Producing and Testing Prototype Tissue-Engineered 3D Tri-Leaflet Valved Stents on Biodegradable Poly-ε-Caprolactone Scaffolds.

Transcatheter pulmonary valve replacement is a minimally-invasive alternative treatment for right ventricular outflow tract dysfunction and has been rapidly evolving over the past years. Heart valve prostheses currently available still have major limitations. Therefore, one of the significant challenges for the future is the roll out of transcatheter tissue engineered pulmonary valve replacement to more patients. In the present study, biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds in the form of a 3D leaflet matrix were successfully seeded with human endothelial colony-forming cells (ECFCs), human induced pluripotent stem cell-derived MSCs (hMSCs), and porcine MSCs (pMSCs) for three weeks for the generation of 3D tissue-engineered tri-leaflet valved stent grafts. The cell adhesion, proliferation, and distribution of these 3D heart leaflets was analyzed using fluorescence microscopy and scanning electron microscopy (SEM). All cell lineages were able to increase the overgrown leaflet area within the three-week timeframe. While hMSCs showed a consistent growth rate over the course of three weeks, ECFSs showed almost no increase between days 7 and 14 until a growth spurt appeared between days 14 and 21. More than 90% of heart valve leaflets were covered with cells after the full three-week culturing cycle in nearly all leaflet areas, regardless of which cell type was used. This study shows that seeded biodegradable PCL nanofiber scaffolds incorporated in nitinol or biodegradable stents will offer a new therapeutic option in the future.

Pulmonary valve reconstruction for acquired pulmonary regurgitation in patients with treated congenital heart disease.

OBJECTIVES: Pulmonary valve regurgitation is a common problem after relief of right ventricular outflow tract (RVOT) obstruction with a transannular patch. Pulmonary valve replacement with a homograft or xenograft is the routine treatment. Longevity of biological valves and the availability of homografts are limited. Alternatives to restore RVOT competence are evaluated. The goal of this study was to present intermediate-term results for pulmonary valve reconstruction (PVr) in patients with severe regurgitation. METHODS: PVr was performed in 24 patients (August 2006‒July 2018). We analysed perioperative data, pre- and postoperative cardiac magnetic resonance (CMR) imaging studies, freedom from valve replacement and risk factors for pulmonary valve dysfunction. RESULTS: The underlying diagnoses were tetralogy of Fallot (n = 18, 75%), pulmonary stenosis (n = 5, 20.8%) and the double outlet right ventricle post banding procedure (n = 1, 4.2%). The median age was 21.5 (14.8-23.7) years. Main (n = 9, 37.5%) and branch pulmonary artery procedures (n = 6, 25%) and surgery of the RVOT (n = 16, 30.2%) were often part of the reconstruction. The median follow-up after the operation was 8.0 (4.7-9.7) years. Freedom from valve failure was 96% at 2 and 90% at 5 years. The mean longevity of the reconstructive surgery was 9.9 years (95% confidence interval: 8.8-11.1 years). CMR before and 6 months after surgery showed a reduction in the regurgitation fraction [41% (33-55) vs 20% (18-27) P = 0.00] and of the indexed right ventricular end-diastolic volume [156 ml/m2 (149-175) vs 116 ml/m2 (100-143), P = 0.004]. Peak velocity across the pulmonary valve (determined by CMR) half a year after surgery was 2.0, unchanged. CONCLUSIONS: PVr can be achieved with acceptable intermediate-term results and may delay pulmonary valve replacement.

Serial Assessment of Right Ventricular Deformation in Patients With Hypoplastic Left Heart Syndrome: A Cardiovascular Magnetic Resonance Feature Tracking Study.

Background As right ventricular dysfunction is a major cause of adverse outcome in patients with hypoplastic left heart syndrome, the aim was to assess right ventricular function and deformation after Fontan completion by performing 2-dimensional cardiovascular magnetic resonance feature tracking in serial cardiovascular magnetic resonance studies. Methods and Results Cardiovascular magnetic resonance examinations of 108 patients with hypoplastic left heart syndrome (female: 31) were analyzed. Short-axis cine images were used for right ventricular volumetry. Two-dimensional cardiovascular magnetic resonance feature tracking was performed using long-axis and short-axis cine images to measure myocardial global longitudinal, circumferential, and radial strain. All patients had at least 2 cardiovascular magnetic resonance examinations after Fontan completion and 41 patients had 3 examinations. Global strain values and right ventricular ejection fraction decreased from the first to the third examination with a significant decline in global longitudinal strain from the first examination to the second examination (median, first, and third quartile: -18.8%, [-20.5;-16.5] versus -16.9%, [-19.3;-14.7]) and from the first to the third examination in 41 patients (-18.6%, [-20.9;-15.7] versus -15.8%, [-18.7;-12.6]; P-values <0.004). Right ventricular ejection fraction decreased significantly from the first to the third examination (55.4%, [49.8;59.3] versus 50.2%, [45.0;55.9]; P<0.002) and from the second to the third examination (53.8%, [47.2;58.7] versus 50.2%, [45.0;55.9]; P<0.0002). Conclusions Serial assessment of cardiovascular magnetic resonance studies in patients with hypoplastic left heart syndrome after Fontan completion demonstrates a significant reduction in global strain values and right ventricular ejection fraction at follow-up. The significant reduction in global longitudinal strain between the first 2 examinations with non-significant changes in right ventricular ejection fraction suggest that global longitudinal strain measured by 2-dimensional cardiovascular magnetic resonance feature tracking might be a superior technique for the detection of changes in myocardial function.

Effect of Leisure Sports on Exercise Capacity and Quality of Life in Patients with a Fontan Circulation.

Despite improvement in survival, patients with a Fontan circulation are at risk for numerous complications, and exercise capacity and quality of life are usually reduced compared with healthy controls. However, only a few studies have assessed the impact of the amount of sporting activity on exercise capacity and health-related quality of life. We analyzed cardiopulmonary exercise tests (CPET) in a large cohort of patients with a Fontan circulation. Questionnaires were used to assess health-related quality of life and sporting activity. A total of 79 patients with a median age of 13.0 (6.5 to 34.4) years at CPET were included (female, n = 31). Questionnaires revealed that 80% of patients (n = 63) do leisure sports with 43% (n = 27) exercising more than 2 hours per /week. In a subgroup analysis on pediatric patients (n = 52) we found that nearly all participate in school sports (n = 51) and report good subjective health (n = 48). In the pediatric subgroup, oxygen uptake at the anaerobic threshold and peak oxygen uptake correlated with subjective health (p <0.05) and the amount of leisure sports activity (p <0.01). In the overall cohort, running time and running distance were significantly associated with the hours of sports per week (p <0.01). CPET results did not significantly differ between single right and single left ventricle patients. Furthermore, an open fenestration was not associated with reduced exercise capacity. In conclusion, most patients with a Fontan circulation participate in leisure sports and report good subjective healthiness. In pediatric patients, increased sports activity is associated with better exercise capacity and subjective healthiness.

Tissue Engineered Transcatheter Pulmonary Valved Stent Implantation: Current State and Future Prospect.

Patients with the complex congenital heart disease (CHD) are usually associated with right ventricular outflow tract dysfunction and typically require multiple surgical interventions during their lives to relieve the right ventricular outflow tract abnormality. Transcatheter pulmonary valve replacement was used as a non-surgical, less invasive alternative treatment for right ventricular outflow tract dysfunction and has been rapidly developing over the past years. Despite the current favorable results of transcatheter pulmonary valve replacement, many patients eligible for pulmonary valve replacement are still not candidates for transcatheter pulmonary valve replacement. Therefore, one of the significant future challenges is to expand transcatheter pulmonary valve replacement to a broader patient population. This review describes the limitations and problems of existing techniques and focuses on decellularized tissue engineering for pulmonary valve stenting.

Surveillance of Fontan Associated Liver Disease in Childhood and Adolescence.

Fontan associated liver disease (FALD) has been recognized as a potentially serious sequela of the Fontan circulation. Prevalence of FALD among different age groups and risk factors for advanced changes were assessed. FALD screening included abdominal ultrasound and laboratory tests. A "liver disease score (LDS)" incorporating items from ultrasound and blood testing was calculated to grade FALD severity (5 items each, maximum score 10 points). 240 patients (male: n = 139, female: n = 101, systemic right ventricle: n = 160) underwent FALD screening 10 (IQR 7-15) years after Fontan surgery. Ultrasound was abnormal in 184 (76.6%) patients (surface nodularity / blunted liver edge: n = 133, 55.4%; heterogeneous parenchyma: n = 93, 38.8%; splenomegaly: n = 68, 28.3%; ascites: n = 23, 9.6%). At least one abnormal laboratory test was detected in 218 (90.8%) patients. Gamma-glutamyl-transpeptidase was elevated in the majority of patients (n = 206, 85.8%). Median LDS was 3 (2-4). Scores ≥5 were observed in 32 (13.3%) patients. Longer follow-up (15 (11-20) vs 9 (6-14) years, P <0.001), higher central venous (13 (11-15) vs 10 (9-12) mmHg, P <0.001) and end-diastolic pressure (8 (5-10) vs 6 (5-7) mmHg, P = 0.001), impaired ventricular function and absence of sinus rhythm were associated with LDS ≥5. Longer follow-up (OR 1.2 (1.1-1.3), P <0.001) and higher central venous pressure (OR 1.6 (1.3-2.1), p < 0.001) were the only independent predictors of advanced FALD. Abdominal ultrasound and laboratory abnormalities suggestive of FALD are common during routine follow-up already in childhood and adolescence irrespective of ventricular morphology. More advanced findings are associated with longer follow-up and higher central venous pressure.

Non-contrast enhanced magnetic resonance imaging for characterization of Fontan associated liver disease.

OBJECTIVES: To evaluate the ability of non-contrast enhanced magnetic resonance imaging (MRI) techniques to characterize Fontan associated liver disease (FALD) in adolescent and adult Fontan patients. METHODS: Fontan patients (n = 29) and healthy controls (n = 13) underwent an MRI protocol with T1, T2 and Apparent Diffusion Coefficient (ADC) mapping. Routine FALD screening included abdominal ultrasound and laboratory testing. RESULTS: Median follow-up after Fontan operation was 15.1 (IQR 12.0-16.8) years. Distinct differences in tissue characteristics were visualized. T1 and T2 relaxation times were prolonged in Fontan patients, particularly of the right lobe (T1: 745 (IQR 715-784) ms vs. 586 (IQR 555-602) ms, p < 0.001; T2: 63 (IQR 59-64) ms vs. 58 (IQR 56-60) ms, p = 0.002). Left lobe ADC was lower in Fontan patients (1.10 (IQR 1.06-1.18) x 10-3 mm2/s vs. 1.23 (IQR 1.19-1.29) x 10-3 mm2/s, p < 0.001). T2 mapping was able to differentiate between controls and Fontan patients with different FALD severity. Right lobe T2 was higher in patients with moderate or severe in comparison to those with no or mild changes and healthy controls (64 (IQR 61-67) ms vs. 60 (IQR 59-63) ms vs. 58 (IQR 56-60) ms, p = 0.001). CONCLUSIONS: Non-contrast enhanced MRI methods are able to visualize regional differences in liver tissue characteristics. T1 and T2 relaxation times were prolonged in Fontan patients suggestive of fibrosis or congestive hepatopathy, while reduced ADC might reflect impaired microperfusion. These methods have promising clinical potential for detection of liver abnormalities in Fontan patients. The usefulness of T2 mapping to grade FALD severity merits further investigation.

Pulmonary vascular disease in Fontan circulation-is there a rationale for pulmonary vasodilator therapies?

The Fontan circulation is a palliative concept for patients with univentricular hearts. The central veins are connected directly to the pulmonary arteries (cavo-pulmonary connection) to separate the pulmonary and the systemic circulation. There is no sub-pulmonary ventricle that generates pressure to drive blood through the pulmonary arteries. Pulmonary blood flow is determined by central venous pressure (CVP) and pulmonary vascular resistance (PVR). The capability of the Fontan circulation to compensate for alterations in PVR is limited, as CVP can only be increased within narrow ranges without adverse clinical consequences. Consequently, systemic ventricular preload and cardiac output are dependent on a healthy lung with low PVR. Failure of the Fontan circulation is relatively common. In addition to ventricular dysfunction, maladaptive pulmonary vascular remodeling resulting in increased pulmonary resistance may play a key role. The pathophysiology of the maladaptive vascular processes remains largely unclear and diagnosis of an increased PVR is challenging in Fontan circulation as accurate measurement of pulmonary arterial blood flow is difficult. In the absence of a sub-pulmonary ventricle, pulmonary artery pressure will almost never reach the threshold conventionally used to define pulmonary arterial hypertension. There is a need for markers of pulmonary vascular disease complementary to invasive hemodynamic data in Fontan patients. In order to treat or prevent failure of the Fontan circulation, pathophysiological considerations support the use of pulmonary vasodilators to augment pulmonary blood flow and systemic ventricular preload and lower CVP. However, to date the available trial data have neither yielded enough evidence to support routine use of pulmonary vasodilators in every Fontan patient nor have they been helpful in defining subgroups of patients that might benefit from such therapies. This review discusses potential pathomechanisms of pulmonary vascular disease; it summarizes the current knowledge of the effects and efficacy of pulmonary vasodilator therapy in Fontan patients and tries to outline areas of potential future research on the diagnosis and treatment of pulmonary vascular disease and Fontan failure.

Transcatheter pulmonary valve replacement: a new polycarbonate urethane valve.

OBJECTIVES: Transcatheter pulmonary valve replacement has become a valid treatment option for right ventricular outflow tract diseases. However, some limitations occur in patients with wide, compliant right ventricular outflow tracts that might be amenable to treatment with self-expanding valved protheses. An experimental ovine study was designed to evaluate a novel dip-coated, low-profile trileaflet polycarbonate urethane (PCU) heart valve mounted into a self-expandable nitinol stent. METHODS: The PCU valves were produced by a dip-coating technique, mounted in a conical-shaped nitinol stent and provided with a leaflet thickness of 100-150 µm. The valved stents were implanted percutaneously via transfemoral access in 6 consecutive sheep divided into 2 groups. Three animals were followed up for 1 month and the remainder, for 6 months. Angiographic measurements and transthoracic echocardiography were performed before and after implantation and at the end of the 1- or 6-month observation period, respectively. RESULTS: Orthotopic positioning of the valve was achieved in all animals. All except 1 had competent valves during the follow-up period. The peak-to-peak gradient across the PCU valved stents was 4.6 ± 1.0 mmHg after 1 month and 4.4 ± 2.3 mmHg after 6 months of follow-up. Macroscopic and microscopic post-mortem evaluation indicated good morphological and structural results. There were no stent fractures, leaflet calcification or thrombus formation. CONCLUSIONS: This study demonstrates successful transcatheter pulmonary valve replacement with a novel dip-coated valved nitinol stent. The trileaflet PCU prostheses indicated good functional and biocompatible properties after a 6-month observation period.

Transcatheter mitral valve replacement: tissue in-growth after 4 weeks.

OBJECTIVES: Tissue reaction to transcatheter mitral valve replacement in the mitral annulus remains to be elucidated. METHODS: Trileaflet porcine pericardial valves were sewn onto self-expanding d-shaped nitinol stents, which were delivered transapically and in an off-pump fashion into the mitral position of 10 pigs. After at least 4 weeks of follow-up, gross pathological assessment and histological examination were performed. The specimens were stained with Movat's pentachrome, Elastica-van-Gieson and von Kossa staining. The leucocytes, B cells, T cells or macrophages were detected by specific immunohistochemical staining. RESULTS: Proper stent positioning in the mitral annulus was achieved in 9/10 animals. Nine of 10 animals survived the desired observation period. In all but one, the mitral valve stent was well integrated into the left atrium and perpendicularly embedded into the annulus by 85 ± 24%. One animal had minor fractures in the nitinol struts and another animal showed tearing of 1 of 4 tethers. Histological examination demonstrated no major tissue reaction with the nitninol struts but well-preserved overall structures around the mitral annulus in 8/9 cases. CONCLUSIONS: This is the first report demonstrating good in-growth of transcatheter-delivered anatomically shaped mitral valve stents after at least 4 weeks of follow-up. Histological examination demonstrated progressive healing and neointimalization.

Transcatheter Correction of Superior Sinus Venosus Atrial Septal Defects as an Alternative to Surgical Treatment.

BACKGROUND: The superior sinus venosus atrial septal defect (SVASD) is characterized by deficiency of the common wall between the superior vena cava (SVC) and the right upper pulmonary vein (RUPV), which is no longer committed to the left atrium. OBJECTIVES: This study sought to evaluate the potential for redirecting the SVC and RUPV flow to the right and left atria, respectively, by implantation of a covered stent in the SVC. METHODS: Review of 48 consecutive adult SVASD patients undergoing assessment for correction. Pre-procedural evaluation included cross-sectional imaging and ex vivo simulation using printed or virtual 3-dimensional models. RESULTS: Transcatheter correction was performed in 25 patients, with a further 6 awaiting stent implantation. Only 8 patients were deemed technically unsuitable. The procedure involved balloon test inflation in the anticipated stent landing zone with simultaneous transesophageal echocardiography and pulmonary venography to confirm defect closure and unobstructed pulmonary venous drainage, followed by deployment of a 10-zig covered Cheatham platinum stent. Stents of lengths between 5 and 8 cm were implanted. A second, uncovered stent was used for anchoring in 9 patients. The RUPV was protected with a high-pressure balloon during stent implantation to prevent pulmonary venous obstruction in 4 patients. The median follow-up period was 1.4 (interquartile range: 0.8 to 1.7) years, with no mortality. Stent embolization occurred in 1 patient; another required drainage of hemopericardium. Cardiac computed tomography after 3 months confirmed unobstructed pulmonary venous return. At latest follow-up, a residual shunt was present in 1 patient. CONCLUSIONS: Transcatheter correction of SVASD may be considered as an alternative to surgery in a substantial proportion of patients.

Right ventricular outflow tract reconstruction with the Labcor® stentless valved pulmonary conduit.

OBJECTIVES: The right ventricular outflow tract reconstruction is a common necessity in congenital cardiac surgery. As homograft availability is limited, alternatives need to be evaluated. The Labcor® conduit consists of a porcine tricomposite valve assembled inside a bovine pericardium tube. This study presents intermediate-term results for its utilization for right ventricular outflow tract reconstruction. METHODS: Labcor conduits were implanted in 53 patients (February 2009-July 2016). We analysed perioperative data, freedom from conduit failure and risk factors for conduit dysfunction. RESULTS: The most common diagnosis was Tetralogy of Fallot (n = 20, 37.7%). The median age at surgery was 10.0 [interquartile range (IQR) 4.9-14.3] years. Pulmonary artery plasty (n = 37, 69.8%) and augmentation of the right ventricular outflow tract (n = 16, 30.2%) were often part of the procedure. The median conduit size was 21 (range 11-25) mm. There was no in-hospital death. The median follow-up after surgery was 4.6 (IQR 3.4-5.6) years. Fourteen patients (27.5%) developed conduit failure with stenosis being the main cause. Freedom from conduit failure was 98.0% at 2 and 80.5% at 5 years. The median longevity of the conduit was 7.4 years (95% confidence interval 5.1-9.8 years). Younger age and smaller conduit size were related to conduit failure. CONCLUSIONS: Utilization of the Labcor conduit revealed acceptable intermediate-term results. The conduit appeared to be functioning sufficiently well within the first 5 years in the majority of patients. The higher rate of failure concerning smaller conduits might be associated with somatic outgrowth; however, conduit degeneration as common and long-term outcome still needs to be evaluated.

Transcatheter mitral valve replacement (TMVR): annular or apical fixation?

AIMS: The aim of this study was to evaluate the impact of two different transcatheter mitral valve replacement (TMVR) fixation strategies on the neo left ventricular outflow tract (neo-LVOT) and aorto-mitral angulation (AMA) after TMVR. METHODS AND RESULTS: Two different self-expanding nitinol valved stents were developed for transapical TMVR. In one group, the stents were fixed with an annular fixation system (ANN group, n=6). These prototypes were compared with an apical tether fixation TMVR system (AP group, n=11) in another group. Echocardiographic evaluation of the AMA and the neo-LVOT was conducted before and one hour after implantation. Maximal and minimal AMA (AMAmax and AMAmin) during the cardiac cycle of the AP group were significantly narrower than those of the ANN group (AMAmax: 39±8° vs 67±15°, p<0.001, AMAmin: 33±10° vs 56±22°, p=0.009). More severe reduction of the neo-LVOT diameter was observed in the ANN group (60±11% vs 26±14%, p<0.001). The ANN group had a higher peak velocity through the neo-LVOT post implantation (200±52 cm/s vs 108±15 cm/s, p<0.001). CONCLUSIONS: The apical fixation system maintains a smaller and more stable aorto-mitral angulation and a larger neo-LVOT, thereby reducing the risk of postoperative neo-LVOT obstruction in this experimental setting.

S100B and its relation to cerebral oxygenation in neonates and infants undergoing surgery for congenital heart disease.

OBJECTIVES: Neonates and infants undergoing surgery for congenital heart disease are at risk for developmental impairment. Hypoxic-ischemic brain injury might be one contributing factor. We aimed to investigate the perioperative release of the astrocyte protein S100B and its relation to cerebral oxygenation. METHODS: Serum S100B was measured before and 0, 12, 24, and 48 hours after surgery. Cerebral oxygen saturation was derived by near-infrared spectroscopy. S100B reference values based on preoperative samples; concentrations above the 75th percentile were defined as elevated. Patients with elevated S100B at 24 or 48 hours were compared to cases with S100B in the normal range. Neonates (≤28 days) and infants (>28 and ≤365 days) were analyzed separately due to age-dependent release of S100B. RESULTS: Seventy-four patients underwent 94 surgical procedures (neonates, n = 38; infants, n = 56). S100B concentrations were higher in neonates before and after surgery at all time points (P ≤ .015). Highest values were noticed immediately after surgery. Postoperative S100B was elevated after 15 (40.5%) surgeries in neonates. There was no difference in pre-, intra-, or postoperative cerebral oxygenation. In infants, postoperative S100B was elevated after 23 (41.8%) procedures. Preoperative cerebral oxygen saturations tended to be lower (53 ± 12% vs 59 ± 12%, P = .069) and arterial-cerebral oxygen saturation difference was higher (35 ± 11% vs 28 ± 11%, P = .018) in infants with elevated postoperative S100B. In the early postoperative course, cerebral oxygen saturation was lower (54 ± 13% vs 63 ± 12%, P = .011) and arterial-cerebral oxygen saturation difference was wider (38 ± 11% vs 30 ± 10%, P = .008). Cerebral oxygen saturation was also lower for the entire postoperative course (62 ± 18% vs 67 ± 9%, P = .047). CONCLUSIONS: Postoperative S100B was elevated in about 40% of neonates and infants undergoing cardiac surgery. Infants with elevated postoperative S100B had impaired perioperative cerebral tissue oxygenation. No relation between S100B and cerebral oxygenation could be demonstrated in neonates.

Glial Fibrillary Acid Protein and Cerebral Oxygenation in Neonates Undergoing Cardiac Surgery.

BACKGROUND: Neonates undergoing surgery for complex congenital heart disease are at risk of developmental impairment. Hypoxic-ischemic brain injury might be a contributing factor. We aimed to investigate the perioperative release of the astrocyte cytoskeleton component glial fibrillary acid protein and its relation to cerebral oxygenation. METHODS: Serum glial fibrillary acid protein levels were measured before and 0, 12, 24, and 48 hours after surgery. Reference values were based on preoperative samples; concentrations above the 95th percentile were defined as elevated. Cerebral oxygenation was derived by near-infrared spectroscopy. RESULTS: Thirty-six neonates undergoing 38 surgeries utilizing cardiopulmonary bypass were enrolled (complete data available for 35 procedures). Glial fibrillary acid protein was elevated after 18 surgeries (arterial switch: 7/12; Norwood: 5/15; others: 6/8; p = 0.144). Age at surgery was higher in cases with elevated serum levels (6 [4-7] vs. 4 [2-5] days, p = 0.009) and intraoperative cerebral oxygen saturation was lower (70 ± 10% vs. 77 ± 7%, p = 0.029). In cases with elevated postoperative glial fibrillary acid protein, preoperative cerebral oxygen saturation was lower for neonates undergoing the arterial switch operation (55 ± 9% vs. 64 ± 4%, p = 0.048) and age at surgery was higher for neonates with a Norwood procedure (7 [6-8] vs. 5 [4-6] days, p = 0.028). CONCLUSIONS: Glial fibrillary acid protein was elevated after ∼50% of neonatal cardiac surgeries and was related to cerebral oxygenation and older age at surgery. The potential value as a biomarker for cerebral injury after neonatal cardiac surgery warrants further investigation; in particular, the association with neurodevelopmental outcome needs to be determined.

Longitudinal Deformation of the Right Ventricle in Hypoplastic Left Heart Syndrome: A Comparative Study of 2D-Feature Tracking Magnetic Resonance Imaging and 2D-Speckle Tracking Echocardiography.

In hypoplastic left heart syndrome (HLHS), long-term outcome is closely related to right ventricular function. Echocardiography and magnetic resonance imaging (MRI) are routinely used for functional assessment. MRI 2D-tissue feature tracking (2D-FT) allows quantification of myocardial deformation but has not yet been applied to HLHS patients. We sought to investigate the feasibility of this technique and to compare the results to 2D-speckle tracking echocardiography (2D-STE). In routine MRI 2D anatomical four chamber view, cine images were recorded in 55 HLHS patients (median age 4.9 years [1.6, 17.0]). Regional and global peak systolic longitudinal strain (LS) and strain rate (LSR) were determined using 2D-FT software. Echocardiographic four chamber view was analyzed with 2D-STE. Visualization of all myocardial segments with MRI was excellent, regional, and global LS and LSR could be assessed in all data sets. In 2D-STE, 28% of apical segments could not be analyzed due to poor image quality. Agreement of 2D-FT MRI and 2D-STE was acceptable for global LS, but poor for global LSR. In MRI, regional LS was lower in the septal segments, while LSR was not different between the segments. GLS and GLSR correlated with ejection fraction (GLS: r = - 0.45 and r < 0.001, GLSR: r = - 0.34 and p = 0.01). With new post-processing options, the assessment of regional and global LS and LSR is feasible in routine MRI of HLHS patients. For LS, results were comparable with 2D-STE. The agreement was poor for LSR, which might relate to differences in temporal resolution between the two imaging modalities.

Neuro-developmental outcome in single-ventricle patients: is the Norwood procedure a risk factor?

OBJECTIVES: Complex neonatal surgery is considered a risk factor for neuro-developmental impairment in single-ventricle patients. Neuro-developmental outcome was compared between preschool-aged Fontan patients who underwent a Norwood procedure and single-ventricle patients not requiring neonatal surgery with cardiopulmonary bypass. METHODS: Verbal, performance and full-scale intelligence quotient (IQ) were evaluated with the Wechsler Preschool and Primary Scale of Intelligence. Cognitive functions were assessed with the German 'Kognitiver Entwicklungstest für das Kindergartenalter' (KET-KID). Risk factors for impaired neuro-development were evaluated. RESULTS: Neuro-developmental assessment was completed in 95 patients (Norwood: n = 69; non-Norwood: n = 26). Median (interquartile range) IQ and KET-KID scores were in the normal range. Except for verbal KET-KID, scores did not differ between Norwood and non-Norwood patients (verbal IQ: 98 (86-105) vs 93 (85-102), P = 0.312; performance IQ: 91 (86-100) vs 96 (86-100), P = 0.932; full-scale IQ: 93 (86-101) vs 89 (84-98), P = 0.314; KET-KID verbal: 48 (17-72) vs 25 (2-54), P = 0.020; KET-KID non-verbal: 33 (18-62) vs 45 (15-54), P = 0.771; KET-KID global: 42 (14-65) vs 28 (6-63), P = 0.208). Full-scale IQ was below average (<85 points) in 14 (20%) Norwood and 9 (35%) non-Norwood cases (P = 0.181). Global KET-KID was below average (<16th percentile) in 19 (28%) and 10 (38%) patients (P = 0.326). Smaller head circumference z-score and complications before neonatal surgery were independently associated with lower scores. CONCLUSIONS: Neuro-developmental outcome of preschool-aged Fontan patients was in the normal range. The Norwood procedure was not a risk factor for neuro-developmental impairment. Preoperative condition and patient-related factors were more important determinants than variables related to surgical palliation.

Restrictive enlargement of the pulmonary annulus at repair of tetralogy of Fallot: a comparative 10-year follow-up study.

OBJECTIVES: Since 1996, our centre performs restrictive enlargement of the pulmonary annulus at surgical repair of tetralogy of Fallot. A transannular patch is only used if the z-score of the pulmonary annulus is smaller than -2. We sought to determine whether this strategy reduces pulmonary insufficiency (PI) and reoperation rate compared to a nationwide contemporary cohort that has not been operated using a uniform strategy. METHODS: Eighty-seven tetralogy of Fallot patients were included in the study (Group 1). One hundred sixty-seven tetralogy of Fallot patients from the Competence Network for Congenital Heart Disease served as controls (Group 2). Clinical, echocardiographic, electrocardiogram, cardiovascular magnetic resonance and outcome data were analysed. RESULTS: Follow-up time since repair was not different between groups [12.9 (7.8-18.8) vs 13.1 (5.2-16.9) years, P = 0.96] while transannular patch rate was significantly lower in Group 1 (32.2% vs 64.7%, P < 0.001). Ten-year freedom from reoperation for PI was significantly higher in our cohort (98% vs 92%, P = 0.01). Multivariable analysis identified restrictive enlargement as the only predictor for no need of reoperation [hazard ratio 0.4 (95% confidence interval 0.24-0.84), P < 0.01]. In Group 1, cardiovascular magnetic resonance-derived volumes were smaller (indexed end-diastolic volume: 103 ± 24 vs 123 ± 31 ml/m2, P < 0.001; indexed end-systolic volume: 53 ± 19 vs 59 ± 20 ml/m2, P = 0.04) and regurgitation fraction was lower (21 ± 14 vs 31 ± 17%, P < 0.001). CONCLUSIONS: Restrictive enlargement of the pulmonary annulus reduces PI and limits the amount of right ventricular dilatation at intermediate-term follow-up. The need for reoperation to alleviate PI is significantly lower compared to a contemporary cohort. Restrictive enlargement strategy has a stronger influence on freedom from reoperation than the use of a transannular patch. CLINICAL TRIAL REGISTRATION: WHO Main ID: DRKS00010087. URL: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00010087.

Decline of Systolic and Diastolic 2D Strain Rate During Follow-Up of HLHS Patients After Fontan Palliation.

Accurate assessment of ventricular function is particularly important in children with hypoplastic left heart syndrome (HLHS) after completion of the total cavopulmonary connection (TCPC). For this purpose, two-dimensional speckle tracking (2DST) is a promising technique as it does not depend on the angle of insonation or the geometry of the ventricle. The objective of this study was to assess changes in systolic and diastolic right ventricular (RV) function within a 5-year follow-up period of HLHS patients after TCPC using conventional and 2DST echocardiography. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), E/A, E/e' and 2DST parameters [global longitudinal peak systolic strain (GS) and strain rate (GSRs), global strain rate in early (GSRe) and late (GSRa) diastole] of 40 HLHS patients were compared at 1.6 and at 5.1 years after TCPC. RVFAC, E/A, E/e' and GS did not change, whereas TAPSE (13.7 ± 3.2 vs. 10.5 ± 2.4 mm/m(2), p < 0.001), GSRs (-1.56 ± 0.28 vs. -1.35 ± 0.31 1/s, p < 0.001), GSRe (2.22 ± 0.49 vs. 1.96 ± 0.44 1/s, p = 0.004) and GSRa (1.19 ± 0.39 vs. 0.92 ± 0.39 1/s, p < 0.001) decreased significantly. Systolic and diastolic RV function parameters of HLHS patients decreased from 1.6 to 5.1 years after TCPC in our patients. Changes in global strain rate parameters may be signaling early RV dysfunction that is not detectable by traditional echocardiography. Further study is needed to verify this and to determine whether these changes are clinically relevant.