Abnormal developmental trajectory and vulnerability to cardiac arrhythmias in tetralogy of Fallot with DiGeorge syndrome.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Ventricular dysfunction and cardiac arrhythmias are well-documented complications in patients with repaired TOF. Whether intrinsic abnormalities exist in TOF cardiomyocytes is unknown.

APLNR marks a cardiac progenitor derived with human induced pluripotent stem cells.

Cardiomyocytes can be readily derived from human induced pluripotent stem cell (hiPSC) lines, yet its efficacy varies across different batches of the same and different hiPSC lines. To unravel the inconsistencies of in vitro cardiac differentiation, we utilized single cell transcriptomics on hiPSCs undergoing cardiac differentiation and identified cardiac and extra-cardiac lineages throughout differentiation. We further identified APLNR as a surface marker for in vitro cardiac progenitors and immunomagnetically isolated them.

Remote Ischemic Conditioning in Pediatric Cancer Patients Receiving Anthracycline Chemotherapy: A Sham-Controlled Single-Blind Randomized Trial.

Background: Anthracycline cardiotoxicity is a concern in survivors of childhood cancers. Recent evidence suggests that remote ischemic conditioning (RIC) may offer myocardial protection.

Objectives: This randomized sham-controlled single-blind study tested the hypothesis that RIC may reduce myocardial injury in pediatric cancer patients receiving anthracycline chemotherapy.

Phenomapping approach to interpreting coronary dimensions in febrile children.

Importance: Coronary artery dilation may occur in febrile children with and without Kawasaki disease (KD).

Objective: We explored the application of unsupervised learning algorithms in the detection of novel patterns of coronary artery phenotypes in febrile children with and without KD.

Methods: A total of 239 febrile children (59 non-KD and 180 KD patients), were recruited.

Managing uncertainty in decision-making of common congenital cardiac defects.

Decision-making in congenital cardiac care, although sometimes appearing simple, may prove challenging due to lack of data, uncertainty about outcomes, underlying heuristics, and potential biases in how we reach decisions. We report on the decision-making complexities and uncertainty in management of five commonly encountered congenital cardiac problems: indications for and timing of treatment of subaortic stenosis, closure or observation of small ventricular septal defects, management of new-onset aortic regurgitation in ventricular septal defect, management of anomalous aortic origin of a coronary artery in an asymptomatic patient, and indications for operating on a single anomalously draining pulmonary vein. The strategy underpinning each lesion and the indications for and against intervention are outlined.

Case Report: Primary Thoracic Low-Grade Fibromyxoid Sarcoma in a Young Girl Presenting With Mediastinal Mass Syndrome.

Low-grade fibromyxoid sarcomas (LGFMSs) are typically adult-onset tumors that arise from the extremities. Here, we report an exceptional case of primary thoracic LGFMS in an 8-year-old girl that resulted in mediastinal syndrome. In reporting this case, we discuss the clinical challenges, role of molecular profiling and review reported cases of pediatric thoracic LGFMSs.

An Unusual Cause of Cyanosis after Fontan Procedure in Right Atrial Isomerism.

• Persistent or worsening cyanosis after Fontan procedure deserves thorough evaluation. • Right-to-left shunt through hepatic vein communication in right atrial isomerism is reported. • Detailed delineation of hepatic venous drainage is essential in pre-Fontan assessment.

Myocardial Deformation Imaging by Speckle-Tracking Echocardiography for Assessment of Cardiotoxicity in Children during and after Chemotherapy: A Systematic Review and Meta-Analysis.

Background: Children with cancer and childhood cancer survivors (CCS) are at risk for developing chemotherapy-induced cardiomyopathy. Myocardial deformation imaging has shown potential in the early detection of subclinical myocardial damage with implications on therapeutic interventions and improvement of outcomes. The aim of this study was to perform a systemic review and meta-analysis of literature on the assessment of left ventricular and right ventricular myocardial deformation by speckle-tracking echocardiography at rest and during stress in children with cancer during and in survivors after chemotherapy.

Native cardiac magnetic resonance T1 mapping and cardiac mechanics as assessed by speckle tracking echocardiography in patients with beta-thalassaemia major.

Background: We hypothesize that cardiac magnetic resonance (CMR) native T1 is associated with myocardial deformation in thalassaemia patients. The present study aimed to compare CMR native T1 values to conventional T2* values in patients with beta-thalassaemia and to explore relationships between these CMR parameters of myocardial iron overload and left ventricular (LV) and left atrial (LA) myocardial deformation.

Methods: Thirty-four (16 males) patients aged 35.

Systolic and diastolic functional reserve of the subpulmonary and systemic right ventricles as assessed by pharmacologic and exercise stress: A systematic review.

We performed a systematic review of the literature on the assessment of subpulmonary and systemic right ventricular (RV) functional reserve during pharmacological and exercise stress in congenital heart patients and patients with pulmonary arterial hypertension (PAH). Literature search was conducted using PubMed, EMBASE, and MEDLINE from their inception up to August 2020. Of 913 records identified, 56 studies with a total of 1730 patients were included.

Right Ventricular-Pulmonary Arterial Coupling in Repaired Tetralogy of Fallot.

We assessed right ventricular (RV)-pulmonary arterial (PA) coupling in patients with repaired tetralogy of Fallot (TOF). Sixty patients (34 males) aged 18.6 ± 8.

Human Pluripotent Stem Cells for Modeling of Anticancer Therapy-Induced Cardiotoxicity and Cardioprotective Drug Discovery.

Anticancer chemotherapies have been shown to produce severe side effects, with cardiotoxicity from anthracycline being the most notable. Identifying risk factors for anticancer therapy-induced cardiotoxicity in cancer patients as well as understanding its underlying mechanism is essential to improving clinical outcomes of chemotherapy treatment regimens. Moreover, cardioprotective agents against anticancer therapy-induced cardiotoxicity are scarce.

Three Decades of Follow-up After Surgical Closure of Subarterial Ventricular Septal Defect.

We determined the occurrence of aortic regurgitation (AR), AR progression and risk factors in patients followed up for up to three decades after closure of subarterial VSD. We reviewed the outcomes of 86 patients categorized into three groups: group I comprised 37 patients without AR and had VSD closure alone, group II comprised 40 patients with AR and had VSD closure without aortic valvoplasty, and group III comprised 9 patients with AR and required both VSD closure and aortic valvoplasty. Patients were followed up for 18.

Interplay between right atrial function and liver stiffness in adults with repaired right ventricular outflow obstructive lesions.

Aims: This study determined the associations between right atrial (RA) and right ventricular (RV) mechanics and liver stiffness in adults with repaired tetralogy of Fallot (TOF), pulmonary atresia with intact ventricular septum (PAVIS), and pulmonary stenosis (PS).

Methods And Results: Ninety subjects including 26 repaired TOF, 24 PAIVS, and 20 PS patients and 20 controls were studied. Hepatic shear wave velocity and tissue elasticity (E), measures of liver stiffness, were assessed by two-dimensional shear wave elastography, while RA and RV mechanics were assessed by speckle tracking echocardiography.

Monoallelic Mutations in Suggest a Novel Role in Human Heterotaxy and Ciliary Dysfunction.

Background: Human heterotaxy is a group of congenital disorders characterized by misplacement of one or more organs according to the left-right axis. The genetic causes of human heterotaxy are highly heterogeneous.

Methods: We performed exome sequencing in a cohort of 26 probands with heterotaxy followed by gene burden analysis for the enrichment of novel rare damaging mutations.

Single-Cell Transcriptomics of Engineered Cardiac Tissues From Patient-Specific Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals Abnormal Developmental Trajectory and Intrinsic Contractile Defects in Hypoplastic Right Heart Syndrome.

Background To understand the intrinsic cardiac developmental and functional abnormalities in pulmonary atresia with intact ventricular septum (PAIVS) free from effects secondary to anatomic defects, we performed and compared single-cell transcriptomic and phenotypic analyses of patient- and healthy subject-derived human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and engineered tissue models. Methods and Results We derived hiPSC lines from 3 patients with PAIVS and 3 healthy subjects and differentiated them into hiPSC-CMs, which were then bioengineered into the human cardiac anisotropic sheet and human cardiac tissue strip custom-designed for electrophysiological and contractile assessments, respectively. Single-cell RNA sequencing (scRNA-seq) of hiPSC-CMs, human cardiac anisotropic sheet, and human cardiac tissue strip was performed to examine the transcriptomic basis for any phenotypic abnormalities using pseudotime and differential expression analyses.

Differential myocardial fibrosis of the systemic right ventricle and subpulmonary left ventricle after atrial switch operation for complete transposition of the great arteries.

Background: This study aimed to assess diffuse myocardial fibrosis of the systemic right ventricle and subpulmonary left ventricle in patients after Senning or Mustard operation for complete transposition of the great artery (TGA) using cardiac magnetic resonance (CMR) T1 mapping.

Methods: Thirty-one adult TGA patients after Senning (n = 24) or Mustard (n = 7) operation were studied at the age of 33.3 ± 4.

Circulating high-sensitivity troponin T and microRNAs as markers of myocardial damage during childhood leukaemia treatment.

Background: We investigated whether plasma high-sensitivity cardiac troponin T (hs-cTnT) and circulating heart-associated microRNA (miRs) are increased in children with leukaemias during anthracycline-based chemotherapeutic treatment.

Methods: In vitro human pluripotent stem cell (hPSC)-derived cardiomyocyte model showed that miR-1, miR-133a, miR-208a, miR-208b, and miR-499 are released from cells into culture medium in a time- and dose-dependent manner on doxorubicin exposure. Left ventricular (LV) myocardial deformation and circulating heart-associated miRs and plasma hs-cTnT during and after completion of chemotherapy were determined in 40 children with newly diagnosed acute leukaemia.

Ventricular Myocardial Deformation Imaging of Patients with Repaired Tetralogy of Fallot.

In patients with repaired tetralogy of Fallot (TOF), dysfunction of the right and left ventricles remains an important issue. Adverse right ventricular (RV) remodeling has been related to RV dilation secondary to pulmonary regurgitation, electromechanical dyssynchrony, and myocardial fibrosis. Left ventricular (LV) dysfunction is attributed among other factors to altered ventricular-ventricular interaction.

Tricuspid Regurgitation in Adults after Repair of Right Ventricular Outflow Obstructive Lesions.

We determined the prevalence and factors associated with tricuspid regurgitation (TR) in adults with repair of right ventricular (RV) outflow obstruction. A total of 256 patients (128 males) were studied at 25.7 ± 7.

Frontal QRS-T angle and ventricular mechanics in congenital heart disease.

Background: The QRS-T angle has been associated with adverse cardiovascular events and sudden cardiac deaths. We determined frontal QRS-T angle in patients with complete transposition of the great arteries (TGA) after atrial switch operation and repaired tetralogy of Fallot (TOF) and explored its relationships with ventricular mechanics.

Methods: Thirty TGA patients aged 32.

Combinatorial Treatment of Human Cardiac Engineered Tissues With Biomimetic Cues Induces Functional Maturation as Revealed by Optical Mapping of Action Potentials and Calcium Transients.

Although biomimetic stimuli, such as microgroove-induced alignment (μ), triiodothyronine (T3) induction, and electrical conditioning (EC), have been reported to promote maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), a systematic examination of their combinatorial effects on engineered cardiac tissue constructs and the underlying molecular pathways has not been reported. Herein, human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs) were used to generate a micro-patterned human ventricular cardiac anisotropic sheets (hvCAS) for studying the physiological effects of combinatorial treatments by a range of functional, calcium (Ca)-handling, and molecular analyses. High-resolution optical mapping showed that combined μ-T3-EC treatment of hvCAS increased the conduction velocity, anisotropic ratio, and proportion of mature quiescent-yet-excitable preparations by 2.