[Long and short QT syndromes : Emergency treatment and secondary prophylaxis]. / Long- und Short-QT-Syndrome : Notfalltherapie und Sekundärprophylaxe.

Long QT syndrome (LQTS) is a rare inherited or acquired channelopathy associated with a relevant mortality if left untreated. Therapy can reduce the sudden cardiac death (SCD) rate significantly. Of 17 subtypes, LQTS1-3 are the most common. Clinical presentation ranges from asymptomatic patients to torsade de pointes (TdP) and SCD. Emergency therapy includes defibrillation, administration of magnesium, betablockers and temporary pacing and sedation. Secondary prevention is based on betablocker therapy and implantation of an implantable cardioverter-defibrillator (ICD), if appropriate. Short QT syndrome (SQTS) is a rare channelopathy that manifests as SCD in 34%. So far 250 cases with mutations in 8 genes have been reported. ICDs are the only reliable protection against SCD. Drug therapy is based on hydroquinidine. Further therapeutic options exist for certain subtypes of both diseases. Patients should be referred to specialized centers.

Genotype-phenotype dilemma in a case of sudden cardiac death with the E1053K mutation and a deletion in the SCN5A gene.

Mutations in the cardiac sodium channel gene SCN5A may result in various arrhythmia syndromes such as long QT syndrome type 3 (LQTS), Brugada syndrome (BrS), sick sinus syndrome (SSS), cardiac conduction diseases (CCD) and possibly dilated cardiomyopathy (DCM). In most of these inherited cardiac arrhythmia syndromes the phenotypical expression may range from asymptomatic phenotypes to sudden cardiac death (SCD). A 16-year-old female died during sleep. Autopsy did not reveal any explanation for her death and a genetic analysis was performed. A variant in the SCN5A gene (E1053K) that was previously described as disease causing was detected. Family members are carriers of the same E1053K variant, some even in a homozygous state, but surprisingly did not exhibit any pathological cardiac phenotype. Due to the lack of genotype-phenotype correlation further genetic studies were performed. A novel deletion in the promoter region of SCN5A was identified in the sudden death victim but was absent in other family members. These findings demonstrate the difficulties in interpreting the results of a family-based genetic screening and underline the phenotypic variability of SCN5A mutations.

Terahertz phase contrast imaging of sorption kinetics in porous coordination polymer nanocrystals using differential optical resonator.

The enhancement of light-matter coupling when light is confined to wavelength scale volumes is useful both for studying small sample volumes and increasing the overall sensing ability. At these length scales, nonradiative interactions are of key interest to which near-field optical techniques may reveal new phenomena facilitating next-generation material functionalities and applications. Efforts to develop novel chemical or biological sensors using metamaterials have yielded innovative ideas in the optical and terahertz frequency range whereby the spatially integrated response over a resonator structure is monitored via the re-radiated or leaked light. But although terahertz waves generally exhibit distinctive response in chemical molecules or biological tissue, there is little absorption for subwavelength size sample and therefore poor image contrast. Here, we introduce a method that spatially resolves the differential near-field phase response of the entire resonator as a spectral fingerprint. By simultaneously probing two metallic ring resonators, where one loaded with the sample of interest, the differential phase response is able to resolve the presence of guest molecules (e.g. methanol) as they are adsorbed or released within the pores of a prototypical porous coordination polymer.

[Short QT syndrome]. / Short-QT-Syndrom.

Short QT syndrome was first described in 2000. It is a sporadic or familial ion channel disease that is associated with abbreviation of the QT interval permanently or transiently. The time of first manifestation of symptoms such as atrial fibrillation or syncope or even sudden death is between the 2nd and 4th decade. Sudden death has also been described for newborns and adolescents. Therapy depends on the severity of the symptoms. The therapy of choice for secondary prevention of sudden death is the implantable cardioverter-defibrillator (ICD). Quinidine has been shown to be effective in preventing arrhythmias in a number of patients. It is mostly used as an adjunct to the ICD but has also been used with considerable success in children and individuals who refused ICD implantation.

Insights into the location of type I ECG in patients with Brugada syndrome: correlation of ECG and cardiovascular magnetic resonance imaging.

BACKGROUND: Brugada syndrome is characterized by ST-segment abnormalities in V1-V3. Electrocardiogram (ECG) leads placed in the 3rd and 2nd intercostal spaces (ICSs) increased the sensitivity for the detection of a type I ECG pattern. The anatomic explanation for this finding is pending. OBJECTIVE: The purpose of the study was to correlate the location of the Brugada type I ECG with the anatomic location of the right ventricular outflow tract (RVOT). METHODS: Twenty patients with positive ajmaline challenge and 10 patients with spontaneous Brugada type I ECG performed by using 12 right precordial leads underwent cardiovascular magnetic resonance imaging (CMRI). The craniocaudal and lateral extent of the RVOT and maximal RVOT area were determined. Type I ECG pattern and maximal ST-segment elevation were correlated to extent and maximal RVOT area, respectively. RESULTS: In all patients, Brugada type I pattern was found in the 3rd ICS in sternal and left-parasternal positions. RVOT extent determined by using CMRI included the 3rd ICS in all patients. Maximal RVOT area was found in 3 patients in the 2nd ICS, in 5 patients in the 4th ICS, and in 22 patients in the 3rd ICS. CMRI predicted type I pattern with a sensitivity of 97.2%, specificity of 91.7%, positive predictive value of 88.6%, and negative predictive value of 98.0%. Maximal RVOT area coincided with maximal ST-segment elevation in 29 of 30 patients. CONCLUSION: RVOT localization determined by using CMRI correlates highly with the type I Brugada pattern. Lead positioning according to RVOT location improves the diagnosis of Brugada syndrome.

[Significance of diagnostic methods in the work-up of syncope]. / Stellenwert diagnostischer Methoden in der Synkopenabklärung.

After the initial evaluation including detailed history, physical examination, electrocardiogram, and orthostatic blood pressure measurements, risk stratification should follow, if the cause of syncope is still unclear in order to define the acuteness and extensiveness of the further diagnostic evaluation. The documentation of arrhythmia during syncope is the gold standard for diagnosis of arrhythmic syncope. The implantable loop recorder should be integrated early in the diagnostic work-up. In patients >40 years with otherwise unexplained syncope, carotid sinus massage is recommended. In suspected reflex-mediated syncope, the tilt test is able to confirm the diagnosis and gives information about the underlying pathomechanisms, while electrophysiological studies have still a proven indication in patients with previous myocardial infarction and preserved left ventricular function. The adenosine triphophate test has no clinical relevance in the diagnostics of syncope. Echocardiography plays an important role in the risk stratification by diagnosing structural cardiac disease. In patients experiencing syncope associated with exertion, exercise stress testing is indicated. Finally, a coronary angiogram should be performed, if ischemia triggered syncope is suspected. A routinely performed neurological evaluation is not recommended.

Arrhythmogenic hereditary syndromes: Brugada Syndrome, long QT syndrome, short QT syndrome and CPVT.

In approximately 10-20% of all sudden deaths no structural cardiac abnormalities can be identified. Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome and catecholaminergic polymorphic ventricular tachyarrhythmias. Each of these cardiac channelopathies is charaterized by unique genetic and clinical features. The resting ECG and the ECG under exercise are pivotal for the diagnosis of ion channel diseases. Molecular genetic screening can reveal underlying mutations in a variable degree among the cardiac ion channel diseases in up to 70% (LQTS) and may identify individuals with incomplete penetration of the disease. In patients with primary electrical diseases specific clinical triggers for arrhythmic events such as syncope or sudden cardiac death have been identified including exercise, strenuous activity, auditory stimuli or increased vagal tone. The significance of programmed ventricular stimulation is at present unclear concerning risk stratification in patients with Brugada syndrome and short QT syndrome and of no significance in long QT syndrome and catecholaminergic polymorphic ventricular tachycardias. The success of medical therapy remains modest for prevention of sudden cardiac death and may necessitate the insertion of an implantable cardioverter. However, side effects with inappropriate therapies in this patient group with often young and active individuals have to be encountered. More insights into the arrhythmogenesis is critical for future development of effective medical treatment strategies.

Evaluation and management of syncope.

Syncope is a common symptom and accounts for approximately 1% of all emergency visits. There are four main causes of syncope: reflex, neurally mediated syncope, orthostatic hypotension and cardiac syncope. The prognosis of patients with reflex syncopes is good, whereas patients with cardiac syncope are at increased risk for sudden cardiac death. The first diagnosic step after transient loss of consciousness the diagnosis syncope has to be established. It has to be differentiated from other forms of loss of consciousness according to current definition. Careful evaluation of the patient with syncope is mandatory. If the underlying cause of syncope can be diagnosed during initial evaluation, the patient should be treated accordingly. If the cause of syncope remains unclear, the patient has to be stratified with respect to the risk of a cardiovascular event and sudden cardiac death and further evaluation initiated. This review gives a comprehensive summary of definition, work-up and treatment of syncope based on the current guidelines for the evaluation of syncope.

Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry.

BACKGROUND: Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. METHODS AND RESULTS: Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. CONCLUSIONS: In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.

[Magnetic navigation in invasive electrophysiological diagnostic and therapy]. / Magnetische Navigation in der elektrophysiologischen Diagnostik und Therapie.

Electrophysiological stimulation and ablation is currently performed with manually deflectable catheters of different lengths and curves. Disadvantages of conventional therapy are catheter stiffness, limited local stability, risk of dislocation or perforation, and reduced tissue contact in regions with difficult access. Fluoroscopy to control catheter movement and position may require substantial radiation times. Magnetic navigation was first applied for right heart catherization in congenital heart disease in 1991; the first electrophysiological application took place in 2003. Today, an ablation electrode with small magnets is aligned in the patient's heart by two external magnets positioned at both sides of the thorax. Antegrade and retrograde movement of the distal catheter tip are performed via an external device on the patient's thigh. Three-dimensional MRI scans acquired before intervention can be merged with electroanatomical reconstruction, leading to further reductions of radiation burden. During treatment of supraventricular tachyarrhythmias high local precision of magnetically guided catheters, good local stability, and a substantially reduced radiation time have been reported. First applications in ventricular tachyarrhythmias and complex congenital cardiac defects indicate a comparable effect. Limitations of this therapy are the application in left atrial procedures (open irrigated ablation catheters not yet available), difficult transaortic retrograde approach (high lead flexibility), and the considerable costs. Magnet-assisted navigation is feasible during percutaneous coronary interventions of tortuous coronary arteries and in positioning guidewires in coronary sinus side branches for resynchronisation therapy. Future applications will be complex left atrial procedures, magnetically guided cardiac stem cell therapy, local drug application, and extracardiac vessel therapy.

[Primary electrical heart disease in adulthood--electrophysiological findings and therapy]. / Primär elektrische Herzerkrankungen im Erwachsenenalter--Elektrophysiologische Befunde und Therapie.

Sudden cardiac death accounts for 100,000 victims in Germany per year. Predominantly, patients with structural heart disease such as coronary artery disease or dilated cardiomyopathy are affected. However, approximately 5-10% of sudden deaths hit patients without structural disease of the heart. The proportion of young patients (< 40 years of age) in this group is even higher (10-20%). In younger patients significantly more diseases like hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia and primary electrical diseases of the heart could be observed such as long QT syndrome, short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. The primary electrical diseases are different concerning their electrocardiographical pattern, clinical triggers of arrhythmias, results of invasive diagnostics and therapy. Meanwhile, molecular genetic screening can reveal specific mutations of ion channels and can identify consecutive functional defects. The significance of programmed ventricular stimulation is at present unclear concerning risk stratification in patients with Brugada syndrome and short QT syndrome and of no significance in long QT syndrome and catecholaminergic polymorphic ventricular tachycardias. The implantable cardioverter defibrillator is the therapy of choice in most symptomatic patients. With increasing knowledge as a result of sophisticated molecular genetic screening, identification of underlying ion channel defects and new details of the mechanisms of arrhythmogenesis, a potential genotype-guided therapy will gain more importance in the future.

The relationship between restrictive and repetitive behaviors in individuals with autism and obsessive compulsive symptoms in parents.

This study investigated the relationship between repetitive behaviors in individuals with autism and obsessive-compulsive behaviors in parents. We hypothesized that repetitive behaviors in probands with autism would be associated with increased obsessive-compulsive behaviors in parents in sporadic families (1 known case of autism per family and no known history of autism). Parents with clinically significant Y-BOCS scores were more likely to have a family history of obsessive-compulsive disorder. The empirically derived Autism Diagnostic Interview-R (ADI-R) factor, Insistence on Sameness, was positively correlated with obsessive-compulsive behaviors in parents. Further, when probands were grouped on the basis of parental Y-BOCS scores (clinically significant versus non-clinically significant), probands whose parents had clinically significant Y-BOCS scores had higher ADI-R Insistence on Sameness factor scores. The findings of the current study of sporadic families extend previous work that has shown an association between restrictive/repetitive behaviors in probands with autism and obsessive-compulsive features in parents.

Incidence and electrophysiological characteristics of spontaneous ventricular tachyarrhythmias in high risk coronary patients and prophylactic implantation of a defibrillator.

OBJECTIVES: To assess the incidence and electrophysiological characteristics of spontaneous ventricular tachyarrhythmias after implantable cardioverter-defibrillator (ICD) implantation for primary prevention. DESIGN: Prospective observational study. PATIENTS: 41 consecutive patients, who fulfilled MADIT (multicenter automatic defibrillator implantation trial) I criteria, except for suppressibility by procainamide, and who received a prophylactic ICD. INTERVENTIONS: Subpectoral implantation of an ICD. MAIN OUTCOME MEASURES: Incidence of ventricular tachyarrhythmias and their electrophysiological characteristics with respect to timing of the arrhythmia, tachyarrhythmia cycle length, mode of termination, and clinical relevance. RESULTS: During a mean (SD) follow up of 30 (21) months 18 of 41 (43.9%) patients experienced 142 appropriate ICD treatments. The mean (SD) time to first event was 9.6 (15.1) months. One patient had ventricular fibrillation (VF), 12 patients ventricular tachycardia (VT), and five both VT and VF. The mean (SD) cycle length of monomorphic VT was 306 (42) ms. Of 142 episodes, 117 (82.3%) were terminated by antitachycardia pacing and another 25 (17.6%) by ICD discharges. Cumulative survival of hypothetical death, defined as treated VT with a cycle length < 260 ms or VF, was 83.2% after one year and 78.4% after two years. CONCLUSIONS: Patients with a left ventricular ejection fraction < 35%, a history of myocardial infarction, non-sustained VT, and inducible VT/VF are at high risk of VT/VF early after implantation. Therefore, implantation of a tiered treatment defibrillator seems to be justified.

The patient's informed consent for pacemakers and ICD implantation: how to write and how to explain it.

Written informed consent for pacemaker and ICD patients should be easy to understand and provided in written form in the patient's language. Comprehensiveness is required. It is essential to address driving and running machines, complication rates, benefits in appropriate hierarchical order and future necessary interventions. Eventually potential risks, e.g., flying, sports, sexual activity should be mentioned. It is important to explain pacemaker systems and ICD devices in details including cardiac resynchronization therapy (CRT) for heart failure. One of the main aspects concerns protection of human subjects participating in clinical studies. Informed consent necessitates a statement that the study involves research. This statement should include explanation of the purposes of the study, expected duration, description of the procedures, identification of experimental procedures, description of foreseeable risks or discomforts, and disclosure of alternative procedures. Further information should be given on psychological concerns, sexual activity, driving and quality of life in pacemaker and ICD patients.

Fine mapping of autistic disorder to chromosome 15q11-q13 by use of phenotypic subtypes.

Autistic disorder (AutD) is a complex genetic disease. Available evidence suggests that several genes contribute to the underlying genetic risk for the development of AutD. However, both etiologic heterogeneity and genetic heterogeneity confound the discovery of AutD-susceptibility genes. Chromosome 15q11-q13 has been identified as a strong candidate region on the basis of both the frequent occurrence of chromosomal abnormalities in that region and numerous suggestive linkage and association findings. Ordered-subset analysis (OSA) is a novel statistical method to identify a homogeneous subset of families that contribute to overall linkage at a given chromosomal location and thus to potentially help in the fine mapping and localization of the susceptibility gene within a chromosomal area. For the present analysis, a factor that represents insistence on sameness (IS)--derived from a principal-component factor analysis using data on 221 patients with AutD from the repetitive behaviors/stereotyped patterns domain in the Autism Diagnostic Interview-Revised--was used as a covariate in OSA. Analysis of families sharing high scores on the IS factor increased linkage evidence for the 15q11-q13 region, at the GABRB3 locus, from a LOD score of 1.45 to a LOD score of 4.71. These results narrow our region of interest on chromosome 15 to an area surrounding the gamma-aminobutyric acid-receptor subunit genes, in AutD, and support the hypothesis that the analysis of phenotypic homogeneous subtypes may be a powerful tool for the mapping of disease-susceptibility genes in complex traits.

Potential device interaction of a dual chamber implantable cardioverter defibrillator in a patient with continuous spinal cord stimulation.

Spinal cord or thalamic deep brain stimulation with a pacemaker is becoming more important in the treatment of drug refractory pain due to peripheral vascular disease, angina pectoris and intractable tremor in patients with neurologic disorders such as Parkinson's disease. An additional indication for a cardiac pacemaker or implantable cardioverter defibrillator raises concerns about possible interactions between the implanted electrical devices. We report on a patient with existing spinal cord stimulation who survived sudden cardiac death and received a dual chamber cardioverter defibrillator capable of delivering tiered therapies in both the atrium and ventricle.