Cardiomyopathies: The Role of Non-Coding RNAs.

Cardiomyopathies are the structural and functional disorders of the myocardium. Etiopathogenesis is complex and involves an interplay of genetic, environmental, and lifestyle factors eventually leading to myocardial abnormalities. It is known that non-coding (Nc) RNAs, including micro (mi)-RNAs and long non-coding (lnc) RNAs, play a crucial role in regulating gene expression. Several studies have explored the role of miRNAs in the development of various pathologies, including heart diseases. In this review, we analyzed various patterns of ncRNAs expressed in the most common cardiomyopathies: dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy. Understanding the role of different ncRNAs implicated in cardiomyopathic processes may contribute to the identification of potential therapeutic targets and novel risk stratification models based on gene expression. The analysis of ncRNAs may also be helpful to unveil the molecular mechanisms subtended to these diseases.

Changes of intracardiac flow dynamics measured by HyperDoppler in patients with aortic stenosis.

Aims: Assessment of intracardiac flow dynamics has recently acquired significance due to the development of new measurement methods based on echocardiography. Recent studies have demonstrated that cardiac abnormalities are associated with changes in intracardiac vortical flows. Yet, no previous study assessed the impact of aortic stenosis (AS) on intracardiac vortices. This study aims to explore the clinical potential of additional information provided by quantifying intracardiac flow dynamics in patients with AS. Methods and results: One hundred and twenty patients with severe AS, sixty patients with concentric ventricular remodelling (VR), and hundred controls (CTRL) were prospectively included and underwent non-invasive evaluation of intracardiac flow dynamics. In addition to standard echocardiography, fluid dynamics were assessed by means of HyperDoppler. Vortex depth (P < 0.001), vortex length (P = 0.003), vortex intensity (P < 0.001), and vortex area (P = 0.049) were significantly increased in AS compared with CTRL. In addition, mean energy dissipation was significantly higher in AS compared with CTRL (P < 0.001) and VR (P = 0.002). At receiver operating characteristic analysis, vortex depth showed the best discrimination capacity for AS (P < 0.001). Conclusion: Changes in fluid dynamics-based HyperDoppler indices can be reliably assessed in patients with AS. Significant changes in vortex depth and intensity can selectively differentiate AS from both concentric remodelling and healthy CTRLs, suggesting that the assessment of intracardiac flow dynamics may provide complementary information to standard echocardiography to better characterize patients' subsets.

Importance of Cardiovascular Magnetic Resonance Applied to Congenital Heart Diseases in Pediatric Age: A Narrative Review.

Congenital heart diseases (CHDs) represent a heterogeneous group of congenital defects, with high prevalence worldwide. Non-invasive imaging is essential to guide medical and surgical planning, to follow the patient over time in the evolution of the disease, and to reveal potential complications of the chosen treatment. The application of cardiac magnetic resonance imaging (CMRI) in this population allows for obtaining detailed information on the defects without the necessity of ionizing radiations. This review emphasizes the central role of CMR in the overall assessment of CHDs, considering also the limitations and challenges of this imaging technique. CMR, with the application of two-dimensional (2D) and tri-dimensional (3D) steady-state free precession (SSFP), permits the obtaining of very detailed and accurate images about the cardiac anatomy, global function, and volumes' chambers, giving essential information in the intervention planning and optimal awareness of the postoperative anatomy. Nevertheless, CMR supplies tissue characterization, identifying the presence of fat, fibrosis, or oedema in the myocardial tissue. Using a contrast agent for angiography sequences or 2D/four-dimensional (4D) flows offers information about the vascular, valvular blood flow, and, in general, the cardiovascular system hemodynamics. Furthermore, 3D SSFP CMR acquisitions allow the identification of coronary artery abnormalities as an alternative to invasive angiography and cardiovascular computed tomography (CCT). However, CMR requires expertise in CHDs, and it can be contraindicated in patients with non-conditional devices. Furthermore, its relatively longer acquisition time and the necessity of breath-holding may limit its use, particularly in children under eight years old, sometimes requiring anesthesia. The purpose of this review is to elucidate the application of CMR during the pediatric age.

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.

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.

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.

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.

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.

Imaging patients with myocardial infarction with non-obstructive coronary arteries (MINOCA).

Myocardial infarction with non-obstructive coronary arteries (MINOCA) defines a heterogeneous group of atherosclerotic and non-atherosclerotic conditions, causing myocardial injury in the absence of obstructive coronary artery disease. Unveiling the mechanisms subtended to the acute event is often challenging; a multimodality imaging approach is helpful to aid the diagnosis. Invasive coronary imaging with intravascular ultrasound or optical coherence tomography should be used, when available, during index angiography to detect plaque disruption or spontaneous coronary artery dissection. Cardiovascular magnetic resonance has instead a key role among the non-invasive modalities, allowing the differentiation between MINOCA and its non-ischaemic mimics and providing prognostic information. This educational paper will provide a comprehensive review of the strengths and limitations of each imaging modality in the evaluation of patients with a working diagnosis of MINOCA.

The Role of Multimodality Imaging in Patients with Congenital Heart Disease and Infective Endocarditis.

Infective endocarditis (IE) represents an important medical challenge, particularly in patients with congenital heart diseases (CHD). Its early and accurate diagnosis is crucial for effective management to improve patient outcomes. Multimodality imaging is emerging as a powerful tool in the diagnosis and management of IE in CHD patients, offering a comprehensive and integrated approach that enhances diagnostic accuracy and guides therapeutic strategies. This review illustrates the utilities of each single multimodality imaging, including transthoracic and transoesophageal echocardiography, cardiac computed tomography (CCT), cardiovascular magnetic resonance imaging (CMR), and nuclear imaging modalities, in the diagnosis of IE in CHD patients. These imaging techniques provide crucial information about valvular and intracardiac structures, vegetation size and location, abscess formation, and associated complications, helping clinicians make timely and informed decisions. However, each one does have limitations that influence its applicability.

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.

The Role of Advanced Cardiovascular Imaging Modalities in Cardio-Oncology: From Early Detection to Unravelling Mechanisms of Cardiotoxicity.

Advances in cancer therapies have led to a global improvement in patient survival rates. Nevertheless, the price to pay is a concomitant increase in cardiovascular (CV) morbidity and mortality in this population. Increased inflammation and disturbances of the immune system are shared by both cancer and CV diseases. Immunological effects of anti-cancer treatments occur with both conventional chemotherapy and, to a greater extent, with novel biological therapies such as immunotherapy. For these reasons, there is growing interest in the immune system and its potential role at the molecular level in determining cardiotoxicity. Early recognition of these detrimental effects could help in identifying patients at risk and improve their oncological management. Non-invasive imaging already plays a key role in evaluating baseline CV risk and in detecting even subclinical cardiac dysfunction during surveillance. The aim of this review is to highlight the role of advanced cardiovascular imaging techniques in the detection and management of cardiovascular complications related to cancer treatment.

CMR reclassifies the majority of patients with suspected MINOCA and non MINOCA.

AIMS: In ∼5-15% of all cases of acute coronary syndromes (ACS) have unobstructed coronaries on angiography. Cardiac magnetic resonance (CMR) has proven useful to identify in most patients the underlying diagnosis associated with this presentation. However, the role of CMR to reclassify patients from the initial suspected condition has not been clarified. The aim of this study was to assess the proportion of patients with suspected MINOCA, or non-MINOCA, that CMR reclassifies with an alternative diagnosis from the original clinical suspicion. METHODS AND RESULTS: A retrospective cohort of patients in a tertiary cardiology centre was identified from a registry database. Patients who were referred for CMR for investigation of suspected MINOCA, and a diagnosis pre- and post-CMR was recorded to determine the proportion of diagnoses reclassified. A total of 888 patients were identified in the registry. CMR reclassified diagnosis in 78% of patients. Diagnosis of MINOCA was confirmed in only 243 patients (27%), whilst most patients had an alternative diagnosis (73%): myocarditis n = 217 (24%), Takotsubo syndrome n = 115 (13%), cardiomyopathies n = 97 (11%), and normal CMR/non-specific n = 216 (24%). CONCLUSION: In a large single-centre cohort of patients presenting with ACS and unobstructed coronary arteries, most patients had a non-MINOCA diagnosis (73%) (myocarditis, Takotsubo, cardiomyopathies, or normal CMR/non-specific findings), whilst only a minority had confirmed MINOCA (27%). Performing CMR led to reclassifying patients' diagnosis in 78% of cases, thus confirming its important clinical role and underscoring the clinical challenge in diagnosing MINOCA and non MINOCA conditions.

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.

The Role of Multimodality Imaging in Pediatric Cardiomyopathies.

Cardiomyopathies are a heterogeneous group of myocardial diseases representing the first cause of heart transplantation in children. Diagnosing and classifying the different phenotypes can be challenging, particularly in this age group, where cardiomyopathies are often overlooked until the onset of severe symptoms. Cardiovascular imaging is crucial in the diagnostic pathway, from screening to classification and follow-up assessment. Several imaging modalities have been proven to be helpful in this field, with echocardiography undoubtedly representing the first imaging approach due to its low cost, lack of radiation, and wide availability. However, particularly in this clinical context, echocardiography may not be able to differentiate from cardiomyopathies with similar phenotypes and is often complemented with cardiovascular magnetic resonance. The latter allows a radiation-free differentiation between different phenotypes with unique myocardial tissue characterization, thus identifying the presence and extent of myocardial fibrosis. Nuclear imaging and computed tomography have a complementary role, although they are less used in daily clinical practice due to the concern related to the use of radiation in pediatric patients. However, these modalities may have some advantages in evaluating children with cardiomyopathies. This paper aims to review the strengths and limitations of each imaging modality in evaluating pediatric patients with suspected or known cardiomyopathies.

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.

Cardiovascular Magnetic Resonance from Fetal to Adult Life-Indications and Challenges: A State-of-the-Art Review.

Cardiovascular magnetic resonance (CMR) imaging offers a comprehensive, non-invasive, and radiation-free imaging modality, which provides a highly accurate and reproducible assessment of cardiac morphology and functions across a wide spectrum of cardiac conditions spanning from fetal to adult life. It minimises risks to the patient, particularly the risks associated with exposure to ionising radiation and the risk of complications from more invasive haemodynamic assessments. CMR utilises high spatial resolution and provides a detailed assessment of intracardiac and extracardiac anatomy, ventricular and valvular function, and flow haemodynamic and tissue characterisation, which aid in the diagnosis, and, hence, with the management of patients with cardiac disease. This article aims to discuss the role of CMR and the indications for its use throughout the different stages of life, from fetal to adult life.