Aveir VR, retrievable leadless pacing in the young.

INTRODUCTION: Successful implantations of the Aveir VR, have been effectively demonstrated in adults; however, there remain limited reports supporting safe and feasible implantation of the Aveir VR in the young population. METHODS: Retrospective, observational study of Aveir VR implantation of young patients (≦21 years old) at UC Davis Medical Center from November 2022 to January 2024 via the internal jugular or femoral vein implantation approaches. Indications for pacing, patient demographics, pacing thresholds and longevity were reported at the time of implantation and last follow-up. RESULTS: A total of 10 patients received the Aveir VR with a median age of years (IQR 12.5-17) and median weight of 50.8 kg (IQR 44.6-60.9) kg. The majority were male (80%). Aveir VR leadless pacemaker occurred via internal jugular venous (90%) or femoral venous (10%) approaches. Indications for placement were intermittent complete heart block (60%) and sinus pauses (40%). Adequate impedance, sensing and thresholds were maintained from implantation to a median follow-up of 9 months. Predicted pacemaker longevity at follow-up median was 23.8 years. There were no complications in any of the 10 patients. CONCLUSION: Aveir VR implantation via the internal jugular and femoral veins is feasible in the young patient population with stable pacing parameters at follow-up.

The Fetus with Ectopia Cordis: Experience and Expectations from Two Centers.

Ectopia cordis (EC) is a rare congenital anomaly often associated with congenital heart disease (CHD). There is a lack of contemporary information on EC diagnosed prenatally. We sought to combine the experiences of two regional referral centers in order to evaluate current outcomes for EC. Clinical, echocardiographic features and perinatal outcomes of fetuses with EC managed at two large cardiac centers from 1995 to 2014 were retrospectively reviewed. Seventeen fetuses with EC were diagnosed at a median gestational age of 23 weeks (range 17-36). There were 6 thoracic EC and 11 thoracoabdominal. Fifteen had associated CHD: 10 conotruncal defects, 2 tricuspid atresia, 1 aortic stenosis, 1 atrial septal defect, and 1 atrioventricular septal defect. There were 2 terminations of pregnancy, 2 fetal deaths, 2 lost to follow-up, and 11 live born. Mean gestational age at birth was 36.4 weeks (range 26-39). Three patients died shortly after birth with comfort care, and 8 were actively managed. Six patients underwent postnatal cardiac intervention and are currently alive with a mean follow-up of 7.3 years (range 1.4-11.4), 2 of them with chronic dependency on ventilatory support. Two patients without CHD died after attempted chest closure. When diagnosed in utero, a high proportion of pregnancy termination or fetal demise is expected. In our cohort, conotruncal anomalies were the most common associated CHD. Though mortality in actively managed patients was not as high as previously reported, and cardiac surgical intervention may be achieved, EC is still associated with high mortality and significant long-term morbidity.

Prevalence of deficient retro-aortic rim and its effects on outcomes in device closure of atrial septal defects.

Deficient retro-aortic rim is of concern as a risk factor for aortic erosion after device closure of atrial septal defects (ASD). However, its prevalence and contribution to technical failure and adverse outcomes have not been delineated. A single-center retrospective cohort study of children and adults undergoing cardiac catheterization for device occlusion of ASD from 1 January 1999 to 1 April 2012 was performed. Risk factors for technical failure and early adverse outcome were assessed using multivariate logistic regression. During the study period, 445 consecutive subjects with a median age of 5.9 years (range, 0.8-80 years) underwent catheterization. Of the subjects with reviewable echocardiograms, 60 % had deficient retro-aortic rim. No attempt at device closure was made for 3.6 % of the subjects. Of the remaining 429 subjects, 96 % underwent successful device occlusion. Major early adverse events occurred in 1.2 % (95 % confidence interval 0.4-2.7 %) of the cases, all of them either device embolization or malposition. Deficient retro-aortic rim was not a risk factor for composite outcome of technical failure or early major adverse event. No deaths, late reinterventions, or erosion events occurred during 2,395 total person-years (median, 5.8 years) of follow-up evaluation. Deficient retro-aortic rim was associated with increased risk of device impingement on the aorta, but no association was seen between device impingement or deficient retro-aortic rim and the development of new/progressive aortic insufficiency. Deficient retro-aortic rim is highly prevalent but did not increase the risk of adverse outcomes. Its contribution to the risk of aortic erosion could not be addressed by this study.

Acute Bowel Ischemia in a Premature Neonate with Miller-Dieker Syndrome and Anomalous Right Coronary Artery From the Pulmonary Artery.

Miller-Dieker syndrome (MDS) is a rare disease characterized by type I lissencephaly, craniofacial dysmorphisms, intellectual disability, seizures, and death in early childhood. We report a case of a premature infant with MDS with an anomalous right coronary artery from the pulmonary artery who developed sudden bowel ischemia. This case prompts the reconsideration of cardiovascular involvement in patients with MDS. In addition, this review highlights key clinical features and reviews the critical manifestations of MDS that persist into childhood. [Pediatr Ann. 2023;52(8):e283-e291.].

Novel scoring tool of hypoxemic respiratory failure and pulmonary hypertension for defining severity of persistent pulmonary hypertension of newborn.

OBJECTIVE: To obtain preliminary validity data for a hypoxemic respiratory failure/pulmonary hypertension (HRF/PH) score for classifying persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: Retrospective chart review of 100 consecutive neonates admitted to a Children's hospital from 2016-2021 with PPHN, gestational age ≥34 weeks, and echocardiograms in the first week. We assessed the correlation between HRF/PH score and short-term outcomes using linear and logistic regressions. RESULTS: HRF/PH scores ranged 2-12 (mean 8.5), and were classified mild (0-5), moderate (6-10), and severe (11-15), with 6%, 77% and 17% infants in respective categories. HRF/PH score category correlated with invasive ventilation, nitric oxide, high frequency ventilation, vasoactive infusions, extracorporeal life support and death. HRF/PH score category did not correlate with duration of support or length of stay. CONCLUSION: The HRF/PH score offers a promising representation of disease severity for PPHN. The tool requires further validation in prospective studies and evaluation for long-term outcomes.

Factors to Consider to Study Preductal Oxygen Saturation Targets in Neonatal Pulmonary Hypertension.

There are potential benefits and risks to the infant with higher and lower oxygen saturation (SpO2) targets, and the ideal range for infants with pulmonary hypertension (PH) remains unknown. Targeting high SpO2 can promote pulmonary vasodilation but cause oxygen toxicity. Targeting lower SpO2 may increase pulmonary vascular resistance, especially in the presence of acidosis and hypothermia. We will conduct a randomized pilot trial to compare two ranges of target preductal SpO2 in late-preterm and term infants with hypoxic respiratory failure (HRF) and acute pulmonary hypertension (aPH) of the newborn. We will assess the reliability of a newly created HRF/PH score that could be used in larger trials. We will assess trial feasibility and obtain preliminary estimates of outcomes. Our primary hypothesis is that in neonates with PH and HRF, targeting preductal SpO2 of 95-99% (intervention) will result in lower pulmonary vascular resistance and pulmonary arterial pressures, and lower the need for pulmonary vasodilators (inhaled nitric oxide-iNO, milrinone and sildenafil) compared to targeting SpO2 at 91-95% (standard). We also speculate that a higher SpO2 target can potentially induce oxidative stress and decrease response to iNO (oxygenation and pulmonary vasodilation) for those patients that still require iNO in this range. We present considerations in planning this trial as well as some of the details of the protocol design (Clinicaltrials.gov (NCT04938167)).

NAFTNet retrospective report on the treatment of anti-Ro/SSA mediated fetal heart block with dexamethasone.

BACKGROUND: Complete atrioventricular block (CAVB) is a complication of maternal antibody positivity and treatment of fetal disease is controversial in terms of efficacy and safety. We hypothesized that dexamethasone treatment for fetal anti-Ro/SSA antibody-mediated cardiac disease leads to better pregnancy outcomes than expectant management. METHODS: A retrospective multi-center cohort study of anti-Ro/SSA antibody positive pregnancies with fetal conduction disease reported by participating North American Fetal Therapy Network (NAFTNet) centers between January 2010 and December 2018. The primary outcomes included: fetal death, oligohydramnios, growth restriction, preterm delivery, and new maternal comorbidities. Secondary outcomes included: pacemaker prior to 28 days, transplantation, and neonatal death in maternal/fetal dyads treated with dexamethasone versus not. RESULTS: In 127 anti-Ro/SSA positive pregnancies, 98 were treated with dexamethasone and 29 were not. Of those treated, 61/96 (63.5%) met the primary outcome including 45/91 (49.4%) premature deliveries; 20 mothers developed comorbidities during treatment (fetal death 5, 10 growth restriction, 14 oligohydramnios, two new/worsening gestational diabetes). In the untreated group, 15/25 (60%) met the primary outcome including 11/22 (50%) premature deliveries and four mothers developing comorbidities during their pregnancy (fetal death 3, one growth restriction, one new onset maternal hypertension). Regarding secondary outcomes, 37/96 (43%) treated fetuses required a pacemaker or died by 28 days, while untreated 13/25 (52%) required pacemaker placement, died prior to 28 days or required listing for transplantation. Excluding terminations, survival without transplant was 17 (68%) in untreated and 85 (89%) in treated patients (p<.01). CONCLUSIONS: While the use of dexamethasone in anti-Ro/SSA positive pregnancies is associated with a high rate of poor pregnancy outcomes, there was an unexpected similarly high rate in untreated positive pregnancies. This suggests that the maternal disease itself is influencing pregnancy complications independent of dexamethasone. Our data, which show that treatment decreases neonatal morbidity and overall mortality without increasing overall pregnancy complications, warrant further study.

Multi-Institutional Practice-Patterns in Fetal Congenital Heart Disease Following Implementation of a Standardized Clinical Assessment and Management Plan.

Background Prenatal diagnosis of congenital heart disease has been associated with early-term delivery and cesarean delivery (CD). We implemented a multi-institutional standardized clinical assessment and management plan (SCAMP) through the University of California Fetal-Maternal Consortium. Our objective was to decrease early-term (37-39 weeks) delivery and CD in pregnancies complicated by fetal congenital heart disease using a SCAMP methodology to improve practice in a high-risk and clinically complex setting. Methods and Results University of California Fetal-Maternal Consortium site-specific management decisions were queried following SCAMP implementation. This contemporary intervention group was compared with a University of California Fetal-Maternal Consortium historical cohort. Primary outcomes were early-term delivery and CD. A total of 496 maternal-fetal dyads with prenatally diagnosed congenital heart disease were identified, 185 and 311 in the historical and intervention cohorts, respectively. Recommendation for later delivery resulted in a later gestational age at delivery (38.9 versus 38.1 weeks, P=0.01). After adjusting for maternal age and site, historical controls were more likely to have a CD (odds ratio [OR],1.8; 95% CI, 2.1-2.8; P=0.004) and more likely (OR, 2.1; 95% CI, 1.4-3.3) to have an early-term delivery than the intervention group. Vaginal delivery was recommended in 77% of the cohort, resulting in 61% vaginal deliveries versus 50% in the control cohort (P=0.03). Among pregnancies with major cardiac lesions (n=373), vaginal birth increased from 51% to 64% (P=0.008) and deliveries ≥39 weeks increased from 33% to 48% (P=0.004). Conclusions Implementation of a SCAMP decreased the rate of early-term deliveries and CD for prenatal congenital heart disease. Development of clinical pathways may help standardize care, decrease maternal risk secondary to CD, improve neonatal outcomes, and reduce healthcare costs.

Key Features on the 3-Vessel View and 3-Vessel Tracheal View of Isolated Right Aortic Arch Anomalies.

Right aortic arch anomalies are a spectrum of malformations that include right aortic arch with mirror image branching, right aortic arch with an aberrant left subclavian artery, and double aortic arch. Although these are rare anomalies, they are of importance as they form vascular rings, which can cause symptoms in the newborn period. These anomalies are not detected with routine cardiac views, and it is only with the 3-vessel, and the 3-vessel tracheal view that they can be identified and characterized. We describe specific sonographic findings of these anomalies on the 3-vessel and the 3-vessel tracheal view.

Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract.

OBJECTIVE: There is substantial epidemiological evidence that infection by Herpes simplex virus type 2 (HSV2) enhances both HIV susceptibility and subsequent sexual transmission. Both infections are extremely common in female sex workers (FSWs) in sub-Saharan Africa, and up to 80% of new HIV infections in urban men in the region are acquired via transactional sex. The present study aimed to elucidate the mucosal immune interactions between HIV and HSV2 in the genital tract. METHODS: Endocervical immune cell populations, cytokine/chemokine protein levels in cervico-vaginal secretions and cervical immune gene expression profiles were measured in a well-defined cohort of HIV-infected and uninfected Kenyan FSWs. Associations between the genital immune milieu and infection by and/or shedding of common genital co-pathogens were examined. RESULTS: HIV-infected FSWs were much more likely to be infected by HSV2, and to shed HSV2 DNA in the genital tract. There was also a profound negative 'mucosal synergy' between these viruses. In HIV uninfected FSWs, HSV2 infection was associated with a ten-fold increase in cervical immature dendritic cells (iDC) expressing DC-SIGN, and a three-fold increase in cervical CD4+ T cells expressing CCR5. HIV infection was associated with iDC depletion in the cervix, and with increased HSV2 genital reactivation, which in turn was associated with HIV shedding levels. CONCLUSIONS: The findings suggest a mucosal vicious circle in which HSV2 infection increases HIV target cells in the genital mucosa, subsequent HIV infection impairs HSV2 mucosal immune control, and local HSV2 reactivation enhances both HSV2 and HIV transmission.

Revisiting the utility of technical performance scores following tetralogy of Fallot repair.

OBJECTIVE: Although an important quality metric, current technical performance scores may not be generalizable and may omit operative factors that influence outcomes. We examined factors not included in current technical performance scores that may contribute to increased postoperative length of stay, major complications, and cost after primary repair of tetralogy of Fallot. METHODS: This is a retrospective single site study of patients younger than age 2 years with tetralogy of Fallot undergoing complete repair between 2007 and 2015. Medical record data and discharge echocardiograms were reviewed to ascertain component and composite technical performance scores. Primary outcomes included postoperative length of stay, major complications, and total hospital costs. Multivariable logistic and linear regression identified determinants of each outcome. RESULTS: Patient population (n = 115) had a median postoperative length of stay of 8 days (interquartile range, 6-10 days), and a median total cost of $71,147. Major complications occurred in 33 patients (29%) with 1 death. Technical performance scores assigned were optimum in 28 patients (25%), adequate in 59 patients (52%), and inadequate in 26 patients (23%). Neither technical performance score components nor composite scores were associated with increased postoperative length of stay. Optimum or adequate repairs versus inadequate had equal risk of a complication (P = .79), and equivalent mean total cost ($100,000 vs $187,000; P = .25). Longer cardiopulmonary bypass time per 1-minute increase (P < .01) was associated with longer postoperative length of stay and reintervention (P = .02). The need to return to bypass also increased total cost (P < .01). CONCLUSIONS: Current tetralogy of Fallot technical performance scores were not associated with selected outcomes in our postoperative population. Although returning to bypass and bypass length are not included as components in the current score, these are important factors influencing complications and resource use in our population. Revisions anticipated from a prospective trial should consider including these variables.

Bacterial vaginosis in HIV-infected women induces reversible alterations in the cervical immune environment.

BACKGROUND: Bacterial vaginosis (BV) has been associated with increased HIV cervicovaginal shedding. We hypothesized that this might relate to BV-associated increases in mucosal activated CD4 T cells, which could enhance local HIV replication. METHODS: Vaginal flora, cytokine/chemokine levels, and mucosal immune cell populations collected by cervical cytobrush were analyzed in 15 HIV-infected Kenyan female sex workers, before and after BV therapy with oral metronidazole. RESULTS: Therapy reduced the Nugent score in all but 1 participant, and BV elimination was associated with reduced genital levels of interleukin 1beta(IL1beta), interleukin 8 (IL-8), and Regulated Upon Activation Normal T-cell Expressed and Secreted (RANTES). In addition, BV elimination reduced the total number of cervical CD4 T cells, including those expressing the HIV coreceptor CCR5 and the activation marker CD69. CONCLUSIONS: BV induces significant and reversible alterations in cervical immune cell populations and local inflammatory cytokines that would be expected to enhance local HIV replication.

Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation.

BACKGROUND: Chronic coinfection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) has been associated with an increased HIV viral load and more rapid disease progression, perhaps related to HSV-2-associated alterations in host immunity. METHODS: Studies were nested within (1) a cross-sectional study of men coinfected with HIV and HSV-2 and (2) women not infected with HIV, both before and after HSV-2 acquisition. HSV-2 infection status was determined by ELISA. HIV-specific CD8(+) T cell epitopes were mapped, and proliferation of HIV-specific cells was also assessed. Systemic inflammatory and regulatory T cell populations were assayed by flow cytometry. RESULTS: The breadth of both the HIV-specific CD8(+) T cell interferon-gamma and proliferative responses was reduced in participants coinfected with HIV and HSV-2, independent of the HIV plasma viral load and CD4(+) T cell count, and the magnitude of the responses was also reduced. HSV-2 infection in this group was associated with increased T cell CD38 expression but not with differences in the proportion of CD4(+) FoxP3(+) regulatory T cells. However, in women not infected with HIV, acquisition of HSV-2 was associated with an increase in the proportion of regulatory T cells. CONCLUSIONS: HSV-2 coinfection was associated with reduced HIV-specific T cell responses and systemic inflammation. The immune effects of HSV-2 may underlie the negative impact that this coinfection has on the clinical course of HIV infection.

Expansion of HIV-specific CD4+ and CD8+ T cells by dendritic cells transfected with mRNA encoding cytoplasm- or lysosome-targeted Nef.

Transfection with synthetic mRNA is a safe and efficient method of delivering antigens to dendritic cells for immunotherapy. Targeting antigens to the lysosome can sometimes enhance the CD4+ T-cell response. We transfected antigen-presenting cells (APCs) with mRNA encoding Gag-p24 and cytoplasmic, lysosomal, and secreted forms of Nef. Antigen-specific cytotoxic T cells were able to lyse the majority of transfected targets, indicating that transfection was efficient. Transfection of APCs with a Nef construct bearing lysosomal targeting signals produced rapid and prolonged antigen presentation to CD4+ and CD8+ T cells. Polyclonal CD4+ and CD8+ T-cell lines recognizing multiple distinct epitopes were expanded by coculture of transfected dendritic cells with peripheral blood mononuclear cells from viremic and aviremic HIV-infected subjects. Importantly, lysosome-targeted antigen drove a significantly greater expansion of Nef-specific CD4+ T cells than cytoplasmic antigen. The frequency of recognition of CD8 but not CD4 epitopes by mRNA-expanded T cells was inversely proportional to sequence entropy and was similar to ex vivo responses from a large chronic cohort. Thus human dendritic cells transfected with mRNA encoding lysosome-targeted HIV antigen can expand a broad, polyclonal repertoire of antiviral T cells, offering a promising approach to HIV immunotherapy.