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. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. RESULTS: From 558 patients (48% female, age at first visit 36 ± 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. CONCLUSIONS: Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.

Rising Burden of Cardiovascular Disease Risk Factors and Acute Cardiac Events in Young Adults With Comorbid Depression: A Comparison Nationwide US Cohorts Hospitalized 10-years Apart.

Depression and coronary artery disease are leading causes of mortality in adults in high-income countries. Due to the paucity of data on the young, we aimed to investigate the prevalence of cardiovascular disease (CVD) risk factors and associated major adverse cardiac and cerebrovascular events (MACCE) in young adults hospitalized with comorbid depression a decade apart. We conducted a retrospective analysis of the National Inpatient Sample Database for the years 2007 and 2017. Young adults (18-44 years) hospitalized with comorbid depression were identified using ICD-9 CM/ICD-10 codes. Frequency and trends in demographics, comorbidities including CVD risk factors, and MACCE have been compared between the 2017 vs 2007 cohorts. A total of 1,274,118 admissions with a median age of 34 years and 68.7% of females were recorded with comorbid depression. When the 2007 cohort was compared with the 2017 cohort, a rising trend in depression was observed (5.5% vs 8.2%, P < 0.001). The 2017 cohort of young adults with depression more often consisted of male, non-white patients. The burden of CVD risk factors such as hypertension, diabetes with chronic complications, smoking, and obesity was also greater in the 2017 cohort. Although the all-cause mortality remained comparable (0.3%) in both cohorts, there was a significantly higher rate and risk of MACCE including acute myocardial infarction (aOR 1.18, 95%CI:1.10-1.26), atrial fibrillation or flutter (aOR 1.47, 95%CI:1.40-1.54) and stroke (aOR 1.33, 95%CI: 1.26-1.40) (P < 0.001) in the 2017 cohort. In conclusion, this nationwide study reveals an alarmingly increased prevalence of CVD risk factors and an increase in the rate and risk of MACCE in 2 cohorts of young adults with comorbid depression studied a decade apart. The burden of mental disorders in young adults has been rising in the last decade and warrants extra vigilance by clinicians to recognize and manage depression to curtail CVD risk and improve MACE-associated outcomes.

Management of the Fontan patient during pregnancy.

PURPOSE OF REVIEW: Patients with single-ventricle Fontan palliation surgery often wish to pursue pregnancy. Pregnancies should be planned with well tolerated and effective contraception, and preconception risk stratification by adult congenital heart disease and maternal foetal medicine specialists. RECENT FINDINGS: Although infertility and foetal complications, including pregnancy loss, preterm birth and foetal growth restriction, are common, most patients with Fontan palliations can successfully complete pregnancy with a team-based approach. Important risk predictors are resting oxygen saturations, baseline functional status and the presence of systemic complications of the Fontan repair, including advanced Fontan associated liver disease, plastic bronchitis and ventricular dysfunction. Common maternal cardiovascular complications include arrhythmia, heart failure and thromboembolism. Delivery planning with input from an obstetric anaesthesiologist who has knowledge of complex congenital heart defects can facilitate appropriate, individualized monitoring and pain control. A vaginal delivery with consideration of an assisted second stage is appropriate for most single ventricle patients, in the absence of obstetric or foetal indications for caesarean delivery. Close postpartum monitoring and follow up is recommended, as the early postpartum period is the highest risk time for cardiovascular complications in patients with congenital heart disease. SUMMARY: A multidisciplinary approach to managing pregnancy and delivery in patients with Fontan circulation facilitates optimal maternal and infant outcomes.

Adsorption of Indigo Carmine Dye by Acacia nilotica sawdust activated carbon in fixed bed column.

A continuous mode fixed-bed up-flow column adsorption analysis was conducted utilizing Acacia nilotica sawdust activated carbon (ASAC) as an adsorbent for the adsorption treatment of toxic Indigo Carmine Dye (ICD). The effect on the adsorption characteristics of ASAC of the influent ICD concentration, flow rate, and column bed depth has been investigated. According to the column study, the highest efficiency of ICD removal was approximately 79.01% at a preliminary concentration of 100 mg/L with a flow rate of 250 mL/h at a bed depth of 30 cm and adsorption power of 24.67 mg/g. The experimental work confirmed the dependency of break-through curves on dye concentration and flow rate for a given bed depth. Kinetic models were implemented by Thomas, Yoon-Nelson, and Bed-depth-service-time analysis along with error analysis to interpret experimental data for bed depth of 15 cm and 30 cm, ICD concentration of 100 mg/L and 200 mg/L and flow rate of 250 mL/h, and 500 mL/h. The analysis predicted the breakthrough curves using a regression basin. It indicated that all three models were comparable for the entire break-through curve depiction. The characteristic parameters determined by process design and error analysis revealed that the Thomas model was better followed by the BDST and Yoon-Nelson models in relating the procedure of ICD adsorption onto ASAC. B-E-T surface area and B-E-T pore volume of ASAC were 737.76 m2/g and 0.2583 cm3/g, respectively. S-E-M and X-R-D analysis reveal the micro-porous and amorphous nature of ASAC. F-T-I-R spectroscope indicate distinctive functional assemblies like -OH group, C-H bond, C-C bond, C-OH, and C-O groups on ASAC. It could be computed that the ASAC can be used efficiently as an alternative option for industrial wastewater treatment.

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. Clinical data from initial and most recent visits were obtained. The composite primary outcome was death, transplantation, or mechanical circulatory support (MCS). RESULTS: From 1,168 patients (38% female, age at first visit 29 ± 7.2 years) during a median 9.2 years of follow-up, 91 (8.8% per 10 person-years) met the outcome (66 deaths, 19 transplantations, 6 MCS). Patients experiencing sudden/arrhythmic death were younger than those dying of other causes (32.6 ± 6.4 years vs 42.4 ± 6.8 years; P < 0.001). There was a long duration between sentinel clinical events and end-stage heart failure. Age, atrial arrhythmia, pacemaker, biventricular enlargement, systolic dysfunction, and tricuspid regurgitation were all associated with the primary outcome. Independent 5-year predictors of primary outcome were prior ventricular arrhythmia, heart failure admission, complex anatomy, QRS duration >120 ms, and severe right ventricle dysfunction based on echocardiography. CONCLUSIONS: For most adults with d-TGA after atrial switch, progress to end-stage heart failure or death is slow. A simplified prediction score for 5-year adverse outcome is derived to help identify those at greatest risk.

New concepts in heart failure with preserved ejection fraction and hypertension.

PURPOSE OF REVIEW: Hypertension (HTN) remains the most common and strongest contributing factor to the development of heart failure with preserved ejection fraction (HFpEF). In this review, we aim to summarize the pathophysiological processes linking HTN to HFpEF and highlight novel concepts in medical and device-based management of HFpEF and HTN. RECENT FINDINGS: Despite the global increase in the prevalence of HFpEF, there has been limited benefit in current medication and device-based therapy for this complex syndrome. The hallmark of HFpEF is an elevated left intra-atrial and ventricular pressure and exertional dyspnea. Traditional medications used for treating HTN in patients with reduced left ventricular ejection fraction have unclear benefits in patients with HFpEF. Careful analysis of emerging medications such as angiotensin receptor-neprilysin inhibitor and sodium-glucose co-transporter-2 inhibitors showed benefit in reducing not only blood pressure but also hospitalizations in patients with HFpEF. Current data on device-based therapy aims to reduce left intra-atrial pressure, ventricular pressure and stimulate baroreceptors to lower blood pressure; however, needs further investigation. SUMMARY: The nexus of HTN and HFpEF remains strong and complex. Although traditional medications for treating HFrEF did not affect long-term outcomes, novel therapies with angiotensin receptor neprilysin-inhibitor and sodium-glucose co-transporter-2 inhibitor offer promising results. Many device-based interventions in the HFpEF population are being developed with the aim to reduce left intra-atrial and ventricular pressure; however, their role in HFpEF hypertensive patients needs to be further investigated.

Mapping Bacterial Biofilm on Features of Orthopedic Implants In Vitro.

Implant-associated infection is a major complication of orthopedic surgery. One of the most common organisms identified in periprosthetic joint infections is Staphylococcus aureus, a biofilm-forming pathogen. Orthopedic implants are composed of a variety of materials, such as titanium, polyethylene and stainless steel, which are at risk for colonization by bacterial biofilms. Little is known about how larger surface features of orthopedic hardware (such as ridges, holes, edges, etc.) influence biofilm formation and attachment. To study how biofilms might form on actual components, we submerged multiple orthopedic implants of various shapes, sizes, roughness and material type in brain heart infusion broth inoculated with Staphylococcus aureus SAP231, a bioluminescent USA300 strain. Implants were incubated for 72 h with daily media exchanges. After incubation, implants were imaged using an in vitro imaging system (IVIS) and the metabolic signal produced by biofilms was quantified by image analysis. Scanning electron microscopy was then used to image different areas of the implants to complement the IVIS imaging. Rough surfaces had the greatest luminescence compared to edges or smooth surfaces on a single implant and across all implants when the images were merged. The luminescence of edges was also significantly greater than smooth surfaces. These data suggest implant roughness, as well as large-scale surface features, may be at greater risk of biofilm colonization.

Cardiac Amyloidosis: Presentations, Diagnostic Work-up and Collaborative Approach for Comprehensive Clinical Management.

Cardiac amyloidosis is a systemic disease characterized by continuous deposition of misfolded proteins called amyloid fibrils in the extracellular space which result in restrictive cardiomyopathy. The most common form of cardiac amyloidosis is light chain (AL) cardiac amyloidosis, a result of continuous deposition of misfolded monoclonal immunoglobulin light chains. Transthyretin-related cardiac amyloidosis (ATTR) results from a point mutation in the transthyretin gene in an autosomal dominant fashion and presents phenotypically similar to AL cardiac amyloidosis. Cardiac amyloidosis is being increasingly recognized due to the advancements in diagnostic cardiac imaging and pharmacotherapy. Clinicians should maintain a high index of suspicion among patients with unexplained diastolic heart failure because earlier diagnosis will allow for the implementation of disease-altering therapy. With established targeted drug therapies and further breakthroughs in immunotherapy, the potential impact of diagnostic and therapeutic advancements on morbidity and mortality of patients with cardiac amyloidosis is promising.

The X-linked acrogigantism-associated gene gpr101 is a regulator of early embryonic development and growth in zebrafish.

We recently described X-linked acrogigantism (X-LAG), a condition of early childhood-onset pituitary gigantism associated with microduplications of the GPR101 receptor. The expression of GPR101 in hyperplastic pituitary regions and tumors in X-LAG patients, and GPR101's normally transient pituitary expression during fetal development, suggest a role in the regulation of growth. Nevertheless, little is still known about GPR101's physiological functions, especially during development. By using zebrafish models, we investigated the role of gpr101 during embryonic development and somatic growth. Transient ectopic gpr101 expression perturbed the embryonic body plan but did not affect growth. Loss of gpr101 led to a significant reduction in body size that was even more pronounced in the absence of maternal transcripts, as well as subfertility. These changes were accompanied by gastrulation and hypothalamic defects. In conclusion, both gpr101 loss- and gain-of-function affect, in different ways, fertility, embryonic patterning, growth and brain development.

Staphylococcus aureus Aggregates on Orthopedic Materials under Varying Levels of Shear Stress.

Periprosthetic joint infection (PJI) occurring after artificial joint replacement is a major clinical issue requiring multiple surgeries and antibiotic interventions. Staphylococcus aureus is the bacterium most commonly responsible for PJI. Recent in vitro research has shown that staphylococcal strains rapidly form aggregates in the presence of synovial fluid (SF). We hypothesize that these aggregates provide early protection to bacteria entering the wound site, allowing them time to attach to the implant surface, leading to biofilm formation. Thus, understanding the attachment kinetics of these aggregates is critical in understanding their adhesion to various biomaterial surfaces. In this study, the number, size, and surface area coverage of aggregates as well as of single cells of S. aureus were quantified under various conditions on different orthopedic materials relevant to orthopedic surgery: stainless steel (316L), titanium (Ti), hydroxyapatite (HA), and polyethylene (PE). It was observed that, regardless of the material type, SF-induced aggregation resulted in reduced aggregate surface attachment and greater aggregate size than the single-cell populations under various shear stresses. Additionally, the surface area coverage of bacterial aggregates on PE was relatively high compared to that on other materials, which could potentially be due to the rougher surface of PE. Furthermore, increasing shear stress to 78 mPa decreased aggregate attachment to Ti and HA while increasing the aggregates' average size. Therefore, this study demonstrates that SF induced inhibition of aggregate attachment to all materials, suggesting that biofilm formation is initiated by lodging of aggregates on the surface features of implants and host tissues.IMPORTANCE Periprosthetic joint infection occurring after artificial joint replacement is a major clinical issue that require repeated surgeries and antibiotic interventions. Unfortunately, 26% of patients die within 5 years of developing these infections. Staphylococcus aureus is the bacterium most commonly responsible for this problem and can form biofilms to provide protection from antibiotics as well as the immune system. Although biofilms are evident on the infected implants, it is unclear how these are attached to the surface in the first place. Recent in vitro investigations have shown that staphylococcal strains rapidly form aggregates in the presence of synovial fluid and provide protection to bacteria, thus allowing them time to attach to the implant surface, leading to biofilm formation. In this study, we investigated the attachment kinetics of Staphylococcus aureus aggregates on different orthopedic materials. The information presented in this article will be useful in surgical management and implant design.