Sex as a main determinant of bi-atrial acute and chronic adaptation to exercise.

PURPOSE: Athlete's heart encompasses multiple physiological cardiac adaptations, although less is known at atrial level. How sex may influence the type and extent of atrial adaptations to exercise stimuli is also unknown. Our objective was to compare gender differences of echocardiographic atrial function indices in response to exercise in endurance athletes (EAs). METHODS: Highly trained (> 10 h/week) endurance athletes performed a maximal cardiopulmonary exercise test (CPET). Echocardiographic evaluation was performed at rest and immediately after exercise. Atria analysis consisted of standard and speckle-tracking echocardiographic assessment of atrial dimensions and contractile, reservoir, and conduit functions with myocardial deformation. RESULTS: 80 EAs (55% women) were enrolled and performed excellent CPET (129.6% of predicted VO2 maximal consumption). At rest, left atrial (LA) volumes and strain were similar between men and women. Women had lower right atrial (RA) volumes (26.7 vs 32.9 ml/m2, p < 0.001) and higher reservoir and conduit strain absolute values. After exercise, women exhibited a larger improvement in reservoir and conduit LA strain, and the same trend was observed for the RA. In EAs with LA dilatation on baseline (~ 50%), women persistently showed higher increase in reservoir and conduit strain profile with exercise compared to men. CONCLUSION: In highly trained EAs, women have similar or even lower atrial dimensions remodelling compared to men, but better function based on reservoir and conduit strain values both at rest and in response to exercise. This phenomenon should be confirmed in larger studies and its potential role in the development of supraventricular arrhythmias, addressed in a specifically designed protocol.

Alpha and beta myosin isoforms and human atrial and ventricular contraction.

Human atrial and ventricular contractions have distinct mechanical characteristics including speed of contraction, volume of blood delivered and the range of pressure generated. Notably, the ventricle expresses predominantly ß-cardiac myosin while the atrium expresses mostly the α-isoform. In recent years exploration of the properties of pure α- & ß-myosin isoforms have been possible in solution, in isolated myocytes and myofibrils. This allows us to consider the extent to which the atrial vs ventricular mechanical characteristics are defined by the myosin isoform expressed, and how the isoform properties are matched to their physiological roles. To do this we Outline the essential feature of atrial and ventricular contraction; Explore the molecular structural and functional characteristics of the two myosin isoforms; Describe the contractile behaviour of myocytes and myofibrils expressing a single myosin isoform; Finally we outline the outstanding problems in defining the differences between the atria and ventricles. This allowed us consider what features of contraction can and cannot be ascribed to the myosin isoforms present in the atria and ventricles.

Functional interaction of H2-receptors and 5HT4-receptors in atrial tissues isolated from double transgenic mice and from human patients.

In the past, we generated transgenic mice that overexpress the human histamine 2 (H2)-receptor (H2-TG) or that overexpress the human serotonin 4 (5-HT4)-receptor (5-HT4-TG) in the heart. Here, we crossbred these lines of mice to generate double transgenic mice that overexpress both receptors (DT). This was done to study a conceivable interaction between these receptors in the mouse heart as a model for the human heart. When in left atria, initially, force of contraction was elevated maximally with 1 µM serotonin, and subsequently, histamine was cumulatively applied; a biphasic effect of histamine was noted: the force of contraction initially decreased, maximally at 10 nM histamine, and thereafter, the force of contraction increased again at 1 µM histamine. Notably, functional interaction between 5-HT and histamine was also identified in isolated electrically stimulated trabeculae carneae from human right atrium (obtained during cardiac surgery). These functional and biochemical data together are consistent with a joint overexpression of inotropically active H2-receptors and 5-HT4-receptors in the same mouse heart. We also describe an antagonistic interaction on the force of contraction of both receptors in the mouse atrium (DT) and in the human atrial muscle strips. We speculate that via this interaction, histamine might act as a "brake" on the cardiac actions of 5-HT via inhibitory GTP-binding proteins acting on the activity of adenylyl cyclase.

Statistical Approach to Incorporating Experimental Variability into a Mathematical Model of the Voltage-Gated Na+ Channel and Human Atrial Action Potential.

The voltage-gated Na+ channel Nav1.5 is critical for normal cardiac myocyte excitability. Mathematical models have been widely used to study Nav1.5 function and link to a range of cardiac arrhythmias. There is growing appreciation for the importance of incorporating physiological heterogeneity observed even in a healthy population into mathematical models of the cardiac action potential. Here, we apply methods from Bayesian statistics to capture the variability in experimental measurements on human atrial Nav1.5 across experimental protocols and labs. This variability was used to define a physiological distribution for model parameters in a novel model formulation of Nav1.5, which was then incorporated into an existing human atrial action potential model. Model validation was performed by comparing the simulated distribution of action potential upstroke velocity measurements to experimental measurements from several different sources. Going forward, we hope to apply this approach to other major atrial ion channels to create a comprehensive model of the human atrial AP. We anticipate that such a model will be useful for understanding excitability at the population level, including variable drug response and penetrance of variants linked to inherited cardiac arrhythmia syndromes.

Morphometric analysis of the His bundle (atrioventricular fascicle) in humans and other animal species. Histological and immunohistochemical study.

The His bundle is a part of the specialized electrical conduction system that provides a connection between the atrial and ventricular myocardial compartments in both normal and abnormal hearts. The aim of this study was to perform a morphometric analysis of His bundle characteristics of in humans, dogs, horses and pigs and compare them in these studied species. Histological sections of 5 µm thickness were obtained and stained with hematoxylin-eosin and Masson's trichrome; the desmin and periodic acid-Schiff methods were also used for precise identification of cells. The His bundle was found to be longer in horses (2.85 ± 1.02 mm) and pigs (1.77 ± 0.9 mm) than in dogs (1.53 ± 0.8 mm) or humans, in which it was shortest (1.06 ± 0.6 mm). The area and diameters in His bundle cells, were significantly larger in pigs and horses than in humans (p < 0.001) or dogs (p < 0.001). We found two organizational patterns of His bundle components: group I, with large cells and a high amount of collagen fibers in ungulates (pigs and horses); and group II, with smaller cells and lower abundance of collagen fibers in humans and dogs. Documenting cell size variations in the His bundle allows us not only to identify this bundle by histological or anatomical location but also to differentiate these cells from others such as nodal or Purkinje cells. Our analysis revealed that His bundle cells have discrete identities based on their morphometric and histological characteristics.

The proarrhythmic effects of hypothermia in atria isolated from 5-HT4-receptor-overexpressing mice.

We investigated whether hypothermia would be arrhythmogenic in mice that overexpress the human 5-HT4 receptor only in their cardiac myocytes (5-HT4-TG). Contractile studies were performed in isolated, electrically driven (1 Hz) left and spontaneously beating right atrial preparations of 5-HT4-TG and littermate wild-type control mice (WT). Hypothermia (23 °C) decreased the force of contraction in the mouse right and left atrial preparations. Moreover, the concentration-dependent positive inotropic effects of 5-HT were blunted but still shifted to lower 5-HT concentrations in the left 5-HT4-TG atria in hypothermia compared to normothermia (37 °C). Furthermore, hypothermia increased the incidence of right atrial arrhythmias in 5-HT4-TG more than in WT mice. In contrast, at 37 °C, lowering the potassium concentration from 5.2 to 2.0 mM also induced arrhythmias in the right atrium, but with a similar incidence in WT and 5-HT4-TG mice. In contrast, 10 µM d,l-sotalol and 300 µM erythromycin did not induce arrhythmias. Hypothermia was accompanied by the increased expression of heat shock protein 70 (HSP70) in WT but not in 5-HT4-TG mice. We concluded that without the stimulation of 5-HT4-receptors by exogenous agonists, a simple temperature reduction can increase arrhythmias in 5-HT4-TG mice. It is tempting to speculate that in human patients, 5-HT4 receptors might contribute to potentially deadly hypothermia-induced arrhythmias.

Reliability of left atrial strain reference values: A 3D echocardiographic study.

BACKGROUND: Standard apical four-chamber and two-chamber views often maximize the long-axis of the left ventricle, resulting in artifactitious foreshortening of the left atrium (LA), which may overestimate LA longitudinal reservoir strain (LALS). We compared LALS values between 2D echocardiography (2DE) and 3D echocardiography (3DE) in healthy subjects to determine whether 2DE speckle tracking analysis overestimates the reference value of LALS. METHODS AND RESULTS: In this study, 4 types of cohorts were included: 1. 105 normal subjects (retrospectively), 2. 53 patients with cardiovascular diseases (retrospectively), 3. 15 patients who received cardiac magnetic resonance (prospectively), and 4. 20 normal subjects (prospectively). LALS and LA length were measured using both 2DE and 3DE in 105 healthy subjects (median age: 42 years). Biplane LALS was measured in apical four- and two-chamber views using 2DE speckle tracking software, and 3DE LALS was measured using new 3DE LA strain software. To determine sensitivity, we also performed the same analysis in 53 patients with cardiovascular disease. The mean value of biplane LALS was 39.6%. LA length at both end-diastole (r = -0.43) and end-systole (r = -0.54) was negatively correlated with biplane LALS. Multivariate regression analysis revealed that both end-diastolic and end-systolic LA length had significant negative relationships with biplane LALS after adjusting for anthropometric and echocardiographic image quality parameters. 3DE LALS (23.7±7.6%) gave significantly lower values than 2DE LALS (39.5±12.0%, p<0.001) with a weak correlation (r = 0.33). LA length measured by 2DE was significantly shorter than that measured by 3DE. The same trend was observed in diseased patients. CONCLUSIONS: Our results revealed that in 2DE, the LA cavity consistently appears longitudinally foreshortened in apical views, potentially overestimating LALS. 3DE may overcome this limitation.

Identifying At-Risk Patients for Sustained Atrial High-Rate Episodes Using the C2HEST Score: The West Birmingham Atrial Fibrillation Project.

Background Sustained atrial high-rate episodes (SAHREs) among individuals with a cardiac implantable electronic device are associated with an increased risk of adverse outcomes. Risk stratification for the development of SAHREs has never been investigated. We aimed to assess the performance of the C2HEST (coronary artery disease or chronic obstructive pulmonary disease [1 point each], hypertension [1 point], elderly [age ≥75 years, 2 points], systolic heart failure [2 points], thyroid disease [1 point]) score in predicting SAHREs in patients with cardiac implantable electronic devices without atrial fibrillation. Methods and Results Five Hundred consecutive patients with cardiac implantable electronic devices in the West Birmingham Atrial Fibrillation Project in the United Kingdom were followed since the procedure to observe the development of SAHREs, defined by atrial high-rate episodes lasting >24 hours. Risk factors and incidence of SAHREs were analyzed. The predictive value of the C2HEST score for SAHRE prediction was evaluated. Over a mean follow-up of 53.1 months, 44 (8.8%) patients developed SAHREs. SAHREs were associated with higher all-cause mortality (P<0.001) and ischemic stroke (P=0.001). Age and heart failure were associated with SAHRE occurrence. The incidence of SAHREs increased by the C2HEST score (39% higher risk per point increase). Among patients with a C2HEST score ≥4, the incidence of SAHREs was 3.62% per year (95% CI, 2.14-5.16). The C2HEST score had moderate predictive capability (area under the curve, 0.73; 95% CI, 0.64-0.81) and discriminative ability (log-rank P=0.003), which was better than other clinical scores (CHA2DS2-VASc, CHADS2, HATCH). Conclusions The C2HEST score predicted SAHRE incidence in patients without atrial fibrillation who had an cardiac implantable electronic device, with the highest risk seen in patients with a C2HEST score ≥4 The benefit of using the C2HEST score in clinical practice in this patient population needs further investigation.

Conserved Role of the Large Conductance Calcium-Activated Potassium Channel, KCa1.1, in Sinus Node Function and Arrhythmia Risk.

BACKGROUND: KCNMA1 encodes the α-subunit of the large-conductance Ca2+-activated K+ channel, KCa1.1, and lies within a linkage interval for atrial fibrillation (AF). Insights into the cardiac functions of KCa1.1 are limited, and KCNMA1 has not been investigated as an AF candidate gene. METHODS: The KCNMA1 gene was sequenced in 118 patients with familial AF. The role of KCa1.1 in normal cardiac structure and function was evaluated in humans, mice, zebrafish, and fly. A novel KCNMA1 variant was functionally characterized. RESULTS: A complex KCNMA1 variant was identified in 1 kindred with AF. To evaluate potential disease mechanisms, we first evaluated the distribution of KCa1.1 in normal hearts using immunostaining and immunogold electron microscopy. KCa1.1 was seen throughout the atria and ventricles in humans and mice, with strong expression in the sinus node. In an ex vivo murine sinoatrial node preparation, addition of the KCa1.1 antagonist, paxilline, blunted the increase in beating rate induced by adrenergic receptor stimulation. Knockdown of the KCa1.1 ortholog, kcnma1b, in zebrafish embryos resulted in sinus bradycardia with dilatation and reduced contraction of the atrium and ventricle. Genetic inactivation of the Drosophila KCa1.1 ortholog, slo, systemically or in adult stages, also slowed the heartbeat and produced fibrillatory cardiac contractions. Electrophysiological characterization of slo-deficient flies revealed bursts of action potentials, reflecting increased events of fibrillatory arrhythmias. Flies with cardiac-specific overexpression of the human KCNMA1 mutant also showed increased heart period and bursts of action potentials, similar to the KCa1.1 loss-of-function models. CONCLUSIONS: Our data point to a highly conserved role of KCa1.1 in sinus node function in humans, mice, zebrafish, and fly and suggest that KCa1.1 loss of function may predispose to AF.

Assessment of right atrial dyssynchrony by 2D speckle-tracking in healthy young men following high altitude exposure at 4100 m.

BACKGROUND: High altitude exposure induces overload of right-sided heart and may further predispose to supraventricular arrhythmia. It has been reported that atrial mechanical dyssynchrony is associated with atrial arrhythmia. Whether high altitude exposure causes higher right atrial (RA) dyssynchrony is still unknown. The aim of study was to investigate the effect of high altitude exposure on right atrial mechanical synchrony. METHODS: In this study, 98 healthy young men underwent clinical examination and echocardiography at sea level (400 m) and high altitude (4100 m) after an ascent within 7 days. RA dyssynchrony was defined as inhomogeneous timing to peak strain and strain rate using 2D speckle-tracking echocardiography. RESULTS: Following high altitude exposure, standard deviation of the time to peak strain (SD-TPS) [36.2 (24.5, 48.6) ms vs. 21.7 (12.9, 32.1) ms, p<0.001] and SD-TPS as percentage of R-R' interval (4.6 ± 2.1% vs. 2.5 ± 1.8%, p<0.001) significantly increased. Additionally, subjects with higher SD-TPS (%) at high altitude presented decreased right ventricular global longitudinal strain and RA active emptying fraction, but increased RA minimal volume index, which were not observed in lower group. Multivariable analysis showed that mean pulmonary arterial pressure and tricuspid E/A were independently associated with SD-TPS (%) at high altitude. CONCLUSION: Our data for the first time demonstrated that high altitude exposure causes RA dyssynchrony in healthy young men, which may be secondary to increased pulmonary arterial pressure. In addition, subjects with higher RA dyssynchrony presented worse RA contractile function and right ventricular performance.

Excitation-contraction coupling and calcium release in atrial muscle.

In cardiac muscle, the process of excitation-contraction coupling (ECC) describes the chain of events that links action potential induced myocyte membrane depolarization, surface membrane ion channel activation, triggering of Ca2+ induced Ca2+ release from the sarcoplasmic reticulum (SR) Ca2+ store to activation of the contractile machinery that is ultimately responsible for the pump function of the heart. Here we review similarities and differences of structural and functional attributes of ECC between atrial and ventricular tissue. We explore a novel "fire-diffuse-uptake-fire" paradigm of atrial ECC and Ca2+ release that assigns a novel role to the SR SERCA pump and involves a concerted "tandem" activation of the ryanodine receptor Ca2+ release channel by cytosolic and luminal Ca2+. We discuss the contribution of the inositol 1,4,5-trisphosphate (IP3) receptor Ca2+ release channel as an auxiliary pathway to Ca2+ signaling, and we review IP3 receptor-induced Ca2+ release involvement in beat-to-beat ECC, nuclear Ca2+ signaling, and arrhythmogenesis. Finally, we explore the topic of electromechanical and Ca2+ alternans and its ramifications for atrial arrhythmia.

Association of Longitudinal Changes in NT-proBNP With Changes in Left Atrial Volume and Function: MESA.

BACKGROUND: The mechanism of left atrial (LA) remodeling is poorly understood. The aim of this longitudinal study was to investigate whether changes in NT-proBNP levels relate to alterations of LA structure and function over time in a multiethnic population. METHODS: From the prospective cohort study, the Multi-Ethnic Study of Atherosclerosis, our analysis included 1,838 participants who underwent cardiac magnetic resonance imaging at the baseline and 10-year examinations, had NT-proBNP levels available at both time points, and did not develop heart failure, myocardial infarction, and/or atrial fibrillation. Multivariable linear regression was used to analyze the association between NT-proBNP level (log-transformed) at the 2 time points and change in LA volumes, LA emptying fractions (total, active, and passive), and LA longitudinal strain. Log NT-proBNP was categorized into Low-Low (N = 681), Low-High (N = 238), High-Low (N = 237), and High-High (N = 682) based on the median value at both time points. RESULTS: With the Low-Low group as the reference group, the High-High group experienced a greater increase in LA maximum and minimum indexed volumes: 3.1 ml/m2 (95% confidence interval 1.98, 4.20) and 2.7 ml/m2 (1.89, 3.51), respectively. The High-High group also experienced a greater decrease in LA total, passive, active emptying fraction, and longitudinal strain: -3.3% (-4.46, -2.11), -0.9% (-1.80, -0.02), -4.2% (-5.55, -2.76), and -2.3% (-3.80, -0.72), respectively. The Low-High group had similar associations, but the effect sizes were not as high. CONCLUSIONS: Adverse LA remodeling over 10 years of follow-up strongly correlates with prolonged elevated levels of intracardiac stress, as assessed by NT-proBNP levels.

Action potential propagation and block in a model of atrial tissue with myocyte-fibroblast coupling.

The electrical coupling between myocytes and fibroblasts and the spacial distribution of fibroblasts within myocardial tissues are significant factors in triggering and sustaining cardiac arrhythmias, but their roles are poorly understood. This article describes both direct numerical simulations and an asymptotic theory of propagation and block of electrical excitation in a model of atrial tissue with myocyte-fibroblast coupling. In particular, three idealized fibroblast distributions are introduced: uniform distribution, fibroblast barrier and myocyte strait-all believed to be constituent blocks of realistic fibroblast distributions. Primary action potential biomarkers including conduction velocity, peak potential and triangulation index are estimated from direct simulations in all cases. Propagation block is found to occur at certain critical values of the parameters defining each idealized fibroblast distribution, and these critical values are accurately determined. An asymptotic theory proposed earlier is extended and applied to the case of a uniform fibroblast distribution. Biomarker values are obtained from hybrid analytical-numerical solutions of coupled fast-time and slow-time periodic boundary value problems and compare well to direct numerical simulations. The boundary of absolute refractoriness is determined solely by the fast-time problem and is found to depend on the values of the myocyte potential and on the slow inactivation variable of the sodium current ahead of the propagating pulse. In turn, these quantities are estimated from the slow-time problem using a regular perturbation expansion to find the steady state of the coupled myocyte-fibroblast kinetics. The asymptotic theory gives a simple analytical expression that captures with remarkable accuracy the block of propagation in the presence of fibroblasts.

A survey of pathways for mechano-electric coupling in the atria.

Mechano-electric coupling (MEC) in atrial tissue has received sparse investigation to date, despite the well-known association between chronic atrial dilation and atrial fibrillation (AF). Of note, no fewer than six different mechanisms pertaining to stretch-activated channels, cellular capacitance and geometric effects have been identified in the literature as potential players. In this mini review, we briefly survey each of these pathways to MEC. We then perform computational simulations using single cell and tissue models in presence of various stretch regimes and MEC pathways. This allows us to assess the relative significance of each pathway in determining action potential duration, conduction velocity and rotor stability. For chronic atrial stretch, we find that stretch-induced alterations in membrane capacitance decrease conduction velocity and increase action potential duration, in agreement with experimental findings. In the presence of time-dependent passive atrial stretch, stretch-activated channels play the largest role, leading to after-depolarizations and rotor hypermeandering. These findings suggest that physiological atrial stretches, such as passive stretch during the atrial reservoir phase, may play an important part in the mechanisms of atrial arrhythmogenesis.

Ventricular and atrial functions assessed by speckle-tracking echocardiography in patients with human immunodeficiency virus.

PURPOSE: Antiretroviral therapy (ART) has dramatically changed the clinical manifestation of human immunodeficiency virus (HIV) associated cardiomyopathy from severe left ventricular (LV) systolic dysfunction to a pattern of subclinical cardiac dysfunction. The aim of this study was to evaluate by speckle tracking echocardiography (STE) LV, right ventricular (RV), and biatrial functions in HIV-infected patients under different ART combinations. METHODS: We consecutively included 128 HIV-infected patients (mean age 44.2 ± 10.1 years, 110 males) and 100 controls (mean age 42.1 ± 9.4 years, 83 males). Ventricular and atrial functions were assessed by both conventional and STE. RESULTS: Although there was not any significant difference in conventional echocardiographic variables, HIV-infected patients had significantly lower LV global longitudinal strain (GLS), RV GLS, left atrial (LA) reservoir and conduit strain, and right atrial conduit strain. HIV patients receiving integrase strand transfer inhibitors and protease inhibitors (PI) had significantly lower LV GLS and LA conduit strain, while patients receiving non-nucleoside reverse transcriptase inhibitors and PI had significantly lower RV GLS than controls. CD4 count at the time of echocardiography was strongly correlated with LV GLS (r = .619, P < .001) and RV GLS (r = .606, P < .001). CONCLUSION: Biventricular and atrial functions are subclinically impaired in HIV-infected patients. ART regimen may also affect myocardial functions.

Haemodynamic determinants of improved aerobic capacity after tricuspid valve surgery in Ebstein anomaly.

BACKGROUND: Although tricuspid valve surgery improves functional capacity in patients with Ebstein anomaly, it is not always associated with improvement in aerobic capacity. The purpose of this study was to identify the determinants of improved aerobic capacity after tricuspid valve surgery in adults with Ebstein anomaly with severe tricuspid regurgitation. METHODS: Retrospective study of patients with severe tricuspid regurgitation due to Ebstein anomaly that had tricuspid valve surgery at Mayo Clinic Rochester (2000-2019) and had preoperative and postoperative cardiopulmonary exercise tests and echocardiograms. The patients were divided into aerobic capacity(+) and aerobic capacity(-) groups depending on whether they had postoperative improvement in %-predicted peak oxygen consumption (VO2). RESULTS: Of 76 patients with severe tricuspid regurgitation due to Ebstein anomaly, 28 (37%) and 48 (63%) were in aerobic capacity(+) and aerobic capacity(-) groups, respectively. The average improvement in peak VO2 was 2.1±1.4 mL/kg/min and -0.9±0.4 mL/kg/min in the in aerobic capacity(+) and aerobic capacity(-) groups, respectively. Although both groups had similar severity of residual tricuspid regurgitation, the aerobic capacity(+) group had more postoperative improvement in right atrial (RA) function, left atrial (LA) function and left ventricular preload and stroke volume. Of the preoperative variables analysed, RA reservoir strain (relative risk 1.12; 95% CI 1.06 to 1.18); LA reservoir strain (relative risk 1.09; 95% CI 1.04 to 1.14) and LV stroke volume index (OR 1.04; 95% CI 1.01 to 1.07) were predictors of postoperative improvement in peak VO2. CONCLUSIONS: One-third of patients with severe tricuspid regurgitation due to Ebstein anomaly had postoperative improvement in aerobic capacity, and atrial function indices were the best predictors of postoperative improvement in aerobic capacity. These data provide new insight into the haemodynamic determinants of exercise capacity and lay the foundation for further studies to determine whether postoperative improvement in aerobic capacity translates to improved long-term survival, and whether timing of tricuspid valve surgery based on these echocardiographic indices will improve long-term outcomes.

Mapping and ablation of clinical spontaneous perimitral atrial tachycardias using an ultra-high-resolution mapping system.

BACKGROUND: Perimitral atrial tachycardias (PMATs) are common atrial tachycardias (ATs), yet their mechanisms vary. OBJECTIVE: The purpose of this study was to characterize clinical spontaneous PMATs using an ultra-high-resolution (UHR) mapping system. METHODS: The study included 32 consecutive PMATs in 31 patients who had undergone AT mapping/ablation using a UHR mapping system. RESULTS: Six, 10, 11, and 5 PMATs occurred in cardiac intervention-naïve (group A), post-lateral/posterior mitral isthmus linear ablation (group B), post-atrial fibrillation ablation without mitral isthmus linear ablation (group C), and post-cardiac surgery (group D) patients, respectively. Group A patients tended to be older, more likely were female, and had sinus node or atrioventricular conduction disturbances more frequently. A 12-lead synchronous isoelectric interval was observed in 15 PMATs (46.9%). Coronary sinus activation was proximal to distal or distal to proximal except in 3 PMATs with straight patterns due to epicardial gaps. Left atrial anterior/septal wall (LAASW) low-voltage areas were smallest in group B. Slow conduction areas (SCAs) were identified in 26 PMATs (81.2%) and were located on the LAASW in all group A and group D patients. Conduction velocity in the SCAs was slowest in group B. In group B, all PMATs were terminated by single applications, and the gaps were located epicardially in 5 of 10 (50%). Anterior (n = 23) or lateral/posterior (n = 9) mitral isthmus linear block was successfully created without any complications in all. Twenty-five concomitant ATs among 18 patients (58.1%) also were eliminated. During a median of 20.0 (11.0-40.0) months of follow-up, 28 patients (90.3%) were free from any atrial tachyarrhythmias. CONCLUSION: An UHR mapping-guided approach with identification of the individual tachycardia mechanism should be the preferred strategy given the distinct and complex arrhythmia mechanisms.

An alternative explanation for the phasic variations in venous flow.

BACKGROUND: Phasic venous flow variation with respiration is surrounded by controversy and not well understood. The current concept assigns a major role to the "abdominal pump." According to this model, inspiratory increases in abdominal pressure compress the vena cava, increasing its internal venous pressure and propelling blood upstream. Some have assigned a secondary role to the "thoracic pump," with the negative intrapleural pressure aiding blood flow toward the heart. The aim of the present study was to examine the phasic changes in flow, pressure, and volume in the central veins and named tributaries. METHODS: Caliber area changes were measured using intravascular ultrasonography in 37 patients undergoing iliac vein stenting. The pressure was measured in 48 patients using transducer tip catheters with electronic zero calibration. Duplex ultrasound flow in the head and neck and truncal and limb veins during inspiration and expiration was measured in 15 normal volunteers. RESULTS: The caliber of the abdominal inferior vena cava had increased by 32% and its lateral pressure had decreased significantly during inspiration. Intravenous pressure in the central veins of the chest and right atrium was positive at 6 to 14 mm Hg. Negative pressures were rarely seen and then only transiently. The internal jugular vein displayed little phasic variation. The upper limb veins displayed weak inspiratory phasicity. Phase polarity was reversed in the lower limbs, with near flow stoppage during inspiration. CONCLUSIONS: These observations conflict with the current notions of venous flow phasicity, which are based on push-pull pressure changes in the abdominal and thoracic veins. The paradoxical inspiratory inferior vena cava caliber increase probably explains the concurrent pressure decrease. Sustained negative pressures in the thoracic central veins and right atrium did not occur. We have proposed an alternate hypothesis for venous flow phasicity based on alternate stretching and relaxation of the mobile section of the great veins with respiratory movement.

Exploring Refractoriness as an Adjunctive Electrical Biomarker for Staging of Atrial Fibrillation.

Patients diagnosed with the same subtype of atrial fibrillation according to our current classification system may differ in symptom severity, severity of the arrhythmogenic substrate, and response to antiarrhythmic therapy. Hence, there is a need for an electrical biomarker as an indicator of the arrhythmogenic substrate underlying atrial fibrillation enabling patient-tailored therapy. The aim of this review is to investigate whether atrial refractoriness, a well-known electrophysiological parameter that is affected by electrical remodeling, can be used as an electrical biomarker of the arrhythmogenic substrate underlying atrial fibrillation. We discuss methodologies of atrial effective refractory period assessment, identify which changes in refractoriness-related parameters reflect different degrees of electrical remodeling, and explore whether these parameters can be used to predict clinical outcomes.