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Life-threatening Arrhythmias (life-threatening + arrhythmias)
Selected AbstractsValidation of a tool to safely triage selected patients with chest pain to unmonitored bedsEMERGENCY MEDICINE AUSTRALASIA, Issue 4 2002Ronald V Sultana Abstract Objective: To externally validate a chest pain protocol that triages low risk patients with chest pain to an unmonitored bed. Methods: Retrospective study of all patients admitted from the emergency department of a tertiary referral public teaching hospital with an admission diagnosis of ,unstable angina' or suspected ischemic chest pain. Data was collected on adverse outcomes and analysed on the basis of intention-to-treat according to the chest pain protocol. Results: There were no life-threatening arrhythmias, cardiac arrests or deaths within the first 72 h of admission in the group assigned to an unmonitored bed by the chest pain protocol ([0/244]; 0.0%: 95% confidence interval 0.0,1.5%). Four patients had an uncomplicated myocardial infarction, two patients had recurrent ischemic chest pain and one patient developed acute pulmonary oedema ([7/244]; 2.9%: 95% confidence interval 1.2,5.8%). Conclusion: This retrospective study externally validated the chest pain protocol. Care in a monitored bed would not have altered outcomes for patients triaged to an unmonitored bed by the chest pain protocol. Compared to current guidelines, application of the chest pain protocol could increase the availability of monitored beds. [source] ,And the beat goes on' The cardiac conduction system: the wiring system of the heartEXPERIMENTAL PHYSIOLOGY, Issue 10 2009Mark R. Boyett The cardiac conduction system (CCS), consisting of the sino-atrial node, atrioventricular node and His,Purkinje system, is responsible for the initiation and co-ordination of the heart beat. In the last decade, our understanding of the CCS has been transformed. Immunohistochemistry, used in conjunction with anatomical techniques, has transformed our understanding of its anatomy; arguably, we now understand the position of the sino-atrial node (not the same as in medical textbooks), and our new understanding of the atrioventricular node anatomy means that we can compute its physiological and pathophysiological behaviour. Ion channel expression in the CCS has been shown to be fundamentally different from that in the working myocardium. Dysfunction of the CCS has previously been attributed to fibrosis, but it is now clear that remodelling of ion channels plays an important role in dysfunction during ageing, heart failure and atrial fibrillation. Differences in ion channel expression may even be responsible for the bradycardia in the athlete and differences in heart rate among different species (such as humans and mice). Recent work has highlighted less well-known components of the CCS, including tricuspid, mitral and aortic rings and even a third (retro-aortic) node. These additional tissues do not participate in the initiation and co-ordination of the heart beat and instead they are likely to be the source of various life-threatening arrhythmias. During embryological development, all parts of the CCS have been shown to develop from the primary myocardium of the linear heart tube, partly under the influence of the transcription factor, Tbx3. [source] Evidence for a Single Nucleotide Polymorphism in the KCNQ1 Potassium Channel that Underlies Susceptibility to Life-Threatening ArrhythmiasJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2001TOMOYUKI KUBOTA M.D. Ion Channel Polymorphism and Cardiac Arrhythmia. Introduction: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion channels. It was suggested recently that common polymorphisms of LQTS-associated genes might modify arrhythmia susceptibility in potential gene carriers. Methods and Results: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon-specific polymerase chain reaction single-strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in , 11% of the Japanese population. This 1727G> A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage-clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S- KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild-type (WT) channels. Coexpression of WT- KCNQ1 and G643S- KCNQ1 with KCNE1 resulted in , 30% reduction in the slow delayed rectifier K+ current IKs without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant-negative effect on the heteromultimeric channel complexes. Conclusion: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild IKs dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life-threatening arrhythmias in a specific population. [source] The evolutionarily conserved residue A653 plays a key role in HERG channel closingTHE JOURNAL OF PHYSIOLOGY, Issue 11 2009Svetlana Z. Stepanovic Human ether-a-go-go- related gene (HERG) encodes the rapid, outwardly rectifying K+ current IKr that is critical for repolarization of the cardiac action potential. Congenital HERG mutations or unintended pharmaceutical block of IKr can lead to life-threatening arrhythmias. Here, we assess the functional role of the alanine at position 653 (HERG-A653) that is highly conserved among evolutionarily divergent K+ channels. HERG-A653 is close to the ,glycine hinge' implicated in K+ channel opening, and is flanked by tyrosine 652 and phenylalanine 656, which contribute to the drug binding site. We substituted an array of seven (I, C, S, G, Y, V and T) amino acids at position 653 and expressed individual variants in heterologous systems to assess changes in gating and drug binding. Substitution of A653 resulted in negative shifts of the V1/2 of activation ranging from ,23.6 (A653S) to ,62.5 (A653V) compared to ,11.2 mV for wild-type (WT). Deactivation was also drastically altered: channels with A653I/C substitutions exhibited delayed deactivation in response to test potentials above the activation threshold, while A653S/G/Y/V/T failed to deactivate under those conditions and required hyperpolarization and prolonged holding potentials at ,130 mV. While A653S/G/T/Y variants showed decreased sensitivity to the IKr inhibitor dofetilide, these changes could not be correlated with defects in channel closure. Homology modelling suggests that in the closed state, A653 forms tight contacts with several residues from the neighbouring subunit in the tetramer, playing a key role in S6 helix packing at the narrowest part of the vestibule. Our study suggests that A653 plays an important functional role in the outwardly rectifying gating behaviour of HERG, supporting channel closure at membrane potentials negative to the channel activation threshold. [source] Usefulness of T-Wave Alternans in Sudden Death Risk Stratification and Guiding Medical TherapyANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2010Ph.D., Tuomo Nieminen M.D. Visible T-wave alternans (TWA), a beat-to-beat alternation in the morphology and amplitude of the ST segment or T wave, has been observed for over a century to occur in association with life-threatening arrhythmias in patients with acute coronary syndrome, heart failure, and cardiac channelopathies. This compelling linkage prompted development of quantitative techniques leading to FDA-cleared commercial methodologies for measuring nonvisible levels of TWA in the frequency and time domains. The first aim of this review is to summarize evidence from more than a hundred studies enrolling a total of >12,000 patients that support the predictivity of TWA for cardiovascular mortality and sudden cardiac death. The second focus is on the usefulness of TWA in guiding therapy. Until recently, TWA has been used primarily in decision making for cardioverter-defibrillator implantation. Its potential utility in guiding pharmacologic therapy has been underappreciated. We review clinical literature supporting the usefulness of TWA as an index of antiarrhythmic effects and proarrhythmia for different drug classes. Beta-adrenergic and sodium channel-blocking agents are the most widely studied drugs in clinical TWA investigations, with both reducing TWA magnitude; the exception is patients in whom sodium channel blockade discloses the Brugada syndrome and provokes macroscopic TWA. An intriguing possibility is that TWA may help to detect beneficial effects of nonantiarrhythmic agents such as the angiotensin II receptor blocker valsartan, which indirectly protects from arrhythmia through improving myocardial remodeling. We conclude that quantitative analysis of TWA has considerable potential to guide pharmacologic intervention and thereby serve as a therapeutic target. Ann Noninvasive Electrocardiol 2010;15(3):276,288 [source] Beat-to-Beat QT Interval Variability Is Primarily Affected by the Autonomic Nervous SystemANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2008Ph.D., Takanao Mine M.D. Background: Beat-to-beat QT interval variability is associated with life-threatening arrhythmias and sudden death, however, its precious mechanism and the autonomic modulation on it remains unclear. The purpose of this study was to determine the effect of drugs that modulate the autonomic nervous system on beat-to-beat QT interval. Method: RR and QT intervals were determined for 512 consecutive beats during fixed atrial pacing with and without propranolol and automatic blockade (propranolol plus atropine) in 11 patients without structural heart disease. Studied parameters included: RR, QTpeak (QRS onset to the peak of T wave), QTend (QRS onset to the end of T wave) interval, standard deviation (SD) of the RR, QTpeak, and QTend (RR-SD, QTpeak-SD, and QTend-SD), coefficients of variation (RR- CV, QTpeak-CV, and QTend-CV) from time domain analysis, total power (TP; RR-TP, QTpeak-TP, and QTend-TP), and power spectral density of the low-frequency band (LF; RR-LF, QTpeak-LF, and QTend-LF) and the high-frequency band (HF; RR-HF, QTpeak-HF and QTend-HF). Results: Administration of propranolol and infusion of atropine resulted in the reduction of SD, CV, TP, and HF of the QTend interval when compared to controlled atrial pacing (3.7 ± 0.6 and 3.5 ± 0.5 vs 4.8 ± 1.4 ms, 0.9 ± 0.1 and 0.9 ± 0.1 vs 1.2 ± 0.3%, 7.0 ± 2.2 and 7.0 ± 2.2 vs 13.4 ± 8.1 ms2, 4.2 ± 1.4 and 4.2 ± 1.2 vs 8.4 ± 4.9 ms2, respectively). Administration of propranolol and atropine did not affect RR interval or QTpeak interval indices during controlled atrial pacing. Conclusions: Beat-to-beat QT interval variability is affected by drugs that modulate the autonomic nervous system. [source] Adrenergic Nervous System Influences on the Induction of Ventricular TachycardiaANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2002Oscar A. Pellizzón M.D. Background: Sudden cardiac death is a major cause of mortality in western countries and the ventricular tachyarrhythmias are mainly involved in this regard. The adrenergic autonomic nervous system has influences in provoking life-threatening arrhythmias, and the prevention of such arrhythmias with beta-blockers supports this viewpoint. To evaluate the effect of the adrenergic nervous system and some catecholamine-releasing stimuli on the induction of ventricular tachycardia, we decided to explore the occurrence of ventricular tachycardia in patients subjected to three consecutive tests, exercise testing, isoproterenol infusion, and mental stress. Methods: Nineteen subjects who experienced exercise test-induced ventricular tachycardia were subjected to an isoproterenol infusion and mental stress. All but one patient had cardiac disease, with 70% due to Chagas'disease. Seventeen of the 19 study subjects had normal ventricular function. Results: Exercise test-induced ventricular tachycardia was nonsustained in 17 patients and sustained in 2 cases. Isoproterenol infusion induced nonsustained ventricular tachycardia in 9 of 19 patients. Mental stress, on its own, was able to induce nonsustained ventricular tachycardia in 2 of 19 patients. Conclusions: Among patients preselected for exercise-induced ventricular tachycardia, almost half could be induced into ventricular tachycardia by isoproterenol infusion. Mental stress was a less powerful inducer of ventricular arrhythmias in this study group. A.N.E. 2002;7(4):281,288 [source] Toward a Consensus Model of the hERG Potassium ChannelCHEMMEDCHEM, Issue 3 2010Anna Stary Dr. Abstract Malfunction of hERG potassium channels, due to inherited mutations or inhibition by drugs, can cause long QT syndrome, which can lead to life-threatening arrhythmias. A three-dimensional structure of hERG is a prerequisite to understand the molecular basis of hERG malfunction. To achieve a consensus model, we carried out an extensive analysis of hERG models based on various alignments of helix,S5. We analyzed seven models using a combination of conventional geometry/packing/normality validation methods as well as molecular dynamics simulations and molecular docking. A synthetic test set with the X-ray crystal structure of Kv1.2 with artificially shifted S5 sequences modeled into the structure served as a reference case. We docked the known hERG inhibitors (+)-cisapride, (S)-terfenadine, and MK-499 into the hERG models and simulation snapshots. None of the single analyses unambiguously identified a preferred model, but the combination of all three revealed that there is only one model that fulfils all quality criteria. This model is confirmed by a recent mutation scanning experiment (P. Ju, G. Pages, R.,P. Riek, P.,C. Chen, A.,M. Torres, P.,S. Bansal, S. Kuyucak, P.,W. Kuchel, J.,I. Vandenberg, J. Biol. Chem. 2009, 284, 1000,1008).1We expect the modeled structure to be useful as a basis both for computational studies of channel function and kinetics as well as the design of experiments. [source] | |||||||||||||