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BACKGROUND: Fetuses with congenital heart defects (CHD) show delayed neurodevelopment, fetal growth restriction (FGR) and placenta related complications. The neurodevelopmental delay may be, partly, attributed to placental factors. AIM: As both placental development and fetal aortic flow/oxygenation influence neurodevelopment, placentas were compared within fetal CHD groups based on aortic oxygenation and flow, aiming to unravel the true effects in the developmental processes. STUDY DESIGN: Placental tissues of pregnancies with fetal CHD and healthy controls were selected from biobanks of two Dutch academic hospitals (LUMC, UMCU). Additionally, biometry and Dopplers were assessed. SUBJECTS: CHD cases with reduced oxygenation (RO) towards the fetal brain were compared to cases with reduced flow (RF) in the aortic arch and healthy controls. Genetic abnormalities, termination of pregnancy, fetal demise and/or multiple pregnancies were excluded. OUTCOME MEASURES: Histological outcomes were related to fetal Dopplers and biometry. A placenta severity score was used to assess the severity of placental abnormalities per case. RESULTS: In CHD, significantly more delayed maturation, maternal vascular malperfusion, fetal hypoxia and higher placenta severity scores (median 14 in RO, 14 in RF, 5 in controls, p < 0.001) were observed. Doppler abnormalities (PI UA > p90, PI MCA < p10, CPR < p10) and FGR were more often found in CHD. There were no differences in placental abnormalities, fetal growth and fetal Dopplers between cases with RO and RF. CONCLUSION: Fetal hemodynamics in the ascending aorta could not be related to placenta characteristics. We hypothesize that placental development influences neurodevelopment in excess of hemodynamics in CHD cases.
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Cardiopatias Congênitas , Placenta , Humanos , Feminino , Gravidez , Placenta/metabolismo , Placenta/irrigação sanguínea , Adulto , Estudos de Casos e Controles , Ultrassonografia Pré-Natal , Oxigênio/metabolismo , Retardo do Crescimento FetalRESUMO
Background: Left ventricular apical pacing (LVAP) is considered to preserve left ventricular (LV) systolic function in both patients with and without congenital heart disease. However, sporadic LVAP-associated cardiac dysfunction in children with complex structural heart disease was recently reported. We present the case of a 2.5-year-old child with complex congenital heart disease and LVAP-induced cardiomyopathy. Case summary: Corrective surgery for double outlet right ventricle, subpulmonary ventricular septal defect, and transposition of the great arteries was done at the age of 1.5 months. Late complete atrioventricular block occurred, necessitating VVI pacemaker insertion with LV apical epicardial leads. He presented with heart failure and dilated cardiomyopathy 1.5 years after pacemaker insertion and required persistent circulatory support with intravenous inotropes. Speckle tracking echocardiography identified an important LV apical to basal dyssynchrony. After excluding any coronary artery involvement, cardiac resynchronization therapy was performed. Speckle tracking echocardiography guided lead placement resulted in improved LV contraction synchrony. Cardiac function recovered progressively in combination with oral heart failure medication and is almost normal at 10-month follow-up. Discussion: Right ventricular pacing is a well-known cause of pacing-induced cardiomyopathy. The LV apex and LV free wall are thought to be most optimal locations for ventricular pacing in children. However, LVAP can also be the cause of a pacing-induced cardiomyopathy and decreased systolic LV function in children with complex congenital heart disease due to lack of LV contraction synchrony. Cardiac resynchronization therapy can reverse this LV dysfunction and remodelling.
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BACKGROUND: There is limited data on the organisation of paediatric echocardiography laboratories in Europe. METHODS: A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs. RESULTS: Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1-12), and echocardiography machines was four (range 1-12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20-60) minutes, and for repeat examination was 20 (5-30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%). CONCLUSION: Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.
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OBJECTIVE: Cardiac surgery may cause temporarily impaired ventricular performance and myocardial injury. We aim to characterise the response to perioperative injury for patients undergoing repair or pulmonary valve replacement (PVR) for tetralogy of Fallot (ToF). METHODS: We enrolled children undergoing ToF repair or PVR from four tertiary centres in a prospective observational study. Assessment-including blood sampling and speckle tracking echocardiography-occurred before surgery (T1), at the first follow-up (T2) and 1 year after the procedures (T3). Ninety-two serum biomarkers were expressed as principal components to reduce multiple statistical testing. RNA Sequencing was performed on right ventricular (RV) outflow tract samples. RESULTS: We included 45 patients with ToF repair aged 4.3 (3.4 - 6.5) months and 16 patients with PVR aged 10.4 (7.8 - 12.7) years. Ventricular function following ToF repair showed a fall-and-rise pattern for left ventricular global longitudinal strain (GLS) (-18±4 to -13±4 to -20±2, p < 0.001 for each comparison) and RV GLS (-19±5 to -14±4 to 20±4, p < 0.002 for each comparison). This pattern was not seen for patients undergoing PVR. Serum biomarkers were expressed as three principal components. These phenotypes are related to: (1) surgery type, (2) uncorrected ToF and (3) early postoperative status. Principal component 3 scores were increased at T2. This increase was higher for ToF repair than PVR. The transcriptomes of RV outflow tract tissue are related to patients' sex, rather than ToF-related phenotypes in a subset of the study population. CONCLUSIONS: The response to perioperative injury following ToF repair and PVR is characterised by specific functional and immunological responses. However, we did not identify factors relating to (dis)advantageous recovery from perioperative injury. TRIAL REGISTRATION NUMBER: Netherlands Trial Register: NL5129.
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Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Pulmonar , Valva Pulmonar , Tetralogia de Fallot , Humanos , Tetralogia de Fallot/genética , Tetralogia de Fallot/cirurgia , Tetralogia de Fallot/complicações , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/cirurgia , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Pulmonar/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Função Ventricular Direita/fisiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Função Ventricular , BiomarcadoresRESUMO
BACKGROUND: Fluid overload (FO) is known to occur frequently after pediatric cardiac surgery and is associated with morbidity and mortality. Fontan patients are at risk to develop FO due to their critical fluid balance. Furthermore, they need an adequate preload in order to maintain adequate cardiac output. This study aimed to identify FO in patients undergoing Fontan completion and the impact of FO on pediatric intensive care unit (PICU) length of stay (LOS) and cardiac events, defined as death, cardiac re-surgery or PICU re-hospitalization during follow-up. METHODS: In this retrospective single center study, the presence of FO was assessed in 43 consecutive children undergoing Fontan completion. RESULTS: Patients with more than 5% maximum FO had an extended PICU LOS (3.9 [2.9-6.9] vs. 1.9 [1.0-2.6] days; p < 0.001) and an increased length of mechanical ventilation (21 [9-121] vs. 6 [5-10] h; p = 0.001). Regression analysis demonstrated that an increase of 1% maximum FO was associated with a prolonged PICU LOS of 13% (95% CI 1.042-1.227; p = 0.004). Furthermore, patients with FO were at higher risk to develop cardiac events. CONCLUSIONS: FO is associated with short-term and long-term complications. Further studies are needed to determine the impact of FO on the outcome in this specific population.
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OBJECTIVE: We aimed to assess current prenatal detection rate (DR) of aortic coarctation (CoA) and its impact on neonatal outcome in the Netherlands to evaluate the efficacy of the Dutch screening protocol in which the cardiac four-chamber view, outflow tracts and three-vessel view are compulsory. METHODS: All prenatally and postnatally diagnosed CoA cases between 2012 and 2021 were extracted from our PRECOR-registry. Annual DRs were calculated with a focus on the trend over time and attributing factors for detection. Postnatal outcome was compared between prenatally detected and undetected cases. RESULTS: 49/116 cases (42.2%) were detected prenatally. A higher chance of detection was found for cases with extracardiac malformations (71.4%; p = 0.001) and the more severe cases with an aortic arch hypoplasia and/or ventricular septal defect (63.2%; p = 0.001). Time-trend analysis showed no improvement in DR over time (p = 0.33). Undetected cases presented with acute circulatory shock in 20.9% and were more likely to have severe lactic acidosis (p = 0.02) and impaired cardiac function (p < 0.001) before surgery. CONCLUSION: Even in a well-organized screening program, the DR of CoA still requires improvement, especially in isolated cases. The increased risk of severe lactic acidosis in undetected cases stresses the need for urgent additions to the current screening program, such as implementation of the three-vessel trachea view and measurement of outflow tracts.
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Acidose Láctica , Coartação Aórtica , Comunicação Interventricular , Gravidez , Recém-Nascido , Feminino , Humanos , Coartação Aórtica/diagnóstico por imagem , Ecocardiografia/métodos , Países Baixos/epidemiologia , Ultrassonografia Pré-Natal/métodos , Estudos RetrospectivosRESUMO
Autosomal dominant variants in LDB3 (also known as ZASP), encoding the PDZ-LIM domain-binding factor, have been linked to a late onset phenotype of cardiomyopathy and myofibrillar myopathy in humans. However, despite knockout mice displaying a much more severe phenotype with premature death, bi-allelic variants in LDB3 have not yet been reported. Here we identify biallelic loss-of-function variants in five unrelated cardiomyopathy families by next-generation sequencing. In the first family, we identified compound heterozygous LOF variants in LDB3 in a fetus with bilateral talipes and mild left cardiac ventricular enlargement. Ultra-structural examination revealed highly irregular Z-disc formation, and RNA analysis demonstrated little/no expression of LDB3 protein with a functional C-terminal LIM domain in muscle tissue from the affected fetus. In a second family, a homozygous LDB3 nonsense variant was identified in a young girl with severe early-onset dilated cardiomyopathy with left ventricular non-compaction; the same homozygous nonsense variant was identified in a third unrelated female infant with dilated cardiomyopathy. We further identified homozygous LDB3 frameshift variants in two unrelated probands diagnosed with cardiomegaly and severely reduced left ventricular ejection fraction. Our findings demonstrate that recessive LDB3 variants can lead to an early-onset severe human phenotype of cardiomyopathy and myopathy, reminiscent of the knockout mouse phenotype, and supporting a loss of function mechanism.
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Cardiomiopatias , Cardiomiopatia Dilatada , Lactente , Camundongos , Animais , Humanos , Criança , Feminino , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Volume Sistólico , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas com Domínio LIM/genética , Função Ventricular EsquerdaRESUMO
In patients with congenital heart disease (CHD), reduced exercise capacity can be a predictor for late complications and may be used to guide interventions. Yet, the interpretation of exercise capacity is challenged by changes in body composition during growth. Our aim was to create an overview of disease-specific exercise capacity in children with CHD. We performed a multicentre retrospective study of exercise capacity of CHD patients, aged 6-18 years, tested between January 2001 and October 2018. Sex-specific distribution graphs were made using the LMS method and height to relate to body size. We included all CHD with N > 50, including severe defects (e.g., univentricular heart, tetralogy of Fallot) and "simple" lesions as ventricular septum defect and atrial septum defect. We included 1383 tests of 1208 individual patients for analysis. The peak oxygen uptake (VO2peak, 37.3 ml/min/kg (25th-75th percentile 31.3-43.8)) varied between specific defects; patients with univentricular hearts had lower VO2peak compared with other CHD. All groups had lower VO2peak compared to healthy Dutch children. Males had higher VO2peak, Wpeak and O2pulsepeak than females. Sex- and disease-specific distribution graphs for VO2peak, Wpeak and O2pulsepeak showed increase in variation with increase in height. Conclusion: Disease-specific distribution graphs for exercise capacity in children with CHD from a large multicentre cohort demonstrated varying degrees of reduced VO2peak and Wpeak. The distribution graphs can be used in the structured follow-up of patients with CHD to predict outcome and identify patients at risk. What is Known: ⢠Children with congenital heart disease (COnHD) are at risk to develop heart failure, arrhytmia's and other complications. Exercise capacity may be an important predictor for outcome in children with ConHD. In children, the interpretation of exercise capacity poses an additional challenge related to physical changes during growth. What is New: ⢠In this report of a multi-center cohort >1300 childrewn with ConHD, we related the changes in exercise capacity to length. We demonstrated that exercise capacity was reduced as compared with healthy children and we observed variation between disease groups. Patients with a univentricular circulation (Fontan) had worse exercise capacity. We constructed disease specific charts of development of exercise capacity throughout childhood, accessible via a web-site. These graphs may help practitioner to guide children with ConHD.
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Cardiopatias Congênitas , Comunicação Interventricular , Criança , Feminino , Humanos , Masculino , Teste de Esforço/métodos , Tolerância ao Exercício , Consumo de Oxigênio , Estudos RetrospectivosRESUMO
BACKGROUND: Although considering the pathophysiology of post-coarctectomy hypertension, ß-blockers should be effective, experience with labetalol for treatment is limited in the literature. METHODS: Retrospective collection and analysis of data in children aged ≤6 years following coarctectomy in our tertiary care university medical center between January 2009 and June 2018. RESULTS: 96 patients were included, 45 were treated with intravenous labetalol and 51 received no treatment. Median time to maximum dose received (median 1.1 mg/kg/h) was 2.7 h, and median time to the reduction of labetalol dose was 8.3 h. No antihypertensives had to be added. In one child, labetalol was switched to nitroprusside due to bronchoconstriction. Of patients receiving intravenous labetalol, 48% had been switched to oral labetalol at discharge. CONCLUSIONS: Intravenous labetalol is a fast, effective, and safe drug to treat hypertension following aortic coarctation repair. Labetalol is easily converted to oral therapy when the continuation of treatment is considered necessary.
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Hipertensão , Labetalol , Criança , Humanos , Labetalol/farmacologia , Labetalol/uso terapêutico , Nitroprussiato/farmacologia , Nitroprussiato/uso terapêutico , Estudos Retrospectivos , Complicações Pós-Operatórias/tratamento farmacológico , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Anti-Hipertensivos/uso terapêutico , Pressão SanguíneaRESUMO
BACKGROUND: This study aimed to describe the current practice and results of genetic evaluation in Dutch children with dilated cardiomyopathy and to evaluate genotype-phenotype correlations that may guide prognosis. METHODS: We performed a multicenter observational study in children diagnosed with dilated cardiomyopathy, from 2010 to 2017. RESULTS: One hundred forty-four children were included. Initial diagnostic categories were idiopathic dilated cardiomyopathy in 67 children (47%), myocarditis in 23 (16%), neuromuscular in 7 (5%), familial in 18 (13%), inborn error of metabolism in 4 (3%), malformation syndrome in 2 (1%), and "other" in 23 (16%). Median follow-up time was 2.1 years [IQR 1.0-4.3]. Hundred-seven patients (74%) underwent genetic testing. We found a likely pathogenic or pathogenic variant in 38 children (36%), most often in MYH7 (n = 8). In 1 patient initially diagnosed with myocarditis, a pathogenic LMNA variant was found. During the study, 39 patients (27%) reached study endpoint (SE: all-cause death or heart transplantation). Patients with a likely pathogenic or pathogenic variant were more likely to reach SE compared with those without (hazard ratio 2.8; 95% CI 1.3-5.8, P = 0.007), while transplant-free survival was significantly lower (P = 0.006). Clinical characteristics at diagnosis did not differ between the 2 groups. CONCLUSIONS: Genetic testing is a valuable tool for predicting prognosis in children with dilated cardiomyopathy, with carriers of a likely pathogenic or pathogenic variant having a worse prognosis overall. Genetic testing should be incorporated in clinical work-up of all children with dilated cardiomyopathy regardless of presumed disease pathogenesis.
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Cardiomiopatia Dilatada , Miocardite , Humanos , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Miocardite/genética , Testes Genéticos , Estudos de Associação Genética , Medição de RiscoRESUMO
BACKGROUND: Many cardiocirculatory mechanisms are involved in the adaptation to orthostatic stress. While these mechanisms may be impaired in Fontan patients. However, it is yet unclear how Fontan patients, who exhibit a critical fluid balance, respond to orthostatic stress. Angiotensin converting enzyme inhibitors are often prescribed to Fontan patients, but they may negatively influence orthostatic tolerance. Therefore, we evaluated the response to orthostatic stress in pediatric Fontan patients before and after treatment with enalapril. METHODS: Thirty-five Fontan patients (aged 14 years) with moderate-good systolic ventricular function without pre-existent enalapril treatment were included. Before and after a three-month enalapril treatment period, the hemodynamic response to head-up tilt test was evaluated by various parameters including cardiac index, blood pressure, cerebral blood flow, aortic stiffness and cardiac autonomous nervous activity. Thirty-four healthy subjects (aged 13 years) served as controls. RESULTS: Fontan patients had a decreased cerebral blood flow and increased aortic stiffness in the supine position compared to controls, while all other factors did not differ. Patients and controls showed a comparable response to head-up tilt test for most parameters. Twenty-seven patients completed the enalapril study with a mean dosage of 0.3±0.1mg/kg/day. Most parameters were unaffected by enalapril, only the percent decrease in cardiac index to tilt was higher after treatment, but the cardiac index during tilt was not lower (3.0L/min/m2 pre-enalapril versus 2.8L/min/m2 after treatment; P = 0.15). CONCLUSION: Pediatric Fontan patients adequately respond to orthostasis with maintenance of blood pressure and cerebral blood flow and sufficient autonomic response. Enalapril treatment did not alter the response. CLINICAL TRIAL INFORMATION: Scientific title: ACE inhibition in Fontan patients: its effect on body fluid regulation (sAFE-study). The Netherlands National Trial Register: Trail NL6415. Registered 2017-07-20. Trial information: https://www.trialregister.nl/trial/6415.
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Inibidores da Enzima Conversora de Angiotensina , Enalapril , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Pressão Sanguínea/fisiologia , Criança , Enalapril/farmacologia , Enalapril/uso terapêutico , Hemodinâmica , Humanos , Teste da Mesa InclinadaRESUMO
Background Ventricular performance is temporarily reduced following surgical atrial septal defect closure. Cardiopulmonary bypass and changes in loading conditions are considered important factors, but this phenomenon is incompletely understood. We aim to characterize biventricular performance following surgical and percutaneous atrial septal defect closure and to relate biomarkers to ventricular performance following intervention. Methods and Results In this multicenter prospective study, children scheduled for surgical or percutaneous atrial septal defect closure were included. Subjects were assessed preoperatively, in the second week postintervention (at 2-weeks follow-up), and 1-year postintervention (1-year follow-up). At each time point, an echocardiographic study and a panel of biomarkers were obtained. Sixty-three patients (median age, 4.1 [interquartile range, 3.1-6.1] years) were included. Forty-three patients underwent surgery. At 2-weeks follow-up, right ventricular global longitudinal strain was decreased for the surgical, but not the percutaneous, group (-17.6±4.1 versus -27.1±3.4; P<0.001). A smaller decrease was noted for left ventricular global longitudinal strain at 2-weeks follow-up for the surgical group (surgical versus percutaneous, -18.6±3.2 versus -20.2±2.4; P=0.040). At 1-year follow-up, left ventricular performance returned to baseline, whereas right ventricular performance improved, but did not reach preintervention levels. Eight biomarkers relating to cardiovascular and immunological processes differed across study time points. Of these biomarkers, only NT-proBNP (N-terminal pro-B-type natriuretic peptide) correlated with less favorable left ventricular global longitudinal strain at 2-weeks follow-up. Conclusions Right, and to a lesser degree left, ventricular performance was reduced early after surgical atrial septal defect closure. Right ventricular performance at 1-year follow-up remained below baseline levels. Several biomarkers showed a pattern over time similar to ventricular performance. These biomarkers may provide insight into the processes that affect ventricular function. Registration URL: https://www.trialregister.nl/; Unique identifier: NL5129.
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Comunicação Interatrial , Biomarcadores , Criança , Pré-Escolar , Ecocardiografia/métodos , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/cirurgia , Ventrículos do Coração , Humanos , Estudos ProspectivosRESUMO
Many Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the present study, we evaluated the short-term effect of enalapril on exercise capacity, vascular and ventricular function in pediatric Fontan patients with moderate-good systolic ventricular function. Fontan patients between 8 and 18 years with moderate-good systolic ventricular function and without previous ACE inhibitor treatment were included and were treated with enalapril for 3 months. During the first 2 weeks, the dosage was titrated according to systolic blood pressure (SBP). Exercise tests, ventricular function assessed by echocardiography, arterial stiffness measurements, and plasma levels of N-terminal pro-B-type natriuretic peptide assessed before and after a 3-month enalapril treatment period was compared. A total of 28 Fontan patients (median age 13.9 years, 6 to 15 years after Fontan operation) completed the study with a mean dosage of 0.3 ± 0.1 mg/kg/d. A total of 6 patients (21%) experienced a significant drop in SBP and 6 others (21%) experienced other adverse events. Enalapril treatment lowered the SBP (from 110 to 104 mmHg, p = 0.003) and levels of N-terminal pro-B-type natriuretic peptide (from 80 to 72 ng/L, p = 0.036). However, enalapril treatment did not improve exercise capacity, ventricular function, or arterial stiffness. In conclusion, short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function.
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Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Enalapril/uso terapêutico , Tolerância ao Exercício/fisiologia , Técnica de Fontan , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Rigidez Vascular/fisiologia , Disfunção Ventricular/tratamento farmacológico , Adolescente , Pressão Sanguínea , Criança , Ecocardiografia , Teste de Esforço , Feminino , Humanos , Hipotensão/induzido quimicamente , Masculino , Sístole , Resultado do Tratamento , Disfunção Ventricular/sangue , Disfunção Ventricular/diagnóstico por imagem , Disfunção Ventricular/fisiopatologiaRESUMO
In fetal aortic stenosis (AS), it remains challenging to predict left ventricular development over the course of pregnancy. Myocardial organization, differentiation and fibrosis could be potential biomarkers relevant for biventricular outcome. We present four cases of fetal AS with varying degrees of severity and associate myocardial deformation on fetal ultrasound with postmortem histopathological characteristics. During routine fetal echocardiography, speckle tracking recordings of the cardiac four-chamber view were performed to assess myocardial strain as parameter for myocardial deformation. After pregnancy termination, postmortem cardiac specimens were examined using immunohistochemical labeling (IHC) of key markers for myocardial organization, differentiation and fibrosis and compared to normal fetal hearts. Two cases with critical AS presented extremely decreased left ventricular (LV) strain on fetal ultrasound. IHC showed overt endocardial fibro-elastosis, which correlated with pathological fibrosis patterns in the myocardium and extremely disturbed cardiomyocyte organization. The LV in severe AS showed mildly reduced myocardial strain and less severe disorganization of the cardiomyocytes. In conclusion, the degree of reduction in myocardial deformation corresponded with high extent to the amount of pathological fibrosis patterns and cardiomyocyte disorganization. Myocardial deformation on fetal ultrasound seems to hold promise as a potential biomarker for left ventricular structural damage in AS.
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BACKGROUND: Although various determinants of exercise limitation in Fontan patients have been studied, most research has been performed in patients who underwent different surgical procedures with differing haemodynamic characteristics. The aim of the current study was to evaluate non-invasively measured cardiovascular parameters and their influence on exercise performance in paediatric Fontan patients with an extracardiac conduit and moderate-good systolic ventricular function. METHODS: Fontan patients, between 8 and 18 years of age, with moderate to good systolic ventricular function and an extracardiac conduit were included. Exercise performance and cardiovascular assessment, comprising echocardiography, aortic stiffness measurement and ambulatory measurement of cardiac autonomous nervous activity were performed on the same day. Healthy subjects served as controls. RESULTS: Thirty-six Fontan patients (age 14.0 years) and thirty-five healthy subjects (age 12.8 years) were included. Compared to controls, Fontan patients had reduced diastolic ventricular function and increased arterial stiffness. No differences were found in heart rate (HR) and cardiac parasympathetic nervous activity. In Fontan patients, maximal as well as submaximal exercise capacity was impaired, with the percentage of predicted capacity ranging between 54 and 72%. Chronotropic competence, however, was good with a peak HR of 174 (94% of predicted). Lower maximal and submaximal exercise capacity was correlated with a higher HR at rest, higher pulse wave velocity of the aorta and a lower ratio of early and late diastolic flow velocity. CONCLUSION: Contemporary paediatric Fontan patients have an impaired exercise capacity with preserved chronotropic competence. Exercise performance correlates with heart rate at rest, diastolic function and aortic stiffness.
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Técnica de Fontan , Cardiopatias Congênitas , Adolescente , Criança , Exercício Físico , Teste de Esforço , Tolerância ao Exercício , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Humanos , Análise de Onda de PulsoRESUMO
In patients after Fontan completion exercise capacity is significantly reduced. Although peak oxygen consumption (VO2peak) is a strong prognostic factor in many cardiovascular diseases, it requires the achievement of a maximal effort. Therefore, submaximal exercise parameters such as oxygen uptake efficiency slope (OUES) may be of value. In the present observational study we evaluated the exercise capacity with maximal and submaximal parameters in a group of Fontan patients with an extracardiac conduit and determined their prognostic value. Sixty Fontan patients followed up in the Leiden University Medical Center who have performed an exercise test were included in this retrospective study. Exercise tests were performed at a median age of 11 years. Fontan patients showed on average lower values for all exercise parameters compared to reference values from a healthy dataset as shown by the %predicted values: VO2peak%:mean 66%(95%CI:64 to 74) and OUES%:mean 72%(95%CI:67 to 77). Twenty percent of the patients were not able to achieve an RER>1.0. RER showed a moderate positive correlation with VO2peak but not with OUES. There was a deterioration of VO2peak% and OUES% over time. OUES was significantly lower in patients with cardiac events in the follow up period. Fontan patients have an impaired exercise performance even at young ages and it deteriorates with age. An important percentage of Fontan patients is not able to reach maximal effort so the use of submaximal parameters, like OUES, should be considered as part of the evaluation. Moreover, OUES could have a prognostic value in this group of patients.
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Tolerância ao Exercício , Técnica de Fontan , Cardiopatias Congênitas/fisiopatologia , Consumo de Oxigênio/fisiologia , Adolescente , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anticoagulantes/uso terapêutico , Criança , Teste de Esforço , Feminino , Cardiopatias Congênitas/terapia , Humanos , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , PrognósticoRESUMO
OBJECTIVES: Functional development of the fetal cardiac autonomic nervous system (cANS) plays a key role in fetal maturation and can be assessed through fetal heart rate variability (fHRV)-analysis, with each HRV parameter representing different aspects of cANS activity. Current available techniques, however, are unable to assess the fHRV parameters accurately throughout the whole pregnancy. This study aims to test the feasibility of color tissue Doppler imaging (cTDI) as a new ultrasound technique for HRV analysis. Secondly, we explored time trends of fHRV parameters using this technique. METHODS: 18 healthy singleton fetuses were examined sequentially every 8 weeks from 10 weeks GA onwards. From each examination, 3 cTDI recordings of the four-chamber view of 10 seconds were retrieved to determine accurate beat-to-beat intervals. The fHRV parameters SDNN, RMSSD, SDNN/RMSSD, and pNN10, each representing different functional aspects of the cANS, were measured, and time trends during pregnancy were explored using spline functions within a linear mixed-effects model. RESULTS: In total, 77% (95% Cl 66-87%) of examinations were feasible for fHRV analysis from the first trimester onwards, which is a great improvement compared to other techniques. The technique is able to determine different maturation rates of the fHRV parameters, showing that cANS function, presumably parasympathetic activity, establishes around 20 weeks GA and matures rapidly until 30 weeks GA. CONCLUSIONS: This is the first study able to assess cANS function through fHRV analysis from the first trimester onwards. The use of cTDI to determine beat-to-beat intervals seems feasible in just 3 clips of 10 seconds, which holds promise for future clinical use in assessing fetal well-being.
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Feto , Frequência Cardíaca Fetal , Sistema Nervoso Autônomo , Feminino , Coração , Humanos , Gravidez , Ultrassonografia DopplerRESUMO
Background: Inherent to its geometry, echocardiographic imaging of the systemic right ventricle (RV) is challenging. Therefore, echocardiographic assessment of systemic RV function may not always be feasible and/or reproducible in daily practice. Here, we aim to validate the usefulness of a comprehensive range of 32 echocardiographic measurements of systemic RV function in a longitudinal cohort by serial assessment of their correlations with cardiac magnetic resonance (CMR)-derived systemic RV ejection fraction (RVEF). Methods: A single-center, retrospective cohort study was performed. Adult patients with a systemic RV who underwent a combination of both CMR and echocardiography at two different points in time were included. Off-line analysis of echocardiographic images was blinded to off-line CMR analysis and vice versa. In half of the echocardiograms, measurements were repeated by a second observer blinded to the results of the first. Correlations between echocardiographic and CMR measures were assessed with Pearson's correlation coefficient and interobserver agreement was quantified with intraclass correlation coefficients (ICC). Results: Fourteen patients were included, of which 4 had congenitally corrected transposition of the great arteries (ccTGA) and 10 patients had TGA late after an atrial switch operation. Eight patients (57%) were female. There was a mean of 8 years between the first and second imaging assessment. Only global systemic RV function, fractional area change (FAC), and global longitudinal strain (GLS) were consistently, i.e., at both time points, correlated with CMR-RVEF (global RV function: r = -0.77/r = -0.63; FAC: r = 0.79/r = 0.67; GLS: r = -0.73/r = -0.70, all p-values < 0.05). The ICC of GLS (0.82 at t = 1, p = 0.006, 0.77 at t = 2, p = 0.024) was higher than the ICC of FAC (0.35 at t = 1, p = 0.196, 0.70 at t = 2, p = 0.051) at both time points. Conclusion: GLS appears to be the most robust echocardiographic measurement of systemic RV function with good correlation with CMR-RVEF and reproducibility.