SK channels contribution to ventricular electrophysiology in heart failure patients

Heart failure (HF) is characterized by deterioration of the electrical and contractile function of the heart due to structural and functional remodelling, leading to development of arrhythmias and increased sudden cardiac death risk. SK channels are a type of calcium-activated potassium channels that do not play a relevant role in normal ventricular electrophysiology. However, it has been hypothesized that these channels become more relevant in pathologies such as HF. Nontheless, their role in human ventricular electrophysiology is not fully characterized

Automatic quantification of cardiomyocyte dimensions and connexin 43 lateralization in fluorescence images

Cardiomyocytes’ geometry and connexin 43 (CX43) amount and distribution are structural features that play a pivotal role in electrical conduction. Their quantitative assessment is of high interest in the study of arrhythmias, but it is usually hampered by the lack of automatic tools. In this work, we propose a software algorithm (Myocyte Automatic Retrieval and Tissue Analyzer, MARTA) to automatically detect myocytes from fluorescent microscopy images of cardiac tissue, measure their morphological features and evaluate the expression of CX43 and its degree of lateralization. The proposed software is based on the generation of cell masks, contouring of individual cells, enclosing of cells in minimum area rectangles and splitting of these rectangles into end-to-end and middle compartments to estimate CX43 lateral-to-total ratio. Application to human ventricular tissue images shows that mean differences between automatic and manual methods in terms of cardiomyocyte length and width are below 4 µm. The percentage of lateral CX43 also agrees between automatic and manual evaluation, with the interquartile range approximately covering from 3% to 30% in both cases. MARTA is not limited by fiber orientation and has an optimized speed by using contour filtering, which makes it run hundreds of times faster than a trained expert. Developed for CX43 studies in the left ventricle, MARTA is a flexible tool applicable to morphometric and lateralization studies of other markers in any heart chamber or even skeletal muscle. This open-access software is available online

Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis

Age-related fibrosis in the left ventricle (LV) has been mainly studied in animals by assessing collagen content. Using second-harmonic generation microscopy and image processing, we evaluated amount, aggregation and spatial distribution of LV collagen in young to old pigs, and middle-age and elder living donors. All collagen features increased when comparing adult and old pigs with young ones, but not when comparing adult with old pigs or middle-age with elder individuals. Remarkably, all collagen parameters strongly correlated with lipofuscin, a biological age marker, in humans. By building patient-specific models of human ventricular tissue electrophysiology, we confirmed that amount and organization of fibrosis modulated arrhythmia vulnerability, and that distribution should be accounted for arrhythmia risk assessment. In conclusion, we characterize the age-associated changes in LV collagen and its potential implications for ventricular arrhythmia development. Consistency between pig and human results substantiate the pig as a relevant model of age-related LV collagen dynamics. © 2022 The Author(s

Impact of the SARS-CoV-2 (COVID19) pandemic on the morbidity and mortality of high risk patients undergoing surgery: a non-inferiority retrospective observational study

Background: During the COVID-19 crisis it was necessary to generate a specific care network and reconvert operating rooms to attend emergency and high-acuity patients undergoing complex surgery. The aim of this study is to classify postoperative complications and mortality and to assess the impact that the COVID-19 pandemic may have had on the results. Methods: this is a non-inferiority retrospective observational study. Two different groups of surgical patients were created: Pre-pandemic COVID and Pandemic COVID. Severity of illness was rated according to the Diagnosis-related Groups (DRG) score. Comparisons were made between groups and between DRG severity score-matched samples. Non-inferiority was set at up to 10 % difference for grade III to V complications according to the Clavien-Dindo classification, and up to 2 % difference in mortality. Results: A total of 1649 patients in the PreCOVID group and 763 patients in the COVID group were analysed; 371 patients were matched for DRG severity score 3-4 (236 preCOVID and 135 COVID). No differences were found in relation to re-operation (22.5 % vs. 21.5 %) or late admission to critical care unit (5.1 % vs. 4.5 %). Clavien grade III to V complications occurred in 107 patients (45.3 %) in the PreCOVID group and in 56 patients (41.5 %) in the COVID group, and mortality was 12.7 % and 12.6 %, respectively. During the pandemic, 3 % of patients tested positive for Covid-19 on PCR: 12 patients undergoing elective surgery and 11 emergency surgery; there were 5 deaths, 3 of which were due to respiratory failure following Covid-19-induced pneumonia. Conclusions: Although this study has some limitations, it has shown the non-inferiority of surgical outcomes during the COVID pandemic, and indicates that resuming elective surgery is safe

Improved Methods for Processing Optical Mapping Signals From Human Left Ventricular Tissues at Baseline and Following Adrenergic Stimulation

Optical mapping (OM) allows ex vivo measurement of electrophysiological signals at high spatio-temporal resolution, but the signal-to-roise ratio is commonly low. A variety of software options have been proposed to extract relevant information from OM recordings, being ElectroMap the most advanced tool currently available. In this study, improved methods are presented for processing OM signals of cardiac transmembrane voltage. A software called OMap is developed that incorporates novel techniques into ElectroMap for improved baseline drift removal, spatiotemporal filtering and characterization of action potential duration (APD) maps. In synthetically generated signals contaminated with baseline wander, white noise and the combination of both, the errors in APD maps between noisy and clean signals are remarkably lower for OMap than for ElectroMap, particularly for high noise levels. In OM signals recorded from human ventricular tissue specimens, OMap allows to clearly characterize the APD shortening effect induced by ß-adrenergic stimulation, whereas ElectroMap renders highly overlapped APD distributions for baseline and ß-adrenergic stimulation. In conclusion, improved methods are proposed and tested to characterize human ventricular electrophysiology from noisy OM recordings.Fil: Perez Zabalza, Maria. Universidad de Zaragoza; EspañaFil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Rhyins, Julia. Northeastern University; Estados UnidosFil: Mountris, Kostantinos A.. Universidad de Zaragoza; EspañaFil: Vallejo Gil, Jose M.. Hospital Miguel Servet; EspañaFil: Fresneda Roldan, Pedro C.. Hospital Miguel Servet; EspañaFil: Fananas-Mastral, Javier. Hospital Miguel Servet; EspañaFil: Matamal Adell, Marta. Hospital Miguel Servet; EspañaFil: Sorribas Berjon, Fernando. Hospital Miguel Servet; EspañaFil: Vazquez Sancho, Manuel. Hospital Miguel Servet; EspañaFil: Ballester Cuenca, Carlos. Hospital Miguel Servet; EspañaFil: Segovia Roldan, Margarita. Universidad de Zaragoza; EspañaFil: Olivan Viguera, Aida. Universidad de Zaragoza; EspañaFil: Pueyo, Esther. Universidad de Zaragoza; Españ

Minimally invasive system to reliably characterize ventricular electrophysiology from living donors

Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. However, access to human ventricular samples is scarce. We aim to demonstrate that slices from small transmural core biopsies collected from living donors during routine cardiac surgery preserve structural and functional properties of larger myocardial specimens, allowing accurate electrophysiological characterization. In pigs, we compared left ventricular transmural core biopsies with transmural tissue blocks from the same ventricular region. In humans, we analyzed transmural biopsies and papillary muscles from living donors. All tissues were vibratome-sliced. By histological analysis of the transmural biopsies, we showed that tissue architecture and cellular organization were preserved. Enzymatic and vital staining methods verified viability. Optically mapped transmembrane potentials confirmed that action potential duration and morphology were similar in pig biopsies and tissue blocks. Action potential morphology and duration in human biopsies and papillary muscles agreed with published ranges. In both pigs and humans, responses to increasing pacing frequencies and ß-adrenergic stimulation were similar in transmural biopsies and larger tissues. We show that it is possible to successfully collect and characterize tissue slices from human myocardial biopsies routinely extracted from living donors, whose behavior mimics that of larger myocardial preparations both structurally and electrophysiologically

Development and validation of a score to predict postoperative respiratory failure in a multicentre European cohort : A prospective, observational study

BACKGROUND Postoperative respiratory failure (PRF) is the most frequent respiratory complication following surgery. OBJECTIVE The objective of this study was to build a clinically useful predictive model for the development of PRF. DESIGN A prospective observational study of a multicentre cohort. SETTING Sixty-three hospitals across Europe. PATIENTS Patients undergoing any surgical procedure under general or regional anaesthesia during 7-day recruitment periods. MAIN OUTCOME MEASURES Development of PRF within 5 days of surgery. PRF was defined by a partial pressure of oxygen in arterial blood (PaO2) less than 8 kPa or new onset oxyhaemoglobin saturation measured by pulse oximetry (SpO(2)) less than 90% whilst breathing room air that required conventional oxygen therapy, noninvasive or invasive mechanical ventilation. RESULTS PRF developed in 224 patients (4.2% of the 5384 patients studied). In-hospital mortality [95% confidence interval (95% CI)] was higher in patients who developed PRF [10.3% (6.3 to 14.3) vs. 0.4% (0.2 to 0.6)]. Regression modelling identified a predictive PRF score that includes seven independent risk factors: low preoperative SpO(2); at least one preoperative respiratory symptom; preoperative chronic liver disease; history of congestive heart failure; open intrathoracic or upper abdominal surgery; surgical procedure lasting at least 2 h; and emergency surgery. The area under the receiver operating characteristic curve (c-statistic) was 0.82 (95% CI 0.79 to 0.85) and the Hosmer-Lemeshow goodness-of-fit statistic was 7.08 (P = 0.253). CONCLUSION A risk score based on seven objective, easily assessed factors was able to predict which patients would develop PRF. The score could potentially facilitate preoperative risk assessment and management and provide a basis for testing interventions to improve outcomes. The study was registered at ClinicalTrials.gov (identifier NCT01346709)