The natural compound TMYX reduces SAN cells rate by antagonizing the cAMP modulation of f-channels

Tongmai Yangxin (TMYX), is a complex compound of a Traditional Chinese Medicine (TCM) used to treat several cardiac rhythm disorders; however, no information regarding its mechanism of action is available. In this study we provide a detailed characterization of the effects of TMYX on the electrical activity of pacemaker cells and unravel its mechanism of action. Single-cell electrophysiology revealed that TMYX elicits a reversible and dose-dependent (2/6 mg/ml) slowing of spontaneous action potentials rate (-20.8/-50.2%) by a selective reduction of the diastolic phase (-50.1/-76.0%). This action is mediated by a negative shift of the If activation curve (-6.7/-11.9 mV) and is caused by a reduction of the cAMP-induced stimulation of pacemaker channels. We provide evidence that TMYX acts by directly antagonizes the cAMP-induced allosteric modulation of the pacemaker channels. Noticeably, this mechanism functionally resembles the pharmacological actions of muscarinic stimulation or β-blockers, but it does not require generalized changes in cytoplasmic cAMP levels thus ensuring a selective action on rate. In agreement with a competitive inhibition mechanism, TMYX exerts its maximal antagonistic action at submaximal cAMP concentrations and then progressively becomes less effective thus ensuring a full contribution of If to pacemaker rate during high metabolic demand and sympathetic stimulation.

Evaluation of the efficiency of a new pulsatile flow‑generating circulatory-assist system in rotary blood pumps. Research on a mathematical model

Objective: to study the effect of a pulsatile flow-generation (PFG) device on the basic hemodynamic parameters of the circulatory system using a mathematical model.Results. Modelling and simulation showed that the use of PFG significantly (76%) increases aortic pulse pressure. The proposed mathematical model adequately describes the dynamics of the circulatory system and metabolism (oxygen debt) on physical activity in normal conditions and heart failure, and the use of non-pulsatile and pulsatile circulatory-assist systems. The mathematical model also shows that the use of PFG device blocks the development of rarefaction in the left ventricular cavity associated with a mismatch of blood inflow and outflow in diastolic phase when there is need to increase systemic blood flow by increasing the rotary pump speed.

Morphometrical observation on the left atrium in human adults

Aim. To determine the left atrial dimensions, their ratios and relationships that characterize anatomy for left atrium structure in the normal human adult using the model of the atrial end-diastolic phase. Methods. We studied 54 heart specimens of subjects aged 3588 years who died from non-cardiac causes. The atrial end-diastolic phase was modeled by filling a specimen fixed in 1% formalin with liquid silicone. After silicone hardened, we performed morphometric measurements by a caliper. The data were processed by using a cluster, correlation and variance analysis. For pairwise comparison, we used the MannWhitney U-test or a two-sided t-test. Results. The article presents mean, standard deviation, median, 25th percentile and 75th percentile and coefficients of variation for the length, width and sagittal size of the left atrium, as well as the values of the distances between the pulmonary vein orifices, which characterize the dimensions of the left atrium posterior wall. Based on the left atrial size differences and their ratios, the specimens were divided into three clusters. The first (n1=23) and second clusters (n2=10) were represented by hearts with a cubic atrium; the second group differed from the first in the larger size of the left atrium. The third cluster (n3=21) included the hearts in which the largest left atrium size was the width, so the shape of the atria resembled a parallelepiped. The typical number of the pulmonary vein ostia we found in 91% of the specimens. The posterior wall of the left atrium, with a common number and topography of the ostia, were rectangle or an unequal trapezium in shape. We analyzed correlations between the sizes of the heart, left atrium and its posterior wall. We concretized the conceptual apparatus concerning the nomenclature and terminology of the left atrium anatomical structures. Conclusion. Based on the size ratio, two shape variations of the left atrium body can be identified: cubic or parallelepiped; cubic atria can be divided into large and small; the co-directional dimensions of the left atrial body and its posterior wall showed the strongest correlations.

COMPARISON OF TWO THICK SHELL MODELS PERFORMANCE IN NONINVASIVE EVALUATION OF MYOCARDIAL WALL STRESS

Coronary artery stenosis is the most common heart disease, leading to altered myocardial mechanics. This study aimed to compare Ghista–Sandler and Mirsky wall stress models and evaluate the discriminant analysis of noninvasive wall stress based on these models. 59 Coronary artery disease (CAD) patients were divided into two groups; moderate stenosis and severe stenosis in the left anterior descending artery proximal part were enrolled in this study. The wall stress in the end-systolic and end-diastolic phases at LV anterior and interventricular septum wall segments calculated by using the equation proposed by Ghista–Sandler and Mirsky. The specificity and sensitivity of wall stress at groups were calculated by Ghista–Sandler and Mirsky models. The wall thickness and principal radius of segments in healthy subjects and patients with severe and moderate stenosis were shown statistically differences in some segments of anterior and septum walls ([Formula: see text]). Statistical analysis showed that calculated stresses in myocardial wall segments of patients with severe and moderate coronary stenosis and healthy people had a significant difference in systole and diastolic phase. Results of the discriminant analysis showed the specificity value obtained by the Ghista–Sandler model were higher in most wall stress combinations than the Mirsky model. Sensitivity in identifying patients with severe stenosis was higher in the Ghista–Sandler model. It is concluded that specificity and sensitivity based on wall stresses calculated by the Ghista–Sandler model were higher in comparison with the Mirsky model. The Ghista–Sandler model has better performance than the Mirsky model in diagnosing patients with stenosis.

A novel ventricular map of electrograms duration as a method to identify areas of slow conduction during ablation of ventricular tachycardia

Funding Acknowledgements Type of funding sources: None. Background – Wave front inhomogeneous propagation is crucial for reentry circuit generation. Bipolar EGM duration is indicative of local conduction delay and may identify areas of low conduction as a functional substrate. This study aimed to create a map of EGM duration during the VT (VEDUM Map) to identify the area of the slowest conduction and to verify if RF delivery at this area allows to rapidly interrupt the VT. Methods – 24 high-density VTs maps (21 patients) were analyzed. Activation maps and voltage maps during SR were performed. An offline remap confirmed with MathLab software was customized to visualize the longest duration electrogram during VT. Results – All of the VTs were interrupted during the first RF delivery (mean time 7,3 ± 5,4 sec (range 3-25 sec)) at the area with the longest EGM duration (212 ± 47 ms (range 113-330 ms)). . In 9 pts (37,5%) the longest EGM was located at the entrance or exit area of the activation maps while in 5 pts (21%) the EGM covered the full diastolic phase. Finally, in 10 pts the longest EGM occurred in the mid-exit-diastolic phase. Conclusions - A novel Ventricular map of Electrograms DUration (VEDUM Map) is highly accurate in defining a conductive vulnerable zone of the VT circuit. The longest EGM duration within the isthmus is highly predictive of rapid VT termination. Quantitative variablesQualitative variablesMeanMedianStandard DeviationAge71738.40BMI26.624.54.02LV EDV16315442.7LV EDD61.2629.9LV EF38.7369.74VT cycle lenght (TCL)35537556.4EGM max. duration in VT21220847EGM max dur / TCL58.260.512Maximum EGM duration localization in CLProto = 12.5%Meso = 33.3%Tele = 25%Full = 20.8%Myocardium voltage characteristics in VEDUM EGMHealthy = 25%Transition = 20.8%Scar = 41.7%Critical Isthmus area12.3107.3VT Interruption during RFYes = 79.2%No = 20.8%Time (seconds) to interruption765Access typeEndo = 58.3%Epi = 29.2%Clinical and procedural dataAbstract Figure.

Abstract 14327: Tricuspid Valve Annular Area Correlations and Determinants in Healthy Controls and Patients With Severe Mitral Regurgitation

Introduction: Concomitant tricuspid valve (TV) repair during mitral valve (MV) surgery based on annular dilation rather than the degree of regurgitation (TR) has been shown to be beneficial and is supported by the guidelines. Hypothesis: Assess the correlations between tricuspid and mitral annular areas (TVA and MVA, respectively) indexed to body surface area (BSA) measured by cardiac computed tomography (CT), and identify the determinants of the TVA in normal and diseased states. Methods: We included 50 consecutive controls (no valvular heart disease undergoing coronary CTA), 50 primary mitral regurgitation (PMR) patients referred for robotic repair, and 25 functional MR (FMR) patients referred for percutaneous therapy, without significant associated TR (≤2+ TR). We used dedicated CT software (Aquarius, TeraRecon) to perform the annular measurements. A mid-diastolic phase acquisition (~70%) was used Results: Patients with FMR were older (median age [25th, 75th] = 70 years [63,77.5] vs. 55 [48,59] in PMR and 48 [38,55] in controls), had more clinical comorbidities, and lower ejection fraction (32% [23,40] vs. >60% in both other groups). TVA was significantly correlated to MVA in controls (r≥0.5; p<0.001), as well as in patients with PMR and FMR. (Figure 1). Table 1 shows the univariate correlations and multivariate determinants of the TVA. In the multivariate analysis, the MVA, RA area, and LVEDV were the independent predictors of TVA. Interestingly, the MVA was the most important predictor (β= 0.420, p<0.001). Conclusion: In individuals without valvular heart disease and in patients with severe MR (PMR and FMR) with ≤ 2+ TR, the TVA was largely determined by the MVA.

Mechanisms, features, and significance of diastolic mitral regurgitation: a case series

Background Diastolic mitral regurgitation (DMR) is a type of functional mitral regurgitation. Its occurrence in the diastolic phase of cardiac cycle renders DMR an easily ignored entity. Confusing it with systolic mitral regurgitation occasionally happens. The reversal of left atrioventricular pressure gradient during diastole and the incomplete closure of mitral valve are the essential conditions for DMR. Diastolic mitral regurgitation develops under various situations, where the mechanisms of diastolic reversal of left atrioventricular pressure gradient differ. Case summary Patient 1 was a 50-year-old man diagnosed with 2:1 second-degree atrioventricular block (AVB). Patient 2 was a 70-year-old man diagnosed with first-degree AVB. Patient 3 was a 66-year-old man diagnosed with atrial fibrillation with long intermission and occasional atrial flutter with unequal conduction. Patient 4 was a 54-year-old woman diagnosed with dilated cardiomyopathy with complete left bundle branch block. Patient 5 was a 36-year-old man diagnosed with severe acute aortic regurgitation secondary to subacute bacterial endocarditis. Discussion Although the degree of DMR is relatively mild, its appearance generally prompts further clinical considerations. The appreciation of DMR has an incremental value for diagnosing and evaluating the underlying cardiovascular disease.

A Rare Cause of Left Atrium Compression: Esophageal Achalasia

Background Extrinsic compression of left atrium (LA) due to esophageal achalasia is uncommon. Patients might present with dysphagia, dyspnea, and even hemodynamic compromise. Prompt detection with thorough differential diagnosis is crucial for subsequent management. We presented a case with LA compression by esophageal achalasia, and literature review regarding the clinical manifestation, diagnosis, and treatment strategy was performed to provide an updating knowledge of the disease.Case presentation A 59-year-old relatively healthy man presented with dysphagia accompanied by chest tightness and breathlessness after a large meal. His chest X-ray film disclosed a widened mediastinum. The barium swallow esophagogram revealed contrast pooling at the esophagogastric junction with a bird beak shape. Meanwhile, the transthoracic echocardiogram showed a round-shaped, well bordered, hyperechogenic, and heterogeneous mass (5.1 cm x 3.8 cm in size) compressing the LA irrespective of the systolic or diastolic phase. A chest contrast-enhanced computed tomography scan showed diffuse esophageal dilatation with a smoothly thickening wall aligned compressing the LA. Due to the abovementioned image findings, extrinsic compression of LA by esophageal achalasia was diagnosed.ConclusionLA compression due to esophageal achalasia is not common. Remarkably, given a patient presenting dysphagia and concurrent dyspnea after meals, the clinicians should keep this differential diagnosis in mind. Echocardiography and esophagography are useful to ensure the diagnosis promptly.

Cardiac Helical Function

Background. The aim of this study was to investigate: a) the starts and ends of the myocardial band; b) the slippage between the band segments, when performing both torsion and ventricular detorsion, implies that there should be an antifriction mechanism that avoids dissipating the energy; c) the electrical activation of the endocardial and epicardial bands and secondarily understand ventricular twist and the mechanism of active suction during the diastolic isovolumic phase. Methods. They were used: a) Ten young-bovine hearts (800-1000 g) and seven human hearts (one embrión, 4 g; one 10 years, 250 g and five adult, 300 g/average); b) five patients with no structural cardiac abnormalities and normal QRS complexes underwent three-dimensional endoepicardial electroanatomic mapping. Results. We have found in all the bovine and human hearts studied a nucleus (fulcrum) underlying the right trigone, whose osseus, chondroid or tendinous histological structure depends on the specimen analyzed. All the hearts studied presented myocardial attachment to the rigid structure of the fulcrum. Hyaluronic acid was found in the cleavage planes between the myocardial bundles.Endo-epicardial mapping demonstrates an electrical activation sequence in the area of the apex loop in agreement with the synchronic contraction of the descending and ascending band segments, consistent with the mechanism of ventricular twist. The late activation of the ascending band segment is consistent with its persistent contraction during the initial period of the isovolumic diastolic phase (the basis of the suction mechanism). Conclusions. The finding of the fulcrum gives support to the spiral myocardial band being the point of fixation that allows the helicoidal torsion. The hyaluronic acid would act as a lubricant and provide great resistance to mechanical pressures. This study explains the ventricular twist and the active suction mechanism during the isovolumic diastolic and early ventricular filling phases.Trial. This work does not correspond to a trial

Detection of the intimal tear in aortic dissection and ulcer-like projection in intramural hematoma: usefulness of full-phase retrospective ECG-gated CT angiography

Purpose To compare the accuracy of non-electrocardiogram (ECG)-gated CT angiography (CTA), single-diastolic-phase ECG-gated CTA, and full-phase ECG-gated CTA in detecting the intimal tear (IT) in aortic dissection (AD) and ulcer-like projection (ULP) in intramural hematoma (IMH). Materials and methods A total of 81 consecutive patients with AD and IMH of the thoracic aorta were included in this single-center retrospective study. Non-ECG-gated CTA, single-diastolic-phase ECG-gated CTA, and full-phase ECG-gated CTA were used to detect the presence of the IT and ULP in thoracic aortic regions including the ascending aorta, aortic arch, and proximal and distal descending aorta. Results The accuracy of detecting the IT and ULP was significantly greater using full-phase ECG-gated CTA (88% [95% CI: 100%, 75%]) than non-ECG-gated CTA (72% [95% CI: 90%, 54%], P = 0.001) and single-diastolic-phase ECG-gated CTA (76% [95% CI: 93%, 60%], P = 0.008). Conclusion Full-phase ECG-gated CTA is more accurate in detecting the IT in AD and ULP in IMH, than non-ECG-gated CTA and single-diastolic-phase ECG-gated CTA.