Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

OBJECTIVES: Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. METHODS: A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. RESULTS: The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. CONCLUSION: Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

Self-assembled multifunctional nanotheranostics against circulating tumor clusters in metastatic breast cancer

Circulating tumor clusters (CTC) disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer. In this study, a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site, which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients. Targeted multiresponsive (magnetic hyperthermia and pH) nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream. A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients. The nanotheranostic system was further evaluated for the targeting property, drug release kinetics, hyperthermia and cytotoxicity against developed CTC model in vitro. In vivo model in BALB/c mice equivalent to stage III and IV human metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system. Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites.

Pediatric Heart Failure Inpatient Mortality: A Cross-Sectional Analysis.

Background Heart failure constitutes significant morbidity and mortality among the pediatric population. Few data exist on the prevalence and mortality rate of pediatric heart failure (pHF) in the United States. Objectives This study aimed to determine the in-hospital mortality and the principal diagnoses in pediatric patients with heart failure who died while being hospitalized in the United States. Methods This is a retrospective cross-sectional study using data from the 2019 Kid Inpatient Database (KID). The KID contained data on hospitalized children below 21 years of age. Using Stata 17 software (StataCorp LLC, College Station, Texas), the data were searched for heart failure diagnoses using International Classification of Diseases 10th revision Clinical Modification (ICD-10-CM) codes. By using the "rank" command in Stata, the most common principal diagnoses were placed in descending order of frequency, and these were further divided into different ICD-10 code categories. Results There were 16,206 pHF admissions in 2019. Of these admissions, 1,023 (6.31%) patients died. The top five principal ICD 10 code categories among all pHF deaths in descending order were circulatory system (17.95%), congenital/chromosomal abnormalities (17.43%), respiratory system (10.28%), infectious diseases (9.24%, and perinatal diseases (7.90%). Among all pHF deaths, sepsis of unspecified organisms (5.14%), hypoplastic left heart syndrome (HLHS) (3.19%), and acute respiratory failure with hypoxia (3.14%) were the most common primary diagnoses. Conclusion and significance Pediatric heart failure in-hospital overall mortality is 6.31%, and sepsis of unspecified organisms, HLHS, and acute respiratory failure are the most common principal diagnoses among these children. Preventive measures and prompt treatment of infections are paramount to reducing pHF mortality.

Patent foramen ovale in children: Unique pediatric challenges and lessons learned from adult literature.

A patent foramen ovale (PFO) is a frequent incidental finding during echocardiography in otherwise healthy children. In most healthy children with a diagnosis of isolated incidental PFO, no further follow-up or intervention is necessary. In some children, PFO is associated with certain clinical syndromes such as cryptogenic stroke, decompression sickness, migraine, and platypnea-orthodeoxia syndrome. This review discusses PFO anatomy, diagnostic imaging, PFO-associated clinical situations, management options, and the role of PFO in certain congenital heart disease. This review also highlights the current deficiency of pediatric data guiding management of these uncommon but important PFO-associated conditions. Future multicenter randomized controlled studies are necessary to guide the management of these unique and challenging PFO-associated conditions.

Case report: Bordetella holmesii: A rare pathogen causing infective endocarditis associated glomerulonephritis.

Infective endocarditis (IE) can cause multiorgan dysfunction and chronic kidney disease, in addition to cardiac sequelae. The presentation may be vague and can manifest as acute glomerulonephritis. While the most common pathogens of infective endocarditis are Staphylococcus and Streptococcus species, we report a rare pathogen Bordetella holmesii causing infective endocarditis associated glomerulonephritis. A 20-year-old male patient with tetralogy of Fallot with pulmonary atresia and aortopulmonary collaterals underwent several cardiac surgeries including prosthetic pulmonary valve replacement in the past. He was admitted for 3 days at an outside hospital for fever, cough, and hemoptysis, and diagnosed with streptococcal pharyngitis, for which he received antibiotics. Five weeks later, he presented to our institution with lower extremity edema and gross hematuria. On examination, he was afebrile, normotensive, had a 7-kg weight gain with anasarca, and a systolic murmur, without rash. Investigations revealed elevated serum creatinine, nephrotic range proteinuria, hematuria, and hypocomplementemia, consistent with acute glomerulonephritis. Given his cardiac history, blood cultures were collected from three sites. Broad-spectrum antibiotics were initiated when he subsequently developed fever. Renal pathology on biopsy showed diffuse proliferative immune complex-mediated glomerulonephritis. Transesophageal echocardiogram visualized a vegetation on the pulmonary valve. Bordetella holmesii was ultimately cultured from the prior and current hospitalization. A serum sample detecting microbial cell-free DNA sequencing confirmed Bordetella holmesii at very high levels. After completing 6 weeks of intravenous antibiotics with concurrent angiotensin receptor blockade, his kidney function recovered with improvement in hypocomplementemia and proteinuria. This case report highlights the early recognition and comprehensive evaluation of a rare organism causing IE-associated GN, which allowed for renal recovery and preserved cardiac function.

Rapid Involution of Large Cardiac Rhabdomyomas With Everolimus Therapy.

Rhabdomyoma of the fetal heart is a rare disease accounting for about 1% of all fetal cardiac structural anomalies. They are often found in association with tuberous sclerosis complex. Large cardiac rhabdomyomas can compromise the cardiac function. We report a case of multiple large rhabdomyomas of the right and left ventricles, affecting the cardiac function, which was successfully treated with the chemotherapeutic and immunosuppressive medication everolimus, in a neonate with genetically confirmed tuberous sclerosis complex with multisystem manifestations. There was rapid involution of the tumors in response to everolimus therapy in this infant.

Patent foramen ovale: is it an incidental finding to ignore or a disease to follow?

The authors briefly present two clinical cases and discuss the approach to the management of an incidental finding of patent foramen ovale (PFO) in a young child. We discuss the current controversies in the management of PFO in this age group.

Aneurysmal Dilatation of Ductus Arteriosus and Pulmonary Artery in Association With ACTA2 Mutation.

Actin α2 (ACTA2) is a protein crucial for proper functioning of contractile apparatus in smooth muscles. A specific mutation resulting in substitution of arginine at position 179 by histidine (p.R179 H) in ACTA2 has been shown to be associated with multisystemic smooth muscle dysfunction syndrome. Characteristic features include aneurysmal arterial disease. Due to rarity of this disease, we report a nine-year-old girl with this rare genetic variant in whom cardiovascular manifestations were identified in fetal life and who needed neonatal cardiac surgical intervention.

Establishment of Myocardial Strain Measurement Data in Pediatric Patients Without Structural Heart Disease: A Single Center Study.

Accurate assessment of LV systolic function remains a challenge, especially in the pediatric population. Myocardial strain measurement by 2D speckle tracking echocardiography (2DSTE) is a relatively new modality for assessment of regional and global myocardial wall motion. This study aims to establish the normative value among various pediatric age groups at a large pediatric tertiary care institution and to describe the challenges encountered in establishing such strain data. Transthoracic echocardiograms were acquired in 121 healthy children (age 0-21 years) and were retrospectively analyzed. The global longitudinal strain (GLS) was obtained by 2D speckle tracking using Philips Epiq7® and QLAB post processing software. The normative value for left ventricular GLS (%) obtained in our study was - 20.8 ± 2.3 (< 1 year); - 21.4 ± 2.2 (1-4 years); - 19.6 ± 2.4 (5-9 years); - 19.4 ± 2.6 (10-14 years); - 18.9 ± 3.0 (15-21 years). There was a statistically significant difference in GLS between the different age groups. The BMI (kg/m2) of assessed subjects were 14.6 ± 2.3 (< 1 year); 16.3 ± 1.5 (1-4 years); 16.7 ± 2.3 (5-9 years); 21.3 ± 4.6 (10-14 years); 23.9 ± 5.9 (15-21 years). There was no significant difference in GLS by gender or by BMI found in our study. We present our experience with establishment of normative values of 2DSTE in our pediatric echocardiography lab. This study shows that age is the major determinant of variation in peak GLS in healthy subjects, emphasizing the importance of establishment of normative data among various age groups in pediatrics.

Congenital ductus arteriosus aneurysm in association with MYH11 mutation: a case report.

Congenital ductus arteriosus aneurysms develop in the third trimester of fetal life, possibly due to abnormal intimal cushion formation or elastin expression in the ductal wall. It is often diagnosed in infants before 2 months of age. Most have a benign course and resolve spontaneously. However, life-threatening complications have been reported. We report a case of large ductal aneurysm diagnosed incidentally in a neonate, in whom there was a novel mutation in the smooth muscle myosin protein gene-MYH11.

Border Medicine: The Pediatric Cardiology Perspective.

Pediatric cardiology and cardiovascular surgery have witnessed significant advancements over the last two decades. In spite of this progress, congenital heart disease (CHD) still remains as one of the major causes of death in infants and young children in the United States. Many patient-related and patient-independent factors influence the outcomes in patients with CHD, one of which is the geographical location. In the US-Mexico border, management and outcomes of patients with CHD are further complicated by additional problems stemming from complex interplay between two different health systems, and socioeconomic disparities. In this article, the authors evaluate the various interplaying factors and describe the difficulties facing the practicing pediatric cardiologists in a US-Mexico border city.

Tetralogy of Fallot With Absent Pulmonary Valve and Nonconfluent Pulmonary Arteries: A Management Conundrum.

Tetralogy of Fallot with absent pulmonary valve syndrome is a rare form of congenital heart disease. Among the different variations with this rare anomaly is nonconfluent pulmonary artery branches with anomalous origin of the left pulmonary artery from the ductus arteriosus. The authors present one such case which was diagnosed prenatally to have tetralogy of Fallot with absent pulmonary valve and identified postnatally to have nonconfluent pulmonary artery branches in addition. We discuss the conundrum of respiratory management in this patient pre- and postoperatively due to a unique ventilation perfusion mismatch problem, which varies between the two lungs.

Early-Onset Marfan Syndrome: A Case Series.

Mutations in fibrillin 1 cause Marfan syndrome (MFS), an autosomal dominant disorder of the connective tissue, with multisystem manifestations. In early-onset MFS, the physical characteristics are expressed much earlier than the classical MFS. Those affected by this form generally have their mutations restricted to the gene "hotspot" region of exons 24 to 32. Historically, affected individuals usually die within the first few years of life due to heart failure secondary to severe valvular insufficiency. We report three patients with early-onset MFS, whose clinical evolution has been remarkably positive, when compared with other reported cases in the literature.

Does myocardial strain remain abnormal long after normalization of ejection fraction in patients with acute myocarditis?

Myocarditis is a common cause for acute heart failure in the pediatric population. Various imaging modalities have evolved over the past 3 decades in order to noninvasively image the myocardium in this patient population. These include standard 2-dimensional echocardiographic imaging, tissue Doppler imaging, and magnetic resonance imaging of the heart. More recently, myocardial speckle tracking also known as strain imaging has been utilized to assess regional wall motion abnormalities with increasing accuracy. We report a case of acute myocarditis in a teenage female in whom progression of myocardial strain findings correlated with the rapidly evolving clinical course of the patient.

Comparison of echocardiographic changes in children with primary hypertension and hypertension due to mild to moderate chronic kidney disease.

BACKGROUND: Chronic systemic hypertension has a well-known association with increased cardiovascular morbidity and mortality. One of the most important target organs affected in systemic hypertension is the heart. In addition, chronic kidney disease (CKD) further increases the mortality from cardiovascular disease. The aim of this study was to evaluate the differences in the cardiovascular changes in pediatric patients with primary hypertension (pHTN) vs. those with secondary hypertension from chronic kidney disease (CKD-HTN). METHODS: This was a retrospective chart review of patients with CKD-HTN and pHTN. The medical records were reviewed for anthropometric data, biochemical assessment of renal function, and for cardiovascular changes on echocardiogram. RESULTS: Twenty-three patients with pHTN and 29 patients with CKD-HTN were included in the study. There were no differences in age, gender, weight, height, body mass index, and blood pressure between the 2 groups. There was a high prevalence of left ventricular diastolic dysfunction among both the groups (CKD-HTN 25 vs. pHTN 26%). Reduced mitral valve inflow Doppler E/A ratio, a marker of left ventricular diastolic dysfunction in echocardiogram, was more pronounced in CKD-HTN patents, in comparison to those with pHTN (p = 0.042). Also, diastolic function worsened with declining glomerular filtration rate in patients with CKD-HTN. Similarly, patients with CKD-HTN had a larger aortic root dimension when compared to patients with pHTN (p = 0.049). CONCLUSIONS: The prevalence of left ventricular diastolic dysfunction is similar in patients with pHTN and CKD-HTN. Patients with CKD-HTN appear to have more severe diastolic dysfunction and larger aortic root dimensions.

Cardioprotective Effects of Paricalcitol Alone and in Combination With FGF23 Receptor Inhibition in Chronic Renal Failure: Experimental and Clinical Studies.

BACKGROUND: In uremic animals, vitamin D receptor (VDR) agonists like paricalcitol (Pc) attenuate cardiac hypertrophy, but this effect has not been replicated consistently in humans with chronic kidney disease. Elevated fibroblast growth factor 23 (FGF23) levels cause cardiac hypertrophy with activation of the myocardial calcineurin/nuclear factor of activated T cell (NFAT) axis and may antagonize the cardioprotective effects of VDR agonist therapy. We hypothesized that the effectiveness of Pc may depend on the prevailing circulating levels of FGF23 and could be potentiated by the combined administration of a pan-FGF23 receptor (FGFR) blocker agent (PD173074). METHODS: In rats with 5/6 nephrectomy treated with Pc or PD173074 or both agents concurrently, myocardial mRNA expression of renin-angiotensin system, VDR, FGFR4, and calcineurin/NFAT target genes was determined. In adolescents on hemodialysis, we analyzed sequential echocardiograms, blood pressures and serial FGF23 measurements, and their relations to the cumulative administered dose of parenteral Pc. RESULTS: The ratio of Pc dose/plasma levels of FGF23 correlated inversely (P < 0.005) with the cardiac mass in uremic rats and in hemodialysis patients, independently of hypertension. Despite persistently elevated FGF23 levels and myocardial FGFR4 activation, Pc suppressed upregulated myocardial calcineurin/NFAT target genes, and the effects were amplified by coadministration of PD173074. CONCLUSIONS: The beneficial effects of Pc on uremic cardiac hypertrophy are counterbalanced by the increased FGF23 levels. Blockade of FGF23-mediated signaling increased the Pc-induced suppression of the myocardial calcineurin/NFAT system. Higher doses of Pc should be considered in the treatment of patients with uremic cardiomyopathy.

Emerging trends in the prenatal diagnosis of complex CHD and its influence on infant mortality in this cohort.

BACKGROUND: Fetal echocardiography is the main modality of prenatal diagnosis of CHD. This study was done to describe the trends and benefits associated with prenatal diagnosis of complex CHD at a tertiary care centre. METHODS: Retrospective chart review of patients with complex CHD over an 18-year period was performed. Rates of prenatal detection along with early and late infant mortality outcomes were studied. RESULTS: Of 381 complex CHD patients born during the study period, 68.8% were diagnosed prenatally. Prenatal detection rate increased during the study period from low-50s in the first quarter to mid-80s in the last quarter (p=0.001). Rate of detection of conotruncal anomalies increased over the study period. No infant mortality benefit was noted with prenatal detection. CONCLUSIONS: Improved obstetrical screening indications and techniques have contributed to higher proportions of prenatal diagnosis of complex CHD. However, prenatal diagnosis did not confer survival benefits in infancy in our study.

Impact of prenatal diagnosis of complex congenital heart disease on neonatal and infant morbidity and mortality.

OBJECTIVES: The objective of this study was to analyze the benefits associated with prenatal diagnosis of complex congenital heart disease (CHD) on preoperative morbidity, 30-day and 1-year mortality in this population. METHOD: This was a retrospective review of patients with complex CHD born at our tertiary care center over a 10-year period. Date analysis using Student t test and chi-square test. RESULTS: The overall rate of prenatal detection of complex CHD was 68.1%. A steady increase in the number of complex CHD diagnosed prenatally was noted during the study period. The prenatal diagnosis of complex CHD was associated with significant reduction in the incidence of the following preoperative parameters: antibiotic use, mechanical ventilation, inotropic support, hepatic and renal dysfunction, and acidosis. These beneficial effects were more significant in ductal-dependent cardiac anomalies. However, there were no neonatal and infant survival benefits in association with prenatal diagnosis. CONCLUSION: Prenatal diagnosis of complex CHD leads to improved preoperative morbidity, especially in patients with ductal-dependent cardiac anomalies. No survival benefits were noted with prenatal diagnosis of complex CHD.

Association of left atrial pressure with left atrial volume and N-terminal prohormone brain natriuretic peptide in children with cardiomyopathy.

BACKGROUND: Enlargement of the left atrium is a non-invasive marker of diastolic dysfunction of the left ventricle, a determinant of prognosis in children with cardiomyopathy. Similarly, N-terminal prohormone brain natriuretic peptide is a useful marker in the management of children with cardiomyopathy and heart failure. The aim of this study is to evaluate the association of left atrial pressures with left atrial volume and N-terminal prohormone brain natriuretic peptide in children with cardiomyopathy. METHODS: This was a retrospective study reviewing the medical records of patients <18 years of age, who were diagnosed with cardiomyopathy or acute myocarditis with eventual development of cardiomyopathy. Left atrial volume by transthoracic echocardiogram and pulmonary capillary wedge pressure, a surrogate of left atrial pressure, obtained by means of cardiac catheterisation were analysed. In addition, N-terminal prohormone brain natriuretic peptide levels obtained at the time of the cardiac catheterisation were also reviewed. Statistical analysis was performed to evaluate the association of left atrial pressures with left atrial volume and N-terminal prohormone brain natriuretic peptide levels. RESULTS: There was a linear correlation of left atrial pressure estimated in the cardiac catheterisation with indexed left atrial volume (r=0.63; p<0.001) and left atrial volume z-scores (r=0.59; p<0.001). We found no statistically significant association between the left atrial pressure and N-terminal prohormone brain natriuretic peptide levels. CONCLUSIONS: Left atrial volume measured non-invasively by echocardiography can be used as a surrogate for left atrial pressure in assessing diastolic dysfunction of the left ventricle in children with cardiomyopathy. The larger the size of the left atrium, worse is the diastolic function of the left ventricle.