EFFICACY OF INTRAVENOUS IMMUNOGLOBULIN ALONE ON CORONARY ARTERY LESION REDUCTION IN KAWASAKI DISEASE.

Background: Though Aspirin and intravenous immunoglobulin (IVIG) remain the standard treatments for Kawasaki Disease (KD) to minimize coronary artery damage, the duration and dosage of aspirin are inconsistent across hospitals. However, the lack of multi-center randomized trials prevents definitive answers to the impact of high-dose aspirin. Methods: This clinical trial was structured as a prospective, evaluator-blinded, multi-center randomized controlled trial with two parallel arms, aiming to assess the effectiveness of IVIG as a standalone primary therapy of KD in comparison to the combination of IVIG with high-dose aspirin therapy. KD patients were enrolled between September, 2016 and August, 2019. A final cohort of 134 patients were randomly assigned to the standard and test groups with 69 and 65 patients, respectively. The Standard group received IVIG (2 g/kg) along with aspirin (80-100 mg/kg/day) until fever subsided for 48 hours. The test group received IVIG (2 g/kg) alone. Following the initial treatment, both groups received a daily aspirin dose (3-5 mg/kg) for six weeks. The primary outcome measure was the occurrence of coronary artery lesions (CAL) at the 6-8 weeks mark. The secondary outcome is IVIG resistance. Results: The overall rate of CAL in test group decreased from 10.8% at diagnosis to 1.5% and 3.1% at 6 weeks and 6 months, respectively. The CAL rate of standard group declined from 13.0% to 2.9% and 1.4%, with no statistically significant difference (P>0.1) in the frequency of CAL between the two groups. Furthermore, no statistically significant differences were found for treatment (P>0.1) and prevention (P>0.1) effect between the two groups. Conclusions: This marks the first prospective multi-center randomized controlled trial comparing the standard treatment of KD using IVIG plus high-dose aspirin against IVIG alone. Our analysis indicates that addition of high-dose aspirin during initial IVIG treatment is neither statistically significant nor clinically meaningful for CAL reduction. Registration: URL: http://www.clinicaltrials.gov ; identifier: NCT02951234. What is New?: This study represents the first multi-center randomized controlled trial investigating the efficacy of high-dose aspirin or intravenous immunoglobulin (IVIG) during the acute stage of KD. This study assessed the impact of discontinuing high-dose aspirin (80-100 mg/kg/day) on the occurrence of CAL during the acute phase treatment of Kawasaki Disease.No significant differences were observed between high-dose aspirin plus IVIG treatment and IVIG alone treatment in terms of the frequency of abnormal coronary artery abnormalities. Additionally, our analysis revealed no statistically significant differences in either the treatment effect (the number of cases successfully treated) or prevention effect (the prevention of new cases) between these two treatments. What Are the Clinical Implications?: Comparison analysis indicated the non-inferiority between two groups with or without high-dose aspirin.Administering the standard 2 g/kg/day IVIG without high-dose aspirin (80-100 mg/kg/day) during the acute phase therapy for KD does not increase the risk of coronary artery lesions, which are a primary cause of morbidity and mortality in KD patients.Addition of high-dose aspirin during initial IVIG treatment is not statistically significant or clinically meaningful.

Global metabolomics revealed deviations from the metabolic aging clock in colorectal cancer patients.

Background: Markers of aging hold promise in the context of colorectal cancer (CRC) care. Utilizing high-resolution metabolomic profiling, we can unveil distinctive age-related patterns that have the potential to predict early CRC development. Our study aims to unearth a panel of aging markers and delve into the metabolomic alterations associated with aging and CRC. Methods: We assembled a serum cohort comprising 5,649 individuals, consisting of 3,002 healthy volunteers, 715 patients diagnosed with colorectal advanced precancerous lesions (APL), and 1,932 CRC patients, to perform a comprehensive metabolomic analysis. Results: We successfully identified unique age-associated patterns across 42 metabolic pathways. Moreover, we established a metabolic aging clock, comprising 9 key metabolites, using an elastic net regularized regression model that accurately estimates chronological age. Notably, we observed significant chronological disparities among the healthy population, APL patients, and CRC patients. By combining the analysis of circulative carcinoembryonic antigen levels with the categorization of individuals into the "hypo" metabolic aging subgroup, our blood test demonstrates the ability to detect APL and CRC with positive predictive values of 68.4% (64.3%, 72.2%) and 21.4% (17.8%, 25.9%), respectively. Conclusions: This innovative approach utilizing our metabolic aging clock holds significant promise for accurately assessing biological age and enhancing our capacity to detect APL and CRC.

Multicenter Study of Survival Benefit of Cardiac Resynchronization Therapy in Pediatric and Congenital Heart Disease.

BACKGROUND: Evidence for the efficacy of cardiac resynchronization therapy (CRT) in pediatric and congenital heart disease (CHD) has been limited to surrogate outcomes. OBJECTIVES: This study aimed to assess the impact of CRT upon the risk of transplantation or death in a retrospective, high-risk, controlled cohort at 5 quaternary referral centers. METHODS: Both CRT patients and control patients were <21 years of age or had CHD; had systemic ventricular ejection fraction <45%; symptomatic heart failure; and significant electrical dyssynchrony (QRS duration z score >3 or single-site ventricular pacing >40%) at enrollment. Patients with CRT were matched with control patients via 1:1 propensity score matching. CRT patients were enrolled at CRT implantation; control patients were enrolled at the outpatient clinical encounter where inclusion criteria were first met. The primary endpoint was transplantation or death. RESULTS: In total, 324 control patients and 167 CRT recipients were identified. Mean follow-up was 4.2 ± 3.7 years. Upon propensity score matching, 139 closely matched pairs were identified (20 baseline indices). Of the 139 matched pairs, 52 (37.0%) control patients and 31 (22.0%) CRT recipients reached the primary endpoint. On both unadjusted and multivariable Cox regression analysis, the risk reduction associated with CRT for the primary endpoint was significant (HR: 0.40; 95% CI: 0.25-0.64; P < 0.001; and HR: 0.44; 95% CI: 0.28-0.71; P = 0.001, respectively). On longitudinal assessment, the CRT group had significantly improved systemic ventricular ejection fraction (P < 0.001) and shorter QRS duration (P = 0.015), sustained to 5 years. CONCLUSIONS: In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplantation-free survival.

Utility of smart watches for identifying arrhythmias in children.

BACKGROUND: Arrhythmia symptoms are frequent complaints in children and often require a pediatric cardiology evaluation. Data regarding the clinical utility of wearable technologies are limited in children. We hypothesize that an Apple Watch can capture arrhythmias in children. METHODS: We present an analysis of patients ≤18 years-of-age who had signs of an arrhythmia documented by an Apple Watch. We include patients evaluated at our center over a 4-year-period and highlight those receiving a formal arrhythmia diagnosis. We evaluate the role of the Apple Watch in arrhythmia diagnosis, the results of other ambulatory cardiac monitoring studies, and findings of any EP studies. RESULTS: We identify 145 electronic-medical-record identifications of Apple Watch, and find arrhythmias confirmed in 41 patients (28%) [mean age 13.8 ± 3.2 years]. The arrythmias include: 36 SVT (88%), 3 VT (7%), 1 heart block (2.5%) and wide 1 complex tachycardia (2.5%). We show that invasive EP study confirmed diagnosis in 34 of the 36 patients (94%) with SVT (2 non-inducible). We find that the Apple Watch helped prompt a workup resulting in a new arrhythmia diagnosis for 29 patients (71%). We note traditional ambulatory cardiac monitors were worn by 35 patients (85%), which did not detect arrhythmias in 10 patients (29%). In 73 patients who used an Apple Watch for recreational or self-directed heart rate monitoring, 18 (25%) sought care due to device findings without any arrhythmias identified. CONCLUSION: We demonstrate that the Apple Watch can record arrhythmia events in children, including events not identified on traditionally used ambulatory monitors.

Wearable devices, such as smart watches, have become popular for the monitoring of health, particularly for people with heart conditions. Wearable devices have been well-studied in adults, however there is less information available on their effectiveness in monitoring children's health. We reviewed the heart electrical recordings of a group of children who submitted recordings obtained from their Apple Watches during moments when they felt as though their heart's rhythm was abnormal. The Apple Watches captured rhythm abnormalities that matched the diagnoses obtained using heart monitors used clinically. This study shows that use of Apple Watches can enable clinicians to identify abnormalities that many traditional at-home monitoring devices do not detect. Thus, wearable devices, such as the Apple Watch, could be used to help identify heart rhythm disorders in children.

Exploring the feasibility of using long-term stored newborn dried blood spots to identify metabolic features for congenital heart disease screening.

Congenital heart disease (CHD) represents a significant contributor to both morbidity and mortality in neonates and children. There's currently no analogous dried blood spot (DBS) screening for CHD immediately after birth. This study was set to assess the feasibility of using DBS to identify reliable metabolite biomarkers with clinical relevance, with the aim to screen and classify CHD utilizing the DBS. We assembled a cohort of DBS datasets from the California Department of Public Health (CDPH) Biobank, encompassing both normal controls and three pre-defined CHD categories. A DBS-based quantitative metabolomics method was developed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). We conducted a correlation analysis comparing the absolute quantitated metabolite concentration in DBS against the CDPH NBS records to verify the reliability of metabolic profiling. For hydrophilic and hydrophobic metabolites, we executed significant pathway and metabolite analyses respectively. Logistic and LightGBM models were established to aid in CHD discrimination and classification. Consistent and reliable quantification of metabolites were demonstrated in DBS samples stored for up to 15 years. We discerned dysregulated metabolic pathways in CHD patients, including deviations in lipid and energy metabolism, as well as oxidative stress pathways. Furthermore, we identified three metabolites and twelve metabolites as potential biomarkers for CHD assessment and subtypes classifying. This study is the first to confirm the feasibility of validating metabolite profiling results using long-term stored DBS samples. Our findings highlight the potential clinical applications of our DBS-based methods for CHD screening and subtype classification.

Outcomes After Development of Ventricular Arrhythmias in Single Ventricular Heart Disease Patients With Fontan Palliation.

BACKGROUND: With the advent of more intensive rhythm monitoring strategies, ventricular arrhythmias (VAs) are increasingly detected in Fontan patients. However, the prognostic implications of VA are poorly understood. We assessed the incidence of VA in Fontan patients and the implications on transplant-free survival. METHODS: Medical records of Fontan patients seen at a single center between 2002 and 2019 were reviewed to identify post-Fontan VA (nonsustained ventricular tachycardia >4 beats or sustained >30 seconds). Patients with preFontan VA were excluded. Hemodynamically unstable VA was defined as malignant VA. The primary outcome was death and heart transplantation. Death with censoring at transplant was a secondary outcome. RESULTS: Of 431 Fontan patients, transplant-free survival was 82% at 15 years post-Fontan with 64 (15%) meeting primary outcome of either death (n=16, 3.7%), at a median 4.6 (0.4-10.2) years post-Fontan, or transplant (n=48, 11%), at a median of 11.1 (5.9-16.2) years post-Fontan. Forty-eight (11%) patients were diagnosed with VA (90% nonsustained ventricular tachycardia, 10% sustained ventricular tachycardia). Malignant VA (n=9, 2.0%) was associated with younger age, worse systolic function, and valvular regurgitation. Risk for VA increased with time from Fontan, 2.4% at 10 years to 19% at 20 years. History of Stage 1 surgery with right ventricular to pulmonary artery conduit and older age at Fontan were significant risk factors for VA. VA was strongly associated with an increased risk of transplant or death (HR, 9.2 [95% CI, 4.5-18.7]; P<0.001), with a transplant-free survival of 48% at 5-year post-VA diagnosis. CONCLUSIONS: Ventricular arrhythmias occurred in 11% of Fontan patients and was highly associated with transplant or death, with a transplant-free survival of <50% at 5-year post-VA diagnosis. Risk factors for VA included older age at Fontan and history of right ventricular to pulmonary artery conduit. A diagnosis of VA in Fontan patients should prompt increased clinical surveillance.

The development and efficacy of a paediatric cardiology fellowship online preparatory course.

BACKGROUND: The transition from residency to paediatric cardiology fellowship is challenging due to the new knowledge and technical skills required. Online learning can be an effective didactic modality that can be widely accessed by trainees. We sought to evaluate the effectiveness of a paediatric cardiology Fellowship Online Preparatory Course prior to the start of fellowship. METHODS: The Online Preparatory Course contained 18 online learning modules covering basic concepts in anatomy, auscultation, echocardiography, catheterisation, cardiovascular intensive care, electrophysiology, pulmonary hypertension, heart failure, and cardiac surgery. Each online learning module included an instructional video with pre-and post-video tests. Participants completed pre- and post-Online Preparatory Course knowledge-based exams and surveys. Pre- and post-Online Preparatory Course survey and knowledge-based examination results were compared via Wilcoxon sign and paired t-tests. RESULTS: 151 incoming paediatric cardiology fellows from programmes across the USA participated in the 3 months prior to starting fellowship training between 2017 and 2019. There was significant improvement between pre- and post-video test scores for all 18 online learning modules. There was also significant improvement between pre- and post-Online Preparatory Course exam scores (PRE 43.6 ± 11% versus POST 60.3 ± 10%, p < 0.001). Comparing pre- and post-Online Preparatory Course surveys, there was a statistically significant improvement in the participants' comfort level in 35 of 36 (97%) assessment areas. Nearly all participants (98%) agreed or strongly agreed that the Online Preparatory Course was a valuable learning experience and helped alleviate some anxieties (77% agreed or strongly agreed) related to starting fellowship. CONCLUSION: An Online Preparatory Course prior to starting fellowship can provide a foundation of knowledge, decrease anxiety, and serve as an effective educational springboard for paediatric cardiology fellows.

Atrial Standstill in the Pediatric Population: A Multi-Institution Collaboration.

BACKGROUND: Atrial standstill (AS) is a rare condition characterized by absence of electrical activity within the atria. Studies to date have been limited. OBJECTIVES: The authors sought to describe the clinical characteristics, genetics, and outcomes of patients with AS. METHODS: This was a retrospective multicenter study of patients <18 years at AS diagnosis, defined as absence of atrial activity documented during an electrophysiology study, device placement, or noninvasive rhythm tracings and confirmed by echocardiogram. Patients with acquired disorders were excluded. Clinical details and genetic variants were recorded and analyzed. RESULTS: Twenty patients were diagnosed at a median age of 6.6 years (IQR: 2.9-10.8 years). Arrhythmias included 16 (80%) with atrial/supraventricular arrhythmias and 8 (40%) with ventricular tachycardia, including 4 with cardiac arrests. A type 1 Brugada pattern was documented in 4. Pacemakers were implanted in 18 (90%). Although atrial leads were attempted in 15, only 4 achieved pacing at implantation. During a median follow-up of 6.9 years (IQR: 1.2-13.3 years), 7 (35%) had thromboembolic events. Of these, none had atrial pacing, 6 were not on anticoagulation, and 1 was on aspirin. Genetic testing identified SCN5A variants in 13 patients (65%). Analyses suggest SCN5A loss-of-function may be one mechanism driving AS. Ventricular arrhythmias and cardiac arrest were more commonly seen in patients with biallelic SCN5A variants. CONCLUSIONS: AS may be associated with loss-of-function SCN5A variants. Patients demonstrate atrial and ventricular arrhythmias, and may present challenges during device placement. Patients without the capacity for atrial pacing are at risk for thromboembolic events and warrant anticoagulation.

Single center blind testing of a US multi-center validated diagnostic algorithm for Kawasaki disease in Taiwan.

Background: Kawasaki disease (KD) is the leading cause of acquired heart disease in children. The major challenge in KD diagnosis is that it shares clinical signs with other childhood febrile control (FC) subjects. We sought to determine if our algorithmic approach applied to a Taiwan cohort. Methods: A single center (Chang Gung Memorial Hospital in Taiwan) cohort of patients suspected with acute KD were prospectively enrolled by local KD specialists for KD analysis. Our previously single-center developed computer-based two-step algorithm was further tested by a five-center validation in US. This first blinded multi-center trial validated our approach, with sufficient sensitivity and positive predictive value, to identify most patients with KD diagnosed at centers across the US. This study involved 418 KDs and 259 FCs from the Chang Gung Memorial Hospital in Taiwan. Findings: Our diagnostic algorithm retained sensitivity (379 of 418; 90.7%), specificity (223 of 259; 86.1%), PPV (379 of 409; 92.7%), and NPV (223 of 247; 90.3%) comparable to previous US 2016 single center and US 2020 fiver center results. Only 4.7% (15 of 418) of KD and 2.3% (6 of 259) of FC patients were identified as indeterminate. The algorithm identified 18 of 50 (36%) KD patients who presented 2 or 3 principal criteria. Of 418 KD patients, 157 were infants younger than one year and 89.2% (140 of 157) were classified correctly. Of the 44 patients with KD who had coronary artery abnormalities, our diagnostic algorithm correctly identified 43 (97.7%) including all patients with dilated coronary artery but one who found to resolve in 8 weeks. Interpretation: This work demonstrates the applicability of our algorithmic approach and diagnostic portability in Taiwan.

Ventricular arrhythmias following transcatheter pulmonary valve replacement with the harmony TPV25 device.

BACKGROUND: Transcatheter pulmonary valve replacement (TPVR) with the Harmony valve (Medtronic, Inc.) was recently approved to treat postoperative native outflow tract pulmonary regurgitation. While the 22 mm Harmony valve Early Feasibility Study demonstrated ventricular tachycardia (VT) in only 5% of patients, little is known about ventricular arrhythmias after TPVR with the larger 25 mm valve (TPV25). METHODS: A single center review was performed of patients with TPV25 implant from 2020 to 2021. Demographic, cardiac, procedural, and postimplant cardiac telemetry data were collected and compared between patients who did and did not have peri-implant ventricular arrhythmia. RESULTS: Thirty patients underwent TPV25 at a median age of 30 years. On postimplant telemetry, VT events were documented in 12 patients (40%); 11 nonsustained VT (NSVT) (median 3 episodes per patient and 6 beats per episode, maximum 157 episodes) and 1 sustained VT (3%), with Torsades de Pointes secondary to a short coupled premature ventricular contraction (PVC). VT events were associated with annular valve positioning (p < 0.001) and increased postimplant PVC burden (p < 0.0001), but there was no association between VT and other demongraphic, historical, or procedural factors. The frequency of NSVT events fell from 3/h from 0 to 12 h postimplant to 0.5/hr from 12 to 24 h (p < 0.001). CONCLUSION: VT occurred commonly (40%) in the first 24 h after TPV25 implant, with self-limited NSVT in 11 of 12 patients and 1 patient with cardiac arrest secondary to Torsades de Pointes. VT only occurred with annular valve positioning. Larger, longer-term studies are needed to determine risk factors for and natural history of post-TPVR VT.

Posttraumatic stress disorder in pediatric patients with implantable cardioverter-defibrillators and their parents.

BACKGROUND: An implantable cardioverter-defibrillator (ICD) in the pediatric patient (and the precipitating events that led to ICD placement) can be traumatic for patients and their families and may lead to posttraumatic stress disorder (PTSD). OBJECTIVES: This study aimed to estimate the prevalence of PTSD in pediatric patients with an ICD and their parents and identify the factors associated with PTSD incidence. METHODS: Pediatric participants with an ICD aged 8-21 years and parents of children aged 0-21 years completed surveys that included demographic characteristics and PTSD measures. Pediatric participants completed additional psychosocial measures, such as anxiety and depression self-report questionnaires. RESULTS: Fifty youth (30% female) and 43 parents (70% female) completed the measures. Six of 50 youth (12%) met the screening criteria for a likely PTSD diagnosis, while 20 of 43 parents (47%) met the cutoff for PTSD on the screening measure. Children with PTSD were more likely to have had a secondary prevention ICD (83% vs 17%; P = .021), meet the clinical cutoff for depression (67% vs 16%; P = .005), and had higher shock anxiety scores (31.7 vs 17.9; P = .003) than children without PTSD. Female gender (57% vs 23%; P = .043) and patient depression (31% vs 5%; P = .042) were associated with PTSD in parents. CONCLUSION: Parents were found to be more likely to meet the criteria for PTSD than youth. In youth, PTSD was associated with medical and psychosocial factors, whereas PTSD in parents was associated with being female and child depression. Clinic-based screenings and management planning of emotional functioning are warranted to address psychological distress in patients and parents.

Cardiac crises: Cardiac arrhythmias and cardiomyopathy during TANGO2 deficiency related metabolic crises.

BACKGROUND: TANGO2 deficiency disorder (TDD) is an autosomal recessive disease associated with metabolic crisis, lethal cardiac arrhythmias, and cardiomyopathy. Data regarding treatment, management, and outcomes of cardiac manifestations of TDD are lacking. OBJECTIVE: The purpose of this study was to describe TDD-related cardiac crises. METHODS: Retrospective multicenter chart review was made of TDD patients admitted with cardiac crises, defined as development of ventricular tachycardia (VT), cardiomyopathy, or cardiac arrest during metabolic crises. RESULTS: Twenty-seven children were admitted for 43 cardiac crises (median age 6.4 years; interquartile range [IQR] 2.4-9.8 years) at 14 centers. During crisis, QTc prolongation occurred in all (median 547 ms; IQR 504-600 ms) and a type I Brugada pattern in 8 (26%). Arrhythmias included VT in 21 (78%), supraventricular tachycardia in 3 (11%), and heart block in 1 (4%). Nineteen patients (70%) developed cardiomyopathy, and 20 (74%) experienced a cardiac arrest. There were 10 deaths (37%), 6 related to arrhythmias. In 5 patients, recalcitrant VT occurred despite use of antiarrhythmic drugs. In 6 patients, arrhythmias were controlled after extracorporeal membrane oxygenation (ECMO) support; 5 of these patients survived. Among 10 patients who survived VT without ECMO, successful treatment included intravenous magnesium, isoproterenol, and atrial pacing in multiple cases and verapamil in 1 patient. Initiation of feeds seemed to decrease VT events. CONCLUSION: TDD-related cardiac crises are associated with a high risk of arrhythmias, cardiomyopathy, cardiac arrest, and death. Although further studies are needed, early recognition and appropriate treatment are critical. Acutely, intravenous magnesium, isoproterenol, atrial pacing, and ECMO as a last resort seem to be the best current treatment options, and early initiation of feeds may prevent VT events.

Implantable Cardioverter Defibrillators in Infants and Toddlers: Indications, Placement, Programming, and Outcomes.

BACKGROUND: Limited data exist regarding implantable cardioverter defibrillator (ICD) usage in infants and toddlers. This study evaluates ICD placement indications, procedural techniques, programming strategies, and outcomes of ICDs in infants and toddlers. METHODS: This is a single-center retrospective review of all patients ≤3 years old who received an ICD from 2009 to 2021. RESULTS: Fifteen patients received an ICD at an age of 1.2 years (interquartile range [IQR], 0.1-2.4; 12 [80%] women; weight, 8.2 kg [IQR, 4.2-12.6]) and were followed for a median of 4.28 years (IQR, 1.40-5.53) or 64.2 patient-years. ICDs were placed for secondary prevention in 12 patients (80%). Diagnoses included 8 long-QT syndromes (53%), 4 idiopathic ventricular tachycardias/ventricular fibrillations (VFs; 27%), 1 recurrent ventricular tachycardia with cardiomyopathy (7%), 1 VF with left ventricular noncompaction (7%), and 1 catecholaminergic polymorphic ventricular tachycardia (7%). All implants were epicardial, with a coil in the pericardial space. Intraoperative defibrillation safety testing was attempted in 11 patients (73%), with VF induced in 8 (53%). Successful restoration of sinus rhythm was achieved in all tested patients with a median of 9 (IQR, 7.3-11.3) J or 0.90 (IQR, 0.68-1.04) J/kg. Complications consisted of 1 postoperative chylothorax and 3 episodes of feeding intolerance. VF detection was programmed to 250 (IQR, 240-250) ms with first shock delivering 10 (IQR, 5-15) J or 1.1 (IQR, 0.8-1.4) J/kg. Three patients (20%) received appropriate shocks for ventricular tachycardia/VF. No patient received an inappropriate shock. There were 2 (13%) ventricular lead fractures (at 2.6 and 4.2 years post-implant), 1 (7%) pocket-site infection, and 2 (13%) generator exchanges. All patients were alive, and 1 patient (7%) received a heart transplant. CONCLUSIONS: ICDs can be safely and effectively placed for sudden death prevention in infants and toddlers with good midterm outcomes.

Identifying an appropriate endpoint for cryoablation in children with atrioventricular nodal reentrant tachycardia: Is residual slow pathway conduction associated with recurrence?

BACKGROUND: Cryoablation is increasingly used to treat atrioventricular nodal reentrant tachycardia (AVNRT) due to its safety profile. However, cryoablation may have higher recurrence than radiofrequency ablation (RFA), and the optimal procedural endpoint remains undefined. OBJECTIVE: The purpose of this study was to identify the association of cryoablation procedural endpoints with postprocedural AVNRT recurrence. METHODS: We performed a single-center, retrospective analysis of pediatric patients following successful first-time cryoablation for AVNRT between January 1, 2011, and December 31, 2019. Preablation inducibility of AVNRT was recorded. Procedural endpoints, including slow pathway (SP) conduction (presence of jump or echo beats) with and without isoproterenol, were identified. Recurrence was established from clinical notes and/or direct patient contact. RESULTS: Of 256 patients, 147 (57%) were assessed on isoproterenol precryoablation, and 171 (47%) were assessed on isoproterenol postcryoablation. Mean cryolesion time was 2586 ± 1434 seconds. Following ablation, 104 (41%) had some evidence of residual SP conduction. With median follow-up time of 1.9 [0.7-3.7] years, recurrence occurred in 14 patients (5%). Complete elimination of SP conduction (with and without isoproterenol) had a hazard ratio for recurrence of 1.26 (95% confidence interval [CI] 0.42-3.8; P = .68) on univariate analysis and 1.39 (95% CI 0.36-5.4; P = .63) on multivariate analysis (including demographics, ablation time, 8-mm cryocatheter, and baseline inducibility). CONCLUSION: The observed AVNRT recurrence rate after cryoablation was comparable to that of RFA. The presence of residual SP conduction was not associated with recurrence. This suggests that jump or single echo beat may be an acceptable endpoint in AVNRT cryoablation.

High-throughput quantitation of serological ceramides/dihydroceramides by LC/MS/MS: Pregnancy baseline biomarkers and potential metabolic messengers.

Ceramides and dihydroceramides are sphingolipids that present in abundance at the cellular membrane of eukaryotes. Although their metabolic dysregulation has been implicated in many diseases, our knowledge about circulating ceramide changes during the pregnancy remains limited. In this study, we present the development and validation of a high-throughput liquid chromatography-tandem mass spectrometric method for simultaneous quantification of 16 ceramides and 10 dihydroceramides in human serum within 5 min. by using stable isotope-labeled ceramides as internal standards. This method employs a protein precipitation method for high throughput sample preparation, reverse phase isocratic elusion for chromatographic separation, and Multiple Reaction Monitoring for mass spectrometric detection. To qualify for clinical applications, our assay has been validated against the FDA guidelines for Lower Limit of Quantitation (1 nM), linearity (R2>0.99), precision (imprecision<15 %), accuracy (inaccuracy<15 %), extraction recovery (>90 %), stability (>85 %), and carryover (<0.01 %). With enhanced sensitivity and specificity from this method, we have, for the first time, determined the serological levels of ceramides and dihydroceramides to reveal unique temporal gestational patterns. Our approach could have value in providing insights into disorders of pregnancy.

Subcutaneous Implantable Cardioverter-Defibrillators in Pediatrics and Congenital Heart Disease: A Pediatric and Congenital Electrophysiology Society Multicenter Review.

OBJECTIVES: The primary goal of this study was to evaluate the implant experience and midterm results of subcutaneous implantable cardioverter-defibrillators (S-ICDs) in pediatric patients and those with congenital heart disease. BACKGROUND: The S-ICD was developed to avoid the lead-related complications associated with transvenous systems. The absence of intravascular or intracardiac components offers potential advantages to pediatric patients and those with congenital heart disease. METHODS: This international, multicenter, retrospective, standard-of-care study was conducted through the Pediatric & Congenital Electrophysiology Society. Complications at 30 and 360 days, inappropriate shocks, and delivery of appropriate therapy were assessed. RESULTS: The study included 115 patients with a median follow-up of 32 (19 to 52) months. Median age was 16.7 years (14.8 to 19.3 years), 29% were female, and 55% had a primary prevention indication. Underlying disease substrate was cardiomyopathy (40%), structural heart disease (32%), idiopathic ventricular fibrillation (16%), and channelopathy (13%). The complication rate was 7.8% at 30 days and 14.7% at 360 days. Overall, inappropriate shocks occurred in 15.6% of patients, with no single clinical characteristic reaching statistical significance. At implant, 97.9% of patients had successful first shock conversion with 96% requiring ≤65 J. Appropriate therapy was delivered to 11.2% of patients with an annual incidence of 3.9% and an acute first shock conversion success rate of 92.5%. CONCLUSIONS: This study found that in a heterogeneous population of pediatric patients and those with congenital heart disease, the S-ICD had comparable rates of complications, inappropriate shocks, and conversion efficacy compared with previously published studies on transvenous systems in similar populations.

Kinetics of SARS-CoV-2 positivity of infected and recovered patients from a single center.

Recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive detection in infected but recovered individuals has been reported. Patients who have recovered from coronavirus disease 2019 (COVID-19) could profoundly impact the health care system. We sought to define the kinetics and relevance of PCR-positive recurrence during recovery from acute COVID-19 to better understand risks for prolonged infectivity and reinfection. A series of 414 patients with confirmed SARS-Cov-2 infection, at The Second Affiliated Hospital of Southern University of Science and Technology in Shenzhen, China from January 11 to April 23, 2020. Statistical analyses were performed of the clinical, laboratory, radiologic image, medical treatment, and clinical course of admission/quarantine/readmission data, and a recurrence predictive algorithm was developed. 16.7% recovered patients with PCR positive recurring one to three times, despite being in strict quarantine. Younger patients with mild pulmonary respiratory syndrome had higher risk of PCR positivity recurrence. The recurrence prediction model had an area under the ROC curve of 0.786. This case series provides characteristics of patients with recurrent SARS-CoV-2 positivity. Use of a prediction algorithm may identify patients at high risk of recurrent SARS-CoV-2 positivity and help to establish protocols for health policy.