[New operative models for the management of anticoagulant prophylaxis]. / Nuovi modelli operativi per la gestione della profilassi anticoagulante.

Anticoagulant therapy has proven to be effective for patients at risk for thromboembolic disease. Nevertheless, in daily clinical practice the oral anticoagulant therapy (OAT) is underused because it is still considered dangerous and difficult to manage, particularly in patients with chronic non-rheumatic atrial fibrillation. In the most important published studies about this topic we found that only 7-55% of patients with atrial fibrillation were treated with antiplatelet drugs, while 9.9-48.4% took anticoagulant prophylaxis; so, despite a favourable temporal trend after large trials have shown a positive prophylactic effect with antithrombotic drugs, they are underused. It has been estimated that in our country 500,000-600.00 potential patients could have indication for this treatment. Nevertheless, the traditional management of oral anticoagulation is fraught with difficulties such as patients' compliance, reliability of laboratory, global management of the treatment. Undoubtedly, this prophylaxis is very heavy for the patient and the physician often don't like this treatment for its dangerous potential, frequent difficulties of the management, obstacles in the communication among laboratory, physician and patient. Other common problems usually are the distance from patient's home-laboratory, its working hours, means of transportation. It is important a suitable organization and a control of the factors contributing to obtain favourable results for assuring a good cost/benefit ratio of OAT. The relationship among patient-physician-laboratory play a fundamental role. Alternative models are therefore prospected: anticoagulation clinic, computerised decision support software or portable coagulometer. Actually available instruments give us immediately the patients' INR and represent a new option and a promising strategy to monitor these large cohort of patients. Thus the management of OAT can be done by family physicians or by anticoagulant clinic or by patients themselves, after a suitable training period permitting a partial or total self management. These new strategies have improved therapeutic control of oral anticoagulation and in addition to the health advantages both also have economic benefits.

[Barriers to cardiovascular prevention]. / Gli ostacoli alla prevenzione cardiovascolare.

Data from observational and clinical trials provide a solid basis for the formulation of recommendations for the prevention of coronary artery disease. Numerous obstacles to the implementation of risk reduction interventions have been identified. These include: the patients, physician and health care organization, financial and social barriers, current government social and health policies, and direct and indirect costs. The strategies to overcome these barriers include the development of predictable clinical guidelines for the management of risk factors, the requirement of expertise in risk factor management in training and certification, the implementation of model programs for risk factor management that have been shown to be effective including those utilizing non physician professionals, the inclusion of risk factor management as a key indicator of the level of care in quality assistance programs and the cost-effectiveness of preventive interventions, physician and nursing education programs, referral clinics with subspeciality services, quality programs and standards, legislation and regulation, implementation of patient compliance. In conclusion, the improvement of risk factor management will require an efficient health care system and a coordinated effort by primary care physicians, other professionals (such as cardiovascular physicians and specialized nurses) and government policy.

[Prognostic evaluation of silent ischemia during exercise in patient with recent infarction. Italian multicenter study. SMISS Group]. / Evaluation du pronostic de l'ischémie silencieuse à l'effort chez des patients avec infarctus récent. Etude italienne multicentrique. Groupe SMISS.

AIM: The aim of the Multicenter Silent Ischemia Study (SMISS), co-ordinated by the Italian Working Group on Cardiac Rehabilitation, was to evaluate prospectively, the prognostic significance of silent myocardial ischemia during exercise testing in patients with proven ischemic cardiac disease. METHODS: Over a period of six months 4389 consecutive patients performing a maximal symptom-limited exercise testing, after drug withdrawal, were enrolled in the 73 ergometric laboratories. All patients were followed up after 12 months, at which time electrocardiogram, examination and clinical history were reassessed. Here we report the results of 1111 patients group with the recent myocardial infarction (inferior 3 months). The follow-up was completed in 1031 (93%) patients. RESULTS: The results of exercise testing were normal in 666 (64.6%) patients; angina alone in 33 (3.2%) patients; silent ischemia in 234 (22.7%) patients; symptomatic ischemia in 98 (9.5%) patients. In 270 patients (26.1%) new events occurred: angina (19.7%); myocardial infarction (3.1%; PTCA (4%); CABG (6%); cardiac death (1.4%). The total events were more common in the patients with exercise induced angina (48.5%) and in those who had exercise induced-symptomatic ischemia (48%), in respect of patients with silent ischemia (29.5%) and of those who had normal testing (20.7%) (p = 0.0001). Myocardial infarction rate was higher in patients with symptomatic ischemia (7.1%) that for those of all other groups (silent ischemia: 1.3%, angina: 3%, normal 3.2%) (p = 0.05). Moreover, the patients with symptomatic ischemia had higher incidence of CABG (p = 0.0001). The mortality rate was low among all patients and did not show differences among the groups. Only among the 31 patients (3%) with blood pressure fall was mortality higher that in patients with a normal blood pressure increase. By multivariate logistic analysis the angina induced by exercise maintained its prognostic significance for all the events, but also other variables were significant: poor exercise tolerance and, between clinical variables angina before myocardial infarction. CONCLUSION: The results showed, in patients who underwent to exercise testing after drug withdrawal, a low incidence of cardiac death and of myocardial infarction on 12 month follow-up; the patients with induced-exercise symptomatic schema had a greater risk for all cardiac events, except for death.

Left atrial and appendage mechanical function after pharmacological or electrical cardioversion in patients with chronic atrial fibrillation: a multicenter, randomized study.

BACKGROUND: Transient atrial and appendage dysfunction occurs after cardioversion of atrial fibrillation. It has been suggested that one component of early dysfunction is related to the method of restoration of sinus rhythm and it is less severe in patients undergoing pharmacological than electrical cardioversion. The aim of this study was to compare left atrial chamber and left atrial appendage mechanical function before and after 48 hours from electrical or pharmacological cardioversion in patients with chronic atrial fibrillation. METHODS: We studied the effects of the mode of cardioversion on Doppler left atrial and appendage function in 19 patients with persistent atrial fibrillation (> or = 4 weeks), who were randomized to pharmacological (quinidine) or electrical cardioversion (protocol: 200, 300, 360 J) after pre-treatment with verapamil. Transthoracic and transesophageal echocardiography were performed before and 48 hours after the restoration of sinus rhythm. To determine left atrial and appendage mechanical dysfunction, the peak A wave velocities were obtained from transmitral flow velocity profiles recorded in the apical 4-chamber view, and peak emptying and filling appendage velocities were measured by the transesophageal approach with the sample volume placed at the orifice of the left atrial appendage. All the patients were pre-treated with verapamil before cardioversion in order to achieve a satisfactory control of heart rate. RESULTS: Mean peak A wave velocities were 0.52 +/- 0.12 m/s in the patients treated electrically and 0.54 +/- 0.08 m/s in those treated pharmacologically (p = NS). Before and after electrical cardioversion, the peak filling velocities of the left atrial appendage were 0.42 +/- 0.17 and 0.43 +/- 0.17 m/s respectively, and the peak emptying velocities 0.30 +/- 0.14 and 0.36 +/- 0.17 m/s respectively; before and after pharmacological treatment, the peak filling velocities were 0.38 +/- 0.1 and 0.43 +/- 0.1 m/s respectively, and the peak emptying velocities were 0.30 +/- 0.13 and 0.43 +/- 0.24 m/s respectively (p = 0.08). CONCLUSIONS: Even a long period of atrial fibrillation does not lead to a marked depression of global left atrial and left atrial appendage function 48 hours after the restoration of sinus rhythm by means of electrical or pharmacological cardioversion. There is no evidence that electrical cardioversion causes greater post-cardioversion atrial and/or appendage dysfunction than pharmacological treatment after 48 hours. Pre-treatment with verapamil may have reduced the dysfunction (probably because of a reduction in mechanical remodeling during atrial fibrillation).

[Congenital quadricuspid aortic valve]. / Valvola aortica quadricuspide congenita.

A case of a 17-year-old asymptomatic man is reported. The patient had no other cardiac congenital abnormalities. Transthoracic echocardiography revealed a rare quadricuspid aortic valve malformation without aortic regurgitation.

[Impact of chronic atrial fibrillation on cardiovacular mortality]. / Impatto della fibrillazione atriale cronica sulla mortalità cardiovascolare.

The largest cohort studies and a number of other epidemiological or clinical studies have found an increased risk of total, cardiovascular and stroke mortality in patients (both men and women of every age) with chronic non-rheumatic atrial fibrillation (AF) compared to heterogeneous individuals in normal sinus rhythm. These studies suggested that AF increases the probability of death without changing the mode of death. Many excess deaths due to non-rheumatic AF occur soon after the diagnosis of the arrhythmia. Non-rheumatic AF is complicated by the heterogeneity of the underlying heart disease and accompanying medications. Prognosis in non-rheumatic AF is dependent upon the age of the patients and the underlying cardiac conditions but non-rheumatic AF is a potent risk factor for stroke. Stroke in patients with non-rheumatic AF is generally more severe and induces higher mortality. A recent Framingham study has shown that an increased mortality rate persists when adjusted for age, hypertension, smoking, myocardial infarction, congestive heart failure, and stroke or transient ischemic attacks. These results demonstrate that non-rheumatic AF is independently associated with a 50 to 90% increase in the risk of death. Also the excess mortality observed in patients with chronic lone AF supports the independent role of the arrhythmia. The higher incidence of a chronic arrhythmia and the known complications of this condition pose serious problems for health care as our population ages. Passive acceptance of non-rheumatic AF is not correct. In all patients with non-rheumatic AF, restoring and maintaining sinus rhythm for as long as possible needs to be taken into serious consideration. New antiarrhythmic drugs and new strategies for the management of non-rheumatic AF are accumulating. When the arrhythmia is chronic, correct anticoagulant prophylaxis is a must, as several randomized trials have demonstrated a significant reduction in thromboembolic stroke incidence and related mortality with an acceptable hemorrhagic risk by using warfarin.

Mortality and cause of death in patients with chronic non-rheumatic atrial fibrillation after a two-year follow-up.

BACKGROUND: Non-rheumatic atrial fibrillation (NRAF) is a very common arrhythmia but its role in the prognosis and cardiovascular mortality is controversial. In particular, cause and predictors of death are not completely known. METHODS: We analyzed the cause of death and the possible predictors of cardiovascular mortality in 664 outpatients (mean age 72 +/- 9 years old) enrolled in the "Trieste Area Study on Non-Rheumatic Atrial Fibrillation" (TASAF), a prospective community study, after a follow-up of 27 +/- 9 months. The mean duration of the arrhythmia at enrollment was 59 months (range 1-360 months). Only 42 patients (6.3%) were on anticoagulants by general practitioners and 205 (30.8%) were on antiplatelet drugs. RESULTS: Of these patients, 110 (16.5%) died: 28 (25.5%) due to a cerebral or peripheral thromboembolism, 10 (8.2%) of sudden death, 46 (42.7%) of expected cardiac death and 25 (22.7%) of non-cardiac causes. In one patient, the cause of death was uncertain. Sixty-nine patients underwent postmortem examination. In univariate analysis, left ventricular dysfunction (p = 0.03) and an enlarged left atrium (p = 0.03) proved to be directly related to increased cardiovascular mortality. Both in univariate and Cox proportional hazards model analysis, aging (odds ratio 1.09, IC 95% 1.05-1.12, p = 0.00001), history of heart failure (odds ratio 1.27, IC 95% 1.01-1.60, p = 0.036), cardiomegaly (odds ratio 1.35, IC 95% 1.01-1.81, p = 0.040), diabetes mellitus (odds ratio 1.35, IC 95% 0.99-1.84, p = 0.058) and previous myocardial infarction (odds ratio 1.56, IC 95% 1.20-2.03, p = 0.0007) were all independent risk factors for cardiovascular mortality. A history of cerebral or systemic embolism (23 versus 12%, p = 0.09) and, above all, one or more recurrences before enrollment (11 versus 2.3%, p = 0.04), were associated with embolic mortality. CONCLUSIONS: Patients with NRAF have an increased risk of cardiovascular death. Aging, the presence of diabetes, cardiomegaly on chest x-ray, heart failure and a previous myocardial infarction were independent risk factors for cardiovascular mortality. A history of embolism at enrollment significantly conditioned the embolic mortality rate but above all, embolic events during follow-up determined a very high percentage of total deaths (25.5% of all causes). A proper anticoagulant therapy should strongly be advised to all patients with no contraindications.

Lone atrial fibrillation: prognostic differences between paroxysmal and chronic forms after 10 years of follow-up.

BACKGROUND: Lone atrial fibrillation (LAF) is defined by the presence of atrial fibrillation unassociated with other evidence of organic heart disease. There are conflicting data concerning the prognostic importance, rate of embolic complications, and survival in subjects affected by this arrhythmia. METHODS AND RESULTS: One hundred forty-five patients younger than 50 years at the time of the first diagnosis were identified; 96 had paroxysmal and 49 had chronic LAF. They were followed up with clinical and echocardiographic controls, and we recorded every thromboembolic complication and death. During the follow-up (10 +/- 8 years) among patients with paroxysmal LAF, 1 (1%) had an ischemic stroke, 2 a transient ischemic attack, and 1 a myocardial infarction. In the group with chronic LAF, 1 patient had moderate heart failure, 2 myocardial infarction, and 1 transient ischemic attack. In this group, 8 embolic complications in 7 (16.3%) patients were observed. One patient with intestinal embolism died during surgery; 2 (6.1%) patients died suddenly. CONCLUSIONS: The prognosis of young patients with paroxysmal LAF appears to be excellent, whereas patients with chronic LAF are at increased risk of embolic complications and higher mortality rates. Our results suggest that LAF is not always a benign disorder, as suggested by previous studies. Subgroups with substantially increased risk for thromboembolic events caused by LAF should be better identified.

[Anticoagulant prophylaxis: from clinical trials to clinical practice]. / La profilassi anticoagulante: dai grandi trial alla pratica clinica.

Anticoagulant therapy has recently undergone a surge in popularity with the confirmation of its importance in preventing cerebral thromboembolism from atrial fibrillation. Unfortunately oral anticoagulants have an extremely narrow therapeutic index and many physicians are reluctant to treat, particularly old patients, because of the fear of hemorrhagic complications and difficulty of management. The anticoagulant clinic, by improving therapeutic effectiveness and reducing complications, hospitalization and emergency room visits, appears to offer important qualitative and cost advantages over routine medical care. New strategies have been developed for managing care. One promising modality employs patients in their own care by performing their prothrombin time measurement by themselves at home. This model, similar to the way diabetics measure their own blood sugar, is possible as a result of a new class of point-of-care instrumentation for prothrombin testing. These portable monitors can measure a prothrombin time from a finger-stick sample of whole blood and provide a result within seconds. However rigorous studies are necessary to confirm the preliminary results of new management strategies to maximize the benefit-risk ratio of anticoagulant therapy.

[A longitudinal study on left atrial thrombosis in patients with non-rheumatic atrial fibrillation treated with anticoagulants]. / Studio osservazionale sulla trombosi atriale sinistra nei pazienti con fibrillazione atriale non reumatica trattati con anticoagulante.

BACKGROUND: Although atrial thrombosis is common in patients with non-rheumatic atrial fibrillation (NRAF) (6-27%), there are no studies about the effect that anticoagulant or antiplatelet drugs have on it. AIM OF THE STUDY: We have investigated the role of anticoagulant therapy, followed by family physicians, on left atrial thrombosis detected via transesophageal echocardiography (TEE) in patients with NRAF. METHODS: Sixty patients enrolled in the TASAF (Trieste Area Study on non-rheumatic Atrial Fibrillation) (60% males, mean age 72 +/- 7 years, 17% with lone atrial fibrillation, duration of arrhythmia 111 +/- 79 months), in whom we found a left atrial and/or left atrial appendage thrombus via TEE, were anticoagulated. The thrombus was in the left atrial appendage in 57 patients and in the left atrium in the others. In 28 of them it was mobile and in 50, the left atrial appendage flow was low or absent. Lastly, in 46 patients we found spontaneous echocontrast and a bilobate appendage was present in 8 of them. At follow-up, we repeated the TEE to evaluate the effect of the therapy on the atrial thrombosis. RESULTS: Only 53 patients received anticoagulant therapy (45 correctly), while 7 were treated with antiplatelet drugs by their family physicians. After a mean follow-up of 16 months, all patients underwent a repeat TEE and the thrombus was no longer evident in 35 cases (58%). The thrombosis disappeared in 26 (58%) of the 45 patients who correctly took anticoagulant therapy and in 5 of the 8 who were not adequately anticoagulated. Moreover, we didn't observe the thrombus in 4 of the 7 patients who were treated with antiplatelet drugs. There was no significant statistical difference between the benefits of anticoagulants and antiplatelet therapy in dissolving left atrial thrombosis. During follow-up, we recorded only one embolic event in the retina. None of the patients on antiplatelet drugs complained of any side effects, whereas in 5 of the 53 on anticoagulant therapy, we recorded one fatal intracranial hemorrhage, one gastric hemorrhage and three minor complications. CONCLUSIONS: Left atrial thrombosis in NRAF disappears in anticoagulated patients in an high percentage of cases (the therapy probably acts on more recent thrombi). Moreover, this therapy decreases the incidence of embolic events, although it increases the risk of hemorrages. Since the management of this preventive treatment in general medicine is very difficult, we hope that our health organization will establish Anticoagulation Clinics for the centralized management of this therapy.

D-dimer and anticoagulation in patients with mechanical prosthetic heart valves. A 2-year follow-up.

The best anticoagulation level in patients with mechanical heart valve prostheses is still being debated. D-dimer, which detects the presence of cross-linked fibrin degradation products, has been demonstrated to be a useful marker of coagulation activation. This study was designed to verify whether heart valve prostheses in anticoagulated patients are associated with abnormalities in D-dimer plasma levels, and if so, whether such levels are related to the anticoagulation level and/or whether they could be predictive of acute vascular or hemorrhagic events. In 132 patients with single and 10 with double mechanical valve replacement, international normalized ratio (INR) and D-dimer plasma levels were determined. The INR levels of the previous 8 months were reviewed to assess the time that each patient spent in the therapeutic range. The D-dimer plasma levels were compared with those obtained from 102 matched control subjects. The patients were then followed up for 2 years to record acute vascular and hemorrhagic events. For the entire group, D-dimer plasma levels in patients were the same as those in the control group. Patients with double valve replacement had higher D-dimer plasma levels than either monovalvular implant patients or control subjects. Patients who had spent < 75% of the time within the assigned anticoagulation range had higher values for D-dimer plasma levels (median, 270 vs 198 ng/mL, P = .02). The major determinants of D-dimer plasma levels were age (R2 = .07, P = .009) and the percentage of time spent below the predetermined INR level (R2 = .09, P = .001). During follow-up, 19 acute vascular and 16 hemorrhagic events occurred. High D-dimer tertile was the only parameter predicting the occurrence of thromboembolic events. In patients with mechanical heart valve prostheses, the D-dimer plasma level depended on the thoroughness of anticoagulation. Patients in the upper tertile of D-dimer values have an approximately 5-fold risk of vascular thromboembolic events. D-dimer determination can therefore be useful in detecting patients who are at a higher risk of severe vascular events.

[Lipid factors and evolution of the atherosclerotic plaque: review of recent trials]. / Fattori lipidici e progressione della placca aterosclerotica: revisione dei recenti trial.

A beneficial impact of lipid-lowering therapy on the incidence of coronary artery disease has been demonstrated in several clinical trials. It has been suggested that lipid lowering therapy not only slows the progression of atherosclerotic lesions, but also promotes its regression. Furthermore, reduced levels of circulating cholesterol (total cholesterol as well as LDL fraction) might decrease plaque volume and growth, restore endothelial function and thus reduce vasomotor tone. The obtained increased plaque stability reduces the risk of disruption and subsequent cardiovascular events. Ongoing ultrasonographic and angioscopic studies will provided further insights into the disease itself and its management.