Massimo Santini

Doppler myocardial imaging to evaluate the effectiveness of pacing sites in patients receiving biventricular pacing

OBJECTIVES The goal of this study was to compare the efficacy of biventricular pacing (BIV) at the most delayed wall of the left ventricle (LV) and at other LV walls. BACKGROUND Biventricular pacing could provide additional benefit when it is applied at the most delayed site. METHODS In 31 patients with advanced nonischemic heart failure, the activation delay was defined, in blind before BIV, by regional noninvasive Tissue Doppler Imaging as the time interval between the end of the A-wave (C point) and the beginning of the E-wave (O point) from the basal level of each wall. The left pacing site was considered concordant with the most delayed site when the lead was inserted at the wall with the greatest regional interval between C and O points (CO(R)). After BIV, patients were divided into group A (13/31) (i.e., paced at the most delayed site) and group B (18/31) (i.e., paced at any other site). RESULTS After BIV, in all patients LV end-diastolic (LVEDV) and end-systolic (LVESV) volumes decreased (p = 0.025 and 0.001), LV ejection fraction (LVEF) increased (p = 0.002), QRS narrowed (p = 0.000), New York Heart Association class decreased (p = 0.006), 6-min walked distance (WD) increased (p = 0.046), the interval between closure and opening of mitral valve (CO) and isovolumic contraction time (ICT) decreased (p = 0.001 and 0.000), diastolic time (EA) and Q-P(2) interval increased (p = 0.003 and 0.000), while Q-A(2) interval and mean performance index (MPI) did not change. Group A showed greater improvement over group B in LVESV (p = 0.04), LVEF (p = 0.04), bicycle stress testing work (p = 0.03) and time (p = 0.08) capacity, CO (p = 0.04) and ICT (p = 0.02). CONCLUSIONS After BIV, LV performance improved significantly in all patients; however, the greatest improvement was found in patients paced at the most delayed site.

A Short‐Term, Randomized, Double‐Blind, Parallel‐Group Study to Evaluate the Efficacy and Safety of Dronedarone versus Amiodarone in Patients with Persistent Atrial Fibrillation: The DIONYSOS Study

Dronedarone versus Amiodarone in Patients with AF.  Introduction: We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF).

Development and prospective validation of a risk stratification system for patients with syncope in the emergency department: the OESIL risk score

AIMS Aim of the present study was the development and the subsequent validation of a simple risk classification system for patients presenting with syncope to the emergency departments. METHODS AND RESULTS A group of 270 consecutive patients (145 females, mean age 59.5 years) presenting with syncope to the emergency departments of six community hospitals of the Lazio region of Italy was used as a derivation cohort for the development of the risk classification system. Data from the baseline clinical history, physical examination and electrocardiogram were used to identify independent predictors of total mortality within the first 12 months after the initial evaluation. Multivariate analysis allowed the recognition of the following predictors of mortality: (1) age >65 years; (2) cardiovascular disease in clinical history; (3) syncope without prodromes; and (4) abnormal electrocardiogram. The OESIL (Osservatorio Epidemiologico sulla Sincope nel Lazio) score was calculated by the simple arithmetic sum of the number of predictors present in every single patient. Mortality increased significantly as the score increased in the derivation cohort (0% for a score of 0, 0.8% for 1 point; 19.6% for 2 points; 34.7% for 3 points; 57.1% for 4 points; p<0,0001 for trend). A similar pattern of increasing mortality with increasing score was prospectively confirmed in a second validation cohort of 328 consecutive patients (178 females; mean age, 57.5 years). CONCLUSIONS Clinical and electrocardiographic data available at presentation to the emergency department can be used for the risk stratification of patients with syncope. The OESIL risk score may represent a simple prognostication tool that could be usefully employed for the triage and management of patients with syncope in emergency departments.

Presence and duration of atrial fibrillation detected by continuous monitoring: Crucial implications for the risk of thromboembolic events

AF and the Risk of Thromboembolic Events. Introduction: Asymptomatic atrial fibrillation (AF) can expose patients to the risk of stroke. The primary objective of this study was to assess the incidence of thromboembolic events in relationship with CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke, or transient ischemic attack) score and AF presence/duration. The secondary objective was to compare intermittent versus continuous monitoring strategies.

Permanent Cardiac Pacing Versus Medical Treatment for the Prevention of Recurrent Vasovagal Syncope A Multicenter, Randomized, Controlled Trial

Background—This clinical investigation was performed to compare the effects of permanent dual-chamber cardiac pacing with pharmacological therapy in patients with recurrent vasovagal syncope. Methods and Results—Patients from 14 centers were randomized to receive either a DDD pacemaker provided with rate-drop response function or the &bgr;-blocker atenolol at the dosage of 100 mg once a day. Inclusion criteria were age >35 years, ≥3 syncopal spells in the preceding 2 years, and positive response to tilt table testing with syncope occurring in association with relative bradycardia. The primary outcome was the first recurrence of syncope after randomization. Enrollment was started in December 1997, and the first formal interim analysis was performed on July 30, 2000. By that time, 93 patients (38 men and 55 women; mean age, 58.1±14.3 years) had been enrolled and randomized, although follow-up data were available for all patients (46 patients in the pacemaker arm, 47 patients in the pharmacological arm). The interim analysis showed a significant effect in favor of permanent cardiac pacing (recurrence of syncope in 2 patients [4.3%] after a median of 390 days) compared with medical treatment (recurrence of syncope in 12 patients [25.5%] after a median of 135 days; OR, 0.133; 95% CI, 0.028 to 0.632;P =0.004). Consequently, enrollment and follow-up were terminated. Conclusions—DDD pacing with rate-drop response function is more effective than &bgr;-blockade for the prevention of syncopal recurrences in highly symptomatic vasovagal fainters with relative bradycardia during tilt-induced syncope.

Identification of Myocardial and Vascular Precursor Cells in Human and Mouse Epicardium

During cardiac development, the epicardium is the source of multipotent mesenchymal cells, which give rise to endothelial and smooth muscle cells in coronary vessels and also, possibly, to cardiomyocytes. The aim of the present study was to determine whether stem cells are retained in the adult human and murine epicardium and to investigate the regenerative potential of these cells following acute myocardial infarction. We show that c-kit+ and CD34+ cells can indeed be detected in human fetal and adult epicardium and that they represent 2 distinct populations. Both subsets of cells were negative for CD45, a cell surface marker that identifies the hematopoietic cell lineage. Immunofluorescence revealed that freshly isolated c-kit+ and CD34+ cells expressed early and late cardiac transcription factors and could acquire an endothelial phenotype in vitro. In the murine model of myocardial infarction, there was an increase in the absolute number and proliferation of epicardial c-kit+ cells 3 days after coronary ligation; at this time point, epicardial c-kit+ cells were identified in the subepicardial space and expressed GATA4. Furthermore, 1 week after myocardial infarction, cells coexpressing c-kit+, together with endothelial or smooth muscle cell markers, were identified in the wall of subepicardial blood vessels. In summary, the postnatal epicardium contains a cell population with stem cell characteristics that retains the ability to give rise to myocardial precursors and vascular cells. These cells may play a role in the regenerative response to cardiac damage.

Prognosis, disease progression, and treatment of atrial fibrillation patients during 1 year: follow-up of the Euro Heart Survey on Atrial Fibrillation

AIMS To gain insight in the prognosis and treatment of atrial fibrillation (AF) patients during 1-year follow-up in the Euro Heart Survey (EHS) on AF. METHODS AND RESULTS The EHS enrolled 5333 AF patients in 2003--2004. One-year follow-up data were available for 80%. Of first detected AF patients, 46% did not have a recurrence during 1 year, paroxysmal AF largely remained paroxysmal AF (80%), and 30% of persistent AF progressed to permanent AF. Many treatment changes occurred since baseline. Oral anticoagulation was started in 19% and discontinued in 16% of all patients. Of patients initially on rhythm control 27% did not receive rhythm control during follow-up, whereas 15% of patients initially on rate control received rhythm control. Mortality was highest in permanent AF (8.2%), but also substantial in first detected AF (5.7%). In multivariable analysis, sinus rhythm at baseline was associated with lower mortality, but no significant effect was observed regarding the application of either rhythm or rate control. CONCLUSION The EHS on AF provides unique prospective observational data on AF progression, long-term treatment, prognosis, and determinants of adverse outcome of the total clinical spectrum of AF in a European cardiology-based patient cohort.

Prophylactic Implantable Defibrillator in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia and No Prior Ventricular Fibrillation or Sustained Ventricular Tachycardia

Background— The role of implantable cardioverter-defibrillator (ICD) in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation (VF) or sustained ventricular tachycardia is an unsolved issue. Methods and Results— We studied 106 consecutive patients (62 men and 44 women; age, 35.6±18 years) with arrhythmogenic right ventricular cardiomyopathy/dysplasia who received an ICD based on 1 or more arrhythmic risk factors such as syncope, nonsustained ventricular tachycardia, familial sudden death, and inducibility at programmed ventricular stimulation. During follow-up of 58±35 months, 25 patients (24%) had appropriate ICD interventions and 17 (16%) had shocks for life-threatening VF or ventricular flutter. At 48 months, the actual survival rate was 100% compared with the VF/ventricular flutter–free survival rate of 77% (log-rank P=0.01). Syncope significantly predicted any appropriate ICD interventions (hazard ratio, 2.94; 95% confidence interval, 1.83 to 4.67; P=0.013) and shocks for VF/ventricular flutter (hazard ratio, 3.16; 95% confidence interval, 1.39 to 5.63; P=0.005). The positive predictive value of programmed ventricular stimulation was 35% for any appropriate ICD intervention and 20% for shocks for VF/ventricular flutter, with a negative predictive value of 70% and 74%. None of the 27 asymptomatic patients with isolated familial sudden death had appropriate ICD therapy. Twenty patients (19%) had inappropriate ICD interventions, and 18 (17%) had device-related complications. Conclusions— One fourth of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior sustained ventricular tachycardia or VF had appropriate ICD interventions. Syncope was an important predictor of life-saving ICD intervention and is an indication for ICD. Prophylactic ICD may not be indicated in asymptomatic patients because of their low arrhythmic risk regardless of familial sudden death and programmed ventricular stimulation findings. Programmed ventricular stimulation had a low predictive accuracy for ICD therapy.

A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry

AIMS Given the advances in atrial fibrillation (AF) management and the availability of new European Society of Cardiology (ESC) guidelines, there is a need for the systematic collection of contemporary data regarding the management and treatment of AF in ESC member countries. METHODS AND RESULTS We conducted a registry of consecutive in- and outpatients with AF presenting to cardiologists in nine participating ESC countries. All patients with an ECG-documented diagnosis of AF confirmed in the year prior to enrolment were eligible. We enroled a total of 3119 patients from February 2012 to March 2013, with full data on clinical subtype available for 3049 patients (40.4% female; mean age 68.8 years). Common comorbidities were hypertension, coronary disease, and heart failure. Lone AF was present in only 3.9% (122 patients). Asymptomatic AF was common, particularly among those with permanent AF. Amiodarone was the most common antiarrhythmic agent used (∼20%), while beta-blockers and digoxin were the most used rate control drugs. Oral anticoagulants (OACs) were used in 80% overall, most often vitamin K antagonists (71.6%), with novel OACs being used in 8.4%. Other antithrombotics (mostly antiplatelet therapy, especially aspirin) were still used in one-third of the patients, and no antithrombotic treatment in only 4.8%. Oral anticoagulants were used in 56.4% of CHA2DS2-VASc = 0, with 26.3% having no antithrombotic therapy. A high HAS-BLED score was not used to exclude OAC use, but there was a trend towards more aspirin use in the presence of a high HAS-BLED score. CONCLUSION The EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of contemporary data regarding the management and treatment of AF by cardiologists in ESC member countries. Oral anticoagulant use has increased, but novel OAC use was still low. Compliance with the treatment guidelines for patients with the lowest and higher stroke risk scores remains suboptimal.

Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: a placebo-controlled study.

OBJECTIVES Our aim was to evaluate the benefits and risks of administering propafenone before electrical defibrillation for chronic atrial fibrillation. BACKGROUND In this context, an antiarrhythmic drug-although potentially useful in preventing early recurrence of arrhythmia-could adversely affect the defibrillation threshold and reduce the cardioversion success rate. METHODS We randomly assigned 100 patients with chronic atrial fibrillation to oral treatment with either placebo (51 patients) or 750 mg/day of propafenone (49 patients) for 48 h before administration of direct current shock. After successful cardioversion, all patients received propafenone therapy and were followed up for 48 h. RESULTS Before defibrillation, three patients in the propafenone group (6.1%) had reversion to sinus rhythm and one had sustained ventricular tachycardia. Shock efficacy (82.4% vs. 84.4%) and the cumulative effective energy (395 +/- 258 vs. 421 +/- 236 J) were not different between the placebo and propafenone groups. In the propafenone group, 11 patients had their arrhythmia transformed into atrial flutter and required a lower energy level for arrhythmia conversion than did the other patients with continued atrial fibrillation (245 +/- 197 vs. 493 +/- 215 J, p < 0.01); the latter patients showed a trend (p < 0.10) toward higher energy requirements than that of patients who received placebo. The incidence of asymptomatic bradyarrhythmias was higher in the propafenone group (28.9% vs. 7.1%, p < 0.02), but more patients who received placebo had early recurrence of atrial fibrillation (16.7% vs. 0%, p < 0.02). Two days after cardioversion, more patients given propafenone (73.5% vs. 52.9%, p < 0.05) were discharged from the hospital with sinus rhythm. During the in-hospital stay, propafenone was withdrawn from six patients (6.6%) because of side effects. CONCLUSIONS Propafenone, given before electrical cardioversion for chronic atrial fibrillation does not affect the mean defibrillation threshold or the rate of successful arrhythmia conversion. It decreases the recurrence of atrial fibrillation early after shock, thus allowing more patients to be discharged from the hospital with sinus rhythm.