The paradox of clopidogrel use in patients with acute coronary syndromes and diabetes: insight from the Diabetes and Acute Coronary Syndrome Registry.

BACKGROUND: Patients with diabetes mellitus (DM) and acute coronary syndromes have a greater level of platelet aggregation and a poor response to oral antiplatelet drugs. Clopidogrel is still widely used in clinical practice, despite the current evidence favoring ticagrelor and prasugrel. AIM: The aim of this study was to investigate the determinants of clopidogrel use in the population of the multicenter prospective 'Acute Coronary Syndrome and Diabetes Registry' carried out during a 9-week period between March and May 2015 at 29 Hospitals. PATIENTS AND METHODS: A total of 559 consecutive acute coronary syndrome patients [mean age: 68.7±11.3 years, 50% ST-elevation myocardial infarction (STEMI)], with 'known DM' (56%) or 'hyperglycemia' at admission, were included in the registry; 460 (85%) patients received a myocardial revascularization. RESULTS: At hospital discharge, dual antiplatelet therapy was prescribed to 88% of the patients (clopidogrel ticagrelor and prasugrel to 39, 38, and 23%, respectively). Differences in P2Y12 inhibitor administration were recorded on the basis of history of diabetes, age, and clinical presentation (unstable angina/non-STEMI vs. non-STEMI). On univariate analysis, age older than 75 years or more, known DM, peripheral artery disease, previous myocardial infarction, previous revascularization, complete revascularization, previous cerebrovascular event, creatinine clearance, unstable angina/non-STEMI at presentation, Global Registry of Acute Coronary Events Score, EuroSCORE, CRUSADE Bleeding Score, and oral anticoagulant therapy were significantly associated with clopidogrel choice at discharge. On multivariate analysis, only oral anticoagulant therapy and the CRUSADE Bleeding Score remained independent predictors of clopidogrel prescription. CONCLUSION: In the present registry of a high-risk population, clopidogrel was the most used P2Y12 inhibitor at hospital discharge, confirming the 'paradox' to treat sicker patients with the less effective drug. Diabetic status, a marker of higher thrombotic risk, did not influence this choice; however, bleeding risk was taken into account.

[Why NAO: Know How. Why and how to choose the new oral anticoagulant in cardiological clinical practice]. / Why NAO: Know How Perché e come scegliere i nuovi anticoagulanti orali nella pratica clinica cardiologica.

Although it is well recognized that warfarin dramatically reduces the risk for ischemic stroke, its use for stroke prevention in patients with atrial fibrillation is often inadequate. Even among patients with other known risk factors for stroke (e.g., high blood pressure) and no contraindications to warfarin, warfarin therapy is prescribed in less than 60% of cases. In addition, safety and efficacy of warfarin therapy depend on adequate anticoagulation effect, but time in therapeutic range is 63%. Notably, major bleeding and intracranial hemorrhage represent a feared, though infrequent, complication. Aspirin monotherapy for stroke prevention in patients with atrial fibrillation should be discouraged, as it does not provide adequate protection against stroke and is associated with a significant increase in bleeding complications. New oral anticoagulants have a favorable risk-benefit profile, resulting in significant reductions in stroke, intracranial hemorrhage and mortality, with similar rates of major bleeding compared to warfarin but increased risk for gastrointestinal bleeding. The present review describes the new oral anticoagulants dabigatran, rivaroxaban, apixaban and edoxaban with a focus on the results from major randomized clinical trials and meta-analyses. It also provides practical suggestions for their use in daily clinical practice, introducing a dedicated, novel application for smartphones and tablets.

Stroke prophylaxis in high-risk patients with atrial fibrillation: rhythm vs. rate control strategy.

PURPOSE: "Rhythm" and "Rate" control strategies require partially different organization, and a different involvement of Specialists and General Practitioners; we verified whether the strategy assignment modified the approach to stroke prophylaxis. METHODS: Survey in general practice: 233 GPs identified all patients with codified atrial fibrillation (AF) diagnosis, checked the diagnosis (ECG/hospital discharge document), and filled a structured questionnaire on stroke risk-factors, prophylactic therapy, and reasons for warfarin non prescription in CHADS ≥2 patients. Data were collected as an "aggregate." RESULTS: Population observed: 295,906 patients aged >14; 6,036 with confirmed AF; 5,888 with complete data about anti-thrombotic prophylaxis are analyzed here. In the "rhythm strategy" group 45.6% of the CHADS score ≥2 patients (594) were on warfarin, vs. 73.2% (1,741) in the "rate strategy" group (p<0.0001). Overall reasons for warfarin non-use were significantly different in the two groups: clinical contraindications (12.3% vs. 19.7%), side effects (5.5% vs. 8.5%), patients' refusal (12.2% vs. 15.2%), unreliable patient/care-giver (14.4% vs. 25.9%); reasons were unknown to the GP in 55.6% in rhythm control vs. 30.9% in rate control group. CONCLUSIONS: Anti-thrombotic prophylaxis in CHADS ≥2 patients is different in subjects assigned to the Rhythm vs. the Rate control strategy, as well as reported reasons for warfarin non use. GPs do not know why warfarin is not used in a large percentage of cases, mainly in the rhythm control strategy group. Improving efforts should probably be differently tailored for patients assigned to the "rhythm" or the "rate" control strategy.

Prevention of syncope through permanent cardiac pacing in patients with bifascicular block and syncope of unexplained origin: the PRESS study.

BACKGROUND: Syncope in patients with bifascicular block (BFB) is a common event whose causes might be difficult to assess. METHODS AND RESULTS: Prevention of syncope through permanent cardiac pacing in patients with bifascicular block (PRESS) is a multicenter, prospective, randomized, single-blinded study designed to demonstrate a reduction in symptomatic events in patients with bifascicular block and syncope of undetermined origin implanted with permanent pacemaker. Device programming mode (NASPE/BPEG code) at DDD with a lower rate of 60 ppm is compared with backup pacing at DDI with a lower rate of 30 ppm. The end point consisted of (1) syncope, (2) symptomatic presyncopal episodes associated with a device intervention (ventricular pacing), and (3) symptomatic episodes associated with intermittent or permanent atrioventricular block (any degree). One hundred one patients were enrolled and randomized. Primary end point events at 2 years were observed in 23 patients, with a significant lower incidence in the study group (hazard ratio, 0.32; 95% confidence interval [CI], 0.10-0.96; P=0.042). Reduction of any symptoms, associated or not with device intervention, was superior in DDD60 compared with DDI30 (hazard ratio, 0.4; 95% confidence interval, 0.25-0.78; P=0.0053). Fourteen patients developed other rhythm diseases and met class I indication for pacing. The annual incidence of rhythm disease development was 7.4%. CONCLUSIONS: In patients with bifascicular block and syncope of undetermined origin, the use of a dual chamber pacemaker programmed to DDD60 led to a significant reduction of syncope or symptomatic events associated with a cardioinhibitory origin, compared with DDI30 programming. Symptoms associated with a new onset of rhythm disease were found in 15% of the population at 2 years.

[Cryoablation: patient selection and current results]. / La crioablazione: selezione dei pazienti ed attuali risultati.

During the last years, cyoablation of atrial fibrillation has become a widely used method for pulmonary vein isolation. This evolution in the use of cryoenergy has been largely justified by the reduction in complications that occurs with radiofrequency energy (pulmonary vein stenosis and atrial-esophageal fistula), in the use of three-dimensional navigation technology, and hence procedural costs. The purpose of this paper is to evaluate the results of this new technology and its safety in terms of its risk-to-benefit profile.

[Provocative tests and electrophysiological study in athletes]. / Test provocativi e studio elettrofisiologico nello sportivo.

Provocative tests can be divided into three main categories: first-level or screening tests, consisting basically of step test, which all athletes undergo during pre-participation screening; second-level tests, which include exercise test (simple or cardiopulmonary), performed on the basis of specific clinical indications or for the assessment of functional capacity; and third-level tests, consisting of complex methods such as myocardial scintigraphy and stress echo (or exercise echo), which are performed in subjects adequately selected according to clinical characteristics or to the results of first- and second-level tests. The electrophysiological endocavitary study has specific indications in sustained or frequent ventricular arrhythmias, while it is not useful in diagnostic evaluation of athletes with supraventricular arrhythmias, where it has been replaced in most cases by transesophageal electrophysiological study.

[Competitive sports and leisure-time physical activity in patients with coronary heart disease]. / Il cardiopatico ischemico: approccio all'attività fisica e sportiva.

During recent years, the central role of exercise in the prevention of cardiovascular disease has gradually been demonstrated, and in 2003 the consensus document of the Council on Clinical Cardiology and Council on Nutrition, Physical Activity and Metabolism on the role of physical exercise in the prevention and treatment of coronary artery disease defined sedentary lifestyle as a modifiable independent cardiovascular risk factor, responsible for 12% of total mortality in the United States and for a 1.9-fold increase in the risk of ischemic heart disease. The reduction in cardiovascular mortality and cardiac ischemic events in subjects who perform regular physical activity is mainly due to the action that exercise plays on the control of cardiovascular risk factors. In particular, physical training has proved capable of improving lipid profile, reducing blood pressure and body weight, and improving glycemic control in diabetic subjects. In patients with coronary artery disease, combined exercise training, including both aerobic activities and strength training, is currently recommended. However, physical training in patients suffering from ischemic heart disease should be carefully prescribed, in order to maximize the positive effects and minimize the risks. It is also important that physical training programs are conducted in suitable facilities, with appropriately trained staff and with technical equipment suitable to deal with any emergency situations.

Use of implantable cardioverter defibrillator and cardiac resynchronization therapy: an Italian survey study on 220 cardiology departments.

OBJECTIVES: To evaluate the criteria for the use of implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy (CRT) and other strategies in order to reduce the incidence of sudden death among adults at high risk and to identify the major barriers for the implementation of quality of care involving Italian cardiology departments in the context of 'Progetto Aritmie Area Scompenso Cardiaco ANMCO'. An additional aim was to evaluate how European Guidelines are applied in 'real-life' scenarios. METHODS: The clinical survey involved 220 centres. An 11-item questionnaire with prespecified multiple choice answers was used. In the specific clinical section, three clinical scenarios were described: the first concerning a patient with non-ischaemic dilated cardiomyopathy and left ventricular ejection fraction (LVEF) 35%; the second, a patient with ischaemic dilated cardiomyopathy and LVEF 30%; and the third, a patient with ischaemic dilated cardiomyopathy and LVEF between 30 and 40%. For each clinical scenario, the centres were asked to indicate whether ICD implantation should be indicated and which diagnostic tests or clinical predictors should be used to stratify the risk. RESULTS: The mean number of procedures (ICD and CRT, ICD alone, CRT alone) performed in each centre was 59 per year with a total number of 11  229 procedures per year. ICD, alone or with CRT, was the most common procedure performed with a mean number of 52 implants per centre per year. Concomitant diseases represented the most frequent (>94% of the cases) contraindication. Arrhythmic risk stratification was tested in 76.4% of the centres. Most of the centres (76.4%) stated that they routinely performed adjunctive tests, in addition to LVEF, to identify individuals at higher risk prior to ICD implantation, whereas 23.6% reported that they did not perform any risk stratification. The tools most frequently used for risk stratification (alone or in combination) were as follows: QRS duration on 12-lead ECG (71% of centres), presence of non-sustained ventricular tachycardia on 24-h recording (90%) and programmed ventricular stimulation (65%). CONCLUSION: This survey reveals a fairly good correspondence between the therapeutic choices made by the Italian centres involved in the study and the recommendations set out in the guidelines of the Italian, European and American scientific societies.

Focus on renin-angiotensin system modulation and atrial fibrillation control after GISSI AF results.

Atrial fibrillation is the most frequently encountered arrhythmia in clinical practice. Given that atrial fibrillation is steadily increasing and that the medium to long-term efficacy of antiarrhythmic drugs has proved poor, it is essential to seek new therapies to prevent its onset and to effectively control recurrences. The study of nonantiarrhythmic drugs that act on the atrial remodeling that constitutes the substrate of the arrhythmia is a new and very interesting field of research. In this regard, several molecules that interact with the renin-angiotensin system at the level of the enzymatic or receptor cascade have been investigated in the past 10 years; some results have been very promising, whereas others have been extremely disappointing. In particular, the publication in 2008 of the results of GISSI AF, a rigorously designed Italian prospective study conducted on a large number of patients, revealed no statistically significant differences between the active drug and a placebo in preventing arrhythmia recurrences. In this study, we reassess the rationale behind the use of this class of drugs for 'antiarrhythmic' purposes, re-examine the most significant results reported in the clinical literature since 1999 and discuss the results of the GISSI AF study in this light.

[Epidemiology, classification and prognosis of palpitations]. / II cardiopalmo: epidemiologia, classificazione e prognosi.

Palpitations can be defined as an unpleasant feeling of heart beat, which is perceived as particularly fast, irregular or intense. This feeling is usually associated with perception of movements and hits in the chest. From the pathophysiological point of view, current knowledge of the neural pathways responsible for the perception of heart beat remains to be clearly elucidated. It has been hypothesized that these pathways include different structures located both at the intracardiac and extracardiac level. Palpitations are a widely diffused complaint in the general population, and particularly in subjects affected by structural heart disease. Clinical presentation makes it possible to divide palpitations into four groups: extrasystolic, tachycardic, anxiety-related, and intense. From the etiological point of view, palpitations may be divided into the following groups: palpitations caused by arrhythmias, by structural heart disease (non-arrhythmic), by psychiatric disease, by systemic noncardiac disease, and by drug or illicit substance assumption. The prompt detection of the causes of palpitations allows to identify clinical conditions potentially at high risk and to choose the most appropriate therapeutic approach.

[Idiopathic ventricular tachycardia: clinical characteristics and management]. / La tachicardia ventricolare idiopatica: significato clinico e terapia.

Outflow tract ventricular tachycardia (VT) is the most common form of idiopathic VT in clinical practice. The correct differential diagnosis with VTs caused by structural heart diseases (particularly arrhythmogenic right ventricular cardiomyopathy) is extremely challenging for the cardiologist. When correctly diagnosed, outflow tract VTs have a favorable prognosis in the majority of patients. At present, technical advancements and improved clinical experience in transcatheter ablation procedures may offer a definite therapy to an increasing number of patients with an acceptable complication rate.

[Atrial fibrillation and flutter in athletes]. / La fibrillazione e il flutter atriale nell'atleta.

Atrial fibrillation (AF) is one of the most frequent findings in the general population, with an incidence of about 0.1% per year and a mean prevalence of 0.95%. However, prevalence values are known to vary with age, being very low (0.1-0.2%) in subjects less than 55 years old, the age group comprising the greatest number of individuals who practice sport at various levels. Long-term, regular, intense physical training determines an increase in vagal tone, leading to bradycardia, and during physical activity, particularly competitive sport, a marked release of catecholamines occurs as a result of both the intense physical effort and the emotional stress involved in competition. Both these adaptive phenomena on the part of the autonomous nervous system may promote the development of AF. Heart diseases with a certain degree of severity are not generally compatible with sport, unless the activity undertaken involves a low expenditure of energy and is noncompetitive. In any case, in the presence of AF, the arrhythmia must be well controlled and well tolerated during performance of the activity.

'Orphan drugs' in cardiology: nadolol and quinidine.

The recent withdrawal from the market of nadolol (Corgard; Bristol-Myers Squibb, Sermoneta, Italy) and quinidine polygalacturonate (Ritmocor; Malesci, Bagno A Ripoli, Italy) has been causing clinical problems to many cardiologists and patients, frequently leading to discontinuance of an effective and well-tolerated pharmacological treatment. Nadolol is useful in the treatment of severe and refractory arrhythmias, particularly in some genetically determined ion-channel diseases, such as long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia.Quinidine is still used in refractory atrial fibrillation recurrences. Recent studies have demonstrated the clinical efficacy of quinidine in the treatment of rare genetically determined ion-channel diseases at high risk of sudden death, such as Brugada syndrome and short-QT syndrome.We hope that scientific societies can influence healthcare and pharmaceutical institutions, in order to restore the availability of two cardiovascular drugs that are extremely important in the care of arrhythmic patients.

Expressed emotion in wives of myocardial infarction patients: an exploratory feasibility study.

INTRODUCTION: We assessed the emotional components expressed by the spouses of patients at the first episode of acute myocardial infarction (AMI) and considered potential underlying links among these components and the course of the cardiac symptoms over time. This was an exploratory prospective cohort study. METHODS: A sample of 50 consecutive male inpatients with a diagnosis of AMI and their wives was studied. At baseline spouses were assessed with the Camberwell Family Interview and ratings of Expressed Emotion were made. Patients completed the State-Trait Anxiety Inventory (STAI XI-X2) and the Beck's Depression Inventory (BDI). After 12 months (T1), during appropriate treatment by a cardiologist blinded to the Expressed Emotion ratings, the existence or absence of serious adverse events (death or hospitalizations because of cardiac causes) were determined as an all-or-none phenomenon. Stepwise logistic regression analysis was performed to estimate associations among illness course and Expressed Emotion subscales, STAI X1-X2, BDI scores and clinical variables. RESULTS: High family Emotional Overinvolvement (EOI) scores were associated with higher study entry levels of depression (P = 0.003) among the patients and high Warmth was related to higher score on state anxiety scale (P = 0.000). Poor illness course at T1 was associated with high EOI [P = 0.005, exp(B) = 0.502, 95% confidence interval 0.308-0.818]. CONCLUSION: The association among wives' emotional profile, patients' psychological variables and illness course suggested the importance of a family assessment and of interventions directed towards changing emotional behaviours which could threaten the patient's psychological adjustment and the clinical course following a heart attack.

Five years of catheter ablation procedures in South-Western Europe: meta-analysis of National Registries.

BACKGROUND: Radiofrequency catheter ablation is a well-established approach to treating several types of cardiac arrhythmias. The aim of our study was to provide data on the diffusion of catheter ablation procedures in clinical practice through a meta-analysis of National Registries of electrophysiological procedures performed over a 5-year period, from 2000 to 2005. METHODS: We found only two national registries of catheter ablation procedures published in the journals indexed in PubMed: The Spanish Catheter Ablation Registry and the Portuguese National Registry on Cardiac Electrophysiology. In addition, we included in our analysis the data from the Italian Registry of Electrophysiological Procedures. RESULTS AND CONCLUSIONS: This meta-analysis revealed a steady increase in the total number of catheter ablation procedures, particularly for the ablation of atrial flutter, of tachycardia due to double nodal pathways, and of the left atrial substrate in atrial fibrillation. However, the progress of catheter ablation and the impetus for additional research and development of new approaches and technologic advances requires further data on clinical indications, methodologic approach, complications, and long-term success rate in the real world.

Right coronary artery aneurysm: percutaneous treatment with graft-coated stent during the acute phase of myocardial infarction.

We report a case of acute myocardial infarction due to acute thrombosis of the right coronary artery just before a large atherosclerotic aneurysm. The patient was treated with primary percutaneous coronary angioplasty (PCA) and deployment of graft-coated stent with optimal final result. Patients with atherosclerotic coronary aneurysms usually show the same cardiovascular risk factors and the same clinical presentation of patients with atherosclerotic obstructive coronary artery disease, but with an increased risk of endovascular thrombosis and consequently more frequent episodes of distal coronary embolism. Furthermore, they may develop other specific complications, such as rapid aneurysm enlargement and rupture leading to cardiac tamponade. In conclusion, our report shows that percutaneous approach to coronary aneurysms with exclusion of aneurismal lumen by placement of graft-coated stent is a feasible and safety procedure even during the acute phase of myocardial infarction, and it may probably reduce the risk of subsequent distal embolization, improving myocardial perfusion.