Efficacy and safety of macitentan in Fontan-palliated patients: 52-week randomized, placebo-controlled RUBATO Phase 3 trial and open-label extension.

Objectives: The efficacy and safety of macitentan, an endothelin receptor antagonist, were assessed in a 52-week, prospective, multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessing the efficacy and safety of macitentan in Fontan-palliated adult and adolescent patients (RUBATO-DB) and an open-label extension trial (RUBATO-OL).

Methods: Patients aged 12 years and older with New York Heart Association functional class II or III underwent total cavopulmonary connection more than 1 year before screening and showed no signs of Fontan failure/clinical deterioration. In RUBATO-DB, the primary efficacy end point was change in peak oxygen consumption from baseline to week 16; secondary end points were change from baseline over 52 weeks in peak oxygen consumption and change in mean count/minute of daily physical activity via accelerometer from baseline to week 16.

Medical Therapy and Monitoring in Adult Congenital Heart Disease Heart Failure.

Heart failure (HF) in adult congenital heart disease (ACHD) is an increasingly common problem facing ACHD and advanced heart disease and transplant providers. Patients are highly nuanced, and therapies are poorly studied. Standard HF medications are often used in patients who are not targets of large clinical trials.

End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study.

Background And Aims: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear.

Methods: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained.

Long-Term Outcomes After Atrial Switch Operation for Transposition of the Great Arteries.

Background: For patients with d-loop transposition of the great arteries (d-TGA) with a systemic right ventricle after an atrial switch operation, there is a need to identify risks for end-stage heart failure outcomes.

Objectives: The authors aimed to determine factors associated with survival in a large cohort of such individuals.

Methods: This multicenter, retrospective cohort study included adults with d-TGA and prior atrial switch surgery seen at a congenital heart center.

COVID-19 in Adults With Congenital Heart Disease.

Background: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications.

Objectives: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes.

Methods: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide.

Transition of Adolescents and Young Adults with Congenital Heart Disease: Challenges, Progress, and Future Improvements.

Congenital heart disease (CHD) is the most common and perhaps most widely variable birth defect. Decades of improved CHD care has resulted in a steady growth in the number and complexity of adults with CHD, and many of these patients require lifelong, specialized follow-up care. This begins with successful transition from pediatric-based to adult-based care.

Progress in the diagnosis and management of pulmonary hypertension in children.

Purpose Of Review: Pulmonary hypertension is a complex disease that extends beyond merely elevated pulmonary blood pressures and right ventricular dysfunction. Its multiple causes and ever-expanding diagnostic tools and therapeutic approaches make it a heterogeneous disease with widely variable clinical sequelae. There are still many unanswered questions that challenge our understanding of this disease.

Perioperative management of shock in two fontan patients with plastic bronchitis.

Plastic bronchitis is potentially a life-threatening complication of long-standing surgically palliated single ventricle congenital heart disease. Patients can present with hypoxia requiring urgent bronchoscopy for removal of bronchial casts. Perioperative care for these patients is challenging and anesthesia is associated with significant cardiac risk.

Bicuspid aortic valve: inter-racial difference in frequency and aortic dimensions.

Objectives: The objective of this study was to examine the similarities and differences in Caucasian (C) and African-American (AA) patients with bicuspid aortic valve (BAV) with respect to morphology, severity of aortic stenosis/insufficiency, and aortic dilation.

Background: BAV is a common congenital valve abnormality, accounting for a large number of valve replacements.

Methods: A total of 229 patients with the diagnostic code BAV were identified retrospectively from our computerized adult echocardiographic database, which consists of 91,896 studies performed at the University of Chicago Medical Center from 1998 to 2009, representing 40,878 patients.

Cardiac sarcoidosis presenting as mitral regurgitation.

Cardiac sarcoidosis is most often clinically silent. When symptomatic, it commonly involves the conduction system. This inflammatory and infiltrative process may be manifest as conduction delays and/or important ventricular ectopy.

Inhibition of protein kinase C epsilon causes ciliated bovine bronchial cell detachment.

This study defines the in vitro phenomenon of ciliated bovine bronchial epithelial cell (BBEC) detachment from the basal epithelium and regulation of cilia motility mediated through protein kinase C epsilon (PKCepsilon). The authors determined the time course of activation and downregulation of PKCepsilon by the known PKC activator phorbol 12-myristate 13-acetate (PMA) and demonstrate that chemical inhibition of PKC by calphostin C or the novel PKC isoform inhibitor Ro 31-8220 induced striking detachment of ciliated BBECs from the basal cell monolayer within 1 hour, independent of apoptosis or necrotic cell death. The results of this study support a possible novel PKCepsilon-mediated signaling pathway through which ciliated cell attachment is maintained.

Ubiquitin-proteasome degradation of serum- and glucocorticoid-regulated kinase-1 (SGK-1) is mediated by the chaperone-dependent E3 ligase CHIP.

SGK-1 (serum- and glucocorticoid-regulated kinase-1) is a stress-induced serine/threonine kinase that is phosphorylated and activated downstream of PI3K (phosphoinositide 3-kinase). SGK-1 plays a critical role in insulin signalling, cation transport and cell survival. SGK-1 mRNA expression is transiently induced following cellular stress, and SGK-1 protein levels are tightly regulated by rapid proteasomal degradation.