Highlights: A genetic variable has been identified as an atrial fibrillation risk factor Rs2200733 is a type of SNP that increases atrial fibrillation risk, whereas rs3853445, rs6838973, and rs17570669 have the reverse effect Abstract: Atrial fibrillation (AF) is a highly prevalent arrhythmia. The involvement of molecular mechanisms in increased AF risk remains uncertain. However, the paired-like homeodomain transcription factor 2 or pituitary homeobox 2 (PITX2) gene has been linked to AF development. A comprehensive search was carried out to identify all eligible case-control studies in order to assess the association between five single-nucleotide polymorphisms (SNPs) in the PITX2 gene and the risk of AF. This meta-analysis employed the Review Manager (RevMan) software version 5.3 (Cochrane). There were 13 clinical studies, with a total of 11,961 subjects, that met the inclusion criteria. These subjects consisted of 4,440 patients with AF and 7,521 controls. The meta-analysis of five SNP types in the PITX2 gene was done using crude odds ratios (ORs). This revealed that rs2200733 increased the risk of AF (OR=1.80; 95% CI=1.53-2.11; p=0.0005; I2=80%). On the other hand, the other three SNPs decreased the risk of AF, namely, rs385344 (OR=0.75; 95% CI=0.59-0.95; p=0.002; I2=85%), rs6838973 (OR=0.64; 95% CI=0.51-0.81; p=0.0001; I2=73%), and rs17570669 (OR=0.80; 95% CI=0.65-0.98; p=0.03; I2=70%). However, there was no significant association between rs10033464 and AF (OR=1.21; 95% CI=0.97-1.50; p=0.13; I2=83%). In conclusion, depending on the type, SNPs in the PITX2 gene correlate with AF risk factors, either by alleviating or reducing the risk.

Background and Aims Stem cells therapy has been studied in the cardiovascular field, but the limitations in terms of survival and risk of rejection make cell-free therapy with secretome worth considering. This study aims to identify the effect of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) derived secretome, ramiprilat, and combination of both on endothelial progenitor cells (EPCs) migration. Methods and Results EPCs were collected from mononuclear cells (MNCs) of the peripheral blood of chronic coronary syndrome patient using density gradient centrifugation method, then cultured in Stemline II medium (Sigma Aldrich, USA). Secretom was made by taking the supernatant from the hUCB-MSCs cell line culture media that had been centrifuged. Cultured EPCs was divided into control group, treatment with 10 µmol Ramiprilat, various concentrations of hUCB-MSCs-derived secretome (2%, 10%, and 20%) and combination of 10 µmol Ramiprilat and each concentration of secretome. EPCs migration was assessed using Boyden chamber assay. Results showed that ramiprilat and all doses of secretome increased EPCs migration compared to the control group (p < 0.001). Secretome 20% had higher EPCs migration than ramiprilat (51.00±5.15 vs 33.80±2.49, p < 0.001), and the combination of ramiprilat and secretome 20% showed the highest number of migrated EPCs among all groups. Conclusion hUCB-MSCs-derived secretome and ramiprilat increase EPCs migration. The combination of those two substances furtherly increased the migrated cells. hUCB-MSCs-derived secretome has the potential as a cell-free cardiovascular treatment for coronary artery disease patients.

Background: Optimal therapy in ST-elevation myocardial infarction (STEMI) patients with extreme age is still a challenge. The presence of comorbidities and multiorgan dysfunction simultaneously increases the risk of ischemia and bleeding. Unfortunately, there are no adequate data for the benefit and reliability of the treatment in elderly patients. Case Summary: We report a case of a 103-year-old patient with substernal chest pain 6 hours before admission. His medical history was unremarkable. The physical examination revealed irregularly irregular pulse. An electrocardiogram showed atrial fibrillation with a moderate ventricular response with ST-elevation and Q waves in inferior lead. The patient was treated conservatively with dual antiplatelet aspirin and clopidogrel, and anticoagulated with fondaparinux. Although medical management was carried out because of family concerns, the best choice of therapy for STEMI patients of extreme ages was still a question. Discussion: Current practice guidelines recommend primary percutaneous coronary intervention as therapy of choice in STEMI patients with no upper age limit, and to start dual antiplatelet therapy using aspirin and a P2Y12 receptor blocker in all patients including the elderly. In a patient with atrial fibrillation, a shorter duration of dual antiplatelet therapy is recommended. Data regarding reperfusion therapy with the best level of efficacy and safety in this group is limited. Trials comparing various treatment strategies with oral anticoagulants are designed to investigate the safety, rather than efficacy. Another option to use single antiplatelet therapy to minimize bleeding risk still has limited data.