Trigger and Substrate Mapping and Ablation for Ventricular Fibrillation in the Structurally Normal Heart.

Sudden cardiac death (SCD) represents approximately 50% of all cardiovascular mortality in the United States. The majority of SCD occurs in individuals with structural heart disease; however, around 5% of individuals have no identifiable cause on autopsy. This proportion is even higher in those <40 years old, where SCD is particularly devastating. Ventricular fibrillation (VF) is often the terminal rhythm leading to SCD. Catheter ablation for VF has emerged as an effective tool to alter the natural history of this disease among high-risk individuals. Important advances have been made in the identification of several mechanisms involved in the initiation and maintenance of VF. Targeting the triggers of VF as well as the underlying substrate that perpetuates these lethal arrhythmias has the potential to eliminate further episodes. Although important gaps remain in our understanding of VF, catheter ablation has become an important option for individuals with refractory arrhythmias. This review outlines a contemporary approach to the mapping and ablation of VF in the structurally normal heart, specifically focusing on the following major conditions: idiopathic ventricular fibrillation, short-coupled ventricular fibrillation, and the J-wave syndromes-Brugada syndrome and early-repolarization syndrome.

High-impedance alerts with pulse generator-Lead mismatch.

Background: Cardiac Implantable Electronic Devices (CIED) include pulse generators and leads. In some implanting centers, it is a common practice to combine devices with leads from different companies. Case series have reported episodic high-impedance changes in Boston Scientific CIEDs with competitor leads. We investigated the incidence of high-impedance abnormalities in matched versus mismatched Boston Scientific Accolade pacemakers. Methods: A retrospective chart review identified all consecutive Boston Scientific Accolade pacemakers implanted between January 2017 and June 2019 at a Canadian tertiary care center. The primary outcome was the occurrence of transient, high-impedance changes which resulted in a switch to unipolar pacing/sensing in the absence of any other identifiable lead issue. Fisher exact tests (two-tailed, α = .05) were used to compare the incidence of outcomes in matched versus mismatched systems. Results: 514 Boston Scientific Accolade pacemakers were associated with 882 individual leads. The primary outcome occurred with 21 leads (20 Medtronic and 1 Abbott), associated with occasional pacing inhibition, presyncope, and/or early surgical revision. Mismatched lead-device pairs were significantly associated with CIED malfunction compared to matched lead-device pairs (3.3% vs. 0%, p = .0019). The median time from implant to unipolar safety switch was 12.4 months. The median follow-up time was 21.6 months. Conclusion: Use of mismatched leads with a Boston Scientific Accolade device was associated with an increased risk of undesirable changes in sensing polarity with occasional inappropriate pacing inhibition. Awareness of this interaction can allow for the institution of appropriate programming remedies and may increase scrutiny of the use of mismatched CIED systems.

Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice.

BACKGROUND: Two anti-cancer agents, doxorubicin (DOX) and trastuzumab (TRZ), are commonly used in the management of breast cancer in women. Despite their efficacy in reducing the morbidity and mortality of individuals with breast cancer, the use of these agents is limited by adverse cardiotoxic side effects. Both the nutraceutical agent flaxseed (FLX) and the pharmaceutical drug perindopril (PER) have been studied individually in the prevention of chemotherapy-mediated cardiac dysfunction. The objective of this study was to determine whether the prophylactic administration of FLX is comparable and/or synergistic with PER in preventing DOX + TRZ-induced cardiotoxicity. METHODS: Over a six-week period, 81 wild-type C57Bl/6 female mice (8-12 weeks old) were randomized to receive regular chow (RC) or 10% FLX-supplemented diets with or without PER (3 mg/kg/week; oral gavage). Starting at week 4, mice were randomized to receive a weekly injection of saline or DOX (8 mg/kg) + TRZ (3 mg/kg). Serial echocardiography was conducted weekly and histological and biochemical analyses were performed at the end of the study. RESULTS: In mice treated with RC + DOX + TRZ, left ventricular ejection (LVEF) decreased from 75 ± 2% at baseline to 37 ± 3% at week 6. However, prophylactic treatment with either FLX, PER, or FLX + PER partially preserved left ventricular systolic function with LVEF values of 61 ± 2%, 62 ± 2%, and 64 ± 2%, respectively. The administration of FLX, PER, or FLX + PER was also partially cardioprotective in preserving cardiomyocyte integrity and attenuating the expression of the inflammatory biomarker NF-κB due to DOX + TRZ administration. CONCLUSION: FLX was equivalent to PER at preventing DOX + TRZ-induced cardiotoxicity in a chronic in vivo murine model.

Evaluating the climate impact of aviation emission scenarios towards the Paris agreement including COVID-19 effects.

Aviation is an important contributor to the global economy, satisfying society's mobility needs. It contributes to climate change through CO2 and non-CO2 effects, including contrail-cirrus and ozone formation. There is currently significant interest in policies, regulations and research aiming to reduce aviation's climate impact. Here we model the effect of these measures on global warming and perform a bottom-up analysis of potential technical improvements, challenging the assumptions of the targets for the sector with a number of scenarios up to 2100. We show that although the emissions targets for aviation are in line with the overall goals of the Paris Agreement, there is a high likelihood that the climate impact of aviation will not meet these goals. Our assessment includes feasible technological advancements and the availability of sustainable aviation fuels. This conclusion is robust for several COVID-19 recovery scenarios, including changes in travel behaviour.

Clinical outcomes of cardiac resynchronization therapy with and without a defibrillator in elderly patients with heart failure.

BACKGROUND: Evidence regarding the incremental benefit of cardiac resynchronization therapy (CRT) with a defibrillator (CRT-D) versus without (CRT-P) in elderly patients with heart failure is limited. We compared mortality and cardiac hospitalisation between CRT-D and CRT-P in the elderly. METHODS: A retrospective chart review identified all consecutive patients with age ≥75 with CRT implantation over the last 10 years at a Canadian tertiary care cardiac centre. Kaplan-Meier survival analyses and cumulative incidence curves were used to compare mortality and time to first cardiac hospitalisation, respectively, with CRT-D versus CRT-P over a 3 year period. Analyses were also repeated with propensity score matching based on age, sex, primary versus secondary prevention, date of implant, and Charlson Comorbidity Index. RESULTS: One hundred and seventy CRT patients were identified. A total of 128 received CRT-D while 42 received CRT-P. Median age was 79 (IQR 77-81), and the majority were male (83%). CRT-P patients had a higher burden of comorbidities (Charlson score 7, IQR 6-8) than CRT-D patients (Charlson score 5, IQR 5-7; P < 0.001). There was no significant difference in survival between the two groups in an unmatched comparison (P = 0.69) and with a propensity score-matched cohort (P = 0.91). Secondary prevention CRT-D patients had a higher risk of hospitalisation compared to primary prevention CRT-D patients; however, there was no significant difference in hospitalisation between the CRT-D and CRT-P groups. CONCLUSION: This study suggests there is no significant difference in mortality or cardiac hospitalisation between CRT-D and CRT-P in elderly patients with heart failure.

Urinary Hepcidin-25 Is Elevated in Patients That Avoid Acute Kidney Injury Following Cardiac Surgery.

BACKGROUND: Acute kidney injury (AKI) following cardiac surgery leads to increased morbidity and mortality. Characterization and validation of early biomarkers of AKI may ultimately facilitate early therapeutic intervention. We have previously identified that elevated urinary hepcidin-25 is inversely and independently associated with the development of AKI in adult cardiac surgery patients. Hepcidin-25 is an antimicrobial peptide that sequesters iron intracellularly, and its elevation following human ischemia reperfusion injury may represent a renoprotective response to minimize renal injury. OBJECTIVE: Our goal was to validate urinary hepcidin-25 as a non-invasive biomarker in an independent cardiac surgery cohort, within the context of clinical AKI predictors. DESIGN: Prospective observational cohort study. SETTING: Adult cardiac surgery program at St. Boniface Hospital, Winnipeg, Manitoba, Canada. PATIENTS: Adult cardiac surgery patients undergoing cardiopulmonary bypass (CPB), n = 306. MEASUREMENTS: Urine hepcidin-25, measured on post-operative day (POD) 1. METHODS: A prospective, observational cohort of adult CPB patients (n = 306) was collected with serial perioperative urine samples. Urine hepcidin-25 at POD 1 was measured by competitive ELISA. Its diagnostic performance was evaluated in conjunction with clinical parameters and the Thakar clinical prediction score, using multivariate logistic regression. RESULTS: Urinary hepcidin-25 is elevated following cardiac surgery in AKI and non-AKI patients. Elevated urinary hepcidin-25 concentration was inversely associated with AKI on both univariate (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.45-0.83, P = .002) and multivariate analysis (OR: 0.67, 95% CI: 0.50-0.95, P = .02). A combined model with clinical risk factors demonstrated that baseline estimated glomerular filtration rate (eGFR), diabetes mellitus, and urinary hepcidin-25 concentration had an overall area under the curve (AUC) of 0.82 (0.75-0.88) for predicting subsequent AKI development, which was superior to clinical prediction alone as determined by the Thakar score. LIMITATIONS: (1) A single-center observational study. (2) Polyclonal antibody-based competitive ELISA. CONCLUSION: Hepcidin-25 is inversely associated with AKI in a multivariate model when combined with eGFR and diabetes mellitus, with an overall AUC of 0.82. Notably, urinary hepcidin-25 improves on clinical AKI prediction compared to the Thakar score alone.

CONTEXTE: L'insuffisance rénale aiguë (IRA) qui survient à la suite d'une chirurgie cardiaque est associée à une augmentation du taux de morbidité et de mortalité. La caractérisation et la validation de biomarqueurs précoces d'une IRA permettraient éventuellement une intervention thérapeutique plus opportune. Nous avions antérieurement déterminé qu'un taux élevé d'hepcidine-25 est inversement et indépendamment associé au développement d'une IRA à la suite d'une chirurgie cardiaque chez les patients adultes. L'hepcidine-25 est un peptide antimicrobien qui capte le fer intracellulaire. L'élévation de sa concentration à la suite d'une lésion d'ischémie-reperfusion pourrait être une réponse rénoprotectrice permettant de limiter les lésions inflammatoires. OBJECTIFS DE L'ÉTUDE: Nous avions pour objectif de valider la qualité de biomarqueur non invasif de l'hépcidine-25 urinaire dans une cohorte indépendante de patients subissant une chirurgie cardiaque, dans le contexte des prédicteurs cliniques de l'IRA. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte observationnelle prospective. CADRE: L'étude a été réalisée au Canada, dans le cadre du programme de chirurgie cardiaque du St. Boniface Hospital de Winnipeg, au Manitoba. PATIENTS: La cohorte était constituée de 306 patients adultes subissant un pontage cardiopulmonaire. MESURES: Le taux d'hepcidine-25 urinaire a été mesuré le jour suivant l'intervention. MÉTHODOLOGIE: Une série d'échantillons d'urine périopératoires a été collectée chez une cohorte prospective et observationnelle constituée de 306 patients adultes subissant un pontage cardiopulmonaire. Le taux d'hepcidine-25 a été mesuré à l'aide d'un test ELISA compétitif, et sa performance diagnostique évaluée conjointement avec les paramètres cliniques et le score prédictif de Thakar en utilisant une régression logistique multivariée. RÉSULTATS: Le taux d'hepcidine-25 urinaire était élevé en post-opératoire chez tous les patients de la cohorte, qu'ils soient ou non atteints d'insuffisance rénale. Une concentration élevée d'hepcidine-25 urinaire a été inversement associée à la survenue d'une IRA tant selon l'analyse univariée (RC=0,61; IC à 95 % 0,45-0,83; p=0,002) que selon l'analyse multivariée (RC=0,67; IC à 95 % 0,50-0,95; p=0,002). Un modèle combinant certains facteurs de risque cliniques a démontré que le DFG initial, le diabète sucré et la concentration d'hepcidine-25 urinaire présentaient une surface sous la courbe (SSC) de 0,82 (0,75-0,88) pour la prédiction du développement d'une IRA à la suite d'une chirurgie cardiaque. Ce niveau d'exactitude s'est avéré supérieur à la prédiction clinique déterminée par le score de Thakar. LIMITES DE L'ÉTUDE: Deux principaux facteurs limitent la portée de l'étude : d'abord, le fait qu'il s'agit d'une étude observationnelle menée dans un seul centre, puis, la variabilité inhérente au test ELISA compétitif pour les anticorps polyclonaux. CONCLUSION: Dans une analyse multivariée, lorsque combinée au DFG et au diabète sucré, l'hepcidine-25 urinaire est inversement associée à la survenue d'une IRA (SSC globale de 0,82). Ainsi, comparativement au score de Thakar utilisé seul, la mesure du taux d'hepcidine-25 urinaire prédit plus exactement le risque d'IRA.

Gas Turbine Engine Nonvolatile Particulate Matter Mass Emissions: Correlation with Smoke Number for Conventional and Alternative Fuel Blends.

This study evaluates the relationship between the emissions parameters of smoke number (SN) and mass concentration of nonvolatile particulate matter (nvPM) in the exhaust of a gas turbine engine for a conventional Jet A-1 and a number of alternative fuel blends. The data demonstrate the significant impact of fuel composition on the emissions and highlight the magnitude of the fuel-induced uncertainty for both SN within the Emissions Data Bank as well as nvPM mass within the new regulatory standard under development. Notwithstanding these substantial differences, the data show that correlation between SN and nvPM mass concentration still adheres to the first order approximation (FOA3), and this agreement is maintained over a wide range of fuel compositions. Hence, the data support the supposition that the FOA3 is applicable to engines burning both conventional and alternative fuel blends without adaptation or modification. The chemical composition of the fuel is shown to impact mass and number concentration as well as geometric mean diameter of the emitted nvPM; however, the data do not support assertions that the emissions of black carbon with small mean diameter will result in significant deviations from FOA3.

Abatement of an aircraft exhaust plume using aerodynamic baffles.

The exhaust jet from a departing commercial aircraft will eventually rise buoyantly away from the ground; given the high thrust/power (i.e., momentum/buoyancy) ratio of modern aero-engines, however, this is a slow process, perhaps requiring ∼ 1 min or more. Supported by theoretical and wind tunnel modeling, we have experimented with an array of aerodynamic baffles on the surface behind a set of turbofan engines of 124 kN thrust. Lidar and point sampler measurements show that, as long as the intervention takes place within the zone where the Coanda effect holds the jet to the surface (i.e., within about 70 m in this case), then quite modest surface-mounted baffles can rapidly lift the jet away from the ground. This is of potential benefit in abating both surface concentrations and jet blast downstream. There is also some modest acoustic benefit. By distributing the aerodynamic lift and drag across an array of baffles, each need only be a fraction of the height of a single blast fence.

Impact of alternative fuels on emissions characteristics of a gas turbine engine - part 1: gaseous and particulate matter emissions.

Growing concern over emissions from increased airport operations has resulted in a need to assess the impact of aviation related activities on local air quality in and around airports, and to develop strategies to mitigate these effects. One such strategy being investigated is the use of alternative fuels in aircraft engines and auxiliary power units (APUs) as a means to diversify fuel supplies and reduce emissions. This paper summarizes the results of a study to characterize the emissions of an APU, a small gas turbine engine, burning conventional Jet A-1, a fully synthetic jet fuel, and other alternative fuels with varying compositions. Gas phase emissions were measured at the engine exit plane while PM emissions were recorded at the exit plane as well as 10 m downstream of the engine. Five percent reduction in NO(x) emissions and 5-10% reduction in CO emissions were observed for the alternative fuels. Significant reductions in PM emissions at the engine exit plane were achieved with the alternative fuels. However, as the exhaust plume expanded and cooled, organic species were found to condense on the PM. This increase in organic PM elevated the PM mass but had little impact on PM number.

Impact of alternative fuels on emissions characteristics of a gas turbine engine - part 2: volatile and semivolatile particulate matter emissions.

The work characterizes the changes in volatile and semivolatile PM emissions from a gas turbine engine resulting from burning alternative fuels, specifically gas-to-liquid (GTL), coal-to-liquid (CTL), a blend of Jet A-1 and GTL, biodiesel, and diesel, to the standard Jet A-1. The data presented here, compares the mass spectral fingerprints of the different fuels as measured by the Aerodyne high resolution time-of-flight aerosol mass spectrometer. There were three sample points, two at the exhaust exit plane with dilution added at different locations and another probe located 10 m downstream. For emissions measured at the downstream probe when the engine was operating at high power, all fuels produced chemically similar organic PM, dominated by C(x)H(y) fragments, suggesting the presence of long chain alkanes. The second largest contribution came from C(x)H(y)O(z) fragments, possibly from carbonyls or alcohols. For the nondiesel fuels, the highest loadings of organic PM were from the downstream probe at high power. Conversely, the diesel based fuels produced more organic material at low power from one of the exit plane probes. Differences in the composition of the PM for certain fuels were observed as the engine power decreased to idle and the measurements were made closer to the exit plane.

Polycyclic aromatic hydrocarbon emissions from the combustion of alternative fuels in a gas turbine engine.

We report on the particulate-bound polycyclic aromatic hydrocarbons (PAH) in the exhaust of a test-bed gas turbine engine when powered by Jet A-1 aviation fuel and a number of alternative fuels: Sasol fully synthetic jet fuel (FSJF), Shell gas-to-liquid (GTL) kerosene, and Jet A-1/GTL 50:50 blended kerosene. The concentration of PAH compounds in the exhaust emissions vary greatly between fuels. Combustion of FSJF produces the greatest total concentration of PAH compounds while combustion of GTL produces the least. However, when PAHs in the exhaust sample are measured in terms of the regulatory marker compound benzo[a]pyrene, then all of the alternative fuels emit a lower concentration of PAH in comparison to Jet A-1. Emissions from the combustion of Jet A-1/GTL blended kerosene were found to have a disproportionately low concentration of PAHs and appear to inherit a greater proportion of the GTL emission characteristics than would be expected from volume fraction alone. The data imply the presence of a nonlinear relation between fuel blend composition and the emission of PAH compounds. For each of the fuels, the speciation of PAH compounds present in the exhaust emissions were found to be remarkably similar (R(2) = 0.94-0.62), and the results do provide evidence to support the premise that PAH speciation is to some extent indicative of the emission source. In contrast, no correlation was found between the PAH species present in the fuel with those subsequently emitted in the exhaust. The results strongly suggests that local air quality measured in terms of the particulate-bound PAH burden could be significantly improved by the use of GTL kerosene either blended with or in place of Jet A-1 kerosene.

Composition of smoke generated by landing aircraft.

A combination of techniques has been used to examine the composition of smoke generated by landing aircraft. A sample of dust from the undercarriage from several commercial airliners was examined with SEM/EDX (Scanning Electron Microscope/Energy Dispersive X-ray) to determine its elemental composition and also with an aerosizer/aerodisperser in order to measure the particle size spectrum. The observed size spectrum was bimodal with equal numbers of particles at peaks of aerodynamic diameter ∼10 µm and ∼50 µm. The EDX analysis suggested that the former peak is carbonaceous, while the latter consists of elements typical of an asphalt concrete runway. In the field, a scanning Lidar, in combination with optical and condensation particle counters, was deployed to obtain limits to the number concentration and size of such particles. Most of the (strong) Lidar signal probably arose from the coarser 50 µm aerosol, while respirable aerosol was too sparse to be detected by the optical particle counters.