Coronary artery disease (CAD) is the leading cause of sudden cardiac death in adults, and new methods of predicting disease and risk-stratifying patients will help guide intervention in order to reduce this burden. Current CAD detection involves multiple modalities, but the consideration of other biomarkers will help improve reliability. The aim of this narrative review is to help researchers and clinicians appreciate the growing relevance of miRNA in CAD and its potential as a biomarker, and also to suggest useful miRNA that may be targets for future study. We sourced information from several databases, namely PubMed, Scopus, and Google Scholar, when collating evidentiary information. MicroRNAs (miRNA) are short, noncoding RNAs that are relevant in cardiovascular physiology and pathophysiology, playing roles in cardiac hypertrophy, maintenance of vascular tone, and responses to vascular injury. CAD is associated with changes in miRNA expression profiles, and so are its risk factors, such as abnormal lipid metabolism and inflammation. Thus, they may potentially be biomarkers of CAD. Nevertheless, there are limitations in using miRNA. These include cost and the presence of several confounding factors that may affect miRNA profiles. Furthermore, there is difficulty in the normalisation of miRNA values between published studies, due to pre-analytical variations in samples.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with mutations in the cardiac ryanodine receptor (RyR2). These result in stress-induced ventricular arrhythmic episodes, with clinical symptoms and prognosis reported more severe in male than female patients. Murine homozygotic RyR2-P2328S (RyR2 S/S) hearts replicate the proarrhythmic CPVT phenotype of abnormal sarcoplasmic reticular Ca 2+ leak and disrupted Ca 2+ homeostasis. In addition, RyR2 S/S hearts show decreased myocardial action potential conduction velocities (CV), all features implicated in arrhythmic trigger and substrate. The present studies explored for independent and interacting effects of RyR2 S/S genotype and sex on expression levels of molecular determinants of Ca 2+ homeostasis (CASQ2, FKBP12, SERCA2a, NCX1, and Ca V 1.2) and CV (Na V 1.5, Connexin (Cx)-43, phosphorylated-Cx43, and TGF-β1) in mice. Expression levels of Ca 2+ homeostasis proteins were not altered, hence implicating abnormal RyR2 function alone in disrupted cytosolic Ca 2+ homeostasis. Furthermore, altered Na V 1.5, phosphorylated Cx43, and TGF-β1 expression were not implicated in the development of slowed CV. By contrast, decreased Cx43 expression correlated with slowed CV, in female, but not male, RyR2 S/S mice. The CV changes may reflect acute actions of the increased cytosolic Ca 2+ on Na V 1.5 and Cx43 function.
Objective We hypothesized that computed tomography-derived (CT) left atrial volume index (LAVI), in combination with other objective parameters, could be used to develop a score able to predict the presence of LVZs. Methods In a large cohort of patients undergoing their first AF ablations, comprehensive echocardiographic evaluations and cardiac CT were performed. During the electrophysiological studies, LA geometry and electroanatomic voltage maps were created. LVZs were defined as areas ≥1cm2 with bipolar peak-to-peak voltage amplitudes ≤0.5 mV. Results In a derivation cohort of 374 patients, predictors of LVZs were identified by regression analysis and used to build the ZAQ score (age≥65 years, female sex and CT LAVI≥57ml/m2). The ZAQ score of 2 points accurately identified the presence and the extent of LVZs (AUC 0.809, 95% CI 0.758-0.861, p<0.001; 3 cm2 [IQR 1.5-4.5] vs 7 cm2 [IQR 4-9], p 0.001). In a validation cohort of 103 patients, the predictive value of the score was confirmed (AUC 0.793, 95% CI 0.709-0.878, p<0.001; 4 cm2 [IQR 2-7] vs 11.5 cm2 [IQR 8-16.5], p 0.001). Conclusions The ZAQ score identifies LVZs and may be useful for planning the ablation strategy ahead of time (single shot PVI vs 3D mapping-guided ablation) regardless of whether the AF pattern is paroxysmal or persistent. Figure legend. Proposed AF ablation workflow independent of the temporal pattern of AF (ie. paroxysmal vs. persistent). (CT) Computed Tomography, (LAVI) Left Atrial Volume Index, (PVI) Pulmonary vein isolation. *Low voltage zones, if present, could be targeted with additional substrate modification ablation
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