Ventricular function and biomarkers in relation to repair and pulmonary valve replacement for tetralogy of Fallot

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 &lt; 0.001 for each comparison) and RV GLS (-19±5 to -14±4 to 20±4, p &lt; 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.</p

Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort:The Use of Genetic Testing in Risk Stratification

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

Assessment of left ventricular functions with tissue Doppler, strain, and strain rate echocardiography in patients with familial Mediterranean fever

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Long-term follow-up after ventricular septal defect repair in children:Cardiac autonomic control, cardiac function and exercise capacity

OBJECTIVES: Survival after surgical repair of a ventricular septal defect (VSD) is good, but, as in almost all congenital heart diseases, late complications are frequent in adulthood. The exact mechanisms, timing and who is at risk are not fully understood. Altered cardiac autonomic nervous system (ANS) activity might play a role in these long-term sequelae. The aim of this study was to extensively evaluate children late after VSD repair including their cardiac ANS activity, cardiac function and exercise capacity. METHODS: Thirty-three patients after surgical VSD repair and 66 healthy age-matched controls underwent 24-h monitoring of ANS control and cardiac output using impedance cardiography, detailed echocardiography and cardiopulmonary exercise testing. RESULTS: Ambulatory cardiac ANS control was not different between the patients and the controls. Right ventricular function, exercise capacity and ambulatory cardiac output were decreased in patients compared with the controls. No relationships were found between cardiac ANS activity and cardiac function. CONCLUSIONS: Long (average time after repair was 9.9 years) after successful surgical correction of a VSD, cardiac ANS control is not different from the controls. Right ventricular function and exercise capacity are impaired in VSD patients. Post-surgical outcome in these patients may be less benign than presently assumed; therefore, follow-up should be continued into adulthood to detect adverse outcomes in a timely fashion

Determinants of exercise limitation in contemporary paediatric Fontan patients with an extra cardiac conduit

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

Does Repeated Measurement of a 6-Min Walk Test Contribute to Risk Prediction in Children with Dilated Cardiomyopathy?

A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in predicting death or heart transplantation in children with DCM. Prospective multicenter cohort study including ambulatory DCM patients ≥ 6 years. A 6MWT was performed 1 to 4 times per year. The distance walked was expressed as percentage of predicted (6MWD%). We compared the temporal evolution of 6MWD% in patients with and without the study endpoint (SE: all-cause death or heart transplantation), using a linear mixed effects model. In 57 patients, we obtained a median of 4 (IQR 2–6) 6MWTs per patient during a median of 3.0 years of observation (IQR 1.5–5.1). Fourteen patients reached a SE (3 deaths, 11 heart transplantations). At any time during follow-up, the average estimate of 6MWD% was significantly lower in patients with a SE compared to patients without a SE. In both patients groups, 6MWD% remained constant over time. An absolute 1% lower 6MWD% was associated with an 11% higher risk (hazard) of the SE (HR 0.90, 95% CI 0.86–0.95 p < 0.001). Children with DCM who died or underwent heart transplantation had systematically reduced 6MWD%. The performance of all patients was stable over time, so repeated measurement of 6MWT within this time frame had little added value over a single test

Cardiac Autonomic Nervous System Activity and Cardiac Function in Children After Coarctation Repair

Background: Coarctation of the aorta (CoA) is one of the most common congenital heart defects. Most patients live into adulthood as a result of improved surgical techniques; however, late complications, including hypertension, recoarctation, and arrhythmias, are common. The autonomic nervous system (ANS) might play a role in the pathology. This study evaluated cardiac ANS activity and cardiac function in children after CoA repair and investigated the relationship between the two. Methods: The study participants were 31 children after CoA repair and 62 healthy controls aged between 8 and 18 years. Ambulatory impedance cardiography was used to measure cardiac ANS activity and cardiac output for 24 hours. Transthoracic echocardiography and cardiac magnetic resonance imaging were used to measure cardiac function. Results: No group differences were found in ambulatory cardiac ANS activity. However, ambulatory cardiac output and left ventricular function were significantly decreased in patients compared with controls. Conclusions: Left ventricular function and ambulatory cardiac output are impaired in patients after CoA repair, despite unchanged cardiac ANS activity in this group. These results underscore the importance of clinical follow-up, even in patients without residual stenosis