at...acid) in individuals with autosomal dominant retinitis pigmentosa , with the ability to expand the enrollment to individuals with autosomal recessive

Malignant ventricular arrhythmias in alcoholic cardiomyopathy.

PubMed

Guzzo-Merello, Gonzalo; Dominguez, Fernando; González-López, Esther; Cobo-Marcos, Marta; Gomez-Bueno, Manuel; Fernandez-Lozano, Ignacio; Millan, Isabel; Segovia, Javier; Alonso-Pulpon, Luis; Garcia-Pavia, Pablo

2015-11-15

Excessive alcohol consumption is a well-known aetiology of atrial arrhythmias but there is little information concerning the prevalence or incidence of malignant ventricular arrhythmias in alcoholic cardiomyopathy (ACM). This study sought to investigate incidence and predictive factors of ventricular arrhythmias in ACM. Retrospective observational study of the clinical characteristics and long-term arrhythmic events in 282 consecutive patients with ACM (94 individuals) and idiopathic dilated cardiomyopathy (IDCM) (188 individuals) evaluated between 1993 and 2011. During a median follow-up of 38months (IQR:12-77), 42 patients died and 79 underwent heart transplantation [31 (33%) with ACM vs 90 (48%) with IDCM; p=0.017]. A total of 37 (13%) patients [18 (19%) ACM vs 20 (11%) IDCM; p=0.048] suffered malignant ventricular arrhythmias. On multivariate analysis, left bundle branch block (LBBB) (OR 2.4; CI95%: 1.2-5; p=0.015) and alcoholic aetiology (OR 2.3; CI95%: 1.1-4.5; p=0.026) were the only independent predictors of malignant ventricular arrhythmic events. A total of 18 (19%) ACM patients experienced 20 malignant ventricular arrhythmic events (4 aborted SCD, 8 SCD and 8 appropriate ICD therapies). At baseline evaluation, the only independent predictor of malignant ventricular arrhythmias in ACM patients was LBBB (OR 11.2; CI95%: 2.6-50; p=0.001). No malignant ventricular arrhythmias were recorded during follow-up in ACM patients if left ventricular ejection fraction (LVEF) had increased or remained ≥40%. Malignant ventricular arrhythmias are more frequent in ACM than in IDCM. LBBB identifies ACM patients with increased risk of SCD. No malignant ventricular arrhythmias were found during follow-up in ACM patients when LVEF was ≥40%. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cardiac arrhythmia and thyroid dysfunction: a novel genetic link

PubMed Central

Purtell, Kerry; Roepke, Torsten K.; Abbott, Geoffrey W.

2010-01-01

Inherited Long QT Syndrome, a cardiac arrhythmia that predisposes to the often lethal ventricular fibrillation, is commonly linked to mutations in KCNQ1. The KCNQ1 voltage-gated K+ channel α subunit passes ventricular myocyte K+ current that helps bring a timely end to each heart-beat. KCNQ1, like many K+ channel α subunits, is regulated by KCNE β subunits, inherited mutations in which also associate with Long QT Syndrome. KCNQ1 and KCNE mutations are also associated with atrial fibrillation. It has long been known that thyroid status strongly influences cardiac function, and that thyroid dysfunction causes abnormal cardiac structure and rhythm. We recently discovered that KCNQ1 and KCNE2 form a thyroid-stimulating hormone-stimulated K+ channel in the thyroid that is required for normal thyroid hormone biosynthesis. Here, we review this novel genetic link between cardiac and thyroid physiology and pathology, and its potential influence upon future therapeutic strategies in cardiac and thyroid disease. PMID:20688187

[Idiopathic ventricular arrhythmia in children. Apropos of 24 cases].

PubMed

Coeurderoy, A; Almange, C; Laurent, M; Biron, Y; Leborgne, P

1985-12-01

The severity and prognosis of idiopathic ventricular arrhythmias in childhood were studied in 24 patients (12 boys, 12 girls) with an average age of 8 years at the time of diagnosis of the arrhythmia. Investigations included clinical assessment and analysis of basal ECG (morphology of the arrhythmias) and dynamic recordings (Holter and exercise stress testing). The clinical course was followed for an average of 3.8 years. The patients were classified in two groups: monomorphic arrhythmias (Group I) and polymorphic arrhythmias (Group II). Group I was divided into 4 subgroups: isolated ventricular extrasystoles (IA), 11 patients; ventricular extrasystoles with bursts of ventricular tachycardia (IB), 6 patients; sustained ventricular tachycardia without intercritical extrasystoles (IC), 1 patient; accelerated idioventricular rhythm (ID), 2 patients. Subgroups IA, IB and ID were characterised by the absence of symptoms, the disappearance of the arrhythmia on exercise, the decreased efficacy of antiarrhythmic drugs and an excellent prognosis. Therapeutic abstention was the rule in these patients. Patients in Group IC were characterised by the variability of their symptoms, the absence of exercise induced arrhythmias, the need for treatment in most cases and a good long-term prognosis. Group II was divided into 2 subgroups: adrenergic polymorphic ventricular tachycardia (IIA), 2 patients, and non-adrenergic polymorphic ventricular tachycardia (IIB), 2 patients. Patients in Subgroup IIA were characterised by syncope on exercise or emotion, the need for betablocker therapy which considerably improved the patients symptoms but which did not usually prevent sudden death.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of Arrhythmias in Heart Failure

PubMed Central

Masarone, Daniele; Limongelli, Giuseppe; Rubino, Marta; Valente, Fabio; Vastarella, Rossella; Ammendola, Ernesto; Gravino, Rita; Verrengia, Marina; Salerno, Gemma; Pacileo, Giuseppe

2017-01-01

Heart failure patients are predisposed to develop arrhythmias. Supraventricular arrhythmias can exacerbate the heart failure symptoms by decreasing the effective cardiac output and their control require pharmacological, electrical, or catheter-based intervention. In the setting of atrial flutter or atrial fibrillation, anticoagulation becomes paramount to prevent systemic or cerebral embolism. Patients with heart failure are also prone to develop ventricular arrhythmias that can present a challenge to the managing clinician. The management strategy depends on the type of arrhythmia, the underlying structural heart disease, the severity of heart failure, and the range from optimization of heart failure therapy to catheter ablation. Patients with heart failure, irrespective of ejection fraction are at high risk for developing sudden cardiac death, however risk stratification is a clinical challenge and requires a multiparametric evaluation for identification of patients who should undergo implantation of a cardioverter defibrillator. Finally, patients with heart failure can also develop symptomatic bradycardia, caused by sinus node dysfunction or atrio-ventricular block. The treatment of bradycardia in these patients with pacing is usually straightforward but needs some specific issue. PMID:29367535

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

PubMed

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

2017-01-29

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.

About Arrhythmia

MedlinePlus

... may shut down or be damaged. View an animation of arrhythmia . Types of Arrhythmias Atrial Fibrillation = upper ... learn about: S tructure of the heart Watch an animation of heart valve anatomy The heart: four chambers, ...

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.

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.

Use of bipolar radiofrequency catheter ablation in treatment of cardiac arrhythmias.

PubMed

Soucek, Filip; Starek, Zdenek

2018-05-23

Background Arrhythmia management is a complex process involving both pharmacological and non-pharmacological approaches. Radiofrequency ablation is the pillar of non-pharmacological arrhythmia treatment. Unipolar ablation is considered to be the gold standard in the treatment of the majority of arrhythmias; however, its efficacy is limited to specific cases. In particular, the creation of deep or transmural lesions to eliminate intramurally originating arrhythmias remains inadequate. Bipolar ablation is proposed as an alternative to overcome unipolar ablation boundaries. Results Despite promising results gained from in vitro and animal studies showing that bipolar ablation is superior in creating transmural lesions, the use of bipolar ablation in daily clinical practice is limited. Several studies have been published showing that bipolar ablation is effective in the treatment of clinical arrhythmias after failed unipolar ablation, however there is inconsistency regarding safety of bipolar ablation within the available research papers. According to research evidence the most common indications for bipolar ablation use are ventricular originating rhythmic disorders in patients with structural heart disease resistant to standard radiofrequency ablation. Conclusions To allow wider clinical application the efficiency and safety of bipolar ablation need to be verified in future studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Feline arrhythmias: an update.

PubMed

Côté, Etienne

2010-07-01

In the cat, electrocardiography is indicated for assessing the rhythm of the heartbeat and identifying and monitoring the effect of certain systemic disorders on the heart. Basic information regarding feline electrocardiography is contained in several textbooks, and the reader is referred to these sources for background reading. This article describes selected clinical advances in feline cardiac arrhythmias and electrocardiography from the past decade.

Arrhythmias in Adults with Congenital Heart Disease: What Are Risk Factors for Specific Arrhythmias?

PubMed

Loomba, Rohit S; Buelow, Matthew W; Aggarwal, Saurabh; Arora, Rohit R; Kovach, Joshua; Ginde, Salil

2017-04-01

An increasing number of patients with congenital heart disease are now surviving into adulthood. This has also led to the emergence of complications from the underlying congenital heart disease, related surgical interventions, and associated combordities. While the prevalence of particular arrhythmias with specific congenital heart disease has been previously described, a detailed analysis of all lesions and a large number of comorbidities has not been previously published. Admissions with congenital heart disease were identified in the National Inpatient Sample. Associated comorbidities were also identified for these patients. Univariate analysis was done to compare those risk factors associated with specific arrhythmias in the setting of congenital heart disease. Next, regression analysis was done to identify what patient characteristics and comorbidities were associated with increased risk of specific arrhythmias. A total of 52,725,227 admissions were included in the analysis. Of these, 109,168 (0.21%) had congenital heart disease. Of those with congenital heart disease, 27,088 (25%) had an arrhythmia at some point. The most common arrhythmia in those with congenital heart disease was atrial fibrillation, which was noted in 86% of those with arrhythmia followed by atrial flutter which was noted in 20% of those with congenital heart disease. The largest burden of arrhythmia was found to be in those with tricuspid atresia with a 51% prevalence of arrhythmia in this group followed by Ebstein anomaly which had an arrhythmia prevalence of 39%. Increasing age, male gender, double outlet right ventricle, atrioventricular septal defect, heart failure, obstructive sleep apnea, transposition of the great arteries, congenitally corrected transposition, and tetralogy of Fallot were frequently noted to be independent risk factors of specific arrhythmias. Approximately, 25% of adult admissions with congenital heart disease are associated with arrhythmia. The burden of

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

PubMed

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

2017-01-01

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

Prevention and Treatment of Arrhythmia

MedlinePlus

... your pulse – especially if you have an artificial pacemaker. Put the second and third fingers of one ... Ablation Devices for Arrhythmia - Implantable Cardioverter Defibrillator (ICD) - Pacemaker Treating Arrhythmias in Children • Arrhythmia Tools & Resources Watch, ...

Effects of dexmedetomidine on heart arrhythmia prevention in off-pump coronary artery bypass surgery: A randomized clinical trial.

PubMed

Soltani, Ghasem; Jahanbakhsh, Saeed; Tashnizi, Mohammad Abbasi; Fathi, Mehdi; Amini, Shahram; Zirak, Nahid; Sheybani, Shima

2017-10-01

Arrhythmia occurring during and after surgery is one of the major complications in open-heart surgery. Dexmedetomidine is an intravenous alpha-2 agonist and very specific short-acting drug to protect the various organs against ischemic injuries and blood reflow. However, the effect of dexmedetomidine for preventing intraoperative heart arrhythmias has not been recognized. This study aimed to determine the effect of dexmedetomidine on the incidence rate of heart arrhythmias and anesthetic required in off-pump coronary artery bypass surgery. This randomized clinical trial was conducted on patients who were candidates for off-pump coronary artery bypass referring to Imam Reza Hospital of Mashhad, Iran, from July 2016 through January 2017. The patients were randomly assigned to two groups of intervention (infusion of 0.5 mcg/kg/h dexmedetomidine together with induction followed by infusion of 0.5 mcg/kg/h by the end of the surgery) or control (saline infusion). Mean arterial pressure (MAP) and heart rate (HR) were measured before induction, during surgery operation and ICU admission. Data were analyzed by SPSS version 18 using Chi Square and independent-samples t-test. A total of 76 patients with a mean age of 59.8 ± 8.2 years (in two groups of 38) were studied. The two groups had no statistically significant difference in terms of background variables. The MAP and HR values before induction, during surgery and ICU admission were significantly higher in the control group than in the intervention group (p=0.001). Out of the studied arrhythmias, the values of PAC (55.2% vs. 15.7%), PVC (81.5% vs. 21.0%), AF (26.3% vs. 7.8%), VTAC (21.0% vs. 2.6%) were significantly lower in dexmedetomidine group (p=0.001). It seems that dexmedetomidine administration during induction and surgery can cause significant reduction in most of the common arrhythmias in off-pump coronary bypass surgery. The use of dexmedetomidine maintains MAP and HR at significantly lower values, and changes

Effects of dexmedetomidine on heart arrhythmia prevention in off-pump coronary artery bypass surgery: A randomized clinical trial

PubMed Central

Soltani, Ghasem; Jahanbakhsh, Saeed; Tashnizi, Mohammad Abbasi; Fathi, Mehdi; Amini, Shahram; Zirak, Nahid; Sheybani, Shima

2017-01-01

Background Arrhythmia occurring during and after surgery is one of the major complications in open-heart surgery. Dexmedetomidine is an intravenous alpha-2 agonist and very specific short-acting drug to protect the various organs against ischemic injuries and blood reflow. However, the effect of dexmedetomidine for preventing intraoperative heart arrhythmias has not been recognized. Objective This study aimed to determine the effect of dexmedetomidine on the incidence rate of heart arrhythmias and anesthetic required in off-pump coronary artery bypass surgery. Methods This randomized clinical trial was conducted on patients who were candidates for off-pump coronary artery bypass referring to Imam Reza Hospital of Mashhad, Iran, from July 2016 through January 2017. The patients were randomly assigned to two groups of intervention (infusion of 0.5 mcg/kg/h dexmedetomidine together with induction followed by infusion of 0.5 mcg/kg/h by the end of the surgery) or control (saline infusion). Mean arterial pressure (MAP) and heart rate (HR) were measured before induction, during surgery operation and ICU admission. Data were analyzed by SPSS version 18 using Chi Square and independent-samples t-test. Results A total of 76 patients with a mean age of 59.8 ± 8.2 years (in two groups of 38) were studied. The two groups had no statistically significant difference in terms of background variables. The MAP and HR values before induction, during surgery and ICU admission were significantly higher in the control group than in the intervention group (p=0.001). Out of the studied arrhythmias, the values of PAC (55.2% vs. 15.7%), PVC (81.5% vs. 21.0%), AF (26.3% vs. 7.8%), VTAC (21.0% vs. 2.6%) were significantly lower in dexmedetomidine group (p=0.001). Conclusion It seems that dexmedetomidine administration during induction and surgery can cause significant reduction in most of the common arrhythmias in off-pump coronary bypass surgery. The use of dexmedetomidine maintains MAP

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

PubMed

Savige, Judy; Dagher, Hayat; Povey, Sue

2014-07-01

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

Sports and arrhythmias: a report of the International Workshop Venice Arrhythmias 2009.

PubMed

Giada, Franco; Biffi, Alessandro; Cannom, David S; Cappato, Riccardo; Capucci, Alessandro; Corrado, Domenico; Delise, Pietro; Drezner, Jonathan A; El-Sherif, Nabil; Estes, Mark; Furlanello, Francesco; Heidbuchel, Hein; Inama, Giuseppe; Lindsay, Bruce D; Maron, Barry J; Maron, Martin S; Mont, Luis; Olshansky, Brian; Pelliccia, Antonio; Thiene, Gaetano; Viskin, Sami; Zeppilli, Paolo; Natale, Andrea; Raviele, Antonio

2010-10-01

This article is a report of an international symposium, endorsed by the Section on Sports Cardiology of the European Association for Cardiovascular Prevention and Rehabilitation, the Italian Society of Sports Cardiology, and the Italian Federation of Sports Medicine, which was held within the 11th International Workshop on Cardiac Arrhythmias (Venice Arrhythmias 2009, Venice, Italy, October 2009). The following main topics were discussed during the symposium: the role of novel diagnostic examinations to assess the risk of sudden death in athletes, controversies on arrhythmic risk evaluation in athletes, controversies on the relationship between sports and arrhythmias, and controversies on antiarrhythmic treatment in athletes.

Arrhythmias

MedlinePlus

... sign of other heart problems, or an immediate danger to your health. ... patient with suspected arrhythmia. In: Goldman L, Schafer AI, eds. Goldman’s Cecil Medicine . 25th ed. Philadelphia, PA: ...

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

Ventricular arrhythmias and sudden cardiac arrest in Takotsubo cardiomyopathy: Incidence, predictive factors, and clinical implications.

PubMed

Jesel, Laurence; Berthon, Charlotte; Messas, Nathan; Lim, Han S; Girardey, Mélanie; Marzak, Halim; Marchandot, Benjamin; Trinh, Annie; Ohlmann, Patrick; Morel, Olivier

2018-04-06

Takotsubo cardiomyopathy (TTC) is a stress-related transient cardiomyopathy. Life-threatening arrhythmias (LTA) can occur and worsen prognosis. The purpose of this study was to assess the incidence and outcome of LTA in TTC, as well as its predictive factors and clinical implications. We studied 214 consecutive cases of TTC over 8 years. The study cohort was divided into 2 groups: those with LTA (LTA group) and those without (non-LTA group). LTA was defined as ventricular tachycardia, ventricular fibrillation, or cardiac arrest. LTA occurred in 10.7% of patients mainly in the first 24 hours of hospitalization: ventricular tachycardia (n = 2), ventricular fibrillation (n = 11), cardiac arrest (n = 10: 5 asystole, 3 complete heart block, and 2 sinoatrial block). LTA were associated with lower left ventricular ejection fraction (LVEF) and a high rate of conduction disturbances. In-hospital (39.1% vs 8.9%; P < .001) and 1-year mortality (47.8% vs 14.1%; P < .001) rates were significantly increased in the LTA group. LVEF and QRS duration >105 ms were independent predictors of LTA. In cases where a device was implanted, conduction disturbances persisted after the index event despite complete recovery of LVEF. There was no ventricular arrhythmia recurrence during follow-up. LTA occur early in patients presenting with TTC and is associated with significantly worse short- and long-term prognosis. Left ventricular impairment and QRS duration >105 ms are independent predictors of LTA. Ventricular arrhythmias occurred in the acute phase without further recurrence recorded in hospital survivors, whereas severe conduction disorders persisted during long-term follow-up. These findings may have implications on the choice of device therapy for this specific patient subgroup. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Drug-induced life-threatening arrhythmias and sudden cardiac death: A clinical perspective of long QT, short QT and Brugada syndromes.

PubMed

Ramalho, Diogo; Freitas, João

2018-05-01

Sudden cardiac death is a major public health challenge, which can be caused by genetic or acquired structural or electrophysiological abnormalities. These abnormalities include hereditary channelopathies: long QT, short QT and Brugada syndromes. These syndromes are a notable concern, particularly in young people, due to their high propensity for severe ventricular arrhythmias and sudden cardiac death. Current evidence suggests the involvement of an increasing number of drugs in acquired forms of long QT and Brugada syndromes. However, drug-induced short QT syndrome is still a rarely reported condition. Therefore, there has been speculation on its clinical significance, since few fatal arrhythmias and sudden cardiac death cases have been described so far. Drug-induced proarrhythmia is a growing challenge for physicians, regulatory agencies and the pharmaceutical industry. Physicians should weigh the risks of potentially fatal outcomes against the therapeutic benefits, when making decisions about drug prescriptions. Growing concerns about its safety and the need for more accurate predictive models for drug-induced fatal outcomes justify further research in these fields. The aim of this article is to comprehensively and critically review the recently published evidence with regard to drug-induced life-threatening arrhythmias and sudden cardiac death. This article will take into account the provision of data to physicians that are useful in the identification of the culprit drugs, and thus, contribute to the prompt recognition and management of these serious clinical conditions. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Hereditary arrhythmias and cardiomyopathies: decision-making about genetic testing.

PubMed

Louis, Clauden; Calamaro, Emily; Vinocur, Jeffrey M

2018-01-01

The modern field of clinical genetics has advanced beyond the traditional teachings familiar to most practicing cardiologists. Increased understanding of the roles of genetic testing may improve uptake and appropriateness of use. Clinical genetics has become integral to the management of patients with hereditary arrhythmia and cardiomyopathy diagnoses. Depending on the condition, genetic testing may be useful for diagnosis, prognosis, treatment, family screening, and reproductive planning. However, genetic testing is a powerful tool with potential for underuse, overuse, and misuse. In the absence of a substantial body of literature on how these guidelines are applied in clinical practice, we use a case-based approach to highlight key lessons and pitfalls. Importantly, in many scenarios genetic testing has become the standard of care supported by numerous class I recommendations; genetic counselors can improve accessibility to and appropriate use and application of testing. Optimal management of hereditary arrhythmias and cardiomyopathies incorporates genetic testing, applied as per consensus guidelines, with involvement of a multidisciplinary team.

Induced pluripotent stem cell technology: Toward the future of cardiac arrhythmias.

PubMed

Gnecchi, Massimiliano; Stefanello, Manuela; Mura, Manuela

2017-06-15

The development of human induced pluripotent stem cell (iPSC) technology has revitalized the efforts made in the last decade to exploit the potential of human embryonic stem cells (ESCs) for scientific research. In the field of cardiac arrhythmias, the possibility of generating an unlimited amount of patient-specific cardiomyocyte-like cells (iPSC-CMs) has clear advantages compared with the use of ESC-derived cardiac cells. In particular, with the introduction and implementation of the large-scale precision medicine initiative, we anticipate that the iPSC technology will play an important role in the advancement of cardiovascular research and medicine. This platform is not free from technical limitations that must be carefully taken into account; however, the utility of iPSC-CMs in disease modeling and drug testing studies is hardly questionable. Here, we summarize some of the progresses made in the field of iPSC technology applied to inherited cardiac arrhythmias, with particular emphasis on the use of iPSC-CMs for modelling the long QT syndrome and for the development of personalized drug and molecular therapies. The growing role of iPSC technology in the practice of precision medicine will also be discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-12-01

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

The Association between Nocturnal Cardiac Arrhythmias and Sleep-Disordered Breathing: The DREAM Study.

PubMed

Selim, Bernardo J; Koo, Brian B; Qin, Li; Jeon, Sangchoon; Won, Christine; Redeker, Nancy S; Lampert, Rachel J; Concato, John P; Bravata, Dawn M; Ferguson, Jared; Strohl, Kingman; Bennett, Adam; Zinchuk, Andrey; Yaggi, Henry K

2016-06-15

To determine whether sleep-disordered breathing (SDB) is associated with cardiac arrhythmia in a clinic-based population with multiple cardiovascular comorbidities and severe SDB. This was a cross-sectional analysis of 697 veterans who underwent polysomnography for suspected SDB. SDB was categorized according to the apnea-hypopnea index (AHI): none (AHI < 5), mild (5 ≥ AHI < 15), and moderate-severe (AHI ≥ 15). Nocturnal cardiac arrhythmias consisted of: (1) complex ventricular ectopy, (CVE: non-sustained ventricular tachycardia, bigeminy, trigeminy, or quadrigeminy), (2) combined supraventricular tachycardia, (CST: atrial fibrillation or supraventricular tachycardia), (3) intraventricular conduction delay (ICD), (4) tachyarrhythmias (ventricular and supraventricular), and (5) any cardiac arrhythmia. Unadjusted, adjusted logistic regression, and Cochran-Armitage testing examined the association between SDB and cardiac arrhythmias. Linear regression models explored the association between hypoxia, arousals, and cardiac arrhythmias. Compared to those without SDB, patients with moderate-severe SDB had almost three-fold unadjusted odds of any cardiac arrhythmia (2.94; CI 95%, 2.01-4.30; p < 0.0001), two-fold odds of tachyarrhythmias (2.16; CI 95%,1.47-3.18; p = 0.0011), two-fold odds of CVE (2.01; 1.36-2.96; p = 0.003), and two-fold odds of ICD (2.50; 1.58-3.95; p = 0.001). A linear trend was identified between SDB severity and all cardiac arrhythmia subtypes (p value linear trend < 0.0001). After adjusting for age, BMI, gender, and cardiovascular diseases, moderate-severe SDB patients had twice the odds of having nocturnal cardiac arrhythmias (2.24; 1.48-3.39; p = 0.004). Frequency of obstructive respiratory events and hypoxia were strong predictors of arrhythmia risk. SDB is independently associated with nocturnal cardiac arrhythmias. Increasing severity of SDB was associated with an increasing risk for any cardiac arrhythmia. © 2016 American Academy of Sleep

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

PubMed

Navas de Solis, C

2016-07-01

Arrhythmias are common in equine athletes during and immediately after exercise. Many of these rhythm variations are not clinically relevant. In horses, a link between different exercising arrhythmias and poor performance or between exercising arrhythmias and sudden cardiac death (SCD) is strongly suspected but not fully understood or proven. SCD during races or competitions is rare, but has catastrophic consequences for the safety of the human partner and public perceptions of welfare during equestrian sports. This review summarises current knowledge of equine exercise arrhythmias and their implications in SCD and compares existing principles and recommendations for equine subjects with those for human athletes. © 2016 EVJ Ltd.

Management of unstable arrhythmias in cardiogenic shock.

PubMed

Saidi, Abdulfattah; Akoum, Nazem; Bader, Feras

2011-08-01

Atrial and ventricular arrhythmias commonly arise in the setting of cardiogenic shock and often result in hemodynamic deterioration. Causative factors include myocardial ischemia, volume overload, and metabolic disturbances. Correcting these factors plays an important role in managing arrhythmias in this setting. Ventricular arrhythmias are more ominous compared to atrial arrhythmias but both require prompt intervention with electrical shock and anti-arrhythmic drug suppression. Coronary reperfusion is key to improving survival, including reducing the risk of sudden cardiac arrest, in acute myocardial infarction. Case series have also demonstrated the value of intra-aortic balloon pump counter-pulsation in suppressing ventricular arrhythmias in cardiogenic shock. The mechanism of arrhythmia suppression may be due to improved coronary perfusion and afterload reduction. Percutaneous ventricular assist device placement may be effective in this setting; however, data addressing this specific endpoint are lacking. Anti-arrhythmic drug options for ventricular and atrial arrhythmia suppression, in the setting of cardiogenic shock, are relatively limited. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone. The other Class III agents, sotalol and dronedarone, are excluded due to associated mortality observed in the SWORD and ANDROMEDA trials, respectively. Dofetilide is renally excreted and causes QT interval prolongation. Care should be taken to avoid excessive drug accumulation due to poor kidney perfusion and function. Dofetilide is approved for use for atrial arrhythmias and has not been studied for ventricular arrhythmia suppression. The DIAMOND-CHF trial established its safety in the setting of heart failure. Amiodarone is very effective in suppressing both atrial and ventricular arrhythmias. It is often the drug of choice in heart

Inherited trombophilic states and pulmonary embolism

PubMed Central

Konecny, Filip

2009-01-01

Pulmonary embolism (PE) and deep vein thrombosis (DVT) are associated with considerable morbidity and mortality, mostly, in case of PE for its lack of sensitivity of its early detection. For as much as twenty-five percent of PE patients the primary clinical appearance is unexpected death. While PE is one of the most avertable causes of hospital associated deaths, its diagnostics can be extremely difficult. Newly increased interest in an inherited thrombophilic states has been provoked by the discovery of several common inherited abnormalities, i.e. the prothrombin (PT) gene G20210A, Factor V Leiden (FVL) mutation (Arg506Gln), hyperhomocystenemia and homocysteiuria, Wein-Penzing defect, Sticky Platelet Syndrome (SPS), Quebec platelet disorder (QPD) and Sickle Cell Disease (SCD). PE incidence rates increase exponentially with age for both men and women, as they might harbor more than one thrombophilic state. Although the impact of genetic factors on PE is to some extent documented with lacking taxonomy, its genetic testing as its prevention strategy fall short. In this review thrombophilic states are divided into inherited or acquired, and only the inherited and newly documented are more closely followed. Factors are further grouped based on its thrombophilic taxonomy into; inherited defects of coagulation, inherited defects of fibrinolysis, inherited defects of enzymatic pathway in relation to development of VTE and PE and inherited defects of platelets in relation to PE. It was beyond the scope of this review to follow all inherited and newly recognized factors and its association to VTE and PE; however the overall taxonomy makes this review clinically valuable i.e. in relation to genetic testing as PE prevention. PMID:21772860

Inherited trombophilic states and pulmonary embolism.

PubMed

Konecny, Filip

2009-01-01

Pulmonary embolism (PE) and deep vein thrombosis (DVT) are associated with considerable morbidity and mortality, mostly, in case of PE for its lack of sensitivity of its early detection. For as much as twenty-five percent of PE patients the primary clinical appearance is unexpected death. While PE is one of the most avertable causes of hospital associated deaths, its diagnostics can be extremely difficult. Newly increased interest in an inherited thrombophilic states has been provoked by the discovery of several common inherited abnormalities, i.e. the prothrombin (PT) gene G20210A, Factor V Leiden (FVL) mutation (Arg506Gln), hyperhomocystenemia and homocysteiuria, Wein-Penzing defect, Sticky Platelet Syndrome (SPS), Quebec platelet disorder (QPD) and Sickle Cell Disease (SCD). PE incidence rates increase exponentially with age for both men and women, as they might harbor more than one thrombophilic state. Although the impact of genetic factors on PE is to some extent documented with lacking taxonomy, its genetic testing as its prevention strategy fall short.In this review thrombophilic states are divided into inherited or acquired, and only the inherited and newly documented are more closely followed. Factors are further grouped based on its thrombophilic taxonomy into; inherited defects of coagulation, inherited defects of fibrinolysis, inherited defects of enzymatic pathway in relation to development of VTE and PE and inherited defects of platelets in relation to PE. It was beyond the scope of this review to follow all inherited and newly recognized factors and its association to VTE and PE; however the overall taxonomy makes this review clinically valuable i.e. in relation to genetic testing as PE prevention.

Determination of myocardium to plasma concentration ratios of five antipsychotic drugs: comparison with their ability to induce arrhythmia and sudden death in clinical practice.

PubMed

Titier, Karine; Canal, Mireille; Déridet, Evelyne; Abouelfath, Abdelilah; Gromb, Sophie; Molimard, Mathieu; Moore, Nicholas

2004-08-15

Reviewing available data shows that most of antipsychotic drugs are associated with arrhythmia and sudden death. Experimental studies have shown a HERG channel blockade, a dose-dependent increase in duration of action potential or of QT interval, with various degrees of indicators of serious arrhythmogenicity. However, it seems difficult to relate these in vitro and in vivo preclinical models to clinical findings, in part, because the relationship between concentrations used and in vivo tissue concentrations during treatment in man is not known. Consequently, we established the myocardium to plasma concentration ratios for a series of antipsychotic drugs by intraperitoneal administration of different level doses to the guinea pig. Then, we compared these values to their ability to induce arrhythmia or torsade de pointes in clinical practice. The myocardium to plasma concentration ratios were 2.2 for clozapine, 2.7 for olanzapine, 3.1 for sertindole, 4.5 for risperidone, and 6.4 for haloperidol. These data suggest that when the ratio is higher than 4, arrhythmia and sudden death may be expected. On the contrary, when the ratio is less than 3, little effect may be predicted. These results underscore the importance of interpreting HERG channel data and electrophysiological data in the context of other pharmacokinetic parameters such as myocardium to plasma distribution.

Effect of magnesium on arrhythmia incidence in patients undergoing coronary artery bypass grafting.

PubMed

Mohammadzadeh, Alireza; Towfighi, Farshad; Jafari, Naser

2018-06-01

Cardiac arrhythmia after coronary artery bypass grafting (CABG) surgery is a common complication of cardiac surgery. The effect of serum magnesium, hypomagnesaemia treatment and prophylactic administration of magnesium in the development and prevention of arrhythmias is controversial and there are many different ideas. This study evaluates the therapeutic effects of magnesium in cardiac arrhythmia after CABG surgery. The clinical trial enrolled 250 patients who underwent CABG. Based on the initial serum levels of magnesium, patients were divided into two groups: hypomagnesium and normomagnesium. Based on bioethics committee requirements, patients in the hypo-magnesium group received magnesium treatments until they attained normal magnesium blood levels. Both groups underwent CABG with normal blood levels of magnesium. After surgery, each group was randomly divided into two subgroups: one subgroup received a bolus dose of magnesium sulphate (30 mg/kg in 5 min) and the other subgroup received a placebo. Subgroups were under observation in the intensive care unit for 3 days and arrhythmias were recorded. Data from all four subgroups were analysed statistically and interpreted. The results of this study showed that the occurrence of arrhythmia was not significantly different among subgroups (P > 0.05). There was no significant relationship between blood levels of magnesium and arrhythmia during the 3 days post-surgery (P > 0.05). The results of this study showed that magnesium sulphate administration did not significantly improve the incidence of arrhythmias in hypo- and normo-magnesium patients after CABG. There was no significant correlation between post-operative serum levels of magnesium and arrhythmia during 3 days. © 2017 Royal Australasian College of Surgeons.

Gout and arrhythmias: In search for causation beyond association.

PubMed

Giannopoulos, Georgios; Angelidis, Christos; Deftereos, Spyridon

2018-06-13

Gout is a systemic disease, characterized by the formation and deposition of crystals in tissues (mainly in and around the joints) of individuals with elevated serum uric acid levels. Lately, a considerable number of reports relating elevated uric acid and/or gout with rhythm disorders, such as atrial fibrillation, have been published. This review summarizes evidence linking common arrhythmias and hyperuricemia/gout and discusses questions or controversies that surround it. Overall, existing evidence may not be overwhelming, but strongly suggests a positive correlation between uric acid levels and common rhythm disorders. Needless to say that such a link - as a univariate association between the two - is to be expected, given the extensive overlap of risk factors and comorbidities of hyperuricemia/gout and arrhythmias. However, the observed associations seem to persist - in most studies - after extensive adjustment for potential confounders. Still, multivariable analyses of epidemiologically collected data cannot substitute for proof coming from basic and clinical studies. There is obviously a need for further basic research to establish a causal relationship between uric acid effects and arrhythmias, as well as translational studies and clinical trials to investigate the therapeutic implications of such a relationship. Simply put, we are fairly certain that there is association, but proof of causation is what we are still in want of. Copyright © 2018. Published by Elsevier Inc.

Biomarkers in electrophysiology: role in arrhythmias and resynchronization therapy

PubMed Central

Bose, Abhishek; Truong, Quynh A.

2015-01-01

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

Asymptomatic Intradialytic Supraventricular Arrhythmias and Adverse Outcomes in Patients on Hemodialysis

PubMed Central

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

2016-01-01

Background and objectives Supraventricular arrhythmias are associated with high morbidity and mortality. Nevertheless, this condition has received little attention in patients on hemodialysis. The objective of this study was to analyze the incidence of intradialysis supraventricular arrhythmia and its long–term prognostic value. Design, setting, participants, & measurements We designed an observational and prospective study in a cohort of patients on hemodialysis with a 10-year follow-up period. All patients were recruited for study participation and were not recruited for clinical indications. The study population comprised 77 patients (42 men and 35 women; mean age =58±15 years old) with sinus rhythm monitored using a Holter electrocardiogram over six consecutive hemodialysis sessions at recruitment. Results Hypertension was present in 68.8% of patients, and diabetes was present in 29.9% of patients. Supraventricular arrhythmias were recorded in 38 patients (49.3%); all of these were short, asymptomatic, and self-limiting. Age (hazard ratio, 1.04 per year; 95% confidence interval, 1.00 to 1.08) and right atrial enlargement (hazard ratio, 4.29; 95% confidence interval, 1.30 to 14.09) were associated with supraventricular arrhythmia in the multivariate analysis. During a median follow-up of 40 months, 57 patients died, and cardiovascular disease was the main cause of death (52.6%). The variables associated with all-cause mortality in the Cox model were age (hazard ratio, 1.04 per year; 95% confidence interval, 1.00 to 1.08), C-reactive protein (hazard ratio, 1.04 per 1 mg/L; 95% confidence interval, 1.00 to 1.08), and supraventricular arrhythmia (hazard ratio, 3.21; 95% confidence interval, 1.29 to 7.96). Patients with supraventricular arrhythmia also had a higher risk of nonfatal cardiovascular events (hazard ratio, 4.32; 95% confidence interval, 2.11 to 8.83) and symptomatic atrial fibrillation during follow-up (hazard ratio, 17.19; 95% confidence interval, 2

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

PubMed

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

2016-12-07

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

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

Computer-assisted education system for arrhythmia (CAESAR).

PubMed

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

1984-08-01

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

Exploring digenic inheritance in arrhythmogenic cardiomyopathy.

PubMed

König, Eva; Volpato, Claudia Béu; Motta, Benedetta Maria; Blankenburg, Hagen; Picard, Anne; Pramstaller, Peter; Casella, Michela; Rauhe, Werner; Pompilio, Giulio; Meraviglia, Viviana; Domingues, Francisco S; Sommariva, Elena; Rossini, Alessandra

2017-12-08

Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder, characterized by the substitution of heart muscle with fibro-fatty tissue and severe ventricular arrhythmias, often leading to heart failure and sudden cardiac death. ACM is considered a monogenic disorder, but the low penetrance of mutations identified in patients suggests the involvement of additional genetic or environmental factors. We used whole exome sequencing to investigate digenic inheritance in two ACM families where previous diagnostic tests have revealed a PKP2 mutation in all affected and some healthy individuals. In family members with PKP2 mutations we determined all genes that harbor variants in affected but not in healthy carriers or vice versa. We computationally prioritized the most likely candidates, focusing on known ACM genes and genes related to PKP2 through protein interactions, functional relationships, or shared biological processes. We identified four candidate genes in family 1, namely DAG1, DAB2IP, CTBP2 and TCF25, and eleven candidate genes in family 2. The most promising gene in the second family is TTN, a gene previously associated with ACM, in which the affected individual harbors two rare deleterious-predicted missense variants, one of which is located in the protein's only serine kinase domain. In this study we report genes that might act as digenic players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations. Validation in larger cohorts is still required to prove the utility of this model.

Living on a knife edge-the daily struggle of coping with symptomatic cardiac arrhythmias.

PubMed

Withers, Kathleen L; Wood, Kathryn A; Carolan-Rees, Grace; Patrick, Hannah; Lencioni, Mauro; Griffith, Michael

2015-06-24

In 2010 a retrospective audit was undertaken to assess the viability of using PROMs in patients with symptomatic cardiac arrhythmias having undergone percutaneous arrhythmia ablation. A response rate of 74 % was achieved, with finding suggesting that arrhythmia patients reported a significant impact on their work, social and family life. To conduct a qualitative cross sectional survey to understand patients' perspectives of how cardiac arrhythmias affect their daily lives, as part of a program to develop a Patient Reported Outcome Measure (PROM). Twenty five patients aged 18 or over, diagnosed with a variety of symptomatic cardiac arrhythmias referred for a cardiac ablation procedure took part in cognitive interviews. These aimed to inform the development of a patient reported outcome measure and to determine factors important to this patient group. Common themes were identified using content analysis. Participants reported that symptoms of their arrhythmia caused them considerable problems and impacted adversely on their quality of life in many ways. This extended through daily routine, work and social activities and also to friends and family, with fear and anxiety being significant factors for most responders. Patients felt their illness was poorly understood, even by health professionals, and often reported that they felt isolated, lacking support and information. Symptomatic cardiac arrhythmias are a source of debilitating and life limiting symptoms, having a negative impact on quality of life. Symptoms and related complications are relevant across different arrhythmia substrates and patient groups. The study is registered on the Clinical Trials website, Identifier NCT01672528.

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.

Cardiac Arrhythmias in Experimental Syncope

DTIC Science & Technology

1958-11-01

cardiac toward respiratory alkalosis . Regardless of arriythmias by stress procedures. It follows these two extremes in the assumed change in that previous...frequently induced by respiratory maneuvers without syncope. Intravenous aidministration of atropine appatently prevented recurrence of cardiac...arrhythmia induced by respiratory maneuvers. Significant cardiac arrhythmia was also noted in simple orthostatic syncope. Loss of consciousness presents a

Carbon monoxide induces cardiac arrhythmia via induction of the late Na+ current.

PubMed

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; Peers, Chris

2012-10-01

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. To understand the cellular basis of CO-induced arrhythmias and to identify an effective therapeutic approach. Patch-clamp electrophysiology and confocal Ca(2+) 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. CO increased the sustained (late) component of the inward Na(+) current, resulting in prolongation of the action potential and the associated intracellular Ca(2+) 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, Na(v)1.5. 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. Our data indicate that the proarrhythmic effects of CO arise from activation of NO synthase, leading to NO-mediated nitrosylation of Na(V)1.5 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.

β1-Adrenoceptor blocker aggravated ventricular arrhythmia.

PubMed

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

2013-11-01

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

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

PubMed

Dijkman, B; Wellens, H J

2000-12-01

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

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.

Patient characteristics associated with false arrhythmia alarms in intensive care

PubMed Central

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

2017-01-01

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

Patient characteristics associated with false arrhythmia alarms in intensive care.

PubMed

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

2017-01-01

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

[Clinical analysis and genetic diagnosis of short-limb inherited short stature diseases in children].

PubMed

Li, Fang; Ma, Hong-Wei; Song, Ying; Hu, Man; Ren, Shuang; Yu, Ya-Fen; Zhao, Gui-Jie

2013-11-01

To analyze the clinical manifestations, bone X-ray findings and genetic analysis results of three short-limb inherited short stature diseases: achondroplasia (ACH), hypochondroplasia (HCH) and pseudoachondroplasia (PSACH). The clinical manifestations, bone X-ray findings, and genetic analysis results of 10 children with genetically confirmed short-limb inherited short stature diseases, including 4 cases of ACH 3 cases of HCH, and 3 cases of PSACH, were analyzed. The 10 patients had a mean body height of -3.69±1.79 SD, a mean sitting height/standing height ratio of 0.65±0.03, and a mean finger spacing/body height ratio of 0.93±0.04. Four ACH cases and 3 PSACH cases showed typical bone X-ray findings; one HCH case showed a smaller sciatic notch, and another HCH case showed no widening of interpedicular distance. G380R mutation in FGFR3 gene was detected in 3 of 4 ACH cases, and Y278C mutation in the other ACH case, N540K mutation in FGFR3 gene was detected in 3 HCH cases, and heterozygous mutations in COMP gene were detected in 3 PSACH cases. Children with ACH and PSACH have severer short stature and skeletal deformities than children with HCH, who have mild, atypical clinical manifestations. Bone X-ray and genetic analysis are helpful for the diagnosis and differential diagnosis of the three diseases. The mutational hotspots in two genes are involved in the three diseases, which is conducive to clinical genetic diagnosis.

Burden of arrhythmia in recreational marijuana users.

PubMed

Desai, Rupak; Patel, Upenkumar; Deshmukh, Abhishek; Sachdeva, Rajesh; Kumar, Gautam

2018-08-01

Marijuana or Cannabis is extensively used as a recreational substance globally. Case reports have reported cardiac arrhythmias immediately following recreational marijuana use. However, the burden of arrhythmias in hospitalized marijuana users have not been evaluated through prospective or cross-sectional studies. Therefore, we planned to measure temporal trends of the frequency of arrhythmias in hospitalized marijuana users using National Inpatient Sample (NIS) database in the United States. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-05-01

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

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

Heterotaxy syndrome and associated arrhythmias in pediatric patients.

PubMed

Niu, Mary C; Dickerson, Heather A; Moore, Judson A; de la Uz, Caridad; Valdés, Santiago O; Kim, Jeffrey J; Bard, David E; Morris, Shaine A; Miyake, Christina Y

2018-04-01

Heterotaxy syndrome (HS) is a rare disorder with complex anatomy involving misarrangements of the cardiac conduction system. Arrhythmias may be related to anatomic variations and contribute to morbidity. The purpose of this study was to investigate the associations between arrhythmias, anatomy, and outcomes in a large HS cohort. A single-center retrospective review of patients ≤21 years of age diagnosed with HS was performed. A total of 337 patients were included in the study. During median follow-up of 7 years (interquartile range 2-16 years), 129 patients (38%) had ≥1 clinically significant rhythm disturbance: tachyarrhythmias in 75 (22%), bradyarrhythmias in 29 (9%), and both in 25 (7%). Factors associated with tachyarrhythmia by multivariate analysis were at least moderate atrioventricular valve regurgitation (hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.11-2.50), single ventricle anatomy (HR 2.30; 95% CI 1.09-4.85), and pulmonary venous obstruction (HR 2.33; 95% CI 1.45-3.76). Isomerism subtype was not associated with tachyarrhythmias. In adjusted and unadjusted analyses, bradyarrhythmias (symptomatic sinus/atrial bradycardia and high-grade or complete heart block) were associated with left atrial isomerism (LAI) compared to right atrial isomerism (HR 7.12; 95% CI 3.01-16.9). The overall transplant-free survival of the cohort was 66%. Tachyarrhythmias, but not bradyarrhythmias, were associated with mortality or need for transplant (HR 2.24; 95% CI 1.45-3.46). Clinically significant arrhythmias are common in HS. Although bradyarrhythmias are associated with LAI, tachyarrhythmia occurrence may depend more on hemodynamic and anatomic factors than isomerism subtype. Tachyarrhythmias, but not bradyarrhythmias, are associated with death or need for transplant. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

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.

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

PubMed Central

Knollmann, Björn C

2013-01-01

As part of the series on Controversies in Cardiovascular Research, the article reviews the strengths and limitations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as models of cardiac arrhythmias. Specifically, the article attempts to answer the following questions: Which clinical arrhythmias can be modeled by iPSC-CM? How well can iPSC-CM model adult ventricular myocytes? What are the strengths and limitations of published iPSC-CM arrhythmia models? What new mechanistic insight has been gained? What is the evidence that would support using iPSC-CM to personalize anti-arrhythmic drug therapy? The review also discusses the pros and cons of using the iPSC-CM technology for modeling specific genetic arrhythmia disorders such as long QT syndrome, Brugada Syndrome or Catecholaminergic Polymorphic Ventricular Tachycardia. PMID:23569106

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.

Devices for Arrhythmia

MedlinePlus

... with recurrent arrhythmias, medical devices such as a pacemaker and implantable cardioverter defibrillator (ICD) can help by ... with an ICD Questions to ask your doctor Pacemakers Learn what an artificial pacemaker is, how it ...

Obstructive sleep apnoea-hypopnoea and arrhythmias: new updates.

PubMed

Vizzardi, Enrico; Sciatti, Edoardo; Bonadei, Ivano; D'Aloia, Antonio; Curnis, Antonio; Metra, Marco

2017-07-01

Obstructive sleep apnoea-hypopnoea (OSAH) is a prevalent condition characterized by repetitive pharyngeal collapse during sleep, leading to hypoxemia, hypercapnia, and persistent inspiratory efforts against an occluded airway until arousal. Several studies demonstrated that OSAH exerts acute and chronic effects on the cardiovascular system. Thus, although being a respiratory problem, the most important consequences of OSAH are cardiovascular, among which there are arrhythmias. The purpose of this review is to systematically analyse what has been recently published about the relationship between OSAH and every cardiac arrhythmia separately. We searched Pubmed, Scopus, Web of Science and Cochrane Collaboration databases for 'OSAHS arrhythmias', 'OSAH arrhythmias' and 'OSA arrhythmias'. We analyse 1298 articles and meta-analyses, excluding already edited reviews. Arrhythmias, especially of ventricular origin, are frequent in OSAH. Ventricular premature beats, couplets and ventricular tachycardia runs are even more frequent in patients suffering from heart failure. They may be due to left heart remodelling, overwork and ischaemia and can explain at least some sudden deaths occurring between midnight and 6 a.m. Sinus pauses and atrioventricular blocks are increased according to the severity of the disturbance and may be reduced by continuous positive airway pressure therapy, preventing pace-maker implantation. Finally, atrial fibrillation, resistance against antiarrhythmic drugs and recurrences after surgical procedures are strongly related to OSAH. Arrhythmias are frequent in OSAH. Treatment of OSAH may reduce some of them. An implantable cardioverter-defibrillator and continuous positive airway pressure should be considered in some patients.

Cardiovascular safety of prokinetic agents: A focus on drug-induced arrhythmias.

PubMed

Giudicessi, J R; Ackerman, M J; Camilleri, M

2018-02-14

Gastrointestinal sensorimotor dysfunction underlies a wide range of esophageal, gastric, and intestinal motility and functional disorders that collectively constitute nearly half of all referrals to gastroenterologists. As a result, substantial effort has been dedicated toward the development of prokinetic agents intended to augment or restore normal gastrointestinal motility. However, the use of several clinically efficacious gastroprokinetic agents, such as cisapride, domperidone, erythromycin, and tegaserod, is associated with unfavorable cardiovascular safety profiles, leading to restrictions in their use. The purpose of this review is to detail the cellular and molecular mechanisms that lead commonly to drug-induced cardiac arrhythmias, specifically drug-induced long QT syndrome, torsades de pointes, and ventricular fibrillation, to examine the cardiovascular safety profiles of several classes of prokinetic agents currently in clinical use, and to explore potential strategies by which the risk of drug-induced cardiac arrhythmia associated with prokinetic agents and other QT interval prolonging medications can be mitigated successfully. © 2018 John Wiley & Sons Ltd.

Gene panel testing for inherited cancer risk.

PubMed

Hall, Michael J; Forman, Andrea D; Pilarski, Robert; Wiesner, Georgia; Giri, Veda N

2014-09-01

Next-generation sequencing technologies have ushered in the capability to assess multiple genes in parallel for genetic alterations that may contribute to inherited risk for cancers in families. Thus, gene panel testing is now an option in the setting of genetic counseling and testing for cancer risk. This article describes the many gene panel testing options clinically available to assess inherited cancer susceptibility, the potential advantages and challenges associated with various types of panels, clinical scenarios in which gene panels may be particularly useful in cancer risk assessment, and testing and counseling considerations. Given the potential issues for patients and their families, gene panel testing for inherited cancer risk is recommended to be offered in conjunction or consultation with an experienced cancer genetic specialist, such as a certified genetic counselor or geneticist, as an integral part of the testing process. Copyright © 2014 by the National Comprehensive Cancer Network.

Idiopathic accelerated idioventricular rhythm or ventricular tachycardia originating from the right bundle branch: unusual type of ventricular arrhythmia.

PubMed

Chen, Minglong; Gu, Kai; Yang, Bing; Chen, Hongwu; Ju, Weizhu; Zhang, Fengxiang; Yang, Gang; Li, Mingfang; Lu, Xinzheng; Cao, Kejiang; Ouyang, Feifan

2014-12-01

Accelerated idioventricular rhythm (AIVR) or ventricular tachycardia (VT) originating from the right bundle branch (RBB) is rare and published clinical data on such arrhythmia are scarce. In this study, we will describe the clinical manifestations, diagnosis, and management of a cohort of patients with this novel arrhythmia. Eight patients (5 men; median age, 25 years) with RBB-AIVR/VT were consecutively enrolled in the study. Pharmacological testing, exercise treadmill testing, electrophysiological study, and catheter ablation were performed in the study patients, and ECG features were characterized. All RBB-AIVR/VTs were of typical left bundle-branch block morphology with atrioventricular dissociation. The arrhythmias, which demonstrated chronotropic variability, were often isorhythmic with sinus rhythm and were accelerated by physical exercise, stress, and intravenous isoprenaline infusion. The rate of RBB-AIVR/VT varied from 45 to 200 beats per minute. Two patients experienced syncope, and 3 had impaired left ventricular function. Metoprolol was proven to be the most effective drug to decelerate the arrhythmia rate and relieve symptoms. Electrophysiology study was performed in 5 patients and the earliest activation with a sharp RBB potential was localized in the mid or distal RBB area. Catheter ablation terminated the arrhythmia with subsequent RBB block morphology during sinus rhythm. During follow-up, patients' symptoms were controlled with normalization of left ventricular function either on metoprolol or by catheter ablation. RBB-AIVR/VT is an unusual type of ventricular arrhythmia. It can result in significant symptoms and depressed ventricular function and can be successfully treated with catheter ablation. © 2014 American Heart Association, Inc.

Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records.

PubMed

Van Driest, Sara L; Wells, Quinn S; Stallings, Sarah; Bush, William S; Gordon, Adam; Nickerson, Deborah A; Kim, Jerry H; Crosslin, David R; Jarvik, Gail P; Carrell, David S; Ralston, James D; Larson, Eric B; Bielinski, Suzette J; Olson, Janet E; Ye, Zi; Kullo, Iftikhar J; Abul-Husn, Noura S; Scott, Stuart A; Bottinger, Erwin; Almoguera, Berta; Connolly, John; Chiavacci, Rosetta; Hakonarson, Hakon; Rasmussen-Torvik, Laura J; Pan, Vivian; Persell, Stephen D; Smith, Maureen; Chisholm, Rex L; Kitchner, Terrie E; He, Max M; Brilliant, Murray H; Wallace, John R; Doheny, Kimberly F; Shoemaker, M Benjamin; Li, Rongling; Manolio, Teri A; Callis, Thomas E; Macaya, Daniela; Williams, Marc S; Carey, David; Kapplinger, Jamie D; Ackerman, Michael J; Ritchie, Marylyn D; Denny, Joshua C; Roden, Dan M

2016-01-05

Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants. To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in arrhythmia susceptibility genes. This prospective cohort study included 2022 individuals recruited for nonantiarrhythmic drug exposure phenotypes from October 5, 2012, to September 30, 2013, for the Electronic Medical Records and Genomics Network Pharmacogenomics project from 7 US academic medical centers. Variants in SCN5A and KCNH2, disease genes for long QT and Brugada syndromes, were assessed for potential pathogenicity by 3 laboratories with ion channel expertise and by comparison with the ClinVar database. Relevant phenotypes were determined from EMRs, with data available from 2002 (or earlier for some sites) through September 10, 2014. One or more variants designated as pathogenic in SCN5A or KCNH2. Arrhythmia or electrocardiographic (ECG) phenotypes defined by International Classification of Diseases, Ninth Revision (ICD-9) codes, ECG data, and manual EMR review. Among 2022 study participants (median age, 61 years [interquartile range, 56-65 years]; 1118 [55%] female; 1491 [74%] white), a total of 122 rare (minor allele frequency <0.5%) nonsynonymous and splice-site variants in 2 arrhythmia susceptibility genes were identified in 223 individuals (11% of the study cohort). Forty-two variants in 63 participants were designated potentially pathogenic by at least 1 laboratory or ClinVar, with low concordance across laboratories (Cohen κ = 0.26). An ICD-9 code for arrhythmia was found in 11 of 63 (17%) variant carriers vs 264 of 1959 (13%) of those without variants (difference, +4%; 95% CI, -5% to +13

Arrhythmia during extracorporeal shock wave lithotripsy.

PubMed

Zeng, Z R; Lindstedt, E; Roijer, A; Olsson, S B

1993-01-01

A prospective study of arrhythmia during extracorporeal shock wave lithotripsy (ESWL) was performed in 50 patients, using an EDAP LT01 piezoelectric lithotriptor. The 12-lead standard ECG was recorded continuously for 10 min before and during treatment. One or more atrial and/or ventricular ectopic beats occurred during ESWL in 15 cases (30%). The occurrence of arrhythmia was similar during right-sided and left-sided treatment. One patient developed multifocal ventricular premature beats and ventricular bigeminy; another had cardiac arrest for 13.5 s. It was found that various irregularities of the heart rhythm can be caused even by treatment with a lithotriptor using piezoelectric energy to create the shock wave. No evidence was found, however, that the shock wave itself rather than vagal activation and the action of sedo-analgesia was the cause of the arrhythmia. For patients with severe underlying heart disease and a history of complex arrhythmia, we suggest that the ECG be monitored during treatment. In other cases, we have found continuous monitoring of oxygen saturation and pulse rate with a pulse oximeter to be perfectly reliable for raising the alarm when depression of respiration and vaso-vagal reactions occur.

Inherited Thrombophilia and Pregnancy Complications: Should We Test?

PubMed

Arachchillage, Deepa R J; Makris, Mike

2018-06-04

Recurrent miscarriages and pregnancy-related complications cause significant stress to couples looking for successful pregnancy outcome as well as to health care professionals. There is conflicting evidence with respect to the presence and the strength of associations between inherited thrombophilia and these complications. A complete thrombophilia screen is expensive, and no proven effective treatment for women with recurrent miscarriage and inherited thrombophilia is currently available. Based on the concept of microvascular thrombosis of the placenta, women with recurrent miscarriage and placenta-related complications frequently get treated with antithrombotic therapy. In this narrative review, the authors explore the evolving understanding and evidence of inherited thrombophilia in recurrent miscarriages and other pregnancy complications, and whether antithrombotic treatment would modify pregnancy outcome in women with inherited thrombophilia. Finally, they provide some personal recommendations based on available evidence for clinical practice. In summary, inherited thrombophilia testing is not required outside a clinical trial for women with recurrent pregnancy losses or late pregnancy complications. The presence of thrombophilia markers does not generally indicate additional therapy during pregnancy, even if a heritable thrombophilic defect is found in women with recurrent miscarriages or late pregnancy complications. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genetic testing in heritable cardiac arrhythmia syndromes: differentiating pathogenic mutations from background genetic noise.

PubMed

Giudicessi, John R; Ackerman, Michael J

2013-01-01

In this review, we summarize the basic principles governing rare variant interpretation in the heritable cardiac arrhythmia syndromes, focusing on recent advances that have led to disease-specific approaches to the interpretation of positive genetic testing results. Elucidation of the genetic substrates underlying heritable cardiac arrhythmia syndromes has unearthed new arrhythmogenic mechanisms and given rise to a number of clinically meaningful genotype-phenotype correlations. As such, genetic testing for these disorders now carries important diagnostic, prognostic, and therapeutic implications. Recent large-scale systematic studies designed to explore the background genetic 'noise' rate associated with these genetic tests have provided important insights and enhanced how positive genetic testing results are interpreted for these potentially lethal, yet highly treatable, cardiovascular disorders. Clinically available genetic tests for heritable cardiac arrhythmia syndromes allow the identification of potentially at-risk family members and contribute to the risk-stratification and selection of therapeutic interventions in affected individuals. The systematic evaluation of the 'signal-to-noise' ratio associated with these genetic tests has proven critical and essential to assessing the probability that a given variant represents a rare pathogenic mutation or an equally rare, yet innocuous, genetic bystander.

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

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

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.

Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism

PubMed Central

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

2016-01-01

Myocardial fibrosis is an important risk factor for cardiac arrhythmias. Previous experimental and numerical studies have shown that the texture and spatial distribution of fibrosis may play an important role in arrhythmia onset. Here, we investigate how spatial heterogeneity of fibrosis affects arrhythmia onset using numerical methods. We generate various tissue textures that differ by the mean amount of fibrosis, the degree of heterogeneity and the characteristic size of heterogeneity. We study the onset of arrhythmias using a burst pacing protocol. We confirm that spatial heterogeneity of fibrosis increases the probability of arrhythmia induction. This effect is more pronounced with the increase of both the spatial size and the degree of heterogeneity. The induced arrhythmias have a regular structure with the period being mostly determined by the maximal local fibrosis level. We perform ablations of the induced fibrillatory patterns to classify their type. We show that in fibrotic tissue fibrillation is usually of the mother rotor type but becomes of the multiple wavelet type with increase in tissue size. Overall, we conclude that the most important factor determining the formation and dynamics of arrhythmia in heterogeneous fibrotic tissue is the value of maximal local fibrosis. PMID:26861111

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.

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

PubMed

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

2012-10-01

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

Ventricular Arrhythmias in the North American Multidisciplinary Study of ARVC

PubMed Central

Link, Mark S.; Laidlaw, Douglas; Polonsky, Bronislava; Zareba, Wojciech; McNitt, Scott; Gear, Kathleen; Marcus, Frank; Mark Estes, NA

2015-01-01

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with sudden cardiac death. However, the selection of patients for implanted cardioverter-defibrillators (ICDs), as well as programming of the ICD, is unclear. OBJECTIVES The objective of this study was to identify predictors, characteristics, and treatment of ventricular arrhythmias in patients with ARVC. METHODS The Multidisciplinary Study of Right Ventricular Cardiomyopathy established the North American ARVC Registry and enrolled patients with a diagnosis of ARVC. Patients were followed prospectively. RESULTS Of 137 patients enrolled, 108 received ICDs. Forty-eight patients had 502 sustained episodes of ventricular arrhythmias, including 489 that were monomorphic and 13 that were polymorphic. In the patients with ICDs, independent predictors of ventricular arrhythmias in follow-up included spontaneous sustained ventricular arrhythmias before ICD implantation and T-wave inversions inferiorly. The only independent predictor for life-threatening arrhythmias, defined as sustained ventricular tachycardia (VT) ≥240 beats/min or ventricular fibrillation, was a younger age at enrollment. Anti-tachycardia pacing (ATP), independent of the cycle length of the VT, was successful in terminating 92% of VT episodes. CONCLUSIONS In the North American ARVC Registry, the majority of ventricular arrhythmias in follow-up are monomorphic. Risk factors for ventricular arrhythmias were spontaneous ventricular arrhythmias before enrollment and a younger age at ICD implantation. ATP is highly successful in terminating VT, and all ICDs should be programmed for ATP, even for rapid VT. PMID:25011714

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.

Tpeak - Tend and Tpeak - Tend /QT ratio as markers of ventricular arrhythmia risk in cardiac resynchronization therapy patients.

PubMed

Barbhaiya, Chirag; Po, Jose Ricardo F; Hanon, Sam; Schweitzer, Paul

2013-01-01

Cardiac resynchronization therapy (CRT) increases transmural dispersion of repolarization (TDR) and can be pro-arrhythmic. However, overall arrhythmia risk was not increased in large-scale CRT clinical trials. Increased TDR as measured by T(peak ) -T(end) (TpTe) was associated with arrhythmia risk in CRT in a single-center study. This study investigates whether QT interval, TpTe, and TpTe/QT ratio are associated with ventricular arrhythmias in patients with CRT-defibrillator (CRT-D). Post-CRT-D implant electrocardiograms of 128 patients (age 71.3 years ± 10.3) with at least 2 months of follow-up at our institution's device clinic (mean follow-up of 28.5 months ± 17) were analyzed for QT interval, TpTe, and TpTe/QT ratio. Incidence of ventricular arrhythmias was determined based on routine and directed device interrogations. Appropriate implantable cardioverter-defibrillator therapy for sustained ventricular tachycardia or ventricular fibrillation was delivered in 18 patients (14%), and nonsustained ventricular tachycardia (NSVT) was detected but did not require therapy in 58 patients (45%). Patients who received appropriate defibrillator therapy had increased TpTe/QT ratio (0.24 ± 0.03 ms vs 0.20 ± 0.04, P = 0.0002) and increased TpTe (105.56 ± 20.36 vs 87.82 ± 22.32 ms, P = 0.002), and patients with NSVT had increased TpTe/QT ratio (0.22 ± 0.04 vs 0.20 ± 0.04, P = 0.016). Increased QT interval was not associated with risk of ventricular arrhythmia. The relative risk for appropriate defibrillator therapy of T(p) T(e) /QT ratio ≥ 0.25 was 3.24 (P = 0.016). Increased TpTe and increased TpTe/QT ratio are associated with increased incidence of ventricular arrhythmias in CRT-D. The utility of TpTe interval and TpTe/QT ratio as potentially modifiable risk factors for ventricular arrhythmias in CRT requires further study. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Inherited metabolic disorders in Thailand.

PubMed

Wasant, Pornswan; Svasti, Jisnuson; Srisomsap, Chantragan; Liammongkolkul, Somporn

2002-08-01

The study of inborn errors of metabolism (IEM) in Thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn Research Institute) and abroad (Japan and the United States). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in Thailand, research and pilot studies in newborn screening in Thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj Hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).

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

Pregnancy complications in women with inherited thrombophilia.

PubMed

Weintraub, Adi Y; Sheiner, Eyal; Levy, Amalia; Yerushalmi, Ronit; Mazor, Moshe

2006-06-01

The purpose of this study was to examine whether women with inherited thrombophilia have an increased risk of developing pregnancy complications. All singleton pregnancies with known inherited thrombophilia were compared to those without inherited thrombophilia for deliveries during the years 2000-2002 in a tertiary medical center. Data regarding inherited thrombophilia (International Classification of Disease 9th revision, Clinical Modification code 286.3) were available from the perinatal database in our center. Women lacking prenatal care were excluded from the analysis. Stratified analysis, using a multiple logistic regression model, was performed to control for confounders. Out of 32,763 singleton deliveries that occurred during the study period, 0.2% (n=57) of the women were diagnosed with inherited thrombophilia. Using a multivariate analysis, with backward elimination, the following conditions were significantly associated with inherited thrombophilia: previous fetal losses [odds ratio (OR)=5.5; 95% confidence interval (CI) 2.9-10.3; P<0.001], recurrent abortions (OR=9.5; 95% CI 5.5-16.3; P<0.001), fertility treatments (OR=3.7; 95% CI 1.3-10.6; P=0.014), and intrauterine growth restriction (OR=7.2; 95% CI 3.4-15; P<0.001). Perinatal mortality was significantly higher in women with inherited thrombophilia than in those without known thrombophilia 5.3% (3/57) versus 0.6% (477/32,763) P=0.017. However, inherited thrombophilia was not found to be an independent risk factor for perinatal mortality (OR=3.05; 95% CI 0.90-10.3; P<0.073) in a multivariate analysis with perinatal mortality as the outcome variable, controlling for recurrent abortions, IUGR, and gestational age. Inherited thrombophilia, associated with previous fetal losses, recurrent abortions, fertility treatments, and intrauterine growth restriction, was not an independent risk factor for perinatal mortality.

Classification of arrhythmia using hybrid networks.

PubMed

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

2011-12-01

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

Electrocardiogram changes and atrial arrhythmias in individuals carrying sodium channel SCN5A D1275N mutation.

PubMed

Vanninen, Sari U M; Nikus, Kjell; Aalto-Setälä, Katriina

2017-09-01

The cardiac sodium channel SCN5A regulates atrioventricular and ventricular depolarization as well as cardiac conduction. Patients with cardiac electrical abnormalities have an increased risk of sudden cardiac death (SCD) and cardio-embolic stroke. Optimal management of cardiac disease includes the understanding of association between the causative mutations and the clinical phenotype. A 12-lead electrocardiogram (ECG) is an easy and inexpensive tool for finding risk patients. A blood sample for DNA extraction was obtained in a Finnish family with 43 members; systematic 12-lead ECG analysis was performed in 13 of the family members carrying an SCN5A D1275N mutation. Conduction defects and supraventricular arrhythmias, including atrial fibrillation/flutter, atrioventricular nodal re-entry tachycardia (AVNRT) and junctional rhythm were searched for. Five (38%) mutation carriers had fascicular or bundle branch block, 10 had atrial arrhythmias; no ventricular arrhythmias were found. Notching of the R- and S waves - including initial QRS fragmentation - and prolonged S-wave upstroke were present in all the affected family members. Notably, four (31%) affected family members had a stroke before the age of 31 and two experienced premature death. A 12-lead ECG can be used to predict arrhythmias in SCN5A D1275N mutation carriers. Key messages The 12-lead ECG may reveal cardiac abnormalities even before clinical symptoms occur. Specific ECG findings - initial QRS fragmentation, prolonged S-wave upstroke as well as supraventricular arrhythmias - were frequently encountered in all SCN5A D1257N mutation carriers. ECG follow-up is recommended for all SCN5A D1275N mutation carriers.

Emotional behavior and arrhythmias induced in cats by hypothalamic stimulation.

PubMed

Tashiro, N; Tanaka, T; Fukumoto, T; Hirata, K; Nakao, H

1985-03-18

As the relationship between emotional behavior and electrocardiographic (ECG) change induced by hypothalamic stimulation is poorly understood, eighty-four points in various areas within the hypothalamus in conscious cats were stimulated electrically through chronically implanted electrodes, the objective being to clarify the behavior accompanying ECG changes, in particular poststimulus arrhythmias. Forty-one of 84 points elicited behavioral patterns such as defense reaction, pseudo-rage and restlessness (classified as group A), and in twenty-one (51%) of these 41 points arrhythmias occurred after cessation of stimulation. Forty-three of 84 points elicited behavioral patterns including predatory, exploratory and other behavioral responses (classified as group B), and in three (7%) of 43 points, poststimulus arrhythmias followed. Under light anesthesia, stimulations of twofold current intensity were applied at these points, and the incidences of the arrhythmias did not change in either group. The arrhythmia-inducing area in the cases of group A was found to lie dorsal and caudal to the optic chiasma and to extend caudally in the fornix. Three points in the cases of group B were located in the outer area of the aforementioned area. These studies showed that arrhythmias and group A behavior were observed mainly from stimulation of the anterior hypothalamus, whereas stimulation of other areas of the hypothalamus, including the lateral and the posterolateral hypothalamus, produced group B behavior and no arrhythmias.

[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.

Arrhythmias in Patients with Atrial Defects.

PubMed

Contractor, Tahmeed; Mandapati, Ravi

2017-06-01

Atrial arrhythmias are common in patients with atrial septal defects. A myriad of factors are responsible for these that include remodeling related to the defect and scar created by the repair or closure. An understanding of potential arrhythmias, along with entrainment and high-density activation mapping can result in accurate diagnosis and successful ablation. Atrial fibrillation is being seen increasingly after patent foramen ovale closure and may be the primary etiology of recurrent stroke in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Family history of atrial fibrillation as a predictor of atrial substrate and arrhythmia recurrence in patients undergoing atrial fibrillation catheter ablation.

PubMed

Kapur, Sunil; Kumar, Saurabh; John, Roy M; Stevenson, William G; Tedrow, Usha B; Koplan, Bruce A; Epstein, Laurence M; MacRae, Calum A; Michaud, Gregory F

2018-06-01

A commonly held notion is that patients with a family history of atrial fibrillation (AF) have worse atrial substrate and higher rates of arrhythmia recurrence following ablation. We sought to examine differences in atrial substrate and catheter ablation outcomes in patients with a 1st degree family member with paroxysmal or persistent AF (PeAF) compared to those without. A total of 256 consecutive patients undergoing their 1st ablation for AF (123 paroxysmal, 133 persistent) with >1 year follow up were included. The presence of one 1st-degree family relative was defined as a 'positive family history'. Clinical characteristics, electroanatomic map findings, ablation characteristics and outcomes were compared in patients with and without a positive family history of AF. Patients with paroxysmal fibrillation with a positive family history (n = 57; 46%) had similar clinical characteristics and arrhythmia recurrence after catheter ablation as those without. Of those that recurred, patients with a positive family history were more likely to have progressed to PeAF (P = 0.05). Patients with PeAF with a positive family history (n = 75; 56%) had similar clinical characteristics, electroanatomic mapping findings and ablation characteristics, but worse long term arrhythmia free survival (P = 0.04). The presence of a 1st-degree family member with AF does not impact the clinical outcomes of catheter ablation for paroxysmal AF. However, a positive family history is associated with worse arrhythmia free survival in patients with PeAF. This finding is not explained by differences in clinical characteristics, atrial substrate assessed by voltage maps or ablation characteristics.

Management of supraventricular arrhythmias in adults with congenital heart disease.

PubMed

Wasmer, Kristina; Eckardt, Lars

2016-10-15

Supraventricular arrhythmias are a frequent complication in adults with congenital heart disease (ACHD). The prevalence increases with time since surgery, complexity of the underlying defect, type of repair and older age at surgery. Arrhythmias are the most frequent reason for hospital admission and along with heart failure the leading cause of death. The arrhythmia-associated increase in morbidity and mortality makes their management a key task in patients with ACHD. Intra-atrial re-entry is the most frequent arrhythmia mechanism. Less common arrhythmia mechanisms are supraventricular tachycardias in the presence of an accessory pathway, atrioventricular nodal re-entrant tachycardia or focal tachycardias. Patient management includes stroke prevention, acute termination and prevention of arrhythmia recurrence. Acute treatment depends on patients' symptoms. In cases of haemodynamic instability, immediate cardioversion is warranted. For stable patients, acute treatment includes rate control and termination by antiarrhythmic drugs or electrical cardioversion. Following a symptomatic arrhythmia, catheter ablation or treatment with antiarrhythmic drugs is recommended to prevent recurrences. Advances in mapping and ablation technology are now associated with high success rates of catheter ablation. In patients with a complex substrate recurrence rates of 50% remain high. However, in the presence of side effects and complications associated with long-term antiarrhythmic drug therapy, redo procedures are encouraged by current guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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.

Emerging molecular therapies targeting myocardial infarction-related arrhythmias.

PubMed

Driessen, Helen E; van Veen, Toon A B; Boink, Gerard J J

2017-04-01

Cardiac disease is the leading cause of death in the developed world. Ventricular arrhythmias associated with myocardial ischaemia and/or infarction are a major contributor to cardiovascular mortality, and require improved prevention and treatment. Drugs, devices, and radiofrequency catheter ablation have made important inroads, but have significant limitations ranging from incomplete success to undesired toxicities and major side effects. These limitations derive from the nature of the intervention. Drugs are frequently ineffective, target the entire heart, and often do not deal with the specific arrhythmia trigger or substrate. Devices can terminate rapid rhythms but at best indirectly affect the underlying disease, while ablation, even when appropriately targeted, induces additional tissue damage. In contrast, exploration of gene and cell therapies are expected to provide a targeted, non-destructive, and potentially regenerative approach to ischaemia- and infarction-related arrhythmias. Although these approaches are in the early stages of development, they carry substantial potential to advance arrhythmia prevention and treatment. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

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

PubMed

Macrae, Calum A

2010-07-01

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

Protective effects of Hawthorn (Crataegus oxyacantha) extract against digoxin-induced arrhythmias in rats.

PubMed

Alp, Hayrullah; Soner, Burak Cem; Baysal, Tamer; Şahin, Ayşe Saide

2015-01-01

Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study is to evaluate the antiarrhythmic effect of Crataegus oxyacantha extract on digoxin-induced arrhythmias in anesthetized Wistar rats. Control and experimental groups were evaluated for arrhythmias induced by digoxin. Fifteen rats (7 as controls and 8 as the experimental group) were included in the study. The dry fruits of 100 mg Crataegus oxyacantha were extracted by percolation method. Digoxin, at a dose of 40 µg/kg/min, was infused to form the arrhythmias in all rats. Simultaneously, the extract was infused into the experimental group, while 0.9% NaCl was infused into control group. Electrocardiographic QRS prolongation and arterial blood pressure changes were analyzed. The experimental group lived longer (62.13±2.20 min) than the controls (p=0.002). On the other hand, the time to beginning of QRS prolongation did not differ between the two groups (p=0.812). Bradycardia was significant in the control group (288.01±10.54 beat/min and p=0.01). The maximum QRS duration was observed in the control group during the digoxin and 0.9% NaCl infusion period (53.29±3.99 ms and p=0.001). Also, the durations of atrial and ventricular arrhythmias were shorter in the experimental group. However, arterial blood pressure dipping was significant in the experimental group (23.67±10.89 mm Hg and p<0.001). Crataegus oxyacantha alcoholic extract produced an antiarrhythmic effect that was induced by digoxin in Wistar rats. However, in the clinical use of this extract, the hypotensive effect should be considered. Also, the alcoholic extract of Crataegus oxyacantha may be an alternative treatment medication for arrhythmias induced by digoxin toxicity in humans.

Protective effects of Hawthorn (Crataegus oxyacantha) extract against digoxin-induced arrhythmias in rats

PubMed Central

Alp, Hayrullah; Soner, Burak Cem; Baysal, Tamer; Şahin, Ayşe Saide

2016-01-01

Objective: Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study is to evaluate the antiarrhythmic effect of Crataegus oxyacantha extract on digoxin-induced arrhythmias in anesthetized Wistar rats. Methods: Control and experimental groups were evaluated for arrhythmias induced by digoxin. Fifteen rats (7 as controls and 8 as the experimental group) were included in the study. The dry fruits of 100 mg Crataegus oxyacantha were extracted by percolation method. Digoxin, at a dose of 40 μg/kg/min, was infused to form the arrhythmias in all rats. Simultaneously, the extract was infused into the experimental group, while 0.9% NaCl was infused into control group. Electrocardiographic QRS prolongation and arterial blood pressure changes were analyzed. Results: The experimental group lived longer (62.13±2.20 min) than the controls (p=0.002). On the other hand, the time to beginning of QRS prolongation did not differ between the two groups (p=0.812). Bradycardia was significant in the control group (288.01±10.54 beat/min and p=0.01). The maximum QRS duration was observed in the control group during the digoxin and 0.9% NaCl infusion period (53.29±3.99 ms and p=0.001). Also, the durations of atrial and ventricular arrhythmias were shorter in the experimental group. However, arterial blood pressure dipping was significant in the experimental group (23.67±10.89 mm Hg and p<0.001). Conclusion: Crataegus oxyacantha alcoholic extract produced an antiarrhythmic effect that was induced by digoxin in Wistar rats. However, in the clinical use of this extract, the hypotensive effect should be considered. Also, the alcoholic extract of Crataegus oxyacantha may be an alternative treatment medication for arrhythmias induced by digoxin toxicity in humans. PMID:25880053

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

PubMed

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

2012-04-01

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

Atrial arrhythmias after lung transplant: underlying mechanisms, risk factors, and prognosis.

PubMed

Orrego, Carlos M; Cordero-Reyes, Andrea M; Estep, Jerry D; Seethamraju, Harish; Scheinin, Scott; Loebe, Matthias; Torre-Amione, Guillermo

2014-07-01

Atrial arrhythmias (AAs) early after lung transplant are frequent and have a significant impact on morbidity and mortality. However, the pathogenesis of AAs after lung transplant remains incompletely understood. In this study we aimed to determine the prevalence of atrial fibrillation (AF) and other AAs, as well as risk factors, clinical outcomes and possible underlying mechanisms associated with AAs after lung transplant. A retrospective analysis was performed on 382 patients who underwent lung transplantation from 2000 to 2010. A 12-lead electrocardiogram (ECG) was obtained and AAs classified as AF and other AAs (atrial flutter [AFL] and supraventricular tachycardia [SVT]). Multivariate logistic regression analysis was performed to determine predictors, and Kaplan-Meier survival curves were constructed. The incidence of AAs was 25%; 17.8% developed AF and 7.6% other AAs (AFL/SVT). The major indication for transplant was idiopathic pulmonary fibrosis (IPF, 35%). Significant predictors of AF were as follows: age; IPF; left atrial enlargement; diastolic dysfunction; and history of coronary artery disease (CAD). Risk factors for other AAs (AFL/SVT) were: age; right ventricle dysfunction; right ventricular enlargement; and elevated right atrial pressure (RAP). One-year mortality was higher in the arrhythmia group (21.5% arrhythmia vs 15.7% no-arrhythmia group; p < 0.05). In addition, patients treated with anti-arrhythmic medications had higher mortality (p < 0.05). AAs are common after lung transplantation. Risk factors for developing either AF or other AAs (AFL/SVT) are different. The development of early AAs post-transplant is associated with prolonged post-operative stay and increased mortality. A rate-control strategy should be used as first-line therapy and anti-arrhythmic agents reserved for those patients who do not respond to the initial treatment. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights

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

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

Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia.

PubMed

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

2016-02-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inheritable cardiac disease predisposing to malignant ventricular arrhythmias. We aimed to explore the incidence and severity of ventricular arrhythmias in patients with CPVT before the initiation of β-blocker treatment, when treated with β1-selective β-blockers, and when treated with nadolol. In this study, 34 patients with CPVT were included (mean age 34 ± 19 years; 15 (44%) women; 30 (88%) ryanodine receptor 2 variant positive). We performed 3 bicycle exercise stress tests in each patient: (1) before the initiation of β-blocker treatment, (2) after >6 weeks of treatment with β1-selective β-blockers and (3) after >6 weeks of treatment with nadolol. We recorded resting and maximum heart rates and the most severe ventricular arrhythmia occurring. Severity of arrhythmias was scored as 1 point for no arrhythmias or only single ventricular extrasystoles, 2 points for >10 ventricular extrasystoles per minute or bigeminy, 3 points for couplets, and 4 points for nonsustained ventricular tachycardia or sustained ventricular tachycardia. Resting heart rate was similar during treatment with nadolol and β1-selective β-blockers (54 ± 10 beats/min vs 56 ± 14 beats/min; P = .50), while maximum heart rate was lower during treatment with nadolol compared with β1-selective β-blockers (122 ± 21 beats/min vs 139 ± 24 beats/min; P = .001). Arrhythmias during exercise stress testing were less severe during treatment with nadolol compared with during treatment with β1-selective β-blockers (arrhythmic score 1.6 ± 0.9 vs 2.5 ± 0.8; P < .001) and before the initiation of β-blocker treatment (arrhythmic score 1.6 ± 0.9 vs 2.7 ± 0.9; P = .001); however, no differences were observed during treatment with β1-selective β-blockers compared with before the initiation of β-blocker treatment (arrhythmic score 2.5 ± 0.8 vs 2.7 ± 0.9; P = .46). The incidence and severity of ventricular arrhythmias decreased

Inheritable and sporadic non-autoimmune hyperthyroidism.

PubMed

Ferraz, Carolina; Paschke, Ralf

2017-03-01

Hyperthyroidism is a clinical state that results from high thyroid hormone levels which has multiple etiologies, manifestations, and potential therapies. Excluding the autoimmune Graves disease, autonomic adenomas account for the most import cause of non-autoimmune hyperthyroidism. Activating germline mutations of the TSH receptor are rare etiologies for hyperthyroidism. They can be inherited in an autosomal dominant manner (familial or hereditary, FNAH), or may occur sporadically as a de novo condition, also called: persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH). These three conditions: autonomic adenoma, FNAH and PSNAH constitute the inheritable and sporadic non-autoimmune hyperthyroidism. Particularities in epidemiology, etiology, molecular and clinical aspects of these three entities will be discussed in this review in order to guide to an accurate diagnosis allowing among others genetic counseling and presymptomatic diagnosis for the affected families. The optimal treatment based on the right diagnosis will avoid consequences of a persistent or relapsing hyperthyroidism. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-08-01

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

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

PubMed Central

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.

2015-01-01

One quarter of deaths associated with Rett syndrome (RTT), an X-linked neurodevelopmental disorder, are sudden and unexpected. RTT is associated with prolonged QTc interval (LQT), and LQT-associated cardiac arrhythmias are a potential cause of unexpected death. The standard of care for LQT in RTT is treatment with β-adrenergic antagonists; however, recent work indicates that acute treatment of mice with RTT with a β-antagonist, propranolol, does not prevent lethal arrhythmias. In contrast, acute treatment with the Na+ channel blocker phenytoin prevented arrhythmias. Chronic dosing of propranolol may be required for efficacy; therefore, we tested the efficacy of chronic treatment with either propranolol or phenytoin on RTT mice. Phenytoin completely abolished arrhythmias, whereas propranolol showed no benefit. Surprisingly, phenytoin also normalized weight and activity, but worsened breathing patterns. To explore the role of Na+ channel blockers on QT in people with RTT, we performed a retrospective analysis of QT status before and after Na+ channel blocker antiepileptic therapies. Individuals with RTT and LQT significantly improved their QT interval status after being started on Na+ channel blocker antiepileptic therapies. Thus, Na+ channel blockers should be considered for the clinical management of LQT in individuals with RTT. PMID:25713300

Link between Hypoglycemia and Cardiac Arrhythmias: An Answer to Why Tight Glycemic Control May Increase Mortality in ...

MedlinePlus

... Cardiac Arrhythmias: An Answer to Why Tight Glycemic Control May Increase Mortality in People with Diabetes and ... funded clinical trial that examined whether tight glycemic control could reduce cardiovascular events in people with type ...

RNA interference-based therapeutics for inherited long QT syndrome.

PubMed

Li, Guoliang; Ma, Shuting; Sun, Chaofeng

2015-08-01

Inherited long QT syndrome (LQTS) is an electrical heart disorder that manifests with syncope, seizures, and increased risk of torsades de pointes and sudden cardiac death. Dominant-negative current suppression is a mechanism by which pathogenic proteins disrupt the function of ion channels in inherited LQTS. However, current approaches for the management of inherited LQTS are inadequate. RNA interference (RNAi) is a powerful technique that is able to suppress or silence the expression of mutant genes. RNAi may be harnessed to knock out mRNAs that code for toxic proteins, and has been increasingly recognized as a potential therapeutic intervention for a range of conditions. The present study reviews the literature for RNAi-based therapeutics in the treatment of inherited LQTS. Furthermore, this review discusses the combined use of RNAi with the emerging technology of induced pluripotent stem cells for the treatment of inherited LQTS. In addition, key challenges that must be overcome prior to RNAi-based therapies becoming clinically applicable are addressed. In summary, RNAi-based therapy is potentially a powerful therapeutic intervention, although a number of difficulties remain unresolved.

RNA interference-based therapeutics for inherited long QT syndrome

PubMed Central

LI, GUOLIANG; MA, SHUTING; SUN, CHAOFENG

2015-01-01

Inherited long QT syndrome (LQTS) is an electrical heart disorder that manifests with syncope, seizures, and increased risk of torsades de pointes and sudden cardiac death. Dominant-negative current suppression is a mechanism by which pathogenic proteins disrupt the function of ion channels in inherited LQTS. However, current approaches for the management of inherited LQTS are inadequate. RNA interference (RNAi) is a powerful technique that is able to suppress or silence the expression of mutant genes. RNAi may be harnessed to knock out mRNAs that code for toxic proteins, and has been increasingly recognized as a potential therapeutic intervention for a range of conditions. The present study reviews the literature for RNAi-based therapeutics in the treatment of inherited LQTS. Furthermore, this review discusses the combined use of RNAi with the emerging technology of induced pluripotent stem cells for the treatment of inherited LQTS. In addition, key challenges that must be overcome prior to RNAi-based therapies becoming clinically applicable are addressed. In summary, RNAi-based therapy is potentially a powerful therapeutic intervention, although a number of difficulties remain unresolved. PMID:26622327

[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.

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.

Simulation system of arrhythmia using ActiveX control.

PubMed

Takeuchi, Akihiro; Hirose, Minoru; Hamada, Atsushi; Ikeda, Noriaki

2005-07-01

A simulation system for arrhythmias has been developed using Windows-based software technology, ActiveX control. The cardiac module consists of six cells, the sinus, atrium, AV node, ventricle, and ectopic foci. The physiological properties of the cells, the automaticity and conduction delay, were modelled, respectively, by the phase response curve and the excitability recovery curve. Cell functions were implemented in the ActiveX control and incorporated into the cardiac module. The system draws the ECG sequence as a ladder diagram in real time. The system interactively shows diverse arrhythmias for various user settings of the cell function and bidirectional conduction between the cells. Users are able to experiment virtually by setting up a so-called electrophysiological stimulation. This system is useful for learning and for teaching the interaction between the cells and arrhythmias.

A novel NaV1.5 voltage sensor mutation associated with severe atrial and ventricular arrhythmias.

PubMed

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

2016-03-01

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. 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. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 possiblymore » for CF carrier screening in the general population. 19 refs., 1 tab.« less

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. Published by Elsevier Inc.

Arrhythmogenic right ventricular cardiomyopathy in monozygotic twin sisters, and persistent left superior vena cava in one complicating implantation of ICD.

PubMed

Astarcıoğlu, Mehmet Ali; Yaymacı, Mehmet; Şen, Taner; Kilit, Celal; Amasyalı, Basri

2015-10-01

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized histologically by fibro-fatty replacement of heart muscle, and clinically by ventricular arrhythmias and right ventricular dysfunction. This report presents monozygotic twins with ARVC, suggesting a genetic abnormality as the most probable cause.

Complicated pregnancies in inherited distal renal tubular acidosis: importance of acid-base balance.

PubMed

Seeger, Harald; Salfeld, Peter; Eisel, Rüdiger; Wagner, Carsten A; Mohebbi, Nilufar

2017-06-01

Inherited distal renal tubular acidosis (dRTA) is caused by impaired urinary acid excretion resulting in hyperchloremic metabolic acidosis. Although the glomerular filtration rate (GFR) is usually preserved, and hypertension and overt proteinuria are absent, it has to be considered that patients with dRTA also suffer from chronic kidney disease (CKD) with an increased risk for adverse pregnancy-related outcomes. Typical complications of dRTA include severe hypokalemia leading to cardiac arrhythmias and paralysis, nephrolithiasis and nephrocalcinosis. Several physiologic changes occur in normal pregnancy including alterations in acid-base and electrolyte homeostasis as well as in GFR. However, data on pregnancy in women with inherited dRTA are scarce. We report the course of pregnancy in three women with hereditary dRTA. Complications observed were severe metabolic acidosis, profound hypokalemia aggravated by hyperemesis gravidarum, recurrent urinary tract infection (UTI) and ureteric obstruction leading to renal failure. However, the outcome of all five pregnancies (1 pregnancy each for mothers n. 1 and 2; 3 pregnancies for mother n. 3) was excellent due to timely interventions. Our findings highlight the importance of close nephrologic monitoring of women with inherited dRTA during pregnancy. In addition to routine assessment of creatinine and proteinuria, caregivers should especially focus on acid-base status, plasma potassium and urinary tract infections. Patients should be screened for renal obstruction in the case of typical symptoms, UTI or renal failure. Furthermore, genetic identification of the underlying mutation may (a) support early nephrologic referral during pregnancy and a better management of the affected woman, and (b) help to avoid delayed diagnosis and reduce complications in affected newborns.

Establishment and evolution of the Australian Inherited Retinal Disease Register and DNA Bank.

PubMed

De Roach, John N; McLaren, Terri L; Paterson, Rachel L; O'Brien, Emily C; Hoffmann, Ling; Mackey, David A; Hewitt, Alex W; Lamey, Tina M

2013-07-01

Inherited retinal disease represents a significant cause of blindness and visual morbidity worldwide. With the development of emerging molecular technologies, accessible and well-governed repositories of data characterising inherited retinal disease patients is becoming increasingly important. This manuscript introduces such a repository. Participants were recruited from the Retina Australia membership, through the Royal Australian and New Zealand College of Ophthalmologists, and by recruitment of suitable patients attending the Sir Charles Gairdner Hospital visual electrophysiology clinic. Four thousand one hundred ninety-three participants were recruited. All participants were members of families in which the proband was diagnosed with an inherited retinal disease (excluding age-related macular degeneration). Clinical and family information was collected by interview with the participant and by examination of medical records. In 2001, we began collecting DNA from Western Australian participants. In 2009 this activity was extended Australia-wide. Genetic analysis results were stored in the register as they were obtained. The main outcome measurement was the number of DNA samples (with associated phenotypic information) collected from Australian inherited retinal disease-affected families. DNA was obtained from 2873 participants. Retinitis pigmentosa, Stargardt disease and Usher syndrome participants comprised 61.0%, 9.9% and 6.4% of the register, respectively. This resource is a valuable tool for investigating the aetiology of inherited retinal diseases. As new molecular technologies are translated into clinical applications, this well-governed repository of clinical and genetic information will become increasingly relevant for tasks such as identifying candidates for gene-specific clinical trials. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

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. © 2016 Wiley Periodicals, Inc.

Genes and inheritance.

PubMed

Middelton, L A; Peters, K F

2001-10-01

The information gained from the Human Genome Project and related genetic research will undoubtedly create significant changes in healthcare practice. It is becoming increasingly clear that nurses in all areas of clinical practice will require a fundamental understanding of basic genetics. This article provides the oncology nurse with an overview of basic genetic concepts, including inheritance patterns of single gene conditions, pedigree construction, chromosome aberrations, and the multifactorial basis underlying the common diseases of adulthood. Normal gene structure and function are introduced and the biochemistry of genetic errors is described.

Dual chamber arrhythmia detection in the implantable cardioverter defibrillator.

PubMed

Dijkman, B; Wellens, H J

2000-10-01

Dual chamber implantable cardioverter defibrillator (ICD) technology extended ICD therapy to more than termination of hemodynamically unstable ventricular tachyarrhythmias. It created the basis for dual chamber arrhythmia management in which dependable detection is important for treatment and prevention of both ventricular and atrial arrhythmias. Dual chamber detection algorithms were investigated in two Medtronic dual chamber ICDs: the 7250 Jewel AF (33 patients) and the 7271 Gem DR (31 patients). Both ICDs use the same PR Logic algorithm to interpret tachycardia as ventricular tachycardia (VT), supraventricular tachycardia (SVT), or dual (VT+ SVT). The accuracy of dual chamber detection was studied in 310 of 1,367 spontaneously occurring tachycardias in which rate criterion only was not sufficient for arrhythmia diagnosis. In 78 episodes there was a double tachycardia, in 223 episodes SVT was detected in the VT or ventricular fibrillation zone, and in 9 episodes arrhythmia was detected outside the boundaries of the PR Logic functioning. In 100% of double tachycardias the VT was correctly diagnosed and received priority treatment. SVT was seen in 59 (19%) episodes diagnosed as VT. The causes of inappropriate detection were (1) algorithm failure (inability to fulfill the PRarrhythmias. Dual chamber detection algorithms evaluated in a subset of diagnostically difficult arrhythmias allow safe detection of double tachycardias but require further extension and programmability to

α-Adrenoceptor blockade modifies neurally induced atrial arrhythmias

PubMed Central

Richer, Louis-Philippe; Vinet, Alain; Kus, Teresa; Cardinal, René; Ardell, Jeffrey L.; Armour, John Andrew

2008-01-01

Our objective was to determine whether neuronally induced atrial arrhythmias can be modified by α-adrenergic receptor blockade. In 30 anesthetized dogs, trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after the P wave of the ECG to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were monitored with 191 atrial unipolar electrodes. Mediastinal nerve sites were identified that reproducibly initiated atrial arrhythmias. These sites were then restimulated following 1 h (time control, n = 6), or the intravenous administration of naftopidil (α1-adrenergic blocker: 0.2 mg/kg, n = 6), yohimbine (α2-adrenergic blocker: 1 mg/kg, n = 6) or both (n = 8). A ganglionic blocker (hexamethonium: 1 mg/kg) was tested in four dogs. Stimulation of mediastinal nerves sites consistently elicited atrial tachyarrhythmias. Repeat stimulation after 1 h in the time-control group exerted a 19% decrease of the sites still able to induce atrial tachyarrhythmias. Hexamethonium inactivated 78% of the previously active sites. Combined α-adrenoceptor blockade inactivated 72% of the previously active sites. Bradycardia responses induced by mediastinal nerve stimulation were blunted by hexamethonium, but not by α1,2-adrenergic blockade. Naftopidil or yohimbine alone eliminated atrial arrhythmia induction from 31% and 34% of the sites (similar to time control). We conclude that heterogeneous activation of the intrinsic cardiac nervous system results in atrial arrhythmias that involve intrinsic cardiac neuronal α-adrenoceptors. In contrast to the global suppression exerted by hexamethonium, we conclude that α-adrenoceptor blockade targets intrinsic cardiac local circuit neurons involved in arrhythmia formation and not the flow-through efferent projections of the cardiac nervous system. PMID:18716036

Alpha-adrenoceptor blockade modifies neurally induced atrial arrhythmias.

PubMed

Richer, Louis-Philippe; Vinet, Alain; Kus, Teresa; Cardinal, René; Ardell, Jeffrey L; Armour, John Andrew

2008-10-01

Our objective was to determine whether neuronally induced atrial arrhythmias can be modified by alpha-adrenergic receptor blockade. In 30 anesthetized dogs, trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after the P wave of the ECG to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were monitored with 191 atrial unipolar electrodes. Mediastinal nerve sites were identified that reproducibly initiated atrial arrhythmias. These sites were then restimulated following 1 h (time control, n = 6), or the intravenous administration of naftopidil (alpha(1)-adrenergic blocker: 0.2 mg/kg, n = 6), yohimbine (alpha(2)-adrenergic blocker: 1 mg/kg, n = 6) or both (n = 8). A ganglionic blocker (hexamethonium: 1 mg/kg) was tested in four dogs. Stimulation of mediastinal nerves sites consistently elicited atrial tachyarrhythmias. Repeat stimulation after 1 h in the time-control group exerted a 19% decrease of the sites still able to induce atrial tachyarrhythmias. Hexamethonium inactivated 78% of the previously active sites. Combined alpha-adrenoceptor blockade inactivated 72% of the previously active sites. Bradycardia responses induced by mediastinal nerve stimulation were blunted by hexamethonium, but not by alpha(1,2)-adrenergic blockade. Naftopidil or yohimbine alone eliminated atrial arrhythmia induction from 31% and 34% of the sites (similar to time control). We conclude that heterogeneous activation of the intrinsic cardiac nervous system results in atrial arrhythmias that involve intrinsic cardiac neuronal alpha-adrenoceptors. In contrast to the global suppression exerted by hexamethonium, we conclude that alpha-adrenoceptor blockade targets intrinsic cardiac local circuit neurons involved in arrhythmia formation and not the flow-through efferent projections of the cardiac nervous system.

Cholinesterase inhibition reduces arrhythmias in asymptomatic Chagas disease.

PubMed

Castro, Renata R T; Porphirio, Graciema; Xavier, Sergio S; Moraes, Ruy S; Ferlin, Elton L; Ribeiro, Jorge P; da Nóbrega, Antonio C L

2017-10-01

Parasympathetic dysfunction may play a role in the genesis of arrhythmias in Chagas disease. This study evaluates the acute effects of pyridostigmine (PYR), a reversible cholinesterase inhibitor, on the occurrence of arrhythmias in patients with Chagas cardiac disease. Following a double-blind, randomized, placebo-controlled, cross-over protocol, 17 patients (age 50±2 years) with Chagas cardiac disease type B underwent 24-hour Holter recordings after oral administration of either pyridostigmine bromide (45 mg, 3 times/day) or placebo (PLA). Pyridostigmine reduced the 24-hours incidence (median [25%-75%]) of premature ventricular beats-PLA: 2998 (1920-4870), PYR: 2359 (940-3253), P=.044; ventricular couplets-PLA: 84 (15-159), PYR: 33 (6-94), P=.046. Although the total number of nonsustained ventricular tachycardia in the entire group was not different (P=.19) between PLA (1 [0-8]) and PYR (0 [0-4]), there were fewer episodes under PYR in 72% of the patients presenting this type of arrhythmia (P=.033). Acute administration of pyridostigmine reduced the incidence of nonsustained ventricular arrhythmias in patients with Chagas cardiac disease. Further studies that address the use of pyridostigmine by patients with Chagas cardiac disease under a more prolonged follow-up are warranted. © 2017 John Wiley & Sons Ltd.

Carbon monoxide and lethal arrhythmias. Research report, Jul 85-Jan 89

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farber, J.P.; Schwartz, P.J.; Vanoli, E.

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 wasmore » 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.« less

Cardiac arrhythmias from a malpositioned Greenfield filter in a traumatic quadriplegic.

PubMed

Bach, J R; Zaneuski, R; Lee, H

1990-10-01

A case study is presented of premature Greenfield filter discharge with intracardiac migration and resulting life-threatening arrhythmias. These arrhythmias also interfered with the patient's transition from ventilatory support via orotracheal intubation to noninvasive positive airway pressure ventilatory support methods. The patient's arrhythmias were controlled by a demand cardiac pacemaker and cardiac glycoside therapy. No anticoagulants were used. She had no further filter migration nor significant complications for 16 months after hospital discharge.

Types of Arrhythmia in Children

MedlinePlus

... even though they may need to keep taking medicine. Your child will probably need periodic check-ups but will ... minute. Understand and manage medications Parents of a child taking medicine for an arrhythmia should give the medicine at ...

Arrhythmia in Stem Cell Transplantation

PubMed Central

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

2015-01-01

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

Increasing Prevalence of Atrial Fibrillation and Permanent Atrial Arrhythmias in Congenital Heart Disease.

PubMed

Labombarda, Fabien; Hamilton, Robert; Shohoudi, Azadeh; Aboulhosn, Jamil; Broberg, Craig S; Chaix, Marie A; Cohen, Scott; Cook, Stephen; Dore, Annie; Fernandes, Susan M; Fournier, Anne; Kay, Joseph; Macle, Laurent; Mondésert, Blandine; Mongeon, François-Pierre; Opotowsky, Alexander R; Proietti, Anna; Rivard, Lena; Ting, Jennifer; Thibault, Bernard; Zaidi, Ali; Khairy, Paul

2017-08-15

Atrial arrhythmias are the most common complication encountered in the growing and aging population with congenital heart disease. This study sought to assess the types and patterns of atrial arrhythmias, associated factors, and age-related trends. A multicenter cohort study enrolled 482 patients with congenital heart disease and atrial arrhythmias, age 32.0 ± 18.0 years, 45.2% female, from 12 North American centers. Qualifying arrhythmias were classified by a blinded adjudicating committee. The most common presenting arrhythmia was intra-atrial re-entrant tachycardia (IART) (61.6%), followed by atrial fibrillation (28.8%), and focal atrial tachycardia (9.5%). The proportion of arrhythmias due to IART increased with congenital heart disease complexity from 47.2% to 62.1% to 67.0% in patients with simple, moderate, and complex defects, respectively (p = 0.0013). Atrial fibrillation increased with age to surpass IART as the most common arrhythmia in those ≥50 years of age (51.2% vs. 44.2%; p < 0.0001). Older age (odds ratio [OR]: 1.024 per year; 95% confidence interval [CI]: 1.010 to 1.039; p = 0.001) and hypertension (OR: 2.00; 95% CI: 1.08 to 3.71; p = 0.029) were independently associated with atrial fibrillation. During a mean follow-up of 11.3 ± 9.4 years, the predominant arrhythmia pattern was paroxysmal in 62.3%, persistent in 28.2%, and permanent in 9.5%. Permanent atrial arrhythmias increased with age from 3.1% to 22.6% in patients <20 years to ≥50 years, respectively (p < 0.0001). IART is the most common presenting atrial arrhythmia in patients with congenital heart disease, with a predominantly paroxysmal pattern. However, atrial fibrillation increases in prevalence and atrial arrhythmias progressively become permanent as the population ages. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

A Noninvasive Imaging Modality for Cardiac Arrhythmias

PubMed Central

Burnes, John E.; Taccardi, Bruno; Rudy, Yoram

2007-01-01

Background The last decade witnessed an explosion of information regarding the genetic, molecular, and mechanistic basis of heart disease. Translating this information into clinical practice requires the development of novel functional imaging modalities for diagnosis, localization, and guided intervention. A noninvasive modality for imaging cardiac arrhythmias is not yet available. Present electrocardiographic methods cannot precisely localize a ventricular tachycardia (VT) or its key reentrant circuit components. Recently, we developed a noninvasive electrocardiographic imaging modality (ECGI) that can reconstruct epicardial electrophysiological information from body surface potentials. Here, we extend its application to image reentrant arrhythmias. Methods and Results Epicardial potentials were recorded during VT with a 490 electrode sock during an open chest procedure in 2 dogs with 4-day-old myocardial infarctions. Body surface potentials were generated from these epicardial potentials in a human torso model. Realistic geometry errors and measurement noise were added to the torso data, which were then used to noninvasively reconstruct epicardial isochrones, electrograms, and potentials with excellent accuracy. ECGI reconstructed the reentry pathway and its key components, including (1) the central common pathway, (2) the VT exit site, (3) lines of block, and (4) regions of slow and fast conduction. This allowed for detailed characterization of the reentrant circuit morphology. Conclusions ECGI can noninvasively image arrhythmic activation on the epicardium during VT to identify and localize key components of the arrhythmogenic pathway that can be effective targets for antiarrhythmic intervention. PMID:11044435

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genome-wide association of implantable cardioverter-defibrillator activation with life-threatening arrhythmias.

PubMed

Murray, Sarah S; Smith, Erin N; Villarasa, Nikki; Nahey, Tara; Lande, Jeff; Goldberg, Harold; Shaw, Marian; Rosenthal, Lawrence; Ramza, Brian; Alaeddini, Jamshid; Han, Xinqiang; Damani, Samir; Soykan, Orhan; Kowal, Robert C; Topol, Eric J

2012-01-01

To identify genetic factors that would be predictive of individuals who require an implantable cardioverter-defibrillator (ICD), we conducted a genome-wide association study among individuals with an ICD who experienced a life-threatening arrhythmia (LTA; cases) vs. those who did not over at least a 3-year period (controls). Most individuals that receive implantable cardioverter-defibrillators never experience a life-threatening arrhythmia. Genetic factors may help identify who is most at risk. Patients with an ICD and extended follow-up were recruited from 34 clinical sites with the goal of oversampling those who had experienced LTA, with a cumulative 607 cases and 297 controls included in the analysis. A total of 1,006 Caucasian patients were enrolled during a time period of 13 months. Arrhythmia status of 904 patients could be confirmed and their genomic data were included in the analysis. In this cohort, there were 704 males, 200 females, and the average age was 73.3 years. We genotyped DNA samples using the Illumina Human660 W Genotyping BeadChip and tested for association between genotype at common variants and the phenotype of having an LTA. We did not find any associations reaching genome-wide significance, with the strongest association at chromosome 13, rs11856574 at P = 5×10⁻⁶. Loci previously implicated in phenotypes such as QT interval (measure of the time between the start of the Q wave and the end of the T wave as measured by electrocardiogram) were not found to be significantly associated with having an LTA. Although powered to detect such associations, we did not find common genetic variants of large effect associated with having a LTA in those of European descent. This indicates that common gene variants cannot be used at this time to guide ICD risk-stratification. ClinicalTrials.gov NCT00664807.

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

PubMed

Armayones, Manuel; Vilaseca, M Antònia; Cutillas, Júlia; Fàbrega, Jordi; Fernández, Jorge Juan; García, Mei; Egea, Natàlia; Pousada, Modesta; Gómez-Zuñiga, Beni; Pérez-Payarols, Jaume; Artuch, Rafael; Palau, Francesc; Serrano, Mercedes

2012-08-21

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.

Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic review of risk factors in clinical practice.

PubMed

Baig, Shanat; Edward, Nicky C; Kotecha, Dipak; Liu, Boyang; Nordin, Sabrina; Kozor, Rebecca; Moon, James C; Geberhiwot, Tarekegn; Steeds, Richard P

2017-10-17

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A enzyme. Cardiovascular (CV) disease is a common cause of mortality in FD, in particular as a result of heart failure and arrhythmia, with a significant proportion of events categorized as sudden. There are no clear models for risk prediction in FD. This systematic review aims to identify the risk factors for ventricular arrhythmia (VA) and sudden cardiac deaths (SCD) in FD. A systematic search was performed following PRISMA guidelines of EMBASE, Medline, PubMed, Web of Science, and Cochrane from inception to August 2016, focusing on identification of risk factors for the development of VA or SCD. Thirteen studies were included in the review (n = 4185 patients) from 1189 articles, with follow-up of 1.2-10 years. Weighted average age was 37.6 years, and 50% were male. Death from any cause was reported in 8.3%. Of these, 75% was due to CV problems, with the majority being SCD events (62% of reported deaths). Ventricular tachycardia was reported in 7 studies, with an average prevalence of 15.3%. Risk factors associated with SCD events were age, male gender, left ventricular hypertrophy, late gadolinium enhancement on CV magnetic resonance imaging, and non-sustained ventricular tachycardia. Although a multi-system disease, FD is a predominantly cardiac disease from a mortality perspective, with death mainly from SCD events. Limited evidence highlights the importance of clinical and imaging risk factors that could contribute to improved decision-making in the management of FD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

Recent Progress in Genome Editing Approaches for Inherited Cardiovascular Diseases.

PubMed

Kaur, Balpreet; Perea-Gil, Isaac; Karakikes, Ioannis

2018-06-02

This review describes the recent progress in nuclease-based therapeutic applications for inherited heart diseases in vitro, highlights the development of the most recent genome editing technologies and discusses the associated challenges for clinical translation. Inherited cardiovascular disorders are passed from generation to generation. Over the past decade, considerable progress has been made in understanding the genetic basis of inherited heart diseases. The timely emergence of genome editing technologies using engineered programmable nucleases has revolutionized the basic research of inherited cardiovascular diseases and holds great promise for the development of targeted therapies. The genome editing toolbox is rapidly expanding, and new tools have been recently added that significantly expand the capabilities of engineered nucleases. Newer classes of versatile engineered nucleases, such as the "base editors," have been recently developed, offering the potential for efficient and precise therapeutic manipulation of the human genome.

Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data.

PubMed

Sessler, Nelson E; Walker, Ekaterina; Chickballapur, Harsha; Kacholakalayil, James; Coplan, Paul M

2017-01-01

Positive-controlled clinical studies have shown a dose dependent effect of buprenorphine transdermal system on QTc interval prolongation. This study provides assessment of the buprenorphine transdermal system and cardiac arrhythmia using US FDA and WHO postmarketing reporting databases. Disproportionality analysis of spontaneously reported adverse events to assess whether the reporting rate of cardiac arrhythmia events was disproportionately elevated relative to expected rates of reporting in both FDA and WHO databases. Cardiac arrhythmia events were identified using the standardized Medical Dictionary for Regulatory Activities query for torsade de pointes and/or QT prolongation (TdP/QTP). The threshold for a signal of disproportionate adverse event reporting was defined as the lower 90% confidence limit ≥ 2 of the Empiric Bayes geometric mean in FDA database and as the lower 95% confidence limit of the Informational Component >0 in WHO database. There were 124 (<1%) and 77 (2%) cardiac arrhythmia event cases associated with buprenorphine transdermal as compared to 3206 (12%) and 2913 (14%) involving methadone in the FDA and WHO databases, respectively. In the FDA database methadone was associated with a signal of disproportionate reporting for TdP/QTP (EB05 3.26); however, buprenorphine transdermal was not (EB05 0.33). In the WHO database methadone was associated with a signal of disproportionate reporting for TdP/QTP (IC025 2.66); however, buprenorphine transdermal was not (IC025 -0.88). Similar trends were observed in sensitivity analyses by age, gender, and specific terms related to ventricular arrhythmia. The signal identified in the transdermal buprenorphine thorough QTc study, which led to a dose limitation in its US label, does not translate into a signal of increased risk for cardiac arrhythmia in real world use, as assessed by this method of analyzing post-market surveillance data.

Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy.

PubMed

Bagnall, Richard D; Crompton, Douglas E; Petrovski, Slavé; Lam, Lien; Cutmore, Carina; Garry, Sarah I; Sadleir, Lynette G; Dibbens, Leanne M; Cairns, Anita; Kivity, Sara; Afawi, Zaid; Regan, Brigid M; Duflou, Johan; Berkovic, Samuel F; Scheffer, Ingrid E; Semsarian, Christopher

2016-04-01

The leading cause of epilepsy-related premature mortality is sudden unexpected death in epilepsy (SUDEP). The cause of SUDEP remains unknown. To search for genetic risk factors in SUDEP cases, we performed an exome-based analysis of rare variants. Demographic and clinical information of 61 SUDEP cases were collected. Exome sequencing and rare variant collapsing analysis with 2,936 control exomes were performed to test for genes enriched with damaging variants. Additionally, cardiac arrhythmia, respiratory control, and epilepsy genes were screened for variants with frequency of <0.1% and predicted to be pathogenic with multiple in silico tools. The 61 SUDEP cases were categorized as definite SUDEP (n = 54), probable SUDEP (n = 5), and definite SUDEP plus (n = 2). We identified de novo mutations, previously reported pathogenic mutations, or candidate pathogenic variants in 28 of 61 (46%) cases. Four SUDEP cases (7%) had mutations in common genes responsible for the cardiac arrhythmia disease, long QT syndrome (LQTS). Nine cases (15%) had candidate pathogenic variants in dominant cardiac arrhythmia genes. Fifteen cases (25%) had mutations or candidate pathogenic variants in dominant epilepsy genes. No gene reached genome-wide significance with rare variant collapsing analysis; however, DEPDC5 (p = 0.00015) and KCNH2 (p = 0.0037) were among the top 30 genes, genome-wide. A sizeable proportion of SUDEP cases have clinically relevant mutations in cardiac arrhythmia and epilepsy genes. In cases with an LQTS gene mutation, SUDEP may occur as a result of a predictable and preventable cause. Understanding the genetic basis of SUDEP may inform cascade testing of at-risk family members. © 2016 American Neurological Association.

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.

Inhibition of Angiotensin-II Production Increases Susceptibility to Acute Ischemia/Reperfusion Arrhythmia

PubMed Central

Taskin, Eylem; Tuncer, Kadir Ali; Guven, Celal; Kaya, Salih Tunc; Dursun, Nurcan

2016-01-01

Background Myocardial ischemia and reperfusion lead to impairment of electrolyte balance and, eventually, lethal arrhythmias. The aim of this study was to investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II) production on heart tissue with ischemia-reperfusion damage, arrhythmia, and oxidative stress. Material/Methods Rats were divided into 4 groups: only ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The drugs were given by gavage 30 min before anesthesia. Blood pressure and electrocardiography (ECG) were recorded during MI/R procedures. The heart tissue and plasma was kept so as to evaluate the total oxidant (TOS), antioxidant status (TAS), and creatine kinase-MB (CK-MB). Results Creatine kinase-MB was not different among the groups. Although TAS was not affected by inhibition of Ang-II production, TOS was significantly lower in the CAP and/or AL groups than in the MI/R group. Furthermore, oxidative stress index was significantly attenuated in the CAP and/or AL groups. Captopril significantly increased the duration of VT during ischemia; however, it did not have any effect on the incidence of arrhythmias. During reperfusion periods, aliskiren and its combinations with captopril significantly reduced the incidence of other types of arrhythmias. Captopril alone had no effect on the incidence of arrhythmias, but significantly increased arrhythmias score and durations of arrhythmias during reperfusion. MAP and heart rate did not show changes in any groups during ischemic and reperfusion periods. Conclusions Angiotensin-II production appears to be associated with elevated levels of reactive oxygen species, but Ang-II inhibitions increases arrhythmia, mainly by initiating ventricular ectopic beats. PMID:27889788

A Case for Pharmacogenomics in Management of Cardiac Arrhythmias

PubMed Central

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

2012-01-01

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

Intracardiac echo-facilitated 3D electroanatomical mapping of ventricular arrhythmias from the papillary muscles: assessing the 'fourth dimension' during ablation.

PubMed

Proietti, Riccardo; Rivera, Santiago; Dussault, Charles; Essebag, Vidal; Bernier, Martin L; Ayala-Paredes, Felix; Badra-Verdu, Mariano; Roux, Jean-François

2017-01-01

Ventricular arrhythmias (VA) originating from a papillary muscle (PM) have recently been described as a distinct clinical entity with peculiar features that make its treatment with catheter ablation challenging. Here, we report our experience using an intracardiac echo-facilitated 3D electroanatomical mapping approach in a case series of patients undergoing ablation for PM VA. Sixteen patients who underwent catheter ablation for ventricular tachycardia (VT) or symptomatic premature ventricular contractions originating from left ventricular PMs were included in the study. A total of 24 procedures (mean 1.5 per patient) were performed: 15 using a retrograde aortic approach and 9 using a transseptal approach. Integrated intracardiac ultrasound for 3D electroanatomical mapping was used in 15 of the 24 procedures. The posteromedial PM was the most frequent culprit for the clinical arrhythmia, and the body was the part of the PM most likely to be the successful site for ablation. The site of ablation was identified based on the best pace map matching the clinical arrhythmia and the site of earliest the activation. At a mean follow-up of 10.5 ± 7 months, only two patients had recurrent arrhythmias following a repeat ablation procedure. An echo-facilitated 3D electroanatomical mapping allows for real-time creation of precise geometries of cardiac chambers and endocavitary structures. This is useful during procedures such as catheter ablation of VAs originating from PMs, which require detailed representation of anatomical landmarks. Routine adoption of this technique should be considered to improve outcomes of PM VA ablation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

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

Capture of activation during ventricular arrhythmia using distributed stimulation.

PubMed

Meunier, Jason M; Ramalingam, Sanjiv; Lin, Shien-Fong; Patwardhan, Abhijit R

2007-04-01

Results of previous studies suggest that pacing strength stimuli can capture activation during ventricular arrhythmia locally near pacing sites. The existence of spatio-temporal distribution of excitable gap during arrhythmia suggests that multiple and timed stimuli delivered over a region may permit capture over larger areas. Our objective in this study was to evaluate the efficacy of using spatially distributed pacing (DP) to capture activation during ventricular arrhythmia. Data were obtained from rabbit hearts which were placed against a lattice of parallel wires through which biphasic pacing stimuli were delivered. Electrical activity was recorded optically. Pacing stimuli were delivered in sequence through the parallel wires starting with the wire closest to the apex and ending with one closest to the base. Inter-stimulus delay was based on conduction velocity. Time-frequency analysis of optical signals was used to determine variability in activation. A decrease in standard deviation of dominant frequencies of activation from a grid of locations that spanned the captured area and a concurrence with paced frequency were used as an index of capture. Results from five animals showed that the average standard deviation decreased from 0.81 Hz during arrhythmia to 0.66 Hz during DP at pacing cycle length of 125 ms (p = 0.03) reflecting decreased spatio-temporal variability in activation during DP. Results of time-frequency analysis during these pacing trials showed agreement between activation and paced frequencies. These results show that spatially distributed and timed stimulation can be used to modify and capture activation during ventricular arrhythmia.

[Catheter ablation in patients with refractory cardiac arrhythmias with radiofrequency techniques].

PubMed

de Paola, A A; Balbão, C E; Silva Netto, O; Mendonça, A; Villacorta, H; Vattimo, A C; Souza, I A; Guiguer Júnior, N; Portugal, O P; Martinez Filho, E E

1993-02-01

evaluate the efficacy of radiofrequency catheter ablation in patients with refractory cardiac arrhythmias. twenty patients with refractory cardiac arrhythmias were undertaken to electrophysiologic studies for diagnosis and radiofrequency catheter ablation of their reentrant arrhythmias. Ten patients were men and 10 women with ages varying from 13 to 76 years (mean = 42.4 years). Nineteen patients had supraventricular tachyarrhythmias: One patient had atrial tachycardia and 1 atrial fibrillation with rapid ventricular rate, 5 patients had reentrant nodal tachycardia, 12 patients had reentrant atrioventricular tachycardia and 1 patient had right ventricular outflow tract tachycardia. the mean time of the procedure was 4.1 hours. The radiofrequency current energy applied was 40-50 V for 30-40 seconds. Ablation was successful in 18/20 (90%) patients; in 15/18 (83%) of successfully treated patients the same study was done for diagnosis and radiofrequency ablation. One patient had femoral arterial occlusion and was treated with no significant sequelae. During a mean follow-up of 4 months no preexcitation or reentrant tachycardia occurred. the results of our experience with radiofrequency catheter ablation of cardiac arrhythmias suggest that this technique can benefit an important number of patients with cardiac arrhythmias.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Contemporary genetic testing in inherited cardiac disease: tools, ethical issues, and clinical applications.

PubMed

Girolami, Francesca; Frisso, Giulia; Benelli, Matteo; Crotti, Lia; Iascone, Maria; Mango, Ruggiero; Mazzaccara, Cristina; Pilichou, Kalliope; Arbustini, Eloisa; Tomberli, Benedetta; Limongelli, Giuseppe; Basso, Cristina; Olivotto, Iacopo

2018-01-01

: Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype-phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, 'real-world' experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines.

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.

Research and development of the device for diagnostics of arrhythmia

NASA Astrophysics Data System (ADS)

Lezhnina, I. A.; Boyakhchyan, A. A.; Overchuk, K. V.; Uvarov, A. A.

2017-08-01

The article describes the results of the research for sensors optimal arrangement during one limb ECG detection. The found placement provides the registration of the enough quality signal sufficient for the diagnosis of arrhythmia, the QRS complex is clearly recognized. Authors also show the test results of the device developed for the diagnosis of arrhythmia and sudden cardiac death.

Impact of remote monitoring on the management of arrhythmias in patients with implantable cardioverter-defibrillator.

PubMed

Marcantoni, Lina; Toselli, Tiziano; Urso, Giulia; Pratola, Claudio; Ceconi, Claudio; Bertini, Matteo

2015-11-01

In the last decade, there has been an exponential increase in cardioverter-defibrillator (ICD) implants. Remote monitoring systems, allow daily follow-ups of patients with ICD. To evaluate the impact of remote monitoring on the management of cardiovascular events associated with supraventricular and ventricular arrhythmias during long-term follow-up. A total of 207 patients undergoing ICD implantation/replacement were enrolled: 79 patients received remote monitoring systems and were followed up every 12 months, and 128 patients were followed up conventionally every 6 months. All patients were followed up and monitored for the occurrence of supraventricular and ventricular arrhythmia-related cardiovascular events (ICD shocks and/or hospitalizations). During a median follow-up of 842 days (interquartile range 476-1288 days), 32 (15.5%) patients experienced supraventricular arrhythmia-related events and 51 (24.6%) patients experienced ventricular arrhythmia-related events. Remote monitoring had a significant role in the reduction of supraventricular arrhythmia-related events, but it had no effect on ventricular arrhythmia-related events. In multivariable analysis, remote monitoring remained as an independent protective factor, reducing the risk of supraventricular arrhythmia-related events of 67% [hazard ratio, 0.33; 95% confidence interval (CI), 0.13-0.82; P = 0.017]. Remote monitoring systems improved outcomes in patients with supraventricular arrhythmias by reducing the risk of cardiovascular events, but no benefits were observed in patients with ventricular arrhythmias.

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

The association between domperidone and ventricular arrhythmia in the postpartum period.

PubMed

Smolina, Kate; Mintzes, Barbara; Hanley, Gillian E; Oberlander, Tim F; Morgan, Steven G

2016-10-01

The aim of this study is to examine the relationship between domperidone (commonly used off-label for lactation stimulation), ventricular arrhythmia and all-cause mortality during the postpartum period. This is a retrospective, population-based cohort study of all women with a live birth between 1 January 2002 and 31 December 2011 in British Columbia, Canada. Cox proportional hazards models, yielding hazard ratios (HRs), were used to estimate the risk of hospitalization for ventricular arrhythmia associated with domperidone exposure within six months postpartum. The study population consisted of 225 532 women with 320 351 live births. There was only one death during the six-month postpartum period among the study population, and thus we did not perform any analyses of all-cause mortality. We identified 21 hospitalizations for ventricular arrhythmia. Adjusting for age, smoking and prior history of ventricular arrhythmia and cardiovascular disease, the risk of ventricular arrhythmia hospitalization was approximately double among those exposed to domperidone, but the results were not statistically significant (HR = 2.25, 95%CI 0.84-6.01). Adjustment for body mass index in the 74% of women for whom it was known further reduced the association (HR = 1.69, 95%CI 0.48-5.96). We found a possible association between exposure to domperidone and hospitalization for ventricular arrhythmia among a cohort of women who have recently given birth. Future studies are needed to confirm this association. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Severe Hypoglycemia–Induced Lethal Cardiac Arrhythmias Are Mediated by Sympathoadrenal Activation

PubMed Central

Reno, Candace M.; Daphna-Iken, Dorit; Chen, Y. Stefanie; VanderWeele, Jennifer; Jethi, Krishan; Fisher, Simon J.

2013-01-01

For people with insulin-treated diabetes, severe hypoglycemia can be lethal, though potential mechanisms involved are poorly understood. To investigate how severe hypoglycemia can be fatal, hyperinsulinemic, severe hypoglycemic (10–15 mg/dL) clamps were performed in Sprague-Dawley rats with simultaneous electrocardiogram monitoring. With goals of reducing hypoglycemia-induced mortality, the hypotheses tested were that: 1) antecedent glycemic control impacts mortality associated with severe hypoglycemia; 2) with limitation of hypokalemia, potassium supplementation could limit hypoglycemia-associated deaths; 3) with prevention of central neuroglycopenia, brain glucose infusion could prevent hypoglycemia-associated arrhythmias and deaths; and 4) with limitation of sympathoadrenal activation, adrenergic blockers could prevent hypoglycemia-induced arrhythmic deaths. Severe hypoglycemia–induced mortality was noted to be worsened by diabetes, but recurrent antecedent hypoglycemia markedly improved the ability to survive an episode of severe hypoglycemia. Potassium supplementation tended to reduce mortality. Severe hypoglycemia caused numerous cardiac arrhythmias including premature ventricular contractions, tachycardia, and high-degree heart block. Intracerebroventricular glucose infusion reduced severe hypoglycemia–induced arrhythmias and overall mortality. β-Adrenergic blockade markedly reduced cardiac arrhythmias and completely abrogated deaths due to severe hypoglycemia. Under conditions studied, sudden deaths caused by insulin-induced severe hypoglycemia were mediated by lethal cardiac arrhythmias triggered by brain neuroglycopenia and the marked sympathoadrenal response. PMID:23835337

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

PubMed Central

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

2014-01-01

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

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 produce...

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 produce...

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 produce...

[Predictors of cardiac arrhythmias in patients with arterial hypertension during exercise stress testing].

PubMed

Kolesnik, M Iu; Sokolova, M V

2014-02-01

Arterial hypertension is an important risk factor for atrial and ventricular arrhythmias. 203 male patients were examined in order to identify predictors of cardiac arrhythmias in patients with arterial hypertension during exercise stress testing. All participants were studied by 24-hour ambulatory blood pressure monitoring, transthoracic echocardiography, an ultrasound scan of the carotid arteries and treadmill test. 47,3% of patients presented cardiac arrhythmias during exercise stress testing. The left ventricular mass, diastolic function and carotid intima-media thickness were found to be independent predictors of exercise-induced arrhythmias. The use of the exercise stress testing may be reasonable for additional risk stratification in hypertensive patients.

Constitutional delay of puberty: presentation and inheritance pattern in 48 familial cases.

PubMed

Winter, Sarah; Ousidhoum, Aldjia; McElreavey, Kenneth; Brauner, Raja

2016-03-12

The mechanism that initiates the onset of puberty is largely unknown but the age of onset is mainly under genetic control and influenced by environmental factors including nutrition. Familial forms of constitutional delay of puberty (CDP) suggest the involvement of genetic factors. The purpose of this study is to describe the presentation and the mode of inheritance of CDP in a series of familial cases. A retrospective, single center study was carried out over 10 years on 48 probands (14 girls and 34 boys) from 48 families seen for CDP with a familial component. Of the 48 probands, 46 (96 %) had at least one affected 1(st) degree relatives and 2 (4 %, 2 boys) had only 2(nd) degree relatives affected. In girls, 11 families (79 %) exhibited exclusive maternal inheritance, 1 (7 %) paternal inheritance and 2 (14 %) both maternal and paternal inheritance. In boys, 14 families (41 %) exhibited exclusive maternal inheritance, 12 (35 %) paternal inheritance and 8 (24 %) both maternal and paternal inheritance. In the boys with bilineal inheritance, the ages at onset of puberty (16 ± 1.41 years) and at evaluation (16.05 ± 2.47 years) were higher than in those with unilineal inheritance (15.25 ± 0.35 and 15.1 ± 0.42 years respectively), but the difference was not significant. In girls exclusive maternal inheritance seems to be the major mode of inheritance whereas for boys the mode of inheritance was almost equally maternal, paternal or bilineal. Clinical phenotype of boys with bilineal inheritance seems to be more severe, but the difference did not reach statistical significance, perhaps because of the small sample size. This greater severity of the phenotype in boys with bilineal inheritance is likely due to inheriting different puberty timing genes from each parent. Future research should be directed at identifying such genes.

[Risk of arrhythmia and domestic low-voltage electrical injury].

PubMed

Claudet, I; Maréchal, C; Debuisson, C; Salanne, S

2010-04-01

Analysis of domestic low-voltage (220-240 V) electrical injury in children admitted to a pediatric emergency department to illustrate the low risk of initial or delayed risk of arrhythmia. Retrospective study between 2001 and 2008 analyzing all children aged less than 15 years admitted for a low-voltage electrical injury. The data collected were age, sex, time and circumstances of the accident, time and day of admission, transport modalities, presence of risk factors for arrhythmia (transthoracic current, wet skin, tetany, loss of consciousness or neurological symptoms, and initial EKG abnormalities), injuries, EKG, muscular and/or cardiac enzyme values, progression and complications. For statistical analysis, data were entered in Microsoft Excel tables. Analysis was done with StatView5.1 (SAS Institute) and Epi Info 6.04fr (VF, ENSP epiconcept). In the descriptive analysis, the data are presented as mean values with SD, median and range. Forty-eight children were included. The mean annual number of admissions was equal to 6 (range, 3-12). The mean age was 6.2 + or - 4.3 years (median, 4.6 years). There was a male predominance: the overall sex ratio was 1.5, i.e., 3 before the age of 2 and 2.6 before the age of 10. The electrical injury occurred after contact with a wire or a connected cord or after the introduction of a metallic object in a wall socket. Ten children had risk factors of arrhythmia (mainly wet skin or thoracic pain). Twenty-nine children suffered from burns to the extremities (digits and hands, 70 %). At admission, 45 children had an EKG performed. The initial EKG was considered abnormal in 8 cases showing: sinusal tachycardia (n=4), incomplete right bundle branch block (n=4), and V(1) negative T waves (n=1). The EKG normalized within the first 12h. Hospitalization for cardiac monitoring was required for 18 children. No delayed arrhythmia occurred. In a mean time of 3.5h after the accident, a troponin dosage was given to 15 children and was normal

Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?

PubMed

Procopio, V; Manti, S; Bianco, G; Conti, G; Romeo, A; Maimone, F; Arrigo, T; Cutrupi, M C; Salpietro, C; Cuppari, C

2018-01-30

Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype-phenotype correlation of FMF disease. To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model. A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3. 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met680Ile/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680Ile/wt genotype reported the most severe clinical phenotype. p.Ala744Ser/wt, p.Glu148Gln/Met680Ile, p.Met680Ile/Met680Ile, p.Met680Ile/Met694Val, p.Pro369Ser/wt, p.Met694Ile/wt, p.Glu148Gln/Glu148Gln, p.Lys695Arg/wt resulted in 100% pathogenicity. The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF. Copyright © 2017 Elsevier B.V. All rights reserved.

The association of air temperature with cardiac arrhythmias

NASA Astrophysics Data System (ADS)

Čulić, Viktor

2017-11-01

The body response to meteorological influences may activate pathophysiological mechanisms facilitating the occurrence of cardiac arrhythmias in susceptible patients. Putative underlying mechanisms include changes in systemic vascular resistance and blood pressure, as well as a network of proinflammatory and procoagulant processes. Such a chain reaction probably occurs within the time window of several hours, so use of daily average values of meteorological elements do not seem appropriate for investigation in this area. In addition, overall synoptic situation, and season-specific combinations of meteorological elements and air pollutant levels probably cause the overall effect rather than a single atmospheric element. Particularly strong interrelations have been described among wind speed, air pressure and temperature, relative air humidity, and suspended particulate matter. This may be the main reason why studies examining the association between temperature and ventricular arrhythmias have found linear positive, negative, J-shaped or no association. Further understanding of the pathophysiological adaptation to atmospheric environment may help in providing recommendations for protective measures during "bad" weather conditions in patients with cardiac arrhythmias.

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

Reduction in dynamin-2 is implicated in ischaemic cardiac arrhythmias

PubMed Central

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

2014-01-01

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. PMID:25092467

Genome-Wide Association of Implantable Cardioverter-Defibrillator Activation With Life-Threatening Arrhythmias

PubMed Central

Murray, Sarah S.; Smith, Erin N.; Villarasa, Nikki; Nahey, Tara; Lande, Jeff; Goldberg, Harold; Shaw, Marian; Rosenthal, Lawrence; Ramza, Brian; Alaeddini, Jamshid; Han, Xinqiang; Damani, Samir; Soykan, Orhan; Kowal, Robert C.; Topol, Eric J.

2012-01-01

Objectives To identify genetic factors that would be predictive of individuals who require an implantable cardioverter-defibrillator (ICD), we conducted a genome-wide association study among individuals with an ICD who experienced a life-threatening arrhythmia (LTA; cases) vs. those who did not over at least a 3-year period (controls). Background Most individuals that receive implantable cardioverter-defibrillators never experience a life-threatening arrhythmia. Genetic factors may help identify who is most at risk. Methods Patients with an ICD and extended follow-up were recruited from 34 clinical sites with the goal of oversampling those who had experienced LTA, with a cumulative 607 cases and 297 controls included in the analysis. A total of 1,006 Caucasian patients were enrolled during a time period of 13 months. Arrhythmia status of 904 patients could be confirmed and their genomic data were included in the analysis. In this cohort, there were 704 males, 200 females, and the average age was 73.3 years. We genotyped DNA samples using the Illumina Human660 W Genotyping BeadChip and tested for association between genotype at common variants and the phenotype of having an LTA. Results and Conclusions We did not find any associations reaching genome-wide significance, with the strongest association at chromosome 13, rs11856574 at P = 5×10−6. Loci previously implicated in phenotypes such as QT interval (measure of the time between the start of the Q wave and the end of the T wave as measured by electrocardiogram) were not found to be significantly associated with having an LTA. Although powered to detect such associations, we did not find common genetic variants of large effect associated with having a LTA in those of European descent. This indicates that common gene variants cannot be used at this time to guide ICD risk-stratification. Trial Registration ClinicalTrials.gov NCT00664807 PMID:22247754

Carbon monoxide and lethal arrhythmias

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farber, J.P.; Schwartz, P.J.; Vanoli, E.

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 aremore » 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)« less

Effect of different doses of oxytocin on cardiac electrophysiology and arrhythmias induced by ischemia.

PubMed

Houshmand, Fariba; Faghihi, Mahdieh; Imani, Alireza; Kheiri, Soleiman

2017-01-01

The onset of acute myocardial ischemia (MI) is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. This study investigated that whether oxytocin (OT) can modulate ischemia-induced arrhythmias and considered relationships between the severity of arrhythmia and the electrocardiogram parameters during ischemia. OT (0.0001-1 μg) was administrated intraperitoneally 30 min before ischemia. To examine receptor involved, a selective OT-receptor antagonist, atosiban (ATO), was infused 10 min before OT. OT caused a significant and biphasic dose-dependent reduction in ectopic heart activity and arrhythmia score. OT doses that reduced ventricular arrhythmia elicited significant increase in QT interval. OT attenuated the electrophysiological changes associated with MI and there was significant direct relationship between QRS duration and arrhythmia score. ATO treatment reduced beneficial effects of OT on arrhythmogenesis. Nevertheless, ATO failed to alter OT effects on premature ventricular contractions. We assume that the ability of OT to modulate the electrical activity of the heart may play an important role in the antiarrhythmic actions of OT.

Effect of different doses of oxytocin on cardiac electrophysiology and arrhythmias induced by ischemia

PubMed Central

Houshmand, Fariba; Faghihi, Mahdieh; Imani, Alireza; Kheiri, Soleiman

2017-01-01

The onset of acute myocardial ischemia (MI) is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. This study investigated that whether oxytocin (OT) can modulate ischemia-induced arrhythmias and considered relationships between the severity of arrhythmia and the electrocardiogram parameters during ischemia. OT (0.0001–1 μg) was administrated intraperitoneally 30 min before ischemia. To examine receptor involved, a selective OT-receptor antagonist, atosiban (ATO), was infused 10 min before OT. OT caused a significant and biphasic dose-dependent reduction in ectopic heart activity and arrhythmia score. OT doses that reduced ventricular arrhythmia elicited significant increase in QT interval. OT attenuated the electrophysiological changes associated with MI and there was significant direct relationship between QRS duration and arrhythmia score. ATO treatment reduced beneficial effects of OT on arrhythmogenesis. Nevertheless, ATO failed to alter OT effects on premature ventricular contractions. We assume that the ability of OT to modulate the electrical activity of the heart may play an important role in the antiarrhythmic actions of OT. PMID:29184844

European Heart Rhythm Association (EHRA) position paper on arrhythmia management and device therapies in endocrine disorders, endorsed by Asia Pacific Heart Rhythm Society (APHRS) and Latin American Heart Rhythm Society (LAHRS).

PubMed

Gorenek, Bulent; Boriani, Giuseppe; Dan, Gheorge-Andrei; Fauchier, Laurent; Fenelon, Guilherme; Huang, He; Kudaiberdieva, Gulmira; Lip, Gregory Y H; Mahajan, Rajiv; Potpara, Tatjana; Ramirez, Juan David; Vos, Marc A; Marin, Francisco

2018-03-16

Endocrine disorders are associated with various tachyarrhythmias, including atrial fibrillation (AF), ventricular tachycardia (VT), ventricular fibrillation (VF), and bradyarrhythmias. Along with underlying arrhythmia substrate, electrolyte disturbances, glucose, and hormone levels, accompanying endocrine disorders contribute to development of arrhythmia. Arrhythmias may be life-threatening, facilitate cardiogenic shock development and increase mortality. The knowledge on the incidence of tachy- and bradyarrhythmias, clinical and prognostic significance as well as their management is limited; it is represented in observational studies and mostly in case reports on management of challenging cases. It should be also emphasized, that the topic is not covered in detail in current guidelines. Therefore, cardiologists and multidisciplinary teams participating in care of such patients do need the evidence-based, or in case of limited evidence expert-opinion based recommendations, how to treat arrhythmias using contemporary approaches, prevent their complications and recurrence in patients with endocrine disorders. In recognizing this close relationship between endocrine disorders and arrhythmias, the European Heart Rhythm Association (EHRA) convened a Task Force, with representation from Asia-Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLAECE), with the remit of comprehensively reviewing the available evidence and publishing a joint consensus document on endocrine disorders and cardiac arrhythmias, and providing up-to-date consensus recommendations for use in clinical practice.

[Clinical evaluation of the anti-arrhythmic properties and cardiohemodynamic effects of the basic anti-arrhythmia agents].

PubMed

Stoliarchuk, A A; Storozhuk, B G; Briskin, V R

1985-01-01

The authors studied the antiarrhythmic and antifibrillatory effects of the known antiarrhythmic agents and the new Soviet coronaroactive drug phenicaberan exhibiting an antiarrhythmic action. All the drugs were examined for side effects and the action on the central and intracardiac hemodynamics in patients with acute myocardial infarction. Recommendations have been given as to the choice of effective drugs for the prophylaxis of arrhythmias depending on the pattern of heart rhythm abnormality and the hemodynamics.

Contemporary genetic testing in inherited cardiac disease: tools, ethical issues, and clinical applications

PubMed Central

Girolami, Francesca; Frisso, Giulia; Benelli, Matteo; Crotti, Lia; Iascone, Maria; Mango, Ruggiero; Mazzaccara, Cristina; Pilichou, Kalliope; Arbustini, Eloisa; Tomberli, Benedetta; Limongelli, Giuseppe; Basso, Cristina; Olivotto, Iacopo

2018-01-01

Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype–phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, ‘real-world’ experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines. PMID:29176389

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

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

PubMed

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

2017-05-01

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

Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia.

PubMed

Kasper, Burkhard S; Kurzbuch, Katrin; Chang, Bernard S; Pauli, Elisabeth; Hamer, Hajo M; Winkler, Jürgen; Hehr, Ute

2013-06-01

Periventricular nodular heterotopia (PNH) is a developmental disorder of the central nervous system, characterized by heterotopic nodules of gray matter resulting from disturbed neuronal migration. The most common form of bilateral PNH is X-linked dominant inherited, caused by mutations in the Filamin A gene (FLNA) and associated with a wide variety of other clinical findings including congenital heart disease. The typical patient with FLNA-associated PNH is female and presents with difficult to treat seizures. In contrast, hemizygous FLNA loss of function mutations in males are reported to be perinatally lethal. In X-linked dominant traits like FLNA-associated PNH the causal mutation is commonly inherited from the mother. Here, we present an exceptional family with paternal transmission of classic bilateral FLNA-associated PNH from a mildly affected father with somatic and germline mosaicism for a c.5686G>A FLNA splice mutation to both daughters with strikingly variable clinical manifestation and PNH extent in cerebral MR imaging. Our observations emphasize the importance to consider in genetic counseling and risk assessment the rare genetic constellation of paternal transmission for families with X-linked dominant inherited FLNA-associated PNH. Copyright © 2013 Wiley Periodicals, Inc.

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

PubMed Central

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

2016-01-01

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

Inherited Congenital Cataract: A Guide to Suspect the Genetic Etiology in the Cataract Genesis

PubMed Central

Messina-Baas, Olga; Cuevas-Covarrubias, Sergio A.

2017-01-01

Cataracts are the principal cause of treatable blindness worldwide. Inherited congenital cataract (CC) shows all types of inheritance patterns in a syndromic and nonsyndromic form. There are more than 100 genes associated with cataract with a predominance of autosomal dominant inheritance. A cataract is defined as an opacity of the lens producing a variation of the refractive index of the lens. This variation derives from modifications in the lens structure resulting in light scattering, frequently a consequence of a significant concentration of high-molecular-weight protein aggregates. The aim of this review is to introduce a guide to identify the gene involved in inherited CC. Due to the manifold clinical and genetic heterogeneity, we discarded the cataract phenotype as a cardinal sign; a 4-group classification with the genes implicated in inherited CC is proposed. We consider that this classification will assist in identifying the probable gene involved in inherited CC. PMID:28611546

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

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.

Ventricular arrhythmias in the absence of structural heart disease.

PubMed

Prystowsky, Eric N; Padanilam, Benzy J; Joshi, Sandeep; Fogel, Richard I

2012-05-15

Ventricular arrhythmia (VA) in structurally normal hearts can be broadly considered under non-life-threatening monomorphic and life-threatening polymorphic rhythms. Monomorphic VA is classified on the basis of site of origin in the heart, and the most common areas are the ventricular outflow tracts and left ventricular fascicles. The morphology of the QRS complexes on electrocardiogram is an excellent tool to identify the site of origin of the rhythm. Although these arrhythmias are common and generally carry an excellent prognosis, rare sudden death events have been reported. Very frequent ventricular ectopy may also result in a cardiomyopathy in a minority of patients. Suppression of VA may be achieved using calcium-channel blockers, beta-adrenergic blockers, and class I or III antiarrhythmic drugs. Radiofrequency ablation has emerged as an excellent option to eliminate these arrhythmias, although certain foci including aortic cusps and epicardium may be technically challenging. Polymorphic ventricular tachycardia (VT) is rare and generally occurs in patients with genetic ion channel disorders including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic VT, and short QT syndrome. Unlike monomorphic VT, these arrhythmic syndromes are associated with sudden death. While the cardiac gross morphology is normal, suggesting a structurally normal heart, abnormalities exist at the molecular level and predispose them to arrhythmias. Another fascinating area, idiopathic ventricular fibrillation and early repolarization syndrome, are undergoing research for a genetic basis. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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

Protective effects of isorhynchophylline on cardiac arrhythmias in rats and guinea pigs.

PubMed

Gan, Runtao; Dong, Guo; Yu, Jiangbo; Wang, Xu; Fu, Songbin; Yang, Shusen

2011-09-01

As one important constituent extracted from a traditional Chinese medicine, Uncaria Rhynchophylla Miq Jacks, isorhynchophylline has been used to treat hypertension, epilepsy, headache, and other illnesses. Whether isorhynchophylline protects hearts against cardiac arrhythmias is still incompletely investigated. This study was therefore aimed to examine the preventive effects of isorhynchophylline on heart arrhythmias in guinea pigs and rats and then explore their electrophysiological mechanisms. In vivo, ouabain and calcium chloride were used to establish experimental arrhythmic models in guinea pigs and rats. In vitro, the whole-cell patch-lamp technique was used to study the effect of isorhynchophylline on action potential duration and calcium channels in acutely isolated guinea pig and rat cardiomyocytes. The dose of ouabain required to induce cardiac arrhythmias was much larger in guinea pigs administered with isorhynchophylline. Additionally, the onset time of cardiac arrhythmias induced by calcium chloride was prolonged, and the duration was shortened in rats pretreated with isorhynchophylline. The further study showed that isorhynchophylline could significantly decrease action potential duration and inhibit calcium currents in isolated guinea pig and rat cardiomyocytes in a dose-dependent manner. In summary, isorhynchophylline played a remarkably preventive role in cardiac arrhythmias through the inhibition of calcium currents in rats and guinea pigs. © Georg Thieme Verlag KG Stuttgart · New York.

Riluzole reduces arrhythmias and myocardial damage induced by coronary occlusion in anaesthetized pigs.

PubMed

Weiss, Steven M; Dahlstrom, Jane E; Saint, David A

2013-12-01

The cardiac persistent sodium current (IN aP ) presents a novel target for cardiac ischaemic protection. Herein we investigated the effects of the IN aP blocker riluzole in a pig model of regional myocardial ischaemia. Landrace or Large White pigs were subjected to 3 h ligation of the left anterior descending coronary artery (LAD). Pigs received either saline (500 mL/h, i.v.) throughout the experiment (control; n = 7) or riluzole (2 mg/kg in 2 mL propylene glycol in 100 mL saline, i.v.; RIL; n = 7) between 15 and 5 min prior to ligation. The arrhythmia score was calculated in 5 min epochs. Myocardial damage was assessed using epicardial image analysis and histological sectioning. In the control group, all seven pigs developed premature ventricular contractions (PVC), seven developed non-sustained arrhythmias and six of seven developed sustained arrhythmias. Of the sustained arrhythmias, 23 of 28 instances were initiated by R-on-T extrasytoles (extrasystoles within the vulnerable period that can trigger re-entrant arrhythmias). In the RIL group, all seven pigs developed PVC, six of seven developed non-sustained arrhythmias and only three developed sustained arrhythmias, of which two of five instances were R-on-T initiated. The riluzole-treated pigs exhibited less myocardial damage than pigs in the control group (65% smaller surface area (P = 0.008) on gross epicardial inspection, 51% less oedema (P = 0.01), 53% less fibre waviness (P = 0.029) assessed by haematoxylin and eosin staining and 79% fewer fragmented nuclei (P = 0.009) assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling). In conclusion, riluzole significantly reduced Phase 2 (the period associated with irreversible damage) ischaemic R-on-T triggered and non-R-on-T arrhythmias and myocardial damage occurring during the 3 h period of regional ischaemia. © 2013 Wiley Publishing Asia Pty Ltd.

Human ex-vivo action potential model for pro-arrhythmia risk assessment.

PubMed

Page, Guy; Ratchada, Phachareeya; Miron, Yannick; Steiner, Guido; Ghetti, Andre; Miller, Paul E; Reynolds, Jack A; Wang, Ken; Greiter-Wilke, Andrea; Polonchuk, Liudmila; Traebert, Martin; Gintant, Gary A; Abi-Gerges, Najah

2016-01-01

While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-arrhythmic risk in man. Human ventricular trabeculae from ethically consented organ donors were used to evaluate the effects of dofetilide, d,l-sotalol, quinidine, paracetamol and verapamil on AP duration (APD) and recognized pro-arrhythmia predictors (short-term variability of APD at 90% repolarization (STV(APD90)), triangulation (ADP90-APD30) and incidence of early afterdepolarizations at 1 and 2Hz to quantitatively identify the pro-arrhythmic risk. Each drug was blinded and tested separately with 3 concentrations in triplicate trabeculae from 5 hearts, with one vehicle time control per heart. Electrophysiological stability of the model was not affected by sequential applications of vehicle (0.1% dimethyl sulfoxide). Paracetamol and verapamil did not significantly alter anyone of the AP parameters and were classified as devoid of pro-arrhythmic risk. Dofetilide, d,l-sotalol and quinidine exhibited an increase in the manifestation of pro-arrhythmia markers. The model provided quantitative and actionable activity flags and the relatively low total variability in tissue response allowed for the identification of pro-arrhythmic signals. Power analysis indicated that a total of 6 trabeculae derived from 2 hearts are sufficient to identify drug-induced pro-arrhythmia. Thus, the human ex-vivo AP-based model provides an integrative translational assay assisting in shaping clinical development plans that could be used in conjunction with the new CiPA-proposed approach. Copyright © 2016 Elsevier Inc. All rights reserved.

Human ex-vivo action potential model for pro-arrhythmia risk assessment

PubMed Central

Page, Guy; Ratchada, Phachareeya; Miron, Yannick; Steiner, Guido; Ghetti, Andre; Miller, Paul E; Reynolds, Jack A; Wang, Ken; Greiter-Wilke, Andrea; Polonchuk, Liudmila; Traebert, Martin; Gintant, Gary A; Abi-Gerges, Najah

2016-01-01

While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-arrhythmic risk in man. Human ventricular trabeculae from ethically consented organ donors were used to evaluate the effects of dofetilide, d,l-sotalol, quinidine, paracetamol and verapamil on AP duration (APD) and recognized pro-arrhythmia predictors (short-term variability of APD at 90% repolarization (STV(APD90)), triangulation (ADP90-APD30) and incidence of early afterdepolarizations at 1 and 2 Hz to quantitatively identify the pro-arrhythmic risk. Each drug was blinded and tested separately with 3 concentrations in triplicate trabeculae from 5 hearts, with one vehicle time control per heart. Electrophysiological stability of the model was not affected by sequential applications of vehicle (0.1% dimethyl sulfoxide). Paracetamol and verapamil did not significantly alter anyone of the AP parameters and were classified as devoid of pro-arrhythmic risk. Dofetilide, d,l-sotalol and quinidine exhibited an increase in the manifestation of pro-arrhythmia markers. The model provided quantitative and actionable activity flags and the relatively low total variability in tissue response allowed for the identification of pro-arrhythmic signals. Power analysis indicated that a total of 6 trabeculae derived from 2 hearts are sufficient to identify drug-induced pro-arrhythmia. Thus, the human ex-vivo AP-based model provides an integrative translational assay assisting in shaping clinical development plans that could be used in conjunction with the new CiPA-proposed approach. PMID:27235787

Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease.

PubMed

Taylor, Rachel L; Parry, Neil R A; Barton, Stephanie J; Campbell, Christopher; Delaney, Claire M; Ellingford, Jamie M; Hall, Georgina; Hardcastle, Claire; Morarji, Jiten; Nichol, Elisabeth J; Williams, Lindsi C; Douzgou, Sofia; Clayton-Smith, Jill; Ramsden, Simon C; Sharma, Vinod; Biswas, Susmito; Lloyd, I Chris; Ashworth, Jane L; Black, Graeme C; Sergouniotis, Panagiotis I

2017-07-01

To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD). Single-center retrospective case series. Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016. Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate. Ocular and extraocular features were recorded using Human Phenotype Ontology terms. Subsequently, multigene panel testing (105 or 177 IRD-associated genes) was performed in an accredited diagnostic laboratory, followed by clinical variant interpretation. Diagnostic yield and clinical usefulness of genetic testing. Overall, 78.8% of patients (n = 67) received a probable molecular diagnosis; 7.5% (n = 5) of these had autosomal dominant disease, 25.4% (n = 17) had X-linked disease, and 67.2% (n = 45) had autosomal recessive disease. In a further 5.9% of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had a spectrum of clinical features consistent with ABCA4 retinopathy. Most participants (84.7%; n = 72) had undergone EDT and 81.9% (n = 59) of these patients received a probable molecular diagnosis. The genes most frequently mutated in the present cohort were CACNA1F and ABCA4, accounting for 14.9% (n = 10) and 11.9% (n = 8) of diagnoses respectively. Notably, in many cases, genetic testing helped to distinguish stationary from progressive IRD subtypes and to establish a precise diagnosis in a timely fashion. Multigene panel testing pointed to a molecular diagnosis in 84.7% of children with IRD. The diagnostic yield in the study population was significantly higher compared with that in previously reported unselected IRD cohorts. Approaches similar to the one described herein are expected to become a standard component of care in pediatric ophthalmology

The RNAi Inheritance Machinery of Caenorhabditis elegans.

PubMed

Spracklin, George; Fields, Brandon; Wan, Gang; Becker, Diveena; Wallig, Ashley; Shukla, Aditi; Kennedy, Scott

2017-07-01

Gene silencing mediated by dsRNA (RNAi) can persist for multiple generations in Caenorhabditis elegans (termed RNAi inheritance). Here we describe the results of a forward genetic screen in C. elegans that has identified six factors required for RNAi inheritance: GLH-1/VASA, PUP-1/CDE-1, MORC-1, SET-32, and two novel nematode-specific factors that we term here (heritable RNAi defective) HRDE-2 and HRDE-4 The new RNAi inheritance factors exhibit mortal germline (Mrt) phenotypes, which we show is likely caused by epigenetic deregulation in germ cells. We also show that HRDE-2 contributes to RNAi inheritance by facilitating the binding of small RNAs to the inheritance Argonaute (Ago) HRDE-1 Together, our results identify additional components of the RNAi inheritance machinery whose conservation provides insights into the molecular mechanism of RNAi inheritance, further our understanding of how the RNAi inheritance machinery promotes germline immortality, and show that HRDE-2 couples the inheritance Ago HRDE-1 with the small RNAs it needs to direct RNAi inheritance and germline immortality. Copyright © 2017 by the Genetics Society of America.

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

Effect of Cardiac Arrhythmia Simulation on Nursing Students' Knowledge Acquisition and Retention.

PubMed

Tubaishat, Ahmad; Tawalbeh, Loai I

2015-09-01

The realistic and practical environment that simulation provides is an extremely useful part of the teaching process. Simulation is widely used in health and nursing education today. This study aims to evaluate the effect of simulation-based teaching on the acquisition and retention of arrhythmia-related knowledge among nursing students. A randomized controlled design involving a pretest-posttest was used. Nursing students were allocated randomly either to the experimental group (n = 47), who attended simulation scenarios on cardiac arrhythmia, or to the control group (n = 44) who received a traditional lecture on the same topic. A paired t test showed that the mean knowledge score at the posttest was significantly higher than at the pretest for both groups. However, participants in the experimental group demonstrated significantly increased knowledge of cardiac arrhythmia in the first and the second posttest compared with those in the control group. Thus, simulation is superior and significantly improves students' arrhythmia knowledge. © The Author(s) 2014.

Interactions between pacing and arrhythmia detection algorithms in the dual chamber implantable cardioverter defibrillator.

PubMed

Dijkman, B; Wellens, H J

2001-09-01

Dual chamber implantable cardioverter defibrillator (ICD) combines the possibility to detect and treat ventricular and atrial arrhythmias with the possibility of modern heart stimulation techniques. Advanced pacing algorithms together with extended arrhythmia detection capabilities can give rise to new types of device-device interactions. Some of the possible interactions are illustrated by four cases documented in four models of dual chamber ICDs. Functioning of new features in dual chamber devices is influenced by the fact that the pacemaker is not a separate device but a part of the ICD system and that both are being used in a patient with arrhythmia. Programming measures are suggested to optimize use of new pacing algorithms while maintaining correct arrhythmia detection.

Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study.

PubMed

Qirjazi, Elena; McArthur, Eric; Nash, Danielle M; Dixon, Stephanie N; Weir, Matthew A; Vasudev, Akshya; Jandoc, Racquel; Gula, Lorne J; Oliver, Matthew J; Wald, Ron; Garg, Amit X

2016-01-01

The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia. We conducted a population-based retrospective cohort study of older adults (mean age 76 years) from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701) or escitalopram (n = 38 436), compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620). After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days. Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29), and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18). Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68), but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18). Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia.

Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study

PubMed Central

Qirjazi, Elena; McArthur, Eric; Nash, Danielle M.; Dixon, Stephanie N.; Weir, Matthew A.; Vasudev, Akshya; Jandoc, Racquel; Gula, Lorne J.; Oliver, Matthew J.; Wald, Ron; Garg, Amit X.

2016-01-01

Background The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia. Methods We conducted a population-based retrospective cohort study of older adults (mean age 76 years) from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701) or escitalopram (n = 38 436), compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620). After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days. Results Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29), and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18). Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68), but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18). Conclusion Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia. PMID:27513855

Ambient Air Pollution and Daily Outpatient Visits for Cardiac Arrhythmia in Shanghai, China

PubMed Central

Zhao, Ang; Chen, Renjie; Kuang, Xingya; Kan, Haidong

2014-01-01

Background Cardiac arrhythmias are cardiac rhythm disorders that comprise an important public health problem. Few prior studies have examined the association between ambient air pollution and arrhythmias in general populations in mainland China. Methods We performed a time-series analysis to investigate the short-term association between air pollution (particulate matter with an aerodynamic diameter less than 10 µm [PM10], sulfur dioxide [SO2], and nitrogen dioxide [NO2]) and outpatient visits for arrhythmia in Shanghai, China. We applied the over-dispersed Poisson generalized additive model to analyze the associations after control for seasonality, day of the week, and weather conditions. We then stratified the analyses by age, gender, and season. Results We identified a total of 56 940 outpatient visits for cardiac arrhythmia. A 10-µg/m3 increase in the present-day concentrations of PM10, SO2, and NO2 corresponded to increases of 0.56% (95% CI 0.42%, 0.70%), 2.07% (95% CI 1.49%, 2.64%), and 2.90% (95% CI 2.53%, 3.27%), respectively, in outpatient arrhythmia visits. The associations were stronger in older people (aged ≥65 years) and in females. This study provides the first evidence that ambient air pollution is significantly associated with increased risk of cardiac arrhythmia in mainland China. Conclusions Our analyses provide evidence that the current air pollution levels have an adverse effect on cardiovascular health and strengthened the rationale for further limiting air pollution levels in the city. PMID:24835409

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

PubMed Central

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

2012-01-01

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

[Application of targeted capture technology and next generation sequencing in molecular diagnosis of inherited myopathy].

PubMed

Fu, Xiaona; Liu, Aijie; Yang, Haipo; Wei, Cuijie; Ding, Juan; Wang, Shuang; Wang, Jingmin; Yuan, Yun; Jiang, Yuwu; Xiong, Hui

2015-10-01

To elucidate the usefulness of next generation sequencing for diagnosis of inherited myopathy, and to analyze the relevance between clinical phenotype and genotype in inherited myopathy. Related genes were selected for SureSelect target enrichment system kit (Panel Version 1 and Panel Version 2). A total of 134 patients who were diagnosed as inherited myopathy clinically underwent next generation sequencing in Department of Pediatrics, Peking University First Hospital from January 2013 to June 2014. Clinical information and gene detection result of the patients were collected and analyzed. Seventy-seven of 134 patients (89 males and 45 females, visiting ages from 6-month-old to 26-year-old, average visiting age was 6 years and 1 month) underwent next generation sequencing by Panel Version 1 in 2013, and 57 patients underwent next generation sequencing by Panel Version 2 in 2014. The gene detection revealed that 74 patients had pathogenic gene mutations, and the positive rate of genetic diagnosis was 55.22%. One patient was diagnosed as metabolic myopathy. Five patients were diagnosed as congenital myopathy; 68 were diagnosed as muscular dystrophy, including 22 with congenital muscular dystrophy 1A (MDC1A), 11 with Ullrich congenital muscular dystrophy (UCMD), 6 with Bethlem myopathy (BM), 12 with Duchenne muscular dystrophy (DMD) caused by point mutations in DMD gene, 5 with LMNA-related congenital muscular dystrophy (L-CMD), 1 with Emery-Dreifuss muscular dystrophy (EDMD), 7 with alpha-dystroglycanopathy (α-DG) patients, and 4 with limb-girdle muscular dystrophy (LGMD) patients. Next generation sequencing plays an important role in diagnosis of inherited myopathy. Clinical and biological information analysis was essential for screening pathogenic gene of inherited myopathy.

Channelopathies from Mutations in the Cardiac Sodium Channel Protein Complex

PubMed Central

Adsit, Graham S.; Vaidyanathan, Ravi; Galler, Carla M.; Kyle, John W.; Makielski, Jonathan C.

2013-01-01

The cardiac sodium current underlies excitability in heart, and inherited abnormalities of the proteins regulating and conducting this current cause inherited arrhythmia syndromes. This review focuses on inherited mutations in non-pore forming proteins of sodium channel complexes that cause cardiac arrhythmia, and the deduced mechanisms by which they affect function and dysfunction of the cardiac sodium current. Defining the structure and function of these complexes and how they are regulated will contribute to understanding the possible roles for this complex in normal and abnormal physiology and homeostasis. PMID:23557754

Development and validation of a risk calculator predicting exercise-induced ventricular arrhythmia in patients with cardiovascular disease.

PubMed

Hermes, Ilarraza-Lomelí; Marianna, García-Saldivia; Jessica, Rojano-Castillo; Carlos, Barrera-Ramírez; Rafael, Chávez-Domínguez; María Dolores, Rius-Suárez; Pedro, Iturralde

2016-10-01

Mortality due to cardiovascular disease is often associated with ventricular arrhythmias. Nowadays, patients with cardiovascular disease are more encouraged to take part in physical training programs. Nevertheless, high-intensity exercise is associated to a higher risk for sudden death, even in apparently healthy people. During an exercise testing (ET), health care professionals provide patients, in a controlled scenario, an intense physiological stimulus that could precipitate cardiac arrhythmia in high risk individuals. There is still no clinical or statistical tool to predict this incidence. The aim of this study was to develop a statistical model to predict the incidence of exercise-induced potentially life-threatening ventricular arrhythmia (PLVA) during high intensity exercise. 6415 patients underwent a symptom-limited ET with a Balke ramp protocol. A multivariate logistic regression model where the primary outcome was PLVA was performed. Incidence of PLVA was 548 cases (8.5%). After a bivariate model, thirty one clinical or ergometric variables were statistically associated with PLVA and were included in the regression model. In the multivariate model, 13 of these variables were found to be statistically significant. A regression model (G) with a X(2) of 283.987 and a p<0.001, was constructed. Significant variables included: heart failure, antiarrhythmic drugs, myocardial lower-VD, age and use of digoxin, nitrates, among others. This study allows clinicians to identify patients at risk of ventricular tachycardia or couplets during exercise, and to take preventive measures or appropriate supervision. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cardiac Arrhythmia Classification by Multi-Layer Perceptron and Convolution Neural Networks.

PubMed

Savalia, Shalin; Emamian, Vahid

2018-05-04

The electrocardiogram (ECG) plays an imperative role in the medical field, as it records heart signal over time and is used to discover numerous cardiovascular diseases. If a documented ECG signal has a certain irregularity in its predefined features, this is called arrhythmia, the types of which include tachycardia, bradycardia, supraventricular arrhythmias, and ventricular, etc. This has encouraged us to do research that consists of distinguishing between several arrhythmias by using deep neural network algorithms such as multi-layer perceptron (MLP) and convolution neural network (CNN). The TensorFlow library that was established by Google for deep learning and machine learning is used in python to acquire the algorithms proposed here. The ECG databases accessible at PhysioBank.com and kaggle.com were used for training, testing, and validation of the MLP and CNN algorithms. The proposed algorithm consists of four hidden layers with weights, biases in MLP, and four-layer convolution neural networks which map ECG samples to the different classes of arrhythmia. The accuracy of the algorithm surpasses the performance of the current algorithms that have been developed by other cardiologists in both sensitivity and precision.

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…

Inherited Disorders of Bilirubin Clearance

PubMed Central

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

2016-01-01

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

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

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.

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

Electrical stimulation-based renal nerve mapping exacerbates ventricular arrhythmias during acute myocardial ischaemia.

PubMed

Huang, Bing; Zhou, Xiaoya; Wang, Menglong; Li, Xuefei; Zhou, Liping; Meng, Guannan; Wang, Yuhong; Wang, Zhuo; Wang, Songyun; Yu, Lilei; Jiang, Hong

2018-06-01

Blood pressure elevation in response to transient renal nerve stimulation (RNS) has been used to determine the ablation target and endpoint of renal denervation. This study aimed to evaluate the safety of transient RNS in canines with normal or ischaemic hearts. In ten normal (Group 1) and six healed myocardial infarction (HMI) (Group 2) canines, a large-tip catheter was inserted into the left or right renal artery to perform transient RNS. The left stellate ganglion neural activity (LSGNA) and ventricular electrophysiological parameters were measured at baseline and during transient RNS. In another 20 acute myocardial infarction (AMI) canines, RNS (Group 3, n = 10) or sham RNS (Group 4, n = 10) was intermittently (1 min ON and 4 min OFF) performed for 1 h following AMI induction. The LSGNA and AMI-induced ventricular arrhythmias were analysed. In normal and HMI canines, although transient RNS significantly increased the LSGNA and facilitated the action potential duration (APD) alternans, it did not induce any ventricular arrhythmias and did not change the ventricular effective refractory period, APD or maximum slope of the APD restitution curve. In AMI canines, transient RNS significantly exacerbated LSG activation and promoted the incidence of ventricular arrhythmias. Transient RNS did not increase the risk of ventricular arrhythmias in normal or HMI hearts, but it significantly promoted the occurrence of ventricular arrhythmias in AMI hearts. Therefore, electrical stimulation-based renal nerve mapping may be unsafe in AMI patients and in patients with a high risk for malignant ventricular arrhythmias.

[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.

[Analysis on regularity of prescriptions in "a guide to clinical practice with medical record" for diarrhoea based on traditional Chinese medicine inheritance support system].

PubMed

He, Lan-Juan; Zhu, Xiang-Dong

2016-06-01

To analyze the regularities of prescriptions in "a guide to clinical practice with medical record" (Ye Tianshi) for diarrhoea based on traditional Chinese medicine inheritance support system(V2.5), and provide a reference for further research and development of new traditional Chinese medicines in treating diarrhoea. Traditional Chinese medicine inheritance support system was used to build a prescription database of Chinese medicines for diarrhoea. The software integration data mining method was used to analyze the prescriptions according to "four natures", "five flavors" and "meridians" in the database and achieve frequency statistics, syndrome distribution, prescription regularity and new prescription analysis. An analysis on 94 prescriptions for diarrhoea was used to determine the frequencies of medicines in prescriptions, commonly used medicine pairs and combinations, and achieve 13 new prescriptions. This study indicated that the prescriptions for diarrhoea in "a guide to clinical practice with medical record" are mostly of eliminating dampness and tonifying deficienccy, with neutral drug property, sweet, bitter or hot in flavor, and reflecting the treatment principle of "activating spleen-energy and resolving dampness". Copyright© by the Chinese Pharmaceutical Association.

Quantitative Assessment of Arrhythmia Using Non-linear Approach: A Non-invasive Prognostic Tool

NASA Astrophysics Data System (ADS)

Chakraborty, Monisha; Ghosh, Dipak

2017-12-01

Accurate prognostic tool to identify severity of Arrhythmia is yet to be investigated, owing to the complexity of the ECG signal. In this paper, we have shown that quantitative assessment of Arrhythmia is possible using non-linear technique based on "Hurst Rescaled Range Analysis". Although the concept of applying "non-linearity" for studying various cardiac dysfunctions is not entirely new, the novel objective of this paper is to identify the severity of the disease, monitoring of different medicine and their dose, and also to assess the efficiency of different medicine. The approach presented in this work is simple which in turn will help doctors in efficient disease management. In this work, Arrhythmia ECG time series are collected from MIT-BIH database. Normal ECG time series are acquired using POLYPARA system. Both time series are analyzed in thelight of non-linear approach following the method "Rescaled Range Analysis". The quantitative parameter, "Fractal Dimension" (D) is obtained from both types of time series. The major finding is that Arrhythmia ECG poses lower values of D as compared to normal. Further, this information can be used to access the severity of Arrhythmia quantitatively, which is a new direction of prognosis as well as adequate software may be developed for the use of medical practice.

Quantitative Assessment of Arrhythmia Using Non-linear Approach: A Non-invasive Prognostic Tool

NASA Astrophysics Data System (ADS)

Chakraborty, Monisha; Ghosh, Dipak

2018-04-01

Accurate prognostic tool to identify severity of Arrhythmia is yet to be investigated, owing to the complexity of the ECG signal. In this paper, we have shown that quantitative assessment of Arrhythmia is possible using non-linear technique based on "Hurst Rescaled Range Analysis". Although the concept of applying "non-linearity" for studying various cardiac dysfunctions is not entirely new, the novel objective of this paper is to identify the severity of the disease, monitoring of different medicine and their dose, and also to assess the efficiency of different medicine. The approach presented in this work is simple which in turn will help doctors in efficient disease management. In this work, Arrhythmia ECG time series are collected from MIT-BIH database. Normal ECG time series are acquired using POLYPARA system. Both time series are analyzed in thelight of non-linear approach following the method "Rescaled Range Analysis". The quantitative parameter, "Fractal Dimension" (D) is obtained from both types of time series. The major finding is that Arrhythmia ECG poses lower values of D as compared to normal. Further, this information can be used to access the severity of Arrhythmia quantitatively, which is a new direction of prognosis as well as adequate software may be developed for the use of medical practice.

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.

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

[Inherited colorectal cancer predisposition syndromes identified in the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima, Peru;].

PubMed

Castro-Mujica, María del Carmen; Sullcahuamán-Allende, Yasser; Barreda-Bolaños, Fernando; Taxa-Rojas, Luis

2014-04-01

Colorectal cancer (CRC) is the fourth most common cancer in the world and is classified according to their origin in sporadic CRC (~ 70%) and genetic CRC (~ 30%), this latter involves cases of familial aggregation and inherited síndromes that predispose to CRC. To describe inherited CRC predisposition syndromes, polyposic and non-polyposic, identified in the Oncogenetics Unit at National Institute of Cancer Disease (INEN). A descriptive observational record from the attentions of the Oncogenetics Unit at INEN during 2009 to 2013. We included patients with personal or familiar history of CRC and/or colonic polyposis who were referred for clinical assessment to the Oncogenetics Unitat INEN. 59.3 % were female, 40.7 % male, 69.8% under 50 years old, 60.5% had a single CRC, 23.2% had more than one CRC or CRC associated with other extracolonic neoplasia and 32.6% had a familiar history of cancer with autosomal dominant inheritance. According to the clinical genetic diagnosis, 93.1% of the included cases were inherited syndromes that predispose to CRC, with 33.8% of colonic polyposis syndromes, 23.3% of hereditary nonpolyposis CRC syndromes (HNPCC) and 36.0% of CCRHNP probable cases. Clinical genetic evaluation of patients with personal or familiar history of CRC and/or colonic polyposis can identify inherited colorectal cancer predisposition syndromes and provide an appropriategenetic counseling to patients and relatives at risk, establishing guidelines to follow-up and prevention strategies to prevent morbidity and mortality by cancer.

User-initialized active contour segmentation and golden-angle real-time cardiovascular magnetic resonance enable accurate assessment of LV function in patients with sinus rhythm and arrhythmias.

PubMed

Contijoch, Francisco; Witschey, Walter R T; Rogers, Kelly; Rears, Hannah; Hansen, Michael; Yushkevich, Paul; Gorman, Joseph; Gorman, Robert C; Han, Yuchi

2015-05-21

Data obtained during arrhythmia is retained in real-time cardiovascular magnetic resonance (rt-CMR), but there is limited and inconsistent evidence to show that rt-CMR can accurately assess beat-to-beat variation in left ventricular (LV) function or during an arrhythmia. Multi-slice, short axis cine and real-time golden-angle radial CMR data was collected in 22 clinical patients (18 in sinus rhythm and 4 patients with arrhythmia). A user-initialized active contour segmentation (ACS) software was validated via comparison to manual segmentation on clinically accepted software. For each image in the 2D acquisitions, slice volume was calculated and global LV volumes were estimated via summation across the LV using multiple slices. Real-time imaging data was reconstructed using different image exposure times and frame rates to evaluate the effect of temporal resolution on measured function in each slice via ACS. Finally, global volumetric function of ectopic and non-ectopic beats was measured using ACS in patients with arrhythmias. ACS provides global LV volume measurements that are not significantly different from manual quantification of retrospectively gated cine images in sinus rhythm patients. With an exposure time of 95.2 ms and a frame rate of > 89 frames per second, golden-angle real-time imaging accurately captures hemodynamic function over a range of patient heart rates. In four patients with frequent ectopic contractions, initial quantification of the impact of ectopic beats on hemodynamic function was demonstrated. User-initialized active contours and golden-angle real-time radial CMR can be used to determine time-varying LV function in patients. These methods will be very useful for the assessment of LV function in patients with frequent arrhythmias.

Prevention of ventricular arrhythmia and calcium dysregulation in a catecholaminergic polymorphic ventricular tachycardia mouse model carrying calsequestrin-2 mutation.

PubMed

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

2011-03-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca(2+) overload and increased Ca(2+) leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. CPVT mouse models that lack CASQ2 were treated with Ca(2+) -channel inhibitors, β-adrenergic inhibitors, or Mg(2+) . Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca(2+) transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca(2+) channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca(2+) content in mutant myocytes, diminished diastolic Ca(2+) overload, increased systolic Ca(2+) amplitude, and prevented Ca(2+) oscillations in stressed mutant myocytes. Ca(2+) channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca(2+) content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca(2+) buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT. © 2010 Wiley Periodicals, Inc.

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2015-10-15

Microelectrode arrays (MEAs) recording extracellular field potentials of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) provide a rich data set for functional assessment of drug response. The aim of this work is the development of a method for a systematic analysis of arrhythmia using MEAs, with emphasis on the development of six parameters accounting for different types of cardiomyocyte signal irregularities. We describe a software approach to carry out such analysis automatically including generation of a heat map that enables quick visualization of arrhythmic liability of compounds. We also implemented signal processing techniques for reliable extraction of the repolarization peak for field potential duration (FPD) measurement even from recordings with low signal to noise ratios. We measured hiPS-CM's on a 48 well MEA system with 5minute recordings at multiple time points (0.5, 1, 2 and 4h) after drug exposure. We evaluated concentration responses for seven compounds with a combination of hERG, QT and clinical proarrhythmia properties: Verapamil, Ranolazine, Flecainide, Amiodarone, Ouabain, Cisapride, and Terfenadine. The predictive utility of MEA parameters as surrogates of these clinical effects were examined. The beat rate and FPD results exhibited good correlations with previous MEA studies in stem cell derived cardiomyocytes and clinical data. The six-parameter arrhythmia assessment exhibited excellent predictive agreement with the known arrhythmogenic potential of the tested compounds, and holds promise as a new method to predict arrhythmic liability. Copyright © 2015 Elsevier Inc. All rights reserved.

[Observation of antiarrhythmic effects of Cinnamomum migao H. W. Li on experimental arrhythmia].

PubMed

Sui, Y; Qiu, D; Xie, C; Chen, K

1998-08-01

To investigate the effects of Cinnamomum migao on experimental arrhythmia. Arrhythmic models of mice, rabbits, guinea pigs and rats were built using chloroform(Chl), adrenalin(Adr), strophanthin-K (Spt-K) and barium chloride (BaCl2). The affected animals were divided randomly into three groups: control group, Cinnamomum migao (CV-3) group and mexiletine (MXL) group, so as to observe and compare the antiarrhythmic effects. CV-3 could reduce the incidence of ventricular fibrillation caused by ch1 in mice and the ventricular tachycardia induced by Adr in rabbits, delay the onset time of this arrhythmia, increase the arrhythmic doses of Spt-K in guinea pigs, reduce the incidence of some arrhythmia caused by BaCl2 in rats and slow down their heart rate. CV-3 has obvious antiarrhythmic effects on experimental arrhythmia. The mechanism of these effects is probably related to the arrest of the intraflow of Na+, Ca2+ in the cardiac cells and the depression of their cardiac autoarrhythmicity and conductivity.

Sleep-Disordered Breathing and Arrhythmia in Heart Failure Patients.

PubMed

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

2017-06-01

Heart failure (HF) treatment remains complex and challenging, with current recommendations aiming at consideration and treatment of comorbidities in patients with HF. Sleep-disordered breathing (SDB) and arrhythmia come into play, as both are associated with quality of life deterioration, and morbidity and mortality increase in patients with HF. Interactions of these diseases are versatile and may appear intransparent in daily practice. Nevertheless, because of their importance for patients' condition and prognosis, SDB and arrhythmia individually, but also through interaction on one another, necessitate attention, following the fact that treatment is requested and desired considering latest research findings and outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Simultaneous Occurence of an Autosomal Dominant Inherited MSX1 Mutation and an X-linked Recessive Inherited EDA Mutation in One Chinese Family with Non-syndromic Oligodontia.

PubMed

Zhang, Xiao Xia; Wong, Sing Wai; Han, Dong; Feng, Hai Lan

2015-01-01

To describe the simultaneous occurence of an autosomal dominant inherited MSX1 mutation and an X-linked recessive inherited EDA mutation in one Chinese family with nonsyndromic oligodontia. Clinical data of characteristics of tooth agenesis were collected. MSX1 and EDA gene mutations were detected in a Chinese family of non-syndromic oligodontia. Mild hypodontia in the parents and severe oligodontia in the son was recorded. A novel missense heterozygous mutation c.517C>A (p.Arg173Ser) was detected in the MSX1 gene in the boy and the father. A homozygous missense mutation c.1001G>A (p.Arg334His) was detected in the EDA gene in the boy and the same mutant occurred heterozygously in the mother. Simultaneous occurence of two different gene mutations with different inheritence patterns, which both caused oligodontia, which occurred in one subject and in one family, was reported.

The Role of NT-proBNP in the Diagnosis of Ventricular Arrhythmias in Patients with Systemic Sclerosis

PubMed Central

MURESAN, Lucian; PETCU, Ana; MURESAN, Crina; RINZIS, Mirela; GUSETU, Gabriel; POP, Dana; ZDRENGHEA, Dumitru; REDNIC, Simona

2017-01-01

Background: In patients with systemic sclerosis, NT-proBNP is a useful diagnostic marker for pulmonary hypertension and ventricular dysfunction, with important prognostic significance. The aim of this study was to assess the relationship between the NT-proBNP levels and the presence and severity of ventricular arrhythmias in patients with scleroderma. Methods: Forty consecutive patients with a diagnostic of systemic sclerosis according to the EULAR criteria admitted at the Rheumatology Clinic of Cluj-Napoca, Romania, from Jan 2014 to Apr 2014 were enrolled. Patients underwent a 12-lead ECG and a 24-hour Holter ECG monitoring for ventricular arrhythmias evaluation. Blood sample testing (including NT-proBNP level measurements), echocardiography, spirometry, chest X-ray and, when considered appropriate, high-resolution chest CT were performed. Results: Sixty percent of patients (n=24) had abnormal NT-proBNP serum levels (>125 pg/ml) and 10 patients had >100 PVC/24 h. There was a statistically significant correlation between the NT-proBNP levels and the total number of premature ventricular contractions (PVC) (r=0.445, P=0.006), total number of isolated PVC (r=0,493, P=0.002), total number of ventricular couplets (r=0.379, P=0.021) and the number of PVC morphologies (r=0.501, P=0.002). The presence of an NT-proBNP serum level >287 pg/ml had a sensitivity of 55% and a specificity of 93% in predicting the presence of complex ventricular arrhythmias on 24-hour Holter ECG monitoring. Conclusion: NT-proBNP levels could become a useful ventricular arrhythmia marker for assessing the arrhythmic risk in patients with systemic sclerosis. PMID:28845401

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

PubMed Central

Aguilar, Martin

2016-01-01

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

Thromboprophylaxis for atrial arrhythmias in congenital heart disease: A multicenter study.

PubMed

Khairy, Paul; Aboulhosn, Jamil; Broberg, Craig S; Cohen, Scott; Cook, Stephen; Dore, Annie; Fernandes, Susan M; Fournier, Anne; Kay, Joseph; Levesque, Sylvie; Macle, Laurent; Marcotte, François; Mondésert, Blandine; Mongeon, François-Pierre; Opotowsky, Alexander R; Proietti, Anna; Rivard, Lena; Ting, Jennifer; Thibault, Bernard; Zaidi, Ali; Hamilton, Robert

2016-11-15

There is a paucity of data to guide decisions regarding thromboprophylaxis for atrial arrhythmias in congenital heart disease. A retrospective multicenter cohort study enrolled patients with documented sustained atrial arrhythmias and congenital heart disease from 12 North American centers to quantify thromboembolic and bleeding rates associated with antiplatelet and anticoagulation therapy, and explore associated factors. A blinded committee adjudicated all qualifying arrhythmias and outcomes. A total of 482 patients, 45.2% female, age 32.0±18.0years, were followed for 11.3±9.4years since the qualifying arrhythmia. Antiplatelet therapy was administered to 37.8%, anticoagulation to 54.4%, and neither to 7.9%. Congenital heart disease complexity was simple, moderate, and severe in 18.5%, 34.4%, and 47.1%, respectively. Freedom from thromboembolic events was 84.7±2.7% at 15years, with no difference between anticoagulation versus antiplatelet therapy (P=0.97). Congenital heart disease complexity was independently associated with thromboembolic events, with rates of 0.00%, 0.93%, and 1.95%/year in those with simple, moderate, and severe forms (P<0.001). CHADS 2 and CHA 2 DS 2 -VASc scores were not predictive of thromboembolic risk. Annualized bleeding rates with antiplatelet and anticoagulation therapy were 0.66% and 1.82% (P=0.039). In multivariable analyses, anticoagulation [hazard ratio (HR) 4.76, 95% CI (1.05-21.58), P=0.043] and HAS-BLED score [HR 3.15, 95% CI (1.02, 9.78), P=0.047] were independently associated with major bleeds. Current management of atrial arrhythmias in congenital heart disease is associated with a modest rate of thromboembolic events, which is predicted by disease complexity but not CHADS 2 /CHA 2 DS 2 -VASc scores. HAS-BLED score is applicable to the congenital population in predicting major bleeds. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Gene therapy for inherited muscle diseases: where genetics meets rehabilitation medicine.

PubMed

Braun, Robynne; Wang, Zejing; Mack, David L; Childers, Martin K

2014-11-01

The development of clinical vectors to correct genetic mutations that cause inherited myopathies and related disorders of skeletal muscle is advancing at an impressive rate. Adeno-associated virus vectors are attractive for clinical use because (1) adeno-associated viruses do not cause human disease and (2) these vectors are able to persist for years. New vectors are now becoming available as gene therapy delivery tools, and recent preclinical experiments have demonstrated the feasibility, safety, and efficacy of gene therapy with adeno-associated virus for long-term correction of muscle pathology and weakness in myotubularin-deficient canine and murine disease models. In this review, recent advances in the application of gene therapies to treat inherited muscle disorders are presented, including Duchenne muscular dystrophy and x-linked myotubular myopathy. Potential areas for therapeutic synergies between rehabilitation medicine and genetics are also discussed.

Short- and medium-term efficacy of specific hydrotherapy in inherited ichthyosis.

PubMed

Bodemer, C; Bourrat, E; Mazereeuw-Hautier, J; Boralevi, F; Barbarot, S; Bessis, D; Blanchet-Bardon, C; Bourdon-Lanoy, E; Stalder, J-F; Ribet, V; Guerrero, D; Sibaud, V

2011-11-01

Management of inherited ichthyoses is symptomatic. Despite treatment, skin symptoms have a major impact on patients' quality of life (QoL). To assess the short- and medium-term efficacy of hydrotherapy on QoL and clinical symptoms of patients with inherited ichthyosis. In this 9-month prospective, open-label, multicentre study, 20 children and 24 adults with ichthyosis were enrolled in several French reference and competence centres, 2 months before undergoing a 3-week treatment with specific hydrotherapeutic management at Avène Hydrotherapy Centre. At baseline (2 months before hydrotherapy), beginning (D0) and end of hydrotherapy (D18), and 3 and 6 months later at the reference and competence centres, patients self-assessed QoL using the Dermatology Life Quality Index (DLQI) or its paediatric version (Children's DLQI), and investigators evaluated ichthyosis severity using a specific clinical ichthyosis score. The DLQI scores were significantly improved not only at the end of the hydrotherapy treatment (-56% vs. baseline; mean ± SD 3·59 ± 4·30 at D18 vs. 8·35 ± 5·71 at D0; P < 0·0001), but also at 3 months (-28% vs. baseline; P = 0·01) and 6 months after hydrotherapy (-26% vs. baseline; mean ± SD 5·21 ± 5·11 vs. 6·89 ± 5·38; P = 0·03) (primary criterion). Clinical symptoms were also significantly improved at all post-treatment visits, with a decrease of the mean clinical ichthyosis score by -38% between D0 and D18, by -30% at 3 months and by -31% at 6 months vs. baseline. A 3-week treatment at Avène Hydrotherapy Centre provided significant and persisting improvement of QoL and clinical symptoms in patients with inherited ichthyoses. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Right Ventricular Myocardial Ischemia with Arrhythmia in an Asphyxiated Newborn

PubMed Central

Solevåg, Anne Lee; Schmölzer, Georg M.; Cheung, Po-Yin

2016-01-01

Background Infant and neonatal myocardial infarction (MI) has been described in association with congenital heart disease, coronary artery abnormalities, myocarditis, and tumors. MI in the perinatal period in a structurally normal heart and with ventricular arrhythmia as a presenting feature has not been thoroughly described. Published case reports describe treatment methods extrapolated from adult MI. However, due to the rare occurrence, the most appropriate acute treatment for both MI and ventricular arrhythmia in newborn infants remains unknown. Case A male term infant with perinatal asphyxia and need for extensive cardiopulmonary resuscitation at birth had ventricular tachyarrhythmia and ST-elevations on electrocardiogram. Four hours after birth, he died from cardiogenic failure. A thrombus at the right coronary artery was found on autopsy. Conclusion MI in the perinatal period in a structurally normal heart is very rare and mortality is high. Although acute treatments extrapolated from adult MI has been described to result in favorable outcomes in newborn infants, guidelines are lacking on how to manage acute MI and associated ventricular arrhythmia. PMID:27280062

The evolutionary implications of epigenetic inheritance.

PubMed

Jablonka, Eva

2017-10-06

The Modern Evolutionary Synthesis (MS) forged in the mid-twentieth century was built on a notion of heredity that excluded soft inheritance, the inheritance of the effects of developmental modifications. However, the discovery of molecular mechanisms that generate random and developmentally induced epigenetic variations is leading to a broadening of the notion of biological heredity that has consequences for ideas about evolution. After presenting some old challenges to the MS that were raised, among others, by Karl Popper, I discuss recent research on epigenetic inheritance, which provides experimental and theoretical support for these challenges. There is now good evidence that epigenetic inheritance is ubiquitous and is involved in adaptive evolution and macroevolution. I argue that the many evolutionary consequences of epigenetic inheritance open up new research areas and require the extension of the evolutionary synthesis beyond the current neo-Darwinian model.

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

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

Sex- and gender-specific research priorities for the emergency management of heart failure and acute arrhythmia: proceedings from the 2014 Academic Emergency Medicine Consensus Conference Cardiovascular Research Workgroup.

PubMed

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

2014-12-01

The emergency department (ED) is the point of first contact for patients with acute heart failure and arrhythmias, with 1 million annual ED visits in the United States. Although the total numbers of men and women living with heart failure are similar, female patients are underrepresented in clinical studies, with current knowledge predominantly based on data from male patients. This has led to an underappreciation of the sex-specific differences in clinical characteristics and pathophysiology-based management of heart failure. Similar disparities have been found in management of acute arrhythmias, especially atrial arrhythmias that lead to an increased risk of stroke in women. Additionally, peripartum and postpartum cardiomyopathy represent a diagnostic and treatment dilemma. This article is the result of a breakout session in the cardiovascular and resuscitation work group of the 2014 Academic Emergency Medicine consensus conference "Gender-Specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes." A nominal group technique was used to identify and prioritize themes and research questions using electronic mail, monthly conference calls, in-person meetings, and Web-based surveys between June 2013 and May 2014. Consensus was achieved through three rounds of nomination followed by the meeting on May 13, 2014, and resulted in seven priority themes that are essential to the common complex clinical syndrome of heart failure for both men and women and include the areas of pathophysiology; presentation and symptomatology; and diagnostic strategies using biomarkers, treatment, and mortality, with special consideration to arrhythmia management and pregnancy. © 2014 by the Society for Academic Emergency Medicine.

Method and apparatus for the guided ablative therapy of fast ventricular arrhythmia

NASA Technical Reports Server (NTRS)

Cohen, Richard J. (Inventor); Barley, Maya (Inventor)

2010-01-01

Method and apparatus for guiding ablative therapy of abnormal biological electrical excitation. The excitation from the previous excitatory wave is significant at the beginning of the next excitation. In particular, it is designed for treatment of fast cardiac arrhythmias. Electrical signals are acquired from recording electrodes, and an inverse dipole method is used to identify the site of origin of an arrhythmia. The location of the tip of an ablation catheter is similarly localized from signals acquired from the recording electrodes while electrical pacing energy is delivered to the tip of the catheter close to or in contact with the cardiac tissue. The catheter tip is then guided to the site of origin of the arrhythmia, and ablative radio frequency energy is delivered to its tip to ablate the site.

Real-time ECG monitoring and arrhythmia detection using Android-based mobile devices.

PubMed

Gradl, Stefan; Kugler, Patrick; Lohmuller, Clemens; Eskofier, Bjoern

2012-01-01

We developed an application for Android™-based mobile devices that allows real-time electrocardiogram (ECG) monitoring and automated arrhythmia detection by analyzing ECG parameters. ECG data provided by pre-recorded files or acquired live by accessing a Shimmer™ sensor node via Bluetooth™ can be processed and evaluated. The application is based on the Pan-Tompkins algorithm for QRS-detection and contains further algorithm blocks to detect abnormal heartbeats. The algorithm was validated using the MIT-BIH Arrhythmia and MIT-BIH Supraventricular Arrhythmia databases. More than 99% of all QRS complexes were detected correctly by the algorithm. Overall sensitivity for abnormal beat detection was 89.5% with a specificity of 80.6%. The application is available for download and may be used for real-time ECG-monitoring on mobile devices.

Respiratory sinus arrhythmia is a limited measure of cardiac parasympathetic control in man.

PubMed Central

Kollai, M; Mizsei, G

1990-01-01

1. Respiratory modulation of cardiac parasympathetic activity and the relationship between respiratory sinus arrhythmia and parasympathetic control has been studied in twenty-nine conscious, healthy young adult subjects. 2. Changes in heart period in propranolol-treated subjects were taken as the measure of changes in cardiac parasympathetic activity; respiratory sinus arrhythmia was quantified as the difference between maximum and minimum heart periods in a given respiratory cycle; cardiac parasympathetic control was defined as the change in heart period after administration of a full dose of atropine. 3. During normal quiet breathing the inspiratory level of cardiac parasympathetic activity was not reduced to zero. The expiratory level was influenced by excitatory inputs whose activation was related to respiratory cycle length. 4. Slow breathing was associated with augmented sinus arrhythmia, but in different individuals the influence on minimum and maximum heart periods varied so that mean heart period was increased in some subjects but decreased in others. This occurred both in control conditions and after administration of a full dose of propranolol. 5. During normal breathing the correlation across subjects between respiratory sinus arrhythmia and parasympathetic control, although significant, was not close (r = 0.61). The relationship was not affected by beta-adrenergic blockade (r = 0.63). The strength of the correlation improved when multiple regression of respiratory sinus arrhythmia was performed on three variables: parasympathetic control, respiratory cycle length and tidal volume (R = 0.93). 6. It is concluded that in conscious human subjects the respiratory modulation of cardiac parasympathetic activity is different from that observed in the anaesthetized dog, and that variations in the amplitude of respiratory sinus arrhythmia do not necessarily reflect proportional changes in cardiac parasympathetic control. PMID:2391653

Reasons for failed ablation for idiopathic right ventricular outflow tract-like ventricular arrhythmias.

PubMed

Yokokawa, Miki; Good, Eric; Crawford, Thomas; Chugh, Aman; Pelosi, Frank; Latchamsetty, Rakesh; Jongnarangsin, Krit; Ghanbari, Hamid; Oral, Hakan; Morady, Fred; Bogun, Frank

2013-08-01

The right ventricular outflow tract (RVOT) is the most common site of origin of ventricular arrhythmias (VAs) in patients with idiopathic VAs. A left bundle branch block, inferior axis morphology arrhythmia is the hallmark of RVOT arrhythmias. VAs from other sites of origin can mimic RVOT VAs, and ablation in the RVOT typically fails for these VAs. To analyze reasons for failed ablations of RVOT-like VAs. Among a consecutive series of 197 patients with an RVOT-like electrocardiographic (ECG) morphology who were referred for ablation, 38 patients (13 men; age 46 ± 14 years; left ventricular ejection fraction 47% ± 14%) in whom a prior procedure failed within the RVOT underwent a second ablation procedure. ECG characteristics of the VA were compared to a consecutive series of 50 patients with RVOT VAs. The origin of the VA was identified in 95% of the patients. In 28 of 38 (74%) patients, the arrhythmia origin was not in the RVOT. The VA originated from intramural sites (n = 8, 21%), the pulmonary arteries (n = 7, 18%), the aortic cusps (n = 6, 16%), and the epicardium (n = 5, 13%). The origin was within the RVOT in 10 (26%) patients. In 2 (5%) patients, the origin could not be identified despite biventricular, aortic, and epicardial mapping. The VA was eliminated in 34 of 38 (89%) patients with repeat procedures. The ECG features of patients with failed RVOT-like arrhythmias were different from the characteristics of RVOT arrhythmias. In patients in whom ablation of a VA with an RVOT-like appearance fails, mapping of the pulmonary artery, the aortic cusps, the epicardium, the left ventricular outflow tract, and the aortic cusps will help identify the correct site of origin. The 12-lead ECG is helpful in differentiating these VAs from RVOT VAs. Copyright © 2013 Heart Rhythm Society. All rights reserved.

Use of New Imaging CARTO® Segmentation Module Software to Facilitate Ablation of Ventricular Arrhythmias.

PubMed

Tovia-Brodie, Oholi; Belhassen, Bernard; Glick, Aharon; Shmilovich, Haim; Aviram, Galit; Rosso, Raphael; Michowitz, Yoav

2017-02-01

A new imaging software (CARTO® Segmentation Module, Biosense Webster) allows preprocedural 3-D reconstruction of all heart chambers based on cardiac CT. We describe our initial experience with the new module during ablation of ventricular arrhythmias. Eighteen consecutive patients with idiopathic ventricular arrhythmias or ischemic ventricular tachycardia (VT) were studied. In the latter group, a combined endocardial and epicardial ablation was performed. Of the 14 patients with idiopathic arrhythmias, 12 were ablated in the outflow tract (OT), 1 in the midseptal left ventricle, and 1 at the left posterior fascicular area; acute successful ablation was achieved in 11 (78.6%) patients. The procedure was discontinued due to close proximity of the arrhythmia origin to the coronary arteries (CA) in 2 patients. Acute successful uncomplicated ablation was achieved in all 4 patients with ischemic VT. During ablation in the coronary cusps commissures, the CARTO® Segmentation Module accurately defined the cusps anatomy. The precise anatomic location provided by the module assisted in successfully ablating when information from activation mapping was not optimal, by ablating at the opposite side of the cusps. In addition, by demonstrating the precise location of the CA, it allowed safe ablation of arrhythmias that originated in close proximity to the CA both in the OT area and the epicardium, eliminating the need for repeat angiography. The CARTO® Segmentation Module is useful for accurate definition of the exact anatomic location of ventricular arrhythmias and for safely ablating them especially in close proximity to the CA. © 2016 Wiley Periodicals, Inc.

Risk of and risk factors for hypoglycemia and associated arrhythmias in patients with type 2 diabetes and cardiovascular disease: a cohort study under real-world conditions.

PubMed

Pistrosch, Frank; Ganz, Xenia; Bornstein, Stefan R; Birkenfeld, Andreas L; Henkel, Elena; Hanefeld, Markolf

2015-10-01

Severe hypoglycemia is one of the strongest predictors of adverse clinical outcomes in patients with type 2 diabetes. Our study addressed the question whether there is a relationship between hypoglycemic events (HE) and severe cardiac arrhythmias in type 2 diabetic patients with established clinical risk factors under real-world conditions. We included 94 patients with type 2 diabetes and documented cardiovascular disease, in which interstitial glucose values and Holter ECG were recorded for 5 days in parallel. Patients received a stable treatment with insulin and/or sulfonylurea and were instructed to record symptoms of hypoglycemia or arrhythmias. Continuous glucose monitoring revealed 54 HE (interstitial glucose <3.1 mmol/l) in a total of 26 patients. Patients perceived only 39 % of HE during the day and 11 % of HE during the night. Patients with HE had a significantly higher number of severe ventricular arrhythmias [ventricular tachycardia (VT) 32.8 ± 60 vs. 0.9 ± 4.2, p = 0.019], and multivariate regression analysis revealed the duration of severe HE and TSH level as independent predictors of the occurrence of a VT. In conclusion, our study suggests that hypoglycemia might be able to trigger at least under certain circumstances, such as low TSH, ventricular arrhythmias under real-world conditions. The large number of unrecognized HE and VT in vulnerable patients treated with insulin or sulfonylurea should encourage the practitioner to focus on stable glucose control and to search for silent HE.

Primer in Genetics and Genomics, Article 4-Inheritance Patterns.

PubMed

Aiello, Lisa B; Chiatti, Beth Desaretz

2017-07-01

Since the completion of the Human Genome Project, much has been uncovered about inheritance of various illnesses and disorders. There are two main types of inheritance: Mendelian and non-Mendelian. Mendelian inheritance includes autosomal dominant, autosomal recessive, X-linked, and Y-linked inheritance. Non-Mendelian inheritance includes mitochondrial and multifactorial inheritance. Nurses must understand the types of inheritance in order to identify red flags that may indicate the possibility of a hereditary disorder in a patient or family.

Variant pathogenicity evaluation in the community-driven Inherited Neuropathy Variant Browser.

PubMed

Saghira, Cima; Bis, Dana M; Stanek, David; Strickland, Alleene; Herrmann, David N; Reilly, Mary M; Scherer, Steven S; Shy, Michael E; Züchner, Stephan

2018-05-01

Charcot-Marie-Tooth disease (CMT) is an umbrella term for inherited neuropathies affecting an estimated one in 2,500 people. Over 120 CMT and related genes have been identified and clinical gene panels often contain more than 100 genes. Such a large genomic space will invariantly yield variants of uncertain clinical significance (VUS) in nearly any person tested. This rise in number of VUS creates major challenges for genetic counseling. Additionally, fewer individual variants in known genes are being published as the academic merit is decreasing, and most testing now happens in clinical laboratories, which typically do not correlate their variants with clinical phenotypes. For CMT, we aim to encourage and facilitate the global capture of variant data to gain a large collection of alleles in CMT genes, ideally in conjunction with phenotypic information. The Inherited Neuropathy Variant Browser provides user-friendly open access to currently reported variation in CMT genes. Geneticists, physicians, and genetic counselors can enter variants detected by clinical tests or in research studies in addition to genetic variation gathered from published literature, which are then submitted to ClinVar biannually. Active participation of the broader CMT community will provide an advance over existing resources for interpretation of CMT genetic variation. © 2018 Wiley Periodicals, Inc.

Multiclass Classification of Cardiac Arrhythmia Using Improved Feature Selection and SVM Invariants.

PubMed

Mustaqeem, Anam; Anwar, Syed Muhammad; Majid, Muahammad

2018-01-01

Arrhythmia is considered a life-threatening disease causing serious health issues in patients, when left untreated. An early diagnosis of arrhythmias would be helpful in saving lives. This study is conducted to classify patients into one of the sixteen subclasses, among which one class represents absence of disease and the other fifteen classes represent electrocardiogram records of various subtypes of arrhythmias. The research is carried out on the dataset taken from the University of California at Irvine Machine Learning Data Repository. The dataset contains a large volume of feature dimensions which are reduced using wrapper based feature selection technique. For multiclass classification, support vector machine (SVM) based approaches including one-against-one (OAO), one-against-all (OAA), and error-correction code (ECC) are employed to detect the presence and absence of arrhythmias. The SVM method results are compared with other standard machine learning classifiers using varying parameters and the performance of the classifiers is evaluated using accuracy, kappa statistics, and root mean square error. The results show that OAO method of SVM outperforms all other classifiers by achieving an accuracy rate of 81.11% when used with 80/20 data split and 92.07% using 90/10 data split option.

Developmental origins of epigenetic transgenerational inheritance

PubMed Central

Hanson, Mark A.; Skinner, Michael K.

2016-01-01

Abstract 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

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

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.

Surgical outcome of Fontan conversion and arrhythmia surgery: Need a pacemaker?

PubMed

Terada, Takafumi; Sakurai, Hajime; Nonaka, Toshimichi; Sakurai, Takahisa; Sugiura, Junya; Taneichi, Tetsuyoshi; Ohtsuka, Ryohei

2014-07-01

Atrial tachyarrhythmias are frequent complications in the late period after the Fontan procedure, and important risk factors for a poor prognosis. The impact of Fontan conversion and arrhythmia surgery in failed Fontan patients has been described in many reports. We evaluated our experience with Fontan conversion procedures, concomitant arrhythmia surgery, and pacemaker implantation. We reviewed the hospital records of 25 consecutive patients who underwent a Fontan conversion procedure from January 2004 to March 2012. Twenty-four patients had arrhythmia surgery using cryoablation and radiofrequency ablation at the time of conversion. A bilateral atrial maze procedure was performed in 6 patients, right-side maze in 15, and isthmus block in 3. Three patients with a diagnosis of corrected transposition of the great arteries underwent simultaneous pacemaker implantation electively. There was no early death and one late death during a mean follow-up period of 21.2 months. Three tachyarrhythmia recurrences developed, and there were 4 occurrences of sinus bradycardia. Five of these patients required postoperative pacemaker implantation. The mid-term results of Fontan conversion and arrhythmia surgery in our institute were satisfactory. The occurrence of unexpected postoperative pacemaker requirement was high in the patients who underwent a right atrial or bilateral atrial maze procedure. Pacemaker or lead implantation is recommended for patients planned to undergo a right-side or full maze procedure. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Epigenetic Inheritance: A Contributor to Species Differentiation?

PubMed Central

Boffelli, Dario

2012-01-01

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

"What is this genetics, anyway?" Understandings of genetics, illness causality and inheritance among British Pakistani users of genetic services.

PubMed

Shaw, Alison; Hurst, Jane A

2008-08-01

Misconceptions about basic genetic concepts and inheritance patterns may be widespread in the general population. This paper investigates understandings of genetics, illness causality and inheritance among British Pakistanis referred to a UK genetics clinic. During participant observation of genetics clinic consultations and semi-structured interviews in Urdu or English in respondents' homes, we identified an array of environmental, behavioral and spiritual understandings of the causes of medical and intellectual problems. Misconceptions about the location of genetic information in the body and of genetic mechanisms of inheritance were common, reflected the range of everyday theories observed for White British patients and included the belief that a child receives more genetic material from the father than the mother. Despite some participants' conversational use of genetic terminology, some patients had assimilated genetic information in ways that conflict with genetic theory with potentially serious clinical consequences. Additionally, skepticism of genetic theories of illness reflected a rejection of a dominant discourse of genetic risk that stigmatizes cousin marriages. Patients referred to genetics clinics may not easily surrender their lay or personal theories about the causes of their own or their child's condition and their understandings of genetic risk. Genetic counselors may need to identify, work with and at times challenge patients' understandings of illness causality and inheritance.

Recurrent ventricular arrhythmias complicating myocardial infarction in the presence of phaeochromocytoma.

PubMed Central

McNeill, A J; Adgey, A A; Wilson, C

1992-01-01

After an acute myocardial infarction a 49 year old man developed late recurrent severe ventricular arrhythmias coincident with transient hypertensive episodes. A phaeochromocytoma was diagnosed on the basis of the urinary concentration of catecholamines and computerised tomography of the adrenal glands. After stabilisation of his cardiac rhythm and blood pressure with alpha and beta adrenergic blockade and anti-arrhythmic treatment the right adrenal gland, which contained the tumour, was successfully resected. The diagnosis of a phaeochromocytoma should be considered when recurrent ventricular arrhythmias are associated with intermittent hypertension after myocardial infarction. PMID:1739535

The ethical framework for performing research with rare inherited neurometabolic disease patients.

PubMed

Giannuzzi, Viviana; Devlieger, Hugo; Margari, Lucia; Odlind, Viveca Lena; Ragab, Lamis; Bellettato, Cinzia Maria; D'Avanzo, Francesca; Lampe, Christina; Cassis, Linda; Cortès-Saladelafont, Elisenda; Cazorla, Ángels Garcia; Barić, Ivo; Cvitanović-Šojat, Ljerka; Fumić, Ksenija; Dali, Christine I; Bartoloni, Franco; Bonifazi, Fedele; Scarpa, Maurizio; Ceci, Adriana

2017-03-01

The need for performing clinical trials to develop well-studied and appropriate medicines for inherited neurometabolic disease patients faces ethical concerns mainly raising from four aspects: the diseases are rare; include young and very young patients; the neurological impairment may compromise the capability to provide 'consent'; and the genetic nature of the disease leads to further ethical implications. This work is intended to identify the ethical provisions applicable to clinical research involving these patients and to evaluate if these cover the ethical issues. Three searches have been performed on the European regulatory/legal framework, the literature and European Union-funded projects. The European legal framework offers a number of ethical provisions ruling the clinical research on paediatric, rare, inherited diseases with neurological symptoms. In the literature, relevant publications deal with informed consent, newborn genetic screenings, gene therapy and rights/interests of research participants. Additional information raised from European projects on sharing patients' data from different countries, the need to fill the gap of the regulatory framework and to improve information to stakeholders and patients/families. Several recommendations and guidelines on ethical aspects are applicable to the inherited neurometabolic disease research in Europe, even though they suffer from the lack of a common ethical approach. What is Known: • When planning and conducting clinical trials, sponsors and researchers know that clinical trials are to be performed according to well-established ethical rules, and patients should be aware about their rights. • In the cases of paediatric patients, vulnerable patients unable to provide consent, genetic diseases' further rules apply. What is New: • This work discusses which ethical rules apply to ensure protection of patient's rights if all the above-mentioned features coexist. • This work shows available data and

Pharmacy Students’ Performance and Perceptions in a Flipped Teaching Pilot on Cardiac Arrhythmias

PubMed Central

Ip, Eric J.; Lopes, Ingrid; Rajagopalan, Vanishree

2014-01-01

Objective. To implement the flipped teaching method in a 3-class pilot on cardiac arrhythmias and to assess the impact of the intervention on academic performance and student perceptions. Design. An intervention group of 101 first-year pharmacy students, who took the class with the flipped teaching method, were supplied with prerecorded lectures prior to their 3 classes (1 class in each of the following subjects: basic sciences, pharmacology, and therapeutics) on cardiac arrhythmias. Class time was focused on active-learning and case-based exercises. Students then took a final examination that included questions on cardiac arrhythmias. The examination scores of the intervention group were compared to scores of the Spring 2011 control group of 105 first-year students who took the class with traditional teaching methods. An online survey was conducted to assess student feedback from the intervention group. Assessment. The mean examination scores of the intervention group were significantly higher than the mean examination scores of the control group for the cardiac arrhythmia classes in pharmacology (with 89.6 ± 2.0% vs 56.8 ± 2.2%, respectively) and therapeutics (89.2 ± 1.4% vs 73.7 ± 2.1%, respectively). The survey indicated higher student satisfaction for flipped classes with highly rated learning objectives, recordings, and in-class activities. Conclusion. Use of the flipped teaching method in a 3-class pilot on cardiac arrhythmias improved examination scores for 2 of the 3 classes (pharmacology and therapeutics). Student satisfaction was influenced by the quality of the learning objectives, prerecorded lectures, and inclass active-learning activities. PMID:25657372

Added value of cardiac magnetic resonance in etiological diagnosis of ventricular arrhythmias.

PubMed

Cabanelas, Nuno; Vidigal Ferreira, Maria João; Donato, Paulo; Gaspar, António; Pinto, Joana; Caseiro-Alves, Filipe; Providência, Luís Augusto

2013-10-01

Cardiac magnetic resonance (CMR) imaging is increasingly important in the diagnostic work-up of a wide range of heart diseases, including those with arrhythmogenic potential. To assess the added value of CMR in etiological diagnosis of ventricular arrhythmias after an inconclusive conventional investigation. Patients undergoing CMR between 2005 and 2011 for investigation of ventricular arrhythmias were included (n=113). All had documented arrhythmias. Those with a definite diagnosis from a previous investigation and those with evidence of coronary artery disease (acute coronary syndrome, typical angina symptoms, increase in biomarkers or positive stress test) were excluded. CMR results were considered relevant when they fulfilled diagnostic criteria. Of the 113 patients, 57.5% were male and mean age was 41.7 ± 16.2 years. Regarding the initial arrhythmia, 38.1% had ventricular fibrillation/sustained ventricular tachycardia (VF/VT) and 61.9% had less complex ventricular ectopy. CMR imaging showed criteria of a specific diagnosis in 42.5% of patients, was totally normal in 36.3%, and showed non-specific alterations in the remainder. In VF/VT patients, specific criteria were found in 60.4%, and in 31.4% of those with less complex ectopy. The most frequent diagnoses were arrhythmogenic right ventricular dysplasia, ventricular non-compaction and myopericarditis. It is worth noting that, although there was no evidence of previous coronary artery disease, 6.2% of patients had a late gadolinium enhancement distribution pattern compatible with myocardial infarction. CMR gives additional and important information in the diagnostic work-up of ventricular arrhythmias after an inconclusive initial investigation. The proportion of patients with diagnostic criteria was 42.5% (60.0% in those with VF/VT), and CMR was completely normal in 36.6%. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

25 CFR 91.9 - Inheritance of improvements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Inheritance of improvements. 91.9 Section 91.9 Indians..., OSAGE RESERVATION, OKLAHOMA § 91.9 Inheritance of improvements. (a) Upon the death of the owner of... of the county courts, State of Oklahoma, and shall be subject to inheritance or bequest in accordance...

Cardiac arrhythmias during aerobatic flight and its simulation on a centrifuge.

PubMed

Zawadzka-Bartczak, Ewelina K; Kopka, Lech H

2011-06-01

It is well known that accelerations during centrifuge training and during flight can provoke cardiac arrhythmias. Our study was designed to investigate both the similarities and differences between heart rhythm disturbances during flights and centrifuge tests. There were 40 asymptomatic, healthy pilots who performed two training flights and were also tested in a human centrifuge according to a program of rapid onset rate acceleration (ROR) and of centrifuge simulation of the actual acceleration experienced in flight (Simulation). During the flight and centrifuge tests ECG was monitored with the Holter method. ECG was examined for heart rhythm changes and disturbances. During flights, premature ventricular contractions (PVCs) were found in 25% of the subjects, premature supraventricular contractions (PSVCs) and PVCs with bigeminy in 5%, and pairs of PVCs in 2.5% of subjects. During the centrifuge tests, PVCs were experienced by 45% of the subjects, PSVCs and pairs of PVCs by 7.5%, and PVCs with bigeminy by 2.5%. Sinus bradycardia was observed during flights and centrifuge tests in 7.5% of subjects. Comparative evaluation of electrocardiographic records in military pilots during flights and centrifuge tests demonstrated that: 1) there were no clinically significant arrhythmias recorded; and 2) the frequency and kind of heart rhythm disturbances during aerobatic flight and its simulation on a centrifuge were not identical and did not occur repetitively in the same persons during equal phases of the tests.

[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.

In vivo and in vitro antiarrhythmic effects of SSR149744C in animal models of atrial fibrillation and ventricular arrhythmias.

PubMed

Gautier, Patrick; Serre, Martine; Cosnier-Pucheu, Sylvie; Djandjighian, Laurent; Roccon, Alain; Herbert, Jean-Marc; Nisato, Dino

2005-02-01

SSR149744C (2-butyl-3-{4-[3-(dibutylamino)propyl]benzoyl}-1-benzofuran-5-carboxylate isopropyl fumarate) is a new noniodinated benzofuran derivative structurally related to amiodarone and dronedarone that is currently undergoing clinical trials as an antiarrhythmic agent. As SSR149744C exhibits electrophysiological and hemodynamic properties of class I, II, III, and IV antiarrhythmic agents, the aim of this study was to evaluate its acute intravenous (IV) or oral (PO) antiarrhythmic activities in in vitro and in vivo animal models of atrial and ventricular arrhythmias. In vagally induced atrial fibrillation (AF) in anesthetized dogs, SSR149744C (3 and 10 mg/kg IV) terminated AF in all 7 dogs and prevented reinduction in 4 out of 7 dogs; effective refractory periods of right atrium were dose-dependently and frequency-independently lengthened. In low-K+ medium-induced AF models, SSR149744C (0.1 to 1 microM) prevented AF in isolated guinea pig hearts in a concentration-dependent manner. At the ventricular level, SSR149744C (0.1 to 10 mg/kg IV and 3 to 90 mg/kg PO) prevented reperfusion-induced arrhythmias in anesthetized rats with a dose-effect relationship, and, at doses of 30 to 90 mg/kg PO, it reduced early (0-24 hours) mortality following permanent left coronary artery ligature in conscious rats. The present results show that SSR149744C is an effective antiarrhythmic agent in atrial fibrillation and in ventricular arrhythmias. Like amiodarone and dronedarone, its efficiency in these animal models of arrhythmias is likely be related to its multifactorial mechanism of action.

Arrhythmia recognition and classification using combined linear and nonlinear features of ECG signals.

PubMed

Elhaj, Fatin A; Salim, Naomie; Harris, Arief R; Swee, Tan Tian; Ahmed, Taqwa

2016-04-01

Arrhythmia is a cardiac condition caused by abnormal electrical activity of the heart, and an electrocardiogram (ECG) is the non-invasive method used to detect arrhythmias or heart abnormalities. Due to the presence of noise, the non-stationary nature of the ECG signal (i.e. the changing morphology of the ECG signal with respect to time) and the irregularity of the heartbeat, physicians face difficulties in the diagnosis of arrhythmias. The computer-aided analysis of ECG results assists physicians to detect cardiovascular diseases. The development of many existing arrhythmia systems has depended on the findings from linear experiments on ECG data which achieve high performance on noise-free data. However, nonlinear experiments characterize the ECG signal more effectively sense, extract hidden information in the ECG signal, and achieve good performance under noisy conditions. This paper investigates the representation ability of linear and nonlinear features and proposes a combination of such features in order to improve the classification of ECG data. In this study, five types of beat classes of arrhythmia as recommended by the Association for Advancement of Medical Instrumentation are analyzed: non-ectopic beats (N), supra-ventricular ectopic beats (S), ventricular ectopic beats (V), fusion beats (F) and unclassifiable and paced beats (U). The characterization ability of nonlinear features such as high order statistics and cumulants and nonlinear feature reduction methods such as independent component analysis are combined with linear features, namely, the principal component analysis of discrete wavelet transform coefficients. The features are tested for their ability to differentiate different classes of data using different classifiers, namely, the support vector machine and neural network methods with tenfold cross-validation. Our proposed method is able to classify the N, S, V, F and U arrhythmia classes with high accuracy (98.91%) using a combined support

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 F 1 hybrids and recovery in the F 2 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. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Circadian and seasonal variation of malignant arrhythmias in a pediatric and congenital heart disease population.

PubMed

Stephenson, Elizabeth A; Collins, Kathryn K; Dubin, Anne M; Epstein, Michael R; Hamilton, Robert M; Kertesz, Naomi J; Alexander, Mark E; Cecchin, Frank; Triedman, John K; Walsh, Edward P; Berul, Charles I

2002-10-01

Recent studies in adult populations have revealed seasonal variation in the frequency of acute cardiovascular events, including life-threatening arrhythmias, demonstrating increased events during winter and early spring. Trends in the time of day that arrhythmias occur also were noted. We sought to establish whether pediatric and young adult congenital heart disease implantable cardioverter defibrillator (ICD) recipients have circadian or seasonal variability in shock frequency, similar to adult populations. Data from ICD patients at six pediatric centers in North America were analyzed to assess the timing of life-threatening arrhythmias. The populations consisted of children and adults with congenital heart disease and ICDs placed for malignant arrhythmias. Data were considered in 46 patients who received appropriate therapy (total 139 episodes) for ventricular tachycardia or ventricular fibrillation. Multiple variables were analyzed, including time of day, day of week, and month of year. In contrast to previously studied adult patients, fewer events occurred in the early morning (7.5%), with the most therapies occurring between 6 P.M. and midnight (35%). An increased frequency of therapies was observed in the fall and winter (September-January), representing 60% of all appropriate shocks. Unlike adult populations, Mondays did not have an increased frequency of malignant arrhythmias. Pediatric and adult congenital heart disease populations have moderate seasonal and 24-hour variation in ICD event rate, with some distinctly different peaks than those seen in typical adult ICD populations. These findings suggest circadian variation in arrhythmia vulnerability that may differ from conventional occupational, physical, or emotional stressors. (J Cardiovasc Electrophysiol, Vol. 13, pp.

A Real-Time Cardiac Arrhythmia Classification System with Wearable Sensor Networks

PubMed Central

Hu, Sheng; Wei, Hongxing; Chen, Youdong; Tan, Jindong

2012-01-01

Long term continuous monitoring of electrocardiogram (ECG) in a free living environment provides valuable information for prevention on the heart attack and other high risk diseases. This paper presents the design of a real-time wearable ECG monitoring system with associated cardiac arrhythmia classification algorithms. One of the striking advantages is that ECG analog front-end and on-node digital processing are designed to remove most of the noise and bias. In addition, the wearable sensor node is able to monitor the patient's ECG and motion signal in an unobstructive way. To realize the real-time medical analysis, the ECG is digitalized and transmitted to a smart phone via Bluetooth. On the smart phone, the ECG waveform is visualized and a novel layered hidden Markov model is seamlessly integrated to classify multiple cardiac arrhythmias in real time. Experimental results demonstrate that the clean and reliable ECG waveform can be captured in multiple stressed conditions and the real-time classification on cardiac arrhythmia is competent to other workbenches. PMID:23112746

Detection of Life Threatening Ventricular Arrhythmia Using Digital Taylor Fourier Transform.

PubMed

Tripathy, Rajesh K; Zamora-Mendez, Alejandro; de la O Serna, José A; Paternina, Mario R Arrieta; Arrieta, Juan G; Naik, Ganesh R

2018-01-01

Accurate detection and classification of life-threatening ventricular arrhythmia episodes such as ventricular fibrillation (VF) and rapid ventricular tachycardia (VT) from electrocardiogram (ECG) is a challenging problem for patient monitoring and defibrillation therapy. This paper introduces a novel method for detection and classification of life-threatening ventricular arrhythmia episodes. The ECG signal is decomposed into various oscillatory modes using digital Taylor-Fourier transform (DTFT). The magnitude feature and a novel phase feature namely the phase difference (PD) are evaluated from the mode Taylor-Fourier coefficients of ECG signal. The least square support vector machine (LS-SVM) classifier with linear and radial basis function (RBF) kernels is employed for detection and classification of VT vs. VF, non-shock vs. shock and VF vs. non-VF arrhythmia episodes. The accuracy, sensitivity, and specificity values obtained using the proposed method are 89.81, 86.38, and 93.97%, respectively for the classification of Non-VF and VF episodes. Comparison with the performance of the state-of-the-art features demonstrate the advantages of the proposition.

Detection of Life Threatening Ventricular Arrhythmia Using Digital Taylor Fourier Transform

PubMed Central

Tripathy, Rajesh K.; Zamora-Mendez, Alejandro; de la O Serna, José A.; Paternina, Mario R. Arrieta; Arrieta, Juan G.; Naik, Ganesh R.

2018-01-01

Accurate detection and classification of life-threatening ventricular arrhythmia episodes such as ventricular fibrillation (VF) and rapid ventricular tachycardia (VT) from electrocardiogram (ECG) is a challenging problem for patient monitoring and defibrillation therapy. This paper introduces a novel method for detection and classification of life-threatening ventricular arrhythmia episodes. The ECG signal is decomposed into various oscillatory modes using digital Taylor-Fourier transform (DTFT). The magnitude feature and a novel phase feature namely the phase difference (PD) are evaluated from the mode Taylor-Fourier coefficients of ECG signal. The least square support vector machine (LS-SVM) classifier with linear and radial basis function (RBF) kernels is employed for detection and classification of VT vs. VF, non-shock vs. shock and VF vs. non-VF arrhythmia episodes. The accuracy, sensitivity, and specificity values obtained using the proposed method are 89.81, 86.38, and 93.97%, respectively for the classification of Non-VF and VF episodes. Comparison with the performance of the state-of-the-art features demonstrate the advantages of the proposition.

ECG signal quality during arrhythmia and its application to false alarm reduction.

PubMed

Behar, Joachim; Oster, Julien; Li, Qiao; Clifford, Gari D

2013-06-01

An automated algorithm to assess electrocardiogram (ECG) quality for both normal and abnormal rhythms is presented for false arrhythmia alarm suppression of intensive care unit (ICU) monitors. A particular focus is given to the quality assessment of a wide variety of arrhythmias. Data from three databases were used: the Physionet Challenge 2011 dataset, the MIT-BIH arrhythmia database, and the MIMIC II database. The quality of more than 33 000 single-lead 10 s ECG segments were manually assessed and another 12 000 bad-quality single-lead ECG segments were generated using the Physionet noise stress test database. Signal quality indices (SQIs) were derived from the ECGs segments and used as the inputs to a support vector machine classifier with a Gaussian kernel. This classifier was trained to estimate the quality of an ECG segment. Classification accuracies of up to 99% on the training and test set were obtained for normal sinus rhythm and up to 95% for arrhythmias, although performance varied greatly depending on the type of rhythm. Additionally, the association between 4050 ICU alarms from the MIMIC II database and the signal quality, as evaluated by the classifier, was studied. Results suggest that the SQIs should be rhythm specific and that the classifier should be trained for each rhythm call independently. This would require a substantially increased set of labeled data in order to train an accurate algorithm.

Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

PubMed

Yu-Wai-Man, Patrick

2016-10-01

Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Remote Navigation for Complex Arrhythmia

PubMed Central

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

2013-01-01

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

Statins as anti-arrhythmics: a systematic review part II: effects on risk of ventricular arrhythmias.

PubMed

Abuissa, Hussam; O'Keefe, James H; Bybee, Kevin A

2009-10-01

Recent studies have demonstrated that statins may possess anti-arrhythmic properties in addition to their lipid-lowering effects. Studies which reported the association of statins with the incidence of ventricular arrhythmias were identified through a systematic review of the published literature. Statins have been associated with a significant reductions in ventricular arrhythmia in cardiomyopathy patients with an implantable cardioverter defibrillator, although randomized trials have not been completed. Published data suggests that statins may possess anti-arrhythmic properties that reduce the propensity for ventricular arrhythmias. Most of this data is observational; more randomized, placebo-controlled trials are needed.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

PubMed

Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

2017-04-01

Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of

Genetics Home Reference: inherited thyroxine-binding globulin deficiency

MedlinePlus

... Health Conditions Inherited thyroxine-binding globulin deficiency Inherited thyroxine-binding globulin deficiency Printable PDF Open All Close ... to view the expand/collapse boxes. Description Inherited thyroxine-binding globulin deficiency is a genetic condition that ...

Abolition of reperfusion-induced arrhythmias in hearts from thiamine-deficient rats.

PubMed

Oliveira, Fernando A; Guatimosim, Silvia; Castro, Carlos H; Galan, Diogo T; Lauton-Santos, Sandra; Ribeiro, Angela M; Almeida, Alvair P; Cruz, Jader S

2007-07-01

Extensive work has been done regarding the impact of thiamine deprivation on the nervous system. In cardiac tissue, chronic thiamine deficiency is described to cause changes in the myocardium that can be associated with arrhythmias. However, compared with the brain, very little is known about the effects of thiamine deficiency on the heart. Thus this study was undertaken to explore whether thiamine deprivation has a role in cardiac arrhythmogenesis. We examined hearts isolated from thiamine-deprived and control rats. We measured heart rate, diastolic and systolic tension, and contraction and relaxation rates. Whole cell voltage clamp was performed in rat isolated cardiac myocytes to measure L-type Ca(2+) current. In addition, we investigated the global intracellular calcium transients by using confocal microscopy in the line-scan mode. The hearts from thiamine-deficient rats did not degenerate into ventricular fibrillation during 30 min of reperfusion after 15 min of coronary occlusion. The antiarrhythmogenic effects were characterized by the arrhythmia severity index. Our results suggest that hearts from thiamine-deficient rats did not experience irreversible arrhythmias. There was no change in L-type Ca(2+) current density. Inactivation kinetics of this current in Ca(2+)-buffered cells was retarded in thiamine-deficient cardiac myocytes. The global Ca(2+) release was significantly reduced in thiamine-deficient cardiac myocytes. The amplitude of caffeine-releasable Ca(2+) was lower in thiamine-deficient myocytes. In summary, we have found that thiamine deprivation attenuates the incidence and severity of postischemic arrhythmias, possibly through a mechanism involving a decrease in global Ca(2+) release.

Metabolic Syndrome Remodels Electrical Activity of the Sinoatrial Node and Produces Arrhythmias in Rats

PubMed Central

Albarado-Ibañez, Alondra; Avelino-Cruz, José Everardo; Velasco, Myrian; Torres-Jácome, Julián; Hiriart, Marcia

2013-01-01

In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of “metabolic syndrome rats”, compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats. We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats. PMID:24250786

Metabolic syndrome remodels electrical activity of the sinoatrial node and produces arrhythmias in rats.

PubMed

Albarado-Ibañez, Alondra; Avelino-Cruz, José Everardo; Velasco, Myrian; Torres-Jácome, Julián; Hiriart, Marcia

2013-01-01

In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of "metabolic syndrome rats", compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats. We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats.

Systemic right ventricular fibrosis detected by cardiovascular magnetic resonance is associated with clinical outcome, mainly new-onset atrial arrhythmia, in patients after atrial redirection surgery for transposition of the great arteries.

PubMed

Rydman, Riikka; Gatzoulis, Michael A; Ho, Siew Yen; Ernst, Sabine; Swan, Lorna; Li, Wei; Wong, Tom; Sheppard, Mary; McCarthy, Karen P; Roughton, Michael; Kilner, Philip J; Pennell, Dudley J; Babu-Narayan, Sonya V

2015-05-01

We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance predicts outcomes in patients with transposition of the great arteries post atrial redirection surgery. These patients have a systemic right ventricle (RV) and are at risk of arrhythmia, premature RV failure, and sudden death. Fifty-five patients (aged 27±7 years) underwent LGE cardiovascular magnetic resonance and were followed for a median 7.8 (interquartile range, 3.8-9.6) years in a prospective single-center cohort study. RV LGE was present in 31 (56%) patients. The prespecified composite clinical end point comprised new-onset sustained tachyarrhythmia (atrial/ventricular) or decompensated heart failure admission/transplantation/death. Univariate predictors of the composite end point (n=22 patients; 19 atrial/2 ventricular tachyarrhythmia, 1 death) included RV LGE presence and extent, RV volumes/mass/ejection fraction, right atrial area, peak Vo(2), and age at repair. In bivariate analysis, RV LGE presence was independently associated with the composite end point (hazard ratio, 4.95 [95% confidence interval, 1.60-15.28]; P=0.005), and only percent predicted peak Vo(2) remained significantly associated with cardiac events after controlling for RV LGE (hazard ratio, 0.80 [95% confidence interval, 0.68-0.95]; P=0.009/5%). In 8 of 9 patients with >1 event, atrial tachyarrhythmia, itself a known risk factor for mortality, occurred first. There was agreement between location and extent of RV LGE at in vivo cardiovascular magnetic resonance and histologically documented focal RV fibrosis in an explanted heart. There was RV LGE progression in a different case restudied for clinical indications. Systemic RV LGE is strongly associated with adverse clinical outcome especially arrhythmia in transposition of the great arteries, thus LGE cardiovascular magnetic resonance should be incorporated in risk stratification of these patients. © 2015 American Heart

Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats.

PubMed

Hu, Zhaoyang; Chen, Mou; Zhang, Ping; Liu, Jin; Abbott, Geoffrey W

2017-04-26

Sudden cardiac death (SCD), a leading cause of global mortality, most commonly arises from a substrate of cardiac ischemia, but requires an additional trigger. Diabetes mellitus (DM) predisposes to SCD even after adjusting for other DM-linked cardiovascular pathology such as coronary artery disease. We previously showed that remote liver ischemia preconditioning (RLIPC) is highly protective against cardiac ischemia reperfusion injury (IRI) linked ventricular arrhythmias and myocardial infarction, via induction of the cardioprotective RISK pathway, and specifically, inhibitory phosphorylation of GSK-3β (Ser 9). We evaluated the impact of acute streptozotocin-induced DM on coronary artery ligation IRI-linked ventricular arrhythmogenesis and RLIPC therapy in rats. Post-IRI arrhythmia induction was similar in nondiabetic and DM rats, but, unexpectedly, DM rats exhibited lower incidence of SCD during reperfusion (41 vs. 100%), suggesting uncontrolled hyperglycemia does not acutely predispose to SCD. RLIPC was highly effective in both nondiabetic and DM rats at reducing incidence and duration of, and increasing latency to, all classes of ventricular tachyarrhythmias. In contrast, atrioventricular block (AVB) was highly responsive to RLIPC in nondiabetic rats (incidence reduced from 72 to 18%) but unresponsive in DM rats. RISK pathway induction was similar in nondiabetic and DM rats, thus not explaining the DM-specific resistance of AVB to therapy. Our findings uncover important acute DM-specific differences in responsiveness to remote preconditioning for ventricular tachyarrhythmias versus AVB, which may have clinical significance given that AVB is a malignant arrhythmia twofold more common in human diabetics than nondiabetics, and correlated to plasma glucose levels >10 mmol/L.

Noninvasive Predictors of Malignant Arrhythmias.

PubMed

Golukhova, Elena Z; Gromova, Olga; Grigoryan, Marina; Merzlyakov, Vadim; Shumkov, Konstantin; Bockeria, Leo; Serebruany, Victor L

2016-01-01

Prediction and potential prevention of sudden cardiac death (SCD) due to malignant ventricular arrhythmia (MVA) represent an obvious unmet medical need. We estimated the prognostic relevance of numerous biomarkers associated with future MVA development in patients with coronary artery disease (CAD) over 2 years of follow-up. Patients with stable documented CAD (n = 97) with a mean age of 61 ± 10 years were prospectively enrolled in a single-center observational cohort study. Heart failure was diagnosed in 68% of the patients (NYHA class II-III). The mean left ventricular ejection fraction (LVEF) was 50 ± 13%, while 20% of patients had LVEF ≤35%. Sixty-two patients underwent myocardial revascularization during the follow-up (mean 25 ± 11 months). Clinical characteristics (age, gender, diabetes, history of coronary disease and arrhythmias, prior interventions and antecedent medications), noninvasive electrophysiological markers [microvolt T-wave alterations, signal-averaged electrocardiography, QT interval duration and alteration, and heart rate turbulence (HRT) and HR variability], laboratory indices [serum creatinine and creatinine clearance, brain natriuretic peptide (BNP), NT-proBNP, and C-reactive protein and troponin T levels] were assessed with regard to the MVA prognosis. MVA was diagnosed in 11 patients during the prospective follow-up. Prior percutaneous coronary intervention (p < 0.05), MVA or syncope (p < 0.05), on-pump coronary artery bypass grafting during follow-up (p < 0.01), LVEF ≤47% (p < 0.01), a left atrium size ≥4.7 cm (p < 0.05), left atrium index (p = 0.01), filtered QRS duration (p < 0.05), abnormal HRT (x03C7;2 = 6.2, p = 0.01) or turbulence slope (x03C7;2 = 9.5, p < 0.01), BNP ≥158 pg/ml (p < 0.01) and NT-proBNP ≥787 pg/ml (x03C7;2 = 4.4, p < 0.05) were significantly associated with MVA risk by univariate analysis. However, only prior MVA or syncope [odds ratio (OR) 11.1; 95% confidence interval (CI) 2.8-44.4; p < 0

Brain-water diffusion coefficients reflect the severity of inherited prion disease

PubMed Central

Hyare, H.; Wroe, S.; Siddique, D.; Webb, T.; Fox, N. C.; Stevens, J.; Collinge, J.; Yousry, T.; Thornton, J. S.

2010-01-01

Objective: Inherited prion diseases are progressive neurodegenerative conditions, characterized by cerebral spongiosis, gliosis, and neuronal loss, caused by mutations within the prion protein (PRNP) gene. We wished to assess the potential of diffusion-weighted MRI as a biomarker of disease severity in inherited prion diseases. Methods: Twenty-five subjects (mean age 45.2 years) with a known PRNP mutation including 19 symptomatic patients, 6 gene-positive asymptomatic subjects, and 7 controls (mean age 54.1 years) underwent conventional and diffusion-weighted MRI. An index of normalized brain volume (NBV) and region of interest (ROI) mean apparent diffusion coefficient (ADC) for the head of caudate, putamen, and pulvinar nuclei were recorded. ADC histograms were computed for whole brain (WB) and gray matter (GM) tissue fractions. Clinical assessment utilized standardized clinical scores. Mann-Whitney U test and regression analyses were performed. Results: Symptomatic patients exhibited an increased WB mean ADC (p = 0.006) and GM mean ADC (p = 0.024) compared to controls. Decreased NBV and increased mean ADC measures significantly correlated with clinical measures of disease severity. Using a stepwise multivariate regression procedure, GM mean ADC was an independent predictor of Clinician's Dementia Rating score (p = 0.001), Barthel Index of activities of daily living (p = 0.001), and Rankin disability score (p = 0.019). Conclusions: Brain volume loss in inherited prion diseases is accompanied by increased cerebral apparent diffusion coefficient (ADC), correlating with increased disease severity. The association between gray matter ADC and clinical neurologic status suggests this measure may prove a useful biomarker of disease activity in inherited prion diseases. GLOSSARY ADAS-Cog = Alzheimer's Disease Assessment Scale–Cognitive subscale; ADC = apparent diffusion coefficient; ADL = Barthel Activities of Daily Living scale; BET = brain extraction tool; BPRS

Inheritance of tristyly in Oxalis tuberosa (Oxalidaceae).

PubMed

Trognitz, B R; Hermann, M

2001-05-01

Frequencies of floral morphs in progenies obtained from a complete set of diallelic crosses among three accessions of tristylous, octoploid oca (Oxalis tuberosa) were used for a Mendelian analysis of floral morph inheritance. The frequencies observed had the best fit to a model of tetrasomic inheritance with two diallelic factors, S, s and M, m, with S being epistatic over M. No explanation could be found for the unexpected formation of a small percentage of short-styled individuals in crosses between the mid-styled and the long-styled parent. For the acceptance of models of disomic and octosomic inheritance several additional assumptions would have to be made and therefore these modes of inheritance are less likely. Dosage-dependent inheritance of floral morph was rejected. Only a small frequency (36%) of the cross progenies flowered, in contrast to the greater propensity for flowering of O. tuberosa accessions held at gene banks.

Percutaneous cardiopulmonary support for catheter ablation of unstable ventricular arrhythmias in high-risk patients.

PubMed

Carbucicchio, Corrado; Della Bella, Paolo; Fassini, Gaetano; Trevisi, Nicola; Riva, Stefania; Giraldi, Francesco; Baratto, Francesca; Marenzi, Giancarlo; Sisillo, Erminio; Bartorelli, Antonio; Alamanni, Francesco

2009-11-01

In patients with severe cardiomyopathy, recurrent episodes of nontolerated ventricular tachycardia (VT) or electrical storm (ES) frequently cause acute heart failure and cardiac death; the suppression of the arrhythmia is therefore lifesaving, but feasibility of catheter ablation (CA) is precluded by the adverse hemodynamic conditions together with the characteristics of the arrhythmia that interdicts efficacious mapping. The use of the percutaneous cardiopulmonary support (CPS) for circulatory assistance may allow patient's stabilization and enhance efficacy and safety of CA in this emergency setting. 19 patients (19 males; mean age 61 +/- 6 years; chronic ischemic cardiomyopathy, eleven patients; primary dilated cardiomyopathy, six patients; arrhythmogenic right ventricular dysplasia/ cardiomyopathy, two patients) with recurrent nontolerated VT episodes undergoing CPS-assisted CA were retrospectively evaluated. Twelve patients had acute hemodynamic failure refractory to inotropic agents and ventilatory assistance, seven patients had undergone a failing nonconventional CA procedure. 14 patients presented with ES, and in twelve the procedure was undertaken under emergency conditions within 24 h from admission. Patients were ventilated under general anesthesia and assisted by a multidisciplinary team. The CPS system consisted in a Medtronic Bio-Medicus centrifugal pump and in a Maxima Plus oxygenator, a 15-F arterial cannula, and a 17-F venous cannula. Flows between 2 and 3 l/min were activated after induction of 56/62 forms of nontolerated VT, achieving hemodynamic stabilization in all patients. CA was mainly guided by conventional activation mapping and was effective in abolishing 45/56 supported VTs; in 10/19 patients all clinical VTs were suppressed by CA. Mean procedural time was 4 h and 20 min. Complete stabilization was achieved in 13 patients (68%) without VT recurrence during a 7-day in-hospital monitoring. A significant clinical improvement was observed in

Intracoronary infusion of catecholamines causes focal arrhythmias in pigs.

PubMed

Doppalapudi, Harish; Jin, Qi; Dosdall, Derek J; Qin, Hao; Walcott, Gregory P; Killingsworth, Cheryl R; Smith, William M; Ideker, Raymond E; Huang, Jian

2008-09-01

Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic. A 504 electrode sock was placed over both ventricles in six open-chest pigs. During control infusion of saline through a catheter in the left anterior descending coronary artery (LAD), no sustained arrhythmias occurred, and the refractory period estimated by the activation recovery interval (ARI) was 175 +/- 14 ms in the LAD bed below the catheter. After infusion of isoproterenol at 0.1 microg/kg/min through the catheter, the ARI in this bed was significantly reduced to 109 +/- 10 ms. A sharp gradient of refractoriness of 43 +/- 10 ms was at the border of the perfused bed. Sustained monomorphic ventricular tachycardia occurred after drug infusion in the perfused bed or near its boundary in all animals with a cycle length of 329 +/- 26 ms and a focal origin. The maximum slope of the ARI restitution curve at the focal origins of the tachyarrhythmias was always <1 (0.62 +/- 0.15). Similar results with a focal arrhythmia origin occurred in two additional pigs in which intramural mapping was performed with 36 plunge needle electrodes in the left ventricular perfused bed. Regional elevation of a catecholamine, which is one of the alterations produced by acute ischemia, can by itself cause tachyarrhythmias. These arrhythmias are closely associated with a shortened refractory period and a large gradient of the spatial distribution of refractoriness but not with a steep restitution curve.

The use of external event monitoring (web-loop) in the elucidation of symptoms associated with arrhythmias in a general population

PubMed Central

Epifanio, Hindalis Ballesteros; Katz, Marcelo; Borges, Melania Aparecida; Corrêa, Alessandra da Graça; Cintra, Fátima Dumas; Grinberg, Rodrigo Leandro; Ludovice, Ana Cristina Pinotti Pedro; Valdigem, Bruno Pereira; da Silva, Nilton José Carneiro; Fenelon, Guilherme

2014-01-01

Objective To correlate arrhythmic symptoms with the presence of significant arrhythmias through the external event monitoring (web-loop). Methods Between January and December 2011, the web-loop was connected to 112 patients (46% of them were women, mean age 52±21 years old). Specific arrhythmic symptoms were defined as palpitations, pre-syncope and syncope observed during the monitoring. Supraventricular tachycardia, atrial flutter or fibrillation, ventricular tachycardia, pauses greater than 2 seconds or advanced atrioventricular block were classified as significant arrhythmia. The association between symptoms and significant arrhythmias were analyzed. Results The web-loop recorded arrhythmic symptoms in 74 (66%) patients. Of these, in only 14 (19%) patients the association between symptoms and significant cardiac arrhythmia was detected. Moreover, significant arrhythmia was found in 11 (9.8%) asymptomatic patients. There was no association between presence of major symptoms and significant cardiac arrhythmia (OR=0.57, CI95%: 0.21-1.57; p=0.23). Conclusion We found no association between major symptoms and significant cardiac arrhythmia in patients submitted to event recorder monitoring. Event loop recorder was useful to elucidate cases of palpitations and syncope in symptomatic patients. PMID:25295448

Evaluation of heart rhythm variability and arrhythmia in children with systemic and localized scleroderma.

PubMed

Wozniak, Jacek; Dabrowski, Rafal; Luczak, Dariusz; Kwiatkowska, Malgorzata; Musiej-Nowakowska, Elzbieta; Kowalik, Ilona; Szwed, Hanna

2009-01-01

To evaluate possible disturbances in autonomic regulation and cardiac arrhythmias in children with localized and systemic scleroderma. There were 40 children included in the study: 20 with systemic and 20 with localized scleroderma. The control group comprised 20 healthy children. In 24-hour Holter recording, the average rate of sinus rhythm was significantly higher in the groups with systemic and localized scleroderma than in the control group, but there was no significant difference between them. The variability of heart rhythm in both groups was significantly decreased. In the group with systemic scleroderma, single supraventricular ectopic beats were observed in 20% and runs were seen in 40% of patients. In the group with localized scleroderma, supraventricular single ectopic beats occurred in 35% of patients and runs in 45% of those studied. Ventricular arrhythmia occurred in 2 children with systemic scleroderma, but in 1 child, it was complex. The most frequent cardiac arrhythmias in both types of scleroderma in children were of supraventricular origin, whereas ventricular arrhythmias did not occur very often. There were no significant differences in autonomic disturbances manifesting as a higher heart rate and decreased heart rate variability between localized and systemic scleroderma.

Neuromuscular imaging in inherited muscle diseases

PubMed Central

Kley, Rudolf A.; Fischer, Dirk

2010-01-01

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

Temporal abstraction and inductive logic programming for arrhythmia recognition from electrocardiograms.

PubMed

Carrault, G; Cordier, M-O; Quiniou, R; Wang, F

2003-07-01

This paper proposes a novel approach to cardiac arrhythmia recognition from electrocardiograms (ECGs). ECGs record the electrical activity of the heart and are used to diagnose many heart disorders. The numerical ECG is first temporally abstracted into series of time-stamped events. Temporal abstraction makes use of artificial neural networks to extract interesting waves and their features from the input signals. A temporal reasoner called a chronicle recogniser processes such series in order to discover temporal patterns called chronicles which can be related to cardiac arrhythmias. Generally, it is difficult to elicit an accurate set of chronicles from a doctor. Thus, we propose to learn automatically from symbolic ECG examples the chronicles discriminating the arrhythmias belonging to some specific subset. Since temporal relationships are of major importance, inductive logic programming (ILP) is the tool of choice as it enables first-order relational learning. The approach has been evaluated on real ECGs taken from the MIT-BIH database. The performance of the different modules as well as the efficiency of the whole system is presented. The results are rather good and demonstrate that integrating numerical techniques for low level perception and symbolic techniques for high level classification is very valuable.

77 FR 14700 - Streamlining Inherited Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-13

... contains notices to the public of #0;the proposed issuance of rules and regulations. The purpose of these... X [Docket No. CFPB-2011-0039] Streamlining Inherited Regulations AGENCY: Bureau of Consumer... the public for streamlining regulations it recently inherited from other Federal agencies (the...

Muscular MRI-based algorithm to differentiate inherited myopathies presenting with spinal rigidity.

PubMed

Tordjman, Mickael; Dabaj, Ivana; Laforet, Pascal; Felter, Adrien; Ferreiro, Ana; Biyoukar, Moustafa; Law-Ye, Bruno; Zanoteli, Edmar; Castiglioni, Claudia; Rendu, John; Beroud, Christophe; Chamouni, Alexandre; Richard, Pascale; Mompoint, Dominique; Quijano-Roy, Susana; Carlier, Robert-Yves

2018-05-25

Inherited myopathies are major causes of muscle atrophy and are often characterized by rigid spine syndrome, a clinical feature designating patients with early spinal contractures. We aim to present a decision algorithm based on muscular whole body magnetic resonance imaging (mWB-MRI) as a unique tool to orientate the diagnosis of each inherited myopathy long before the genetically confirmed diagnosis. This multicentre retrospective study enrolled 79 patients from referral centres in France, Brazil and Chile. The patients underwent 1.5-T or 3-T mWB-MRI. The protocol comprised STIR and T1 sequences in axial and coronal planes, from head to toe. All images were analyzed manually by multiple raters. Fatty muscle replacement was evaluated on mWB-MRI using both the Mercuri scale and statistical comparison based on the percentage of affected muscle. Between February 2005 and December 2015, 76 patients with genetically confirmed inherited myopathy were included. They were affected by Pompe disease or harbored mutations in RYR1, Collagen VI, LMNA, SEPN1, LAMA2 and MYH7 genes. Each myopathy had a specific pattern of affected muscles recognizable on mWB-MRI. This allowed us to create a novel decision algorithm for patients with rigid spine syndrome by segregating these signs. This algorithm was validated by five external evaluators on a cohort of seven patients with a diagnostic accuracy of 94.3% compared with the genetic diagnosis. We provide a novel decision algorithm based on muscle fat replacement graded on mWB-MRI that allows diagnosis and differentiation of inherited myopathies presenting with spinal rigidity. • Inherited myopathies are rare, diagnosis is challenging and genetic tests require specialized centres and often take years. • Inherited myopathies are often characterized by spinal rigidity. • Whole body magnetic resonance imaging is a unique tool to orientate the diagnosis of each inherited myopathy presenting with spinal rigidity. • Each inherited

Vector platforms for gene therapy of inherited retinopathies

PubMed Central

Trapani, Ivana; Puppo, Agostina; Auricchio, Alberto

2014-01-01

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

Influence of ambient temperature and diurnal temperature range on incidence of cardiac arrhythmias

NASA Astrophysics Data System (ADS)

Kim, Jayeun; Kim, Ho

2017-03-01

We investigated the association between ambient temperature and diurnal temperature range (DTR) and the exacerbation of arrhythmia symptoms, using data from 31,629 arrhythmia-related emergency department (ED) visits in Seoul, Korea. Linear regression analyses with allowances for over-dispersion were applied to temperature variables and ED visits, adjusted for various environmental factors. The effects were expressed as percentage changes in the risk of arrhythmia-related ED visits up to 5 days later, with 95 % confidence intervals (CI), per 1 °C increase in DTR and 1 °C decrease in mean temperature. The overall risk of ED visits increased by 1.06 % (95 % CI 0.39 %, 1.73 %) for temperature and by 1.84 % (0.34, 3.37 %) for DTR. A season-specific effect was detected for temperature during both fall (1.18 % [0.01, 2.37 %]) and winter (0.87 % [0.07, 1.67 %]), and for DTR during spring (3.76 % [0.34, 7.29 %]). Females were more vulnerable, with 1.57 % [0.56, 2.59 %] and 3.84 % [1.53, 6.20 %] for the changes in temperature and DTR, respectively. An age-specific effect was detected for DTR, with 3.13 % [0.95, 5.36 %] for age ≥ 65 years, while a greater increased risk with temperature decrease was observed among those aged <65 (1.08 % [0.17, 2.00 %]) than among those aged ≥65 (1.02 % [0.06, 1.99 %]). Cardiac arrest was inversely related with temperature (1.61 % [0.46, 2.79 %]), while other cardiac arrhythmias depended more on the change in DTR (4.72 % [0.37, 9.26 %]). These findings provide evidence that low-temperature and elevated DTR influence the occurrence of arrhythmia exacerbations or symptoms, suggesting a possible strategy for reducing risk by encouraging vulnerable populations to minimize exposure.

A novel algorithm for reducing false arrhythmia alarms in intensive care units.

PubMed

Srivastava, Chandan; Sharma, Sonal; Jalali, Ali

2016-08-01

Alarm fatigue in intensive care units (ICU) is one of the top healthcare issues in the US. False alarms in ICU will decrease the quality of care and staff response time over the alarms. Normally, false alarm will cause desensitization of the clinical staff which leads to warnings and misleading, if the triggered alarm is true. In this study, we have proposed a multi-model ensemble approach to reduce the false alarm rate in monitoring systems. We have used 750 patient records from PhysioNet database. At First arrhythmia based features from electrocardiogram (ECG), arterial blood pressure (ABP) and photoplethysmogram (PPG) features were extracted from the records. Next, the dataset has been separated into two subsets on the basis of available features information. The first dataset (DS1) is the combination of ECG physiological, ABP and PPG features. Their correlation coefficient and p-values criteria have been applied for relevant alarm-wise feature-set selection, and random forest classifier was used for model development and validation. The threshold based approach was used on second dataset (DS2) which is the combination of arrhythmia, ABP and PPG features. The developed ensemble model is able to achieve sensitivity 83.33-100 % (average 95.56 %) being true alarms and suppress false alarms rate 66.67-89% (average 77.25%). The predictability of classifier shows the advantage to deal with unbalanced set of information, therefore overall model performance has reached to 83.96% accuracy.

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.

Symmetrical compression distance for arrhythmia discrimination in cloud-based big-data services.

PubMed

Lillo-Castellano, J M; Mora-Jiménez, I; Santiago-Mozos, R; Chavarría-Asso, F; Cano-González, A; García-Alberola, A; Rojo-Álvarez, J L

2015-07-01

The current development of cloud computing is completely changing the paradigm of data knowledge extraction in huge databases. An example of this technology in the cardiac arrhythmia field is the SCOOP platform, a national-level scientific cloud-based big data service for implantable cardioverter defibrillators. In this scenario, we here propose a new methodology for automatic classification of intracardiac electrograms (EGMs) in a cloud computing system, designed for minimal signal preprocessing. A new compression-based similarity measure (CSM) is created for low computational burden, so-called weighted fast compression distance, which provides better performance when compared with other CSMs in the literature. Using simple machine learning techniques, a set of 6848 EGMs extracted from SCOOP platform were classified into seven cardiac arrhythmia classes and one noise class, reaching near to 90% accuracy when previous patient arrhythmia information was available and 63% otherwise, hence overcoming in all cases the classification provided by the majority class. Results show that this methodology can be used as a high-quality service of cloud computing, providing support to physicians for improving the knowledge on patient diagnosis.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes.

PubMed

Christie, Joshua R; Beekman, Madeleine

2017-03-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes-specifically their organization into host cells and their uniparental (maternal) inheritance-enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller's ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes-despite their asexual mode of reproduction-can readily undergo adaptive evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Comparison of two teaching methods for cardiac arrhythmia interpretation among nursing students.

PubMed

Varvaroussis, Dimitrios P; Kalafati, Maria; Pliatsika, Paraskevi; Castrén, Maaret; Lott, Carsten; Xanthos, Theodoros

2014-02-01

The aim of this study was to compare the six-stage method (SSM) for instructing primary cardiac arrhythmias interpretation to students without basic electrocardiogram (ECG) knowledge with a descriptive teaching method in a single educational intervention. This is a randomized trial. Following a brief instructional session, undergraduate nursing students, assigned to group A (SSM) and group B (descriptive teaching method), undertook a written test in cardiac rhythm recognition, immediately after the educational intervention (initial exam). Participants were also examined with an unannounced retention test (final exam), one month after instruction. Altogether 134 students completed the study. Interpretation accuracy for each cardiac arrhythmia was assessed. Mean score at the initial exam was 8.71±1.285 for group A and 8.74±1.303 for group B. Mean score at the final exam was 8.25±1.46 for group A vs 7.84±1.44 for group B. Overall results showed that the SSM was equally effective with the descriptive teaching method. The study showed that in each group bradyarrhythmias were identified correctly by more students than tachyarrhythmias. No significant difference between the two teaching methods was seen for any specific cardiac arrhythmia. The SSM effectively develops staff competency for interpreting common cardiac arrhythmias in students without ECG knowledge. More research is needed to support this conclusion and the method's effectiveness must be evaluated if being implemented to trainee groups with preexisting basic ECG interpretation knowledge. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Emulating multiple inheritance in Fortran 2003/2008

DOE PAGES

Morris, Karla

2015-01-24

Although the high-performance computing (HPC) community increasingly embraces object-oriented programming (OOP), most HPC OOP projects employ the C++ programming language. Until recently, Fortran programmers interested in mining the benefits of OOP had to emulate OOP in Fortran 90/95. The advent of widespread compiler support for Fortran 2003 now facilitates explicitly constructing object-oriented class hierarchies via inheritance and leveraging related class behaviors such as dynamic polymorphism. Although C++ allows a class to inherit from multiple parent classes, Fortran and several other OOP languages restrict or prohibit explicit multiple inheritance relationships in order to circumvent several pitfalls associated with them. Nonetheless, whatmore » appears as an intrinsic feature in one language can be modeled as a user-constructed design pattern in another language. The present paper demonstrates how to apply the facade structural design pattern to support a multiple inheritance class relationship in Fortran 2003. As a result, the design unleashes the power of the associated class relationships for modeling complicated data structures yet avoids the ambiguities that plague some multiple inheritance scenarios.« less

Discrete potentials guided radiofrequency ablation for idiopathic outflow tract ventricular arrhythmias.

PubMed

Liu, Enzhao; Xu, Gang; Liu, Tong; Ye, Lan; Zhang, Qitong; Zhao, Yanshu; Li, Guangping

2015-03-01

Discrete potentials (DPs) have been recorded and targeted as the site of ablation of the outflow tract arrhythmias. The aim of the present study was to investigate the significance of DPs with respect to mapping and ablation for idiopathic outflow tract premature ventricular contractions (PVCs) or ventricular tachycardias (VTs). Seventeen consecutive patients with idiopathic right or left ventricular outflow tract PVCs/VTs who underwent radiofrequency catheter ablation were included. Intracardiac electrograms during the mapping and ablation were analysed. During sinus rhythm, sharp high-frequency DPs that displayed double or multiple components were recorded following or buried in the local ventricular electrograms in all of the 17 patients, peak amplitude 0.51 ± 0.21 mV. The same potential was recorded prior to the local ventricular potential of the PVCs/VTs. Spontaneous reversal of the relationship of the DPs to the local ventricular electrogram during the arrhythmias was noted. The DPs were related to a region of low voltage showed by intracardiac high-density contact mapping. At the sites with DPs, lower unipolar and bipolar ventricular voltage of sinus beats were noted compared with the adjacent regions without DPs (unipolar: 6.1 ± 1.8 vs. 8.3 ± 2.3 mV, P < 0.05; bipolar: 0.62 ± 0.45 vs. 1.03 ± 0.60 mV, P < 0.05). The targeted DPs were still present in 12 patients after successful elimination of the ectopies. Discrete potentials were not present in seven controls. Discrete potentials and related low-voltage regions were common in idiopathic outflow tract ventricular arrhythmias. Discrete potential- and substrate-guided ablation strategy will help to reduce the recurrence of idiopathic outflow tract arrhythmias. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

[Intravenous nitroglycerin infusion suppresses exercise-induced arrhythmia in patients with ischemic cardiopathy: indications for chronic treatment ].

PubMed

Bonetti, F; Margonato, A; Mailhac, A; Vicedomini, G; Cianflone, D; Scarpazza, P; Chierchia, S L

1990-05-01

In patients with ischemic heart disease and arrhythmias, selection of antiarrhythmic treatment is often difficult as it is hard to separate "primary" from ischemic arrhythmias. We studied 20 patients with ischemic heart disease, who developed ventricular arrhythmias consistently during exercise test. Exercise test was performed twice during infusion of placebo and then during intravenous administration of nitroglycerin, titrated to reduce systolic blood pressure by 10 mmHg. Exercise duration was 7.8 +/- 1.7 and 7.9 +/- 1.5 min, in the 2 placebo tests (NS). Angina developed in 5 patients and ischemic ST changes in 10. With nitroglycerin exercise duration increased to 8.4 +/- 20 min (p less than 0.05), diagnostic ST segment depression was observed in 2 patients and only 1 had angina. In all 20 patients, ventricular arrhythmias were consistently present during both tests on placebo, that were markedly reduced by nitroglycerin. In fact, ventricular ectopic beats were 455 (mean 35.8 +/- 16.8) and 418 (mean 34.4 +/- 11.1) in the 2 exercise tests with placebo, and 11 during nitroglycerin infusion (mean 0.6 +/- 0.1; p less than 0.001). Couplets were 28 and 29 during placebo (NS) and 0 during nitroglycerin (p less than 0.001). Ventricular tachycardia was present in 6 and 8 patients during placebo but in none during nitroglycerin (p less than 0.001). Reduction of exercise-induced arrhythmias was maintained during chronic treatment with oral vasodilators. Prevention of exercise-related arrhythmias by nitroglycerin infusion appears a good indicator of their ischemic origin and may provide valuable information for long-term profilaxis with oral vasodilators, then avoiding the use of antiarrhythmic agents and their potential side effects.

Detection of mild inherited disorders of blood coagulation: current options and personal recommendations.

PubMed

Lippi, Giuseppe; Pasalic, Leonardo; Favaloro, Emmanuel J

2015-08-01

Although assessment of prior personal and familial bleeding history is an important aspect of the diagnosis of bleeding disorders, patients with mild inherited bleeding disorders are sometimes clinically asymptomatic until presented with a hemostatic challenge. However, bleeding may occur after incursion of trauma or surgery, so detection of these conditions reflects an important facet of clinical and laboratory practice. Mild bleeding disorders may be detected as a result of family studies or following identification of abnormal values in first-line screening tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and global platelet function screen testing, such as the platelet function analyzer. Following determination of abnormal screening tests, subsequent investigation should follow a systematic approach that targets specific diagnostic tests, and including factor assays, full platelet function assays and more extensive specialized hemostasis testing. The current report provides a personal overview on inherited disorders of blood coagulation and their detection.

Random forests ensemble classifier trained with data resampling strategy to improve cardiac arrhythmia diagnosis.

PubMed

Ozçift, Akin

2011-05-01

Supervised classification algorithms are commonly used in the designing of computer-aided diagnosis systems. In this study, we present a resampling strategy based Random Forests (RF) ensemble classifier to improve diagnosis of cardiac arrhythmia. Random forests is an ensemble classifier that consists of many decision trees and outputs the class that is the mode of the class's output by individual trees. In this way, an RF ensemble classifier performs better than a single tree from classification performance point of view. In general, multiclass datasets having unbalanced distribution of sample sizes are difficult to analyze in terms of class discrimination. Cardiac arrhythmia is such a dataset that has multiple classes with small sample sizes and it is therefore adequate to test our resampling based training strategy. The dataset contains 452 samples in fourteen types of arrhythmias and eleven of these classes have sample sizes less than 15. Our diagnosis strategy consists of two parts: (i) a correlation based feature selection algorithm is used to select relevant features from cardiac arrhythmia dataset. (ii) RF machine learning algorithm is used to evaluate the performance of selected features with and without simple random sampling to evaluate the efficiency of proposed training strategy. The resultant accuracy of the classifier is found to be 90.0% and this is a quite high diagnosis performance for cardiac arrhythmia. Furthermore, three case studies, i.e., thyroid, cardiotocography and audiology, are used to benchmark the effectiveness of the proposed method. The results of experiments demonstrated the efficiency of random sampling strategy in training RF ensemble classification algorithm. Copyright © 2011 Elsevier Ltd. All rights reserved.

Gene therapy for inherited retinal degenerations: initial successes and future challenges

NASA Astrophysics Data System (ADS)

Gupta, Priya R.; Huckfeldt, Rachel M.

2017-10-01

Inherited retinal degenerations are a clinically and genetically heterogeneous group of conditions that have historically shared an untreatable course. In recent years, however, a wide range of therapeutic strategies have demonstrated efficacy in preclinical studies and entered clinical trials with a common goal of improving visual function for patients affected with these conditions. Gene therapy offers a particularly elegant and precise opportunity to target the causative genetic mutations underlying these monogenic diseases. The present review will provide an overview of gene therapy with particular emphasis on key clinical results to date and challenges for the future.

26 CFR 1.102-1 - Gifts and inheritances.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

Multicentric Castleman's disease associated with inherited epidermolysis bullosa.

PubMed

Kawakami, Yoshio; Nishibu, Akiko; Kikuchi, Satoshi; Ohtsuka, Mikio; Nakamura, Koichiro; Nozawa, Yoshihiro; Abe, Masafumi; Iwatsuki, Keiji; Kaneko, Fumio

2003-09-01

Multicentric Castleman's disease (MCD) is a rare disorder characterized by fever, polyclonal hypergammaglobulinemia, and generalized lymphadenopathy. It has three histological characteristics: a recognizable architecture, germinal center abnormalities, and plasmacytosis. Inherited epidermolysis bullosa (EB) is also a rare disorder caused by a genetic defect. We report a 43-year-old patient with dystrophic EB, non-Hallopeau-Siemens recessive type or dominant type, displaying clinicopathologic features of MCD. In addition, his serum interleukin-6, which is thought to be responsible for the clinical symptoms in MCD, was elevated.

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

PubMed

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

2013-09-01

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. 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. 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). 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.

Effects of child maltreatment and inherited liability on antisocial development: an official records study.

PubMed

Jonson-Reid, Melissa; Presnall, Ned; Drake, Brett; Fox, Louis; Bierut, Laura; Reich, Wendy; Kane, Phyllis; Todd, Richard D; Constantino, John N

2010-04-01

Evidence is steadily accumulating that a preventable environmental hazard, child maltreatment, exerts causal influences on the development of long-standing patterns of antisocial behavior in humans. The relationship between child maltreatment and antisocial outcome, however, has never previously been tested in a large-scale study in which official reports (rather than family member reports) of child abuse and neglect were incorporated, and genetic influences comprehensively controlled for. We cross-referenced official report data on child maltreatment from the Missouri Division of Social Services (DSS) with behavioral data from 4,432 epidemiologically ascertained Missouri twins from the Missouri Twin Registry (MOTWIN). We performed a similar procedure for a clinically ascertained sample of singleton children ascertained from families affected by alcohol dependence participating in the Collaborative Study on the Genetics of Alcoholism (COGA; n = 428) to determine whether associations observed in the general population held true in an "enriched" sample at combined inherited and environmental risk for antisocial development. For both the twin and clinical samples, the additive effects (not interactive effects) of maltreatment and inherited liability on antisocial development were confirmed and were highly statistically significant. Child maltreatment exhibited causal influence on antisocial outcome when controlling for inherited liability in both the general population and in a clinically ascertained sample. Official report maltreatment data represents a critical resource for resolving competing hypotheses on genetic and environmental causation of child psychopathology, and for assessing intervention outcomes in efforts to prevent antisocial development.

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.

Plants and their bioactive compounds with the potential to enhance mechanisms of inherited cardiac regeneration.

PubMed

Zhou, Zhen; Li, Dianbin; Zhou, Hua; Lin, Xiaoli; Li, Censing; Tang, Mingfeng; Feng, Zhou; Li, Ming

2015-06-01

This article reviews the current progress and research indications in the application of natural plant compounds with the potential for the treatment of cardiovascular diseases. Our understanding of how to apply natural plant compounds to enhance mechanisms of inherited cardiac regeneration, which is physiologically pertinent to myocyte turnover or minor cardiac repair, for substantial cardiac regeneration to repair pathological heart injuries is discussed. Although significant progress has been made in the application of natural plant compounds for therapy of heart diseases, the understanding or the application of these compounds specifically for enhancing mechanisms of inherited cardiac regeneration for the treatment of cardiovascular diseases is little. Recent recognition of some natural plant compounds that can repair damaged myocardial tissues through enhancing mechanisms of inherited cardiac regeneration has offered an alternative for clinical translation. Application of natural plant compounds, which show the activity of manipulating gene expressions in such a way to enhance mechanisms of inherited cardiac regeneration for cardiac repair, may provide a promising strategy for the reconstruction of damaged cardiac tissues due to cardiovascular diseases. Georg Thieme Verlag KG Stuttgart · New York.

A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases.

PubMed

Bullich, Gemma; Domingo-Gallego, Andrea; Vargas, Iván; Ruiz, Patricia; Lorente-Grandoso, Laura; Furlano, Mónica; Fraga, Gloria; Madrid, Álvaro; Ariceta, Gema; Borregán, Mar; Piñero-Fernández, Juan Alberto; Rodríguez-Peña, Lidia; Ballesta-Martínez, Maria Juliana; Llano-Rivas, Isabel; Meñica, Mireia Aguirre; Ballarín, José; Torrents, David; Torra, Roser; Ars, Elisabet

2018-05-22

Molecular diagnosis of inherited kidney diseases remains a challenge due to their expanding phenotypic spectra as well as the constantly growing list of disease-causing genes. Here we develop a comprehensive approach for genetic diagnosis of inherited cystic and glomerular nephropathies. Targeted next generation sequencing of 140 genes causative of or associated with cystic or glomerular nephropathies was performed in 421 patients, a validation cohort of 116 patients with previously known mutations, and a diagnostic cohort of 207 patients with suspected inherited cystic disease and 98 patients with glomerular disease. In the validation cohort, a sensitivity of 99% was achieved. In the diagnostic cohort, causative mutations were found in 78% of patients with cystic disease and 62% of patients with glomerular disease, mostly familial cases, including copy number variants. Results depict the distribution of different cystic and glomerular inherited diseases showing the most likely diagnosis according to perinatal, pediatric and adult disease onset. Of all the genetically diagnosed patients, 15% were referred with an unspecified clinical diagnosis and in 2% genetic testing changed the clinical diagnosis. Therefore, in 17% of cases our genetic analysis was crucial to establish the correct diagnosis. Complex inheritance patterns in autosomal dominant polycystic kidney disease and Alport syndrome were suspected in seven and six patients, respectively. Thus, our kidney-disease gene panel is a comprehensive, noninvasive, and cost-effective tool for genetic diagnosis of cystic and glomerular inherited kidney diseases. This allows etiologic diagnosis in three-quarters of patients and is especially valuable in patients with unspecific or atypical phenotypes. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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…

The role of inheritance in structuring hyperextended rift systems

NASA Astrophysics Data System (ADS)

Manatschal, Gianreto; Lavier, Luc; Chenin, Pauline

2015-04-01

A long-standing question in Earth Sciences is related to the importance of inheritance in controlling tectonic processes. In contrast to physical processes that are generally applicable, assessing the role of inheritance suffers from two major problems: firstly, it is difficult to appraise without having insights into the history of a geological system; and secondly all inherited features are not reactivated during subsequent deformation phases. Therefore, the aim of our presentation is to give some conceptual framework about how inheritance may control the architecture and evolution of hyperextended rift systems. We use the term inheritance to refer to the difference between an "ideal" layer-cake type lithosphere and a "real" lithosphere containing heterogeneities and we define 3 types of inheritance, namely structural, compositional and thermal inheritance. Moreover, we assume that the evolution of hyperextended rift systems reflects the interplay between their inheritance (innate/"genetic code") and the physical processes at play (acquired/external factors). Thus, by observing the architecture and evolution of hyperextended rift systems and integrating the physical processes, one my get hints on what may have been the original inheritance of a system. Using this approach, we focus on 3 well-studied rift systems that are the Alpine Tethys, Pyrenean-Bay of Biscay and Iberia-Newfoundland rift systems. For the studied examples we can show that: 1) strain localization on a local scale and during early stages of rifting is controlled by inherited structures and weaknesses 2) the architecture of the necking zone seems to be influenced by the distribution and importance of ductile layers during decoupled deformation and is consequently controlled by the thermal structure and/or the inherited composition of the curst 3) the location of breakup in the 3 examples is not significantly controlled by the inherited structures 4) inherited mantle composition and rift

Arctigenin, a potential anti-arrhythmic agent, inhibits aconitine-induced arrhythmia by regulating multi-ion channels.

PubMed

Zhao, Zhenying; Yin, Yongqiang; Wu, Hong; Jiang, Min; Lou, Jianshi; Bai, Gang; Luo, Guo'an

2013-01-01

Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (I(Na)), L-type calcium current (I(Ca, L)) and transient outward potassium current (I(to)) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited I(Na) and I(Ca,L) and attenuated the aconitine-increased I(Na) and I(Ca,L) by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine. Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, I(Na), I(Ca, L), and I(to) may be multiple targets of arctigenin, leading to its antiarrhythmic effect. © 2013 S. Karger AG, Basel.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes

PubMed Central

Christie, Joshua R.; Beekman, Madeleine

2017-01-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes—specifically their organization into host cells and their uniparental (maternal) inheritance—enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller’s ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes—despite their asexual mode of reproduction—can readily undergo adaptive evolution. PMID:28025277

The effect of Cardiac Arrhythmias Simulation Software on the nurses' learning and professional development.

PubMed

Bazrafkan, Leila; Hemmati, Mehdi

2018-04-01

One of the important tasks of nurses in intensive care unit is interpretation of ECG. The use of training simulator is a new paradigm in the age of computers. This study was performed to evaluate the impact of cardiac arrhythmias simulator software on nurses' learning in the subspecialty Vali-Asr Hospital in 2016. This study was conducted by quasi-experimental randomized Salomon four group design with the participation of 120 nurses in subspecialty Vali-Asr Hospital in Tehran, Iran in 2016 that were selected purposefully and allocated in 4 groups. By this design other confounding factors such as the prior information, maturation and the role of sex and age were controlled by Solomon 4 design. The valid and reliable multiple choice test tools were used to gather information; the validity of the test was approved by experts and its reliability was obtained by Cronbach's alpha coefficient 0.89. At first, the knowledge and skills of the participants were assessed by a pre-test; following the educational intervention with cardiac arrhythmias simulator software during 14 days in ICUs, the mentioned factors were measured for the two groups again by a post-test in the four groups. Data were analyzed using the two way ANOVA. The significance level was considered as p<0.05. Based on randomized four-group Solomon designs and our test results, using cardiac arrhythmias simulator software as an intervention was effective in the nurses' learning since a significant difference was found between pre-test and post-test in the first group (p<0.05). Also, other comparisons by ANOVA test showed that there was no interaction between pre-test and intervention in all of the three knowledge areas of cardiac arrhythmias, their treatments and their diagnosis (P>0.05). The use of software-based simulator for cardiac arrhythmias was effective in nurses' learning in light of its attractive components and interactive method. This intervention increased the knowledge of the nurses in cognitive

Nandrolone Plus Moderate Exercise Increases the Susceptibility to Lethal Arrhythmias

PubMed Central

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

2015-01-01

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

Possible influence of the polarity reversal of the solar magnetic field on the various types of arrhythmias

NASA Astrophysics Data System (ADS)

Giannaropoulou, E.; Papailiou, M.; Mavromichalaki, H.; Gigolashvili, M.; Tvildiani, L.; Janashia, K.; Preka-Papadema, P.; Papadima, Th

2013-02-01

Over the last few years various researches have reached the conclusion that cosmic ray variations and geomagnetic disturbances are related to the condition of the human physiological state. In this study medical data concerning the number of incidents of different types of cardiac arrhythmias for the time period 1983 - 1992 which refer to 1902 patients in Tbilisi, Georgia were used. The smoothing method and the Pearson r-coefficients were used to examine the possible effect of different solar and geomagnetic activity parameters and cosmic ray intensity variations on the different types of arrhythmias. The time interval under examination was separated into two different time periods which coincided with the polarity reversal of the solar magnetic field that occurred in the years 1989-1990 and as a result a different behavior of all the above mentioned parameters as well as of the different types of arrhythmias was noticed during the two time intervals. In addition, changing of polarity sign of the solar magnetic field was found to affect the sign of correlation between the incidence of arrhythmias and the aforementioned parameters. The primary and secondary maxima observed in the solar parameters during the solar cycle 22, also appeared in several types of arrhythmias with a time lag of about five months.

Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension

PubMed Central

Benoist, David; Stones, Rachel; Drinkhill, Mark J.; Benson, Alan P.; Yang, Zhaokang; Cassan, Cecile; Gilbert, Stephen H.; Saint, David A.; Cazorla, Olivier; Steele, Derek S.; Bernus, Olivier

2012-01-01

Pulmonary hypertension provokes right heart failure and arrhythmias. Better understanding of the mechanisms underlying these arrhythmias is needed to facilitate new therapeutic approaches for the hypertensive, failing right ventricle (RV). The aim of our study was to identify the mechanisms generating arrhythmias in a model of RV failure induced by pulmonary hypertension. Rats were injected with monocrotaline to induce either RV hypertrophy or failure or with saline (control). ECGs were measured in conscious, unrestrained animals by telemetry. In isolated hearts, electrical activity was measured by optical mapping and myofiber orientation by diffusion tensor-MRI. Sarcoplasmic reticular Ca2+ handling was studied in single myocytes. Compared with control animals, the T-wave of the ECG was prolonged and in three of seven heart failure animals, prominent T-wave alternans occurred. Discordant action potential (AP) alternans occurred in isolated failing hearts and Ca2+ transient alternans in failing myocytes. In failing hearts, AP duration and dispersion were increased; conduction velocity and AP restitution were steeper. The latter was intrinsic to failing single myocytes. Failing hearts had greater fiber angle disarray; this correlated with AP duration. Failing myocytes had reduced sarco(endo)plasmic reticular Ca2+-ATPase activity, increased sarcoplasmic reticular Ca2+-release fraction, and increased Ca2+ spark leak. In hypertrophied hearts and myocytes, dysfunctional adaptation had begun, but alternans did not develop. We conclude that increased electrical and structural heterogeneity and dysfunctional sarcoplasmic reticular Ca2+ handling increased the probability of alternans, a proarrhythmic predictor of sudden cardiac death. These mechanisms are potential therapeutic targets for the correction of arrhythmias in hypertensive, failing RVs. PMID:22427523

Mitochondrial DNA inheritance in the human fungal pathogen Cryptococcus gattii.

PubMed

Wang, Zixuan; Wilson, Amanda; Xu, Jianping

2015-02-01

The inheritance of mitochondrial DNA (mtDNA) is predominantly uniparental in most sexual eukaryotes. In this study, we examined the mitochondrial inheritance pattern of Cryptococcus gattii, a basidiomycetous yeast responsible for the recent and ongoing outbreak of cryptococcal infections in the US Pacific Northwest and British Columbia (especially Vancouver Island) in Canada. Using molecular markers, we analyzed the inheritance of mtDNA in 14 crosses between strains within and between divergent lineages in C. gattii. Consistent with results from recent studies, our analyses identified significant variations in mtDNA inheritance patterns among strains and crosses, ranging from strictly uniparental to biparental. For two of the crosses that showed uniparental mitochondrial inheritance in standard laboratory conditions, we further investigated the effects of the following environmental variables on mtDNA inheritance: UV exposure, temperature, and treatments with the methylation inhibitor 5-aza-2'-deoxycytidine and with the ubiquitination inhibitor ammonium chloride. Interestingly, one of these crosses showed no response to these environmental variables while the other exhibited diverse patterns ranging from complete uniparental inheritance of the MATa parent mtDNA, to biparental inheritance, and to a significant bias toward inheritance of the MATα parental mtDNA. Our results indicate that mtDNA inheritance in C. gattii differs from that in its closely related species Cryptococcus neoformans. Copyright © 2015 Elsevier Inc. All rights reserved.

Occurrence of plastids in the sperm cells of Caprifoliaceae: biparental plastid inheritance in angiosperms is unilaterally derived from maternal inheritance.

PubMed

Hu, Yingchun; Zhang, Quan; Rao, Guangyuan; Sodmergen

2008-06-01

It is widely held that organelles inherit from the maternal lineage. However, the plastid genome in quite a few angiosperms appears to be biparentally transmitted. It is unclear how and why biparental inheritance of the genome became activated. Here, we detected widespread occurrence of plastids in the sperm cells (a cellular prerequisite for biparental inheritance) of traditional Caprifoliaceae. Of the 12 genera sampled, the sperm cells of Abelia, Dipelta, Heptacodium, Kolkwitzia, Leycesteria, Linnaea, Lonicera, Symphoricarpos, Triosteum and Weigela possessed inheritable plastids. The other genera, Sambucus and Viburnum, lacked plastids in sperm cells. Interestingly, such exclusion of plastids in the sperm cells of some Caprifoliaceae appeared to be associated with the divergence of Dipsacales phylogeny. Closer examination of Weigela florida revealed that both plastids and plastid DNA were highly duplicated in the generative cells. This implies that the appearance of plastids in sperm cells involved cellular mechanisms. Because such mechanisms must enhance the strength of plastid transmission through the paternal lineage and appear ubiquitous in species exhibiting biparental or potential biparental plastid inheritance, we presume that biparental plastid genetics may be a derived trait in angiosperms. This is consistent with our extended phylogenetic analysis using species with recently discovered modes of potential plastid inheritance. The results show that basal and early angiosperms have maternal plastid transmission, whereas all potential biparental transmission occurs at terminal branches of the tree. Thus, unlike previous studies, we suggest that biparental plastid inheritance in angiosperms was unilaterally converted from the maternal transmission mode during late angiosperm evolution.

Hyperkalaemia, cardiac arrhythmias, and cerebral lesions in high risk neonates.

PubMed Central

Shortland, D; Trounce, J Q; Levene, M I

1987-01-01

The case notes of 20 infants with hyperkalaemia (defined as two successive serum potassium measurements of greater than 7.5 mmol/l) were reviewed. The incidence of hyperkalaemia was also looked at in an unselected population of 200 low birthweight infants. The mean gestational age of the 20 affected infants was 29 weeks and the mean birth weight 1235 g. The incidence of hyperkalemia in the cohort of 200 infants weighing less than 1500 g at birth was 3.5%. Hyperkalaemia was associated with a high incidence of cardiac arrhythmia (60%), impaired renal function (50%), and changes on cerebral ultrasonography (88%). Hyperkalaemia responds slowly to conventional treatment with dextrose, insulin, and exchange resins. There is a close temporal relation in some infants between hyperkalaemia and cardiac arrhythmias and periventricular leukomalacia, suggesting a causal association. PMID:3688918

Selection against Heteroplasmy Explains the Evolution of Uniparental Inheritance of Mitochondria

PubMed Central

Christie, Joshua R.; Schaerf, Timothy M.; Beekman, Madeleine

2015-01-01

Why are mitochondria almost always inherited from one parent during sexual reproduction? Current explanations for this evolutionary mystery include conflict avoidance between the nuclear and mitochondrial genomes, clearing of deleterious mutations, and optimization of mitochondrial-nuclear coadaptation. Mathematical models, however, fail to show that uniparental inheritance can replace biparental inheritance under any existing hypothesis. Recent empirical evidence indicates that mixing two different but normal mitochondrial haplotypes within a cell (heteroplasmy) can cause cell and organism dysfunction. Using a mathematical model, we test if selection against heteroplasmy can lead to the evolution of uniparental inheritance. When we assume selection against heteroplasmy and mutations are neither advantageous nor deleterious (neutral mutations), uniparental inheritance replaces biparental inheritance for all tested parameter values. When heteroplasmy involves mutations that are advantageous or deleterious (non-neutral mutations), uniparental inheritance can still replace biparental inheritance. We show that uniparental inheritance can evolve with or without pre-existing mating types. Finally, we show that selection against heteroplasmy can explain why some organisms deviate from strict uniparental inheritance. Thus, we suggest that selection against heteroplasmy explains the evolution of uniparental inheritance. PMID:25880558

Use of sodium bicarbonate to treat tricyclic antidepressant-induced arrhythmias in a patient with alkalosis.

PubMed Central

Molloy, D W; Penner, S B; Rabson, J; Hall, K W

1984-01-01

Sodium bicarbonate has been recommended for the treatment of arrhythmias induced by tricyclic antidepressants. It is unclear, however, whether this therapy is effective only in the presence of acidosis. A case is presented in which there was an immediate response to sodium bicarbonate in three episodes of ventricular tachycardia despite the presence of alkalosis on two of the three occasions. Given the poor response to conventional therapy of arrhythmias induced by tricyclic antidepressants the use of sodium bicarbonate may be reasonable even in the presence of alkalosis. However, in the presence of pre-existing respiratory or metabolic alkalosis, such therapy is not without risk, and it is suggested that it be reserved for life-threatening situations when the arrhythmia has failed to respond to hyperventilation or antiarrhythmics or both. PMID:6329501

Inherited cardiomyopathies and sports participation.

PubMed

Zorzi, A; Pelliccia, A; Corrado, D

2018-03-01

Competitive sports activity is associated with an increased risk of sudden cardiovascular death in adolescents and young adults with inherited cardiomyopathies. Many young subjects aspire to continue competitive sport after a diagnosis of cardiomyopathy and the clinician is frequently confronted with the problem of eligibility and the request of designing specific exercise programs. Since inherited cardiomyopathies are the leading cause of sudden cardiovascular death during sports performance, a conservative approach implying disqualification of affected athletes from most competitive athletic disciplines is recommended by all the available international guidelines. On the other hand, we know that the health benefits of practicing recreational sports activity can overcome the potential arrhythmic risk in these patients, provided that the type and level of exercise are tailored on the basis of the specific risk profile of the underlying cardiomyopathy. This article will review the available evidence on the sports-related risk of sudden cardiac death and the recommendations regarding eligibility of individuals affected by inherited cardiomyopathies for sports activities.

Unique Association of Rare Cardiovascular Disease in an Athlete With Ventricular Arrhythmias.

PubMed

Santomauro, V; Contursi, M; Dellegrottaglie, S; Borsellino, G

2015-01-01

Ventricular arrhythmias are a leading cause of non-elegibility to competitive sport. The failure to detect a significant organic substrate in the initial stage of screening does not preclude the identification of structural pathologies in the follow-up by using advanced imaging techniques. Here we report the case of a senior athlete judged not elegible because an arrhythmia with the morphology consistent with the origin of the left ventricle, in which subsequent execution of a cardiac MR and a thoracic CT scan has allowed the identification of an unique association between an area of myocardial damage, probable site of origine of the arrhythma, and a rare aortic malformation.

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.

Design of a hybrid model for cardiac arrhythmia classification based on Daubechies wavelet transform.

PubMed

Rajagopal, Rekha; Ranganathan, Vidhyapriya

2018-06-05

Automation in cardiac arrhythmia classification helps medical professionals make accurate decisions about the patient's health. The aim of this work was to design a hybrid classification model to classify cardiac arrhythmias. The design phase of the classification model comprises the following stages: preprocessing of the cardiac signal by eliminating detail coefficients that contain noise, feature extraction through Daubechies wavelet transform, and arrhythmia classification using a collaborative decision from the K nearest neighbor classifier (KNN) and a support vector machine (SVM). The proposed model is able to classify 5 arrhythmia classes as per the ANSI/AAMI EC57: 1998 classification standard. Level 1 of the proposed model involves classification using the KNN and the classifier is trained with examples from all classes. Level 2 involves classification using an SVM and is trained specifically to classify overlapped classes. The final classification of a test heartbeat pertaining to a particular class is done using the proposed KNN/SVM hybrid model. The experimental results demonstrated that the average sensitivity of the proposed model was 92.56%, the average specificity 99.35%, the average positive predictive value 98.13%, the average F-score 94.5%, and the average accuracy 99.78%. The results obtained using the proposed model were compared with the results of discriminant, tree, and KNN classifiers. The proposed model is able to achieve a high classification accuracy.

Long Oskar Controls Mitochondrial Inheritance in Drosophila melanogaster.

PubMed

Hurd, Thomas Ryan; Herrmann, Beate; Sauerwald, Julia; Sanny, Justina; Grosch, Markus; Lehmann, Ruth

2016-12-05

Inherited mtDNA mutations cause severe human disease. In most species, mitochondria are inherited maternally through mechanisms that are poorly understood. Genes that specifically control the inheritance of mitochondria in the germline are unknown. Here, we show that the long isoform of the protein Oskar regulates the maternal inheritance of mitochondria in Drosophila melanogaster. We show that, during oogenesis, mitochondria accumulate at the oocyte posterior, concurrent with the bulk streaming and churning of the oocyte cytoplasm. Long Oskar traps and maintains mitochondria at the posterior at the site of primordial germ cell (PGC) formation through an actin-dependent mechanism. Mutating long oskar strongly reduces the number of mtDNA molecules inherited by PGCs. Therefore, Long Oskar ensures germline transmission of mitochondria to the next generation. These results provide molecular insight into how mitochondria are passed from mother to offspring, as well as how they are positioned and asymmetrically partitioned within polarized cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Extended inheritance from an organizational point of view.

PubMed

Pontarotti, Gaëlle

2015-12-01

In this paper, I argue that the increasing data about non-genetic inheritance requires the construction of a new conceptual framework that should complement the inclusive approaches already discussed in the literature. More precisely, I hold that this framework should be epistemologically relevant for evolutionary biologists in capturing the limits of extended inheritance and in reassessing the boundaries of biological systems that transmit traits to their offspring. I outline the first elements of an organizational account of extended inheritance. In this account, the category of inherited factors is neither restricted to genes nor extended to stable resources related to trans-generational similarities. Instead, it includes persisting constitutive elements appearing as difference makers for heterogeneous organizational constraints, namely for heterogeneous constitutive parts whose specific role is to harness flows of matter and energy across generations of clearly delimited extended organized systems. This both inclusive and restrictive framework opens an additional way to apprehend how extended inheritance may affect evolutionary trajectories.

Why does biparental plastid inheritance revive in angiosperms?

PubMed

Zhang, Quan; Sodmergen

2010-03-01

It is widely believed that plastid and mitochondrial genomes are inherited through the maternal parent. In plants, however, paternal transmission of these genomes is frequently observed, especially for the plastid genome. A male gametic trait, called potential biparental plastid inheritance (PBPI), occurs in up to 20% of angiosperm genera, implying a strong tendency for plastid transmission from the male lineage. Why do plants receive organelles from the male parents? Are there clues in plastids that will help to elucidate the evolution of plants? Reconstruction of the ancestral state of plastid inheritance patterns in a phylogenetic context provides insights into these questions. In particular, a recent report demonstrated the unilateral occurrence of PBPI in angiosperms. This result implies that nuclear cytoplasmic conflicts, a basic driving force for altering the mode of organelle inheritance, might have arisen specifically in angiosperms. Based on existing evidence, it is likely that biparental inheritance may have occurred to rescue angiosperm species with defective plastids.

Widow inheritance and HIV/AIDS in rural Uganda.

PubMed

Mabumba, E D; Mugyenyi, P; Batwala, V; Mulogo, E M; Mirembe, J; Khan, F A; Liljestrand, J

2007-10-01

Despite current efforts to combat HIV/AIDS through behavioural change, ingrained socio-cultural practices such as widow inheritance in south-western Uganda has not changed. Low education, unemployment, dowry, widows' socioeconomic demands and the inheritor's greed for the deceased's wealth, influence widow inheritance. Voluntary counselling and testing is needed for the widows and their inheritors; formal dowry should be removed from marriage and widow inheritance stripped of its sexual component.

Privacy-Preserving Electrocardiogram Monitoring for Intelligent Arrhythmia Detection.

PubMed

Son, Junggab; Park, Juyoung; Oh, Heekuck; Bhuiyan, Md Zakirul Alam; Hur, Junbeom; Kang, Kyungtae

2017-06-12

Long-term electrocardiogram (ECG) monitoring, as a representative application of cyber-physical systems, facilitates the early detection of arrhythmia. A considerable number of previous studies has explored monitoring techniques and the automated analysis of sensing data. However, ensuring patient privacy or confidentiality has not been a primary concern in ECG monitoring. First, we propose an intelligent heart monitoring system, which involves a patient-worn ECG sensor (e.g., a smartphone) and a remote monitoring station, as well as a decision support server that interconnects these components. The decision support server analyzes the heart activity, using the Pan-Tompkins algorithm to detect heartbeats and a decision tree to classify them. Our system protects sensing data and user privacy, which is an essential attribute of dependability, by adopting signal scrambling and anonymous identity schemes. We also employ a public key cryptosystem to enable secure communication between the entities. Simulations using data from the MIT-BIH arrhythmia database demonstrate that our system achieves a 95.74% success rate in heartbeat detection and almost a 96.63% accuracy in heartbeat classification, while successfully preserving privacy and securing communications among the involved entities.

Arrhythmia Classification Based on Multi-Domain Feature Extraction for an ECG Recognition System.

PubMed

Li, Hongqiang; Yuan, Danyang; Wang, Youxi; Cui, Dianyin; Cao, Lu

2016-10-20

Automatic recognition of arrhythmias is particularly important in the diagnosis of heart diseases. This study presents an electrocardiogram (ECG) recognition system based on multi-domain feature extraction to classify ECG beats. An improved wavelet threshold method for ECG signal pre-processing is applied to remove noise interference. A novel multi-domain feature extraction method is proposed; this method employs kernel-independent component analysis in nonlinear feature extraction and uses discrete wavelet transform to extract frequency domain features. The proposed system utilises a support vector machine classifier optimized with a genetic algorithm to recognize different types of heartbeats. An ECG acquisition experimental platform, in which ECG beats are collected as ECG data for classification, is constructed to demonstrate the effectiveness of the system in ECG beat classification. The presented system, when applied to the MIT-BIH arrhythmia database, achieves a high classification accuracy of 98.8%. Experimental results based on the ECG acquisition experimental platform show that the system obtains a satisfactory classification accuracy of 97.3% and is able to classify ECG beats efficiently for the automatic identification of cardiac arrhythmias.

Arrhythmia Classification Based on Multi-Domain Feature Extraction for an ECG Recognition System

PubMed Central

Li, Hongqiang; Yuan, Danyang; Wang, Youxi; Cui, Dianyin; Cao, Lu

2016-01-01

Automatic recognition of arrhythmias is particularly important in the diagnosis of heart diseases. This study presents an electrocardiogram (ECG) recognition system based on multi-domain feature extraction to classify ECG beats. An improved wavelet threshold method for ECG signal pre-processing is applied to remove noise interference. A novel multi-domain feature extraction method is proposed; this method employs kernel-independent component analysis in nonlinear feature extraction and uses discrete wavelet transform to extract frequency domain features. The proposed system utilises a support vector machine classifier optimized with a genetic algorithm to recognize different types of heartbeats. An ECG acquisition experimental platform, in which ECG beats are collected as ECG data for classification, is constructed to demonstrate the effectiveness of the system in ECG beat classification. The presented system, when applied to the MIT-BIH arrhythmia database, achieves a high classification accuracy of 98.8%. Experimental results based on the ECG acquisition experimental platform show that the system obtains a satisfactory classification accuracy of 97.3% and is able to classify ECG beats efficiently for the automatic identification of cardiac arrhythmias. PMID:27775596

Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance.

PubMed

Crompton, Douglas E; Scheffer, Ingrid E; Taylor, Isabella; Cook, Mark J; McKelvie, Penelope A; Vears, Danya F; Lawrence, Kate M; McMahon, Jacinta M; Grinton, Bronwyn E; McIntosh, Anne M; Berkovic, Samuel F

2010-11-01

Temporal lobe epilepsy is the commonest partial epilepsy of adulthood. Although generally perceived as an acquired disorder, several forms of familial temporal lobe epilepsy, with mesial or lateral seizure semiology, have been described. Descriptions of familial mesial temporal lobe epilepsy have varied widely from a benign epilepsy syndrome with prominent déjà vu and without antecedent febrile seizures or magnetic resonance imaging abnormalities, to heterogeneous, but generally more refractory epilepsies, often with a history of febrile seizures and with frequent hippocampal atrophy and high T₂ signal on magnetic resonance imaging. Compelling evidence of a genetic aetiology (rather than chance aggregation) in familial mesial temporal lobe epilepsy has come from twin studies. Dominant inheritance has been reported in two large families, though the usual mode of inheritance is not known. Here, we describe clinical and neurophysiological features of 20 new mesial temporal lobe epilepsy families including 51 affected individuals. The epilepsies in these families were generally benign, and febrile seizure history was infrequent (9.8%). No evidence of hippocampal sclerosis or dysplasia was present on brain imaging. A single individual underwent anterior temporal lobectomy, with subsequent seizure freedom and histopathological evidence of hippocampal sclerosis was not found. Inheritance patterns in probands' relatives were analysed in these families, together with 19 other temporal lobe epilepsy families previously reported by us. Observed frequencies of epilepsies in relatives were lower than predicted by dominant Mendelian models, while only a minority (8/39) of families could be compatible with recessive inheritance. These findings strongly suggest that complex inheritance, similar to that widely accepted in the idiopathic generalized epilepsies, is the usual mode of inheritance in familial mesial temporal lobe epilepsy. This disorder, which appears to be

Partnering in oncogenetic research--the INHERIT BRCAs experience: opportunities and challenges.

PubMed

Avard, Denise; Bridge, Peter; Bucci, Lucie M; Chiquette, Jocelyne; Dorval, Michel; Durocher, Francine; Easton, Doug; Godard, Béatrice; Goldgar, David; Knoppers, Bartha Maria; Laframboise, Rachel; Lespérance, Bernard; Plante, Marie; Tavtigian, Sean V; Vézina, Hélène; Wilson, Brenda; Simard, Jacques

2006-01-01

Today it is common to conduct research in collaboration with colleagues from different disciplines and institutions. The INterdisciplinary HEalth Research International Team on BReast CAncer susceptibility (INHERIT BRCAs), involves Canadian and international experts from diverse fields working with health service providers, patients and collaborators from the World Health Organization and other European networks. Evidence-based information and knowledge transfer drive our efforts to advance genomic research to understand the genetic basis of cancer susceptibility and treatment response. Several goals reveal the interdisciplinary team approach: (a) to estimate the prevalence and penetrance of BRCA1 and BRCA2 mutations and their deleterious impact upon different populations; (b) to pinpoint novel breast cancer susceptibility loci; (c) to assess the efficacy of clinical interventions; (d) to address changes in quality of life and health-related behaviour from the decision to undergo genetics testing and during follow-up; (e) to evaluate legal, social and ethical implications; and, finally; (f) to promote professional and public education by facilitating the transfer of research findings to clinical practice and informing policy makers. The lessons learned by the INHERIT research team and future challenges are presented.

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

PubMed

Gold, Azgad; Appelbaum, Paul S

2011-07-01

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

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

Arrhythmia Evaluation in Wearable ECG Devices

PubMed Central

Sadrawi, Muammar; Lin, Chien-Hung; Hsieh, Yita; Kuo, Chia-Chun; Chien, Jen Chien; Haraikawa, Koichi; Abbod, Maysam F.; Shieh, Jiann-Shing

2017-01-01

This study evaluates four databases from PhysioNet: The American Heart Association database (AHADB), Creighton University Ventricular Tachyarrhythmia database (CUDB), MIT-BIH Arrhythmia database (MITDB), and MIT-BIH Noise Stress Test database (NSTDB). The ANSI/AAMI EC57:2012 is used for the evaluation of the algorithms for the supraventricular ectopic beat (SVEB), ventricular ectopic beat (VEB), atrial fibrillation (AF), and ventricular fibrillation (VF) via the evaluation of the sensitivity, positive predictivity and false positive rate. Sample entropy, fast Fourier transform (FFT), and multilayer perceptron neural network with backpropagation training algorithm are selected for the integrated detection algorithms. For this study, the result for SVEB has some improvements compared to a previous study that also utilized ANSI/AAMI EC57. In further, VEB sensitivity and positive predictivity gross evaluations have greater than 80%, except for the positive predictivity of the NSTDB database. For AF gross evaluation of MITDB database, the results show very good classification, excluding the episode sensitivity. In advanced, for VF gross evaluation, the episode sensitivity and positive predictivity for the AHADB, MITDB, and CUDB, have greater than 80%, except for MITDB episode positive predictivity, which is 75%. The achieved results show that the proposed integrated SVEB, VEB, AF, and VF detection algorithm has an accurate classification according to ANSI/AAMI EC57:2012. In conclusion, the proposed integrated detection algorithm can achieve good accuracy in comparison with other previous studies. Furthermore, more advanced algorithms and hardware devices should be performed in future for arrhythmia detection and evaluation. PMID:29068369

Determination of epigenetic inheritance, genetic inheritance, and estimation of genome DNA methylation in a full-sib family of Cupressus sempervirens L.

PubMed

Avramidou, Evangelia V; Doulis, Andreas G; Aravanopoulos, Filippos A

2015-05-15

Genetic inheritance and epigenetic inheritance are significant determinants of plant evolution, adaptation and plasticity. We studied inheritance of restriction site polymorphisms by the f-AFLP method and epigenetic DNA cytosine methylation inheritance by the f-MSAP technique. The study involved parents and 190 progeny of a Cupressus sempervirens L. full-sib family. Results from AFLP genetic data revealed that 71.8% of the fragments studied are under Mendelian genetic control, whereas faithful Mendelian inheritance for the MSAP fragments was low (4.29%). Further, MSAP fragment analysis showed that total methylation presented a mean of 28.2%, which was higher than the midparent value, while maternal inheritance was higher (5.65%) than paternal (3.01%). Interestingly de novo methylation in the progeny was high (19.65%) compared to parental methylation. Genetic and epigenetic distances for parents and offspring were not correlated (R(2)=0.0005). Furthermore, we studied correlation of total relative methylation and CG methylation with growth (height, diameter). We found CG/CNG methylation (N: A, C, T) to be positively correlated with height and diameter, while total relative methylation and CG methylation were positively correlated with height. Results are discussed in light of further research needed and of their potential application in breeding. Copyright © 2015 Elsevier B.V. All rights reserved.

Venturing into ventricular arrhythmia storm: a systematic review and meta-analysis.

PubMed

Nayyar, Sachin; Ganesan, Anand N; Brooks, Anthony G; Sullivan, Thomas; Roberts-Thomson, Kurt C; Sanders, Prashanthan

2013-02-01

Ablation has substantial evidence base in the management of ventricular arrhythmia (VA). It can be a 'lifesaving' procedure in the acute setting of VA storm. Current reports on ablation in VA storm are in the form of small series and have relative small representation in a large observational series. The purpose of this study was to systematically synthesize the available literature to appreciate the efficacy and safety of ablation in the setting of VA storm. The medical electronic databases through 31 January 2012 were searched. Ventricular arrhythmia storm was defined as recurrent (≥ 3 episodes or defibrillator therapies in 24 h) or incessant (continuous >12 h) VA. Studies reporting data on VA storm patients at the individual or study level were included. A total of 471 VA storm patients from 39 publications were collated for the analysis. All VAs were successfully ablated in 72% [95% confidence interval (CI) 71-89%] and 9% (95% CI: 3-10%) had a failed procedure. Procedure-related mortality occurred in three patients (0.6%). Only 6% patients had a recurrence of VA storm. The recurrence of VA was significantly higher after ablation for arrhythmic storm of monomorphic ventricular tachycardia (VT) relative to ventricular fibrillation or polymorphic VT with underlying cardiomyopathy (odds ratio 3.76; 95% CI: 1.65-8.57; P = 0.002). During the follow-up (61 ± 37 weeks), 17% of patients died (heart failure 62%, arrhythmias 23%, and non-cardiac 15%) with 55% deaths occurring within 12 weeks of intervention. The odds of death were four times higher after a failed procedure compared with those with a successful procedure (95% CI: 2.04-8.01, P < 0.001). Ventricular arrhythmia storm ablation has high-acute success rates, with a low rate of recurrent storms. Heart failure is the dominant cause of death in the long term. Failure of the acute procedure carries a high mortality.

The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility

PubMed Central

Lefta, Mellani; Zhang, Xiping; Bartos, Daniel; Feng, Han-Zhong; Zhao, Yihua; Patwardhan, Abhijit; Jin, Jian-Ping; Esser, Karyn A.; Delisle, Brian P.

2013-01-01

The molecular clock mechanism underlies circadian rhythms and is defined by a transcription-translation feedback loop. Bmal1 encodes a core molecular clock transcription factor. Germline Bmal1 knockout mice show a loss of circadian variation in heart rate and blood pressure, and they develop dilated cardiomyopathy. We tested the role of the molecular clock in adult cardiomyocytes by generating mice that allow for the inducible cardiomyocyte-specific deletion of Bmal1 (iCSΔBmal1). ECG telemetry showed that cardiomyocyte-specific deletion of Bmal1 (iCSΔBmal1−/−) in adult mice slowed heart rate, prolonged RR and QRS intervals, and increased episodes of arrhythmia. Moreover, isolated iCSΔBmal1−/− hearts were more susceptible to arrhythmia during electromechanical stimulation. Examination of candidate cardiac ion channel genes showed that Scn5a, which encodes the principle cardiac voltage-gated Na+ channel (NaV1.5), was circadianly expressed in control mouse and rat hearts but not in iCSΔBmal1−/− hearts. In vitro studies confirmed circadian expression of a human Scn5a promoter-luciferase reporter construct and determined that overexpression of clock factors transactivated the Scn5a promoter. Loss of Scn5a circadian expression in iCSΔBmal1−/− hearts was associated with decreased levels of NaV1.5 and Na+ current in ventricular myocytes. We conclude that disruption of the molecular clock in the adult heart slows heart rate, increases arrhythmias, and decreases the functional expression of Scn5a. These findings suggest a potential link between environmental factors that alter the cardiomyocyte molecular clock and factors that influence arrhythmia susceptibility in humans. PMID:23364267

Inherited retinal dysplasia and persistent hyperplastic primary vitreous in Miniature Schnauzer dogs.

PubMed

Grahn, Bruce H; Storey, Eric S; McMillan, Catherine

2004-01-01

The objectives of this study were to define the clinical syndrome of retinal dysplasia and persistent primary vitreous in Miniature Schnauzer dogs and determine the etiology. We examined 106 Miniature Schnauzers using a biomicroscope and indirect ophthalmoscope. The anterior and posterior segments of affected dogs were photographed. Four enucleated eyes were examined using routine light microscopy and scanning electron microscopy. A pedigree was constructed and related dogs were test-bred to define the mode of inheritance of this syndrome. Congenital retinal dysplasia was confirmed in 24 of 106 related Miniature Schnauzer dogs. Physical and postmortem examinations revealed that congenital abnormalities were limited to the eyes. Biomicroscopic, indirect ophthalmoscopic, and neuro-ophthalmic examinations confirmed that some of these dogs were blind secondary to bilateral retinal dysplasia and detachment (nonattachment) (n = 13), and the remainder had generalized retinal dysplasia (n = 11). Fifteen of these dogs were also diagnosed with unilateral (n = 9) or bilateral (n = 6) persistent hyperplastic primary vitreous. Nutritional, infectious, or toxic etiologies were not evident on physical, postmortem, light microscopic, or transmitting and scanning electron microscopic examination of four affected Miniature Schnauzers. We examined the pedigree and determined that an autosomal recessive mode of inheritance was most likely. Three test-bred litters including those from affected parents, carrier and affected parents, and carrier parents confirmed this mode of inheritance. This study confirms that retinal dysplasia and persistent hyperplastic primary vitreous is a congenital abnormality that is inherited as an autosomal recessive condition in Miniature Schnauzers.

Respiratory sinus arrhythmia in Chagas disease.

PubMed

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

2014-10-01

We applied the respiratory sinus arrhythmia (RSA) quantification algorithm to 24-hour ECG recordings of Chagas disease (ChD) patients with (G1, n=148) and without left ventricular dysfunction (LVD) (G2, n=33), and in control subjects (G0, n=28). Both ChD groups displayed a reduced RSA index; G1=299 (144-812); G2=335 (162-667), p=0.011, which was correlated with vagal indexes of heart rate variability analysis. RSA index is a marker of vagal modulation in ChD patients. Copyright © 2014 Elsevier B.V. All rights reserved.

[Arrhythmias and heart blocks in flying personnel with mitral valve prolapses].

PubMed

Zakharov, V P; Karlov, V N; Bondareva, S V; Vlasov, V D

1999-01-01

Investigated were 76 pilots with ECG-verified mitral valve prolapses (MVP) of the 1st and 2nd degree (w/o profound regurgitation). There were various heart blocks and ECG repolarization changes in 35 cases. Comparison of results of the cardiovascular functional investigations of flyers with MVP displayed non-specific cardiac rhythm and conductance disturbances that were registered more often during ECG-monitoring or test loading. According to the data of this study, bicycle and treadmill ergometry revealed "pseudoischemic" shifts in ECG. Literary indications of a significant loss in human endurance of physical loads due to MVP combined with the strain-induced arrhythmia received the experimental confirmation. Probably, arrhythmias in flyers with diagnosed MVP are predominantly associated with electric instability of the myocardium against the autonomous dysfunction with prevailing adrenergic effects.

Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: cohort study.

PubMed

Andersen, Kasper; Rasmussen, Finn; Held, Claes; Neovius, Martin; Tynelius, Per; Sundström, Johan

2015-09-16

To investigate the associations of exercise capacity and muscle strength in late adolescence with risk of vascular disease and arrhythmia. Cohort study. General population in Sweden. 1.1 million men who participated in mandatory military conscription between 1 August 1972 and 31 December 1995, at a median age of 18.2 years. Participants were followed until 31 December 2010. Associations between exercise capacity and muscle strength with risk of vascular disease and subgroups (ischaemic heart disease, heart failure, stroke, and cardiovascular death) and risk of arrhythmia and subgroups (atrial fibrillation or flutter, bradyarrhythmia, supraventricular tachycardia, and ventricular arrhythmia or sudden cardiac death). Maximum exercise capacity was estimated by the ergometer bicycle test, and muscle strength was measured as handgrip strength by a hand dynamometer. High exercise capacity or muscle strength was deemed as above the median level. During a median follow-up of 26.3 years, 26 088 vascular disease events and 17 312 arrhythmia events were recorded. Exercise capacity was inversely associated with risk of vascular disease and its subgroups. Muscle strength was also inversely associated with vascular disease risk, driven by associations of higher muscle strength with lower risk of heart failure and cardiovascular death. Exercise capacity had a U shaped association with risk of arrhythmia, driven by a direct association with risk of atrial fibrillation and a U shaped association with bradyarrhythmia. Higher muscle strength was associated with lower risk of arrhythmia (specifically, lower risk of bradyarrhythmia and ventricular arrhythmia). The combination of high exercise capacity and high muscle strength was associated with a hazard ratio of 0.67 (95% confidence interval 0.65 to 0.70) for vascular events and 0.92 (0.88 to 0.97) for arrhythmia compared with the combination of low exercise capacity and low muscle strength. Exercise capacity and muscle strength

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...

Evidence of reversible bradycardia and arrhythmias caused by immunogenic proteins secreted by T. cruzi in isolated rat hearts.

PubMed

Rodríguez-Angulo, Héctor O; Toro-Mendoza, Jhoan; Marques, Juan A; Concepción, Juan L; Bonfante-Cabarcas, Rafael; Higuerey, Yoliver; Thomas, Luz E; Balzano-Nogueira, Leandro; López, José R; Mijares, Alfredo

2015-02-01

Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients.

Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts

PubMed Central

Rodríguez-Angulo, Héctor O.; Toro-Mendoza, Jhoan; Marques, Juan A.; Concepción, Juan L.; Bonfante-Cabarcas, Rafael; Higuerey, Yoliver; Thomas, Luz E.; Balzano-Nogueira, Leandro; López, José R.; Mijares, Alfredo

2015-01-01

Rationale Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. Objective The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. Methods and Results We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. Conclusions These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients. PMID:25647069

Adaptive optics imaging of inherited retinal diseases.

PubMed

Georgiou, Michalis; Kalitzeos, Angelos; Patterson, Emily J; Dubra, Alfredo; Carroll, Joseph; Michaelides, Michel

2017-11-15

Adaptive optics (AO) ophthalmoscopy allows for non-invasive retinal phenotyping on a microscopic scale, thereby helping to improve our understanding of retinal diseases. An increasing number of natural history studies and ongoing/planned interventional clinical trials exploit AO ophthalmoscopy both for participant selection, stratification and monitoring treatment safety and efficacy. In this review, we briefly discuss the evolution of AO ophthalmoscopy, recent developments and its application to a broad range of inherited retinal diseases, including Stargardt disease, retinitis pigmentosa and achromatopsia. Finally, we describe the impact of this in vivo microscopic imaging on our understanding of disease pathogenesis, clinical trial design and outcome metrics, while recognising the limitation of the small cohorts reported to date. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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, ...

Effect of long-term application of Crataegus oxyacantha on ischemia and reperfusion induced arrhythmias in rats.

PubMed

Rothfuss, M A; Pascht, U; Kissling, G

2001-01-01

The effect of long-term application of Crataegus oxyacantha on ischemia and reperfusion induced arrhythmias was investigated in Wistar rats on the heart in situ and on Langendorff preparations. Seventeen rats were fed for 8 weeks with 0.5 g/kg b.w. Crataegus extract per day, standardised to 2.2% flavonoids. Twenty age-matched untreated rats served as controls. In the hearts in situ as well as in the Langendorff preparations the left anterior descending coronary artery (LAD) was ligated for 20 min and subsequently reperfused for 30 min. ECG was continuously recorded and the time spent between start of ischemia and onset of arrhythmias was measured. In addition, during ischemia and reperfusion the number of ventricular premature beats and bigemini and the duration of salvos and ventricular flutter and fibrillation were determined. The ischemic area was evaluated in all experiments and coronary flow was measured in Langendorff preparations. In the present experiments, no cardioprotective effects of Crataegus oxyacantha could be detected, neither in the heart in situ nor in the Langendorff preparations. Although the ischemic areas were identical, arrhythmias occurred even earlier in the Crataegus collectives than in the controls. Also the number and duration of ischemia and reperfusion induced arrhythmias tended to occur longer and more frequently in the Crataegus collectives, whilst coronary flow remained unchanged. The phenomenon that Crataegus rather aggravates than prevents arrhythmias may be reduced to a Crataegus induced increase in intracellular Ca(2+)-concentration proven true for the positive inotropic effects of Crataegus.

An arrhythmia classification algorithm using a dedicated wavelet adapted to different subjects.

PubMed

Kim, Jinkwon; Min, Se Dong; Lee, Myoungho

2011-06-27

Numerous studies have been conducted regarding a heartbeat classification algorithm over the past several decades. However, many algorithms have also been studied to acquire robust performance, as biosignals have a large amount of variation among individuals. Various methods have been proposed to reduce the differences coming from personal characteristics, but these expand the differences caused by arrhythmia. In this paper, an arrhythmia classification algorithm using a dedicated wavelet adapted to individual subjects is proposed. We reduced the performance variation using dedicated wavelets, as in the ECG morphologies of the subjects. The proposed algorithm utilizes morphological filtering and a continuous wavelet transform with a dedicated wavelet. A principal component analysis and linear discriminant analysis were utilized to compress the morphological data transformed by the dedicated wavelets. An extreme learning machine was used as a classifier in the proposed algorithm. A performance evaluation was conducted with the MIT-BIH arrhythmia database. The results showed a high sensitivity of 97.51%, specificity of 85.07%, accuracy of 97.94%, and a positive predictive value of 97.26%. The proposed algorithm achieves better accuracy than other state-of-the-art algorithms with no intrasubject between the training and evaluation datasets. And it significantly reduces the amount of intervention needed by physicians.

An arrhythmia classification algorithm using a dedicated wavelet adapted to different subjects

PubMed Central

2011-01-01

Background Numerous studies have been conducted regarding a heartbeat classification algorithm over the past several decades. However, many algorithms have also been studied to acquire robust performance, as biosignals have a large amount of variation among individuals. Various methods have been proposed to reduce the differences coming from personal characteristics, but these expand the differences caused by arrhythmia. Methods In this paper, an arrhythmia classification algorithm using a dedicated wavelet adapted to individual subjects is proposed. We reduced the performance variation using dedicated wavelets, as in the ECG morphologies of the subjects. The proposed algorithm utilizes morphological filtering and a continuous wavelet transform with a dedicated wavelet. A principal component analysis and linear discriminant analysis were utilized to compress the morphological data transformed by the dedicated wavelets. An extreme learning machine was used as a classifier in the proposed algorithm. Results A performance evaluation was conducted with the MIT-BIH arrhythmia database. The results showed a high sensitivity of 97.51%, specificity of 85.07%, accuracy of 97.94%, and a positive predictive value of 97.26%. Conclusions The proposed algorithm achieves better accuracy than other state-of-the-art algorithms with no intrasubject between the training and evaluation datasets. And it significantly reduces the amount of intervention needed by physicians. PMID:21707989

The association of ambient temperature with incidence of cardiac arrhythmias in a short timescale

NASA Astrophysics Data System (ADS)

Kim, Jayeun; Kim, Ho

2017-11-01

The body response time and an association between the exposure to outdoor temperature and cardiac arrhythmia were not fully understood. Hence, we further investigated the association between ambient temperature and the exacerbations of arrhythmia symptoms on a short timescale using the emergency department (ED) visit data. We used a total of 17,088 arrhythmia-related ED visits in Seoul, from 2008 to 2011 and fitted the model adjusting for other meteorological variables and air pollutants under the case-crossover analysis with the same year-month time stratification. The association was presented as an odds ratio (OR) with a 95% confidence interval (CI) by a 5 °C decrease in the ambient temperature. The delay time (h) between exposure and the onset of arrhythmia exacerbation was considered with time blocks for every 3 h as 1-3 h, up to 118-120 h; and daily lags (1 day), from 25-48 h to 97-120 h, as a multi-time average of exposures. The overall association was increased at lag 4-6 h and the increased association was statistically significant at lag 40-42 h (OR 1.027, 95% CI 1.003-1.051) and the adverse association continued at 97-120 h (OR 1.053, 95% CI 1.027-1.080). However, the delay of several days between ambient temperature and body response should be further investigated considering the modification according to varied demographic characteristics or different environmental circumstances.

Inheritance of congenital cataracts and microphthalmia in the Miniature Schnauzer.

PubMed

Gelatt, K N; Samuelson, D A; Bauer, J E; Das, N D; Wolf, E D; Barrie, K P; Andresen, T L

1983-06-01

Congenital cataracts and microphthalmia in the Miniature Schnauzer were inherited as an autosomal recessive trait. Eighteen matings of affected X affected Miniature Schnauzers resulted in 87 offspring with congenital cataracts and microphthalmia (49 males/38 females). Two matings of congenital cataractous and microphthalmic Miniature Schnauzers (2 females) X a normal Miniature Schnauzer (1 male) yielded 11 clinically normal Miniature Schnauzers (7 males/4 females). Eighteen matings of congenital cataractous and microphthalmic Miniature Schnauzers (6 males) X carrier Miniature Schnauzers (9 females) produced 81 offspring; 39 exhibited congenital cataracts and microphthalmia (20 males/19 females) and 42 had clinically normal eyes (17 males/25 females).

Epigenetic Inheritance across the Landscape.

PubMed

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.

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

Epac2-Rap1 Signaling Regulates Reactive Oxygen Species Production and Susceptibility to Cardiac Arrhythmias

PubMed Central

Yang, Zhaokang; Kirton, Hannah M.; Al-Owais, Moza; Thireau, Jérôme; Richard, Sylvain; Peers, Chris

2017-01-01

Abstract Aims: In the heart, β1-adrenergic signaling involves cyclic adenosine monophosphate (cAMP) acting via both protein kinase-A (PKA) and exchange protein directly activated by cAMP (Epac): a guanine nucleotide exchange factor for the small GTPase Rap1. Inhibition of Epac-Rap1 signaling has been proposed as a therapeutic strategy for both cancer and cardiovascular disease. However, previous work suggests that impaired Rap1 signaling may have detrimental effects on cardiac function. The aim of the present study was to investigate the influence of Epac2-Rap1 signaling on the heart using both in vivo and in vitro approaches. Results: Inhibition of Epac2 signaling induced early afterdepolarization arrhythmias in ventricular myocytes. The underlying mechanism involved an increase in mitochondrial reactive oxygen species (ROS) and activation of the late sodium current (INalate). Arrhythmias were blocked by inhibition of INalate or the mitochondria-targeted antioxidant, mitoTEMPO. In vivo, inhibition of Epac2 caused ventricular tachycardia, torsades de pointes, and sudden death. The in vitro and in vivo effects of Epac2 inhibition were mimicked by inhibition of geranylgeranyltransferase-1, which blocks interaction of Rap1 with downstream targets. Innovation: Our findings show for the first time that Rap1 acts as a negative regulator of mitochondrial ROS production in the heart and that impaired Epac2-Rap1 signaling causes arrhythmias due to ROS-dependent activation of INalate. This has implications for the use of chemotherapeutics that target Epac2-Rap1 signaling. However, selective inhibition of INalate provides a promising strategy to prevent arrhythmias caused by impaired Epac2-Rap1 signaling. Conclusion: Epac2-Rap1 signaling attenuates mitochondrial ROS production and reduces myocardial arrhythmia susceptibility. Antioxid. Redox Signal. 27, 117–132. PMID:27649969

Coagulation disorders in pregnancy: acquired and inherited thrombophilias.

PubMed

Benedetto, Chiara; Marozio, Luca; Tavella, Anna Maria; Salton, Loredana; Grivon, Sara; Di Giampaolo, Francesca

2010-09-01

Both acquired and inherited thrombophilias are associated with an increased risk of pregnancy-related venous thromboembolism (VTE) as well as with adverse pregnancy outcome. However, the extension of attributable risk for each thrombophilia and outcome is still a question of debate. Thrombophilias have been investigated in connection with VTE and pregnancy complications such as: recurrent and nonrecurrent early pregnancy loss, late fetal death, placental abruption, fetal growth restriction, and preeclampsia. This review discusses the evidence of association between thrombophilias and pregnancy outcome together with issues as to clinical management and preventive strategies. © 2010 New York Academy of Sciences.

[Inherited primitive and secondary polycythemia].

PubMed

Barba, T; Boileau, J-C; Pasquet, F; Hot, A; Pavic, M

2016-07-01

Myeloproliferative disorders and secondary polycythemia cover most of the polycythemia cases encountered in daily practice. Inherited polycythemias are rare entities that have to be suspected when the classical causes of acquired polycythemia have been ruled out. Recent advances were made in the understanding of these pathologies, which are still little known to the physicians. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of inherited polycythemia. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

T-wave alternans and beat-to-beat variability of repolarization: pathophysiological backgrounds and clinical relevance.

PubMed

Floré, Vincent; Willems, Rik

2012-12-01

In this review, we focus on temporal variability of cardiac repolarization. This phenomenon has been related to a higher risk for ventricular arrhythmia and is therefore interesting as a marker of sudden cardiac death risk. We review two non-invasive clinical techniques quantifying repolarization variability: T-wave alternans (TWA) and beat-to-beat variability of repolarization (BVR). We discuss their pathophysiological link with ventricular arrhythmia and the current clinical relevance of these techniques.

Selective sweeps of mitochondrial DNA can drive the evolution of uniparental inheritance.

PubMed

Christie, Joshua R; Beekman, Madeleine

2017-08-01

Although the uniparental (or maternal) inheritance of mitochondrial DNA (mtDNA) is widespread, the reasons for its evolution remain unclear. Two main hypotheses have been proposed: selection against individuals containing different mtDNAs (heteroplasmy) and selection against "selfish" mtDNA mutations. Recently, uniparental inheritance was shown to promote adaptive evolution in mtDNA, potentially providing a third hypothesis for its evolution. Here, we explore this hypothesis theoretically and ask if the accumulation of beneficial mutations provides a sufficient fitness advantage for uniparental inheritance to invade a population in which mtDNA is inherited biparentally. In a deterministic model, uniparental inheritance increases in frequency but cannot replace biparental inheritance if only a single beneficial mtDNA mutation sweeps through the population. When we allow successive selective sweeps of mtDNA, however, uniparental inheritance can replace biparental inheritance. Using a stochastic model, we show that a combination of selection and drift facilitates the fixation of uniparental inheritance (compared to a neutral trait) when there is only a single selective mtDNA sweep. When we consider multiple mtDNA sweeps in a stochastic model, uniparental inheritance becomes even more likely to replace biparental inheritance. Our findings thus suggest that selective sweeps of beneficial mtDNA haplotypes can drive the evolution of uniparental inheritance. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Mitral valve prolapse and electrolyte abnormality: a dangerous combination for ventricular arrhythmias

PubMed Central

Rajani, Ali Raza; Murugesan, Vagishwari; Baslaib, Fahad Omar; Rafiq, Muhammad Anwer

2014-01-01

A 27-year-old woman with a history of bileaflet mitral valve prolapse and moderate mitral regurgitation presented to our emergency with untractable polymorphic wide complex tachycardia and unstable haemodynamics. After cardiopulmonary resuscitation, return of spontaneous circulation was achieved 30 min later. Her post-resuscitation ECG showed a prolonged QT interval which progressively normalised over the same day. Her laboratory investigations revealed hypocalcaemia while other electrolytes were within normal limits. A diagnosis of ventricular arrhythmia secondary to structural heart disease further precipitated by hypocalcaemia was made. Further hospital stay did not reveal a recurrence of prolonged QT interval or other arrhythmias except for an episode of non-sustained ventricular tachycardia. However, the patient suffered diffuse hypoxic brain encephalopathy secondary to prolonged cardiopulmonary resuscitation. PMID:24827670

Prevalence and prognostic value of exercise-induced ventricular arrhythmias.

PubMed

Partington, Sara; Myers, Jonathan; Cho, Shaun; Froelicher, Victor; Chun, Sung

2003-01-01

The purpose of this study was to determine the prevalence and prognostic significance of exercise-induced ventricular arrhythmias (EIVAs) in patients referred for exercise testing, considering the arrhythmic substrate and exercise-induced ischemia. EIVAs are frequently observed during exercise testing, but their prognostic significance is uncertain. The design of this study was a retrospective analysis of prospectively collected data, and it took place in 2 university-affiliated Veterans Affairs Medical Centers. Patients comprised 6213 consecutive males referred for exercise tests. We measured clinical exercise test responses and all-cause mortality after a mean follow-up of 6 +/- 4 years. EIVAs were defined as frequent premature ventricular contractions (PVCs) constituting >10% of all ventricular depolarizations during any 30 second electrocardiogram recording, or a run of > or =3 consecutive PVCs during exercise or recovery. A total of 1256 patients (20%) died during follow-up. EIVAs occurred in 503 patients (8%); the prevalence of EIVAs increased in older patients and in those with cardiopulmonary disease, resting PVCs, and ischemia during exercise. EIVAs were associated with mortality irrespective of the presence of cardiopulmonary disease or exercise-induced ischemia. In those without cardiopulmonary disease, mortality differed more so later in follow up than earlier. In those without resting PVCs, EIVAs were also predictive of mortality, but in those with resting PVCs, poorer prognosis was not worsened by the presence of EIVAs. Exercise induced ischemia does not affect the prognostic value of EIVAs, whereas the arrhythmic substrate does. EIVAs and resting PVCs are both independent predictors of mortality after consideration of other clinical and exercise-test variables. These findings are of limited clinical significance because of the modest change in risk and the lack of any established intervention. However, they explain some of the previous controversy

Molecular mechanisms for protein-encoded inheritance

PubMed Central

Wiltzius, Jed J. W.; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R.; Apostol, Marcin I.; Goldschmidt, Lukasz; Soriaga, Angela B.; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David

2013-01-01

Strains are phenotypic variants, encoded by nucleic acid sequences in chromosomal inheritance and by protein “conformations” in prion inheritance and transmission. But how is a protein “conformation” stable enough to endure transmission between cells or organisms? Here new polymorphic crystal structures of segments of prion and other amyloid proteins offer structural mechanisms for prion strains. In packing polymorphism, prion strains are encoded by alternative packings (polymorphs) of β-sheets formed by the same segment of a protein; in a second mechanism, segmental polymorphism, prion strains are encoded by distinct β-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring “conformations,” capable of encoding strains. These molecular mechanisms for transfer of information into prion strains share features with the familiar mechanism for transfer of information by nucleic acid inheritance, including sequence specificity and recognition by non-covalent bonds. PMID:19684598

The Role of Spatial Dispersion of Repolarization in Inherited and Acquired Sudden Cardiac Death Syndromes

PubMed Central

Antzelevitch, Charles

2007-01-01

This review examines the role of spatial electrical heterogeneity within ventricular myocardium on the function of the heart in health and disease. The cellular basis for transmural dispersion of repolarization (TDR) is reviewed and the hypothesis that amplification of spatial dispersion of repolarization underlies the development of life-threatening ventricular arrhythmias associated with inherited ion channelopathies is evaluated. The role of TDR in the long QT, short QT and Brugada syndromes as well as catecholaminergic polymorphic ventricular tachycardia (CPVT) are critically examined. In the long QT Syndrome, amplification of TDR is often secondary to preferential prolongation of the action potential duration (APD) of M cells, whereas in the Brugada Syndrome, it is thought to be due to selective abbreviation of the APD of right ventricular (RV) epicardium. Preferential abbreviation of APD of either endocardium or epicardium appears to be responsible for amplification of TDR in the short QT syndrome. In catecholaminergic polymorphic VT, reversal of the direction of activation of the ventricular wall is responsible for the increase in TDR. In conclusion, the long QT, short QT, Brugada and catecholaminergic polymorphic VT syndromes are pathologies with very different phenotypes and etiologies, but which share a common final pathway in causing sudden cardiac death. PMID:17586620

Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

PubMed

Roell, Wilhelm; Klein, Alexandra M; Breitbach, Martin; Becker, Torsten S; Parikh, Ashish; Lee, Jane; Zimmermann, Katrin; Reining, Shaun; Gabris, Beth; Ottersbach, Annika; Doran, Robert; Engelbrecht, Britta; Schiffer, Miriam; Kimura, Kenichi; Freitag, Patricia; Carls, Esther; Geisen, Caroline; Duerr, Georg D; Sasse, Philipp; Welz, Armin; Pfeifer, Alexander; Salama, Guy; Kotlikoff, Michael; Fleischmann, Bernd K

2018-05-08

Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45 + cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.

Cardiac arrhythmia beat classification using DOST and PSO tuned SVM.

PubMed

Raj, Sandeep; Ray, Kailash Chandra; Shankar, Om

2016-11-01

The increase in the number of deaths due to cardiovascular diseases (CVDs) has gained significant attention from the study of electrocardiogram (ECG) signals. These ECG signals are studied by the experienced cardiologist for accurate and proper diagnosis, but it becomes difficult and time-consuming for long-term recordings. Various signal processing techniques are studied to analyze the ECG signal, but they bear limitations due to the non-stationary behavior of ECG signals. Hence, this study aims to improve the classification accuracy rate and provide an automated diagnostic solution for the detection of cardiac arrhythmias. The proposed methodology consists of four stages, i.e. filtering, R-peak detection, feature extraction and classification stages. In this study, Wavelet based approach is used to filter the raw ECG signal, whereas Pan-Tompkins algorithm is used for detecting the R-peak inside the ECG signal. In the feature extraction stage, discrete orthogonal Stockwell transform (DOST) approach is presented for an efficient time-frequency representation (i.e. morphological descriptors) of a time domain signal and retains the absolute phase information to distinguish the various non-stationary behavior ECG signals. Moreover, these morphological descriptors are further reduced in lower dimensional space by using principal component analysis and combined with the dynamic features (i.e based on RR-interval of the ECG signals) of the input signal. This combination of two different kinds of descriptors represents each feature set of an input signal that is utilized for classification into subsequent categories by employing PSO tuned support vector machines (SVM). The proposed methodology is validated on the baseline MIT-BIH arrhythmia database and evaluated under two assessment schemes, yielding an improved overall accuracy of 99.18% for sixteen classes in the category-based and 89.10% for five classes (mapped according to AAMI standard) in the patient

Alcohol effects on the epigenome in the germline: role in the inheritance of alcohol-related pathology

PubMed Central

Chastain, Lucy G.; Sarkar, Dipak K.

2017-01-01

Excessive alcohol exposure has severe health consequences, and clinical and animal studies have demonstrated that disruptions in the epigenome of somatic cells, such as those in brain, are an important factor in the development of alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal alcohol spectrum disorders (FASDs). It is also well known that alcohol-related health problems are passed down across generations in human populations, but the complete mechanisms for this phenomenon are currently unknown. Recent studies in animal models have suggested that epigenetic factors are also responsible for the transmission of alcohol-related pathologies across generations. Alcohol exposure has been shown to induce changes in the epigenome of sperm of exposed male animals, and these epimutations are inherited in the offspring. This paper reviews evidence for multigenerational and transgenerational epigenetic inheritance of alcohol-related pathology through the germline. We also review the literature on the epigenetic effects of alcohol exposure on somatic cells in brain, and its contribution to AUDs and FASDs. We note gaps in knowledge in this field, such as the lack of clinical studies in human populations and the lack of data on epigenetic inheritance via the female germline, and we suggest future research directions. PMID:28431793

Ventricular arrhythmias and changes in heart rate preceding ventricular tachycardia in patients with an implantable cardioverter defibrillator.

PubMed

Lerma, Claudia; Wessel, Niels; Schirdewan, Alexander; Kurths, Jürgen; Glass, Leon

2008-07-01

The objective was to determine the characteristics of heart rate variability and ventricular arrhythmias prior to the onset of ventricular tachycardia (VT) in patients with an implantable cardioverter defibrillator (ICD). Sixty-eight beat-to-beat time series from 13 patients with an ICD were analyzed to quantify heart rate variability and ventricular arrhythmias. The episodes of VT were classified in one of two groups depending on whether the sinus rate in the 1 min preceding the VT was greater or less than 90 beats per minute. In a subset of patients, increased heart rate and reduced heart rate variability was often observed up to 20 min prior to the VT. There was a non-significant trend to higher incidence of premature ventricular complexes (PVCs) before VT compared to control recordings. The patterns of the ventricular arrhythmias were highly heterogeneous among different patients and even within the same patient. Analysis of the changes of heart rate and heart rate variability may have predictive value about the onset of VT in selected patients. The patterns of ventricular arrhythmia could not be used to predict onset of VT in this group of patients.

Epigenetic Inheritance and the Intergenerational Transfer of Experience

ERIC Educational Resources Information Center

Harper, Lawrence

2005-01-01

Currently, behavioral development is thought to result from the interplay among genetic inheritance, congenital characteristics, cultural contexts, and parental practices as they directly impact the individual. Evolutionary ecology points to another contributor, epigenetic inheritance, the transmission to offspring of parental phenotypic responses…

Obesity and exercise-induced ectopic ventricular arrhythmias in apparently healthy middle aged adults.

PubMed

Sabbag, Avi; Sidi, Yechezkel; Kivity, Shaye; Beinart, Roy; Glikson, Michael; Segev, Shlomo; Goldenberg, Ilan; Maor, Elad

2016-03-01

Obesity and overweight are strongly associated with cardiovascular morbidity and mortality. However, there are limited data on the association between excess weight and the risk of ectopic ventricular activity. We investigated the association between body mass index (BMI) and the risk for ectopic ventricular activity (defined as multiple ventricular premature beats (≥3), ventricular bigeminy, nonsustained ventricular tachycardia or sustained ventricular tachycardia) during exercise stress testing among 22,516 apparently healthy men and women who attended periodic health screening examinations between the years 2000 and 2014. All subjects had completed maximal exercise stress testing annually according to the Bruce protocol. Subjects were divided at baseline into three groups: normal weight (BMI ≥ 18.5 kg/m(2) and<25; N = 9,994), overweight (BMI ≥ 25 and < 30; N = 9,613) and obese (BMI ≥ 30; N = 2,906). The mean age of study subjects was 47 ± 10 years and 72% were men. Kaplan-Meier survival analysis showed that the cumulative probability for the development of exercise-induced ectopic ventricular activity arrhythmias was highest among obese subjects, intermediate among overweight subjects and lowest among subjects with normal weight (3.4%, 2.7% and 2.2% respectively; p < 0.001). Multivariate binary logistic regression with repeated measures of 92,619 ESTs, showed that obese subjects were 33% more likely to have ectopic ventricular arrhythmias during exercise compared with subjects with normal weight (p = 0.005), and that each 1 kg/m(2) increase in BMI was associated with a significant 4% (p = 0.002) increased adjusted risk for exercise-induced ventricular arrhythmias. Obesity is independently associated with increased likelihood of ectopic ventricular arrhythmia during exercise. © The European Society of Cardiology 2015.

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.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Privacy-Preserving Electrocardiogram Monitoring for Intelligent Arrhythmia Detection †

PubMed Central

Son, Junggab; Park, Juyoung; Oh, Heekuck; Bhuiyan, Md Zakirul Alam; Hur, Junbeom; Kang, Kyungtae

2017-01-01

Long-term electrocardiogram (ECG) monitoring, as a representative application of cyber-physical systems, facilitates the early detection of arrhythmia. A considerable number of previous studies has explored monitoring techniques and the automated analysis of sensing data. However, ensuring patient privacy or confidentiality has not been a primary concern in ECG monitoring. First, we propose an intelligent heart monitoring system, which involves a patient-worn ECG sensor (e.g., a smartphone) and a remote monitoring station, as well as a decision support server that interconnects these components. The decision support server analyzes the heart activity, using the Pan–Tompkins algorithm to detect heartbeats and a decision tree to classify them. Our system protects sensing data and user privacy, which is an essential attribute of dependability, by adopting signal scrambling and anonymous identity schemes. We also employ a public key cryptosystem to enable secure communication between the entities. Simulations using data from the MIT-BIH arrhythmia database demonstrate that our system achieves a 95.74% success rate in heartbeat detection and almost a 96.63% accuracy in heartbeat classification, while successfully preserving privacy and securing communications among the involved entities. PMID:28604628

Familial mental retardation in a family with an inherited chromosome rearrangement

PubMed Central

Chudley, A. E.; Bauder, F.; Ray, M.; McAlpine, Phyllis J.; Pena, S. D. J.; Hamerton, J. L.

1974-01-01

A family of three generations has been described with an insertional type of chromosome rearrangement involving chromosomes 11 and 18[46,XX or XY, ins(11;18)(p15;q11q21)] detected by G-banding using a trypsin digestion method. Four members of this family with clinical features of 18q− have inherited the der(18) from their father and are thus deficient for (18)(q11q21). Three other family members have inherited the der(11) and thus have a duplication of the same segment [(18)(q11q21)]. Genetic marker studies on this family, show no significant segregation of any of the markers studied with either the der(11) or der(18). Eight family members had the PepA8PepA1 genotype and four of these were carrying the der(18), indicating that the PepA locus which had been previously assigned to chromosome 18, does not lie in the segment q11→q21. Images PMID:4140909

22 CFR 71.3 - American claimants to foreign estates and inheritances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... inheritances. 71.3 Section 71.3 Foreign Relations DEPARTMENT OF STATE PROTECTION AND WELFARE OF AMERICANS....3 American claimants to foreign estates and inheritances. Where treaty provisions, local laws, or... foreign estates and inheritances. ...

Arrhythmia as a cardiac manifestation in MELAS syndrome.

PubMed

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

2015-09-01

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

Cardiac Arrhythmias in Adults With Congenital Heart Disease: Scope, Specific Problems, and Management.

PubMed

Lindsay, Ian; Moore, Jeremy P

2015-12-01

Progressive advances in the field of congenital heart disease (CHD) have led to a dramatic rise in the number of affected patients surviving well into adulthood. Groundbreaking and innovative achievements in the medical, surgical, and interventional management of these patients have allowed them to lead full adult lives that have included raising families, completing degrees in higher education, and maintaining successful careers. As patients are living longer, arrhythmias have emerged as one of the most significant factors affecting their morbidity, mortality, and quality of life. This article aims to review the current understanding of arrhythmia within the adult congenital heart disease (ACHD) population, emphasizing recent advances and providing recommendations pertaining to the management of these patients.

Classification of ECG signal with Support Vector Machine Method for Arrhythmia Detection

NASA Astrophysics Data System (ADS)

Turnip, Arjon; Ilham Rizqywan, M.; Kusumandari, Dwi E.; Turnip, Mardi; Sihombing, Poltak

2018-03-01

An electrocardiogram is a potential bioelectric record that occurs as a result of cardiac activity. QRS Detection with zero crossing calculation is one method that can precisely determine peak R of QRS wave as part of arrhythmia detection. In this paper, two experimental scheme (2 minutes duration with different activities: relaxed and, typing) were conducted. From the two experiments it were obtained: accuracy, sensitivity, and positive predictivity about 100% each for the first experiment and about 79%, 93%, 83% for the second experiment, respectively. Furthermore, the feature set of MIT-BIH arrhythmia using the support vector machine (SVM) method on the WEKA software is evaluated. By combining the available attributes on the WEKA algorithm, the result is constant since all classes of SVM goes to the normal class with average 88.49% accuracy.

Regulation, cell differentiation and protein-based inheritance.

PubMed

Malagnac, Fabienne; Silar, Philippe

2006-11-01

Recent research using fungi as models provide new insight into the ability of regulatory networks to generate cellular states that are sufficiently stable to be faithfully transmitted to daughter cells, thereby generating epigenetic inheritance. Such protein-based inheritance is driven by infectious factors endowed with properties usually displayed by prions. We emphasize the contribution of regulatory networks to the emerging properties displayed by cells.

LiteNet: Lightweight Neural Network for Detecting Arrhythmias at Resource-Constrained Mobile Devices.

PubMed

He, Ziyang; Zhang, Xiaoqing; Cao, Yangjie; Liu, Zhi; Zhang, Bo; Wang, Xiaoyan

2018-04-17

By running applications and services closer to the user, edge processing provides many advantages, such as short response time and reduced network traffic. Deep-learning based algorithms provide significantly better performances than traditional algorithms in many fields but demand more resources, such as higher computational power and more memory. Hence, designing deep learning algorithms that are more suitable for resource-constrained mobile devices is vital. In this paper, we build a lightweight neural network, termed LiteNet which uses a deep learning algorithm design to diagnose arrhythmias, as an example to show how we design deep learning schemes for resource-constrained mobile devices. Compare to other deep learning models with an equivalent accuracy, LiteNet has several advantages. It requires less memory, incurs lower computational cost, and is more feasible for deployment on resource-constrained mobile devices. It can be trained faster than other neural network algorithms and requires less communication across different processing units during distributed training. It uses filters of heterogeneous size in a convolutional layer, which contributes to the generation of various feature maps. The algorithm was tested using the MIT-BIH electrocardiogram (ECG) arrhythmia database; the results showed that LiteNet outperforms comparable schemes in diagnosing arrhythmias, and in its feasibility for use at the mobile devices.

LiteNet: Lightweight Neural Network for Detecting Arrhythmias at Resource-Constrained Mobile Devices

PubMed Central

Zhang, Xiaoqing; Cao, Yangjie; Liu, Zhi; Zhang, Bo; Wang, Xiaoyan

2018-01-01

By running applications and services closer to the user, edge processing provides many advantages, such as short response time and reduced network traffic. Deep-learning based algorithms provide significantly better performances than traditional algorithms in many fields but demand more resources, such as higher computational power and more memory. Hence, designing deep learning algorithms that are more suitable for resource-constrained mobile devices is vital. In this paper, we build a lightweight neural network, termed LiteNet which uses a deep learning algorithm design to diagnose arrhythmias, as an example to show how we design deep learning schemes for resource-constrained mobile devices. Compare to other deep learning models with an equivalent accuracy, LiteNet has several advantages. It requires less memory, incurs lower computational cost, and is more feasible for deployment on resource-constrained mobile devices. It can be trained faster than other neural network algorithms and requires less communication across different processing units during distributed training. It uses filters of heterogeneous size in a convolutional layer, which contributes to the generation of various feature maps. The algorithm was tested using the MIT-BIH electrocardiogram (ECG) arrhythmia database; the results showed that LiteNet outperforms comparable schemes in diagnosing arrhythmias, and in its feasibility for use at the mobile devices. PMID:29673171

The effect of inhibitors of endogenous opioid degradation, bacitracin, bestatin, captopril, and D-phenylalanine, on digoxin-induced arrhythmias in guinea pigs.

PubMed

Rabkin, S W; Redston, M

1989-08-01

The purpose of this study was to investigate the effect of inhibition of endogenous opioid degradation on digitalis-induced arrhythmias, utilizing the inhibitors bacitracin, bestatin, captopril, and D-phenylalanine. Guinea pigs, anesthetized with pentobarbital, 50 mg/kg i.p., and breathing spontaneously received intracerebroventricular (i.c.v.) injection of bacitracin (6.8 mg/kg), bestatin (1 mg/kg), captopril (2 mg/kg), D-phenylalanine (1.2 mg/kg) or the diluent, saline. Digitalis arrhythmias were induced by a 50 micrograms/kg i.v. bolus of digoxin followed by 500 micrograms.kg-1.h-1 i.v. Bacitracin and bestatin, but not captopril or D-phenylalanine, significantly (p less than 0.05) altered the relationship between the digoxin dose and the first occurrence of arrhythmias, i.e., digoxin-induced ventricular arrhythmias became manifest at lower digoxin doses. The mean digoxin dose and ED50s, at which arrhythmias first occurred, were significantly (p less than 0.05) reduced by bacitracin and bestatin. The findings were similar for fatal arrhythmias, although D-phenylalanine appeared to decrease the digoxin dose at the development of fatal arrhythmias. The opioid antagonist naloxone, in a 50 micrograms/kg bolus and 50 micrograms.kg-1.h-1 i.c.v., completely prevented these effects of bacitracin and reduced the effect of bestatin. The relationship to arrhythmias could not be ascribed to an effect on blood pressure, as the blood pressure response to digoxin was the same in bestatin, D-phenylalanine, and control groups. To examine whether systemic administration of an inhibitor of opioid degradation had similar effects, a second protocol was selected with systemic administration of bacitracin because it altered the dose effect relationship after i.c.v. administration and systemic concentrations could be readily attained. Bacitracin, in a 13.5 mg/kg i.v. bolus and 135 mg.kg-1.h-1 i.v., was followed by 100 micrograms/kg digoxin i.v. every 15 min.(ABSTRACT TRUNCATED AT 250

Inheritance on processes, exemplified on distributed termination detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomsen, K.S.

1987-02-01

A multiple inheritance mechanism on processes is designed and presented within the framework of a small object oriented language. Processes are described in classes, and the different action parts of a process inherited from different classes are executed in a coroutine-like style called alternation. The inheritance mechanism is a useful tool for factorizing the description of common aspects of processes. This is demonstrated within the domain of distributed programming by using the inheritance mechanism to factorize the description of distributed termination detection algorithms from the description of the distributed main computations for which termination is to be detected. A clearmore » separation of concerns is obtained, and arbitrary combinations of terminations detection algorithms and main computations can be formed. The same termination detection classes can also be used for more general purposes within distributed programming, such as detecting termination of each phase in a multi-phase main computation.« less

Arrhythmias and hemodialysis: role of potassium and new diagnostic tools.

PubMed

Buemi, Michele; Coppolino, Giuseppe; Bolignano, Davide; Sturiale, Alessio; Campo, Susanna; Buemi, Antoine; Crascì, Eleonora; Romeo, Adolfo

2009-01-01

Cardiovascular diseases represent the main causes of death in patients affected by renal failure, and arrhythmias are frequently observed in patients undergoing hemodialysis. Dialytic treatment per se can be considered as an arrhythmogenic stimulus; moreover, uraemic patients are characterized by a "pro-arrhythmic substrate" because of the high prevalence of ischaemic heart disease, left ventricular hypertrophy and autonomic neuropathy. One of the most important pathogenetic element involved in the onset of intra-dialytic arrhythmias is the alteration in electrolytes concentration, particularly calcium and potassium. It may be very useful to monitor the patient's cardiac activity during the whole hemodilaytic session. Nevertheless, the application of an extended intradialytic electrocardiographic monitoring is not simple because of several technical and structural impairments. We tried to overcome these difficulties using Whealthy, a wearable system consisting in a t-shirt composed of conductors and piezoresistive materials, integrated to form fibers and threads connected to tissutal sensors, electrodes, and connectors. ECG and pneumographic impedance signals are acquired by the electrodes in the tissue, and the data are registered by a small computer and transmitted via GPRS or Bluetooth.

[Kurschmann-Steinert myotonic dystrophia and Adams-Stoke attacks. Successful treatment of arrhythmia by means of pacemaker implantation].

PubMed

Bieler, M; Sefidpar, M; Engel, U R; Reutter, F W

1976-11-20

The case is reported of a 39-year-old male with Steinert's dystrophia myotonica complicated by cardiac arrhythmias manifested by high-degree a-v block with Stokes-Adams attacks. Implantation of a demand-type cardiac pacemaker brought prompt relief from cardiac symptoms and the patient was able to resume work. The pathologico-anatomical findings in dystrophia myotonica are discussed, together with their possible connection with the type of arrhythmias described.

The Coffin-Lowry syndrome: an inherited faciodigital mental retardation syndrome.

PubMed

Temtamy, S A; Miller, J D; Hussels-Maumenee, I

1975-05-01

Eight patients in three families had mental retardation, characteristic facies and hands, and skeletal changes; the clinical features suggested to us that they had a syndrome previously thought to represent two entities described by Lowry and associates and by Coffin and associates, respectively. New findings include skeletal, orodental, and dermatoglyphic abnormalities and histopathologic changes suggesting that the syndrome is a heritable disorder of connective tissue. Severe expression in males and transmission through mildly affected females suggest X-linked or sex-influenced autosomal dominant inheritance.

[Patients with inherited trombophilia and recurrent pregnancy loss: incidence].

PubMed

Flores-Alatriste, José Daniel; Jacobo-Nájera, Sara; Segura-Rodríguez, Rubén; Stern-Colin y Nunes, Jorge Jaroslav

2014-06-01

Inherited thrombophilia is a genetic tendency to suffer thrombotic events clinically evident at an early age, with frequent re- currences without apparent cause. In recent years thrombophilia has earned a place as a primary risk factor for abnormal pregnancy. To determine the incidence of hereditary thrombophilia in patients with recurrent pregnancy loss. A retrospective, linear and descriptive study was conducted at Clinic of Reproduction IMMUNOREP with patients treated from January 2007 to December 2012. The study included patients with a diagnosis of recurrent pregnancy loss and inherited thrombophilia with laboratory studies of thrombophilia including different genes: G1619A (factor V Leiden), R2 H1299R (factor V polymorphism), C677T (methylenetetrahydrofolate reductase enzyme polymorphism), A1298C (methylenetetrahydrofolate reductase enzyme mutation), G20210A (mutation of the prothrombin gene), V34L (factor XIII polymorphism), 455G > A (fibrinogen gene mutation), 4G/5G (plasminogen activator inhibitor) and a/b L33P (ribosomal polymorphism of methylenetetrahydrofolate reductase enzyme). 211 files were reviewed and only 10.4% of patients were negative for hereditary thrombophilia, a percentage that is consistent with the results of different series of studies in patients with unexplained recurrent pregnancy loss. The most prevalent genetic condition was 4G/5G (plasminogen activator inhibitor, 85.5%) in homozygous and heterozygous with 63.4% (120) and 22.4% (42), respectively. It was demonstrated the direct relationship between thrombophilia and recurrent pregnancy loss depending on whether the patient is heterozygous or homozygous for the disease.

Occupational Inheritance in Service Academy Cadets and Midshipmen

ERIC Educational Resources Information Center

Roller, Brain; Doerries, Lee E.

2008-01-01

Occupational inheritance refers to the phenomenon where sons and daughters follow in the career paths of their parents. Historically this has been documented in the areas of engineering, medicine and education. This study investigated the phenomenon of occupational inheritance as it pertains to military service. Archival data provided by the…

GPU based cloud system for high-performance arrhythmia detection with parallel k-NN algorithm.

PubMed

Tae Joon Jun; Hyun Ji Park; Hyuk Yoo; Young-Hak Kim; Daeyoung Kim

2016-08-01

In this paper, we propose an GPU based Cloud system for high-performance arrhythmia detection. Pan-Tompkins algorithm is used for QRS detection and we optimized beat classification algorithm with K-Nearest Neighbor (K-NN). To support high performance beat classification on the system, we parallelized beat classification algorithm with CUDA to execute the algorithm on virtualized GPU devices on the Cloud system. MIT-BIH Arrhythmia database is used for validation of the algorithm. The system achieved about 93.5% of detection rate which is comparable to previous researches while our algorithm shows 2.5 times faster execution time compared to CPU only detection algorithm.

Data-driven models of dominantly-inherited Alzheimer's disease progression.

PubMed

Oxtoby, Neil P; Young, Alexandra L; Cash, David M; Benzinger, Tammie L S; Fagan, Anne M; Morris, John C; Bateman, Randall J; Fox, Nick C; Schott, Jonathan M; Alexander, Daniel C

2018-05-01

accurately than predictions that used familial estimates: root mean squared error of 1.35 years versus 5.54 years. The models reveal hidden detail on dominantly-inherited Alzheimer's disease progression, as well as providing data-driven systems for fine-grained patient staging and prediction of symptom onset with great potential utility in clinical trials.

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.

Recommendations regarding dietary intake and caffeine and alcohol consumption in patients with cardiac arrhythmias: what do you tell your patients to do or not to do?

PubMed

Glatter, Kathryn A; Myers, Richard; Chiamvimonvat, Nipavan

2012-10-01

The etiology of arrhythmias including atrial fibrillation is multifactorial. Most arrhythmias are associated with comorbid illnesses like hypertension, diabetes, thyroid disease, or advanced age. Although it is tempting to blame a stimulant like caffeine as a trigger for arrhythmias, the literature does not support this idea. There is no real benefit to having patients with arrhythmias limit their caffeine intake. Caffeine is a vasoactive substance that also may promote the release of norepinephrine and epinephrine. However, acute ingestion of caffeine (as coffee or tea) does not cause atrial fibrillation. Even patients suffering a myocardial infarction do not have an increased incidence of ventricular or other arrhythmias after ingesting several cups of coffee. Large epidemiologic studies have also failed to find a connection between the amount of coffee/caffeine used and the development of arrhythmias. As such, it does not make sense to suggest that patients with palpitations, paroxysmal atrial fibrillation, or supraventricular tachycardia, abstain from caffeine use. Energy drinks are a new phenomenon on the beverage market, with 30-50 % of young adults and teens using them regularly. Energy drinks are loaded with caffeine, sugar, and other chemicals that can stimulate the cardiac system. There is an increasing body of mainly anecdotal case reports describing arrhythmias or even sudden death triggered by exercise plus using energy drinks. Clearly, there must be more study in this area, but it is wise to either limit or avoid their use in patients with arrhythmias. Moderate to heavy alcohol use seems to be associated with the development of atrial fibrillation. The term "holiday heart" was coined back in 1978, to describe patients who had atrial fibrillation following binge alcohol use. Thus, it is reasonable to recommend to patients with arrhythmias that they limit their alcohol use, although unfortunately this treatment will likely not completely resolve their

Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome.

PubMed

Le Scouarnec, Solena; Karakachoff, Matilde; Gourraud, Jean-Baptiste; Lindenbaum, Pierre; Bonnaud, Stéphanie; Portero, Vincent; Duboscq-Bidot, Laëtitia; Daumy, Xavier; Simonet, Floriane; Teusan, Raluca; Baron, Estelle; Violleau, Jade; Persyn, Elodie; Bellanger, Lise; Barc, Julien; Chatel, Stéphanie; Martins, Raphaël; Mabo, Philippe; Sacher, Frédéric; Haïssaguerre, Michel; Kyndt, Florence; Schmitt, Sébastien; Bézieau, Stéphane; Le Marec, Hervé; Dina, Christian; Schott, Jean-Jacques; Probst, Vincent; Redon, Richard

2015-05-15

The Brugada syndrome (BrS) is a rare heritable cardiac arrhythmia disorder associated with ventricular fibrillation and sudden cardiac death. Mutations in the SCN5A gene have been causally related to BrS in 20-30% of cases. Twenty other genes have been described as involved in BrS, but their overall contribution to disease prevalence is still unclear. This study aims to estimate the burden of rare coding variation in arrhythmia-susceptibility genes among a large group of patients with BrS. We have developed a custom kit to capture and sequence the coding regions of 45 previously reported arrhythmia-susceptibility genes and applied this kit to 167 index cases presenting with a Brugada pattern on the electrocardiogram as well as 167 individuals aged over 65-year old and showing no history of cardiac arrhythmia. By applying burden tests, a significant enrichment in rare coding variation (with a minor allele frequency below 0.1%) was observed only for SCN5A, with rare coding variants carried by 20.4% of cases with BrS versus 2.4% of control individuals (P = 1.4 × 10(-7)). No significant enrichment was observed for any other arrhythmia-susceptibility gene, including SCN10A and CACNA1C. These results indicate that, except for SCN5A, rare coding variation in previously reported arrhythmia-susceptibility genes do not contribute significantly to the occurrence of BrS in a population with European ancestry. Extreme caution should thus be taken when interpreting genetic variation in molecular diagnostic setting, since rare coding variants were observed in a similar extent among cases versus controls, for most previously reported BrS-susceptibility genes. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Complex ventricular arrhythmias and carvedilol: efficacy in hemodialyzed uremic patients].

PubMed

Cice, G; Tagliamonte, E; Ferrara, L; Di Benedetto, A; Iacono, A

1998-06-01

Carvedilol has been shown to be effective in systemic hypertension and coronary artery disease in patients with end-stage renal disease, on maintenance hemodialysis. The aim of our study was to assess the effects of carvedilol on ventricular arrhythmias in these patients. Ninety-eight uremic patients maintained on hemodialysis, with complex ventricular arrhythmias (class III, IV and V of Lown's classification), not only during dialysis, were included in the study. They were divided into two groups, with mild-to-moderate hypertension or coronary artery disease. The efficacy and safety of carvedilol (50 mg/day) was compared to placebo in a 6-week randomized, double-blind study. Carvedilol significantly reduced, in both hypertensive and ischemic patients, total ventricular premature contractions (82.7 +/- 11.3 vs 358.1 +/- 73.9, p < 0.001; 88.3 +/- 24.4 vs 369.9 +/- 77.8, p < 0.001), repetitive ventricular premature contractions (1.3 +/- 1.3 vs 6.3 +/- 3.5, p < 0.001; 1.2 +/- 0.7 vs 6.9 +/- 2.6, p < 0.001) and episodes of ventricular tachycardia (1.1 +/- 1.2 vs 11.8 +/- 7.5, p < 0.001; 1.4 +/- 1.2 vs 14.0 +/- 8.3, p < 0.001). In placebo-treated patients, instead, these parameters were not significantly changed (329.1 +/- 76.5 vs 361.7 +/- 71.7, NS, and 324.6 +/- 79.7 vs 359.3 +/- 58.1, NS; 6.2 +/- 3.7 vs 7.3 +/- 3.7, NS, and 4.9 +/- 2.2 vs 6.1 +/- 3.2, NS; 9.8 +/- 6.3 vs 13.3 +/- 8.0, NS, and 9.0 +/- 6.2 vs 12.4 +/- 7.8, NS). Carvedilol confirmed a significant effect on myocardial ischemia and systemic hypertension. No significant side effects were reported. Ventricular arrhythmias are frequent in patients with end-stage renal disease maintained on hemodialysis. They are often due to an underlying cardiac disease, namely systemic hypertension with left ventricular hypertrophy and coronary artery disease. The results of our study show that the antiarrhythmic effect of carvedilol is linked, at least partly, to an improvement of the underlying cardiac disease. Uremic

Environmental Factors Can Influence Mitochondrial Inheritance in the Saccharomyces Yeast Hybrids.

PubMed

Hsu, Yu-Yi; Chou, Jui-Yu

2017-01-01

Mitochondria play a critical role in the generation of metabolic energy and are crucial for eukaryotic cell survival and proliferation. In most sexual eukaryotes, mitochondrial DNA (mtDNA) is inherited from only one parent in non-Mendelian inheritance in contrast to the inheritance of nuclear DNA. The model organism Saccharomyces cerevisiae is commonly used to study mitochondrial biology. It has two mating types: MATa and MATα. Previous studies have suggested that the mtDNA inheritance patterns in hybrid diploid cells depend on the genetic background of parental strains. However, the underlying mechanisms remain unclear. To elucidate the mechanisms, we examined the effects of environmental factors on the mtDNA inheritance patterns in hybrids obtained by crossing S. cerevisiae with its close relative S. paradoxus. The results demonstrated that environmental factors can influence mtDNA transmission in hybrid diploids, and that the inheritance patterns are strain dependent. The fitness competition assay results showed that the fitness differences can explain the mtDNA inheritance patterns under specific conditions. However, in this study, we found that fitness differences cannot fully be explained by mitochondrial activity in hybrids under stress conditions.

Environmental Factors Can Influence Mitochondrial Inheritance in the Saccharomyces Yeast Hybrids

PubMed Central

Hsu, Yu-Yi; Chou, Jui-Yu

2017-01-01

Mitochondria play a critical role in the generation of metabolic energy and are crucial for eukaryotic cell survival and proliferation. In most sexual eukaryotes, mitochondrial DNA (mtDNA) is inherited from only one parent in non-Mendelian inheritance in contrast to the inheritance of nuclear DNA. The model organism Saccharomyces cerevisiae is commonly used to study mitochondrial biology. It has two mating types: MATa and MATα. Previous studies have suggested that the mtDNA inheritance patterns in hybrid diploid cells depend on the genetic background of parental strains. However, the underlying mechanisms remain unclear. To elucidate the mechanisms, we examined the effects of environmental factors on the mtDNA inheritance patterns in hybrids obtained by crossing S. cerevisiae with its close relative S. paradoxus. The results demonstrated that environmental factors can influence mtDNA transmission in hybrid diploids, and that the inheritance patterns are strain dependent. The fitness competition assay results showed that the fitness differences can explain the mtDNA inheritance patterns under specific conditions. However, in this study, we found that fitness differences cannot fully be explained by mitochondrial activity in hybrids under stress conditions. PMID:28081193

Inheritance for software reuse: The good, the bad, and the ugly

NASA Technical Reports Server (NTRS)

Sitaraman, Murali; Eichmann, David A.

1992-01-01

Inheritance is a powerful mechanism supported by object-oriented programming languages to facilitate modifications and extensions of reusable software components. This paper presents a taxonomy of the various purposes for which an inheritance mechanism can be used. While some uses of inheritance significantly enhance software reuse, some others are not as useful and in fact, may even be detrimental to reuse. The paper discusses several examples, and argues for a programming language design that is selective in its support for inheritance.

CZ: Multimethods and Multiple Inheritance Without Diamonds

DTIC Science & Technology

2009-12-01

Language. Digital Press, second edition , 1990. 31 [48] C. Szyperski, S. Omohundro, and S. Murer. Engineering a programming language: The type and class...CZ:Multimethods andMultiple Inheritance Without Diamonds 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Expressiveness is retained through two features: a “requires” construct that provides a form of subtyping without inheritance (in- spired by Scala [39]), and a

Congenital Deafness with Cardiac Arrhythmias: The Jervell and Lange-Nielsen Syndrome.

ERIC Educational Resources Information Center

Wahl, Richard A.; Macdonald, Dick, II

1980-01-01

The Jervell and Lange-Nielsen syndrome, affecting 0.3 percent of congenitally deaf persons, consists of severe cardiac arrhythmias and sensorineural hearing loss. The authors recommend that every congenitally deaf child with suspicious symptoms receive an electrocardiogram and that professionals who work with deaf children not only inform…

AV-block and conduction slowing prevail over TdP arrhythmias in the methoxamine-sensitized pro-arrhythmic rabbit model.

PubMed

Varkevisser, Rosanne; Vos, Marc A; Beekman, Jet D; Tieland, Ralph G; Van Der Heyden, Marcel A

2015-01-01

The methoxamine-sensitized rabbit model is widely used to screen drugs for proarrhythmic properties, especially repolarization-dependent TdP arrhythmias. With the change of anesthesia and/or sensitizing agent, conduction disturbances have been reported as well. Therefore, we compared currently available in-house anesthetics in order to preserve arrhythmia sensitivity and preclude conduction disturbances. Rabbits were randomly assigned to 3 groups: (1) 35 mg/kg ketamine + 5 mg/kg xylazine; (2) 0.5 mL/kg hypnorm + 3 mg/kg midazolam; (3) 35 mg/kg ketamine + 20 mg/kg propofol. Anesthesia was maintained by 1.5% isoflurane. Concomitant infusion of methoxamine (17 μg/kg/min for 40 minutes) and dofetilide (10 μg/kg/min for 30 minutes) was used to induce arrhythmias. Sole methoxamine infusion exclusively decreased HR in groups 1 and 3. Dofetilide lengthened repolarization, followed in time by PQ/QRS prolongation, second-degree AV block, and subsequently TdP arrhythmias. TdP was seen in 80%, 0%, and 33% of the rabbits in groups 1, 2, and 3, respectively. Decreasing the dose of dofetilide to 5 μg/kg/min in ketamine/xylazine anesthetized rabbits resulted in a drop in TdP incidence (25%) while conduction disturbances persisted. Flunarizine (n = 6) suppressed all TdP arrhythmias while conduction disturbances remained present. TdP incidence in the methoxamine-sensitized rabbit could be dramatically influenced by anesthesia, drug dose, and flunarizine, while conduction slowing remained present. Thus, conduction slowing seems to be the integral outcome in this model. © 2014 Wiley Periodicals, Inc.

[Approach of gene medical treatment in neurological diseases with the neurologist's. "Approach of support to the patients with inherited and incurable neurological diseases"].

PubMed

Hazama, Takanori; Sawada, Jin-ichi; Toda, Tatsushi

2009-11-01

Advancements in medical genetics have increased access to genetic diagnosis in clinical neurology and accompanying genetic counseling. However, its use has not yet spread and the frequency of general biochemistry inspection in medical treatment and by patients remains low. Many problems remain for doctors, though sociocultural and other various causes exist. Thus, a network of care specialists for inherited and incurable neurological diseases has been established, consisting of multi-occupational categories in medical treatment, health, and welfare such as clinical inheritance specialists, psychiatrists, public health nurses, and medical social workers, to meet the rise in availability of such methods. Businesses in areas such as training, consultation, and field research have arisen. An educational campaign for neurologists who have taken a central role in treatment of inherited and incurable neurological diseases, and related information have been disseminated to those working in fields related to regional welfare of neurological medicine, and patients are now supported totally by team and regional counseling. These new developments in support systems for inherited and incurable neurological diseases, have steadily achieved the respective goals. We aim to promote its evolution to a more advanced network to promote the independence of individual patients in the future.

Alport syndrome: impact of digenic inheritance in patients management.

PubMed

Fallerini, C; Baldassarri, M; Trevisson, E; Morbidoni, V; La Manna, A; Lazzarin, R; Pasini, A; Barbano, G; Pinciaroli, A R; Garosi, G; Frullanti, E; Pinto, A M; Mencarelli, M A; Mari, F; Renieri, A; Ariani, F

2017-07-01

Alport syndrome (ATS) is a genetically heterogeneous nephropathy with considerable phenotypic variability and different transmission patterns, including monogenic (X-linked/autosomal) and digenic inheritance (DI). Here we present a new series of families with DI and we discuss the consequences for genetic counseling and risk assessment. Out of five families harboring variants in more than one COL4 gene detected by next generation sequencing (NGS), minigene-splicing assay allowed us to identify four as true digenic. Two families showed COL4A3/A4 mutations in cis, mimicking an autosomal dominant inheritance with a more severe phenotype and one showed COL4A3/A4 mutations in trans, mimicking an autosomal recessive inheritance with a less severe phenotype. In a fourth family, a de novo mutation (COL4A5) combined with an inherited mutation (COL4A3) triggered a more severe phenotype. A fifth family, predicted digenic on the basis of silico tools, rather showed monogenic X-linked inheritance due to a hypomorphic mutation, in accordance with a milder phenotype. In conclusion, this study highlights the impact of DI in ATS and explains the associated atypical presentations. More complex inheritance should be therefore considered when reviewing prognosis and recurrence risks. On the other side, these findings emphasize the importance to accompany NGS with splicing assays in order to avoid erroneous identification of at risk members. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Territory inheritance in clownfish.

PubMed

Buston, Peter M

2004-05-07

Animal societies composed of breeders and non-breeders present a challenge to evolutionary theory because it is not immediately apparent how natural selection can preserve the genes that underlie non-breeding strategies. The clownfish Amphiprion percula forms groups composed of a breeding pair and 0-4 non-breeders. Non-breeders gain neither present direct, nor present indirect benefits from the association. To determine whether non-breeders obtain future direct benefits, I investigated the pattern of territory inheritance. I show that non-breeders stand to inherit the territory within which they reside. Moreover, they form a perfect queue for breeding positions; a queue from which nobody disperses and within which nobody contests. I suggest that queuing might be favoured by selection because it confers a higher probability of attaining breeding status than either dispersing or contesting. This study illustrates that, within animal societies, individuals may tolerate non-breeding positions solely because of their potential to realize benefits in the future.

Territory inheritance in clownfish.

PubMed Central

Buston, Peter M

2004-01-01

Animal societies composed of breeders and non-breeders present a challenge to evolutionary theory because it is not immediately apparent how natural selection can preserve the genes that underlie non-breeding strategies. The clownfish Amphiprion percula forms groups composed of a breeding pair and 0-4 non-breeders. Non-breeders gain neither present direct, nor present indirect benefits from the association. To determine whether non-breeders obtain future direct benefits, I investigated the pattern of territory inheritance. I show that non-breeders stand to inherit the territory within which they reside. Moreover, they form a perfect queue for breeding positions; a queue from which nobody disperses and within which nobody contests. I suggest that queuing might be favoured by selection because it confers a higher probability of attaining breeding status than either dispersing or contesting. This study illustrates that, within animal societies, individuals may tolerate non-breeding positions solely because of their potential to realize benefits in the future. PMID:15252999

Non-contact arrhythmia assessment in natural settings: a step toward preventive cardiac care

NASA Astrophysics Data System (ADS)

Amelard, Robert; Hughson, Richard L.; Clausi, David A.; Wong, Alexander

2017-02-01

Cardiovascular disease is a major contributor to US morbidity. Taking preventive action can greatly reduce or eliminate the impact on quality of life. However, many issues often go undetected until the patient presents a physical symptom. Non-intrusive continuous cardiovascular monitoring systems may make detecting and monitoring abnormalities earlier feasible. One candidate system is photoplethysmographic imaging (PPGI), which is able to assess arterial blood pulse characteristics in one or multiple individuals remotely from a distance. In this case study, we showed that PPGI can be used to detect cardiac arrhythmia that would otherwise require contact-based monitoring techniques. Using a novel system, coded hemodynamic imaging (CHI), strong temporal blood pulse waveform signals were extracted at a distance of 1.5 m from the participant using 850-1000 nm diffuse illumination for deep tissue penetration. Data were recorded at a sampling rate of 60 Hz, providing a temporal resolution of 17 ms. The strong fidelity of the signal allowed for both temporal and spectral assessment of abnormal blood pulse waveforms, ultimately to detect the onset of abnormal cardiac events. Data from a participant with arrhythmia was analyzed and compared against normal blood pulse waveform data to validate CHI's ability to assess cardiac arrhythmia. Results indicate that CHI can be used as a non-intrusive continuous cardiac monitoring system.

The Effects of Respiratory Sinus Arrhythmia on Anger Reactivity and Persistence in Major Depression

PubMed Central

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

2016-01-01

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

Maternal telomere length inheritance in the king penguin.

PubMed

Reichert, S; Rojas, E R; Zahn, S; Robin, J-P; Criscuolo, F; Massemin, S

2015-01-01

Telomeres are emerging as a biomarker for ageing and survival, and are likely important in shaping life-history trade-offs. In particular, telomere length with which one starts in life has been linked to lifelong survival, suggesting that early telomere dynamics are somehow related to life-history trajectories. This result highlights the importance of determining the extent to which telomere length is inherited, as a crucial factor determining early life telomere length. Given the scarcity of species for which telomere length inheritance has been studied, it is pressing to assess the generality of telomere length inheritance patterns. Further, information on how this pattern changes over the course of growth in individuals living under natural conditions should provide some insight on the extent to which environmental constraints also shape telomere dynamics. To fill this gap partly, we followed telomere inheritance in a population of king penguins (Aptenodytes patagonicus). We tested for paternal and maternal influence on chick initial telomere length (10 days old after hatching), and how these relationships changed with chick age (at 70, 200 and 300 days old). Based on a correlative approach, offspring telomere length was positively associated with maternal telomere length early in life (at 10 days old). However, this relationship was not significant at older ages. These data suggest that telomere length in birds is maternally inherited. Nonetheless, the influence of environmental conditions during growth remained an important factor shaping telomere length, as the maternal link disappeared with chicks' age.

Update on gene therapy of inherited immune deficiencies.

PubMed

Engel, Barbara C; Kohn, Donald B; Podsakoff, Greg M

2003-10-01

Gene therapy has been under development as a way to correct inborn errors for many years. Recently, patients with two forms of inherited severe combined immunodeficiency (SCID), adenosine deaminase and X-linked, treated by three different clinical investigative teams, have shown significant immune reconstitution leading to protective immunity. These advances irrefutably prove the concept that hematopoietic progenitor cell gene therapy can ameliorate these diseases. However, due to proviral insertional oncogenesis, two individuals in one of the X-SCID studies developed T-cell leukemia more than two years after the gene transfer. Depending upon the results of long-term follow-up, the successes together with the side effects highlight the relative merits of this therapeutic approach.

An Inherited Platelet Function Defect in Basset Hounds

PubMed Central

Johnstone, I. B.; Lotz, F.

1979-01-01

An inherited platelet function defect occurring in a family of basset hounds has been described. The trait is transmitted as an autosomal characteristic and appears to be expressed clinically only in the homozygous state. The characteristics of this platelet defect include: 1) marked bleeding tendencies and prolonged skin bleeding times in either male or female dogs. 2) normal blood coagulation mechanism. 3) adequate numbers of circulating platelets which appear morphologically normal by light microscopy. 4) normal whole blood clot retraction. 5) deficient in vivo platelet consumption and in vitro platelet retention in glass bead columns. 6) defective ADP-induced platelet aggregation in homozygotes, apparently normal ADP response in heterozygotes, and defective collagen-induced platelet aggregation in both. PMID:509382

QT dispersion and ventricular arrhythmias in children with primary mitral valve prolapse

PubMed Central

İmamoğlu, Ebru Yalın; Eroğlu, Ayşe Güler

2016-01-01

Aim: To investigate ventricular arrhythmias in children with primary mitral valve prolapse and to evaluate its relation with QT length, QT dispersion, autonomic function tests and heart rate variability measurements. Material and Methods: Fourty two children with mitral valve prolapse and 32 healthy children were enrolled into the study. Twelve-lead electrocardiograms, autonomic function tests, echocardiography and 24-hour rhythm Holter tests were performed. Electrocardiograms were magnified digitally. The QT length was corrected according to heart rate. The patients were grouped according to the number of premature ventricular contractions and presence of complex ventricular arhythmia in the 24-hour rhythm Holter monitor test. Heart rate variability measurements were calculated automatically from the 24-hour rhythm Holter monitor test. Orthostatic hypotension and resting heart rate were used as autonomic function tests. Results: The mean age was 13.9±3.3 years in the patient group and 14.6±3.1 years in the control group (p>0.05). Thirty four of the patients (81%) were female and eight (19%) were male. Twenty five of the control subjects (78%) were female and seven (22%) were male. The QT dispersion and heart rate corrected QT interval were found to be significantly increased in the children with primary mitral valve prolapse when compared with the control group (56±16 ms vs. 43±11 ms, p=0.001; 426±25 ms vs. 407±26 ms, p=0.002, respectively). In 24-hour rhythm Holter monitor tests, ventricular arrhythmias were found in 21 out of 42 patients (50%) and 6 out of 32 control subjects (18.8%) (p=0.006). QT dispersion was found to be significantly increased in patients with premature ventricular contractions ≥ 10/day and/or complex ventricular arrhythmias compared to the control group without ventricular premature beats (p=0.002). There was no significant difference in autonomic function tests and heart rate variability measurements between the patient and control

High level of oxygen treatment causes cardiotoxicity with arrhythmias and redox modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapalamadugu, Kalyan C.; Panguluri, Siva K.; Bennett, Eric S.

2015-01-01

Hyperoxia exposure in mice leads to cardiac hypertrophy and voltage-gated potassium (Kv) channel remodeling. Because redox balance of pyridine nucleotides affects Kv function and hyperoxia alters cellular redox potential, we hypothesized that hyperoxia exposure leads to cardiac ion channel disturbances and redox changes resulting in arrhythmias. In the present study, we investigated the electrical changes and redox abnormalities caused by 72 h hyperoxia treatment in mice. Cardiac repolarization changes were assessed by acquiring electrocardiogram (ECG) and cardiac action potentials (AP). Biochemical assays were employed to identify the pyridine nucleotide changes, Kv1.5 expression and myocardial injury. Hyperoxia treatment caused marked bradycardia,more » arrhythmia and significantly prolonged (ms) the, RR (186.2 ± 10.7 vs. 146.4 ± 6.2), PR (46.8 ± 3.1 vs. 39.3 ± 1.6), QRS (10.8 ± 0.6 vs. 8.5 ± 0.2), QTc (57.1 ± 3.5 vs. 40 ± 1.4) and JT (13.4 ± 2.1 vs. 7.0 ± 0.5) intervals, when compared with normoxia group. Hyperoxia treatment also induced significant increase in cardiac action potential duration (APD) (ex-APD{sub 90}; 73.8 ± 9.5 vs. 50.9 ± 3.1 ms) and elevated levels of serum markers of myocardial injury; cardiac troponin I (TnI) and lactate dehydrogenase (LDH). Hyperoxia exposure altered cardiac levels of mRNA/protein expression of; Kv1.5, Kvβ subunits and SiRT1, and increased ratios of reduced pyridine nucleotides (NADH/NAD and NADPH/NADP). Inhibition of SiRT1 in H9C2 cells using Splitomicin resulted in decreased SiRT1 and Kv1.5 expression, suggesting that SiRT1 may mediate Kv1.5 downregulation. In conclusion, the cardiotoxic effects of hyperoxia exposure involve ion channel disturbances and redox changes resulting in arrhythmias. - Highlights: • Hyperoxia treatment leads to arrhythmia with prolonged QTc and action potential duration. • Hyperoxia treatment alters cardiac pyridine nucleotide [NAD(P)H/NAD(P)] levels. • SiRT1 and Kv1.5 are co

Genetic testing for inherited ocular disease: delivering on the promise at last?

PubMed

Gillespie, Rachel L; Hall, Georgina; Black, Graeme C

2014-01-01

Genetic testing is of increasing clinical utility for diagnosing inherited eye disease. Clarifying a clinical diagnosis is important for accurate estimation of prognosis, facilitating genetic counselling and management of families, and in the future will direct gene-specific therapeutic strategies. Often, precise diagnosis of genetic ophthalmic conditions is complicated by genetic heterogeneity, a difficulty that the so-called 'next-generation sequencing' technologies promise to overcome. Despite considerable counselling and ethical complexities, next-generation sequencing offers to revolutionize clinical practice. This will necessitate considerable adjustment to standard practice but has the power to deliver a personalized approach to genomic medicine for many more patients and enhance the potential for preventing vision loss. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing

PubMed Central

Walsh, Tom; Lee, Ming K.; Casadei, Silvia; Thornton, Anne M.; Stray, Sunday M.; Pennil, Christopher; Nord, Alex S.; Mandell, Jessica B.; Swisher, Elizabeth M.; King, Mary-Claire

2010-01-01

Inherited loss-of-function mutations in the tumor suppressor genes BRCA1, BRCA2, and multiple other genes predispose to high risks of breast and/or ovarian cancer. Cancer-associated inherited mutations in these genes are collectively quite common, but individually rare or even private. Genetic testing for BRCA1 and BRCA2 mutations has become an integral part of clinical practice, but testing is generally limited to these two genes and to women with severe family histories of breast or ovarian cancer. To determine whether massively parallel, “next-generation” sequencing would enable accurate, thorough, and cost-effective identification of inherited mutations for breast and ovarian cancer, we developed a genomic assay to capture, sequence, and detect all mutations in 21 genes, including BRCA1 and BRCA2, with inherited mutations that predispose to breast or ovarian cancer. Constitutional genomic DNA from subjects with known inherited mutations, ranging in size from 1 to >100,000 bp, was hybridized to custom oligonucleotides and then sequenced using a genome analyzer. Analysis was carried out blind to the mutation in each sample. Average coverage was >1200 reads per base pair. After filtering sequences for quality and number of reads, all single-nucleotide substitutions, small insertion and deletion mutations, and large genomic duplications and deletions were detected. There were zero false-positive calls of nonsense mutations, frameshift mutations, or genomic rearrangements for any gene in any of the test samples. This approach enables widespread genetic testing and personalized risk assessment for breast and ovarian cancer. PMID:20616022

Routine clinical heart examinations using SQUID magnetocardiography at University of Tsukuba Hospital

NASA Astrophysics Data System (ADS)

Inaba, T.; Nakazawa, Y.; Yoshida, K.; Kato, Y.; Hattori, A.; Kimura, T.; Hoshi, T.; Ishizu, T.; Seo, Y.; Sato, A.; Sekiguchi, Y.; Nogami, A.; Watanabe, S.; Horigome, H.; Kawakami, Y.; Aonuma, K.

2017-11-01

A 64-channel Nb-based DC-SQUID magnetocardiography (MCG) system was installed at the University of Tsukuba Hospital (UTH) in March 2007 after obtaining Japanese pharmaceutical approval and insurance reimbursement approval. In the period between 2008 and 2016, the total number of patients was 10 085. The heart diseases diagnosed in fetuses as well as adults are mainly atrial arrhythmia, abnormal repolarization, ventricular arrhythmia, and fetal arrhythmia. In most cases of insufficient diagnostic accuracy with electrocardiography, SQUID MCG precisely revealed these heart diseases as an abnormal electrical current distribution. Based on success in routine examinations, SQUID MCG is now an indispensable clinical instrument with diagnostic software tuned up during routine use at UTH.

Genome editing: the breakthrough technology for inherited retinal disease?

PubMed

Smith, Andrew J; Carter, Stephen P; Kennedy, Breandán N

2017-10-01

Genetic alterations resulting in a dysfunctional retinal pigment epithelium and/or degenerating photoreceptors cause impaired vision. These juxtaposed cells in the retina of the posterior eye are crucial for the visual cycle or phototransduction. Deficits in these biochemical processes perturb neural processing of images capturing the external environment. Notably, there is a distinct lack of clinically approved pharmacological, cell- or gene-based therapies for inherited retinal disease. Gene editing technologies are rapidly advancing as a realistic therapeutic option. Areas covered: Recent discovery of endonuclease-mediated gene editing technologies has culminated in a surge of investigations into their therapeutic potential. In this review, the authors discuss gene editing technologies and their applicability in treating inherited retinal diseases, the limitations of the technology and the research obstacles to overcome before editing a patient's genome becomes a viable treatment option. Expert opinion: The ability to strategically edit a patient's genome constitutes a treatment revolution. However, concerns remain over the safety and efficacy of either transplanting iPSC-derived retinal cells following ex vivo gene editing, or with direct gene editing in vivo. Ultimately, further refinements to improve efficacy and safety profiles are paramount for gene editing to emerge as a widely available treatment option.

Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy

PubMed Central

Sames, Lori; Moore, Allison; Arnold, Renee; Ekins, Sean

2014-01-01

Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can

Klotho protein lowered in senile patients with brady sinus arrhythmia.

PubMed

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

2015-01-01

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

[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.

Classification of cardiac arrhythmias using competitive networks.

PubMed

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

2010-01-01

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

Peripheral neuropathy in complex inherited diseases: an approach to diagnosis.

PubMed

Rossor, Alexander M; Carr, Aisling S; Devine, Helen; Chandrashekar, Hoskote; Pelayo-Negro, Ana Lara; Pareyson, Davide; Shy, Michael E; Scherer, Steven S; Reilly, Mary M

2017-10-01

Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy, for example, spasticity, the type of neuropathy and the other neurological and non-neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy, for example, cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Inhalation of diluted diesel engine emission impacts heart rate variability and arrhythmia occurrence in a rat model of chronic ischemic heart failure.

PubMed

Anselme, Frédéric; Loriot, Stéphane; Henry, Jean-Paul; Dionnet, Frédéric; Napoleoni, Jean-Gérard; Thuillez, Christian; Morin, Jean-Paul

2007-04-01

Both increase in cardiac arrhythmia incidence and decrease in heart rate variability (HRV) have been described following human and experimental animal exposures to air pollutants. However, the potential causal relationship between these two factors remains unclear. Incidence of ventricular arrhythmia and HRV were evaluated during and after a 3 h period of Diesel engine exhaust exposure in ten healthy and ten chronic ischemic heart failure (CHF, 3 months after coronary ligation) Wistar rats using implantable ECG telemetry. Air pollutants were delivered to specifically designed whole body individual exposure chambers at particulate matter concentrations similar to those measured inside cabins of cars inserted in congested urban traffic. Recordings were obtained from unrestrained and unsedated vigil rats. Immediate decrease in RMSSD was observed in both healthy (6.64 +/- 2.62 vs. 4.89 +/- 1.67 ms, P < 0.05) and CHF rats (8.01 +/- 0.89 vs. 6.6 +/- 1.37 ms, P < 0.05) following exposure. An immediate 200-500% increase in ventricular premature beats was observed in CHF rats only. Whereas HRV progressively returned to baseline values within 2.5 h after exposure start, the proarrhythmic effect persisted as late as 5 h after exposure termination in CHF rats. Persistence of ventricular proarrhythmic effects after HRV normalization suggests that HRV reduction is not the mechanism of cardiac arrhythmias in this model. Our methodological approach, closely reflecting the real clinical situations, appeared to be a unique tool to provide further insight into the pathophysiological mechanisms of traffic related airborne pollution health impact.

Magnetic navigation in adults with atrial isomerism (heterotaxy syndrome) and supraventricular arrhythmias.

PubMed

Suman-Horduna, Irina; Babu-Narayan, Sonya V; Ueda, Akiko; Mantziari, Lilian; Gujic, Marko; Marchese, Procolo; Dimopoulos, Konstantinos; Gatzoulis, Michael A; Rigby, Michael L; Ho, Siew Yen; Ernst, Sabine

2013-06-01

We analysed the type and mechanism of supraventricular arrhythmias encountered in a series of symptomatic adults with atrial isomerism undergoing catheter ablation procedures. The study population included consecutive adults with atrial isomerism who had previously undergone surgical repair or palliation of the associated anomalies. Patients underwent electrophysiological study for symptomatic arrhythmia in our institution between 2010 and 2012 using magnetic navigation in conjunction with CARTO RMT and three-dimensional (3D) image integration. Eight patients (five females) with a median age of 33 years [interquartile range (IQR) 24-39] were studied. Access to the cardiac chambers of interest was obtained retrogradely via the aorta using remotely navigated magnetic catheters in six patients. Radiofrequency ablation successfully targeted twin atrioventricular (AV) nodal reentrant tachycardia in two patients, atrial fibrillation (AF) in three, focal atrial tachycardia (AT) mainly originating in the left-sided atrium in four patients, and macro-reentrant AT dependent on a right-sided inferior isthmus in three patients. The median fluoroscopy time was 3.0 min (IQR 2-11). After a median follow-up of 10 months (IQR 6-21), five of the ablated patients are free from arrhythmia; two patients experienced episodes of self-terminated AF and AT, respectively, within one month post-ablation; the remaining patient had only non-sustained AT during the electrophysiological study and was managed medically. Various supraventricular tachycardia mechanisms are possible in adults with heterotaxy syndrome, all potentially amenable to radiofrequency ablation. The use of remote magnetic navigation along with 3D mapping facilitated the procedures and resulted in a short radiation time.

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... a visible or audible signal or alarm when atrial or ventricular arrhythmia, such as premature contraction or ventricular fibrillation, occurs. (b) Classification. Class II (special controls). The guidance...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... a visible or audible signal or alarm when atrial or ventricular arrhythmia, such as premature contraction or ventricular fibrillation, occurs. (b) Classification. Class II (special controls). The guidance...

Use/disuse paradigms are ubiquitous concepts in characterizing the process of inheritance.

PubMed

Veigl, Sophie Juliane

2017-12-02

In recent years, a Lamarckian theme has found its way back into academic discourse on evolution and inheritance. Especially the emerging field of transgenerational small RNAs has provided at least a proof of concept for the inheritance of acquired traits. Yet it remains unclear whether the Lamarckian concept of inheritance will in fact have its rennaisance or whether it will remain the rallying cry for the outlaws, heretics and enfants terribles of molecular biology. As unclear as the future of Lamarckian theory is its content and reference. Since the formulation of the Philosophie Zoologique, Lamarckian thought has been de- and reconfiguring in and out of the scientific literature and become an umbrella-term for all kinds of unconventional modes of inheritance. This essay will argue that heritable small RNAs might in fact provide a case of genuine Lamarckian inheritance. Moreover, it will be claimed that not only the very broad concept of "inheritance of acquired traits" applies, but also that Lamarck's mechanistic insight into a use/disuse relation might help to explain a specific mode of transgenerational inheritance.

Fractional populations in multiple gene inheritance.

PubMed

Chung, Myung-Hoon; Kim, Chul Koo; Nahm, Kyun

2003-01-22

With complete knowledge of the human genome sequence, one of the most interesting tasks remaining is to understand the functions of individual genes and how they communicate. Using the information about genes (locus, allele, mutation rate, fitness, etc.), we attempt to explain population demographic data. This population evolution study could complement and enhance biologists' understanding about genes. We present a general approach to study population genetics in complex situations. In the present approach, multiple allele inheritance, multiple loci inheritance, natural selection and mutations are allowed simultaneously in order to consider a more realistic situation. A simulation program is presented so that readers can readily carry out studies with their own parameters. It is shown that the multiplicity of the loci greatly affects the demographic results of fractional population ratios. Furthermore, the study indicates that some high infant mortality rates due to congenital anomalies can be attributed to multiple loci inheritance. The simulation program can be downloaded from http://won.hongik.ac.kr/~mhchung/index_files/yapop.htm. In order to run this program, one needs Visual Studio.NET platform, which can be downloaded from http://msdn.microsoft.com/netframework/downloads/default.asp.

Effect of heterogeneity and assumed mode of inheritance on lod scores.

PubMed

Durner, M; Greenberg, D A

1992-02-01

Heterogeneity is a major factor in many common, complex diseases and can confound linkage analysis. Using computer-simulated heterogeneous data we tested what effect unlinked families have on a linkage analysis when heterogeneity is not taken into account. We created 60 data sets of 40 nuclear families each with different proportions of linked and unlinked families and with different modes of inheritance. The ascertainment probability was 0.05, the disease had a penetrance of 0.6, and the recombination fraction for the linked families was zero. For the analysis we used a variety of assumed modes of inheritance and penetrances. Under these conditions we looked at the effect of the unlinked families on the lod score, the evaluation of the mode of inheritance, and the estimate of penetrance and of the recombination fraction in the linked families. 1. When the analysis was done under the correct mode of inheritance for the linked families, we found that the mode of inheritance of the unlinked families had minimal influence on the highest maximum lod score (MMLS) (i.e., we maximized the maximum lod score with respect to penetrance). Adding sporadic families decreased the MMLS less than adding recessive or dominant unlinked families. 2. The mixtures of dominant linked families with unlinked families always led to a higher MMLS when analyzed under the correct (dominant) mode of inheritance than when analyzed under the incorrect mode of inheritance. In the mixtures with recessive linked families, assuming the correct mode of inheritance generally led to a higher MMLS, but we observed broad variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine disruptor induction of epigenetic transgenerational inheritance of disease.

PubMed

Skinner, Michael K

2014-12-01

Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Endocrine Disruptor Induction of Epigenetic Transgenerational Inheritance of Disease

PubMed Central

Skinner, Michael K.

2014-01-01

Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease. PMID:25088466

Critical analysis of dual-chamber implantable cardioverter-defibrillator arrhythmia detection : results and technical considerations.

PubMed

Wilkoff, B L; Kühlkamp, V; Volosin, K; Ellenbogen, K; Waldecker, B; Kacet, S; Gillberg, J M; DeSouza, C M

2001-01-23

One of the perceived benefits of dual-chamber implantable cardioverter-defibrillators (ICDs) is the reduction in inappropriate therapy due to new detection algorithms. It was the purpose of the present investigation to propose methods to minimize bias during such comparisons and to report the arrhythmia detection clinical results of the PR Logic dual-chamber detection algorithm in the GEM DR ICD in the context of these methods. Between November 1997 and October 1998, 933 patients received the GEM DR ICD in this prospective multicenter study. A total of 4856 sustained arrhythmia episodes (n=311) with stored electrogram and marker channel were classified by the investigators; 3488 episodes (n=232) were ventricular tachycardia (VT)/ventricular fibrillation (VF), and 1368 episodes (n=149) were supraventricular tachycardia (SVT). The overall detection results were corrected for multiple episodes within a patient with the generalized estimating equations (GEE) method with an exchangeable correlation structure between episodes. The relative sensitivity for detection of sustained VT and/or VF was 100.0% (3488 of 3488, n=232; 95% CI 98.3% to 100%), the VT/VF positive predictivity was 88.4% uncorrected (3488 of 3945, n=278) and 78.1% corrected (95% CI 73.3% to 82.3%) with the GEE method, and the SVT positive predictivity was 100.0% (911 of 911, n=101; 95% CI 96% to 100%). A structured approach to analysis limits the bias inherent in the evaluation of tachycardia discrimination algorithms through the use of relative VT/VF sensitivity, VT/VF positive predictivity, and SVT positive predictivity along with corrections for multiple tachycardia episodes in a single patient.

Epicardial phrenic nerve displacement during catheter ablation of atrial and ventricular arrhythmias: procedural experience and outcomes.

PubMed

Kumar, Saurabh; Barbhaiya, Chirag R; Baldinger, Samuel H; Koplan, Bruce A; Maytin, Melanie; Epstein, Laurence M; John, Roy M; Michaud, Gregory F; Tedrow, Usha B; Stevenson, William G

2015-08-01

Arrhythmia origin in close proximity to the phrenic nerve (PN) can hinder successful catheter ablation. We describe our approach with epicardial PN displacement in such instances. PN displacement via percutaneous pericardial access was attempted in 13 patients (age 49±16 years, 9 females) with either atrial tachycardia (6 patients) or atrial fibrillation triggered from a superior vena cava focus (1 patient) adjacent to the right PN or epicardial ventricular tachycardia origin adjacent to the left PN (6 patients). An epicardially placed steerable sheath/4 mm-catheter combination (5 patients) or a vascular or an esophageal balloon (8 patients) was ultimately successful. Balloon placement was often difficult requiring manipulation via a steerable sheath. In 2 ventricular tachycardia cases, absence of PN capture was achieved only once the balloon was directly over the ablation catheter. In 3 atrial tachycardia patients, PN displacement was not possible with a balloon; however, a steerable sheath/catheter combination was ultimately successful. PN displacement allowed acute abolishment of all targeted arrhythmias. No PN injury occurred acutely or in follow up. Two patients developed acute complications (pleuro-pericardial fistula 1 and pericardial bleeding 1). Survival free of target arrhythmia was achieved in all atrial tachycardia patients; however, a nontargeted ventricular tachycardia recurred in 1 patient at a median of 13 months' follow up. Arrhythmias originating in close proximity to the PN can be targeted successfully with PN displacement with an epicardially placed steerable sheath/catheter combination, or balloon, but this strategy can be difficult to implement. Better tools for phrenic nerve protection are desirable. © 2015 American Heart Association, Inc.

Inherited Paediatric Motor Neuron Disorders: Beyond Spinal Muscular Atrophy

PubMed Central

Sampaio, Hugo; Mowat, David; Roscioli, Tony

2017-01-01

Paediatric motor neuron diseases encompass a group of neurodegenerative diseases characterised by the onset of muscle weakness and atrophy before the age of 18 years, attributable to motor neuron loss across various neuronal networks in the brain and spinal cord. While the genetic underpinnings are diverse, advances in next generation sequencing have transformed diagnostic paradigms. This has reinforced the clinical phenotyping and molecular genetic expertise required to navigate the complexities of such diagnoses. In turn, improved genetic technology and subsequent gene identification have enabled further insights into the mechanisms of motor neuron degeneration and how these diseases form part of a neurodegenerative disorder spectrum. Common pathophysiologies include abnormalities in axonal architecture and function, RNA processing, and protein quality control. This review incorporates an overview of the clinical manifestations, genetics, and pathophysiology of inherited paediatric motor neuron disorders beyond classic SMN1-related spinal muscular atrophy and describes recent advances in next generation sequencing and its clinical application. Specific disease-modifying treatment is becoming a clinical reality in some disorders of the motor neuron highlighting the importance of a timely and specific diagnosis. PMID:28634552

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.

Genetic instability in inherited and sporadic leukemias.

PubMed

Popp, Henning D; Bohlander, Stefan K

2010-12-01

Genetic instability due to increased DNA damage and altered DNA repair is of central significance in the initiation and progression of inherited and sporadic human leukemias. Although very rare, some inherited DNA repair insufficiency syndromes (e.g., Fanconi anemia, Bloom's syndrome) have added substantially to our understanding of crucial mechanisms of leukemogenesis in recent years. Conversely, sporadic leukemias account for the main proportion of leukemias and here DNA damaging reactive oxygen species (ROS) play a central role. Although the exact mechanisms of increased ROS production remain largely unknown and no single pathway has been detected thus far, some oncogenic proteins (e.g., the activated tyrosine kinases BCR-ABL1 and FLT3-ITD) seem to play a key role in driving genetic instability by increased ROS generation which influences the disease course (e.g., blast crisis in chronic myeloid leukemia or relapse in FLT3-ITD positive acute myeloid leukemia). Of course other mechanisms, which promote genetic instability in leukemia also exist. A newly emerging mechanism is the genome-wide alteration of epigenetic marks (e.g., hypomethylation of histone H3K79), which promotes chromosomal instability. Taken together genetic instability plays a critical role both in inherited and sporadic leukemias and emerges as a common theme in both inherited and sporadic leukemias. Beyond its theoretical impact, the analysis of genetic instability may lead the way to the development of innovative therapy strategies. © 2010 Wiley-Liss, Inc.

AANA Journal Course: update for nurse anesthetists. Arrhythmia management devices and electromagnetic interference.

PubMed

Mattingly, Emily

2005-04-01

The technological complexity of implantable arrhythmia management devices, specifically pacemakers and defibrillators, has increased dramatically since their introduction only a few decades ago. Patients with such devices are encountered much more frequently in hospitals and surgery centers, yet anesthesia provider knowledge of safe and proper management is often incomplete. Anesthesia textbooks and references may provide only short paragraphs on arrhythmia management devices that do not address important perioperative management strategies for this ever-growing patient population. It is no longer satisfactory to simply place a magnet over an implanted device during surgery and assume that this action protects the patient from harm due to electromagnetic interference from inappropriate device function. This AANA Journal course serves as a concise review of basic device function, the sources and effects of electromagnetic interference in the operative setting, and patient management recommendations from current literature.

Analysis of electrolyte abnormalities and the mechanisms leading to arrhythmias in heart failure. A literature review.

PubMed

Urso, C; Canino, B; Brucculeri, S; Firenze, A; Caimi, G

2016-01-01

About 50% of deaths from heart failure (HF) are sudden, presumably referable to arrhythmias. Electrolyte and acid-base abnormalities are a frequent and potentially dangerous complication in HF patients. Their incidence is almost always correlated with the severity of cardiac dysfunction; furthermore leading to arrhythmias, these imbalances are associated with a poor prognosis. The frequency of ventricular ectopic beats and sudden cardiac death correlate with both plasma and whole body levels of potassium, especially in alkalemia. The early recognition of these alterations and the knowledge of the pathophysiological mechanisms are useful for the management of these HF patients.

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.

Gene Editing: A View Through the Prism of Inherited Metabolic Disorders.

PubMed

Davison, James

2018-04-01

Novel technological developments mean that gene editing - making deliberately targeted alterations in specific genes - is now a clinical reality. The inherited metabolic disorders, a group of clinically significant, monogenic disorders, provide a useful paradigm to explore some of the many ethical issues that arise from this technological capability. Fundamental questions about the significance of the genome, and of manipulating it by selection or editing, are reviewed, and a particular focus on the legislative process that has permitted the development of mitochondrial donation techniques is considered. Ultimately, decisions about what we should do with gene editing must be determined by reference to other non-genomic texts that determine what it is to be human - rather than simply to undertake gene editing because it can be done.

Transgenerational epigenetic inheritance: how important is it?

PubMed Central

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

2014-01-01

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. PMID:23416892

Risk of malignant arrhythmias in initially symptomatic patients with Wolff-Parkinson-White syndrome: results of a prospective long-term electrophysiological follow-up study.

PubMed

Pappone, Carlo; Vicedomini, Gabriele; Manguso, Francesco; Baldi, Mario; Pappone, Alessia; Petretta, Andrea; Vitale, Raffaele; Saviano, Massimo; Ciaccio, Cristiano; Giannelli, Luigi; Calovic, Zarko; Tavazzi, Luigi; Santinelli, Vincenzo

2012-02-07

The available amount of detailed long-term data in patients with Wolff-Parkinson-White syndrome is limited, and no prospective electrophysiological studies looking at predictors of malignant arrhythmia are available. Among 8575 symptomatic Wolff-Parkinson-White patients with atrioventricular reentrant tachycardia referred for electrophysiological test, 369 (mean age, 23±12.5 years) declined catheter ablation and were followed up. The primary end point of the study was to evaluate over a 5-year follow-up the predictors and characteristics of patients who develop malignant arrhythmias. After a mean follow-up of 42.1±10 months, malignant arrhythmias developed in 29 patients (mean age, 13.9±5.6 years; 26 male), resulting in presyncope/syncope (25 patients), hemodynamic collapse (3 patients), or cardiac arrest caused by ventricular fibrillation (1 patient). Of the remaining 340 patients, 168 (mean age, 34.2±9.0 years) remained asymptomatic up to 5 years, and 172 (mean age, 13.6±5.1 years) had benign recurrence, including sustained atrioventricular reentrant tachycardia (132 patients) or atrial fibrillation (40 patients). Compared with the group with no malignant arrhythmias, the group with malignant arrhythmias showed shorter accessory-pathway effective refractory period (P<0.001) and more often exhibited multiple accessory pathways (P<0.001), and atrioventricular reentrant tachycardia triggering sustained pre-excited atrial fibrillation was more frequently inducible (P<0.001). Multivariable analysis demonstrated that short accessory-pathway effective refractory period (P<0.001) and atrioventricular reentrant tachycardia triggering sustained pre-excited atrial fibrillation (P<0.001) were independent predictors of malignant arrhythmias. Symptomatic patients with Wolff-Parkinson-White syndrome generally have a good outcome, and predictors of malignant arrhythmias are similar to those reported for asymptomatic patients with ventricular pre-excitation.

Brief Report: Emotion Regulation and Respiratory Sinus Arrhythmia in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Guy, Lisa; Souders, Margaret; Bradstreet, Lauren; DeLussey, Christine; Herrington, John D.

2014-01-01

Emotion regulation (ER) may be an important transdiagnostic factor for understanding mental and behavioral health given its association with several psychiatric disorders, including autism spectrum disorder (ASD). However, there is limited research on ER in ASD, particularly using biomarkers such as respiratory sinus arrhythmia (RSA). The aim of…

Do defects in ion channel glycosylation set the stage for lethal cardiac arrhythmias?

PubMed

Fozzard, Harry A; Kyle, John W

2002-04-30

Many ion channels are modified by the addition of carbohydrate residues. Fozzard and Kyle discuss evidence that sialic acid residues on glycosylated cardiac sodium and potassium channels may be important for preventing early after-depolarizations that can result in cardiac arrhythmias.

The IK1/Kir2.1 channel agonist zacopride prevents and cures acute ischemic arrhythmias in the rat

PubMed Central

Zhai, Xu-Wen; Zhang, Li; Guo, Yun-Fei; Yang, Ying; Wang, Dong-Ming; Zhang, Yan; Li, Pan; Niu, Yi-Fan; Feng, Qi-Long; Wu, Bo-Wei; Cao, Ji-Min; Liu, Qing-Hua

2017-01-01

Arrhythmogenesis in acute myocardial infarction (MI) is associated with depolarization of resting membraine potential (RMP) and decrease of inward rectifier potassium current (IK1) in cardiomyocytes. However, clinical anti-arrhythmic agents that primarily act on RMP by enhancing the IK1 channel are not currently available. We hypothesized that zacopride, a selective and moderate agonist of the IK1/Kir2.1 channels, prevents and cures acute ischemic arrhythmias. To test this viewpoint, adult Sprague-Dawley (SD) rats were subjected to MI by ligating the left main coronary artery. The antiarrhythmic effects of zacopride (i.v. infusion) were observed in the settings of pre-treatment (zacopride given 3 min prior to coronary occlusion), post-treatment (zacopride given 3 min after coronary occlusion) and therapeutic treatment (zacopride given 30 s after the onset of the first sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) post MI). In all the three treatment modes, zacopride (15 μg/kg) inhibited MI-induced ventricular tachyarrhythmias, as shown by significant decreases in the premature ventricular contraction (PVC) and the duration and incidence of VT or VF. In Langendorff perfused rat hearts, the antiarrhythmic effect of 1 μmol/L zacopride were reversed by 1 μmol/L BaCl2, a blocker of IK1 channel. Patch clamp results in freshly isolated rat ventricular myocytes indicated that zacopride activated the IK1 channel and thereby reversed hypoxia-induced RMP depolarization and action potential duration (APD) prolongation. In addition, zacopride (1 μmol/L) suppressed hypoxia- or isoproterenol- induced delayed afterdepolarizations (DADs). In Kir2.x transfected Chinese hamster ovary (CHO) cells, zacopride activated the Kir2.1 homomeric channel but not the Kir2.2 or Kir2.3 channels. These results support our hypothesis that moderately enhancing IK1/Kir2.1 currents as by zacopride rescues ischemia- and hypoxia- induced RMP depolarization, and thereby

Neocentromeres and epigenetically inherited features of centromeres

PubMed Central

Burrack, Laura S.; Berman, Judith

2012-01-01

Neocentromeres are ectopic sites where new functional kinetochores assemble and permit chromosome segregation. Neocentromeres usually form following genomic alterations that remove or disrupt centromere function. The ability to form neocentromeres is conserved in eukaryotes ranging from fungi to mammals. Neocentromeres that rescue chromosome fragments in cells with gross chromosomal rearrangements are found in several types of human cancers, and in patients with developmental disabilities. In this review, we discuss the importance of neocentromeres to human health and evaluate recently developed model systems to study neocentromere formation, maintenance, and function in chromosome segregation. Additionally, studies of neocentromeres provide insight into native centromeres; analysis of neocentromeres found in human clinical samples and induced in model organisms distinguishes features of centromeres that are dependent on centromere DNA from features that are epigenetically inherited together with the formation of a functional kinetochore. PMID:22723125

Inheritance of microsatellite loci in the polyploid lake sturgeon (Acipenser fulvescens)

USGS Publications Warehouse

Pyatskowit, J.D.; Krueger, C.C.; Kincaid, H.L.; May, B.

2001-01-01

Inheritance in the expression of amplicons for four microsatellite primer pairs was determined using 10 families created from gametes of wild lake sturgeon (Acipenser fulvescens). Loci Afu34 and Afu68 expressed a maximum of two even-intensity bands per individual and had progeny genotype ratios that fit disomic inheritance (P > 0.05). Some variation exhibited at Afu34 and Afu68 was attributable to a null allele. Genotype expression at both loci also indicated that one female parent had transmitted unreduced gametes. Primer Afu39 amplified products that exhibited four gene doses, where genotype counts fit expected ratios for disomic inheritance (P > 0.05) indicating amplification of products from two disomic loci that share alleles. Meiotic drive was evident at the Afu39 loci based on a test for random segregation (P < 0.05). Only the expression of Afu19 gave evidence of tetrasomic inheritance based on a single progeny potentially produced by a double reduction gamete. No evidence for proposed octoploid inheritance was observed.

Inheritance-mode specific pathogenicity prioritization (ISPP) for human protein coding genes.

PubMed

Hsu, Jacob Shujui; Kwan, Johnny S H; Pan, Zhicheng; Garcia-Barcelo, Maria-Mercè; Sham, Pak Chung; Li, Miaoxin

2016-10-15

Exome sequencing studies have facilitated the detection of causal genetic variants in yet-unsolved Mendelian diseases. However, the identification of disease causal genes among a list of candidates in an exome sequencing study is still not fully settled, and it is often difficult to prioritize candidate genes for follow-up studies. The inheritance mode provides crucial information for understanding Mendelian diseases, but none of the existing gene prioritization tools fully utilize this information. We examined the characteristics of Mendelian disease genes under different inheritance modes. The results suggest that Mendelian disease genes with autosomal dominant (AD) inheritance mode are more haploinsufficiency and de novo mutation sensitive, whereas those autosomal recessive (AR) genes have significantly more non-synonymous variants and regulatory transcript isoforms. In addition, the X-linked (XL) Mendelian disease genes have fewer non-synonymous and synonymous variants. As a result, we derived a new scoring system for prioritizing candidate genes for Mendelian diseases according to the inheritance mode. Our scoring system assigned to each annotated protein-coding gene (N = 18 859) three pathogenic scores according to the inheritance mode (AD, AR and XL). This inheritance mode-specific framework achieved higher accuracy (area under curve  = 0.84) in XL mode. The inheritance-mode specific pathogenicity prioritization (ISPP) outperformed other well-known methods including Haploinsufficiency, Recessive, Network centrality, Genic Intolerance, Gene Damage Index and Gene Constraint scores. This systematic study suggests that genes manifesting disease inheritance modes tend to have unique characteristics. ISPP is included in KGGSeq v1.0 (http://grass.cgs.hku.hk/limx/kggseq/), and source code is available from (https://github.com/jacobhsu35/ISPP.git). mxli@hku.hkSupplementary information: Supplementary data are available at Bioinformatics online. © The Author

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

PubMed

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

2016-03-01

The term inherited cardiovascular disease encompasses a group of cardiovascular diseases (cardiomyopathies, channelopathies, certain aortic diseases, and other syndromes) with a number of common characteristics: they have a genetic basis, a familial presentation, a heterogeneous clinical course, and, finally, can all be associated with sudden cardiac death. The present document summarizes some important concepts related to recent advances in sequencing techniques and understanding of the genetic bases of these diseases. We propose diagnostic algorithms and clinical practice recommendations and discuss controversial aspects of current clinical interest. We highlight the role of multidisciplinary referral units in the diagnosis and treatment of these conditions. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

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.

Arrhythmia Mechanism and Scaling Effect on the Spectral Properties of Electroanatomical Maps With Manifold Harmonics.

PubMed

Sanroman-Junquera, Margarita; Mora-Jimenez, Inmaculada; Garcia-Alberola, Arcadio; Caamano, Antonio J; Trenor, Beatriz; Rojo-Alvarez, Jose L

2018-04-01

Spatial and temporal processing of intracardiac electrograms provides relevant information to support the arrhythmia ablation during electrophysiological studies. Current cardiac navigation systems (CNS) and electrocardiographic imaging (ECGI) build detailed 3-D electroanatomical maps (EAM), which represent the spatial anatomical distribution of bioelectrical features, such as activation time or voltage. We present a principled methodology for spectral analysis of both EAM geometry and bioelectrical feature in CNS or ECGI, including their spectral representation, cutoff frequency, or spatial sampling rate (SSR). Existing manifold harmonic techniques for spectral mesh analysis are adapted to account for a fourth dimension, corresponding to the EAM bioelectrical feature. Appropriate scaling is required to address different magnitudes and units. With our approach, simulated and real EAM showed strong SSR dependence on both the arrhythmia mechanism and the cardiac anatomical shape. For instance, high frequencies increased significantly the SSR because of the "early-meets-late" in flutter EAM, compared with the sinus rhythm. Besides, higher frequency components were obtained for the left atrium (more complex anatomy) than for the right atrium in sinus rhythm. The proposed manifold harmonics methodology opens the field toward new signal processing tools for principled EAM spatiofeature analysis in CNS and ECGI, and to an improved knowledge on arrhythmia mechanisms.

Klotho protein lowered in senile patients with brady sinus arrhythmia

PubMed Central

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

2015-01-01

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

hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

PubMed

Nogawa, Hisashi; Kawai, Tomoyuki

2014-10-15

Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

"You're saying something by giving things to them:" communication and family inheritance.

PubMed

de Witt, Lorna; Campbell, Lori; Ploeg, Jenny; Kemp, Candace L; Rosenthal, Carolyn

2013-09-01

The study purpose was to contribute to a more complete understanding of the experience and meaning of family inheritance. The aim of this article is to describe and discuss the meaning of communication in inheritance experiences among Canadian families. A constructivist/interpretive methodological approach guided this research. Participants were recruited through purposive, convenience sampling from two cities and one town in southern and southwestern Ontario, Canada. Fifty face-to-face, semi-structured, audio-taped, in-depth interviews were conducted between June 2006 and April 2007. NVivo software was used to organize and analyze the data. A content analysis method guided data analysis. Participants interpreted the meaning of family structure, relationships, feelings, and past inheritance experiences to construct their family inheritance communication. Analysis of the findings revealed four themes regarding the role of communication in family inheritance including: (a) avoiding conflict and preserving biological ties , (b) resisting conversations about possessions , (c) achieving confidence with possession communication , and (d) lasting effects. Participants from non-blended and blended families experienced similar inheritance communication challenges related to past experience with their parents' wills and distribution of their own possessions. Participants with past positive inheritance experiences with parents adopted similar strategies when communicating their own inheritance wishes. Negative messages conveyed to participants by their parent's wills inspired participants to communicate in opposite ways in their own inheritance planning. The study findings are useful for gerontologists, lawyers, family counselors, and estate planners.

Interpreting phenotypic antibiotic tolerance and persister cells as evolution via epigenetic inheritance.

PubMed

Day, Troy

2016-04-01

Epigenetic inheritance is the transmission of nongenetic material such as gene expression levels, RNA and other biomolecules from parents to offspring. There is a growing realization that such forms of inheritance can play an important role in evolution. Bacteria represent a prime example of epigenetic inheritance because a large array of cellular components is transmitted to offspring, in addition to genetic material. Interestingly, there is an extensive and growing empirical literature showing that many bacteria can form 'persister' cells that are phenotypically resistant or tolerant to antibiotics, but most of these results are not interpreted within the context of epigenetic inheritance. Instead, persister cells are usually viewed as a genetically encoded bet-hedging strategy that has evolved in response to a fluctuating environment. Here I show, using a relatively simple model, that many of these empirical findings can be more simply understood as arising from a combination of epigenetic inheritance and cellular noise. I therefore suggest that phenotypic drug tolerance in bacteria might represent one of the best-studied examples of evolution under epigenetic inheritance. © 2016 John Wiley & Sons Ltd.

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

PubMed

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

2016-10-01

The experience of anger during a depressive episode has recently been identified as a poor prognostic indicator of illness course. Given the clinical implications of anger in major depressive disorder (MDD), understanding the mechanisms involved in anger reactivity and persistence is critical for improved intervention. Biological processes involved in emotion regulation during stress, such as respiratory sinus arrhythmia (RSA), may play a role in maintaining negative moods. Clinically depressed (MDD; n = 49) and nondepressed (non-MDD; n = 50) individuals were challenged with a stressful computer task shown to increase anger, while RSA (high frequency range 0.15-0.4 Hz) was collected. RSA predicted future anger, but was unrelated to current anger. That is, across participants, low baseline RSA predicted anger reactivity during the task, and in depressed individuals, those with low RSA during the task had a greater likelihood of anger persistence during a recovery period. These results suggest that low RSA may be a psychophysiological process involved in anger regulation in depression. Low RSA may contribute to sustained illness course by diminishing the repair of angry moods. © 2016 Society for Psychophysiological Research.

Widow cleansing and inheritance among the Luo in Kenya: the need for additional women-centred HIV prevention options

PubMed Central

Perry, Brian; Oluoch, Lennah; Agot, Kawango; Taylor, Jamilah; Onyango, Jacob; Ouma, Lilian; Otieno, Caroline; Wong, Christina; Corneli, Amy

2014-01-01

Introduction The customs of widow cleansing and widow inheritance are practiced in several communities throughout sub-Saharan Africa. In the Nyanza Province of Kenya, according to tradition, Luo widows are expected to engage in sexual intercourse with a “cleanser,” without the use of a condom, in order to remove the impurity ascribed to her after her husband's death. Luo couples, including widows, are also expected to engage in sex preceding specific agricultural activities, building homes, funerals, weddings, and other significant cultural and social events. Widows who are inherited for the purpose of fulfilling cultural obligation have a higher prevalence of HIV than those who remain un-inherited or are inherited for the purpose of companionship. Methods As part of a larger descriptive qualitative study to inform study procedures for FEM-PrEP, an HIV prevention pre-exposure prophylaxis clinical trial, we conducted 15 semi-structured interviews (SSIs) with widows, 15 SSIs with inheritors, and four focus group discussions with widows in the Bondo and Rarieda districts in Nyanza Province to explore the HIV risk context within widow cleansing and inheritance practices. Thematic qualitative analysis was used to analyze the data. Results The majority of widows reported in the demographic questionnaire being inherited, and most widows in the SSIs described participating in the cleansing ritual. We identified two main themes related to HIV prevention within the context of widow cleansing and inheritance: 1) widows must balance limiting their risk for HIV infection with meeting cultural expectations and ensuring that their livelihood needs are met, and 2) sexual abstinence undermines cultural expectations in widowhood while the use of condoms is deemed inappropriate in fulfilling culturally prescribed sexual rituals, and is often beyond the widow's ability to negotiate. Conclusions Women-controlled HIV prevention methods such as antiretroviral-based oral pre

Widow cleansing and inheritance among the Luo in Kenya: the need for additional women-centred HIV prevention options.

PubMed

Perry, Brian; Oluoch, Lennah; Agot, Kawango; Taylor, Jamilah; Onyango, Jacob; Ouma, Lilian; Otieno, Caroline; Wong, Christina; Corneli, Amy

2014-01-01

The customs of widow cleansing and widow inheritance are practiced in several communities throughout sub-Saharan Africa. In the Nyanza Province of Kenya, according to tradition, Luo widows are expected to engage in sexual intercourse with a "cleanser," without the use of a condom, in order to remove the impurity ascribed to her after her husband's death. Luo couples, including widows, are also expected to engage in sex preceding specific agricultural activities, building homes, funerals, weddings, and other significant cultural and social events. Widows who are inherited for the purpose of fulfilling cultural obligation have a higher prevalence of HIV than those who remain un-inherited or are inherited for the purpose of companionship. As part of a larger descriptive qualitative study to inform study procedures for FEM-PrEP, an HIV prevention pre-exposure prophylaxis clinical trial, we conducted 15 semi-structured interviews (SSIs) with widows, 15 SSIs with inheritors, and four focus group discussions with widows in the Bondo and Rarieda districts in Nyanza Province to explore the HIV risk context within widow cleansing and inheritance practices. Thematic qualitative analysis was used to analyze the data. The majority of widows reported in the demographic questionnaire being inherited, and most widows in the SSIs described participating in the cleansing ritual. We identified two main themes related to HIV prevention within the context of widow cleansing and inheritance: 1) widows must balance limiting their risk for HIV infection with meeting cultural expectations and ensuring that their livelihood needs are met, and 2) sexual abstinence undermines cultural expectations in widowhood while the use of condoms is deemed inappropriate in fulfilling culturally prescribed sexual rituals, and is often beyond the widow's ability to negotiate. Women-controlled HIV prevention methods such as antiretroviral-based oral pre-exposure prophylaxis, vaginal gels, and vaginal rings

Does Deep Bradycardia Increase the Risk of Arrhythmias and Syncope in Endurance Athletes?

PubMed

Matelot, D; Schnell, F; Khodor, N; Endjah, N; Kervio, G; Carrault, G; Thillaye du Boullay, N; Carre, F

2016-09-01

The aim of this study was to evaluate whether endurance athletes who exhibit deep bradycardia are more prone to arrhythmias and reflex syncope than their non-bradycardic peers. 46 healthy men (ages 19-35) were divided into 3 groups based on whether they were sedentary (SED,<2 h/week) or endurance trained (ET,>6 h/week), and non-bradycardic (NB, resting heart rate (HR)≥60 bpm) or bradycardic (B, resting HR<50 bpm). Resting HR was lower in ETB vs. ETNB and SED (43.8±3.1, 61.3±3.3, 66.1±5.9 bpm, respectively; p<0.001). Thus, 16 SED, 13 ETNB and 17 ETB underwent resting echocardiography, maximal exercise test, tilt test (TT) and 24 h-Holter ECG. Subjects were followed-up during 4.7±1.1 years for training, syncope and cardiac events. Our results showed that incidence of arrhythmias and hypotensive susceptibility did not differ between groups. During follow-up, no episode of syncope or near-syncope was reported. However, cardio-inhibitory syncope occurrence tended to be higher in ETB. Left ventricular end-diastolic diameter index was increased in ETB vs. ETNB and was correlated with resting HR (r=- 0.64; p<0.001). As a result, athletes with deep bradycardia do not present more arrhythmias and more hypotensive susceptibility than their non-bradycardic peers. Cardiac enlargement and autonomic alteration both seem to be involved in an athlete's bradycardia. © Georg Thieme Verlag KG Stuttgart · New York.

Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry.

PubMed

Han, Lianshu; Han, Feng; Ye, Jun; Qiu, Wenjuan; Zhang, Huiwen; Gao, Xiaolan; Wang, Yu; Ji, Wenjun; Gu, Xuefan

2015-03-01

Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants. © 2014 Wiley Periodicals, Inc.

Association between activities of SOD, MDA and Na+-K+-ATPase in peripheral blood of patients with acute myocardial infarction and the complication of varying degrees of arrhythmia.