Percutaneous closure of simple congenital heart diseases under echocardiographic guidance.

Congenital heart disease (CHD), birth defect with the highest incidence rates worldwide, and is mainly characterized by the abnormal internal structure of the heart or/and the anatomical structure of great vessels. In the past few decades, CHD repair surgery through standard median sternotomy incision combined with cardiopulmonary bypass (CPB) technology has been considered the gold standard for surgical correction of heart and great vessels. With the promotion and clinical application of interventional catheterization technology, transcatheter closure of CHD under radioactive radiation has gradually been recognized and applied. However, its radiation exposure and potential complications related to arteriovenous vessels still face challenges. In recent years, an increasing number of surgeons have explored new surgical procedures, for the safe and effective treatment of CHD, as far as possible to reduce surgical trauma, avoid radiation exposure, and improve the cosmetic effect. Therefore, on the premise of satisfactory exposure or guidance, how to integrate ultrasound and percutaneous interventional technology remained the focus of the exploration. This mini-review highlights and summarizes the signs of progress of ultrasound intervention in the last decade that have proven the effectiveness and operability of a well-established procedure for percutaneous closure of congenital heart diseases under echocardiographic guidance only. We discuss potential diseases that will benefit from this emerging procedure based on this progress. Owing to the crucial advantages played by this strategy in the treatment of CHD, better understanding and promotion of this less exploited field may contribute to the development of therapeutics targeting CHD, improve medical utilization rate, promote the optimization of medical resources, and ultimately achieve precise and efficient medical treatment.

Application of an F0-based genetic assay in adult zebrafish to identify modifier genes of an inherited cardiomyopathy.

Modifier genes contribute significantly to our understanding of pathophysiology in human diseases; however, effective approaches to identify modifier genes are still lacking. Here, we aim to develop a rapid F0-based genetic assay in adult zebrafish using the bag3 gene knockout (bag3e2/e2) cardiomyopathy model as a paradigm. First, by utilizing a classic genetic breeding approach, we identified dnajb6b as a deleterious modifier gene for bag3 cardiomyopathy. Next, we established an F0-based genetic assay in adult zebrafish through injection of predicted microhomology-mediated end joining (MMEJ)-inducing single guide RNA/Cas9 protein complex. We showed that effective gene knockdown is maintained in F0 adult fish, enabling recapitulation of both salutary modifying effects of the mtor haploinsufficiency and deleterious modifying effects of the dnajb6b gene on bag3 cardiomyopathy. We finally deployed the F0-based genetic assay to screen differentially expressed genes in the bag3 cardiomyopathy model. As a result, myh9b was identified as a novel modifier gene for bag3 cardiomyopathy. Together, these data prove the feasibility of an F0 adult zebrafish-based genetic assay that can be effectively used to discover modifier genes for inherited cardiomyopathy.

A phenotype-based forward genetic screen identifies Dnajb6 as a sick sinus syndrome gene.

Previously we showed the generation of a protein trap library made with the gene-break transposon (GBT) in zebrafish (Danio rerio) that could be used to facilitate novel functional genome annotation towards understanding molecular underpinnings of human diseases (Ichino et al, 2020). Here, we report a significant application of this library for discovering essential genes for heart rhythm disorders such as sick sinus syndrome (SSS). SSS is a group of heart rhythm disorders caused by malfunction of the sinus node, the heart's primary pacemaker. Partially owing to its aging-associated phenotypic manifestation and low expressivity, molecular mechanisms of SSS remain difficult to decipher. From 609 GBT lines screened, we generated a collection of 35 zebrafish insertional cardiac (ZIC) mutants in which each mutant traps a gene with cardiac expression. We further employed electrocardiographic measurements to screen these 35 ZIC lines and identified three GBT mutants with SSS-like phenotypes. More detailed functional studies on one of the arrhythmogenic mutants, GBT411, in both zebrafish and mouse models unveiled Dnajb6 as a novel SSS causative gene with a unique expression pattern within the subpopulation of sinus node pacemaker cells that partially overlaps with the expression of hyperpolarization activated cyclic nucleotide gated channel 4 (HCN4), supporting heterogeneity of the cardiac pacemaker cells.

Case Report: Anomalous Origin of the Right Coronary Artery From the Left Sinus of Valsalva With Aortic Dissection: New Myocardial Ischemia Mechanism.

The aortic anomaly of the right coronary artery (AAORCA) originating from the left aortic sinus (LCS) is a rare malformation that may result in sudden cardiac death (SCD), which may be due to the dilated aorta-pulmonary artery affecting the blood supply of the coronary artery. However, there are still some disputes about the treatment of the AAORCA. Herein, we present a rare case of AAORCA from the LCS with aortic dissection (AD). Considering the risk of dissection rupture and SCD, an emergency surgery of aortic replacement and coronary anomaly correction was performed successfully for the patient. This report illustrated that AAORCA complicated with acute AD (AAD) is lethal and may promote the occurrence of coronary ischemia or sudden death by a new "double-kill" mechanism that myocardial ischemia was based on the extent of a fixed and a dynamic component like slit-like ostium, proximal narrowing, acute take-off angle and intramural course with the elliptic vessel shape. There is no doubt that surgery is the best treatment option for the AAORCA with AAD.

Strategies to rare primary cardiac lipomas in the left ventricle in a patient: case report.

BACKGROUND: Primary cardiac tumors are rare in all age groups and are usually benign. Symptoms are usually related to tumor size, location, invasiveness, number, and growth rate. While histologically benign, cardiac arrest may be caused by blocked inflow or outflow or malignant ventricular arrhythmia. Surgical resection of left ventricular tumors, especially those involving the outflow tract, is challenging. CASE PRESENTATION: Herein, we present a rare case of an asymptomatic, 39-year-old woman who was referred to our cardiovascular department for a huge left ventricular cardiac mass incidentally discovered during the physical examination. Images showed a huge mass that quasi-circular low-density focus with a clear boundary and regular shape in the left ventricular cavity and fortunately had no significant effect on the peripheral valves and hemodynamics. CONCLUSIONS: This illustrative report highlights the exact surgical management of a cardiac tumor depends largely on the site and extent of the mass. Mechanical compromise and not the neoplastic potential should be considered. A conservative approach and follow-up regularly are advocated to ensure that the patient gets the best diagnosis and treatment, however, surgery is indicated only for severely symptomatic patients with hemodynamic compromise.

MicroRNAs in hypertrophic cardiomyopathy: pathogenesis, diagnosis, treatment potential and roles as clinical biomarkers.

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and is characterized by increased left ventricular wall thickness, but existing diagnostic and treatment approaches face limitations. MicroRNAs (miRNAs) are type of noncoding RNA molecule that plays crucial roles in the pathological process of cardiac remodelling. Accordingly, miRNAs related to HCM may represent potential novel therapeutic targets. In this review, we first discuss the different roles of miRNAs in the development of HCM. We then summarize the roles of common miRNAs as diagnostic and clinical biomarkers in HCM. Finally, we outline current and future challenges and potential new directions for miRNA-based therapeutics for HCM.

Inhibition of mTOR or MAPK ameliorates vmhcl/myh7 cardiomyopathy in zebrafish.

Myosin heavy chain 7 (MYH7) is a major causative gene for hypertrophic cardiomyopathy, but the affected signaling pathways and therapeutics remain elusive. In this research, we identified ventricle myosin heavy chain like (vmhcl) as a zebrafish homolog of human MYH7, and we generated vmhcl frameshift mutants. We noted vmhcl-based embryonic cardiac dysfunction (VEC) in the vmhcl homozygous mutants and vmhcl-based adult cardiomyopathy (VAC) phenotypes in the vmhcl heterozygous mutants. Using the VEC model, we assessed 7 known cardiomyopathy signaling pathways pharmacologically and 11 candidate genes genetically via CRISPR/Cas9 genome editing technology based on microhomology-mediated end joining (MMEJ). Both studies converged on therapeutic benefits of mTOR or mitogen-activated protein kinase (MAPK) inhibition of VEC. While mTOR inhibition rescued the enlarged nuclear size of cardiomyocytes, MAPK inhibition restored the prolonged cell shape in the VEC model. The therapeutic effects of mTOR and MAPK inhibition were later validated in the VAC model. Together, vmhcl/myh7 loss of function is sufficient to induce cardiomyopathy in zebrafish. The VEC and VAC models in zebrafish are amenable to both efficient genetic and chemical genetic tools, offering a rapid in vivo platform for discovering candidate signaling pathways of MYH7 cardiomyopathy.

Case Report: An Anomalous Left Hepatic Venous Connection in a Patient With Unexpected Cyanosis.

An anomalous left hepatic venous (LHV) connection is an extremely rare cardiac malformation, and left hepatic venous route abnormalities not associated with other cardiac lesions do not require surgical treatment because they are physiologically benign. However, when venous route abnormalities exist with associated cardiac lesions, the conduct of the cardiac surgical repair must accommodate the abnormal venous anatomy, especially in total cavopulmonary connection patients. Herein, we present a rare case of a 7-year-old Chinese boy about 1 year post bilateral superior vena cava pulmonary anastomosis who presented with severe cyanosis and was referred to our department. However, the patient showed an unexpected gradual decrease in blood oxygen saturation to 60-70% after the extracardiac total cavopulmonary connection (ETCPC) operation. Emergency echocardiography and computed tomography confirmed that the LHV entered the right atrium. Subsequently, the patient undergone completion of a staged TCPC with intra-atrial tunnel technique. This illustrative report highlights the essence of improving the preoperative accurate diagnosis to avoid unplanned reoperation in China, especially for the remote rural areas of eastern countries where the level of health care and services is relatively backward. Failure to identify anomalous LHV connection, in this case, will delay effective treatment past the optimal treatment time.