Vulnerability of Coronary Circulation After Norwood Operation

Saiki, Hiroshi; Kuwata, Seiko; Kurishima, Clara; Masutani, Satoshi; Senzaki, Hideaki

doi:10.1016/j.athoracsur.2015.10.077

Cited by 11 publications

(6 citation statements)

References 29 publications

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“…As our report is the first describing the loss of the regenerative compartment in the process of heart failure, the molecular or physiological mechanisms that lead to a significant reduction in CMCs in the failing ventricle are unknown. Inherent in most forms of heart failure is an imbalance of blood/nutrient demand in relation to delivery, and the coronary circulation after the first stage repair in HLHS (post-Norwood procedure) is vulnerable as a result of elevated ventricular impedance and impaired subendocardial blood flow [ 20 ]. Related to these metabolic changes, redox or ischemic stress and a pro-inflammatory microenvironment have been shown to deplete stem cell capacity and impair cardiomyogenic differentiation in mouse models of heart failure [ 21 ] and in human samples [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Cardiac regenerative capacity is age- and disease-dependent in childhood heart disease

et al. 2018

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ObjectiveWe sought to define the intrinsic stem cell capacity in pediatric heart lesions, and the effects of diagnosis and of age, in order to inform evidence-based use of potential autologous stem cell sources for regenerative medicine therapy.MethodsVentricular explants derived from patients with hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TF), dilated cardiomyopathy (DCM) and ventricular septal defect (VSD) were analyzed following standard in vitro culture conditions, which yielded cardiospheres (C-spheres), indicative of endogenous stem cell capacity. C-sphere counts generated per 5 mm3 tissue explant and the presence of cardiac progenitor cells were correlated to patient age, diagnosis and echocardiographic function.ResultsCardiac explants from patients less than one year of age with TF and DCM robustly generated c-kit- and/or vimentin-positive cardiac mesenchymal cells (CMCs), populating spontaneously forming C-spheres. Beyond one year of age, there was a marked reduction or absence of cardiac explant-derivable cardiac stem cell content in patients with TF, VSD and DCM. Stem cell content in HLHS and DCM strongly correlated to the echocardiographic function in the corresponding ventricular chamber, with better echocardiographic function correlating to a more robust regenerative cellular content.ConclusionsWe conclude that autologous cardiomyogenic potential in pediatric heart lesions is robust during the first year of life and uniformly declines thereafter. Depletion of stem cell content occurs at an earlier age in HLHS with the onset of ventricular failure in a chamber-specific pattern that correlates directly to ventricular dysfunction. These data suggest that regenerative therapies using autologous cellular sources should be implemented in the neonatal period before the potentially rapid onset of single ventricle failure in HLHS or the evolution of biventricular failure in DCM.

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Section: Discussionmentioning

confidence: 99%

Cardiac regenerative capacity is age- and disease-dependent in childhood heart disease

et al. 2018

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“…PBF is ensured by a modified Blalock-Tausig shunt (mBTS) or by a (right) ventricle-to-pulmonary artery shunt (RVPAS). The RVPAS reduces diastolic run-off with subsequent coronary arterial steal phenomenon, which is common in mBTS, but at expense of a ventriculotomy; a potential risk of single ventricular dysfunction and arrhythmia generation [ 25 ]. Based on the immense data of Pediatric Heart Network [ 26 , 27 ], adequate 12-month follow-up data with multiple endpoints such as mortality or heart transplantation (HTx) are available.…”

Section: Traditional Norwood Stage-i Palliation and Follow-up Resultsmentioning

confidence: 99%

Hypoplastic Left Heart: Stage-I Will be Performed Interventionally, Soon

2021

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The hypoplasia of left-sided heart structures shows great variability and complexity. What the many variants have in common is that their heart structures are neither fully developed before nor after birth. Fetuses and newborns require an individual therapy depending on anatomy and function of the heart. Fetal interventions focus on improving left heart structures by catheter-based interventions and maternal hyperoxygenation which promotes growth as the left ventricular preload and blood flow within the cavity increase. Stage-I management of newborns with single ventricle physiology is usually based on the Norwood/Sano surgery or the Hybrid approach. Two more steps are required to ultimately achieve a Fontan circulation. Some centers also use the Hybrid approach for subsequent Norwood operation beyond the neonatal period. After the Hybrid approach, a comprehensive stage-II or corrective surgery is performed, the latter if a bi-ventricular circulation is possible. With progressively improved catheter-based interventions, particularly ductal stenting and manipulations of the atrial septum, the next advance is to develop a bespoke flow restrictor that can be easily inserted into the branches of the pulmonary artery. The main goal is to avoid complex heart operations under general anesthesia, followed by substantial intensive care in the neonatal period, especially for patients with complex heart defects. Based on the current state of the art of surgical treatment of hypoplastic left heart syndrome and variants with the Norwood surgery or the Hybrid approach, our main focus is on an alternative percutaneous transcatheter technique in the sense of a completely non-surgical stage-I approach.

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“…This finding should not be surprising, given that either the cause of or result of cardiac arrest requiring CPR would likely convey an increased risk of mortality. Coronary blood flow, for example, in patients with Norwood circulation can be tenuous, 21 and the occurrence of cardiac arrest requiring CPR in the postoperative period could be a surrogate marker for patients in which the balance between coronary blood flow and myocardial oxygen demand is most fragile. In other words, ECMO-associated morbidity might be more related to system factors that could potentially be improved, whereas cardiac arrest requiring CPR is likely more related to patient factors that may be less modifiable.…”

Section: Discussionmentioning

confidence: 99%

Improved outcomes in neonates who require venoarterial extracorporeal membrane oxygenation after the Norwood procedure

et al. 2019

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Background: Extracorporeal membrane oxygenation after the Norwood procedure has historically been associated with poor outcomes, with reported hospital survival rates of 13%–48%. We hypothesized that contemporary outcomes in this population have improved. We aimed to compare clinical outcomes of contemporary cohorts of patients with functional single ventricle physiology who did and did not receive extracorporeal membrane oxygenation after the Norwood procedure. Methods: Single-center retrospective cohort study of patients with single ventricle anatomy who underwent the Norwood procedure between 2009 and 2017 was performed. Kaplan–Meier survival curves were constructed, and Cox proportional hazard regression analyses were performed to compare transplant-free survival in patients who did and did not receive venoarterial extracorporeal membrane oxygenation. Results: In total, 85 patients met inclusion criteria. Venoarterial extracorporeal membrane oxygenation was utilized in 25 patients (29%). A total of 18 patients (72%) who received venoarterial extracorporeal membrane oxygenation survived to hospital discharge, compared to 54 patients (92%) who did not receive venoarterial extracorporeal membrane oxygenation (p = 0.013). Post-discharge transplant-free survival was not significantly different between patients who did and did not receive venoarterial extracorporeal membrane oxygenation (log-rank p value = 0.28). Cox proportional hazard regression analysis revealed that the occurrence of cardiac arrest requiring cardiopulmonary resuscitation (hazard ratio = 4.5; 95% confidence interval = 2.0–10.1) during the perioperative period was independently associated with death or transplantation, whereas venoarterial extracorporeal membrane oxygenation was not an independent risk factor for death or transplantation (hazard ratio = 2.0; 95% confidence interval = 0.8–4.9). Conclusion: In our cohort of children who received venoarterial extracorporeal membrane oxygenation after the Norwood procedure, hospital survival was improved compared to historical data. In addition, venoarterial extracorporeal membrane oxygenation utilization was not independently associated with worse outcomes.

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Vulnerability of Coronary Circulation After Norwood Operation

Abstract: Myocardial oxygen supply-demand imbalance is intrinsic to Norwood circulation but may be improved by technical refinement of aortic reconstruction or afterload-reducing medication with renin-angiotensin-aldosterone system blockade.

Cited by 11 publications

References 29 publications

Cardiac regenerative capacity is age- and disease-dependent in childhood heart disease

Cardiac regenerative capacity is age- and disease-dependent in childhood heart disease

Hypoplastic Left Heart: Stage-I Will be Performed Interventionally, Soon

Improved outcomes in neonates who require venoarterial extracorporeal membrane oxygenation after the Norwood procedure

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