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Introduction Left atrial appendage (LAA) is a finger-like muscular extension of the left atrium (LA). It acts as blood reservoir, modulates LA pressure and elicits adaptive responses to stress. Several LAA shapes and variants have been described. We report a case of congenital absence of LAA diagnosed by transesophageal echocardiography (TEE) and confirmed by computed tomography (CT). Case report A 55-year-old male patient with history of hypertension was admitted to our hospital for an episode of atrial fibrillation (AF). TEE was performed and showed normal LA volume, absence of thrombi and spontaneous echo contrast in the LA, but, despite acquiring three-dimensional (3D) en-face views, we were unable to identify LAA. Congenital absence of LAA was suspected and multidetector cardiac CT confirmed the abnormality. Discussion Congenital absence of LAA is an extremely rare condition: only eighteen cases were described on a review of the literature published in 2020. Associations with other congenital abnormalities or with atrial fibrillation have been reported, but a causal relationship cannot be established. Multiple imaging modalities can be used to define the anatomy and function of LAA, to detect or rule out in situ thrombosis and to guide catheter-based therapies, but the most widely used technique is TEE. Among intracardiac thrombi in patients with non-valvular atrial fibrillation, more than 90% are identified in the LAA, meaning that the remaining 10% may develop in other sites of the LA. The congenital absence of LAA could be considered similar to LAA percutaneous occlusion or surgical exclusion; because of the few published randomized controlled trials, the current ESC guidelines on atrial fibrillation are unclear about the true thrombotic risk in these cases. Since LAA percutaneous occlusion is actually indicated only in cases of contraindications for long-term anticoagulant treatment, in our opinion in patients with non-valvular AF, LAA congenital absence, high stroke risk and low bleeding risk, anticoagulant therapy should be considered. Conclusion Congenital absence of LAA is an extremely rare condition and its pathophysiological role, especially with regard to antithrombotic therapy in patients with AF, is still not well defined.

AIMS: Presentation with an acute coronary syndrome (ACS) on chronic aspirin therapy is an independent predictor of adverse short-term outcomes. Whether this finding applies to chronic thienopyridine use, and with the contemporary invasive management of ACS, is unknown. METHODS AND RESULTS: In ACUITY, 13819 patients with moderate and high-risk ACS were studied; patients transferred from an outside hospital were excluded from the present analysis, given uncertain preadmission antiplatelet status. Endpoints included major adverse cardiovascular events (MACE: death, myocardial infarction, or unplanned revascularization), major bleeding, and net adverse clinical events (NACE). Among 11313 study patients, 31 % were naive for antiplatelet agent, 49% were receiving aspirin alone, and 20% were on dual antiplatelet therapy. Chronic antiplatelet users were older and had a higher risk profile. After adjusting for baseline differences, chronic antiplatelet therapy (single or dual) was not associated with an increased incidence of 30-day MACE, bleeding, or NACE. However, patients on chronic aspirin or dual antiplatelet therapy at presentation had significantly higher 1-year rates of MACE [odds ratio (95% confidence interval) = 1.17 (1.01–1.36), P = 0.03 and 1.29 (1.02–1.64), P = 0.03, respectively]. Patients presenting on dual antiplatelet therapy had significantly greater adjusted MACE at 1-year than those on aspirin alone [odds ratio (95% confidence interval) = 1.34 (1.15–1.56), P

61 MicroRNA-216a: a cardiac-specific post-transcriptional regulator of capillary rarefaction associated with heart failure {#article-title-2} Background: While cardiomyocytes have been the main subject of extensive research in the past, the role of other cardiac cell types in the pathogenesis of heart failure received considerable less attention. Multiple other cell types, including fibroblasts, endothelial cells and vascular smooth muscle cells make up the heart and increasing evidence suggests that these cell types contribute to myocardial health and disease. Angiogenesis is an important adaptive mechanism of the myocardium to conditions of sustained increased demand. A select number of microRNAs were found to participate in post-myocardial angiogenesis but to date, it is unclear, however, if microRNAs regulate cardiac angiogenesis in the non-ischemic failing myocardium, which represents a clinically more relevant question. Purpose: Establish that non-coding RNAs are main orchestrators of vascular integrity and hemostasis in the heart and changes in expression of the non-coding RNA content in different cardiac cell types underlie defects in neovascularization and progression to heart failure. Results: To identify cardiac angiomiRs we recently completed a functional, genome-wide microRNA knockdown screen in cultured mouse cardiac microvascular endothelial cells. In this setup, we performed the scratch assay by fully automated scratch induction and image capturing and identified several candidate microRNAs. miR-216a, one of those candidates affecting endothelial cell migration, is consistently downregulated in a mouse model of cardiac pressure overload induced by transverse aortic constriction. We generated mice with a somatic gene deletion of miR-216a (miR-216-/-). Ablation of miR-216a induced dramatic effects on cardiac morphology and function. In addition to spontaneous development of pathological cardiac remodeling at baseline, miR-216-/- mice are also extremely sensitive to cardiac stress and die 1-2 weeks after pressure overload or develop severe cardiac phenotypes 3-4 weeks after myocardial infarction. Interestingly, the defects observed correlate with vascular defects including capillary rarefaction and reduced angiogen­­­­ic activity. By combining photoacoustics with high-frequency ultrasound we observed different levels of hypoxia throughout the cardiac tissue confirming lower oxygenation of the miR-216a-/- hearts. The observed effects of miR-216 modulation seem to be related to altered autophagic activity in cardiac endothelial cells. Conclusions: We identified a new angiogenesis-related gene regulatory network where miR-216a underlies the vascular changes associated with pathological cardiac remodeling and/or heart failure. # 62 Divergent effects of pre- and post-conditioning on microvascular function {#article-title-3} Background: A short period of ischemia/reperfusion (I/R) that occurs before a prolonged ischemia (preconditioning; preC) or at reflow (postconditioning; postC) reduces tissue necrosis through activation of regulatory kinases cascades, also reciprocally related, including the GPCR-PKG-PKC cascade and the RISK pathway. In this setting, an important role is played by nitric oxide (NO), which is also the main mediator of endothelium-dependent vasodilation. PreC may also protect microcirculation against I/R injury, while the impact of postC is less clear, and mechanism underlying these effects are not completely elucidated. Purpose: To study the influence of preC and postC on postichemic microcirculation, by specifically evaluating leukocyte recruitment and vasodilating reserve, and to correlate these effects with activation of regulatory kinases. Methods: In rats, cremaster muscle was prepared for in vivo videomicroscopy leaving vascular and neural connections intact. Animals were divided in 4 groups: 1- controls, in which muscle was subjected to 90 min of I and 90 min of R; 2- preC, in which preC was induced before I by 5 min of I and 10 min of R; 3- postC, in which postC was induced at R with 5 cycles of 10 seconds R and 5 seconds I; 4- sham, observed after surgery for an equivalent period of time. Leukocyte recruitment was monitored during I/R; at the end of R, vasodilating endothelium-dependent and -independent reserve was assessed by local superfusion with 10-4 µM acetylcholine and 10-5 µM sodium nitroprusside. Phosphorylation of ERK-1/2, Akt, eNOS, PKCe and GSK3β was measured by Western Blotting on muscle homogenates obtained at the end of experiment in a second set of experiments in which, to avoid possible confounding effects of acetylcholine and sodium nitroprusside on kinase activation, rats were divided in 4 groups as described above but vasodilating challenge was not performed. Results: I/R activated leukocyte recruitment (data not shown) and reduced vasodilating reserve, both endothelium-dependent and independent. Both preC and postC activated kinases and eNOS in a similar degree, and reduced leukocyte recruitment. However, only preC preserved vasodilating reserve (both endothelium-dependent and independent) (*=p