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1.
ACS Appl Mater Interfaces ; 16(6): 8109-8118, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38315970

ABSTRACT

Heat dissipation plays a crucial role in the performance and reliability of high-power GaN-based electronics. While AlN transition layers are commonly employed in the heteroepitaxial growth of GaN-on-SiC substrates, concerns have been raised about their impact on thermal transport across GaN/SiC interfaces. In this study, we present experimental measurements of the thermal boundary conductance (TBC) across GaN/SiC interfaces with varying thicknesses of the AlN transition layer (ranging from 0 to 73 nm) at different temperatures. Our findings reveal that the addition of an AlN transition layer leads to a notable increase in the TBC of the GaN/SiC interface, particularly at elevated temperatures. Structural characterization techniques are employed to understand the influence of the AlN transition layer on the crystalline quality of the GaN layer and its potential effects on interfacial thermal transport. To gain further insights into the trend of TBC, we conduct molecular dynamics simulations using high-fidelity deep learning-based interatomic potentials, which reproduce the experimentally observed enhancement in TBC even for atomically perfect interfaces. These results suggest that the enhanced TBC facilitated by the AlN intermediate layer could result from a combination of improved crystalline quality at the interface and the "phonon bridge" effect provided by AlN that enhances the overlap between the vibrational spectra of GaN and SiC.

2.
Resusc Plus ; 7: 100148, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34286310

ABSTRACT

BACKGROUND: Research priority setting in health care has historically been done by expert health care providers and researchers and has not involved patients, family or the public. Survivors & family members have been particularly absent from this process in the field of resuscitation research and specifically adult out of hospital cardiac arrest (OHCA). As such, we sought to conduct a priority setting exercise in partnership with survivors, lay responders and their families in order to ensure that their priorities were visible. We partnered with the James Lind Alliance (UK) and used their commonly used consensus methodology for Public Priority Setting Partnerships (PSPs) to identify research priorities that reflected the perspectives of all stakeholders. METHODS: We used two rounds of public and health care professional surveys to create the initial priority lists. The initial survey collected open-ended questions while the second round consolidated the list of initial questions into a refined list for prioritization. This was done by reviewing existing evidence and thematic categorization by the multi-disciplinary steering committee. An in-person consensus workshop was conducted to come to consensus on the top ten priorities from all perspectives. The McMaster PPEET tool was used to measure engagement. RESULTS: The initial survey yielded more than 425 responses and 1450 "questions" from survivors and family members (18%), lay responders, health care providers and others. The second survey asked participants to rank a short list of 125 questions. The final top 25 questions were brought to the in-person meeting, and a top ten were selected through the JLA consensus process. The final list of top ten questions included how to improve the rate of lay responder CPR, what interventions used at the scene of an arrest can improve resuscitation and survival, how survival can be improved in rural areas of Canada, what resuscitation medications are most effective, what care patient's family members need, what post-discharge support is needed for survivors, how communication should work for everyone involved with a cardiac arrest, what factors best predict neurologically intact survival, whether biomarkers/genetic tests are effective in predicting OHCA and more research on the short and long-term psycho-social impacts of OHCA on survivors. The PPEET showed overwhelmingly positive results for the patient and family engagement experience during the final workshop. CONCLUSIONS: This inclusive research priority setting provides essential information for those doing resuscitation research internationally. The results provide a guide for priority areas of research and should drive our community to focus on questions that matter to survivors and their families in our work. In particular the Canadian Resuscitation Outcomes Consortium will be incorporating the top ten list into its strategic plan for the future.

3.
Can. j. cardiol ; 36(12): 1847-1948, Dec. 1, 2020.
Article in English | BIGG - GRADE guidelines | ID: biblio-1146651

ABSTRACT

The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.


Le programme de lignes directrices de la Société canadienne de cardiologie (SCC) en matière de fibrillation auriculaire (FA) a été élaboré pour aider les cliniciens à prendre en charge ces patients complexes, ainsi que pour orienter les décideurs politiques et les systèmes de soins de santé sur des questions connexes. La dernière édition complète des lignes directrices de la SCC en matière de FA a été publiée en 2010. Depuis lors, des mises à jour périodiques ont été publiées, traitant de domaines en évolution rapide. Cependant, en 2020, un grand nombre de développements s'y étaient ajoutés, couvrant un large éventail de domaines, ce qui a motivé le comité à créer une refonte complète des lignes directrices. L'édition 2020 des lignes directrices de la SCC en matière de FA représente un renouvellement complet qui intègre, met à jour et remplace les lignes directrices, les recommandations et les conseils pratiques des dix dernières années. Elle est destinée à être utilisée par les cliniciens praticiens de toutes les disciplines qui s'occupent de patients souffrant de FA. L'approche GRADE (Gradation des Recommandations, de l'Appréciation, du Développement et des Évaluations) a été utilisée pour évaluer la pertinence des recommandations et la qualité des résultats. Les domaines d'intérêt incluent : la classification et les définitions de la FA, son épidémiologie, sa physiopathologie, l'évaluation clinique, le dépistage de la FA, la détection et la gestion des facteurs de risque modifiables, l'approche intégrée de la gestion de la FA, la prévention des accidents vasculaires cérébraux, la gestion de l'arythmie, les différences entre les sexes et la FA dans des populations particulières. Des tableaux et figures ont été largement utilisés pour synthétiser les éléments importants et présenter les concepts clés. Ce document devrait représenter une aide importante pour l'intégration des connaissances et un outil pour aider à améliorer la gestion clinique de cette arythmie importante et difficile à traiter.


Subject(s)
Humans , Male , Female , Atrial Fibrillation/diagnosis , Atrial Fibrillation/therapy , Atrial Fibrillation/classification , Atrial Fibrillation/physiopathology , Atrial Fibrillation/epidemiology , Risk Groups , Algorithms , Sex Factors , Risk Factors , Critical Pathways , Stroke/prevention & control
4.
J Electrocardiol ; 56: 115-120, 2019.
Article in English | MEDLINE | ID: mdl-31394411

ABSTRACT

BACKGROUND: Atrial arrhythmias occur at a higher than expected prevalence amongst endurance athletes. Few studies have examined both atrial structure and arrhythmias in middle-aged endurance athletes. We examined the relationship between P-wave duration, atrial dimensions, and the presence of atrial ectopy in long-standing, middle-aged endurance athletes. METHODS: Middle-aged athletes with a minimum of 10 years of competitive endurance sport history and no history of structural heart disease or clinical atrial arrhythmias, had 12-lead ECGs to assess P-wave duration, signal-averaged ECGs (SAECG) to assess filtered P-wave duration, a 24 h Holter monitor to assess atrial ectopy, and echocardiography and cardiac magnetic resonance imaging to assess atrial structural characteristics. RESULTS: Amongst endurance athletes (n = 104; mean age = 54 ±â€¯5 years; 63% male), filtered P-wave duration on SAECG was correlated with P-wave duration on 12-lead ECG (r = 0.36, p, 0.0001), as well as with larger CMR-derived RA areas (r = 0.30, p = 0.01) and volumes (r = 0.24, p < 0.05). There was no correlation between filtered P-wave duration and any LA measures on imaging (p > 0.05). There was no correlation between the incidence of atrial ectopy (premature atrial contractions or atrial tachycardia) and any electrocardiographic or structural measures. CONCLUSION: Longer filtered P-wave duration was associated with larger RA areas and volumes, without an increase in atrial ectopy.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Arrhythmias, Cardiac/diagnostic imaging , Athletes , Echocardiography , Electrocardiography , Female , Humans , Male , Middle Aged
5.
Can J Cardiol ; 32(10)oct. 2016.
Article in English | BIGG - GRADE guidelines | ID: biblio-965099

ABSTRACT

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in AF management. This 2016 Focused Update deals with: (1) the management of antithrombotic therapy for AF patients in the context of the various clinical presentations of coronary artery disease; (2) real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4) digoxin as a rate control agent; (5) perioperative anticoagulation management; and (6) AF surgical therapy including the prevention and treatment of AF after cardiac surgery. The recommendations were developed with the same methodology used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards, individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included in the Supplementary Material, and on the CCS Web site. The section on concomitant AF and coronary artery disease was developed in collaboration with the CCS Antiplatelet Guidelines Committee. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF Guidelines recommendations, from 2010 to the present 2016 Focused Update


Subject(s)
Humans , Atrial Fibrillation , Atrial Fibrillation/therapy , Postoperative Complications/prevention & control , Atrial Fibrillation/complications , Algorithms , Coronary Artery Disease/complications , Platelet Aggregation Inhibitors , Platelet Aggregation Inhibitors/therapeutic use , Cardiac Pacing, Artificial , Cardiotonic Agents , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/adverse effects , Catheter Ablation , Atrial Appendage/surgery , Stroke/prevention & control , Digoxin , Digoxin/administration & dosage , Digoxin/adverse effects , Drug Therapy, Combination , Acute Coronary Syndrome/therapy , Fibrinolytic Agents/therapeutic use , Percutaneous Coronary Intervention , Factor Xa Inhibitors , Factor Xa Inhibitors/therapeutic use , ST Elevation Myocardial Infarction/therapy , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Magnesium , Magnesium/therapeutic use , Anticoagulants , Anticoagulants/therapeutic use
6.
Article in English | MEDLINE | ID: mdl-25570146

ABSTRACT

Marine derived long chain polyunsaturated fatty acids (PUFAs) were found to have benefits in reducing inducibility and maintenance of atrial fibrillation (AF) in a dog model. This study was conducted to evaluate the effect of PUFAs on local atrial electrical conduction properties acquired via a multi-electrode plaque sutured to the posterior wall of the left atrium of the heart in these dogs. Eleven dogs underwent simultaneous atrioventricular pacing (SAVP) for 2 weeks, and were organized into 2 groups: 5 dogs received no PUFAs (SAVP-PLACEBO), 6 dogs received Eicosapentaenoic or Docosahexaenoic acid derived from fish oils (SAVP-PUFA), where PUFAs were given for 21 days, starting 1 week prior to pacing and during the 2 week pacing period. Three features were extracted, which were the average conduction velocity, average intra atrial conduction time, and total activation time. The PUFA group had a faster average conduction velocity (0.82±0.19 m/s) than the PLACEBO group (0.47±0.21 m/s, P=0.02). Using the average conduction velocity feature, classification was performed with a linear classifier and leave-one-out method. In the SAVP-PLACEBO group, 60% of the dogs were correctly classified, and 66% of the dogs were correctly classified in SAVP-PUFA group, leading to an overall classification accuracy of 63.5%.


Subject(s)
Atrial Fibrillation/drug therapy , Docosahexaenoic Acids/administration & dosage , Eicosapentaenoic Acid/administration & dosage , Animals , Atrial Fibrillation/physiopathology , Disease Models, Animal , Dogs , Drug Evaluation, Preclinical , Heart Atria/physiopathology , Myocardial Contraction
7.
Article in English | MEDLINE | ID: mdl-24111065

ABSTRACT

Ventricular Fibrillation (VF) is a cardiac arrhythmia for which the only available treatment option is defibrillation by electrical shock. Existing literature indicates that VF could be the manifestation of different sources controlling the heart with different degrees of organization. In this work we test the hypothesis that the pre-shock waveforms of successful and unsuccessful shock outcomes could be related to the number of independent sources present in these waveforms. The proposed method uses Blind Source Separation (BSS) to extract independent components in frequency direction from a pig database consisting of 20 pre-shock waveforms. The slope of the energy capture curve was used as an indicator to demonstrate the number of independent sources required to model the pre-shock waveforms. The results were also quantified by performing a linear discriminant analysis based classification achieving an overall classification accuracy of 75%. The results indicate that successful cases can be modeled with less number of independent sources compared to unsuccessful cases.


Subject(s)
Algorithms , Electric Countershock , Electrocardiography , Ventricular Fibrillation/diagnostic imaging , Wavelet Analysis , Animals , Signal Processing, Computer-Assisted , Sus scrofa , Ultrasonography , Ventricular Fibrillation/physiopathology
8.
Anaesthesia ; 68(7): 723-35, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23590519

ABSTRACT

Cardiac arrest is associated with a very high rate of mortality, in part due to inadequate tissue perfusion during attempts at resuscitation. Parameters such as mean arterial pressure and end-tidal carbon dioxide may not accurately reflect adequacy of tissue perfusion during cardiac resuscitation. We hypothesised that quantitative measurements of tissue oxygen tension would more accurately reflect adequacy of tissue perfusion during experimental cardiac arrest. Using oxygen-dependent quenching of phosphorescence, we made measurements of oxygen in the microcirculation and in the interstitial space of the brain and muscle in a porcine model of ventricular fibrillation and cardiopulmonary resuscitation. Measurements were performed at baseline, during untreated ventricular fibrillation, during resuscitation and after return of spontaneous circulation. After achieving stable baseline brain tissue oxygen tension, as measured using an Oxyphor G4-based phosphorescent microsensor, ventricular fibrillation resulted in an immediate reduction in all measured parameters. During cardiopulmonary resuscitation, brain oxygen tension remained unchanged. After the return of spontaneous circulation, all measured parameters including brain oxygen tension recovered to baseline levels. Muscle tissue oxygen tension followed a similar trend as the brain, but with slower response times. We conclude that measurements of brain tissue oxygen tension, which more accurately reflect adequacy of tissue perfusion during cardiac arrest and resuscitation, may contribute to the development of new strategies to optimise perfusion during cardiac resuscitation and improve patient outcomes after cardiac arrest.


Subject(s)
Capillaries/metabolism , Cardiopulmonary Resuscitation , Cerebrovascular Circulation/physiology , Heart Arrest/metabolism , Oxygen Consumption/physiology , Animals , Arterial Pressure/physiology , Brain Chemistry/physiology , Carotid Arteries/physiology , Coronary Circulation/physiology , Electrocardiography , Epinephrine/pharmacology , Female , Male , Metalloporphyrins , Microcirculation , Muscle, Skeletal/blood supply , Muscle, Skeletal/metabolism , Regional Blood Flow/physiology , Swine , Tongue/blood supply , Tongue/metabolism , Vasoconstrictor Agents/pharmacology
9.
Article in English | MEDLINE | ID: mdl-22254297

ABSTRACT

Ventricular fibrillation (VF) is a lethal cardiac arrhythmia that if untreated within minutes of its occurrence will lead to sudden cardiac death. Defibrillation using electric shocks is the only choice of treatment to restore the heart to normal rhythm especially in out-of-the-hospital VF incidents. Refibrillation (i.e., recurrence of VF) is a common and significant problem in cardiac resuscitation as it negatively impacts the survival rates. In such refibrillation cases administration of anti-arrhythmic drugs could improve the shock outcomes or prevent refibrillation. In cases of prolonged VF, cardio pulmonary resuscitation (CPR) prior to the shocks have been shown to improve the survival rates. The proposed work using wavelet analysis of the pre-shock VF electrograms attempts to predict the shock outcomes as successful, refibrillation, and unsuccessful categories. This feedback in real-time would be of immense assistance to the Emergency Medical Services (EMS) personnel in choosing the right combination of therapies (i.e., shock, CPR, pharmacology interventions) in improving the shock outcomes. Using a real-word database of 34 pre-shock VF electrograms obtained from Toronto area EMS personnel, the proposed method achieved classification accuracies of 76.5% and 75% for a two level binary classification of the three groups.


Subject(s)
Cardiopulmonary Resuscitation/methods , Electric Countershock/methods , Models, Cardiovascular , Therapy, Computer-Assisted/methods , Ventricular Fibrillation/prevention & control , Ventricular Fibrillation/physiopathology , Combined Modality Therapy/methods , Computer Simulation , Humans
10.
Article in English | MEDLINE | ID: mdl-21097215

ABSTRACT

During cardiac resuscitation from ventricular fibrillation (VF) it would be helpful if we could monitor and predict the optimal state of the heart to be shocked into a perfusing rhythm. Real-time feedback of this state to the emergency medical staff (EMS) could improve the survival rate after resuscitation. In this paper, using real world out-of-the-hospital human VF data obtained during resuscitation by EMS personnel, we present the results of applying wavelet markers in predicting the shock outcomes. We also performed comparative analysis of 5 existing techniques (spectral and correlation based approaches) against the proposed wavelet markers. A database of 29 human VF tracings was extracted from the defibrillator recordings collected by the EMS personnel and was used to validate the waveform markers. The results obtained by the comparison of the wavelet based features with other spectral, and correlation-based features indicates that the proposed wavelet features perform well with an overall accuracy of 79.3% in predicting the shock outcomes and hence demonstrate potential to provide near real-time feedback to EMS personnel in optimizing resuscitation outcomes.


Subject(s)
Cardiopulmonary Resuscitation/instrumentation , Cardiopulmonary Resuscitation/methods , Signal Processing, Computer-Assisted , Ventricular Fibrillation , Algorithms , Canada , Databases, Factual , Electric Countershock/instrumentation , Emergency Medical Services , Heart Arrest/mortality , Humans , Models, Statistical , Reproducibility of Results , Resuscitation , Treatment Outcome
11.
J Cardiovasc Electrophysiol ; 21(12): 1344-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20662988

ABSTRACT

BACKGROUND: increasingly, ICD implantation is performed without defibrillation testing (DT). OBJECTIVES: To determine the current frequency of DT, the risks associated with DT, and to understand how physicians select patients to have DT. METHODS: between January 2007 and July 2008, all patients in Ontario, Canada who received an ICD were enrolled in this prospective registry. RESULTS: a total of 2,173 patients were included; 58% had new ICD implants for primary prevention, 25% for secondary prevention, and 17% had pulse generator replacement. DT was carried out at the time of ICD implantation or predischarge in 65%, 67%, and 24% of primary, secondary, and replacement cases respectively (P = <0.0001). The multivariate predictors of a decision to conduct DT included: new ICD implant (OR = 13.9, P < 0.0001), dilated cardiomyopathy (OR = 1.8, P < 0.0001), amiodarone use (OR = 1.5, P = 0.004), and LVEF > 20% (OR = 1.3, P = 0.05). A history of atrial fibrillation (OR = 0.58, P = 0.0001) or oral anticoagulant use (OR = 0.75, P = 0.03) was associated with a lower likelihood of having DT. Age, gender, NYHA class, and history of stroke or TIA did not predict DT. Perioperative complications, including death, myocardial infarction, stroke, tamponade, pneumothorax, heart failure, infection, wound hematoma, and lead dislodgement, were similar among patients with (8.7%) and without (8.3%) DT (P = 0.7) CONCLUSIONS: DT is performed in two-thirds of new ICD implants but only one-quarter of ICD replacements. Physicians favored performance of DT in patients who are at lower risk of DT-related complications and in those receiving amiodarone. DT was not associated with an increased risk of perioperative complications.


Subject(s)
Defibrillators, Implantable/standards , Electric Countershock/standards , Monitoring, Intraoperative/standards , Registries/standards , Aged , Electric Countershock/methods , Female , Humans , Male , Middle Aged , Monitoring, Intraoperative/methods , Ontario , Prospective Studies , Time Factors
12.
Org Lett ; 12(1): 52-5, 2010 Jan 01.
Article in English | MEDLINE | ID: mdl-19968321

ABSTRACT

The diastereomeric epoxycyclohexenols 3a/b (obtained via a Wharton rearrangement of a bis-epoxycyclohexanone precursor) were shown to undergo interconversion via a facile vinylogous Payne rearrangement. Mechanistic issues were probed; the doubly O-deuterated analogues underwent this equilibration more slowly than the parent dihydroxy compounds. It was possible to kinetically resolve the mixture of 3a/b under equilibrating conditions by use of Amano PS. This DKR is additionally noteworthy because it sets four stereocenters in a single event.


Subject(s)
Amides/chemistry , Amides/chemical synthesis , Pyrones/chemistry , Pyrones/chemical synthesis , Catalysis , Kinetics , Molecular Structure , Sphingomyelin Phosphodiesterase/antagonists & inhibitors , Stereoisomerism
13.
Article in English | MEDLINE | ID: mdl-19963687

ABSTRACT

Ventricular fibrillation (VF) is the most lethal of cardiac arrhythmias that leads to sudden cardiac death if untreated within minutes of its occurrence. Defibrillation using electric shock resets the heart to return to spontaneous circulation (ROSC) state, however the success of which depends on various factors such as the viability of myocardium and the time lag between the onset of VF to defibrillation. Recent studies have reported that performing cardio pulmonary resuscitation (CPR) procedure prior to applying shock increases the survival rate especially when VF is untreated for more than 5 minutes. Considering the limited time within which the VF has to be treated for better survival rates, the choice of the right therapy (shock parameters, shock first or CPR first, drug administration) is vital. In aiding this choice, it would be of immense help for emergency medical staff (EMS) if an objective feedback could be provided at near real-time rate on the VF characteristics and its relation to the shock outcomes. Existing works in the literature have demonstrated correlation between the characteristics of the VF waveform and the outcome (ROSC) of the defibrillation. The proposed work improves on this by attempting to arrive at a near real-time monitoring tool in aiding the EMS staff. Using data collected from 16 pigs during VF, the proposed wavelet methodology achieved an overall accuracy of 94% in successfully predicting the shock outcomes.


Subject(s)
Cardiopulmonary Resuscitation/methods , Electrocardiography/methods , Animals , Discriminant Analysis , Humans , Sus scrofa , Time Factors , Treatment Outcome , Ventricular Fibrillation/therapy
16.
Br J Pharmacol ; 155(8): 1185-94, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18836478

ABSTRACT

BACKGROUND AND PURPOSE: The slow delayed rectifier K(+) current (I(Ks)) contributes to ventricular repolarization when the action potential (AP) is prolonged. I(Ks) block during drug-induced AP prolongation may promote Torsades de Pointes (TdP), but whether this is due to additional AP prolongation is uncertain. EXPERIMENTAL APPROACH: In bradycardic perfused rabbit ventricles, the incidence of spontaneous TdP, monophasic AP duration at 90% repolarization (MAPD(90)) and ECG interval between the peak and the end of T wave (T(peak-end)) (index of dispersion of repolarization) were measured after the administration of veratridine (125 nM, slows Na(+) channel inactivation), dofetilide (7.5 or 10 nM, a rapid delayed rectifier blocker) and HMR 1556 (HMR, 100 nM, an I(Ks) blocker), alone or in combinations (n=6 each). KEY RESULTS: HMR did not prolong MAPD(90), whereas veratridine or 7.5 nM dofetilide prolonged MAPD(90) (P<0.01) without inducing TdP. Veratridine+7.5 nM dofetilide additively prolonged MAPD(90) (P<0.05), induced 4+/-6 TdP per heart and prolonged T(peak-end) by 12+/-10 ms. Subsequent addition of HMR did not further prolonged MAPD(90), but increased the number of TdP to 22+/-18 per heart and increased T(peak-end) by 39+/-21 ms (P<0.05). Increasing dofetilide concentration from 7.5 to 10 nM (added to veratridine) produced a longer MAPD(90), but fewer TdP (5+/-5 per heart) and less T(peak-end) prolongation (17+/-8 ms) compared to the veratridine+7.5 nM dofetilide+HMR group (P<0.05). CONCLUSIONS AND IMPLICATIONS: Adding I(Ks) block markedly increases TdP incidence in hearts predisposed to TdP development by increasing the dispersion of repolarization, but without additional AP prolongation.


Subject(s)
Chromans/pharmacology , Heart Ventricles/drug effects , Potassium Channel Blockers/pharmacology , Sulfonamides/pharmacology , Torsades de Pointes/chemically induced , Animals , Heart Ventricles/physiopathology , Male , Phenethylamines/pharmacology , Rabbits , Veratridine/pharmacology
17.
J Eval Clin Pract ; 12(2): 190-5, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16579828

ABSTRACT

OBJECTIVE: To estimate the baseline risk of arrhythmic death required for prophylactic implantable cardiac defibrillators (ICDs) to result in clinically meaningful survival benefits in the population. BACKGROUND: While proven efficacious, the absolute survival impact of ICDs for the primary prevention of sudden cardiac death among patients with left ventricular (LV) dysfunction is highly dependent upon patient's baseline risk of arrhythmic death. METHODS: Using echocardiographic data from a random sample of patients identified from community echocardiographic laboratories, patients with moderate or severe LV dysfunction (ejection fraction < 35%) were linked to administrative databases to characterize baseline mortality risk (median follow-up duration of 4.85 years). Relative efficacy was ascertained from meta-analysis and clinical trial data. The baseline annual risk of arrhythmic death required for prophylactic ICDs to result in clinically meaningful survival benefits in the population was estimated at different ranges of relative efficacy and numbers needed to treat (NNTs) thresholds. RESULTS: LV dysfunction was a significant independent predictor of adverse outcomes. In total, 35.4% of the patients with moderate to severe LV dysfunction died during the follow-up period. Assuming a base-case relative efficacy of 66%, we estimated that the baseline risk for arrhythmic death required to exert a clinically meaningful NNT threshold of 50 in order to prevent one death (from any cause) was 3% per year or higher. CONCLUSIONS: The survival impact and cost-effectiveness of prophylactic ICDs in the population will depend upon the ability to risk-stratify and identify patients whose baseline risk for sudden cardiac death exceed 3% per year.


Subject(s)
Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable/standards , Ventricular Dysfunction, Left/therapy , Echocardiography/methods , Female , Humans , Male , Middle Aged , Risk Assessment , Risk Factors
18.
J Org Chem ; 70(15): 6034-9, 2005 Jul 22.
Article in English | MEDLINE | ID: mdl-16018700

ABSTRACT

A practical synthesis of 2-[3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol (1), an oral GABA(A) alpha(2/3)-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.


Subject(s)
GABA Agonists/chemical synthesis , Palladium/chemistry , Propanols/chemical synthesis , Pyrimidines/chemical synthesis , Allosteric Regulation , Boronic Acids/chemistry , Catalysis , Imidazoles/chemistry , Molecular Structure , Oxidation-Reduction , Pyridines/chemistry , Pyrimidines/chemistry , Stereoisomerism
19.
Eur Respir J ; 26(1): 95-100, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15994394

ABSTRACT

The effect of standard cardiac resynchronisation therapy (CRT) on the severity of Cheyne-Stokes respiration (CSR) in patients with congestive heart failure was studied. It was hypothesised that CRT, through its known beneficial effects on cardiac function, would stabilise the control of breathing and reduce CSR. Twenty-eight patients who were eligible for CRT and receiving optimised medical treatment for congestive heart failure were referred for overnight polysomnography, including monitoring of thoracic and abdominal movements to identify CSR and obstructive sleep apnoea events. Patients underwent repeat polysomnography after 6 months of CRT to re-evaluate sleep quality and sleep-disordered breathing. Twelve of the 28 patients had significant CSR (43%); 10 patients had a successful implantation and underwent repeat polysomnography a mean+/-SD 27+/-7 weeks after continuous biventricular pacing. Six of the 10 patients experienced a significant decrease in CSR severity following CRT, associated with correction of congestive heart failure-related hyperventilation and hypocapnia. Circulation time, oxygen saturation, frequency of obstructive apnoeas and sleep quality did not change. In conclusion, cardiac resynchronisation therapy is associated with a reduction in Cheyne-Stokes respiration, which may contribute to improved clinical outcome in patients treated with cardiac resynchronisation therapy.


Subject(s)
Cardiac Pacing, Artificial/methods , Cheyne-Stokes Respiration/diagnosis , Heart Failure/diagnosis , Heart Failure/therapy , Aged , Analysis of Variance , Blood Gas Analysis , Cheyne-Stokes Respiration/etiology , Chi-Square Distribution , Cohort Studies , Female , Follow-Up Studies , Heart Failure/complications , Heart Function Tests , Humans , Male , Middle Aged , Monitoring, Physiologic/methods , Polysomnography/methods , Probability , Prospective Studies , Pulmonary Gas Exchange , Risk Assessment , Severity of Illness Index , Statistics, Nonparametric , Treatment Outcome
20.
Can J Cardiol ; 21 Suppl A: 19A-24A, 2005 May.
Article in English | MEDLINE | ID: mdl-15953940

ABSTRACT

The Canadian Cardiovascular Society is the national professional society for cardiovascular specialists and researchers in Canada. In the spring of 2004, the Canadian Cardiovascular Society Council formed an Access to Care Working Group in an effort to use the best science and information to establish reasonable triage categories and safe wait times for access to common cardiovascular services and procedures. The Working Group has elected to publish a series of commentaries to initiate a structured national discussion on this very important issue. Access to treatment with implantable cardioverter defibrillators is the subject of the present commentary. The prevalence pool of potentially eligible patients is discussed, along with access barriers, regional disparities and waiting times. A maximum recommended waiting time is proposed and the framework for a solution-oriented approach is presented.


Subject(s)
Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Health Services Accessibility/statistics & numerical data , Canada , Humans , Time Factors , Waiting Lists
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