Interindividual Age-Independent Differences in Human CX43 Impact Ventricular Arrhythmic Risk.

Connexin 43 (CX43) is one of the major components of gap junctions, the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle. There is limited information on the histological changes of CX43 with age and their effect on electrophysiology, especially in humans. Here, we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling. We assessed its quantity, degree of lateralization, and spatial heterogeneity together with fibrotic deposition. We observed no significant age-related remodeling of CX43. Only spatial heterogeneity increased slightly with age, and this increase was better explained by biological age than by chronological age. Importantly, we found that CX43 features varied considerably among individuals in our population with no relevant relationship to age or fibrosis content, in contrast to animal species. We used our experimental results to feed computational models of human ventricular electrophysiology and to assess the effects of interindividual differences in specific features of CX43 and fibrosis on conduction velocity, action potential duration, and arrhythmogenicity. We found that larger amounts of fibrosis were associated with the highest arrhythmic risk, with this risk being increased when fibrosis deposition was combined with a reduction in CX43 amount and/or with an increase in CX43 spatial heterogeneity. These mechanisms underlying high arrhythmic risk in some individuals were not associated with age in our study population. In conclusion, our data rule out CX43 remodeling as an age-related arrhythmic substrate in the population beyond midlife, but highlight its potential as a proarrhythmic factor at the individual level, especially when combined with increased fibrosis.

Quality of Life and Post-Surgical Complications in Patients on Chronic Antiplatelet Therapy with Proximal Femur Fracture: 12-Month Follow-Up after Implementing a Strategy to Shorten the Time to Surgery.

BACKGROUND: We evaluated a strategy to shorten the time from admission to surgery in patients with proximal femur fractures on chronic antiplatelet therapy. We reported a 12-month follow-up on complications and quality of life (QoL). METHODS: Multicentre, open-label, randomized, parallel clinical trial. Patients were randomized to either early platelet function-guided surgery (experimental group) or delayed surgery (control group). Medical and surgical complications and QoL (EQ-5D-5L questionnaire) were assessed during the hospital stay, and after hospital discharge at 30 days, and 6 and 12 months. RESULTS: From 156 randomized patients, 143 patients underwent surgery. The mean age was 85.5 (7.8) years and 68.0% were female. After hospital discharge, 5.7% of patients had surgical wound complications and 55.9% had medical complications, with 42.7% having serious adverse events. QoL improved significantly after surgery, with the best scores at the six-month follow-up. The overall mortality was 32.2%. There were no differences between early and delayed surgery groups in any assessed outcomes. CONCLUSION: It seems safe to reduce the time of surgery under neuraxial anaesthesia in patients with hip fractures on chronic antiplatelet therapy by platelet function testing. QoL in particular improves in the first six months after surgery.

Impacto del uso de la mascarilla durante la realización de la prueba de esfuerzo en tapiz rodante / Impact of face masks during the treadmill exercise tests

Introducción y objetivos: Existe poca literatura sobre el uso de la mascarilla en la realización de una prueba de esfuerzo (PE) durante la pandemia de COVID-19. El objetivo de este estudio es analizar el impacto del uso de la mascarilla durante la realización de una PE en un grupo de pacientes que han realizado al menos una PE con y sin mascarilla.MétodosEstudio observacional retrospectivo unicéntrico de pacientes sometidos a una PE con tapiz rodante. El criterio de inclusión fue tener más de 16años y haber realizado al menos una PE en época prepandemia (sin mascarilla) y pospandemia (con mascarilla).ResultadosUn total de 1.655 pacientes fueron incluidos en el estudio; 935 (56,5%) eran varones y 720 (43,5%) eran mujeres. La edad media fue de 57,3±14,9 años y el tiempo medio de seguimiento fue de 15,4 meses. El 53% de los pacientes presentaron antecedentes personales de hipertensión arterial; el 20%, dislipemia; el 12%, diabetes mellitus; el 8%, hábito tabáquico; el 19%, cardiopatía isquémica; el 5%, EPOC; el 8%, asma bronquial, y el 8%, fibrilación auricular. En la casi totalidad de las variables estudiadas en la PE, incluida la aparición de arritmias ventriculares, no se evidenciaron diferencias significativas, ni por edad ni por sexo, salvo la existencia de una muy leve disminución en la capacidad de ejercicio con el uso de mascarilla en los pacientes de mayor edad (>65años).ConclusionesEl uso de mascarillas quirúrgicas o FFP2 durante la PE no afectó a la capacidad funcional, a la presión arterial, a la frecuencia cardiaca ni incrementó las arritmias ventriculares. (AU)

Introduction and objective: There is little literature on the use of face masks in a treadmill test (TMT) during the COVID-19 pandemic. The objective of this study is to analyze the impact of face masks during a TMT performed during the prepandemic (without face mask) and postpandemic (with face mask) era.MethodsRetrospective observational unicentric study of patients undergoing TMT. The inclusion criterion were being over 16years old and having performed at least one TMT in the prepandemic and postpandemic period.ResultsOne thousand six hundred fifty-five patients were included in the study. Nine hundred thirty-five (56.5%) were men and 720 (43.5%) women. The mean age was 57.3±14.9 and the mean follow-up time was 15.4 months. Fifty-three percent patients had arterial hypertension, 20% dyslipidemia, 12% diabetes mellitus, 8% smoking habit, 19% personal history of ischemic heart disease, 5% COPD, 8% bronchial asthma, and 8% atrial fibrillation. In almost all the variables studied in PE, including the appearance of ventricular arrhythmias, no significant differences were found, neither by age nor sex, except for the existence of a very slight decrease in exercise capacity with mask use in older patients (>65years).ConclusionsThe use of surgical or FFP2 face masks during the TMT did not affect functional capacity, blood pressure, heart rate, or increased ventricular arrhythmias. (AU)

Avanzamos en salud gracias a la aplicación salud infantil papi: programa de actividades preventivas de la infancia y adolescencia / We advance in health thanks to the PAPI children's health application

Introducción: La estructura familiar y la crianza están cambiando en la sociedad, se incrementa el sedentarismo, el uso de pantallas y de redes sociales. Las familias y los profesionales sanitarios deben aprender a educar, adaptando sus consejos de salud al nuevo entorno social y digital. Material y métodos: Para renovar el Programa de Salud Infantil (PSI) de la Asociación Española de Pediatría de Atención Primaria (AEPap) se envió una encuesta a los representantes de más de 5.000 pediatras. Se incorporaron aportaciones de los programas preventivos de Andalucía, Baleares y Asturias. Se distribuyeron las diferentes intervenciones y consejos en 9 grupos etarios. Resultados: Parte de las recomendaciones están basadas en el trabajo del grupo PrevInfad, llevadas a cabo con metodología de medicina basada en la evidencia, mediante la evaluación y la síntesis de la evidencia de las actividades preventivas propuestas. La AEPap considera que el PSI debe realizarse por el equipo de pediatría: pediatra y enfermera/o, potenciándose así las competencias específicas. La OMS considera primordial empoderar a las personas, familias y comunidades para que optimicen su salud al convertirlas en cuidadoras de sí mismas y de otros, dotándolas de herramientas que protegen el bienestar. Conclusiones: Por todo ello se decide plasmar el PSI en formato de app para dispositivos móviles gratuita, como método innovador y asequible de divulgación de salud infantojuvenil. Se informa sobre consejos de crianza para los familiares, para los niños/as y adolescentes y describe las revisiones de salud para los sanitarios. (AU)

Introduction: The family structure and parenting are changing in society, sedentary lifestyle, the use of screens and social networks is increasing. Families and health professionals must learn to educate, adapting their health advice to the new social and digital environment. Materials and methods: A survey was sent to the representatives of more than 5000 paediatricians to renew the Well Child Visits Program of the Spanish Association of Primary Care Paediatrics (AEPap). Contributions from preventive programs from Andalusia, the Balearic Islands and Asturias were incorporated. The different interventions and advice were distributed in nine age groups. Results: Part of the recommendations are based on the work of the PrevInfad group. It uses the methodology of evidence-based medicine and performs the evaluation and synthesis of the evidence in the proposed preventive activities. The AEPap considers that the Well Child Program should be carried out by the paediatric team: the paediatrician and the nurse, thus enhancing specific skills. The WHO considers it is essential to empower individuals, families, and communities to optimize their health by making them caretakers of themselves and others, equipping them with tools that protect their well-being. Conclusions: Hence, it was decided to capture the Well Child Program in the format of a free APP for mobile devices, as an innovative and affordable method of disseminating child and adolescent health. Information is given on parenting advice for family members, for children and adolescents and describes health check-ups for health workers. (AU)

We advance in health thanks to the PAPI children's health application.

INTRODUCTION: The family structure and parenting are changing in society, sedentary lifestyle, the use of screens and social networks is increasing. Families and health professionals must learn to educate, adapting their health advice to the new social and digital environment. MATERIALS AND METHODS: A survey was sent to the representatives of more than 5000 paediatricians to renew the Well Child Visits Programme of the Spanish Association of Primary Care Paediatrics (AEPap). Contributions from preventive programmes from Andalusia, the Balearic Islands and Asturias were incorporated. The different interventions and advice were distributed in nine age groups. RESULTS: Part of the recommendations are based on the work of the PrevInfad group. It uses the methodology of evidence-based medicine and performs the evaluation and synthesis of the evidence in the proposed preventive activities. The AEPap considers that the Well Child Programme should be carried out by the paediatric team: the paediatrician and the nurse, thus enhancing specific skills. The WHO considers it essential to empower individuals, families, and communities to optimize their health by making them caretakers of themselves and others, equipping them with tools that protect their well-being. CONCLUSION: Hence, it was decided to capture the Well Child Programme in the format of a free APP for mobile devices, as an innovative and affordable method of disseminating child and adolescent health. Information is given on parenting advice for family members, for children and adolescents and describes health check-ups for health workers.

Impact of face masks during the treadmill exercise tests. / Impacto del uso de la mascarilla durante la realización de la prueba de esfuerzo en tapiz rodante.

INTRODUCTION AND OBJECTIVE: There is little literature on the use of face masks in a treadmill test (TMT) during the COVID-19 pandemic. The objective of this study is to analyze the impact of face masks during a TMT performed during the prepandemic (without face mask) and postpandemic (with face mask) era. METHODS: Retrospective observational unicentric study of patients undergoing TMT. The inclusion criterion were being over 16years old and having performed at least one TMT in the prepandemic and postpandemic period. RESULTS: One thousand six hundred fifty-five patients were included in the study. Nine hundred thirty-five (56.5%) were men and 720 (43.5%) women. The mean age was 57.3±14.9 and the mean follow-up time was 15.4 months. Fifty-three percent patients had arterial hypertension, 20% dyslipidemia, 12% diabetes mellitus, 8% smoking habit, 19% personal history of ischemic heart disease, 5% COPD, 8% bronchial asthma, and 8% atrial fibrillation. In almost all the variables studied in PE, including the appearance of ventricular arrhythmias, no significant differences were found, neither by age nor sex, except for the existence of a very slight decrease in exercise capacity with mask use in older patients (>65years). CONCLUSIONS: The use of surgical or FFP2 face masks during the TMT did not affect functional capacity, blood pressure, heart rate, or increased ventricular arrhythmias.

A Common Variant at the 3'untranslated Region of the CCL7 Gene (rs17735770) Is Associated With Decreased Susceptibility to Coronary Heart Disease.

Monocytes participate in the development of atherosclerosis through the action of cytokines and other inflammatory mediators. Among them, CCR2 and its ligands, CCL2 and CCL7 play an important role, so the main objective of this work was to determine whether genetic variants affecting their activity were associated with cardiovascular disease. A cohort of 519 patients that have suffered coronary events was analyzed under a propensity score-matching protocol selecting a homogeneous set of cases and controls, according to age, sex, smoking status, dyslipidemia, arterial hypertension and type 2 diabetes as risk factors. While dyslipidemia and arterial hypertension were more prevalent among patients with angina pectoris, current smoking status and elevated inflammatory markers, including total leukocyte and monocyte counts, were more likely associated with acute coronary events. Propensity score matching analysis, performed to eliminate the influence of these risk factors and highlight genetic modifiers, revealed that a single nucleotide variant, rs17735770 at the 3'untranslated region of the CCL7 gene transcript, was associated with decreased cardiovascular risk in a group represented mostly by men, with an average age of 57, and without significant differences in traditional risk factors. Furthermore, the presence of this variant altered the local mRNA structure encompassing a binding site for miR-23ab, resulting in increased translation of a reporter gene in a miR23 independent fashion. The rs17735770 genetic variant led to increased expression of CCL7, a potential antagonist of CCR2 at inflammatory sites, where it could play a meaningful role during the evolution of atherosclerosis.

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.

COVID-19 in children: clinical and epidemiological spectrum in the community.

Most publications on pediatric COVID-19 in Spain were performed at the beginning of the pandemic when some diagnostic tools were not widely available. This study aims to show the real spectrum of the infection based on wide detection of cases due to symptoms and contact tracing. A descriptive and analytical observational study was performed including pediatric cases (0 to 14 years) from the region of Aragón between May 12 and October 31, 2020. Diagnostics was by PCR detection of viral RNA, rapid antigen detection test, or positive IgG serology. There were 5933 positive children included. Of them, 49.03% were women. The mean age was 7.53 ± 4.28 years. The source of infection could not be determined in 17.8% of cases. As for the rest, was determined to be within the family environment in 67.8%. The percentage of asymptomatic patients was 50.3%. Among symptomatic patients, fever (58.1%) and cough (46.7%) were the most frequent symptoms. Hospitalization was required in 0.52% of infected, intensive care unit admission was on 0.05%, and there was one death (0.02%). Children under the age of one presented some symptoms more frequently (71.6% vs 48.5%; OR 2.68; 95% CI 2.08 to 3.45; p < 0.001) and required more hospitalizations (3.9% vs 0.34%; OR 11.52; 95% CI 5.65 to 23.52; p < 0.001).Conclusion: In our environment, SARS-CoV-2 infection is like other mild respiratory viral infections in the population under the age of 15. The contagion occurs mainly in the family environment, the number of asymptomatic is high, being the symptoms mild and the complications very infrequent. What is Known: • Pediatric infection produced by SARS-CoV-2 has manifested as a mild disease in relation to adult age, although with higher affectation at the youngest ages. • Nearly all studies on epidemiology and clinical spectrum of the disease were conducted with patients diagnosed at the beginning of the pandemic. By then, diagnostic tools were only available in hospitals and in emergency units. What is New: • Once diagnostic means were available in primary care medicine and were used not only for the diagnosis of clinical symptoms of the patient, but for the tracing of case contacts, a much more precise approach to the epidemiology and clinical manifestations of the disease was allowed, as described in this study.

Mental well-being among patients with congenital heart disease and heart failure during the COVID-19 pandemic.

Patients with congenital heart disease (CHD) show increasing survival. We evaluated the influence of COVID-19 confinement on the mental well-being of patients with CHD. Descriptive, cross-sectional, observational epidemiological study in a cohort of 242 patients with CHD over 14 years old recruited consecutively from a single adolescent and adult CHD outpatient unit. Patients were sent an online questionnaire to determine clinical, demographic and the 12-element general health questionnaire (GHQ-12) data during the COVID-19 quarantine. 242 out of 407 (59%) patients with CHD, to whom the questionnaire was sent, responded to the survey. 98 (42%) patients were between 14 and 24 years old and 133 (58%) were over 25 years old. Of the total, 119 (51%) were male. 123 (51%), 88 (36%) and 31 (13%) patients with CHD had mild, moderate, and severe anatomical complexity respectively. 11 (4.5%) out of 242 patients with CC presented heart failure (HF) symptoms, requiring 18% of them admission to the hospital emergency department during the pandemic (P=0.002). In relation to the GHQ-12 questionnaire, patients with CHD and HF enjoyed less their daily activities (81% vs. 51%, P=0.043) and had less self-confidence (46% vs. 18%, P=0.041) than those without HF symptoms. In conclusion, patients with CHD and HF, during the COVID-19 quarantine, presented a lower capacity to enjoy daily activities and self-confidence than CHD without HF symptoms.

Early Surgery with Neuraxial Anaesthesia in Patients on Chronic Antiplatelet Therapy with a Proximal Femur Fracture: Multicentric Randomised Clinical Trial.

BACKGROUND: Patients with proximal femur fracture on antiplatelet treatment benefit from early surgery. Our goal was to perform early surgery under neuraxial anaesthesia when indicated by the platelet function test. METHODS: We conducted a multicentre randomised open-label parallel clinical trial. Patients were randomised to either early platelet function-guided surgery (experimental group) or delayed surgery (control group). Early surgery was programmed when the functional platelet count (as measured by Plateletworks) was >80 × 109/L. The primary outcome was the emergency admission-to-surgery interval. Secondary outcomes were platelet function, postoperative bleeding, medical and surgical complications, and mortality. RESULTS: A total of 156 patients were randomised, with 78 in each group, with a mean (SD) age of 85.96 (7.9) years, and 67.8% being female. The median (IQR) time to surgery was 2.3 (1.5-3.7) days for the experimental group and 4.9 (4.4-5.6) days for the control group. One-third of patients did not achieve the threshold functional platelet count on the first day of admission, requiring more than one test. There was no difference in clinical outcomes between groups. CONCLUSIONS: A strategy individualised according to the platelet function test shortens the time to proximal femur fracture surgery under neuraxial anaesthesia in patients on chronic antiplatelet treatment. Better powered randomised clinical trials are needed to further evaluate the clinical impact and safety of this strategy.

Trends in Food Preferences and Sustainable Behavior during the COVID-19 Lockdown: Evidence from Spanish Consumers.

The COVID-19 pandemic poses a threat to global food security, and it changes consumers' food buying and consumption behavior. This research not only investigates trends in Spanish consumers' general food shopping and consumption habits during the lockdown, but also investigates these trends from the perspective of sustainable purchasing. Specifically, total food consumption (C), food expenditure (E), and purchase of food with sustainable attributes (S) were measured. Data were collected from a semi-structured questionnaire which was distributed online among 1203 participants. The logit models showed that gender, age, employment status, and consumers' experiences were associated with total food consumption and expenditure during the lockdown. In addition, consumers' risk perceptions, shopping places, trust level in information sources, and risk preference were highly essential factors influencing consumers' preferences and sustainable behavior. Consumers' objective knowledge regarding COVID-19 was related to expenditure. Furthermore, family structure only affected expenditure, while income and place of residence influenced food consumption. Mood was associated with expenditure and the purchase of sustainable food. Household size affected purchasing behavior towards food with sustainable attributes. This research provides references for stakeholders that help them to adapt to the new COVID-19 situation.

Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution.

Aging is the main risk factor for cardiovascular diseases. In humans, cardiac aging remains poorly characterized. Most studies are based on chronological age (CA) and disregard biological age (BA), the actual physiological age (result of the aging rate on the organ structure and function), thus yielding potentially imperfect outcomes. Deciphering the molecular basis of ventricular aging, especially by BA, could lead to major progresses in cardiac research. We aim to describe the transcriptome dynamics of the aging left ventricle (LV) in humans according to both CA and BA and characterize the contribution of microRNAs, key transcriptional regulators. BA is measured using two CA-associated transcriptional markers: CDKN2A expression, a cell senescence marker, and apparent age (AppAge), a highly complex transcriptional index. Bioinformatics analysis of 132 LV samples shows that CDKN2A expression and AppAge represent transcriptomic changes better than CA. Both BA markers are biologically validated in relation to an aging phenotype associated with heart dysfunction, the amount of cardiac fibrosis. BA-based analyses uncover depleted cardiac-specific processes, among other relevant functions, that are undetected by CA. Twenty BA-related microRNAs are identified, and two of them highly heart-enriched that are present in plasma. We describe a microRNA-gene regulatory network related to cardiac processes that are partially validated in vitro and in LV samples from living donors. We prove the higher sensitivity of BA over CA to explain transcriptomic changes in the aging myocardium and report novel molecular insights into human LV biological aging. Our results can find application in future therapeutic and biomarker research.

Correlation between PlateletWorks® and PFA-100® for Measuring Platelet Function before Urgent Surgery in Patients with Chronic Antiplatelet Therapy.

Hemostasis is crucial for reducing bleeding during surgical procedures. The points-of-care based on the platelet function test could be useful to minimize the complications related to chronic antiplatelet therapy during surgery. The present study is aimed at comparing two point-of-care platelet function devices-Platelet Function Analyzer PFA-100® (Siemens Canada, Mississauga, ON, Canada) and Plateletworks®(Helena Laboratories, Beaumont, TX, USA). Our objective is to evaluate if they provide comparable and useful information to manage anti-aggregate patients before surgery. We included patients with a femoral fracture receiving chronic antiplatelet therapy and a median age of 89 years (range from 70 to 98). A platelet function evaluation was performed on all patients before surgery using both devices-Plateletworks® and PFA-100®. The correlation between Plateletworks® and PFA-100® was performed using Cohen's Kappa coefficient. Twenty consecutive patients participated in the trial; 16 patients were under treatment with 75 mg/day of clopidogrel, three with >300 mg/day of acetylsalicylic acid (ASA), and only one was in treatment with both antiplatelet agents. Cohen's Kappa coefficient was 0.327 comparing PFA-100®-ADP (adenosine diphosphate) and Plateletworks® and, 0.200 comparing PFA-100®-EPI (epinephrine) and Plateletworks®. In conclusion, we found a weak concordance comparing PFA-100® and Plateletworks®. This could partially be due to the advanced age of the included patients. However, given the limited sample size, more studies are necessary to confirm these results.

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.

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.