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.

Thromboembolism in Atrial Fibrillation: Role of the Left Atrial Appendage.

Atrial fibrillation (AF) is the most common arrhythmia. Patients with AF have a higher risk for thromboembolism than individuals without AF. The left atrial appendage (LAA) is the main source of thromboembolism because of its anatomic, mechanical, and electrophysiologic properties, and accounts for more than 90% of thrombus formation in patients with AF. Advancement in imaging expands knowledge about anatomic and physiologic characteristics of LAA. The risk of thromboembolism events in patients with AF depends on clinical comorbidities and structural and physiologic parameters of atria, especially LAA. This article discusses AF-related thromboembolic events and the role of the LAA.

Role of the Left Atrial Appendage in Systemic Homeostasis, Arrhythmogenesis, and Beyond.

The left atrial appendage (LAA) affects body homeostasis via atrial natriuretic peptide and the renin-angiotensin-aldosterone system and plays an important role in atrial compliance. Approximately 90% of clots in nonvalvular atrial fibrillation (AF) are formed in the LAA. AF is the most common sustained cardiac arrhythmia and is frequently associated with stroke. Because anticoagulation for stroke prophylaxis carries a higher bleeding risk, LAA closure via epicardial and endocardial approaches has gained popularity and is being increasingly pursued for arrhythmogenic, homeostatic, and stroke-reduction benefits. This review discusses the homeostatic role of the LAA and its involvement in arrhythmogenesis and thrombus formation.

Epicardial versus Endocardial Closure: Is One Better than the Other?

Left atrial appendage occlusion is an evolving technology with demonstrable benefits of stroke prophylaxis in patients with atrial fibrillation unsuitable for anticoagulation. This has resulted in the development of a plethora of transcatheter devices to achieve epicardial exclusion and endocardial occlusion. In this review, the authors summarize the differences in technique, target patient population, outcomes, and complication profiles of endocardial and epicardial techniques.

[Echocardiographic evaluation of the right atrial appendage and its clinical consequences]. / A jobb pitvari fülcse echokardiográfiás vizsgálata és annak klinikai jelentosége.

In case of atrial fibrillation, there is a higher risk of thrombus formation, which could affect the right heart as well. Visualization of the right atrial appendage is difficult; the aim of the present review was to demonstrate the role of routine echocardiographic techniques and to show related clinical data. Orv Hetil. 2019; 160(12): 443-447.

Mitochondrial and Contractile Function of Human Right Atrial Tissue in Response to Remote Ischemic Conditioning.

Background Remote ischemic preconditioning ( RIPC ) by repeated brief cycles of limb ischemia/reperfusion attenuates myocardial ischemia/reperfusion injury. We aimed to identify a functional parameter reflecting the RIPC -induced protection in human. Therefore, we measured mitochondrial function in right atrial tissue and contractile function of isolated right atrial trabeculae before and during hypoxia/reoxygenation from patients undergoing coronary artery bypass grafting with RIPC or placebo, respectively. Methods and Results One hundred thirty-seven patients under isoflurane anesthesia underwent RIPC (3×5 minutes blood pressure cuff inflation on the left upper arm/5 minutes deflation, n=67) or placebo (cuff uninflated, n=70), and right atrial appendages were harvested before ischemic cardioplegic arrest. Myocardial protection by RIPC was assessed from serum troponin I/T concentrations over 72 hours after surgery. Atrial tissue was obtained for isolation of mitochondria ( RIPC /placebo: n=10/10). Trabeculae were dissected for contractile function measurements at baseline and after hypoxia/reoxygenation (60 min/30 min) and for western blot analysis after hypoxia/reoxygenation ( RIPC /placebo, n=57/60). Associated with cardioprotection by RIPC (26% decrease in the area under the curve of troponin I/T), mitochondrial adenosine diphosphate-stimulated complex I respiration (+10%), adenosine triphosphate production (+46%), and calcium retention capacity (+37%) were greater, whereas reactive oxygen species production (-24%) was less with RIPC than placebo. Contractile function was improved by RIPC (baseline, +7%; reoxygenation, +24%). Expression and phosphorylation of proteins, which have previously been associated with cardioprotection, were not different between RIPC and placebo. Conclusions Cardioprotection by RIPC goes along with improved mitochondrial and contractile function of human right atrial tissue. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 01406678.

Different Responses of Left Atrium and Left Atrial Appendage to Radiofrequency Catheter Ablation of Atrial Fibrillation: a Follow Up MRI study.

Atrial fibrillation (AF) is known to cause adverse remodeling of left atrium (LA). Radiofrequency catheter ablation (RFCA) of AF is associated with decrease in LA volume. However, the impact of RFCA on left atrial appendage (LAA) volume and hemodynamic function is not fully understood. We analyzed 123 patients who underwent cardiac magnetic resonance imaging (MRI) evaluation before and after RFCA in Korea University Anam Hospital. LA and LAA volume were measured before and after RFCA based on cardiac MRI. Baseline LA volume was 99.5 ± 38.4 cm3 and decreased to 74.6 ± 28.5 cm3 after RFCA (p < 0.001). LA diameter measured with transthoracic echocardiography was also decreased after RFCA (43.3 ± 6.2 mm at baseline and 39.9 ± 5.9 mm at follow up; p < 0.001). However, LAA volume was significantly increased after RFCA (19.4 ± 8.5 cm3 at baseline and 23.7 ± 13.3 cm3 at follow up; p < 0.001). Total ablation time and additional substrate modification was associated with change in LA volume. After RFCA, average LAA velocity measured by transesophageal echocardiography was increased to 51.0 cm/sec from 41.1 cm/sec (p < 0.001). In conclusion, LAA volume was increased after RFCA in contrast to LA volume. Our data raise a concern about worsening hemodynamics of LA and LAA following RFCA and long term clinical significance of enlarged LAA after RFCA needs further evaluation.

Anatomy and Physiologic Roles of the Left Atrial Appendage: Implications for Endocardial and Epicardial Device Closure.

The left atrial appendage has been implicated as a major nidus for thrombus formation, particularly in atrial fibrillation. This discovery has prompted substantial interest in the development of left atrial appendage exclusion devices aimed at decreasing systemic thromboembolism risk. Its deceptively simple appearance belies the remarkable complexity that characterizes its anatomy and physiology. We highlight the key anatomic features and variations of the left atrial appendage as well as its relationships with surrounding structures. We also summarize crucial anatomic factors that should be taken into account by the interventional cardiologist when planning for or performing left atrial appendage exclusion procedures.

The Left Atrial Appendage Revised.

Nonvalvular atrial fibrillation is associated with a 4- to 5-fold strokes increase and may be responsible for 15% to 20% of all strokes in the elderly. In this scenario, the left atrial appendage thrombus would be the associated with 90% of cases. The use of anticoagulants, percutaneous devices, and the left atrial appendage surgical exclusion is still an open discussion. For left atrial appendage procedures, relevant anatomic spatial relationships have to be emphasized, besides the chance of the normal physiological functioning would be eliminated with the proceedings. There are evidences that the left atrial appendage closure during routine cardiac surgery is significantly associated with an increased risk of early postoperative atrial fibrillation. Therefore, the purpose of this review is to focus basic aspects for continuous medical education. In summary, the rationale of this text is to emphasize anatomical and pharmacological aspects involved in the simple surgical exclusion of left atrial appendage under cardiopulmonary bypass. There are several operative techniques, but to conclude this revision it will present one of them based on the discussed basic sciences.

The left atrial appendage revised

Abstract Nonvalvular atrial fibrillation is associated with a 4- to 5-fold strokes increase and may be responsible for 15% to 20% of all strokes in the elderly. In this scenario, the left atrial appendage thrombus would be the associated with 90% of cases. The use of anticoagulants, percutaneous devices, and the left atrial appendage surgical exclusion is still an open discussion. For left atrial appendage procedures, relevant anatomic spatial relationships have to be emphasized, besides the chance of the normal physiological functioning would be eliminated with the proceedings. There are evidences that the left atrial appendage closure during routine cardiac surgery is significantly associated with an increased risk of early postoperative atrial fibrillation. Therefore, the purpose of this review is to focus basic aspects for continuous medical education. In summary, the rationale of this text is to emphasize anatomical and pharmacological aspects involved in the simple surgical exclusion of left atrial appendage under cardiopulmonary bypass. There are several operative techniques, but to conclude this revision it will present one of them based on the discussed basic sciences.

The left atrial appendage: from embryology to prevention of thromboembolism.

The left atrial appendage (LAA) is the main source of thromboembolism in patients with non-valvular atrial fibrillation (AF). As such, the LAA can be the target of specific occluding device therapies. Optimal management of patients with AF includes a comprehensive knowledge of the many aspects related to LAA structure and thrombosis. Here we provide baseline notions on the anatomy and function of the LAA, and then focus on current imaging tools for the identification of anatomical varieties. We also describe pathogenetic mechanisms of LAA thrombosis in AF patients, and examine the available evidence on treatment strategies for LAA thrombosis, including the use of non-vitamin K antagonist oral anticoagulants and interventional approaches.

Macrophage precursor cells from the left atrial appendage of the heart spontaneously reprogram into a C-kit+/CD45- stem cell-like phenotype.

BACKGROUND: The developmental origin of the c-kit expressing progenitor cell pool in the adult heart has remained elusive. Recently, it has been discovered that the injured heart is enriched with c-kit(+) cells, which also express the hematopoietic marker CD45. METHODS AND RESULTS: In this study, we characterize the phenotype and transcriptome of the c-kit+/CD45+/CD11b+/Flk-1+/Sca-1±(B-type) cell population, originating from the left atrial appendage. These cells are defined as cardiac macrophage progenitors. We also demonstrate that the CD45+ progenitor cell population activates heart development, neural crest and pluripotency-associated pathways in vitro, in conjunction with CD45 down-regulation, and acquire a c-kit+/CD45-/CD11b-/Flk-1-/Sca-1+ (A-type) phenotype through cell fusion and asymmetric division. This putative spontaneous reprogramming evolves into a highly proliferative, partially myogenic phenotype (C-type). CONCLUSIONS: Our data suggests that A-type cells and cardiac macrophage precursor cells (B-type) have a common lineage origin, possibly resolving some current conundrums in the field of cardiac regeneration.

Endolysosomal two-pore channels regulate autophagy in cardiomyocytes.

KEY POINTS: Two-pore channels (TPCs) were identified as a novel family of endolysosome-targeted calcium release channels gated by nicotinic acid adenine dinucleotide phosphate, as also as intracellular Na(+) channels able to control endolysosomal fusion, a key process in autophagic flux. Autophagy, an evolutionarily ancient response to cellular stress, has been implicated in the pathogenesis of a wide range of cardiovascular pathologies, including heart failure. We report direct evidence indicating that TPCs are involved in regulating autophagy in cardiomyocytes, and that TPC knockout mice show alterations in the cardiac lysosomal system. TPC downregulation implies a decrease in the viability of cardiomyocytes under starvation conditions. In cardiac tissues from both humans and rats, TPC transcripts and protein levels were higher in females than in males, and correlated negatively with markers of autophagy. We conclude that the endolysosomal channels TPC1 and TPC2 are essential for appropriate basal and induced autophagic flux in cardiomyocytes, and also that they are differentially expressed in male and female hearts. ABSTRACT: Autophagy participates in physiological and pathological remodelling of the heart. The endolysosomal two-pore channels (TPCs), TPC1 and TPC2, have been implicated in the regulation of autophagy. The present study aimed to investigate the role of TPC1 and TPC2 in basal and induced cardiac autophagic activity. In cultured cardiomyocytes, starvation induced a significant increase in TPC1 and TPC2 transcripts and protein levels that paralleled the increase in autophagy identified by increased LC3-II and decreased p62 levels. Small interfering RNA depletion of TPC2 alone or together with TPC1 increased both LC3II and p62 levels under basal conditions and in response to serum starvation, suggesting that, under conditions of severe energy depletion (serum plus glucose starvation), changes in the autophagic flux (as assessed by use of bafilomycin A1) occurred either when TPC1 or TPC2 were downregulated. The knockdown of TPCs diminished cardiomyocyte viability under starvation and simulated ischaemia. Electron micrographs of hearts from TPC1/2 double knockout mice showed that cardiomyocytes contained large numbers of immature lysosomes with diameters significantly smaller than those of wild-type mice. In cardiac tissues from humans and rats, TPC1 and TPC2 transcripts and protein levels were higher in females than in males. Furthermore, transcript levels of TPCs correlated negatively with p62 levels in heart tissues. TPC1 and TPC2 are essential for appropriate basal and induced autophagic flux in cardiomyocytes (i.e. there is a negative effect on cell viability under stress conditions in their absence) and they are differentially expressed in male and female human and murine hearts, where they correlate with markers of autophagy.

Assessment of normal left atrial appendage anatomy and function over gender and ages by dynamic cardiac CT.

OBJECTIVES: The aim of this study was to evaluate variations in anatomy and function according to age and gender using cardiac computed tomography (CT) in a large prospective cohort of healthy patients. BACKGROUND: The left atrial appendage (LAA) is considered the most frequent site of intracardiac thrombus formation. However, variations in normal in vivo anatomy and function according to age and gender remain largely unknown. METHODS: Three-dimensional (3D) cardiac reconstructions of the LAA were performed from CT scans of 193 consecutive patients. Parameters measured included LAA number of lobes, anatomical position of the LAA tip, angulation measured between the proximal and distal portions, minimum (iVolmin) and maximum (iVolmax) volumes indexed to body surface area (BSA), and ejection fraction (LAAEF). Relationship with age was assessed for each parameter. RESULTS: We found that men had longer and wider LAAs. The iVolmin and iVolmax increased by 0.23 and 0.19 ml per decade, respectively, while LAAEF decreased by 2% per decade in both sexes. CONCLUSIONS: Although LAA volumes increase, LAAEF decreases with age in both sexes. KEY POINTS: • Variations in normal left atrial appendage in vivo anatomy and function remain largely unknown. • Cardiac CT is reliable for left atrial appendage volume measurements. • Although LAA volumes increase, LAAEF decreases with age in both sexes.

Cardiac atrial appendage stem cells engraft and differentiate into cardiomyocytes in vivo: A new tool for cardiac repair after MI.

BACKGROUND: This study assessed whether autologous transplantation of cardiac atrial appendage stem cells (CASCs) preserves cardiac function after myocardial infarction (MI) in a minipig model. METHODS AND RESULTS: CASCs were isolated from right atrial appendages of Göttingen minipigs based on high aldehyde dehydrogenase activity and expanded. MI was induced by a 2h snare ligation of the left anterior descending coronary artery. Upon reperfusion, CASCs were intramyocardially injected under NOGA guidance (MI-CASC, n=10). Non-transplanted pigs (MI, n=8) received sham treatment. 3D electromechanical mapping (EMM) and cardiac MRI were performed to assess left ventricular (LV) function. MI pigs developed LV dilatation at 2 months (2M), while in the MI-CASC group volumes remained stable. Global LV ejection fraction decreased by 16 ± 8% in MI animals vs 3 ± 10% in MI-CASC animals and regional wall thickening in border areas was better preserved in the MI-CASC group. EMM showed decreased viability and wall motion in the LV for both groups POST-MI, whereas at 2M these parameters only improved in the MI-CASC. Substantial cell retention was accompanied by cardiomyogenic differentiation in 98±1% of the transplanted CASCs, which functionally integrated. Second harmonic generation microscopy confirmed the formation of mature sarcomeres in transplanted CASCs. Absence of cardiac arrhythmias indicated the safety of CASC transplantation. CONCLUSION: CASCs preserve cardiac function by extensive engraftment and cardiomyogenic differentiation. Our data indicate the enormous potential of CASCs in myocardial repair.

The role of connexin40 in developing atrial conduction.

Connexin40 (Cx40) is the main connexin expressed in the murine atria and ventricular conduction system. We assess here the developmental role of Cx40 in atrial conduction of the mouse. Cx40 deficiency significantly prolonged activation times in embryonic day 10.5, 12.5 and 14.5 atria during spontaneous activation; the severity decreased with increasing age. In a majority of Cx40 deficient mice the impulse originated from an ectopic focus in the right atrial appendage; in such a case the activation time was even longer due to prolonged activation. Cx40 has thus an important physiological role in the developing atria.