Complete Transposition of the Great Arteries in the Pediatric Field: A Multimodality Imaging Approach.

The complete transposition of the great arteries (C-TGA) is a congenital cardiac anomaly characterized by the reversal of the main arteries. Early detection and precise management are crucial for optimal outcomes. This review emphasizes the integral role of multimodal imaging, including fetal echocardiography, transthoracic echocardiography (TTE), cardiovascular magnetic resonance (CMR), and cardiac computed tomography (CCT) in the diagnosis, treatment planning, and long-term follow-up of C-TGA. Fetal echocardiography plays a pivotal role in prenatal detection, enabling early intervention strategies. Despite technological advances, the detection rate varies, highlighting the need for improved screening protocols. TTE remains the cornerstone for initial diagnosis, surgical preparation, and postoperative evaluation, providing essential information on cardiac anatomy, ventricular function, and the presence of associated defects. CMR and CCT offer additional value in C-TGA assessment. CMR, free from ionizing radiation, provides detailed anatomical and functional insights from fetal life into adulthood, becoming increasingly important in evaluating complex cardiac structures and post-surgical outcomes. CCT, with its high-resolution imaging, is indispensable in delineating coronary anatomy and vascular structures, particularly when CMR is contraindicated or inconclusive. This review advocates for a comprehensive imaging approach, integrating TTE, CMR, and CCT to enhance diagnostic accuracy, guide therapeutic interventions, and monitor postoperative conditions in C-TGA patients. Such a multimodal strategy is vital for advancing patient care and improving long-term prognoses in this complex congenital heart disease.

Pediatric Hypertension: A Condition That Matters.

Systemic hypertension has been considered mainly as an adult health issue for a long time, but it is now being increasingly acknowledged as a significant problem also among pediatric patients. The frequency of pediatric hypertension has grown mostly because of increases in childhood obesity and sedentary lifestyles, but secondary forms of hypertension play a role as well. Considering that unaddressed hypertension during childhood can result in enduring cardiovascular complications, timely identification and intervention are essential. Strategies for addressing this disease encompass not only lifestyle adjustments, but also the use of medications when needed. Lifestyle modifications entail encouraging a nutritious diet, consistent physical activity, and the maintenance of a healthy weight. Moreover, educating both children and their caregivers about monitoring blood pressure at home can aid in long-term management. Thus, the aim of this review is to discuss the etiologies, classification, and principles of the treatment of hypertension in pediatric patients.

Repaired Tetralogy of Fallot: Have We Understood the Right Timing of PVR?

Despite many advances in surgical repair during the past few decades, the majority of tetralogy of Fallot patients continue to experience residual hemodynamic and electrophysiological abnormalities. The actual issue, which has yet to be solved, is understanding how this disease evolves in each individual patient and, as a result, who is truly at risk of sudden death, as well as the proper timing of pulmonary valve replacement (PVR). Our responsibility should be to select the most appropriate time for each patient, going above and beyond imaging criteria used up to now to make such a clinically crucial decision. Despite several studies on timing, indications, procedures, and outcomes of PVR, there is still much uncertainty about whether PVR reduces arrhythmia burden or improves survival in these patients and how to appropriately manage this population. This review summarizes the most recent research on the evolution of repaired tetralogy of Fallot (from adolescence onwards) and risk factor variables that may favor or delay PVR.

Mechanisms of Cardiovascular Calcification and Experimental Models: Impact of Vitamin K Antagonists.

Cardiovascular calcification is a multifactorial and complex process involving an array of molecular mechanisms eventually leading to calcium deposition within the arterial walls. This process increases arterial stiffness, decreases elasticity, influences shear stress events and is related to an increased risk of morbidity and mortality associated with cardiovascular disease. In numerous in vivo and in vitro models, warfarin therapy has been shown to cause vascular calcification in the arterial wall. However, the exact mechanisms of calcification formation with warfarin remain largely unknown, although several molecular pathways have been identified. Circulating miRNA have been evaluated as biomarkers for a wide range of cardiovascular diseases, but their exact role in cardiovascular calcification is limited. This review aims to describe the current state-of-the-art research on the impact of warfarin treatment on the development of vascular calcification and to highlight potential molecular targets, including microRNA, within the implicated pathways.

The mechanics of congenital heart disease: from a morphological trait to the functional echocardiographic evaluation.

Advances in pediatric cardiac surgery have resulted in a recent growing epidemic of children and young adults with congenital heart diseases (CHDs). In these patients, congenital defects themselves, surgical operations and remaining lesions may alter cardiac anatomy and impact the mechanical performance of both ventricles. Cardiac function significantly influences outcomes in CHDs, necessitating regular patient follow-up to detect clinical changes and relevant risk factors. Echocardiography remains the primary imaging method for CHDs, but clinicians must understand patients' unique anatomies as different CHDs exhibit distinct anatomical characteristics affecting cardiac mechanics. Additionally, the use of myocardial deformation imaging and 3D echocardiography has gained popularity for enhanced assessment of cardiac function and anatomy. This paper discusses the role of echocardiography in evaluating cardiac mechanics in most significant CHDs, particularly its ability to accommodate and interpret the inherent anatomical substrate in these conditions.

Underlying mechanisms and cardioprotective effects of SGLT2i and GLP-1Ra: insights from cardiovascular magnetic resonance.

Originally designed as anti-hyperglycemic drugs, Glucagon-Like Peptide-1 receptor agonists (GLP-1Ra) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated protective cardiovascular effects, with significant impact on cardiovascular morbidity and mortality. Despite several mechanisms have been proposed, the exact pathophysiology behind these effects is not yet fully understood. Cardiovascular imaging is key for the evaluation of diabetic patients, with an established role from the identification of early subclinical changes to long-term follow up and prognostic assessment. Among the different imaging modalities, CMR may have a key-role being the gold standard for volumes and function assessment and having the unique ability to provide tissue characterization. Novel techniques are also implementing the possibility to evaluate cardiac metabolism through CMR and thereby further increasing the potential role of the modality in this context. Aim of this paper is to provide a comprehensive review of changes in CMR parameters and novel CMR techniques applied in both pre-clinical and clinical studies evaluating the effects of SGLT2i and GLP-1Ra, and their potential role in better understanding the underlying CV mechanisms of these drugs.

Multimodality Imaging Assessment of Tetralogy of Fallot: From Diagnosis to Long-Term Follow-Up.

Tetralogy of Fallot (TOF) is the most common complex congenital heart disease with long-term survivors, demanding serial monitoring of the possible complications that can be encountered from the diagnosis to long-term follow-up. Cardiovascular imaging is key in the diagnosis and serial assessment of TOF patients, guiding patients' management and providing prognostic information. Thorough knowledge of the pathophysiology and expected sequalae in TOF, as well as the advantages and limitations of different non-invasive imaging modalities that can be used for diagnosis and follow-up, is the key to ensuring optimal management of patients with TOF. The aim of this manuscript is to provide a comprehensive overview of the role of each modality and common protocols used in clinical practice in the assessment of TOF patients.

Childhood Obesity and Congenital Heart Disease: A Lifelong Struggle.

Congenital heart disease (CHD) affects approximately one in every one hundred infants worldwide, making it one of the most prevalent birth abnormalities globally. Despite advances in medical technology and treatment choices, CHD remains a significant health issue and necessitates specialized care throughout an individual's life. Childhood obesity has emerged as a novel global epidemic, becoming a major public health issue, particularly in individuals with lifelong conditions such as CHD. Obesity has profound effects on cardiac hemodynamics and morphology, emphasizing the importance of addressing obesity as a significant risk factor for cardiovascular health. Obesity-induced alterations in cardiac function can have significant implications for cardiovascular health and may contribute to the increased risk of heart-related complications in obese individuals. Moreover, while diastolic dysfunction may be less apparent in obese children compared to adults, certain parameters do indicate changes in early left ventricular relaxation, suggesting that obesity can cause cardiac dysfunction even in pediatric populations. As most children with CHD now survive into adulthood, there is also concern about environmental and behavioral health risk factors in this particular patient group. Addressing obesity in individuals with CHD is essential to optimize their cardiovascular health and overall quality of life. This review aims to succinctly present the data on the impact of obesity on CHD and to enhance awareness of this perilous association among patients, families, and healthcare providers.

Unusual case of severe aortic regurgitation in a child with bicuspid aortic valve.

Aortic regurgitation (AR) is common after aortic balloon valvuloplasty in children and it has been associated with large balloon/annulus ratio, abnormal valve morphology and aortic valve prolapse. We present a rare case of severe AR after aortic balloon valvuloplasty due to aortic strands rupture, causing prolapse of the co-joined cusp.  These findings were identified by 3D echocardiography, highlighting the importance of this imaging technique even in pediatric patients.

Cardiac Function Evaluation after SARS-CoV-2 mRNA Vaccination in Children and Adolescents: A Prospective Speckle-Tracking Echocardiography Study.

BACKGROUND: Possible cardiac impairment after SARS-CoV-2 mRNA vaccination is a common driver of parental vaccine hesitancy. We performed a comprehensive echocardiographic evaluation of biventricular function in vaccinated children with or without previous COVID-19 compared to healthy controls. METHODS: We conducted a single-center, prospective, case-control study enrolling children and adolescents aged 5-18 years attending the pediatric clinic of the University Hospital of Padua from April to June 2022. Three months after receiving the primary mRNA vaccination or booster dose, the patients underwent a cardiac assessment, including standard echocardiography and speckle-tracking echocardiography (STE). A pre-pandemic historical cohort of age- and gender-matched healthy children were used as a control. RESULTS: A total of 39 post-VACCINE cases (24, 61% female), mean age 12.6 ± 2.6 years (range 8-17), were enrolled in the study. Ninety percent (N = 35) of patients were previously healthy. No differences in left ventricular diameters, left ventricular ejection fraction (LVEF), and tricuspid annular plane systolic excursion (TAPSE) were observed between cases and controls. Global longitudinal strain (GLS) was in the normal range in all individuals, with no differences between post-VACCINE cases and controls (-21.7 ± 2.3% vs. 21.2 ± 1.8%; p = 0.338). However, GLS was found to be slightly but significantly reduced in post-VACCINE children with a previous COVID-19 compared to naïve-vaccinated individuals (post-VACCINE+COVID-19: -19.9 ± 1.1% vs. post-VACCINE-only: -22.0 ± 2.3%; p = 0.002). CONCLUSIONS: We did not observe an impairment in GLS or in other indices of LV structure or function after mRNA COVID-19 vaccination.

Left Atrial Strain in Cardiomyopathies and Congenital Heart Disease: A Call for Its Integration into Clinical Practice.

Despite the long-standing neglect, there is now a mounting interest in the left atrium (LA) physiology.

Acute Changes in Right Ventricular Function in Pediatric Patients with Pulmonary Valve Stenosis Undergoing Percutaneous Valvuloplasty: A Speckle-Tracking Study.

INTRODUCTION: Pulmonary valve stenosis determines multiple effects on the right ventricular dimension and function. Percutaneous balloon valvuloplasty is the treatment of choice in severe pulmonary valve stenosis in patients of all ages. However, little is known regarding right ventricular function immediate changes after percutaneous balloon dilation. Pediatric patients with isolated pulmonary valve stenosis represent a pure clinical model of chronic RV pressure overload not affected by other confounders or comorbidities. AIM OF THE STUDY: This study seeks to explore right ventricle (RV) mechanics in pediatric patients early after percutaneous balloon pulmonary valvuloplasty (BPV) for valvar pulmonary stenosis (PS). MATERIALS AND METHODS: Forty-three pediatric patients (19 males), mean age 3.2 ± 4.9 years old, with severe pulmonary valve stenosis and indication for percutaneous balloon valvuloplasty were recruited. All patients underwent standard transthoracic echocardiography (TTE), and speckle-tracking echocardiography (STE) with an analysis of right ventricle free-wall longitudinal strain (RVFWLS) one day before and one day after the procedure. For each patient, we collected invasive parameters during the interventional procedure before and after BPV. RESULTS: After the procedure, there was an immediate significant reduction in both peak-to-peak transpulmonary gradient (peak-to-peak PG) and ratio between the right ventricle and aortic systolic pressure (RV/AoP) with a drop of ∆29.3 ± 14.67 mmHg and ∆0.43 ± 0.03, respectively. Post-procedural echocardiography showed peak and mean transvalvar pressure gradient drop (∆50 ± 32.23 and ∆31 ± 17.97, respectively). The degree of pulmonary valve regurgitation was mild in 8% of patients before the procedure, affecting 29% of our patients post-BPV (p = 0.007). The analysis of right ventricular mechanics showed a significant improvement of fractional area change (FAC) immediately after BPV (40.11% vs. 44.42%, p = 0.01). On the other hand, right ventricular longitudinal systolic function parameters, TAPSE and global RVFWLS, did not improve significantly after intervention. The segmental analysis of the RVFWLS showed a significant regional increase in the myocardial deformation of the apical segments. CONCLUSIONS: Percutaneous BPV represents an efficient and safe procedure to relieve severe pulmonary valve stenosis. The analysis of the right ventricular function on echocardiography demonstrated an immediate global systolic function improvement, while longitudinal systolic function was persistently impaired 24 h after intervention, possibly due to the necessity of a longer recovery time.

Polarizing Macrophage Functional Phenotype to Foster Cardiac Regeneration.

There is an increasing interest in understanding the connection between the immune and cardiovascular systems, which are highly integrated and communicate through finely regulated cross-talking mechanisms. Recent evidence has demonstrated that the immune system does indeed have a key role in the response to cardiac injury and in cardiac regeneration. Among the immune cells, macrophages appear to have a prominent role in this context, with different subtypes described so far that each have a specific influence on cardiac remodeling and repair. Similarly, there are significant differences in how the innate and adaptive immune systems affect the response to cardiac damage. Understanding all these mechanisms may have relevant clinical implications. Several studies have already demonstrated that stem cell-based therapies support myocardial repair. However, the exact role that cardiac macrophages and their modulation may have in this setting is still unclear. The current need to decipher the dual role of immunity in boosting both heart injury and repair is due, at least for a significant part, to unresolved questions related to the complexity of cardiac macrophage phenotypes. The aim of this review is to provide an overview on the role of the immune system, and of macrophages in particular, in the response to cardiac injury and to outline, through the modulation of the immune response, potential novel therapeutic strategies for cardiac regeneration.

Cellular and Molecular Mechanisms Underlying Tricuspid Valve Development and Disease.

Tricuspid valve (TV) disease is highly prevalent in the general population. For ages considered "the forgotten valve" because of the predominant interest in left-side valve disease, the TV has now received significant attention in recent years, with significant improvement both in diagnosis and in management of tricuspid disease. TV is characterized by complex anatomy, physiology, and pathophysiology, in which the right ventricle plays a fundamental role. Comprehensive knowledge of molecular and cellular mechanisms underlying TV development, TV disease, and tricuspid regurgitation-related right-ventricle cardiomyopathy is necessary to enhance TV disease understanding to improve the ability to risk stratify TR patients, while also predicting valve dysfunction and/or response to tricuspid regurgitation treatment. Scientific efforts are still needed to eventually decipher the complete picture describing the etiopathogenesis of TV and TV-associated cardiomyopathy, and future advances to this aim may be achieved by combining emerging diagnostic imaging modalities with molecular and cellular studies. Overall, basic science studies could help to streamline a new coherent hypothesis underlying both the development of TV during embryogenesis and TV-associated disease and its complications in adult life, providing the conceptual basis for the ultimate and innovative field of valve repair and regeneration using tissue-engineered heart valves.

Clinical Application of Circular RNAs as Biomarkers in Acute Ischemic Stroke.

Despite the substantial improvement in diagnosis and treatment within the last decades, ischemic stroke still represents a challenge, responsible still for a high burden of morbidity and mortality. Among the unmet clinical needs are the difficulties in identifying those subjects with the greatest risk of developing a stroke, the challenges in obtaining a timely diagnosis, the prompt recognition of the different clinical forms of stroke, the assessment of the response to treatments and the prognostic assessment. All these issues might be improved with appropriate smart biomarkers that could better inform clinical management. The present article offers an overview of the potential role of circular RNAs as disease biomarkers in stroke. A systematic approach was adopted to gather all potentially relevant information in order to provide a panoramic view on this class of promising molecules.

Myocardial work in children with Wolff-Parkinson-White syndrome.

Wolff-Parkinson-White Syndrome (WPW) has been associated with reduced local myocardial deformation, and when left ventricular dysfunction is present, catheter ablation of the accessory pathway may be required, even in asymptomatic patients. We aimed to evaluate the diagnostic value of non-invasive myocardial work in predicting subtle abnormalities in myocardial performance in children with WPW.Seventy-five paediatric patients (age 8.7 ± 3.5 years) were retrospectively recruited for the study: 25 cases with manifest WPW and 50 age- and sex- matched controls (CTR). Global myocardial work index (MWI) was measured as the area of the left ventricle (LV) pressure-strain loops. From MWI, global Myocardial Constructive Work (MCW), Wasted Work (MWW), and Work Efficiency (MWE) were estimated. In addition, standard echocardiographic parameters of LV function were evaluated. Despite normal LV ejection fraction (EF) and global longitudinal strain (GLS), children with WPW had worse MWI, MCW, MWW, and MWE. At multivariate analysis, MWI and MCW were associated with GLS and systolic blood pressure, and QRS was the best independent predictor of low MWE and MWW. In particular, a QRS > 110 ms showed good sensitivity and specificity for worse MWE and MWW values. In children with WPW, myocardial work indices were found significantly reduced, even in the presence of normal LV EF and GLS. This study supports the systematic use of myocardial work during the follow-up of paediatric patients with WPW. Myocardial work analysis may represent a sensitive measure of LV performance and aid in decision-making.

Chronic Heart Failure in Children: State of the Art and New Perspectives.

Pediatric heart failure (HF) is an important clinical condition with high morbidity and mortality. Compared to adults, pediatric HF shows different etiologies characterized by different physiology, a different clinical course, and deeply different therapeutic approaches. In the last few years, new drugs have been developed and new therapeutic strategies have been proposed with the goal of identifying an individualized treatment regimen. The aim of this article is to review the new potential drugs and non-pharmacological therapies for pediatric heart failure in children.

Primary and secondary paediatric hypertension.

High blood pressure (BP) or hypertension is a well known risk factor for developing heart attack, stroke, atrial fibrillation and renal failure. Although in the past hypertension was supposed to develop at middle age, it is now widely recognized that it begins early during childhood. As such, approximately 5-10% of children and adolescents are hypertensive. Unlike that previously reported, it is now widely accepted that primary hypertension is the most diffuse form of high BP encountered even in paediatric age, while secondary hypertension accounts just for a minority of the cases. There are significant differences between that outlined by the European Society of Hypertension (ESH), the European Society of Cardiology (ESC), and the last statement by the American Academy of Pediatrics (AAP) concerning the BP cut-offs to identify young hypertensive individuals. Not only that, but the AAP have also excluded obese children in the new normative data. This is undoubtedly a matter of concern. Conversely, both the AAP and ESH/ESC agree that medical therapy should be reserved just for nonresponders to measures like weight loss/salt intake reduction/increase in aerobic exercise. Secondary hypertension often occurs in aortic coarctation or chronic renal disease patients. The former can develop hypertension despite early effective repair. This is associated with significant morbidity and is arguably the most important adverse outcome in about 30% of these subjects. Also, syndromic patients, for example those with Williams syndrome, may suffer from a generalized aortopathy, which triggers increased arterial stiffness and hypertension. This review summarizes the state-of-the-art situation regarding primary and secondary paediatric hypertension.