Physiology Of Heart Research Articles

Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish.

Mutations in the synaptic machinery gene syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1), are linked to childhood epilepsies and other neurodevelopmental disorders. Zebrafish STXBP1 homologs (stxbp1a and stxbp1b) have highly conserved sequence and are prominently expressed in the larval zebrafish brain. To understand the functions of stxbp1a and stxbp1b, we generated loss-of-function mutations using CRISPR/Cas9 gene editing and studied brain electrical activity, behavior, development, heart physiology, metabolism, and survival in larval zebrafish. Homozygous stxbp1a mutants exhibited a profound lack of movement, low electrical brain activity, low heart rate, decreased glucose and mitochondrial metabolism, and early fatality compared to controls. On the other hand, homozygous stxbp1b mutants had spontaneous electrographic seizures, and reduced locomotor activity response to a movement-inducing “dark-flash” visual stimulus, despite showing normal metabolism, heart rate, survival, and baseline locomotor activity. Our findings in these newly generated mutant lines of zebrafish suggest that zebrafish recapitulate clinical phenotypes associated with human syntaxin-binding protein 1 mutations.

Commentary: Heart Failure with Preserved Ejection Fraction Induces Beiging in Adipose Tissue.

Commentary: Heart Failure with Preserved Ejection Fraction Induces Beiging in Adipose Tissue.

High throughput physiological screening of iPSC-derived cardiomyocytes for drug development

Cardiac drug discovery is hampered by the reliance on non-human animal and cellular models with inadequate throughput and physiological fidelity to accurately identify new targets and test novel therapeutic strategies. Similarly, adverse drug effects on the heart are challenging to model, contributing to costly failure of drugs during development and even after market launch. Human induced pluripotent stem cell derived cardiac tissue represents a potentially powerful means to model aspects of heart physiology relevant to disease and adverse drug effects, providing both the human context and throughput needed to improve the efficiency of drug development. Here we review emerging technologies for high throughput measurements of cardiomyocyte physiology, and comment on the promises and challenges of using iPSC-derived cardiomyocytes to model disease and introduce the human context into early stages of drug discovery. This article is part of a Special Issue entitled: Cardiomyocyte biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Pulmonary Artery Branch Stent Implantation in Congenital Heart Disease: A 10-Year Multicenter Experience

Background: Stent implant is considered the treatment of choice for most cases of congenital or postoperative pulmonary artery branch stenosis in patients with congenital heart defects. However, there are still doubts on the clinical effectiveness and the incidence of complications of this technique that need to be elucidated.Methods: This multicenter study has a descriptive, observational and retrospective design. The procedures were performed between January 2005 and April 2015. Twenty-five patients with pulmonary artery branch stenosis underwent stent implant and were followed-up both clinically and by different imaging tests. Persistent clinical and/or anatomic improvement defined clinical effectiveness.Results: Average age was 9.48 years (2 months-34 years), mean weight was 27.54 kg (3-104 kg) and 44% were women. The most frequent congenital heart defects in the treated cohort were tetralogy of Fallot and its variants, followed by single ventricle heart physiology after bidirectional Glenn shunt and/or Fontan-Kreutzer procedures. Right ventricular systolic and pulmonary artery pressure decreased significantly after the intervention (from 68.35 mmHg to 45.8 mmHg and from 47.4 mm Hg to 32 mm Hg, respectively) (p < 0.0001). The initial minimum diameter of the treated pulmonary artery branch increased significantly after the procedure (from 3.98 mm to 9.82 mm, p < 0.0001). The incidence of complications was 8% (n = 2) and the clinical effectiveness of the procedure was good in 22 patients (88%).Conclusions: Stent implant in pulmonary artery branch stenosis is a safe and feasible though challenging technique, with significant clinical and anatomic improvement. The procedure represents an alternative to surgery and decreases the need for reinterventions in patients with congenital heart defects.

Speaking, Thinking, Writing: Meditative Surgery and Intercorporeal Circulation in Henry Duke of Lancaster's Livre de Seyntz Medicines (1354)

Henry of Lancaster's Livre de Seyntz Medicines is a vividly medicalized penitential narrative composed by a leading lay nobleman of fourteenth-century England. Grounded in the physiology of the medieval heart, Lancaster's understudied Livre demonstrates how medieval medical discourses could act as a vehicle for spiritual and psychophysiological change. Combining cognitive theories that view the heart as the tablet of memory with a physiology of the heart as a breathing organ that creates and circulates spirit, the Livre synthesizes medicine, natural philosophy, and theology into a program for the reform of memory, imagination, and will. As it articulates this process of reform through a series of meditative surgeries, the text adapts sophisticated Latinate clerical discourses for lay use and consciously uses physiological processes to make its program of spiritual self-reform available in physically and spiritually concrete ways to those who read or hear the text.

Hemolymph circulation in insect flight appendages: physiology of the wing heart and circulatory flow in the wings of the mosquito Anopheles gambiae.

The wings of insects are composed of membranes supported by interconnected veins. Within these veins are epithelial cells, nerves and tracheae, and their maintenance requires the flow of hemolymph. For this purpose, insects employ accessory pulsatile organs (auxiliary hearts) that circulate hemolymph throughout the wings. Here, we used correlative approaches to determine the functional mechanics of hemolymph circulation in the wings of the malaria mosquito Anopheles gambiae Examination of sectioned tissues and intravital videos showed that the wing heart is located underneath the scutellum and is separate from the dorsal vessel. It is composed of a single pulsatile diaphragm (indicating that it is unpaired) that contracts at 3 Hz and circulates hemolymph throughout both wings. The wing heart contracts significantly faster than the dorsal vessel, and there is no correlation between the contractions of these two pulsatile organs. The wing heart functions by aspirating hemolymph out of the posterior wing veins, which forces hemolymph into the wings via anterior veins. By tracking the movement of fluorescent microspheres, we show that the flow diameter of the wing circulatory circuit is less than 1 µm, and we present a spatial map detailing the flow of hemolymph across all the wing veins, including the costa, sub-costa, ambient costa, radius, media, cubitus anterior, anal vein and crossveins. We also quantified the movement of hemolymph within the radius and within the ambient costa, and show that hemolymph velocity and maximum acceleration are higher when hemolymph is exiting the wing.

Hydrogen Sulfide: Biogenesis, Physiology, and Pathology

The seminal studies by Kimura's group in the late 1990s [1, 2] ushered in a new era of biological signaling mediated by hydrogen sulfide (H2S). H2S has been described as the third “gasotransmitter” along with nitric oxide (NO) and carbon monoxide (CO; [3]). While none of these molecules actually signal as a gas, their hydrophilicity and lipophilicity enable them to readily traverse intracellular compartments where they serve in a variety of autocrine and paracrine signals capacities.

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels.

The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca(2+)-activated K(+) channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

Abstract 18016: Cell and Hydrogel-based Therapies Employing Cathelicidin Related Antimicrobial Peptide (CRAMP) Attenuate Cardiac Dysfunction in a Mouse Model of Myocardial Infarction: Potential Therapeutic Targets in Ischemic Heart Disease

Introduction: Limited stem cell retention following intracoronary administration has reduced the clinical efficacy of this novel therapy. Cathelicidins related antimicrobial proteins (CRAMPs) have been shown to prime bone marrow Derived mononuclear Cells (BMMNC) migration towards low gradients of SDF-1 suggesting a potential role in BMMNC retention. Here, we assessed the therapeutic efficacy of CRAMP in the context of BMMNC recruitment and retention via intracardiac delivery of CRAMP-treated BMMNCs or CRAMP-packed hydrogels (HG) post-myocardial infarction (MI). Methods and Results: During the in vivo cell studies, mice were randomized into 3 groups: MI followed by injection of PBS, BMMNCs alone, and BMMNCs incubated with CRAMP. During the in vivo HG studies, BM GFP chimera mice were randomized into 4 groups: MI followed by injection of HG alone, HG + SDF-1, HG + SDF-1 + CRAMP, HG + CRAMP. Changes in infarct size and cardiac function between 5 days and 5 weeks after MI were assessed using cardiac MRI (CMR) and echocardiography respectively. Treatment of BMMNCs with CRAMP enhanced their migration towards low, yet physiological, levels of SDF-1 in vitro (Fig 1A). In vivo, BMMNC+CRAMP therapy was associated with significant increase in capillary density as compared to the BMMNC-alone and control groups (Fig 1B). Moreover, BMMNC+CRAMP administration led to improvement in cardiac function and reduction in infarct size as compared to other groups (Fig 1C-D). Similar to the BMMNCs+CRAMP cell therapy, HG + SDF-1 + CRAMP administration post-MI led to improvement of cardiac function and reduction in infarct size compared with other groups (Fig 1E-F). Conclusion: Cathelicidins enhance BMMNC retention and recruitment after intramyocardial administration post-MI resulting in improvements in heart physiology and recovery. Therapies employing these strategies may represent an attractive method for improving outcomes of regenerative therapies in human studies.

Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr -/- and in utero TCDD-exposed Ahr +/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr -/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

Heart disease: recruitment of MEF2 activity by β-blockers wards off cardiomyocyte death.

Heart disease: recruitment of MEF2 activity by β-blockers wards off cardiomyocyte death.

Sequential Binding of MEIS1 and NKX2-5 on the Popdc2 Gene: A Mechanism for Spatiotemporal Regulation of Enhancers during Cardiogenesis.

SummaryThe homeobox transcription factors NKX2-5 and MEIS1 are essential for vertebrate heart development and normal physiology of the adult heart. We show that, during cardiac differentiation, the two transcription factors have partially overlapping expression patterns, with the result that as cardiac progenitors from the anterior heart field differentiate and migrate into the cardiac outflow tract, they sequentially experience high levels of MEIS1 and then increasing levels of NKX2-5. Using the Popdc2 gene as an example, we also show that a significant proportion of target genes for NKX2-5 contain a binding motif recognized by NKX2-5, which overlaps with a binding site for MEIS1. Binding of the two factors to such overlapping sites is mutually exclusive, and this provides a simple regulatory mechanism for spatial and temporal synchronization of a common pool of targets between NKX2-5 and MEIS1.

In This Issue

HomeCirculation ResearchVol. 117, No. 5In This Issue Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBIn This Issue Originally published14 Aug 2015https://doi.org/10.1161/RES.0000000000000070Circulation Research. 2015;117:389Optogenetic Voltage Sensing in Cardiac Myocytes (p 401)Download figureDownload PowerPointLiao et al measure electrical activity of heart cells and whole hearts with a fluorescent reporter.Monitoring electrical activity of the heart or cardiomyocytes in culture provides important information about normal and pathological cardiac physiology. But each recording method has limitations. Extracellular electrodes are non-invasive but have poor resolution. Intracellular recordings provide good resolution but are time-consuming, invasive and resource-intensive. Genetically-encoded voltage indicators (GEVI), however, may provide the best of both. They have been used to non-invasively measure electrical activity in brain cells of the mouse and fly, and now Liao and colleagues have tested one GEVI—called VSFP2.3—in whole mouse hearts and heart cells. Similar to VSFP2.3’s behavior in neurons, the protein’s fluorescent signal altered upon heart cell membrane depolarization: yellow emission increased and cyan decreased. This measurable change in fluorescence enabled the team to perform optical cardiograms on whole ex vivo mouse hearts, and on live mice—via optical fibers inserted into the animals’ chests. Lastly, the team used VSFP2.3 to monitor electrical activity of induced pluripotent stem cell-derived cardiomyocytes in vitro. Together the results provide a proof of principle that the use of GEVIs can provide high resolution monitoring of cardiovascular activity in vitro and in vivo.Methods to Study Cardiac Myocyte Epigenomics (p 413)Download figureDownload PowerPointPreissl et al investigate the epigenetic code and transcription profile of cardiomyocyte nuclei.The identity of a cell does not just come down to the proteins it expresses but to the genetic and epigenetic mechanisms that regulate protein expression. A thorough understanding of the epigenetic landscape of cardiomyocytes and how that landscape changes during development and disease could thus offer valuable insights into heart physiology. To gain such an understanding, Preissl and colleagues first devised a method for isolating highly pure cardiomyocyte nuclei, which relied on cold conditions and avoided enzymatic digestion to preserve the structural integrity of the nuclei and chromatin therein. The team separated cardiomyocyte nuclei from those of other heart cell types on the basis of expression of a specific marker protein—PCM1—and then analyzed nuclear mRNA expression, cellular mRNA expression and a number of epigenetic marks. Their study revealed that the pattern of epigenetic marks correlated more closely with nuclear mRNA expression than cellular mRNA, confirming that the former is a more accurate reflection of the transcription activity of cells. The procedure described in this paper serves as a springboard for further epigenetic analyses of cardiomyocytes from different stages of development or under different pathological conditions, say the authors.Role of miR-34a Post-MI (p 470)Download figureDownload PowerPointMicroRNA-34a impairs heart regeneration after myocardial infarction, report Yang et al.The hearts of newborn mice can almost entirely recover from injury, but by one week of age this regenerative capacity diminishes and remains lost throughout adulthood. If researchers could understand what makes regeneration possible in young mice they might be able to recapitulate regeneration in human hearts after myocardial infarctions. To this end, Yang et al have now investigated the role of microRNA miR34a in mouse heart regeneration. Mir34a is a suppressor of cell proliferation known to increase in expression in the heart with age. Furthermore, suppression of miR34a reduces age-associated cardiomyocyte death. The team showed that levels of miR34a are low in the newborn mouse heart and rise to adult levels within a week of birth. Over-expression of miR34a in the newborn mice prevented heart regeneration, whereas inhibition of miR34a in the adult heart improved cardiac function after infarction. Lastly, the team identified direct targets of miR34a repression—Sirt1, cyclinD1, and Bcl2—which are known to be involved in cell aging, proliferation and survival. Inhibition of miR34a in adult hearts led to the upregulation of these genes. Together the results suggest that inhibiting miR34a, or boosting its targets, may offer therapeutic routes to improve heart recovery after myocardial infarction. Previous Back to top Next FiguresReferencesRelatedDetails August 14, 2015Vol 117, Issue 5 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000070 Originally publishedAugust 14, 2015 PDF download Advertisement

Abstract 216: Genetic Deletion of Cardiomyocyte Mineralocorticoid Receptors Prevents Cardiac Dysfunction and Premature Death in Mice Lacking Glucocorticoid Receptors in the Heart

Heart failure is one of the leading causes of death in the Western world, and stress is increasingly associated with adverse cardiac outcomes. Glucocorticoids are primary stress hormones, but their direct role in heart physiology and pathology is poorly understood. The actions of glucocorticoids are mediated classically by the glucocorticoid receptor (GR); however, in cardiomyocytes glucocorticoid occupancy and activation of the mineralocorticoid receptor (MR) may also contribute to the observed glucocorticoid response. To elucidate the in vivo function of glucocorticoid signaling in the heart, we generated mice with cardiomyocyte-specific deletion of GR (cardioGRKO). The cardioGRKO mice spontaneously develop cardiac hypertrophy by 2 months of age and left ventricular systolic dysfunction and dilatation between 3-6 months of age, and they die prematurely from heart failure. The mean survival age of the cardioGRKO mice was 9.3 months, and 97% (38 of 39) of the mice died prior to reaching 12 months of age. Loss of GR in the heart was not accompanied by an increase in fibrosis. To investigate whether cardiomyocyte MR signaling contributes to the pathology in the cardioGRKO mice, we generated for the first time mice lacking both GR and MR in the heart (cardioGRMRKO). Despite showing increased expression of classic hypertrophic marker genes, the cardioGRMRKO mice were protected from the development of cardiac hypertrophy, and no major alterations were observed in the function and chamber size of the left ventricle. Moreover, the cardioGRMRKO mice were protected from premature death as 94% (15 of 16) of the mice survived past the 13 month study endpoint. Microarray analysis revealed marked differences in gene expression profiles between the cardioGRKO and cardioGRMRKO hearts. These findings reveal that cardiomyocyte MR signaling, when unopposed by GR signaling, plays a major role in the progression of cardiac disease. Moreover, they suggest that combining GR agonists with MR antagonists may represent an improved therapeutic approach for treating heart failure.

Ah Receptor Signaling Controls the Expression of Cardiac Development and Homeostasis Genes.

Congenital heart disease (CHD) is the most common congenital abnormality and one of the leading causes of newborn death throughout the world. Despite much emerging scientific information, the precise etiology of this disease remains elusive. Here, we show that the aryl hydrocarbon receptor (AHR) regulates the expression of crucial cardiogenesis genes and that interference with endogenous AHR functions, either by gene ablation or by agonist exposure during early development, causes overlapping structural and functional cardiac abnormalities that lead to altered fetal heart physiology, including higher heart rates, right and left ventricle dilation, higher stroke volume, and reduced ejection fraction. With striking similarity between AHR knockout (Ahr(-/-)) and agonist-exposed wild type (Ahr(+/+)) embryos, in utero disruption of endogenous AHR functions converge into dysregulation of molecular mechanisms needed for attainment and maintenance of cardiac differentiation, including the pivotal signals regulated by the cardiogenic transcription factor NKH2.5, energy balance via oxidative phosphorylation and TCA cycle and global mitochondrial function and homeostasis. Our findings suggest that AHR signaling in the developing mammalian heart is central to the regulation of pathways crucial for cellular metabolism, cardiogenesis, and cardiac function, which are potential targets of environmental factors associated with CHD.

Quantitative assessment of atrial conduit function: a new index of diastolic dysfunction.

BackgroundHeart failure (HF) epidemic has increased need for accurate diastolic dysfunction (DD) quantitation. Cardiac MRI can elucidate left atrial (LA) phasic function, and accurately quantify its conduit contribution to left ventricular (LV) filling, but has limited availability. We hypothesized that the percentage of LV stroke volume due to atrial conduit volume (LACV), as assessed using 3D-echocardiography, can differentiate among progressive degrees of DD in HF patients.Methods and resultsSixty-three subjects (66 ± 12 years) with DD and ejection fraction (EF) ranging 14–62 % underwent full-volume 3D-echocardiography. Simultaneous LA and LV volume curves as function of time (t) were calculated, with LACV as {text{LACV}}left( t right) , = , left[ {{text{LV}}left( t right){-}{text{LV minimum}}} right] , - , left[ {{text{LA maximum }} - {text{ LA}}left( t right)} right], expressed as % of stroke volume. Patients were assigned to four (0–3, from none to severe) DD grades, according to classical Doppler parameters. In this population DD is linked to LACV, with progressively higher percentages of conduit contribution to stroke volume associated with higher degrees of DD (p = 0.0007). Patients were then dichotomized into no-mild (n = 26) or severe (n = 37) DD groups. Apart from atrial volume, larger (p < 0.02) in severe DD group, no differences between groups were found for LV diastolic and stroke volume, EF, mass and flow propagation velocity. However, a significant difference was found for LACV expressed as % of LV stroke volume (29 ± 15 vs. 43 ± 23 %, p = 0.016).ConclusionsOur study confirms that LACV contribution to stroke volume increases along with worsening DD, as assessed in the context of (near) constant-volume four-chamber heart physiology. Thus, LACV can serve as new parameter for DD grading severity in HF patients.

Patient specific physics-based model for interactive visualization of cardiac dynamics.

Cardiac disorders result mainly from defects in cardiac structure or failure to generate and regulate electrical impulses. Knowledge of the structure, motion patterns, local deformation, and associated electrical activation patterns of the heart is necessary for precise diagnosis and treatment. Electrical and mechanical performance of the heart is strongly influenced by the anisotropic nature of myocardial tissue. Diffusion-encoded MR imaging provides in vivo myocardial fiber track information that can be used for precise simulation of cardiac conduction and contraction. We propose a method that incorporates such fiber track information with a physics-based deformable model to realistically simulate cardiac contraction and subsequent relaxation. The simulation aims to reproduce the myocardial deformation during the heartbeat. The system allows interactive visualization of dynamic 3-D heart structures during the cardiac cycle. In procedures such as catheter ablation, the interactive 4-D model provides updated anatomy and physiology of the patient's heart simultaneously, and can be used to guide the procedure for efficient targeting of the treatment regions.

From ATP to PTP and Back: A Dual Function for the Mitochondrial ATP Synthase.

Mitochondria not only play a fundamental role in heart physiology but are also key effectors of dysfunction and death. This dual role assumes a new meaning after recent advances on the nature and regulation of the permeability transition pore, an inner membrane channel whose opening requires matrix Ca(2+) and is modulated by many effectors including reactive oxygen species, matrix cyclophilin D, Pi (inorganic phosphate), and matrix pH. The recent demonstration that the F-ATP synthase can reversibly undergo a Ca(2+)-dependent transition to form a channel that mediates the permeability transition opens new perspectives to the field. These findings demand a reassessment of the modifications of F-ATP synthase that take place in the heart under pathological conditions and of their potential role in determining the transition of F-ATP synthase from and energy-conserving into an energy-dissipating device.

Echocardiographic reference ranges for normal cardiac Doppler data: results from the NORRE Study.

Reference values for Doppler parameters according to age and gender are recommended for the assessment of heart physiology, specifically for left ventricular (LV) diastolic function. In this study, we report normal reference ranges for Doppler parameters obtained in a large group of healthy volunteers. Echocardiographic data were acquired using state-of-the-art cardiac ultrasound equipment following Doppler acquisition and measurement protocols approved by the European Association of Cardiovascular Imaging. A total of 449 (mean age: 45.8 ± 13.7 years) healthy volunteers (198 men and 251 women) were enrolled at the collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was obtained from all subjects following predefined protocols. The majority of the Doppler diastolic parameters (e', E/e') as well as right ventricle systolic s' wave velocity were similar in men and women. Left ventricle s' wave velocity was higher in men than in women. E wave and e' were higher in younger subjects and decreased progressively in the older ones. E/e' ratio increased with ageing. Septal e' <8 cm/s was present in 19.7% of the subjects in the 40-60 year group and in 55% of those in the ≥60 year group. However, the cut-off value of average E/e' or lateral E/e' remained <15 or 13, respectively, in the majority of patients. The NORRE study provides the reference values for the most useful Doppler parameters in the evaluation of heart physiology. These data highlight the need of using age-specific reference values especially for the diagnosis of LV systolic and diastolic dysfunction and for the estimation of LV filling pressures.

Using Echocardiography as a Promising Adjunctive Teaching Tool for Cardiac Anatomy and Physiology

A transformation in medical education is currently underway which prioritizes competency and clinical integration with basic sciences. Here we are exploring the feasibility of early echocardiography (Echo) experience as an adjunct tool for teaching heart anatomy and physiology to second year medical students.The study was conducted on 100 students in a problem‐based learning curriculum. Students were introduced to cardiac anatomy and physiology as well as the basic principles of ultrasonography before the Echo sessions. A pretest was conducted at the beginning of the Echo theoretical session, consisting of 10 questions on Echo images. The practical sessions included hands‐on experience on standardized patients with a checklist of structures that are commonly demonstrated in left parasternal and apical four chamber windows. A post‐test with the same questions was repeated after the clinical sessions.The post‐test outcome revealed a significant improvement in identifying the cardiac structures and function in comparison to the pre‐test (P value 蠄 0.0001) imageAlthough the students were very accurate in identifying heart chambers and valves without assistance, the pulmonary artery and valve in the parasternal short axis were mostly able to be identified with assistance. Furthermore 95% of students admitted that prior basic knowledge is essential for Echo images identification and 86% stated that integrating this experience is helpful in consolidating different phases of the cardiac cycle.ConclusionSpatial orientation offered by Echo with prior basic knowledge seems to provide an effective tool in consolidating medical student's understanding of heart anatomical relations and cardiac physiology.