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method of treating timber before applying a coating has been developed and tested. An organofunctional silane coupling compound was found that was capable of reacting and forming bonds with both wood and a range of coatings. Wet and dry adhesion strength between a range of coatings and wood has been determined by the direct pull-off test under a variety of test conditions. The data presented show how the bridging of the interface between wood and coating can, with some coatings, improve not only the initial bond strength but also provide significantly higher wet adhesion strength and long-term bond durability. [ABSTRACT FROM AUTHOR]

Objective: To identify the incidence of left heart abnormalities in patients with Ebstein anomaly, recognizing that left-sided lesions in this patient group have been overlooked.Patients and Methods: According to the echocardiography database at the Mayo Clinic in Rochester, Minn, 106 consecutive patients with Ebstein anomaly underwent echocardiography between July 1, 2001, and February 28, 2003. Clinical data as well as electrocardiographic and echocardiographic reports and images were reviewed.Results: Ebstein anomaly was severe in 76 patients (72%). Previous tricuspid valve surgery was reported in 46 patients (43%), and previous closure of an atrial septal defect or patent foramen ovale was reported in 34 patients (32%). Left ventricular (LV) myocardial changes resembling noncompaction occurred in 19 patients (17.9%), LV systolic dysfunction in 7 patients (7%), LV diastolic dysfunction in 34 (36%) of 95 patients, and LV dilatation in 4 patients (4%). Additional left-sided cardiac lesions included mitral valve prolapse in 16 patients (15%), bicuspid aortic valve in 8 (8%), mitral valve dysplasia in 4 (4%), and ventricular septal defect in 8 (8%). Wolff-Parkinson-White syndrome occurred in 22 patients (21%). The QRS axis tended to be different in LV noncompaction with a mean +/- SD axis of 12 degrees +/- 74 degrees vs 36 degrees +/- 66 degrees overall (P=.08). Otherwise, there were no differences in clinical or surgical data between the groups with normal and abnormal LV myocardium.Conclusions: In patients with Ebstein anomaly, left heart abnormalities involving the myocardium or valves were observed in 39% of patients. Ebstein anomaly should not be regarded as a disease confined to the right side of the heart. [ABSTRACT FROM AUTHOR]

Left atrial (LA) enlargement is an indicator of chronic elevation in left ventricular (LV) end-diastolic pressure as well as diastolic dysfunction. There is a lack of data on the significance of LA volume in the pediatric population. The objective of this study was to elucidate the relation between LA volume and diastolic dysfunction, clinical symptoms, and exercise capacity in young patients with hypertrophic cardiomyopathy. All patients aged <20 years with obstructive hypertrophic cardiomyopathy who underwent evaluation at the Mayo Clinic from 2002 to 2006 were retrospectively identified. Reviews of the LA volume index and other traditional diastolic Doppler echocardiographic parameters, as well as clinical data, were performed. A total of 88 patients (66 male) were studied. The median age at evaluation was 14 years. The mean LA volume index was 39 +/- 19 ml/m(2). Additional echocardiographic parameters included a mean LV outflow gradient of 55 +/- 51 mm Hg, a mean E/E' ratio of 14.0 +/- 7.6, and a mean maximal septal wall thickness of 23 +/- 9 mm. On univariate linear regression analysis, LA volume index had an excellent correlation with diastolic dysfunction grade (p <0.001, r(2) = 0.6), LV outflow tract gradient, mitral E/E', and the degree of mitral regurgitation. LA volume index was also positively associated with symptom score (p = 0.005) and maximal oxygen consumption on exercise test (n = 22; p = 0.01). On multivariate analysis, LA volume index was related to diastolic dysfunction grade (p <0.001) and mean mitral regurgitation grade (p = 0.05). In conclusion, this study demonstrates the potential clinical importance of LA volume index in pediatric hypertrophic cardiomyopathy as a marker of the severity of underlying diastolic dysfunction, symptom score, and decreased exercise capacity. LA volume index has significant diagnostic and prognostic value in these patients. [ABSTRACT FROM AUTHOR]

Solitary myofibromas are rare, benign, mesenchymal tumors typically found in the head and neck regions. We report an exceptionally rare case of a solitary cardiac myofibroma and its short-term management and outcome. A two-month-old infant was referred due to a murmur. Echocardiography revealed a 2 × 1 cm solitary mass originating from a mitral papillary muscle, causing severe regurgitation. Magnetic resonance imaging showed the mass to be homogeneous on T1, hyperintense on T2, and hypointense on first-pass perfusion imaging with no enhancement on delayed postcontrast imaging. The mass was surgically excised partially due to its involvement with the mitral valve. Postoperative recovery was uneventful, with echocardiography four months later showing no tumor recurrence and trivial mitral regurgitation. This report provides valuable imaging and pathology examples to aid in the recognition of this rare tumor and demonstrates that successful surgical excision is possible, even with significant cardiac involvement., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: There are no criteria guiding the timing of heart transplant referral for Fontan patients, nor are there any characteristics of those deferred or declined listing reported. This study examines comprehensive transplant evaluations for Fontan patients of all ages, listing decisions, and outcomes to inform referral practices., Methods: Retrospective review of 63 Fontan patients formally assessed by the advanced heart failure service and presented at Mayo Clinic transplant selection committee meetings (TSM) January 2006 to April 2021. The study is compliant with the Helsinki Congress and Declaration of Istanbul and included no prisoners. Statistical analysis was performed with Wilcoxon Rank Sum and Fisher's Exact tests., Results: Median age at TSM was 26 years (17.5, 36.5). Most were approved (38/63 [60%]); 9 of 63 (14%) were deferred and 16 of 63 (25%) were declined. Approved patients more commonly were <18 years old at TSM (15/38 [40%] vs 1/25 [4%], P = .002) compared with those deferred/declined. Complications of Fontan circulatory failure were less common in approved vs deferred/declined patients: ascites (15/38 [40%] vs 17/25 [68%], P = .039), cirrhosis (16/38 [42%] vs 19/25 [76%], P = .01), and renal insufficiency (6/38 [16%] vs 11/25 [44%], P = .02). Ejection fraction and atrioventricular valve regurgitation did not differ between groups. Pulmonary artery wedge pressure was overall high normal (12 mm Hg [9,16]) but higher in deferred/declined vs approved patients, 14.5 (11, 19) vs 10 (8, 13.5) mm Hg, P = .015. Overall survival was significantly lower in deferred/declined patients (P = .0018)., Conclusion: Fontan patient referral for heart transplant at younger age and before the onset of end-organ complications is associated with increased approval for transplant listing., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There is currently no consensus regarding the use of surveillance cross-sectional imaging in pediatric patients after bidirectional cavopulmonary connection (BDCPC). We sought to determine how computed tomography with angiography (CTA) and cardiac magnetic resonance (CMR) imaging impacted the clinical management of pediatric patients after BDCPC., Methods: A single-center retrospective study including patients with single ventricle who had BDCPC between 2010 and 2019, and CTA/CMR studies obtained in these patients, at ≤5 years of age, and with Glenn physiology. Repeat studies on the same patient were included if the clinical situation had changed. The impact of CTA/CMR studies was categorized as major , minor, or none ., Results: Twenty-four patients (63% male) and 30 imaging studies (22 CTAs) were included. 60% were obtained in patients with hypoplastic left heart syndrome (HLHS); most common indication was Follow-up after an intervention (23%). 6 CMRs were performed on stable HLHS patients as part of a research protocol, with no clinical concerns. The overall impact of CTA/CMR studies was major in 13 cases (43.3%). CTA/CMR studies performed ≥1 year of age (62.5% vs 21.4%, P  = .02) and in non-HLHS patients (66.7% vs 27.8%, P  = .035) were associated with major impact. Also, 2/6 Research studies were associated with a major impact., Conclusions: CTA/CMR imaging in pediatric patients with SV after BDCPC was associated with significant clinical impact in over 40% of cases, with a higher impact if obtained in patients ≥1 year of age and in non-HLHS patients. We cannot disregard the possibility of CMR as a surveillance imaging modality in this population.

Aorto-ventricular tunnels are rare, congenital extracardiac connections arising from the tubular ascending aorta, above the sinotubular junction, which communicate directly with the ventricular cavity. We present long-term follow-up in a series of five adults undergoing pediatric repair and describe the cardiovascular features and outcomes. Significant aortic regurgitation, ascending aortic aneurysm and left ventricular noncompaction were found to be highly prevalent, emphasizing the need for ongoing surveillance following repair of this anomaly., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: The objective of this study is to assess the safety and early impact of intramyocardial delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) at time of surgical Ebstein repair., Methods: Patients with Ebstein anomaly (ages 6 months to 30 years) scheduled to undergo repair of the tricuspid valve were eligible to participate in this open-label, non-randomized phase I clinical trial. BM-MNC target dose was 1-3 million cells/kg. Ten patients have undergone surgical intervention and cell delivery to the right ventricle (RV) and completed 6-month follow-up., Results: All patients underwent surgical tricuspid valve repair and uneventful BM-MNC delivery; there were no ventricular arrhythmias and no adverse events related to study product or delivery. Echocardiographic RV myocardial performance index improved and RV fractional area change showed an initial decline and then through study follow-up. There was no evidence of delayed myocardial enhancement or regional wall motion abnormalities at injection sites on 6-month follow-up magnetic resonance imaging., Conclusions: Intramyocardial delivery of BM-MNC after surgical repair in Ebstein anomaly can be performed safely. Echocardiography variables suggest a positive impact of cell delivery on the RV myocardium with improvements in both RV size and wall motion over time. Additional follow-up and comparison to control groups are required to better characterize the impact of cell therapy on the myopathic RV in Ebstein anomaly., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To define the impact of tricuspid valve cone reconstruction (CR) on ventricular performance in Ebstein anomaly, both independently and after stem cell therapy., Patients and Methods: The control group included 257 patients who had CR between June 2007 and December 2019. Ten subjects of a phase I stem cell therapy trial (May 2017 - March 2019) were compared with the controls to assess the echocardiographic impact on ventricular remodeling., Results: After CR, right ventricular (RV) size decreased and left ventricular (LV) volume increased in all patients. Apical and biplane RV fractional area change (FAC) initially decreased, but rebounded by 6 months postoperation. Short-axis FAC increased early and was maintained at 6 months post-CR in the control group. At 6 months post-CR, cell therapy patients showed a significantly larger increase in short-axis FAC (24.4% vs 29.9%, P=.003). In addition, whereas LV ejection fraction (EF) was unchanged at 6 months post-CR in controls, cell therapy patients showed a significant increase in EF relative to baseline and to controls (55.6% vs 65.0%, P=.007)., Conclusion: Cone reconstruction reduces tricuspid regurgitation and RV size, but is also associated with increased RV FAC and LV volume. Furthermore, injection of bone marrow-derived stem cells augmented the increase in RV FAC and was associated with improved LV EF at 6 months post-CR. This is evidence of a favorable interventricular interaction. These findings provide motivation for continued investigation into the potential benefits of stem cell therapy in Ebstein anomaly and other congenital cardiac malformations., Trial Registration: clinicaltrials.gov identifier: NCT02914171., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: There is a paucity of literature regarding systemic semilunar valve (SSLV) dysfunction in patients with Fontan circulation. We sought to describe our center's 47-year experience with systemic semilunar valve replacement or repair (SSLVR) in patients with Fontan circulation. Methods: The Mayo Clinic Fontan Database is a comprehensive institutional database that stores clinical information of 1176 patients from 1973 to 2021. It was reviewed to identify patients who had a SSLV intervention at the time of or after Fontan. A cohort of 15 patients was identified and a retrospective review of their records was performed. Results: Fourteen patients had SSLV replacement (all mechanical) and one had a repair. SSLVR occurred up to 29 years following the Fontan (mean 11.3 ± 9 years, median 14 years). Thirteen of 14 with SSLVR were performed after Fontan and one was done at the time of initial Fontan. This was an older cohort and mean age at the time of Fontan was 8.7 ± 9.4 years (median 4 years). Indication for the operation was > moderate SSLV regurgitation in all patients. Six patients had decreased ventricular function (EF < 50%) prior to SSLVR and 8 had reduced function after SSLVR. Conclusion: Fortunately, the need for SSLV intervention after Fontan was rare, as evidenced by our small cohort extracted from a large single-institution database spanning a 47-year time period. Reduced preoperative and postoperative ejection fraction was common but did not seem to impact the outcome. Optimal timing for SSLV intervention after Fontan remains unclear.

Preservation of right ventricle function (RV) is a key to favorable outcome in Hypoplastic Left Heart Syndrome (HLHS), but methods to preserve or improve RV function are limited. Our goal was to assess the clinical and functional impact of autologous umbilical cord blood-derived mononuclear cells (UCB-MNC) therapy when given to patients with HLHS at Stage II surgery. UCB-MNC patients were enrolled prospectively in a phase I, FDA monitored trial as previously described (Burkhart et al., 2019). Matched retrospective controls were identified by review of clinical databases. Growth and RV echocardiographic variables were assessed in both groups prestage II through the first 6 months postoperatively. Statistical comparisons between the groups at similar postoperative time points were made to define potential impact of the cell therapy. There were 7 UCB-MNC patients and 17 controls. Prestage II, most parameters showed no differences between groups, although median fractional area change (FAC) was slightly greater in the controls (FAC: controls = 45% vs UCB-MNC = 41% P= 0.02). At dismissal, FAC and estimated Ejection Fraction (EF) decreased in controls, while both were unchanged from baseline in UCB-MNC patients (ΔFAC: -5% vs -1%, P < 0.01; ΔEF: -8% vs 0%, P = 0.03, respectively). Subsequently, median FAC increased slightly in UCB-MNC patients over the 6 month follow-up period, while it decreased in controls (ΔFAC: UCB-MNC +3% vs control -5%, P = 0.03). Preoperative weight percentiles were similar in both groups (UCB-MNC 34%ile vs controls 22%ile, P = 0.93). However, by 6 months postoperative, median weight percentile improved to 63% in the UCB-MNC treated group, but declined to 8% in controls (P = 0.02). UCB-MNC therapy appears to limit the initial negative impact on RV FAC and EF seen after stage II surgery. During early follow up, FAC and weight percentile improved in UCB-MNC patients relative to controls, suggesting a beneficial effect of UCB-MNC therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Myocardial strain offers new insights into ventricular performance, There are software packages from several different companies used to ascertain this, and little data is available in patients with single right ventricle (sRV) physiology. We aimed to compare the analysis of two strain software applications using a cohort of patients with sRV for both inter-vendor and inter-observer variability. Echocardiograms from 85 patients with sRV (122 separate studies) were prospectively evaluated. All had Glenn and/or Fontan palliation. Longitudinal 4-chamber (4LS), inflow/outflow (IO), circumferential, and radial strain were assessed using Velocity Vector Imaging (VVI, Seimens, Munich) and Automated Functional Imaging (AFI, General Electric, Boston) software. In a subset of 45 patients (61 separate studies), strain measurements were obtained by two sonographers so a paired "inter-observer" analysis could be performed. A moderate correlation between measurements made by the two systems was observed. Circumferential strain assessment had the highest R value (0.77) with all others having R values < 0.6. Both software packages showed modest inter-observer reproducibility for longitudinal and circumferential strain. VVI intraclass correlation coefficients (ICC) for 4LS and average circumferential strain (ACS) were 0.6 and 0.58, compared to 0.68 and 0.59 for AFI. Other than radial strain and VVI IO inferior strain, mean strain differences between AFI and VVI were ≤ 1%. Inter-observer variability is modest, however, mean differences are minimal suggesting reasonable clinical reliability. Inter-vendor variability is greater and not as clinically reliable. In patients with sRV, serial assessments with strain should be performed using the same software., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Accurate assessment of the right ventricular (RV) volume and function is important in patients with hypoplastic left heart syndrome (HLHS). We sought to investigate the effect of ventriculotomy on the correlation of RV functional assessments by two-dimensional echocardiography (2DE) to cardiac magnetic resonance (CMR)-derived RV ejection fraction (EF) in patients with HLHS. A retrospective re-analysis of CMR imaging with matched 2DE was performed from the institutional HLHS registry. Echocardiographic RV functional parameters were analyzed and correlated with CMR-derived EF. Intraclass correlation coefficient was used to determine interobserver reliability. A total of 58 matched echocardiograms and CMR imaging studies from 46 patients was evaluated. Median duration between CMR imaging and echocardiogram was 1 day (range 0-6 days). No significant difference was seen in CMR RV EF between patients with and without a ventriculotomy (EF - 43.6% vs 44.7%, p = 0.85). The presence of a ventriculotomy significantly decreased the correlation of biplane FAC (r = 0.86 vs 0.52; p = 0.02), triplane FAC (r = 0.84 vs 0.49; p = 0.03), and 2DE visually estimated EF (r = 0.83 vs 0.49; p = 0.02). The correlation of circumferential and longitudinal strains to CMR-derived EF was not significantly affected by the presence of a ventriculotomy. A prior ventriculotomy significantly affected correlation between 2DE FAC and visually estimated EF with CMR-derived EF. The dyskinetic myocardial segment due to ventriculotomy, which is often not visualized by 2DE, may be the reason for this discrepancy.

Left ventricular (LV) morphology may affect right ventricular (RV) function before and after Fontan palliation in patients with hypoplastic left heart syndrome (HLHS). We sought to assess the potential impact of LV morphology on RV function in patients with HLHS using cardiac magnetic resonance (CMR) imaging. A retrospective analysis of available CMR scans from all patients with HLHS was performed. LV morphology was categorized as absent/slit-like or globular/miniaturized. Volumetric analysis was performed using manual disc-summation method on steady-state free precession (SSFP) stack obtained in short-axis orientation of the ventricles. 4-chamber and short-axis SSFP images were used to measure strain on a semi-automated feature-tracking (FT) module. Two sample t-test was used to compare the groups. A total of 48 CMR scans were analyzed. Of those, 12 patients had absent/slit-like and 36 had globular/miniaturized LV morphology. Averaged 4-chamber longitudinal RV strain was significantly higher for absent/slit-like (- 17.6 ± 4.7%) than globular/miniaturized (- 13.4 ± 3.5; P = 0.002). Averaged 4-chamber radial RV strain was also significantly higher for absent/slit-like (33.1 ± 14.9%) than globular/miniaturized (21.6 ± 7.1; P = 0.001). For globular/miniaturized LV morphology, the decreases of 4-chamber longitudinal and radial strains were mainly attributable to the septal basilar and septal mid-ventricular segments. No differences were found in short-axis RV global circumferential strain between the morphologic subtypes (absent/slit-like - 15.0 ± 6.5, globular/miniaturized - 15.7 ± 4.7; P = 0.68). Larger LV remnants, with globular/miniaturized LV morphology, demonstrated diminished strain in the septal base and mid-ventricle segments. Patients with globular/miniaturized LV morphology may benefit with closer monitoring and lower threshold to start heart failure medications. These results exemplify the utility of including both septal and regional deformation in systemic RV strain analysis.

Background: Hypoplastic left heart syndrome (HLHS) with risk of poor outcome has been linked to MYH6 variants, implicating overlap in genetic etiologies of structural and myopathic heart disease., Methods: Whole genome sequencing was performed in 197 probands with HLHS, 43 family members, and 813 controls. Data were filtered for rare, segregating variants in 3 index families comprised of an HLHS proband and relative(s) with cardiomyopathy. Whole genome sequencing data from cases and controls were compared for rare variant burden across 56 cardiomyopathy genes utilizing a weighted burden test approach, accounting for multiple testing using a Bonferroni correction., Results: A pathogenic MYBPC3 nonsense variant was identified in the first proband who underwent cardiac transplantation for diastolic heart failure, her father with left ventricular noncompaction, and 2 fourth-degree relatives with hypertrophic cardiomyopathy. A likely pathogenic RYR2 missense variant was identified in the second proband, a second-degree relative with aortic dilation, and a fourth-degree relative with dilated cardiomyopathy. A pathogenic RYR2 exon 3 in-frame deletion was identified in the third proband diagnosed with catecholaminergic polymorphic ventricular tachycardia and his father with left ventricular noncompaction and catecholaminergic polymorphic ventricular tachycardia. To further investigate HLHS-cardiomyopathy gene associations in cases versus controls, rare variant burden testing of 56 genes revealed enrichment in MYH6 ( P =0.000068). Rare, predicted-damaging MYH6 variants were identified in 10% of probands in our cohort-4 with familial congenital heart disease, 4 with compound heterozygosity (3 with systolic ventricular dysfunction), and 4 with MYH6 - FLNC synergistic heterozygosity., Conclusions: Whole genome sequencing in multiplex families, proband-parent trios, and case-control cohorts revealed defects in cardiomyopathy-associated genes in patients with HLHS, which may portend impaired functional reserve of the single-ventricle circulation.

Objectives: Staged surgical palliation for hypoplastic left heart syndrome results in an increased workload on the right ventricle serving as the systemic ventricle. Concerns for cardiac dysfunction and long-term heart failure have generated interest in first-in-infant, cell-based therapies as an additional surgical treatment modality., Methods: A phase 1 clinical trial was conducted to evaluate the safety and feasibility of direct intramyocardial injection of autologous umbilical cord blood-derived mononuclear cells in 10 infants with hypoplastic left heart syndrome at the time of stage II palliation., Results: All 10 patients underwent successful stage II palliation and intramyocardial injection of umbilical cord blood-derived mononuclear cells. Operative mortality was 0%. There was a single adverse event related to cell delivery: An injection site epicardial bleed that required simple oversew. The cohort did not demonstrate any significant safety concerns over 6 months. Additionally, the treatment group did not demonstrate any reduction in cardiac function in the context of the study related intramyocardial injections of autologous cells., Conclusions: This phase 1 clinical trial showed that delivering autologous umbilical cord blood-derived mononuclear cells directly into the right ventricular myocardium during planned stage II surgical palliation for hypoplastic left heart syndrome was safe and feasible. Secondary findings of preservation of baseline right ventricular function throughout follow-up and normalized growth rates support the design of a phase 2b follow-up trial., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Hypoplastic left heart syndrome is one of the most complex congenital heart diseases and requires several cardiac surgeries for survival. The diagnosis is usually established prenatally or shortly after birth. Each stage of surgery poses a unique hemodynamic situation that requires deeper understanding to manage common pediatric problems such as dehydration and respiratory infections. Careful multidisciplinary involvement in the care of these complex patients is improving their outcome; however, morbidity and mortality are still substantial. In this review, we focus on the hemodynamic aspects of various surgical stages that a primary care provider should know to manage these challenging patients., (© American Academy of Pediatrics, 2019. All rights reserved.)

Background: Diastolic dysfunction is felt to be part of the natural history of patients with prior Fontan operation. Despite that, data on noninvasive assessment of diastolic function and ventricular filling pressures in Fontan patients are limited., Methods: We included 45 adult Fontan patients who underwent right heart catheterization with pulmonary artery wedge pressure (PAWP) measurement and transthoracic echo-Doppler assessment within 7 days. Offline measurement of systemic atrioventricular valve pulsed-wave (PW) and medial/lateral atrioventricular annular tissue Doppler velocities was performed and correlated to PAWP., Results: Median age was 31.4 years (IQR 24.8-37); 51% of patients were females. Median ventricular ejection fraction was 55% (IQR 50.3-57.5) and median PAWP was 10 mm Hg (IQR 8-11). PW Doppler E velocity (r = 0.64, p ≤ 0.0001), deceleration time (r = -0.40, p = 0.008), and E/A ratio (r = 0.33, p = 0.03) correlated with PAWP. Median medial and lateral E/e' ratios also correlated to PAWP (r = 0.71, p = 0.002 and r = 0.75, p < 0.0001; respectively). An E velocity >75 cm/s had 88% sensitivity and 86% specificity [97% negative predictive value (NPV); 58% positive predictive value (PPV)], E/A ratio >1.7 had 100% sensitivity and 61% specificity (100% NPV; 26% PPV), and deceleration time <135 ms had 88% sensitivity and 83% specificity (97% NPV; 58% PPV) for predicting PAWP >12 mm Hg., Conclusion: Our data suggest that PW Doppler atrioventricular E velocity, E/A ratio, and deceleration time could be used to identify adult Fontan patients with normal filling pressures. However, PPVs for PAWP >12 mm Hg were poor. Further studies, particularly prospective, simultaneous echo-catheterization correlation, are critically needed., (Copyright © 2018. Published by Elsevier B.V.)

Unicuspid aortic valve (UAV) is a rare malformation that is often difficult to distinguish from a bicuspid aortic valve (BAV) with commissural fusion by echocardiography or intraoperative surgical inspection. This study assessed the accuracy of intraoperative surgical inspection and two-dimensional echocardiography in diagnosing UAV compared to a gold standard of pathological diagnosis. The Mayo Clinic echocardiographic database, tissue registry database and electronic medical record were searched for all patients assigned a diagnosis of UAV by any technique. Transthoracic (TTE), transesophageal (TEE) echocardiographic, and surgical diagnoses were compared to pathological diagnosis as the standard. A clinical diagnosis of UAV was applied to 380 patients by 1 or more method and in 196 (52%) a pathologic evaluation was available to compare to the clinical description given by TTE, TEE, or surgical inspection. Of these 196 patients, only 58 (30%) had a pathological diagnosis of UAV; the majority were found to be BAVs by pathologic evaluation (n = 132, 67%). For diagnosing UAV, the sensitivity and specificity were 15% and 87% for TTE, 28%, and 82% for TEE, and 52% and 51% for surgical inspection, respectively. Valves with bicuspid morphology and extensive commissural fusion were frequently misclassified as UAV by all methods. In conclusion, intraoperative surgical inspection and echocardiography have limitations for diagnosing UAV due to difficulties in accurately assigning a correct morphological diagnosis, which suggests that the current understanding of the natural history of UAV may be inaccurate., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Hypoplastic left heart syndrome (HLHS) with intact atrial septum (HLHS-IAS) carries a high risk of mortality and affects about 6% of all patients with HLHS. Fetal interventions, postnatal transcatheter interventions, and postnatal surgical resection have all been used, but the mortality risk continues to be high in this subgroup of patients. We describe a novel, sequential approach to manage HLHS-IAS and progressive fetal hydrops. A 28-year-old, gravida 4 para 2 mother was referred to Mayo Clinic for fetal HLHS. Fetal echocardiography at 28 weeks of gestation demonstrated HLHS-IAS with progressive fetal hydrops. The atrial septum was thick and muscular with no interatrial communication. Ultrasound-guided fetal atrial septostomy was performed with successful creation of a small atrial communication. However, fetal echocardiogram at 33 weeks of gestation showed recurrence of a pleural effusion and restriction of the atrial septum. We proceeded with an Ex uteroIntrapartum Treatment (EXIT) delivery and open atrial septectomy. This was performed successfully, and the infant was stabilized in the intensive care unit. The infant required venoarterial extracorporeal membrane oxygenator support on day of life 1. The patient later developed hemorrhagic complications, leading to his demise on day of life 9. This is the first reported case of an EXIT procedure and open atrial septectomy performed without cardiopulmonary bypass for an open-heart operation and provides a promising alternative strategy for the management of HLHS-IAS in select cases., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Ebstein anomaly is a congenital disorder of right ventricular myocardial development, which affects the tricuspid valve in addition to the right ventricular myocardium. Cardiac imaging by transthoracic echocardiography and cardiac magnetic resonance imaging are the key modalities used to assess timing and type of surgery. In this article, we review the current standards of echocardiographic and magnetic resonance imaging in Ebstein anomaly., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Ebstein anomaly has heterogeneous anatomy and numerous operative techniques are described. Cone repair provides a near anatomic tricuspid valve repair. The purpose of this study was to examine our experience with cone repair., Methods: Cone repair was performed in 235 consecutive patients with Ebstein anomaly, 134 children (57%) and 101 adults (43%), from June 2007 to October 2015. Median age was 15.6 years (range, 6 months to 73 years). Cone repair was the first operation in 192 patients (82%), the second in 41 (17%), and the third in 2 (1%). Previous tricuspid valve repair had been performed in 27 (12%). Echocardiograms were obtained preoperatively and at hospital dismissal for all patients and for a subgroup of patients at least 6 months after cone repair (n = 81)., Results: Leaflet augmentation was done in 67 patients (28%), Sebening stitch in 57 (24.2%), neochordae in 49 (21%), and annuloplasty band in 158 (67%). Bidirectional cavopulmonary shunt was performed in 46 patients (20%). There was 1 early death (0.4%). Early reoperation was required in 14 patients (5.9%); re-repair was possible in 7 (50%). The majority of early reoperations (11 of 14; 79%) occurred in the first third of the series. Mean follow-up was 3.5 ± 2.5 years. There was sustained reduction in tricuspid regurgitation (p < 0.0001), a progressive decline in right ventricle size (p < 0.0001), and late increase in right ventricle fractional area change after initial decline (p < 0.0001). Freedom from late reoperation was 97.9% at 6 years., Conclusions: Cone repair is safe, and the learning curve is significant. Sustained reduction in tricuspid regurgitation and favorable changes in the right ventricle at follow-up suggest that cone repair has an advantageous impact on right ventricular remodeling., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Myocardial dysfunction after Fontan palliation for univentricular congenital heart disease is a challenging clinical problem. The medical treatment has a limited impact, with cardiac transplant being the ultimate management step. Cell-based therapies are evolving as a new treatment for heart failure. Phase 1 clinical trials using regenerative therapeutic strategies in congenital heart disease are ongoing. We report the first case of autologous bone marrow-derived mononuclear cell administration for ventricular dysfunction, 23 years after Fontan operation in a patient with hypoplastic left heart syndrome. The cells were delivered into the coronary circulation by cardiac catheterization. Ventricular size decreased and several parameters reflecting ventricular function improved, with maximum change noted 3 months after cell delivery. Such regenerative therapeutic options may help in delaying and preventing cardiac transplant.

Hypertrophic cardiomyopathy (HCM) occurs in 1 of 500 adults and is considered to be one of the most common causes of death in young people under 35 years of age. Children with HCM are usually asymptomatic and the overall annual mortality beyond the first year of life is 1%. Septal myectomy is safe and effective in children with obstructive HCM and published data shows improved late survival compared to untreated HCM. Patient selection and surgical expertise remain critical components to ensuring successful outcomes of septal myectomy, particularly when considering prophylactic myectomy in a seemingly asymptomatic patient., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

We performed a retrospective review of outcomes after heart transplantation during long-term follow-up of a surgical cohort of 1138 Fontan patients who were followed at the Mayo Clinic. Follow-up information was obtained from medical records and a clinical questionnaire that was mailed to patients not known to be deceased at the initiation of the study. Forty-four of 1138 Fontan patients with initial or subsequent evaluation at Mayo had cardiac transplantation between 1988 and 2014 (mean age at transplantation was 23.2 ± 12 yr, median was 19.8 yr; mean interval between Fontan and transplantation was 13.0 ± 7.7 yr, median was 13.1 yr). Two patients had combined organ transplantation (one heart-lung, one heart-liver). Twelve of the 44 (27%) patients had PLE prior to transplantation. There was no difference in post-bypass Fontan pressures or incidence of late reoperations for AVV repair/replacement between transplanted and non-transplanted patients. There were 16 (36%) deaths in the transplantation cohort; seven occurred within 30 days of transplantation. Overall one, five, 10, and 15 yr post-transplantation survival was 80%, 72%, 69%, and 55%, respectively. Although this is a challenging group of patients, intermediate-term results suggest that cardiac transplantation remains a reasonable option for patients with a failed Fontan circulation., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In athletes, ECG changes from physiological cardiac remodelling are common but can overlap with findings from a pathological disorder. We compared ECG findings in a group of elite high school athletes to a cohort of adolescents with hypertrophic cardiomyopathy (HCM)., Methods/results: We prospectively performed 15-lead ECGs and echocardiograms in 147 elite high school athletes. Student-athlete ECGs were compared in blinded fashion to ECGs of 148 adolescents with HCM of similar age and ethnicity. Standard ECG hypertrophy criteria and established expert opinion guidelines (European Society of Cardiology, ESC and Seattle criteria) were analysed. All student-athletes had normal echocardiograms. Overall, 77/147 (52%) of student-athletes met standard ECG criteria for ventricular hypertrophy compared to 126/148 (85%) adolescents with HCM (p<0.0001). There were 112/148 (76%) adolescents with HCM who had pathological Q-waves, T-wave inversion and/or ST-segment depression compared to 1/147 (1%) athletes (p<0.0001). Most patients with HCM (84%, 124/148) had ≥1 abnormal ECG finding(s) according to Seattle criteria, compared to 1% of student-athletes (2/147). Similarly, 130/148 (88%) patients with HCM met group-2 ESC criteria (abnormal), compared to 36/147 (24%) student-athletes (p<0.0001)., Conclusions: Over 50% of elite high school athletes with echocardiographically confirmed normal hearts satisfied standard voltage criteria for ventricular hypertrophy. Pathological Q-waves, T-wave inversion or ST-segment depression were most helpful in distinguishing adolescents with HCM from normals. Both ESC and Seattle criteria successfully stratified the student-athlete and HCM cohorts, however each had a false-negative rate >10% for the HCM cohort. The Seattle criteria demonstrated a significantly lower false-positive rate (1%) than the ESC criteria (24%)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Obstructive left-sided congenital heart lesions exhibit familial clustering, and familial echocardiographic screening for bicuspid aortic valve has become standard practice. Hypoplastic left heart syndrome (HLHS) is a severe left-sided obstructive lesion; however, familial screening is not universally recommended. The purpose of this study was to define the incidence of cardiovascular malformations (CVMs) in first-degree relatives of HLHS probands. First-degree relatives were screened for CVM by transthoracic echocardiography. Screening was completed in 152 family members (97 parents and 55 siblings) of 52 probands. Of these, 17 of 152 (11%) had CVM. Anomalies detected included: bicuspid aortic valve in 5 (3%), isolated dilated ascending aorta in 4 (3%), coarctation of the aorta in 1, partial anomalous pulmonary venous connection in 1, anomalous, intramural coronary artery in 1, bicuspid pulmonary valve in 1, and other anomalies in 4. Most were previously undiagnosed (11 of 17, 65%). Fourteen of 52 families (27%) had ≥1 relative with CVM. Overall, 7 of 55 siblings (13%), 5 of 46 fathers (11%) and 5 of 51 mothers (10%) had CVM. Although the incidence of CVM in first-degree relatives of HLHS probands was lower in this cohort than previously reported, it remained substantial, with at least one additional member having CVM in 27% of families. The frequent occurrence of undiagnosed CVM highlights the importance of routine familial screening in HLHS. In fact, even if screening was done in childhood, it may be appropriate to screen again in the third or fourth decade to exclude isolated enlargement of the ascending aorta., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: There are limited long-term, single-cohort, follow-up studies available about patients after the Fontan operation., Objectives: This study sought to determine the long-term outcome of all patients who had a Fontan operation at the Mayo Clinic., Methods: Records of all patients who had a modified Fontan operation between 1973 and 2012 were reviewed. A follow-up questionnaire was mailed to all patients alive at the time of the study., Results: Overall, 10-, 20-, and 30-year survival for 1,052 patients was 74%, 61%, and 43%, respectively. Factors associated with decreased overall or late survival in multivariate analysis included pre-operative diuretic use, longer cardiopulmonary bypass time, operation prior to 1991, atrioventricular valve (AVV) replacement at the time of Fontan operation, elevated post-bypass Fontan (>20 mm Hg) or left atrial (>13 mm Hg) pressures, prolonged chest tube drainage (>21 days), post-operative ventricular arrhythmias, renal insufficiency, and development of protein-losing enteropathy (PLE). Pre-operative and intraoperative sinus rhythm were associated with improved survival. Long-term survival was similar for patients regardless of ventricular morphology. The most common reoperations were pacemaker insertion/revision in 212 patients (20%), Fontan revision/conversion in 117 patients (11%), and AVV repair/replacement in 66 patients (5%). Clinically significant late atrial or ventricular arrhythmias occurred in 468 patients (44%). Ninety-five patients (9%) developed PLE, and 5-, 10-, and 20-year survival after diagnosis of PLE was 50%, 35%, and 19%, respectively., Conclusions: As the surgical techniques for the Fontan operation have changed over the last 40 years, survival has improved. However, development of PLE and arrhythmias and the need for reoperation during long-term follow-up pose significant management challenges., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Ebstein anomaly accounts for 1% of all congenital heart disease. It is a right ventricular myopathy with failure of tricuspid valve delamination and highly variable tricuspid valve morphology that usually results in severe regurgitation. It is the only congenital heart lesion that has a range of clinical presentations, from the severely symptomatic neonate to an asymptomatic adult. Neonatal operation has high operative mortality, whereas operation performed beyond infancy and into adulthood has low operative mortality. Late survival and quality of life for hospital survivors are excellent for the majority of patients in all age brackets. Atrial tachyarrhythmias are the most common late complication. There have been more techniques of tricuspid repair reported in the literature than any other congenital or acquired cardiac lesion. This is largely due to the infinite anatomic variability encountered with this anomaly. The cone reconstruction of Ebstein anomaly can achieve near anatomic restoration of the tricuspid valve anatomy. Early and intermediate results with these repairs are promising. Reduced right ventricular function continues to be a challenge for some patients, as is the need for reoperation for recurrent tricuspid regurgitation. The purpose of this article is to outline the current standard of care for diagnosis and treatment of Ebstein anomaly and describe innovative strategies to address poor right ventricular function and associated right-sided heart failure.

Approximately 20% to 30% of patients with Noonan syndrome (NS) have asymmetric left ventricular hypertrophy (LVH) and LV outflow tract obstruction (LVOTO). The role of surgical myectomy in such patients is unknown. We sought to compare clinical features and outcomes of patients with NS and LVOTO with age- and gender-matched patients with nonsyndromic, obstructive hypertrophic cardiomyopathy (HC) after myectomy. Two cohorts were selected and retrospectively analyzed using Mayo Clinic databases from 1996 to 2014. Subjects included patients with NS with LVH and LVOTO and nonsyndromic controls with obstructive HC. Twenty-three patients with NS and LVH were identified, of whom 12 (8 males) underwent myectomy (10 septal and 2 combined septal/apical) for severe LVOTO (10 pediatric and 2 adults; 13 ± 10 year old [range 1 to 39]). Similar echocardiographic improvements were noted in both groups. There were no perioperative deaths. Residual gradients were slightly higher in patients with NS. No improvement was noted in left atrial volume after myectomy in patients with NS. At early follow-up, the majority showed improvement in the New York Heart Association class (88% in NS vs 82% in HC, median of 6 and 2 months, respectively). At late follow-up (median of 7 years), the survival rate was 92% in NS and 100% in HC. In patients with NS with LVH and symptomatic LVOTO, myectomy reduces both gradient and the New York Heart Association class, similar to patients with nonsyndromic obstructive HC. Residual gradients were slightly higher, and left atrial dilation persisted in patients with NS. In conclusion, myectomy should be considered in patients older than 1 year with NS and symptomatic LVOTO., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD) that necessitates staged, single ventricle surgical palliation. An increased frequency of bicuspid aortic valve (BAV) has been observed among relatives. We postulated number of mutant alleles as a molecular basis for variable CHD expression in an extended family comprised of an HLHS proband and four family members who underwent echocardiography and whole-genome sequencing (WGS). Dermal fibroblast-derived induced pluripotent stem cells (iPSC) were procured from the proband-parent trio and bioengineered into cardiomyocytes. Cardiac phenotyping revealed aortic valve atresia and a slit-like left ventricular cavity in the HLHS proband, isolated bicuspid pulmonary valve in his mother, BAV in a maternal 4° relative, and no CHD in his father or sister. Filtering of WGS for rare, functional variants that segregated with CHD and were compound heterozygous in the HLHS proband identified NOTCH1 as the sole candidate gene. An unreported missense mutation (P1964L) in the cytoplasmic domain, segregating with semilunar valve malformation, was maternally inherited and a rare missense mutation (P1256L) in the extracellular domain, clinically silent in the heterozygous state, was paternally inherited. Patient-specific iPSCs exhibited diminished transcript levels of NOTCH1 signaling pathway components, impaired myocardiogenesis, and a higher prevalence of heterogeneous myofilament organization. Extended, phenotypically characterized families enable WGS-derived variant filtering for plausible Mendelian modes of inheritance, a powerful strategy to discover molecular underpinnings of CHD. Identification of compound heterozygous NOTCH1 mutations and iPSC-based functional modeling implicate mutant allele burden and impaired myogenic potential as mechanisms for HLHS.

Background: The molecular underpinnings of hypoplastic left heart are poorly understood. Staged surgical palliation has dramatically improved survival, yet eventual failure of the systemic right ventricle necessitates cardiac transplantation in a subset of patients. We sought to identify genetic determinants of hypoplastic left heart with latent right ventricular dysfunction in individuals with a Fontan circulation., Methods and Results: Evaluation of cardiac structure and function by echocardiography in patients with hypoplastic left heart and their first-degree relatives identified 5 individuals with right ventricular ejection fraction ≤40% after Fontan operation. Whole genome sequencing was performed on DNA from 21 family members, filtering for genetic variants with allele frequency <1% predicted to alter protein structure or expression. Secondary family-based filtering for de novo and recessive variants revealed rare inherited missense mutations on both paternal and maternal alleles of MYH6, encoding myosin heavy chain 6, in 2 patients who developed right ventricular dysfunction 3 to 11 years postoperatively. Parents and siblings who were heterozygous carriers had normal echocardiograms. Protein modeling of the 4 highly conserved amino acid substitutions, residing in both head and tail domains, predicted perturbation of protein structure and function., Conclusions: In contrast to dominant MYH6 mutations with variable penetrance identified in other congenital heart defects and dilated cardiomyopathy, this study reveals compound heterozygosity for recessive MYH6 mutations in patients with hypoplastic left heart and reduced systemic right ventricular ejection fraction. These findings implicate a shared molecular basis for the developmental arrest and latent myopathy of left and right ventricles, respectively., (© 2015 American Heart Association, Inc.)

Objective: To evaluate the utility of magnetic resonance elastography (MRE) in screening patients for hepatic fibrosis, cirrhosis, and hepatocellular carcinoma after the Fontan operation., Patients and Methods: Hepatic MRE was performed in conjunction with cardiac magnetic resonance imaging in patients who had undergone a Fontan operation between 2010 and 2014. Liver stiffness was calculated using previously reported techniques. Comparisons to available clinical, laboratory, imaging, and histopathologic data were made., Results: Overall, 50 patients at a median age of 25 years (range, 21-33 years) who had undergone a Fontan operation were evaluated. The median interval between Fontan operation and MRE was 22 years (range, 16-26 years). The mean liver stiffness values were increased: 5.5 ± 1.4 kPa relative to normal participants. Liver stiffness directly correlated with liver biopsy-derived total fibrosis score, time since operation, mean Fontan pressure, γ-glutamyltransferase level, Model for End-Stage Liver Disease score, creatinine level, and pulmonary vascular resistance index. Liver stiffness was inversely correlated with cardiac index. All 3 participants with hepatic nodules exhibiting decreased contrast uptake on delayed postcontrast imaging and increased nodule stiffness had biopsy-proven hepatocellular carcinoma., Conclusion: The association between hepatic stiffness and fibrosis scores, Model for End-Stage Liver Disease scores, and γ-glutamyltransferase level suggests that MRE may be useful in detecting (and possibly quantifying) hepatic cirrhosis in patients after the Fontan operation. The correlation between stiffness and post-Fontan time interval, mean Fontan pressure, pulmonary vascular resistance index, and reduced cardiac index suggests a role for long-term hepatic congestion in creating these hepatic abnormalities. Magnetic resonance elastography was useful in detecting abnormal nodules ultimately diagnosed as hepatocellular carcinoma. The relationship between stiffness with advanced fibrosis and hepatocellular carcinoma provides a strong argument for additional study and broader application of MRE in these patients., (Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Tricuspid annular plane systolic excursion measured by M-mode (MM-TAPSE) has been validated as a marker of right ventricular systolic performance. A similar measurement by 2D imaging (2D-TAPSE) can be obtained. We sought to determine the correlation and strength of agreement between MM-TAPSE and 2D-TAPSE in children., Methods: Echocardiographic studies performed for clinical indications were reviewed retrospectively. All consecutive subjects ≤18 years of age were included. The cohort was divided into those with normal echocardiographic findings and those with disorders affecting the right ventricle. Digitally recorded images were analyzed for both MM-TAPSE and 2D-TAPSE. Measurements of 2D-TAPSE were made in an apical four-chamber view, from the tricuspid valve annulus to a consistent point at the apex of the imaging sector at end-diastole and end-systole, with the difference representing the 2D-TAPSE value., Results: A total of 329 subjects (mean age 9.0 ± 6.1 years) met entry criteria. Correlation coefficient between MM-TAPSE and 2D-TAPSE was 0.90. Bland-Altman analysis showed agreement between the two methods to be within 1.2 ± 2.6 mm (mean percentage difference of 6.5%). About 1 mm difference between MM-TAPSE and 2D-TAPSE was consistently observed in all diagnostic subgroups, and across all age categories., Conclusion: MM-TAPSE and 2D-TAPSE correlate strongly, with 2D-TAPSE being consistently about 1 mm less than values obtained by the M-mode technique. We conclude that 2D-TAPSE can provide a reliable alternative to MM-TAPSE to quantitatively measure right ventricular systolic function and may be especially useful in situations where retrospective comparisons are sought., (© 2014, Wiley Periodicals, Inc.)

Congenital heart diseases (CHDs) requiring surgical palliation mandate new treatment strategies to optimize long-term outcomes. Despite the mounting evidence of cardiac regeneration, there are no long-term safety studies of autologous cell-based transplantation in the pediatric setting. We aimed to establish a porcine pipeline to evaluate the feasibility and long-term safety of autologous umbilical cord blood mononuclear cells (UCB-MNCs) transplanted into the right ventricle (RV) of juvenile porcine hearts. Piglets were born by caesarean section to enable UCB collection. Upon meeting release criteria, 12 animals were randomized in a double-blinded fashion prior to surgical delivery of test article (n=6) or placebo (n=6). The UCB-MNC (3×10(6) cells per kilogram) or control (dimethyl sulfoxide, 10%) products were injected intramyocardially into the RV under direct visualization. The cohorts were monitored for 3 months after product delivery with assessments of cardiac performance, rhythm, and serial cardiac biochemical markers, followed by terminal necropsy. No mortalities were associated with intramyocardial delivery of UCB-MNCs or placebo. Two animals from the placebo group developed local skin infection after surgery that responded to antibiotic treatment. Electrophysiological assessments revealed no arrhythmias in either group throughout the 3-month study. Two animals in the cell-therapy group had transient, subclinical dysrhythmia in the perioperative period, likely because of an exaggerated response to anesthesia. Overall, this study demonstrated that autologous UCB-MNCs can be safely collected and surgically delivered in a pediatric setting. The safety profile establishes the foundation for cell-based therapy directed at the RV of juvenile hearts and aims to accelerate cell-based therapies toward clinical trials for CHD., (©AlphaMed Press.)

Background: Patients with Ebstein malformation (EM) and severe RV dilatation and dysfunction have increased operative risk. Early results with right ventricular unloading utilizing the bidirectional cavopulmonary shunt (BCPS) during repair of EM have been encouraging. We report our experience of the 1.5-ventricle repair strategy for this difficult group of patients., Methods: Between July 1999 and January 2013, 62 patients with severe EM underwent BCPS at the time of tricuspid repair. Median age was 21.5 years (range, 9 months to 57 years), 51.6% were male, and 72.5% were children. Severe RV dilatation was present in all patients; severe RV dysfunction was present in 72.5% (n=45) and moderate to severe RV dysfunction in 22.5% (n=14). Mean RV systolic pressure was 32.7±0.7 mm Hg and mean PA pressure was 15.6±2.1 mm Hg. Mean preoperative left ventricular ejection fraction (LVEF) was 0.536±0.071; it was less than 40% in 10 patients (16.1%). New York Heart Association class III/IV heart failure was present in 43 patients (69.3%) preoperatively and 20 patients (32.2%) were initially referred for heart transplant evaluation. Prior EM surgery occurred in 35.4% (n=22; 8 prior valve repair, 8 prior valve replacement, Blalock-Taussig shunt in 4, atrial septal defect (ASD) closure in 2)., Results: Tricuspid repair was performed in 51.6% (n=32, 5 had re-repair). Bioprosthetic valve replacement was performed in 48.4% (n=30, 8 had rereplacement). The BCPS was a planned procedure in 53 patients (85.5%) because of RV dysfunction; BCPS was added after unsuccessful weaning from bypass in 7 (11.2%), and in the early postoperative period due to hemodynamic instability in 2. Concomitant procedures included ASD closure in 48.3%, maze in 38.7%, and mitral valve repair in 6.4%. Postoperative extracorporeal membrane oxygenation support was needed in 8 patients. Delayed chest closure was performed in 25.8%. Early mortality was 1.6% (n=1). Mean mechanical ventilation time was 69.7 hours. Mean intensive care unit and hospital stays were 5.4±3.5 and 10.7±3.5 days, respectively. Mean follow-up was 3.6±2.6 years (maximum, 12.8 years). Patients (n=10) with low preoperative LVEF (0.362±0.035) improved to 0.517±0.042 postoperatively (p=0.001). There was 1 late death in a patient with cystic fibrosis. Late reintervention was needed in 5 patients (8%). Late follow-up was available in 95% (n=59); all were acyanotic and 88% were in New York Heart Association functional class I/II., Conclusions: Concomitant BCPS is a useful adjunct in repair of advanced EM with severe RV dilatation and dysfunction. Operation can be performed with low early mortality. Intermediate-term survival and quality of life is good to excellent, and transplantation can be delayed or avoided in the majority., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Valve repair for pediatric patients with Ebstein anomaly has historically yielded varied results. The cone reconstruction (CR) first described by Da Silva has revolutionized the surgical approach to these patients. This study reports our recent experience with CR in children and young adults with Ebstein anomaly., Design: Electronic medical records were reviewed for all patients < 21 years old who had surgery to repair Ebstein anomaly at Mayo Clinic Rochester between June 2007 and December 2012. Clinical data including preoperative demographics, intraoperative procedures, and postoperative outcomes were recorded., Results: Eighty-four patients initially had a cone reconstruction (54% male, mean age 10.1 ± 5.9 years). Indications for operation included cardiomegaly (42%), cyanosis (19%), and heart failure (19%). The preoperative echocardiogram demonstrated severe tricuspid regurgitation in 91% of patients. There was one early death and 3 early CR breakdowns requiring reoperation (2 re-repair, 1 tricuspid replacement). Eighty-two patients (98%) had successful CR at the time of hospital discharge. Patient age, gender, cardiopulmonary bypass time, and aortic cross-clamp time were not associated with early CR failure. Use of a partial or eccentric annuloplasty ring correlated with successful initial CR (P = .01). There have been no early CR breakdowns since 2010. Follow-up information was available for 77 patients (longest follow-up 6.5 years; mean 0.8 ± 0.2 years). The most recent postoperative echocardiogram demonstrated mild or no tricuspid regurgitation in 83%. Tricuspid stenosis (mean gradient > 5 mm Hg) was present in 6 patients. There was one late death (motor vehicle accident) and one late re-repair of the tricuspid valve 4 years after initial operation., Conclusions: CR in children and young adults with Ebstein anomaly can be performed with low early mortality and excellent durability at short-term follow-up. CR represents an important surgical option for young patients. It is applicable to patients with a broad range of anatomic variability and precludes valve replacement in the vast majority. CR should be considered prior to the deleterious effects of chronic right ventricular volume overload and the development of systolic dysfunction, which hamper long-term prognosis. Therefore, early referral for surgical evaluation is recommended., (© 2013 Wiley Periodicals, Inc.)

Objective: To report our single-center experience with patients who had cardiac and multiorgan transplantation for end-stage congenital heart disease (CHD)., Patients and Methods: We reviewed records for all patients with CHD who had undergone heart transplantation at Mayo Clinic, Rochester, Minnesota, from November 1, 1990, through June 30, 2012. Patients with cardiomyopathy were excluded, unless CHD was present., Results: Overall, 45 patients had cardiac transplantation for end-stage CHD (mean age, 26.1±18.4 years; range, 1 month to 65 years). Two patients (4%) had combined heart/liver transplantation; 1 (2%) had heart/kidney transplantation. Six patients (13%) had no previous cardiac operation; the remaining 39 patients had a mean of 3 (range, 1-8) previous cardiac operations. Patient survival (95% CI) at 1, 5, and 10 years was 89% (80%-98%), 89% (80%-98%), and 72% (56%-87%), respectively, while graft survival at 1, 5, and 10 years was 89% (80%-98%), 89% (80%-98%), and 61% (44%-78%), respectively. During the same era, the International Society for Heart & Lung Transplantation reported that survival in patients undergoing transplant for non-congenital diagnoses was 85%, 72%, and 56%, respectively. Over a mean follow-up of 8.7±6.2 years, rejection requiring treatment was documented in 35 patients (78%). Eleven patients (24%) have been diagnosed with neoplasia (8 skin, 1 blood, 1 lymph, and 1 other), and 3 patients (7%) have required retransplantation. Four patients (9%) have developed significant coronary vasculopathy; 1 successfully underwent retransplantation, and 3 died 6, 8, and 14 years after transplantation., Conclusion: With appropriate patient selection and posttransplant monitoring, survival has improved for patients with complex end-stage CHD. Multiorgan transplantation is an option for selected patients with CHD., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Sirolimus is used in heart transplant patients with CAV and CNI-induced nephropathy. However, little is known regarding the tolerability, rejection rate, and effect on renal function when used empirically in children. We describe our experience with the empiric use of a sirolimus-based immunosuppressive regimen in pediatric heart transplantation recipients. We reviewed records of patients in whom conversion was attempted to a CNI-free sirolimus-based regimen. Rejection episodes and measures of renal function were recorded. We attempted to convert 20 patients, of which 16 were successful. In total, six of 20 patients (30%) experienced adverse effects. Of the 16 converted, four patients converted to sirolimus due to CNI-induced disease (three nephropathy, one CAV), while 12 patients (mean age 5.5 yr, range 0.1-21 yr; 33% female; 33% with a history of congenital heart disease) were empirically switched to sirolimus at a mean of 2.3 yr after transplant. Follow-up was available for a mean of 2.5 yr after conversion (range 0.5-8.3 yr). The rate of rejection while taking CNIs was 0.18 rejection episodes per patient-year (total of five episodes), compared with 0.03 rejection episodes per patient-year (total of one episode) while on sirolimus. Renal function, in terms of GFR, significantly improved after sirolimus conversion at latest follow-up (from 86 ± 37 mL/min to 130 ± 49 mL/min, p = 0.02). Here, we demonstrate the potential benefit of empiric use of sirolimus in pediatric heart transplant patients in a CNI-free regimen. Larger and longer studies are needed to further clarify risks of rejection and adverse effect profiles., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Successful tricuspid repair for Ebstein malformation (EM) is challenging. Cone repair has recently emerged as the most anatomic repair technique. There are no data on tricuspid re-repair in EM. We reviewed our experience with tricuspid valve (TV) re-repair using a cone technique., Methods: Between June 2007 and October 2012, 134 patients underwent cone repair. Prior TV repair was performed in 20 patients (10 female, 50%). Median age was 15 years (range, 4 to 68 years). Four patients (20%) had prior bidirectional cavopulmonary anastomosis (BDCPA). Preoperative heart failure was present in 8 patients (40%). Recurrent tricuspid regurgitation (TR) was due to incomplete leaflet coaptation with tethered anterior leaflet in all patients; and 10 patients (50%) had diminutive septal leaflet. Prior repair techniques consisted of annuloplasty maneuvers in all patients with no or incomplete surgical delamination in all patients., Results: The TV re-repair using cone technique was possible in all patients. Plication of atrialized right ventricle was done in 6 patients (30%). Modifications included annuloplasty band in 16 patients (80%) and TV leaflet augmentation in 8 (40%). The BDCPA was performed in 3 patients (15%) and modified Cox-maze procedure was done in 10 (50%). There were no mortalities or reoperations. Mean follow-up was 7.7 ± 10.7 months; during follow-up, 18 patients had no or mild TR and 2 had moderate TR., Conclusions: TV re-repair in EM using the cone technique is feasible, particularly when there has been no surgical leaflet delamination at initial operation. Leaflet augmentation facilitates and annuloplasty band stabilizes a competent TV re-repair. Longer follow-up is required to assess durability., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Posterior reversible encephalopathy syndrome (PRES) is a disorder characterized by gray and white matter abnormalities in the temporal, parietal, and occipital lobes of the brain. Its etiology has been attributed to renal failure, immunosuppressive drugs such as cyclosporine and tacrolimus, and other potential entities leading to acute hypertension. Clinical findings include headaches, altered mental status, seizures, visual changes, and focal neurologic deficits. We report the case of a child who developed PRES with intracerebral and subarachnoid hemorrhages associated with tacrolimus exposure 10 days after heart transplantation for restrictive cardiomyopathy. The patient initially presented with complex partial seizures, headache, agitation, and hypertension. Head MRI was suggestive of PRES along with intracerebral and subarachnoid hemorrhages. Tacrolimus was discontinued and blood pressure was controlled. The patient's encephalopathy resolved, but he has had ongoing neurologic symptoms secondary to hemorrhage. Generally, PRES is less common in children than in the adult population and is a rare complication of calcineurin inhibitors (CNI). Presentation with secondary hemorrhage also can occur. In children receiving CNIs presenting with new neurologic symptoms, PRES should be considered as prompt discontinuation of the offending agent can induce resolution of symptoms. Children can develop hemorrhage in the context of PRES, leading to increased morbidity., (© 2013 John Wiley & Sons A/S.)

Background: Reproducible repair of Ebstein's malformation is challenging and numerous surgical techniques have been described. We reviewed our experience with the cone reconstruction., Methods: Between June 2007 and December 2011, 89 patients (47 female; 53%) underwent cone reconstruction (median age 19 years; range, 19 days to 68 years). Indication for operation was progressive cardiomegaly in 43 (48%), cyanosis in 29 (33%), and heart failure in 13 (15%). Prior tricuspid valve repair was performed in 12 patients (13%). Severe tricuspid regurgitation (TR) was present in 75 patients (84%)., Results: All patients underwent cone reconstruction (360-degree leaflet tissue repair anchored at true annulus). Modifications included ringed annuloplasty in 57 patients (64%), leaflet augmentation in 28 patients (31%), and autologous chordae in 17 patients (19%). Bidirectional cavopulmonary anastomosis was performed in 21 patients (24%). Early mortality occurred in 1 patient (1%). Early reoperation for recurrent TR occurred in 12 patients (13%); re-repair was performed in 6 patients (50%), and 6 (50%) required replacement. Mean follow-up was 19.7 ± 24.7 months. There was no late mortality or reoperation. At follow-up, 72 patients (87%) had no or mild TR, 9 (11%) had moderate TR, and 2 patients (2%) had severe TR. Ringed annuloplasty was associated with less than moderate TR at dismissal (p = 0.01)., Conclusions: The learning curve for cone reconstruction is steep, but early mortality is low. Cone reconstruction with ringed annuloplasty results in less TR and should be used whenever possible. Longer follow-up is essential to determine late durability of cone reconstruction., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Diffuse cutaneous systemic sclerosis (SSc) is rare in children, but has a poor prognosis when cardiomyopathy is present., Methods: We reviewed the case of a 14-year-old female with progressive skin thickening/tightness and dyspnea on exertion who was diagnosed with SSc., Results: Our patient was found to have severe restrictive cardiomyopathy with poor left ventricular systolic function (ejection fraction = 20%), unresponsive to the immunosuppression used to treat her SSc. There was no evidence of pulmonary fibrosis. The patient underwent orthotopic cardiac transplantation, with improvement in systemic symptoms. Two years after transplantation, she had elevated filling pressures during a surveillance catheterization, with no evidence of cellular rejection or coronary artery vasculopathy. Four months later, she developed severe ventricular dysfunction and dyspnea, despite a negative biopsy and negative C4d immunofluorescence staining. Her immunosuppression was intensified with improvement of cardiac function. Despite this, 1 month later she had sudden pulseless cardiac arrest from which she could not be revived. The family declined an autopsy., Discussion: We report a 14-year-old female with SSc who had cardiac transplantation. The etiology behind her recurrent restrictive physiology, cardiac dysfunction, and subsequent cardiac arrest remains unclear., (© 2011 Wiley Periodicals, Inc.)