Questing for Circadian Dependence in ST-Segment–Elevation Acute Myocardial Infarction

Rationale: Four monocentric studies reported that circadian rhythms can affect left ventricular infarct size after ST-segment-elevation acute myocardial infarction (STEMI). Objective: To further validate the circadian dependence of infarct size after STEMI in a multicentric and multiethnic population. Methods and Results: We analyzed a prospective cohort of subjects with first STEMI from the First Acute Myocardial Infarction study that enrolled 1099 patients (ischemic time <6 hours) in Italy, Scotland, and China. We confirmed a circadian variation of STEMI incidence with an increased morning incidence (from 6: 00 am till noon). We investigated the presence of circadian dependence of infarct size plotting the peak creatine kinase against time onset of ischemia. In addition, we studied the patients from the 3 countries separately, including 624 Italians; all patients were treated with percutaneous coronary intervention. We adopted several levels of analysis with different inclusion criteria consistent with previous studies. In all the analyses, we did not find a clear-cut circadian dependence of infarct size after STEMI. Conclusions: Although the circadian dependence of infarct size supported by previous studies poses an intriguing hypothesis, we were unable to converge toward their conclusions in a multicentric and multiethnic setting. Parameters that vary as a function of latitude could potentially obscure the circadian variations observed in monocentric studies. We believe that, to assess whether circadian rhythms can affect the infarct size, future study design should not only include larger samples but also aim to untangle the molecular time-dynamic mechanisms underlying such a relation.Cardiac & Cardiovascular SystemsHematologyPeripheral Vascular DiseaseSCI(E)10ARTICLE10E110-E11411

Alternative Splicing Changes Promoted by NOVA2 Upregulation in Endothelial Cells and Relevance for Gastric Cancer

Angiogenesis is crucial for cancer progression. While several anti-angiogenic drugs are in use for cancer treatment, their clinical benefits are unsatisfactory. Thus, a deeper understanding of the mechanisms sustaining cancer vessel growth is fundamental to identify novel biomarkers and therapeutic targets. Alternative splicing (AS) is an essential modifier of human proteome diversity. Nevertheless, AS contribution to tumor vasculature development is poorly known. The Neuro-Oncological Ventral Antigen 2 (NOVA2) is a critical AS regulator of angiogenesis and vascular development. NOVA2 is upregulated in tumor endothelial cells (ECs) of different cancers, thus representing a potential driver of tumor blood vessel aberrancies. Here, we identified novel AS transcripts generated upon NOVA2 upregulation in ECs, suggesting a pervasive role of NOVA2 in vascular biology. In addition, we report that NOVA2 is also upregulated in ECs of gastric cancer (GC), and its expression correlates with poor overall survival of GC patients. Finally, we found that the AS of the Rap Guanine Nucleotide Exchange Factor 6 (RapGEF6), a newly identified NOVA2 target, is altered in GC patients and associated with NOVA2 expression, tumor angiogenesis, and poor patient outcome. Our findings provide a better understanding of GC biology and suggest that AS might be exploited to identify novel biomarkers and therapeutics for anti-angiogenic GC treatments

Stress Echocardiography in Italian Echocardiographic Laboratories: A Survey of the Italian Society of Echocardiography and Cardiovascular Imaging

Background: The Italian Society of Echography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand the volumes of activity, modalities and stressors used during stress echocardiography (SE) in Italy. Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved through an electronic survey based on a structured questionnaire, uploaded on the SIECVI website. Results: Data were obtained from 228 echocardiographic laboratories, and SE examinations were performed in 179 centers (80.6%): 87 centers (47.5%) were in the northern regions of Italy, 33 centers (18.4%) were in the central regions, and 61 (34.1%) in the southern regions. We annotated a total of 4057 SE. We divided the SE centers into three groups, according to the numbers of SE performed: <10 SE (low-volume activity, 40 centers), between 10 and 39 SE (moderate volume activity, 102 centers) and >= 40 SE (high volume activity, 37 centers). Dipyridamole was used in 139 centers (77.6%); exercise in 120 centers (67.0%); dobutamine in 153 centers (85.4%); pacing in 37 centers (21.1%); and adenosine in 7 centers (4.0%). We found a significant difference between the stressors used and volume of activity of the centers, with a progressive increase in the prevalence of number of stressors from low to high volume activity (P = 0.033). The traditional evaluation of regional wall motion of the left ventricle was performed in all centers, with combined assessment of coronary flow velocity reserve (CFVR) in 90 centers (50.3%): there was a significant difference in the centers with different volume of SE activity: the incidence of analysis of CFVR was significantly higher in high volume centers compared to low - moderate - volume (32.5%, 41.0% and 73.0%, respectively, P < 0.001). The lung ultrasound (LUS) was assessed in 67 centers (37.4%). Furthermore for LUS, we found a significant difference in the centers with different volume of SE activity: significantly higher in high volume centers compared to low - moderate - volume (25.0%, 35.3% and 56.8%, respectively, P < 0.001). Conclusions: This nationwide survey demonstrated that SE was significantly widespread and practiced throughout Italy. In addition to the traditional indication to coronary artery disease based on regional wall motion analysis, other indications are emerging with an increase in the use of LUS and CFVR, especially in high-volume centers