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Osteogenesis imperfecta is a heterogeneous group of connective tissue disorders; it is characterized by blue scleras, bone fragility and deformity secondary to recurring fractures. A case of osteogenesis imperfecta personally observed at the 21st week of gestation is presented.

MitraClip system is the only catheter-based device for percutaneous mitral valve repair available for clinical use, after receipt of the CE Mark in 2008, while it is currently under review for FDA approval in the US. To date, over 3500 MitraClip implants have been performed worldwide, mainly in high risk surgical patients. The aim of this review is to review all the current evidences of the MitraClip therapy in an aim to define its clinical role in the treatment of mitral regurgitation (MR).

A case of GM2 gangliosidosis is reported: the diagnosis has been made by clinical findings showing macular cherry-red spot and a progressive neurologic symptomatology with epilepsy, by electron microscopic observation in conjunctival fibroblasts of numerous vacuoles ("zebra bodies") and by absence of total hexosaminidase activity in leukocytes. An abnormal increase of urinary oligosaccharides has also been found.

The emerging concept of opioid peptides as a new class of chemical messengers of the neuroimmune axis and the presence of a number of immunological abnormalities in infantile autism prompted us to correlate biological (hormonal and immunological) determinations and behavioural performances during treatment with the potent opiate antagonist, naltrexone (NAL). Twelve autistic patients ranging from 7 to 15 years, diagnosed according to DSM-III-R, entered a double-blind crossover study with NAL at the doses of 0.5, 1.0 and 1.5 mg/kg every 48 hours. The behavioural evaluation was conducted using the specific BSE and CARS rating scales NAL treatment produced a significant reduction of the autistic symptomatology in seven ("responders") out of 12 children. The behavioural improvement was accompanied by alterations in the distribution of the major lymphocyte subsets, with a significant increase of the T-helper-inducers (CD4+CD8-) and a significant reduction of the T-cytotoxic-suppressor (CD4-CD8+) resulting in a normalization of the CD4/CD8 ratio. Changes in natural killer cells and activity were inversely related to plasma beta-endorphin levels. It is suggested that the mechanisms underlying opioid-immune interactions are altered in this population of autistic children and that an immunological screening may have prognostic value for the pharmacological therapy with opiate antagonists.

Background Little is known about the pathogenesis of scleromyxedema, a life-threatening fibromucinosis disease with immunological dysregulation. Objectives To investigate on T-cell phenotype, function and cytokine biology in search of new insights supporting the immunopathogenesis of the disease. Methods We analysed the frequency of circulating lymphocyte subsets, the T-cell maturation stage, the generation of antigen-specific T-cell lines and T-cell cytokine secretion. Results The analysis of T-cell maturation stage and the TCR spectratyping findings revealed that scleromyxedema patients showed clear immunological signs of long-lasting immune system activation and stimulation leading to a skewed T-cell repertoire. Moreover, these analyses showed that both CD4+ and CD8+ T cells from scleromyxedema patients have a profound deficiency (even after stimulation) relatively to the production of IFN-γ and IL17 with respect to healthy donor control cells, while they are massively skewed towards IL4 secretion after stimulation. Conclusions Our data indicate that a chronic Th2-skewed T-cell response against an unknown target antigen leading to abnormally high IL4 secretion, a pro-fibrotic cytokine, is a main immunological hallmark of scleromyxedema patients. These results, never reported before, may have a translational therapeutic value due to the availability of anti-IL4 agents such as dupilumab.

Motivational interviewing (MI) is devised to change unhealthy behaviors by increasing motivation. We adapted MI to a group format for the treatment of relapse during the behavioral treatment of obesity and performed a clinical audit to evaluate its effectiveness in stopping weight regain. The program was structured in seven weekly sessions, plus a 6-month follow-up. Patients (n = 86) completed a questionnaire on motivation to change in both healthy diet and physical activity, and a self-reported measurement of calorie intake and physical activity at baseline, at program end and at 6-month follow-up. The attendance to the program was high, with only 13 patients (15%) not completing the program and 24% not attending the 6-month follow-up. By the end of follow up, the prevalence of patients in either precontemplation or contemplation was reduced from over 60% at enrollment to approximately 20%, whereas the sum of patients in action or maintenance stages was increased from 9.5% in healthy diet and 14% in physical activity to 39.7% and 41.3%, respectively. These changes translated into significant behavioral changes (mean calorie intake, &minus, 13%, total physical activity, +125%, sedentary time, &minus, 8%) and finally into reduced body weight ( &minus, 3%). We conclude that MI programs adapted for groups may be used to stop relapse in individuals following a behavioral intervention for obesity.

Background Steroid resistant nephrotic syndrome (SRNS) is a frequent cause of end stage renal disease in children and post-transplant disease recurrence is a major cause of graft loss. Methods We identified all children with SRNS who underwent renal transplantation in Italy, between 2005 and 2017. Data were retrospectively collected for the presence of a causative gene mutation, sex, histology, duration of pre-transplant dialysis, age at onset and transplant, HLA matching, recurrence, therapy for recurrence, and graft survival. Results 101 patients underwent a first and 22 a second renal transplant. After a median follow-up of 58.5 months, the disease recurred on the first renal transplant in 53.3% of patients with a non-genetic and none with a genetic SRNS. Age at transplant > 9 years and the presence of at least one HLA-AB match were independent risk factors for recurrence. Duration of dialysis was longer in children with relapse, but did not reach statistical significance. Overall, 24% of patients lost the first graft, with recurrence representing the commonest cause. Among 22 patients who underwent a second transplant, 5 suffered of SRNS recurrence. SRNS relapsed in 5/9 (55%) patients with disease recurrence in their first transplant and 2 of them lost the second graft. Conclusions Absence of a causative mutation represents the major risk factor for post-transplant recurrence in children with SRNS, while transplant can be curative in genetic SRNS. A prolonged time spent on dialysis before transplantation has no protective effect on the risk of relapse and should not be encouraged. Retransplantation represents a second chance after graft loss for recurrence.

OBJECTIVES Recurrent mitral regurgitation (MR) is common after surgical and percutaneous (MitraClip) treatment of functional MR (FMR). However, the Everest II trial suggested that, in patients with secondary MR and initially successful MitraClip therapy, the results were sustained at 4 years and were comparable with surgery in terms of late efficacy. The aim of this study was to assess whether both those findings were confirmed by our own experience. METHODS We reviewed 143 patients who had an initial optimal result (residual MR ≤ 1+ at discharge) after MitraClip therapy (85 patients) or surgical edge-to-edge (EE) repair (58 patients) for severe secondary MR (mean ejection fraction 28 ± 8.5%). Patients with MR ≥ 2+ at hospital discharge were excluded. The two groups were comparable. Only age and logistic EuroSCORE were higher in the MitraClip group. RESULTS Follow-up was 100% complete (median 3.2 years; interquartile range 1.8;6.1). Freedom from cardiac death at 4 years (81 ± 5.2 vs 84 ± 4.6%, P = 0.5) was similar in the surgical and MitraClip group. The initial optimal MitraClip results did not remain stable. At 1 year, 32.5% of the patients had developed MR ≥ 2+ (P = 0.0001 compared with discharge). Afterwards, patients with an echocardiographic follow-up at 2 years (60 patients), 3 years (40 patients) and 4 years (21 patients) showed a significant increase in the severity of MR compared with the corresponding 1 year grade (all P < 0.01). Freedom from MR ≥ 3+ at 4 years was 75 ± 7.6% in the MitraClip group and 94 ± 3.3% in the surgical one (P = 0.04). Freedom from MR ≥ 2+ at 4 years was 37 ± 7.2 vs 82 ± 5.2%, respectively (P = 0.0001). Cox regression analysis identified the use of MitraClip as a predictor of recurrence of MR ≥ 2+ [hazard ratio (HR) 5.2, 95% confidence interval (CI) 2.5-10.8, P = 0.0001] as well as of MR ≥ 3 (HR 3.5, 95% CI 0.9-13.1, P = 0.05). CONCLUSIONS In patients with FMR and optimal mitral competence after MitraClip implantation, the recurrence of significant MR at 4 years is not uncommon. This study does not confirm previous observations reported in the Everest II randomized controlled trial indicating that, if the MitraClip therapy was initially successful, the results were sustained at 4 years. When compared with the surgical EE combined with annuloplasty, MitraClip therapy provides lower efficacy at 4 years.

Aims: The aim of this study was to report the feasibility and the preliminary outcomes after transcatheter aortic valve implantation (TAVI) in the frail and unique high-risk population of patients with systemic sclerosis (SSc) and severe aortic stenosis (AS). Methods and results: All patients with SSc and severe AS treated with TAVI between November 2007 and June 2013 in our centre were included in the current study. Outcomes were assessed using the Valve Academic Research Consortium 2 (VARC-2) definitions. Of 526 surgical high-risk patients treated in the study period, only six had SSc (1.1%). All SSc patients underwent transfemoral TAVI under conscious sedation. The procedure was successfully performed in all patients. There was one case of a major vascular complication. During a median follow-up time of 550 days (interquartile range 390-1,009 days), five of the six patients were alive, free from any complications and with an NYHA Class I or II. One patient died at 670 days from a stroke of unknown aetiology. Conclusions: The present case series suggests that the TAVI procedure is feasible in patients with SSc and severe AS. OI Giustino, Gennaro/0000-0002-5400-9516

OBJECTIVES To compare the surgical and percutaneous edge-to-edge (EE) repair in patients with severe left ventricular (LV) dysfunction and secondary mitral regurgitation (MR). METHODS We reviewed the prospectively collected data of the first 120 consecutive patients (age: 65 ± 9.8 years, EF: 28 ± 8.2%) treated with surgical (65 patients) or percutaneous (55 patients) EE repair for severe secondary MR in our institution. Age (P = 0.005) and logistic European System for Cardiac Operative Risk Evaluation (P < 0.0001) were significantly higher in the MitraClip group. LVEF (P = 0.37), end-diastolic (P = 0.83) and end-systolic (P = 0.68) volumes and systolic pulmonary artery pressure (SPAP) (P = 0.58) were similar. The follow-up was 100% complete [median: 4 years; interquartile range (IQR): 2.2-7.2]. RESULTS The length of hospital stay was 10 days (IQR: 8-13) for surgery and 5 days (IQR: 3.9-7.8) for MitraClip (P < 0.0001). Hospital mortality (3 vs 0%, P = 0.49) and freedom from cardiac death at 4 years (80.8 ± 4.9% vs 79.1 ± 5.9%, P = 0.9) were not significantly different in the surgical and MitraClip group, respectively. Residual MR ≥ 2+ at hospital discharge was 7.6% for surgery and 29% for MitraClip (P = 0.002). At 4 years, freedom from MR ≥ 2+ (74.9 ± 5.6% vs 51.4 ± 7.4%, P = 0.01) and freedom from MR ≥ 3+ (92.8 ± 3.4% vs 68.1 ± 7%, P = 0.002) were both significantly higher in the surgical group. Multivariate analysis identified the use of MitraClip as an independent predictor of recurrence of MR ≥ 2+ [Hazard ratio (HR): 2.1, 95% confidence interval (CI): 1.1-3.9, P = 0.02] as well as of MR ≥ 3 (HR: 6.1, 95% CI: 1.5-24.3, P = 0.01). In the surgical group, no predictors of cardiac mortality were identified. In the MitraClip group, left ventricular end-diastolic diameter (HR: 1.1, 95% CI: 1-1.2, P = 0.005) and SPAP (HR: 1, 95% CI: 1-1.1, P = 0.005) were independent predictors of cardiac death at the follow-up. CONCLUSIONS MitraClip therapy is a safe therapeutic option in selected high-risk patients with secondary MR and relevant comorbidities. The surgical EE provides higher efficacy both postoperatively and at the mid-term follow-up.

Background Scleromyxedema is a primary fibro-mucinosis whose therapy is still challenging. Objective To evaluate the safety and efficacy of high-dose intravenous immunoglobulin (IVIg) for the management of scleromyxedema prospectically using an objective score. Methods In a prospective open-label study, IVIg was administered to 8 patients with scleromyxedema in a dose of 2 gr/Kg per month. The patients were followed up to a minimum of 6 months and their disease activity and response to treatment were assessed using the Physician's Global Assessment of disease severity (PGA) and a modified objective skin scoring system for patients with scleroderma (modified Rodnan score system for scleromyxedema or mRSSS). We used a stringent statistical nonparametric test, the Mann-Whitney test, to assess the changes in the mRSSS following therapy with IVIg. Results Eight patients were included (5 males) with a mean age of 59 years. Mean duration of scleromyxedema was 19 months (6-37 months). The mean duration of treatment was 36.5 months (range 7-74 months).The patients were followed-up for a minimum of 15 months to a maximum of 87 months (mean 44 months). The mean baseline mRSSS of our cohort was 82.38 (37-145, standard deviation 40.763) at the start of treatment, and this significantly decreased to 14.88 (0-37, standard deviation 12.988) (p=0.012) at the last clinical evaluation with a decrease of mRSSS of 81.6%. No considerable side effects were noted. Paraproteinemia remained substantially unchanged. In 6 cases, maintenance infusions were required to preserve disease control while in two patients therapy was stopped after 7 and 11 months. Relapses, however, occurred respectively after 6 and 25 months. Conclusions Our study is the first to demonstrate a statistically clinical objective improvement of clinical symptoms of scleromyxedema with IVIg. This article is protected by copyright. All rights reserved.

Introduction the prevalence of malnutrition in children and its impact on clinical outcomes is underrecognized by clinicians in Italy as well as worldwide. A novel definition of pediatric malnutrition has been recently proposed by a working group of the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), based on the correlation between illness and the use of zscores of anthropometric measurements. Aim to investigate the prevalence of malnutrition and related nutritional support among hospitalized children in Italy, in a nationwide survey performed in a single day (16/4/2015). Methods an open access website (http://nday.biomedia.net) was used to collected data from 73 hospitals and 101 wards in 14 Italian regions (1994 patients). Anonymous information was collected on hospitals' characteristics, patient's anthropometry, admission diagnosis, presence of chronic diseases and use of nutritional support: oral nutritional supplements (ONS), enteral nutrition (EN) or parenteral nutrition (PN). Z-scores of anthropometric measurements, calculated with Epi Info 7.1.5, defined nutritional status: wasting was identified by BMI or Weight-for-Length z-score (

Conduction disorders and permanent pacemaker implantation are common complications in patients who undergo transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the incidence and clinical significance of new bundle branch block in patients who underwent TAVI with the Medtronic CoreValve Revalving System (MCRS) or the Edwards SAPIEN valve (ESV). Data from 238 patients with no previous pacemaker implantation, left bundle branch block (LBBB) or right bundle branch block at baseline electrocardiography who underwent TAVI with either MCRS (n = 87) or ESV (n = 151) bioprostheses from 2007 to 2011 were analyzed. New-onset LBBB occurred in 26.5% patients (n = 63): 13.5% with the ESV (n = 20) and 50.0% with the MCRS (n = 43) (p = 0.001). Permanent pacemaker implantation was required in 12.7% of patients (n = 8) because of complete atrioventricular block (ESV n = 2, MCRS n = 4), LBBB and first degree atrioventricular block (MCRS n = 1) and new-onset LBBB associated with sinus bradycardia (MCRS n = 1). At discharge, LBBB persisted in 8.6% of ESV patients (n = 13) and 32.2% of MCRS patients (n = 28) (p = 0.001). On multivariate analysis, the only predictor of LBBB was MCRS use (odds ratio 7.2, 95% confidence interval 2.9 to 17.4, p

Objectives The aim of this multicentre study is to report the clinical experiences of all patients undergoing transcatheter aortic valve implantation (TAVI) with a balloon-expandable device in Italy. Methods The Italian Transcatheter balloon-Expandable valve Registry (ITER) is a real-world registry that includes patients who have undergone TAVI with the Sapien (Edwards Lifesciences, Irvine, CA, USA) bioprosthesis in Italy since it became available in clinical practice. From 2007 to 2012, 1904 patients were enrolled to undergo TAVI in 33 Italian centres. Outcomes were classified according to the updated Valve Academic Research Consortium (VARC-2) definitions. A multivariable analysis was performed to identify independent predictors of all-cause mortality. Results Mean age was 81.7 (SD:6.2) years, and 1147 (60.2%) patients were female. Mean Logistic EuroSCORE was 21.1% (SD:13.7). Transfemoral, transapical, transaortic and transaxillary TAVI was performed in 1252 (65.8%), 630 (33.1%), 18 (0.9%) and 4 (0.2%) patients, respectively. Operative mortality was 7.2% (137 patients). The VARC-2 outcomes were as follows: device success, 88.1%; disabling stroke, 1.0%; life-threatening and major bleeding 9.8 and 10.5%, respectively; major vascular complication, 9.7%; acute kidney injury, 8.2%; acute myocardial infarction ≤72 h, 1.5%. Perioperative pacemaker implantation was necessary in 116 (6.1%) patients. At discharge, the mean transprosthetic gradient was 10.7 (SD:4.5) mmHg. Incidence of postoperative mild, moderate or severe paravalvular leak was, respectively, 32.1, 5.0 and 0.4%. A total of 444/1767 (25.1%) deaths after hospital discharge were reported: of these, 168 (37.8%) were classified as cardiac death. Preoperative independent predictors of all-cause mortality were male gender (HR: 1.395; 95% CI:1.052-1.849); overweight, BMI 25-30 kg/m2 (HR: 0.775; 95% CI: 0.616-0.974); serum creatinine level (every 1 mg/dl increase; HR: 1.314; 95% CI:1.167-1.480); haemoglobin level (every 1 g/dl increase; HR: 0.905; 95% CI:0.833-0.984); critical preoperative state (HR: 2.282; 95% CI: 1.384-3.761); neurological dysfunction (HR: 1.552; 95% CI:1.060-2.272); atrial fibrillation (HR: 1.556; 95% CI:1.213-1.995); pacemaker rhythm (HR: 1.948; 95% CI:1.310-2.896); NYHA Class III or IV (HR: 1.800; 95% CI:1.205-2.689 or HR: 2.331; 95% CI:1.392-3.903, respectively). Conclusions TAVI with a balloon-expandable device in the 'real world' shows good mid-term outcomes in terms of survival, technical success, valve-related adverse events and haemodynamic performance.

Aims Reoperation for bioprosthetic heart valve failure is associated with significant morbidity and mortality, particularly in high-risk patients. Transcatheter valve-in-valve (VIV) implantation may offer a less invasive alternative. The aim of this study was to report our initial experience with transcatheter VIV implantation to treat degenerated tissue valves. Methods and results VIV implantation with the Edwards SAPIEN transcatheter heart valve (THV; Edwards Lifesciences Inc, Irvine, CA, USA) was performed in 18 high-risk patients (STS 8.2±5.2%; logistic EuroSCORE 37.4±20.8%) with symptomatic bioprosthetic failure (17 aortic, one mitral). Valve Academic Research Consortium (VARC) definitions were applied for endpoint adjudication. Transfemoral access was the preferred vascular approach (16 patients, with the mitral VIV delivered anterogradely through the femoral vein; one transaxillary and one transapical). The majority (83%) of procedures were performed under local anaesthesia and sedation. Device success was achieved in all but one patient who had a final transaortic gradient ≥20mmHg. Acute kidney injury occurred in three patients (Stage 3 in 1), life-threatening or major bleeding in four patients, while major vascular complications occurred in one patient. Permanent pacemaker implantation was required in two patients. There were no deaths or neurological events at 30-day follow-up. At a median follow-up of 11 months (interquartile range 6-16), the mortality rate was 5.6% and all patients were in NYHA class II or lower. Conclusions Transcatheter implantation of the Edwards THV within a degenerated aortic bioprosthesis, performed predominantly via the transfemoral route, is feasible and associated with good periprocedural and clinical outcomes in high-risk surgical patients.

Objectives The aim of this study was to analyze the short-term outcomes after transcatheter aortic valve implantation with the Edwards Sapien THV (ESV), compared with the Sapien XT THV (SXT) (Edwards Lifesciences, Irvine, California). Background The SXT has been recently commercialized in Europe, but there are no studies analyzing the efficacy and safety of SXT, compared with ESV. Methods All consecutive patients (n = 120) who underwent transcatheter aortic valve implantation in our center via the transfemoral approach with either ESV (n = 66) or SXT (n = 54). Valve Academic Research Consortium endpoints were used. Results Mean age was 80 ± 8 years, and mean Logistic-European System for Cardiac Operative Risk Evaluation was 24.9 ± 17.0. The ilio-femoral artery minimal lumen diameter was smaller in patients treated with the SXT (7.27 ± 1.09 mm vs. 7.94 ± 1.08 mm, p = 0.002). Device success was high in both groups (96.3% vs. 92.4%, p = 0.45). Major vascular events were 3-fold lower in the SXT group (11.1% vs. 33.3%, relative risk: 0.40, 95% confidence interval: 0.28 to 0.57; p = 0.004). Life-threatening and major bleeding events were not significantly different between groups (18.5% vs. 27.3% and 35.2% vs. 40.9%, respectively). The SXT group had a lower 30-day Valve Academic Research Consortium combined safety endpoint (20.4% vs. 45.5%; relative risk: 0.44, 95% confidence interval: 0.24 to 0.80; p = 0.004). The 30-day mortality was 1.7% (n = 2). At 30 days, mean transaortic gradient was approximately 10 mm Hg in both groups and the aortic regurgitation was mild-to-moderate in 70.2% of SXT and 76.3% of ESV. Conclusions The new SXT valve has the same short-term performance as the ESV but seems to be associated with a lower risk of major vascular complications and thus has a broader clinical application.

Objective: Despite its efficacy and swiftness, bipolar radiofrequency is generally not used on the left isthmus for concern of injuring a coronary branch. Incomplete lesion sets or use of an additional unipolar device are often considered. We report a technique to perform a full left lesion set involving the mitral line using a standard bipolar radiofrequency device. Methods: An innovative complete left atrial lesion set was performed using only bipolar radiofrequency in 70 consecutive patients (study group). In 67/70 patients (96%) mitral valve disease was the main indication to surgery. Atrial fibrillation was permanent in 42 patients (60%), persistent in 25 (36%) and paroxysmal in three patients (4%). After beating-heart pulmonary vein isolation on-pump, the coronary-free area of the AV groove was marked epicardially by sticking a needle into the left atrial wall, behind the coronary sinus. The projection of the needle marker on the mitral annulus was then identified through the atriotomy and an endo-epicardial ablation was performed with the bipolar device involving the atrial wall, the coronary sinus, up to the annulus. The lesion set was then completed by connecting the encirclings and the left appendage, which was then sutured. Follow-up was 100% complete. Results were compared with those of a control group of 33 patients receiving bipolar radiofrequency left atrial ablations and a mitral connecting line with a second unipolar device. Results: All patients survived. No major complication occurred. Haematoma of the AV groove was observed during retrograde cardioplegia in one case. No myocardial ischaemia or re-exploration for bleeding (median 325 cc, interquartile range 250-442) occurred. Two out of 70 patients required a permanent pacemaker for AV block. Freedom from atrial fibrillation was 84% (95% CI: 75%, 93%) at 6 months and 81% (95% CI: 70%, 93%) at 1 year. One patient had left flutter. Comparison with the control group did not show any difference in clinical outcomes, but revealed bipolar ablation to the mitral annulus to abate the per patient cost of the ablation devices (1245 ± 50 ∈ vs 2403 ± 17 ∈; p < 0.0001). Conclusions: Performing the mitral line with bipolar radiofrequency is safe and cost-effective. A complete left atrial ablation with a single bipolar radiofrequency device yields excellent clinical mid-term results.

Background— Coronary artery disease (CAD) screening is required before transcatheter aortic valve implantation (TAVR). Although invasive coronary angiography (CA) remains the gold standard for CAD assessment, computed tomographic CA (CTCA) could be a safe and effective noninvasive alternative for CAD screening in patients undergoing TAVR. Methods and Results— From November 2007 to May 2013, all patients undergoing TAVR at our institution were included in the study cohort. CTCA was used as first-line imaging tool for CAD screening. Invasive CA was performed when any of the following were present: coronary anatomy at CTCA was not evaluable and presence of significant CAD at CTCA. The primary objective was to compare major adverse cardiovascular and cerebrovascular events at 30 days and 1 year between patients who performed CTCA as only screening test and those who performed CTCA and invasive CA. Of 491 patients treated with TAVR, 375 (76.3%) performed only CTCA, whereas 116 (21.7%) underwent also CA. No differences were present in crude major adverse cardiovascular and cerebrovascular event rates at 30 days and 1 year between the 2 groups. After multivariable adjustment, CTCA performed alone was not associated with higher risk of MACE at 1 year of follow-up (hazard ratio, 0.89; 95% confidence interval, 0.49–1.60; P =0.69). Conclusions— CTCA performed as a routine noninvasive imaging tool in patients undergoing TAVR seems safe and effective allowing, with a single test, acquisition of information on aortic annulus anatomy, peripheral access sites, and evaluation of coronary anatomy.

Objectives This study sought to evaluate the impact of baseline activated clotting time (ACT)-guided heparin administration on major bleeding after transfemoral transcatheter aortic valve implantation (TAVI). Background Bleeding after TAVI is frequent and associated with unfavorable prognosis. Proper intraprocedural heparin dose administration may reduce the risk of potential overdosing in this frail study group. Methods Of the patients who underwent transfemoral TAVI in our center from November 1, 2007 to June 31, 2012, 362 were retrospectively analyzed. Because abnormally high baseline ACT values were noted, heparin was administered at the operator's discretion, according to baseline ACT (ACT-guided, n = 174) or patient's body weight (non-ACT-guided, n = 188). The primary study objective was 30-day major bleeding as defined by the Valve Academic Research Consortium criteria. Secondary objectives were any life-threatening, and minor bleeding, and other Valve Academic Research Consortium outcomes at 30 days. Results Bleeding occurred in 167 (46.1%) patients; of these, 76 (21.0%) had major bleeding. The ACT-guided group had a significantly lower occurrence of major (7.5% vs. 33.5%, p < 0.001), life-threatening (12.1% vs. 20.2%, p = 0.04), and any bleeding (25.9% vs. 64.9%, p < 0.001). Conversely, no differences were noted in the other study objectives. After adjustment for potential confounders, the protective odds ratio for ACT-guided therapy on major bleeding was 6.4 (95% confidence interval: 2.3 to 17.9; p < 0.001) at 30 days. Conclusions In our experience, heparin administration according to baseline ACT was correlated with a significantly lower occurrence of major bleeding in transfemoral TAVI. This strategy might be a useful tool in reducing bleeding in this high-risk study group. (C) 2014 by the American College of Cardiology Foundation OI Giustino, Gennaro/0000-0002-5400-9516

OBJECTIVES: The aim of this retrospective multicenter study was to assess how the development of transcatheter aortic valve implantation (TAVI) influenced the characteristics and outcomes of patients undergoing aortic valve procedures. METHODS: We reviewed 1395 patients who underwent isolated surgical aortic valve replacement (SAVR) or TAVI in three centres with a high-volume TAVI programme. Patients were divided into two groups: ‘Pre-TAVI’ (395 patients, 28.3%) and ‘Post-TAVI’ (1000 patients, 71.7%) operated on before and after the introduction of TAVI into clinical practice. We evaluated age, logistic EuroSCORE I (LES) and hospital mortality according to time periods and the procedure performed, whether SAVR or TAVI. RESULTS: ‘Post-TAVI’ patients were older (78.2 ± 7.8 vs 76.8 ± 6.7 years; P= 0.002) and with a significantly higher LES (17.8 ± 14.7 vs 9.1 ± 9.2%; P< 0.001) than ‘Pre-TAVI’ patients. Hospital mortality was not significantly different between groups (‘Pre-TAVI’ vs ‘Post-TAVI’: 2 vs 3.4%; P= 0.17). Of the 1000 ‘Post-TAVI’ patients, 605 (60.5%) underwent TAVI and 395 (39.5%), SAVR. Patients undergoing TAVI were older (79.9 ± 7.1 vs 75.5 ± 9.2 years; P< 0.001) and with a higher LES (22.9 ± 15.3 vs 9.7 ± 9.3%; P< 0.001) than ‘Post-TAVI’ SAVR patients, but their hospital mortality was similar (3.9 vs 2.5%; P= 0.22). LES was similar between ‘Pre-TAVI’ and ‘Post-TAVI’ SAVR patients (9.1 ± 9.2 vs 9.7 ± 9.3%; P= 0.26). Furthermore, we did not find significant differences in the overall hospital mortality between SAVR and TAVI patients: 2.3 vs 3.9%, P= 0.08. CONCLUSIONS: This analysis shows that the development of TAVI has caused an increase in the preoperative risk profile of patients scheduled for aortic valve procedures (SAVR or TAVI) without increasing hospital mortality.

Patients who undergo transcatheter aortic valve implantation are generally discharged on dual-antiplatelet therapy. However, many of these patients also have indications for anticoagulant therapy, and it is unclear what the best antithrombotic strategy is in these cases. Data from 360 patients who underwent transcatheter aortic valve implantation were retrospectively analyzed, of whom 60 (16.7%) had indications for anticoagulant treatment, mainly because of atrial fibrillation. The antithrombotic regimen was decided according to clinical evaluation of thrombotic and hemorrhagic risk; most of these patients (n = 43) were discharged with warfarin plus a single antiplatelet drug. Their outcomes were compared to those in a group with no indications for anticoagulation (n = 300) treated with dual-antiplatelet therapy. During the follow-up period (median 11 months), 53 patients (15%) died; mortality was not associated with antithrombotic regimen. The incidence of cerebral events or intracranial hemorrhage (4.6% and 1.1%, respectively) was low in the study population, and no significant differences were detected between groups; the bleeding rate was also unaffected by antithrombotic therapy. In conclusion, when anticoagulation is indicated after transcatheter aortic valve implantation, many variables must be taken into account. The most frequent scenario in this study was patients in atrial fibrillation, most of whom were discharged with warfarin plus a single antiplatelet medication. When bleeding was a concern, especially in the absence of coronary disease, warfarin alone was prescribed. These results suggest that this approach is safe, but data from larger, randomized studies are needed.

Background. Vascular and bleeding complications remain important complications in patients undergoing percutaneous transfemoral transcatheter aortic valve implantation (TF-TAVI). Platelets play an important role in bleeding events. Mean platelet volume (MPV) is an indicator of platelet activation. The objective of this study was to assess whether low MPV is an indicator of major vascular and bleeding complications following TF-TAVI.Methods. A retrospective cohort study of 330 subjects undergoing TF-TAVI implantation was performed. The primary study endpoint was the occurrence of combined safety endpoint (CSEP); secondary endpoints included major vascular complications and life-threatening bleeding. Endpoints were defined according to Valve Academic Research Consortium 2.Results. The CSEP at 30 days was reached in 30.9%; major vascular complications were observed in 14.9% while life-threatening bleeding occurred in 20.6%. Logistic Euroscore and MPV were independent predictors of CSEP. Predictors of vascular complications were female sex, previous myocardial infarction, red blood cell distribution width (RDW), and MPV while predictors of life-threatening bleeding were peripheral arterial disease, RDW, and MPV.Conclusion. A low baseline MPV was shown for the first time to be a significant predictor of CSEP, major vascular complications, and life-threatening bleeding following TF-TAVI.

"OBJECTIVE:. TAVI is the alternative option in pts with AS deemed ineligible for surgery. Although mortality and morbidity are measures to assess the effectiveness of treatments, quality of life (QOL) should be an additional target. We assessed clinical outcome and QOL in octogenarians following TAVI.. DESIGN:. All octogenarians with a risk profile considered by the Heart Team to be unacceptable for surgery entered in this registry. QOL was assessed by questionnaires concerning physical and psychic performance.. PATIENTS:. A hundred forty-five octogenarians (age: 84.7 ± 3.4 years; male: 48.3%) underwent TAVI for AS (97.2%) or isolated AR (2.8%). NYHA class: 2.8 ± 0.6; Logistic EuroScore: 26.1 ± 16.7; STS score: 9.2 ± 7.7.Echocardiographic assessments included AVA (0.77 ± 0.21 cm2), mean\/peak gradients (54.5 ± 12.2\/88 ± 19.5 mm Hg), LVEF (21%=EF ≤ 40%), sPAP (43.1 ± 11.6 mmHg).. INTERVENTIONS:. All pts underwent successful TAVI using Edward-SAPIEN valve (71.2%) or Medtronic CoreValve (28.8%).. MAIN OUTCOME MEASURES:. Rates of mortality at 30 days, 6 months and 1 year were 2.8%, 11.2% and 17.5%.. RESULTS:. At 16-month follow up, 85.5% survived showing improved NYHA class (2.8 ± 0.6 vs 1.5 ± 0.7; p

OBJECTIVES: Computed tomography (CT) is an increasingly utilized method for the evaluation of patient suitability for transcatheter aortic valve implantation (TAVI). The aim of this study was to analyse the role of CT in the choice of prosthesis and the prevention of residual aortic regurgitation (RAR). METHODS: From November 2007 to September 2010, 115 patients (median age 81 years, inter-quantile range (IQR) 76–85; median ejection fraction 55%, IQR 45–60; median logistic EuroSCORE 19.7, IQR 11.0–32.1) undergoing TAVI were evaluated with a pre-procedural CT. An aortic complex was evaluated with multi-planar reconstructions, and we defined significant early RAR as RAR ≥ 2, and prosthesis/annulus mismatch (PAM) as the ratio between prosthesis size and mean annular size. All analyses were conducted for the whole sample and then separately for the two types of prosthesis implanted. RESULTS: An Edwards-SAPIEN ® prosthesis was implanted in 62 patients (54.7%), and a Medtronic CoreValve ® in 52 (45.2%). Aortic annulus minimum and maximum diameters were 22.6 ± 2.1 and 26.0 ± 2.3 mm, respectively. The aortic annulus diameter and the length of the free edge of the aortic cusps were linearly related to a 1:1 ratio (P< 0.0001). Significant RAR (34 patients, 30%) appeared directly related to the annulus diameters (particularly maximum and medium diameters, P= 0.0003 and P= 0.0010, respectively) and cusp length (P= 0.0007) but inversely correlated with PAM (P= 0.0006). Prosthesis/annulus oversizing was associated with a reduction in RAR, with a cut-off of 7% as the limit below which RAR increases; moreover, we observed different cut-off values for the Edwards and CoreValve prostheses, although statistical significance was not reached for the CoreValve (respectively, 2% with P< 0.0001, 11% with P= 0.16). No association was found between PAM and possible PAM-related complications. CONCLUSIONS: CT evaluation prior to TAVI showed that RAR was directly correlated with aortic root dimensions (particularly maximum and medium annulus diameters and cusp lengths) and inversely correlated with PAM. Oversizing the prosthesis by at least 7% reduces the risk of RAR. CT is an essential and invaluable tool in the assessment of patients undergoing TAVI.

Background Limited real-world data comparing outcomes after transcatheter (TAVR) and surgical aortic valve replacement (SAVR) in intermediate-surgical-risk patients with aortic stenosis are available. Methods We identified 182 consecutive patients who underwent TAVR via the transfemoral (TF) route (November 2007-February 2011) and 111 moderate-to-high-risk historical case controls undergoing SAVR (August 2003-July 2008). Using propensity score matching based on clinical characteristics and surgical risk scores, we compared clinical outcomes in 111 matched patients. Valve Academic Research Consortium definitions were applied for end point adjudication. Results Baseline clinical characteristics, in particular Logistic European System for Cardiac Operative Risk Evaluation (23.2 +/- 15.1 vs 24.4 +/- 13.4) and Society of Thoracic Surgeons score (4.6 +/- 2.3 vs 4.6 +/- 2.6), were well matched between groups. Transfemoral TAVR was associated with more vascular complications (33.3% vs 0.9%, P < .001). On the other hand, acute kidney injury was more frequent after SAVR (8.1% vs 26.1%, P < .001). The rates of all-cause mortality in both TF-TAVR and SAVR groups was1.8% at 30 days (P = 1.00) and 6.4% and 8.1%, respectively, at 1 year (P = .80). At 1 year, the rate of cerebrovascular events was similar in the 2 groups (4.6% vs 9.1%, P = .19). Conclusions In this real-world cohort of intermediate-surgical-risk patients with aortic stenosis, TF-TAVR and SAVR were associated with similar mortality rates during follow-up but with a different spectrum of periprocedural complications. Furthermore, the survival rate after TF-TAVR in this group of elderly patients with intermediate Society of Thoracic Surgeons score was encouraging. (Am Heart J 2012;164:910-7.)

AIMS The aim of the study was to investigate the changes in quality of life (QoL) following transcatheter aortic valve implantation (TAVI) up to two years' follow-up. METHODS AND RESULTS One hundred consecutive patients (46 females, mean age 79.7 ± 6.1 years) with at least two years' follow-up who underwent TAVI in our institution, between November 2007 and September 2009, were enrolled in this study. Peak and mean aortic gradients were 87.8 ± 25.8 mmHg and 53.3 ± 15.4 mmHg, respectively. Mean log EuroSCORE was 27.9 ± 15.9. Patients had multiple comorbidities. All patients underwent a standardised prospective screening pathway, including QoL evaluation with the 36-item short-form health survey (SF-36v2(®)) and the Minnesota Living with Heart Failure Questionnaires (MLHFQ). The scores obtained preoperatively were compared with those obtained at two years' follow-up. An Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA, USA) was implanted in 67 patients (55 transfemoral and 12 transapical) and a CoreValve (Medtronic, Inc., Minneapolis, MN, USA) was implanted in 33 patients (26 transfemoral and seven transaxillary). Thirty-day mortality was 4%. Actuarial survival was 80.6 ± 4.1%, 72.6 ± 4.7% and 63.2 ± 6.3% at one, two and three years, respectively. Mean SF36-physical improved from 31.9 ± 8.8 to 51.5 ± 9.5 (p

AIMS To assess outcomes after transcatheter aortic valve implantation (TAVI) according to sex, with the two available valves and four recognised delivery approaches. METHODS AND RESULTS VARC outcomes are reported according to sex for 305 high-risk patients consecutively treated in our centre, via available access routes utilising the Edwards SAPIEN™/SAPIEN™ XT or the Medtronic CoreValve ReValving System® devices. Three hundred and five patients underwent TAVI: 52.1% male and 47.9% female. Females had a smaller body surface area (1.84±0.16 m² vs. 1.70±0.16 m²; p

Progressive multifocal leukoencephalopathy (PML) associated with polyomavirus JC (JCV) infection has been reported to be usually fatal in allogeneic hematopoietic SCT (HSCT) recipients. We present the case of a 19-year-old HSCT patient diagnosed with JCV-associated PML after prolonged immunosuppression for severe GVHD. No short-term neurological improvement was observed after antiviral treatment and discontinuation of immunosuppressive therapy. Donor-derived JCV Ag-specific CTLs were generated in vitro after stimulation with 15-mer peptides derived from VP1 and large T viral proteins. After adoptive CTL infusion, virus-specific cytotoxic cells were shown in the peripheral blood, JCV-DNA was cleared in the cerebrospinal fluid and the patient showed remarkable improvement. Adoptive T-lymphocyte therapy with JCV-specific CTLs was feasible and had no side effects. This case suggests that adoptive transfer of JCV-targeted CTLs may contribute to restore JCV-specific immune competence and control PML in transplanted patients.Bone Marrow Transplantation. Progressive multifocal leukoencephalopathy (PML) associated with polyomavirus JC (JCV) infection has been reported to be usually fatal in allogeneic hematopoietic SCT (HSCT) recipients. We present the case of a 19-year-old HSCT patient diagnosed with JCV-associated PML after prolonged immunosuppression for severe GVHD. No short-term neurological improvement was observed after antiviral treatment and discontinuation of immunosuppressive therapy. Donor-derived JCV Ag-specific CTLs were generated in vitro after stimulation with 15-mer peptides derived from VP1 and large T viral proteins. After adoptive CTL infusion, virus-specific cytotoxic cells were shown in the peripheral blood, JCV-DNA was cleared in the cerebrospinal fluid and the patient showed remarkable improvement. Adoptive T-lymphocyte therapy with JCV-specific CTLs was feasible and had no side effects. This case suggests that adoptive transfer of JCV-targeted CTLs may contribute to restore JCV-specific immune competence and control PML in transplanted patients. Bone Marrow Transplantation (2011) 46, 987-992; doi: 10.1038/bmt.2010.221; published online 4 October 2010

Objective: Trans-catheter aortic valve implantation (TAVI) is an alternative for patients not eligible for surgical aortic valve replacement. When peripheral access is not amenable by the transfemoral route (TF-TAVI), the most-used approaches are the trans-apical (TAp-TAVI) and the trans-axillary (TAx-TAVI). The aim of this study is to report the outcomes in a single-center series of consecutive patients treated by TAVI using the different approaches. Methods: From November 2007 to June 2010, 177 patients underwent TAVI by the same multispeciality valve team. TApTAVI was performed in the operative room, while TF-TAVI and TAx-TAVI were done in the catheterization laboratory. Follow-up was 100% complete (mean 6.0 6.8 months). Results: TF-TAVI, TAx-TAVI, and TAp-TAVI were performed in 140 (79.1%), 19 (10.7%), and 16 patients (9.1%), respectively. Thegroupswerenotdifferentintermsofage(p = 0.6),leftventricularejectionfraction(LVEF)(p = 0.6),Log-EuroSCORE(European System for Cardiac Operative Risk Evaluation) (p = 0.3), and Society of Thoracic Surgeons (STS) score (p = 0.7), while peripheral artery disease was higher in the TAp-TAVI and TAx-TAVI groups compared with the TF-TAVI group (p < 0.0001). The Charlson score was 10.7 14.9, 5.8 1.2, and 5.9 1.8 for TAp-TAVI, TAx-TAVI, and TF-TAVI, respectively (p = 0.02). In-hospital (30-day) mortality was 1.4% (2/140), 12.5% (2/16), and 5.3% (1/19) for TF, Tap, and TAx, respectively (p = 0.03). At follow-up, 6 months’ actuarial survival was 72.2 12.0%, 67.4 17.4%, and 88.4 3.1% for TAp-TAVI, TAx-TAVI, and TF-TAVI, respectively (p = 0.3). Conclusions: Similar to findings from recent, larger trials, patients undergoing TF-TAVI in high-risk patients had excellent 6-month results. Although TAx-TAVI was associated with lower hospital mortality, it shared the same 6-month outcomes of TAp-TAVI, probably due to a similar selection bias. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

OBJECTIVES: Our aim was to assess clinical outcome after transcatheter aortic valve implantation (TAVI) performed with the 2 commercially available valves with 3 delivery approaches selected in a stepwise fashion.BACKGROUND: Limited data exist on the results of a comprehensive TAVI program using different valves with transfemoral, transapical, and transaxillary approaches for treatment of severe aortic stenosis.METHODS: We report 30-day and 6-month outcomes of high-risk patients consecutively treated in a single center with either the Medtronic-CoreValve (MCV) (Medtronic, Minneapolis, Minnesota) or Edwards-SAPIEN valve (ESV) (Edwards Lifesciences, Irvine, California) delivered via the transfemoral or transaxillary approaches and ESV via the transapical approach.RESULTS: A total of 137 patients underwent TAVI: 107 via transfemoral (46 MCV and 61 ESV), 15 via transaxillary (12 MCV and 3 ESV), and 15 via transapical approach. After the transfemoral approach, the procedural success rate was 93.5%, and major vascular complication rate was 20.6%. No intra-procedural deaths occurred. The procedural success rates of transapical and transaxillary approaches were 86.6% and 93.3%, respectively. The 30-day mortality rate was 0.9% in transfemoral group and 13.3% in transapical, and no deaths occurred after transaxillary access. Cumulative death rate at 6 months was 12.2% in transfemoral, 26.6% in transapical, and 18.2% in transaxillary groups. At multivariable analysis, logistic European System for Cardiac Operative Risk Evaluation, body surface area, and history of cerebrovascular disease were significantly associated with an increased risk of major adverse cardiac and cerebrovascular events.CONCLUSIONS: Routine TAVI using both MCV and ESV with a selection of approaches is feasible and allows treatment of a wide range of patients with good overall procedural success rates and 30-day and 6-month outcomes.

Objective: The left atrial appendage is a significant source of cardioembolic thrombi. Open mitral valve surgery presents an opportune time to exclude this appendage from cardiovascular circulation. However, sparse randomized trial support exists for this concomitant procedure. We therefore designed a randomized controlled trial to assess the short- and long-term outcomes of concomitant left atrial appendage exclusion. This report details early outcomes of the pilot trial. Methods: Forty-three patients were randomized to either undergo concomitant suture exclusion of their left atrial appendage under direct vision or not during their open mitral valve surgery. Clinical and biochemical postoperative outcomes, including hemodynamic and hemostatic parameters, were analyzed. Results: There were no deaths in either group. The incidence of cerebrovascular events, myocardial infarction, respiratory failure, and acute renal injury were similar between groups; a composite outcome of 10 major postoperative complications occurred in 32% of the left atrial appendage exclusion group versus 38% of the control group (p = 0.75). Intensive care (median stay 2 days vs 1 day in the control group,p = 0.55) and hospital lengths of stay (median stay 9 days in both groups,p = 0.98) were also similarbetweengroups.Specifically, no additional hemodynamic alterations (need forintra-aortic balloonpumpin 1 vs2 patientsinthe control group, p = 0.61) or hemostatic complications (no re-operations for bleeding in either group, need for blood product transfusion in 2 vs 1 patient in the control group, p = 1.0) were noted in the left atrial appendage exclusion group. Conclusions: This pilot trial demonstrates the safety of and feasibility of a larger trial powered to detect clinically relevant short- and long-term outcomesof concomitant left atrial appendage exclusion with open mitral valve surgery. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.