826 research outputs found
Saving lives and reducing inappropriate device therapy: The MADIT family of implantable cardioverter-defibrillator and cardiac resynchronization therapy trials
QTc Prolongation and Sudden Cardiac Death The Association Is in the DetailââEditorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Long QT Syndrome
The hereditary long QT syndrome (LQTS) is a genetic channelopathy with variable penetrance that is associated with increased propensity to syncope, polymorphous ventricular tachycardia (torsades de pointes), and sudden arrhythmic death. This inherited cardiac disorder constitutes an important cause of malignant ventricular arrhythmias and sudden cardiac death in young individuals with normal cardiac morphology. Risk assessment in affected LQTS patients relies upon a constellation of electrocardiographic, clinical, and genetic factors. Administration of beta-blockers is the mainstay therapy in affected patients, and primary prevention with an implantable cardioverter defibrillator or left cervicothoracic sympathetic denervation are therapeutic options in patients who remain symptomatic despite beta-blocker therapy. Accumulating data from the International LQTS Registry have recently facilitated a comprehensive analysis of risk factors for aborted cardiac arrest or sudden cardiac death in pre-specified age groups, including the childhood, adolescence, adulthood, and post-40 periods. These analyses have consistently indicated that the phenotypic expression of LQTS is time dependent and age specific, warranting continuous risk assessment in affected patients. Furthermore, the biophysical function, type, and location of the ion-channel mutation are currently emerging as important determinants of outcome in genotyped patients. These new data may be used to improve risk stratification and for the development of gene-specific therapies that may reduce the risk of life-threatening cardiac events in patients with this inherited cardiac disorder
Modelling the role of ion transport in controlling airway surface liquid
ATP and protease activity in the airway surface liquid (ASL), are thought to control ASL depth. Many experiments have examined this control system by measuring absorption rates when excess fluid is added to the ASL. However, these experiments often use saline solutions that are not well matched to the ASL ion composition. We have developed a simple mathematical model of ion transport (Figure 1) and simulated the impact of changing ion composition alone without any ASL regulatory pathways
BK channel modulation as a theraputic target for Cystic Fibrosis
Background. Cystic fibrosis and is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel present on the apical membrane of airway epithelia. Loss of CFTR function reduces anion secretion into the airway surface liquid (ASL), causing ASL dehydration and an impairment of the innate immune response. CFTR modulator drugs seek to increase the number of functional channels at the cell membrane and the CFTR open probability. However, the apical membrane potential sits close to the reversal potential for chloride. Thus, physiologically, it seems that the co-activation of potassium channels is necessary to provide the driving force for anion secretion. Therefore, another way to increase anion secretion is to increase activation of these channels. One such target is the large conductance calcium-activated potassium channel (BK channel) [1] that also resides on the apical membrane of human bronchial epithelium. /
Aim. To investigate the role of BK channels both theoretically and experimentally. /
Theory. We first examined BK channel modulation by extending a model of ion transport in epithelial cells first developed by OâDonoghue et al. [2]. The extended model included an ASL compartment where depth and ion concentrations could be predicted. /
Experiment. We next tested BK channel activation experimentally using CF-donor cells carrying R334W/ÎF508 CFTR mutation. Cells were grown in PneumaCultTM-Ex Plus and PneumaCultâ˘-ALI Medium to create air-liquid interface (ALI) cultures in the absence of antibiotics and antimycotic agents. We used BK channel activator GoSlo-SR-5-6 [4] (GoSlo) to modulate the BK channel. GoSlo lowers the voltage required for half maximal activation for all BK channels, independent of their subunit composition, by about 50 mV, allowing them to stay open at relatively hyperpolarised potentials. To measure ASL depth we used the method of Ivanova et al. [3].
We investigated the effect on ASL depth on HBE cultures by measuring a control with DMSO (vehicle) applied to the basolateral side of the culture vs GoSlo (10 uM), also applied basolaterally or GoSlo applied first vs DMSO only 24 hrs later. /
Results and conclusion. A simple theoretical model of ion transport in airway epithelia predicts that activation of basolateral BK channels will increase airway hydration, in agreement with data published by Manzanares and colleagues [1]. This prediction is well-matched by experiment which shows a ~77% increase in ASL depth from the DMSO baseline. BK channel activation may thus be therapeutically useful in cystic fibrosi
2002-2003 North American Music Festival Philharmonia Orchestra
Program New Dawn (A Tone Poem for Orchestra, 2001) / Lawrence Moss Trumpet Concerto / Arthur Weisberg Marc Reese, trumpet Second Symphony (1991) / Aaron Jay Kernis
North American New Music Festival April 23, 2003 - Spotlight on Aaron Jay Kernis April 24, 2003 - Student Concert April 25, 2003 - Philharmonia Orchestra April 26, 2003 - Faculty Concert
Composers featured in this festival John Stafford, II Kari Juusela Mary J. van Appledorn Daniel Adams Joaquin Turina John McGinn David Heuserhttps://spiral.lynn.edu/conservatory_philharmonia/1115/thumbnail.jp
T wave alternans in idiopathic long QT syndrome
AbstractObjectives. The study evaluates the association between T wave alternans and the risk of cardiac events (syncope, aborted cardiac arrest or cardiac death) in a large population of patients with idiopathic long QT syndrome.Background. T wave alternans is an infrequently recorded electrocardiographic (ECG) finding in patients with delayed repolarization, and its clinical significance is not clear.Methods. A total of 4,656 ECG recordings in 2,442 patients enrolled in the International Long QT Syndrome Registry were reviewed for episodes of T wave alternans. To determine the risk associated with T wave alternans, independent of corrected QT interval (QTc) duration, patients with T wave alternans were matched for QTc value (every 0.025 s1/2) to patients with long QT syndrome without T wave alternans.Results. T wave alternans was identified in 39 patients (25 of whom had a QTc interval >0.50 s1/2). A strong association between QTc prolongation and T wave alternans was observed (odds ratio 1.23 per 0.01-s1/2unit increase in QTc, p < 0.0001). Conditional logistic regression analyses with adjustment for age, gender, status and QTc value revealed that T wave alternans did not make a significant independent contribution to the risk of cardiac events. The risk of experiencing a major cardiac event was primarily related to length of QTc.Conclusions. T wave alternans, a marker of electrical instability and regional heterogeneity of repolarization, identifies a high risk subset of patients with prolonged repolarization. Patients with T wave alternans have an increased risk of cardiac events, but this risk is primarily related to the magnitude of repolarization delay (QTc prolongation). T wave alternans does not make an independent contribution to the risk of cardiac events after adjustment for QTc length
Efficacy of Different Beta-Blockers in the Treatment of Long QT Syndrome
AbstractBackgroundIn LQTS, β-blocker therapy is effective in reducing the risk of cardiac events (syncope, aborted cardiac arrest, sudden cardiac death). Limited studies have compared the efficacy of different β-blockers.ObjectivesThe goal of this study was to compare the efficacy of different β-blockers in long QT syndrome (LQTS) and in genotype-positive patients with LQT1 and LQT2.MethodsThe study included 1,530 patients from the Rochester, New Yorkâbased LQTS Registry who were prescribed common β-blockers (atenolol, metoprolol, propranolol, or nadolol). Time-dependent Cox regression analyses were used to compare the efficacy of different β-blockers with the risk of cardiac events in LQTS.ResultsRelative to being off β-blockers, the hazard ratios and 95% confidence intervals (CIs) for first cardiac events for atenolol, metoprolol, propranolol, and nadolol were 0.71 (0.50 to 1.01), 0.70 (0.43 to 1.15) 0.65 (0.46 to 0.90), and 0.51 (0.35 to 0.74), respectively. In LQT1, the risk reduction for first cardiac events was similar among the 4 β-blockers, but in LQT2, nadolol provided the only significant risk reduction (hazard ratio: 0.40 [0.16 to 0.98]). Among patients who had a prior cardiac event while taking β-blockers, efficacy for recurrent events differed by drug (p = 0.004), and propranolol was the least effective compared with the other β-blockers.ConclusionsAlthough the 4 β-blockers are equally effective in reducing the risk of a first cardiac event in LQTS, their efficacy differed by genotype; nadolol was the only β-blocker associated with a significant risk reduction in patients with LQT2. Patients experiencing cardiac events during β-blocker therapy are at high risk for subsequent cardiac events, and propranolol is the least effective drug in this high-risk group
RISK OF HEART FAILURE HOSPITALIZATION OR DEATH FOLLOWING NON-CARDIOVASCULAR HOSPITALIZATION IN PATIENTS WITH MILDLY SYMPTOMATIC HEART FAILURE TREATED WITH CARDIAC RESYNCHRONIZATION THERAPY
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