Balloon Valvuloplasty in Congenital Critical Aortic Valve Stenosis in Neonates and Infants: A Rescue Procedure for the Left Ventricle.

Congenital critical aortic valve stenosis (CAVS) is a life-threatening disease requiring urgent treatment. First-line therapy is still controversial. The aim of our study was (1) to analyze retrospectively the patients of our institution who underwent balloon aortic valvuloplasty (BAV) due to CAVS and (2) describe the techniques for improved feasibility of intervention using microcatheters and retrieval loops. Twelve patients underwent 23 BAVs: 1 BAV was performed in 3 patients, 2 BAVs were performed in 7 patients, and 3 BAVs were performed in 2 patients. The peak trans-valvular pressure gradient (Δp) and left ventricular shortening fraction (LVSF) improved significantly in the first two interventions. In the first BAV, Δp decreased from 73.7 ± 34.5 mmHg to 39.8 ± 11.9 mmHg (p = 0.003), and the LVSF improved from 22.3 ± 13.5% to 31.6 ± 10.2% (p = 0.001). In the second BAV, Δp decreased from 73.2 ± 33.3 mmHg to 35.0 ± 20.2 mmHg (p < 0.001), and the LVSF increased from 26.7 ± 9.6% to 33.3 ± 7.4% (p = 0.004). Cardiac surgery during the neonatal period was avoided for all children. The median time to valve surgery was 5.75 years. Few complications occurred, namely mild-to-moderate aortic regurgitation, one remediable air embolism, and one intimal injury to the ascending aorta. We conclude that BAV is a successful emergency treatment for CAVS, resulting in left ventricular relief, clinical stabilization, and a time gain until cardiac surgery.

Clinical course and follow-up of pediatric patients with COVID-19 vaccine-associated myocarditis compared to non-vaccine-associated myocarditis within the prospective multicenter registry-"MYKKE".

BACKGROUND: Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents. METHODS: Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis "MYKKE." Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non-vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics. RESULTS: From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45%-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (P = .003), arrhythmias (P = .031), left ventricular dilatation (P = .045), lower LVEF (P < .001) and major cardiac adverse events (P = .102). CONCLUSIONS: Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non-vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications.

Clinical characteristics and outcome of biopsy-proven myocarditis in children - Results of the German prospective multicentre registry "MYKKE".

BACKGROUND: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. METHODS: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. RESULTS: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. CONCLUSIONS: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

Cardiovascular magnetic resonance in children with suspected myocarditis: current practice and applicability of adult protocols.

BACKGROUND: Cardiovascular magnetic resonance serves as a useful tool in diagnosing myocarditis. Current adult protocols are yet to be validated for children; thus, it remains unclear if the methods used can be applied with sufficient image quality in children. This study assesses the use of cardiovascular magnetic resonance in children with suspected myocarditis. METHODS: Image data from clinical cardiovascular magnetic resonance studies performed in children enrolled in Mykke between June 2014 and April 2019 were collected and analysed. The quality of the data sets was evaluated using a four-point quality scale (4: excellent, 3: good, 2: moderate, 1: non-diagnostic). RESULTS: A total of 102 patients from 9 centres were included with a median age (interquartile range) of 15.4(10.7-16.6) years, 137 cardiovascular magnetic resonance studies were analysed. Diagnostic image quality was found in 95%. Examination protocols were consistent with the original Lake Louise criteria in 58% and with the revised criteria in 35%. Older patients presented with better image quality, with the best picture quality in the oldest age group (13-18 years). Sedation showed a negative impact on image quality in late gadolinium enhancement and oedema sequences. No such correlation was seen in cardiac function assessment sequences. In contrast to initial scans, in follow-up examinations, the use of parametric mapping increased while late gadolinium enhancement and oedema sequences decreased. CONCLUSION: Cardiovascular magnetic resonance protocols for the assessment of adult myocarditis can be applied to children without significant constraints in image quality. Given the lack of specific recommendations for children, cardiovascular magnetic resonance protocols should follow recent recommendations for adult cardiovascular magnetic resonance.

A New Technique of Aortoventricular Patch Enlargement and Root Replacement for Annular Hypoplasia.

The Ross-Konno operation is effective for enlargement of a hypoplastic aortic annulus and left ventricular outflow tract. It is, however, an invasive operation with the potential for early and late cardiac morbidity. We propose a new technique of annular and outflow tract enlargement that avoids the septal incision while effectively opening up the outflow tract and aortic annulus.

Severe heart failure and the need for mechanical circulatory support and heart transplantation in pediatric patients with myocarditis: Results from the prospective multicenter registry "MYKKE".

Myocarditis represents an important cause for acute heart failure. MYKKE, a prospective multicenter registry of pediatric patients with myocarditis, aims to gain knowledge on courses, diagnostics, and therapy of pediatric myocarditis. The role of mechanical circulatory support (MCS) in children with severe heart failure and myocarditis is unclear. The aim of this study was to determine characteristics and outcome of patients with severe heart failure requiring MCS and/or heart transplantation. The MYKKE cohort between September 2013 and 2016 was analyzed. A total of 195 patients were prospectively enrolled by 17 German hospitals. Twenty-eight patients (14%) received MCS (median 1.5 years), more frequently in the youngest age group (0-2 years) than in the older groups (P < 0.001; 2-12 and 13-18 years). In the MCS group, 50% received a VAD, 36% ECMO, and 14% both, with a survival rate of 79%. The weaning rate was 43% (12/28). Nine (32%) patients were transplanted, one had ongoing support, and six (21%) died. Histology was positive for myocarditis in 63% of the MCS group. Patients within the whole cohort with age <2 years and/or ejection fraction <30% had a significantly worse survival with high risk for MCS, transplantation, and death (P < 0.001). Myocarditis represents a life-threatening disease with an overall mortality of 4.6% in this cohort. The fulminant form more often affected the youngest, leading to significantly higher rate of MCS, transplantation, and mortality. MCS represents an important and life-saving therapeutic option in children with myocarditis with a weaning rate of 43%.

The analysis of heterotaxy patients reveals new loss-of-function variants of GRK5.

G protein-coupled receptor kinase 5 (GRK5) is a regulator of cardiac performance and a potential therapeutic target in heart failure in the adult. Additionally, we have previously classified GRK5 as a determinant of left-right asymmetry and proper heart development using zebrafish. We thus aimed to identify GRK5 variants of functional significance by analysing 187 individuals with laterality defects (heterotaxy) that were associated with a congenital heart defect (CHD). Using Sanger sequencing we identified two moderately frequent variants in GRK5 with minor allele frequencies <10%, and seven very rare polymorphisms with minor allele frequencies <1%, two of which are novel variants. Given their evolutionarily conserved position in zebrafish, in-depth functional characterisation of four variants (p.Q41L, p.G298S, p.R304C and p.T425M) was performed. We tested the effects of these variants on normal subcellular localisation and the ability to desensitise receptor signalling as well as their ability to correct the left-right asymmetry defect upon Grk5l knockdown in zebrafish. While p.Q41L, p.R304C and p.T425M responded normally in the first two aspects, neither p.Q41L nor p.R304C were capable of rescuing the lateralisation phenotype. The fourth variant, p.G298S was identified as a complete loss-of-function variant in all assays and provides insight into the functions of GRK5.

Right and Left Ventricular Function and Mass in Male Elite Master Athletes: A Controlled Contrast-Enhanced Cardiovascular Magnetic Resonance Study.

BACKGROUND: It is under debate whether the cumulative effects of intensive endurance exercise induce chronic cardiac damage, mainly involving the right heart. The aim of this study was to examine the cardiac structure and function in long-term elite master endurance athletes with special focus on the right ventricle by contrast-enhanced cardiovascular magnetic resonance. METHODS AND RESULTS: Thirty-three healthy white competitive elite male master endurance athletes (age range, 30-60 years) with a training history of 29±8 years, and 33 white control subjects pair-matched for age, height, and weight underwent cardiopulmonary exercise testing, echocardiography including tissue-Doppler imaging and speckle tracking, and cardiovascular magnetic resonance. Indexed left ventricular mass and right ventricular mass (left ventricular mass/body surface area, 96±13 and 62±10 g/m(2); P<0.001; right ventricular mass/body surface area, 36±7 and 24±5 g/m(2); P<0.001) and indexed left ventricular end-diastolic volume and right ventricular end-diastolic volume (left ventricular end-diastolic volume/body surface area, 104±13 and 69±18 mL/m(2); P<0.001; right ventricular end-diastolic volume/body surface area, 110±22 and 66±16 mL/m(2); P<0.001) were significantly increased in athletes in comparison with control subjects. Right ventricular ejection fraction did not differ between athletes and control subjects (52±8 and 54±6%; P=0.26). Pathological late enhancement was detected in 1 athlete. No correlations were found for left ventricular and right ventricular volumes and ejection fraction with N-terminal pro-brain natriuretic peptide, and high-sensitive troponin was negative in all subjects. CONCLUSIONS: Based on our results, chronic right ventricular damage in elite endurance master athletes with lifelong high training volumes seems to be unlikely. Thus, the hypothesis of an exercise-induced arrhythmogenic right ventricular cardiomyopathy has to be questioned.

Left ventricular systolic dysfunction in asymptomatic Marfan syndrome patients is related to the severity of gene mutation: insights from the novel three dimensional speckle tracking echocardiography.

BACKGROUND: In asymptomatic Marfan syndrome (MFS) patients we evaluated the relationship between the types of fibrillin-1 (FBN1) gene mutation and possible altered left ventricular (LV) function as assessed by three-dimensional speckle tracking echocardiography (3D-STE). METHODS AND RESULTS: Forty-five MFS patients (mean age 24 ± 15 years) and 40 age-matched healthy controls were studied. Genetic evaluation for the FBN1 gene was carried on 32 MFS patients. Gene mutation (n = 15, 47%) was classified as mild when the mutation resulted in nearly normally functioning protein, while mutations resulting in abnormally function protein were considered to be severe (n = 17, 53%). All patients and controls underwent 3D-STE for evaluation of LV function by an echocardiographer blinded to the results of the genetic testing. Compared to controls, MFS patients had significantly lower 3D-STE derived LV ejection fraction (EF, 57.43 ± 7.51 vs. 62.69 ± 4.76%, p = 0.0001), global LV longitudinal strain (LS, 14.85 ± 2.89 vs. 17.90 ± 2.01%, p = 0.0001), global LV circumferential strain (CS, 13.93 ± 2.81 vs. 16.82 ± 2.17%, p = 0.0001) and global LV area strain (AS, 25.76 ± 4.43 vs. 30.51 ± 2.61%, p = 0.0001). Apart from the global LV LS all these parameters were significantly lower in patients with severe gene mutation than in those with mild mutation (p < 0.05). In the multivariate linear regression analysis only the type of mutation had a significant influence on the 3D-STE derived LVEF (p = 0.017), global CS (p = 0.005) and global AS (p = 0.03). CONCLUSIONS: In asymptomatic MFS patients latent LV dysfunction can be detected using 3D STE. The LV dysfunction is mainly related to the severity of gene mutation, suggesting possible primary cardiomyopathy in MFS patients.

Assessment of inter-atrial, inter-ventricular, and atrio-ventricular interactions in tetralogy of Fallot patients after surgical correction. Insights from two-dimensional speckle tracking and three-dimensional echocardiography.

BACKGROUND: We aimed to assess biatrial size and function, interactions on atrial and ventricular levels, and atrio-ventricular coupling in patients after tetralogy of Fallot repair. METHODS: A total of 34 patients with a mean age of 20.9±9 years, and 35 healthy controls, underwent two-dimensional speckle tracking echocardiography for ventricular and atrial strain measurements and real-time three-dimensional echocardiography to assess ventricular and atrial volumes. RESULTS: When compared with controls, tetralogy of Fallot patients had significantly reduced right atrial peak atrial longitudinal strain (p<0.01), right atrial peak atrial contraction strain (p<0.01), right atrial ejection fraction (p<0.01), left atrial peak atrial longitudinal strain (p<0.01), left atrial peak atrial contraction strain (p<0.05), and left atrial ejection fraction (p<0.01). In the tetralogy of Fallot group, left ventricular ejection fraction was negatively related to the right ventricular end-systolic volume normalised to body surface area (r=-0.62, p<0.01). An association was found in patients between the right atrial peak longitudinal strain and mean right ventricular strain (r=0.64, p<0.01). In patients, the left atrial peak longitudinal strain correlated negatively with right atrial end-diastolic volume normalised to body surface area (r=-0.67, p<0.01), whereas the left atrial ejection fraction correlated weakly with left ventricular ejection fraction (r=0.41, p<0.05). CONCLUSIONS: In asymptomatic tetralogy of Fallot patients, biatrial dysfunction exists and can be quantified via two-dimensional speckle tracking echocardiography as well as real-time three-dimensional echocardiography. Different forms of interactions on atrial and ventricular levels are evident among such cohorts.

Effect of bosentan therapy on ventricular and atrial function in adults with Eisenmenger syndrome. A prospective, multicenter study using conventional and Speckle tracking echocardiography.

BACKGROUND: The effect of bosentan on the ventricular and atrial performance in patients with Eisenmenger syndrome is unclear. In adult patients with Eisenmenger syndrome, we aimed to evaluate the midterm effect of bosentan on physical exercise, ventricular and atrial function, and pulmonary hemodynamics. METHODS: Forty adult patients before and after 24 weeks bosentan therapy underwent 6 min walk test, two-dimensional speckle tracking echocardiography, plasma NT-proBNP measurement and cardiac catheterization. RESULTS: After 24 weeks, bosentan therapy an improvement was observed regarding the 6 min walk distance from a median (quartile 1-quartile 3) of 382.5 (312-430) to 450 (390-510) m (p = 0.0001), NT-proBNP from 527.5 (201-1,691.25) to 369 (179-1,246) pg/ml (p = 0.021), right ventricular mean longitudinal systolic strain from 18 (13-22) to 19 (14.5-25) % (p = 0.004), left ventricular mean longitudinal systolic strain from 16 (12-21) to 17 (16-22) % (p = 0.001), right atrial mean peak longitudinal strain from 26 (18-34) to 28 (22-34) % (p = 0.01) and right atrial mean peak contraction strain from 11 (8-16) to 13 (11-16) % (p = 0.005). The invasively obtained Qp:Qs and Rp:Rs did not significantly change under bosentan therapy. CONCLUSIONS: In adult patients with Eisenmenger syndrome, bosentan therapy improves ventricular and atrial functions resulting in enhancement of physical exercise and reduction in the NT-proBNP level, while the pulmonary vascular resistance does not change substantially.

Altered right ventricular function in the long-term follow-up evaluation of patients after delayed aortic reimplantation of the anomalous left coronary artery from the pulmonary artery.

This study aimed to evaluate regional and global ventricular functions in the long term after aortic reimplantation of the anomalous left coronary artery from the pulmonary artery (ALCAPA) and to assess whether the time of surgical repair influences ventricular performance.The study examined 20 patients with a median age of 15 years (range 3-37 years) who had a corrected ALCAPA and 20 age-matched control subjects using echocardiography and tissue Doppler imaging (TDI). The median follow-up period after corrective surgery was 6 years (range 2.6-15 years). Seven patients underwent surgery before the age of 3 years (early-surgery group), whereas 13 patients had surgery after that age (late-surgery group). The TDI-derived myocardial strain of the interventricular septum (IVS), lateral wall of the left ventricle (LV), and lateral wall of the right ventricle (RV) in the basal and mid regions were examined, and a mean was calculated. The pulsed Doppler-derived Tei index was used to assess global left ventricular function. No significant differences were found between the early-surgery group and the control group regarding the regional myocardial strain or the Tei index. Compared with the early-surgery group, the late-surgery group had a significantly higher Tei index (mean 0.37; range 0.31-0.42 vs. mean 0.52; range 0.39-0.69; p < 0.005), a lower strain percentage of the lateral wall of the LV (mean 29; range 17-30 vs. mean 9; range 7-23), IVS (mean 23; range 21-31 vs. mean 19; range 13-25), and lateral wall of the RV (mean 23; range 21-31 vs. mean 19; range 13-25). The age at operation correlated significantly with the Tei index (r = 0.84, p < 0.001) and inversely with the mean strain of the lateral wall of the LV (r = -0.53, p = 0.028), IVS (r = -0.68, p = 0.003), and lateral wall of the RV (r = -0.68, p = 0.003). At the midterm follow-up evaluation after corrective surgery of ALCAPA, not only the left but also the right ventricular function seemed to be affected in patients with delayed diagnosis and late surgical repair but preserved among the younger patients with early diagnosis and corrective surgery.

Regional analysis of longitudinal systolic function of the right ventricle after corrective surgery of tetralogy of Fallot using myocardial isovolumetric acceleration index.

To assess regional longitudinal systolic function of the right ventricle in patients with repaired tetralogy of Fallot (TOF) by tissue Doppler imaging-derived isovolumetric acceleration (IVA) index and determine the effect of right-ventricular (RV) enlargement on regional systolic function. In 30 consecutive TOF patients and 30 age-matched controls, myocardial velocity of the RV ventricular free wall in the basal and middle regions were examined in the apical four-chamber view. Peak myocardial velocity during IVA was recorded on the free RV wall. IVA index was calculated as the difference between baseline and peak velocity divided by their time interval. In 23 of the studied TOF patients, magnetic resonance imaging was performed on the same day to determine global RV volume and ejection fraction. IVA index of the RV lateral free wall was significantly lower in the basal (8.31 ± 6.00 vs. 19.00 ± 10.85 m/s(2), p = 0.0001) and middle segments (6.56 ± 5.22 vs. 16.17 ± 7.44 m/s(2), p = 0.0001) in patients than in controls. Among TOF patients, a negative correlation was found between IVA index in the middle segment and RV end-diastolic volume/body surface area (r = -0.549, p < 0.01). Similar to other longitudinal RV wall parameters, the IVA index showed a decreased value in the RV free wall, which is related to the impaired regional and global longitudinal RV systolic dysfunction. RV enlargement adversely affects regional longitudinal systolic function.

The novel two-dimensional strain reflects improvement and remodeling of left-ventricular function better than conventional echocardiographic parameters after aortic valve repair in pediatric patients.

We aimed to evaluate the outcome and regional and global left-ventricular (LV) function after aortic valve repair in children with congenital aortic valve disease. Thirty-two consecutive patients with a mean age of 12.62 years (4 months to 18 years) undergoing aortic valve repair due to valve stenosis (AS group, n = 21) or aortic regurgitation (AR group, n = 11) were studied during a follow-up period of 12 months regarding change and adaptation of myocardial function using conventional and novel echocardiographic methods, including two-dimensional (2D) strain echocardiogram. Conventional and 2D strain echocardiographic studies were performed and analyzed off-line using commercially available software (EchoPac 6.1.0, GE). Peak aortic valve gradient decreased from 62.04 ± 30.34 mmHg before surgery to 22.80 ± 14.13 mmHg 2 weeks after surgery and to 35.73 ± 22.11 mmHg 12 months after surgery (p = 0.01). The degree of AR decreased significantly to grade 0 in 20 children and to grade I in 12. There was a significant decrease of thickness of the interventricular septum (IVS) and posterior wall resulting in improvement of LV mass index (p = 0.007, p = 0.043, and p = 0.001, respectively). Significant decrease of myocardial thickness was found, especially in the IVS, in the AS group (p = 0.008), and a significant decrease in LV end-diastolic dimension (EDD) was found in the AR group (p = 0.007). 2D strain analysis showed that global peak strain, global systolic strain rate, and global early diastolic strain rates improved significantly for all patients during the study period after aortic valve repair (p < 0.001, p = 0.037, and p = 0.018, respectively). The global strain and strain rates correlated significantly to IVS thickness (r = 0.002 and r = 0.003, respectively), LV mass index (r = 0.02 and r = 0.015, respectively), and EDD (r = 0.26 and r = 0.005, respectively). Aortic valve repair surgery in pediatric patients results in improvement of global and regional systolic and diastolic LV parameters, which was better shown by 2D strain parameters rather than conventional echocardiographic parameters.

Diastolic asynchrony and myocardial dysfunction in patients with univentricular heart after Fontan operation.

BACKGROUND: We aimed to assess the existence of myocardial dysfunction and intra-univentricular diastolic asynchrony in patients after Fontan operation. METHODS: Twenty patients after Fontan procedure and 30 age-matched controls were included in the study. The global function of the univentricular heart was analyzed by the Tei index. Regional myocardial velocities and strain of the univentricular heart including the rudimentary right ventricle (RV) were quantified by tissue Doppler imaging. Intra-univentricular or intra left ventricular (LV) diastolic delay was measured from the difference of diastolic intervals (time to peak early diastolic velocity), measured at LV lateral wall and the rudimental RV wall in patients, or LV lateral wall and the ventricular septum in controls. RESULTS: Compared to the control group, patients after Fontan operation had significantly elevated Tei index (0.24 ± 0.02 vs. 0.41 ± 0.1, p < 0.001). On the other hand, the regional myocardial velocities and strains of the univentricular heart including the rudimentary RV were significantly reduced (p < 0.001). Among patients, there was a significant correlation between the Tei index of the univentricular ventricle and rudimentary RV strain (r = -0.66, p = 0.01). The heart rate-corrected intra-univentricular diastolic delay was significantly prolonged among patients when compared to the intra-LV diastolic delay in controls (0.01 ± 0.9 vs. 1 ± 1.1, p = 0.005). CONCLUSIONS: Myocardial dysfunctions and intra-univentricular diastolic asynchrony of the univentricular heart in patients after Fontan procedure are evident. The rudimentary RV in patients after Fontan procedure plays an important role in the determination of the global function of the univentricular heart.

Right ventricular function in grown-up patients after correction of congenital right heart disease.

AIMS: We investigated whether a correlation exists between biomarkers of the neurohumoral system and clinical markers in grown-up patients with congenital heart disease (GUCH) and right ventricular function. METHODS AND RESULTS: Prospective, cross-sectional, multicenter study of 104 GUCH patients (median) 16 years (range 6-43 years) after corrective surgery with RV pressure and/or volume overload and 54 healthy controls. Clinical, functional, and laboratory parameters were assessed. Natriuretic peptide levels were significantly increased in GUCH patients (NTproBNP 101 vs. 25 pg/ml, p < 0.001), but we observed no differences in norepinephrine, aldosterone, angiotensin II and Endothelin-1 levels. NTproBNP correlated significantly with clinical markers such as NYHA classification, prolonged QRS duration and reduced exercise capacity (VO(2) peak) (all p < 0.001), as well as self-reported quality of life (p < 0.001). MRI and echocardiography derived RV volumes were elevated and ejection fraction reduced in the patients (both p < 0.001). Tissue Doppler parameter showed significantly restricted ventricular longitudinal systolic function (longitudinal tricuspid valve movement, 1.7 vs. 2.3 cm, p < 0.001), suggesting stiffness and reduced RV compliance. CONCLUSION: In conclusion, grown-up patients with congenital right heart disease NTproBNP correlates well with various clinical markers of RV failure, such as prolongation of QRS duration, exercise capacity, echocardiography and MRI parameters, and quality of life.

Assessment of interventricular and right-intraventricular dyssynchrony in patients with surgically repaired tetralogy of Fallot by two-dimensional speckle tracking.

AIMS: We aimed to assess interventricular and right-intraventricular dyssynchrony in patients after tetralogy of Fallot (TOF) repair by two-dimensional (2D) speckle tracking and to identify factors associated with dyssynchrony. METHODS AND RESULTS: Forty-two patients after TOF repair with a mean age of 19.8 years and 42 age-matched healthy controls were studied. Longitudinal myocardial deformation (strain) and time-to-peak intervals were assessed by 2D speckle tracking and tissue Doppler imaging (TDI) in an apical four-chamber view. Dyssynchrony was defined as delay above 3 standard deviations of mean values in the control group. Magnetic resonance imaging (MRI) was performed for evaluation of ventricular function. Using 2D speckle tracking, 22 patients (52%) showed interventricular dyssynchrony and 16 (38%) had right-intraventricular dyssynchrony. The interventricular delay correlated significantly with right ventricular (RV) strain (r = 0.687, P < 0.001), RV systolic pressure (r = 0.535, P = 0.001), QRS duration (r = 0.466, P = 0.002), RV end-diastolic (r = 0.377, P = 0.018), and RV end-systolic volumes (r = 0.452, P = 0.004) as well as RV ejection fraction (r = -0.378, P = 0.018). Similarly, the right-intraventricular delay correlated significantly with RV strain (r = 0.534, P < 0.001), QRS duration (r = 0.428, P = 0.005), RV end-systolic volume (r = 0.34, P = 0.038), and RV systolic pressure (r = 0.413, P = 0.015). In multivariate regression analysis, reduced RV strain and prolonged QRS duration remained the main determinant factors predicting dyssynchrony. Moreover, 2D speckle tracking and TDI showed a significant correlation in the assessment of the interventricular (r = 0.738, P < 0.001) and right-intraventricular delay (r = 0.747, P < 0.001). CONCLUSION: Interventricular and right-intraventricular dyssynchrony are detectable in patients after TOF repair by 2D speckle tracking. Reduced RV myocardial deformation and QRS prolongation are the main factors associated with the observed dyssynchrony.

Assessment of left ventricular dyssynchrony and function using real-time 3-dimensional echocardiography in patients with congenital right heart disease.

BACKGROUND: Patients after repair of congenital right heart disease (CRHD) may exhibit left ventricular (LV) dyssynchrony (LVD). However, the diagnosis of LVD is difficult and its reliability limited because current methods do not assess LVD of the whole LV simultaneously. The aim of the study was to assess LVD according to a novel global systolic dyssynchrony index (SDI) derived from real-time 3-dimensional echocardiography in patients after repaired CRHD. METHODS: Two-dimensional echocardiography and real-time 3-dimensional echocardiography were performed in 30 patients after CRHD repair and in 30 matched healthy controls. Real-time 3-dimensional echocardiography data sets provided time-volume curves, and 2 global SDIs were derived from the dispersion of time to reach minimal systolic volume according to a 16- or 17-LV segment model. RESULTS: Both SDIs were significantly elevated in the patient as compared with the control group (P < .001). A cutoff value for both SDIs was calculated and LVD defined as one of the SDIs exceeding cutoff. Left ventricular dyssynchrony was present in 5 (100%) of 5 patients with a LV ejection fraction (EF) <50% and 13 (52%) of 25 patients with preserved LVEF, thus being diagnosed in a total of 18 (60%) of 30 patients. Moreover, patients with LVD showed a significantly higher degree of pulmonary regurgitation (P = .01) with elevated right ventricular volumes and altered septal motion. Stepwise multivariate analysis identified LVEF (P = .005) and the degree of pulmonary regurgitation (P = .02) as independent predictors of LVD. CONCLUSIONS: Left ventricular dyssynchrony can be detected in about 60% of patients after CRHD repair and is mainly due to significant pulmonary regurgitation resulting in an altered septal motion and systolic LV function.

Noninvasive assessment of liver fibrosis in patients with Fontan circulation using transient elastography and biochemical fibrosis markers.

OBJECTIVE: Studies have shown that patients with failing Fontan circulation may develop liver cirrhosis with its sequelae. Therefore, early detection of fibrosis is essential to identify patients at risk. Transient elastography has been evaluated for noninvasive staging of liver fibrosis in a multitude of studies. METHODS: A total of 39 patients who underwent the Fontan procedure were included in the study. All patients underwent an abdominal ultrasound, transient elastography, and detailed laboratory testing. Conventional echocardiography assessment of inflow and outflow and ventricular function were performed. RESULTS: Significant signs of liver fibrosis were found in 36 of 39 children according to the elastography method and in 28 of 39 children according to the measured biochemical fibrosis markers. The Spearman correlation coefficient between the liver stiffness measured with transient elastography and the time interval since the Fontan operation was highly significant (0.514, P = 0.001). CONCLUSION: The present study shows that patients who undergo the Fontan procedure are at increased risk of developing liver fibrosis and liver cirrhosis. The risk increases with the age of the patient and the time interval since the Fontan procedure. The noninvasive measurement of liver fibrosis using transient elastography and fibrosis marker scores can be a useful tool to identify patients at risk and for noninvasive surveillance.