The clinical anatomy of the left atrial structures used as landmarks in ablation of arrhythmogenic substrates and cardiac invasive procedures

Background: The clinical anatomy of the left atrium is of special interest since many invasive procedures are performed within this chamber. Pulmonary vein isolation, linear transcatheter ablations, transcatheter mitral valve repair procedures and left atrial appendage occlusions are examples of highly effective procedures done within the left atrial chamber. Methods: This narrative literature review seeks to discuss the latest articles about the anatomy of left atrial structures. Results: This article reviews recent morphological studies about the pulmonary venous ostia, the myocardial sleeves of the pulmonary veins, the mitral isthmus, the left atrial appendage isthmus, the left atrial medial isthmus and the other left atrial isthmuses together with spatial relationships of blood vessels within the isthmus lines. This review touch upon the clinical relevance of the left lateral ridge and the left atrial appendage. Conclusion: A thorough understanding of local anatomy is essential for safe electrophysiologic invasive procedures. Clinical anatomy of the left atrium is treacherous, difficult and its unfamiliarity can cause serious intraoperative complications. Some anatomical features of the left atrium may significantly impede invasive transcatheter interventions, especially ablation procedures

Connexins and the atrioventricular node

The structure and functioning of the atrioventricular (AV) node has remained mysterious owing to its high degree of complexity. In this review article, we integrate advances in knowledge regarding connexin expression in the AV node. Complex patterning of 4 different connexin isoforms with single channel conductances ranging from ultralow to high explains the dual pathway electrophysiology of the AV node, the presence of 2 nodal extensions, longitudinal dissociation in the penetrating bundle, and, most importantly, how the AV node maintains slow conduction between the atria and the ventricles. It is shown that the complex patterning of connexins is the consequence of the embryonic development of the cardiac conduction system. Finally, it is argued that connexin dysregulation may be responsible for AV node dysfunction

Atrioventricular node dysfunction in pressure overload-induced heart failure—Involvement of the immune system and transcriptomic remodelling

Heart failure is associated with atrioventricular (AV) node dysfunction, and AV node dysfunction in the setting of heart failure is associated with an increased risk of mortality and heart failure hospitalisation. This study aims to understand the causes of AV node dysfunction in heart failure by studying changes in the whole nodal transcriptome. The mouse transverse aortic constriction model of pressure overload-induced heart failure was studied; functional changes were assessed using electrocardiography and echocardiography and the transcriptome of the AV node was quantified using RNAseq. Heart failure was associated with a significant increase in the PR interval, indicating a slowing of AV node conduction and AV node dysfunction, and significant changes in 3,077 transcripts (5.6% of the transcriptome). Many systems were affected: transcripts supporting AV node conduction were downregulated and there were changes in transcripts identified by GWAS as determinants of the PR interval. In addition, there was evidence of remodelling of the sarcomere, a shift from fatty acid to glucose metabolism, remodelling of the extracellular matrix, and remodelling of the transcription and translation machinery. There was evidence of the causes of this widespread remodelling of the AV node: evidence of dysregulation of multiple intracellular signalling pathways, dysregulation of 109 protein kinases and 148 transcription factors, and an immune response with a proliferation of neutrophils, monocytes, macrophages and B lymphocytes and a dysregulation of 40 cytokines. In conclusion, inflammation and a widespread transcriptional remodelling of the AV node underlies AV node dysfunction in heart failure

What have we learned from two-pore potassium channels? Their molecular configuration and function in the human heart

Two-pore domain potassium channels (K2P) control excitability, stabilize the resting membrane potential below firing threshold, and accelerate repolarisation in different cells. Until now, fifteen different genes for the six K2P channel subfamily were cloned. The pore-forming part is translated from two genes and they are built up from a dimer of two two-unit transmembrane domains functioning with a wide spectrum of physiological profiles. K2P ion channels were discovered in the last two decades and gave novel opportunity to recognize the complex molecular mechanism of the potassium ion flux, and may lead to the design of individual drug targeting in the future. In this review, we summarise the structure, function, channelopathies and pharmacological silhouette of the two-pore potassium channels in the human tissues. In addition, we present the computer model of the partially reconstructed wild type K2P1/TWIK1 lacking the intracellular C and N terminal loop

MiR-486-3p and MiR-938—Important Inhibitors of Pacemaking Ion Channels and/or Markers of Immune Cells

From MDPI via Jisc Publications RouterHistory: accepted 2021-11-26, pub-electronic 2021-12-01Publication status: PublishedFunder: British Heart Foundation; Grant(s): FS/17/67/33483Funder: Fondation Leducq; Grant(s): THE FANTACY 19CVD03The sinus node (SN) is the heart’s primary pacemaker and has a unique expression of pacemaking ion channels and immune cell markers. The role of microribonucleic acids (miRNAs) in control of ion channels and immune function of the sinus node is not well understood. We have recently shown that hsa-miR-486-3p downregulates the main pacemaking channel HCN4 in the SN. In addition, we recently demonstrated that immune cells are significantly more abundant in the SN compared to the right atrium. The aim of this study was to validate the previously predicted interactions between miRNAs and mRNAs of key Ca2+ ion channels (involved in peacemaking) and mRNA of TPSAB1—(a mast cells marker) using luciferase assay. We now show that miR-486 significantly downregulates Cav1.3, Cav3.1, and TPSAB1-mediated luciferase activity, while miR-938 significantly downregulates only TPSAB1-mediated luciferase activity. This makes miR-486-3p a potential therapeutic target in the treatment of SN dysfunctions

Pilot erfemissie van bloembollenbedrijven in Noord-Holland (Breezand)

In het Noordelijk Zandgebied in Noord-Holland worden voor enkele gewasbeschermingsmiddelen de waterkwaliteitsnormen (MTR) geregeld overschreden. In 2009 zijn telers uit een deel van de Westpolder van Anna Paulowna in de Kop van Noord Holland een samenwerkingsproject gestart om inzicht te krijgen in emissieroutes van gewasbeschermingsmiddelen vanaf het erf om daarmee emissie via deze routes te voorkomen en de waterkwaliteit in de polder te verbeteren. Eind 2010 hebben zich vier gewasbeschermingsmiddelenfabrikanten aangesloten bij de samenwerking: Certis, Bayer, Syngenta en BASF

Identification of key small non-coding MicroRNAs controlling pacemaker mechanisms in the human sinus node

BACKGROUND: The sinus node (SN) is the primary pacemaker of the heart. SN myocytes possess distinctive action potential morphology with spontaneous diastolic depolarization because of a unique expression of ion channels and Ca2+-handling proteins. MicroRNAs (miRs) inhibit gene expression. The role of miRs in controlling the expression of genes responsible for human SN pacemaking and conduction has not been explored. The aim of this study was to determine miR expression profile of the human SN as compared with that of non-pacemaker atrial muscle. METHODS AND RESULTS: SN and atrial muscle biopsies were obtained from donor or post-mortem hearts (n=10), histology/ immunolabeling were used to characterize the tissues, TaqMan Human MicroRNA Arrays were used to measure 754 miRs, Ingenuity Pathway Analysis was used to identify miRs controlling SN pacemaker gene expression. Eighteen miRs were significantly more and 48 significantly less abundant in the SN than atrial muscle. The most interesting miR was miR-486-3p predicted to inhibit expression of pacemaking channels: HCN1 (hyperpolarization-activated cyclic nucleotide-gated 1), HCN4, voltage-gated calcium channel (Cav )1.3, and Cav 3.1. A luciferase reporter gene assay confirmed that miR-486-3p can control HCN4 expression via its 3′ untranslated region. In ex vivo SN preparations, transfection with miR-486-3p reduced the beating rate by ≈35±5% (P<0.05) and HCN4 expression (P<0.05). CONCLUSIONS: The human SN possesses a unique pattern of expression of miRs predicted to target functionally important genes. miR-486-3p has an important role in SN pacemaker activity by targeting HCN4, making it a potential target for therapeutic treatment of SN disease such as sinus tachycardia.</p

Topographical anatomy of the left ventricular summit: implications for invasive procedures

Background: Recent clinical reports have emphasized the clinical significance of the left ventricular summit (LVS), a specific triangular epicardial area, as the source of ventricular arrhythmias where radiofrequency ablation is of great difficulty. Materials and methods: The macroscopic morphology of the LVS has been assessed in 80 autopsied and 48 angio-CT human hearts. According to Yamada’s equation, the size was calculated based on the distance to the first, most prominent septal perforator. Results: The size of the LVS varies from 33.69 to 792.2 mm2, is highly variable, and does not correlate with BMI, sex, or age in general. The mean size of the LVS was 287.38 ± 144.95mm2 in autopsied and angio-CT (p=0.44). LVS is mostly disproportionately bisected by cardiac coronary veins to superior – inaccessible and inferior–accessible areas. The superior aspect dominates over the inferior in both groups (p=0.04). The relation between superior and inferior groups determines three possible arrangements: the most common type is superior domination (50.2%), then inferior domination (26.6%), and finally, equal distribution (17.2%). In 10.9 %, the inferior aspect is absent. Only 16.4% of the LVS were empty, without additional trespassing coronary arteries. Conclusions: The difference in size and content of the LVS is significant, with no correlation to any variable. The size depends on the anatomy of the most prominent septal perforator artery. The superior, inaccessible aspect dominates, and the LVS is seldom free from additional coronary vessels, thus making this region hazardous for electrophysiological procedures