Cilia and Nodal Flow in Asymmetry: An Engineering Perspective.

Over the past several years, cilia in the primitive node have become recognized more and more for their contribution to development, and more specifically, for their role in axis determination. Although many of the mechanisms behind their influence remain undocumented, it is known that their presence and motion in the primitive node of developing embryos is the determinant of the left-right axis. Studies on cilial mechanics and nodal fluid dynamics have provided clues as to how this asymmetry mechanism works, and more importantly, have shown that direct manipulation of the flow field in the node can directly influence physiology. Although relatively uncommon, cilial disorders have been shown to have a variety of impacts on individuals from chronic respiratory infections to infertility, as well as situs inversus which is linked to congenital heart disease. After first providing background information pertinent to understanding nodal flow and information on why this discussion is important, this paper aims to give a review of the history of nodal cilia investigations, an overview of cilia mechanics and nodal flow dynamics, as well as a review of research studies current and past that sought to understand the mechanisms behind nodal cilia's involvement in symmetry-breaking pathways through a biomedical engineering perspective. This discussion has the additional intention to compile interdisciplinary knowledge on asymmetry and development such that it may encourage more collaborative efforts between the sciences on this topic, as well as provide insight on potential paths forward in the field.

Tailoring left ventricular assist device cannula implantation using coupled multi-scale multi-objective optimization.

BACKGROUND: The frequent occurrence of thromboembolic cerebral events continues to limit the widespread implementation of Ventricular Assist Devices (VAD) despite continued advancements in VAD design and anti-coagulation treatments. Recent studies point to the optimal positioning of the outflow graft (OG) as a potential mitigator of post implantation thromboembolism. OBJECTIVE: This study aims to examine the tailoring of the OG implantation orientation with the goal of minimizing the number of thrombi reaching the cerebral vessels by means of a formal shape optimization scheme incorporated into a multi-scale hemodynamics analysis. METHODS: A 3-D patient-specific computational fluid dynamics model is loosely coupled in a two-way manner to a 0-D lumped parameter model of the peripheral circulation. A Lagrangian particle-tracking scheme models and tracks thrombi as non-interacting solid spheres. The loose coupling between CFD and LPM is integrated into a geometric shape optimization scheme which aims to optimize an objective function that targets a drop in cerebral embolization, and an overall reduction in particle residence times. RESULTS: The results elucidate the importance of OG anastomosis orientation and placement particularly in the case that studied particle release from the OG, as a fivefold decrease in cerebral embolization was observed between the optimal and non-optimal implantations. Another case considered particle release from the ventricle and aortic root walls, in which optimal implantation was achieved with a shallow insertion angle. Particle release from all three origins was investigated in the third case, demonstrating that the optimal configurations were generally characterized by VAD flow directed along the central lumen of the aortic arch. Because optimal configurations depended on the anatomic origin of the thrombus, it is important to determine, in clinical studies, the most likely sites of thrombus formation in VAD patients.

Invited Commentary: Notwithstanding the Significance of Anatomy in Anomalous Aortic Origin of a Coronary Artery, Physiology Is Important, Too.

The management strategies for anomalous aortic origin of a coronary artery (AAOCA) are based on anatomy, symptoms, and stress tests for evidence of ischemia. These strategies remain associated with low levels of evidence. Stress tests for ischemia or ventricular dysfunction, the only widely used physiological tests, are not adequately reliable. Additional physiological metrics are needed to build reliable strategies. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are physiological measurements that are used in assessing acquired coronary artery disease (CAD). In this commentary, we describe FFR and iFR and review studies supporting their utility in assessing CAD. We describe a few small studies of their use in assessing AAOCA. Finally, we comment on the unique features of AAOCA that mandate further investigation on how to conduct and interpret FFR/iFR measurements. Even at a point where we understand how to do this, determining the effectiveness of these measurements in improving outcomes and guiding management will require lengthy and challenging trials. A collective effort of institutions that manage AAOCA will be essential.

The Academic Impact of Congenital Heart Surgeons' Society (CHSS) Studies.

PURPOSE: We reviewed all 64 articles ever published by The Congenital Heart Surgeons' Society (CHSS) Data Center to estimate the academic impact of these peer-reviewed articles. MATERIALS AND METHODS: The Congenital Heart Surgeons' Society has performed research based on 12 Diagnostic Inception Cohorts. The first cohort (Transposition) began enrolling patients on January 1, 1985. We queried PubMed to determine the number of publications that referenced each of the 64 journal articles generated by the datasets of the 12 Diagnostic Inception Cohorts that comprise the CHSS Database. Descriptive summaries of the data were tabulated using mean with standard deviation and median with range. RESULTS: Sixty-four peer-reviewed papers have been published based on the CHSS Database. Fifty-nine peer-reviewed articles have been published based on the 12 Diagnostic Inception Cohorts, and five additional articles have been published based on Data Science. Excluding the recently established Diagnostic Inception Cohort for patients with Ebstein malformation of tricuspid valve, the number of papers published per cohort ranged from 1 for coarctation to 11 for transposition of the great arteries. The 11 articles generated from the CHSS Transposition Cohort were referenced by a total of 111 articles (median number of references per journal article = 9 [range = 0-22, mean = 10.1]). Overall, individual articles were cited by an average of 11 (mean), and a maximum of 41 PubMed-listed publications. Overall, these 64 peer-reviewed articles based on the CHSS Database were cited 692 times in PubMed-listed publications. The first CHSS peer-reviewed article was published in 1987, and during the 35 years from 1987 to 2022, inclusive, the annual number of CHSS publications has ranged from 0 to 7, with a mean of 1.8 publications per year (median = 1, mode = 1). CONCLUSION: Congenital Heart Surgeons' Society studies are widely referenced in the pediatric cardiac surgical literature, with over 10 citations per published article. These cohorts provide unique information unavailable in other sources of data. A tool to access this analysis is available at: [https://data-center.chss.org/multimedia/files/2022/CAI.pdf].

Research Enterprise of the Congenital Heart Surgeons' Society 2018 to 2023: History, Accomplishments, Transformation, and Challenges.

The history of the research arm of the Congenital Heart Surgeons' Society (CHSS) through 2017 was contained within two prior publications that covered CHSS history in general. The present article is the first to focus explicitly on the research enterprise, with emphasis on the period 2018 to 2023. During this time, the challenges of continuing to build multiple cohorts with lifelong follow-up and to transform the enterprise to a premiere research organization became manifest. Although continuing its commitment to produce impactful research results and to educate the Kirklin/Ashburn Fellow, the research team devoted considerable effort to defining the problems of cohort relevance, workflow, data management, long-term patient follow-up, CHSS member engagement, and the regulatory burden. The team wrote a proposal outlining ways to solve the challenges. A major change from a single-institution "Data Center" to a two-institution Center for Research & Quality (CRQ) was made, assuring increased faculty members and resources. The proposed changes to structure and process began execution in mid-2022. A second Kirklin/Ashburn Fellowship position was created. Between 2018 and 2022, the CRQ produced 17 publications and launched five new research initiatives. This article chronicles the exciting five-year period in which the CHSS research enterprise began a transformation with the intent to become the premiere research organization in the world in the specialty of congenital cardiac surgery.

A dynamic Norwood mortality estimation: Characterizing individual, updated, predicted mortality trajectories after the Norwood operation.

Objective: Post-Norwood mortality remains high and unpredictable. Current models for mortality do not incorporate interstage events. We sought to determine the association of time-related interstage events, along with (pre)operative characteristics, with death post-Norwood and subsequently predict individual mortality. Methods: From the Congenital Heart Surgeons' Society Critical Left Heart Obstruction cohort, 360 neonates underwent Norwood operations from 2005 to 2016. Risk of death post-Norwood was modeled using a novel application of parametric hazard analysis, in which baseline and operative characteristics and time-related adverse events, procedures, and repeated weight and arterial oxygen saturation measurements were considered. Individual predicted mortality trajectories that dynamically update (increase or decrease) over time were derived and plotted. Results: After the Norwood, 282 patients (78%) progressed to stage 2 palliation, 60 patients (17%) died, 5 patients (1%) underwent heart transplantation, and 13 patients (4%) were alive without transitioning to another end point. In total, 3052 postoperative events occurred and 963 measures of weight and oxygen saturation were obtained. Risk factors for death included resuscitated cardiac arrest, moderate or greater atrioventricular valve regurgitation, intracranial hemorrhage/stroke, sepsis, lower longitudinal oxygen saturation, readmission, smaller baseline aortic diameter, smaller baseline mitral valve z-score, and lower longitudinal weight. Each patient's predicted mortality trajectory varied as risk factors occurred over time. Groups with qualitatively similar mortality trajectories were noted. Conclusions: Risk of death post-Norwood is dynamic and most frequently associated with time-related postoperative events and measures, rather than baseline characteristics. Dynamic predicted mortality trajectories for individuals and their visualization represent a paradigm shift from population-derived insights to precision medicine at the patient level.

Hybrid palliation versus nonhybrid management for a multi-institutional cohort of infants with critical left heart obstruction.

OBJECTIVE: To compare patient characteristics and overall survival for infants with critical left heart obstruction after hybrid palliation (bilateral pulmonary artery banding with or without ductal stenting) versus nonhybrid management (eg, Norwood, primary transplantation, biventricular repair, or transcatheter/surgical aortic valvotomy). METHODS: From 2005 to 2019, 1045 infants in the Congenital Heart Surgeons' Society critical left heart obstruction cohort underwent interventions across 28 institutions. Using a balancing score propensity analysis, 214 infants who underwent hybrid palliation and 831 infants who underwent nonhybrid management were proportionately matched regarding variables significantly associated with mortality and variables noted to significantly differ between groups. Overall survival between the 2 groups was adjusted by applying balancing scores to nonparametric estimates. RESULTS: Compared with the nonhybrid management group, infants who underwent hybrid palliation had lower birth weight, smaller gestational age, and higher prevalence of in-utero interventions, noncardiac comorbidities, preoperative mechanical ventilation, absent interatrial communication, and moderate or severe mitral valve stenosis (all P values < .03). Unadjusted 12-year survival after hybrid palliation and nonhybrid management, was 55% versus 69%, respectively. After matching, 12-year survival after hybrid palliation versus nonhybrid management was 58% versus 63%, respectively (P = .37). Among matched infants born weighing <2.5 kg, 2-year survival after hybrid palliation versus nonhybrid management was 37% versus 51%, respectively (P = .22). CONCLUSIONS: Infants born with critical left heart obstruction who undergo hybrid palliation have more high-risk characteristics and anatomy versus infants who undergo nonhybrid management. Nonetheless, after adjustment, there was no significant difference in 12-year survival after hybrid palliation versus nonhybrid management. Mortality remains high, and hybrid palliation confers no survival advantage, even for lower-birth-weight infants.

Norwood operation versus comprehensive stage II after bilateral pulmonary artery banding palliation for infants with critical left heart obstruction.

OBJECTIVE: To determine patient characteristics and outcomes after Norwood versus comprehensive stage II (COMPSII) for infants with critical left heart obstruction who had prior hybrid palliation (bilateral pulmonary artery banding ± ductal stent). METHODS: From 23 Congenital Heart Surgeons' Society institutions (2005-2020), 138 infants underwent hybrid palliation followed by either Norwood (n = 73, 53%) or COMPSII (n = 65). Baseline characteristics were compared between Norwood and COMPSII groups. Parametric hazard model with competing risk methodology was used to determine risk and factors associated with outcomes of Fontan, transplantation, or death. RESULTS: Infants who underwent Norwood versus COMPSII had a higher prevalence of prematurity (26% vs 14%, P = .08), lower birth weight (median 2.8 vs 3.2 kg, P < .01) and less frequent ductal stenting (37% vs 99%; P < .01). Norwood was performed at a median age of 44 days and median weight of 3.5 kg, versus COMPSII at 162 days and 6.0 kg (both P < .01). Median follow-up was 6.5 years. At 5 years after Norwood and COMPSII, respectively; 50% versus 68% had Fontan (P = .16), 3% versus 5% had transplantation (P = .70), 40% versus 15% died (P = .10), and 7% versus 11% are alive without transition, respectively. For factors associated with either mortality or Fontan, only preoperative mechanical ventilation occurred more frequently in the Norwood group. CONCLUSIONS: Higher prevalence of prematurity, lower birth weight, and other patient-related characteristics in the Norwood versus COMPSII groups may influence differences in outcomes that were not statistically significant for this limited risk-adjusted cohort. The clinical decision regarding Norwood versus COMPSII after initial hybrid palliation remains challenging.

In-Silico and In-Vitro Analysis of the Novel Hybrid Comprehensive Stage II Operation for Single Ventricle Circulation.

Single ventricle (SV) anomalies account for one-fourth of all congenital heart disease cases. The existing palliative treatment for this anomaly achieves a survival rate of only 50%. To reduce the trauma associated with surgical management, the hybrid comprehensive stage II (HCSII) operation was designed as an alternative for a select subset of SV patients with the adequate antegrade aortic flow. This study aims to provide better insight into the hemodynamics of HCSII patients utilizing a multiscale Computational Fluid Dynamics (CFD) model and a mock flow loop (MFL). Both 3D-0D loosely coupled CFD and MFL models have been tuned to match baseline hemodynamic parameters obtained from patient-specific catheterization data. The hemodynamic findings from clinical data closely match the in-vitro and in-silico measurements and show a strong correlation (r = 0.9). The geometrical modification applied to the models had little effect on the oxygen delivery. Similarly, the particle residence time study reveals that particles injected in the main pulmonary artery (MPA) have successfully ejected within one cardiac cycle, and no pathological flows were observed.

Toward More Granular Guidelines in AAOCA: Associating Anatomical Details With Specific Surgical Strategies.

Patients with anomalous aortic origin of a coronary artery (AAOCA) require imaging to clarify the multiple potential anatomic sites of obstruction (fixed or dynamic). Once repaired, the pathway of blood to the myocardium must not encounter: (1) intrinsic ostial stenosis, (2) obstruction from compression or distortion near the commissure or the intercoronary pillar, (3) stenosis where the artery exits the aortic wall (due to an acutely angled "take-off"), (4) compression due to a pathway between the great vessels, (5) stenosis or compression along an intramural course, or (6) compression due to an intramuscular (intraseptal/intraconal) course. Detailed anatomic evaluation of each of these locations allows the surgeon to select an appropriate repair strategy, and each of these abnormal anatomic features should be "matched" with a particular surgical correction. We speculate that the most common surgical repair, unroofing with or without tacking, is often inadequate, as in isolation, it may not allow for correction with a large orifice from the appropriate sinus, without an interarterial course. While the evidence base is insufficient to call these recommendations formal guidelines, these recommendations should serve as a basis for further validity testing, and ultimate evolution to more granular guidelines on AAOCA management.

Mycotic Pseudoaneurysm: Rare Complication of a Norwood/Sano Graft Stump.

The Sano variant of the stage 1 Norwood procedure is commonly performed as initial palliation for hypoplastic left heart syndrome. We present a case of a 2-year-old who developed a mycotic pseudoaneurysm of the Sano graft and discuss the importance of imaging and operative management of this rare presentation. Localization and full description of the lesion require compulsive, often multimodality imaging.

Persistent Hypoxia After Blunt Thoracic Trauma due to Flail Tricuspid Valve Leaflet and Patent Foramen Ovale.

Structural cardiac injury after blunt trauma is uncommon but usually life-threatening. While tricuspid injury is very rare and potentially lethal, the right heart can accommodate larger volumes and higher pressures in acute tricuspid insufficiency and facilitate initial stabilization prior to definitive valvular repair. ECMO may be used to ameliorate resulting right heart failure. The traumatic force required to cause cardiac structural injury is also associated with pulmonary complications related to pneumothorax, hemothorax, effusion, acute pain secondary to rib fractures, and pulmonary contusions causing hypoxia. We present an unusual case of hypoxia in a trauma patient caused by acute tricuspid regurgitation with pre-existing patent foramen ovale.

Congenital Left Main Coronary Atresia: Rare Cause of Sudden Cardiac Arrest.

A 13-month-old male sustained cardiac arrest under general anesthesia and was found to have left main coronary artery atresia with collateralization from the right coronary artery. After protracted recovery, the patient underwent coronary ostioplasty. Postoperative imaging confirmed patency of the newly established artery without stenosis. At 12 months, no changes in the vessel were noted. Ventricular function remains mildly decreased and stable.

Joint programmes in paediatric cardiac surgery: an update and descriptive analysis.

OBJECTIVE: Joint programmes are an alternative model that may aid in improving congenital cardiac surgery outcomes while avoiding the potential resource and accessibility challenges that could result from regionalisation. This study aims to characterise current joint programmes, identify factors that are associated with joint programme success and failure, and gauge attitudes within the profession regarding joint programmes as an alternative. METHODS: A multiple choice survey with 23 standard questions for all programmes and additional 42 additional questions for each participant hospital in a joint programme was addressed to paediatric cardiac surgeons in the United States of America. Questions were designed to qualitatively and quantitatively characterise congenital cardiac surgery joint programmes. RESULTS: Of the 34 unique congenital cardiac surgery programmes identified in this survey, 14 have participated in a joint programme and 50% of those joint programmes existed for more than 10 years. Most joint programmes (86%) participate or participated in a model where the hospital participants are engaged in a "mother-daughter" relationship in both perception and case volume distribution. In three out of four defunct joint programmes, there were case complexity limitations placed on partner institutions, but the now independent partner institutions operate with no limitation on complexity. Most (71%) hospital participants in a joint programme felt that the joint programme produced better outcomes than two separate programmes; however, among those who participate or have participated in a joint programme, only 18% felt that joint programmes were the optimal model for delivery of congenital cardiac surgical care.

Outcomes Following Norwood Procedures: Analysis of a "Small Volume" Program.

BACKGROUND: Institutional survival following Norwood procedures is traditionally correlated with a center's surgical volume. Multiple single and multi-institutional studies conducted at large-volume centers have recently demonstrated improved survival following Norwood procedures. We report both short- and long-term outcomes at a single, small-volume institution and comment on factors potentially influencing outcomes at this institution. METHODS: All patients undergoing Norwood procedures from January 1, 2005, to January 1, 2020, at our institution were included in this study. Kaplan-Meier survival and Cox regression risk factor analyses were performed in addition to first interstage risk factor scoring to compare observed versus expected survival. RESULTS: The cohort included 113 patients. Kaplan-Meier freedom from death or transplant was 88%, 80%, and 76% at 1, 5, and 10 years, respectively. Freedom from death following hospital discharge after Norwood procedures was 94%, 87%, and 83% at 1, 5, and 10 years, respectively. The presence of genetic syndromes was a significant risk factor for mortality. First interstage observed-to-expected mortality following discharge was 0.57 (P = .04). Postoperative length of stay was comparable to that reported for the period 2015 to 2018 in the Society of Thoracic Surgeons Database. CONCLUSIONS: Survival outcomes at this single, small-volume institution were similar to those reported by large-volume centers and multi-institutional collaborative studies. These results may be related to structural and functional features that have been demonstrated to influence outcomes in other studies. These factors are achievable by small-volume programs with sufficient resource allocation.

Passive high-frequency microrheology of blood.

Indicative of various pathologies, blood properties are under intense scrutiny. The hemorheological characteristics are traditionally gauged by bulk, low-frequency indicators that average out critical information about the complex, multi-scale, and multi-component structure. In particular, one cannot discriminate between the erythrocytes contribution to global rheology and the impact of plasma. Nevertheless, in their fast stochastic movement, before they encounter each other, the erythrocytes probe the subtle viscoelasticity of their protein-rich environment. Thus, if these short time scales can be resolved experimentally, the plasma properties could be determined without having to separate the blood components; the blood is practically testing itself. This microrheological description of blood plasma provides a direct link between the composition of whole blood and its coagulability status. We present a parametric model for the viscoelasticity of plasma, which is probed by the erythrocytes over frequency ranges of kilohertz in a picoliter-sized volume. The model is validated both in vitro, using artificial hemo-systems where the composition is controlled, as well as on whole blood where continuous measurements provide real-time information. We also discuss the possibility of using this passive microrheology as an in vivo assay for clinically relevant situations where the blood clotting condition must be observed and managed continuously for diagnosis or during therapeutic procedures at different stages of hemostatic and thrombotic processes.