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Background: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. Results: The median age was 68 years, 23% of participants were women, 51% had ST-segment–elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71–1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69–1.61]). Conclusions: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search ; Unique identifier: 2019-003244-79.

Background Anthracycline-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in cancer patients. Cardioprotective strategies in primary and secondary prevention are still needed in clinical practice to improve cancer patient survival an to avoid drug therapy discontinuation. Sodium-glucose cotransporter 2 (SGLT2) inhibitors exerts multiple cardiometabolic benefits in patients with/without type 2 diabetes, chronic kidney disease, and heart failure with reduced ejection fraction. We hypothesized that Dapagliflozin, administered before and during doxorubicin therapy, could improve cardiac function and reduce pro-necrotic pathways in preclinical models Methods Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), DAPA at 12 mg/kg (DAPA, n=6) or doxorubicin combined to DAPA (DOXO-DAPA, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, DAMPs (galectine 3 and calgranulinS100) and systemic chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified through ELISA methods. Immunohistochemical stains (IHC) of NF-kB was performed in heart and kidney tissues. Results DAPA improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88, DAMPs and NF-kB in cardiac tissues was seen in DOXO-DAPA group compared to DOXO mice (p Conclusion DAPA is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. IHC analysis clearly indicates anti-inflammatory properties of DAPA in cardiac and renal tissues. The overall picture of the study pushes the use of DAPA in primary prevention of cardiomyopathies induced by anthracyclines in cancer patients.

Background: The itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice. Hypothesis: The safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines. Methods: Adults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two-thirds of the enrollment period are presented. Results: A total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1–2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor. Conclusions: The interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings.

At the end of 2019 a new Coronavirus appeared in China and, from there, it spread to the rest of the world On 24th May, 2020, the confirmed cases in the world were more than 5 million and the deaths almost 350 000 At the end of May, Italy reported more than 27 000 cases among healthcare professionals and 163 deaths among physicians The National Health Systems from almost all over the world, including Italy's, were unprepared for this pandemic, and this generated important consequences of organizational nature All elective and urgent specialized activities were completely reorganized, and many hospital units were partially or completely converted to the care of the COVID-19 patients A significant reduction in hospital admissions for acute heart disease were recorded during the SARS-CoV-2 pandemic and, in order to gradually resume hospital activities, the Italian National Phase 2 Plan for the partial recovery of activities, must necessarily be associated with a Phase 2 Health Plan In regards to the cardiac outpatient activities we need to identify short term goals, i e reschedule the suspended outpatient activities, revise the waiting lists, review the 'timings' of the bookings This will reduce the number of available examinations compared to the pre-Covid-19 era The GP's collaboration could represent an important resource, a structured telephone follow-up plan is advisable with the nursing staff's involvement It is equally important to set medium-long term goals, the pandemic could be an appropriate moment for making a virtue of necessity It is time to reason on prescriptive appropriateness, telemedicine implementation intended as integration to the traditional management It is time to restructure the cardiological units related to the issue of structural adjustment to the needs for functional isolation Moreover, the creation of 'grey zones' with multidisciplinary management according to the intensity of care levels seems to be necessary as well as the identification of Covid dedicated cardiologies Finally, the pandemic could represent the opportunity for a permanent renovation of the cardiological and territorial medicine activities © 2020 Oxford University Press All rights reserved

Among acute coronary syndrome (ACS) patients, 15% have concomitant cancer, especially in the first 6 months after their diagnosis, as well as in advanced metastatic stages. Lung, gastric, and pancreatic cancers are the most frequent malignancies associated with ACS. Chemotherapy and radiotherapy exert prothrombotic, vasospastic, and proinflammatory actions. The management of cancer patients with ACS is quite challenging: percutaneous revascularization is often underused, and antiplatelet and anticoagulant pharmacological therapy should be individually tailored to the thrombotic risk and to the bleeding complications. Sometimes oncological patients also show different degrees of thrombocytopenia, which further complicates the pharmacological strategies. The aim of this review is to summarize the current evidence regarding the treatment of ACS in cancer patients and to suggest the optimal management and therapy to reduce the risk of adverse coronary events after ACS in this high-risk population.

Aims To assess the number of admissions to the emergency room (ER) of patients with atrial fibrillation (AF) or atrial flutter (af) and their subsequent management. To evaluate the clinical profile and the use of antithrombotics and antiarrhythmic therapy in patients with AF admitted to cardiology wards. Methods and results BLITZ-AF is a multicentre, observational study conducted in 154 centres on patients with AF/af. In each centre, data were collected, retrospectively for 4 weeks in ER and prospectively for 12 weeks in cardiology wards. In ER, there were 6275 admissions. Atrial fibrillation was the main diagnosis in 52.9% of the cases, af in 5.9%. Atrial fibrillation represented 1.0% of all ER admissions and 1.7% of all hospital admissions. A cardioversion has been performed in nearly 25% of the cases. Out of 4126 patients, 52.2% were admitted in cardiology ward; mean age was 74 ± 11 years, 41% were females. Patients with non-valvular AF were 3848 (93.3%); CHA2DS2-VASc score was ≥2 in 87.4%. Cardioversion was attempted in 38.8% of the patients. In-hospital mortality was 1.2%. At discharge, 42.6% of the patients were treated with vitamin K antagonists, 39.5% with direct oral anticoagulants, 13.6% with other antithrombotic drugs, and 4.2% did not take any antithrombotic agent. Rate control strategy was pursued in 47.2%, rhythm control in 44.0%, 45.6% were discharged in sinus rhythm. Conclusion Atrial fibrillation still represents a significant burden on health care system. Oral anticoagulant use increased over time even if compliance with guidelines, with respect to prevention of the risk of stroke, remains suboptimal.

Atherosclerotic cardiovascular disease still represents the leading cause of death in western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proven effective in improving clinical outcomes. This document is focused on the clinical management of hypercholesterolemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors have considered with particular attention the role of hypercholesterolemia in the genesis of atherosclerotic cardiovascular disease. Besides, the implications of high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analyzed, while all available therapeutic options for blood cholesterol reduction and cardiovascular risk mitigation have been considered. Finally, this document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolemia.

The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including (i) their mechanism of action, pharmacodynamics, and pharmacokinetics; (ii) the use in the acute phase with the ‘double drug single dose’ approach or with ‘single drug double dose’; (iii) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; (iv) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance > 30 mL/min), the elderly (>75 years); (v) they propose a possible laboratory clinical pathway for follow-up; and (vi) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the use of NOACs both in the acute phase and in the extended phase is equally effective to conventional therapy and associated with fewer major bleeding events, which make their use in patients at higher risk of recurrences safer.

Mitral valve prolapse is generally a benign condition characterized by fibromyxomatous changes of the mitral leaflet with displacement into the left atrium and late-systolic regurgitation. Although it is an old clinical entity, it still arouses perplexity in diagnosis and clinical management. Complications, such as mitral regurgitation (MR), atrial fibrillation, congestive heart failure, endocarditis, ventricular arrhythmias, and sudden cardiac death (SCD), have been reported. A large proportion of the overall causes of SCD in young competitive athletes is explained by mitral valve prolapse. Recent studies have shown the fibrosis of the papillary muscles and inferobasal left ventricular wall in mitral valve prolapse, suggesting a possible origin of ventricular fatal arrhythmias. Athletes with mitral valve prolapse and MR should undergo annual evaluations including physical examination, echocardiogram, and exercise stress testing to evaluate the cardiovascular risks of competitive sports and obtain the eligibility. In this setting, multimodality imaging techniques - echocardiography, cardiac magnetic resonance, and cardiac computed tomography - should provide a broad spectrum of information, from diagnosis to clinical management of the major clinical profiles of the disease.

Dual antiplatelet therapy (DAPT) is a cornerstone of treatment for patients with acute coronary syndromes (ACS). Mounting evidences have opened the debate about the optimal DAPT duration. Considering the ACS-pathophysiology, the most recent guidelines recommend DAPT in all ACS patients for at least 12 months unless there are contraindications such as excessive risk of bleeding. Thus, it can be considered acceptable earlier discontinuation if the risk of morbidity from bleeding outweighs the anticipated benefit. On the other hand, several studies have clearly indicated that a significant burden of platelet related-events, such as stroke and new ACS might occur after this period, suggesting that potential benefits might derive by prolonging DAPT beyond 12 months (Long DAPT). Indeed, although current guidelines give some indications about patients eligible for Long DAPT, they do not embrace several real-life clinical scenarios. Thus, in such scenarios, how to decide whether a patient is eligible for Long DAPT or not might be still challenging for clinicians. This position paper presents and discusses various “real-life” clinical scenarios in ACS patients, in order to propose several possible recommendations to overcome guidelines potential limitations.

Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is the first medication to demonstrate a mortality benefit in patients with chronic heart failure and reduced ejection fraction (HFrEF) since the early 2000s. Sacubitril/valsartan simultaneously suppresses renin-angiotensin-aldosterone system activation through blockade of angiotensin II type 1 receptors and enhances the activity of vasoactive peptides including natriuretic peptides, through inhibition of neprilysin, the enzyme responsible for their degradation. In the landmark PARADIGM-HF trial, patients with HFrEF treated with sacubitril/valsartan had a 20% reduction in the primary composite endpoint of cardiovascular death or heart failure hospitalization, a 20% lower risk of cardiovascular death, a 21% to 20% lower risk of a first heart failure hospitalization, and a 16% to 20% lower risk of death from any cause, compared with subjects allocated to enalapril (all p0.001).Following the trial, new international guidelines endorsed sacubitril/valsartan as a class I recommendation for the management of patients with HFrEF who remain symptomatic despite optimal medical management. In Italy, sacubitril/valsartan is reimbursed by the National Health Service since March 2017 within criteria set by the Italian Medicines Agency subject to patient inclusion in a dedicated monitoring registry. Although numerous post-hoc analyses of the original trial suggested that the benefits of this innovative medication may extend across a variety of subgroups, many questions do not yet have an evidence-based answer.In this position paper, we discuss the current role of sacubitril/valsartan in the management of chronic HFrEF, treatment eligibility and the modulating role of patients' characteristics. Moreover, we address concerns elicited by the PARADIGM-HF study and shortcomings of this novel drug, to clarify the place of this new therapy in the context of global care of heart failure in Italy. Our aim is to provide clinical cardiologists with a concise and practical guidance on when and how to use sacubitril/valsartan, to assist clinicians in closing the gap between scientific innovation and real-world experience.

The incidence of ST-segment elevation myocardial infarction (STEMI) has significantly decreased. Conversely, the rate of non-STEMI (NSTEMI) has increased. Patients with NSTEMI have lower short-term mortality compared to patients with STEMI, whereas at long-term follow-up, the mortality becomes comparable. This might be due to the differences in baseline characteristics, including older age and a greater prevalence of comorbidities in the NSTEMI population. Although antithrombotic strategies used in patients with NSTEMI have been well studied in clinical trials and updated guidelines are available, patterns of use and outcomes in clinical practice are less well described. Thus, a panel of Italian cardiology experts assembled under the auspices of the "Campania NSTEMI Study Group" for comprehensive discussion and consensus development to provide practical recommendations, for both clinical and interventional cardiologists, regarding optimal management of antithrombotic therapy in patients with NSTEMI. This position article presents and discusses various clinical scenarios in patients with NSTEMI or unstable angina, including special subsets (eg, patients aged ≥85 years, patients with chronic renal disease or previous cerebrovascular events, and patients requiring triple therapy or long-term antithrombotic therapy), with the panel recommendations being provided for each scenario. The incidence of ST-segment elevation myocardial infarction (STEMI) has significantly decreased. Conversely, the rate of non-STEMI (NSTEMI) has increased. Patients with NSTEMI have lower short-term mortality compared to patients with STEMI, whereas at long-term follow-up, the mortality becomes comparable. This might be due to the differences in baseline characteristics, including older age and a greater prevalence of comorbidities in the NSTEMI population. Although antithrombotic strategies used in patients with NSTEMI have been well studied in clinical trials and updated guidelines are available, patterns of use and outcomes in clinical practice are less well described. Thus, a panel of Italian cardiology experts assembled under the auspices of the "Campania NSTEMI Study Group" for comprehensive discussion and consensus development to provide practical recommendations, for both clinical and interventional cardiologists, regarding optimal management of antithrombotic therapy in patients with NSTEMI. This position article presents and discusses various clinical scenarios in patients with NSTEMI or unstable angina, including special subsets (eg, patients aged ≥85 years, patients with chronic renal disease or previous cerebrovascular events, and patients requiring triple therapy or long-term antithrombotic therapy), with the panel recommendations being provided for each scenario.

Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336.

Although outcomes of acute coronary syndromes (ACS) have greatly improved, bleeding is still an issue. Thus, this study aims to evaluate in-hospital management and outcomes of unselected patients with ACS focusing on antithrombotic therapies and bleeding.From 22 April 2009 to 29 December 2010, 6394 consecutive Italian patients were prospectively enrolled and followed for 6 months. Most patients (55.3%) had non-ST-elevation (NSTE) ACS. Of the ST-elevation (STE) ACS patients, 79.8% received reperfusion (mainly mechanical). In-hospital and 6-month unadjusted total mortality rates were 4.2 and 7.8% for STE-ACS and 2.5 and 6.4% for NSTE-ACS, respectively. During hospitalization, TIMI major bleeding rate was 1.2% (1.4% STE-ACS and 1.1% NSTE-ACS, respectively) and TIMI minor bleeding was 3.1%. In-hospital and 6-month unadjusted total mortality rates were 3.1 and 6.7% for patients without bleeding, 1.5 and 8.6% for minor bleeding, and 19.0 and 26.6% for TIMI major bleeding, respectively (p0.0001). Notably, TIMI major bleeding was one of the strongest predictors of the 6-month composite end point (death or reinfarction) (STE-ACS hazard ratio, HR, 2.86, 95% confidence interval, 95% CI, 1.57-5.23; NSTE-ACS HR, 2.71, 95% CI 1.52-4.80). Predictors of in-hospital TIMI major bleeding were weight (odds ratio, OR, 0.97, 95% CI 0.95-0.99), female gender (OR 1.80, 95% CI 1.09-2.96), history of peripheral vasculopathy (OR 2.95, 95% CI 1.83-4.78), switching anticoagulant therapy (OR 2.62, 95% CI 1.36-5.05), intra-aortic balloon pump implantation (OR 4.44, 95% CI 1.85-10.69), and creatinine ≥2 mg/dl on admission (OR 3.68, 95% CI 1.84-7.33).Despite aggressive management, the rate of bleeding remains relatively low in an unselected ACS population. However, major bleeding adversely affects prognosis and physicians should tailor treatments to reduce it.

Atherosclerotic cardiovascular disease still represents the leading cause of death in western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proven effective in improving clinical outcomes. This document is focused on the clinical management of hypercholesterolemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors have considered with particular attention the role of hypercholesterolemia in the genesis of atherosclerotic cardiovascular disease. Besides, the implications of high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analyzed, while all available therapeutic options for blood cholesterol reduction and cardiovascular risk mitigation have been considered. Finally, this document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolemia.

The wide availability of drugs effective in reducing cardiovascular events and the use of myocardial revascularization have greatly improved the prognosis of patients with coronary artery disease. However, the combination of antithrombotic drugs to be administered before the exact knowledge of the coronary anatomy and before the consequent therapeutic strategy can, on one hand, allow to anticipate an optimal treatment but, on the other hand, may expose the patient to a bleeding risk not always necessary. In patients with ST-elevation acute coronary syndrome with an indication to primary angioplasty, the administration of unfractionated heparin and aspirin is considered the pre-procedural standard treatment. The upstream administration of an oral P2Y12 inhibitor, even if not supported by randomized controlled trials, appears reasonable in view of the very high likelihood of treatment with angioplasty. In patients with non-ST elevation acute coronary syndrome, in which it is not always chosen an invasive strategy, the occurrence of bleeding can significantly weigh on prognosis, even more than the theoretical benefit of pretreatment. Fondaparinux is the anticoagulant with the most favorable efficacy/safety profile. Antiplatelet pretreatment must be selective, guided by the ischemic risk conditions, the risk of bleeding and the time schedule for coronary angiography.In patients with stable coronary artery disease, generally treated with aspirin, pretreatment with clopidogrel is advisable in case of already scheduled angioplasty, and it appears reasonable in case of high likelihood, at least in patients at low bleeding risk. In patients candidate to surgical revascularization, aspirin is typically maintained and the oral P2Y12-inhibitor discontinued, with i.v. antiplatelet drug bridging in selected cases.Anti-ischemic drugs are useful in controlling symptoms, but they have no specific indications with regard to revascularization procedures. Statins showed protective effects on periprocedural damage and late clinical events, when administered early. Although randomized data are lacking, it seems reasonable their pre-procedural administration, due to potential advantages without significant adverse effects.

AIMS Several studies have shown sex differences in acute coronary syndromes (ACS), but their understanding is far from complete. Thus, the study aims to evaluate sex differences in management and outcomes of unselected patients with ACS. METHODS AND RESULTS From 22 April 2009 to 29 December 2010, 6394 consecutive patients with ACS (44.7% ST-elevation myocardial infarction) were prospectively enrolled and followed for 6 months. Women (N = 1894, 29.6%) were older, had more comorbidities, and worse clinical presentation than men. Fewer women underwent reperfusion [68.0% women vs. 84.1% men, P

The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including 1) their mechanism of action, pharmacodynamics and pharmacokinetics; 2) the use in the acute phase with the "double drug single dose" approach or with "single drug double dose"; 3) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; 4) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance30 ml/min), the elderly (75 years); 5) they propose a possible laboratory clinical pathway for follow-up; 6) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the use of NOACs both in the acute phase and in the extended phase is equally effective to conventional therapy and associated with fewer major bleeding events, which make their use in patients at higher risk of recurrences safer.

Background— In patients with implantable cardioverter-defibrillators (ICDs), antitachycardia pacing (ATP) is highly effective in terminating fast ventricular tachycardias (FVTs) and lowers the use of high-energy shocks, without increasing the risk of arrhythmia acceleration or syncope. Methods and Results— The aim of the PITAGORA ICD trial was to randomly compare 2 ATP strategies (88% coupling interval burst versus 91% coupling interval ramp, both 8 pulses) in terms of ATP efficacy, arrhythmia acceleration, and syncope. Two hundred six ICD patients (83% male, 67�11 years) were enrolled. FVT episodes with cycle lengths between 240 and 320 ms were treated by 1 ATP sequence and, in the event of failure, by shocks. Over a median follow-up of 36 months, 829 spontaneous ventricular tachyarrhythmia episodes were detected in 79 patients. Episode review identified 595 episodes as true ventricular arrhythmias in 72 patients; devices classified 111 (18.7%) episodes as VF, 216 (36.3%) as FVT, and 268 (45.0%) as VT. Fifty-six patients had 214 treated FVT episodes—2 FVTs self-terminated before ATP release; 44 (79%) of these had at least 1 effective ATP intervention, and 34 (61%) were spared ICD shocks. Burst terminated 100 of 133 (75.2%) FVT episodes, whereas ramp terminated 44 of 81 (54.3%; P =0.015). Acceleration occurred in 9 of 214 (4.2%) FVT episodes treated: 6 episodes in 3 ramp patients and 3 episodes in 3 burst patients. Two patients—1 in each group—suffered 1 syncopal event associated to a nonterminated FVT episode. Conclusions— Burst is significantly more efficacious than ramp in terminating FVT episodes. As the first therapy for FVT episodes, ATP carries a low risk of acceleration or syncopal events.

Objectives. To offer a snapshot of the personal health habits of Italian cardiologists, the Survey on Cardiac Risk Profile and Lifestyle Habits in a Cohort of Italian Cardiologists (SOCRATES) study was undertaken. Background. Cardiologists’ cardiovascular profile and lifestyle habits are poorly known worldwide. Methods. A Web-based electronic self-reported survey, accessible through a dedicated website, was used for data entry, and data were transferred via the web to a central database. The survey was divided in 4 sections: baseline characteristics, medical illnesses and traditional cardiovascular risk factors, lifestyle habits and selected medication use. The e-mail databases of three national scientific societies were used to survey a large and representative sample of Italian cardiologists. Results. During the 3-month period of the survey, 1770 out of the 5240 cardiologists contacted (33.7%) completed and returned one or more sections of the questionnaire. More than 49% of the participants had 1 out of 5 classical risk factors (e.g. hypertension, hypercholesterolemia, active smoking, diabetes and previous vascular events). More than 28% of respondents had 2 to 5 risk factors and only 22.1% had none and therefore, according to age and sex, could be considered at low-intermediate risk. Despite the reported risk factors, more than 90% of cardiologists had a self-reported risk perception quantified as mild, such as low or intermediate. Furthermore, overweight/obesity, physical inactivity and stress at work or at home were commonly reported, as well as a limited use of cardiovascular drugs, such as statins or aspirin. Conclusions. The average cardiovascular profile of Italian cardiologist is unlikely to be considered ideal or even favorable according to recent statements and guidelines regarding cardiovascular risk. Thus, there is a large room for improvement and a need for education and intervention.

Background Many clinical variables have been proposed as prognostic factors in patients with congestive heart failure. Among these, complete left bundle-branch block and atrial fibrillation are known to impair significantly left ventricular performance in patients with congestive heart failure. However, their combined effect on mortality has been poorly investigated. The aim of this study was to determine whether left bundle-branch block associated with atrial fibrillation had an independent, cumulative effect on mortality for congestive heart failure. Methods and Results We analysed the Italian Network on congestive heart failure (IN-CHF) Registry that was established by the Italian Association of Hospital Cardiologists in 1995. One-year follow-up data were available for 5517 patients. Complete left bundle-branch block and atrial fibrillation were associated in 185 (3·3%) patients. In this population the cause of congestive heart failure was dilated cardiomyopathy (38·4%), ischaemic heart disease (35·1%), hypertensive heart disease (17·3%), and other aetiologies (9·2%). This combination of electrical defects was associated with an increased 1-year mortality from any cause (hazard ratio, HR: 1·88; 95% CI 1·37–2·57) and sudden death (HR: 1·89; 95% CI 1·17–3·03) and 1-year hospitalization rate (HR: 1·83; 95% CI 1·26–2·67). Conclusions In patients with congestive heart failure, the contemporary presence of left bundle-branch block and atrial fibrillation was associated with a significant increase in mortality. This synergistic effect remained significant after adjusting for clinical variables usually associated with advanced heart failure. We can conclude that this combination of electrical disturbances identifies a congestive heart failure specific population with a high risk of mortality. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved

The introduction in the therapeutic armamentarium of three new oral anticoagulants for the prevention of thromboembolism in atrial fibrillation (AF) has stimulated the development of this position paper from the Italian Association of Hospital Cardiologists (ANMCO). First, the pathophysiology of arterial thromboembolism in AF is reviewed, describing the mechanisms of action of the new oral anticoagulants, their pharmacology and pharmacokinetics, and highlighting differences and similarities observed in preclinical studies and trials. Stratification of thromboembolic and bleeding risk is made using different risk scores; a comprehensive analysis of the various international guidelines should emphasize convergences or divergences. An in-depth examination of the limitations of current therapeutic strategies for the prevention of stroke in non-valvular AF provides insight into the difficulty in maintaining adequate adherence to therapy with warfarin and a constant and effective anticoagulation, without wide fluctuations in prothrombin time international normalized ratio (INR) values. Clinical trials of new oral anticoagulants for AF are discussed in detail in the present document, with a focus on similarities and differences, efficacy and safety data, and the net clinical benefit of each new oral anticoagulant. Results obtained in elderly patients, or in patients with renal, liver and ischemic heart disease or previous stroke are reported separately, as well as those regarding combination therapy with antiplatelet agents. Finally, this document provides indications, practical applications and cost-effectiveness analysis of each new oral anticoagulant. It is of utmost importance to know how treatment should be started, how you should switch from warfarin, which patients should be maintained on warfarin, how and when cardioversion, catheter ablation or appendage closure should be performed, what drug and food interactions may affect these medications, and how treatment adherence may be improved to avoid therapy discontinuation. An accurate examination of the risk of bleeding is also provided, with special reference to laboratory monitoring of renal and hepatic function, timing for discontinuing these medications prior to surgery, and treatment of patients with major and minor bleeding.

Oral anticoagulants offer the best long-term protection against ischemic stroke in patients with atrial fibrillation (AF). However, vitamin K antagonists (VKA) are cumbersome to use and their prescription is far from guidelines recommendations. We report the results of a large survey on the attitudes of prescription of VKA in patients with AF.7148 patients were enrolled by 196 Internal Medicine (MED) and 164 Cardiology (CARD) centers, and VKA specifically analyzed. Thrombotic and hemorrhagic risks were evaluated by means of CHADS2 and CHA2DS2VASc scores, and a study-specific bleeding score (modified HAS-BLED).63.9% of non-valvular patients had a CHADS2 score≥2 (MED: 75.3%-CARD: 53.1%), and 28.4% a bleeding score≥3 (41.9% MED-15.8% CARD). VKA were prescribed in 55.5% of non-valvular patients (46.3% MED and 64.2% CARD), in 81% of high-risk valvular patients and in 58.8% of the overall study population. Among patients at high risk of bleeding (score≥3), VKA were prescribed in 26.9% of subjects, while, in the subgroup at high risk of thrombosis (CHADS2 Score2), these were prescribed in 54.4%. Age≥75, paroxysmal AF, cognitive impairment, need for assistance, CHADS22 and bleeding score≥3 were independent predictors of non-use of VKA.Oral anticoagulants are more frequently used in CARD than in MED, plausibly due to greater complexity of MED patients. Stratification of thrombotic and hemorrhagic risk significantly drives the choice for VKA. However the fraction of patients in whom prescription or non-prescription is based on other individual characteristics is not negligible.

The management of antiplatelet therapy in patients with coronary stents undergoing surgery is a growing clinical problem and often represents a matter of debate between cardiologists and surgeons. It has been estimated that about 4-8% of patients undergoing coronary stenting need to undergo surgery within the next year. Surgery represents one of the most common reasons for premature antiplatelet therapy discontinuation, which is associated with a significant increase in mortality and major adverse cardiac events, in particular stent thrombosis. In addition, surgery confers an additional risk of perioperative cardiac ischemic events, being high in these patients because of the pro-inflammatory and pro-thrombotic effects of surgery. Current international guidelines recommend to postpone non-urgent surgery for at least 6 weeks after bare metal stent implantation and for 6-12 months after drug-eluting stent implantation. However, these recommendations provide little support with regard to managing antiplatelet therapy in the perioperative phase in case of urgent operations and/or high hemorrhagic risk. Furthermore, ischemic and hemorrhagic risk is not defined in detail on the basis of clinical and procedural characteristics. Finally, guidelines shared with cardiologists and surgeons are lacking. The present consensus document provides practical recommendations on the management of antiplatelet therapy in the perioperative period in patients with coronary stents undergoing surgery. Cardiologists and surgeons contributed equally to its creation. An ischemic risk stratification has been provided on the basis of clinical and procedural data. All surgical interventions have been defined on the basis of the hemorrhagic risk. A consensus on the most appropriate antiplatelet regimen in the perioperative phase has been reached on the basis of the ischemic and hemorrhagic risk. Dual antiplatelet therapy should not be withdrawn for surgery at low bleeding risk, whereas aspirin should be continued perioperatively in the majority of surgical operations. In the event of interventions at high risk for both bleeding and ischemic events, when oral antiplatelet therapy withdrawal is required, perioperative treatment with short-acting intravenous glycoprotein IIb/IIIa inhibitors (tirofiban or eptifibatide) should be considered.

To assess and promote compliance of Italian cardiological intensive care units (CCUs) with evidence-based guidelines for the management of acute myocardial infarction (MI).The process of diagnosis and treatment of MI was prospectively evaluated in 163 CCUs by use of 30 indicators during two enrolment phases, each followed by a feedback of both local and general performance. Overall, 5854 patients with ST-segment elevation MI (STEMI) and 5852 with non-ST-segment elevation MI (NSTEMI) were consecutively enrolled. The target for each indicator was defined as compliance with the relevant recommendations in ≥90% of suitable patients and it was met for nine (30%) and 10 (33.3%) indicators in the first and second phases, respectively. Regardless of target, a significant improvement in compliance was observed in the second phase in 10 out of 30 indicators (33.3%). Use of pre-hospital ECG, expedite delivery of reperfusion therapy, dosage of antithrombotic drugs, and non-pharmacological implementation of secondary prevention were often off target. Similar in-hospital mortality was observed in phases I and II, both in patients with STEMI (4.0 vs. 4.2%, p=0.79) and NSTEMI (1.8 vs. 2.4%, p=0.11). Overall, 30-day mortality were 5.7% for patients with STEMI and 3.4% with NSTEMI.Performance indicators can accurately weigh the whole process of diagnosis and treatment of patients with MI and monitor the improvements in the quality of care. In our large population of consecutive patients, satisfactory 30-day outcomes were observed despite suboptimal adherence to guidelines for some indicators of recognised prognostic relevance.

Atrial fibrillation (AF) is associated with a high risk of stroke and mortality.To describe the difference in AF management of patients (pts) referred to Cardiology (CARD) or Internal Medicine (MED) units in Italy.From May to July 2010, 360 centers enrolled 7148 pts (54% in CARD and 46% in MED). Median age was 77 years (IQR 70-83). Hypertension was the most prevalent associated condition, followed by hypercholesterolemia (28.9%), heart failure (27.7%) and diabetes (24.3%). MED pts were older, more frequently females and more often with comorbidities than CARD pts. In the 4845 pts with nonvalvular AF, a CHADS2 score ≥ 2 was present in 53.0% of CARD vs 75.3% of MED pts (p.0001). Oral anticoagulants (OAC) were prescribed in 64.2% of CARD vs 46.3% of MED pts (p.0001); OAC prescription rate was 49.6% in CHADS2 0 and 56.2% in CHADS2 score ≥ 2 pts. At the adjusted analysis patients managed in MED had a significantly lower probability to be treated with OAC. Rate control strategy was pursued in 51.4% of the pts (60.5% in MED and 43.6% in CARD) while rhythm control was the choice in 39.8% of CARD vs 12.9% of MED pts (p.0001).Cardiologists and internists seem to manage pts with large epidemiological differences. Both CARD and MED specialists currently fail to prescribe OAC in accordance with stroke risk. Patients managed by MED specialists have a lower probability to receive an OAC treatment, irrespective of the severity of clinical conditions.

Heart failure and myocardial infarction result in considerable consumption of healthcare resources. Therefore, there is interest in the availability of drug therapies that can favorably modify their prognosis in the post-acute phase, reducing mortality and rehospitalization rates. Aldosterone antagonists represent a class of drugs which offer advantages in these settings, in addition to those obtained with beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, even though attention should be drawn to their potential adverse effects. In particular, eplerenone exhibits a better safety profile than spironolactone. Since it has very little affinity for glucocorticoid, androgen and progesterone receptors, eplerenone has less antiandrogenic and progestagenic effects, resulting in a lower incidence of gynecomastia. The EPHESUS study showed that eplerenone can reduce mortality in the short and long term and the rate of new hospitalizations after a myocardial infarction complicated by heart failure. In addition, in the EMPHASIS-HF study eplerenone reduced cardiovascular mortality and hospitalizations after mild heart failure (NYHA class IIa). Despite these important results, which confirmed those obtained with spironolactone in severe heart failure in the RALES study, aldosterone antagonists are still underutilized. In particular, eplerenone is not yet available in Italy, although it is recommended by the latest European Society of Cardiology guidelines.

Systemic sclerosis (SSc) is a multi-system disorder characterized by widespread vascular lesions and fibrosis of skin and distinct internal organs. The aim of the present study was to analyze possible associations of left ventricular (LV) myocardial function with coronary flow reserve (CFR) and endothelial function in asymptomatic patients with SSc. Thirty healthy subjects and 33 age- and sex-comparable asymptomatic SSc patients underwent standard Doppler Myocardial Imaging, Strain Rate (SR) Imaging of interventricular septum (IVS) and LV lateral wall, transthoracic CFR of left anterior descending coronary vessel, and brachial artery vasodilatation measurement. In SSc patients, LV myocardial early diastolic peak velocity, peak systolic SR and strain were both reduced in basal and middle IVS, and in basal and middle LV lateral wall (p0.001). In addition, both CFR (p0.0001) and endothelial flow-mediated dilatation (p0.001) were significantly lower in SSc patients. By stepwise forward multivariate analyses, CFR (p0.001) and endothelial function (p0.001) were powerful independent determinants of middle LV strain of SSc patients. In conclusion, SR Imaging, transthoracic CFR and brachial artery flow-mediated dilatation are valuable non-invasive and easy-repeatable tools for detecting early LV myocardial and vascular involvement caused by SSc.

Coronary blood flow exhibits a biphasic pattern at rest with a higher diastolic and a smaller systolic component. In the present investigation, we evaluated whether a decreased diastolic to systolic velocity ratio of basal coronary flow may be useful in the identification of subjects with significant left anterior descending coronary artery (LAD) stenosis.One hundred and twenty-nine consecutive patients (62 with unstable angina, 25 with acute myocardial infarction and 42 with chronic coronary artery disease) were included in the study. Blood flow velocities were recorded in the mid-distal portion of the LAD using an ATL 5000 CV HDI ultrasound system. All patients underwent coronary angiography and were divided into two groups according to the absence (group 1) or the presence (group 2) of significant LAD stenosis (lumen narrowingor = 70%). In 60 of the 129 patients, coronary flow reserve was evaluated non-invasively.Adequate Doppler recordings in the LAD were obtained by transthoracic echocardiography in 113 patients. There were no differences between groups with regard to sex, cardiovascular risk factors, left ventricular mass and volumes, ejection fraction, whereas the diastolic to systolic velocity ratio of basal coronary flow was significantly lower in group 2 patients (1.41 +/- 4.7 vs. 2.08 +/- 0.64, P0.00001). The receiver operating characteristic curve showed that a diastolic to systolic velocity ratio1.6 had a sensitivity of 77%, a specificity of 91%, a positive predictive value of 77%, a negative predictive value of 97%, and a diagnostic accuracy of 84% for the presence of significant LAD stenosis. In 55/60 patients, results of basal coronary flow and coronary flow reserve were concordant. On multivariate logistic regression analysis, the diastolic to systolic velocity ratio was a strong independent predictor of LAD stenosisor = 70% (odds ratio 4.90, 95% confidence interval 1.65-7.30).The present findings suggest that assessment of basal coronary flow in the LAD may be useful to rule out the presence of significant stenosis.

The magnitude of benefit on mortality of combined angiotensin-converting enzyme inhibitor (ACEI) and beta-blocker (BB) therapy for heart failure cannot be reliably assessed from prospective randomized trials of individual drugs with intent-to-treat analysis. The placebo arm of the Valsartan Heart Failure Trial (Val-HeFT) included patients who remained on background therapy with ACEIs, BBs, neither, or both. The outcomes in these four subgroups should provide a better guide to mortality benefit. Overall mortality (mean follow-up, 23 months) was 31.6% in those receiving neither neurohormonal blocker, 29% and 39% lower in those on ACEIs or BBs, respectively, and 62% lower (11.9% mortality) in those receiving both drugs. In the neither neurohormonal inhibitor group, 48% of the heart failure-related deaths were adjudicated as sudden, whereas in the group receiving ACEIs and BBs, 79% of the deaths were sudden, and pump failure mortality was only 1% per year. The combination of ACEIs and BBs exerts a greater mortality reduction than suggested from clinical trials and reduces pump failure mortality to 1% per year.

The aim of this study was to assess the long-term predictive values of supine bicycle exercise stress echocardiography (ESE), and the ESE additional role compared to other traditional clinical and rest echocardiographic variables, in 607 patients with low, intermediate and high pretest risk of cardiac events.Clinical status and long-term outcome were assessed for a mean period of 46 months (range 12-60 months). ESE was performed for the diagnosis of suspected coronary artery disease (CAD) in 267 patients (43.9%), and for risk stratification of known CAD in 340 patients (56.1%). At baseline, the mean value of wall motion score index (WMSI) was 1.22 +/- 0.36, and the mean left ventricular ejection fraction was 58.5 +/- 10.9%.ESE was positive for ischemia in 210 patients (34.9%), while ECG was suggestive for ischemia in 157 patients (25.8%). During the test only 97 patients (15.9%) experienced angina. At peak effort, the mean WMSI was 1.38 +/- 0.46. A low workload was achieved by 158 patients (26.1%). During the follow-up period there were 222 events, including 82 hard events (36.9%), 48 deaths (21.6%) and 34 acute non-fatal myocardial infarction (15.3%). At stepwise multivariate model, cigarette smoking (p0.01), peak WMSI (p0.001), ESE positive for ischemia (p0.001) and low workload (p0.01) were the only independent predictors of cardiac death, while positive ESE, peak WMSI, angina during the test and hypercholesterolemia were the only independent determinants of hard cardiac events. The cumulative 5-year mean survival rate according to ESE response was 95.9% in patients with negative ESE, and 83.7% in patients with positive ESE (log rank 13.6; p0.00001).ESE yields prognostic information in known or suspected CAD, especially in patients with intermediate pretest risk level. The combined evaluation of clinical variables and other ESE variables, such as peak WMSI and exercise capacity, may further select patients at greatest risk of cardiac death in the overall population.

Background Beta-blockers are underused in HF patients, thus strategies to implement their use are needed. Objectives To improve beta-blocker use in elderly and/or patients with severe heart failure (HF) and to evaluate safety and outcome. Methods Patients with symptomatic HF and age ≥ 70 years or left ventricular EF < 25% and symptoms at rest were enrolled, including those already on beta-blocker treatment. Patients who were not receiving a beta-blocker were considered for carvedilol treatment. All patients were followed up for 1-year. Results Of the 1518 elderly patients, 505 were already on beta-blockers, and carvedilol was newly prescribed in 419 patients. At 1-year, patients treated with carvedilol had a lower incidence of death [10.8% vs. 18.0% in already treated (adjusted RR 0.68; 95%CI 0.49–0.96) and 11.2% in newly treated patients (adjusted RR 0.68; 95%CI 0.48–0.97)]. Of the 709 patients with severe HF, 38.4% were already on beta-blockers, and carvedilol was newly prescribed in 189 patients. Patients not treated with carvedilol showed the worst clinical outcome. Total rate of discontinuation (including adverse reaction and non-compliance) was 14% and 9%, respectively, in elderly and severe patients. Conclusions In a real world setting, beta-blocker treatment was not associated with an increased risk of adverse events in elderly and severe HF patients.

The majority of patients with heart failure are elderly. In order to point out the clinical characteristics and the quality of care of elderly heart failure patients we evaluated available data from national databases and observational studies. Elderly patients have more severe clinical manifestations, multiple etiologies and comorbid diseases, frequent hospital admissions, and a worse prognosis. As many as 30-50% of elderly patients with heart failure may have normal systolic function. In the elderly, evidence-based treatments are relatively underused with often inappropriately low doses. However, this "underuse" largely depends on the higher "frailty" of these patients (i.e. multiple coexisting diseases, disability, socio-environmental factors) and the lack of definite evidence on efficacy and safety of treatments in the very elderly. Several studies have documented the efficacy of specialized multidisciplinary heart failure disease management programs in terms of reducing hospital utilization, improving quality of life, functional capacity, patient satisfaction, compliance with diet and medications, and decreasing cost of care. Thus, there are opportunities to improve quality in many aspects of care, such as instrumental and multidimensional assessment and out-of-hospital management. Targeted clinical trials and rigorous observational studies with the aim at favoring the implementation of specific guidelines into clinical practice and continuity of care in the elderly are needed.

Systemic sclerosis (SSc) is a multisystem disorder characterized by widespread vascular lesions and fibrosis of the skin and specific internal organs. Cardiac involvement is a common finding in SSc, but often clinically occult. The aim of the present study was to analyze both left and right ventricular (RV) myocardial function in patients with SSc, and their relation to other instrumental features of the disease.Twenty-five healthy subjects and 23 age- and sex-comparable asymptomatic patients classified as having either diffuse (11 patients) or limited cutaneous (12 patients) SSc underwent clinical examination, serological analysis, high-resolution chest computed tomography, standard Doppler echocardiography and pulsed Doppler myocardial imaging (DMI) of both the mitral and tricuspid annuli. SSc was classified using the modified Rodnan skin score (mRSS) into high mRSS (scoreor = 10) and low mRSS (score10).Serological antibody analysis revealed the presence of antinuclear antibody in all patients, an anticentromere pattern in 8 patients, and anti-Scl-70 antibodies in 15 patients. Eleven patients were diagnosed with interstitial pulmonary fibrosis at chest computed tomography. Standard Doppler echocardiography revealed that the left ventricular mass index and ejection fraction were comparable between the two groups, while the RV end-diastolic diameter was increased in SSc (p0.01). The tricuspid inflow peak E and E/A ratio were slightly decreased in SSc (p0.01), while the systolic pulmonary pressure was increased (p0.0001). DMI analysis revealed, in SSc, an impaired RV myocardial early-diastolic (Em) peak velocity (p0.001) as well as a prolonged myocardial relaxation time (RTm) (p0.001) only at the tricuspid annulus level, even after correction for age, sex, heart rate and left ventricular mass index. Independent inverse associations of the RV Em peak velocity with both the Rodnan skin score (beta coefficient = -0.62, p0.0005) and the pulmonary systolic pressure (beta coefficient = 0.71, p0.0001), as well as the independent inverse correlation of the same RV Em peak velocity with interstitial pulmonary fibrosis (odds ratio 0.68, 95% confidence interval 0.45-0.83, p0.0005) in SSc patients were assessed at multivariate analysis. In addition, the RV Em velocity was an independent predictor of the anti-Scl-70 antibody pattern (odds ratio 0.68, 95% confidence interval 0.45-0.83, p0.01). Of note, a RV Em peak velocity0.11 m/s well selected SSc patients with pulmonary artery pressure35 mmHg, pulmonary fibrosis, a high mRSS, and an anti-Scl-70 antibody pattern.The relationships of RV myocardial diastolic dysfunction with both skin and pulmonary involvement as well as with the serological antibody pattern emphasizes the ability of DMI to identify patients with a more diffuse and severe form of SSc. This issue may be critical for the early identification of those SSc patients who are at higher risk of cardiac impairment, ideally when they are still asymptomatic before developing severe vasculopathy.

We sought to assess the indexes of myocardial activation delay, using Doppler myocardial imaging (DMI), as potential predictors of cardiac events in patients with hypertrophic cardiomyopathy (HCM). The distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with HCM, which results in heterogeneity of regional LV systolic function.The study population included 123 HCM patients (39.4+/-5.9 years) and 123 age- and sex-matched healthy subjects, followed up for 48.4+/-8.8 months. By use of pulsed DMI, the following regional parameters were evaluated in six different basal myocardial segments: myocardial peak velocities and systolic time-intervals; myocardial intraventricular (intra-V-Del) and interventricular (inter-V-Del) systolic delays. DMI analysis in HCM showed lower myocardial systolic and early-diastolic peak velocities of all the segments. As for time intervals, HCM showed significant inter- and intra-V delays (P0.0001), whereas homogeneous systolic activation of the ventricular walls was assessed in controls. During the follow-up, 16 cardiac deaths (12 sudden deaths) were observed in HCM patients. InHCM, DMI intra-V-Del was the most powerful independent predictor of sudden cardiac death (P0.0001). In particular, an intra-V-Del45 ms is identified with high sensitivity and specificity in HCM patients at higher risk of ventricular tachycardia and sudden cardiac death (test accuracy: 88.8%).In HCM patients, DMI indexes of intra-V-Del may provide additional information for selecting subgroups of HCM patients at increased risk of ventricular arrhythmias and sudden cardiac death at follow-up. Accordingly, such patients may be more actively identified for early intensive treatment and survey.

Aims To assess the prognostic significance of supine bicycle exercise stress echocardiography (ESE) for cardiac events, and the ESE additional role compared to other traditional clinical and echo variables, in patients with proven or suspected coronary artery disease (CAD). Methods and results Clinical status and long-term outcome were assessed in 607 patients, for a mean period of 49.9±12.5 months. ESE was performed for the diagnosis of suspected CAD in 267 patients, and for the risk stratification in 340 patients. At baseline, the mean value of WMSI was 1.22±0.36, and the mean left ventricular ejection fraction was 58.2±10.9%. The ESE was positive for ischemia in 210 patients (34.9%), while the ECG was suggestive for ischemia in 157 patients. At peak effort, the mean WMSI was 1.38±0.46. Low work load was achieved by 158 patients (26.1%). During the follow-up period there were 222 events, including 48 cardiac deaths and 34 acute non-fatal myocardial infarction. By multivariable model, cigarette smoking, peak WMSI, positive ESE for ischemia and low work load were the only independent predictors of cardiac death. The cumulative 5-year mean survival rate according to ESE response was 95.9% in patients with negative ESE, and 81.7% in positive ESE ( p

Little is known about the clinical profile, use of resources, management and outcome of a large population of diabetic patients with heart failure managed in a community setting.A prospective cross-sectional survey in the setting of acute hospital admissions for heart failure to 167 cardiology and 250 internal medicine departments between February 14 and 25, 2000.Among the 2127 consecutively admitted patients, 603 (28.4%) had a history of diabetes; they were significantly younger, had a lower rate of atrial fibrillation, and a more frequent ischemic etiology than non-diabetics. Just as non-diabetic patients, diabetics underwent invasive and non-invasive procedures in a low percentage of cases, even though slightly more frequently when managed by cardiologists. Diabetic patients were less frequently prescribed amiodarone and anticoagulants, and more frequently prescribed nitrates and antiplatelets. The all-cause in-hospital mortality rate was similar among diabetics and non-diabetics (5.3 vs 5.7%, p = NS). Adjusted analysis confirmed that diabetes is not independently associated with a worse outcome.In a community setting diabetes per se has only a slight impact on the management and outcome of patients with heart failure.

Hemodynamic overload due to long-term training usually involves both left and right ventricles, inducing changes in cardiac structure such as an increase in internal cavity diameters, wall thickness and mass. Standard Doppler echocardiography has been widely used to identify the athlete's heart and to distinguish it from left ventricular pathologies. Pulsed Doppler myocardial imaging (DMI) extends Doppler applications beyond the analysis of cardiac blood flows to the measurement of myocardial wall motion. Recent reports have documented the usefulness of DMI in the evaluation of the athlete's heart. In particular, DMI analysis of trained subjects may represent a valid noninvasive tool in the following fields of application: 1) to assess differences in myocardial function in diverse forms of both physiological and pathological left ventricular hypertrophy; 2) to predict left ventricular performance during effort; 3) to analyze the effects of different training protocols on ventricular regional function; 4) to evaluate biventricular cooperation; 5) to detect myocardial dysfunction associated with pathological genotype in cardiomyopathies.

The purpose pf the current article is to describe the clinical profile, use of resources, management and outcome in a population of real-world inpatients with heart failure.With a prospective, cross-sectional survey on acute hospital admissions, we evaluated the overall and provider-related differences in patient characteristics, diagnostic work-up, treatment and inhospital outcome of 2127 patients with heart failure admitted to 167 cardiology departments and 250 internal medicine departments between February 14 and 25, 2000. Patients admitted to cardiology units were younger (56.3%70 years vs 76.2%, P.0001), had more severe symptoms (NYHA IV 35% vs 29%, P =.00014), and more often underwent evaluation of ventricular function (89.3% vs 54.8%, P.0001) and coronary angiography (7.5% vs 0.9%, P.0001) than those admitted to medical units. Moreover, they were more often prescribed beta-blockers (17.8% vs 8.7%, P.0001). However, prescription of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (78.7% vs 81.5%, P = not significant [NS]) and inhospital mortality (5.2% vs 5.9%, P = NS) were similar. A 6-month follow-up visit was performed in 56.4% of cases (68.2% of cardiology vs 49.4% of medicine patients, P.0001); 6-month readmission (43.7% vs 45.4%, P = NS) and mortality (13.9% vs 16.7%, P = NS) rates were similar.Patients with heart failure admitted to cardiology and internal medicine units represent 2 clearly different populations. In both groups, diagnostic procedures and evidence-based treatments, such as beta-blockers, appeared to be underused, and there was a lack of structured follow-up, as well as a poor 6-month prognosis.

Background: Physicians are still concerned about prescribing β-blockers in diabetic patients with heart failure. Methods: In the outcome research study (the Beta-Blockers in Patients With Congestive Heart Failure: Guided Use in Clinical Practice [BRING-UP] study), the responsible clinicians could decide whether to start β-blocker treatment and which agent to use. A total of 3091 patients were enrolled by 202 cardiologic centers: 25% of the recruited patients were already on β-blockers, 28% started treatment at the enrollment visit, and 47% were not started on β-blockers. Results: The 1-year mortality, hospitalization rate, and the combined end point of mortality or hospitalization were higher in diabetic patients (15.8% versus 10.9%; relative risk [RR] = 1.44; 95% confidence intervals [CI] 1.16-1.78, P =.001) (31.0% versus 24.0%; RR = 1.28; 95% CI 1.11-1.49; P =.0009) (40.5% versus 30.1%; RR = 1.35; 95% CI 1.19-1.51; P =.0001). The event-free analysis of the 4 groups (diabetic patients not treated with β-blockers, diabetic patients treated with β-blockers, nondiabetic patients not treated with β-blockers, nondiabetic patients treated with β-blockers) showed that patients treated with β-blockers had a higher event-free probability than patients not treated with β-blockers regardless the presence of diabetes ( P Conclusions: On the basis of post hoc analysis, diabetic patients with chronic heart failure benefit from β-blockers even if at a lower degree. Thus, there are no justifications to avoid β-blockers in heart failure patients in the presence of diabetes.

The aim of this study was to evaluate the patency of left and right internal mammary artery grafts respectively on the left anterior descending and right coronary artery by noninvasive transthoracic color Doppler echocardiography.Thirty eight patients (34 males, 4 females, mean age 59 +/- 2 years), with a history of coronary artery bypass grafting for a total of 42 mammary artery grafts, were studied by means of color Doppler echocardiography at baseline and after vasodilation with dipyridamole infusion (0.56 mg/kg i.v. over 4 min). The evaluated echocardiographic parameters included: systolic (SPV) and diastolic peak velocities (DPV), systolic (SVI) and diastolic velocity-time integrals (DVI), and the DPV/SPV and DVI/SVI ratios. We also calculated the dipyridamole infusion to baseline ratio of the diastolic peak velocities (DPVdip/DPVbaseline), the index of internal mammary artery graft blood flow reserve and the percent DPV increment as an index of graft stenosis.On the basis of coronary angiography, two groups were selected: group A (36 mammary grafts) with patent grafts and group B (6 mammary grafts) with moderate or severe stenosis of the grafts. Group A had a predominant diastolic pattern with a DPV of 0.24 +/- 0.13 m/s, whereas group B had a predominant systolic pattern with a reduced DPV of 0.12 +/- 0.03 m/s (p0.01). Dipyridamole induced an increase in the DPV respectively of 86.8 +/- 64.4% in group A and 13.8 +/- 15.9% in group B (p0.001). Statistical analysis (Mann-Whitney test) revealed a significant difference between the two groups for the baseline DPV (p0.01), DVI (p0.05), DPV/SPV ratio (p0.005), DVI/SVI ratio (p0.05), and for the after dipyridamole infusion values: DPV (p0.0001), DVI (p0.005), DPV/SPV ratio (p0.001), and DVI/SVI ratio (p0.05). Multivariate analysis showed that the percent DPV increment, the DPVdip/DPVbaseline ratio and the baseline DPV were independent determinants of the stenosis as evaluated at angiography (beta = -0.38, p0.01; beta = -0.37, p0.01, and beta = -0.33, p0.05, respectively; cumulative r2 = 0.25, standard error 0.30 m/s, p0.005).The echocardiographic evaluation of the mammary grafts is a simple, noninvasive method for the assessment of the graft patency and of the functional status of the vessel. The percent DPV increment and baseline DPV were independent determinants of mammary graft stenosis.

Despite the well-established benefits of ACE-inhibitors in chronic heart failure (CHF), current treatment rates and prescribed doses are lower than those proven to improve survival. We evaluated whether participation in a specialist network and the use of a common database would impact on the compliance with CHF guidelines.We analyzed the rate and determinants of ACE-inhibitor use and prescribed doses among 8102 patients with CHF enrolled at 133 cardiology centers participating in a national network.6625 patients (82%) took ACE-inhibitors, most commonly enalapril (41%, mean dose 16 +/- 9 mg), captopril (25%, mean dose 74 +/- 44 mg) and lisinopril (14%, mean dose 13 +/- 8 mg). The predictors of the non-prescription of ACE-inhibitors were: female gender (odds ratio--OR 1.46, 95% confidence interval-CI 1.28-1.67), older age (OR 1.01, 95% CI 1.01-1.02), valvular etiology (OR 1.87, 95% CI 1.60-2.20), NYHA class III-IV (OR 1.25, 95% CI 1.09-1.42) and creatinine levels2.5 mg/dl (OR 5.19, 95% CI 3.36-8.02). Conversely a left ventricular ejection fraction30% (OR 0.78, 95% CI 0.65-0.94) and a hypertensive (OR 0.69, 95% CI 0.55-0.86) or idiopathic (OR 0.67, 95% CI 0.57-0.78) etiology increased the rate of ACE-inhibitor prescription. Low ACE-inhibitor doses were prescribed to 26.4% of cases.The IN-CHF database, an educational and organizational effort led by a national cardiology society, demonstrates that high rates of ACE-inhibitor treatment may be achieved in routine clinical practice in a cardiology setting.