Gastrointestinal syndromes preceding a diagnosis of Parkinson's disease: testing Braak's hypothesis using a nationwide database for comparison with Alzheimer's disease and cerebrovascular diseases.

OBJECTIVE: Braak's hypothesis states that Parkinson's disease (PD) originates in the gastrointestinal (GI) tract, and similar associations have been established for Alzheimer's disease (AD) and cerebrovascular diseases (CVD). We aimed to determine the incidence of GI syndromes and interventions preceding PD compared with negative controls (NCs), AD and CVD. DESIGN: We performed a combined case-control and cohort study using TriNetX, a US based nationwide medical record network. Firstly, we compared subjects with new onset idiopathic PD with matched NCs and patients with contemporary diagnoses of AD and CVD, to investigate preceding GI syndromes, appendectomy and vagotomy. Secondly, we compared cohorts with these exposures to matched NCs for the development of PD, AD and CVD within 5 years. RESULTS: We identified 24 624 PD patients in the case-control analysis and matched 18 cohorts with each exposure to their NCs. Gastroparesis, dysphagia, irritable bowel syndrome (IBS) without diarrhoea and constipation showed specific associations with PD (vs NCs, AD and CVD) in both the case-control (odds ratios (ORs) vs NCs 4.64, 3.58, 3.53 and 3.32, respectively, all p<0.0001) and cohort analyses (relative risks (RRs) vs NCs 2.43, 2.27, 1.17 and 2.38, respectively, all p<0.05). While functional dyspepsia, IBS with diarrhoea, diarrhoea and faecal incontinence were not PD specific, IBS with constipation and intestinal pseudo-obstruction showed PD specificity in the case-control (OR 4.11) and cohort analysis (RR 1.84), respectively. Appendectomy decreased the risk of PD in the cohort analysis (RR 0.48). Neither inflammatory bowel disease nor vagotomy were associated with PD. CONCLUSION: Dysphagia, gastroparesis, IBS without diarrhoea and constipation might specifically predict Parkinson's disease.

Long-Term Consequences of Acute Kidney Injury After Pediatric Cardiac Surgery: A Systematic Review.

OBJECTIVE: The objective of this study was to evaluate the available data on long-term kidney dysfunction, hypertension, and mortality after cardiac surgery-associated acute kidney injury (AKI) in the pediatric population. STUDY DESIGN: PubMed/MEDLINE, Embase, Scopus, and reference lists of relevant articles were searched for eligible studies published from inception through March 2022. Long-term outcomes after pediatric cardiac surgery complicated by AKI and those without were investigated. RESULTS: We identified 14 studies published between 2013 and 2022 that included a total of 6701 patients (AKI: 1376 patients; no AKI: 5325 patients). These studies used different well-established classifications to define AKI. All the studies suggested that AKI after heart surgery is common in the pediatric patient population and reported a potential link between cardiac surgery-associated AKI and important clinical outcomes. However, only 4 out of 11 studies found a strong association between (absence of recovery from) cardiac surgery-associated AKI and risk of developing chronic kidney disease, and 3 out of 5 studies found a significant increase in mortality rates for pediatric patients who developed AKI after cardiac surgery. Only 1 out of 4 studies found an association between AKI and hypertension at 12 months postoperatively, but found no association at later follow-up times. CONCLUSIONS: Although there is a trend, evidence on the long-term consequences of cardiac surgery-associated AKI in the pediatric population is mixed. Genetic syndromes, preexisting kidney disease, univentricular or cyanotic heart conditions, and/or high-complexity surgery may be more important for the development of kidney dysfunction by adolescence and early adulthood. Regardless, these children may benefit from a long-term kidney follow-up.

Preterm Birth Is Associated With Adverse Cardiac Remodeling and Worse Outcomes in Patients With a Functional Single Right Ventricle.

OBJECTIVE: To assess the effects of preterm birth on cardiac structure and function and transplant-free survival in patients with hypoplastic left heart syndrome and associated anomalies throughout the staged palliation process. STUDY DESIGN: Data from the Single Ventricle Reconstruction trial were used to assess the impact of prematurity on echocardiographic measures at birth, Norwood, Stage II, and 14 months in 549 patients with a single functional right ventricle. Medical history was recorded once a year using medical records or telephone interviews. Cox regression models were applied to analyze transplant-free survival to age 6 years. Causal mediation analysis was performed to estimate the mediating effect of birth weight within this relationship. RESULTS: Of the 549 participants, 64 (11.7%) were born preterm. Preterm-born participants had lower indexed right ventricle end-diastolic volumes at birth but higher volumes than term-born participants by age 14 months. Preterm-born participants had an increased risk of death or heart transplantation from birth to age 6 years, with an almost linear increase in the observed risk as gestational age decreased below 37 weeks. Of the total effect of preterm birth on transplant-free survival, 27.3% (95% CI 2.5-59.0%) was mediated through birth weight. CONCLUSIONS: Preterm birth is associated with adverse right ventricle remodeling and worse transplant-free survival throughout the palliation process, in part independently of low birth weight. Further investigation into this vulnerable group may allow development of strategies that mitigate the impact of prematurity on outcomes in patients with hypoplastic left heart syndrome.

Cusp-overlap versus coplanar view in transcatheter aortic valve implantation with self-expandable valves: A meta-analysis of comparative studies.

BACKGROUND: Permanent pacemaker implantation (PPI) is a common complication after transcatheter aortic valve implantation (TAVI). The cusp-overlap view (COV) was adopted to reduce PPI risk after TAVI with self-expandable valves (SEVs); however, the evidence remains scarce. We performed a systematic review with meta-analysis comparing COV and the standard coplanar view (CPV) technique to evaluate their effectiveness and safety. METHODS: Following the PRISMA statement, data were extracted from studies published by August 2022 and found in PubMed/MEDLINE, EMBASE, CENTRAL/CCTR, ClinicalTrials.gov, SciELO, LILACS, and Google Scholar. The primary outcome of interest was post-procedural PPI and the secondary outcomes were new left bundle branch block (LBBB), moderate/severe paravalvular leak (PVL), valve dislocation (pop-out); need of second transcatheter heart valve, 30-day mortality, stroke, conversion to surgery, coronary obstruction, implantation depth (mm), and post-TAVI mean gradients (mmHg). RESULTS: Eleven studies met our eligibility criteria and included 1464 patients in the COV group and 1743 patients in the CPV group. Patients who underwent TAVI with COV had lower risk of PPI (odds ratio 0.48; 95% confidence interval [CI] 0.33-0.70; p = 0.001) and higher implantation depths with COV (mean difference -0.83; 95% CI -1.2 to -0.45; p < 0.001). We did not observe any statistically significant differences in the rates of new LBBB, moderate/severe PVL, valve dislocation, need of second transcatheter heart valve, 30-day mortality, stroke, conversion to surgery, coronary obstruction, and post-TAVI mean gradients (mmHg). CONCLUSION: In TAVI with SEVs, the application of COV is associated with lower risk of PPI compared with the standard CPV without increasing risk for adverse outcomes.

Computed tomography-derived membranous septum length as predictor of conduction abnormalities and permanent pacemaker implantation after TAVI: A meta-analysis of observational studies.

BACKGROUND: Permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) is associated with higher risk of mortality and rehospitalization for heart failure. Efforts to prevent conduction abnormalities (CA) requiring PPI after TAVI should be made. The membranous septum (MS) length and its interaction with implantation depth (ID-ΔMSID) could provide useful information about the risk of CA/PPI following TAVI. OBJECTIVES: To identify MS length and ΔMSID as predictors of CA/PPI following TAVI. METHODS: Study-level meta-analysis of studies published by September 30, 2022. RESULTS: Eighteen studies met our eligibility including 5740 patients. Shorter MS length was associated with a significantly higher risk of CA/PPI (per 1 mm decrease: odds ratio [OR] 1.60, 95% confidence interval [CI] 1.28-1.99, p < 0.001). Similarly, lower ΔMSID was associated with a significantly higher risk of CA/PPI (per 1 mm decrease: OR 1.75, 95% CI 1.32-2.31, p < 0.001). Meta-regression analyses revealed a statistically significant modulation of the effect of shorter MS length and lower ΔMSID on the outcome (CA/PPI) by balloon postdilatation (positive regression coefficients with p < 0.001); with increasing use of balloon postdilatation, the effect of shorter MS length and lower ΔMSID on the outcome increased. MS length and ΔMSID demonstrated excellent discriminative abilities, with diagnostic ORs equaling 9.49 (95% CI 4.73-19.06), and 7.19 (95% CI 3.31-15.60), respectively. CONCLUSION: Considering that short MS length and low ΔMSID are associated with higher risk of CA and PPI, we should include measurement of MS length in the pre-TAVI planning with MDCT and try to establish optimal ID values before the procedure to avoid CA/PPI.

Machine learning-based prediction of mortality after heart transplantation in adults with congenital heart disease: A UNOS database analysis.

BACKGROUND: Machine learning (ML) is increasingly being applied in Cardiology to predict outcomes and assist in clinical decision-making. We sought to develop and validate an ML model for the prediction of mortality after heart transplantation (HT) in adults with congenital heart disease (ACHD). METHODS: The United Network for Organ Sharing (UNOS) database was queried from 2000 to 2020 for ACHD patients who underwent isolated HT. The study cohort was randomly split into derivation (70%) and validation (30%) datasets that were used to train and test a CatBoost ML model. Feature selection was performed using SHapley Additive exPlanations (SHAP). Recipient, donor, procedural, and post-transplant characteristics were tested for their ability to predict mortality. We additionally used SHAP for explainability analysis, as well as individualized mortality risk assessment. RESULTS: The study cohort included 1033 recipients (median age 34 years, 61% male). At 1 year after HT, there were 205 deaths (19.9%). Out of a total of 49 variables, 10 were selected as highly predictive of 1-year mortality and were used to train the ML model. Area under the curve (AUC) and predictive accuracy for the 1-year ML model were .80 and 75.2%, respectively, and .69 and 74.2% for the 3-year model, respectively. Based on SHAP analysis, hemodialysis of the recipient post-HT had overall the strongest relative impact on 1-year mortality after HΤ, followed by recipient-estimated glomerular filtration rate, age and ischemic time. CONCLUSIONS: ML models showed satisfactory predictive accuracy of mortality after HT in ACHD and allowed for individualized mortality risk assessment.

Midterm Outcomes of Endovascular vs. Medical Therapy for Uncomplicated Type B Aortic Dissection: Meta-Analysis of Reconstructed Time to Event Data.

OBJECTIVE: To evaluate outcomes of thoracic endovascular aortic repair (TEVAR) vs. medical therapy in uncomplicated type B aortic dissections (TBAD). DATA SOURCES: PubMed/MEDLINE, EMBASE, SciELO, LILACS, CENTRAL/CCTR, Google Scholar, and reference lists of relevant articles. REVIEW METHODS: This was a pooled meta-analysis of time to event data extracted from studies published by December 2022 for the following outcomes: all cause mortality, aortic related mortality, and late aortic interventions. Certainty of evidence was evaluated through the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. RESULTS: Ten studies met the eligibility criteria (eight observational; two randomised trials), comprising 17 906 patients (2 332 patients in the TEVAR groups and 15 574 patients in the medical therapy group). Compared with patients who received medical therapy, patients who underwent TEVAR had a statistically significantly lower risk of all cause death (HR 0.79, 95% CI 0.72 - 0.87, p < .001; GRADE certainty: low) and lower risk of aortic related death (HR 0.43, 95% CI 0.30 - 0.62, p < .001; GRADE certainty: low) without statistically significant difference in the risk of late aortic interventions (HR 1.05, 95% CI 0.88 - 1.26, p = .56; GRADE certainty: low). In the subgroup analyses, TEVAR was associated with lower risk of all cause death when randomised controlled trials only were pooled (HR 0.44, 95% CI 0.23 - 0.83, p = .012; GRADE certainty: moderate), younger patients only (HR 0.56, 95% CI 0.47 - 0.67, p < .001; GRADE certainty: low), Western populations only (HR 0.85, 95% CI 0.77 - 0.93, p = .001; GRADE certainty: low) and non-Western populations only (HR 0.47, 95% CI 0.35 - 0.62, p < .001; GRADE certainty: low). For all cause mortality and aortic related mortality, restricted mean survival time was overall 396 days and 398 days longer with TEVAR (p < .001), respectively, which means that TEVAR was associated with lifetime gain. CONCLUSION: TEVAR may be associated with better midterm survival and lower risk of aortic related death in the follow up of patients treated for uncomplicated TBAD compared with medical therapy; however, randomised controlled trials with larger sample sizes and longer follow up are still warranted.

Long-term outcomes of acute kidney injury in children.

PURPOSE OF REVIEW: Acute kidney injury (AKI) affects up to 35% of all critically ill children and is associated with substantial short-term morbidity and mortality. However, the link between paediatric AKI and long-term adverse outcomes remains incompletely understood. This review highlights the most recent clinical data supporting the role of paediatric AKI as a risk factor for long-term kidney and cardiovascular consequences. In addition, it stresses the need for long-term surveillance of paediatric AKI survivors. RECENT FINDINGS: Recent large-scale studies have led to an increasing understanding that paediatric AKI is a significant risk factor for adverse outcomes such as hypertension, cardiovascular disease and chronic kidney disease (CKD) over time. These long-term sequelae of paediatric AKI are most often observed in vulnerable populations, such as critically ill children, paediatric cardiac surgery patients, children who suffer from severe infections and paediatric cancer patients. SUMMARY: A growing body of research has shown that paediatric AKI is associated with long-term adverse outcomes such as CKD, hypertension and cardiovascular disease. Although therapeutic pathways tailored to individual paediatric AKI patients are yet to be validated, we provide a framework to guide monitoring and prevention in children at the highest risk for developing long-term kidney dysfunction.

Sex disparities in left ventricular assist device implantation outcomes: A systematic review and meta-analysis of over 50 000 patients.

BACKGROUND: Left ventricular assist devices (LVAD) represent an important therapeutic option for patients progressing to end-stage heart failure. Women have been historically underrepresented in LVAD studies, and have been reported to have worse outcomes despite technological optimisation. We aimed to systematically explore the evidence on sex disparities in the use and outcomes of LVAD implantation. METHODS: A systematic database search with meta-analysis was conducted of comparative original articles of men versus women undergoing LVAD implantation, in EMBASE, MEDLINE, Cochrane database and Google Scholar, from inception to July 2022. Primary outcomes were stroke (haemorrhagic and ischaemic) and early/overall mortality. Secondary outcomes were LVAD thrombosis, right VAD implantation, major bleeding, kidney dysfunction, and device/driveline infection. RESULTS: Our search yielded 137 relevant studies, including 22 meeting the inclusion criteria with a total of 53 227 patients (24.2% women). Overall mortality was higher in women (odds ratio [OR] 1.35, 95% confidence interval [CI] 1.05-1.62, p = 0.02), as was overall stroke (OR 1.32, 95%CI 1.06-1.66, p = 0.01), including ischemic (OR 1.80, 95%CI 1.22-2.64, p = 0.003) and haemorrhagic (OR 1.72, 95%CI 1.09-2.70, p = 0.02). Women had more frequent right VAD implantation (OR 2.11, 95%CI 1.24-3.57, p = 0.006) and major bleeding (OR 1.40, 95%CI 1.06-1.85, p = 0.02). Kidney dysfunction, LVAD thrombosis, and device/driveline infections were comparable between sexes. CONCLUSIONS: Our analysis suggests that women face a greater risk of adverse events and mortality post-LVAD implantation. Although the mechanisms remain unclear, the difference in outcomes is thought to be multifactorial. Further research, that includes comprehensive pre-operative characteristics and post-operative outcomes, is encouraged.

Somatic growth in single ventricle patients: A systematic review and meta-analysis.

AIM: To map somatic growth patterns throughout Fontan palliation and summarise evidence on its key modifiers. METHODS: Databases were searched for relevant articles published from January 2000 to December 2021. Height and weight z scores at each time point (birth, Glenn procedure, Fontan procedure and >5 years after Fontan completion) were pooled using a random effects meta-analysis. A random effects meta-regression model was fitted to model the trend in z scores over time. RESULTS: Nineteen studies fulfilled eligibility criteria, yielding a total of 2006 participants. The z scores for height and weight were markedly reduced from birth to the interstage period, but recovered by about 50% following the Glenn procedure. At >10 years after the Fontan procedure, the z scores for weight seemed to normalise despite persistent lower height, resulting in increased body mass index. The review revealed a number of modifiers of somatic growth, including aggressive nutritional management, timing of Glenn/Fontan, prompt resolution of complications and obesity prevention programmes in adolescence and adulthood. CONCLUSION: This review mapped the somatic growth of single ventricle patients and summarised key modifiers that may be amendable to improvement. These data provide guidance on strategies to further optimise somatic growth in this population and may serve as a benchmark for clinical follow-up.

Artificial intelligence in pediatric cardiology: taking baby steps in the big world of data.

PURPOSE OF REVIEW: Artificial intelligence (AI) has changed virtually every aspect of modern life, and medicine is no exception. Pediatric cardiology is both a perceptual and a cognitive subspecialty that involves complex decision-making, so AI is a particularly attractive tool for this medical discipline. This review summarizes the foundational work and incremental progress made as AI applications have emerged in pediatric cardiology since 2020. RECENT FINDINGS: AI-based algorithms can be useful for pediatric cardiology in many areas, including: (1) clinical examination and diagnosis, (2) image processing, (3) planning and management of cardiac interventions, (4) prognosis and risk stratification, (5) omics and precision medicine, and (6) fetal cardiology. Most AI initiatives showcased in medical journals seem to work well in silico, but progress toward implementation in actual clinical practice has been more limited. Several barriers to implementation are identified, some encountered throughout medicine generally, and others specific to pediatric cardiology. SUMMARY: Despite barriers to acceptance in clinical practice, AI is already establishing a durable role in pediatric cardiology. Its potential remains great, but to fully realize its benefits, substantial investment to develop and refine AI for pediatric cardiology applications will be necessary to overcome the challenges of implementation.

Early and late outcomes of surgical aortic valve replacement with sutureless and rapid-deployment valves versus transcatheter aortic valve implantation: Meta-analysis with reconstructed time-to-event data of matched studies.

Sutureless/rapid-deployment (SURD) valves are options different from the stented prostheses included in the pivotal trials comparing surgical aortic valve replacement (AVR) and transcatheter aortic valve implantation (TAVI). We performed a meta-analysis with reconstructed time-to-event data of matched studies published by November 2021 to compare SURD-AVR and TAVI. Primary endpoints were 30-day mortality and overall survival in the follow-up. Secondary endpoints included: 30-day stroke, acute kidney injury (AKI), major bleeding, permanent pacemaker implantation (PPI), paravalvular leak (PVL), prosthesis-patient mismatch (PPM), postoperative aortic valve area (AVA), and mean gradients. Ten studies met our eligibility criteria, including a total of 5134 patients (2567 underwent SURD-AVR and 2567 underwent TAVI). Pooled risk of 30-day mortality did not favor any group (odds ratio [OR]: 0.69; 95% confidence interval [CI]: 0.31-1.53; p = 0.360). Patients undergoing SURD-AVR had lower risk of PVL (OR: 0.09; 95% CI: 0.05-0.17; p < 0.001). No statistically significant differences were observed for 30-day stroke, AKI, major bleeding, PPI, PPM, and postoperative AVA. In the follow-up, we observed a higher risk of mortality (hazard ratio: 1.74; 95% CI: 1.26-2.40; p < 0.001) with TAVI. Patients who underwent SURD-AVR experienced better survival, however, the interpretation of these results warrant caution due to the fact that SURD-AVR patients tended to be younger than TAVI patients. Structural heart surgeons and interventional cardiologists should consider initial risk and life expectancy when referring patients for one approach over the other.

Pre-clinical In Vitro Models of Vascular Graft Coating in the Prevention of Vascular Graft Infection: A Systematic Review.

OBJECTIVE: Vascular graft infection (VGI) is a feared complication. Prevention is of the utmost importance and vascular graft coatings (VGCs) could offer a potential to do this, with in vitro research a first crucial step. The aim of this study was to summarise key features of in vitro models investigating coating strategies to prevent VGI in order to provide guidance for the setup of future translational research. DATA SOURCES: A comprehensive search was performed in MEDLINE, Embase, and Web of Science. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. For each database, a specific search strategy was developed. Quality was assessed with the Toxicological data Reliability Assessment Tool (ToxRTool). In vitro models using a VGC and inoculation of the graft with a pathogen were included. The type of graft, coating, and pathogen were summarised. The outcome assessment in each study was evaluated. RESULTS: In total, 4 667 studies were identified, of which 45 papers met the inclusion criteria. The majority used polyester grafts (68.2%). Thirty-one studies (68.9%) included antibiotics, and nine studies (20%) used a commercial silver graft in their protocol. New antibacterial strategies (e.g., proteolytic enzymes) were investigated. A variety of testing methods was found and focused mainly on bacterial adherence, coating adherence and dilution, biofilm formation, and cytotoxicity. Ninety-three per cent of the studies (n = 41) were considered unreliable. CONCLUSION: Polyester is the preferred type of graft to coat on. The majority of coating studies are based on antibiotics; however, new coating strategies (e.g., antibiofilm coating) are coming. Many in vitro setups are available. In vitro studies have great potential, they can limit the use, but cannot replace in vivo studies completely. This paper can be used as a guidance document for future in vitro research.

Risk factors for acute kidney injury after pediatric cardiac surgery: a meta-analysis.

BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) is associated with increased morbidity and mortality in both adults and children. OBJECTIVES: This study aimed to identify clinical risk factors for AKI following cardiac surgery in the pediatric population. DATA SOURCES: PubMed/MEDLINE, Embase, Scopus, and reference lists of relevant articles were searched for studies published by August 2020. STUDY ELIGIBILITY CRITERIA: Studies were included if (1) the population consisted of pediatric patients (< 18 years old), (2) patients underwent cardiac surgery, (3) risk factors were compared between patients who developed AKI and those who did not, and (4) studies were prospective or retrospective observational studies or randomized controlled trials. PARTICIPANTS AND INTERVENTIONS: Children undergoing pediatric cardiac surgery. STUDY APPRAISAL AND SYNTHESIS METHODS: Random-effects meta-analysis was performed, comparing potential risk factors between pediatric patients who developed CS-AKI and those who did not. RESULTS: Sixty-one publications including a total of 19,680 participants (AKI: 7257 participants; no AKI: 12,423 participants) were included from studies published between 2008 and 2020. The pooled estimated incidence of AKI was 34.3% (95% confidence interval 30.0-38.8%, I2 = 96.8%). Binary risk factors that were significantly and consistently associated with AKI were the presence of pulmonary hypertension, cyanotic heart disease, univentricular heart, risk adjustment for congenital heart surgery 1 (RACHS-1) score ≥ 3, vasopressor use, cardiopulmonary bypass use, reoperation, and sepsis. Significant continuous risk factors included younger age, lower body weight, lower preoperative creatinine, higher preoperative estimated glomerular filtration rate (eGFR), higher RACHS-1 score, longer surgery time, longer cardiopulmonary bypass time, longer aortic cross-clamp time, and higher red blood cell transfusion volume. LIMITATIONS: Results are limited by heterogeneity and potential residual confounding. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Our meta-analysis identified clinical risk factors that are associated with AKI in children undergoing cardiac surgery. This might help clinicians anticipate and manage more carefully this population and implement standardized preventive strategies. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42021262699. A higher resolution version of the Graphical abstract is available as Supplementary information.

Biomarkers of acute kidney injury after pediatric cardiac surgery: a meta-analysis of diagnostic test accuracy.

Acute kidney injury (AKI) occurs frequently after cardiac surgery in children. Although current diagnostic criteria rely on serum creatinine and urine output, changes occur only after considerable loss of kidney function. This meta-analysis aimed to synthesize the knowledge on novel biomarkers and compare their ability to predict AKI. PubMed/MEDLINE, Embase, Scopus, and reference lists were searched for relevant studies published by March 2021. Diagnostic accuracy parameters were extracted and analyzed using hierarchical summary receiver operating characteristic (HSROC) method. Pooled estimates of the area under the curve (AUC) were calculated using conventional random-effects meta-analysis. Fifty-six articles investigating 49 biomarkers in 8617 participants fulfilled our eligibility criteria. Data from 37 studies were available for meta-analysis. Of the 10 biomarkers suitable for HSROC analysis, urinary neutrophil gelatinase-associated lipocalin (uNGAL) to creatinine (Cr) ratio yielded the highest diagnostic odds ratio (91.0, 95% CI 90.1-91.9), with a sensitivity of 91.3% (95% CI 91.2-91.3%) and a specificity of 89.7% (95% CI 89.6-89.7%). These results were confirmed in pooled AUC analysis, as uNGAL-to-Cr ratio and uNGAL were the only elaborately studied biomarkers (> 5 observations) with pooled AUCs ≥ 0.800. Liver fatty acid-binding protein (L-FABP), serum cystatin C (sCysC), serum NGAL (sNGAL), and interleukin-18 (IL-18) all had AUCs ≥ 0.700. CONCLUSION: A variety of biomarkers have been proposed as predictors of cardiac surgery-associated AKI in children, of which uNGAL was the most prominent with excellent diagnostic qualities. However, more consolidatory evidence will be required before these novel biomarkers may eventually help realize precision medicine in AKI management. WHAT IS KNOWN: • Acute kidney injury (AKI) occurs in about 30-60% of children undergoing cardiac surgery and is associated with increased in-hospital mortality and adverse short-term outcomes. However, in current clinical practice, AKI definitions and detection often rely on changes in serum creatinine and urine output, which are late and insensitive markers of kidney injury. • Although various novel biomarkers have been studied for the diagnosis of AKI in children after cardiac surgery, it remains unclear how these compare to one another in terms of diagnostic accuracy. WHAT IS NEW: • Pooled analyses suggest that for the diagnosis of AKI in children who underwent cardiac surgery, NGAL is the most accurate among the most frequently studied biomarkers. • A number of other promising biomarkers have been reported, although they will require further research into their diagnostic accuracy and clinical applicability.

Left ventricular myocardial work indices in pediatric hypertension: correlations with conventional echocardiographic assessment and subphenotyping.

Myocardial work (MW) is a novel parameter that incorporates non-invasive estimates of left ventricular (LV) systolic pressure into the interpretation of strain, thus overcoming the limitations of load dependency traditionally encountered with LV fractional shortening (LVFS), ejection fraction (LVEF), and global longitudinal strain (GLS). However, data on MW in the pediatric population with hypertension are lacking. Conventional markers of LV function and MW indices were obtained from 88 echocardiographic examinations in 76 children with hypertension (47 males, 15.5 ± 2.96 years). When compared with a previously published cohort of 52 healthy controls, global work index (GWI) and global constructive work (GCW) were both significantly elevated while LVEF and GLS were not impaired but rather mildly increased. On multivariable analysis, GWI was correlated with systolic blood pressure (slope = + 16, p < 0.001) and GLS (slope = -100, p < 0.001), while GCW was correlated with systolic blood pressure (slope = + 18, p < 0.001), GLS (slope = -101, p < 0.001), male sex (slope = -75, p = 0.016), and LV mass (slope = -0.93, p < 0.001). Global wasted work (GWW) was correlated with age at echo visit (slope = -4.5, p = 0.005) and GLS (slope = + 5.5, p < 0.001). The opposite occurred for global work efficiency (GWE; slope = + 0.20, p = 0.011, and slope = -0.48, p < 0.001, respectively). Principal component analysis and k-means clustering revealed 4 subphenotypes which differed in terms of etiology, afterload, and compensation stage of the disease.    Conclusion: Non-invasive MW shows a good correlation with conventional markers of LV function and may help refine the assessment of hypertensive heart disease in children. What is Known: • Myocardial work (MW) is a novel parameter that incorporates non-invasive estimates of left ventricular (LV) systolic pressure into the interpretation of strain, thereby accounting for both deformation and afterload. • Although the usefulness of MW in the assessment of myocardial function beyond conventional markers has been demonstrated in various clinical populations, data in the pediatric population with hypertension are currently lacking. What is New: • Compared to normal values in healthy children, global work index and global constructive work were increased in those with hypertension, while LV ejection fraction and global longitudinal strain were not impaired. • Machine learning identified 4 subphenotypes which differed in terms of etiology, afterload, and compensation stage of the disease.

Initial experience with CytoSorb therapy in patients receiving left ventricular assist devices.

BACKGROUND: The use of left ventricular assist devices (LVAD) in patients with advance heart failure is still associated with an important risk of immune dysregulation and infections. The aim of this study was to determine whether extracorporeal blood purification using the CytoSorb device benefits patients after LVAD implantation in terms of complications and overall survival. MATERIALS AND METHODS: Between August 2010 and January 2020, 207 consecutive patients underwent LVAD implantation, of whom 72 underwent CytoSorb therapy and 135 did not. Overall survival, major adverse events, and laboratory parameters were compared between 112 propensity score-matched patients (CytoSorb: 72 patients; non-CytoSorb: 40 patients). RESULTS: WBC (p = .033), CRP (p = .001), and IL-6 (p < .001), significantly increased with LVAD implantation, while CytoSorb did not influence this response. In-hospital mortality and overall survival during follow-up were similar with CytoSorb. However, patients treated with CytoSorb were more likely to develop respiratory failure (54.2% vs. 30.0%, p = .024), need mechanical ventilation for longer than 6 days post-implant (50.0% vs. 27.5%, p = .035), and require tracheostomy during hospitalization (31.9% vs. 12.5%, p = .040). No other significant differences were observed with regard to major adverse events during follow-up. CONCLUSIONS: Overall, our results showed that CytoSorb might not convey a significant morbidity or mortality benefit for patients undergoing LVAD implantation.

Late Outcomes After Aortic Root Enlargement During Aortic Valve Replacement: Meta-Analysis With Reconstructed Time-To-Event Data.

OBJECTIVES: The present authors aimed to assess the late outcomes of patients undergoing aortic root enlargement (ARE) at the time of surgical aortic valve replacement (SAVR). DESIGN: Study-level meta-analysis with reconstructed time-to-event data. SETTING: Follow-up of patients after surgical procedure. PARTICIPANTS: Adult patients with aortic valve disease requiring surgery. INTERVENTIONS: SAVR with ARE versus SAVR without ARE. MEASUREMENTS AND MAIN RESULTS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. The following databases were searched for studies meeting the authors' inclusion criteria and published by November 30, 2021: PubMed/MEDLINE, Embase, SciELO, LILACS, CCTR/CENTRAL, and Google Scholar. Nine nonrandomized studies met the authors' eligibility criteria. All studies were nonrandomized. A total of 213,134 patients (SAVR with ARE: 7,556 patients; SAVR without ARE: 205,578 patients) were included from studies published from 1997 to 2021. The total rate of AAE was 3.7%, varying in the studies from 2.9% to 28.1%. The studies consisted of patients whose mean age varied from 63 to 79 years. Patients in the SAVR with ARE group had a significantly better overall survival (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90-0.99, p = 0.016) in the unmatched populations, but the matched analysis revealed no difference between SAVR with/without ARE in terms of overall survival (HR, 1.06; 95% CI, 0.90-1.25; p = 0.474). CONCLUSIONS: In the context of patients undergoing SAVR with or without ARE, patients who undergo ARE do not experience worse late outcomes. Further randomized controlled trials are needed to confirm or refute the authors' current findings.

Pericardiectomy and Pericardial Window for the Treatment of Pericardial Disease in the Contemporary Era.

PURPOSE OF REVIEW: To summarize the contemporary practice of pericardiectomy and pericardial window. We discuss the indications, preoperative planning, procedural aspects, postprocedural management, and outcomes of each procedure. RECENT FINDINGS: Surgical approaches for the treatment of pericardial disease have been around even before the emergence of cardiopulmonary bypass. Since the forthcoming of cardiopulmonary bypass, there have been significant changes in the epidemiology and diagnostic approach of pericardial diseases as well as advancements in the surgical techniques and perioperative management used in the care of these patients. Pericardiectomy has an average mortality of almost 7% and is typically performed in patients with advanced symptoms from constrictive pericarditis and relatively few comorbidities. Pericardial window is a safe procedure for the treatment of pericardial effusion that can be performed with different approaches.

Sternal-sparing aortic valve replacement with sutureless valve in bicuspid valve.

Over the last decade, sutureless valves (Perceval, LivaNova PLC) were brought to the market as an alternative to stented valves for patients requiring surgical aortic valve replacement (SAVR). However, Perceval demands special steps for implantation, among which we can mention specific training for the surgical team members. Sternal-sparing cardiac procedures are conceived to limit surgical trauma, but the technical requirements and preoperative planning are more challenging than those for conventional sternotomy. SAVR is frequently carried out through an upper hemisternotomy, but the right anterior thoracotomy (RAT) represents an even less traumatic, technical advancement. In the context of SAVR with RAT, Perceval has been considered the "perfect marriage." In patients with bicuspid aortic valve (BAV), some surgeons initially avoided the Perceval valve but, with growing experience, the prosthesis has been used for a wide variety of indications. According to an international consensus statement recently published, there are 3 BAV types: the fused BAV, the 2-sinus BAV and the partial-fusion BAV, each with specific phenotypes. The 2-sinus BAV has 2 cusps, roughly equal in size and shape, each cusp occupying 180° of the annular circumference, with only 2 aortic sinuses, resulting in a 2-sinus/2-cusp valve without raphe and with 180° commissural angles. Since the elliptic aortic annulus in BAV patients poses a challenge for sutureless valves and the RAT approach has been increasingly adopted for minimally invasive SAVR, our description of the surgical technique focuses on the specific procedural details in the scenario of 2-sinus BAV laterolateral phenotype.