Palliation of a Heterotaxy Single Ventricle Neonate with Pulmonary Atresia and Obstructed TAPVR.

Patients born with obstructed total anomalous pulmonary venous return have a high risk of morbidity and mortality in the neonatal period, which only increases when combined with single ventricle physiology and non-cardiac congenital anomalies such as heterotaxy syndrome. Despite advances in management of congenital heart disease, surgery within the first weeks of life to repair the pulmonary venous connection and establish pulmonary blood flow with a systemic-to-pulmonary shunt has historically led to disappointing outcomes. A multidisciplinary approach with pediatric interventional cardiology and cardiac surgery is required to reduce morbidity and mortality in this extremely high-risk patient population. Extending the time between birth and cardiac surgery can lessen postoperative complications and mortality risk, especially in patients with abnormal thoracoabdominal relationships. Our team was able to successfully utilize transcatheter stent placement in a vertical vein and patent ductus arteriosus to delay and stage cardiac surgeries in an infant born with obstructed total anomalous pulmonary venous return, unbalanced atrioventricular septal defect with pulmonary atresia and heterotaxy, thus reducing the morbidity and mortality associated with this diagnosis.

X-ray fused with MRI guidance of pre-selected transcatheter congenital heart disease interventions.

OBJECTIVES: To determine whether X-ray fused with MRI (XFM) is beneficial for select transcatheter congenital heart disease interventions. BACKGROUND: Complex transcatheter interventions often require three-dimensional (3D) soft tissue imaging guidance. Fusion imaging with live X-ray fluoroscopy can potentially improve and simplify procedures. METHODS: Patients referred for select congenital heart disease interventions were prospectively enrolled. Cardiac MRI data was overlaid on live fluoroscopy for procedural guidance. Likert scale operator assessments of value were recorded. Fluoroscopy time, radiation exposure, contrast dose, and procedure time were compared to matched cases from our institutional experience. RESULTS: Forty-six patients were enrolled. Pre-catheterization, same day cardiac MRI findings indicated intervention should be deferred in nine patients. XFM-guided cardiac catheterization was performed in 37 (median age 8.7 years [0.5-63 years]; median weight 28 kg [5.6-110 kg]) with the following prespecified indications: pulmonary artery (PA) stenosis (n = 13), aortic coarctation (n = 12), conduit stenosis/insufficiency (n = 9), and ventricular septal defect (n = 3). Diagnostic catheterization showed intervention was not indicated in 12 additional cases. XFM-guided intervention was performed in the remaining 25. Fluoroscopy time was shorter for XFM-guided intervention cases compared to matched controls. There was no significant difference in radiation dose area product, contrast volume, or procedure time. Operator Likert scores indicated XFM provided useful soft tissue guidance in all cases and was never misleading. CONCLUSIONS: XFM provides operators with meaningful three-dimensional soft tissue data and reduces fluoroscopy time in select congenital heart disease interventions.

Management of a large atrial septal occluder embolized to the left ventricular outflow tract without the use of cardiac surgery.

Transcatheter closure of secundum-type atrial septal defects (ASDs) using the AMPLATZER™ Septal Occluder (ASO) has been in use for more than a decade since its US Food and Drug Administration approval in 2001. Device embolization remains an uncommon complication, which can sometimes occur after the initial deployment. Previous reports of ASO devices embolized to the left ventricle have primarily been managed by open-heart surgical retrieval. We present a case of an ASO device embolized to the left ventricular outflow tract (LVOT) 18 hr after initial implantation, which was successfully retrieved percutaneously, followed by successful closure of the ASD using a larger device.

Renal artery stenosis in children: therapeutic percutaneous balloon and stent angioplasty.

BACKGROUND: Renal artery stenosis (RAS) accounts for 10 % of cases of systemic hypertension in children. Initial management involves anti-hypertensive therapy. Percutaneous interventions are documented for the treatment of RAS in the adult population. In children, case reports suggest benefit. METHODS: This is a retrospective analysis of consecutive patients referred for catheterization for RAS between 2002 and 2010 at a single institution. Recorded variables included: age, weight, systemic blood pressure, minimal luminal diameter, interventional devices, antihypertensive medications, contrast volume, and complications. RESULTS: Twelve patients (median age 8.2, IQR 6-12.4 years); median weight 42.8 kg, IQR: 25-47.4 kg) were referred for renal artery catheterization and underwent percutaneous intervention. Overall, minimal luminal diameter (MLD) increased by 1.2 ± 0.9 mm for all patients (p < 0.05) and by 1.3 ± 0.9 mm for post-renal transplant patients (p < 0.05). Only stent angioplasty patients demonstrated significant improved blood pressure (p < 0.05). One patient had stent thrombosis requiring re-intervention with repeat balloon angioplasty. CONCLUSIONS: This retrospective analysis suggests that percutaneous intervention might play a role in the management of RAS, with an improvement in MLD in children with RAS. Transcatheter intervention is technically feasible with low morbidity. A prospective, longitudinal study is warranted to compare standard medical therapy with percutaneous interventions.

Percutaneous management of coronary sinus atrial septal defect: two cases representing the spectrum for device closure and a review of the literature.

Coronary sinus atrial septal defects are the rarest defects of the atrial septum comprising <1% of the five different types of atrial septal defects. Despite the widespread adoption of percutaneous device closure of secundum atrial septal defects, the published experience with percutaneous device closure of coronary sinus atrial septal defects is limited to only a few isolated case reports because of uncertainty regarding safety and efficacy. Open-heart surgical repair remains the treatment of choice for coronary sinus atrial septal defects, although this may not be the only treatment option in selected cases. Herein we describe our own experience with two patients with different clinical presentations and our method of successful percutaneous coronary sinus atrial septal defect closure in each. We then present a review of the anatomic spectrum of coronary sinus atrial septal defects along with a review of contemporary surgical and percutaneous device treatment.

Percutaneous endovascular intervention for left ventricular assist device outflow graft obstruction: A single-center experience.

BACKGROUND: Outflow graft obstruction (OGO) is an uncommon yet life-threatening complication in patients with left ventricular assist devices (LVADs). In this retrospective, single-center case series, we identify the baseline demographics and presenting features of patients who develop LVAD OGO and the procedural details and outcomes surrounding percutaneous endovascular intervention (PEI). METHODS: We conducted a retrospective review of patients with LVADs at our institution between January 2010 and February 2023 who developed OGO and were treated with PEI. Details of the PEI including procedure time, fluoroscopy time, contrast use, stent size, number of stents, change in gradient, and change in flow after intervention were collected. RESULTS: A total of 12 patients who had 14 cases of OGO were identified from January 2010 to February 2023. The average age at presentation was 64.78 years. Nine of the 14 cases occurred in male patients. Eleven of the 14 cases occurred with Heartware devices (2 recurrences), 2 in Heartmate 2 and 1 in Heartmate 3. Notable procedural details include a mean procedure time of 90.86 min and mean contrast use of 162.5 mL. The initial gradient across the OGO was reduced by an average of 72 %, to a mean post-PEI of 11.57 mmHg. The average number of stents to achieve this gradient was around 2.08, with the most common stent diameter being 10 mm. Thirty-day mortality after PEI was 7 % (1/14) in this high-risk patient population. CONCLUSION: In our single-center experience, PEI can be a safe and effective treatment for LVAD OGO.

Gender disparities related to clinical characteristics and outcomes of patients undergoing transseptal procedures.

PURPOSE: Explore gender disparities in patients undergoing transseptal puncture (TSP) for selected transcatheter cardiac intervention procedures. METHODS: Patients who underwent TSP from January 2015 through September 2021 were reviewed. Primary outcomes were procedural and in-hospital major adverse events. Secondary endpoints were procedural success and hospitalization length of stay (LOS) >1 day. Unadjusted and multivariable-adjusted logistic regression analyses were performed to assess gender differences for in-hospital adverse events. RESULTS: The study cohort comprised 510 patients (mean [SD] age, 74 [14.0] years); 246 women (48 %) underwent TSP for left atrial appendage occlusion (LAAO) or transcatheter edge-to-edge-repair (TEER). Compared with men, women were younger, had higher CHA2DS2-VASc scores, and were more likely to have had a prior ischemic stroke, but were less likely to have paroxysmal atrial fibrillation. After multivariable adjustment, there were no differences between genders in aborted or canceled procedures (odds ratio [OR]: 0.43; 95 % confidence interval [CI]: 0.10-1.96; p = 0.277), any adverse events (OR: 1.00; 95 % CI: 0.58-1.70; p = 0.98), major adverse events (OR: 1.60; 95 % CI: 0.90-2.80; p = 0.11), or death (OR: 1.00; 95 % CI: 0.20-5.00; p = 0.31). Subgroup analysis for LAAO procedures showed that at 30 days, women had higher rates of adverse events, major adverse cardiac events, and LOS >1 day. CONCLUSIONS: Men and women showed no differences in procedural success and in-hospital adverse outcomes in unadjusted analysis and after multivariable adjustment, despite women having a higher risk profile among patients undergoing TSP. However, compared with men, women undergoing LAAO experienced a higher rate of in-hospital adverse events irrespective of TSP.

Stent angioplasty to relieve left pulmonary artery obstruction caused by patent ductus arteriosus device occlusion: bipartisan teamwork by two interventional devices.

A 7-month-old patient in congestive heart failure due to a moderate sized patent ductus arteriosus (PDA) underwent uncomplicated implantation of an Amplatzer Ductal Occluder (ADO1). Two months after percutaneous device PDA closure, left pulmonary artery (LPA) stenosis was discovered. Rather than spontaneous improvement as reported in previous cases, our patient's LPA stenosis progressed in severity 7 months after ADO1 placement. A catheterization demonstrated a 32 mm Hg peak gradient from her main pulmonary artery to her LPA. She underwent successful stent angioplasty of her LPA with an excellent result and preserved PDA closure. This case demonstrates that stent angioplasty is a feasible an effective method of relieving LPA obstruction caused by a PDA occluder device. Additionally, despite slight deflection by the stent, the ADO1 device continued to provide complete ductal closure. Stent angioplasty should be considered in patients who have LPA stenosis caused by ADO1 occluder device that does not improve over time.

Transthoracic delivery of large devices into the left ventricle through the right ventricle and interventricular septum: preclinical feasibility.

BACKGROUND: We aim to deliver large appliances into the left ventricle through the right ventricle and across the interventricular septum. This transthoracic access route exploits immediate recoil of the septum, and lower transmyocardial pressure gradient across the right versus left ventricular free wall. The route may enhance safety and allow subxiphoid rather than intercostal traversal. METHODS: The entire procedure was performed under real-time CMR guidance. An "active" CMR needle crossed the chest, right ventricular free wall, and then the interventricular septum to deliver a guidewire then used to deliver an 18Fr introducer. Afterwards, the right ventricular free wall was closed with a nitinol occluder. Immediate closure and late healing of the unrepaired septum and free wall were assessed by oximetry, angiography, CMR, and necropsy up to four weeks afterwards. RESULTS: The procedure was successful in 9 of 11 pigs. One failed because of refractory ventricular fibrillation upon needle entry, and the other because of inadequate guidewire support. In all ten attempts, the right ventricular free wall was closed without hemopericardium. There was neither immediate nor late shunt on oximetry, X-ray angiography, or CMR. The interventricular septal tract fibrosed completely. Transventricular trajectories planned on human CT scans suggest comparable intracavitary working space and less acute entry angles than a conventional atrial transseptal approach. CONCLUSION: Large closed-chest access ports can be introduced across the right ventricular free wall and interventricular septum into the left ventricle. The septum recoils immediately and heals completely without repair. A nitinol occluder immediately seals the right ventricular wall. The entry angle is more favorable to introduce, for example, prosthetic mitral valves than a conventional atrial transseptal approach.

Dexmedetomidine for patients undergoing diagnostic cardiac procedures: a noninferiority study.

When anesthetizing children with congenital heart disease for diagnostic cardiac catheterization, anesthesiologists and cardiologists seek to use anesthetic regimens that yield minimal hemodynamic changes and allow for spontaneous ventilations. Recently, dexmedetomidine has been used as an anesthesia adjunct because of its sedative and analgesic properties and minimal ventilatory depressive effects. We tested the hypothesis that the combination of sevoflurane and dexmedetomidine is non-inferior to sevoflurane alone as it refers to hemodynamic measurements during diagnostic cardiac catheterization in children with a transplanted heart, one ventricle (Fontan procedure), or normal cardiac physiology. Patients were anesthetized with inhalation of sevoflurane in nitrous oxide/oxygen and, after baseline hemodynamic measurements, successive boluses of dexmedetomidine followed by continuous infusion were administered. In this study, non-inferiority was shown when differences at steady-state (dexmedetomidine + sevoflurane) compared to baseline (sevoflurane alone) and its associated 95% confidence interval fell completely within the range of plus or minus 20%. Forty-one (26 normal physiology, 9 cardiac transplantation, and 6 Fontan) patients were enrolled. Non-inferiority of sevoflurane + dexmedetomidine compared with sevoflurane alone was shown for heart rate, but not for arterial blood pressure in patients with normal and cardiac transplant physiology. In patients with normal cardiac physiology, non-inferiority was demonstrated for bispectral index. Therefore, while the lack of depressive respiratory effects and non-inferiority for heart rate are desirable, the lack of non-inferiority of dexmedetomidine + sevoflurane combination for arterial blood pressure do not justify the routine use of this combination compared with sevoflurane alone for children with congenital heart disease undergoing cardiac catheterization.

Active delivery cable tuned to device deployment state: enhanced visibility of nitinol occluders during preclinical interventional MRI.

PURPOSE: To develop an active delivery system that enhances visualization of nitinol cardiac occluder devices during deployment under real-time magnetic resonance imaging (MRI). MATERIALS AND METHODS: We constructed an active delivery cable incorporating a loopless antenna and a custom titanium microscrew to secure the occluder devices. The delivery cable was tuned and matched to 50Ω at 64 MHz with the occluder device attached. We used real-time balanced steady state free precession in a wide-bore 1.5T scanner. Device-related images were reconstructed separately and combined with surface-coil images. The delivery cable was tested in vitro in a phantom and in vivo in swine using a variety of nitinol cardiac occluder devices. RESULTS: In vitro, the active delivery cable provided little signal when the occluder device was detached and maximal signal with the device attached. In vivo, signal from the active delivery cable enabled clear visualization of occluder device during positioning and deployment. Device release resulted in decreased signal from the active cable. Postmortem examination confirmed proper device placement. CONCLUSION: The active delivery cable enhanced the MRI depiction of nitinol cardiac occluder devices during positioning and deployment, both in conventional and novel applications. We expect enhanced visibility to contribute to the effectiveness and safety of new and emerging MRI-guided treatments.

Transhepatic Access: Alternative Approach for Right Heart Catheterization and Pulmonary Angiography.

Peripheral vascular disease, chronic large-bore venous access, and small body habitus can limit traditional venous access methods for right heart catheterization. We present a patient with chronic renal failure, small body habitus due to developmental delay, and multiple central vein stenoses due to chronic indwelling catheters and heparin-induced thrombocytopenia, who required right heart catheterization for workup of possible intracardiac shunt, pulmonary hypertension, and pulmonary embolism. We performed right heart catheterization and pulmonary angiography via transhepatic approach. The hepatic vein was accessed with a Chiba biopsy needle, and hepatic vein access was confirmed by contrast injection under fluoroscopy. A long 8-French sheath was advanced to the cavoatrial junction, and a balloon-tipped right heart catheter was used for pressure measurement, serial oxygen saturations, and angiography. Pulmonary pressures and angiography were normal, and there was no intracardiac shunt. Access-tract hemostasis was achieved with vascular plugs, embolization coils, and manual pressure. We demonstrate successful right heart catheterization and pulmonary angiography via transhepatic access. This is a valuable alternative access for patients with limited traditional options.

Characterizing heterogeneous cellular responses to perturbations.

Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

Catheter Selection and Angiographic Views for Anomalous Coronary Arteries: A Practical Guide.

Although congenital coronary artery anomalies are relatively rare, they are the second most common cause of sudden cardiac death among young athletes. When encountered in the cardiac catherization laboratory, they are often challenging to selectively engage, requiring multiple catheters, plus increased contrast volume and radiation exposure. In the setting of acute coronary syndromes, it is not infrequent that percutaneous intervention is delayed because of the inability to engage an anomalous coronary artery. The aim of this review is to provide a comprehensive and concise overview of coronary artery anomalies, with particular attention to diagnostic and guide catheter selection for each type of anomaly and recommendations on how to recognize the vessel course angiographically.

Stenting of aortic coarctation: acute, intermediate, and long-term results of a prospective multi-institutional registry--Congenital Cardiovascular Interventional Study Consortium (CCISC).

INTRODUCTION: Since the 1980s, stent implantation has evolved as an important therapeutic strategy for coarctation of the aorta. However, available data is frequently flawed by short follow-up, lack of adequate follow-up imaging, and retrospective nature of data collection. METHODS: Data was prospectively collected using a multicenter registry congenital cardiovascular interventional study consortium (CCISC). Between 2000 and 2009, 302 patients from 34 centers with a median weight of 58 kg underwent stent implantation for coarctation. Eligible patients (44%) completed intermediate follow-up (3-18 months) with integrated imaging (cath, CT, MRI), whereas 21% completed long-term follow-up (>18-60 months). Procedural success was defined as UL/LL systolic gradient of less than 20 mm Hg, lack of significant recurrent obstruction, and freedom from unplanned repeat intervention. RESULTS: Acute procedural success was 96%. Cumulative intermediate success was 86%, and cumulative long-term success was 77%. Unplanned repeat interventions were required in 4%, and aortic wall complications were seen in 1% of patients (dissection n = 1 and aneurysm n = 3). Other adverse events (n = 15) occurred mainly acutely and included technical complications such as stent malposition (n = 9). At long-term follow-up, 23% of patients continued to have systolic blood pressure above the 95th centile, 9% had an upper-to-lower limb blood pressure gradient in excess of 20 mm Hg, and 32% were taking antihypertensive medication. CONCLUSIONS: This study documented acute, intermediate, and long-term outcome data comparable or superior with other surgical or interventional series. However, even with successful initial stent therapy, patients continue to require long-term follow-up and have associated long-term morbidity, relating to aortic wall complications, systemic hypertension, recurrent obstruction as well as need for repeat intervention.

Detection of carbon monoxide during routine anesthetics in infants and children.

BACKGROUND: Carbon monoxide (CO) can be produced in the anesthesia circuit when inhaled anesthetics are degraded by dried carbon dioxide absorbent and exhaled CO can potentially be rebreathed during low-flow anesthesia. Exposure to low concentrations of CO (12.5 ppm) can cause neurotoxicity in the developing brain and may lead to neurodevelopmental impairment. In this study, we aimed to quantify the amount of CO present within a circle system breathing circuit during general endotracheal anesthesia in infants and children with fresh strong metal alkali carbon dioxide absorbent and define the variables associated with the levels detected. METHODS: Fifteen infants and children (aged 4 months to 8 years) undergoing mask induction followed by general endotracheal anesthesia were evaluated in this observational study. CO was measured in real time from the inspiratory limb of the anesthesia circuit every 5 minutes for 1 hour during general anesthesia. Carboxyhemoglobin (COHb) levels were measured at the 1-hour time point and compared with baseline. RESULTS: CO was detected in all patients older than 2 years (0-18 ppm, mean 3.7 +/- 4.8 ppm) and rarely detected in patients younger than 2 years (0-2 ppm, mean 0.2 +/- 0.6 ppm). Only the relationship between CO concentration and fresh gas flow to minute ventilation ratio (FGF:(.)VE) remained significant after adjustment in longitudinal regression analysis (P < 0.001). Although not powered to determine such a relationship, CO levels were weakly associated with the use of desflurane and female sex. There was no significant association between CO concentration and anesthetic concentration. Baseline COHb levels were higher in children younger than 2 years and decreased significantly at the 1-hour time point compared with baseline and children older than 2 years. However, COHb levels increased significantly from baseline in a predictable manner consistent with CO exposure in children older than 2 years. FGF:(.)VE correlated significantly with change in COHb using simple linear regression (r = 0.62; P < 0.02). CONCLUSIONS: CO was detected routinely during general anesthesia in infants and children when FGF:(.)VE was <1. Peak CO levels measured in the anesthesia breathing circuit were in the range thought to impair the developing brain. Further study is required to identify the source of CO detected (CO produced by degradation of volatile anesthetic versus rebreathing CO from endogenous sources or both). However, these findings suggest that avoidance of low-flow anesthesia will prevent rebreathing of exhaled CO, and use of carbon dioxide absorbents that lack strong metal hydroxide could limit inspired CO if detection was attributable to degradation of volatile anesthetic.

Comparative analysis of the human serine hydrolase OVCA2 to the model serine hydrolase homolog FSH1 from S. cerevisiae.

Over 100 metabolic serine hydrolases are present in humans with confirmed functions in metabolism, immune response, and neurotransmission. Among potentially clinically-relevant but uncharacterized human serine hydrolases is OVCA2, a serine hydrolase that has been linked with a variety of cancer-related processes. Herein, we developed a heterologous expression system for OVCA2 and determined the comprehensive substrate specificity of OVCA2 against two ester substrate libraries. Based on this analysis, OVCA2 was confirmed as a serine hydrolase with a strong preference for long-chain alkyl ester substrates (>10-carbons) and high selectivity against a variety of short, branched, and substituted esters. Substitutional analysis was used to identify the catalytic residues of OVCA2 with a Ser117-His206-Asp179 classic catalytic triad. Comparison of the substrate specificity of OVCA2 to the model homologue FSH1 from Saccharomyces cerevisiae illustrated the tighter substrate selectivity of OVCA2, but their overlapping substrate preference for extended straight-chain alkyl esters. Conformation of the overlapping biochemical properties of OVCA2 and FSH1 was used to model structural information about OVCA2. Together our analysis provides detailed substrate specificity information about a previously, uncharacterized human serine hydrolase and begins to define the biological properties of OVCA2.

Severe tricuspid valve stenosis secondary to pacemaker leads presenting as ascites and liver dysfunction: a complex problem requiring a multidisciplinary therapeutic approach.

Tricuspid stenosis secondary to ventricular pacemaker leads is uncommon. We present a unique case of iatrogenic tricuspid stenosis secondary to fusion of the valve leaflets to transvenous implanted pacing leads. This occurred in an adult with childhood repaired Tetralogy of Fallot and high grade surgical heart block following multiple pacemaker procedures. The case was complicated by superior vena cava (SVC) and innominate vein stenosis secondary to implanted pacing leads, severe tricuspid valve (TV) stenosis, perforation of the heart by one of the implanted transvenous ventricular pacing leads, prolapse of the transvenous atrial pacing lead into the right ventricle, and unusual coronary sinus anatomy. We describe a multidisciplinary approach to management.