Massive pericardial effusion in an infant with Aymé-Gripp syndrome: A case report and review of the literature.

Aymé-Gripp syndrome (AYGRPS) is a multisystemic disorder caused by a subset of pathogenic variants in the MAF gene. Major clinical features include bilateral early cataracts, sensorineural hearing loss (SNHL), and a characteristic facial appearance along with variable neurodevelopmental delay. Pericarditis resulting in pericardial effusion of varying degree has been observed in a subset of affected individuals and could represent a severe feature in neonatal or infantile age. Here, we describe a syndromic infant with massive pericardial effusion and craniofacial features that oriented toward the suspicion of AYGRPS, which was subsequently confirmed by the molecular analysis of MAF. Pericardial effusion was first observed prenatally and documented to be recurrent, progressive, and severe in the first months of life, thus requiring pericardiocentesis and surgical procedures. In this report, we provide further delineation of the minor clinical characteristics, particularly focusing on cardiac features of AYGRPS. A dedicated cardiac surveillance of these findings may help reduce the morbidity and mortality of this rare condition.

Mitophagy modulation for the treatment of cardiovascular diseases.

BACKGROUND: Defects of mitophagy, the selective form of autophagy for mitochondria, are commonly observed in several cardiovascular diseases and represent the main cause of mitochondrial dysfunction. For this reason, mitophagy has emerged as a novel and potential therapeutic target. METHODS: In this review, we discuss current evidence about the biological significance of mitophagy in relevant preclinical models of cardiac and vascular diseases, such as heart failure, ischemia/reperfusion injury, metabolic cardiomyopathy and atherosclerosis. RESULTS: Multiple studies have shown that cardiac and vascular mitophagy is an adaptive mechanism in response to stress, contributing to cardiovascular homeostasis. Mitophagy defects lead to cell death, ultimately impairing cardiac and vascular function, whereas restoration of mitophagy by specific compounds delays disease progression. CONCLUSIONS: Despite previous efforts, the molecular mechanisms underlying mitophagy activation in response to stress are not fully characterized. A comprehensive understanding of different forms of mitophagy active in the cardiovascular system is extremely important for the development of new drugs targeting this process. Human studies evaluating mitophagy abnormalities in patients at high cardiovascular risk also represent a future challenge.

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.

Myocardial Functional Imaging in Pediatric Nuclear Cardiology.

The role of nuclear medicine in pediatric cardiology has grown rapidly over the years, providing useful functional and prognostic information and playing a complementary role to morphological imaging in the evaluation of myocardial perfusion, cardiovascular inflammation and infections, and cardiac sympathetic innervation. The aim of this narrative review is to summarize and highlight the most important evidence on pediatric nuclear cardiology, describing clinical applications and the possibilities, advantages, and limitations of nuclear medicine techniques. Moreover, a special focus will be given to the minimization of radiation exposure in pediatric nuclear cardiology imaging, a critical topic in children.

Similarities and differences between myocarditis following COVID-19 mRNA vaccine and multiple inflammatory syndrome with cardiac involvement in children.

Despite the multiple benefits of vaccination, cardiac adverse Events Following COVID-19 Immunization (c-AEFI) have been reported. These events as well as the severe cardiac involvement reported in Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. Herein, we firstly report on the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Proteins related to systemic inflammation were found higher in MIS-C compared to c-AEFI, whereas a higher level in proteins related to myocardial injury was found in c-AEFI. In addition, higher levels of DHEAS, DHEA, and cortisone were found in c-AEFI which persisted at follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. Overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results to be well restricted on heart and to persist months after the acute event.

Changes in the Cath Lab in the Treatment of Adult Patients with Congenital Heart Disease: A 12-Year Experience in a Single Referral Center with the Establishment of a Dedicated Working Group.

BACKGROUND: Adults with congenital heart disease (ACHD) are a growing population needing ongoing care. The aim of this study was to investigate if a dedicated ACHD team impacted the timing and indication of invasive cardiology procedures in these patients at our hospital. METHODS: Our retrospective single-center study enrolled adult patients with moderate or complex congenital heart disease and with at least one cardiac catheterization between January 2010 and December 2021. According to the period, procedures were labeled as group A (2010 to 2015) or group B (2016 to 2021) and further divided into diagnostic (DCC) and interventional cardiac catheterizations (ICC). RESULTS: 594 patients were eligible for the study. Both DCC (p < 0.05) and ICC increased between groups A and B (p < 0.05). In group B: Fontan patients accounted for the majority of DCC (p < 0.001), while DCC decreased in arterial switch repair (p < 0.001). In Fontan patients, conduit stenting was prevalent (p < 0.001), while fenestration closures dropped (p < 0.01). In patients with tetralogy of Fallot and native outflow tract, percutaneous pulmonary valve implantations (PPVI) increased, with a concurrent reduction in pulmonary valve replacements (p < 0.001 vs. surgical series). In right ventricular conduits, ICC increased (p < 0.01), mainly due to PPVI. Among Mustard/Senning patients, baffle stenting increased from Group A to Group B (p < 0.001). In patients with pulmonary atresia and biventricular repair, ICC often increased for pulmonary artery stenting. CONCLUSIONS: A dedicated working group could improve ACHD patients' indications for interventional procedures, leading to tailored treatment, better risk stratification and optimizing time until heart transplantation.

Acute Changes on Left Atrial Function during Incremental Exercise in Patients with Heart Failure with Mildly Reduced Ejection Fraction: A Case-Control Study.

BACKGROUND: the aim of this study was to assess acute changes in left atrial (LA) function during incremental aerobic exercise in patients with heart failure with mildly reduced ejection fraction (HFmrEF) in comparison to healthy subjects (HS). METHODS: twenty patients with established HFmrEF were compared with 10 HS, age-matched controls. All subjects performed a stepwise exercise test on a cycle ergometer. Echocardiography was performed at baseline, during submaximal effort, at peak of exercise, and after 5 min of recovery. RESULTS: HS obtained a higher value of METs at peak exercise than HFmrEF (7.4 vs. 5.6; between group p = 0.002). Heart rate and systolic blood pressure presented a greater increase in the HS group than in HFmrEF (between groups p = 0.006 and 0.003, respectively). In the HFmrEF group, peak atrial longitudinal strain (PALS) and conduit strain were both increased at submaximal exercise (p < 0.05 for both versus baseline) and remained constant at peak exercise. Peak atrial contraction strain (PACS) did not show significant changes during the exercise. In the HS group, PALS and PACS increased significantly at submaximal level (p < 0.05 for both versus baseline), but PALS returned near baseline values at peak exercise; conduit strain decreased progressively during the exercise in HS. Stroke volume (SV) increased in both groups at submaximal exercise; at peak exercise, SV remained constant in the HFmrEF, while it decreased in controls (between groups p = 0.002). CONCLUSIONS: patients with HFmrEF show a proper increase in LA reservoir function during incremental aerobic exercise that contributes to maintain SV throughout the physical effort.

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.

The Improvement of Left Atrial Function after Twelve Weeks of Supervised Concurrent Training in Patients with Heart Failure with Mid-Range Ejection Fraction: A Pilot Study.

Left atrial dysfunction is associated with exercise intolerance and poor prognosis in heart failure (HF). The effects of exercise training on atrial function in patients with HF with mid-range ejection fraction (HFmrEF) are unknown. The purpose of the present study was to assess the effects of a supervised concurrent training (SCT) program, lasting 12 weeks, on left atrial function of patients with HFmrEF. The study included 70 stable patients, who were randomly assigned into two groups: SCT with (three sessions/week) or a control (CON) group directed to follow contemporary exercise preventive guidelines at home. Before starting the training program and at 12 weeks, all patients performed an ergometric test, a 6 min walk test, and echocardiography. Between-group comparisons were made by analysis of variance (ANOVA). At 12 weeks, the duration of the ergometric test and distance walked at 6 min walk test presented a significant greater increase in SCT compared to the control (between-group p 0.0001 and p 0.004 respectively). Peak atrial longitudinal strain and conduit strain presented an increase of 29% and 34%, respectively, in the SCT, and were unchanged in CON (between-group p 0.008 and p 0.001, respectively). Peak atrial contraction strain increased by 21% in SCT, with no changes in CON (between-group p 0.002). Left ventricular global longitudinal strain increased significantly in SCT compared to control (between-groups p 0.03). In conclusions, SCT improved left atrial and left ventricular function in HFmrEF. Further studies are needed in order to verify whether these favourable effects of SCT on LA function are sustained and whether they will translate into clinical benefits for patients with HFmrEF.

Pregnancy in Patients with Moderate and Highly Complex Congenital Heart Disease.

Although not completely devoid of risk, pregnancy can be managed in virtually all patients affected by even the most complex forms of congenital heart disease. It is not however advisable in patients with any form of pulmonary arterial hypertension. Pregnancy is even manageable in patients with univentricular heart converted to Fontan circulation. A personalised risk stratification should be performed, and patients affected by advanced NYHA functional class appropriately warned of the potential risks. In this setting, metabolomics might represent a novel tool for use in conducting personalised risk stratification. All pregnancies, particularly those at higher risk, should be managed in a tertiary care centre capable of providing the necessary assistance to both the mother and infant. With a few rare exceptions, vaginal delivery is to be preferred over caesarean section due to the lower degree of maternal and foetal complications. The desire for motherhood, at times extreme in women with congenital heart disease, may often be accomplished, thus providing a ray of hope in the lives of these patients.

Relapsing myocarditis following initial recovery of post COVID-19 vaccination in two adolescent males - Case reports.

Whilst there has been significant public health benefits associated with global use of COVID-19 spike protein vaccines, potential serious adverse events following immunization have been reported. Acute myocarditis is a rare complication of COVID19 vaccines and often it is self-limiting. We describe two cases experiencing recurrent myocarditis following mRNA COVID-19 vaccine despite a prior episode with full clinical recovery. Between September 2021-September 2022 we observed two male adolescents with recurrent myocarditis related to mRNA-based-COVID19 vaccine. During the first episode both patients presented with fever and chest pain few days after their second dose of BNT162b2 mRNA Covid-19 Vaccine (Comirnaty®). The blood exams showed increased cardiac enzymes. In addition, complete viral panel was run, showing HHV7 positivity in a single case. The left ventricular ejection fraction (LVEF) was normal at echocardiogram but cardiac magnetic resonance scanning (CMR) was consistent with myocarditis. They were treated with supportive treatment with full recovery. The 6 months follow-up demonstrated good clinical conditions with normal cardiological findings. The CMR showed persistent lesions in left ventricle 's wall with LGE. After some months the patients presented at emergency department with fever and chest pain and increased cardiac enzymes. No decreased LVEF was observed. The CMR showed new focal areas of edema in the first case report and stable lesions in the second one. They reached full recovery with normalization of cardiac enzymes after few days. These case reports outline the need of strict follow-up in patients with CMR consistent with myocarditis after mRNA-based-COVID19 vaccine. More efforts are necessary to depict the underlying mechanisms of myocarditis after SARS-CoV2 vaccination to understand the risk of relapsing and the long-term sequelae.

Bempedoic Acid: An Emerging Therapy for Uncontrolled Low-Density Lipoprotein (LDL) Cholesterol.

Atherosclerotic cardiovascular disease (ASCVD) is a silent epidemic, which is progressing relentlessly across the globe. Developing countries such as India have a high prevalence of dyslipidemia and consequently a huge burden of coronary artery disease (CAD) and ASCVD. Low-density lipoprotein is regarded as the primary culprit in the genesis of ASCVD, and statins are the first line therapy for LDL-C lowering. Statin therapy has unequivocally demonstrated the benefit of lowering LDL-C in patients across the spectrum of CAD and ASCVD. Muscle symptoms and worsening of glycemic homeostasis could be challenges with statin therapy, especially with the use of high doses. A large fraction of patients are also unable to achieve their LDL goals with statins alone in clinical practice. Moreover, LDL-C goals have become aggressive over years, necessitating a combination of lipid lowering therapies. PCSK-9 inhibitors and Inclisiran have emerged as robust and safe lipid-lowering agents, but parenteral administration and high cost precludes their widespread use. Bempedoic acid is a novel lipid-lowering agent working upstream of statins by inhibiting the enzyme ATP citrate lyase (ACL). The drug produces an average LDL lowering of 22-28% in statin-naïve patients and 17-18% when given to preexisting statin users. Because skeletal muscles lack the ACL enzyme, there is minimal risk of muscle-related symptoms. In combination with ezetimibe, the drug synergistically reduced LDL-C by 39%. Moreover, the drug has no adverse effect on glycemic parameters and lowers hsCRP (inflammation) like statin. The series of four randomized CLEAR trials, involving >4000 patients, have shown consistent LDL lowering across the spectrum of ASCVD patients with or without background therapy. The large and only cardiovascular outcome trial of the drug (CLEAR Outcomes) has recently demonstrated a 13% reduction of MACE at 40 months. Rise in levels of uric acid (four times) and acute gout (three times) are more common compared to placebo with the drug, owing to competitive renal transportation by OAT 2. In a nutshell, Bempedoic acid represents a value addition to the inventory of dyslipidemia management.

The Autonomic Coumel Triangle: A New Way to Define the Fascinating Relationship between Atrial Fibrillation and the Autonomic Nervous System.

Arrhythmogenic substrate, modulating factors, and triggering factors (the so-called Coumel's triangle concept) play a primary role in atrial fibrillation (AF) pathophysiology. Several years have elapsed since Coumel and co-workers advanced the concept of the relevance of autonomic nervous system (ANS) influences on atrial cells' electrophysiological characteristics. The ANS is not only associated with cardiac rhythm regulation but also exerts an important role in the triggering and maintenance of atrial fibrillation. This review aims to describe in detail the autonomic mechanisms involved in the pathophysiology of atrial fibrillation (AF), starting from the hypothesis of an "Autonomic Coumel Triangle" that stems from the condition of the fundamental role played by the ANS in all phases of the pathophysiology of AF. In this article, we provide updated information on the biomolecular mechanisms of the ANS role in Coumel's triangle, with the molecular pathways of cardiac autonomic neurotransmission, both adrenergic and cholinergic, and the interplay between the ANS and cardiomyocytes' action potential. The heterogeneity of the clinical spectrum of the ANS and AF, with the ANS playing a relevant role in situations that may promote the initiation and maintenance of AF, is highlighted. We also report on drug, biological, and gene therapy as well as interventional therapy. On the basis of the evidence reviewed, we propose that one should speak of an "Autonomic Coumel's Triangle" instead of simply "Coumel's Triangle".

Transthyretin Stabilizers and Seeding Inhibitors as Therapies for Amyloid Transthyretin Cardiomyopathy.

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a progressive and increasingly recognized cause of heart failure which is associated with high mortality and morbidity. ATTR-CM is characterized by the misfolding of TTR monomers and their deposition within the myocardium as amyloid fibrils. The standard of care for ATTR-CM consists of TTR-stabilizing ligands, such as tafamidis, which aim at maintaining the native structure of TTR tetramers, thus preventing amyloid aggregation. However, their efficacy in advanced-staged disease and after long-term treatment is still a source of concern, suggesting the existence of other pathogenetic factors. Indeed, pre-formed fibrils present in the tissue can further accelerate amyloid aggregation in a self-propagating process known as "amyloid seeding". The inhibition of amyloidogenesis through TTR stabilizers combined with anti-seeding peptides may represent a novel strategy with additional benefits over current therapies. Finally, the role of stabilizing ligands needs to be reassessed in view of the promising results derived from trials which have evaluated alternative strategies, such as TTR silencers and immunological amyloid disruptors.

Effects of Concurrent, Within-Session, Aerobic and Resistance Exercise Training on Functional Capacity and Muscle Performance in Elderly Male Patients with Chronic Heart Failure.

BACKGROUND: The best format of exercise training (ET) in the setting of cardiac rehabilitation in patients with chronic heart failure (CHF) is still to be defined. Current guidelines recommend aerobic exercises, such as running and cycling, including some sessions per week of resistance exercise. AIM: The aim of this study was to address the effectiveness of a concurrent exercise training program utilizing a circuit of sequential endurance and resistance exercises on functional capacity and muscular strength in patients with CHF. METHODS: Ninety-five consecutive male patients (age 63.1 ± 6 years) with CHF (EF < 40%) in NYHA functional class II/III, were randomly assigned on 1:1 basis to a 12-week aerobic continuous training (AT) or concurrent CT), aerobic + resistance, training (CT), three times a week, with each session lasting 80 min. We used high quality, specifically designed ergometers, connected with each other and governed by a central console, and managed by a single physiotherapist. Before and after training all patients performed a symptoms-limited exercise test on a treadmill and a 6-min walking test (6MWT). Patients in the CT group also performed resistance exercises of upper and lower body. RESULTS: The 6MWT and exercise duration at ergometric test increased significantly in both AT and CT groups, with the increase being greater in CT group (p < 0.001; ES = 0.13; p < 0.01; ES = 0.07). Muscular strength increased significantly in the CT group, particularly in the lower body muscular districts (p < 0.001). Quality of life improved in both groups, with a significantly greater improvement in the CT group (p < 0.05). No side effects leading to discontinuation of training were observed. CONCLUSIONS: These findings indicate that concurrent, within-session training results in larger improvements in functional capacity, in addition to muscle performance, in patients with CHF, in comparison to single-mode aerobic training.

The Use of Stress Cardiovascular Imaging in Pediatric Population.

Although not frequent in the pediatric population, ischemia could occur in children due to several congenital and acquired disease. Stress imaging is key for the non-invasive evaluation of myocardial abnormalities and perfusion defect in this clinical setting. Moreover, beyond ischemia assessment, it can provide complementary diagnostic and prognostic information in valvular heart disease and cardiomyopathies. When performed using cardiovascular magnetic resonance, it could detect, in addition, myocardial fibrosis and infarction, increasing the diagnostic yield. Several imaging modalities are currently available for the evaluation of stress myocardial perfusion. Advances in technologies have also increased the feasibility, safety and availability of these modalities in the pediatric age group. However, despite the established role of stress imaging and its increasing use in daily clinical practice, there are currently no specific guidelines, and little data are available in the literature on this topic. The aim of this review is to summarize the most recent evidence on pediatric stress imaging and its clinical application with a focus on the advantages and limitations of each imaging modality currently available.

Anticoagulation for Left Ventricle Thrombus-Case Series and Literature Review for Use of Direct Oral Anticoagulants.

Left ventricular thrombus is a known complication following acute myocardial infarction that can lead to systemic thromboembolism. To obviate the risk of thromboembolism, the patient needs anticoagulation in addition to dual antiplatelet therapy. However, combining antiplatelets with anticoagulants substantially increases the bleeding risk. Traditionally, vitamin K antagonists (VKAs) have been the sheet anchor for anticoagulation in this scenario. The use of direct oral anticoagulants has significantly attenuated the bleeding risk associated with anticoagulation for atrial fibrillation and venous thromboembolism. Furthermore, in patients with atrial fibrillation undergoing percutaneous coronary intervention, the use of direct oral anticoagulants (DOACs) in conjunction with antiplatelets has been found to be noninferior in reducing ischemic events while significantly attenuating the bleeding compared with VKA. After initial case reports, multiple observational and nonrandomized studies have now safely and effectively utilized direct oral anticoagulants for anticoagulation in left ventricular thrombus. Here, we report a series of two cases presenting with left ventricular thrombus following acute myocardial infarction. In this case series, we try to address the issues concerning the choice and duration of anticoagulation in the case of postinfarct left ventricular thrombus. Pending the results of large randomized control trials, the judicious use of direct oral anticoagulant is warranted when taking into consideration the ischemic and bleeding profile in an individualized approach.

Inflammageing and Cardiovascular System: Focus on Cardiokines and Cardiac-Specific Biomarkers.

The term "inflammageing" was introduced in 2000, with the aim of describing the chronic inflammatory state typical of elderly individuals, which is characterized by a combination of elevated levels of inflammatory biomarkers, a high burden of comorbidities, an elevated risk of disability, frailty, and premature death. Inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and rapid progression to heart failure. The great experimental and clinical evidence accumulated in recent years has clearly demonstrated that early detection and counteraction of inflammageing is a promising strategy not only to prevent cardiovascular disease, but also to slow down the progressive decline of health that occurs with ageing. It is conceivable that beneficial effects of counteracting inflammageing should be most effective if implemented in the early stages, when the compensatory capacity of the organism is not completely exhausted. Early interventions and treatments require early diagnosis using reliable and cost-effective biomarkers. Indeed, recent clinical studies have demonstrated that cardiac-specific biomarkers (i.e., cardiac natriuretic peptides and cardiac troponins) are able to identify, even in the general population, the individuals at highest risk of progression to heart failure. However, further clinical studies are needed to better understand the usefulness and cost/benefit ratio of cardiac-specific biomarkers as potential targets in preventive and therapeutic strategies for early detection and counteraction of inflammageing mechanisms and in this way slowing the progressive decline of health that occurs with ageing.