Two years' effect of dimethyl fumarate on focal and diffuse gray matter pathology in multiple sclerosis.

BACKGROUND: Data on the effect of dimethyl fumarate (DMF) on focal and diffuse gray matter (GM) damage, a relevant pathological substrate of multiple sclerosis (MS)-related disability are lacking. OBJECTIVE: To evaluate the DMF effect on cortical lesions (CLs) accumulation and global and regional GM atrophy in subjects with relapsing-remitting MS. METHODS: A total of 148 patients (mean age 38.1 ± 9.7 years) treated with DMF ended a 2-year longitudinal study. All underwent regular Expanded Disability Status Scale (EDSS assessment), and at least two 3T-magnetic resonance imaging (MRI) at 3 and 24 months after DMF initiation. CLs and changes in global and regional atrophy of several brain regions were compared with 47 untreated age and sex-matched patients. RESULTS: DMF-treated patients showed lower CLs accumulation (median 0[0-3] vs 2[0-7], p < 0.001) with respect to controls. Global cortical thickness (p < 0.001) and regional thickness and volume were lower in treated group (cerebellum, hippocampus, caudate, and putamen: p < 0.001; thalamus p = 0.03). Lower relapse rate (14% vs 40%, p < 0.001), EDSS change (0.2 ± 0.4 vs 0.4 ± 0.9, p < 0.001), and new WM lesions (median 0[0-5] vs 2[0-6], p < 0.001) were reported. No severe adverse drug reactions occurred. CONCLUSIONS: Beyond the well-known effect on disease activity, these results provide evidence of the effect of DMF through reduced progression of focal and diffuse GM damage.

Experimental Characterization of the FRCM-Concrete Interface Bond Behavior Assisted by Digital Image Correlation.

Digital Image Correlation (DIC) provides measurements without disturbing the specimen, which is a major advantage over contact methods. Additionally, DIC techniques provide full-field maps of response quantities like strains and displacements, unlike traditional methods that are limited to a local investigation. In this work, an experimental application of DIC is presented to investigate a problem of relevant interest in the civil engineering field, namely the interface behavior between externally bonded fabric reinforced cementitious mortar (FRCM) sheets and concrete substrate. This represents a widespread strengthening technique of existing reinforced concrete structures, but its effectiveness is strongly related to the bond behavior between composite fabric and underlying concrete. To investigate this phenomenon, a set of notched concrete beams are realized, reinforced with FRCM sheets on the bottom face, subsequently cured in different environmental conditions (humidity and temperature) and finally tested up to failure under three-point bending. Mechanical tests are carried out vis-à-vis DIC measurements using two distinct cameras simultaneously, one focused on the concrete front face and another focused on the FRCM-concrete interface. This experimental setup makes it possible to interpret the mechanical behavior and failure mode of the specimens not only from a traditional macroscopic viewpoint but also under a local perspective concerning the evolution of the strain distribution at the FRCM-concrete interface obtained by DIC in the pre- and postcracking phase.

Diffuse gliomas in patients aged 55 years or over: A suggestion for IDH mutation testing.

Diffuse gliomas are defined on the isocitrate dehydrogenase (IDH) gene (IDH) mutational mutational status. The most frequent IDH mutation is IDH1 R132H, which is detectable by immunohistochemistry; other IDH mutations are rare (10%). IDH mutant gliomas have better prognosis. Further, IDH wild-type low-grade (II/III) gliomas have clinical behaviors similar to those of glioblastoma (GBM) and it was suggested that they are submitted to similar post-surgical treatment. The incidence of IDH mutant gliomas (2%) and that of GBMs with non-canonical IDH mutations (< 1%) are very low in patients ≥ 55 years. For this reason, it was suggested that immunohistochemistry against IDH1 R132H is sufficient to classify GBM as IDH wild-type in this age group. However, no indication was provided for IDH mutational testing in low-grade diffuse gliomas. To address this issue, 273 diffuse gliomas were tested for IDH1 R132H immunohistochemistry. 2/4 diffuse astrocytomas (DAs), 4/9 anaplastic astrocytomas (AAs), 2/256 GBMs, and 4/4 oligodendrogliomas had positive staining. No other IDH mutations were found in immuno-negative low-grade cases by DNA sequencing. To validate our findings, we considered 311 diffuse gliomas in patients ≥ 55 years in The Cancer Genome Atlas database. Fifty-five out of 311 gliomas had IDH R132H mutations (9/16 DAs; 8/48 AAs; 3/211 GBMs; 35/36 oligodendrogliomas), one DA, and one oligodendroglioma had other IDH mutations. IDH mutant gliomas had significantly higher frequency of O-6-methylguanine-DNA methyltransferase promoter methylation (P = 0.0008) and longer overall survival (P < 0.0001). In conclusion, low-grade gliomas are a minor part of gliomas (117/584) in patients ≥ 55 years, albeit they represent most IDH mutant gliomas in this age group (64/69 cases). IDH non-canonical mutations can be found in immunonegative low-grade gliomas (2/54). In view of its significance for prognosis and therapeutic management, our results suggest that IDH mutational status is assessed in all diffuse gliomas in patients ≥ 55 years by immunohistochemistry, followed by IDH sequencing in low-grade immunonegative cases.

Effect of PR interval and pacing mode on persistent atrial fibrillation incidence in dual chamber pacemaker patients: a sub-study of the international randomized MINERVA trial.

AIMS: Per standard of care, dual-chamber pacemakers are programmed in DDDR mode with fixed atrioventricular (AV) delay or with long AV delay to minimize ventricular pacing. We aimed to evaluate whether the PR interval may be a specific criterion of choice between standard DDDR, to preserve AV synchrony in long PR patients, and managed ventricular pacing (MVP), to avoid ventricular desynchronization imposed by right ventricle apical pacing, in short PR patients. METHODS AND RESULTS: In the MINERVA trial, 1166 patients were randomized to Control DDDR, MVP, or atrial anti-tachycardia pacing plus MVP (DDDRP + MVP). We evaluated the interaction of PR interval with pacing mode by comparing the risk of atrial fibrillation (AF) longer than 7 consecutive days as a function of PR interval. Out of 906 patients with available data, the median PR interval was 180 ms. The PR interval was found to significantly (P = 0.012) interact with pacing mode for AF incidence: the risk of AF > 7 days was lower [hazard ratio (HR) 0.58, 95% confidence interval (95% CI) 0.34-0.99; P = 0.047] in patients with short PR (shorter than median PR) if programmed in MVP mode compared with DDDR mode and it was lower (HR 0.65, 95% CI 0.43-0.99; P = 0.049) in patients with long PR (equal to or longer than median PR) if programmed in DDDR mode compared with MVP. CONCLUSION: Our data show that PR interval may be used as a selection criterion to identify the optimal physiological pacing mode. Persistent AF incidence was lower in short PR patients treated by right ventricular pacing minimization and in long PR patients treated by standard dual-chamber pacing.

The influence of age on the psychological profile of patients with cardiac implantable electronic devices: results from the Italian population in a multicenter study conducted by the European Heart Rhythm Association.

BACKGROUND: Cardiac implantable electronic devices (CIEDs) are widely used to treat bradyarrhythmias or improve the prognosis of patients with heart failure (HF). AIMS: To evaluate age-related (≤ 75 vs. > 75 years) attitudes, worries, psychological effects and needs in an Italian CIEDs population. METHODS: Patients attending their periodical ambulatory evaluation received a questionnaire conceived by the European Heart Rhythm Association Scientific Initiatives Committee as part of a multicenter, multinational snapshot survey. Seven countries participated in the study, and 1646 replies were collected. Of these, 437 (27%) were from Italy. Present results refer to the Italian population only. CIEDs were stratified into devices to treat bradycardia or HF. RESULTS: The use of CIEDs was more common in advanced age. Older patients needed less information about CIEDs than younger ones (p = 0.044), who would prefer to be better informed about CIEDs-related consequences on psychologic profile (p = 0.045), physical (p < 0.001) and sexual (p < 0.001) activities, and driving limitations (p = 0.003). When compared to older subjects, younger individuals experienced more difficulties (p = 0.035), especially in their professional (p < 0.001) and private life (p = 0.033), feeling their existence was limited by the device (p < 0.001). Conversely, quality of life (HRQL) more often improved in the elderly (p = 0.001). Information about what to do with CIEDs at the end of life is scant independently of age. CONCLUSIONS: HRQL after CIEDs implantation improves more frequently in older patients, while the psychological burden of CIEDs is usually higher in younger patients. End of life issues are seldom discussed.

A microRNA signature from serum exosomes of patients with glioma as complementary diagnostic biomarker.

Malignant gliomas, the most frequent primary brain tumors, are characterized by a dismal prognosis. Reliable biomarkers complementary to neuroradiology in the differential diagnosis of gliomas and monitoring for post-surgical progression are unmet needs. Altered expression of several microRNAs in tumour tissues from patients with gliomas compared to normal brain tissue have been described, thus supporting the rationale of using microRNA-based biomarkers. Although different circulating microRNAs were proposed in association with gliomas, they have not been introduced into clinical practice so far. Blood samples were collected from patients with high and low grade gliomas, both before and after surgical resection, and the expression of miR-21, miR-222 and miR-124-3p was measured in exosomes isolated from serum. The expression levels of miR-21, miR-222 and miR-124-3p in serum exosomes of patients with high grade gliomas were significantly higher than those of low grade gliomas and healthy controls and were sharply decreased in samples obtained after surgery. The analysis of miR-21, miR-222 and miR-124-3p in serum exosomes of patients affected by gliomas can provide a minimally invasive and innovative tool to help the differential diagnosis of gliomas at their onset in the brain and predict glioma grading and non glial metastases before surgery.

Primary versus secondary mechanical thrombectomy for anterior circulation stroke in children: An update.

This review of the literature on the use of mechanical thrombectomy (MT) in children with acute ischemic stroke from occlusion of the internal carotid artery and the proximal middle cerebral artery (MCA) compares the efficacy and safety of primary and secondary MT. We analyzed the data reported for 24 case reports from 20 relevant articles published up to 31 December 2016 and the data of a patient treated at our institution. Eighteen cases received primary MT and 7 received secondary MT. The proportions of complete MCA recanalization, small infarcts, and asymptomatic intracranial hemorrhage were similar in both MT groups (73% [11/15] vs. 67% [4/6], 58% [7/12] vs. 60% [3/5], and 15% [2/13] vs. 17% [1/6], respectively). The proportion of favorable neurological outcomes was higher for the primary MT group (69% [11/16] vs. 43% [3/7]). We found no substantial differences in efficacy and safety between primary and secondary MT for anterior circulation stroke in children.

Recurrences in the Blanking Period and 12-Month Success Rate by Continuous Cardiac Monitoring After Cryoablation of Paroxysmal and Non-Paroxysmal Atrial Fibrillation.

INTRODUCTION: Recurrences within the blanking period (early recurrences) are common after atrial fibrillation (AF) ablation by pulmonary vein isolation (PVI), but their clinical significance is still controversial. We aimed at evaluating the significance of within-blanking recurrences at 12-month follow-up after cryoballoon (CB) PVI, and to assess the real procedural success rate by continuous monitoring of cardiac rhythm. METHODS AND RESULTS: Sixty consecutive AF patients (34 paroxysmal, 56.7%) underwent their first CB-PVI at one Italian center (May 2013 to April 2015), and subsequent implantation of an implantable loop recorder (ILR). Overall, 12-month success rate after the blanking period was 55%. The shortest detected event was 7 minutes long. Late recurrences were more frequent in non-paroxysmal (19/26, 73.1%) than in paroxysmal AF (8/34, 23.5%; P <0.001). Early recurrences occurred in 17 (28.3%) patients, with 14 also having late recurrences (82.3%), while only 13 out of 43 (30.2%) without within-blanking recurrences experienced post-blanking events (P <0.001). Overall, early recurrences showed 51.8% sensitivity (95% CI 31.9-71.3%) and 90.9% specificity (95% CI 75.7-98.1%) for later recurrences, with 82.3% (95% CI 56.6-96.2%) positive and 69.8% (95% CI 53.9-82.8%) negative predictive value. The positive likelihood ratio was 5.7 (95% CI 1.8-17.8). At multivariable analysis, non-paroxysmal AF (HR: 3.113; 95% CI 1.309-7.403; P = 0.010) and within-blanking recurrences (HR: 3.453; 95% CI 1.544-7.722; P = 0.003) were independent predictors of post-blanking AT/AF. CONCLUSION: CB-PVI for paroxysmal AF shows a 12-month success rate of 76.5% after one single procedure, as assessed by continuous cardiac rhythm monitoring. Within-blanking recurrences predict the ablation failure in more than 80% of patients.

Impact of haemodynamic SonR sensor on monitoring of left ventricular function in patients undergoing cardiac resynchronization therapy.

AIMS: The haemodynamic SonR sensor is able to measure myocardial contractility. The isometric effort is useful in quantifying left ventricular (LV) performance. We investigated the amplitude changes in SonR signal over time and during static exercise according to the recovery of the left ventricle. METHODS AND RESULTS: Twenty five patients [18 male, 70 ± 8 years, LV ejection fraction (LVEF) 29 ± 5%, in sinus rhythm] underwent biventricular SonR implantable cardioverter defibrillator implant. After procedure and at 6 months, each patient underwent detection of SonR signal and continuous measurement of blood pressure, at rest and during isometric effort. During evaluation at baseline device was programmed in VVI at 40 bpm while in DDD at 60 bpm at follow-up. At 6 months, LV reverse remodelling was investigated. Cardiac resynchronization therapy patients were considered responders when an absolute improvement in LV ejection fraction ≥ 5% occurred. At 6 months, 14 (56%) patients were responders and 11 (44%) non-responders (mean LVEF 40 ± 10% vs. 27 ± 6%, respectively). In responders, SonR value did not significantly change at follow-up compared to baseline (P = 0.894). At follow-up, SonR value was not significantly different between two groups (P = 0.651). SonR signal significantly increased during isometric effort in responders (P = 0.002) while it slightly decreased in non-responders at follow-up (P = 0.572). No differences were observed in response to isometric effort between two groups at baseline (P = 0.182, P = 0.069, respectively). CONCLUSIONS: The absolute SonR amplitude provides limited information on the status of LV performance. The variation in SonR signal during static exercise is more likely to identify responders at follow-up.

Hemodynamics of His Bundle pacing.

This review will focus on the feasibility of long term His bundle pacing and its effects on left ventricle (LV) hemodynamics. Compared with right ventricular pacing, His bundle pacing results in a more physiological electro-mechanical activation that contributes to preserve LV function. Moreover some studies showed a similar effect to biventricular pacing in patients with heart failure and left bundle branch block. Recent observations indicate that His bundle pacing should be considered as an optimal site to pace right ventricle in patients who are candidates for cardiac resynchronization therapy.

Prognostic Impact of QRS Axis Deviation in Patients Treated With Cardiac Resynchronization Therapy.

INTRODUCTION: QRS duration and morphology are currently recognized as recommended criteria for the selection of CRT candidates. It has recently been shown that patients with left bundle branch block (LBBB) derive substantial clinical benefit from CRT. The aim of this study is to investigate the prognostic impact of QRS axis deviation (AD) in HF patients with LBBB undergoing CRT. METHODS AND RESULTS: We retrospectively evaluated 707 HF patients with LBBB who underwent CRT at five centers. Baseline QRS axis was defined as normal (NA: -30° to 90°), right axis deviation (RAD: 90° to 180°) and left axis deviation (LAD: <-30°). The primary endpoint was a composite of all cause death/HF hospitalization. The risk of endpoint by AD was evaluated with both Kaplan-Meier and Cox proportional hazard analysis. Among 707 patients (73% M, median age: 71 [62,77] years), 323 (46%) had NA, 359 (51%) LAD, and 25 (3.5%) RAD. Baseline clinical characteristics were similar between the three groups. Over a mean follow-up of 32 ± 25 months, 141 deaths occurred (21%) and 36% (n = 255) met with the composite endpoint. A significantly higher proportion of RAD patients (52%) reached the endpoint (LAD 40%, NA 30%). KM analysis showed that RAD and LAD patients had worse event free survival and in multivariate analysis both LAD (HR: 1.40; 95% CI: 1.05-1.86; P = 0.021) and RAD (HR: 2.49; 95% CI: 1.31-4.74; P = 0.005) were independently associated with worse clinical outcome. CONCLUSIONS: Right or left axis deviation in the presence of LBBB in HF patients undergoing CRT are independent predictors of poor prognosis.

Assessment of Myocardial Contractility by SonR Sensor in Patients Undergoing Cardiac Resynchronization Therapy.

BACKGROUND: SonR sensor signal correlates well with myocardial contractility expressed in terms of left ventricular (LV) dP/dt max. The aim of our study was to evaluate the changes in myocardial contractility during isometric effort in heart failure patients undergoing cardiac resynchronization therapy (CRT) with right atrial SonR sensor. METHODS: Thirty-one patients (19 men, 65 ± 7 years, LV ejection fraction [LVEF] 28% ± 5%, in sinus rhythm) were implanted with a CRT-defibrillator (CRT-D) device equipped with SonR sensor, which was programmed in VVI mode at 40 beats/min. Twenty-four hours after implantation, each patient underwent a noninvasive hemodynamic evaluation at rest and during isometric effort, including: (1) measurement of beat-to-beat endocavitary SonR signal; (2) echocardiographic assessment; and (3) continuous measurement of blood pressure with Nexfin method (BMEYE, Amsterdam, the Netherlands). The following contractility parameters were considered: (1) mean value of beat-to-beat SonR signal; (2) mean value of LV dP/dt by Nexfin system; and (3) fractional shortening (FS) by echocardiography. RESULTS: At the third minute of the isometric effort, mean value of SonR signal significantly increased from baseline (P < 0.001). Similarly, mean value of both LV dP/dt by Nexfin and FS significantly increased compared to the resting condition (P < 0.001; P < 0.001). While in 27 (88%) patients SonR signal increased at the third minute of the isometric effort, in four (12%) patients SonR signal decreased. In these patients, both LV dP/dt by Nexfin and FS consensually decreased. CONCLUSIONS: In CRT patients, SonR sensor is able to detect changes in myocardial contractility in a consensual way like noninvasive methods such as Nexfin system and echocardiography.

Autoantibodies against ß1-Adrenergic Receptors: Response to Cardiac Resynchronization Therapy and Renal Function.

BACKGROUND: Cardiac resynchronization therapy (CRT) nonresponse remains a major clinical problem. Autoantibodies specific for the ß1-adrenergic (ß1-AAbs) and muscarinic (M2-AAbs) receptors are found in patients with chronic heart failure (HF) of various etiologies. MATERIALS AND METHODS: We retrospectively analyzed 73 HF patients (median age 67 years, 84% males, New York Heart Association II-IV, in sinus rhythm, left ventricular ejection fraction <35%) who received CRT defibrillator (CRT-D) from 2010 to 2013. ß1-AAbs and M2-AAbs were measured by enzyme-linked immunosorbent assay. Echocardiography was used to assess CRT response (reduction >15% in left ventricular end-systolic volume at 6 months follow-up). Renal function (RF) parameters (creatinine [Cr], blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR Modified Diet in Renal Disease], cystatin C [Cys-C], and neutrophil gelatinase-associated lipocalin [NGAL]) were also evaluated. RESULTS: A significantly higher percentage of patients positive for ß1-AAbs (OD sample/OD reference ratio >2.1) in nonresponders than in responder patients was observed (57% vs 27%, P = 0.004). No influence of M2-AAbs on CRT-D response was demonstrated. ß1-AAbs were predictive of a poor CRT-D response (odds ratio [OR] [95% confidence interval (CI)] 3.64 [1.49-8.88], P = 0.005), also after adjustment for RF parameters (OR [95% CI] 4.95 [1.51-16.26], P = 0.008) observed to influence CRT-D response (Cr P = 0.03, BUN P = 0.009, Cys-C P = 0.02). The positive rates of ß1-AABs in patients with abnormal blood level of Cr, eGFR, Cys-C, and NGAL were significantly higher than those with normal levels (P = 0.03, P = 0.02, P = 0.001, P = 0.007, respectively). CONCLUSIONS: Our study suggests that (1) the evaluation of ß1-AAb is useful to identify responders to CRT-D; (2) the presence of ß1-AAbs is in relationship with elevated renal function parameters.

Disentangling the Role of Cortico-Basal Ganglia Loops in Top-Down and Bottom-Up Visual Attention: An Investigation of Attention Deficits in Parkinson Disease.

It is solidly established that top-down (goal-driven) and bottom-up (stimulus-driven) attention mechanisms depend on distributed cortical networks, including prefrontal and frontoparietal regions. On the other hand, it is less clear whether the BG also contribute to one or the other of these mechanisms, or to both. The current study was principally undertaken to clarify this issue. Parkinson disease (PD), a neurodegenerative disorder primarily affecting the BG, has proven to be an effective model for investigating the contribution of the BG to different brain functions; therefore, we set out to investigate deficits of top-down and bottom-up attention in a selected cohort of PD patients. With this objective in mind, we compared the performance on three computerized tasks of two groups of 12 parkinsonian patients (assessed without any treatment), one otherwise pharmacologically treated and the other also surgically treated, with that of a group of controls. The main behavioral tool for our study was an attentional capture task, which enabled us to tap the competition between top-down and bottom-up mechanisms of visual attention. This task was suitably combined with a choice RT and a simple RT task to isolate any specific deficit of attention from deficits in motor response selection and initiation. In the two groups of patients, we found an equivalent increase of attentional capture but also comparable delays in target selection in the absence of any salient distractor (reflecting impaired top-down mechanisms) and movement initiation compared with controls. In contrast, motor response selection processes appeared to be prolonged only in the operated patients. Our results confirm that the BG are involved in both motor and cognitive domains. Specifically, damage to the BG, as it occurs in PD, leads to a distinct deficit of top-down control of visual attention, and this can account, albeit indirectly, for the enhancement of attentional capture, reflecting weakened ability of top-down mechanisms to antagonize bottom-up control.

Cardiac resynchronization therapy acutely improves ventricular-arterial coupling by reducing the arterial load: assessment by pressure-volume loops.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been demonstrated to improve ventricular-arterial coupling by reducing effective arterial elastance (Ea) on long-term follow-up. Detailed invasive studies showing possible acute peripheral effects of CRT are not available. We evaluated the hemodynamic effects of CRT in patients with systolic dysfunction, in order to investigate the impact on ventricular-arterial coupling and, in particular, on Ea immediately after the initiation of pacing. METHODS: We studied 37 heart failure patients undergoing CRT implantation based on conventional criteria. On implantation, left ventricular (LV) pressure and volume data were determined via a conductance catheter. Twelve patients with a standard indication for electrophysiologic study and preserved LV function served as a control group. RESULTS: In comparison with the control group, heart failure patients showed reduced systolic and diastolic function. LV end-systolic elastance (Ees: end-systolic pressure/volume) was impaired (0.79 ± 0.33 mm Hg/mL vs 1.84 ± 0.89 mm Hg/mL, P = 0.012) and Ees/Ea reduced (0.36 ± 0.17 vs 1.19 ± 1.81, P = 0.022). In heart failure patients, CRT immediately improved systolic function, increasing stroke work from 3.9 ± 1.8 L*mm Hg to 6.9 ± 3.3 L*mm Hg (P < 0.001) and Ees to 1.02 ± 0.62 mm Hg/mL (P = 0.001). Ea decreased from 2.59 ± 1.35 mm Hg/mL to 1.68 ± 0.91 mm Hg/mL (P < 0.001), leading to an increase in Ees/Ea to 0.70 ± 0.38 (P < 0.001). CONCLUSION: Our data indicate that switching CRT on induces an immediate reduction in arterial load, conceivably as a consequence of restored autonomic balance.

Cardiac memory in cardiac resynchronization therapy: A vectorcardiographic comparison of biventricular and left ventricular pacing.

INTRODUCTION: "Cardiac memory" (CM) refers to a change in repolarization induced by an altered pathway of activation, manifested after resumption of spontaneous ventricular activation (SVA). AIMS: To investigate for the first time in humans the effects of left ventricular (LV) pacing on CM development through vectorcardiography (VCG). METHODS: We studied 28 patients with heart failure (HF) and left bundle branch block (LBBB) treated with cardiac resynchronization therapy (CRT). Fourteen patients underwent biventricular (BIV) stimulation; the other 14 underwent LV stimulation only. VCG was acquired during SVA at baseline and during AAI and DDD pacing immediately after and 7 and 90 days after the implant. RESULTS: At baseline, in both groups, the QRS and T vectors angles were those specific of LBBB pattern. During DDD pacing, QRS vector angle changed to the right and upward in BIV patients while no significant differences were observed in LV patients. During AAI pacing, T vector angle changed significantly in BIV patients, following the direction of the paced QRS and amplitude significantly increased. In LV patients no significant differences in T vector angles were observed. Only T vector amplitude significantly increased at 7 days (p=0.03) and at 90 days (p=0.008 vs baseline). CONCLUSION: In patients with LBBB, BIV pacing induces cardiac memory development as a significant change in T vector magnitude and angle, while LV pacing doesn't induce significant modifications in QRS and T vector angles and CM is manifested only as a significant T vector amplitude change.

Simplified Selvester Score: a practical electrocardiographic instrument to predict response to CRT.

AIMS: To investigate the LBBB Selvester Scoring System (LBBB-SSc) and the Simplified-SSc prognostic impact in predicting response to CRT, all cause and cardiac mortality, heart failure (HF) hospitalizations and onset of arrhythmias in HF patients undergoing CRT. METHODS: We retrospectively evaluated LBBB-SSc and Simplified-SSc of 172 consecutive HF patients with true-LBBB who underwent CRT. Response to CRT was defined as the improvement of LVEF of at least 10% or as the reduction of LVESV of at least 15% at 6-month follow-up. Logistic regression analysis and Cox proportional hazard analysis were performed to evaluate each endpoint related risk according to LBBB-SSc and Simplified-SSc. RESULTS: The LBBB-SSc and the Simplified-SSc were inversely correlated with response to CRT. Myocardial scar at both scores was independently associated to non-response to CRT. No correlation was observed between LBBB-SSc or Simplified-SSc and other endpoints. CONCLUSIONS: In HF patients with true-LBBB, Simplified-SSc is able to predict response to CRT.

CHADS2 and CHA2DS2-VASc scores to predict morbidity and mortality in heart failure patients candidates to cardiac resynchronization therapy.

AIMS: CHADS2 and CHA2DS2-VASc scores are pivotal in assessing the risk of stroke in atrial fibrillation patients, and were recently proved to predict hospitalizations and mortality in specific clinical settings. Aim of this study was to evaluate whether these scores could predict clinical outcomes [first hospitalization for heart failure (HF) and a combined event of HF hospitalization and death for any cause] in patients candidates to cardiac resynchronization therapy and implantable defibrillator (CRT-D). METHODS AND RESULTS: In a retrospective multicentre Italian study, we enrolled 559 consecutive HF patients candidates to CRT-D, and we grouped them in three pre-specified risk classes: low (CHADS2/CHA2DS2-VASc 1-2), moderate (CHADS2/CHA2DS2-VASc 3-4), and high (CHADS2 5-6/CHA2DS2-VASc 5-8). All patients underwent regular follow-up at implanting centres every 6 months; data collection was extended till the 72th month of follow-up. At a median FU of 30 months, 143 patients (25.4%) were hospitalized for HF and 110 (19.5%) died. Event-free survival analysis showed a significant difference according to baseline CHADS2 and CHA2DS2-VASc scores (Log-Rank for HF P < 0.001 for CHADS2 and CHA2DS2-VASc; Log-Rank for combined end-point P = 0.001 for CHADS2, P < 0.001 for CHA2DS2-VASc). At multivariate analysis, independent predictors of endpoints were: previous atrial fibrillation (AF) or AF at implant, NYHA class, QRS duration and the CHA2DS2-VASc score (for HF hospitalization P = 0.013; for the combined event, P = 0.007), while the CHADS2 score was not independently associated with either the end-points. CONCLUSION: In CRT-D patients, pre-implant CHA2DS2-VASc score is an independent predictor of major clinical events at 30-month follow-up.

The use of electrical source imaging in targeting lesional mesial temporal epilepsy for radiosurgical treatment.

Gamma knife radiosurgery (GK-RS) is a technique applied in selected cases of mesial-temporal epilepsy, although still limited to centres with adequate instrumentation and expertise. Here, we report a case of radio surgery targeted with the aid of electrical source imaging that localizes the cortical area generating the scalp epileptic discharges. The patient, a 39-year-old male, presented with a right mesio-temporal lesion; electrical source imaging localization partially overlapped with the lesional area but showed an important activation of the omolateral frontal area, concordant with the epileptic network. The patient underwent GK-RS, with good neurosurgical and clinical results. A radiosurgical ellipsoidal treatment volume area of 2 × 2 × 2 cm³, located over the right temporo-mesial region within a centre showing abnormal signal intensity, was considered. Seven months after treatment, the patient developed brain oedema that gradually resolved after one year. After three years of follow-up, the patient was seizure-free (Engel class I). Our very preliminary experience suggests that electrical source imaging appears to be a useful supporting tool for the definition of the radiosurgical treatment volume in selected patients with temporo-mesial lesional epilepsy.

S-ICD Implantation in Secondary Prevention in a Young Patient With Recent Surgically Repaired Pectus Excavatum.

We report a case of successful implantation of a subcutaneous implantable cardioverter-defibrillator in a young patient with severe pectus excavatum presenting with out-of-hospital ventricular fibrillation arrest who was recently surgically repaired with a MIRPE-Nuss procedure. No complications in lead positioning were observed, and the device was tested to determine that it functioned properly.