The long-term cardiovascular impairment of COVID 19: need for clarity in definition and terminology.

Clinical experience and several large studies in the field have found that SARS-CoV-2 infection can cause long-term persistent cardiovascular (CV) impairment beyond the acute phase of the disease. This has resulted in a major public health concern worldwide. Regarding COVID-related long-term involvement of various organs and systems, using specific definitions and terminology is crucial to point out time relationships, lingering damage, and outcome, mostly when symptoms and signs of CV disease persist beyond the acute phase. Due to a lack of a common standardized definition, investigators have used interchangeable terms such as "long COVID," "post-COVID," or "post-acute sequelae of COVID-19" to describe CV involvement, thus causing some confusion. For the sake of clarity, the aim of this paper is to discuss the definition and terminology used in defining sequelae after the acute phase of COVID-19, thus pointing out the meaning of definitions like acute cardiac injury, post-acute sequelae of COVID-19, long COVID syndrome, and increased risk of atherosclerotic cardiovascular disease.

COVID-19 and hepatic damage: what we know?

INTRODUCTION: Since the end of 2019, a new disease outbreak has been spreading worldwide, after starting from Wuhan, China. The viral pathogen responsible for the disease was named as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), and for the illness the acronym COVID-19 was coined (COronaVIrus Disease 2019). Viral pathogenesis, epidemiology, and clinics are still somewhat obscure, when occurring during childhood the most. The aim of this study was to evaluate the features of liver involvement and damage in course of COVID-19. EVIDENCE ACQUISITION: An insight into what is known as to COVID-19 and hepatic damage in adulthood as well as pediatric age was given. All the most relevant papers up to 15/10/2020 were identified and discussed. An extensive search strategy was carried out to identify all paper published from December 1st, 2019, to September 5, 2020, combining the key words "coronavirus," "coronavirus infection," "SARS-CoV-2," "COVID-19," "liver," "liver injury," "hepatic injury," "children," "pediatric" in key electronic bibliographic databases (PubMed, Google Scholar), following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. EVIDENCE SYNTHESIS: Establishing whether liver damage is due to a direct viral action or host immune system inflammatory reaction or consequence of the administered drugs or secondary to another organ failure (for example the heart) is difficult. What is sure is the fact that liver function should be checked at the time of admission to hospital and during hospitalization. CONCLUSIONS: In conclusion, liver involvement during COVID-19 is likely due to a multifactorial origin. An aberrant immune system reaction to SARS-CoV-2 is probably the most important underlying trigger, though more extended studies are needed for a definitive confirmation. The markers of liver injury should be carefully in each patient admitted for COVID-19: in fact, in case of altered hepatic markers, a specific therapy to protect liver is needed.

Emerging Role of Cardiac Magnetic Resonance Imaging in Diagnosing Myocarditis: A Blunder or The Way To Get the Problem Sorted?

Acute myocarditis is a disease affecting the myocardial tissue, which is caused by infections, rheumatic diseases, especially sarcoidosis, or certain therapies. Its diagnosis may be difficult, owing to its variable clinical presentation. In this setting, cardiac magnetic resonance plays a pivotal role in detecting myocardial inflammation through qualitative, semiquantitative, and quantitative parameters, in particular with the new quantitative techniques such as T1 and T2 mapping, combined or not with late gadolinium enhancement evaluation. This is in accordance with the revised Lake Louise criteria. In this review, the emerging role of the new cutting-edge cardiac magnetic resonance imaging techniques in diagnosing myocarditis is extensively presented.

Tricuspid valve in congenital heart disease: multimodality imaging and electrophysiological considerations.

The tricuspid valve (TV) has been neglected for many years. Only recently, new studies demonstrated the prognostic role of the tricuspid valve lesions. In addition to that, new interventional approaches offer the possibility to noninvasively treat tricuspid valve disease. In this review, our aim was to summarize the role of different imaging techniques in the assessment of tricuspid valve with particular regards to congenital heart diseases. Finally, we analyze the importance of the TV and its adjacent regions from an electrophysiological point of view, both in structurally normal hearts and in congenital heart diseases. The most relevant transthoracic echocardiography (TTE) views to visualize the TV are the "modified" parasternal long axis, the apical views and subcostal projections, such as right oblique or left oblique views. However, simultaneous visualization of the three leaflets is possible only with three-dimensional TTE or, sometimes, in parasternal short axis and subcostal short axis views in children. 3D echocardiography is promising in this field. Indeed, its unique projections, such as en-face views from the right ventricular and atrial perspectives, are able to define the spatial relationship of the tricuspid leaflets with the surrounding structures. Moreover, multimodality imaging assessment has been recently proposed for the diagnostic assessment of the TV, especially before percutaneous intervention. Cardiac computed tomography provides valuable anatomic spatial information of the TV apparatus. Cardiac magnetic resonance is able to provide, noninvasively, detailed morphological and functional information of the valve.

Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: Differences in Global and Segmental Myocardial Strain by Cardiac Magnetic Resonance Feature Tracking.

PURPOSE: To evaluate any significant differences in myocardial strain between hypertrophic obstructive cardiomyopathy (HOCM) and nonobstructive ones (HNCM), as assessed by cardiac magnetic resonance feature tracking (CMR-FT). MATERIALS AND METHODS: A total of 17 patients (mean age: 54±14 y) with echocardiographic diagnosis of HOCM (left ventricular outflow tract obstruction peak gradient ≥30 mm Hg), 19 patients (mean age: 49±16 y) with HNCM (peak gradient <30 mm Hg), and 18 age-matched and gender-matched healthy controls (mean age: 42±14 y). All patients underwent cardiac MRI with SSFP-cine to assess left ventricular global and segmental strain analysis by CMR-FT. Late gadolinium enhancement (LGE) sequences were used for semiautomatic quantification of LGE volume, mass, and percentage. RESULTS: The magnitude of global radial, circumferential, and longitudinal strain as well as strain rate were significantly lower in all patients in comparison to controls (P<0.001), except for radial and circumferential strain between HOCM and controls (P=0.270; P=0.154). The latter strain parameters were significantly higher in HOCM than HNCM (radial strain: 31.67±7.55 vs. 21.26±7.10, P<0.001; circumferential strain: -17.94±2.78 vs. -13.46±3.42, P<0.001). Radial and circumferential strain and circumferential diastolic strain rate were higher in mid-anterior (P<0.001), mid-anteroseptal (P<0.001), and all apical segments (P<0.005) between the 2 groups of patients. Moreover, longitudinal strain was higher only in apical segments in HOCM (P<0.02). CONCLUSIONS: HOCM patients showed higher left ventricular apical, mid-anterior, and mid-anteroseptal strain parameters compared with HNCM. These differences were independent of corresponding segmental thickness and LGE amount.

The Deadly Quartet (Covid-19, Old Age, Lung Disease, and Heart Failure) Explains Why Coronavirus-Related Mortality in Northern Italy Was So High.

Since its outbreak in China at the end of 2019, the new coronavirus disease (COVID-19) was characterized by both easy spreading and high mortality. The latter proved to be way more elevated in the North of Italy -with a peak of 18.4% in region Lombardia and even 31% in the city of Bergamo and surrounding county- than in the rest of the world. In an attempt to conceptualize the reasons for such a dramatic situation, four key elements have been identified: COVID-19 itself, old age, lung disease, and heart failure. Their harmful combination has been named "The deadly quartet". The underlying risk factors, among which a lot of them are distinctive features of the population in northern Italy, have been summarized as "unmodifiable", "partially modifiable", and "modifiable", for the sake of clarity. Up-to-date scientific evidence in this field has been described in the form of a narrative and easy-to-read review.

COVID-19, thromboembolic risk, and Virchow's triad: Lesson from the past.

COronavirus Infectious Disease which started in 2019 (COVID-19) usually presents with the signs and symptoms of pneumonia. However, a growing number of recent reports highlight the fact that the infection may be by far more than only a respiratory disease. There is evidence of an increased thromboembolic risk in COVID-19 patients, with a variety of manifestations in terms of ischemic stroke, deep vein thrombosis, acute pulmonary embolism, acute myocardial infarction, systemic arterial embolism, and placental thrombosis. The German physician Rudolph Virchow, about two centuries ago, described three pivotal factors contributing together to thromboembolic risk: endothelial injury, hypercoagulability, and blood stasis. COVID-19-associated hypercoagulability is unique and distinctive, and has its own features involving the immune system. Many of the drugs proposed and currently undergoing evaluation for the treatment of COVID-19 have one or more of the Virchow's triad elements as a target. The three factors outlined by Virchow are still able to explain the venous and arterial hypercoagulable state in the dramatic COVID-19 setting. Nowadays, we have decidedly more sophisticated diagnostic tools than Virchow had, but many of the challenges that we are facing are the same as Virchow faced in the 19th century.

What have we learnt 50 years after the first Fontan procedure?

The Fontan procedure is often the only definitive palliative surgical option for patients with a variety of complex CHD sharing in common, a single, dominant ventricle. In recent decades, imaging and therapeutic improvement have played a crucial role in those patients in whom many complications can hamper their life. After 50 years from the first procedure, heart transplantation remains the only definitive treatment for those with a failing Fontan circulation.

Gender Differences in Hemodynamic Regulation and Cardiovascular Adaptations to Dynamic Exercise.

Exercise is a major challenge for cardiovascular apparatus since it recruits chronotropic, inotropic, pre-load, and afterload reserves. Regular physical training induces several physiological adaptations leading to an increase in both cardiac volume and mass. It appears that several genderrelated physiological and morphological differences exist in the cardiovascular adjustments and adaptations to dynamic exercise in humans. In this respect, gender may be important in determining these adjustments and adaptations to dynamic exercise due to genetic, endocrine, and body composition differences between sexes. Females seem to have a reduced vasoconstriction and a lower vascular resistance in comparison to males, especially after exercise. Significant differences exist also in the cardiovascular adaptations to physical training, with trained women showing smaller cardiac volume and wall thickness compared with male athletes. In this review, we summarize these differences.

Factors Predisposing to Hypertension in Subjects Formerly Born Preterm: Renal Impairment, Arterial Stiffness, Endothelial Dysfunction or Something Else?

Subjects formerly born preterm subsequently develop arterial - particularly isolated systolic- hypertension more frequently than their peers born at term. Numerous factors may influence this predisposition, including an incomplete nephrogenesis, implying the presence of kidneys with a reduced number of nephrons and consequent reduction in haematic filtration, increased sodium absorption and activation of renin-angiotensin-aldosterone system, increased arterial rigidity produced by an elastin deficiency previously observed in anatomic specimens of human immature aorta, and reduced endothelial nitric oxide excretion, due to high blood levels of ADMA, a strong direct inhibitor of nitric oxide that exerts a vasoconstrictor effect. Other possible factors (i.e. excretion of neuroendocrine compounds) may also be implicated. The aim of this paper was to review all possible mechanisms involved in the observed increase in blood pressure in individuals who had been born preterm and/or with intrauterine growth restriction. The outlook for new and promising laboratory techniques capable of identifying alterations in the metabolic pathways regulating blood pressure levels, such as metabolomics, is also provided.

Metabolomic Approach to Redox and Nitrosative Reactions in Cardiovascular Diseases.

Metabolomics, also referred to as metabonomics, is one of the most recent innovative technologies in medicine. It offers a direct functional read-out of phenotypes by the detection, identification, and quantification of a large number of metabolites within a biological sample such as urine and blood. Metabolites (<1500 Da) represent the output of cellular metabolism, accounting for expression and activity of genes, transcripts, and proteins, and offering unique insights into small molecule regulation, which may uncover new biochemical patterns. Metabolomics research has considerable potential for translating the metabolic fingerprint into personalized therapeutic strategies. Within the field of interest, cardiovascular disease (CVD) is one of the most developed areas. However, CVD remains the leading cause of death worldwide with a marked increase in mortality rates over the past six decades. In this scenario, recent findings indicate the important role of redox and nitrosative (RN) reactions in CVD development and progression. RN reactions are generally involved in the homeostatic modulation of a wide number of cellular and organ functions. Conversely, the imbalance of these reactions may lead to a condition of allostasis that in turn can cause CVD. The aim of this review is to highlight how the use of metabolomics may be useful for the study of RN reactions related to CVD, providing a tool to understand the mechanisms underlying reactions that could lead to impaired ROS or RNS formation.

Impaired Endothelial Function in Hereditary Angioedema During the Symptom-Free Period.

Introduction: The presence of coronary endothelial dysfunction was previously shown in Hereditary Angioedema (HAE) patients. The aim of our study was to evaluate the effect of HAE on systemic endothelial function and whether there was a relationship among endothelial function, asymmetric dimethylarginine (ADMA) -which is a strong inhibitor of nitric oxide synthesis-, and disease severity scores. Methods: Twenty-four HAE patients (18 females, aged 47.9 ± 2 years) without factors known to interfere with endothelial function were studied and compared with 24 healthy peers age- and gender-matched. Endothelial function was assessed by means of non-invasive finger plethysmography (reactive hyperaemia index: RHI) and ADMA levels by high-performance liquid chromatography. HAE severity scores have been calculated according to published literature. Results: In HAE patients RHI was lower (2.03 ± 0.46 vs. 2.82 ± 0.34, p < 0.0001) and ADMA higher (0.636 ± 7 vs. 585 ± 5 micromol/L, p < 0.01) than in controls. A statistically significant inverse correlation was revealed between RHI and patients' ADMA levels (r = -0.516, p = 0.009) as well as between RHI and patients' chronological age (r = -0.49, p = 0.015). A statistically significant correlation between RHI and ADMA was confirmed even when excluding the possible influence of cholesterol (r = -0.408, p = 0.048). No other significant correlations were found with the examined laboratory and clinical parameters (chronological age, age at disease onset, disease duration, severity scores, and gender). Conclusion: The dysfunction previously shown in HAE patients at the coronary arteries seems to involve the peripheral vessels as well, without a correlation with disease severity.

Chemotherapy-induced cardiotoxicity: new insights into mechanisms, monitoring, and prevention.

: Chemotherapy-induced cardiotoxicity (CTX) remains a determining factor for the quality of life and mortality of patients treated with potentially cardiotoxic drugs. Considerable advances have been made in this field with increase in awareness regarding chemotherapy-induced CTX, which has changed the treatment approach to include cardiovascular risk among the first factors to be evaluated before therapy. Moreover, a better understanding of the pathophysiology of chemotherapy-induced CTX has also facilitated early identification of patients at risk with the help of new imaging technologies. The newly developed imaging tools in cardio-oncology have led to the introduction of novel parameters for evaluation of myocardial function. This, together with a renewed standardization of measurements, has increased the adherence to monitoring protocols. With respect to treatment and prevention, researchers have started focusing attention on the development of new strategies as well as new cardioprotective agents that will play a crucial role in the prevention of CTX in the near future.

Nordic walking for individuals with cardiovascular disease: A systematic review and meta-analysis of randomized controlled trials.

Background Exercise is the cornerstone of rehabilitation programmes for individuals with cardiovascular disease (IwCVD). Although conventional cardiovascular rehabilitation (CCVR) programmes have significant advantages, non-conventional activities such as Nordic walking (NW) may offer additional health benefits. Our aim was to appraise research evidence on the effects of Nordic walking for individuals with cardiovascular disease. Design Systematic review and meta-analysis. Methods A literature search of clinical databases (PubMed, MEDLINE, Scopus, Web of Science, Cochrane) was conducted to identify any randomized controlled trials, including: (i) individuals with cardiovascular disease, (ii) analyses of the main outcomes arising from Nordic walking (NW) programmes. Data from the common outcomes were extracted and pooled in the meta-analysis. Standardized mean differences (SMDs) were calculated and pooled by random effects models. Results Fifteen randomized controlled trials were included and eight trials entered this meta-analysis. Studies focused on coronary artery disease, peripheral arterial disease, heart failure and stroke. In coronary artery disease, significant differences between NW+CCVR and CCVR were found in exercise capacity (SMD: 0.49; p = 0.03) and dynamic balance (SMD: 0.55; p = 0.01) favouring NW+CCVR. In peripheral artery disease, larger changes in exercise duration (SMD: 0.93; p < 0.0001) and oxygen uptake (SMD: 0.64; p = 0.002) were observed following NW compared with controls. In heart failure, no significant differences were found between NW and CCVR or usual care for peak VO2 and functional mobility. In post-stroke survivors, functional mobility was significantly higher following treadmill programmes with poles rather than without (SMD: 0.80; p = 0.03). Conclusions These data portray NW as a feasible and promising activity for individuals with cardiovascular disease. Further studies are necessary to verify whether NW may be incorporated within CCVR for individuals with cardiovascular disease.