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Introduction: The recently released classification has revised the nosology of tremor, defining essential tremor (ET) as a syndrome and fueling an enlightened debate about some newly conceptualized entities such as ET-plus. As a result, precise information of demographics, clinical features, and about the natural history of these conditions are lacking., Methods: The ITAlian tremor Network (TITAN) is a multicenter data collection platform, the aim of which is to prospectively assess, according to a standardized protocol, the phenomenology and natural history of tremor syndromes., Results: In the first year of activity, 679 patients have been recruited. The frequency of tremor syndromes varied from 32% of ET and 41% of ET-plus to less than 3% of rare forms, including focal tremors (2.30%), task-specific tremors (1.38%), isolated rest tremor (0.61%), and orthostatic tremor (0.61%). Patients with ET-plus were older and had a higher age at onset than ET, but a shorter disease duration, which might suggest that ET-plus is not a disease stage of ET. Familial aggregation of tremor and movement disorders was present in up to 60% of ET cases and in about 40% of patients with tremor combined with dystonia. The body site of tremor onset was different between tremor syndromes, with head tremor being most commonly, but not uniquely, associated with dystonia., Conclusions: The TITAN study is anticipated to provide clinically relevant prospective information about the clinical correlates of different tremor syndromes and their specific outcomes and might serve as a basis for future etiological, pathophysiological, and therapeutic research., (© 2022. The Author(s).)

Introduction: Previous cardiovascular disease (CVD) and myocardial involvement are common in coronavirus disease-19 (COVID-19). We investigated relationships between CVD, cardiac biomarkers and outcome in COVID-19., Methods: We analyzed n = 252 patients from a multicenter study and provided comparison according to the presence or absence of underlying CVD. Cardiac biomarkers high-sensitivity Troponin [upper reference of normality (URN) 35 pg/ml for Troponin I and 14 pg/ml for Troponin T] and natriuretic peptides (Nt-pro-B-type natriuretic peptide, URN 300 pg/ml and B-type natriuretic peptide, URN 100 pg/ml) were both available in n = 136., Results: Mean age was 69 ± 16 years (56% men, 31% with previous CVD). Raised hs-Troponin and natriuretic peptides were detected in 36 and 50% of the cases respectively. Age, chronic obstructive pulmonary disease, hemoglobin, hs-Troponin and natriuretic peptides were independently associated with underlying CVD (P < 0.05 for all). Compared with the normal biomarkers subgroups, patients with isolated hs-Troponin elevation had higher in-hospital mortality (31 vs. 4%, P < 0.05), similar CVD prevalence (15 vs. 11%) and trend towards higher D-dimer (930 vs. 397 ng/ml, P = 0.140). Patients with both biomarkers elevated had higher age, D-dimer, CVD and in-hospital mortality prevalence compared with other subgroups (all P < 0.05 for trend). Outcome analysis revealed previous CVD [model 1: OR 2.72 (95% CI 1.14-6.49), P = 0.024. model 2: OR 2.65 (95% CI 1.05-6.71), P = 0.039], hs-Troponin (log10) [OR 2.61 (95% CI 1.21-5.66), P = 0.015] and natriuretic peptides (log10) [OR 5.84 (95%CI 2.43-14), P < 0.001] to be independently associated with in-hospital mortality., Conclusion: In our population, previous CVD was part of a vulnerable phenotype including older age, comorbidities, increased cardiac biomarkers and worse prognosis. Patients with isolated increase in hs-Troponin suffered higher mortality rates despite low prevalence of CVD, possibly explained by higher COVID-19-related systemic involvement., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: Midwall fractional shortening (MWFS) is a measure of left ventricular (LV) systolic function that is more reliable in case of concentric LV geometry compared to LV ejection fraction (LVEF). We hypothesized that MWFS might predict heart failure (HF) and death in a high-risk asymptomatic population, beyond other echocardiographic parameters., Methods and Results: Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, electrocardiogram, N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiogram. Mean age of the population was 69 ± 7 years, 56% were men, 88% had hypertension, mean LVEF was 61 ± 9%, and mean MWFS 16.2 ± 3.3. During a median follow-up of 5.7 years, 95 subjects experienced HF/death events. At Cox analysis, lower MWFS was the only echocardiographic parameter, among structural/functional ones, associated with higher risk of HF/death [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.84-0.95, Padjusted < 0.001]. The risk of HF/death related to clinical data and NT-proBNP (baseline model) was reclassified by echocardiography only when MWFS was included into the model (baseline C-statistics 0.761; adding conventional structural/functional echocardiographic data 0.776, P = 0.09; adding MWFS 0.791, P = 0.007). Compared to subjects with normal LVEF and MWFS, only subjects with combined systolic dysfunction (11% of the population) were at higher risk (P = 0.001 for both abnormal; P > 0.24 for either LVEF or MWFS abnormal)., Conclusion: DAVID-Berg data suggest to include MWFS assessment in clinical practice, a simple and reliable echocardiographic parameter able to improve risk stratification in subjects at high risk for HF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: This study examined incidence of AF following cavotricuspid isthmus (CTI) ablation alone or CTI plus prophylactic pulmonary vein isolation (PVI) in patients presenting with isolated atrial flutter (AFL) with no history of AF., Methods and Results: We enrolled 216 patients with isolated typical atrial flutter and randomized them to CTI alone (group 1, n = 108, 61.2 ± 9.7 year, 75% male) or CTI+PVI ablation (group 2, n = 108, 62.4 ± 9.3 year, 73% male). Insertible loop recorder (ILR) was implanted in 21 and 19 patients from groups 1 and 2, respectively. Remaining patients were monitored with event recorders, ECG, 7-day Holter. Follow-up period was for 18 ± 6 months. Compared to group 1, group 2 had significantly longer procedural duration (75.9 ± 33 min vs. 161 ± 48 min [P < 0.001]) and fluoroscopy time (15.9 ± 12.3 min vs. 56.4+21 min [P < 0.001]). At the end of follow-up, 65 (60.2%) in group 1 and 77 (71.3%) in group 2 were arrhythmia free off-AAD (log-rank P = 0.044). A subgroup analysis was performed with 55 year age cut-off. In the <55 age group the CTI only population had similar success as in CTI+PVI, (21 of 24 [83.3%] vs. 19 of 22 [86.4%], respectively, log-rank P = 0.74). In the ≥55 group, having CTI+PVI showed significantly higher success compared to CTI only; 45 of 84 (53.6%) were AF/AT free in CTI only group versus 58 of 86 (67.4%) with CTI+PVI (log-rank P = 0.029)., Conclusion: Prophylactic PVI reduced new-onset AF in patients with lone atrial flutter., (© 2015 Wiley Periodicals, Inc.)

Purpose: Small single-center comparative studies suggest improved outcomes in cardiac resynchronization therapy (CRT) patients implanted with a quadripolar left ventricular (LV) lead in comparison with non-quadripolar (bipolar) leads. This study represents the first large multicenter prospective registry comparing implant and 6-month postoperative lead performance following CRT-defibrillator (CRT-D) implantation with quadripolar vs. bipolar leads., Methods: During a 39-month period, 418 consecutive patients having CRT-D implantation attempts with either a quadripolar (n = 230) or bipolar LV lead (n = 188) were enrolled in the registry. The primary outcome of the study was LV lead failure defined as any abnormality, excluding infection, resulting in surgical lead revision or CRT termination. Additionally, operative and follow-up data were analyzed for significant difference between groups., Results: Baseline characteristics of both groups were similar. In 72.9 % of quadripolar leads versus 65.0 % of bipolar leads, the LV lead successfully engaged the predefined ideal target side branch (p = 0.47). Implant duration and fluoroscopy times were significantly shorter when a quadripolar lead was used (p = 0.007 and p = 0.001, respectively). The primary end point occurred in six patients (2.7 %) in the quadripolar group and in 14 patients (8.0 %) in the bipolar group (p = 0.02). Clinically significant phrenic nerve stimulation (PNS) occurred in 4.6 vs. 14.2 % of quadripolar vs. bipolar patients, respectively (p = 0.002); all PNS were resolved noninvasively through programming in the quadripolar group vs. 84 % in bipolar group (p = 0.75). The use of a bipolar lead was associated with a higher risk of surgical LV lead revision (6.3 vs. 2.3 %; p = 0.057) and a higher incidence of dislodgment (5.7 vs. 2.7 %; p = 0.16)., Conclusions: This multicenter study demonstrates that the use of a quadripolar LV lead results in significantly lower rates of lead-related problems and reduced procedural and fluoroscopic times for biventricular system implantation. This has important implications for LV pacing lead choice.

Aims: This study compares, from a prospective, observational, non-randomized registry, the post-implant hospitalization rates and associated healthcare resource utilization of cardiac resynchronization therapy-defibrillator (CRT-D) patients with quadripolar (QUAD) vs. bipolar (BIP) left ventricular (LV) leads., Methods and Results: Between January 2009 and December 2012, 193 consecutive patients receiving de novo CRT-D implants with either a QUAD (n = 116) or a BIP (n = 77) LV lead were enrolled at implant and followed until July 2013 at a single-centre, university hospital. Post-implant hospitalizations related to heart failure (HF) or LV lead surgical revision and associated payer costs were identified using ICD-9-CM diagnosis and procedure codes. Italian national reimbursement rates were determined. Propensity scores were estimated using a logistic regression model based upon 11 pre-implant baseline characteristics and were used to derive a 1 : 1 matched cohort of QUAD (n = 77) and BIP (n = 77) patients. Hospitalization rates for the two groups were compared using negative binomial regression and associated payer costs were compared using non-parametric bootstrapping (×10 000) and one-sided hypothesis test. Hospitalization rates of the QUAD group [0.15/ patient (pt)-year] were lower than those of the BIP group (0.32/ pt-year); the incidence rate ratio was 0.46, P = 0.04. The hospitalization costs for the QUAD group (434 ± 128 €/pt-year) were lower than those for the BIP group (1136 ± 362 €/pt-year). The average difference was 718 €/pt-year, P = 0.016., Conclusions: In this comparative effectiveness assessment of well-matched groups of CRT-D patients with quadripolar and bipolar LV leads, QUAD patients experienced a lower rate of hospitalizations for HF and LV lead surgical revision, and a lower cost burden. This has important implications for LV pacing lead choice., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Serious concerns have been recently raised about the reliability of the silicone-polyurethane copolymer (Optim™) lead insulation system. We sought to identify insulation defects and Optim-lead failures by systematic fluoroscopic and electrical assessment in a prospectively defined cohort of implantable cardioverter-defibrillator (ICD) patients., Methods and Results: Between July 2007 and December 2011, 234 patients were implanted with 413 optim-coated leads as part of an ICD system at a single centre. Fluoroscopic screening with high-resolution cine-fluoroscopy at 30 frames per second was offered to all patients. In addition, the electrical integrity of all implanted leads was assessed. Durata, Riata ST Optim, and low-voltage Optim leads were implanted in 199, 26, and 188 cases, respectively. During a total follow-up of 10 036 lead-months, there were 7 Optim-lead failures (defined as electrical malfunction resulting in lead replacement) and 31 deaths; no cases of electrical noises were encountered. The overall incidence of lead failure was 1.2 vs. 0.3 per 100 lead-years, for high- and low-voltage leads, respectively (P = 0.1). One hundred fifty-one patients agreed to undergo fluoroscopy screening; none of the 264 analysed Optim leads were found to have any fluoroscopically visible structural defects after an average of 31 months post-implant., Conclusion: This study represents the first systematic screening of Optim-coated leads in a large unselected cohort of ICD patients. Over a 5-year period few lead failures were observed and normal fluoroscopic appearance was present in all patients.

Whether and to what extent patients with asymptomatic atrial fibrillation (AF) would benefit from catheter ablation has not been investigated. This is the first multicenter prospective study reporting on the outcome of catheter ablation in patients with asymptomatic AF. Consecutive patients (n = 545) referred for AF ablation were prospectively enrolled in a multicenter Italian registry. Of these patients, 54 have asymptomatic AF and composed our patient population. At 24 month follow-up, catheter ablation in asymptomatic AF patients resulted to be as safe and effective as in patients with drug refractory symptomatic AF. Our study provides significant insights on the role of AF ablation in asymptomatic patients. Further studies in much larger cohorts are needed to validate our conclusions., (© 2013.)

Objectives: We investigated whether the reverse remodeling after cardiac resynchronization therapy (CRT) might reduce the occurrence of ventricular arrhythmias (VAs)., Background: It is currently debated whether CRT has an effect on the burden of VAs., Methods: The study included 398 patients treated with a CRT defibrillator and with a follow-up of at least 12 months. Spontaneous VAs detected by the device were reviewed and validated., Results: A significant reduction in VA episodes and shock therapies was evident during the follow-up with greater decrease after 1 month. After 6 months of CRT, 227 patients (57%) showed a reduction in end-systolic volume of >or=10% and were defined as "responders." The baseline characteristics were similar between the responders and the nonresponders. Nonetheless, the proportion of patients with recurrence of VA after 1 month of CRT was significantly lower in responders (32% vs. 43%, p = 0.024). Among baseline variables no parameters emerged as predictors of tachyarrhythmia recurrence. However, receiver-operating curve analysis recognized a reduction of left ventricular end-systolic volume at 6 months of 13% as the best cutoff to identify the reduction of VAs (with a sensitivity of 58% and a specificity of 54%)., Conclusions: In patients treated with CRT defibrillators, a reduction in ventricular arrhythmic events occurs during the initial 12 months after implant and is correlated with the degree of ventricular remodeling induced by the therapy. Patients demonstrating reverse remodeling at midterm follow-up show a reduction in arrhythmias soon after the implant, pronounced improvements at long-term, and a better survival.

Background: Rate-responsive pacemakers (PMs) are often supplied with accelerometer (XL) and minute ventilation (MV) sensors to provide a physiologic rate response according to patient needs. No information is available about the real benefit of dual-sensor rate-responsive pacing on the daily life of patients., Methods: DUSISLOG (Dual Sensor vs Single Sensor comparison using patient activity LOGbook) is a two-arm prospective, randomized, multicenter study that enrolled 105 patients who received a rate-responsive PM (Insignia), Guidant Corp.). After 1 month of DDD pacing at 60 ppm lower rate, a single sensor (XL or MV, randomized) was activated for 3 months at the manufacturer's suggested nominal settings, followed by a 3-month period with dual sensors optimized with automatic response. During the last month of each period, the following data concerning patient physical activity were retrieved from PM diagnostics (Activity Log): mean percentage of physical activity, mean intensity of activity. Quality of life (QoL) scores and 6-minute walk test (WT) were also recorded., Results: Single-sensor rate-responsive pacing resulted in symptomatic benefit equally with XL and MV sensors while no additional benefit was found using dual sensor. In a subgroup analysis, patients (17%) with marked chronotropic incompetence and with 0% atrial sensing received benefits from single sensor with an additional advantage from sensor (QoL: +21 +/- 14% P < 0.05; WT: +17 +/- 7% P < 0.02)., Conclusion: In most patients with rate-responsive devices, a single sensor is sufficient to achieve a satisfactory rate response. A dual sensor combination and optimization provides an additional benefit only in a selected population with an advanced atrial chronotropic disease.

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)