Surgical strategies to address re-operative complex left ventricular outflow tract and thoracic aortic pathology: Cleveland Clinic children's experience.

BACKGROUND: Complex patients requiring operations on the left ventricular outflow tract, aortic valve, or thoracic aorta after previous repair of aortopathy constitute a challenging group, with limited information guiding decision-making. We aimed to use our institutional experience to highlight management challenges and describe surgical pearls to address them. METHODS: Forty-one complex patients with surgery on the left ventricular outflow tract, aortic valve, or aorta at Cleveland Clinic Children's between 2016 and 2021 following previous repair of aortic pathology were retrospectively reviewed. Patients with known connective tissue disease or single ventricle circulation were excluded. RESULTS: Median age at index procedure was 23 years (range 0.25-48) with median of 2 prior sternotomies. Previous aortic operations included subvalvular (n = 9), valvular (n = 6), supravalvular (n = 13), and multi-level surgeries (n = 13). Four deaths occurred in median follow-up of 2.5 years. Mean left ventricular outflow tract gradients improved significantly for patients with obstruction (34.9 ± 17.5 mmHg versus 12.6 ± 6.0 mmHg; p < 0.001). Technical pearls include the following: 1) liberal use of anterior aortoventriculoplasty with valve replacement; 2) primarily anterior aortoventriculoplasty following the subpulmonary conus in contrast to more vertical incision for post-arterial switch operation patients; 3) pre-operative imaging of mediastinum and peripheral vasculature for cannulation and sternal re-entry; and 4) proactive use of multi-site peripheral cannulation. CONCLUSIONS: Operation to address the left ventricular outflow tract, aortic valve, or aorta following prior congenital aortic repair can be accomplished with excellent outcomes despite high complexity. These procedures commonly include multiple components, including concomitant valve interventions. Cannulation strategies and anterior aortoventriculoplasty in specific patients require modifications.

Evaluation of the relationship of cholinergic metabolites in urine and urgency urinary incontinence.

INTRODUCTION AND HYPOTHESIS: To investigate differences in urine cholinergic metabolites in women with urinary urgency incontinence (UUI) and responders (R) and non-responders (NR) to anti-cholinergic medications (AC). METHODS: Patients with UUI and age-matched controls were evaluated pre- and post-treatment using OABSS, UDI-6 and IIQ-7. Controls were defined as having a cumulative OABSS of zero. Patients with UUI were treated with AC and followed for 12 weeks. Responders were those with a > 50% decrease in the total OABSS score. Urine samples were collected from all participants for evaluation. Metabolite detection was accomplished using commercial assay kits. Wilcoxon-rank sum test and Fisher's exact test were used to express differences between groups. Spearman's rho correlation coefficient was used to determine the relationship between acetylcholine (Ach), choline (Ch), acetylcholinesterase (AchE) and questionnaire scores. RESULTS: We recruited 39 with UUI and 33 controls. We found concentrations of Ch [29.0 (IQR: 24.2-42.5) µmol vs. 15.2 (IQR: 7.5-24.1) µmol] and Ach [65.8 (IQR: 30.4-101.8) nmol and 33.1 (IQR: 11.9-43.8) nmol] were higher in the UUI group compared to controls (p = 0.003 and p < 0.001, respectively] and no differences in AchE concentrations. In the UUI group, 43.6% responded to AC after 12 weeks of therapy. There were no differences in Ch or AchE levels between R and NR; Ach levels were higher in the R group [82.1 nmol (IQR: 54.8-118.1) vs. 50.3 nmol (IQR: 29.9-68.2), p = 0.007]. Ch and Ach were positively associated with pre-treatment OABSS parameters. CONCLUSIONS: Urine Ach is higher in responders to anti-cholinergic therapy, and urine cholinergic metabolites were higher in the UUI patients compared to controls.

Perioperative sildenafil therapy in pulmonary hypertension associated with congenital cardiac disease: An updated meta-analysis.

To provide an updated meta-analysis to evaluate the efficacy and safety of sildenafil on pediatric patients with pulmonary hypertension (PH) associated with congenital heart disease (CHD). To assess the efficacy and safety of sildenafil, five outcomes, time duration of post-operative need for mechanical ventilation, time duration of post-operative ICU stay, length of hospitalization (LOH), the incidence of mortalities and pulmonary arterial pressure to aortic pressure ratio (PAP/AoP) were regarded as primary efficacy outcomes. Standardized mean difference (SMD) was calculated for continuous data. In comparison to the control group (CG), there was a significant decrease in the time duration of ICU stay in the sildenafil group (SG) (SMD = -0.61 [95% CI -1.17, 0.04]; P < 0.01, I2 = 85%). Length of hospitalization was assessed in the sildenafil and control groups (SMD = -0.18 [95% CI -0.67, 0.31] P = 0.05, I2 = 62%). However, there was no significant difference seen in mortality rates between the SG and CG (SMD = 0.53 [ 95% CI 0.13, 2.17] p = 0.61, I2 = 0%), in the time duration of postoperative mechanical ventilation between the SG and CG (SMD = -0.23 [95% CI -0.49, 0.03] p = 0.29, I2 = 19%), or PAP/AoP ratio between the SG and CG (SMD = -0.42 [95% CI -1.35, 0.51] P < 0.01, I2 = 90%). Based on our analysis, sildenafil has little to no effect in reducing postoperative morbidity and mortality due to PH in infants and children with CHD.

Anterior Scalene Anomaly in a Patient With Arterial and Neurogenic Thoracic Outlet Syndrome.

Compression of the neurovascular structures of the upper extremity as they pass through the thoracic outlet result in thoracic outlet syndrome. The myriad of symptoms associated with the syndrome vary based on the structure(s) compressed: the subclavian artery/vein or the inferior trunk of the brachial plexus. This is a common site of compression especially in the presence of upper extremity injury, overuse or anatomical abnormalities. Majority of patients present with neurogenic pain and weakness; herein, we present the case of a patient with symptoms of both arterial and neurogenic compression caused by aberrant anterior scalene anatomy. These patients are excellent surgical candidates for first rib resection and anterior scalenectomy. A transaxillary approach offers the clinician an adequate window to identify anatomical abnormalities intraoperatively and safely excise the first rib and anterior scalene muscle.

Characterizing the anatomic spectrum, surgical treatment, and long-term clinical outcomes for patients with Shone's syndrome.

OBJECTIVE: Shone's syndrome (SS) has a varied anatomic spectrum without consensus on need and timing for mitral valve intervention (MVI). We sought to (1) characterize the anatomic spectrum and treatment pathways; (2) describe long-term outcomes and their determinants; and (3) define the impact of MVI timing on survival. METHODS: In total, 121 patients with SS who underwent operation at Cleveland Clinic between 1956 and 2021 were reviewed. Multivariable parametric hazard analyses including time-varying covariables, and modulated renewal to account for repeated events, were performed. End points included time-related survival and reintervention. RESULTS: Median follow-up was 9.9 years. Mitral stenosis (MS) (98%), coarctation (80%), and aortic stenosis (70%) predominated. The most common combination was MS + aortic stenosis + coarctation (26%). Median initial mean mitral and aortic gradients were 3.6 (15th/85th percentiles: 2.0/6.8) and 9.0 (2.1/46) mm Hg, respectively. Median initial surgery age was 0.041 (0.011/3.2) years. Initial surgeries included coarctation repair (43%), arch repair (18%), and staged biventricular repair (18%). Overall survival was 92% at 20 years. Freedom from reoperation was 66% and 24% at 1 and 20 years. Patients with no MVI or initial MVI (N = 7) tended to be associated with better early survival compared with those with MVI at subsequent operation (N = 29) (P = .06). Risk factors for early reintervention included initial Norwood operation, with younger age and arch hypoplasia increasing later reintervention. CONCLUSIONS: Despite excellent long-term survival, reoperation in SS is frequent and occurs most commonly on left ventricular outflow tract and mitral valve. Although MS is present in most, few require MVI. Delaying MVI may compromise early survival.

Critical Care Among Disadvantaged Minority Groups Made Equitable: Trends Throughout the COVID-19 Pandemic.

BACKGROUND: US racial and ethnic minorities have well-established elevated rates of comorbidities, which, compounded with healthcare access inequity, often lead to worse health outcomes. In the current COVID-19 pandemic, it is important to understand existing disparities in minority groups' critical care outcomes and mechanisms behind these-topics that have yet to be well-explored. OBJECTIVE: Assess for disparities in racial and ethnic minority groups' COVID-19 critical care outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 2125 adult patients who tested positive for COVID-19 via RT-PCR between March and December 2020 and required ICU admission at the Cleveland Clinic Hospital Systems were included. MAIN MEASURES: Primary outcomes were mortality and hospital length of stay. Cohort-wide analysis and subgroup analyses by pandemic wave were performed. Multivariable logistic regression models were built to study the associations between mortality and covariates. KEY RESULTS: While crude mortality was increased in White as compared to Black patients (37.5% vs. 30.5%, respectively; p = 0.002), no significant differences were appraised after adjustment or across pandemic waves. Although median hospital length of stay was comparable between these groups, ICU stay was significantly different (4.4 vs. 3.4, p = 0.003). Mortality and median hospital and ICU length of stay did not differ significantly between Hispanic and non-Hispanic patients. Neither race nor ethnicity was associated with mortality due to COVID-19, although APACHE score, CKD, malignant neoplasms, antibiotic use, vasopressor requirement, and age were. CONCLUSIONS: We found no significant differences in mortality or hospital length of stay between different races and ethnicities. In a pandemic-influenced critical care setting that operated outside conditions of ICU strain and implemented standardized protocol enabling equitable resource distribution, disparities in outcomes often seen among racial and ethnic minority groups were successfully mitigated.

Double Switch in Congenitally Corrected Transposition of the Great Arteries With Incomplete Atrioventricular Septal Defect, Ebsteinoid Tricuspid Valve, Ventricular Outflow Tract Obstructions, and Multiple VSDs.

We describe the management of a 2 month-old male (BSA 0.27 m2) with congenitally corrected transposition of the great arteries (CCTGA), left and right ventricular outflow tract obstruction, incomplete atrioventricular (AV) canal defect, Ebsteinoid left AV valve, and multiple VSDs. In short, the patient presented with respiratory failure, metabolic acidosis with worsening AV valve regurgitation, and acute decompensation from pulmonary overcirculation. We performed a complex double switch operation described below. Despite the unique anatomical complexities, the patient's successful course demonstrates the importance of multidisciplinary discourse, preoperative imaging and planning, and intraoperative decision making from patient selection to anatomic repair.

Coronary artery disease in adults with anomalous aortic origin of a coronary artery.

Objectives: This study sought to characterize coronary artery disease (CAD) among adults diagnosed with an anomalous aortic origin of a coronary artery (AAOCA). We hypothesized that coronaries with anomalous origins have more severe CAD stenosis than coronaries with normal origins. Methods: This single-center study of 763 adults with AAOCA consisted of 620 patients from our cardiac catheterization database (1958-2009) and 273 patients from electronic medical records query (2010-2021). Within left main, anterior descending, circumflex, and right coronary arteries, the CAD stenosis severity, assessed by invasive or computer tomography angiography, was modeled with coronary-level variables (presence of an anomalous origin) and patient-level variables (age, sex, comorbidities, and which of the four coronaries was anomalous). Results: Of the 763 patients, 472 (60%) had obstructive CAD, of whom, 142/472 (30%) had obstructive CAD only in the anomalous coronary. Multivariable modeling showed similar CAD stenosis severity between coronaries with anomalous versus normal origins (P = .8). Compared with AAOCA of other coronaries, the anomalous circumflex was diagnosed at older ages (59.7 ± 11.1 vs 54.3 ± 15.8 years, P < .0001) and was associated with increased stenosis in all coronaries (odds ratio, 2.7; 95% confidence interval, 2.2-3.4, P < .0001). Conclusions: Among adults diagnosed with AAOCA, the anomalous origin did not appear to increase the severity of CAD within the anomalous coronary. In contrast to the circumflex, AAOCA of the other vessels may contribute a greater ischemic burden when they present symptomatically at younger ages with less CAD. Future research should investigate the interaction between AAOCA, CAD, and ischemic risk to guide interventions.

Pandemic Superimposed on Epidemic: Covid-19 Disparities in Black Americans.

Health and healthcare disparities are variances in the health of a population or the care rendered to a population. Disparities result in a disproportionately higher prevalence of disease or lower standard of care provided to the index group. Multiple theories exist regarding the genesis of this disturbing finding. The COVID-19 pandemic has had the unfortunate effect of amplifying health inequity in vulnerable populations. African Americans, who make up approximately 12% of the US population are reportedly being diagnosed with COVID-19 and dying at disproportionately higher rates. Viewed holistically, multiple factors are contributing to the perfect storm: 1) Limited availability of public testing, 2) A dramatic increase in low wage worker unemployment/health insurance loss especially in the service sector of the economy, 3) High rates of preexisting chronic disease states/reduced access to early healthcare and 4) Individual provider and structural healthcare system bias. Indeed, COVID-19 represents a pandemic superimposed on a historic epidemic of racial health inequity and healthcare disparities. Therapeutic solutions are not expected in the near term. Thus, identifying the genesis and magnitude of COVID-19's impact on African American communities is the requisite first step toward crafting an immediate well designed response. The mid and long term approach should incorporate population health based tactics and strategies.

Children with Narcolepsy type 1 have increased T-cell responses to orexins.

Narcolepsy type 1 (NT1) is caused by severe loss of the orexin neurons, and is highly associated with HLA DQB1*06:02. Using intracellular cytokine staining, we observed a higher frequency of IFN-γ- and TNF-α-producing CD4+ and CD8+ T-cells in response to orexins in 27 children with NT1 compared to 15 healthy control children. Conversely, no such difference was observed between 14 NT1 and 16 HC adults. In addition, priming with flu peptides amplified the T-cell response to orexins in children with NT1. Our data suggests that NT1 may be caused by an autoimmune T-cell response to orexins, possibly triggered by flu antigens.