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.

Evaluation of cardiac function by global longitudinal strain before and after treatment with sofosbuvir-based regimens in HCV infected patients.

BACKGROUND: Possible cardiotoxicity of sofosbuvir in humans has not been demonstrated yet. Also, since HCV can exert deleterious effects on hearth function, it is of interest to know whether HCV eradication provides any benefits using global longitudinal strain (GLS), a measure of left ventricular function more reliable than ejection fraction (EF). METHODS: Patients eligible for treatment with the combination therapy for HCV were invited to perform a transthoracic cardiac ultrasound at four different time points: before starting treatment, after one month, at the end of treatment and, after six month. Left ventricular function was measured with both EF and GLS. RESULTS: From March 2015 to December 2016, 82 patients were enrolled. Fifty-six percent patients were males. Mean age was 66.12 (SD: 9.25) years. About 20% patients did not present any cardiovascular risk factors or comorbidities. A worsening trend of GLS was observed. Variations were not found to be statistically significant when EF was studied along the follow-up. However, when GLS was studied, its variations were found to be statistically significant indicating a worsening effect, albeit with different trends in patients who underwent treatment for three months compared to six months. Worsening of GLS was found to be statistically significant even after adjusting for body mass index and liver fibrosis, independently from treatment duration. CONCLUSIONS: Our results showed unexpected worsening of left ventricular function when measured through GLS after HCV treatment response induced by DAAs including sofosbuvir. Although this result is not proven to be clinically significant, the safety profile of sofosbuvir-based regimens needs to be studied further.

HMGA1 is a novel candidate gene for myocardial infarction susceptibility.

BACKGROUND: Acute Myocardial infarction (AMI), a leading cause of morbidity and mortality worldwide, is a dreadful acute complication of coronary atherosclerosis. Type 2 diabetes mellitus (T2DM) is associated with an increased risk of developing AMI. The architectural transcription factor high-mobility-group AT-hook 1 (HMGA1) has been involved in atherosclerosis, plaque formation, inflammation, and in the pathogenesis of insulin resistance and T2DM. An association of the HMGA1 rs146052672 variant with T2DM has been recently reported. Thus, our aim was to evaluate whether this variant was also associated with AMI. METHODS AND RESULTS: In a case-control study from Calabria (Southern Italy), we enrolled 254 consecutive, unrelated, patients with first diagnosis of AMI, and 508 age, sex-matched controls. Genotyping of the rs146052672 was performed using the TaqMan allelic discrimination method. We found that this variant was present in 7.9% of AMI patients and in 3.1% of controls (p=0.003). Multiple logistic regression confirmed that the rs146052672 was significantly associated with AMI (OR=2.54; p=0.002), and this association was independent of classical cardiovascular risk factors such as gender, hypertension, obesity and T2DM (for all, p<0.05). CONCLUSIONS: Our findings demonstrate that a relationship exists between the HMGA1 rs146052672 variant and AMI, suggesting that defects at the HMGA1 locus may play a pathogenetic role in AMI, in the absence of T2DM and other cardiovascular risk factors.

[Obesity and ischemic heart disease. Is there a link between wellness' diseases?]. / Obesità e cardiopatia ischemica. Esiste un legame tra le malattie del benessere?

Obesity, the most common nutritional disorder in Western countries, is usually associated to cardiovascular diseases. However, the precise molecular pathways underlying this close association remain poorly understood. Nowadays, the adipose tissue is considered as an endocrine organ able to produce substances called adipo(cyto)kines that have different effects on lipid metabolism, closely involved in metabolic syndrome, and cardiovascular risk. The increased cardiovascular risk can be related also to peculiar dysfunction in the endocrine activity of adipose tissue observed in obesity responsible of vascular impairment (including endothelial dysfunction), prothrombotic tendency, and low-grade chronic inflammation. The present review aims at providing an up-dated overview on the adipocyte-derived molecules potentially involved in cardiovascular pathophysiology.

Percutaneous approach to treatment of coronary disease in a patient with uremic cardiomyopathy.

Uremic cardiomyopathy is chronic ischemic left ventricular dysfunction characterized by heart failure, myocardial ischemia, hypotension in dialysis and arrhythmia. This nosologic entity represents a leading cause of morbidity and mortality among patients with end-stage renal disease receiving long-term hemodialysis. It is intuitive that revascularization in the presence of coronary artery disease in these patients represents an effective option for improving their prognosis. Although the surgical option seems to be followed by the best clinical outcome, some patients refuse this option and others are not good candidates for surgery. The present report describes the case of a patient affected by uremic cardiomyopathy and severe coronary artery disease in whom revascularization with percutaneous coronary angioplasty was followed by a significant improvement in quality of life.

Neopterin: from forgotten biomarker to leading actor in cardiovascular pathophysiology.

Inflammation plays a role at all stages of atherosclerosis. Neopterin, a pteridine mainly synthesized by activated macrophages, is a marker of inflammation, immune system activation and an active participant in cardiovascular disease. Measurement of neopterin levels may help follow the evolution of specific inflammatory conditions (e.g. viral infection, renal transplant rejection, systemic inflammatory diseases, nephritic syndrome and autoimmune diseases). Serum levels of neopterin are elevated also in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). Moreover, plasma levels of this molecule might predict adverse cardiovascular events in patients with CAD, acute coronary syndromes or severe PAD. In addition, neopterin levels are related to the development of heart failure. We provide an updated overview on neopterin and, its links with CAD, left ventricular dysfunction, and PAD. We also describe its potential role in cardiac regenerative strategies with using bone marrow cells.

Successful use of the Cardiva Boomerang™ vascular closure device to close a brachial artery puncture site after emergency PTCA.

Brachial artery access is a good alternative for performing percutaneous transluminal angioplasty when femoral access is contraindicated or not feasible. Although several closure devices are available for femoral access, haemostasis for brachial artery access is still achieved by manual compression with several potential complications, such as bleeding, pseudo-aneurysm formation, especially in patients in which heparin is administered, or thrombotic vessel occlusion. This first-in-human report describes the off-label brachial use of the Cardiva Boomerang™, a novel vascular closure device, which provides haemostasis using a temporary intravascular tampon, thus permitting the easier physiological closure of the puncture site without any important complications.

Pro-atherothrombotic effects of leptin in human coronary endothelial cells.

Adipocytes are nowadays recognised as cells able to produce and secrete a large variety of active substances termed adipokines, which exert direct effects on vascular cells. Among these adipokines, leptin has been proposed to play a role in the pathophysiology of acute coronary syndromes, as well as in increasing cardiovascular risk. At the moment, however, the mechanisms linking leptin to cardiovascular disease are not completely understood. This study investigates the effects of leptin, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk or measurable in patients with acute coronary syndromes, on tissue factor (TF) and cellular adhesion molecules (CAMs) expression in human coronary endothelial cells (HCAECs). We demonstrate that leptin induces transcription of mRNA for TF and CAMs by real-time PCR. In addition, we show that this adipokine promotes surface expression of TF and CAMs that are functionally active since we observed increased procoagulant activity and leukocyte adhesion on cell surface. Leptin effects appear modulated by eNOS-production of oxygen free radicals through the activation of the transcription factor, nuclear factor(NF)-kappaB, since L-NAME, Superoxide Dismutase and NF-kappaB inhibitors suppressed CAMs and TF expression. Data of the present study, although in vitro , indicate that leptin may exert direct effects on human coronary endothelial cells by promoting CAMs and TF expression and support the hypothesis that this adipokines, besides being involved in the pathophysiology of obesity, might play a relevant role as an active mediator linking obesity to cardiovascular disease.

Tissue Factor/Factor FVII Complex Inhibitors in Cardiovascular Disease. Are Things Going Well?

Blood coagulation is a complex biological mechanism aimed to avoid bleeding in which a highly regulated and coordinated interplay of specific proteins and cellular components respond quickly to a vascular injury. However, when this mechanisms occurs in the coronary circulation, it has not a "protective" effect, but rather, it plays a pivotal role in determining acute coronary syndromes. Coagulation recognizes Tissue Factor (TF), the main physiological initiator of the extrinsic coagulation pathway, as its starter.Since TF:VIIa complex is the critical point of the blood coagulation cascade, it is a pharmacological attractive issue for the development of agents with anti thrombotic properties that can exert their activity by inhibiting complex formation and/or its catalytic activity. In fact, it is intuitive that an antithrombotic agent able to inhibit this initial step of the coagulation pathway has several theoretical, extremely important, advantages if compared with drugs active downstream the coagulation pathway, such as FXa or thrombin. The present report gives a brief overview of TF pathophysiology, highlighting the most recent advances in the field of inhibitors of the complex TF/VIIa potentially useful in cardiovascular disease.