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Patent foramen ovale (PFO) is the most common congenital cardiac abnormality found approximately in 25% of the adult population The pathophysiological role of paradoxical embolization through the PFO in ischemic stroke is well established. "Self-expanding double disk" and, more recently, suture-based "deviceless" systems are used for PFO closure in the setting of secondary prevention after ischemic stroke likely related to paradoxical embolization. Ultrasound plays a significant role in PFO assessment, indication to treatment, intra-procedural guidance, and follow-up for those undergoing PFO closure. Three different techniques are frequently used for these purposes: transesophageal echocardiography, transthoracic echocardiogram, and transcranial Doppler. In this review, advantages and limits of these techniques are discussed in detail to improve our skills in detection and treatment of this important condition by using ultrasound.

Ellis grade III coronary artery perforations (G3-CAP) remain a life-threatening complication of percutaneous coronary intervention (PCI), with high morbidity and mortality and lack of consensus regarding optimal treatment strategies. We reviewed all PCIs performed in 10 European centers from 1993 to 2019 recording all G3-CAP along with management strategies, in-hospital and long-term outcome according to Device-related perforations (DP) and Guidewire-related perforations (WP). Among 106,592 PCI (including 7,773 chronic total occlusions), G3-CAP occurred in 311 patients (0.29%). DP occurred in 194 cases (62.4%), more commonly in proximal segments (73.2%) and frequently secondary to balloon dilatation (66.0%). WP arose in 117 patients (37.6%) with chronic total occlusions guidewires involved in 61.3% of cases. Overall sealing success rate was 90.7% and usually required multiple maneuvers (80.4%). The most commonly adopted strategies to obtain hemostasis were prolonged balloon inflation (73.2%) with covered stent implantation (64.4%) in the DP group, and prolonged balloon inflation (53.8%) with coil embolization (41%) in the WP group. Procedural or in-hospital events arose in 38.2% of cases: mortality was higher after DP (7.2% vs 2.6%, p = 0.05) and acute stent thrombosis 3-fold higher (3.1% vs 0.9%, p = 0.19). At clinical follow-up, median 2 years, a major cardiovascular event occurred in one-third of cases (all-cause mortality 8.2% and 7.1% respectively, without differences between groups). In conclusion, although rare and despite improved rates of adequate perforation sealing G3-CAP cause significant adverse events. DP and WP result in different patterns of G3-CAP and management strategies should be based on this classification.

Among the most common causes of death worldwide, ischemic heart disease (IHD) is recognized to rank first. Even if atherosclerotic disease of the epicardial arteries is known as the leading cause of IHD, the presence of myocardial infarction with non-obstructive coronary artery disease (MINOCA) is increasingly recognized. Notwithstanding the increasing interest, MINOCA remains a puzzling clinical entity that can be classified by distinguishing different underlying mechanisms, which can be divided into atherosclerotic and non-atherosclerotic. In particular, coronary microvascular dysfunction (CMD), classifiable in non-atherosclerotic mechanisms, is a leading factor for the pathophysiology and prognosis of patients with MINOCA. Genetic susceptibility may have a role in primum movens in CMD. However, few results have been obtained for understanding the genetic mechanisms underlying CMD. Future studies are essential in order to find a deeper understanding of the role of multiple genetic variants in the genesis of microcirculation dysfunction. Progress in research would allow early identification of high-risk patients and the development of pharmacological, patient-tailored strategies. The aim of this review is to revise the pathophysiology and underlying mechanisms of MINOCA, focusing on CMD and actual knowledge about genetic predisposition to it.

Background Since the body of evidence addressing the coagulation derangements caused by Coronavirus disease (COVID-19) has been constantly growing, we investigated whether pre-hospitalization oral anticoagulation (OAC) or in-hospital heparin treatment could have a protective role among COVID-19 patients. Method In this cohort study, consecutive COVID-19 patients admitted to four different Italian Institutions were enrolled. Baseline demographic, clinical, laboratory, and radiological characteristics, as well as in-hospital treatment and outcomes were evaluated. The primary outcome was mortality. Results A total of 844 COVID-19 patients were enrolled as study cohort, n = 65 (7.7%) taking OACs prior to hospitalization. Regarding clinical outcomes, OAC patients developed acute hypoxemic respiratory failure (AHRF) more frequently than non-OAC patients as well as presenting a higher mortality rate (44.6% vs 19.8%, p, Highlights • Evidence on a prothrombotic asset caused by COVID-19 has been constantly growing. • In our cohort, OACs appeared to be ineffective in reducing mortality rate. • Heparin resulted to be a useful treatment when lung disease was sufficiently severe. • Microthrombosis may have a crucial role in COVID-19. • Due to the relatively small sample size of OAC patients included, larger studies are needed.

Background: Heart failure (HF) patients are predisposed to recurrences and disease destabilizations, especially during the COVID-19 outbreak period. In this scenario, telemedicine could be a proper way to ensure continuous care. The purpose of the study was to compare two modalities of HF outpatients’ follow up, the traditional in-person visits and telephone consultations, during the COVID-19 pandemic period in Italy. Methods: We conducted an observational study on consecutive HF outpatients. The follow up period was 12 months, starting from the beginning of the COVID-19 Italy lockdown. According to the follow up modality, and after the propensity matching score, patients were divided into two groups: those in G1 (n = 92) were managed with traditional in-person visits and those in G2 (n = 92) were managed with telephone consultation. Major adverse cardiovascular events (MACE) were the primary endpoints. Secondary endpoints were overall mortality, cardiovascular death, cardiovascular hospitalization, and hospitalization due to HF. Results: No significant differences between G1 and G2 have been observed regarding MACE (p = 0.65), cardiovascular death (p = 0.39), overall mortality (p = 0.85), hospitalization due to acute HF (p = 0.07), and cardiovascular hospitalization (p = 0.4). Survival analysis performed by the Kaplan–Meier method also did not show significant differences between G1 and G2. Conclusions: Telephone consultations represented a valid option to manage HF outpatients during COVID-19 pandemic, comparable to traditional in-person visits.

Systemic inflammatory response syndrome (SIRS) could affect mortality after transcatheter aortic valve implantation (TAVI) up to 12 months of follow-up. The aim of this study was to evaluate the prevalence of SIRS after TAVI and its impact on all-cause mortality up to 24 months follow-up.We retrospectively enrolled 132 patients with symptomatic severe aortic stenosis undergoing TAVI. SIRS development during the first 72 h after the intervention was evaluated. Other postoperative complications were defined according to the Valve Academic Research Consortium 2 (VARC2). All patients underwent follow-up at 30 days and 24 months. Endpoints were 30-days and 24-months mortality.Post-TAVI SIRS developed in 27 patients (20%). At 30-day follow-up, all-cause death occurred in 10 (8%) patients and SIRS occurred more frequently in patients with adverse short-term outcome (60 vs. 17%; P = 0.001). Twenty-four months all-cause death occurred in 25 (19%) patients. SIRS resulted as an independent predictor of long-term outcome [hazard ratio 3.7; 95% confidence interval (95% CI) 1.5-9; P = 0.004], along with major vascular complications (hazard ratio 4; 95% CI 1.6-9.9; P = 0.003), relevant bleedings (hazard ratio 6.4; 95% CI 1.5-28; P = 0.013) and baseline pulmonary hypertension (hazard ratio 2.4; 95% CI 1.05-5.6; P = 0.039).Postoperative SIRS was more frequent in patients who died at 30 days follow-up. Moreover, SIRS resulted as a predictor of 24-month mortality along with vascular complications, relevant bleedings and baseline pulmonary hypertension.

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future.

Renin-angiotensin-aldosterone system (RAAS) inhibition is a mainstay of the pharmacological treatment of heart failure with reduced ejection fraction (HFrEF). In the last years RAAS blockade has been improved by the introduction of the Angiotensin Receptor-Neprilysin Inhibitor (ARNI) sacubitril/valsartan, that combines RAAS inhibition with the block of neprilysin, boosting the positive effects of natriuretic peptides. The PARADIGM-HF trial demonstrated a significant advantage of sacubitril/valsartan over enalapril on the reduction of cardiovascular (CV) mortality and heart failure hospitalizations rates. Then, several randomized clinical trials and observational studies investigated its role in different clinical settings and its efficacy has been fully recognized in the most recent HFrEF European and USA guidelines. The effects of sacubitril/valsartan on major CV outcomes are associated with reduction of NT-proBNP levels and reverse cardiac remodeling and mitral regurgitation, recognized as one of the mechanistic effects of the drug explaining the favorable prognostic effects. A careful evaluation of patients' clinical profile is relevant to implement the use of ARNI in the clinical practice and to obtain the maximal treatment efficacy. The present Position Paper reports the opinion of the Italian Society of Cardiology on the optimal blockade of the RAAS system in HF patients with the aim of fostering widespread implementation of scientific evidence and practice guidelines in the medical community.

Proper therapeutic management of patients with heart failure (HF) is a major challenge for cardiologists. Current guidelines indicate to start therapy with angiotensin converting enzyme inhibitors/angiotensin receptor neprilysin inhibitors (ACEi/ARNI), beta blockers (BB), mineralocorticoid receptor antagonists (MRAs) and sodium glucose cotransporter 2 inhibitors (SGLT2i) to reduce the risk of death and hospitalization due to HF. However, certain aspects still need to be defined. Current guidelines propose therapeutic algorithms based on left ventricular ejection fraction values and clinical presentations. However, these last do not always reflect the precise hemodynamic status of patients and pathophysiological mechanisms involved, particularly in the acute setting. Even in the field of chronic management there are still some critical points to discuss. The guidelines do not specify which of the four pillar drugs to start first, nor at what dosage. Some authors suggest starting with SGLT2i and BB, others with ACEi or ARNI, while one of the most recent approach proposes to start with all four drugs together at low doses. The aim of this review is to revise current gaps and perspectives regarding pharmacological therapy management in HF patients, in both the acute and chronic phase.

Background: The impact of percutaneous mitral valve repair (PMVr) on long-term prognosis in patients with functional mitral regurgitation (FMR) is still unclear. Recently, a new conceptual framework classifying FMR as proportionate (P-MR) and disproportionate (D-MR) was proposed, according to the effective regurgitant orifice area/left ventricular end-diastolic volume (EROA/LVEDV) ratio. The aim was to assess its possible influence on PMVr efficacy. Methods: A total of 56 patients were enrolled. MV annulus, LV volumes and function were assessed. Global longitudinal strain (GLS) was also calculated. Patients were divided into two groups, according to the EROA/LVEDV ratio. Echocardiographic follow-up was performed after 6 months, and adverse events were collected after 12 months. Results: D-MR patients (n = 28, 50%) had a significantly more elliptical MV annulus (p = 0.048), lower tenting volume (p = 0.01), higher LV ejection fraction (LVEF: 32 ± 7 vs. 26 ± 5%, p = 0.003), lower LVEDV, LV end-systolic volume (LVESV) and mass (LVEDV/i: 80 ± 20 vs. 126 ± 27 mL, p = 0.001; LVESV/i: 60 ± 20 vs. 94 ± 23 mL, p < 0.001; LV mass: 249 ± 63 vs. 301 ± 69 gr, p = 0.035). GLS was more impaired in P-MR (p = 0.048). After 6 months, P-MR patients showed a higher rate of MR recurrence. After 12 months, the rate of CV death and rehospitalization due to HF was significantly higher in P-MR patients (46% vs. 7%, p < 0.001). P-MR status was strongly associated with CV death/rehospitalization (HR = 3.4, CI 95% = 1.3–8.6, p = 0.009). Conclusions: Patients with P-MR seem to have worse outcomes after PVMr than D-MR patients. Our study confirms the importance of the EROA/LVEDV ratio in defining different subsets of FMR based on the anatomical characteristic of MV and LV.

Aims Significant concern has been raised about the effect of pre-existing cardiovascular diseases (CVD), cardiovascular (CV) risk factors and CV therapies on COVID-19 course. On the other hand, COVID-19 could worse pre-existing CVD or trigger the development of new-onset CVD. The aim of this study was to evaluate the relationship between pre-existing CVD, CV risk factors, and CV therapy with the clinical course of hospitalized COVID-19 patients. Methods and results Consecutive hospitalized COVID-19 patients admitted to the Cardiovascular COVID-19 Unit at Policlinico Umberto I of Rome between December 2020 and April 2021 were enrolled. All patients underwent a cardiovascular evaluation including troponin, electrocardiogram (ECG), and echocardiogram. Data on medical history, pre-existing CVD, CV risk factors, and therapy were collected. Admission to the Intensive Care Unit (ICU) or Cardiac Intensive Care Unit (CICU), as well as the development of new-onset CVD, were considered as endpoint of the study. Among n = 229 patients enrolled, 22 (10%) died. Nearly half of patients (112, 49%) were admitted to the ICU/CICU. The presence of prior ischaemic heart disease nearly doubled the probability of hospitalization in the ICU/CICU (HR: 2.09, 95% CI: 1.132–3.866, P 0.018). In regards of therapy, beta blockers reduced the likelihood of admission in the ICU/CICU (HR: −1016, 95% CI: 0.192–10.682, P 0.002). However, neither the use of RAAS blockers, heparin or dexamethasone influenced the risk of ICU/CICU admission (respectively, HR: 0.85, 95% CI: 0.498–1.450, P 0.551; HR: 0.768, 95% CI: 0.435–1.356, P 0.363; HR: 0.861, 95% CI: 0.453–1.635, P 0.647). N = 89 patients (39%) experienced a new onset CVD including arrythmias (18.3%) with nearly half experiencing atrial fibrillation, acute coronary syndrome (10.9%), acute pulmonary embolism (5.3%), heart failure (HF) (3%), and myocarditis and pericarditis (1.3%). A pre-existing diagnosis of HF substantially increased the likelihood of new onset CVD (HR: 2.380, 95% CI: 1.004–5.638, P 0.049). However, treatment with heparin or dexamethasone reduced the risk of new onset CVD (HR: 0.482 95% CI: 0.268–0.867, P 0.015; HR: 0.487, 95% CI: 0.253–0.937, P 0.031, respectively). Conclusions Our study found that hospitalized COVID-19 patients who have at least one CV risk factor or pre-existing CVD had a greater likelihood of being admitted to the ICU/CICU and experiencing new onset CVD.

Aims The outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic forced a reorganization of the healthcare system. In order to prevent potential risk of exposure, virtual visit (VV) has been implemented in the treatment and follow-up of COVID-19 patients with cardiovascular diseases. The aim of this study is to evaluate the feasibility and efficacy of VV in the management of post COVID-19 cardiovascular patients. Methods and results We enrolled all patients with cardiovascular comorbidities tested negative for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) and discharged from our Cardiology Department from January 2021 to June 2021. We scheduled a VV after 30 days from discharge to check the clinical status of the patients, optimize therapy, and establish a Follow-up protocol. Blood pressure, arterial oxygen saturation, heart rate and body weight were registered. To evaluate the patients’ satisfaction of VV, a questionnaire was administered. We performed 25 VVs in the study period; the mean age of patients was 67.5 ± 15.6 and male were 15 (65.2%). The mean duration of VV was 25.9 ± 4.6 min. The caregiver had an active role in nine (36%) cases. No urgent/emergent in-person examinations were performed. A high degree of patient satisfaction was reached and VV was preferred to in-person evaluation. Conclusions VV visit was useful to Follow-up post COVID-19 cardiovascular patients. A high degree of patient satisfaction was reached without jeopardizing quality of care.

Aims IHD is determined by inadequate coronary blood supply to myocardium and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Results validation on larger cohorts and new population is needed. The aim of the study is to evaluate the association among the allelic variants of eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility, and its clinical presentation. Methods A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); G3, control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG, and TT of rs1799983 for NOS3 gene, encoding for eNOS has been performed. Results rs1799983_GT is significantly more expressed by ischaemic groups (G1 and G2) compared with G3. The TT variant is significantly more expressed by G1 group, compared with G2 group. Among ischaemic patients, GT is significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentation. At multivariate analysis, the allelic variant GT may represent an independent predictor of IHD and ACS presentation. Conclusions The SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently from cardiovascular risk factors. These results may be useful for the prediction of IHD development, in particular with acute clinical manifestation. It may allow the early identification of patients at high risk to develop IHD with an ACS, promoting a genetic-based prevention strategy against IHD.

Aims A possible interference between ACE-i or ARBs with ACE-2 receptor and SARS-CoV-2 pathway has been raised. Despite data have shown no clinical impact of therapy with ACE-I or ARBs on COVID-19, these drugs are often discontinued upon hospitalization or diagnosis. To evaluate the effects of cardiovascular risk factors (CVRF) and prior outpatient therapy with RAAS inhibitors on the chest CT severity score performed within 24 h of diagnosis of SARS-CoV-2 infection (before stopping medications or starting specific therapy for COVID-19) and on 1-year survival. Methods and results This is a multicentre, prospective, observational study. All admitted patients diagnosed with SARS-CoV-2 infection who performed chest CT within 24 h of arrival were consecutively enrolled from 1 March to 1 June 2020. A severity score was attributed to Chest CT by two radiologists in blind to the patient’s clinical information and a cut-off value of 19.5 was considered to define severe radiological pneumonia. A 1-year telephone follow-up was performed in order to evaluate the determinants of 1-year survival. 590 patients with a mean age of 63 ± 14 years were included. Seventy-three (12.4%) patients were treated with ACE-I, 85 (14.4%) with ARBs and 62 (10.5%) with CCB. Cox regression analysis showed that male gender (OR: 1.4; 95% CI: from 1.02 to 2.07; P = 0.035), diabetes (OR: 1.6; 95% CI: from 1.03 to 2.7; P = 0.037), age (OR: 1.02; 95% CI: from 1.008 to 1.033; P = 0.001), and obesity (OR: 3.04; 95% CI: from 1.3 to 6.7; P Conclusions ACE-I and ARBs do not influence the chest CT presentation of COVID-19 patients at the time of diagnosis. Furthermore, ACE-I and ARBs do not influence 1-year survival of COVID-19 survivors.

Aims Following the COVID-19 pandemic-related lockdown period in Italy, people have experienced psycho-physical distress. Many hospitals were converted in COVID-19 healthcare places and many specialist outpatient’s services were drastically reduced. Virtual visits may represent a strategy to overcome the lack of HF outpatient’s services, during this period. Our own experience underlines the importance of virtual visits to face the clinical and health status deterioration, associated with COVID-19, in HF outpatients. Methods and results We conducted an observational study, enrolling consecutive HF outpatients, previously hospitalized at the Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences of Sapienza University of Rome, who were discharged within 31 March 2019, and 30 April 2019. Two follow-up periods were scheduled: (i) within 20–30 days after the beginning of lockdown (ii) at 3 months after lockdown’s end. Virtual visits were conducted through telephone, assessing changes in clinical and health status; the latter was assessed through the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). According to the presence of at least one sign of HF deterioration, patients were divided into two groups: Group 1: patients who experienced a modification in at least one clinical parameter suggestive of HF deterioration. Group 2: patients who do not experienced any modification of HF deterioration clinical parameter. KCCQ-12 mean scores were compared between the two groups, at both scheduled virtual visits, in order to evaluate any change in HF outpatients’ health status, during and after the COVID-19-related-lockdown. 160 HF outpatients have been included in the study: 63 in the group 1, 97 in the group 2. At the first virtual visit, group 1 reported significantly lower mean KCCQ-12 score, compared to group 2 [46.2 (±14.6) vs. 53.8 (±11); CI: 95% 11.6 to − 3.6; P = 0.0003]. At the second virtual visit, group 1 patients reported a slightly, but not statistically significant, lower mean KCCQ-12 score, compared to group 2 [52.2 (± 13.3) vs. 53.1(±14.4); 95% CI: −5.4 to 3.6; P = 0.69]. Comparing the KCCQ-12 mean scores of each group between the two scheduled virtual visits, group 1 reported a statistically significant increase at the second visit, compared to the first [52.2 (±13.3) vs. 46.2 (±14.6); CI: 95% 1.1–11; P = 0.017]. Group 2 showed no statistically significant variation of mean KCCQ-12 score between the two follow-up periods [53.1 (±14.4) vs. 53.8 (±11); CI: 95% −4.3 to 3; P = 0.704]. Conclusions we observed a significant worsening of health status in HF outpatients who have experienced clinical deterioration. Therefore, patients were either hospitalized or received the optimization of diuretic and anti-hypertensive therapies. A significant health status improvement was observed at three months after the end of the lockdown, suggesting the importance of virtual visit as an adequate method to follow-up HF outpatients, reporting particular benefits in those with worsening of HF clinical signs and health status.

AIMS Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease and have a worse prognosis after percutaneous coronary interventions (PCI). The BioFreedom polymer-free biolimus-A9-eluting stent (PF-BES) has shown promising results in patients at high bleeding risk; however, its performance in CKD patients has yet to be analyzed. METHODS The all-comers RUDI-FREE registry documented patients undergoing PCI with PF-BES in routine clinical practice. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR): preserved renal function, mild renal insufficiency (RI), and with moderate to severe RI (eGFR ≥ 90, between 90 and 45, and

Background: Advanced heart failure (HF) is a condition often requiring elevated doses of loop diuretics. Therefore, these patients often experience poor diuretic response. Both conditions have a detrimental impact on prognosis and hospitalization. Aims: This retrospective, multicenter study evaluates the effect of the addition of oral metolazone on diuretic response (DR), clinical congestion, NTproBNP values, and renal function over hospitalization phase. Follow-up analysis for a 6-month follow-up period was performed. Methods: We enrolled 132 patients with acute decompensated heart failure (ADHF) in advanced NYHA class with reduced ejection fraction (EF &lt, 40%) taking a mean furosemide amount of 250 ± 120 mg/day. Sixty-five patients received traditional loop diuretic treatment plus metolazone (Group M). The mean dose ranged from 7.5 to 15 mg for one week. Sixty-seven patients continued the furosemide (Group F). Congestion score was evaluated according to the ESC recommendations. DR was assessed by the formula diuresis/40 mg of furosemide. Results: Patients in Group M and patients in Group F showed a similar prevalence of baseline clinical congestion (3.1 ± 0.7 in Group F vs. 3 ± 0.8 in Group M) and chronic kidney disease (CKD) (51% in Group M vs. 57% in Group F, p = 0.38). Patients in Group M experienced a better congestion score at discharge compared to patients in Group F (C score: 1 ± 1 in Group M vs. 3 ± 1 in Group F p &gt, 0.05). Clinical congestion resolution was also associated with weight reduction (−6 ± 2 in Group M vs. −3 ± 1 kg in Group F, p &lt, 0.05). Better DR response was observed in Group M compared to F (940 ± 149 mL/40 mgFUROSEMIDE/die vs. 541 ± 314 mL/40 mgFUROSEMIDE/die, p &lt, 0.01), whereas median ΔNTproBNP remained similar between the two groups (−4819 ± 8718 in Group M vs. −3954 ± 5560 pg/mL in Group F NS). These data were associated with better daily diuresis during hospitalization in Group M (2820 ± 900 vs. 2050 ± 1120 mL p &lt, 0.05). No differences were found in terms of WRF development and electrolyte unbalance at discharge, although Group M had a significant saline solution administration during hospitalization. Follow-up analysis did not differ between the group but a reduced trend for recurrent hospitalization was observed in the M group (26% vs. 38%). Conclusions: Metolazone administration could be helpful in patients taking an elevated loop diuretics dose. Use of thiazide therapy is associated with better decongestion and DR. Current findings could suggest positive insights due to the reduced amount of loop diuretics in patients with advanced HF.

Background: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated. Methods: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h. Results: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO2, O2Hb and SaO2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells. Conclusions: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients’ survival depends mainly on the levels of pO2, O2Hb and SaO2. SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome responsible for high mortality and morbidity rates. It has an ever growing social and economic impact and a deeper knowledge of molecular and pathophysiological basis is essential for the ideal management of HFpEF patients. The association between HFpEF and traditional cardiovascular risk factors is known. However, myocardial alterations, as well as pathophysiological mechanisms involved are not completely defined. Under the definition of HFpEF there is a wide spectrum of different myocardial structural alterations. Myocardial hypertrophy and fibrosis, coronary microvascular dysfunction, oxidative stress and inflammation are only some of the main pathological detectable processes. Furthermore, there is a lack of effective pharmacological targets to improve HFpEF patients’ outcomes and risk factors control is the primary and unique approach to treat those patients. Myocardial tissue characterization, through invasive and non-invasive techniques, such as endomyocardial biopsy and cardiac magnetic resonance respectively, may represent the starting point to understand the genetic, molecular and pathophysiological mechanisms underlying this complex syndrome. The correlation between histopathological findings and imaging aspects may be the future challenge for the earlier and large-scale HFpEF diagnosis, in order to plan a specific and effective treatment able to modify the disease’s natural course.

Heart failure is a multifaceted syndrome addressing for a high rate of death among the general population. The common approach to this disease has been always based on the evaluation of the left ventricular ejection fraction by two-dimensional echocardiography with Simpson’s method. Mounting evidences have demonstrated the pitfalls of this method and have suggested that the management of heart failure requires a deep knowledge of the pathophysiological insights of the disease and cannot rely only on the evaluation of the left ventricular ejection fraction. Several advanced imaging technologies overwhelm the evaluation of ejection fraction and could provide a better understanding of the myocardial abnormalities underlying heart failure. Considering the limitation of left ventricular ejection fraction and the systemic involvement of heart failure, classifications of heart failure based on ejection fraction should be substituted with a comprehensive “staging” of multiorgan damage, not only considering the heart but also the lungs, kidneys, and liver, such as the HLM staging system. Such a holistic approach based on the HLM staging system and multimodality imaging can provide a global assessment of patient features allowing for targeted therapies and better heart failure management.

BACKGROUND Chronic pre-procedural and acute post-procedural myocardial injury are frequently observed in patients with aortic stenosis undergoing trans-catheter aortic valve implantation (TAVI). The aim of our study was to investigate the prognostic role of high sensitivity cardiac troponins (hs-cTns) elevation before and after TAVI. METHODS 106 patients with severe aortic stenosis who underwent TAVI were enrolled. High sensitivity cardiac troponin T (hs-cTnT) was measured before and after TAVI (6, 24, 48, 72 hours). Post-procedural myocardial damage was defined as a 15-fold rise in hs-cTnT upper reference limit (URL) after TAVI. The clinical endpoints were all cause death, cardiovascular death and rehospitalization at 24 months follow-up. RESULTS Before TAVI, hs-cTnT median value was 0.03 μg/L (2.3 ± 2.1 fold over URL). After TAVI procedure, myocardial damage (MD), as defined by VARC-2 criteria, was observed in 40 patients (38%) (MD group). In our population, logarithmically transformed hs-cTnTs were independently associated with all-cause mortality at 24 months F/U (pre-TAVI hs-cTnT: Hazard ratio [HR] 2.2, 95% confidence interval [CI]: 1.1 to 4.4, p=0.027). No significant differences were observed between the MD and non-MD groups for the three endpoints of all cause death (p log rank: 0.15), cardiovascular death (p log rank: 0.86) and re-hospitalization (p log rank: 0.87). CONCLUSIONS Only baseline hs-cTnT levels correlated with outcomes at 24 months of follow-up. Chronic pre-procedural myocardial injury significantly affects prognosis after TAVI.

Given human immunodeficiency virus‐1 (HIV‐1)‐infected patients have alterations in the type I interferon (IFN‐I) pathway and are also at elevated risk of atherosclerosis, we evaluated IFN‐I response and subclinical cardiovascular disease (CVD) association in HIV‐1‐infected patients. Transcript levels of IFN‐α/β and IFN‐stimulated gene 56 (ISG56) were evaluated by RT/real‐time PCR in peripheral blood mononuclear cells collected from asymptomatic HIV‐1‐positive male patients at high risk of developing CVD (n = 34) and healthy subjects (n = 21). Stenosis degree (≥ or .05). Dysregulation of IFN‐I response might participate in the pathogenesis of HIV‐1‐associated CVD.

ObjectiveApproximately 3.4% of adults aged >75 years suffer from aortic stenosis (AS). Guideline indications for aortic valve replacement (AVR) distinguish between patients with symptomatic and asymptomatic severe AS. The present analysis aims to assess contemporary practice in the treatment of severe AS across Europe and identify characteristics associated with treatment decisions, namely denial of AVR in symptomatic patients and assignment of asymptomatic patients to AVR.MethodsParticipants of the prospective, multinational IMPULSE database of patients with severe AS were grouped according to AS symptoms, and stratified into subgroups based on assignment to/denial of AVR.ResultsOf 1608 symptomatic patients, 23.8% did not undergo AVR and underwent medical treatment. Denial was independently associated with multiple factors, including severe frailty (p=0.024); mitral (p=0.002) or tricuspid (p=0.004) regurgitation grade III/IV, and the presence of renal impairment (p=0.017). Of 392 asymptomatic patients, 86.5% had no prespecified indication for AVR. Regardless, 36.3% were assigned to valve replacement. Those with an indexed aortic valve area (AVA; p=0.045) or left ventricular ejection fraction (LVEF; pConclusionsThere may be considerable discrepancies between guideline-based recommendations and clinical practice decision-making in the treatment of AS. It appears that guidelines may not fully capture the complete clinical spectrum of patients with AS. Thus, there is a need to find ways to increase their acceptance and the rate of adoption.

Background Rivaroxaban is a direct inhibitor of activated Factor X (FXa), an anti-inflammatory protein exerting a protective effect on the cardiac valve and vascular endothelium. We compare the effect of Warfarin and Rivaroxaban on inflammation biomarkers and their contribution to heart valve calcification progression and renal preservation in a population of atrial fibrillation (AF) patients with chronic kidney disease (CKD) stage 3b – 4. Methods This was an observational, multicenter, prospective study enrolling 347 consecutive CKD stage 3b – 4 patients newly diagnosed with AF: 247 were treated with Rivaroxaban and 100 with Warfarin. Every 12 months, we measured creatinine levels and cardiac valve calcification via standard trans-thoracic echocardiogram, while plasma levels of inflammatory mediators were quantified by ELISA at baseline and after 24 months. Results Over a follow-up of 24 months, long-term treatment with Rivaroxaban was associated with a significative reduction of cytokines. Patients treated with Rivaroxaban experienced a more frequent stabilization/regression of valve calcifications comparing with patients treated with Warfarin. Rivaroxaban use was related with an improvement in kidney function in 87.4% of patients, while in those treated with Warfarin was reported a worsening of renal clearance in 98% of cases. Patients taking Rivaroxaban experienced lower adverse events (3.2% vs 49%, p-value Conclusions Our findings suggest that Rivaroxaban compared to Warfarin is associated with lower levels of serum markers of inflammation. The inhibition of FXa may exert an anti-inflammatory effect contributing to reduce the risk of cardiac valve calcification progression and worsening of renal function.

Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure, profoundly differ with respect to clinical indications and procedural aspects. Yet, patients undergoing transcatheter cardiac interventions require antithrombotic therapy before, during, or after the procedure to prevent thromboembolic events. However, these therapies are associated with an increased risk of bleeding complications. To date, challenges and controversies exist regarding balancing the risk of thrombotic and bleeding complications in these patients such that the optimal antithrombotic regimens to adopt in each specific procedure is still unclear. In this review, we summarize current evidence on antithrombotic therapies for device-based transcatheter interventions targeting structural heart disease and emphasize the importance of a tailored approach in these patients.

The current COVID-19 pandemic has renewed interest in providing healthcare services based on the implementation of innovative technologies. Such strategy capillarizes the therapeutic opportunities for larger urban areas, mostly when people are living under extraordinarily difficult circumstances. Improving care delivery in cardiovascular diseases appears particularly feasible when telemedicine is pursued, especially with regard to baseline standard 12-lead electrocardiography, ambulatory electrocardiographic monitoring, and 24-hour ambulatory blood pressure monitoring. Nowadays, these first-line cardiovascular examinations are also available in health centers and pharmacies, and in recent months, there has been an increasing demand of such local services in the absence of specific rules and regulations regarding technical requirements and standards of interpretation that ensure a high quality clinical consultation.The purpose of this position paper is to provide critical requirements for the type/model of devices to be used, training dedicated to healthcare personnel, ensuring security of sensitive data, highlighting type of platforms to be used, as well as for maintaining high reporting quality and standards.

IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Validation of results in larger cohorts and new populations is needed. The aim of this study is to evaluate the associations between the allelic variants of the eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility and its clinical presentation. Methods: A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD), G2, coronary microvascular dysfunction (CMD), and G3, a control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG and TT, of rs1799983 for the NOS3 gene, encoding for eNOS, was performed. Results: rs1799983_GT was significantly more expressed by the ischemic groups (G1 and G2) compared to G3. The TT variant was significantly more expressed by the G1 group, compared to the G2 group. Among ischemic patients, GT was significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentations. In the multivariate analysis, the allelic variant GT was found to potentially represent an independent predictor of IHD and ACS presentation. Conclusion: The presence of the SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently of cardiovascular risk factors. These results may be useful for the prediction of IHD development, particularly with an acute clinical manifestation. They may allow the early identification of patients at high risk of developing IHD with an ACS, promoting a genetic-based prevention strategy against IHD.

Aim This review represents a joint effort of the Italian Societies of Cardiology (SIC) and Diabetes (SID) to define the state of the art in a field of great clinical and scientific interest which is experiencing a moment of major cultural advancements, the cardiovascular risk management in type 2 diabetes mellitus. Data synthesis Consists of six chapters that examine various aspects of pathophysiology, diagnosis and therapy which in recent months have seen numerous scientific innovations and several clinical studies that require extensive sharing. Conclusions The continuous evolution of our knowledge in this field confirms the great cultural vitality of these two cultural spheres, which requires, under the leadership of the scientific Societies, an ever greater and effective collaboration.

The coronavirus disease (COVID-19) pandemic has caused 2.69 million deaths and 122 million infections. Great efforts have been made worldwide to promptly develop effective vaccines and reduce morbidity and mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Available vaccines have proven highly effective at preventing symptomatic disease in clinical trials and real-world reports and are playing an essential role in flattening the epidemiology curve and, mostly, in reducing COVID-19 hospitalizations. Some concerns have been raised after very rare cases of myocarditis and pericarditis recently reported by the Centers for Disease Control and Prevention (CDC) as potentially associated with COVID-19 mRNA vaccinations, namely the Pfizer-BioNTech mRNA vaccine (BNT162b2) and the Moderna mRNA vaccine (mRNA-1273). Therefore, the aim of this document is to explore the possible link between COVID-19 mRNA vaccination and the development of myocarditis and/or pericarditis by performing a critical analysis of available data and to provide indications for specific subgroups of individuals.

Background Cardiovascular disease (CVD) can occur in COVID-19 and has impact on clinical course. Data on CVD prevalence in hospitalized COVID-19 patients and sequelae in survivors is limited. Aim of this prospective study carried out on consecutive unselected COVID-19 population, was to assess: 1) CVD occurrence among hospitalized COVID-19 patients, 2) persistence or new onset of CVD at one-month and one-year follow-up. Methods Over 30 days n = 152 COVID-19 patients underwent cardiovascular evaluation. Standard electrocardiogram (ECG), Troponin and echocardiography were integrated by further tests when indicated. Medical history, arterial blood gas, blood tests, chest computed tomography and treatment were recorded. CVD was defined as the occurrence of a new condition during the hospitalization for COVID-19. Survivors attended a one-month follow-up visit and a one-year telephone follow-up. Results Forty-two patients (28%) experienced a wide spectrum of CVD with acute myocarditis being the most frequent. Death occurred in 32 patients (21%) and more frequently in patients who developed CVD (p = 0.032). After adjustment for confounders, CVD was independently associated with death occurrence. At one-month follow-up visit, 7 patients (9%) presented persistent or delayed CVD. At one-year telephone follow-up, 57 patients (48%) reported persistent symptoms. Conclusion Cardiovascular evaluation in COVID-19 patients is crucial since the occurrence of CVD in hospitalized COVID-19 patients is common (28%), requires specific treatment and increases the risk of in-hospital mortality. Persistence or delayed presentation of CVD at 1-month (9%) and persistent symptoms at 1-year follow-up (48%) suggest the need for monitoring COVID-19 survivors.

Patients with severely calcified coronary lesions undergoing percutaneous revascularization have a substantial risk of adverse outcomes, both during the procedure and in the long term. Over the last decade, a renewed interest has been observed about devices for plaque modification and lesion preparation, new technologies have been introduced in clinical practice and well-known devices have undergone technical and procedural improvements. The available tools for intravascular imaging allow a detailed evaluation of the calcific plaques within all the layers of the vessel wall. The complementary use of all these tools is ultimately aimed at optimizing the mechanics of balloon angioplasty and the delivery and expansion of drug-eluting stents. It has been fully demonstrated that rotational atherectomy improves procedural success when treating heavily calcified lesions. Intravascular lithotripsy, techniques and materials used during complex procedures such as chronic total occlusions, increasing operators' experience, as well as new drug-eluting stents with excellent mechanical characteristics, have further contributed to the feasibility and the safety of treating most fibrotic and heavily calcified vessels. We finally propose an algorithm for evaluation and treatment of severely calcific coronary lesions to demonstrate how such percutaneous revascularization procedures are planned and performed.

Background Epidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications. Objective We aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality. Methods In this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts. Results Among 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2–6] vs 3 [IQR 2–5], p

Background Coronavirus disease 2019 (COVID-19) has caused an unprecedented change in the apparent epidemiology of acute coronary syndromes (ACS). However, the interplay between this disease, changes in pollution, climate, and aversion to activation of emergency medical services represents a challenging conundrum. We aimed at appraising the impact of COVID-19, weather, and environment features on the occurrence of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in a large Italian region and metropolitan area. Methods and results Italy was hit early on by COVID-19, such that state of emergency was declared on January 31, 2020, and national lockdown implemented on March 9, 2020, mainly because the accrual of cases in Northern Italy. In order to appraise the independent contribution on changes in STEMI and NSTEMI daily rates of COVID-19, climate and pollution, we collected data on these clinical events from tertiary care cardiovascular centers in the Lazio region and Rome metropolitan area. Multilevel Poisson modeling was used to appraise unadjusted and adjusted effect estimates for the daily incidence of STEMI and NSTEMI cases. The sample included 1448 STEMI and 2040 NSTEMI, with a total of 2882 PCI spanning 6 months. Significant reductions in STEMI and NSTEMI were evident already in early February 2020 (all p, Highlights • COVID-19 has caused an unprecedented change in the epidemiology of acute coronary syndromes. • The interplay between this disease, pollution, climate, and aversion to emergency medical services represents a challenging conundrum. • Reductions in STEMI and NSTEMI in the COVID-19 pandemic may depend on different concomitant mechanisms.

Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), is an ongoing global pandemic with high morbidity and mortality.1 Patients with preexist...

In the early stages of COVID-19 pneumonia, hypoxemia has been described in absence of dyspnea ("silent" or "happy" hypoxemia). Our aim was to report its prevalence and outcome in a series of hypoxemic patients upon Emergency Department admission.In this retrospective observational cohort study we enrolled a study population consisting of 213 COVID-19 patients with PaOinf2/inf/FiOinf2/infratio300 mmHg at hospital admission. Two groups (silent and dyspneic hypoxemia) were defined. Symptoms, blood gas analysis, chest X-ray (CXR) severity, need for intensive care and outcome were recorded.Silent hypoxemic patients (68-31.9%) compared to the dyspneic hypoxemic patients (145-68.1%) showed greater frequency of extra respiratory symptoms (myalgia, diarrhea and nausea) and lower plasmatic LDH. PaOinf2/inf/FiOinf2/infratio was 225±68 mmHg and 192±78 mmHg in silent and dyspneic hypoxemia respectively (P=0.002). Eighteen percent of the patients with PaOinf2/inf/FiOinf2/inffrom 50 to 150 mmHg presented silent hypoxemia. Silent and dyspneic hypoxemic patients had similar PaCOinf2/inf(34.2±6.8 mmHg vs. 33.5±5.7 mmHg, P=0.47) but different respiratory rates (24.6±5.9 bpm vs. 28.6±11.3 bpm respectively, P=0.002). Even when CXR was severely abnormal, 25% of the population was silent hypoxemic. Twenty-six point five percent and 38.6% of silent and dyspneic patients were admitted to the ICU respectively (P=0.082). Mortality rate was 17.6% and 29.7% (log-rank P=0.083) in silent and dyspneic patients.Silent hypoxemia is remarkably present in COVID-19. The presence of dyspnea is associated with a more severe clinical condition.

We proposed a combined cardiothoracic-MRI (CaTh-MRI) protocol for the comprehensive assessment of cardiovascular structures, lung parenchyma, and pulmonary arterial tree, in COVID-19 patients with progressive worsening of clinical conditions and/or suspicion of acute-onset myocardial inflammation. A 25-minutes fast protocol was also conceived for unstable or uncooperative patients by restricting the number of sequences to those necessary to rule out myocardial and to assess pulmonary involvement. In patients requiring CMR characterization of myocardial damage, the addition of lung and thoracic vessel evaluation is of clinical benefit at a minimal time expense.

BackgroundContemporary data regarding the impact of comorbidities on the clinical presentation and management of patients with severe aortic stenosis (AS) are scarce.MethodsProspective registry of severe patients with AS across 23 centres in nine European countries.ResultsOf the 2171 patients, chronic kidney disease (CKD 27.3%), left ventricular ejection fraction (LVEF) ConclusionsComorbidities in severe patients with AS affect the presentation and management of patients with severe AS. TAVI was offered more often than SAVR and performed within a shorter time period.

Early risk stratification for complications and death related to Coronavirus disease 2019 (COVID-19) infection is needed. Because many patients with COVID-19 who developed acute respiratory distress syndrome have diffuse alveolar inflammatory damage associated with microvessel thrombosis, we aimed to investigate a common clinical tool, the CHA(2)DS(2)-VASc, to aid in the prognostication of outcomes for COVID-19 patients. We analyzed consecutive patients from the multicenter observational CORACLE registry, which contains data of patients hospitalized for COVID-19 infection in 4 regions of Italy, according to data-driven tertiles of CHA(2)DS(2)-VASc score. The primary outcomes were inpatient death and a composite of inpatient death or invasive ventilation. Of 1045 patients in the registry, 864 (82.7%) had data available to calculate CHA(2)DS(2)-VASc score and were included in the analysis. Of these, 167 (19.3%) died, 123 (14.2%) received invasive ventilation, and 249 (28.8%) had the composite outcome. Stratification by CHA(2)DS(2)-VASc tertiles (T1: ≤1; T2: 2 to 3; T3: ≥4) revealed increases in both death (8.1%, 24.3%, 33.3%, respectively; p