Consensus Document ANMCO/ANCE/ARCA/GICR-IACPR/GISE/SICOA: Long-term Antiplatelet Therapy in Patients with Coronary Artery Disease.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of pharmacologic management of patients with acute coronary syndrome (ACS) and/or those receiving coronary stents. Long-term (>1 year) DAPT may further reduce the risk of stent thrombosis after a percutaneous coronary intervention (PCI) and may decrease the occurrence of non-stent-related ischaemic events in patients with ACS. Nevertheless, compared with aspirin alone, extended use of aspirin plus a P2Y12 receptor inhibitor may increase the risk of bleeding events that have been strongly linked to adverse outcomes including recurrent ischaemia, repeat hospitalisation and death. In the past years, multiple randomised trials have been published comparing the duration of DAPT after PCI and in ACS patients, investigating either a shorter or prolonged DAPT regimen. Although the current European Society of Cardiology guidelines provide a backup to individualised treatment, it appears to be difficult to identify the ideal patient profile which could safely reduce or prolong the DAPT duration in daily clinical practice. The aim of this consensus document is to review contemporary literature on optimal DAPT duration, and to guide clinicians in tailoring antiplatelet strategies in patients undergoing PCI or presenting with ACS.

ANMCO/ISS/AMD/ANCE/ARCA/FADOI/GICR-IACPR/SICI-GISE/SIBioC/SIC/SICOA/SID/SIF/SIMEU/SIMG/SIMI/SISA Joint Consensus Document on cholesterol and cardiovascular risk: diagnostic-therapeutic pathway in Italy.

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 proved effective in improving clinical outcomes. This document focuses on the clinical management of hypercholesterolaemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors discuss in detail the role of hypercholesterolaemia in the genesis of atherosclerotic cardiovascular disease. In addition, the implications for high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analysed, while all available therapeutic options for blood cholesterol reduction and cardiovascular risk mitigation have been explored. Finally, this document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolaemia.

A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial).

AIMS: AUGMENT-HF was an international, multi-centre, prospective, randomized, controlled trial to evaluate the benefits and safety of a novel method of left ventricular (LV) modification with alginate-hydrogel. METHODS: Alginate-hydrogel is an inert permanent implant that is directly injected into LV heart muscle and serves as a prosthetic scaffold to modify the shape and size of the dilated LV. Patients with advanced chronic heart failure (HF) were randomized (1 : 1) to alginate-hydrogel (n = 40) in combination with standard medical therapy or standard medical therapy alone (Control, n = 38). The primary endpoint of AUGMENT-HF was the change in peak VO2 from baseline to 6 months. Secondary endpoints included changes in 6-min walk test (6MWT) distance and New York Heart Association (NYHA) functional class, as well as assessments of procedural safety. RESULTS: Enrolled patients were 63 ± 10 years old, 74% in NYHA functional class III, had a LV ejection fraction of 26 ± 5% and a mean peak VO2 of 12.2 ± 1.8 mL/kg/min. Thirty-five patients were successfully treated with alginate-hydrogel injections through a limited left thoracotomy approach without device-related complications; the 30-day surgical mortality was 8.6% (3 deaths). Alginate-hydrogel treatment was associated with improved peak VO2 at 6 months-treatment effect vs. CONTROL: +1.24 mL/kg/min (95% confidence interval 0.26-2.23, P = 0.014). Also 6MWT distance and NYHA functional class improved in alginate-hydrogel-treated patients vs. Control (both P < 0.001). CONCLUSION: Alginate-hydrogel in addition to standard medical therapy for patients with advanced chronic HF was more effective than standard medical therapy alone for improving exercise capacity and symptoms. The results of AUGMENT-HF provide proof of concept for a pivotal trial. TRIAL REGISTRATION NUMBER: NCT01311791.

[HCF-ANMCO/AICPR/GIEC/ITAHFA/SICOA/SICP/SIMG/SIT Cardiological Societies Council Consensus document: Anticoagulant therapy in venous thromboembolism and atrial fibrillation of the patient with cancer. Current knowledge and new evidence]. / Documento di consenso della Consulta delle Società Cardiologiche HCF-ANMCO/AICPR/GIEC/ITAHFA/SICOA/SICP/SIMG/SIT: La terapia anticoagulante nel tromboembolismo venoso e nella fibrillazione atriale del paziente con cancro. Le attuali conoscenze e le nuove evidenze.

Venous thromboembolism (VTE), including pulmonary embolism and deep venous thrombosis, either symptomatic or incidental, is a common complication in the history of cancer disease. The risk of VTE is 4-7-fold higher in oncology patients, and it represents the second leading cause of death, after cancer itself. In cancer patients, compared with the general population, VTE therapy is associated with higher rates of recurrent thrombosis and/or major bleeding. The need for treatment of VTE in patients with cancer is a challenge for the clinician because of the multiplicity of types of cancer, the disease stage and the imbricated cancer treatment. Historically, in cancer patients, low molecular weight heparins have been preferred for treatment of VTE. More recently, in large randomized clinical trials, direct oral anticoagulants (DOACs) demonstrated to reduce the risk of VTE. However, in the "real life", uncertainties remain on the use of DOACs, especially for the bleeding risk in patients with gastrointestinal cancers and the potential drug-to-drug interactions with specific anticancer therapies.In cancer patients, atrial fibrillation can arise as a perioperative complication or for the side effect of some chemotherapy agents, as well as a consequence of some associated risk factors, including cancer itself. The current clinical scores for predicting thrombotic events (CHA2DS2-VASc) or for predicting bleeding (HAS-BLED), used to guide antithrombotic therapy in the general population, have not yet been validated in cancer patients. Encouraging data for DOAC prescription in patients with atrial fibrillation and cancer are emerging: recent post-hoc analysis showed safety and efficacy of DOACs for the prevention of embolic events compared to warfarin in cancer patients. Currently, anticoagulant therapy of cancer patients should be individualized with multidisciplinary follow-up and frequent reassessment. This consensus document represents an advanced state of the art on the subject and provides useful notes on clinical practice.

[ANMCO/ANCE/ARCA/GICR-IACPR intersociety consensus document: long-term antiplatelet therapy in patients with coronary artery disease]. / Documento di consenso intersocietario ANMCO/ANCE/ARCA/GICR-IACPR/GISE/SICOA: La terapia antiaggregante a lungo termine nel paziente con malattia coronarica.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of the pharmacologic management of patients with acute coronary syndrome (ACS) and/or receiving coronary stents. Long-term (>1 year) DAPT may further reduce the risk of stent thrombosis after percutaneous coronary intervention (PCI) and may decrease the occurrence of non-stent-related ischemic events in patients with ACS. Nevertheless, compared with aspirin alone, extended use of aspirin plus a P2Y12 receptor inhibitor may increase the risk of bleeding events that have been strongly linked to adverse outcomes including recurrent ischemia, repeat hospitalization, and death. Over the last years, multiple randomized clinical trials have been published comparing duration of DAPT after PCI and in ACS patients investigating either a shorter or prolonged DAPT regimen.Although current European Society of Cardiology guidelines provide backup to individualize treatment, it seems difficult to identify the ideal patient profile who could safely reduce or prolong DAPT duration in daily clinical practice. The aim of this consensus document is to review the contemporary literature on optimal DAPT duration and to guide clinicians in tailoring antiplatelet strategies in patients undergoing PCI or presenting with ACS.

[The slow acceptance of new oral anticoagulants in Italy: a critical analysis of a problem]. / La lenta accettazione dei nuovi anticoagulanti orali in Italia: analisi critica di un problema.

The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into clinical practice has revolutionized the prevention and the therapeutic approaches to thromboembolic events in patients with nonvalvular atrial fibrillation and represents with no doubts one of the most remarkable advances in the history of cardiovascular medicine over the last years. NOACs beyond a comparable efficacy with vitamin K antagonists allow to overcome the limitations of this last category of drugs owing to their less drug to drug interactions and a predictable anticoagulant effect that allows a fixed dose administration without the need for continuous monitoring. However, the penetration of NOACs into the Italian market is still lower than predicted with respect to their use in other European countries.The aim of this review is to critically analyze the reasons behind this attitude through the adoption of the nominal group technique, a methodology that permits to reach an official consensus.

[The Italian Survey on Cardiac Rehabilitation - 2013 (ISYDE.13-Directory): national availability and organization of cardiac rehabilitation facilities]. / Italian Survey on Cardiac Rehabilitation (ISYDE.13-Directory): report su strutture, organizzazione e programmi di cardiologia riabilitativa in Italia.

BACKGROUND: The Italian Association for Cardiovascular Prevention, Rehabilitation and Epidemiology (GICR-IACPR) and the Italian Society of Cardiologists of Accredited Hospitals (SICOA) developed the ISYDE.13 survey with the purpose to take a detailed snapshot of number, distribution, facilities, staffing levels, organization, and program details of cardiac rehabilitation (CR) units in Italy. METHODS: The study was carried out using a web-based questionnaire running on the GICR-IACPR website for 4 weeks from September 2 to 29, 2013. RESULTS: Out of 221 CR centers existing in Italy (+14% vs 2008), 191 (86%) participated in the survey. On a national basis, there is a CR unit every 268 852 inhabitants. The majority of CR units are located in public hospitals (57.1%), the remaining 42.9% in private hospitals; 130 CR centers (68%) provide inpatients care and account for 3527 beds (5.9 per 100 000 inhabitants): of these 374 are day-hospital beds and 408 are sub-intensive beds. Forty-one of the Italian in-hospital CR centers offer also outpatient programs and 61 centers (32%) offer only outpatient CR programs; 131 of the CR units (68.6%) are linked to dedicated cardiology divisions and in 77% of cases the head is a cardiologist. Home-based programs are offered by 9 centers (4.7%) and CR programs with telecare supervision by 16 (8.4%). Long-term secondary prevention follow-up programs are provided by 94 of CR services (49.2%). During one week of activity, the 191 centers completed 1335 inpatient CR programs and 971 outpatient CR programs. According to these data, it may be assumed that in Italy approximately 100 000 patients are referred annually to CR programs. CONCLUSIONS: ISYDE.13 showed an incremental trend of CR provision in Italy, particularly in outpatient programs. However, at present, the national network of CR units covers only one third of the potential requirements defined by current secondary prevention recommendations.

Incidence and clinical presentation of myocardial ischemia in patients with chronic CAD in Italy: the ISPICA survey study.

AIM: This survey study was performed to provide an overall picture on the incidence of symptoms, with or without typical angina, in the real-life clinical practice and to identify clinical factors associated with atypical presentations in an unselected population of consecutive outpatients with chronic coronary artery disease (CAD). METHODS: Thirty-six cardiology units located in different geographic areas of Italy enrolled a total of 1475 outpatients (73.6% men and 26.3% women; mean age 71 ±â€Š10 and 67 ±â€Š9 years in men and women, respectively) with a documented diagnosis of chronic CAD. Each patient underwent a medical history, with a detailed investigation as to the presence of typical angina or ischemic equivalents defined as sensation of chest pressure, or arm, neck, or jaw pain. RESULTS: At admission, symptoms suggesting ischemic episodes were reported by 24.4% of patients. After an in-depth medical history collection by the specialist, the prevalence of combined typical or atypical myocardial ischemic episodes was ascertained in 39.3% of the overall population.Typical angina was reported by 13.6% of men and 22.7% of women (P < 0.0001), whereas ischemic equivalents were present in 7.3 and 12.9% of male and female patients, respectively (P < 0.001). Previous coronary artery bypass grafting (CABG; P < 0.001) and fewer medical visits by cardiologists (P = 0.02) were independent predictors of atypical presentations. CONCLUSION: The ISPICA study shows that in an Italian population of real-world patients with chronic CAD, ischemic episodes, with both typical and atypical presentation, are still present in nearly 50% of patients, despite optimal medical therapy, and that atypical presentations of angina are linked to fewer visits by specialists and previous CABG. These findings would suggest to encourage patients with chronic CAD and general practitioners to consider more frequent cardiology specialist visits and to take into account the possibility of atypical presentations, particularly in patients with previous CABG.

High-sensitive cardiac troponin T (hs-cTnT) assay as serum biomarker to predict cardiac risk in myotonic dystrophy: A case-control study.

BACKGROUND: Myotonic dystrophy (DM) is a genetic disorder caused by nucleotide repeats expansion. Sudden death represents the main cause of mortality in DM patients. Here, we investigated the relationship between serum cardiac biomarkers with clinical parameters in DM patients. METHODS: Case-control study included 59 DM patients and 22 healthy controls. An additional group of 62 controls with similar cardiac defects to DM were enrolled. RESULTS: NT-proBNP, hs-cTnT and CK levels were significantly increased in DM patients compared to healthy subjects (p=0.0008, p<0.0001, p<0.0001). Also, hs-cTnT levels were significantly higher in DM compared to control group with cardiac defects (p=0.0003). Positive correlation was found between hs-cTnT and hs-cTnI in both DM patients and controls (p=0.019, p=0.002). Independently from the age, the risk of DM disease was positively related to an increase in hs-cTnT (p=0.03). On the contrary, the risk of DM was not related to hs-cTnI, but was evidenced a role of PR interval (p=0.03) and CK (p=0.08). CONCLUSIONS: The levels of hs-cTnT were significantly higher in DM patients. Analysis, with anti-cTnT, shows that this increase might be linked to heart problems. This last finding suggests that hs-cTnT might represent a helpful serum biomarker to "predict" cardiac risk in DM disease.

One-year follow-up results from AUGMENT-HF: a multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure.

AIMS: AUGMENT-HF was an international, multicentre, prospective, open-label, randomized, controlled evaluation testing the hypothesis that Algisyl (injectable calcium alginate hydrogel) is superior to standard medical therapy (SMT) for improving functional capacity and clinical outcomes in patients with advanced heart failure (HF). We previously reported results following 6 months of follow-up. This report presents the results from 1 year of extended follow up for this clinical trial. METHODS AND RESULTS: We enrolled 78 patients with advanced HF, randomized (1:1), to Algisyl with SMT or SMT alone as previously reported. Patient inclusion criteria were LVEF ≤35%, peak VO2 of 9.0-14.5 mL/min/kg and LV end-diastolic diameter (LVEDD) index 30-40 mm/m(2) (LVEDD/body surface area). Patients must have been on stable, evidence-based therapy for HF. A total of 58 patients, mean age 62.3 ± 9.6 years, with ischaemic (57.7%) or non-ischaemic (42.3%) HF completed 12 months of follow-up. Treatment with Algisyl was associated with improved peak VO2 at 12 months; treatment effect vs. control of +2.10 mL/kg/min (95% confidence interval 0.96-3.24, P < 0.001). Statistically significant improvements were observed for VO2 at anaerobic threshold, 6-min walk test distance, and NYHA functional class (all P < 0.001). Through 12 months of follow-up there were 4 (10.5%) deaths in the control group and 9 (22.5%) deaths in the Algisyl group. CONCLUSIONS: Algisyl in addition to SMT was more effective than SMT alone for providing sustained 1-year benefits in exercise capacity, symptoms, and clinical status for patients with advanced HF. These data support larger clinical evaluations of this novel therapy.

[ANMCO/ISS/AMD/ANCE/ARCA/FADOI/GICR-IACPR/SICI-GISE/SIBioC/SIC/SICOA/SID/SIF/SIMEU/SIMG/SIMI/SISA Consensus document. Hypercholesterolemia and cardiovascular risk: diagnostic and therapeutic pathways in Italy]. / Documento di consenso intersocietario ANMCO/ISS/AMD/ANCE/ARCA/FADOI/ GICR-IACPR/SICI-GISE/SIBioC/SIC/SICOA/ SID/SIF/SIMEU/SIMG/SIMI/SISA Colesterolo e rischio cardiovascolare: percorso diagnostico-terapeutico in Italia.

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.

Anticoagulation in "real world" patients with atrial fibrillation in Italy: results from the ISPAF (Indagine Sicoa Paziente Con Fibrillazione Atriale) survey study.

BACKGROUND: Atrial fibrillation (AF) is associated with a high risk of stroke and other thrombo-embolic events and their prevention relies on antithrombotic therapy, at present mainly with vitamin K antagonists (VKA). The aim of this study was to provide an overall picture on the extent to which current recommendations on oral anticoagulation (OAC) therapy with VKA in AF correspond to actually prescribed OAC in an unselected, real world, population of consecutive patients with AF in Italy. Secondary objective was to assess the rate of "optimal" anticoagulation. METHODS: Sixty-three cardiology units located in different geographic areas of Italy enrolled a total of 2046 outpatients with nonvalvular AF (54% males and 46% females, age 73.3±10.2 years). RESULTS: OAC with VKAs was prescribed in 1394 (68%) of patients and was progressively more frequent on going from paroxysmal (46%) to persistent (71%) and permanent AF (78%)(P<0.001). A high prescription rate (88%) occurred in patients with CHA2DS2-VASc >2. In patients with CHA2DS2-VASc=0 and HAS-BLED<3, still 59% were on OAC, whereas in 33% of patients with CHA2DS2-VASc ≥2 and HAS-BLED<3, OAC therapy was not prescribed. In patients with CHA2DS2-VASc ≥2 and HAS-BLED>3, the preference was towards OAC prescription. 66% of patients were at target for INR. CONCLUSIONS: The ISPAF study shows that in an Italian population of real world patients with AF adherence to current guidelines on OAC therapy based on stroke-risk scoring system is rather high, although rate of prescription should be increased. However, contrary to recommendations, in a high proportion of low-risk patients OAC therapy is still prescribed, and this might expose patients to unjustified risks.

Myocardial blood flow and infarct size after CD133+ cell injection in large myocardial infarction with good recanalization and poor reperfusion: results from a randomized controlled trial.

OBJECTIVE: Large acute ST-elevation myocardial infarction (STEMI) sometimes leaves extensive ischemic damage despite timely and successful primary angioplasty. This clinical picture of good recanalization with incomplete reperfusion represents a good model to assess the reparative potential of locally administered cell therapy. Thus, we conducted a randomized controlled trial aimed at evaluating the effect of intracoronary administration of CD133 stem cells on myocardial blood flow and function in this setting. METHODS: Fifteen patients with large anterior STEMI, myocardial blush grade 0-1 and more than 50% ST-elevation recovery after optimal coronary recanalization (TIMI 3 flow) with stenting were randomly assigned to receive CD133 cells from either bone marrow (group A) or peripheral blood (group B), or to stay on drug therapy alone (group C). The cells were intracoronary injected within 10-14 days of STEMI. Infarct-related myocardial blood flow (MBF) was evaluated by NH positron emission tomography 2-5 days before cell administration and after 1 year. RESULTS: MBF increased in the infarct area from 0.419 (0.390-0.623) to 0.544 (0.371-0.729) ml/min per g in group A, decreased from 0.547 (0.505-0.683) to 0.295 (0.237-0.472) ml/min per g in group B and only slightly changed from 0.554 (0.413-0.662) to 0.491 (0.453-0.717) ml/min per g in group C (A vs. C: P = 0.023; B vs. C: P = 0.066). Left ventricular volume tended to increase more in groups B and C than in group A, ejection fraction and wall motion score index remained stable in the three groups. CONCLUSION: These findings support the hypothesis that intracoronary administration of bone marrow-derived, but not peripheral blood-derived CD133 cells 10-14 days after STEMI may improve long-term perfusion.

The role of PET with 13N-ammonia and 18F-FDG in the assessment of myocardial perfusion and metabolism in patients with recent AMI and intracoronary stem cell injection.

UNLABELLED: Over the last decade, the effects of stem cell therapy on cardiac repair after acute myocardial infarction (AMI) have been investigated with different imaging techniques. We evaluated a new imaging approach using (13)N-ammonia and (18)F-FDG PET for a combined analysis of cardiac perfusion, metabolism, and function in patients treated with intracoronary injection of endothelial progenitors or with conventional therapy for AMI. METHODS: A total of 15 patients were randomly assigned to 3 groups based on different treatments (group A: bone marrow-derived stem cells; group B: peripheral blood-derived stem cells; group C: standard therapy alone). The number of scarred and viable segments, along with the infarct size and the extent of the viable area, were determined on a 9-segment (13)N-ammonia/(18)F-FDG PET polar map. Myocardial blood flow (MBF) was calculated for each segment on the ammonia polar map, whereas a global evaluation of left ventricular function was obtained by estimating left ventricular ejection fraction (LVEF) and end-diastolic volume, both derived from electrocardiography-gated (18)F-FDG images. Both intragroup and intergroup comparative analyses of the mean values of each parameter were performed at baseline and 3, 6, and 12 mo after AMI. During follow-up, major cardiac events were also registered. RESULTS: A significant decrease (P < 0.05) in the number of scarred segments and infarct size was observed in group A, along with an increase in MBF (P < 0.05) and a mild improvement in cardiac function. Lack of infarct size shrinkage in group B was associated with a marked impairment of MBF (P = 0.01) and cardiac dysfunction. Ambiguous changes in infarct size, MBF, and LVEF were found in group C. No differences in number of viable segments or in extent of viable area were found among the groups. At clinical follow-up, no major cardiac events occurred in group A patients, whereas 2 patients of group B experienced in-stent occlusion and one patient of group C received a transplant for heart failure. CONCLUSION: Our data suggest that a single nuclear imaging technique accurately analyzes changes in myocardial perfusion and metabolism occurring after stem cell transplantation.