Neonatal cardiac hypertrophy: the role of hyperinsulinism-a review of literature.

Hypertrophic cardiomyopathy (HCM) in neonates is a rare and heterogeneous disorder which is characterized by hypertrophy of heart with histological and functional disruption of the myocardial structure/composition. The prognosis of HCM depends on the underlying diagnosis. In this review, we emphasize the importance to consider hyperinsulinism in the differential diagnosis of HCM, as hyperinsulinism is widely associated with cardiac hypertrophy (CH) which cannot be distinguished from HCM on echocardiographic examination. We supply an overview of the incidence and treatment strategies of neonatal CH in a broad spectrum of hyperinsulinemic diseases. Reviewing the literature, we found that CH is reported in 13 to 44% of infants of diabetic mothers, in approximately 40% of infants with congenital hyperinsulinism, in 61% of infants with leprechaunism and in 48 to 61% of the patients with congenital generalized lipodystrophy. The correct diagnosis is of importance since there is a large variation in prognoses and there are various strategies to treat CH in hyperinsulinemic diseases.Conclusion: The relationship between CH and hyperinsulism has implications for clinical practice as it might help to establish the correct diagnosis in neonates with cardiac hypertrophy which has both prognostic and therapeutic consequences. In addition, CH should be recognized as a potential comorbidity which might necessitate treatment in all neonates with known hyperinsulinism.What is Known:• Hyperinsulinism is currently not acknowledged as a cause of hypertrophic cardiomyopathy (HCM) in textbooks and recent Pediatric Cardiomyopathy Registry publications.What is New:• This article presents an overview of the literature of hyperinsulinism in neonates and infants showing that hyperinsulinism is associated with cardiac hypertrophy (CH) in a broad range of hyperinsulinemic diseases.• As CH cannot be distinguished from HCM on echocardiographic examination, we emphasize the importance to consider hyperinsulinism in the differential diagnosis of HCM/CH as establishing the correct diagnosis has both prognostic and therapeutic consequences.

Spectrum of heart diseases in children presenting to a paediatric cardiac echocardiography clinic in the Lake Zone of Tanzania: a 7 years overview.

BACKGROUND: Congenital heart diseases (CHD) are among the most common congenital malformations. It is estimated that the incidence of CHD is constant worldwide, but data are rare for most African countries including Tanzania. Even less data are available on the prevalence of acquired heart diseases (AHD) in African children. Rheumatic heart disease (RHD) is the leading cause of AHD and is remaining a public health concern in Sub-Saharan Africa affecting especially the younger population. Both, CHD and AHD contribute substantially to morbidity and mortality during infancy and childhood. METHODS: This hospital-based, retrospective review of the registry at the paediatric cardiac clinic of Bugando Medical Centre in the Lake Zone of Tanzania analysed the spectrum of heart diseases of paediatric patients during their first presentation by using simple descriptive statistics. RESULTS: Between September 2009 and August 2016, a total of 3982 patients received cardiac evaluation including echocardiography studies. 1830 (46.0%) pathologic findings were described, out of these 1371 (74.9%) patients had CHD, whereas 459 (25.1%) presented with AHD. 53.9% of the patients with CHD were female and the most common associated syndrome was Down syndrome in 12.8% of patients. In 807 patients (58.9%) diagnosis of CHD was established within the first year of life. The majority of patients (60.1%) were in need of surgical or interventional therapy at time of diagnosis and 6.3% of patients were judged inoperable at the time of first presentation. Nearly 50% of cases with AHD were RHDs followed by dilated cardiomyopathy and pulmonary hypertension without underlying CHD. CONCLUSIONS: The spectrum of CHD and AHD from one centre in Tanzania is comparable to findings reported in other countries from the African continent. Echocardiography is a valuable diagnostic tool and the widespread use of it should be enhanced to diagnose heart diseases in a large number and reasonable time. Most patients present late and majority is in need of surgical or interventional treatment, which is still not readily available. Untreated heart diseases contribute substantially to morbidity and mortality during infancy and childhood. Adequate cardiac services should be established and strengthened.

Long-term outcome of transvenous pacemaker implantation in infants: a retrospective cohort study.

AIM: Evaluation of long-term outcome of transvenous pacemaker (PM) implantation in infants. METHODS AND RESULTS: A retrospective analysis of all transvenous PM implantations in infants <10 kg between September 1997 and October 2001 was made. Indications for PM implantation, age at implantation, and determinants of long-term outcome including cardiac function, PM function, and PM (system) complications were noted. Seven patients underwent transvenous VVI(R) PM implantation. Median age at implantation was 3 days (range: 1 day to 14 months), median weight 3.5 kg (range: 2.3-8.7 kg), and median follow-up 14 years (range: 12.3-16.3 years). Pacemaker indications were congenital complete atrioventricular block (n = 4), long QT syndrome with heart block (n = 2), and post-operative complete atrioventricular block with sinus node dysfunction (n = 1). No procedural complications were noted. Today all patients are alive and symptom free with good PM and cardiac function. Two patients underwent PM generator relocation for imminent skin necrosis and skin traction. Two patients suffered from asymptomatic left subclavian vein occlusion and developed thrombosis on the PM electrode. Three patients were converted to an epicardial PM system, due to atrial perforation after upgrading procedure (n = 1), syncope with need for implantable cardioverter defibrillator implantation (n = 1), and systolic dysfunction with development of dilated cardiomyopathy, which normalized under cardiac resynchronization therapy pacing (n = 1). Two patients needed atrioventricular (AV) valve repair for severe insufficiency. Two patients underwent repositioning of dysfunctional PM leads. In five patients, transvenous leads were removed. Indications were elective lead replacement (n = 1), atrial perforation (n = 1), and switch to an epicardial system (n = 3). CONCLUSION: Transvenous PM implantation in infants (<10 kg) is associated with a high incidence of vascular occlusion, thrombosis, and severe atrioventricular valve regurgitation during long-term follow-up. We advocate an epicardial approach for PM implantation in small children.

Interventional VSD-Closure with the Nit-Occlud® Lê VSD-Coil in 110 Patients: Early and Midterm Results of the EUREVECO-Registry.

In August 2010, the Nit-Occlud® Lê (EUREVECO) became available for transcatheter coil occlusion of ventricular septal defects (VSDs). Retrospective European Registry for VSD Closure using the Nit-Occlud® Lê-VSD-Coil; analysis of the feasibility, results, safety and follow-up of VSD-closure over a 3-year period in 18 European centers. In 102 of 111 patients (female 66), successful VSD closure was performed (mean age 8.2 years, mean weight 28.82 kg), 81 perimembranous VSDs (48 with aneurysm), 30 muscular VSDs, mean procedure time was 121.1 min, and mean fluoroscopy time was 26.3 min. Short- and midterm term follow-up was possible in 100/102 patients, there was 1 embolization and 1 explantation after 24 months. Immediate complete closure occurred in 49 of 101 patients (48.5%), trivial residual shunt was present in 51 (50.0%), closure rate was 95% after 6 months and 97% after 1 year. Out of the 102 patients, there were 2 severe complications (1.8%) (1 severe hemolysis, 1 embolization) and 8 moderate/transient (=7.2%) including 1 transient AV block. During a mean follow-up period of 31.3 months (range 24-48) and a total follow-up time of 224.75 patient years, no further problems occurred. VSD closure with the Nit-Occlud® Lê VSD coil is feasible and safe with a minimal risk of severe side effects. The long-term effects and safety require further clinical follow-up studies.

Transcatheter embolization of a large aneurysm in a congenital coronary cameral fistula from the left coronary artery to the right ventricle.

A congenital coronary cameral fistula (CCCF) is characterized by left ventricular dysfunction, electrocardiographic changes due to a reduced left coronary blood flow and impaired physical activity. CCCF's with a giant aneurysm are very rarely seen. The presence of a giant aneurysm imposes even greater health risks. We report a case of a CCCF from the left coronary artery to the right ventricle with a large distal aneurysm in a 20-year-old woman that we closed percutaneously with coils for the closure of ventricular septal defects (VSD) and persistent ductus arteriosus (PDA).

Fetal heart disease: severity, associated anomalies and parental decision.

OBJECTIVE: This study describes the association between the complexity of congenital cardiac and extracardiac malformations, and the parental decision of pregnancy continuation or termination. METHODS: Congenital heart defects (CHD) was diagnosed by ultrasound in 251 fetuses before the 24th week (23 + 6 weeks) of gestation during the four year period from 2007 to 2010. All fetuses from the Utrecht region were referred to our center due to a strict referral pattern. The complexity and severity of the cardiac and possible extracardiac malformations were retrospectively categorized by a pediatric cardiologist and a perinatologist who were blinded to the pregnancy outcome. The groups with and without termination of pregnancy were compared using a univariate analysis and multivariate logistic regression. RESULTS: In 119 (47%) of the 251 fetuses, parents opted for termination of pregnancy. In 103 of these cases (87%) there was a high complex or lethal cardiac, or a major or lethal extracardiac malformation. Of the 132 continued pregnancies, 42 fetuses (32%) had a high complex or lethal cardiac, or a major or lethal extracardiac malformation. There were significantly more terminations of pregnancy in case of a high or lethal complex cardiac or extracardiac anomaly (71 vs. 15%, p <0.001). CONCLUSION: Parents opted for termination of pregnancy significantly more often in cases with high complex cardiac and extracardiac malformations. It was rare for parents to opt for pregnancy termination in the absence of a severe cardiac or extracardiac malformation.

Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients.

BACKGROUND: Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome. METHODS AND RESULTS: We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000-2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1-21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age < 20 weeks, ventricular rate ≤ 50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥ 1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4 ± 2.9 versus 24.9 ± 4.9 weeks; P=0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy. CONCLUSIONS: Risk factors associated with a poor outcome were gestation < 20 weeks, ventricular rate ≤ 50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen.

Chiari's network as a cause of fetal and neonatal pathology.

Chiari's network is a remnant of the eustachian valve located in the right atrium. Incomplete involution of the fetal sinus venosus valves results in "redundant" Chiari's network, which may compromise cardiovascular function. This report describes a case with the novel finding of prenatal compromise due to redundant Chiari's network and an uncommon case with significant postnatal symptoms. In both cases, the symptoms (fetal hydrops and postnatal cyanosis) resolved spontaneously. The variety of cardiovascular pathologies described in the literature is believed to be associated with persistence of a Chiari network. Knowledge about this not always harmless structure is important for perinatologists, pediatricians, and pediatric cardiologists alike. The clinical importance of this rare pathology is that prenatal counseling may anticipate a generally positive outcome and that surgical intervention generally should be avoided.

Juxtaductal coarctation of both pulmonary arteries in a cat.

A 4-year-old, male, neutered cat was referred because of recurrent episodes of dyspnea. Physical examination revealed a harsh systolic murmur, with the point of maximal intensity in the left heart base, with an intensity of 4 out of 6. Echocardiographic diagnosis was severe supravalvular pulmonary artery stenosis. A selective right ventricular angiocardiogram showed an absence of arterial blood flow to the left lung lobes. A balloon dilatation of the localized stenosis of the right pulmonary artery was attempted with cardiac catheterization. However, when the catheter was passed through the stenosis, the blood flow to the lungs temporarily completely ceased, which led to death. Postmortem examination revealed a circumscribed stenosis of both pulmonary arteries at the site of the bifurcation, where the ligamentum arteriosum was attached. Histopathology showed that the localized ridge-like stenosis at the pulmonary artery bifurcation was caused by connective tissue. The suspected cause of this congenital anomaly is the presence of ectopic ductal tissue in the wall of the pulmonary artery. When the ductus arteriosus closes at birth, pulmonary artery stenosis developed because of constriction of the ectopic ductal tissue.

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.

Midterm Follow-Up After Biventricular Repair of the Hypoplastic Left Heart Complex.

BACKGROUND: In neonates with hypoplastic left heart complex (HLHC), biventricular repair is considered superior to univentricular repair. The Z-scores of the mitral and the aortic valve annulus are primary factors for the choice of repair. Predictive cutoff values for the feasibility and optimal outcome of biventricular repair are unknown. This study assesses the growth of left side heart structures and the midterm outcome after biventricular repair with an interatrial fenestration in our HLHC population. METHODS: Retrospective study of 19 HLHC patients who underwent biventricular repair in a single tertiary referral center between 2004 and 2013. The cardiac dimensions (mitral and aortic valve annulus, left ventricle inlet length, left ventricular internal diastolic dimension) were measured before and at 6, 12, 24, and 48 months after biventricular repair. RESULTS: The follow-up ranged from 2 to 98 months. There was no early mortality, and the midterm survival rate was 95%. One patient died of a noncardiac- and nonintervention-related cause. Seven patients (37%) required a total of 8 reinterventions because of recurring or residual obstructive lesions. After biventricular repair, the left cardiac structures grew significantly. CONCLUSIONS: Neonatal biventricular repair is successful and safe in HLHC patients, even with preoperative mitral and aortic valve annulus Z-scores of -4.5 and -5.5, respectively. Residual or restenosis required reintervention in 37% of our HLHC population, but was not significantly correlated with the magnitude of the preoperative Z-scores. Within the first 6 months of follow-up, the Z-scores almost normalized.

Comparability of Z-score equations of cardiac structures in hypoplastic left heart complex.

BACKGROUND: Hypoplastic left heart complex (HLHC) is characterized by a mitral valve or an aortic valve annular Z score < -2, antegrade flow in the ascending aorta, ductal dependency, coarctation or aortic arch hypoplasia, and absence of significant (sub)valvar stenosis. The Z scores of the mitral and aortic valve annuli are major determinants of HLHC. Therefore, the algorithm for Z-score calculation is essential for diagnosis. However, no single universal method of calculation is in use. In the scientific literature addressing HLHC, various Z-score calculation methods have been applied. The aim of this study was to evaluate Z scores derived from two-dimensional echocardiographic dimensions in patients with HLHC. METHODS: To compare the different published methods using two-dimensional echocardiographic measures for Z-score calculation, a cohort of 18 newborns diagnosed with HLHC was retrospectively evaluated. In addition, the methods to determine body surface area in newborns were evaluated. RESULTS: Three Z-score calculation methods were included and compared. Using the method of Daubeney et al. to calculate Z scores in our cohort illustrated a lack of correlation beyond a Z score < 0, compared with the methods of Zilberman et al. and Pettersen et al. Z scores calculated using Zilberman et al.'s and Pettersen et al.'s methods were fairly consistent. The equations used by Pettersen et al. are based on the largest population of neonates. CONCLUSION: Although the different methods for calculating Z scores for mitral and aortic valve dimensions correspond fairly well in the normal range, Z scores < -2 diverge substantially. A useful scientific comparison of published data and outcomes of patients with HLHC remains elusive. The Z-score calculation algorithms used by Pettersen et al. appear to be the most appropriate for use in an evaluation of HLHC. Because these different methods can yield different values, reporting the method as well as the Z score is essential for an accurate diagnosis. Similarly, the method used to determine body surface area should be reported.

Prognosis for neonates with enterovirus myocarditis.

OBJECTIVE: To assess the severity of the disease and the long-term cardiac prognosis for neonates who developed enterovirus (EV) myocarditis within the first weeks of life. DESIGN: Clinical presentation, echocardiographic and ECG findings and the outcome of seven infants with EV myocarditis admitted to the intensive care unit are reported. Additionally, 28 previously reported cases are described. RESULTS: Seven neonates presented with cardiac failure within 17 days after birth requiring respiratory and circulatory support. Echocardiography showed dilatation and severe dysfunction of the left ventricle in all and mitral regurgitation in six. In six patients the echocardiographic pattern resembled myocardial infarction. ECG showed complete loss of the R-wave and a new Q-wave in the left precordial leads in all. Two infants died and five developed long-term cardiac sequelae requiring medication. In all survivors aneurysm formation in the left ventricular wall was found weeks to months later. One patient is awaiting heart transplantation. Coxsackie virus B was detected in blood, cerebrospinal fluid, nasopharyngeal swab or stool by PCR or culture. The mortality of previously described neonates combined with our seven cases was 31% (11/35). Among the survivors 66% (16/24) developed severe cardiac damage. Only 23% (8/35) of the infants fully recovered. CONCLUSIONS: EV myocarditis is a rare but severe disease in the neonatal period, which often leads to death or results in serious chronic cardiac sequelae like chronic heart failure, aneurysm formation within the left ventricle and mitral regurgitation. Chronic cardiac drug therapy is necessary in the majority of these patients.