Phenotypic expression, genotypic profiling and clinical outcomes of infantile hypertrophic cardiomyopathy: a retrospective study.

BACKGROUND: Infantile hypertrophic cardiomyopathy (HCM) is a heterogeneous disorder. Apart from registries in high-income nations, there is a shortage of data on the aetiological basis of infantile HCM in low- and middle-income nations. This study attempts to characterise the phenotypic expression, genetic architecture and short-term clinical outcomes of infantile HCM from a South Asian tertiary referral centre. METHODS: This study includes all infants from the Amrita HCM cohort between January 2011 and July 2021. Clinical history, ECG, echocardiographic data, and genetic analyses were evaluated. RESULTS: 34 patients with infantile HCM were diagnosed at a median age of 3.7 months (IQR 1-6 months). Underlying aetiologies were RASopathy (n=13; 38%), non-syndromic (n=12; 35%) and inborn errors of metabolism (n=9; 27%). Genetic analysis was done in 20 patients (59%) with a yield of 90%. Clinical presentation included failure to thrive (n=29; 85%), dyspnoea on exertion (n=23; 68%) and clinical heart failure (n=24; 71%). Echo showed concentric left ventricular hypertrophy in 22 patients (65%), obstructive HCM in 11 patients (32%) and left ventricular systolic dysfunction in 6 patients (18%). The mortality rate was 10.0 deaths per 100 patient years over a median follow-up period of 3.1 years. The main risk markers for mortality were the age at diagnosis, gender and concentric Left ventricular hypertrophy. CONCLUSIONS: This cohort demonstrates the morphological, functional and genetical heterogeneity of infantile HCM, enunciating the need for integration of cardiology, metabolic and genetic services to achieve optimum outcomes in these patients.

Utility of the novel fetal heart quantification (fetal HQ) technique in diagnosing ventricular interdependence and biventricular dysfunction in a case of prenatally diagnosed Uhl's anomaly.

Uhl's anomaly is characterized by complete or partial absence of right ventricular myocardium. We describe a case of prenatally diagnosed Uhl's anomaly with biventricular dysfunction which was quantified with speckle tracking echocardiography using a novel fetal heart quantification (fetal HQ) technique.

Incremental value of fetal spatiotemporal image correlation echocardiography in the diagnosis of tetralogy of Fallot with disconnected pulmonary arteries with ductus arteriosus supplying the left pulmonary artery.

Disconnected branch pulmonary arteries are sparsely reported cases in prenatal diagnosis literature. We report a case of tetralogy of Fallot with disconnected branch pulmonary arteries, the left pulmonary artery (LPA) arising from an indirect ductus arteriosus (DA) from the base of the innominate artery in a right aortic arch, diagnosed by fetal echocardiography with 3D/4D spatiotemporal image correlation (STIC) imaging. Prenatal diagnosis led to early neonatal intervention to maintain blood flow to the LPA by stenting of the DA. Fetal echocardiographic evaluation (Voluson E10 systems, GE Healthcare, Zipf) with acquisition of images and volumes in the right ventricular outflow tract and three-vessel trachea view with rendering of 3D/4D STIC volume datasets to display images in high-definition color format. Prenatal evaluation was initially done at 17-week gestation in a 28-year-old pregnant female which showed tetralogy of Fallot (TOF). Subsequent evaluation at 34 weeks with 3D/4D STIC datasets showed a small main pulmonary artery (MPA) continuing into an adequately sized right pulmonary artery. The LPA was very small (Z-score -2.63), with no visible connection to MPA. Rendering of the 3D/4D STIC datasets revealed disconnected pulmonary arteries with the vertical DA from the base of the innominate artery in a right aortic arch, continuing as the LPA. Findings were confirmed on postnatal high-resolution CT pulmonary angiography and cardiac catheterization with subsequent stenting of the ductus. This report highlights the incremental benefit of advanced 3D/4D STIC rendering in accurate prenatal diagnosis of a rare anomaly of TOF with disconnected pulmonary arteries, leading to early neonatal intervention to preserve the blood supply to the left lung.

Clinical presentation, conventional/4D spatio-temporal image correlation imaging findings, pregnancy and early postnatal outcomes in fetuses having anomalies of systemic venous return in the absence of significant intracardiac defects: A retrospective study from two centres in Southern India.

BACKGROUND: Recent advances in fetal ultrasound imaging, especially four-dimensional (4D) spatio-temporal image correlation techniques permit detailed evaluation of the fetal venous system and its abnormalities. In this report, we present the clinical presentation, conventional/4D spatio-temporal image correlation imaging findings, pregnancy, and early postnatal outcomes in fetuses having anomalies of systemic venous return in the absence of significant intracardiac defects from two centres in southern India. OBJECTIVES: To report the clinical presentation, conventional/4D spatio-temporal image correlation imaging findings, pregnancy, and early postnatal outcomes in fetuses having anomalies of systemic venous return in the absence of significant intracardiac defects from two centres in Southern India. METHODS: Retrospective study (October 2017 to March 2022). All fetuses referred with abnormal cardiac imaging findings who were diagnosed to have anomalies of systemic venous return in the absence of significant intracardiac defects were included. Imaging techniques like 2D with color and 4D spatio-temporal image correlation fetal imaging were used to evaluate systemic venous anomalies. Systemic venous anomalies were grouped into cardinal venous anomalies and umbilico-portosystemic venous anomalies. RESULTS: Thirty-nine fetuses were included; this represented 4.4% of all cardiac anomalies diagnosed during the study period. Cardinal venous anomalies were seen in 29 fetuses (74%); the mean gestation age at diagnosis was 25.5 ± 3.4 weeks. Absent dilated coronary sinus was associated with anomalous drainage of superior caval vein through completely unroofed coronary sinus into the left atrium (n = 3) which resulted in cyanosis after birth in all infants. Among the three cases, one underwent surgery at 6 months of age due to a progressive increase in cyanosis (Spo2 78%) and others are awaiting surgery. A prenatal genetic evaluation was performed in 17 (58.6%). Cardinal venous anomalies were not associated with genetic abnormalities. Live births occurred in all fetuses with cardinal venous anomalies. Umbilico-portosystemic venous anomalies were seen in 10 (26%). The mean gestation age at diagnosis was 26.5 ± 4.5 weeks. Except in a fetus with the extrahepatic portosystemic shunt (umbilical vein to iliac vein), the genetic evaluation was normal in our cohort. Extracardiac anomalies (n = 3/10; 30%) were seen in both intra (n = 1) and extrahepatic portosystemic shunts (n = 2). CONCLUSION: Anomalies of systemic venous return in the absence of significant intracardiac, extracardiac, and genetic abnormalities carried an overall favorable prognosis in our cohort. Precise characterization of anatomic details using advanced imaging techniques helps in the understanding of this complex three-dimensional anatomy and in the prognostication of these anomalies.

Three-dimensional/four-dimensional spatiotemporal image correlation morphology of the ductus arteriosus in fetuses with pulmonary atresia undergoing neonatal ductal stenting.

Background: The value of prenatal identification of morphology of ductus arteriosus in fetuses with congenital heart defects (CHD) with pulmonary atresia and duct-dependent pulmonary circulation (DDPC) in planning neonatal ductal stenting procedure is untested. The aim of the study is to analyze the utility of three-dimensional/four-dimensional (3D/4D) spatiotemporal image correlation (STIC) fetal echocardiography in delineating the morphology of ductus arteriosus in fetuses with DDPC undergoing neonatal ductal stenting. Methods: In this retrospective study (2017-22), prenatal imaging of pulmonary artery (PA) anatomy, aortic arch sidedness, and morphology of ductus arteriosus (ductal origin was classified as vertical/horizontal and ductal course as tortuous/straight) was done using 3D/4D STIC imaging and volume datasets. Prenatal findings were correlated with angiographic findings during stenting and the degree of agreement was calculated. Results: We included 27 fetuses with a prenatal diagnosis of CHD with DDPC who underwent neonatal ductal stenting. The accuracy of prenatal assessment of PA anatomy, branch PA stenosis, and arch sidedness was 100%, 92.6%, and 88.9%, respectively. The accuracy of prenatal assessment of ductal origin and course, compared with angiography, was 85.2% and 88.9%, respectively. Prenatal imaging had a diagnostic accuracy of 100% for vertical straight and horizontal tortuous ducts, 84.6% for vertical tortuous, and 67% for horizontal straight ducts. Duct stenting was successful in 25 (92.6%) babies; two died after the procedure from stent occlusion. Conclusion: Fetal echocardiography using 3D/4D STIC imaging enables accurate delineation of the morphology of ductus arteriosus in fetuses with DDPC, thereby aiding parental counseling and planning neonatal ductal stenting.

Prenatal diagnosis lowers neonatal cardiac care costs in resource-limited settings.

BACKGROUND: Prenatal diagnosis of critical CHDs and planned peripartum care is an emerging concept in resource-limited settings. OBJECTIVE: To report the impact of prenatal diagnosis and planned peripartum care on costs of neonatal cardiac care in a resource-limited setting. METHODS: Prospective study (October 2019 to October 2020). Consecutive neonates undergoing surgery or catheter-based interventions included. Patients were divided into prenatal (prenatal diagnosis) and post-natal (diagnosis after birth) groups. Costs of cardiac care (total, direct, and indirect) and health expenses to income ratio were compared between study groups; factors impacting costs were analysed. RESULTS: A total of 105 neonates were included, including 33 in prenatal group. Seventy-seven neonates (73.3%) underwent surgical procedures while the rest needed catheter-based interventions. Total costs were 16.2% lower in the prenatal group (p = 0.008). Direct costs were significantly lower in the prenatal group (18%; p = 0.02), especially in neonates undergoing surgery (20.4% lower; p = 0.001). Health expenses to income ratio was also significantly lower in the prenatal group (2.04 (1.03-2.66) versus post-natal:2.58 (1.55-5.63), p = 0.01);, particularly in patients undergoing surgery (prenatal: 1.58 (1.03-2.66) vs. post-natal: 2.99 (1.91-6.02); p = 0.002). Prenatal diagnosis emerged as the only modifiable factor impacting costs on multivariate analysis. CONCLUSION: Prenatal diagnosis and planned peripartum care of critical CHD is feasible in resource-limited settings and is associated with significantly lower costs of neonatal cardiac care. The dual benefit of improved clinical outcomes and lower costs of cardiac care should encourage policymakers in resource-limited settings towards developing more prenatal cardiac services.

Prenatal diagnosis of transposition of great arteries with left anterior aorta (SDL-TGA).

We report a case with prenatal diagnosis of transposition of great arteries (TGA) with L-posed aorta (SDL-TGA) which was confirmed by postnatal echocardiography. The anatomic findings were confirmed during the successful arterial switch operation (ASO). The technical challenges of ASO in the L-posed aorta are also described.

Prenatal diagnosis of obstructed supracardiac total anomalous pulmonary venous connection at 23 weeks with successful immediate postnatal surgical correction.

Diagnosis of isolated total anomalous pulmonary venous connections (TAPVCs) is relatively rare in fetal life, especially in early gestation. We report a case of a fetus diagnosed with the supracardiac type of TAPVC at 23 weeks gestation, with evidence of obstruction to connection of the common vertical vein to the superior vena cava. The neonate had a critical presentation at birth and underwent an emergency surgical repair immediately after birth with excellent outcome on short term follow-up with the resolution of pulmonary artery hypertension.

Prenatal diagnosis of double outlet right ventricle with intact ventricular septum in two foetuses.

We describe two cases of an unusual variant of double outlet right ventricle with intact ventricular septum diagnosed prenatally and confirmed by foetal autopsy in a case. The first case had mitral valve atresia, slit-like left ventricle, and normally related great arteries. The second case had mitral valve atresia, hypoplastic left ventricle, parallel outflows with an interrupted aortic arch.

Pregnancy and early post-natal outcomes of fetuses with functionally univentricular heart in a low-and-middle-income country.

BACKGROUND: Care of children with functionally univentricular hearts is resource-intensive. OBJECTIVES: To analyse pregnancy and early post-natal outcomes of fetuses with functionally univentricular hearts in the setting of a low-middle-income country. METHODS: A retrospective study was conducted during the period of January 2008-October 2019. Study variables analysed included gestational age at diagnosis, maternal and fetal comorbidities and cardiac diagnosis including morphologic type of single ventricle. Outcomes analysed included pregnancy outcomes, type of post-natal care and survival status on the last follow-up. RESULTS: A total of 504 fetuses were included. Mean maternal age was 27.5 ± 4.8 years and mean gestational age at diagnosis was 25.6 ± 5.7 weeks. Pregnancy outcomes included non-continued pregnancies (54%), live births (42.7%) and loss to follow-up (3.3%). Gestational age at diagnosis was the only factor that impacted pregnancy outcomes (non-continued pregnancies 22.5 ± 3.5 vs. live births 29.7 ± 5.7 weeks; p < 0.001). Of the 215 live births, intention-to-treat was reported in 119 (55.3%) cases; of these 103 (86.6%) underwent cardiac procedures. Seventy-nine patients (36.7%) opted for comfort care. On follow-up (median 10 (1-120) months), 106 patients (21%) were alive. Parental choice of intention-to-.treat or comfort care was the only factor that impacted survival on follow-up. CONCLUSIONS: Prenatal diagnosis of functionally univentricular hearts was associated with overall low survival status on follow-up due to parental decisions on not to continue pregnancy or non-intention-to-treat after birth. Early detection of these complex defects by improved prenatal screening can enhance parental options and reduce resource impact in low-and-middle-income countries.

Prenatal diagnosis of asplenia syndrome with sliding hiatus hernia in a fetus.

We report a case of right isomerism with a complex congenital heart disease associated with hiatus hernia in a 19-week-old fetus with relevant review of literature. This report highlights the importance of having a proper checklist for prenatal identification of extracardiac manifestations of isomerism syndromes. This will enable us to provide an effective family-centered counseling for perinatal management of these complex lesions. To our knowledge, prenatal sonographic detection of a sliding hiatal hernia in a fetus with right isomerism has not been reported previously.

Right aortic arch, bilateral ductus arteriosus, and anomalous origin of left pulmonary artery from innominate artery in a fetus with normal intracardiac anatomy.

Right aortic arch (RAA) with right ductus arteriosus (RDA) is one of the least frequently diagnosed cardiac abnormalities prenatally. We describe here a case of RAA, bilateral ductus arteriosus (BDA), and anomalous origin of left pulmonary artery from innominate artery in a fetus with normal intracardiac anatomy.

Prenatal diagnosis and planned peri-partum care as a strategy to improve pre-operative status in neonates with critical CHDs in low-resource settings: a prospective study.

BACKGROUND: Prenatal diagnosis and planned peri-partum care is an unexplored concept for care of neonates with critical CHDs in low-middle-income countries. OBJECTIVE: To report the impact of prenatal diagnosis on pre-operative status in neonates with critical CHD. METHODS: Prospective observational study (January 2017-June 2018) in tertiary paediatric cardiac facility in Kerala, India. Neonates (<28 days) with critical CHDs needing cardiac interventions were included. Pre-term infants (<35 weeks) and those without intention to treat were excluded. Patients were grouped into those with prenatal diagnosis and diagnosis after birth. Main outcome measure was pre-operative clinical status. RESULTS: Total 119 neonates included; 39 (32.8%) had prenatal diagnosis. Eighty infants (67%) underwent surgery while 32 (27%) needed catheter-based interventions. Pre-operative status was significantly better in prenatal group; California modification of transport risk index of physiological stability (Ca-TRIPS) score: median 6 (0-42) versus 8 (0-64); p < 0.001; pre-operative assessment of cardiac and haemodynamic status (PRACHS) score: median 1 (0-4) versus 3 (0-10), p < 0.001. Age at cardiac procedure was earlier in prenatal group (median 5 (1-26) versus 7 (1-43) days; p = 0.02). Mortality occurred in 12 patients (10%), with 3 post-operative deaths (2.5%). Pre-operative mortality was higher in postnatal group (10% versus 2.6%; p = 0.2) of which seven (6%) died due to suboptimal pre-operative status precluding surgery. CONCLUSION: Prenatal diagnosis and planned peri-partum care had a significant impact on the pre-operative status in neonates with critical CHD in a low-resource setting.

Early Neurodevelopmental Outcomes After Corrective Cardiac Surgery In Infants.

OBJECTIVE: To assess neurodevelopmental status in Indian infants undergoing corrective surgery for congenital heart disease (CHD) and to analyze factors associated with neurodevelopmental delay. DESIGN: Cross-sectional study. SETTING: Tertiary-care pediatric cardiology facility. PARTICIPANTS: Consecutive infants undergoing corrective surgery for CHD (January 2013 -December 2014). Palliative procedures, and patients with known genetic syndromes were excluded. MAIN OUTCOME MEASURES: Neurodevelopmental evaluation 3 months, and one year after surgery using Developmental Assessment Scales for Indian Infants (DASII); scores were categorized as delayed if ≤70. RESULTS: Of the 162 children enrolled, delayed PDI and MDI scores were observed in 33.5% and 19.6% of patients at 3 months, respectively; this reduced to 14.5%on 1-year follow-up. On multivariate analysis, delayed PDI outcome at one year was predicted by early term birth and one-year postoperative head circumference Z-score <-2. Delayed MDI was associated with higher mean perfusion pressure on cardiopulmonary bypass. Cardiac diagnosis and peri-operative factors did not impact neurodevelopmental outcomes. CONCLUSIONS: Neurodevelopmental status is delayed in 14.5% of infants one year after corrective infant heart surgery.

Clinical presentation, management, and postnatal outcomes of fetal tachyarrhythmias: A 10-year single-center experience.

BACKGROUND: Limited information is available regarding the prevalence and outcomes of fetal tachyarrhythmias from the developing countries. AIMS: This study aims to report referral patterns, management protocols, and pregnancy outcomes of fetuses with tachyarrhythmias reporting to a single center in South India. METHODS: All fetuses with documented sustained fetal tachyarrhythmia during the study period (2008-2017) were included. Arrhythmia characterization and hemodynamic evaluation were done using fetal echocardiography. Patients were grouped into supraventricular tachycardia (SVT) and atrial flutter (AF) groups. Patient characteristics, transplacental therapy (TPT), pregnancy, and postnatal outcomes were analyzed. RESULTS: Total of 19 fetuses included; 11 had SVT and 8 AF. Mean gestational age at referral was higher for AF (32.5 ± 3.2 vs. 29.6 ± 3.3 weeks; P = 0.05). Hydrops fetalis was present 8 (42%) fetuses; 4 in each group. TPT was instituted in 18 fetuses; 12 (66.7%) received combination therapy; 4 (21%) received direct fetal therapy. Eighteen fetuses (91%) were born alive with one intrauterine death in a fetus with SVT and severe hydrops. Seven (87.5%) fetuses with hydrops survived. Twelve patients (66.7%) were delivered in sinus rhythm. Six babies (33.3%) had tachycardia at birth requiring anti-arrhythmic therapy. All patients survived the neonatal period. Duration of trans-placental therapy (3.8 + 3.3 vs. 7.3 + 3.4 weeks) was shorter in the AF group. CONCLUSIONS: Aggressive TPT using combination of drugs achieves excellent pregnancy and postnatal outcomes in fetuses with tachyarrhythmia. Early diagnosis and prompt referral before hemodynamic decompensation is critical for ensuring optimal outcomes.

Management of undernutrition and failure to thrive in children with congenital heart disease in low- and middle-income countries.

Poor growth with underweight for age, decreased length/height for age, and underweight-for-height are all relatively common in children with CHD. The underlying causes of this failure to thrive may be multifactorial, including innate growth potential, severity of cardiac disease, increased energy requirements, decreased nutritional intake, malabsorption, and poor utilisation of absorbed nutrition. These factors are particularly common and severe in low- and middle-income countries. Although nutrition should be carefully assessed in all patients, failure of growth is not a contraindication to surgical repair, and patients should receive surgical repair where indicated as soon as possible. Close attention should be paid to nutritional support - primarily enteral feeding, with particular use of breast milk in infancy - in the perioperative period and in the paediatric ICU. This nutritional support requires specific attention and allocation of resources, including appropriately skilled personnel. Thereafter, it is essential to monitor growth and development and to identify causes for failure to catch-up or grow appropriately.