Cardiovascular prevention in childhood: a consensus document of the Italian Society of Cardiology Working Group on Congenital Heart Disease and Cardiovascular Prevention in Paediatric Age.

Cardiovascular diseases (CVD) may be manifested from a very early age. Genetic and environmental (epigenetic) factors interact to affect development and give rise to an abnormal phenotypical expression of genetic information, although not eliciting changes in the nucleotide sequence of DNA. It has been scientifically proven that increased oxidative stress (OS) caused by disease (overweight, obesity, diabetes), nutritional imbalances, unhealthy lifestyles (smoking, alcohol, substance abuse) in the mother during pregnancy may induce placental dysfunction, intrauterine growth restriction, prematurity, low birth weight, postnatal adiposity rebound, metabolic alterations and consequent onset of traditional cardiovascular risk factors. OS represents the cornerstone in the onset of atherosclerosis and manifestation of CVD following an extended asymptomatic period. OS activates platelets and monocytes eliciting the release of pro-inflammatory, pro-atherogenic and pro-oxidising substances resulting in endothelial dysfunction, decrease in flow-mediated arterial dilatation and increase in carotid intima-media thickness. The prevention of CVD is defined as primordial (aimed at preventing risk factors development), primary (aimed at early identification and treatment of risk factors), secondary (aimed at reducing risk of future events in patients who have already manifested a cardiovascular event), and tertiary (aimed at limiting the complex outcome of disease). Atherosclerosis prevention should be implemented as early as possible. Appropriate screening should be carried out to identify children at high risk who are apparently healthy and implement measures including dietary and lifestyle changes, addition of nutritional supplements and, lastly, pharmacological treatment if risk profiles fail to normalise. Reinstating endothelial function during the reversible stage of atherosclerosis is crucial.

Familial Hypercholesterolaemia in Children and Adolescents: Current and Future Perspectives.

Familial hypercholesterolemia (FH) is a genetic disease, the underlying cause of which is represented by mutations capable of influencing the metabolism of low-density lipoproteins (LDL). The distinguishing characteristic of FH has increased LDL cholesterol blood levels since birth, triggering early development of atherosclerosis-related diseases. Diagnosis of FH is frequently either missed or made with a considerable delay. Prompt identification of the disease is pivotal in implementing early prevention measures. Safe and effective drugs have been approved for use in children and adolescents, with statins, with or without ezetimibe, representing first-line therapy. At times, however, these medications may not be sufficient to achieve the therapeutic target, particularly in homozygous FH patients. Lipoprotein apheresis, which has proved safe and efficient, is strongly suggested in such cases. New drugs still at the investigational stage may represent a promising and personalised therapy. Lowering cholesterol levels in childhood hampers the formation of arterial atherosclerotic plaques, thus reducing cardiovascular events later in life. Accordingly, early detection, diagnosis, and therapy in FH subjects are priority aims.

Metabolomics: A New Tool in Our Understanding of Congenital Heart Disease.

Although the genetic origins underpinning congenital heart disease (CHD) have been extensively studied, genes, by themselves, do not entirely predict phenotypes, which result from the complex interplay between genes and the environment. Consequently, genes merely suggest the potential occurrence of a specific phenotype, but they cannot predict what will happen in reality. This task can be revealed by metabolomics, the most promising of the "omics sciences". Though metabolomics applied to CHD is still in its infant phase, it has already been applied to CHD prenatal diagnosis, as well as to predict outcomes after cardiac surgery. Particular metabolomic fingerprints have been identified for some of the specific CHD subtypes. The hallmarks of CHD-related pulmonary arterial hypertension have also been discovered. This review, which is presented in a narrative format, due to the heterogeneity of the selected papers, aims to provide the readers with a synopsis of the literature on metabolomics in the CHD setting.

Ventricular tachycardia triggered by the first dose of an adenoviral vector-based COVID-19 vaccine in an adult patient with congenital heart disease.

A unique adverse event of adenoviral COVID-19 vaccine in an adult patient with congenital heart disease is reported.

Micra pacemaker in adult congenital heart disease patients: A case series.

INTRODUCTION: Implantation of transvenous endocardial or epicardial pacemakers presents specific challenges in adult congenital heart disease (ACHD) patients. Micra leadless permanent pacemakers (Micra PPM) may overcome some of these difficulties. METHODS: Fifteen ACHD patients who underwent Micra PPM insertion were retrospectively evaluated. RESULTS: Males 53.3%. Mean age at study: 37.5 ± 10.7 years. Mean age at Micra PPM insertion: 35.5 ± 11.0 years. Mean follow-up so far: 2.0 ± 0.3 years. Concerning the ACHD patients, 6.7% had a simple defect, 66.6% had a moderately complex defect, 26.7% were complex. Four patients (26.7%) had a previous PPM implantation. Three patients (20%) had a systemic right ventricle. Two patients (13.3%) had a single ventricle physiology. Five (33.3%) had Trisomy 21. The most commonly used Micra PPM modality was single chamber ventricular pacemaker (73.3%). Mean threshold post implantation was 0.48 V [range: 0.25-1.13 V], while mean threshold at 6 months control was 0.60 V [range: 0.38-1.13 V] (p = ns). Mean R wave postimplantation was 10.3 V [range: 3.25-19.4 V], whilst mean R wave at 6 months follow-up was 10.1 V [range: 3.5-19.0 V] (p = ns). No major peri and postprocedural complications were encountered. CONCLUSIONS: since ACHD patients are living longer and surviving into adulthood, the incidence of conduction disorders continues to increase, as part of the natural history of some lesions or as early or late complication of surgery. The Micra leadless PPM can be successfully implanted in ACHD patients and have significant theoretical advantages. They should be considered when transvenous and epicardial pacing are either contraindicated or represent an otherwise suboptimal approach.

Systolic and diastolic function during cycling at the respiratory threshold between elderly and young healthy individuals.

The hemodynamic consequences of aging have been extensively investigated during maximal incremental exercise. However, less is known about the effects of aging on hemodynamics during submaximal steady-state exercise. The aim of the present investigation was to compare the hemodynamics of healthy elderly and young subjects during an exercise bout conducted at the gas threshold (GET) intensity. Two groups of healthy, physically active subjects were studied: the elderly group-EG (n = 11; > 60 years old) and the young group-YG (n = 13; < 35 years old). Both groups performed a 5-min rectangular exercise test at the GET intensity. Hemodynamics were measured using echocardiography. The main finding was that stroke volume responses were higher in the YG than the EG (72.5 ± 16.7 vs. 52.4 ± 8.4 ml, respectively). The increased stroke volume capacity in the YG was the consequence of a greater capacity to increase cardiac preload and contractility and, to a lesser extent, to reduce systemic vascular resistance. Importantly, the atrial contribution to ventricular diastolic filling was substantially higher in the YG when compared to the EG.

Cerebral Venous Sinus Thrombosis following COVID-19 Vaccination: Analysis of 552 Worldwide Cases.

To date, billions of vaccine doses have been administered to restrain the current COVID-19 pandemic worldwide. Rare side effects, including intravascular blood clots, were reported in the general population after vaccination. Among these, cerebral venous sinus thrombosis (CVST) has been considered the most serious one. To shed further light on such an event, we conducted a literature search for case descriptions of CVST in vaccinated people. Findings were analyzed with emphasis on demographic characteristics, type of vaccine, site of thrombosis, clinical and histopathological findings. From 258 potential articles published till September 2021, 41 studies were retrieved for a total of 552 patients. Of these, 492 patients (89.1%) had received AZD1222/Vaxzevria, 45 (8.2%) BNT162b2/CX-024414 Spikevax, 15 (2.7%) JNJ-78436735, and 2 (0.3%) Covishield vaccine. CVST occurred in 382 women and 170 men (mean aged 44 years), and the median timing from the shot was 9 days (range 2-45). Thrombi were predominantly seen in transverse (84%), sigmoid (66%), and/or superior sagittal (56%) sinuses. Brain injury (chiefly intracranial bleeding) occurred in 32% of cases. Of 426 patients with detailed clinical course, 63% were discharged in good clinical conditions, at times with variable neurological sequelae, whereas 37% deceased, largely due to brain injury. This narrative review confirmed CVST as a rare event after (adenoviral vector) COVID-19 vaccination, with a women/men rate ratio of 2.25. Though the pathogenesis of thrombosis is still under discussion, currently available histopathological findings likely indicate an underlying immune vasculitis.

Concerning the unexpected prothrombotic state following some coronavirus disease 2019 vaccines.

Currently, the world is coping with the COVID-19 pandemic with a few vaccines. So far, the European Medicine Agency has approved four of them. However, following widespread vaccination with the recombinant adenoviral vector-based Oxford-AstraZeneca vaccine, available only in the United Kingdom and Europe, many concerns have emerged, especially the report of several cases of the otherwise rare cerebral sinus vein thrombosis and splanchnic vein thrombosis. The onset of thrombosis particularly at these unusual sites, about 5--14 days after vaccination, along with thrombocytopenia and other specific blood test abnormalities, are the main features of the vaccine side effects. The acronym vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) has been coined to name this new condition, with the aim of highlighting the difference from the classic heparin-induced thrombocytopenia (HIT). VIPIT seems to primarily affect young to middle-aged women. For this reason, the vaccine administration has been stopped or limited in a few European countries. Coagulopathy induced by the Oxford-AstraZeneca vaccine (and probably by Janssen/Johnson & Johnson vaccine as well in the USA) is likely related to the use of recombinant vector DNA adenovirus, as experimentally proven in animal models. Conversely, Pfizer and Moderna vaccines use mRNA vectors. All vaccine-induced thrombotic events should be treated with a nonheparin anticoagulant. As the condition has some similarities with HIT, patients should not receive any heparin or platelet transfusion, as these treatments may potentially worsen the clinical course. Aspirin has limited rational use in this setting and is not currently recommended. Intravenous immunoglobulins may represent another potential treatment, but, most importantly, clinicians need to be aware of this new unusual postvaccination syndrome.

Anderson-fabry disease: role of traditional and new cardiac MRI techniques.

Anderson-Fabry (FD) disease is a rare X-linked disorder caused by different mutations in the Galactosidase α (GLA) gene, which leads to α-galactosidase A enzyme deficiency and the storage of glycosphingolipids in different kinds of organs, included the heart. This results in myocardial inflammation and left ventricular hypertrophy (LVH) and fibrosis. Echocardiography and cardiac magnetic resonance (C-MRI), in particular with new techniques, such as mapping analysis, late gadolinium enhancement (LGE) assessment and strain imaging, are important tools that allow a correct diagnosis, discriminating FD from other hypertrophic heart conditions. C-MRI is able to detect tissue alterations in the early stages of the disease, when an appropriate treatment could be more effective, and it has a fundamental role in monitoring therapy.

[Preoperative dental screening in patients waiting for elective cardiovascular procedures: presentation of the SIC-ANMCO-SICCH-AIE-SIE-SidP intersociety consensus document]. / Lo screening dentale preoperatorio nei pazienti in attesa di interventi chirurgici cardiovascolari elettivi: presentazione del documento di consenso intersocietario SIC-ANMCO-SICCH-AIE-SIE-SidP.

The Italian scientific societies of cardiology (SIC and ANMCO), cardiothoracic surgery, endodontics, and periodontology realized that a specific protocol addressing preoperative dental/peri-dental screening in patients undergoing elective cardiothoracic surgery was lacking in the literature. As a consequence, they projected and then realized in 2019 a consensus document to establish the modalities for such a diagnostic and therapeutic screening, whose related options and timing depend on the patient's physical conditions as well as the time available before surgery. A high level of agreement was reached by the experts involved in the release of the consensus document and each clinical issue was addressed adequately. Three tables were released, with the aim of sharing a standardized protocol for the perioperative dental/peri-dental screening of patients who are waiting for elective cardiothoracic procedures. The authors of the consensus document, which has been widely diffused by all the involved scientific societies, hope that it can be largely accepted and applied, during the multidisciplinary phase preceding cardiovascular surgery the most.

Pulmonary hypertension in pediatrics. A feasible approach to bridge the gap between real world and guidelines.

Pulmonary hypertension (PH) is quite infrequent in pediatric age and its most common etiologies include idiopathic pulmonary arterial hypertension, PH related to congenital heart diseases, bronchopulmonary dysplasia (chronic lung disease), persistence of pulmonary hypertension of the newborn, and congenital diaphragmatic hernia. The developed for adult patients PH classification shows limitations when applied to pediatric subjects since the underlying causes are markedly different between the two ages. In 2011, the Pulmonary Vascular Research Institute Panama Task Force outlined the first specific pediatric pulmonary hypertensive vascular disease diagnostic classification, including 10 main categories and 109 subcategories, thus testifying PH complex pathophysiology during newborns/children growth and development. The unique, distinctive features of pediatric PH were recognized also during the fifth World Symposium on pulmonary hypertension in 2013 and then confirmed in the recent 2018 sixth World Symposium. For the sake of uniformity, an attempt to adapt the adult classification to pediatric patients was made. However, all these commendable classifications are very complex and maybe not of quick comprehension for clinicians. A clinical simpler and simplified method is now suggested, comprising only five groups: neonatal, cardiac, developmental, idiopathic, and syndromic PH. This approach is not aimed at replacing the already existing classifications but is mainly based on the kind of specialized physician (neonatologist, pediatric cardiologist, pediatrician, pulmonologist, general practitioner) who first faces and looks after the child with suspected PH. What is dramatically known is that pediatric PH is a severe disease which, when untreated or undertreated, may lead to increased morbidity and mortality.

Cardiac MRI prior to liver biopsy in a Fontan patient: A case report.

The management of adults with complex congenital heart disease requires a multidisciplinary team (Heart Team).

A brief bout of exercise in hypoxia reduces ventricular filling rate and stroke volume response during muscle metaboreflex activation.

PURPOSE: The hemodynamic consequences of exercise in hypoxia have not been completely investigated. The present investigation aimed at studying the hemodynamic effects of contemporary normobaric hypoxia and metaboreflex activation. METHODS: Eleven physically active, healthy males (age 32.7 ± 7.2 years) completed a cardiopulmonary test on an electromagnetically braked cycle-ergometer to determine their maximum workload (Wmax). On separate days, participants performed two randomly assigned exercise sessions (3 minutes pedalling at 30% of Wmax): (1) one in normoxia (NORMO), and (2) one in normobaric hypoxia with FiO2 set to 13.5% (HYPO). After each session, the following protocol was randomly assigned: either (1) post-exercise muscle ischemia (PEMI) to study the metaboreflex, or (2) a control exercise recovery session, i.e., without metaboreflex activation. Hemodynamics were assessed with impedance cardiography. RESULTS: The main result was that the HYPO session impaired the ventricular filling rate (measured as stroke volume/diastolic time) response during PEMI versus control condition in comparison to the NORMO test (31.33 ± 68.03 vs. 81.52 ± 49.23 ml·s-1,respectively, p = 0.003). This caused a reduction in the stroke volume response (1.45 ± 9.49 vs. 10.68 ± 8.21 ml, p = 0.020). As a consequence, cardiac output response was impaired during the HYPO test. CONCLUSIONS: The present investigation suggests that a brief exercise bout in hypoxia is capable of impairing cardiac filling rate as well as stroke volume during the metaboreflex. These results are in good accordance with recent findings showing that among hemodynamic modulators, ventricular filling is the most sensible variable to hypoxic stimuli.

Multimodality Imaging Diagnosis of Multiple Ventricular Thrombosis and Massive Stroke after Gemcitabine and Cisplatin Chemotherapy for Urothelial Cancer.

Cancer and chemotherapy are known to be risk factors for developing coagulative disorders, venous thrombosis, adverse cardiovascular events, and cardiotoxicity. Combined modality gemcitabine-cisplatin chemotherapy is often administered to treat a few solid tumors. We report the unusual case of a man suffering from urothelial cancer and admitted for chemotherapy, who developed an ischemic stroke after the last chemotherapeutical cycle. During his hospital stay, at echocardiographic examination, left ventricular transient hypokinesia and two intraventricular thrombi were detected, without evidence of acute coronary syndrome. Multimodality imaging approach (i.e., transthoracic echo, transoesophageal echo, computed tomography, and cardiac magnetic resonance imaging) played a pivotal role for a clear diagnosis and prompt decision-making. This is the first report of an intraventricular-related arterial thromboembolic event in a patient treated with the combination gemcitabine-cisplatin.

Does gender affect the prognosis and risk of complications in patients with congenital heart disease in the modern era?

Gender differences in the outcome of acquired cardiovascular disease are well known, but available literature on the influence of gender in congenital heart disease (CHD) is limited. Registries have provided valuable, albeit at times conflicting data. Higher mortality rates have been reported in older males with CHD, while sudden cardiac death is more prevalent in young males. However, mortality around surgery for CHD is higher in girls compared to boys, likely due to smaller body size. Women are at higher risk of developing pulmonary arterial hypertension, but at lower risk of adverse aortic outcomes, even though they are less likely to receive aortic surgery. Finally, women have a lower risk of presenting with infective endocarditis compared to men. The underlying reasons for gender differences in CHD can be attributed to genetic, hormonal, behavioural and other causes. The aim of the present paper is to provide an overview of available evidence on gender differences in CHD and their impact on outcome.

Pharmacological Treatment of Vagal Hyperactivity, a Rare but Potentially Fatal Cause of Sudden Cardiac Death.

Vasovagal reaction, resulting in bradycardia and/or hypotension in response to a number of stimuli, is usually self-limiting, but potentially life-threatening exceptions have been described. Pharmacological treatment of proven efficacy is still lacking and the administered compounds are often chosen on the basis of either case reports or outdated small studies with a short-term follow up. In refractory cases, pacemaker implantation may be considered, although no responder patients represent a severe challenge for clinicians. The aim of this review is to examine the state of the art about this controversial issue.

Supraventricular tachycardia during the first year of life: is subclinical inflammation the trigger?

BACKGROUND: Neutrophil/lymphocyte ratio (NLR) and red cell distribution width (RDW) may be associated with the onset of arrhythmias in adults, thus underlining a possible inflammatory etiology. Paroxysmal supraventricular tachycardia (SVT) is the most frequent pathological tachycardia in childhood. AIM: To verify NLR and RDW levels in a group of children (<1 year) affected by SVT with a structurally normal heart and without fever or inflammatory diseases; to compare NLR and RDW before and after SVT resolution, to verify whether the latter was related with the reduction in inflammatory state; to identify - in SVT subtypes caused by a reentry mechanism - an NLR and RDW cutoff point beyond which adenosine was ineffective in preventing SVT recurrence. METHODS: Eighteen SVT patients were recruited (mean age 18.9 ± 3.2 days; 50% males) and compared with 18 healthy peers. RESULTS: NLR was higher in SVT group than in controls (p < 0.03). A significant difference was revealed between NLR values obtained on admission and at discharge (p < 0.05). On the contrary, no significant differences were found for RDW. It was not possible to identify NLR or RDW cutoffs capable of predicting SVT recurrence. However, all patients featuring SVT recurrence following adenosine injection presented with a lymphocyte count >6000/mm3. CONCLUSIONS: Elevated NLR is associated with an increased risk of SVT during the first year of life, while its decline looks like to lead the SVT resolution. A subclinical inflammatory status, as assessed by lymphocytes count, influences SVT recurrence. These results provide further support for an inflammatory etiology of SVT in babies.

Altered Aortic Upper Wall TDI Velocity Is Inversely Related with Left Ventricular Diastolic Function in Operated Tetralogy of Fallot.

OBJECTIVE: Postoperative tetralogy of Fallot (TOF) patients often develop progressive aortic root dilatation due to an impairment in aortic elastic properties. AIMS: (1) to assess aortic elasticity at the level of the aortic upper wall by tissue Doppler imaging (TDI); (2) to evaluate the influence of aortic elasticity on left ventricular (LV) diastolic function in TOF patients. DESIGN: Twenty-eight postoperative TOF patients (14 males, 14 females. Mean age: 25.7 ± 1.6 years) and 28 age- and sex-matched normal subjects were examined. Aortic distensibility and stiffness index were calculated. Aortic wall systolic and diastolic velocities, LV systolic and diastolic parameters were assessed by TDI. RESULTS: Aortic distensibility was significantly lower (P = .024), and aortic stiffness index significantly higher (P = .036) in TOF patients compared to controls. E/E' was significantly higher in TOF than in control group (P < .001). Aortic upper wall early diastolic velocity (AWEDV) was significantly correlated with aortic stiffness index (r: -0.42; P < .03), aortic distensibility (r = 0.54; P < .004), left atrial volume (r = -0.62; P = .0004), and E/E' ratio (r = -0.87; P < .0001). The latter relationship remained significant even when excluding the influence of age at surgery (r = -0.60; P < .0007) and of previous palliative surgery (r = -0.53; P < .02). CONCLUSIONS: Aortic elastic properties can be directly assessed using TDI to measure AWEDV. Aortic elasticity is significantly lower in postoperative TOF patients, exerting a negative effect also on LV diastolic function, with a potential long-term influence on clinical status.

Daily assessment of arterial distensibility in a pediatric population before and after smoking cessation.

OBJECTIVES: Cigarette smoking is an important modifiable cardiovascular risk factor associated with increased stiffness of the large arteries in adulthood. This study aimed to 1) evaluate arterial distensibility and echocardiographic measures in adolescent smokers before and after participation in a successful smoking cessation program and to 2) compare the findings obtained with data from a control population of healthy non-smokers. METHODS: A total of 31 young smoking subjects (58.1% male; range: 11-18 years old; mean: 16.5±1.4 years old; mean tobacco consumption: 2.6±0.6 years) were examined before commencing and after taking part for at least 1 year in a smoking cessation program (mean: 1.4±0.3 years). Arterial stiffness was measured using the previously validated QKd100-60 method. Twenty-four-hour ambulatory blood pressure monitoring and transthoracic echocardiography were also performed. RESULTS: (Smokers before abuse cessation vs. smokers after abuse cessation) systolic blood pressure: p<0.004; diastolic blood pressure: p<0.02; mean blood pressure: p<0.01; QKd100-60 value: 183±5 vs. 196±3 msec, p<0.009; p = ns for all echocardiographic parameters. (Smokers after abuse cessation vs. controls) systolic blood pressure: p<0.01; diastolic blood pressure: p<0.03; mean blood pressure: p<0.02; QKd100-60 value: 196±3 vs. 203±2 msec, p<0.04; p<0.02, p<0.01, and p<0.05 for the interventricular septum, posterior wall, and left ventricular mass, respectively. CONCLUSIONS: Despite successful participation in a smoking cessation program, arterial distensibility improved but did not normalize. This finding underlines the presence of the harmful effect of arterial rigidity in these individuals, despite their having quit smoking and their young ages, thus resulting in the subsequent need for a lengthy follow-up period.

Daily assessment of arterial distensibility in a pediatric population before and after smoking cessation

OBJECTIVES: Cigarette smoking is an important modifiable cardiovascular risk factor associated with increased stiffness of the large arteries in adulthood. This study aimed to 1) evaluate arterial distensibility and echocardiographic measures in adolescent smokers before and after participation in a successful smoking cessation program and to 2) compare the findings obtained with data from a control population of healthy non-smokers. METHODS: A total of 31 young smoking subjects (58.1% male; range: 11-18 years old; mean: 16.5±1.4 years old; mean tobacco consumption: 2.6±0.6 years) were examined before commencing and after taking part for at least 1 year in a smoking cessation program (mean: 1.4±0.3 years). Arterial stiffness was measured using the previously validated QKd100-60 method. Twenty-four-hour ambulatory blood pressure monitoring and transthoracic echocardiography were also performed. RESULTS: (Smokers before abuse cessation vs. smokers after abuse cessation) systolic blood pressure: p<0.004; diastolic blood pressure: p<0.02; mean blood pressure: p<0.01; QKd100-60 value: 183±5 vs. 196±3 msec, p<0.009; p = ns for all echocardiographic parameters. (Smokers after abuse cessation vs. controls) systolic blood pressure: p<0.01; diastolic blood pressure: p<0.03; mean blood pressure: p<0.02; QKd100-60 value: 196±3 vs. 203±2 msec, p<0.04; p<0.02, p<0.01, and p<0.05 for the interventricular septum, posterior wall, and left ventricular mass, respectively. CONCLUSIONS: Despite successful participation in a smoking cessation program, arterial distensibility improved but did not normalize. This finding underlines the presence of the harmful effect of arterial rigidity in these individuals, despite their having quit smoking and their young ages, thus resulting in the subsequent need for a lengthy follow-up period. .