Aortic valve implantation-induced conduction block as a framework towards a uniform electrocardiographic definition of left bundle branch block.

INTRODUCTION: New-onset left bundle branch block (LBBB) following transcatheter or surgical aortic valve replacement (LBBBAVI) implies a proximal pathogenesis of LBBB. This study compares electrocardiographic characteristics and concordance with LBBB definitions between LBBBAVI and non-procedure-induced LBBB controls (LBBBcontrol). METHODS: All LBBBAVI patients at Ghent University Hospital between 2013 and 2019 were enrolled in the study. LBBBAVI patients were matched for age, sex, ischaemic heart disease and ejection fraction to LBBBcontrol patients in a 1:2 ratio. For inclusion, a non-strict LBBB definition was used (QRS duration ≥ 120 ms, QS or rS in V1, absence of Q waves in V5-6). Electrocardiograms were digitally analysed and classified according to three LBBB definitions: European Society of Cardiology (ESC), Strauss and American Heart Association (AHA). RESULTS: A total of 177 patients (59 LBBBAVI and 118 LBBBcontrol) were enrolled in the study. LBBBAVI patients had more lateral QRS notching/slurring (100% vs 85%, p = 0.001), included a higher percentage with a QRS duration ≥ 130 ms (98% vs 86%, p = 0.007) and had a less leftward oriented QRS axis (-15° vs -30°, p = 0.013) compared to the LBBBcontrol group. ESC and Strauss criteria were fulfilled in 100% and 95% of LBBBAVI patients, respectively, but only 18% met the AHA criteria. In LBBBcontrol patients, concordance with LBBB definitions was lower than in the LBBBAVI group: ESC 85% (p = 0.001), Strauss 68% (p < 0.001) and AHA 7% (p = 0.035). No differences in electrocardiographic characterisation or concordance with LBBB definitions were observed between LBBBAVI and LBBBcontrol patients with lateral QRS notching/slurring. CONCLUSION: Non-uniformity exists among current LBBB definitions concerning the detection of proximal LBBB. LBBBAVI may provide a framework for more consensus on defining proximal LBBB.

Air pollution and ST-elevation myocardial infarction: A case-crossover study of the Belgian STEMI registry 2009-2013.

BACKGROUND: Previous studies have shown that air pollution particulate matter (PM) is associated with an increased risk for myocardial infarction. The effects of air pollution on the risk of ST-elevation myocardial infarction (STEMI), in particular the role of gaseous air pollutants such as NO2 and O3 and the susceptibility of specific populations, are still under debate. METHODS: All patients entered in the Belgian prospective STEMI registry between 2009 and 2013 were included. Based on a validated spatial interpolation model from the Belgian Environment Agency, a national index was used to address the background level of air pollution exposure of Belgian population. A time-stratified and temperature-matched case-crossover analysis of the risk of STEMI was performed. RESULTS: A total of 11,428 STEMI patients were included in the study. Each 10µg/m3 increase in PM10, PM2.5 and NO2 was associated with an increased odds ratio (ORs) of STEMI of 1.026 (CI 95%: 1.005-1.048), 1.028 (CI 95%: 1.003-1.054) and 1.051 (CI 95%: 1.018-1.084), respectively. No effect of O3 was found. STEMI was associated with PM10 exposure in patients ≥75y.o. (OR: 1.046, CI 95%: 1.002-1.092) and with NO2 in patients ≤54y.o. (OR: 1.071, CI 95%: 1.010-1.136). No effect of air pollution on cardiac arrest or in-hospital STEMI mortality was found. CONCLUSION: PM2.5 and NO2 exposures incrementally increase the risk of STEMI. The risk related to PM appears to be greater in the elderly, while younger patients appear to be more susceptible to NO2 exposure.

PLGA nanoparticles and nanosuspensions with amphotericin B: Potent in vitro and in vivo alternatives to Fungizone and AmBisome.

This paper describes the development of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) and nanosuspensions with the polyene antibiotic amphotericin B (AmB). The nanoformulations were prepared using nanoprecipitation and were characterised with respect to size, zeta potential, morphology, drug crystallinity and content. Standard in vitro sensitivity tests were performed on MRC-5 cells, red blood cells, Leishmania infantum promastigotes and intracellular amastigotes and the fungal species Candida albicans, Aspergillus fumigatus and Trichophyton rubrum. The in vivo efficacy was assessed and compared to that of Fungizone and AmBisome in the acute A. fumigatus mouse model at a dose of 2.5 and 5.0mg/kg AmB equivalents. The developed AmB nanoformulations were equivalently or more effective against the different Leishmania stages and axenic fungi in comparison with the free drug. The in vitro biological activity, and especially hemolytic activity, clearly depended on the preparation parameters of the different nanoformulations. Further, we demonstrated that the superior in vitro antifungal activity could be extrapolated to the in vivo situation. At equivalent dose, the optimal AmB-loaded PLGA NP was about two times and the AmB nanosuspension about four times more efficacious in reducing the total burden than AmBisome. The developed AmB nanomedicines could represent potent and cost-effective alternatives to Fungizone and AmBisome.

Automatic segmentation of in-vivo intra-coronary optical coherence tomography images to assess stent strut apposition and coverage.

The implantation of intracoronary stents is currently the standard approach for the treatment of coronary atherosclerotic disease. The widespread adoption of this technology has boosted an intensive research activity in this domain, with continuous improvements in the design of these devices, aiming at reducing problems of restenosis (re-narrowing of the stented segment) and thrombosis (sudden occlusion due to thrombus formation). Recently, a new, light-based intracoronary imaging modality, optical coherence tomography (OCT), was developed and introduced into clinical practice. Due to its very high axial resolution (10-15 µm), it allows for in vivo evaluation of both stent strut apposition and neointima coverage (a marker of healing of the treated segment). As such, it provides valuable information on proper stent deployment, on the behaviour of different stent types in-vivo and on the effect of new types of stents (e.g. drug-eluting stents) on vessel wall healing. However, the major drawback of the current OCT methodology is that analysis of these images requires a tremendous amount of-currently manual-post-processing. In this manuscript, an algorithm is presented that allows for fully automated analysis of stent strut apposition and coverage in coronary arteries. The vessel lumen and stent struts are automatically detected and segmented through analysis of the intensity profiles of the A-lines. From these data, apposition and coverage can then be measured automatically. The algorithm was validated using manual assessments by two experienced operators as a reference. High Pearson's correlation coefficients were found (R = 0.96-0.97) between the automated and manual measurements while Bland-Altman analysis showed no significant bias with good limits of agreement. As such, it was shown that the presented algorithm provides a robust and fast tool to automatically estimate apposition and coverage of stent struts in in-vivo OCT pullbacks. This will be important for the integration of this technology in clinical routine and for the analysis of datasets of larger clinical trials.

Iatrogenic left main coronary artery dissection.

We present a case of iatrogenic left main coronary artery dissection, successfully treated by prompt bail-out stenting, and provide a brief discussion on its occurrence and treatment, as well as the immediate and long-term outcome of percutaneous coronary intervention, including our own single-centre experience, for this potentially catastrophic complication.

Solution calorimetry as an alternative approach for dissolution testing of nanosuspensions.

The formulation of poorly soluble drugs as nanocrystals/nanosuspensions has rapidly evolved during the past decade into a mature drug-delivery strategy. The major characteristic of these systems is the high drug dissolution rate, enabling bioavailability enhancement after oral administration. It is therefore of great importance to have access to analytical methodology that is able to accurately monitor the extreme fast dissolution process of such formulations. The aim of the present study was to evaluate solution calorimetry as a novel approach to measure the dissolution rate of nanosuspensions by recording the temperature change in the dissolution vessel during the dissolution process of the nanocrystals. The applicability was tested on different nanosuspensions made up of three model drugs: naproxen, cinnarizine and an investigational API, i.e. compound A. The dissolution process of all nanosuspensions investigated was completed within less than 1 min. During this period, sufficient data points were collected to transform temperature offset data to cumulative heat of solution pointing to the potential of this technique. However, of significant concern is the fact that this technique measures the total heat produced or consumed by all processes that occur during the dissolution, e.g. the heat of mixing when the nanosuspension comes in contact with the dissolution medium. Erroneous conclusions will result if phenomena other than dissolution are not accounted for.