Use and Prescription of Direct Oral Anticoagulants in Older and Frail Patients with Atrial Fibrillation: A Multidisciplinary Consensus Document.

In the last twelve years the clinical management of patients with atrial fibrillation has been revolutionised by the introduction of direct oral anticoagulants. Despite the large amount of evidence produced, some populations remain relatively poorly explored regarding the effectiveness and safety of direct oral anticoagulants, such as the oldest and/or frailest individuals. Frailty is clinical syndrome characterized by a reduction of functions and physiological reserves which results in individuals having higher vulnerability. While current evidence underlines a relationship between atrial fibrillation and frailty, particularly in determining a higher risk of adverse outcomes, data regarding effectiveness and safety of direct oral anticoagulants in frailty atrial fibrillation patients are still lacking, leaving uncertainty about how to guide prescription in this specific subgroup. On these premises, this multidisciplinary consensus document explains why it would be useful to integrate the clinical evaluation performed through comprehensive geriatric assessment to gather further elements to guide prescription of direct oral anticoagulants in such a high-risk group of patients.

Evaluation of the immune response to COVID-19 vaccine mRNA BNT162b2 and correlation with previous COVID-19 infection.

BACKGROUND: The kinetics of immune response after vaccination with mRNA-BNT162b2 (Comirnaty®) and the correlation with previous COVID-19 infection are still unclear. METHODS: Thirty-six subjects receiving mRNA-BNT162b2 were prospectively studied [10 days after the first dose (Time 1), 7 days and 16 weeks after the second dose (Time 2 and Time 3)] to determine antibody titers against nucleocapside, trimeric spike protein (TSP) and receptor-binding-domain (RBD) of the spike protein. Ten subjects had a previous COVID-19 infection not requiring hospitalization (Group 1) and 26 did not (Group 2). RESULTS: At Time 1 all subjects in Group 1 had IgG against TSP > 800 AU/mL compared to 11/26 (42.3%) in Group 2, whilst at Time 2 all subjects in both groups had > 800 AU/mL. The mean IgG against TSP titer at Time 3 was 711 AU/mL (95% CI 652-800) in Group 1 and 240 AU/mL (95% CI 112-375) in Group 2 (p < 0.0001). However, all subjects in both groups maintained antibody titers above the lower threshold limit at each time-point considered. These results were confirmed also using anti-RBD antibodiy tests. Antibodies against nucleocapside were reactive only in subjects in Group 1 and remained stable during the study period. No subject had a new onset of COVID-19 infection within 16 weeks of follow-up. CONCLUSIONS: Subjects with previous COVID-19 infection have a more rapid immune response to mRNA-BNT162b2 than others and maintained higher antibody titers during 16 weeks of follow-up. However, no new COVID-19 infection also in subjects with lower antibody titers.

Healthy Promotion for Fighting Metabolic Syndrome: Insights from Multi-Center HeRO-FiT Cohort.

We know that metabolic syndrome (MS) is a modern cardiovascular (CV) "epidemic", especially in western populations. MS is indeed strictly related to the risk of developing CV diseases (CVD) and/or diabetes. Therefore, the aim of our multi-center study was to promote a "healthy style" for fighting MS. Each participating center analyzed its own database of outpatients and globally we have pulled out 100 volunteers to participate in the study. Before starting, we collected their written consent. Enrolled subjects have not any history of overt CVD and/or diabetes, but they matched National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP) criteria for MS. After enrolment (t0), subjects were randomly divided into two homogeneous groups: a) only diet suggestions; b) both diet and exercise prescription. Later, we measured for each subject: blood pressure (BP), heart rate (HR), height, weight, body mass index (BMI), waist circumference (WC), waist hip ratio (WHR), six-minute walking test (WT6M), distance and common blood tests such as fasting plasma glucose, high-density lipoproteins (HDL) and triglycerides (T1 assessments). At six months (T2), the same parameters were measured and then statistical comparisons were performed. Attention to diet caused significant changes only in WC and WHR, whilst a coupling of exercise and diet revealed a statistically significant improvement in HR, BP, BMI, blood samplings and WT6M too. In conclusion, a healthy lifestyle should be more encouraged by physicians and/or collaborators (such as dieticians) operating in preventive settings. Diet and physical activity may be early useful strategies in the "battle" against MS even before any medication choices. Further studies will be necessary in order to better address the topic.

Individualized Breakfast Programs or Glycogen Super-Compensation: Which Is the Better Performing Strategy? Insights from an Italian Soccer Referees Cohort.

The role of soccer referees has grown in importance in the last decades, as has attention to their performance, which may be influenced and improved with specific and evolved training programs. Today, multiple specialists are working as a team in order to develop effective training programs. Moreover, for athletes, it is becoming more and more important to be attentive to nutrition. By considering such items, in this study, we aimed to investigate the nutritional habits of a group of referees belonging to the Italian Soccer Referees' Association (on behalf of AIA-FIGC). Our main aim was to spread a "culture of nutrition" in refereeing, starting with a survey on referees' breakfast attitudes and in order to disseminate such a "culture", we chose top-level elite referees who were younger subjects (despite the average 4 years' experience). Therefore, we enrolled 31 subjects (aged 22.74 ± 1.79, BMI 22.30 ± 1.53) and asked them about their breakfast habits. Then, for measuring their performance, we used the conventional fitness test named Yo-Yo (YYiR1), performed in three different sessions (test 1, test 2, test 3). Test 1 was carried out without any nutritional indications, test 2 was given after individualized breakfast suggestions by a designed dietician, and test 3 after an individualized glycogen super-compensation strategy. The Wilcoxon statistical analysis indicates that following an individualized breakfast strategy may enhance referees' performance (p < 0.0001), whereas no significant effects were observed with the glycogen super-compensation option. However, further studies will be necessary to better address this topic and clarify whether high-carbohydrates (high-CHO) intake may be useful in other sports.

Cardiovascular Consequences of Autoimmune Rheumatic Diseases.

The increased risk of cardiovascular disease (CVD) among patients with autoimmune rheumatic diseases such as rheumatoid arthritis, spondyloarthritis and systemic lupus erythematosus has been extensively documented. Sub-clinical atherosclerosis can be assessed using various non-invasive imaging techniques. However, the mechanisms underlying the higher risk of atherosclerotic CVD in patients with autoimmune rheumatic diseases are not fully known, although they seem to include chronic low-grade systemic inflammation leading to prolonged endothelial activation, accompanied by a pro-thrombotic/pro-coagulant and autoantibody state. Furthermore, sub-clinical atherosclerosis is also influenced by other traditional risk factors for CVD. Including the individual components of the metabolic syndrome (MetS: obesity, impaired glucose metabolism, dyslipidemia and high blood pressure), the degree of which is higher in these patients than in controls. The aim of this narrative review is to discuss the CV manifestations and risk factors involved in the increased risk of CVD among patients with autoimmune rheumatic diseases.

Noninvasive imaging methods for evaluating cardiovascular involvement in patients with rheumatoid arthritis before and after anti-TNF drug treatment.

AIM: To use 2D speckle-tracking echocardiography, and conventional and tissue Doppler echocardiography to detect subclinical left ventricular myocardial dysfunction in patients with rheumatoid arthritis (RA). METHODS: Thirty RA outpatients were assessed before and after 18 months of treatment with anti-TNF drugs, along with 30 healthy controls. Cardiovascular risk was assessed by means of ultrasound carotid assessment and comprehensive echocardiographic evaluation (conventional and speckle-tracking calculation). RESULTS: The speckle-tracking analyses were significantly different between the two groups, with global longitudinal strain deformation in the apical four-chamber view being significantly lower in the RA patients (median: 18.78%, interquartile range [IQR]: 15.80-20.82% vs 20.16%, IQR: 19.03-21.89%; [p < 0.05]). After 18 months of biological treatment, global longitudinal strain showed a significant improvement (18.78%, IQR: 15.80-20.82 vs 19.24%, IQR: 18.23-19.98; [p < 0.01]), such as for DAS28 (4.80, IQR: 4.65-5.22 vs 2.78; IQR: 2.52-2.99; [p < 0.01]). CONCLUSION: Speckle-tracking echocardiography showed that left ventricular myocardial longitudinal strain was impaired in the RA patients.

Correction of hypovitaminosis D improved global longitudinal strain earlier than left ventricular ejection fraction in cardiovascular older adults after orthopaedic surgery.

BACKGROUND: Cardiovascular diseases and insufficient levels of vitamin D are risk factors for adverse surgical outcomes, and they are both commonly present among older adults undergoing orthopaedic surgery. Giving the cardiovascular effects of vitamin D, pre-operative diagnosis of hypovitaminosis D would be a valuable step for the implementation of supplementation protocols. We investigated if the normalization of serum 25 [OH] D could ameliorate cardiac performance of older adults suffering from cardiovascular diseases. METHODS: We enrolled 47 older adults scheduled for major orthopaedic surgery and suffering from hypovitaminosis D. Patients underwent 6-months calcifediol supplementation with a starting dose at first post-operative day of 50 µg/die in liquid preparation. Down-titration to 20 µg/die at 3-months assessment was planned. Cardiac performance was evaluated by measuring left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) during pre-operative assessments and at 1-month, 3-months, 6-months follow-ups. RESULTS: Six months of calcifediol supplementation were associated with a significant improvement of both LVEF (+ 3.94%; 95% CI: -4.0789 to -0.8232; P < 0.01) and GLS (+ 18.56%; Z = -5.895; P < 0.0001). CONCLUSIONS: Calcifediol supplementation normalized serum 25 [OH] D concentration after 1-month treatment. GLS offered better insights into myocardial contractile amelioration than LVEF, thus being useful for detecting earlier subclinical changes that may anticipate hemodynamic modifications.

Foot and Soccer Referees': A Pilot Study Searching "Performance" Throughout Prevention.

Soccer refereeing is a "not-conventional" sport in which aerobic workload is prevalent. Along the years, several studies have attempted to define best markers of referees' performance. Many studies focused their attention on field tests and their relationship with aerobic power. Instead, in this study, starting by a medical assessment satisfying the FIFA 11+ criteria for injuries prevention, we have investigated the foot of soccer referees and we have also wanted to find possible and/or unexpected improvements in performance. As performance marker, we have used the referral field test for soccer referees that is internationally validated and known as Yo-Yo test (YYiR1). While standardized foot posture index (FPI) questionnaire was used for screening foot referees conditions (40 young, all men by sex, with mean age 23.47 ± 4.36). Analyzing collected data, we have demonstrated by means of Read-Cressie Chi square test that neutral FPI is an important favor item affecting YYiR1 results. Further studies will be necessary in order to confirm our pilot investigation.

Cardiovascular Imaging Techniques in Systemic Rheumatic Diseases.

The risk of cardiovascular (CV) events and mortality is significantly higher in patients with systemic rheumatic diseases than in the general population. Although CV involvement in such patients is highly heterogeneous and may affect various structures of the heart, it can now be diagnosed earlier and promptly treated. Various types of assessments are employed for the evaluation of CV risk such as transthoracic or transesophageal echocardiography, magnetic resonance imaging (MRI), and computed tomography (CT) to investigate valve abnormalities, pericardial disease, and ventricular wall motion defects. The diameter of coronary arteries can be assessed using invasive quantitative coronarography or intravascular ultrasound, and coronary flow reserve can be assessed using non-invasive transesophageal or transthoracic ultrasonography (US), MRI, CT, or positron emission tomography (PET) after endothelium-dependent vasodilation. Finally, peripheral circulation can be measured invasively using strain-gauge plethysmography in an arm after the arterial infusion of an endothelium-dependent vasodilator or non-invasively by means of US or MRI measurements of flow-mediated vasodilation of the brachial artery. All of the above are reliable methods of investigating CV involvement, but more recently, introduced use of speckle tracking echocardiography and 3-dimensional US are diagnostically more accurate.

Left ventricular longitudinal strain in soccer referees.

Along the years, the analysis of soccer referees perfomance has interested the experts and we can find several types of studies in literature using in particular cardiac imaging. The aim of this retrospective study was to observe relationship between VO2max uptake and some conventional and not-conventional echocardiographic parameters. In order to perform this evaluation, we have enrolled 20 referees, belonging to Italian Soccer Referees' Association and we have investigated cardiovascular profile of them. We found a strong direct relationship between VO2max and global longitudinal strain of left ventricle assessed by means of speckle tracking echocardiographic analysis (R2=0.8464). The most common classic echocardiographic indexes have showed mild relations (respectively, VO2max vs EF: R2=0.4444; VO2max vs LV indexed mass: R2=0.2268). Therefore, our study suggests that longitudinal strain could be proposed as a specific echocardiographic parameter to evaluate the soccer referees performance.

Investigating the potential side effects of anti-TNF therapy for rheumatoid arthritis: cause for concern?

There are now five anti-TNF drugs available for clinical use, and it will not be long before they are joined by biosimilar drugs. Some patients treated with selective TNF drugs may develop adverse events such as infections, malignancies, acute infusion and injection reactions, autoimmunity and cardiovascular effects. Registry data consistently show that, particularly during the first 6 months, anti-TNF drugs slightly increase the risk of serious infections of the skin, soft tissues and joints, but it does not seem to increase the risk of cancer other than nonmelanoma skin cancers. A number of studies have shown that the administration of biological agents can lead to the formation of neutralizing and nonneutralizing antibodies. Lipid levels increase, but the atherogenic index remains stable and qualitative changes to lipid particles may reduce the risk of cardiovascular diseases. Patients treated with anti-TNF drugs therefore need to be monitored regularly.

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross-sectional study.

OBJECTIVE: An association between systemic autoimmune diseases and atherosclerosis has been described in many connective tissue diseases, and this association is known to lead to increased cardiovascular morbidity and mortality. Systemic sclerosis (SSc) is characterized by multisystem organ inflammation, endothelial wall damage, and vasculopathy. There are many markers of endothelial dysfunction and/or atherosclerotic risk, such as asymmetric dimethylarginine (ADMA), arterial stiffness parameters, carotid intima-media thickness (CIMT), and coronary flow reserve (CFR) assessed by transthoracic echocardiography. The aim of this pilot study was to use various endothelial and atherosclerosis markers to identify early cardiovascular involvement in a group of SSc patients. METHODS: The study involved 20 patients (2 men and 18 women with a mean ± SD age of 52.96 ± 12.51 years) with diffuse SSc who had no signs or symptoms of cardiovascular disease (CVD) and 20 age- and sex-matched controls. All subjects underwent a dipyridamole echocardiographic stress test that included a determination of CFR and an evaluation of CIMT, arterial stiffness, and plasma ADMA levels. RESULTS: All of the arterial wall measurements of the patients with diffuse SSc were significantly different from those of the controls, and both right and left CIMT, pulse wave velocity, and stiffness index (ß) were significantly elevated in the SSc patients compared to the healthy controls. Moreover, in patients with diffuse SSc, CFR was significantly lower (P = 0.0033) and plasma ADMA levels were higher (P < 0.0001) than in healthy controls. CONCLUSION: SSc patients without any clinical evidence of CVD seem to have had subclinical atherosclerosis, which was suggested by early impairment of coronary microcirculation and macrovascular involvement.

Cardiovascular injury in systemic autoimmune diseases: an update.

It is well known in literature that systemic autoimmune diseases (SADs) are associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease. Cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality in SADs. There is considerable evidence suggesting a pathogenetic role of chronic inflammation and immune dysregulation for enhanced atherosclerosis in SADs, as demonstrated in several recent studies. Moreover, chronic inflammation, accelerated atherosclerosis and functional abnormalities of the endothelium suggest a subclinical CV involvement beginning rapidly soon after the onset of the disease and progressing with disease duration.

Coronary flow reserve and asymmetric dimethylarginine levels: new measurements for identifying subclinical atherosclerosis in patients with psoriatic arthritis.

OBJECTIVE: To identify the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) and healthy controls using intima-media thickness (IMT), coronary flow reserve (CFR), and the plasma concentration of asymmetric dimethylarginine (ADMA), to evaluate the correlations among ADMA, IMT, and CFR. METHODS: The study involved 22 patients who fulfilled the ClASsification of Psoriatic ARthritis study group criteria for PsA and a cohort of 35 healthy controls with no history or current signs of coronary artery disease (CAD). Common carotid IMT was measured using high-resolution B-mode ultrasonography. Dipyridamole transthoracic stress echocardiography was used to evaluate CFR. Blood samples were obtained to assess ADMA levels. The clinical manifestations were recorded. All patients were treated with disease-modifying antirheumatic drug, but none had received any biological or steroid therapy. RESULTS: Plasma ADMA levels were significantly higher in the patients with PsA (0.71 ± 0.07 µmol/l vs 0.48 ± 0.07 µmol/l; p = 0.00) and CFR was significantly reduced in that group (2.86 ± 0.70 vs 3.3 ± 0.43; p < 0.01) compared to controls. Common carotid IMT was greater in the patients with PsA, but the difference was not significant (0.64 ± 0.26 mm vs 0.62 ± 0.5 mm; p = 0.65). There was a significant correlation between CFR and plasma ADMA levels in the PsA group (R = 0.28; p < 0.01), but no correlation between plasma ADMA levels and IMT (R = 0.02; p = 0.32), Disease Activity Score 28 (p = 0.52), or Psoriasis Area and Severity Index (p = 0.98). CONCLUSION: Our patients with PsA showed a profile of subclinical atherosclerosis. ADMA may be a useful marker of endothelial dysfunction in PsA.

Role of cardiovascular imaging in systemic autoimmune diseases.

Systemic autoimmune diseases are characterized by an excess of cardiovascular (CV) morbidity and mortality compared to the general population, mainly due to chronic inflammation that promotes the development of endothelial dysfunction and enhanced atherosclerosis. Early diagnosis of silent CV involvement is mandatory to improve the long term prognosis of these patients and CV imaging provides valuable information as a reliable diagnostic tool. Transthoracic echocardiography, with several applications (e.g. coronary flow reserve evaluation, tissue Doppler imaging, speckle tracking and the transesophageal approach), represents a first line evaluation, in association with biomarkers of endothelial dysfunction, such as asymmetric dimethylarginine. Nuclear medicine provides useful information on myocardial perfusion. The aim of this editorial is to provide a brief but complete review of the diagnostic tools available for screening and follow up of CV involvement in systemic autoimmune diseases.

The heart in rheumatoid arthritis.

Morbidity and mortality rates are higher in rheumatoid arthritis (RA) patients than in the general population. Many studies have shown that coronary artery disease is one of the most common causes of death in RA and seems to occur at a younger age than in the general population. RA per se is as much a cardiovascular (CV) risk factor as diabetes, arterial hypertension and dyslipidemia etc., and so it is necessary to plan a follow-up using the same diagnostic and therapeutic approaches as those commonly used for primary and secondary prevention in non-RA patients at high CV risk. All of the cardiac structures can be affected during the course of RA (valves, the conduction system, the myocardium, endocardium and pericardium, and the coronary arteries), and cardiac complications include a variety of clinical manifestations. As these are all associated with an unfavourable prognosis, it is essential to detect subclinical cardiac involvement in still asymptomatic RA patients in order to assure adequate long-term treatment.