Capacity building for pediatric neuro-oncology in Pakistan- a project by my child matters program of Foundation S.

Introduction: Initiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant. Methods: We aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints. Results: A total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three. Discussion: The initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

Arrhythmogenic cardiomyopathy and differential diagnosis with physiological right ventricular remodelling in athletes using cardiovascular magnetic resonance.

To describe the overlap between structural abnormalities typical of arrhythmogenic right ventricular cardiomyopathy (ARVC) and physiological right ventricular adaptation to exercise and differentiate between pathologic and physiologic findings using CMR. We compared CMR studies of 43 patients (mean age 49 ± 17 years, 49% males, 32 genotyped) with a definitive diagnosis of ARVC with 97 (mean age 45 ± 16 years, 61% males) healthy athletes. CMR was abnormal in 37 (86%) patients with ARVC, but only 23 (53%) fulfilled a major or minor CMR criterion according to the TFC. 7/20 patients who did not fulfil any CMR TFC showed pathological finding (RV RWMA and fibrosis in the LV or LV RWMA). RV was affected in isolation in 17 (39%) patients and 18 (42%) patients showed biventricular involvement. Common RV abnormalities included RWMA (n = 34; 79%), RV dilatation (n = 18; 42%), RV systolic dysfunction (≤ 45%) (n = 17; 40%) and RV LGE (n = 13; 30%). The predominant LV abnormality was LGE (n = 20; 47%). 22/32 (69%) patients exhibited a pathogenic variant: PKP2 (n = 17, 53%), DSP (n = 4, 13%) and DSC2 (n = 1, 3%). Sixteen (16%) athletes exceeded TFC cut-off values for RV volumes. None of the athletes exceeded a RV/LV end-diastolic volume ratio > 1.2, nor fulfilled TFC for impaired RV ejection fraction. The majority (86%) of ARVC patients demonstrate CMR abnormalities suggestive of cardiomyopathy but only 53% fulfil at least one of the CMR TFC. LV involvement is found in 50% cases. In athletes, an RV/LV end-diastolic volume ratio > 1.2 and impaired RV function (RVEF ≤ 45%) are strong predictors of pathology.

Prevalence and clinical correlates of exercise-induced ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

Exercise has a deleterious effect on the phenotypic expression of arrhythmogenic right ventricular cardiomyopathy (ARVC) and increases the risk of sudden death. The aim of the study was to determine the prevalence and correlates of exercise-induced arrhythmias during exercise tolerance test (ETT) in patients with ARVC. Between 2010 and 2019, 30 (47% males, mean age 42 ± 12 years) consecutive patients with a definite diagnosis of ARVC underwent a full genotypic and phenotypic characterization at our center. Exercise-induced arrhythmic response (EIAR) was defined by the development of complex or repetitive ventricular arrhythmias after stage 2 of exercise. A heart rate ≥ 85% of predicted was achieved by 23 (77%) patients. In 16 (53%) cases, a desmosomal pathogenic variant was found [most commonly PKP2 (n = 7) and DSP (n = 3)]. In 12 (40%) cases, an EIAR was observed. In 2 (6%) patients, ETT was interrupted due to the onset of ventricular tachycardia (sustained with a LBBB/inferior axis pattern in one case, and non-sustained LBBB/superior axis pattern in the other). Mean body surface area (BSA)-indexed left ventricular (LV) end-diastolic volumes (EDV) were higher in the EIAR group (92 ± 12 ml/m2 vs 80 ± 7 ml/m2, p = 0.002), as well as right ventricular EDV/BSA (110 ± 18 ml/m2 vs 91 ± 27 ml/m2, p = 0.04). Subepicardial/mid-wall LV late gadolinium enhancement (LGE) was more common in the EIAR group (67% vs 22%, p = 0.01). ARVC patients commonly exhibit exercise-induced ventricular arrhythmias. Patients with more significant RV remodeling and LV involvement (based on the presence of LV dilatation and LGE) appear more susceptible to exercise-induced arrhythmias.

Cardiac magnetic resonance in patients with ARVC and family members: the potential role of native T1 mapping.

Left ventricular (LV) involvement in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is not evaluated in the revised Task Force Criteria, possibly leading to underdiagnosis. This study explored the diagnostic role of myocardial native T1 mapping in patients with ARVC and their first-degree relatives. Thirty ARVC patients (47% males, mean age 45 ± 27 years) and 59 first-degree relatives not meeting diagnostic criteria underwent CMR with native T1 mapping. C MR was abnormal in 26 (87%) patients with ARVC. The right ventricle was affected in isolation in 13 (43%) patients. Prior to T1 mapping assessment, 2 (7%) patients exhibited isolated LV involvement and 11 (36%) patients showed features of biventricular disease. Left ventricular involvement was manifest as detectable LV late gadolinium enhancement (LGE) in 12 out of 13 cases. According to pre-specified inter-ventricular septal (IVS) T1 mapping thresholds, 11 (37%) patients revealed raised native T1 values including 5 out of the 17 patients who would otherwise have been classified as exhibiting a normal LV by conventional imaging parameters. Native septal T1 values were elevated in 22 (37%) of the 59 first-degree relatives included. Biventricular involvement is commonly observed in ARVC; native myocardial T1 values are raised in more than one third of patients, including a significant proportion of cases that would have been otherwise classified as exhibiting a normal LV using conventional CMR techniques. The significance of abnormal T1 values in first-degree relatives at risk will need validation through longitudinal studies.

The electrocardiogram in the diagnosis and management of patients with hypertrophic cardiomyopathy.

In an era of rapid technological development and evolving diagnostic possibilities, the electrocardiogram (ECG) is living an authentic "renaissance" in myocardial diseases. To date, the ECG remains an irreplaceable first step when evaluating patients with hypertrophic cardiomyopathy (HCM) and an abnormal ECG may be the only manifestation of disease at an early stage. In some instances, specific electrical anomalies may differentiate HCM from phenocopies such as cardiac amyloidosis and glycogen storage diseases. The exponential growth in knowledge of the complexity of HCM has led to new challenges in terms of early identification of the disease, differential diagnosis, risk stratification, and development of targeted therapies. In this scenario, the apparently "old fashioned" ECG and the array of ECG-based techniques, ranging from Holter monitoring and loop recorders to exercise testing, are as contemporary as ever. In the present review, we discuss the current role of the ECG in the diagnosis and management of HCM, focusing on various clinical settings where its appropriate use and interpretation can make a difference.

Anterior T-Wave Inversion in Young White Athletes and Nonathletes: Prevalence and Significance.

BACKGROUND: Anterior T-wave inversion (ATWI) on electrocardiography (ECG) in young white adults raises the possibility of cardiomyopathy, specifically arrhythmogenic right ventricular cardiomyopathy (ARVC). Whereas the 2010 European consensus recommendations for ECG interpretation in young athletes state that ATWI beyond lead V1 warrants further investigation, the prevalence and significance of ATWI have never been reported in a large population of asymptomatic whites. OBJECTIVES: This study investigated the prevalence and significance of ATWI in a large cohort of young, white adults including athletes. METHODS: Individuals 16 to 35 years of age (n = 14,646), including 4,720 females (32%) and 2,958 athletes (20%), were evaluated by using a health questionnaire, physical examination, and 12-lead ECG. ATWI was defined as T-wave inversion in ≥2 contiguous anterior leads (V1 to V4). RESULTS: ATWI was detected in 338 individuals (2.3%) and was more common in women than in men (4.3% vs. 1.4%, respectively; p < 0.0001) and more common among athletes than in nonathletes (3.5% vs. 2.0%, respectively; p < 0.0001). T-wave inversion was predominantly confined to leads V1 to V2 (77%). Only 1.2% of women and 0.2% of men exhibited ATWI beyond V2. No one with ATWI fulfilled diagnostic criteria for ARVC after further evaluation. During a mean follow-up of 23.1 ± 12.2 months none of the individuals with ATWI experienced an adverse event. CONCLUSIONS: ATWI confined to leads V1 to V2 is a normal variant or physiological phenomenon in asymptomatic white individuals without a relevant family history. ATWI beyond V2 is rare, particularly in men, and may warrant investigation.

Clinical Differentiation Between Physiological Remodeling and Arrhythmogenic Right Ventricular Cardiomyopathy in Athletes With Marked Electrocardiographic Repolarization Anomalies.

BACKGROUND: Physiological cardiac adaptation to regular exercise, including biventricular dilation and T-wave inversion (TWI), may create diagnostic overlap with arrhythmogenic right ventricular cardiomyopathy (ARVC). OBJECTIVES: The goal of this study was to assess the accuracy of diagnostic criteria for ARVC when applied to athletes exhibiting electrocardiographic TWI and to identify discriminators between physiology and disease. METHODS: The study population consisted of athletes with TWI (n = 45), athletes without TWI (n = 35), and ARVC patients (n = 35). Subjects underwent electrocardiography (ECG), signal-averaged electrocardiography (SAECG), echocardiography, cardiac magnetic resonance imaging (CMRI), Holter monitoring, and exercise testing. RESULTS: There were no electrical, structural, or functional cardiac differences between athletes exhibiting TWI and athletes without TWI. When athletes were compared with ARVC patients, markers of physiological remodeling included early repolarization, biphasic TWI, voltage criteria for right ventricular (RV) or left ventricular hypertrophy, and symmetrical cardiac enlargement. Indicators of RV pathology included the following: syncope; Q waves or precordial QRS amplitudes <1.8 mV; 3 abnormal SAECG parameters; delayed gadolinium enhancement, RV ejection fraction ≤45%, or wall motion abnormalities at CMRI; >1,000 ventricular extrasystoles (or >500 non-RV outflow tract) per 24 h; and symptoms, ventricular tachyarrhythmias, or attenuated blood pressure response during exercise. Nonspecific parameters included the following: prolonged QRS terminal activation; ≤2 abnormal SAECG parameters; RV dilation without wall motion abnormalities; RV outflow tract ectopy; and exercise-induced T-wave pseudonormalization. CONCLUSIONS: TWI and balanced biventricular dilation are likely to represent benign manifestations of training in asymptomatic athletes without relevant family history. Diagnostic criteria for ARVC are nonspecific in such individuals. Comprehensive testing using widely available techniques can effectively differentiate borderline cases.

Comparison of three current sets of electrocardiographic interpretation criteria for use in screening athletes.

BACKGROUND: An increasing number of sporting bodies report unacceptably high levels of false-positive ECGs when undertaking pre-participation cardiac screening. To address this issue, modified ECG interpretation criteria have become available for use within athletes. OBJECTIVE: This study assessed the accuracy of the new 2014 'Refined Criteria' against the 2013 Seattle Criteria and the 2010 European Society of Cardiology (ESC) recommendations in a cohort of Arabic, black and Caucasian athletes. METHODS: 2491 male athletes (1367 Arabic, 748 black and 376 Caucasian) undertook pre-participation screening including a 12-lead ECG, with further investigation(s) upon indication. RESULTS: Ten athletes (0.4%) were identified with cardiac pathology; seven with hypertrophic cardiomyopathy (HCM; five black and two Arabic) and three Arabs with Wolff-Parkinson-White syndrome (WPW). All three ECG criteria were 100% sensitive identifying all cases of HCM and WPW. The 2014 Refined Criteria reduced (p<0.0001) the prevalence of an abnormal ECG to 5.3% vs 11.6% (Seattle Criteria) and 22.3% (2010 ESC recommendations). The 2014 Refined Criteria significantly (p<0.0001) improved specificity (94.0%) across all ethnicities compared with the Seattle Criteria (87.5%) and ESC recommendations (76.6%). Black athletes continue to present a higher prevalence (p<0.0001) of abnormal ECGs compared with Arabic and Caucasian athletes (10% vs 3.6% and 2.1%). CONCLUSIONS: The 2014 Refined Criteria for athlete ECG interpretation outperformed both the 2013 Seattle Criteria and the 2010 ESC recommendations by significantly reducing the number of false-positive ECGs in Arabic, black and Caucasian athletes while maintaining 100% sensitivity for serious cardiac pathologies.

Clinical significance of electrocardiographic right ventricular hypertrophy in athletes: comparison with arrhythmogenic right ventricular cardiomyopathy and pulmonary hypertension.

AIMS: Pre-participation cardiovascular screening of young athletes may prevent sports-related sudden cardiac deaths. Recognition of physiological electrocardiography (ECG) changes in healthy athletes has improved the specificity of screening while maintaining sensitivity for disease. The study objective was to determine the clinical significance of electrocardiographic right ventricular hypertrophy (RVH) in athletes. METHODS AND RESULTS: Between 2010 and 2012, 868 subjects aged 14-35 years (68.8% male) were assessed using ECG and echocardiography (athletes; n = 627, sedentary controls; n = 241). Results were compared against patients with established right ventricular (RV) pathology (arrhythmogenic right ventricular cardiomyopathy, n = 68; pulmonary hypertension, n = 30). Sokolow-Lyon RVH (R[V1]+S[V5orV6] > 1.05 mV) was more prevalent in athletes than controls (11.8 vs. 6.2%, P = 0.017), although RV wall thickness (RVWT) was similar (4.0 ± 1.0 vs. 3.9 ± 0.9 mm, P = 0.18). Athletes exhibiting electrocardiographic RVH were predominantly male (95.9%), and demonstrated similar RV dimensions and function to athletes with normal electrocardiograms (RVWT; 4.0 ± 1.1 vs. 4.0 ± 0.9 mm, P = 0.95, RV basal dimension; 42.7 ± 5.2 vs. 42.1 ± 5.9 mm, P = 0.43, RV fractional area change; 40.6 ± 7.6 vs. 42.2 ± 8.1%, P = 0.14). Sensitivity and specificity of Sokolow-Lyon RVH for echocardiographic RVH (>5 mm) were 14.3 and 88.2%, respectively. Further evaluation including cardiac magnetic resonance imaging did not diagnose right ventricular pathology in any athlete. None of the cardiomyopathic or pulmonary hypertensive patients exhibited voltage RVH without additional ECG abnormalities. CONCLUSION: Electrocardiographic voltage criteria for RVH are frequently fulfilled in healthy athletes without underlying RV pathology, and should not prompt further evaluation if observed in isolation. Recognition of this phenomenon should reduce the burden of investigations after pre-participation ECG screening without compromising sensitivity for disease.

Overview of sudden cardiac death in young athletes.

Sudden cardiac death is the leading cause of nontraumatic mortality in young athletes. The estimated incidence varies; however, recent studies have provided more accurate data. Most cases are attributed to silent hereditary or congenital cardiac disorders, many of which may be detected through preparticipation screening programs. This article provides a comprehensive review of the incidence and etiology of sudden cardiac death in young athletes, with practical advice regarding evaluation and management in light of a large number of recent advances. A brief outline of current perspectives on preparticipation screening programs and prevention is included.

Propionibacterium acnes endocarditis of a prosthetic aortic valve.

In the few reported cases of Propionibacterium infective endocarditis involving prosthetic aortic valves, abscess is common and frequently requires surgery. We report a case of P. acnes infective endocarditis identified on prolonged blood cultures with aortic root abscess involving a Starr-Edwards valve. Intravenous antibiotics and valve replacement led to recovery.