Mechanical circulatory support (MCS) restores flow using blood pumps with ventriculoarterial (VA) uncoupling and unloading. Blood contact contributes to bleeding, thromboembolism, and infection. Direct mechanical ventricular actuation (DMVA) maintains VA coupling and augments ventricular expansion and end-diastolic geometry. These effects differ from conventional MCS. This study evaluated postsupport cardiac function following DMVA compared with a clinically available left ventricular assist device (LVAD) in a chronic heart failure (HF) model. Chronic HF was induced in adult canines using rapid ventricular pacing or serial coronary microembolization. Animals were assigned to 2 hours of DMVA or LVAD. Hemodynamic measurements, pressure-volume analyses, and dobutamine stress responses were assessed postsupport. Support was successfully maintained in all animals. After device removal, DMVA was associated with significant improvements in preload-recruitable stroke work and end-diastolic pressure-volume relationships. Dobutamine responsiveness was preserved after DMVA but blunted following LVAD. No postsupport improvements in systolic or diastolic function were observed after LVAD support. Direct mechanical ventricular actuation resulted in salutary effects on systolic and diastolic function in chronically failing hearts, whereas LVAD support did not. Unlike LVAD support, DMVA maintains VA coupling and exerts salutary effects on the failing heart, notably improving diastolic function. Synchronous DMVA support may further enhance these effects.

Unfractionated heparin has long been the conventional anticoagulant for pediatric mechanical circulatory support (MCS). As bivalirudin has gained traction in ventricular assist devices (VAD) management, its role in extracorporeal membrane oxygenation (ECMO) is less well defined. We conducted a retrospective, single-center study investigating the safety and outcomes of bivalirudin, a direct thrombin inhibitor, compared to heparin in a pediatric cardiothoracic intensive care unit (ICU). Outcomes included thrombotic and bleeding events, neurologic complications, survival to decannulation/transplant, and discharge. There were 122 patients for a total of 130 ECMO runs. Bivalirudin was used in 30% of ECMO runs, and bivalirudin demonstrated a 33% risk reduction in major bleeding (95% confidence interval: [−49.9, −16.0], p < 0.01) with fewer circuit component changes per 10 ECMO days (0.64 [0.4–0.7] vs . 2.6 [1.9–5.0], p < 0.01). Extracorporeal membrane oxygenation patients on bivalirudin had greater odds of survival to decannulation (odds ratio [OR]: 3.7 [1.4, 11.5], p = 0.01) and discharge (OR: 3.1 [1.4, 7.2], p < 0.01). The use of bivalirudin for ECMO in the pediatric cardiothoracic ICU population appears safe with fewer major bleeding and thrombotic complications and may be associated with improved survival compared to heparin.

Actin polymerization is often associated with membrane proteins containing capping-protein-interacting (CPI) motifs, such as capping protein, Arp2/3, myosin I linker (CARMIL), CD2AP, and WASHCAP/Fam21. CPI motifs bind directly to actin-capping protein (CP), and this interaction weakens the binding of CP to barbed ends of actin filaments, lessening the ability of CP to functionally cap those ends. The protein V-1/myotrophin binds to the F-actin-binding site on CP and sterically blocks CP from binding barbed ends. CPI-motif proteins also weaken the binding between V-1 and CP, which decreases the inhibitory effects of V-1, thereby freeing CP to cap barbed ends. Here, we address the question of whether CPI-motif proteins on a surface analogous to a membrane lead to net activation or inhibition of actin assembly nucleated by Arp2/3 complex. Using reconstitution with purified components, we discovered that CARMIL at the surface promotes and enhances actin assembly, countering the inhibitory effects of V-1 and thus activating CP. The reconstitution involves the presence of an Arp2/3 activator on the surface, along with Arp2/3 complex, V-1, CP, profilin, and actin monomers in solution, recreating key features of cell physiology.

Importance Patients with underlying cardiac disease form a considerable proportion of pediatric patients who experience in-hospital cardiac arrest. In pediatric patients after cardiac surgery, CPR with abdominal compressions alone (AC-CPR) may provide an alternative to standard chest compression CPR (S-CPR) with additional procedural and physiologic advantages. Objective Quantitatively describe hemodynamics during cardiopulmonary resuscitation (CPR) and outcomes of infants who received only abdominal compressions (AC-CPR). Design This is a sub-group analysis of the prospective, observational cohort from the ICU-RESUS trial NCT028374497. Setting & Patients A single site quaternary care pediatric cardiothoracic intensive care unit enrolled in the ICU-RESUS trial. Patients less than 1 year of age with congenital heart disease who required compressions during cardiac arrest. Interventions Use of AC-CPR during cardiac arrest resuscitation. Measurements and Main Results Invasive arterial line waveforms during CPR were analyzed for 11 patients (10 surgical cardiac and 1 medical cardiac). Median weight was 3.3 kg [IQR 3.0, 4.0]; and median duration of CPR was 5.0 [3.0, 20.0] minutes. Systolic (median 57 [IQR 48, 65] mmHg) and diastolic (median 32 [IQR 24, 43] mmHg) blood pressures were achieved with a median rate of 114 [IQR 100, 124] compressions per minute. Return of spontaneous circulation was obtained in 9 of 11 (82%) patients; 2 patients (18%) were cannulated for extracorporeal cardiopulmonary resuscitation (ECPR) and 6 (55%) survived to hospital discharge with favorable neurologic outcome. Conclusions AC-CPR may offer an alternative method to maintain perfusion for infants who experience cardiac arrest. This may have particular benefit in pediatric patients after cardiac surgery for whom external chest compressions may be harmful due to anatomic and physiologic considerations.

Surgical intervention is often used in the management of heart failure in patients with adult congenital heart disease. This review addresses anatomic variations and complications due to prior surgical interventions, including sternal reentry, collateral vessels, and the neo-aortic root after the Damus-Kaye-Stansel procedure. Surgical considerations for systemic atrioventricular valvular surgery, Fontan revision, and advanced heart failure therapies including ventricular assist devices, heart transplant, and combined heart-liver transplant are discussed, with a focus on unique patient populations including those with systemic right ventricles and those with Fontan circulation.

Cannula stabilization for extracorporeal membrane oxygenation (ECMO) is important for patient mobilization and rehabilitation. Limitations to mobilization on ECMO include staff discomfort and cannula instability. We utilized the technique of negative pressure therapy for ECMO cannula stabilization to improve mobilization. Negative pressure therapy for ECMO cannula stabilization can be utilized safely for a variety of cannulation sites in any patient age from newborns to adults. This wound management strategy may facilitate patient mobilization and rehabilitation therapies in addition to extending cannula site duration.

Background: Infective endocarditis (IE) is an uncommon disease in children that, when present, is accompanied by significant morbidity and mortality. The presence of congenital heart disease often complicates management. The aim of the present study is to describe the characteristics and outcomes of children undergoing sur-gery for IE.Methods: A retrospective chart review from 2004 to 2020 was conducted to iden-tify consecutive patients younger than age 20 years with IE undergoing surgery.Results: A total of 94 patients with IE were identified, of whom 47 underwent sur-gery at a median age of 16.7 years. Thirty-one patients (65.95%) had congenital heart disease. Vegetation and embolic phenomena occurred in 41 and 29 patients (87.23% and 61.7%), respectively, with the brain as most common location (57.1%). Native valve involvement had a greater tendency to embolize (P<.001). Staphylo-coccus spp was the most common organism (49%). The mitral valve was the most affected (31.9%). Seven (14.9%) patients had multivalvar involvement and valve replacement was the most common procedure performed (37 patients; 78.7%). There were 3 operative deaths (6.4%). Median length of hospital stay was 21 days. Risk factors for prolonged hospital stay were time to surgery in days (P<.001) and native valvar involvement (P 1/4 .05). Five patients (10.6%) had post-operative recurrent IE. Survival at 1 and 5 years was 93.6% and 89.4%, respectively.Conclusions: Children with IE can undergo surgery with acceptable results. The morbidity, but not mortality, is driven by embolic complications. Staphylococcus spp and native valve involvement are significant risk factors. (J Thorac Cardiovasc Surg 2023;165:275-84)

Objective: Pulmonary artery reconstruction during comprehensive stage 2 (CS2) procedure can be challenging. Since 2017, we have employed preemptive left pulmonary artery (LPA) stenting. We hypothesized that LPA stenting promotes adequate growth and without compromising Fontan candidacy. Herewith, we report our midterm results. Methods: From 2002 to 2020, 159 patients underwent CS2. Patients were divided as follows: no stent (n = 122; Group 1) and perioperative LPA stent (n = 37; Group 2). Group 2 was subdivided according to unplanned stent (n = 17; Group 2a) or preemptive stent (n = 20; Group 2b). Relevant perioperative data was reviewed. Nonparametric statistics were utilized. Results: Median age and weight at surgery and hospital length of stay after CS2 did not differ between groups. Median cardiopulmonary bypass and crossclamp times were significantly greater in Group 1 (265 vs 243 minutes [P = .021] and 46 vs 26 minutes [P = .008]). In-hospital mortality was similar between Groups 1 and 2 (9.0% vs 18.9%, respectively [P = .1348]). Group 2b demonstrated a superior survival compared to Group 2a (P = .0335) but not Group 1 (P > .9999). Preemptive stenting significantly increased median hilar LPA diameter at CS2 exit angiogram compared with no stenting (P < .0001). Groups 2a and 2b significantly increased the pre-Fontan diameter of the hilar LPA when compared with Group 1 (6.1 and 6.8 vs 5.7 mm, respectively [P < .0001]). A further 120 patients underwent Fontan operation (75%). Median follow-up for Groups 1 and 2 were 7.4 and 3.0 years, respectively. Conclusions: Perioperative LPA stenting during CS2 does not adversely affect pulmonary growth. Preemptive stenting seems advantageous for LPA growth in preparation for Fontan completion.

The Crescent dual lumen right atrial (RA) cannula has recently been introduced for the support of pediatric patients in need of venovenous extracorporeal membrane oxygenation (VV ECMO) support. We present the first pediatric case series illustrating utility of the Crescent RA cannula in the pediatric patient population at a single institution over a 10 month period. From December 2021 to August 2022, six pediatric patients were adequately supported on seven VV ECMO runs at our institution with the Crescent RA cannula. ECMO cannulation, circuit design, anticoagulation management, ECMO circuit pressures, flow rates, and recirculation were similar to our standard of care for VV ECMO. The Crescent RA cannula can be used safely and effectively to provide adequate support for pediatric patients requiring VV ECMO.

Introduction:Patients following the Fontan procedure have a physiology that results in prolonged pleural effusion, often delaying hospital discharge. The hospital length of stay (LOS) of patients following the Fontan procedure at our institution was significantly longer than the Society of Thoracic Surgery benchmark. This quality improvement project aimed to decrease hospital LOS in patients following the Fontan procedure from a baseline of 23 days to 7 days by January 1, 2021, and sustain indefinitely. Methods:We implemented standardized postoperative clinical practice guidelines in April 2020. We designed guidelines using previously published protocols. Key features included an ambulatory PleurX drain (BD, Franklin Lakes, N.J.), diuresis with fluid restriction, and pulmonary vasodilation with supplemental oxygen and sildenafil. All patients were discharged from the hospital with a PleurX drain in place. We compared clinical outcome variables before and after guideline implementation. As a balancing measure, we tracked 30-day readmissions. Results:One hundred seven patients underwent the Fontan procedure before guideline implementation from January 2015 to January 2020, with an average hospital LOS of 23 days. Postguideline implementation, 35 patients underwent the Fontan procedure from April 2020 to July 2022, with an average hospital LOS of 8 days in 2020, which further improved to an average hospital LOS of 7 days. There was no change in 30-day readmission after guideline implementation (24% pre versus 23% post; P = 0.86). Conclusion:Implementing clinical practice guidelines for patients following the Fontan procedure led to an over 50% reduction in hospital LOS without increasing 30-day readmission.

Actin capping protein (CP) can be regulated by steric and allosteric mechanisms. The molecular mechanism of the allosteric regulation at a biophysical level includes linkage between the binding sites for three ligands: F-actin, Capping-Protein-Interacting (CPI) motifs, and V-1/myotrophin, based on biochemical functional studies and solvent accessibility experiments. Here, we investigated the mechanism of allosteric regulation at the atomic level using single-molecule Förster resonance energy transfer (FRET) and molecular dynamics (MD) to assess the conformational and structural dynamics of CP in response to linked-binding site ligands. In the absence of ligand, both single-molecule FRET and MD revealed two distinct conformations of CP in solution; previous crystallographic studies revealed only one. CPI-motif peptide association induced conformational changes within CP that propagate in one direction, while V-1 association induced conformational changes in the opposite direction. Comparing CPI-motif peptides from different proteins, we identified variations in CP conformations and dynamics that are specific to each CPI motif. MD simulations for CP alone and in complex with a CPI motif and V-1 reveal atomistic details of the conformational changes. Analysis of the interaction of CP with wildtype (wt) and chimeric CPI-motif peptides using single-molecule FRET, isothermal calorimetry (ITC) and MD simulation indicated that conformational and affinity differences are intrinsic to the C-terminal portion of the CPI-motif. We conclude that allosteric regulation of CP involves changes in conformation that disseminate across the protein to link distinct binding-site functions. Our results provide novel insights into the biophysical mechanism of the allosteric regulation of CP.

Purpose Donor-derived cell-free DNA (dd-cfDNA) is utilized by some adult lung transplant (LTX) centers as a biomarker of allograft injury or dysfunction. An elevated level of dd-cfDNA may be predictive of acute cellular rejection, antibody mediated rejection (AMR), chronic lung allograft dysfunction , or acute infection. Therefore, dd-cfDNA may have a role as a surrogate test for graft surveillance versus invasive methods including bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBX). While there is an existing body of literature on the role of dd-cfDNA in adult LTX, there is limited understanding of its utility in pediatric patients. Non-invasive testing such as dd-cfDNA may be particularly helpful in young children with inherent challenges with TBBX. Methods Our center performed three bilateral LTX in pediatric patients in which we used dd-cfDNA as an adjunctive method of graft surveillance. All were females, ranging in age from 2-11 years. We obtained dd-cfDNA levels prior to bronchoscopy, BAL and TBBX . The % dd-cfDNA was evaluated in conjunction with clinical symptoms, BAL and TBBX results, and measurements of panel reactive antibody (cPRA) and donor specific antibodies. Results The specific diagnoses leading to transplant were interstitial lung disease related to juvenile idiopathic arthritis, post-infectious bronchiolitis obliterans, and alveolar capillary dysplasia. Results of data collected are summarized in Table 1. Conclusion In this small cohort of pediatric LTX recipients, we found consistently elevated dd-cfDNA levels. In two patients, dd-cfDNA levels did not correlate with histological evidence of graft dysfunction. However, in one patient, sustained high dd-cfDNA values may have signaled ongoing graft injury from AMR as a precedent to the onset of symptoms, subsequent respiratory failure, and ultimate clinical demise. Further investigation into dd-cfDNA as a biomarker of allograft injury in pediatric LTX recipients is needed.

Background:Right ventricular (RV) failure after heart transplantation (HT) is common in those with pretransplantation elevated pulmonary vascular resistance (PVR). Mechanical circulatory support has been used as a bridge to recovery, with mixed outcomes. We describe a patient with failed single-ventricle palliation in whom severe RV failure developed after HT. We review the current literature and outline our post-HT strategy. Methods:An infant with trisomy 21, severely unbalanced right dominant atrioventricular septal defect, and hypoplastic aortic arch was palliated with a hybrid procedure. At 6 months of age, cardiac catheterization measured PVR index of 5.47 Wood units × m2 on maximal medical therapy. The patient was deemed unsuitable for second-stage palliation and underwent HT at 18 months of age. Despite preemptive medical therapies, acute RV failure developed, necessitating extracorporeal membrane oxygenation. He was quickly converted to main pulmonary artery to left atrial cannulation. Unloaded RV function normalized; he was weaned from support and discharged home 5 weeks after HT. Results:Failure of medical therapy in RV failure after HT requires escalation to mechanical circulatory support. We review the literature on RV failure and support after HT. We also describe a novel cannulation strategy to provide a reliable way to directly reduce RV afterload, to allow physiologic training of the right ventricle to a higher PVR, and to maintain normal left ventricular coupling and loading. Conclusions:In pediatric patients with elevated PVR undergoing HT, advanced therapies can be used effectively to treat acute RV failure. Unique cannulation strategies may play a role in improving survival of similar patients.

Dendritic spines are small actin-rich protrusions essential for the formation of functional circuits in the mammalian brain. During development, spines begin as dynamic filopodia-like protrusions that are then replaced by relatively stable spines containing an expanded head. Remodeling of the actin cytoskeleton plays a key role in the formation and modification of spine morphology, however many of the underlying regulatory mechanisms remain unclear. Capping protein (CP) is a major actin regulating protein that caps the barbed ends of actin filaments, and promotes the formation of dense branched actin networks. Knockdown of CP impairs the formation of mature spines, leading to an increase in the number of filopodia-like protrusions and defects in synaptic transmission. Here, we show that CP promotes the stabilization of dendritic protrusions, leading to the formation of stable mature spines. However, the localization and function of CP in dendritic spines requires interactions with proteins containing a capping protein interaction (CPI) motif. We found that the CPI motif-containing protein Twinfilin-1 (Twf1) also localizes to spines where it plays a role in CP spine enrichment. The knockdown of Twf1 leads to an increase in the density of filopodia-like protrusions and a decrease in the stability of dendritic protrusions, similar to CP knockdown. Finally, we show that CP directly interacts with Shank and regulates its spine accumulation. These results suggest that spatiotemporal regulation of CP in spines not only controls the actin dynamics underlying the formation of stable postsynaptic spine structures, but also plays an important role in the assembly of the postsynaptic apparatus underlying synaptic function.

Introduction Overall survival and quality of life has been improving in patients with Duchenne Muscular Dystrophy (DMD) in recent years in the setting of increased treatment with steroids and non-invasive positive pressure. Cardiac disease is now the primary cause of death. Given this shift, advanced cardiac therapies such as ventricular assist devices (VADs) and transplantation are being increasingly considered in selected individuals. Case Report A 9-year-old, ambulatory male with DMD, treated with prednisone and eteplirsen (exon-skipping agent), had rapid progression of ventricular dysfunction over a 6 month period. Given the patient's young age, additional work-up was done to rule out secondary causes. Viral myocarditis labs were unremarkable, but cardiac MRI demonstrated diffuse fibrosis consistent with DMD cardiomyopathy. Despite optimized oral medications, he was hospitalized twice for decompensated heart failure, ultimately requiring intravenous inotropic support. Given that his cardiomyopathy was rapidly progressive and out of proportion to his skeletal muscle disease (remained ambulatory with minimal respiratory muscle weakness), the family opted for VAD implantation with the possibility of subsequent transplant. For successful device placement, a subdiaphragmatic Gore-Tex pericardial pocket extension was created intraoperatively to fit the HeartMate3 LVAD given his small size (45 kg, BSA 1.35/m2). He was extubated on POD#1 and on baseline nocturnal BiPAP by POD#2. He was discharged with improved exercise tolerance and remains ambulatory. The patient was listed for heart transplant 3 months after VAD placement and had no unplanned readmissions. Summary In a carefully selected population of muscular dystrophy patients, even at small size and age, VAD placement can be safely performed with good outcomes. VAD support can be used as destination therapy, or in some cases, as bridge to transplantation. Transplantation may be appropriate for those DMD patients with cardiac disease out of proportion to skeletal and respiratory muscle disease, particularly if they are expected to have reasonable longevity from a non-cardiac standpoint. VAD support may allow for full evaluation of these non-cardiac co-morbidities in the absence of heart failure and thus may be helpful in the proper selection of appropriate transplant candidates.

Button batteries (BBs) are found in many households and are a source of esophageal foreign body in the pediatric population. Upon ingestion, significant caustic injury can occur within 2 hours leading to tissue damage and severe, potentially fatal sequelae. Aortoesophageal fistula (AEF) is a rare complication that nearly always results in mortality. We report a rare case of a toddler who developed an AEF after BB ingestion and survived following staged aortic repair. There should be a high index of suspicion for this complication with the history of BB ingestion and presence of hematemesis, hemoptysis, or melena.