Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation

MicroRNAs have been explored in different organisms and are involved as molecular switches modulating cellular specification and differentiation during the embryonic development, including the cardiovascular system. In this study, we analyze the expression profiles of different microRNAs during early cardiac development. By using whole mount in situ hybridization in developing chick embryos, with microRNA-specific LNA probes, we carried out a detailed study of miR-23b, miR-130a, miR-106a, and miR-100 expression during early stages of embryogenesis (HH3 to HH17). We also correlated those findings with putative microRNA target genes by means of mirWalk and TargetScan analyses. Our results demonstrate a dynamic expression pattern in cardiac precursor cells from the primitive streak to the cardiac looping stages for miR-23b, miR-130a, and miR-106a. Additionally, miR-100 is later detectable during cardiac looping stages (HH15-17). Interestingly, the sinus venosus/inflow tract was shown to be the most representative cardiac area for the convergent expression of the four microRNAs. Through in silico analysis we revealed that distinct Hox family members are predicted to be targeted by the above microRNAs. We also identified expression of several Hox genes in the sinus venosus at stages HH11 and HH15. In addition, by means of gain-of-function experiments both in cardiomyoblasts and sinus venosus explants, we demonstrated the modulation of the different Hox clusters, Hoxa, Hoxb, Hoxc, and Hoxd genes, by these microRNAs. Furthermore, we correlated the negative modulation of several Hox genes, such as Hoxa3, Hoxa4, Hoxa5, Hoxc6, or Hoxd4. Finally, we demonstrated through a dual luciferase assay that Hoxa1 is targeted by miR-130a and Hoxa4 is targeted by both miR-23b and miR-106a, supporting a possible role of these microRNAs in Hox gene modulation during differentiation and compartmentalization of the posterior structures of the developing venous pole of the heart.

Fatal disseminated paradoxical embolism in inferior sinus venosus atrial septal defect

Inferior sinus venosus arterial septal defect (ASD) is a rare congenital cardiac anomaly. As with other types of ASDs and patent foramen ovale (PFO), this defect results in arteri-venous shunting with the risk of developing paradoxical embolism (PDE) to the systemic circulation from venous emboli. We report a case of a 67-year-old lady presented to emergency department (ED) with massive pulmonary embolism (PE) and recurrent acute limb ischaemia. On CT pulmonary angiography (CTPA), an incidental finding of inferior sinus venosus ASD was discovered that has caused the PDE. Thrombolysis was administered followed by open mechanical thrombectomy. The patient developed massive lower gastrointestinal bleed post thrombolysis then passed away despite embolization. This case report describes the catastrophic effect of PDE to cause disseminated multisystem thromboembolism. It also emphasizes the importance of early detection of a possible right-to-left shunt in patients presented with recurrent acute limb ischaemia. Transthoracic echocardiography has reduced sensitivity for inferior sinus venosus ASD requiring further assessment with transoesophageal echocardiography in selected cases.

Paradoxial embolism as a cause of ischemic stroke in patient with sinus venosus atrial septal defect

We present a case report of a middle-aged patient with a rare sinus venosus atrial septal defect (ASD) and ischemic stroke that developed due to paradoxical embolism. Occlusion of the anterior cerebral artery led to a stroke with cognitive impairment, acalculia, and apraxia. Diagnostic ultrasound features of this anomaly in suspected cases are discussed. In the presented case, verification of the stroke cause became possible due to the contrast-enhanced computed tomography of the heart. ASD detection made it possible to refer the patient to the surgical treatment necessary to prevent both recurrent cerebral accidents and the progression of pulmonary hypertension, and the prevention of the development of right ventricular heart failure.

Superior Sinus Venosus Atrial Septal Defect with Partial Anomalous Pulmonary Venous Drainage—Minimally Invasive Approach—Case Report

The atrial septal defect is, after bicuspid aortic valve disease, the most common congenital cardiac disease present in the adult population. The most common atrial septal defects are the ostium secundum type (75–80%), followed by the ostium primum type (15%). The sinus venosus atrial septal defects (SV-ASD), defined as a communication in the posterior part of the interatrial septum, account for about 5 to 10% of atrial septal defects. Approximately 90% of SV-ASDs are associated with partial anomalous pulmonary venous drainage (PAPVD). The minimally invasive approach has gained ground in the treatment of ASDs, especially those of the ostium secundum type. The sinus venosus type is a relatively uncommon form of ASD, which, when associated with a PAPVD, is considered a complex cardiac malformation, and is usually treated in a classical manner, through median sternotomy. We describe the case of a 45-year-old woman diagnosed in adolescence with SV-ASD with PAPVD, who successfully underwent minimally invasive repair with fresh autologous pericardial patch reconstruction through an anterolateral mini-thoracotomy incision. The patient presented with shortness of breath and fatigue after heavy exertions, episodes of paroxysmal nocturnal dyspnea, palpitations during effort and at rest, and had a history of syncope dating from 17 years previously. Echocardiography revealed an SV-ASD with PAPVD in the right atrium and the intraoperative examination discovered that both right pulmonary veins were draining into the superior vena cava.