Right Ventricular Myocardial Involvement in Anderson-Fabry Disease at Diagnosis: Evaluation with Three-Dimensional Strain Imaging.

Background: Right ventricular (RV) involvement in Anderson-Fabry disease (AFD) is well known in the advanced stages of the disease RV hypertrophies, but little is known about the early involvement. The aim of our study was to assess RV function in AFD patients at diagnosis. Methods: A total of 23 AFD patients and 15 controls comparable for age and sex were recruited. A complete 2D standard echo with 3D volumetric and strain analysis of RV was performed. Results: Two patient populations, comparable for clinical baseline characteristics were considered. RV free wall thickness was significantly increased in the AFD group. No significant differences in standard RV indices (TAPSE, transverse diameter, tissue Doppler velocities of the lateral tricuspid annulus) were found. A 3D volumetric analysis showed reduced RV ejection fraction and lower values of longitudinal septal, free wall and global longitudinal strain (GLS) in AFD patients. RV free wall thickness significantly correlated with both free wall RV LS and RV GLS. In multiple linear regression analysis, RV free wall thickness was independently associated with RV GLS even after correction for age and heart rate. Conclusions: In AFD patients, 3D echocardiography allows for the identification of early subclinical functional impairment of RV. RV dysfunction is independently associated with RV hypertrophy.

A Rare Case of Tricuspid Valve Libman-Sacks Endocarditis in a Pregnant Woman with Primary Antiphospholipid Syndrome.

Antiphospholipid Antibody Syndrome (APS) is a systemic autoimmune disease characterized by acquired hypercoagulability with the possible development of venous, arterial, and microvascular thrombosis. We report a rare case of Libman-Sacks tricuspid valve endocarditis in a 38-year-old pregnant woman at 15 weeks gestation with unknown primary antiphospholipid syndrome. During a routine cardiac examination and echocardiography performed for a previous episode of pleuropericarditis, a large, mobile mass with irregular edges was found at the level of the tricuspid valve. Three main differential diagnoses for intramyocardial mass were examined: tumor, infective endocarditis, and nonbacterial thrombotic endocarditis (NTBE). Cardiac magnetic resonance imaging (CMR) with contrast raised the suspicion of a thrombus. The woman was hospitalized urgently at the Cardiac Intensive Care Unit of the Federico II University Hospital, and anticoagulant and antiplatelet therapy were started. The thrombophilic screening performed and medical history confirmed the diagnosis of primary antibody syndrome (APS). A multidisciplinary consultation with obstetricians, cardiologists, anesthetists, and cardiac surgeons was required. The patient decided not to terminate the pregnancy despite the risk to her health and to undergo cardiac surgery during pregnancy. Histological examination confirmed the presence of nonbacterial thrombotic endocarditis. Weekly obstetric scans were performed after surgery to verify fetal well-being. An emergency cesarean section was performed at the 35th week of gestation due to repeated deceleration and abnormal short-term variability on c-CTG in a pregnancy complicated by fetal growth restriction and gestational hypertension. A newborn weighing 1290 g was born. She was hospitalized in Neonatal Intensive Care and discharged after two months; currently, she enjoys good health. The management of patients with antiphospholipid antibody syndrome has not yet been standardized, but there is a general consensus that patients who do not have thrombocytopenia, thromboembolic phenomena, or pregnancy should not undergo any treatment or should take only low doses of acetylsalicylic acid. In the presence of any of the above conditions, various treatment regimens have been used based on the severity and individuality of the case.

An Emergent Form of Cardiotoxicity: Acute Myocarditis Induced by Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. ICIs have shown great promise in the treatment of several advanced malignancies. However, therapy with these immunomodulatory antibodies may lead to a wide spectrum of immune-related adverse events in any organ and any tissue. Cardiologic immune-related events include pericarditis, pericardial effusion, various types of arrhythmias including the occurrence of complete atrioventricular block, myocardial infarction, heart failure, and myocarditis. Although relatively rare, myocarditis is associated with a very high reported mortality in comparison to other adverse events. Myocarditis often presents significant diagnostic complexity and may be under-recognized. When confronted with an unexpected change in the clinical picture, the physician must differentiate between immune-related adverse events, cancer worsening, or other causes unrelated to the cancer or its therapy. However, this is not always easy. Therefore, with the increasing use of checkpoint inhibitors in cancer, all providers who care for patients with cancer should be made aware of this rare, but potentially fatal, cardiologic immune-related adverse event, and able to recognize when prompt consultation with a cardiologist specialist is indicated. In this review, we evaluate currently available scientific evidence and discuss clinical manifestations and new potential approaches to the diagnosis and therapy of acute myocarditis induced by ICIs. Temporary or permanent discontinuation of the ICIs and high-dose steroids have been administered to treat myocarditis, but symptoms may worsen in some patients despite therapy.

Cardiac Imaging in Anderson-Fabry Disease: Past, Present and Future.

Anderson-Fabrydisease is an X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-galactosidase A. This results in pathological accumulation of glycosphingolipids in several tissues and multi-organ progressive dysfunction. The typical clinical phenotype of Anderson-Fabry cardiomyopathy is progressive hypertrophic cardiomyopathy associated with rhythm and conduction disturbances. Cardiac imaging plays a key role in the evaluation and management of Anderson-Fabry disease patients. The present review highlights the value and perspectives of standard and advanced cardiovascular imaging in Anderson-Fabry disease.

Epidemiology, prognosis, and clinical manifestation of cardiovascular disease in COVID-19.

INTRODUCTION: At the end of 2019, a novel coronavirus was identified as the cause of a pneumonia cluster in Wuhan, China. Since then, the contagion has rapidly spread all over the world resulting in a global pandemic. Since frequent cardiovascular (CV) system involvement has soon been detected in patients occurring coronavirus disease 2019 (COVID-19), we would provide a simple review available to cardiologists who are going to be involved in the management of COVID-19 patients from several levels: from diagnosis to prevention and management of CV complications. AREAS COVERED: We investigate the role of CV diseases in COVID-19: from the incidence of CV comorbidities to their negative impact on prognosis. We also search Literature in order to identify the main CV manifestations in patients occurring virus infection and their management by cardiologists. EXPERT OPINION: Specific treatments for CV involvement associated with COVID-19 are still debated. Results from ongoing trials are needed to further clarify issues about the therapeutic approach, which is constantly changing according to the continuous flow of published evidence. Finally, it seems necessary to sensitize all population to raise awareness on CV diseases in the COVID era, to hinder the underestimation of both new-onset acute CV diseases and the consequences of chronic mistreated CV diseases.

77 Routine outpatients visits during SARS-CoV2 global pandemic.

Aims: The inability to carry office visits was collateral damage caused by the Coronavirus (COVID-19) pandemic. Tele-health is a relatively new, and yet fundamental amid the current crisis, resource to bridge the gap between phisicians and patients. Methods and results: We report our experience with telemedicine and describe the major events occured in our patients. 121 consecutive adult patients with arterial hypertension (F/M: 56/65; mean age: 66.8 years) were enrolled. 33 patients (27%) had also diabetes, 94 (78%) were also affected from dyslipidemia and 11 (9%) had CAD. They all referred to our ambulatory of hypertension, in most of case for several years. Given the impossibility to continue routine outpatient visits during lockdown, they were all phone called by three residents in order to detect their state of health or any events they could have experienced over this period. They were all asked about their own blood pressure values, the occurrence of new symptoms and of new-onset both cardiovascular and non cardiovascular events. We also followed a self-made preset form. 31 of them (26%) experienced cardiovascular symptoms/events during this period: 11 had hypertensive peaks, in one case associated with nausea and vomiting while 2 of them had hypotensive episodes; 10 had typical angina and/or dyspnoea while 4 had atypical angina; 6 had palpitations; 1 of them developed new onset atrial fibrillation resolved with pharmacologic cardioversion during hospitalization; 1 had syncope; 1 patient reported new onset peripheral oedema; 2 patients died during lockdown for non cardiovascular causes. 17 of them also developed non cardiovascular symptoms, 7 of whom were severe anxiety and/or panic attacks. Almost all patients had important lifestyle changes, in 15 cases (12.3%) associated with weight increase. Conclusion: The impossibility to access to routine outpatient visits during lockdown due to global pandemic of SARS-CoV2, has brought out the risk of underestimating consequences of chronic disease, in absence of appropriate Follow-up. Nevertheless, the two deaths we report were not related to cardiovascular disease. The risk is that both the missing of cardiovascular control visit and the extension of the waiting list, could provoke serious complications in patients suffering from chronic cardiovascular disease.

Lipoprotein(a) concentration does not differ between sexes in healthy offspring of patients with premature myocardial infarction.

AIMS: Although a family history of coronary artery disease (CAD) is an established factor influencing lipoprotein(a) [Lp(a)] levels, the effect of sex on Lp(a) concentration remains unclear. A potential cause of the conflicting findings regarding the effect of sex on this novel CAD risk factor is the limited ability of the studies, to date, to adequately control for the potential confounding effect of CAD familial predisposition. Our purpose was to evaluate the influence of sex on Lp(a) concentration in healthy young individuals by controlling for family history of CAD. In order to achieve our goal, we compared Lp(a) levels in pairs of brothers and sisters with a positive parental history of premature myocardial infarction (PHPMI). METHODS: We measured Lp(a) concentration in 77 healthy brother-sister pairs with PHPMI (mean age: brothers: 18.4 ± 6.2 years and sisters: 18.1 ± 5.8 years). Total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein (Apo) A-I and B were also measured. RESULTS: Lp(a) levels did not differ between siblings of different sex (male vs. female sex: 0.994 ± 1.29 vs. 0.860 ± 0.82 µmol/l, P = 0.940); moreover, the prevalence of elevated (>1.071 µmol/l) Lp(a) concentrations between sexes was the same (29.9%). As expected, compared to female sex, male sex showed higher total/HDL-cholesterol ratio (3.642 ± 0.99 vs. 3.329 ± 0.89, P = 0.017) and lower HDL-cholesterol (1.221 ± 0.24 vs. 1.343 ± 0.28 mmol/l, P = 0.001), Apo A-I (1.390 ± 0.20 vs. 1.474 ± 0.23 g/l, P = 0.003) concentrations and Apo A-I/Apo B ratio (1.632 ± 0.49 vs. 1.830 ± 0.66, P = 0.016). CONCLUSION: Our results show that healthy young men with PHPMI have a similar Lp(a) levels but worse lipid profile than women.

Sex hormones and lipoprotein(a) concentration.

INTRODUCTION: increased level of lipoprotein(a) (Lp(a)) constitutes an emerging, independent risk factor for coronary artery disease. Recently, it has been recommended to lower increased (> 50 mg/dl) Lp(a) concentration. Most lipid lowering agents - except niacin - have little or no effect whereas sex hormones significantly reduce Lp(a) level. The effect of sex hormones on Lp(a) level is related to the setting, the drug, the dose and the way of administration. Androgen esters, oral estrogens, alone or in combination with progestogens, and tibolone constantly decrease Lp(a) level, especially in postmenopausal women. AREAS COVERED: this paper reviews the pathophysiology, structure and metabolism of Lp(a). Clinical studies evaluating, in various settings, the effect of exogenous administration of androgens, estrogens - alone or in combination with progestogens - selective receptor estrogen modulators (SERMs), aromatase inhibitors (AIs) and tibolone on Lp(a) level are analyzed. EXPERT OPINION: the results obtained for SERMs are conflicting whereas AIs do not seem to reduce Lp(a) concentration. The effect of hormonal therapy on lipids is complex, depending on drugs and way of administration. Moreover, both androgens and estrogen could determine, in specific settings, severe adverse effects. These drugs are not currently recommended either for treatment of dyslipidemias with increased Lp(a) level or for the prevention of cardiovascular disease.

Age-related differences in factors associated with cigarette smoking among Italian high school students.

INTRODUCTION: Adolescents' cigarette smoking is related to several factors. The aim of this study among high school students was to test the hypothesis that factors related to smoking behavior could differ in early (14-16-year-old students, younger age group) vs. late (17-21-year-old students, older age group) adolescence. METHODS: The smoking behavior of 910 students was evaluated by a questionnaire. Students were categorized on the basis of their lifetime smoking behavior as never, former, occasional and regular smoker. Data were analyzed using Student's t-test, chi-square test and multinomial logistic regression analysis. RESULTS: In multinomial logistic regression analysis, variables related to adolescents' smoking behavior for both age groups were: positive attitude toward smoking (P < 0.001), illicit drug use (younger age group, P < 0.001; older age group, P = 0.003), smoking at home with parents (younger age group, P = 0.038; older age group, P < 0.001) and get drunk at least once (younger age group, P = 0.002; older age group, P = 0.026). In the younger age group, a significant association was also found between students' smoking behavior and having smoked a cigar at least once (P = 0.006) and smoking behavior of the best friend of the same sex (P = 0.001), whereas the relationship with the hours spent with friends of the opposite sex was of borderline significance (P = 0.058). In the older age group, other factors related to adolescent's smoking behavior were minimizing health consequences of smoking (P = 0.002) and the hours spent with friends of the same sex (P = 0.026). CONCLUSION: Our study demonstrates that, as adolescence advances, factors related to smoking behavior can vary.

Vascular and metabolic effects of angiotensin II receptor blockers.

Angiotensin II receptor blockers (ARBs) are widely used in patients with hypertension, heart failure and type 2 diabetes mellitus (T2DM). Several large clinical trials have demonstrated that these agents are effective in reducing cardiovascular mortality and morbidity. These benefits are partly independent of the degree of blood pressure reduction and most likely related to ARBs' anti-inflammatory, metabolic and vascular effects. Clinical studies showed that the anti-inflammatory effect of ARBs could be related to the dosage and/or the length of the treatment. In large clinical trials, ARBs have inconsistently reduced the risk of new-onset T2DM. Among ARBs, only losartan significantly reduced serum uric acid levels. Moreover, it has been demonstrated that ARBs improve endothelial dysfunction in patients with hypertension and/or coronary artery disease (CAD), while all but one of the studies proved that these agents could usually, after 6-12 months of therapy, induce regression of vascular hypertrophy in hypertensive patients. These positive effects could be relevant to vascular protection and, together with the blood pressure reduction, constitute the background of the improved outcome observed in clinical studies on mortality and/or morbidity in hypertensive, high-risk and CAD patients. The clinical significance of the different potency of ARBs needs to be investigated further in specific and adequately powered trials.