Differentiating primary sarcomeric hypertrophic cardiomyopathy from Noonan syndrome: can the electrocardiogram be of use?

Noonan syndrome is a multi-system genetic disorder and patients may suffer from hypertrophic cardiomyopathy. Previous studies have identified electrocardiographic features that may support a diagnosis of Noonan syndrome. In this two-centre retrospective study, we analysed typical Noonan syndrome-related electrocardiographic features in 30 patients with Noonan syndrome with hypertrophic cardiomyopathy and compared these with the electrocardiographic features in 15 children with sarcomeric hypertrophic cardiomyopathy. Typical Noonan syndrome-related electrocardiographic features are a negative aVF, small left precordial R-waves, large right precordial S-waves, and abnormal Q-wave. We also analysed electrocardiographic features of hypertrophic cardiomyopathy: ST-segment abnormalities and T-wave abnormalities. A negative aVF was seen in 83% of patients with Noonan syndrome-related hypertrophic cardiomyopathy in contrast to 27% of patients with primary sarcomeric hypertrophic cardiomyopathy (p < 0.001). An extreme QRS axis in the north-west was seen only in patients with Noonan syndrome-related hypertrophic cardiomyopathy. This QRS axis deviation is likely to be determined by the Noonan syndrome-related hypertrophic cardiomyopathy and not by the type of hypertrophic cardiomyopathy. There were no differences between the two groups in the frequency of large right precordial S-waves and small R-waves in the left precordial leads V5 and V6. However, an abnormal R/S ratio was more often seen in patients with Noonan syndrome-related hypertrophic cardiomyopathy (p < 0.001). Pathologic Q-waves were seen statistically more frequently in patients with sarcomeric hypertrophic cardiomyopathy (p = 0.009). The occurrence of ST-segment and T-wave pathology did not statistically differ between the two groups. Electrography can be of use in differentiating sarcomeric hypertrophic cardiomyopathy from Noonan syndrome-related hypertrophic cardiomyopathy.

The effect of electro-anatomical mapping on the success rate and fluoroscopy time in supra-ventricular tachycardia ablation in children: single centre retrospective study.

AIMS: To evaluate the effect of electro-anatomical mapping on success rate and fluoroscopy time in ablation of supraventricular tachycardia substrates in a large group of children. METHODS: Patients referred from multiple centres in the Netherlands and who received a first ablation for supraventricular tachycardia substrates in the Leiden University Medical Center between 2014 and 2020 were included in this retrospective cohort study. They were divided in procedures in patients with fluoroscopy and procedures in patients using electro-anatomical mapping. RESULTS: Outcomes of ablation of 373 electro-anatomical substrates were analysed. Acute success rate in the fluoro-group (n = 170) was 95.9% compared to 94.5% in the electro-anatomical mapping group (n = 181) (p = 0.539); recurrence rate was 6.1% in the fluoro-group and 6.4% in the electro-anatomical mapping group (p = 0.911) after a 12-months follow-up. Redo-ablations were performed in 12 cases in the fluoro-group and 10 cases in the electro-anatomical mapping group, with a success rate of 83.3% versus 80.0%, resulting in an overall success rate of 95.9% in the fluoro-group and 92.8% in the electro-anatomical mapping group (p = 0.216) after 12 months. Fluoroscopy time and dose area product decreased significantly from 16.00 ± 17.75 minutes (median ± interquartile range) to 2.00 ± 3.00 minutes (p = 0.000) and 210.5 µGym2 ± 249.3 to 32.9 µGym2 ± 78.6 (p = 0.000), respectively. In the fluoro-group, four complications occurred (2.0%) and in the electro-anatomical mapping group no complications occurred. CONCLUSION: These results demonstrate that ablations of supraventricular tachycardia substrates in children remain a highly effective and safe treatment after the introduction of electro-anatomical mapping as a standard of care, while significantly reducing fluoroscopy time and dose area product.

[Heart failure in young children; a serious cause of feeding problems]. / Hartfalen bij jonge kinderen.

Feeding problems in children are usually harmless and common, but can rarely exist as a result of pathology. Heart failure is one of them and has to be recognized early because of its many consequences. We present a 15-week-old female infant who was seen at the outpatient clinic. She had already been evaluated several times by a youth doctor and general practitioner because of feeding problems and transpiration, for which several nutritional interventions had already been carried out. With no effect of nutritional interventions she was referred to a pediatrician. Physical examination showed clear signs of heart failure and echocardiogram showed a severe dilation of the left ventricle, with poor contractility of the lateral wall and papillary muscle, with end stage heart failure due to an Anomalous Left Coronary Artery from the Pulmonary Artery (ALPACA). In this article we discuss the clinical presentation of heart failure: stagnant growth, exercise intolerance, tachypnea and sometimes hepatomegaly, edema, murmurs or cyanosis. In addition, when a patient does not respond to initial therapy, we recommend to reconsider differential diagnosis and/or refer to a pediatrician.

Comprehensive Evaluation of Pediatric Patients with Ebstein Anomaly Requires Both Echocardiography and Cardiac Magnetic Resonance Imaging.

With the trend towards childhood surgery in patients with Ebstein anomaly (EA), thorough imaging is crucial for patient selection. This study aimed to assess biventricular function by echocardiography and cardiac magnetic resonance (CMR) and compare EA severity classifications. Twenty-three patients (8-17 years) underwent echocardiography and CMR. Echocardiographic parameters included tricuspid annular plane systolic excursions (TAPSE), fractional area change of the functional right ventricle (fRV-FAC), fRV free wall peak systolic myocardial velocity (fRVs'), and tricuspid regurgitation (TR). End-diastolic and end-systolic volume (EDV resp. ESV), fRV- and LV ejection fraction (EF) and TR were obtained by CMR. EA severity classifications included displacement index, Celermajer index and the total-right/left-volume index. Median fRV-FAC was 38% (IQR 33-42). TAPSE and fRVs' were reduced in 39% and 75% of the patients, respectively. Echocardiographic TR was visually graded as mild, moderate, or severe in nine, six and eight patients, respectively. By CMR, median fRVEF was 49% (IQR 36-58) and TR was graded as mild, moderate, or severe in nine, twelve and two patients, respectively. In 70% of cases, fRV-EDV was higher than LV-EDV. LVEF was decreased in 17 cases (74%). There was excellent correlation between echocardiography-derived fRV-FAC and CMR-derived fRVEF (rho = 0.812, p < 0.001). While echocardiography is a versatile tool in the complex geometry of the Ebstein heart, it has limitations. CMR offers a total overview and has the advantage of reliable volume assessment of both ventricles. Comprehensive evaluation of pediatric patients with EA may therefore require a synergistic implementation of echocardiography and CMR.

Exercise capacity in a cohort of children with congenital heart disease.

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.

Endocarditis Caused by Nontypeable Streptococcus pneumoniae.

The Streptococcus pneumoniae capsule is regarded as indispensable in bacteremia. We report an infant with a ventricular septal defect and infective endocarditis caused by nontypeable S. pneumoniae. In-depth investigation confirmed a deficient capsule yet favored pneumococcal fitness for causing infective endocarditis, rather than a host immune disorder, as the cause of infective endocarditis in this case.

Cardiac abnormalities in girls with Turner syndrome: ECG abnormalities, myocardial strain imaging, and karyotype-phenotype associations.

Turner syndrome (TS) is a chromosomal condition which is associated with an increased prevalence of cardiac morbidity and mortality. In this cross-sectional study, Minnesota-based electrocardiographic (ECG) abnormalities, aortic dimensions, routine- and myocardial strain echocardiographic parameters, and karyotype-cardiac phenotype associations were assessed in girls with TS. In total, 101 girls with TS (0-18 years) were included. The prevalence of major ECG abnormalities was 2% (T-wave abnormalities) and 39% had minor ECG abnormalities. Dilatation of the ascending aorta (z-score > 2) was present in 16%, but the prevalence was much lower when using TS-specific z-scores. No left ventricular hypertrophy was detected and the age-matched global longitudinal strain was reduced in only 6% of the patients. Cardiac abnormalities seemed more common in patients with a non-mosaic 45,X karyotype compared with other karyotypes, although no statistically significant association was found. Lowering the frequency of echocardiography and ECG screening might be considered in girls with TS without cardiovascular malformations and/or risk factors for aortic dissection. Nevertheless, a large prospective study is needed to confirm our results. The appropriate z-score for the assessment of aortic dilatation remains an important knowledge gap. The karyotype was not significantly associated with the presence of cardiac abnormalities, therefore cardiac screening should not depend on karyotype alone.

No QTc Prolongation in Girls and Women with Turner Syndrome.

CONTEXT: Turner syndrome (TS) is a genetic condition that is reported to be associated with a prolonged rate-corrected QT (QTc) interval. OBJECTIVES: To evaluate the prevalence of QTc prolongation in patients with TS, to compare their QTc intervals with healthy controls, and to investigate whether QTc prolongation is associated with a monosomy 45,X karyotype. METHOD: Girls (n = 101) and women (n = 251) with TS visiting our center from 2004-2018 were included in this cross-sectional study. QT intervals of 12-leaded electrocardiograms were measured manually, using Bazett's and Hodges formulas to correct for heart rate. A QTc interval of >450 ms for girls and >460 ms for women was considered prolonged. Corrected QT (QTc) intervals of patients with TS were compared to the QTc intervals of healthy girls and women from the same age groups derived from the literature. RESULTS: In total, 5% of the population with TS had a prolonged QTc interval using Bazett's formula and 0% using Hodges formula. Mean QTc intervals of these patients were not prolonged compared with the QTc interval of healthy individuals from the literature. Girls showed shorter mean QTc intervals compared with women. We found no association between monosomy 45,X and prolongation of the QTc interval. CONCLUSIONS: This study shows that the QTc interval in girls and women with TS is not prolonged compared with the general population derived from the literature, using both Bazett's and Hodges formulas. Furthermore, girls show shorter QTc intervals compared with women, and a monosomy 45,X karyotype is not associated with QTc prolongation.

Follow-up after biventricular repair of the hypoplastic left heart complex.

OBJECTIVES: In hypoplastic left heart complex patients, biventricular repair is preferred over staged-single ventricle palliation; however, there are too few studies to support either strategy. Therefore, we retrospectively characterized our patient cohort with hypoplastic left heart complex after biventricular repair to measure left-sided heart structures and assess our treatment strategy. METHODS: Patients with hypoplastic left heart complex who had biventricular repair between 2004 and 2018 were retrospectively reviewed. Operative results were evaluated and echocardiographic mitral valve (MV) and aortic valve (AoV) dimensions, left ventricular length and left ventricular internal diastolic diameter (LVIDd) were measured preoperatively and during follow-up after 0.5, 1, 3, 5 and 10 years. RESULTS: In 32 patients, the median age at surgery was 10 (interquartile range 5.0) days. The median follow-up was 6.19 (interquartile range 6.04) years. During the 10-year follow-up, the mean Z-scores increased from -2.82 to -1.49 and from -2.29 to 0.62 for MV and AoV, respectively. Analysis of variance results with post hoc paired t-tests showed that growth of left-sided heart structures was accelerated in the first year after repair, but was not equal, with the MV lagging behind the AoV (P = 0.033), resulting in significantly smaller MV Z-scores compared with AoV Z-scores at 10-year follow-up (P < 0.001). There were 2 (6%) early deaths. The major adverse events occurred in 4 (13%) patients. The surgical or catheter-based reintervention was required in 14 (44%) patients. CONCLUSIONS: The growth rate of heart structures was most prominent during the first year after biventricular repair with lower growth rate of the MV compared with the AoV.

Pulmonary endarterectomy in a 12-year-old boy with multiple comorbidities.

A 10-year-old boy, with multiple comorbidities presented with fever, exertional dyspnea, fatigue and an obliterated brachiocephalic and inferior caval vein. Chronic thromboembolic pulmonary hypertension (CTEPH) was diagnosed. Nadroparine, antibiotics and supplemental oxygen were successfully started. Aged 12 years, supplemental oxygen was permanently needed with progressive exertional dyspnea and fatigue. In the country of residence the patient was considered as inoperable. The right ventricle was severely dilated, hypocontractile and hypertrophic. Mean pulmonary artery pressure (mPAP) was 79 mmHg and cardiac output 2.2 L/min. Pulmonary endarterectomy was uneventful. Four days later, mPAP was 33 mmHg and cardiac output 6.4 L/min. Three months later the boy restarted his education without supplemental oxygen. Six months after surgery right ventricular size and function and mPAP (14 mmHg) were normal. We demonstrated that pulmonary endarterectomy in young aged children is feasible and well-tolerated, even in the presence of severe co-morbidities. CTEPH should be an important diagnostic consideration in symptomatic children with a known hypercoaguable state, a history of thrombo-embolism or venous catheter placement, and/or a diagnosis of pulmonary hypertension. Hesitating to refer children for surgical consideration, or attempting to treat them by medication, only postpones the single potentially curable treatment and may worsen their prognosis.

Cardiac function in paediatric patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency.

BACKGROUND: Hyperandrogenism and exogenous glucocorticoid excess may cause unfavourable changes in the cardiovascular risk profile of patients with congenital adrenal hyperplasia (CAH). OBJECTIVE: To evaluate the cardiac function in paediatric patients with CAH. PATIENTS AND METHODS: Twenty-seven paediatric patients with CAH, aged 8-16 years, were evaluated by physical examination, electrocardiogram (ECG), conventional echocardiography, tissue Doppler imaging and two-dimensional (2D) myocardial strain (rate) imaging. Results were compared to 27 age- and gender- matched healthy controls. RESULTS: No signs of left ventricular hypertrophy or dilatation were detected on echocardiography. ECG revealed a high prevalence (25.9%) of incomplete right bundle branch block. Left ventricular posterior wall thickness in diastole (LVPWd) was significantly lower in patients with CAH compared to controls (5.55 vs 6.53 mm; P = .009). The LVPWd Z-score was significantly lower in patients with CAH yet within the normal range (-1.12 vs -0.35; P = .002). Isovolumetric relaxation time was significantly lower in patients with CAH (49 vs 62 ms; P = .003). Global longitudinal, radial and circumferential strain was not significantly different compared to controls. Global radial strain rate was significantly higher compared to healthy controls (2.58 vs 2.06 1/s; P = .046). Global longitudinal strain was negatively correlated with 24-hour blood pressure parameters. CONCLUSION: Cardiac evaluation of paediatric patients with CAH showed no signs of left ventricular hypertrophy or ventricular dilatation. LVPWd was lower in patients with CAH than in controls but within the normal range. A shorter isovolumetric relaxation time in patients with CAH may be a sign of mild left ventricular diastolic dysfunction.

Fatal dissection of the descending aorta after implantation of a stent in a 19-year-old female with Turner's syndrome.

We report a fatal dissection of the descending aorta as a complication after a two-staged implantation of a stent to relieve aortic coarctation in a young female with Turner's syndrome. Implantation of the stent, with dilation up to 70 percent, and half a year later re-dilation to 100 percent, was without any complication. A week after the re-dilation, however, the patient suffered acute dissection of the descending aorta. We initially stabilized the situation, but some days later her condition deteriorated, and she died. We discuss the various options for treating coarctation and re-coarctation. As far as we know, this is the first description of implantation of a stent in the setting of coarctation in Turner's syndrome, albeit with an unfortunate conclusion.