Predictors of post-operative left atrioventricular valve regurgitation in pediatric patients with complete atrioventricular canal defects.

BACKGROUND: In infants with complete atrioventricular canal (CAVC) defects, post-operative left atrioventricular valve regurgitation (LAVVR) is a known major cause of morbidity and mortality and a common indication for re-operation. However, there is scarce data to identify risk factors for poor outcomes. Our study aims to find echocardiographic characteristics that predict post-operative LAVVR at discharge and 1-year follow-up. METHODS: Retrospective cohort study of patients with initial CAVC repair at our hospital who were followed for 1 year between 2013 and 2022. Patients with major co-morbid conditions were excluded. Serial echocardiograms were reviewed. Anatomic details, quantitative and qualitative measure of LAVVR including the number of regurgitant jets, regurgitant jet length and vena contracta width, and ventricular function were collected. The time points measured include pre-operative transthoracic echocardiogram (TTE), post-operative transesophageal echocardiogram (PO-TEE), routine protocol based post-operative day 1 (POD1) TTE, discharge TTE and 1-year post-operative (1yPO) TTE. Paired t-tests, chi-square analysis, and linear regression analysis were performed comparing measured variables to LAVVR outcomes. RESULTS: Fifty-two patients were included; 92% had Trisomy 21. The majority were classified as Rastelli A (71%), others Rastelli C (29%). Only two patients had moderate or greater LAVVR pre-operatively. The mean age at repair was 125 ± 44 days. Pre-operative LAVVR was the only significant predictor of LAVVR severity at 1 year after backward stepwise regression. Of those with < moderate LAVVR on PO-TEE, 20% had worsening to ≥ moderate at discharge, but only 9% remained that way at 1 year. Of those with ≥ moderate LAVVR on PO-TEE, 40% improved to < moderate by 1 year. Two patients who worsened at 1 year, both secondary to likely cleft suture dehiscence. Only one patient required reoperation in the immediate post-operative period secondary to severe LAVVR due to suture dehiscence. Routine protocol-based POD1 echo did not have any association with altered outcomes. CONCLUSION: Pre-operative LAVVR was the only significant predictor of LAVVR severity at 1 year. A significant percentage (40%) of patient with ≥ moderate LAVVR on PO-TEE improved to < moderate by 1 year. Furthermore, routine protocol-based POD1 echo did not have any association with altered outcomes.

Development of the Cardiac Conduction System.

The electrical impulses that coordinate the sequential, rhythmic contractions of the atria and ventricles are initiated and tightly regulated by the specialized tissues of the cardiac conduction system. In the mature heart, these impulses are generated by the pacemaker cardiomyocytes of the sinoatrial node, propagated through the atria to the atrioventricular node where they are delayed and then rapidly propagated to the atrioventricular bundle, right and left bundle branches, and finally, the peripheral ventricular conduction system. Each of these specialized components arise by complex patterning events during embryonic development. This chapter addresses the origins and transcriptional networks and signaling pathways that drive the development and maintain the function of the cardiac conduction system.

Molecular Pathways and Animal Models of Ebstein's Anomaly.

Ebstein's anomaly is a congenital malformation of the tricuspid valve characterized by abnormal attachment of the valve leaflets, resulting in varying degrees of valve dysfunction. The anatomic hallmarks of this entity are the downward displacement of the attachment of the septal and posterior leaflets of the tricuspid valve. Additional intracardiac malformations are common. From an embryological point of view, the cavity of the future right atrium does not have a direct orifice connected to the developing right ventricle. This chapter provides an overview of current insight into how this connection is formed and how malformations of the tricuspid valve arise from dysregulation of molecular and morphological events involved in this process. Furthermore, mouse models that show features of Ebstein's anomaly and the naturally occurring model of canine tricuspid valve malformation are described and compared to the human model. Although Ebstein's anomaly remains one of the least understood cardiac malformations to date, the studies summarized here provide, in aggregate, evidence for monogenic and oligogenic factors driving pathogenesis.

Molecular Pathways and Animal Models of Tricuspid Atresia and Univentricular Heart.

The process of valve formation is a complex process that involves intricate interplay between various pathways at precise times. Although we have not completely elucidated the molecular pathways that lead to normal valve formation, we have identified a few major players in this process. We are now able to implicate TGF-ß, BMP, and NOTCH as suspects in tricuspid atresia (TA), as well as their downstream targets: NKX2-5, TBX5, NFATC1, GATA4, and SOX9. We know that the TGF-ß and the BMP pathways converge on the SMAD4 molecule, and we believe that this molecule plays a very important role to tie both pathways to TA. Similarly, we look at the NOTCH pathway and identify the HEY2 as a potential link between this pathway and TA. Another transcription factor that has been implicated in TA is NFATC1. While several mouse models exist that include part of the TA abnormality as their phenotype, no true mouse model can be said to represent TA. Bridging this gap will surely shed light on this complex molecular pathway and allow for better understanding of the disease process.

Cardiac Development and Animal Models of Congenital Heart Defects.

The major events of cardiac development, including early heart formation, chamber morphogenesis and septation, and conduction system and coronary artery development, are briefly reviewed together with a short introduction to the animal species commonly used to study heart development and model congenital heart defects (CHDs).

Cardiac Transcription Factors and Regulatory Networks.

Cardiac development is a fine-tuned process governed by complex transcriptional networks, in which transcription factors (TFs) interact with other regulatory layers. In this chapter, we introduce the core cardiac TFs including Gata, Hand, Nkx2, Mef2, Srf, and Tbx. These factors regulate each other's expression and can also act in a combinatorial manner on their downstream targets. Their disruption leads to various cardiac phenotypes in mice, and mutations in humans have been associated with congenital heart defects. In the second part of the chapter, we discuss different levels of regulation including cis-regulatory elements, chromatin structure, and microRNAs, which can interact with transcription factors, modulate their function, or are downstream targets. Finally, examples of disturbances of the cardiac regulatory network leading to congenital heart diseases in human are provided.

Cardiac magnetic resonance predictors for successful primary biventricular repair of unbalanced complete common atrioventricular canal.

BACKGROUND: Patients with unbalanced common atrioventricular canal can be difficult to manage. Surgical planning often depends on pre-operative echocardiographic measurements. We aimed to determine the added utility of cardiac MRI in predicting successful biventricular repair in common atrioventricular canal. METHODS: We conducted a retrospective cohort study of children with common atrioventricular canal who underwent MRI prior to repair. Associations between MRI and echocardiographic measures and surgical outcome were tested using logistic regression, and models were compared using area under the receiver operator characteristic curve. RESULTS: We included 28 patients (median age at MRI: 5.2 months). The optimal MRI model included the novel end-diastolic volume index (using the ratio of left ventricular end-diastolic volume to total end-diastolic volume) and the left ventricle-right ventricle angle in diastole (area under the curve 0.83, p = 0.041). End-diastolic volume index ≤ 0.18 and left ventricle-right ventricle angle in diastole ≤ 72° yield a sensitivity of 83% and specificity of 81% for successful biventricular repair. The optimal multimodality model included the end-diastolic volume index and the echocardiographic atrioventricular valve index with an area under the curve of 0.87 (p = 0.026). CONCLUSIONS: Cardiac MRI can successfully predict successful biventricular repair in patients with unbalanced common atrioventricular canal utilising the end-diastolic volume index alone or in combination with the MRI left ventricle-right ventricle angle in diastole or the echocardiographic atrioventricular valve index. A prospective cardiac MRI study is warranted to better define the multimodality characteristic predictive of successful biventricular surgery.

Anatomic considerations in the management of complete atrioventricular canal.

OBJECTIVE: Patients with complete atrioventricular canal have a variable clinical course prior to repair. Many patients balance their circulations well prior to elective repair. Others manifest clinically significant pulmonary over circulation early in life and require either palliative pulmonary artery banding or complete repair. The objective of this study was to assess anatomic features that impact the clinical course of patients. METHODS: In total, 222 patients underwent complete atrioventricular canal repair between 2012 and 2022 at a single institution. Twenty-seven (12%) patients underwent either pulmonary artery banding (n = 15) or complete repair (n = 12) at less than 3 months of age (Group 1). The remaining 195 (88%) underwent repair after 3 months of age (Group 2). Patient records and imaging were reviewed. RESULTS: The median post-operative length of stay following complete repair was 25 [7,46] days for those patients in Group 1 and 7 [5,12] days for those in Group 2 (p < 0.0001). There was relative hypoplasia of left-sided structures in Group 1 versus Group 2. Mean z-score for the ascending aorta was -1.2 (±0.8) versus -0.3 (±0.9) (p < 0.0001), the aortic isthmus was -2.1 (±0.8) versus -1.4 (±0.8) (p = 0.005). The pulmonary valve to aortic valve diameter ratio was median 1.47 [1.38,1.71] versus 1.38 [1.17,1.53] (p 0.008). CONCLUSIONS: Echocardiographic evaluation of the systemic and pulmonary outflow of patients with complete atrioventricular canal may assist in predicting the clinical course and need for early repair vs pulmonary artery banding.

Laterality defect of the heart in non-teleost fish.

Dextrocardia is a rare congenital malformation in humans in which most of the heart mass is positioned in the right hemithorax rather than on the left. The heart itself may be normal and dextrocardia is sometimes diagnosed during non-related explorations. A few reports have documented atypical positions of the cardiac chambers in farmed teleost fish. Here, we report the casual finding of a left-right mirrored heart in an 85 cm long wild-caught spiny dogfish (Squalus acanthias) with several organ malformations. Macroscopic observations showed an outflow tract originating from the left side of the ventricular mass, rather than from the right. Internal inspection revealed the expected structures and a looped cavity. The inner curvature of the loop comprised a large trabeculation, the bulboventricular fold, as expected. The junction between the sinus venosus and the atrium appeared normal, only mirrored. MRI data acquired at 0.7 mm isotropic resolution and subsequent 3D-modeling revealed the atrioventricular canal was to the right of the bulboventricular fold, rather than on the left. Spurred by the finding of dextrocardia in the shark, we revisit our previously published material on farmed Adriatic sturgeon (Acipenser naccarii), a non-teleost bony fish. We found several alevins with inverted (left-loop) hearts, amounting to an approximate incidence of 1%-2%. Additionally, an adult sturgeon measuring 90 cm in length showed abnormal topology of the cardiac chambers, but normal position of the abdominal organs. In conclusion, left-right mirrored hearts, a setting that resembles human dextrocardia, can occur in both farmed and wild non-teleost fish.

Cardiac magnetic resonance parameters associated with successful conversion from a single ventricular to a one-and-a-half or biventricular circulation in patients with a hypoplastic right ventricle.

BACKGROUND: Some patients with pulmonary atresia with an intact ventricular septum (PA/IVS) or a left ventricle dominant atrioventricular canal defect (LDAVC) with a hypoplastic right ventricle (RV) and univentricular (1 V) circulation may be candidates for conversion to either a complete biventricular (2 V) repair or a one-and-a-half ventricle repair (1.5 V). We sought to identify pre-operative cardiovascular magnetic resonance (CMR) findings associated with successful conversion from 1V to 1.5V or 2V circulation. METHODS: In this single center retrospective study, subjects with PA/IVS or LDAVC and no conotruncal abnormalities were included if they had a 1 V circulation at the time of CMR followed by a surgical intervention intended to convert them to a 1.5 V or 2 V circulation. Conversion failure was defined as any of the following: (1) oxygen saturation < 90% at the most recent follow-up, (2) conversion back to a 1.5 V or 1 V circulation, or (3) death. RESULTS: In the PA/IVS cohort (n = 15, median age 1.32 years), 10 patients underwent surgical conversion to a 1.5 V circulation and 5 to a 2 V circulation. In the attempted 1.5 V group, there were 2 failures, and these cases had a lower RV mass (p = 0.04). In the attempted 2 V group, there was 1 failure, and no CMR parameters were significantly different compared to the successes. Among the successful 2 V group patients, the minimum RV end-diastolic volume (EDV) was 27 ml/m2. In the LDAVC cohort (n = 15, median age 1.0 years), 1 patient underwent surgical conversion to a 1.5 V circulation and 14 patients to a 2 V circulation. In the attempted 1.5 V group, the 1 conversion was a failure and had an RV EDV of 15 ml/m2. In the attempted 2 V group, there were 2 failures, and these cases had a smaller RV:LV stroke volume ratio (p = 0.05) and a lower RV ejection fraction (p = 0.05) compared to the successes. Among the successful 2 V group patients, the minimum RV EDV was 22 ml/m2. CONCLUSIONS: We identified multiple CMR parameters associated with successful conversion from 1 V circulation to 1.5 V or 2 V circulation in patients with PA/IVS and LDAVC. This information may improve patient selection for conversion procedures and encourage larger studies to better define the role of CMR.

Predictors of increased postoperative length of stay after complete atrioventricular canal repair.

BACKGROUND: The optimal timing of surgical repair for infants with complete atrioventricular canal defect remains controversial, as there are risks to both early and late repair. We address this debate by investigating the association of various risk factors, including age and weight at surgery, markers of failure to thrive, and pulmonary vascular disease, with postoperative length of stay following complete atrioventricular canal repair. METHODS: Infants who underwent repair of complete atrioventricular canal were identified from our institutional Society of Thoracic Surgeons Congenital Heart Surgery Database. Additional clinical data were collected from the electronic medical record. Descriptive statistics were computed. Associations between postoperative length of stay and covariates of interest were evaluated using linear regression with bootstrap aggregation. RESULTS: From 2001 to 2020, 150 infants underwent isolated complete atrioventricular canal repair at our institution. Pre-operative failure to thrive and evidence of pulmonary disease were common. Surgical mortality was 2%. In univariable analysis, neither weight nor age at surgery were associated with mortality, postoperative length of stay, duration of mechanical ventilation, or post-operative severe valvular regurgitation. In multivariable analysis of demographic and preoperative clinical factors using bootstrap aggregation, increased postoperative length of stay was only significantly associated with previous pulmonary artery banding (33.9 day increase, p = 0.03) and preoperative use of supplemental oxygen (19.9 day increase, p = 0.03). CONCLUSIONS: Our analysis shows that previous pulmonary artery banding and preoperative use of supplemental oxygen were associated with increased postoperative length of stay after complete atrioventricular canal repair, whereas age and weight were not. These findings suggest operation prior to the onset of pulmonary involvement may be more important than reaching age or weight thresholds.

Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region.

The atrioventricular canal (AVC) is the site where key structures responsible for functional division between heart regions are established, most importantly, the atrioventricular (AV) conduction system and cardiac valves. To elucidate the mechanism underlying AVC development and function, we utilized transgenic zebrafish line sqet31Et expressing EGFP in the AVC to isolate this cell population and profile its transcriptome at 48 and 72 hpf. The zebrafish AVC transcriptome exhibits hallmarks of mammalian AV node, including the expression of genes implicated in its development and those encoding connexins forming low conductance gap junctions. Transcriptome analysis uncovered protein-coding and noncoding transcripts enriched in AVC, which have not been previously associated with this structure, as well as dynamic expression of epithelial-to-mesenchymal transition markers and components of TGF-ß, Notch, and Wnt signaling pathways likely reflecting ongoing AVC and valve development. Using transgenic line Tg(myl7:mermaid) encoding voltage-sensitive fluorescent protein, we show that abolishing the pacemaker-containing sinoatrial ring (SAR) through Isl1 loss of function resulted in spontaneous activation in the AVC region, suggesting that it possesses inherent automaticity although insufficient to replace the SAR. The SAR and AVC transcriptomes express partially overlapping species of ion channels and gap junction proteins, reflecting their distinct roles. Besides identifying conserved aspects between zebrafish and mammalian conduction systems, our results established molecular hallmarks of the developing AVC which underlies its role in structural and electrophysiological separation between heart chambers. This data constitutes a valuable resource for studying AVC development and function, and identification of novel candidate genes implicated in these processes.

Dosing of Opioid Medications During and After Pediatric Cardiac Surgery for Children With Down Syndrome.

OBJECTIVE: To determine whether children with Down syndrome (DS) receive higher doses of opioid medications compared with children without DS for repair of complete atrioventricular canal (CAVC). DESIGN: A retrospective chart review of children with and without DS who underwent primary repair of CAVC. The exclusion criteria included unbalanced CAVC and patients undergoing biventricular staging procedures. The primary outcome was oral morphine equivalents (OME) received in the first 24 hours after surgery. The secondary outcomes included intraoperative OME, OME at 48 and 72 hours, nonopioid analgesic and sedative medications received, pain scores, time to extubation, and length of stay. SETTING: A pediatric academic medical center in the United States. PARTICIPANTS: One hundred thirty-one patients with DS and 24 without, all

The effect of surgical technique, age, and Trisomy 21 on early outcome of surgical management of complete atrioventricular canal defect.

BACKGROUND: The optimal timing, surgical technique, and the influence of Trisomy 21 on the outcome of surgical repair of Complete Atrioventricular Canal Defect remains uncertain. We reviewed our experience in the repair of CAVC to identify the influence of these factors on operative outcomes. METHODS: A prospective study included 70 patients, who underwent repair of CAVC at our institute between July, 2016 and October, 2019. Primary endpoint was mortality and the secondary endpoint was a degree of left atrioventricular valve regurgitation. RESULTS: No significant difference was noted between patients operated on, at the first 6 months of age versus later, regarding mortality or LAVV regurgitation. Surgical repair by modified single-patch technique showed a significant reduction in bypass time (71.13 ± 13.507 min versus 99.19 ± 27.092 min, p-value = 0.001). Compared to closure of cleft only, posterior annuloplasty used for repair of LAVV resulted in significant reduction in the occurrence of post-operative valve regurgitation during the early period (LAVV 2 + 43 versus 7 %, p-value = 0.03) and at 6 months of follow-up (LAVV 2 + 35.4 versus 0 %, p-value = 0.01), respectively. CONCLUSIONS: Early intervention, in the first 6 months in patients with CAVC by surgical repair gives comparable acceptable results to later repair; Trisomy 21 was not found to be a risk factor for early intervention. Repair of common AV valve by cleft closure with posterior LAVV annuloplasty showed better results with a significant decrease in post-operative LAVV regurgitation and early mortality in comparison to the closure of cleft only.

Post-operative course of pulmonary artery pressure after complete atrioventricular canal defect repair.

Complete atrioventricular canal defect is a CHD associated with intra-cardiac shunting of blood, which can lead to irreversible changes in pulmonary vascular resistance and pulmonary artery hypertension if unrepaired. Patients with Trisomy 21 are at risk for early development of pulmonary artery hypertension if left uncorrected.1,2. OBJECTIVES: The purpose of this study is to describe the evolution of pulmonary artery hypertension after repair of complete atrioventricular canal defect and to determine the time to normalisation of pulmonary artery pressure in both patients with and without Trisomy 21. METHODS: This is a single centre, retrospective analysis of patients with complete atrioventricular canal defect admitted for surgical repair at the University of Maryland Medical Center from 2005 to 2015. T-test or Mann-Whitney test and Chi-Square or Fisher's exact tests were used to compare the two groups (patients with Trisomy 21 and those without). Repeated measures of analysis of variance and serial measurement analysis were performed. RESULTS: Twenty-nine patients meeting the inclusion criteria underwent repair of complete atrioventricular defects during the study period. The right ventricular pressure estimate remained elevated over time and did not show a significant difference between the two groups. Right ventricular to systolic blood pressure ratios for all patients remained > 0.5 over the time periods assessed. CONCLUSIONS: Our study suggests that in patients with complete atrioventricular canal defects, the right ventricular pressure remains elevated and does not normalise on echocardiograms performed up to one year after surgery, suggesting a sustained elevation in pulmonary vascular resistance.

A case of a complete atrioventricular canal defect in a ferret.

BACKGROUND: Atrioventricular canal defect is a rare congenital disorder of the heart and describes the presence of an atrial septal defect, a variable presentation of ventricular septal alterations including ventricular septal defect malformations in the mitral and tricuspid valves. The defect has been described in human beings, dogs, cats, pigs, and horses. CASE PRESENTATION: This paper describes the case of a complete atrioventricular canal defect in a four-year-old intact male pet ferret (Mustela putorius furo), which was presented due to posterior weakness, ataxia, and decreased appetite. A loud systolic murmur, dyspnea, and hind limb paraparesis were detected during the clinical examination. Thoracic radiographs showed generalized cardiomegaly and lung edema. ECG showed sinus rhythm with prolonged P waves and QRS complexes. Echocardiography showed a large atrial septal defect, atrioventricular dysplasia, and a ventricular septal defect. Palliative treatment with oxygen, furosemide, spironolactone, enalapril, diltiazem, and supportive care was chosen as the therapy of choice. The ferret recovered gradually during hospitalization. A follow-up examination at three and six months showed stabilization of cardiac function. CONCLUSIONS: To the authors knowledge, this is the first time an atrioventricular canal defect has been described in a pet ferret.

Gradually Progressive Dyspnea and Exercise Intolerance in an Otherwise Active Middle-Aged Woman: Why Was the Presentation of Congenital Heart Disease Delayed?

Patients with congenital heart disease (CHD) increasingly are surviving into adulthood. In the United States alone, there are more than one million adult patients living with CHD with the number increasing about 5% each year. With more than 85% of infants with CHD surviving into adulthood with their disease, encounters with these patients in the operating room for cardiac and noncardiac operative procedures is becoming more commonplace. Most of these patients receive corrective surgery early in life, although some may live with uncorrected CHD with no-to-relatively mild symptoms and present at a later time in life with symptoms of heart failure or pulmonary hypertension. The authors present an adult patient with uncorrected CHD presenting with late onset of heart failure symptoms. The authors also review the patient's complex congenital heart lesion, transesophageal echocardiography findings, and intraoperative management.

From Other Journals: A Review of Recent Articles by Our Editorial Team.

In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our hope is to provide a summary of the latest articles published recently in other journals in our field. The articles address (1) outcomes for COVID-19 infection in adults with congenital heart disease which showed no increased mortality compared to the general population, (2) hepatorenal dysfunction before transplantation in patients with Fontan is associated with increased mortality, (3) abnormal Von Willebrand factor metabolism and angiopoietin signaling may contribute to pulmonary AVM formation in children with a Glenn circulation, (4) low cardiac output after the Norwood procedure which improves with higher hemoglobin and with milrionone, (5) a comparison of staged versus complete repair in neonatal tetralogy of Fallot reveiling the pros and cons of each strategy, (6) the long-term outcomes of early repair of complete atrioventricular canal show no difference in outcomes in patients who were repaired below 3 months of life.

From Other Journals: A Review of Recent Articles by Our Editorial Team.

In this review we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our hope is to provide a summary of the latest articles published recently in other journals in our field. The articles address (1) a summary of a scientific statement of the American Heart Association for diagnosis and treatment of myocarditis, (2) development of a perioperative risk score for in-hospital mortality after cardiac surgery in adults with congenital heart disease, (3) using a machine learning algorithm to predict cardiopulmonary deterioration in patients in the interstage period 1-2 h in advance using hospital monitor generated data, (4) risk factors for reoperation after the arterial switch operation, (5) the effect of mitochondrial transplantation for cardiogenic shock in pediatric patients, (6) comparing outcomes of primary or staged repair in tetralogy of Fallot with pulmonary atresia.

Selective His-bundle pacing in an adult with atrioventricular canal defect via retrograde His localization.

Adult congenital heart disease patients may undergo numerous fluoroscopically guided procedures including pacemaker implantation during their lifetime. One alternative to traditional pacemaker setup which may improve long-term pacing outcomes is His bundle pacing. Given the altered His-bundle location, and given increased radiation exposure over a lifetime, we used 3-dimensional mapping to locate the His and to minimize fluoroscopy for placement of a His-bundle pacemaker system in a 31-year old patient with atrioventricular canal defect and complete heart block with 100% RV pacing and epicardial lead fracture. METHODS: An Octapolar Livewire catheter (Abbott, Minneapolis, USA) was used for mapping and location of the His bundle from a right femoral venous access on the EnSite Precision system 3-dimensional mapping system (Abbott Medical, Abbott Park, IL). The same map was used to guide 3830 lead placement into the posterior-inferior His-bundle position. RESULTS: Successful placement of a His-bundle pacing system with thresholds of 1Volt@0.4ms for both the atrial and ventricular leads with selective His-bundle pacing noted. Ten-month follow-up demonstrated His-bundle capture at 0.75V@0.4ms with stable impedance, sensing and with 100% right ventricular pacing a projected longevity of 12 years total. CONCLUSIONS: Successful placement of selective His-bundle pacing can be achieved in an adult patient with atrioventricular canal defect using 3-dimensional mapping.