Clarifying the Anatomy of Tetralogy of Fallot with S-shaped Ascending Aorta.

We recently encountered several cases of tetralogy of Fallot with an abnormally oriented S-shaped ascending aorta. In this retrospective study, we sought to clarify morphology of this unusual under-recognized variant. Databases were reviewed to identify all patients with tetralogy of Fallot having an S-shaped ascending aorta. Computed tomographic angiography was used for the assessment of cardiac morphology. Out of the 21 patients, 18 (86%) had a right aortic arch, 2 (9%) had a left aortic arch, and the remaining patient (5%) had a double aortic arch. Patients with a right aortic arch, compared to age and sex-matched patients with a right aortic arch but normally oriented ascending aorta, had lesser aortic override (29.3 ± 14% vs 54.8 ± 13.2%; p = 0.0001) and a wider ascending aorta (25.2 ± 6.9 vs 18.0 ± 3.2 mm; p = 0.0003). The S-shaped ascending aorta was located posteriorly, with a higher sterno-aortic distance (25.5 ± 7.7 vs 9.9 ± 4.5 mm; p = 0.0001). The ascending aorta among patients with tortuosity was longer (4.12 ± 1.7 vs 3.07 ± 0.82, p = 0.03) but with similar tortuosity index (1.22 ± 0.19 vs 1.15 ± 0.17, p = 0.23). Of the cases with right aortic arch and S-shaped ascending aorta, 16 (89%) had extrinsic compression of the right pulmonary artery (p = 0.0001), while 7 (39%) had crossed pulmonary arteries (p = 0.008), with no such findings among those with normally oriented ascending aorta. Tetralogy of Fallot with an S-shaped ascending aorta is a variant with lesser aortic override and a more posteriorly located ascending aorta. Compression of the right pulmonary artery and crossed pulmonary arteries is frequent in the presence of a right-sided aortic arch. These findings have important implications for optimal diagnosis and surgical repair.

Newborns with congenital complete heart block: Advice for perinatal care providers.

Congenital complete heart block (CCHB) is a rare, but a potentially life-threatening manifestation of autoimmune diseases in neonates. Bradycardia in CCHB can be misdiagnosed as foetal distress in utero and thus precipitating a Caesarean section. We report a case series of three neonates with bradycardia without any electrolyte abnormalities and structurally normal hearts with favourable outcomes.

Pulmonary hypertension.

Pulmonary hypertension encompasses a range of conditions directly or indirectly leading to elevated pressures within the pulmonary arteries. Five main groups of pulmonary hypertension are recognized, all defined by a mean pulmonary artery pressure of >20 mmHg: pulmonary arterial hypertension (rare), pulmonary hypertension associated with left-sided heart disease (very common), pulmonary hypertension associated with lung disease (common), pulmonary hypertension associated with pulmonary artery obstructions, usually related to thromboembolic disease (rare), and pulmonary hypertension with unclear and/or multifactorial mechanisms (rare). At least 1% of the world's population is affected, with a greater burden more likely in low-income and middle-income countries. Across all its forms, pulmonary hypertension is associated with adverse vascular remodelling with obstruction, stiffening and vasoconstriction of the pulmonary vasculature. Without proactive management this leads to hypertrophy and ultimately failure of the right ventricle, the main cause of death. In older individuals, dyspnoea is the most common symptom. Stepwise investigation precedes definitive diagnosis with right heart catheterization. Medical and surgical treatments are approved for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. There are emerging treatments for other forms of pulmonary hypertension; but current therapy primarily targets the underlying cause. There are still major gaps in basic, clinical and translational knowledge; thus, further research, with a focus on vulnerable populations, is needed to better characterize, detect and effectively treat all forms of pulmonary hypertension.

2023 World Heart Federation guidelines for the echocardiographic diagnosis of rheumatic heart disease.

Rheumatic heart disease (RHD) is an important and preventable cause of morbidity and mortality among children and young adults in low-income and middle-income countries, as well as among certain at-risk populations living in high-income countries. The 2012 World Heart Federation echocardiographic criteria provided a standardized approach for the identification of RHD and facilitated an improvement in early case detection. The 2012 criteria were used to define disease burden in numerous epidemiological studies, but researchers and clinicians have since highlighted limitations that have prompted a revision. In this updated version of the guidelines, we incorporate evidence from a scoping review, an expert panel and end-user feedback and present an approach for active case finding for RHD, including the use of screening and confirmatory criteria. These guidelines also introduce a new stage-based classification for RHD to identify the risk of disease progression. They describe the latest evidence and recommendations on population-based echocardiographic active case finding and risk stratification. Secondary antibiotic prophylaxis, echocardiography equipment and task sharing for RHD active case finding are also discussed. These World Heart Federation 2023 guidelines provide a concise and updated resource for clinical and research applications in RHD-endemic regions.

COVID-19 associated renal artery stenosis in infancy - A report of two cases.

Organ-specific vasculitis is an uncommon, delayed complication of COVID-19 infection. It is usually seen in mildly symptomatic or asymptomatic patients. Underlying endothelitis is the most likely pathophysiological mechanism for such a manifestation. We report two infants with renal artery stenosis, most likely consequent to COVID-19 infection.

Identifying Challenges and Potential Solutions for Sustainable Kidney Nutrition Care Delivery in Selected Asian Countries.

BACKGROUND: Recent surveys highlight gross workforce shortage of dietitians in global kidney health and significant gaps in renal nutrition care, with disparities greater in low/low-middle income countries. OBJECTIVE: This paper narrates ground experiences gained through the Palm Tocotrienols in Chronic Hemodialysis (PaTCH) project on kidney nutrition care scenarios and some Asian low-to-middle-income countries namely Bangladesh, India, and Malaysia. METHOD: Core PaTCH investigators from 3 universities (USA and Malaysia) were supported by their postgraduate students (n = 17) with capacity skills in kidney nutrition care methodology and processes. This core team, in turn, built capacity for partnering hospitals as countries differed in their ability to deliver dietitian-related activities for dialysis patients. RESULTS: We performed a structural component analyses of PaTCH affiliated and nonaffiliated (Myanmar and Indonesia) countries to identify challenges to kidney nutrition care. Deficits in patient-centered care, empowerment processes and moderating factors to nutrition care optimization characterized country comparisons. Underscoring these factors were some countries lacked trained dietitians whilst for others generalist dietitians or nonclinical nutritionists were providing patient care. Resolution of some challenges in low-to-middle-income countries through coalition networking to facilitate interprofessional collaboration and task sharing is described. CONCLUSIONS: We perceive interprofessional collaboration is the way forward to fill gaps in essential dietitian services and regional-based institutional coalitions will facilitate culture-sensitive capacity in building skills. For the long-term an advanced renal nutrition course such as the Global Renal Internet Course for Dietitians is vital to facilitate sustainable kidney nutrition care.

Pulmonary arterial compliance in patients of CHD with increased pulmonary blood flow.

INTRODUCTION: Pulmonary arterial compliance, the dynamic component of pulmonary vasculature, remains inadequately studied in patients with left to right shunts. We sought to study the pulmonary arterial compliance in patients with left to right shunt lesions and its utility in clinical decision-making. MATERIALS AND METHODS: In this single-centre retrospective study, we reviewed cardiac catheterisation data of consecutive patients of left to right shunt lesions catheterised over one year. In addition to the various other parameters, pulmonary arterial compliance was calculated, as indexed pulmonary flow (Qpi) / (Heart rate × pulse pressure in the pulmonary artery). RC time was also calculated, as the product of pulmonary arterial compliance and pulmonary vascular resistance index. Patients were divided into "operable," "borderline," and "inoperable" based on the decision of the treating team, and the pulmonary arterial compliance values were evaluated in these groups to study if it can be utilised to refine the operability decision. RESULTS: 298 patients (Median age 16 years, 56% <18 years) with various acyanotic shunt lesions were included. Overall, the pulmonary arterial compliance varied with Qpi, pulmonary artery mean pressure, and pulmonary vascular resistance index, but did not vary with age, type of lesion, or transpulmonary gradients. The median pulmonary arterial compliance in patients with normal pulmonary artery pressure (Mean pulmonary artery pressure less than 20 mmHg) was 4.1 ml/mmHg/m2 (IQR 3.2). The median pulmonary arterial compliance for operable patients was 2.67 ml/mmHg/m2 (IQR 2.2). Median pulmonary arterial compliance was significantly lower in both inoperable (0.52 ml/mmHg/m2, IQR 0.34) and borderline (0.80 ml/mmHg/m2, IQR 0.36) groups when compared to operable patients (p < 0.001). A pulmonary arterial compliance value lower than 1.18 ml/mmHg/m2 identified inoperable patients with high sensitivity and specificity (95%, AUC 0.99). However, in borderline cases, assessment by this value did not agree with empirical clinical assessment.The median RC time for the entire study population was 0.47 S (IQR 0.30). RC time in operable patients was significantly lower than that in the inoperable patients (Median 0.40 IQR 0.23 in operable, 0.73 0.25 in inoperable patients (p < 0.001). CONCLUSIONS: Addition of pulmonary arterial compliance to the routine haemodynamic assessment of patients with shunt lesions may improve our understanding of the pulmonary circulation and may have clinical utility.

Enzobiotics-A Novel Therapy for the Elimination of Uremic Toxins in Patients with CKD (EETOX Study): A Multicenter Double-Blind Randomized Controlled Trial.

Design, participants, setting, and measurements: Predialysis adult participants with chronic kidney disease (CKD) and mean estimated glomerular filtration rate (eGFR) <45 mL/min per 1.73 m2) were recruited in 2019 to a multicentric double-blinded randomized controlled trial of enzobiotic therapy (synbiotics and proteolytic enzymes) conducted over 12 weeks. The primary objective was to evaluate the efficacy and safety of enzobiotics in reducing the generation of p-cresol sulfate (PCS) and indoxyl sulfate (IS), stabilizing renal function, and improving quality of life (QoL), while the secondary objective was to evaluate the feasibility of the diagnostic prediction of IS and PCS from CKD parameters. Results: Of the 85 patients randomized (age 48.76 years, mean eGFR 23.24 mL/min per 1.73 m2 in the placebo group; age 54.03 years, eGFR 28.93 mL/min per 1.73 m2 in the enzobiotic group), 50 completed the study. The absolute mean value of PCS increased by 12% from 19 µg/mL (Day 0) to 21 µg/mL (Day90) for the placebo group, whereas it decreased by 31% from 23 µg/mL (Day 0) to 16 µg/mL (Day 90) for the enzobiotic group. For IS, the enzobiotic group showed a decrease (6.7%) from 11,668 to 10,888 ng/mL, whereas the placebo group showed an increase (8.8%) from 11,462 to 12,466 ng/mL (Day 90). Each patient improvement ratio for Day 90/Day 0 analysis showed that enzobiotics reduced PCS by 23% (0.77, p = 0.01). IS levels remained unchanged. In the placebo group, PCS increased by 27% (1.27, p = 0.14) and IS increased by 20% (1.20, p = 0.14). The proportion of individuals beyond the risk threshold for PCS (>20 µg/mL) was 53% for the placebo group and 32% for the enzobiotic group. The corresponding levels for IS risk (threshold >20,000 ng/mL) were 35% and 24% for the placebo and enzobiotic groups, respectively. In the placebo group, eGFR decreased by 7% (Day 90) but remained stable (1.00) in the enzobiotic group. QoL as assessed by the adversity ratio decreased significantly (p = 0.00), highlighting an improvement in the enzobiotic group compared to the placebo group. The predictive equations were as follows: PCS (Day 0 = −5.97 + 0.0453 PC + 2.987 UA − 1.310 Creat; IS (Day 0) = 756 + 1143 Creat + 436.0 Creat2. Conclusion: Enzobiotics significantly reduced the PCS and IS, as well as improved the QoL.

Effect of Dietary Phosphorous Restriction on Fibroblast Growth 2 Factor-23 and sKlotho Levels in Patients with Stages 1-2 Chronic Kidney Disease.

Hyperphosphatemia has emerged as an independent risk factor for cardiovascular disease (CVD) and excess mortality in chronic kidney disease (CKD). The study evaluates the effect of dietary phosphorus (Ph) restriction (DPhR) at an early stage as a therapeutic strategy for delaying CKD progression and preventing CVD. Methods: This was a one-year interventional study conducted on 79 stage 1 and 2 CKD patients. The dietary phosphorus intake (DPhI), fibroblast growth factor-23 (FGF-23), sKlotho and serum phosphorous (SP) levels were analyzed. Patients were categorized into two groups based on their DPhI, recommended DPhI (RPhI) with <1000 mg/day of dietary phosphorous (dietary counselling) and high DPhI (HPhI) with >1000 mg/day (dietary intervention). For comparisons of differences between the two groups, independent t-test; for correlation analysis, Pearson correlation; for identifying the significant associated risk factors for CKD, binary logistic regression analysis and for comparing the means across the three visits, repeated measures ANOVA were used for statistical analysis. Results: The mean age and glomerular filtration rate (GFR) of CKD patients were 38 ± 12 years and 82.95 ± 16.93 mL/min/1.73 m2. FGF-23, SP, dietary protein and DPhI were significantly higher and sKlotho was significantly lower in HPhI group than RPhI group. In HPhI group; GFR, sKlotho, SP and FGF-23 correlated significantly with DPhI. Risk factors with a statistical bearing on the progression of CKD were animal-based diet, family history of CKD and hypertension. In HPhI group; GFR, DPhI, SP and FGF-23 levels significantly improved within the intervention period whereas a significant increase in sKlotho levels was observed in both the groups. Conclusion: Restricting DPhI emerged as a favorable therapeutic strategy for CKD patients for improving renal function and controlling hyperphosphatemia. The results of the present study may serve as the basis for future interventional studies with dietary phosphate restriction in the initial stages of CKD that would preserve renal function. Highlights: Early restriction of dietary phosphorus prevents decline in eGFR, elevation in FGF23 and increases Klotho levels.

Neurodevelopmental outcomes in children with cyanotic congenital heart disease following open heart surgery.

Background: Neurodevelopmental abnormalities are common in congenital heart disease (CHD), more so in cyanotic CHDs. Perioperative factors have been known to affect neurodevelopmental outcomes. Aim: We aimed to determine the neurodevelopmental outcomes following open-heart surgery in cyanotic CHD. Methods: In this prospective observational study, eligible infants and children ≤21 months with cyanotic CHD planned for open-heart surgery underwent preoperative neurodevelopmental assessment using Developmental Assessment Scale for Indian Infants (DASII) to look for any motor and/or mental delay. A second neurodevelopmental assessment was performed after 9 months ± 2 weeks of cardiac surgery. Follow-up DASII was conducted through interactive video conferencing in 23 of 60 patients due to COVID-19 pandemic. The univentricular and biventricular repair groups were compared in terms of their neurodevelopmental outcomes. Perioperative factors were compared between neurodevelopmental "delay" and "no delay" groups. Results: Of the 89 children enrolled, preoperative motor and mental delay were present in 29 and 24 children, respectively. Follow-up DASII could be performed in 60 children. At follow-up, motor delay was present in seven and mental delay in four children. Overall, there was a significant improvement in both motor and mental developmental quotient at follow-up. There was no significant difference in either motor or mental domains between univentricular and biventricular groups. Among the perioperative variables, only the postoperative length of stay in intensive care unit was significantly different between neurodevelopmental "delay" and "no delay" groups (P = 0.04). Conclusion: Neurodevelopmental delay occurred substantially among unoperated children with cyanotic CHD. The neurodevelopmental status improved significantly following open-heart surgery among the survivors. Delay was associated with length of stay in intensive care following cardiac surgery.

Utility of pulse-oximetry screening in newborns with nonductus-dependent cyanotic congenital heart defects: A reason to alarm?

Objectives: We aimed to compare the performance of pulse-oximetry screening in detecting nonductus-dependent cyanotic congenital heart defects (CCHDs). Methods: In a prospective cross-sectional study, we recorded post ductal saturation of neonates (<48 h old) born at a community hospital in northern India. Subsequently, all underwent clinical examination and echocardiogram by a trained cardiologist. A saturation <95% was considered a "failed" screen. Results: Ten neonates were identified to have nonductus-dependent CCHD on echocardiogram, five of whom had passed pulse-oximetry screen. This translated to a sensitivity of 50% (95% confidence interval [CI] 23.7%-76.3%) and a positive predictive value of 0.08 (95% CI 0.03-0.2), both of which were significantly less compared to that in ductus-dependent congenital heart defect. Conclusions: Up to half of the nonductus-dependent CCHD may be missed if screened only using pulse oximetry. Parents should not be reassured regarding the absence of CCHD only based on a "pass" in pulse-oximetry screening.

Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial).

BACKGROUND: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. METHODS: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. RESULTS: The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. CONCLUSIONS: Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020).

A Century With Craniopagus Twin Separation Surgeries: Nihilism to Optimism.

Craniopagus conjoined twins are extremely rare, reported 1 in 2.5 million live births. To date, 62 separation attempts in 69 well-documented cases of craniopagus twins have been made. Of these, 34 were performed in a single-stage approach, and 28 were attempted in a multistage approach. One or both twins died of massive intraoperative blood loss and cardiac arrest in 14 cases. We report our surgical experience with conjoined craniopagus twins (JB) with type III total vertical joining and shared circumferential/circular sinus with left-sided dominance. A brief review of the literature is also provided. In our twins, the meticulous preoperative study and planning by the multidisciplinary team consisting of 125-member, first-staged surgical separation consisted of creation of venous conduit to bypass part of shared circumferential sinus and partial hemispheric disconnection. Six weeks later, twin J manifested acute cardiac overload because of one-way fistula development from blocked venous bypass graft necessitating emergency final separation surgery. Unique perioperative issues were abnormal anatomy, hemodynamic sequelae from one-way fistula development after venous bypass graft thrombosis, cardiac arrest after massive venous air embolism requiring prolonged cardiopulmonary resuscitation, and return of spontaneous circulation at 15 minutes immediately after separation. This is the first Indian craniopagus separation surgery in a complex total vertical craniopagus twin reported by a single-center multidisciplinary team. Both twins could be sent home, but one remained severely handicapped. Adequate perioperative planning and multidisciplinary team approach are vital in craniopagus twin separation surgeries.

Early repolarization syndrome, epilepsy, and atrial fibrillation in a young girl with novel KCND3 mutation managed with quinidine.

A 6-year-old girl presented with a difficult to control epilepsy syndrome. On evaluation, additional presyncope episodes associated with polymorphic ventricular tachycardia were also noted. A diagnosis of early repolarization syndrome (ERS) was made with an early repolarization pattern on electrocardiogram, documented VT episodes, and clinical presyncope (proposed Shanghai score 7). Paroxysmal atrial fibrillation (AF) was also noted on 24-h Holter recordings. The child was stabilized with isoprenaline infusion and was later discharged with arrhythmia control on quinidine and cilostazol. The genetic evaluation revealed a potassium channel KCND3 gene missense mutation. The case highlights the association of epilepsy syndrome and AF with ERS; the possible association of KCND3 gene mutation with a malignant phenotype; and management issues in a small child.

Effect of Yoga on Clinical Outcomes and Quality of Life in Patients With Vasovagal Syncope (LIVE-Yoga).

OBJECTIVES: This study aims to determine the impact of yoga as an adjunct to standard therapy versus standard therapy alone on the symptomatic burden in patients with recurrent vasovagal syncope (VVS). BACKGROUND: There is a significant reduction in the quality of life (QoL) of patients with recurrent VVS. Existing management therapies have been largely ineffective. Recent trials have demonstrated the efficacy of yoga in diseases with autonomic imbalance, suggesting its possible utility in VVS. METHODS: Patients with recurrent VVS were randomized to receive either a specialized yoga training program in addition to current guideline-based therapy (intervention arm, group 1) or current guideline-based therapy alone (control arm, group 2). The primary outcome was a composite of the number of episodes of syncope and presyncope at 12 months. Secondary outcomes included QoL assessment by World Health Organization Quality of Life Brief Field questionnaire (WHOQoL-BREF) scores and Syncope Functional Status Questionnaire scores at 12 months, head up tilt test, and heart rate variability at 6 weeks. RESULTS: A total of 55 patients underwent randomization. The mean number of syncopal or presyncopal events at 12 months was 0.7 ± 0.7 in the intervention arm compared to 2.52 ± 1.93 in the control arm (P < 0.01). In the intervention arm, 13 (43.3%) patients remained free of events versus 4 (16.0%) patients in the control arm (P = 0.02). QoL at 12 months showed significant improvement of all Syncope Functional Status Questionnaire scores and 2 domains of WHOQoL-BREF scores (P < 0.05). CONCLUSIONS: Yoga as adjunctive therapy is superior to standard therapy alone in reducing the symptomatic burden and improving QoL in patients with recurrent VVS.