Optimization of Absolute Coronary Blood Flow Measurements to Assess Microvascular Function: In Vivo Validation of Hyperemia and Higher Infusion Speeds.

BACKGROUND: Reliable assessment of coronary microvascular function is essential. Techniques to measure absolute coronary blood flow are promising but need validation. The objectives of this study were: first, to validate the potential of saline infusion to generate maximum hyperemia in vivo. Second, to validate absolute coronary blood flow measured with continuous coronary thermodilution at high (40-50 mL/min) infusion speeds and asses its safety. METHODS: Fourteen closed-chest sheep underwent absolute coronary blood flow measurements with increasing saline infusion speeds at different dosages under general anesthesia. An additional 7 open-chest sheep underwent these measurements with epicardial Doppler flow probes. Coronary flows were compared with reactive hyperemia after 45 s of coronary occlusion. RESULTS: Twenty milliliters per minute of saline infusion induced a significantly lower hyperemic coronary flow (140 versus 191 mL/min; P=0.0165), lower coronary flow reserve (1.82 versus 3.21; P≤0.0001), and higher coronary resistance (655 versus 422 woods units; P=0.0053) than coronary occlusion. On the other hand, 30 mL/min of saline infusion resulted in hyperemic coronary flow (196 versus 192 mL/min; P=0.8292), coronary flow reserve (2.77 versus 3.21; P=0.1107), and coronary resistance (415 versus 422 woods units; P=0.9181) that were not different from coronary occlusion. Hyperemic coronary flow was 40.7% with 5 mL/min, 40.8% with 10 mL/min, 73.1% with 20 mL/min, 102.3% with 30 mL/min, 99.0% with 40 mL/min, and 98.0% with 50 mL/min of saline infusion when compared with postocclusive hyperemic flow. There was a significant bias toward flow overestimation (Bland-Altman: bias±SD, -73.09±30.52; 95% limits of agreement, -132.9 to -13.27) with 40 to 50 mL/min of saline. Occasionally, ischemic changes resulted in ventricular fibrillation (9.5% with 50 mL/min) at higher infusion rates. CONCLUSIONS: Continuous saline infusion of 30 mL/min but not 20 mL/min induced maximal hyperemia. Absolute coronary blood flow measured with saline infusion speeds of 40 to 50 mL/min was not accurate and not safe.

Value of clinical applications of differential pressure and relative pressure imaging in the left ventricle.

Regional pressure differences between sites within the left ventricular cavity have long been identified, and the potential clinical value of diastolic and systolic intraventricular pressure differences (IVPDs) is of increasing interest. This study concluded that the IVPD plays an important role in ventricular filling and emptying and is a reliable indicator of ventricular relaxation, elastic recoil, diastolic pumping, and effective left ventricular filling. Relative pressure imaging, as a novel and potentially clinically applicable measure of left IVPDs, enables early and more comprehensive identification of the temporal and spatial characteristics of IVPD. In the future, as research related to relative pressure imaging continues, this measurement method has the possibility to become more refined and serve as an additional clinical aid that can replace the gold standard cardiac catheterization technique for the diagnosis of diastolic dysfunction.

Remote monitoring technologies for measuring cardiovascular functions in community-dwelling adults: a systematic review.

Remote monitoring technologies (RMTs) allow continuous, unobtrusive, and real-time monitoring of the cardiovascular system. An overview of existing RMTs measuring cardiovascular physiological variables is lacking. This systematic review aimed to describe RMTs measuring cardiovascular functions in community-dwelling adults. An electronic search was conducted via PubMed, EMBASE, and Cochrane Library from January 1, 2020, to April 7, 2022. Articles reporting on non-invasive RMTs used unsupervised in community-dwelling adults were included. Reviews and studies in institutionalized populations were excluded. Two reviewers independently assessed the studies and extracted the technologies used, cardiovascular variables measured, and wearing locations of RMTs. Validation of the RMTs was examined based on the COSMIN tool, and accuracy and precision were presented. This systematic review was registered with PROSPERO (CRD42022320082). A total of 272 articles were included representing 322,886 individuals with a mean or median age from 19.0 to 88.9 years (48.7% female). Of all 335 reported RMTs containing 216 distinct devices, photoplethysmography was used in 50.3% of RMTs. Heart rate was measured in 47.0% of measurements, and the RMT was worn on the wrist in 41.8% of devices. Nine devices were reported in more than three articles, of which all were sufficiently accurate, six were sufficiently precise, and four were commercially available in December 2022. The top four most reported technologies were AliveCor KardiaMobile®, Fitbit Charge 2, and Polar H7 and H10 Heart Rate Sensors. With over 200 distinct RMTs reported, this review provides healthcare professionals and researchers an overview of available RMTs for monitoring the cardiovascular system.

Nitrate-rich beet juice intake on cardiovascular performance in response to exercise in postmenopausal women with arterial hypertension: study protocol for a randomized controlled trial.

BACKGROUND: There is no evidence of the use of beetroot juice with a previously recommended dose of nitrate (NO3) (> 300 mg) on the cardiovascular performance during and recovery following exercise in postmenopausal women with systemic arterial hypertension (SAH). METHODS: We will investigate the effects of beetroot juice rich in NO3 acutely (800 mg) and during a week with daily doses (400 mg) on blood pressure, heart rate (HR), cardiac autonomic control, endothelial function, inflammatory, hormonal, and stress biomarkers oxidative stress and enzymes involved in nitric oxide synthesis and mitochondrial regulation, under resting conditions, as well as mediated by submaximal aerobic exercise sessions. Through a randomized, crossover, triple-blind, placebo-controlled clinical trial, 25 physically inactive women with SAH will undergo an acute and 1-week trial, each with two intervention protocols: (1) placebo and (2) beetroot, in which will ingest beet juice with or without NO3 in its composition with a 7-day washout interval. On collection days, exercise will be performed on a treadmill for 40 min at a speed corresponding to 65-70% of VO2peak. The collection of variables (cardiovascular, autonomic, and blood samples for molecular analyses) of the study will take place at rest (135 min after ingestion of the intervention), during exercise (40 min), and in the effort recovery stage (during 60 min) based on previously validated protocols. The collections were arranged so that the measurement of one variable does not interfere with the other and that they have adequate intervals between them. DISCUSSION: The results of this research may help in the real understanding of the nutritional compounds capable of generating safety to the cardiovascular system during physical exercise, especially for women who are aging and who have cardiovascular limitations (e.g., arterial hypertension) to perform physical exercise. Therefore, our results will be able to help specific nutritional recommendations to optimize cardiovascular health. TRIAL REGISTRATION: ClinicalTrials.gov NCT05384340. Registered on May 20, 2022.

Monitoring one heart to help two: heart rate variability and resting heart rate using wearable technology in active women across the perinatal period.

BACKGROUND: Characterizing normal heart rate variability (HRV) and resting heart rate (RHR) in healthy women over the course of a pregnancy allows for further investigation into disease states, as pregnancy is the ideal time period for these explorations due to known decreases in cardiovascular health. To our knowledge, this is the first study to continuously monitor HRV and RHR using wearable technology in healthy pregnant women. METHODS: A total of 18 healthy women participated in a prospective cohort study of HRV and RHR while wearing a WHOOP® strap prior to conception, throughout pregnancy, and into postpartum. The study lasted from March 2019 to July 2021; data were analyzed using linear mixed models with splines for non-linear trends. RESULTS: Eighteen women were followed for an average of 405.8 days (SD = 153). Minutes of logged daily activity decreased from 28 minutes pre-pregnancy to 14 minutes by third trimester. A steady decrease in daily HRV and increase in daily RHR were generally seen during pregnancy (HRV Est. = - 0.10, P < 0.0001; RHR Est. = 0.05, P < 0.0001). The effect was moderated by activity minutes for both HRV and RHR. However, at 49 days prior to birth there was a reversal of these indices with a steady increase in daily HRV (Est. = 0.38, P < 0.0001) and decrease in daily RHR (Est. = - 0.23, P < 0.0001), regardless of activity level, that continued into the postpartum period. CONCLUSIONS: In healthy women, there were significant changes to HRV and RHR throughout pregnancy, including a rapid improvement in cardiovascular health prior to birth that was not otherwise known. Physical activity minutes of any type moderated the known negative consequences of pregnancy on cardiovascular health. By establishing normal changes using daily data, future research can now evaluate disease states as well as physical activity interventions during pregnancy and their impact on cardiovascular fitness.

Cardiovascular response in mid and long-distance runners under training / Resposta cardiovascular em corredores de média e longa distância sob treinamento / Respuesta cardiovascular en corredores de media y larga distancia en entrenamiento

ABSTRACT Introduction: Research on the effects of exercise on the cardiovascular system has a long history that has recently been expanded with echocardiography. Research using Doppler echocardiography has been increasing because of the safe and non-invasive method of examination to study cardiac morphology and function. However, few studies on functional cardiac changes in mid and long-distance runners under training are still few. Objective: Study the monitoring of cardiovascular response in middle and long-distance runners during training. Methods: The CFOCS-I cardiovascular function detector was used to observe 24 indices of cardiac pump function, vascular function, and microcirculation in 12 female middle-distance runners. Results: According to the test results, diastolic force, systolic force, systolic function, left ventricular ejection fraction increased during the proposed loading exercise. The mean systolic and mean pulse pressures increased significantly with exercise load (P<0.01). Conclusion: Mid and long-distance runners demonstrated significant cardiac changes in ventricular shape, size, and systolic function, accompanied by significant changes in diastolic function when subjected to intense exercise. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMO Introdução: A pesquisa dos efeitos do exercício sobre o sistema cardiovascular tem uma longa história que recentemente foi expandida com o uso da ecocardiografia. Pesquisas utilizando a ecocardiografia por doppler têm crescido devido ao método de exame apresentar-se seguro e não-invasivo para estudo de morfologia e função cardíaca. Porém ainda há poucos estudos sobre as alterações cardíacas funcionais em corredores de média e longa distância sob treinamento. Objetivo: Estudar o monitoramento da resposta cardiovascular nos corredores de média e longa distância durante o treinamento. Métodos: O detector de função cardiovascular CFOCS-I foi usado para observar 24 índices de função da bomba cardíaca, função vascular, e microcirculação em 12 corredoras de média distância do sexo feminino. Resultados: De acordo com os resultados dos testes, a força diastólica, a força sistólica, a função sistólica, a fração de ejeção do ventrículo esquerdo aumentaram durante o exercício de carga proposto. A pressão sistólica média e a pressão de pulso média aumentaram significativamente com a carga de exercício (P<0,01). Conclusão: Os corredores de média e longa distância demonstraram alterações cardíacas significativas no formato, tamanho e função sistólica dos ventrículos, acompanhado por mudanças significativas na função diastólica quando submetidos ao exercício intenso. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción: La investigación sobre los efectos del ejercicio en el sistema cardiovascular tiene una larga historia que se ha ampliado recientemente con el uso de la ecocardiografía. La investigación con ecocardiografía Doppler ha ido en aumento debido a que es un método de examen seguro y no invasivo para estudiar la morfología y la función cardíacas. Sin embargo, todavía hay pocos estudios sobre los cambios funcionales cardíacos en corredores de media y larga distancia bajo entrenamiento. Objetivo: Estudiar el seguimiento de la respuesta cardiovascular en corredores de media y larga distancia durante el entrenamiento. Métodos: Se utilizó el detector de función cardiovascular CFOCS-I para observar 24 índices de la función de la bomba cardíaca, la función vascular y la microcirculación en 12 corredoras de media distancia. Resultados: Según los resultados de la prueba, la fuerza diastólica, la fuerza sistólica, la función sistólica y la fracción de eyección del ventrículo izquierdo aumentaron durante el ejercicio de carga propuesto. La presión sistólica media y la presión de pulso media aumentaron significativamente con la carga de ejercicio (P<0,01). Conclusión: Los corredores de media y larga distancia mostraron cambios cardíacos significativos en la forma, el tamaño y la función sistólica del ventrículo, acompañados de cambios significativos en la función diastólica cuando se sometieron a un ejercicio intenso. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

The Variation in the Diastolic Period with Interventricular Septal Displacement and Its Relation to the Right Ventricular Function in Pulmonary Hypertension: A Preliminary Cardiac Magnetic Resonance Study.

Background: Pulmonary hypertension (PH) is known to alter the biventricular shape and temporal phases of the cardiac cycle. The presence of interventricular septal (IVS) displacement has been associated with the severity of PH. There has been limited cardiac magnetic resonance (CMR) data regarding the temporal parameters of the cardiac cycle in PH. This study aimed to quantify the temporal changes in the cardiac cycle derived from CMR in PH patients with and without IVS displacement and sought to understand the mechanism of cardiac dysfunction in the cardiac cycle. Methods: Patients with PH who had CMR and right heart catheterization (RHC) examinations were included retrospectively. Patients were divided into an IVS non-displacement (IVSND) group and an IVS displacement (IVSD) group according to IVS morphology, as observed on short-axis cine CMR images. Additionally, age-matched healthy volunteers were included as the health control (HC). Temporal parameters, IVS displacement, ventricular volume and functional parameters were obtained by CMR, and pulmonary hemodynamics were obtained by RHC. The risk stratification of the PH patients was also graded according to the guidelines. Results: A total of 70 subjects were included, consisting of 33 IVSD patients, 15 IVSND patients, and 22 HC patients. In the IVSND group, only the right ventricle ejection fraction (RVEF) was decreased in the ventricular function, and no temporal change in the cardiac cycle was found. A prolonged isovolumetric relaxation time (IRT) and shortened filling time (FT) in both ventricles, along with biventricular dysfunction, were detected in the IVSD group (p < 0.001). The IRT of the right ventricle (IRTRV) and FT of the right ventricle (FTRV) in the PH patients were associated with pulmonary vascular resistance, right cardiac index, and IVS curvature, and the IRTRV was also associated with the RVEF in a multivariate regression analysis. A total of 90% of the PH patients in the IVSD group were stratified into intermediate- and high-risk categories, and they showed a prolonged IRTRV and a shortened FTRV. The IRTRV was also the predictor of the major cardiovascular events. Conclusions: The temporal changes in the cardiac cycle were related to IVS displacement and mainly impacted the diastolic period of the two ventricles in the PH patients. The IRT and FT changes may provide useful pathophysiological information on the progression of PH.

Educational impact of an active learning session with 6-lead mobile electrocardiography on medical students' knowledge of cardiovascular physiology during the COVID-19 pandemic in the United States: a survey-based observational study

Mobile electrocardiogram (ECG) devices are valuable tools for teaching ECG interpretation. The primary purpose of this follow-up study was to determine if an ECG active learning session could be safely and effectively performed during the coronavirus disease 2019 (COVID-19) pandemic using a newly developed mobile 6-lead ECG device. Additionally, we examined the educational impact of these active learning sessions on student knowledge of cardiovascular physiology and the utility of the mobile 6-lead ECG device in a classroom setting. In this study, first-year medical students (MS1) performed four active learning activities using the new mobile 6-lead ECG device. Data were collected from 42 MS1s through a quantitative survey administered in September 2020. Overall, students felt the activity enhanced their understanding of the course material and that the activity was performed safely and in compliance with local COVID-19 guidelines. These results emphasize student preference for hands-on, small group learning activities in spite of the pandemic.

COVID-19 y complicaciones cardiovasculares / COVID-19 and cardiovascular complications

RESUMEN Objetivo: Analizar el COVID - 19 y complicaciones cardiovasculares. Método: revisión sistemática. Análisis de los resultados: Una gran proporción de pacientes tiene enfermedad cardiovascular subyacente y factores de riesgo cardíaco. Los factores asociados con la mortalidad incluyen el sexo masculino, la edad avanzada y la presencia de comorbilidades como las enfermedades cardiovasculares. La lesión cardíaca aguda determinada por niveles elevados de troponina de alta sensibilidad se observa comúnmente en casos graves y está fuertemente asociada con la mortalidad, al igual que el síndrome de dificultad respiratoria aguda. Conclusión: La infección por el SARS-CoV-2 presenta una baja mortalidad en la mayoría de los casos, pero un porcentaje significativo de los infectados sufren una enfermedad pulmonar con diferentes grados de afección sistémica que sí conlleva mayor mortalidad. Estos pacientes presentan grados variables de afección miocárdica, tanto directa por el virus como por la situación sistémica grave, que incrementan el riesgo de muerte.

Objective: To analyze COVID-19 and cardiovascular complications. Methods: Systematic review. Analysis of results: A large proportion of patients have underlying cardiovascular disease and cardiac risk factors. Factors associated with mortality include male sex, advanced age and the presence of comorbidities such as cardiovascular disease. Acute cardiac injury as determined by elevated high-sensitivity troponin levels is commonly seen in severe cases and is strongly associated with mortality, as is acute respiratory distress syndrome. Conclusion: SARS-CoV-2 infection has a low mortality in most cases, but a significant percentage of those infected have pulmonary disease with varying degrees of systemic involvement that does lead to increased mortality. These patients have varying degrees of myocardial involvement, both direct from the virus and from the severe systemic situation, which increase the risk of death.

Pacientes con corazón univentricular sometidos a cirugía de Glenn / Patients with univentricular heart submitted to Glenn surgery

Resumen Objetivo: Describir las características clínicas, quirúrgicas y posquirúrgicas de pacientes univentriculares sometidos a cirugía de Glenn en un centro de referencia cardiovascular. Método: Estudio descriptivo, retrospectivo, llevado a cabo entre enero de 2012 y diciembre de 2016, en pacientes menores de 18 años que consultaron a una clínica de cuarto nivel, con cardiopatías de fisiología univentricular, definidos por ecocardiografía institucional, presentados en junta médico-quirúrgica, operados o no como primer estadio de paliación y seguidos en el programa de ventrículo único de la institución, posterior a un cateterismo cardiaco para ser presentado en junta médica que definió la realización de cirugía de Glenn. De la historia clínica se recolectaron datos de ecocardiogramas diagnósticos, cateterismos cardiacos, descripciones quirúrgicas y evoluciones. Resultados: Se analizaron 88 pacientes univentriculares, de los cuales el 63% eran hombres y el 36% eran mujeres. La anatomía del ventrículo funcional univentricular derecho estuvo presente en el 38.6% y la morfología funcional izquierda en el 61.4%. Entre las características asociadas con la mortalidad se verificó que el 1.1% tuviera insuficiencia moderada de la válvula atrioventricular y que el 3.4% tuviera insuficiencia grave de la válvula atrioventricular. El 38.6% presentó cifras de presión pulmonar elevadas, medidas por cateterismo cardiaco, y el 46% tenían resistencia vascular pulmonar aumentada. Se usó terapia vasopresora antes de la cirugía de Glenn en nueve pacientes; todos recibieron milrinona. La mortalidad posquirúrgica fue del 18%. Conclusiones: Este estudio evidencia que el diagnóstico y la intervención temprana contribuyen a reducir la morbimortalidad en los pacientes con diagnóstico de corazón univentricular, puesto que sin intervención de segundo estadio de paliación sería mortal para la mayoría de ellos. Así mismo, evidencia la importancia de la implementación de un programa integral para la atención de enfermedades cardiovasculares complejas.

Abstract Objective: To describe the clinical, surgical and post-surgical characteristics of univentricular patients undergoing Glenn’s surgery in a cardiovascular reference center. Method: Descriptive, retrospective study from January 2012 to December 2016, in patients under 18 who consulted a fourth level clinic with cardiopathies of univentricular physiology defined by institutional echocardiography, presented at the surgical medical board, operated or not as the first stage of palliation, followed in the single ventricle program of the institution, later performed a cardiac catheterization to be presented at the medical board that defined the performance of Glenn’s surgery. From the clinical history, data of diagnostic echocardiograms, cardiac catheterizations, surgical descriptions, and evolutions were collected. Results: A total of 88 univentricular patients were analyzed, of which 63% were men and 36% women. The anatomy of the right univentricular functional ventricle was present in 38.6% and 61.4% of left functional morphology. Among the characteristics associated with mortality, it was verified that 1.1% had moderate atrioventricular valve insufficiency and 3.4% had severe atrioventricular valve insufficiency in the patients who participated in the study. 38.6% had pulmonary arterial hypertension detected by cardiac catheterization and 46% had increased pulmonary vascular resistance. The use of vasopressor therapy before Glenn’s surgery was present in 9 patients and of them, the whole had milrinone. The postoperative mortality was 18%. Conclusions: This study shows that diagnosis and early intervention reduce morbidity and mortality in patients with a diagnosis of univentricular heart since without intervention of the second stage of palliation would be fatal for the vast majority of patients. It also demonstrates the importance of a comprehensive program for the care of complex cardiovascular pathologies.

Cardiovascular Proteomics: A Post Hoc Analysis from a Phase II Randomized Clinical Trial Comparing GnRH Antagonist vs GnRH Agonist among Men with Advanced Prostate Cancer.

PURPOSE: Recent studies demonstrated reduced cardiovascular (CV) risk with gonadotropin-releasing hormone (GnRH) antagonist, yet the underlying mechanism remains undetermined. The objective of this study was to examine longitudinal changes over time in established CV related proteins among men treated with GnRH agonists vs GnRH antagonist. MATERIALS AND METHODS: We performed a proteomics analysis of serum samples collected during a phase II randomized study among 80 men with advanced prostate cancer and preexisting CV disease who were randomized to receive a GnRH agonist (39) or GnRH antagonist (41) for 1 year. Serum samples were collected at baseline and at 3, 6 and 12 months following treatment, and analyzed levels of 188 proteins using the CV panel II and III of the Olink Multiplex platform (Olink Proteomics AB, Uppsala, Sweden). We fitted a linear mixed effects model to assess evidence of a treatment effect across CV related protein values. This included terms for treatment arm, protein levels and time-by-treatment interaction. Results were corrected for multiple testing using the Benjamini-Hochberg method. RESULTS: The CV proteomics analysis included 283 samples from 78 subjects. We identified 5 proteins with distinct patterns over time depending on study arm: human chitotriosidase, macrophage receptor with collagenous structure, cathepsin D, superoxide dismutase 2 and hydroxyacid oxidase 1. All 5 are associated with plaque stability and demonstrated an increased level among subjects in the GnRH antagonist arm compared to agonist. CONCLUSIONS: We compared longitudinal changes in CV proteins among men using androgen deprivation therapy. Our results support a direct protective effect of GnRH antagonist on plaque stability rather than a hazardous consequence of GnRH agonists on plaque rupture. This is a hypothesis generating study, and requires further confirmation.

Bicuspid aortic valve annulus: assessment of geometry and size changes during the cardiac cycle as measured with a standardized method to define the annular plane.

PURPOSE: Bicuspid aortic valve (BAV) is a complex malformation affecting not merely the aortic valve. However, little is known regarding the dynamic physiology of the aortic annulus in these patients and whether it is similar to tricuspid aortic valves (TAV). Determining the BAV annular plane is more challenging than for TAV. Our aim was to present a standardized methodology to determine BAV annulus and investigate its changes in shape and dimensions during the cardiac cycle. METHODS: BAV patients were prospectively included and underwent an ECG-gated cardiac CTA. The annulus plane was manually identified on reconstructions at 5% intervals of the cardiac cycle with a new standardized method for different BAV types. Based on semi-automatically defined contours, maximum and minimum diameter, area, area-derived diameter, perimeter, asymmetry ratio (AR), and relative area were calculated. Differences of dynamic annular parameters were assessed also per BAV type. RESULTS: Of the 55 patients included (38.4 ± 13.3 years; 58% males), 38 had BAV Sievers type 1, 10 type 0, and 7 type 2. The minimum diameter, perimeter, area, and area-derived diameter were significantly higher in systole than in diastole with a relative change of 13.7%, 4.8%, 13.7%, and 7.2% respectively (all p < 0.001). The AR was ≥ 1.1 in all phases, indicating an elliptic shape, with more pronounced flattening in diastole (p < 0.001). Different BAV types showed comparable dynamic changes. CONCLUSIONS: BAV annulus undergo significant changes in shape during the cardiac cycle with a wider area in systole and a more elliptic conformation in diastole regardless of valve type. KEY POINTS: • A refined method for the identification of the annulus plane on CT scans of patients with bicuspid aortic valves, tailored for the specific anatomy of each valve type, is proposed. • The annulus of patients with bicuspid aortic valves undergoes significant changes during the cardiac cycle with a wider area and more circular shape in systole regardless of valve type. • As compared to previously published data, the bicuspid aortic valve annulus has physiological dynamics similar to that encountered in tricuspid valves but with overall larger dimensions.

Computational fluid dynamics: a primer for congenital heart disease clinicians.

Computational fluid dynamics has become an important tool for studying blood flow dynamics. As an in-silico collection of methods, computational fluid dynamics is noninvasive and provides numerical values for the most important parameters of blood flow, such as velocity and pressure that are crucial in hemodynamic studies. In this primer, we briefly explain the basic theory and workflow of the two most commonly applied computational fluid dynamics techniques used in the congenital heart disease literature: the finite element method and the finite volume method. We define important terminology and include specific examples of how using these methods can answer important clinical questions in congenital cardiac surgery planning and perioperative patient management.

La preeclampsia es precedida por alteración de la función cardiovascular / Preeclampsia is Preceded by Cardiovascular Function Abnormalities

RESUMEN Introducción: La preeclampsia (PE) se acompaña de cambios en la función cardiovascular (FCV). Sin embargo, es desconocido si los cambios preceden y persisten a la manifestación clínica de PE. Objetivos: Evaluar las diferencias en la FCV, en la semana 22 de gestación (22sg) y un año posterior al parto (1app) en las pacientes que evolucionaron a la PE vs. a la normotensión (N). También, la asociación entre la FCV en 22sg y la evolución a PE. Material y métodos: Estudio prospectivo, que incluyó 260 primíparas normotensas. Se midió en la semana 22sg y a 1app: laboratorio de rutina, proteinuria de 24horas, presión arterial (PA). Por cardiografía por impedancia: índice cardíaco (IC) y de resistencia vascular sistémica (IRVS), velocidad de onda de pulso (VOP). Se formaron 3 grupos según la evolución a: PE, G1, HTA gestacional (HG) G2, y N, G3. Los resultados se presentan como media ± DS, ANOVA y test post hoc, p < 0,05. Resultados: 12 pacientes evolucionaron a PE, 18 a HG y 220 a N. El G1 presentó en los dos tiempos de medición, valores inferiores de IC y superiores de PA, IRP y VOP comparados al G3. El G2 presentó valores intermedios entre el G1 y el G3. La VOP y el IRP en la 22sg de gestación resultaron predictores de PE. Conclusiones: Las pacientes que evolucionaron a PE presentaron en fase temprana del embarazo diferente FCV respecto a las normotensas. El diagnóstico temprano de estos cambios contribuiría a predecir la PE y prevenir sus complicaciones.

ABSTRACT Background: Preeclampsia (PE) is associated with changes in cardiovascular function (CVF), but whether these changes precede and persist in the clinical phase of the disease is still unknown. Objectives: The aim of this study was to evaluate the differences in CVF during 22 weeks of gestation and one year after delivery in patients who developed PE vs. those with normotension (N). The association between CVF on 22 weeks of gestation and the development of PE was also analyzed. Methods: We conducted a prospective study including 260 normotensive primiparous women. Routine laboratory tests, 24-hour urine protein and blood pressure (BP) were measured on 22 weeks and one year after delivery. Cardiac index (CI) systemic vascular resistance index (SVRI) and pulse wave velocity (PWV) were measured by impedance cardiography. The population was divided into three groups according to the outcome during pregnancy: PE: G1, gestational hypertension (GH): G2 and normotension: G3. The results are presented as mean ± SD, ANOVA and post hoc test, p < 0.05. Results: Twelve patients evolved to PE, 18 to GH and 220 remained with N. In G1, CI was lower and BP, SVRI and PWV were higher than in G3 on 22 weeks and one year after delivery. In G2, values were always intermediate between G1 and G3. PWV and SVRI measured on 22 weeks resulted predictors of PE. Conclusions: Patients who developed PE had different CVF in the early stage of pregnancy than those with normotension. The early diagnosis of those changes could predict PE and thus contribute to prevent its complications.

Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere protein genes that evoke hypercontractility, poor relaxation, and increased energy consumption by the heart and increased patient risks for arrhythmias and heart failure. Recent studies show that pathogenic missense variants in myosin, the molecular motor of the sarcomere, are clustered in residues that participate in dynamic conformational states of sarcomere proteins. We hypothesized that these conformations are essential to adapt contractile output for energy conservation and that pathophysiology of HCM results from destabilization of these conformations. METHODS: We assayed myosin ATP binding to define the proportion of myosins in the super relaxed state (SRX) conformation or the disordered relaxed state (DRX) conformation in healthy rodent and human hearts, at baseline and in response to reduced hemodynamic demands of hibernation or pathogenic HCM variants. To determine the relationships between myosin conformations, sarcomere function, and cell biology, we assessed contractility, relaxation, and cardiomyocyte morphology and metabolism, with and without an allosteric modulator of myosin ATPase activity. We then tested whether the positions of myosin variants of unknown clinical significance that were identified in patients with HCM, predicted functional consequences and associations with heart failure and arrhythmias. RESULTS: Myosins undergo physiological shifts between the SRX conformation that maximizes energy conservation and the DRX conformation that enables cross-bridge formation with greater ATP consumption. Systemic hemodynamic requirements, pharmacological modulators of myosin, and pathogenic myosin missense mutations influenced the proportions of these conformations. Hibernation increased the proportion of myosins in the SRX conformation, whereas pathogenic variants destabilized these and increased the proportion of myosins in the DRX conformation, which enhanced cardiomyocyte contractility, but impaired relaxation and evoked hypertrophic remodeling with increased energetic stress. Using structural locations to stratify variants of unknown clinical significance, we showed that the variants that destabilized myosin conformations were associated with higher rates of heart failure and arrhythmias in patients with HCM. CONCLUSIONS: Myosin conformations establish work-energy equipoise that is essential for life-long cellular homeostasis and heart function. Destabilization of myosin energy-conserving states promotes contractile abnormalities, morphological and metabolic remodeling, and adverse clinical outcomes in patients with HCM. Therapeutic restabilization corrects cellular contractile and metabolic phenotypes and may limit these adverse clinical outcomes in patients with HCM.

Análise da variabilidade da frequência cardíaca em crianças submetidas a jogos eletrônicos / Heart rate variability analysis in children submitted to electronic games

Objetivo: avaliar a função autonômica do coração de crianças sadias em situações de jogos eletrônicos, mediante a análise de Variabilidade da Frequência cardíaca. Métodos: participaram deste estudo 60 crianças sadias, que foram monitoradas por um monitor de frequência cardíaca digital e submetidas ao experimento com o jogo eletrônico. A análise da Variabilidade da Frequência cardíaca foi calculada com emprego da transformada Wavelet Contínua. Resultados: pode-se observar um aumento na intensidade dos valores de baixa frequência/alta frequência, sugerindo influência das fases do protocolo, de modo que houve uma elevação nos valores da fase de Repouso para a fase de Jogo, mas não foi encontrado um valor significativo. Entre as fases de Repouso (1,52±0,97 ms²) e Recuperação (1,89±1,04 ms²) houve um aumento significativo obtendo um valor de p=0,003. Comparando os valores de baixa frequência/alta frequência entre as fases Jogo 2,37±1,20 ms² e Recuperação 1,89±1,04 ms², verificou-se uma redução significativa da relação (p = 0,016). Conclusão: conclui-se que Jogos eletrônicos podem provocar um aumento da atividade simpática, diminuindo a Variabilidade da Frequência cardíaca das crianças estudadas, sugerindo uma situação estressante.

Aims: to evaluate the autonomic heart function of healthy children in electronic games situations, by analyzing Heart Rate Variability. Methods: sixty healthy children participated in this study, who were monitored by a digital heart rate monitor and subjected to the experiment with the electronic game. Heart rate variability analysis was calculated using the Continuous Wavelet transform. Results: an increase in the intensity of the Low frequency / High Frequency values can be observed, suggesting influence of the protocol phases, so that there was an increase in the values from the Rest phase to the Game phase, but no significant value was found. Between the Rest (1.52±0.97 ms²) and Recovery (1.89±1.04 ms²) phases there was a significant increase obtaining a value of p=0.003. Comparing the values of Low frequency / High Frequency between the phases Game 2.37±1.20 and Recovery 1.89±04 ms², there was a significant reduction of the ratio (p =0.016). Conclusion: it is concluded that electronic games can cause an increase in sympathetic activity, decreasing the heart rate variability of the studied children, suggesting a stressful situation.

Novas angiotensinas e suas implicações fisiológicas / Novel angiotensin peptides and their physiological implications

Introdução: O sistema renina-angiotensina (SRA) é a maior rede regulatória da pressão arterial, do balanço hidroeletrolítico e da homeostase do organismo. Desde que o papel do SRA na regulação da função cardiovascular foi descrito, os componentes do eixo endócrino do sistema, em especial a angiotensina II - na regulação e fisiologia cardiovascular e renal, têm sido foco de pesquisa. Os achados das últimas décadas, no entanto, mostraram que o sistema é muito mais complexo e intricado do que se imaginava. Objetivo: Apresentar, através de uma revisão da literatura, alguns dos novos elementos que compõem o SRA e suas implicações fisiológicas, atualizando o leitor sobre o estado da arte. Material de Métodos:Revisão bibliográfica abordando as principais publicações, indexadas pelo PubMed, relacionadas aos novos peptídeos do SRA. Resultados: Dentre os novos componentes do SRA, encontram-se a angiotensina­(1-9), um nonapeptídeo que promove vasodilatação, ação anti-hipertrófica em cardiomiócitos e ação anti-hipertensiva. A Angiotensina-(1-7), por sua vez, apesar de se diferenciar da Ang II apenas pela ausência de um único aminoácido, é responsável por efeitos fisiológicos opostos aos observados com a Ang II. A Angiotensina A, outro peptídeo biologicamente ativo, é formado a partir da descarboxilação do aspartato, desempenhando efeitos semelhantes à Ang II. A Alamandina, também derivada de uma descarboxilação, é um heptapeptídeo vasodilatador, anti-hipertensivo e cardioprotetor. Conclusão: Os achados envolvendo as novas angiotensinas permitem o entendimento do sistema como uma extensa rede composta de vias e eixos alternativos, muitos dos quais, ainda sem esclarecimento científico. O enfoque em novas vias de formação de produtos com funções biológicas poderá ser útil para o desenvolvimento de novas estratégias terapêuticas e, descobertas no campo da fisiologia e fisiopatologia de uma série de condições.

Introdution: The renin-angiotensin system (RAS) is the major regulatory system of arterial blood pressure, hydroelectrolytic balance, and body homeostasis. Since the role of the RAS in the cardiovascular function has been described, much of the research in this area has focused on the role of its endocrine axis components, mainly angiotensin II (Ang II), in the cardiovascular and renal physiology. Over the last decades, the findings have shown that the system is much more intricate than thought. Objective:To present, upon a literature review, some of the new elements about the RAS and its physiological implications, updating the reader about the state of the art. Methods Material: Bibliographic review addressing the main PubMed publications related of the novels angiotensin-peptides. Results: Among the novel RAS components, angiotensin­(1-9) is a nonapeptide that exerts antihypertrophy effects in cardiomyocytes, and vasodilatory and anti-hypertensive actions. Angiotensin-(1-7), which differs from Ang II due to the absence of only one aminoacid, is responsible for physiological effects opposite to those of Ang II. Angiotensin A, another biologically active peptide, is synthesized through aspartate decarboxylation, and exerts effects similar to those of Ang II. Alamandine, also formed through decarboxylation, is a heptapeptide showing vasodilatory, antihypertensive, and cardioprotective effects. Conclusion: The discovery of novel angiotensins sheds more light on the view that the RAS is an extensive regulatory system with pathways and alternative axis, much of which without scientific knowledge. Scientific efforts envisioning novel formation pathways of biologically active products may be useful for development of innovative therapeutic strategies and discoveries in the field of several physiological and pathological conditions.

Bases fisiológicas de la desfibrilación ventricular / Physiological bases of ventricular defibrillation

La desfibrilación ventricular es un procedimiento básico para una adecuada reanimación cardiopulmocerebral, pero sus principios no son comúnmente abordados en la literatura. Este trabajo tuvo como objetivo describir las bases fisiológicas de la desfibrilación ventricular para lo cual se realizó, en el primer cuatrimestre del 2018, una revisión documental que incluyó 21 referencias bibliográficas. Se concluyó que las bases fisiológicas integran a las funciones celulares propias del corazón, las modificaciones físico-moleculares celulares que condicionan la arritmia o se generan por la hipoxia, a los cambios que sobre el tejido cardiaco produce el paso de electricidad y a las características de la onda de choque eléctrica del desfibrilador. La desfibrilación detiene la actividad eléctrica cardiaca y permite el inicio de potenciales de acción de sus células marcapaso. La eficacia del procedimiento depende del estado metabólico del miocardio (dado por causa y tiempo de la parada cardiaca), y de la correcta realización del protocolo de desfibrilación.

Ventricular defribrillation is a basic procedure from an adequate cardio-pulmonary-cerebral resuscitation, but its principles are not commonly approached in literature. This work was aimed at describing the physiological basis of ventricular defibrillation for which it was, in the first quarter of 2018, a documentary review which included 21 bibliographical references. It was concluded that these bases integrate the cellular functions of the heart, the physical-molecular cellular modifications which condition arrythmia or are produced due to hypoxia, the changes on the cardiac tissue which allow the passage of electrical cardiac activity and the characteristics of the electrical shock wave of the defibrillator. Defibrillation stops cardiac electrical activity and allows the action potential start of its pacemaker cells.. The efficacy of the procedure depends on the metabolic condition of the myocardium (due to the cause and the time cardiac failure) and the correct performance of the defibrillation protocol.

Frequência cardíaca máxima medida versus estimada por diferentes equações durante o teste de exercício cardiopulmonar em adolescentes obesos / Maximum heart rate measured versus estimated by different equations during the cardiopulmonary exercise test in obese adolescents

RESUMO Objetivo: Comparar os valores de frequência cardíaca máxima (FCmáx) medidos e estimados por diferentes equações durante o teste de exercício cardiopulmonar (TECP) em adolescentes obesos. Métodos: Trata-se de um estudo transversal. Foram incluídos adolescentes, de idades entre 15 e 18 anos, com obesidade (escore-Z do índice de massa corpórea - IMC>2,0). Coletaram-se dados demográficos e antropométricos, seguidos da realização do TECP, pela qual foi registrada a FCmáx. O valor mais elevado de frequência cardíaca (FC) atingida no pico do exercício foi considerado como a FCmáx. A comparação entre os valores de FCmáx medidos e os estimados pelas equações foi realizada empregando-se quatro equações prévias. Utilizaram-se a estatística descritiva e o teste de ANOVA (pós-teste de Bonferroni). Resultados: Foram incluídos 59 adolescentes obesos, sendo 44% do sexo masculino. A média de idade foi de 16,8±1,2 anos e a do IMC (escore-Z), de 3,0±0,7. No pico do exercício, a média de FCmáx (batimentos por minuto - bpm) foi de 190,0±9,2, o coeficiente de troca respiratória de 1,2±0,1 e o consumo máximo de oxigênio - VO2máx (mL/kg/min) - de 26,9±4,5. Ao comparar-se os valores medidos de FCmáx com os estimados pelas diferentes fórmulas, demonstrou-se que as equações "220-idade", "208-0,7 x idade" e a "207-0,7 x idade" superestimam (p<0,001) os resultados medidos de FCmáx em adolescentes obesos. Apenas a equação "200-0,48 x idade" apresentou resultados similares (p=0,103) com os valores mensurados no TECP. Conclusões: Os achados do presente estudo demonstram que a equação "200-0,48 x idade" parece ser mais adequada para estimar a FCmáx em adolescentes obesos.

ABSTRACT Objective: To compare the values of measured maximum heart rate (HRmax) and maximum heart rate estimated by different equations during the cardiopulmonary exercise test (CPET) in obese adolescents. Methods: This is a cross-sectional study. Adolescents aged between 15 and 18 years old, with obesity (BMI Z-score>2.0) were included. Demographic and anthropometric data were collected, followed by CPET, recording HRmax. The highest heart rate reached at peak exercise was considered as HRmax. The comparison between measured and estimated HRmax values was performed using four previous equations. Descriptive statistics and the ANOVA test (Bonferroni post-test) were used. Results: Fifty-nine obese adolescents were included, 44% of them male. The mean age was 16.8±1.2 years old and the BMI (Z-score) was 3.0±0.7. At peak exercise, the mean HRmax (bpm) was 190.0±9.2, the respiratory coefficient was 1.2±0.1, and the VO2max (mL/kg/min) was 26.9±4.5. When comparing the measured values of HRmax with those estimated by the different formulas, the equations "220-age", "208-0.7 x age" and "207-0.7 x age" were shown to overestimate (p<0.001) the measured HRmax results in obese adolescents. Only the "200-0.48 x age" equation presented similar results (p=0.103) with the values measured in the CPET. Conclusions: The findings of the present study demonstrate that the equation "200-0.48 x age" seems to be more adequate to estimate HRmax in obese adolescents.