The Impact of Dominant Ventricular Morphology on the Early Postoperative Course After the Glenn Procedure.

The dominant ventricular morphology affects both the early and late outcomes of the Fontan procedure, but its impact on the patients' status immediately following the Glenn procedure is unknown. This study aims to evaluate the effect of the infants' dominant ventricular morphology on the immediate course after undergoing the Glenn procedure. This single-center, retrospective study included all patients who underwent the Glenn procedure between October 2003 and May 2016. The patients were divided into two groups according to their dominant ventricular morphology. Their postoperative records were reviewed and compared. Out of the 89 patients who underwent the Glenn procedure during the study period, 40 (44.9%) had dominant right ventricular morphology and 49 (55.1%) had left ventricular morphology. There were no significant group differences in baseline characteristics or operative data. The maximal postoperative vasoactive-inotropic score was significantly higher and the extent of ventricular dysfunction was significantly more severe in the dominant right ventricle group (P < 0.05). The length of hospitalization was slightly but not significantly longer in the hypoplastic LV group. It is concluded that patients with a dominant LV morphology had a superior ventricular function and required less inotropic support compared to that of a dominant RV morphology in the immediate postoperative course following the Glenn procedure. Survival was not affected by these differences. Further study to determine the pathophysiologic basis for these differences is warranted.

The Fate of Mitral Valve Surgery in the Pediatric Age: A 25-Year Single-Center Experience.

Background: The aim of this study was to evaluate the natural history of patients after mitral valve intervention in the pediatric age. Methods: This is a retrospective study including all patients who underwent mitral valve surgery from 1998 to 2022. The patients' surgical reports, postoperative records, and ambulatory visits were reviewed. The endpoints of the study were survival and freedom from mitral valve reoperation. Results: Of the 70 patients included in the cohort, 61 patients (86.7%) had congenital mitral valve disease, of whom 46 patients (75.4%) had a predominantly mitral regurgitation lesion, and 15 patients (24.6%) had a predominantly mitral stenosis. In the mitral regurgitation group, all of the patients underwent valve repair with an operative mortality of one patient (2.1%), and with median follow-up of 4 years (range, 0.5-13 years), there was 4.3% mortality (n = 2) and 71.2% freedom from reoperation. In the mitral stenosis group, 11 patients underwent mitral valve repair, and 4 patients underwent valve replacement. There was an operative mortality of two patients (13.3%). With a 2-year median follow-up (range: 0.1-23 years), there were no additional mortality cases in the mitral stenosis group. All three patients who survived primary mitral valve replacement (100%) and four patients who survived a primary repair (40.0%) underwent reoperation. Conclusions: This study demonstrates encouraging outcomes for mitral valve repair. The mortality of patients with congenital mitral valve disease may also be related to a difficult postoperative course, rather than the MV lesion itself.

Egr1 regulates regenerative senescence and cardiac repair.

Senescence plays a key role in various physiological and pathological processes. We reported that injury-induced transient senescence correlates with heart regeneration, yet the multi-omics profile and molecular underpinnings of regenerative senescence remain obscure. Using proteomics and single-cell RNA sequencing, here we report the regenerative senescence multi-omic signature in the adult mouse heart and establish its role in neonatal heart regeneration and agrin-mediated cardiac repair in adult mice. We identified early growth response protein 1 (Egr1) as a regulator of regenerative senescence in both models. In the neonatal heart, Egr1 facilitates angiogenesis and cardiomyocyte proliferation. In adult hearts, agrin-induced senescence and repair require Egr1, activated by the integrin-FAK-ERK-Akt1 axis in cardiac fibroblasts. We also identified cathepsins as injury-induced senescence-associated secretory phenotype components that promote extracellular matrix degradation and potentially assist in reducing fibrosis. Altogether, we uncovered the molecular signature and functional benefits of regenerative senescence during heart regeneration, with Egr1 orchestrating the process.

Novel cfDNA Methylation Biomarkers Reveal Delayed Cardiac Cell Death after Open-heart Surgery.

The use of cardiopulmonary bypass (CPB) is thought to cause delayed cardiac damage. DNA methylation-based liquid biopsies are novel biomarkers for monitoring acute cardiac cell death. We assessed cell-free DNA molecules as markers for cardiac damage after open-heart surgery. Novel cardiomyocyte-specific DNA methylation markers were applied to measure cardiac cfDNA in the plasma of 42 infants who underwent open-heart surgery. Cardiac cfDNA was elevated following surgery, reflecting direct surgery-related tissue damage, and declined thereafter in most patients. The concentration of cardiac cfDNA post-surgery correlated with the duration of CPB and aortic cross clamping. Strikingly, cardiac cfDNA at 6 h predicted duration of mechanical ventilation and maximal vasoactive-inotropic score better than did maximal troponin levels. Cardiac cfDNA reveals heart damage associated with CPB, and can be used to monitor cardiac cell death, to predict clinical outcome of surgery and to assess performance of cardioprotective interventions.

Normothermic Versus Hypothermic Norwood Procedure.

BACKGROUND: Either deep hypothermia with circulatory arrest or hypothermic perfusion with antegrade selective cerebral perfusion is used during the Norwood procedure for hypoplastic left heart syndrome. Normothermic perfusion has been described for pediatric patients. The aim of this study was to compare the early outcomes of patients undergoing the Norwood procedure with antegrade selective cerebral perfusion under hypothermia with the procedure under normothermia. METHODS: From 2005 to 2020, 117 consecutive patients with hypoplastic left heart syndrome underwent the Norwood procedure: 68 (58.2%) under hypothermia and 49 (41.8%) under normothermia. Antegrade selective cerebral perfusion flow was adjusted to maintain right radial arterial pressure above 50 mm Hg, and a flow rate of 40 to 50 mL kg-1 min-1. Baseline characteristics, operative data, and postoperative outcomes including lactate recovery time were compared. RESULTS: The baseline characteristics and cardiovascular diagnosis were similar in both groups. The normothermic group had a significantly shorter bypass time (in minutes) of 90.31 (±31.60) versus 123.63 (±25.33), a cross-clamp time of 45.24 (±16.35) versus 81.93 (±16.34), and an antegrade selective cerebral perfusion time of 25.61 (±13.84) versus 47.30 (±14.35) (P < .001). There were no statistically significant differences in the immediate postoperative course, or in terms of in-hospital mortality, which totaled 9 (18.4%) in the normothermic group, and 10 (14.9%) in the hypothermic group (P = .81). CONCLUSION: The normothermic Norwood procedure with selective cerebral perfusion is feasible and safe in terms of in-hospital mortality and short-term outcomes. It is comparable to the standard hypothermic Norwood with selective cerebral perfusion.

Dominant Ventricular Morphology and Early Postoperative Course After the Fontan Procedure.

BACKGROUND: Single ventricle heart disease comprises a wide variety of critical heart defects that lead to the provision of systemic cardiac output by one dominant ventricle. It requires staged surgical palliation that culminates in Fontan circulation. Dominant ventricular morphology in single ventricle patients reportedly has an impact on postoperative morbidity and mortality with varying results. The objectives of this study were to examine the association between ventricular morphology and the early postoperative course after the Fontan procedure. METHODS: A retrospective cohort study in a tertiary referral pediatric medical center that included 98 consecutive patients who underwent Fontan procedure between October 2009 and May 2016. Postoperative outcomes were compared between patients with left ventricular morphology and those with right ventricular morphology (crude effect and regression analysis). RESULTS: Patients with right ventricular morphology had longer postoperative hospitalizations compared to patients with left ventricular morphology (26.5 days vs 18.2 days, respectively, P = .028), higher postoperative maximal vasoactive-inotropic scores (25.6 vs 12.4, P = .02), higher serum lactate levels (7.7 mmol/L vs 6.4 mmol/L, P = .03), higher proportions of ventilation throughout 24 h or more (16 patients [38%] vs 8 patients [14%], P = .009), higher proportions of ventricular dysfunction (12 patients [29%] vs 5 patients [9%], P = .0001), and lower blood oxygen saturation levels at discharge (87% vs 92%, P = .03). CONCLUSIONS: The Fontan procedure in patients with right ventricular morphology is associated with longer postoperative hospitalization and worse early postoperative characteristics (ventricular dysfunction and atrioventricular valve regurgitation) as well as higher rates of early, transient signs of sub-optimal postoperative hemodynamics compared to those with left ventricular morphology.

The horizon of pediatric cardiac critical care.

Pediatric Cardiac Critical Care (PCCC) is a challenging discipline where decisions require a high degree of preparation and clinical expertise. In the modern era, outcomes of neonates and children with congenital heart defects have dramatically improved, largely by transformative technologies and an expanding collection of pharmacotherapies. Exponential advances in science and technology are occurring at a breathtaking rate, and applying these advances to the PCCC patient is essential to further advancing the science and practice of the field. In this article, we identified and elaborate on seven key elements within the PCCC that will pave the way for the future.

Point of care testing in children undergoing cardiopulmonary bypass.

BACKGROUND: Excessive hemorrhage is a major complication after cardiac surgery requiring cardiopulmonary bypass (CPB). The aim of this study was to define the potential role of the cone and platelet analyzer (CPA) and the rotating thromboelastogram (ROTEM) point of care tests in children undergoing CPB. PROCEDURE: We prospectively studied 15 pediatric patients aged 1 month to 10 years. Blood count, blood coagulation tests (prothrombin time [PT], activated partial thromboplastin time, fibrinogen, thrombin time), CPA and ROTEM parameters were measured before and after CPB. Demographic and surgical data were recorded as were those on perioperative blood loss and blood product transfusion. RESULTS: Low body weight, longer duration on CPB and lower core body temperature were associated with an increased bleeding risk. The ROTEM test showed a significant prolongation of clotting time and decreased maximal clot firmness (MCF) postoperatively in children with increased bleeding. The coagulation parameters associated with increased bleeding were: prolonged PT, lower fibrinogen levels, prior to surgery, and lower MCF after surgery. CPA test findings were not associated with postoperative bleeding in our patients. CONCLUSIONS: CPA did not serve as a prognostic tool for predicting bleeding risk in children undergoing CPB. The change in ROTEM's post-CPB results associated with bleeding tendency, and they may predict for poorer clot formation and stability.

Catheter-directed thrombolysis for in situ pulmonary artery thrombosis in children.

In situ pulmonary artery thrombosis (ISPAT) is a unique form of pulmonary embolism characterized by local formation of thrombus in the pulmonary arteries. We present here a baby with hypoplastic left heart syndrome who developed ISPAT after Glenn surgery. The patient underwent catheter-directed thrombolysis, followed by systemic anticoagulation with excellent results.

A randomized trial of outcomes of anesthetic management directed to very early extubation after cardiac surgery in children.

OBJECTIVES: Intraoperative management directed to early extubation of children undergoing cardiac surgery has been suggested as a viable alternative to prolonged postoperative mechanical ventilation. The authors evaluated the safety and efficacy of this approach in a randomized prospective trial. DESIGN: A prospective randomized observational study. SETTING: A single university-affiliated hospital. PARTICIPANTS: One hundred consecutive pediatric patients (age 1 month-15 years, weight 3.0-51 kg) requiring cardiac surgery. Patients younger than 1 month of age and those requiring mechanical ventilation before the operation were considered ineligible for the study. INTERVENTIONS: Patients were randomly allocated to a group with anesthetic management and extubation in the operating room (early group [EG]) and a group with elective prolonged mechanical ventilation (control group [CG]). MEASUREMENTS AND MAIN RESULTS: A difference in outcome as reflected by the pediatric intensive care unit (PICU) and hospital lengths of stay and postoperative morbidity and mortality was analyzed. A separate analysis was performed in children younger than 3 years old. The extubation time in the CG was 25.0 +/- 26.9 hours. No differences in mortality, the need for re-exploration for bleeding, the need for reintubation, the incidence of abnormal chest radiographic findings, or cardiac and septic complications between groups were found. PICU and postoperative hospital lengths of stay were significantly shorter in patients in the EG (3.3 +/- 1.9 days in the EG v 5.8 +/- 4.1 in the CG, p < 0.001, and 7.4 +/- 2.9 days in the EG v 11.2 +/- 6.8 days in the CG, p = 0.009). CONCLUSIONS: In children undergoing cardiac surgery, anesthetic management with early cessation of mechanical ventilation appears to be safe and decreases hospital and PICU length of stay. However, because the size of the study did not allow for the detection of possible differences in perioperative mortality, only a large multicenter study may provide a definite answer to this question. The present study may be treated as a pilot for such a trial.

Transfusion-related acute hepatic injury following postoperative platelets administration in pediatric patients undergoing the Fontan procedure.

OBJECTIVE: The final common pathway of single ventricle patients is the Fontan procedure. Among the immediate postoperative complications is acute hepatic injury presented by marked elevation of liver enzymes (alanine transaminase [ALT] and aspartate transaminase [AST]). We aimed to determine the contribution of blood products transfusion to acute hepatic injury. DESIGN: Single center retrospective cohort study. SETTING: Pediatric Cardiac Intensive Care Unit at a tertiary medical center. PATIENTS: Ninety-nine pediatric patients undergoing the Fontan procedure between January 2009 and December 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of the four types of blood products, transfusion of platelets was found to significantly affect postoperative levels of ALT and AST. Additional factors included postoperative administration of sodium bicarbonate, decreased flow through the Fontan canal and decreased urine output. Preoperative pulmonary artery pressure and pulmonary vascular resistance, cardiopulmonary bypass time, aortic cross-clamp time, amount of postoperative bleeding, and vasoactive-inotropic score did not influence liver enzymes levels CONCLUSIONS: In pediatric Fontan patients, platelets transfusions contribute to an acute hepatic injury. The relation between platelets and transfusion-related acute lung injury (TRALI) has been well described, but this is the first time it is being described in regard to acute hepatic injury (TRAHI). Changing platelet transfusion strategy could decrease morbidity in Fontan patients but further research is needed.

Accessory mitral valve tissue: a case report and an updated review of literature.

Accessory mitral valve tissue is an unusual congenital cardiac anomaly and a rare cause responsible for left ventricular outflow tract obstruction. An 18-year-old patient was referred to this hospital due to an occasionally noted heart murmur in a medical examination. Echocardiography facilitated the diagnosis of accessory mitral valve tissue. To relieve the left ventricular outflow tract obstruction, an operation including resection of the accessory mitral valve tissue, implantation of artificial chordae tendineae, and mitral valve annuloplasty was performed successfully. Postoperative echocardiography showed a complete relief of the mitral valve leaflets and a wide patent left ventricular outflow tract. However, transient ischemic attack and Horner's syndrome complicated the patient early postoperatively. He was administered with a high dose of aspirin, and he recovered shortly. Surgical removal is in so much mandatory as a definite diagnosis of accessory mitral valve tissue with left ventricular outflow tract obstruction is established. A prophylactic treatment should be applied to the patients with accessory mitral valve tissue in virtue of their susceptibility to neurological events.

Heparin-induced thrombocytopenia complicating children after the Fontan procedure: Single-center experience and review of the literature.

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin therapy. The risk for HIT correlates with the cumulative dosage of heparin exposure. In Fontan patients, recurrent systemic anticoagulation, traditionally with heparin, is used to alleviate the thrombotic complications that may occur postoperatively when the venous pressure rises and the systemic venous flow into the pulmonary arteries becomes sluggish, putting them at increased risk. As a pressure gradient-dependent circulation, elevation in systemic venous pressure, most often by venous thrombosis, contributes to circuit failure. Therefore, when HIT complicates patients after the Fontan procedure, it is associated with a high thrombotic morbidity and mortality; thus, a high index of suspicion is mandatory, based on the clinical signs of HIT. It is crucial to intervene early with alternative anticoagulants when HIT is suspected as this step may improve outcome in these patients.

Dehydration as a Rare Cause of Pulmonary Artery Thrombosis in a 2-Week-Old Term Neonate.

Pulmonary arterial thrombosis is an extremely rare occurrence in the neonatal population. We describe a 2-week-old female neonate who presented in critical condition with severe cyanosis and dehydration and was found to have a large thrombus in the main branches of the pulmonary arteries. She was successfully treated with surgical embolectomy. Pulmonary arterial thrombosis should always be considered in the differential diagnosis of a dehydrated neonate presenting with severe cyanosis and evidence of pulmonary hypertension.

Site-specific delivery of dexamethasone from biodegradable implants reduces formation of pericardial adhesions in rabbits.

Repeated sternotomy often leads to serious complications in patients due to the formation of cardiac adhesions. In this study we characterized dexamethasone-loaded biodegradable poly(lactide)-poly(ethyleneglycol) copolymer films for site-specific drug delivery and examined their efficacy in the rabbit model of postoperative cardiac adhesions. Tritiated dexamethasone-loaded films were used to determine the in vitro release and in vivo drug distribution. Dexamethasone release in serum was biphasic with 69% drug released after 72 hr. The implants produced sustained drug levels at the implantation site with low distribution into the peripheral tissues. The matrices were implanted in rabbits between the epicardium and the sternum following sternotomy, pericardiectomy and epicardium abrasion, with the drug-releasing surface facing the epicardium. The tenacity and density of the adhesions was examined 21 days post procedure in comparison to both groups of untreated and rabbits implanted with blank matrices. Similarly tenacious and dense adhesions were observed in both control groups. In contrast, epicardial adhesions' formation was significantly reduced and the anatomy was preserved in the treated animals. It is concluded that local delivery of dexamethasone from biodegradable implants provides a promising approach for the prevention of pericardial adhesions while potentially minimizing the systemic adverse effects inherent to systemic therapy or high blood levels of the drug.

Prolonged 24-hour subzero preservation of heterotopically transplanted rat hearts using antifreeze proteins derived from arctic fish.

BACKGROUND: Arctic fish survive subzero temperatures by producing a family of antifreeze proteins (AFPs) that noncolligatively lower the freezing temperature of their body fluids. We report 24-hour storage of mammalian hearts for transplantation at subzero temperatures using AFPs derived from arctic fish. METHODS: Forty-two heterotopic transplantations were performed in isoimmune Sprague-Dawley rats. Harvested hearts were retrogradely infused with cold 4 degrees C University of Wisconsin (UW) solution and were preserved in a specialized cooling bath at two target temperatures, 4 degrees C and -1.3 degrees C for 12,18, and 24 hours (6 experiments/group). Preservation solutions were UW alone for the 4 degrees C group, and UW with 15 mg/mL AFP III for the -1.3 degrees C group. After hypothermic storage the hearts were heterotopically transplanted into isoimmune rats. Viability was assessed and graded on a scale of 0 to 6 (0 = no contractions to 6 = excellent contractions). Transplanted hearts were then fixed in vivo and were subject to electron microscopy and histopathologic examination. RESULTS: None of the hearts preserved at -1.3 degrees C in UW/AFP III solution froze. All control hearts preserved at -1.3 degrees C without AFP protection froze and died at reperfusion. Viability of hearts preserved at -1.3 degrees C in UW/AFP III solution was significantly better after 18 hours of preservation, 30 and 60 minutes after reperfusion (median, 5 versus 3 and 6 versus 3, respectively; p < 0.05) and after 24 hours of preservation 30 and 60 minutes after reperfusion (median, 4.5 versus 1.5 and 5 versus 2, respectively; p < 0.05). Histologic and electron microscopy studies demonstrated better myocyte structure and mitochondrial integrity preservation with UW/AFP III solution. CONCLUSIONS: Antifreeze proteins prevent freezing in subzero cryopreservation of mammalian hearts for transplantation. Subzero preservation prolongs ischemic times and improves posttransplant viability.

Prolonged prostaglandin E1 therapy in a neonate with pulmonary atresia and ventricular septal defect and the development of antral foveolar hyperplasia and hypertrophic pyloric stenosis.

Prostaglandin E1 (alprostadil) is widely used for maintaining the patency of ductus arteriosus in ductus-dependent congenital heart defects in neonates to improve oxygenation. Among more common side effects are fever, rash, apnoea, diarrhoea, jitteriness, and flushing. More severe side effects are brown fat necrosis, cortical hyperostosis, and gastric outlet obstruction, most commonly the result of antral foveolar hyperplasia or hypertrophic pyloric stenosis. We report on an infant with a ductus-dependent congenital heart defect who developed symptoms and sonographic evidence of focal foveolar hyperplasia and hypertrophic pyloric stenosis after prolonged treatment with prostaglandin E1. Gastrointestinal symptoms persisted after corrective cardiac surgery, and pyloromyotomy was required. Study of the case and of available literature showed an association between the total dose of prostaglandin E1 administered and duration of treatment and the development of gastric outlet obstruction. We conclude that if patients are treated with a prostaglandin E1 infusion, careful monitoring for symptoms and signs of gastric outlet obstruction is required.