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Introduction Immune checkpoint inhibitors (ICIs) are widely used in the treatment of many cancers as they improve clinical outcomes. However, ICIs have also been associated with the development of immune-related adverse drug reactions (ADRs). Among immune-related ADRs, cardiac immune-related ADRs are rare, but also associated with high mortality rates. Objective The objective of this study was to evaluate the occurrence of cardiac ADRs reported with ICIs in the European spontaneous reporting system. Methods We retrieved individual case safety reports on ICI-induced cardiac ADRs from the website of suspected ADR (www.adrreports.eu) of the European pharmacovigilance database (Eudravigilance). Data were retrieved from the date of marketing authorization of each ICI (ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and cemiplimab) to 14 March, 2020. The reporting odds ratio and its 95% confidence interval were computed to assess the reporting frequency of cardiac ADRs for each ICI compared to all other ICIs. Results A total of 2478 individual case safety reports with at least one ICI as the suspected drug were retrieved from Eudravigilance, of which 249 (10%) reported more than one ICI. The three most reported ICIs were nivolumab (43.2%), pembrolizumab (32.5%), and the association of nivolumab/ipilimumab (9.4%). A total of 3388 cardiac ADRs were identified. Cardiac ADRs were serious (99.4%) and had a fatal outcome (30.1%). The most reported cardiac events were myocarditis, cardiac failure, atrial fibrillation, pericardial effusion, and myocardial infarction. Nivolumab was reported with a small increased reporting frequency of individual case safety reports with cardiac ADRs compared to all other ICIs (reporting odds ratio 1.09, 95% confidence interval 1.01–1.18). Conclusions Immune checkpoint inhibitor-induced cardiac ADRs were serious and had unfavorable outcomes. In our study, nivolumab was the only ICI with a small increased reporting frequency of individual case safety reports with cardiac ADRs compared to all other ICIs. In this regard, further head-to-head studies are needed. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01086-8.

The coronavirus disease 2019 (COVID-19) pandemic has profoundly affected all health care professionals. The outbreak required a thorough reorganization of the Italian regional local health care system to preserve resources such as ventilators, beds in intensive care units and surgical and anaesthesiological staff. Levels of priority were created, together with a rigorous triage procedure for patients with COVID-19, which led to postponement of all elective procedures. Urgent cases were discussed with the local heart team and percutaneous approaches were selected as the first treatment option to reduce hospital stay. COVID-19 and COVID-19-free pathways were created, including adequate preparation of the operating room, management of anaesthesiological procedures, transportation of patients and disinfection. It was determined that patients with chronic diseases were at increased risk of adverse outcomes. Systemic inflammation, cytokine storm and hypercoagulability associated with COVID-19 increased the risk of heart failure and cardiac death. In this regard, the early use of extracorporeal membrane oxygenation could be life-saving in patients with severe forms of acute respiratory distress syndrome or refractory heart failure. The goal of this paper was to report the Italian experience during the COVID-19 pandemic in the setting of cardiovascular surgery., Coronavirus disease 2019 (COVID-19) is a new pandemic infectious disease caused by a novel beta-coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1].

This study aims to identify baseline medications that, as a proxy for the diseases they are dispensed for, are associated with increased risk of mortality in COVID-19 patients from two regions in Spain and Italy using real-world data. We conducted a cross-country, retrospective, observational study including 8570 individuals from both regions with confirmed SARS-CoV-2 infection between 4 March and 17 April 2020, and followed them for a minimum of 30 days to allow sufficient time for the studied event, in this case death, to occur. Baseline demographic variables and all drugs dispensed in community pharmacies three months prior to infection were extracted from the PRECOVID Study cohort (Aragon, Spain) and the Campania Region Database (Campania, Italy) and analyzed using logistic regression models. Results show that the presence at baseline of potassium-sparing agents, antipsychotics, vasodilators, high-ceiling diuretics, antithrombotic agents, vitamin B12, folic acid, and antiepileptics were systematically associated with mortality in COVID-19 patients from both countries. Treatments for chronic cardiovascular and metabolic diseases, systemic inflammation, and processes with increased risk of thrombosis as proxies for the conditions they are intended for can serve as timely indicators of an increased likelihood of mortality after the infection, and the assessment of pharmacological profiles can be an additional approach to the identification of at-risk individuals in clinical practice.

Remdesivir was recommended for hospitalized patients with COVID-19. As already reported in the Summary of Product Characteristics, most of remdesivir’s safety concerns are hepatoxicity and nephrotoxicity related. However, some cases have raised concerns regarding the potential cardiac events associated with remdesivir, therefore, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency requested to investigate all available data. Therefore, we analyzed all Individual Case Safety Reports (ICSRs) collected in the EudraVigilance database focusing on cardiac adverse events. From April to December 2020, 1375 ICSRs related to remdesivir were retrieved from EudraVigilance, of which 863 (62.8%) were related to male and (43.3%) adult patients. A total of 82.2% of all AEs (N = 2604) was serious and one third of the total ICSRs (N = 416, 30.3%) had a fatal outcome. The most frequently reported events referred to hepatic/hepatobiliary disorders (19.4%,), renal and urinary disorders (11.1%) and cardiac events (8.4%). Among 221 cardiac ICSRs, 69 reported fatal outcomes. Other drugs for cardiovascular disorders were reported as suspected/concomitant together with remdesivir in 166 ICSRs (75.1%), 62 of which were fatal. Moreover, the mean time to overall cardiac event was 3.3 days (±2.2). Finally, disproportionality analysis showed a two-fold increased risk of reporting a cardiac adverse event associated with remdesivir compared to both hydroxychloroquine and azithromycin. This study showed that remdesivir could be associated to risk of cardiac events, suggesting a potential safety signal which has not been completely evaluated yet. Further studies are needed to confirm these findings.

Coronavirus disease 2019 (COVID-19) has substantially challenged healthcare systems worldwide. By investigating population characteristics and prescribing profiles, it is possible to generate hypotheses about the associations between specific drug-utilisation profiles and susceptibility to COVID-19 infection. A retrospective drug-utilisation study was carried out using routinely collected information from a healthcare database in Campania (Southern Italy). We aimed to discover the prevalence of drug utilisation (monotherapy and polytherapy) in COVID-19 versus non-COVID-19 patients in Campania (~ 6 million inhabitants). The study cohort comprised 1532 individuals who tested positive for COVID-19. Drugs were grouped according to the Anatomical Therapeutic Chemical (ATC) classification system. We noted higher prevalence rates of the use of drugs in the ATC categories C01, B01 and M04, which was probably linked to related comorbidities (i.e., cardiovascular and metabolic). Nevertheless, the prevalence of the use of drugs acting on the renin-angiotensin system, such as antihypertensive drugs, was not higher in COVID-19 patients than in non-COVID-19 patients after adjustments for age and sex. These results highlight the need for further case–control studies to define the effects of medications and comorbidities on susceptibility to and associated mortality from COVID-19.

COVID-19 is a complex disease, and many difficulties are faced today especially in the proper choice of pharmacological treatments. The role of antiviral agents for COVID-19 is still being investigated and evidence for immunomodulatory and anti-inflammatory drugs is quite conflicting, whereas the use of corticosteroids is supported by robust evidence. The use of heparins in hospitalized critically ill patients is preferred over other anticoagulants. There are conflicting data on the use of convalescent plasma and vitamin D. According to the World Health Organization (WHO), many vaccines are in Phase III clinical trials, and some of them have already received marketing approval in European countries and in the United States. In conclusion, drug repurposing has represented the main approach recently used in the treatment of patients with COVID-19. At this moment, analysis of efficacy and safety data of drugs and vaccines used in real-life context is strongly needed. LINKED ARTICLES: This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc.

Claudio Napoli,1 Paola Bontempo,2 Vittorio Palmieri,3 Enrico Coscioni,4 Ciro Maiello,5 Francesco Donatelli,6 Giuditta Benincasa1 1Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, 80138, Italy; 2Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, 80138, Italy; 3Department of Cardiac Surgery and Transplantation, Heart Transplantation Unit in Adults of the ‘Ospedali dei Colli Monaldi-Cotugno-CTO’, Naples, Italy; 4Department of Cardiac Surgery, Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy; 5Department of Cardiovascular Surgery and Transplants, Monaldi Hospital, Azienda dei Colli, Naples, Italy; 6Chair of Cardiac Surgery, Department of Cardiothoracic Center, Istituto Clinico Sant’Ambrogio, University of Milan, Milan, ItalyCorrespondence: Giuditta BenincasaDepartment of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, ItalyTel +390815667916Email giuditta.benincasa@unicampania.itAbstract: Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy (“epidrugs”) is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials isevaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF.Keywords: heart failure, personalized therapy, epidrugs

Heart transplantation (HTx) is considered the gold-standard therapy for the treatment of advanced heart failure (HF). The long-term survival in HTx is hindered by graft failure which represents one of the major limitations of the long-term efficacy of HTx. Endomyocardial biopsy (EMB) and the evaluation of donor-specific antibodies (DSA) are currently considered the essential diagnostic tools for surveillance of graft rejection. Recently, new molecular biomarkers (including cell-free DeoxyriboNucleic Acid, exosomes, gene profiling microarray, nanostring, reverse transcriptase multiplex ligation-dependent probe amplification, proteomics and immune profiling by quantitative multiplex immunofluorescence) provide useful information on mechanisms of graft rejection. The ambitious role of a similar change of perspective is aimed at a better and longer graft preservation.

Purpose of review Cardiovascular diseases (CVDs) are typically caused by multifactorial events including mutations in a large number of genes. Epigenetic-derived modifications in the cells are normal but can be amended by aging, lifestyle, and exposure to toxic substances. Major epigenetic modifications are DNA methylation, histone modification, chromatin remodeling as well as the noncoding RNAs. These pivotal players are involved in the epigenetic-induced modifications observed during CVDs. Nevertheless, despite impressive efforts capitalized in epigenetic research in the last 50 years, clinical applications are still not satisfactory. Recent findings Briefly, we present some of the recent steps forward in the epigenetic studies of CVDs. There is an increased appreciation for the contribution of epigenetic alterations in the development of CVDs. Now, we have novel epigenetic biomarkers and therapeutic trials with the use of statins, metformin, and some compounds affecting epigenetic pathways including a BET inhibitor apabetalone. The new knowledge of epigenetic regulation is also discussed in the light of precision medicine of CVDs. Summary Epigenetic studies of CVDs have the promise to yield both mechanistic insights as well as adjunct treatments (repurposed drugs and apabetalone). The overall concept of precision medicine is not widely recognized in routine medical practice and the so-called reductionist approach remains the most used way to treat CVD patients.

Background The novel coronavirus (SARS-CoV-2) pandemic spread rapidly worldwide increasing exponentially in Italy. To date, there is lack of studies describing clinical characteristics of the people at high risk of infection. Hence, we aimed (i) to identify clinical predictors of SARS-CoV-2 infection risk, (ii) to develop and validate a score predicting SARS-CoV-2 infection risk, and (iii) to compare it with unspecific scores. Methods Retrospective case-control study using administrative health-related database was carried out in Southern Italy (Campania region) among beneficiaries of Regional Health Service aged over than 30 years. For each person with SARS-CoV-2 confirmed infection (case), up to five controls were randomly matched for gender, age and municipality of residence. Odds ratios and 90% confidence intervals for associations between candidate predictors and risk of infection were estimated by means of conditional logistic regression. SARS-CoV-2 Infection Score (SIS) was developed by generating a total aggregate score obtained from assignment of a weight at each selected covariate using coefficients estimated from the model. Finally, the score was categorized by assigning increasing values from 1 to 4. Discriminant power was used to compare SIS performance with that of other comorbidity scores. Results Subjects suffering from diabetes, anaemias, Parkinson’s disease, mental disorders, cardiovascular and inflammatory bowel and kidney diseases showed increased risk of SARS-CoV-2 infection. Similar estimates were recorded for men and women and younger and older than 65 years. Fifteen conditions significantly contributed to the SIS. As SIS value increases, risk progressively increases, being odds of SARS-CoV-2 infection among people with the highest SIS value (SIS = 4) 1.74 times higher than those unaffected by any SIS contributing conditions (SIS = 1). Conclusion Conditions and diseases making people more vulnerable to SARS-CoV-2 infection were identified by the current study. Our results support decision-makers in identifying high-risk people and adopting of preventive measures to minimize the spread of further epidemic waves.

AIMS: Chronic kidney disease (CKD) is associated with increased thrombotic events and seems to influence platelet reactivity. Conflicting results have been published on platelet response in CKD patients with stable coronary artery disease. The aim of our study was to investigate the impact of CKD on platelet aggregation in acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy, included the more potent P2Y12 inhibitors. METHODS: We enrolled 206 patients with ACS, divided in two groups, according to the presence or the absence of moderate/severe CKD. Platelet aggregation was performed with light transmission aggregometry and results are expressed as percentage of maximum platelet aggregation. High residual platelet reactivity (HRPR) was defined as maximum platelet aggregation more than 59%. RESULTS: Patients with CKD [estimate glomerular filtration rate (eGFR)

Background There is an ever-growing number of patients requiring aortic valve replacement (AVR). Limited data is available on the long-term outcomes and structural integrity of bioprosthetic valves in younger patients undergoing surgical AVR. Methods The INSPIRIS RESILIA Durability Registry (INDURE) is a prospective, open-label, multicentre, international registry with a follow-up of 5 years to assess clinical outcomes of patients younger than 60 years who undergo surgical AVR using the INSPIRIS RESILIA aortic valve. INDURE will be conducted across 20–22 sites in Europe and Canada and intends to enrol minimum of 400 patients. Patients will be included if they are scheduled to undergo AVR with or without concomitant root replacement and/or coronary bypass surgery. The primary objectives are to 1) determine VARC-2 defined time-related valve safety at one-year (depicted as freedom from events) and 2) determine freedom from stage 3 structural valve degeneration (SVD) presenting as morphological abnormalities and severe haemodynamic valve degeneration at 5 years. Secondary objectives include the assessment of the haemodynamic performance of the valve, all stages of SVD, potential valve-in-valve procedures, clinical outcomes (in terms of New York Heart Association [NYHA] function class and freedom from valve-related rehospitalisation) and change in patient quality-of-life. Discussion INDURE is a prospective, multicentre registry in Europe and Canada, which will provide much needed data on the long-term performance of bioprosthetic valves in general and the INSPIRIS RESILIA valve in particular. The data may help to gather a deeper understanding of the longevity of bioprosthetic valves and may expand the use of bioprosthetic valves in patients under the age of 60 years. Trial registration ClinicalTrials.gov identifier: NCT03666741 (registration received September, 12th, 2018).

Background: Immune checkpoint inhibitors (ICIs) are widely used in the treatment of many cancers as they improve clinical outcomes. However, ICIs have also been associated with the development of immune-related adverse drug reactions (irADRs). Among irADRs, cardiac ones are rare, but also associated with higher mortality rates. Here, we evaluate the occurrence of cardiac ADRs associated with ICIs. Methods: We retrieved Individual Case Safety Reports (ICSRs) on ICIs-induced cardiac ADRs from the website of suspected ADR (www.adrreports.eu) of the European pharmacovigilance database (Eudravigilance, EV). Data were retrieved from the date of marketing authorization of each ICI (ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and cemiplimab) to March 14th, 2020. The Reporting Odds Ratio (ROR) and its’ 95% confidence interval (95%CI) was computed to assess the reporting probability of cardiac ADRs for each ICI compared to all other ICIs. Findings: A total of 2,478 ICSRs with at least one ICI as suspected drug were retrieved from EV, of which 249 (10%) were related to combined treatments. The three most reported ICIs were nivolumab (43 . 2%), pembrolizumab (32 . 5%), and the association nivolumab and ipilimumab (9 . 4%). A total of 3,388 cardiac ADRs were identified. Cardiac ADRs were serious (99%) and associated with a fatal outcome (30 . 1%). The most reported cardiac events were myocarditis, cardiac failure, atrial fibrillation, pericardial effusion, and myocardial infarction. Nivolumab was associated with a small increased reporting probability of ICSRs with cardiac ADRs compared to all other ICIs (ROR 1 . 09, 95%CI 1 . 01–1 . 18). Interpretation: ICIs-induced cardiac ADRs were serious and associated with unfavorable outcomes. In our study, nivolumab was the only ICI associated with a small increased reporting probability of ICSRs with cardiac ADRs compared to all other ICIs. In this regards, further head-to-head studies are needed. Funding: This research was funded under grant n. 2017NR7W5K_002 (PRIN 2017) from MIUR, Italy. Declaration of Interests: No conflict to declare. Ethics Approval Statement: Safety data deriving from the spontaneous reporting system are anonymous and in compliance with the ethical standard. Therefore, no further ethical measure was required.

Different and several public health strategies have been planned to reduce transmission of pandemic due to SARS-CoV-2 since it started. None drugs have been confirmed as able to prevent viral transmission. Hydroxychloroquine with its immunomodulatory properties has been proposed as potential anti-viral drug in particular for prevention once viral exposure has been happen or in first phases of infection. Furthermore, in several immunological systemic disease hydroxychloroquine was able to reduce the number of thrombotic complications. So, because COVID-19 was associated to immunological imbalance and to thrombotic complications, we retrospectively analyzed the rate of infection in those patients being under treatment with this drug during COVID-19 epidemic outbreak from 8 March until 28 April in particular comparing those with pre-exposure to this treatment and those that were not taking this medication before SARS-CoV-2 viral infections.

We hypothesized that the spread of SARS-CoV-2 in urine during a severe COVID-19 infection may be the expression of the worsening disease evolution. Therefore, the aim of this study was to verify if the COVID-19 disease severity is related to the viral presence in urine samples. We evaluated the clinical evolution in acute COVID-19 patients admitted in the sub-intensive care and intensive care units between 28 of December 2020 and 15th of February 2021 and being positive for SARS-CoV-2 RNA in the respiratory tract, including repeated endotracheal aspirates (ETA), sputum, nasopharyngeal swabs (NPS) and urine. We found that those subjects with SARS-COV-2 in the urine at admittance (8 out of 60 eligible patients) had a more severe disease than those with negative SARS-CoV-2 in urine. Further, they showed an increase in fibrinogen and (C-reactive Protein) CRP serum levels, requiring mechanic ventilation. Of those with positive SARS-CoV-2 in the urine, 50% died. According to our preliminary results, it seems that the presence of SARS-CoV-2 in the urine characterizes patients with a more severe disease and is also related to a higher death rate.

Aims Surgical endarterectomy is the therapy of choice for atherosclerotic common femoral artery (CFA) obstruction. Recently, some large single-centre series have shown encouraging results for the percutaneous treatment of CFA obstructions. The purpose of this study was to evaluate the safety, feasibility, and one-year efficacy of the endovascular treatment of CFA obstructions with combined use of directional atherectomy (DA) and a paclitaxel-coated balloon (DCB). Methods and results Between January 2012 and July 2014, 30 consecutive patients with severely calcified obstructions of the common femoral artery were treated in our centre using DA followed by DCB dilatation. Provisional stenting was allowed in the case of a suboptimal result. Twenty cases (66%) were isolated CFA interventions, whereas five (17%) and five (17%) also involved inflow and outflow vessels, respectively. Chronic total CFA occlusions (CTO) were recanalised in six cases (20%). Procedural success was achieved in all cases; stenting was needed in three cases (10%). At one year, restenosis and target lesion revascularisation were observed in two of 30 (6.6%) and one of 30 (3.3%) patients, respectively. The secondary patency rate was 96.7%. Conclusions This single-centre prospective study suggests that the combined use of DA and DCB is a safe and effective alternative to surgery, a treatment option for common femoral artery lesions and provides encouraging results in this setting.

Despite the availability of several therapies for the management of blood glucose in diabetic patients, most of the treatments do not show benefits on diabetic cardiomyopathy, while others even favor the progression of the disease. New pharmacological targets are needed that might help the management of diabetes and its cardiovascular complications at the same time. GRK2 appears a promising target, given its established role in insulin resistance and in systolic heart failure. Using a custom peptide inhibitor of GRK2, we assessed in vitro in L6 myoblasts the effects of GRK2 inhibition on glucose extraction and insulin signaling. Afterwards, we treated diabetic male mice (db/db) for 2 weeks. Glucose tolerance (IGTT) and insulin sensitivity (ITT) were ameliorated, as was skeletal muscle glucose uptake and insulin signaling. In the heart, at the same time, the GRK2 inhibitor ameliorated inflammatory and cytokine responses, reduced oxidative stress, and corrected patterns of fetal gene expression, typical of diabetic cardiomyopathy. GRK2 inhibition represents a promising therapeutic target for diabetes and its cardiovascular complications.

Technological advances and the increasing operators of the experience allow to minimize the risk of cerebral embolic events after carotid artery stenting (CAS), making it a valuable alternative to carotid endo-atherectomy (CEA). The Achilles heel of this technique is that it can be complicated by cerebral embolism. The introduction of embolic protection devices (EPD) reduced the rate of procedure related cerebral embolic events and their use is recommended by available guidelines. Distal EPD (filter or occlusion balloons) and proximal EPD are currently available. Among distal EPDs, a theoretical advantage of filter as compared to occlusion balloons is the maintenance of antegrade flow during the procedure, minimizing the chances of acute hemispheric cerebral ischemia. As of today, the distal filter devices are the most commonly used EPDs for carotid stenting, some disadvantages of distal filters are possible embolization during lesion crossing or device retrieval, difficulty in navigating severely stenosed or tortuous vessels and spasm or dissection of the ICA. Proximal EPD carry the theoretical benefit of establishing embolic protection prior to any manipulation of the carotid lesion with wires, catheters or other devices, potential drawbacks of proximal EPDSs are patient intolerance to carotid occlusion. It has been suggested that proximal EPD could be particularly useful in symptomatic or thrombotic lesions.

Food supply in the Mediterranean area has been recently modified by big retail distribution; for instance, industrial retail has favored shipments of groceries from regions that are intensive producers of mass food, generating a long supply chain (LSC) of food that opposes short supply chains (SSCs) that promote local food markets. However, the actual functional role of food retail and distribution in the determination of the risk of developing metabolic syndrome (MetS) has not been studied hitherto. The main aim of this study was to test the effects of food chain length on the prevalence of MetS in a population accustomed to the Mediterranean diet. We conducted an observational study in Southern Italy on individuals adhering to the Mediterranean diet. We examined a total of 407 subjects (41% females) with an average age of 56 ± 14.5 years (as standard deviation) and found that being on the Mediterranean diet with a SSC significantly reduces the prevalence of MetS compared with the LSC (SSC: 19.65%, LSC: 31.46%; p: 0.007). Our data indicate for the first time that the length of food supply chain plays a key role in determining the risk of MetS in a population adhering to the Mediterranean diet.

Background: Heart Failure (HF) and cognitive impairment (CI) represent two high incident diseases worldwide, with extremely elevated mortality and morbidity rates. Their prevalence is expected to further increase in the next years due to the aging population, thus they pose enormous clinical, social and economic challenges. Sympathetic nervous system hyperactivity is known to play a pivotal role in HF pathophysiology and progression. In fact, increased cardiac and circulating catecholamine levels are responsible for several molecular and structural abnormalities with detrimental effects on the failing heart. The proof of this latter concept is represented by the clinical success of -Blocker therapy that is able to attenuate HF-related morbidity and mortality. Recently, adrenergic system alterations have been implied also in the pathogenesis of CI and dementia opening the window for new fascinating and promising therapeutic opportunities. Objective: Assess the state of the art on the relationship between cognitive impairment and heart failure. Method: In the present manuscript, we propose an updated review of literature and patent on the role of sympathetic nervous system derangement in the pathogenesis of HF and CI. Conclusion: We have discussed recent findings allowing the identification of new molecular targets that hopefully will contribute to the generation of effective therapeutic strategies for HF and dementia. In this article, the patents US20100048479, US7060871, WO2006052857, US7351401, US5721243, WO1994009155, US5449604, WO1999058981, US5985581, EP2319511, EP2377534, EP2650303, WO2006004939, WO2010132128 and EP1779858 are summarized.

Highlights • The management of carotid in-stent restenosis remains challenging, with several potential management strategies available, but none clearly best. • Bioresorbable vascular scaffolds have proved safe and effective in patients with coronary artery disease, but their use for carotid in-stent restenosis is unprecedented, yet promising. • Bioresorbable vascular scaffolds could become a useful adjunct to the armamentarium of endovascular specialists, including those managing patients with carotid in-stent restenosis, especially if further refinements in sizes and designs are achieved., Introduction Carotid in-stent restenosis is associated with substantial risk of recurrent restenosis, even after drug-eluting balloon usage. Presentation of case We hereby report the case of a patient with recurrent carotid in-stent restenosis and drug-eluting balloon failure treated with a coronary bioresorbable vascular scaffold, achieving a satisfactory acute and long-term result, as disclosed by duplex ultrasound scan performed more than 1 year after the procedure. Discussion/conclusion While awaiting for external validation, this clinical vignette supports expanding the armamentarium of endovascular specialists focusing on carotid artery disease, while providing further proof of the safety and efficacy of current bioresorbable vascular scaffolds.

25-Hydroxyvitamin D insufficiency and increased cardiovascular risk (CVR) association is still debated. The vitamin D (VitD)-dependent parathyroid hormone (PTH) is considered as the possible actuator of VitD effects on CVR. To investigate the association of CVR, PTH and VitD, we carried out blood pressure measurements and blood samples and collected information on dietary habits, anamnestic, clinical and metabolic data of 451 participants in the Salerno area (Southern Italy) during the World Hypertension Day (17 May). CVR was calculated according to the Framingham CVR charts. The overall population mean age was 51.6 ± 0.7 years, and female sex was slightly prevalent (55%). VitD deficiency (

In recent years, the number of advocates for a more business-like management of healthcare organizations has significantly increased.

It is known that patients with rheumatoid arthritis (RA) have a higher risk of coronary heart disease and sudden cardiac death. Abnormalities in cardiac geometry appear to be involved in the setting of the cardiovascular risk, but it has never been specifically investigated in RA. We enrolled 44 patients with RA compared to 131 subjects without RA (normal, N): The RA aged between 18 and 70 years (mean 48.3 ± 2.1), 25 females, BMI 27.6 ± 0.9; N, of equal age (48.6 ± 1.2, n.s.), included 80 females (BMI 26.7 ± 0.2, ns). Cardiac Ultrasounds showed an increase of the diameter of the left ventricle but not in the septum with reduction of relative wall thickness (RWT) in the RA population compared to N. Relative wall thickness inversely correlates with biochemical parameters of inflammatory response (gamma globulin, p

Clinical and epidemiological studies demonstrate that short- and long-term exposure to air pollution increases mortality due to respiratory and cardiovascular diseases. Given the increased industrialization and the increased sources of pollutants (i.e., cars exhaust emissions, cigarette smoke, industry emissions, burning of fossil fuels, incineration of garbage), air pollution has become a key public health issue to solve. Among pollutants, the particulate matter (PM) is a mixture of solid and liquid particles which differently affects human health depending on their size (i.e., PM10 with a diameter

Inflammation is a key mechanism of cardiovascular diseases. It is an essential component of atherosclerosis and a significant risk factor for the development of cardiovascular events. In the crosstalk between inflammation and cardiovascular diseases, the transcription factor NFκB seems to be a key player since it is involved in the development and progression of both inflammation and cardiac and vascular damage. In this review, we deal with the recent findings of the role of inflammation in cardiac diseases, focusing, in particular, on NFκB as a functional link. We describe strategies for the therapeutic targeting of NFκB as a potential strategy for the failing heart.

Introduction: Less than 40% of hypertensive on antihypertensive treatment have pressure Methods: To verify the impact of home care strategy to improve pressure control, from February 1 to March 31 2016 we selected patients who accessed the Outpatient Clinic for Hypertension at the AOU San Giovanni e Ruggi in Salerno, those with 1) poor BP control >140 and/or DBP>90 mmHg) after at least three follow-up visits in the last year, 2) optimal drug therapy, 3) poor adherence to therapy, 4) at least one concurrently treated chronic condition. Patients who signed informed consent received “Beyond Silos” home care program, including a weekly nurse access, for four weeks, and telemonitoring through 3G-connected devices of systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) and body weight measuring and Oxygen Saturation. Each patient was instructed to scheduled self-assesment of the above parameters that were stored on the Local Health Authority server of Salerno. Treatment compliance was verified weekly by the nurse through drug blister count. After 4 weeks, patients were evaluated at the hospital premises. Results: We selected seven patients (M/F=5/2; age 73.4 ± 2.3 years). In this population BP control that went from ambulatory SBP/DBP 155±5/74±4mmHg to 111±1.7/95.9±2.7mmHg, p Conclusion: Our data show that patients with a hitory of loose BP control despite optimal therapy can achieve controlled BP through Beyond Silos home care program within a month. This suggest that strategies of ICT based home care might represent a real breackthrough in the management of chronic conditions, in particular for multimorbid, poor compliant patients. Future large scale studies are needed for assessing long term effects on cardiovascular outcome.

Aims Preliminary data on Sapien 3 valve (S3-THV) use for transcatheter aortic valve implantation have shown an increased permanent pacemaker implantation (PPMI) rate with respect to Sapien XT valve. Aim of this study was to investigate the role of S3-THV position in the left ventricular outflow tract (LVOT) on electrocardiographic changes suggestive of atrioventricular (ΔPR) and/or intraventricular (ΔQRS) conduction abnormalities and 30 days PPMI rate. Methods and results Eighty-six consecutive patients treated with S3-THV were included in the study. All patients underwent clinical and electrocardiogram evaluation. Left ventricular outflow tract prosthesis depth was assessed by fluoroscopy and expressed quantitatively (mm) and as aorto-ventricular ratio (AVR). Eight patients (9.3%) needed PPMI at 30 days. A low AVR (≤60/40) predicted PPMI (OR = 6.09, 95% CI 1.19–31.01, P = 0.030) and resulted into higher PPMI rate, compared with higher AVR (30.0 vs. 6.6%, P = 0.017). For each millimetre increase in the LVOT prosthesis depth PPMI risk increased by 1.41 times (95% CI 1.06–1.87, P = 0.017). In patients with low AVR, ΔPR was higher than in those with higher AVR (33.4 ± 56.7 vs. 12.1 ± 19.4 ms, P = 0.021) and ΔPR was associated to LVOT prosthesis depth ( β = 0.286, P = 0.009). Furthermore, ΔPR was associated with risk of PPMI (OR = 1.03, 95% CI 1.01–1.06, P = 0.024). Conclusions A low AVR is associated to higher ΔPR and PPMI rates. The correlation between LVOT prosthesis depth with ΔPR and higher PPMI rate suggests the need of a careful S3-THV implantation.

Background: Drug-eluting stents (DES) are now considered the most promising device to treat peripheral artery disease (PAD) and minimize restenosis. There is uncertainty however on the best antirestenotic drug for such devices. In particular, biolimus (i.e. umirolimus) and everolimus are two of the most promising agents, given the extensive data in support of their coronary safety and efficacy, but their comparative effectiveness for peripheral interventions is not established. Methods: Building upon our extensive experience in the percutaneous treatment of infra-inguinal artery disease with DES, we compared the acute and longterm outlook of patients treated with biolimus-eluting stents (BES) and everolimus-eluting stents (EES). We collected baseline, procedural and outcome details on all patients undergoing infra-inguinal BES or EES implantation. The endpoints of interest were death, amputation, revascularization, their composite, and change in Fontaine class. A total of 80 patients were included (20 treated with BES and 60 with EES). Most features were similar in the two groups, despite longer lesions in the EES group. Unadjusted analysis showed similar results irrespective of the drug used, with composite endpoint occurring, respectively, in 4 (20.0%) and 10 (16.7%) (p=0.741). Results and Conclusion: However, analysis with inverse probability of treatment weighting showed significant differences in the risk of revascularization (hazard ratio of BES vs EES=9.55 [95% confidence interval 2.16-42.23], p=0.003) and composite endpoint (hazard ratio=5.11 [1.33-19.62], p=0.018). In conclusion, EES appear superior to BES for endovascular therapy of infrainguinal artery disease. Dedicated randomized trials are required to definitely confirm or disprove these findings.

Several devices are available for infrainguinal endovascular therapy, with drug-eluting stents (DES) among the most promising. Bioresorbable vascular scaffolds (BVS) may further improve outcomes. We have liberally used in our practice coronary DES and BVS for infrainguinal endovascular therapy and hereby report our preliminary results. We conducted an observational study by retrospectively identifying characteristics of patients undergoing infrainguinal implantation of coronary DES or BVS. We compared the risk of major adverse events (MAE: death, amputation, or target vessel revascularization [TVR]) and components of MAE in the overall sample and after propensity matching. We included a total of 204 patients (207 limbs), 148 (72.5%) treated with DES and 56 (27.5%) with BVS. Bivariate analysis showed that TVR was less common in the DES group (41.9% vs 18.4%, P = .014). However, propensity-matched analysis showed nearly identical risks of MAE, amputation, TVR, or symptom burden with DES and BVS (all P > .05). In conclusion, the present pilot experience with coronary BVS suggests that they could provide acceptable results for infrainguinal endovascular procedures, comparable to those obtained by their metallic counterpart.

Vitamin K-dependent antagonists (VKAs) are the most commonly used oral anticoagulants. Non-VKA oral anticoagulants (NOACs), directly target factor IIa (dabigatran) or Xa (rivaroxaban, apixaban, and edoxaban) have predictable pharmacological effects and relatively few drug and food interactions compared with VKA. Among NOACs, dabigatran has been extensively tested for stroke prevention in patients with non-valvular atrial fibrillation eligible for oral anticoagulation with VKA. Dabigatran is at least as effective as warfarin at preventing stroke with advantages of less serious bleeding except for gastrointestinal bleeding, which occurs more often than with warfarin. The findings of dabigatran use in randomized trials, post market registries and specific clinical settings are discussed in this article.

Background: The use of inhibitors of glycoprotein IIb/IIIa (GPIIb/IIIa) has provided dramatic results in terms of the prevention of acute stent thrombosis and a reduction in major adverse coronary events in patients subjected to percutaneous coronary intervention. GPIIb/IIIa or αIIbβ3 is a member of the β3 subfamily of integrins, which also includes αVβ3. GPIIb/IIIa functions as a receptor for fibrinogen and several adhesion proteins sharing an arginine-glycine-aspartic acid (RGD) sequence. GPIIb/IIIa antagonists, through blockade of the receptor, prevent platelet aggregation. Among the three GPIIb/IIIa antagonists used in therapy, abciximab is an anti-β3 monoclonal antibo dy, while tirofiban and eptifibatide mimic the binding sequence of the fibrinogen ligand. Although antiplatelet aggregation represents the central function of GPIIb/IIIa inhibitors, further actions have been documented for these compounds. Objective: The aim of the present article is to review the structures and functions of GPIIb/IIIa antagonists and to highlight the clinical outcomes and results of randomized trials with these compounds. Hypotheses on the unexplored potential of GPIIb/IIIa antagonists will be put forward. Conclusion: GPIIb/IIIa inhibitors were developed to prevent platelet aggregation, however, these compounds can exert further biological functions, both platelet- and non-platelet-related. Large-scale studies comparing the efficacy and safety of GPIIb/IIIa antagonists are lacking. More insights into the functions of these compounds may lead to generation of novel small molecules able to antagonize platelet aggregation while promoting vascular repair.

Background: the theoretical advantages of mini-invasive cardiac surgery are shorter hospitalisation, better surgical results and costs reduction. In November 1997 we started a non-coronary mini-invasive surgery program using a partial upper median sternotomy. This study has been conceived to retrospectively compare two groups of patients who underwent isolate aortic valve replacement using the conventional and the mini-invasive technique. Material and methods: in Group A 100 patients (mean age 62±12 years; 58 male) underwent isolated aortic valve replacement through a partial upper median sternotomy. Group B was composed by the last 100 patients (mean age 63±8 years; 56 male) who underwent the same operation through a conventional median sternotomy. For both groups we recorded the ECC and ischaemic times, postoperative intubation time, total postoperative bleeding, intensive care unit length of stay and total hospitalisation time. Major and minor complications were reported. Results: operating times, were significantly longer in Group A (pConclusions: in our experience, partial upper median sternotomy does not increase surgical risks but failed to demonstrate clear advantages. Apart for an increase in operating times, the surgical results are similar to those of a conventional median sternotomy with only improvement in the aesthetical aspect. In our opinion, this supports the conviction that this approach can be proposed to selected patients, to obtain a better cosmethical result for the same given risk.

Objective To analyze the risk reduction of cardiopulmonary bypass complications between on-pump and off-pump coronary artery bypass grafting in high-risk patients. Methods This multicenter, prospective, randomized, parallel trial enrolled patients for elective or urgent isolated coronary artery bypass grafting with an additive European System for Cardiac Operative Risk Evaluation of 6 or more. The patients in cardiogenic shock were excluded. The composite primary end point included operative mortality, myocardial infarction, stroke, renal failure, reoperation for bleeding and adult respiratory distress syndrome within 30 days after surgery. The total sample size was 693 patients, according to a scheduled interim analysis at 400 patients enrolled (α-spending = 0.029, Pocock method). Results A total of 411 patients were included in the interim analysis. Randomization assigned 203 patients to on-pump and 208 patients to off-pump treatment. Of the 411 patients, 24 crossed over; thus, 195 patients were actually treated on-pump and 216 off-pump. According to the intention to treat analysis, the rate of the composite primary end point was significantly lower (unadjusted P = .009, adjusted P = .010) in the off-pump group (5.8% vs 13.3%). The risk of experiencing the primary end point was significantly greater for the on-pump group (unadjusted odds ratio, 2.51; 95% confidence interval, 1.23–5.10; P = .011; adjusted odds ratio, 3.07; 95% confidence interval, 1.32–7.14; P = .009). Conclusions Off-pump coronary artery bypass grafting reduces early mortality and morbidity in high-risk patients.