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BACKGROUND Mitral valve (MV) repair with MitraClip system is a safe treatment option for high-risk patients with significant mitral regurgitation (MR). We aimed to characterize, by three-dimensional echocardiography (3D-E), changes occurring in MV after implantation of third generation MitraClip XTR device, with specific reference to the underlying MR mechanism (functional vs degenerative, FMR vs DMR). METHODS We prospectively enrolled 59 patients, who underwent intra-procedural 3D-E before and after device deployment. Three-D datasets were analyzed off-line, using a dedicated semiautomatic software, to obtain parametric quantification of mitral anatomy. RESULTS Post-procedural MR of mild or lesser degree was achieved in 40 patients (68%), with no differences between FMR and DMR (p 0.9). After MitraClip XTR implantation, the FMR group experienced an immediate annular resizing, with reduction of antero-posterior diameter (p 0.024) and sphericity index (p 0.017), next to a recovery of physiological saddle-shape, defined by lower non-planar angle (p ≤0.001) and higher annulus height to commissural width ratio (p ≤0.001). On the opposite, the DMR group revealed a significant decrease of maximum annular velocity (p 0.027), addressing a mechanic effect of the device deployment. Finally, baseline anterior mitral leaflet angle was found as an independent predictor of acute procedural result (OR 6.7, [CI 1.01-44.33], p 0.049). CONCLUSIONS MitraClip XTR implantation acts in restoring the original mitral geometry, with distinctive effects according to MR mechanism. Three-D parametric quantification of MV sheds new light on changes occurring in the valvular apparatus, and helps identifying possible new predictors of acute procedural success.

AIMS The Italian Society of Interventional Cardiology (GIse) registry Of Transcatheter treatment of mitral valve regurgitaTiOn (GIOTTO) was conceived in order to assess the safety and efficacy of MitraClip therapy in Italy. The aim of this study was to assess procedural and mid-term outcomes, and clinical and echocardiographic predictors of mid-term mortality after MitraClip therapy, stratifying the results according to the diagnosis of functional and degenerative mitral regurgitation (FMR vs. DMR). METHODS AND RESULTS Between January 2016 and March 2020, 1659 patients were prospectively included in the GIOTTO registry (FMR 59.4% vs. DMR 40.6%). Acute Mitral Valve Academic Research Consortium (MVARC) technical success was achieved in 97.2% of patients, without differences between FMR and DMR and with sustained results at 30 days. In the study population, all-cause mortality was 4.0%, 17.5% and 34.6% at 30 days, 1 year and 2 years, respectively. Cardiovascular death was the most frequent cause of mortality. Overall hospitalization rates were 6.3%, 23.4% and 31.7% at 30 days, 1 year and 2 years, respectively. The most frequent cause of hospitalization was heart failure, particularly in the first 30 days. FMR and MVARC structural and functional failure were strongly associated with 1-year mortality. Residual mitral regurgitation 1+ (rMR) was independently related to a reduced risk of 1-year mortality (hazard ratio 0.62; P = 0.005). Coherently, at 2-year follow up, FMR was associated with worse outcomes than DMR, and Kaplan-Meier all-cause mortality was related to rMR. CONCLUSIONS Functional mitral regurgitation aetiology affects 1-year mortality after MitraClip implantation, and differences in mortality and hospitalization rates between FMR and DMR can be observed within 2 years. Optimal rMR 1+ was correlated to a more favourable mid-term outcome, particularly in FMR.

OBJECTIVES We aimed to evaluate the use of bare metal stent (BMS) implantation in current percutaneous coronary intervention (PCI) era, focusing on indications for use and clinical outcomes. BACKGROUND Limited data on BMS usage in current clinical practice are available. METHODS All patients who underwent PCI with at least one BMS implantation in 18 Italian centers from January 1, 2013 to December 31, 2017, were included in our registry. Rates of BMS use and reasons for BMS implantations were reported for the overall study period and for each year. Primary outcomes were mortality, bleeding (Bleeding Academic Research Consortium-BARC and Thrombolysis in Myocardial Infarction-TIMI non-CABG definitions), and major adverse cardiac events (MACE) defined as the composite of all-cause and cardiac death, any myocardial infarction, target vessel revascularization, or any stent thrombosis. RESULTS Among 58,879 patients undergoing PCI in the study period, 2,117 (3.6%) patients (mean age 73 years, 69.7% males, 73.3% acute coronary syndrome) were treated with BMS implantation (2,353 treated lesions). The rate of BMS implantation progressively decreased from 10.1% (2013) to 0.3% (2017). Main reasons for BMS implantation were: ST-elevation myocardial infarction (STEMI) (23.1%), advanced age (24.4%), and physician's perception of high-bleeding risk (34.0%). At a mean follow-up of 2.2 ± 1.5 years, all-cause and cardiac mortality were 25.6 and 12.7%, respectively; MACE rate was 35.3%, any bleeding rate was 13.0% (BARC 3-5 bleeding 6.3%, TIMI non-CABG major bleeding 6.1%). CONCLUSION In a large, contemporary, real-world, multicenter registry, BMS use progressively reduced over the last 5 years. Main reasons for BMS implantation were STEMI, advanced age, and physician's perception of high-bleeding risk. High rates of mortality and MACE were observed in this real-world high-risk population.

OBJECTIVES To evaluate outcome and its predictors of bioprosthetic valve fracture (BVF) in patients undergoing valve-in-valve transcatheter aortic valve replacement (VIV-TAVR). BACKGROUND BVF is feasible and reduces transvalvular gradients in VIV-TAVR-procedures, but follow-up-data and information on factors influencing the outcome are missing. METHODS The 81 cases of BVF-VIV-TAVR were collected from 14 international centers. RESULTS Predominantly transcatheter heart valve (THV) was implanted first, followed by BVF. VARC-2 defined device success was 93%, most failures were attributed to residual high gradients. Mean gradients decreased from 37��������13���mmHg to 10.8��������5.9���mmHg (p��

OBJECTIVE This study sought to investigate the procedural and mid-term outcomes of transcatheter aortic valve implantation for failed surgical bioprostheses (TAVI-ViV) with Portico device. BACKGROUND Limited evidence coming from early experience on Portico system does not allow to fully assess safety and efficacy of this device in this ViV patients. METHODS From January 2016 up to June 2019, 56 consecutive patients undergoing TAVI-ViV with Portico were prospectively included in our institutional TAVI database. RESULTS The prevalent mechanism of failure was stenosis (58.9%); true internal diameter (ID) was

Objectives We report procedural and 30-day clinical outcomes following transcatheter aortic valve replacement (TAVR) with Lotus Valve system in a high-risk population. Background Lotus valve is a second-generation TAVR fully repositionable and retrievable device. RELEVANT (REgistry of Lotus valvE for treatment of aortic VAlve steNosis with Tavr) study is an Italian prospective multicentre registry. Methods Five major centers performing TAVR using Lotus participated. All high-risk symptomatic patients with severe aortic stenosis were evaluated by a heart team and screened for eligibility for TAVR. Primary end-points were procedural and 30-day mortality. Secondary endpoints included procedural and 30-day safety/effectiveness metrics according to Valve Academic Research Consortium (VARC)−2 criteria. Results Two hundred and twenty-five patients undergoing TAVR with Lotus were enrolled. Mean age was 82.6 ± 6.3 years, 51.6% females. Mean STS score for mortality was 8.3 ± 5.6. Procedural success was achieved in 98.7% of patients. All-cause mortality was 2.2% at discharge and 2.7% at 30-day. Stroke rate was 2.2% at discharge and 3.1% at 30-day. Patients requiring a new permanent pacemaker implantation were 30.7% at discharge and 31.8% at 30-day. Paravalvular regurgitation (PVR) was trace/mild in 99.1% of patients at discharge. Only two patients (0.9%) had moderate PVR at discharge and at 30-day, whereas none had severe PVR. Conclusions RELEVANT study showed that TAVR using Lotus, in a real-world population of patients with severe aortic stenosis at high surgical risk, was associated with excellent device success implantation and early safety according to VARC-2 definition. The pacemaker implantation rate was about a third of patients. © 2017 Wiley Periodicals, Inc.

The Portico system (St. Jude Medical, Minneapolis, MN, USA) consists of a self-expanding valve prosthesis and a delivery system designed for transcatheter aortic valve replacement (TAVR). We describe this system, its 10-steps implantation procedure, and provide tips and tricks based on our personal experience with this system.

Background The use of embolic protection devices ( EPD ) may theoretically reduce the occurrence of cerebral embolic lesions during transcatheter aortic valve implantation. Available evidence from single studies is inconclusive. The aim of the present meta‐analysis was to assess the safety and efficacy profile of current EPD . Methods and Results Major medical databases were searched up to December 2017 for studies that evaluated patients undergoing transcatheter aortic valve implantation with or without EPD . End points of interest were 30‐day mortality, 30‐day stroke, the total number of new lesions, the ischemic volume per lesion, and the total volume of lesions. Eight studies involving 1285 patients were included. The EPD delivery success rate was reported in all studies and was achieved in 94.5% of patients. The use of EPD was not associated with significant differences in terms of 30‐day mortality (odds ratio 0.43 [0.18–1.05], P =0.3) but it was associated with a lower rate of 30‐day stroke (odds ratio 0.55 [0.31–0.98], P =0.04). No differences were detected with respect to the number of new lesions (standardized mean difference −0.19 [−0.71 to 0.34], P =0.49). The use of EPD was associated with a significantly smaller ischemic volume per lesion (standardized mean difference, −0.52 [−0.85 to −0.20], P =0.002) and smaller total volume of lesions (standardized mean difference, −0.23 [−0.42 to −0.03], P =0.02). Conclusions The use of EPD is not associated with a reduced rate of mortality and new ischemic cerebral lesions. The use of EPD during transcatheter aortic valve implantation seems to be associated with a lower 30‐day stroke rate, although this result is driven by a single nonrandomized study. The use of EPD is associated with a smaller volume of ischemic lesions, and smaller total volume of ischemic lesions.

Objectives/Background To compare the 1-year clinical outcomes after implantation of the amphilimus, polymer-free stent (Cre8) versus new generation everolimus-eluting stents (EESs) in a real-world patient registry. Methods A total of 187 consecutive patients treated with Cre8 between January 2011 and August 2013 in four Italian centers were included. These were propensity matched with 150 patients treated with new generation EES during the same period. Primary outcome was 1-year major adverse cardiovascular events (MACE), defined as all-cause death, myocardial infarction, and target vessel revascularization. Results Both groups had similar baseline characteristics, including diabetes (28% Cre8 vs. 27.3% EES, P = 0.972) and previous percutaneous coronary intervention (56% Cre8 vs. 58% EES, P = 0.726). There was a higher prevalence of B2/C lesions in the EES group (70.1% vs. 83.8%, P

The number of percutaneous coronary interventions (PCI) is increasing worldwide. Follow-up strategies after PCI are extremely heterogeneous and can greatly affect the cost of medical care. Of note, clinical evaluations and non-invasive exams are often performed to low risk patients. In the present consensus document, practical advises are provided with respect to a tailored follow-up strategy on the basis of patients' risk profile. Three strategies follow-up have been defined and types and timing of clinical and instrumental evaluations are reported. Clinical and interventional cardiologists, cardiac rehabilitators, and general practitioners, who are in charge to manage post-PCI patients, equally contributed to the creation of the present document.

Background The impact of female sex on mortality after transcatheter aortic valve implantation (TAVI) is controversial. Post-procedural aortic regurgitation (AR) ≥ 2 has been associated with poor outcomes. Whether sex differences in post-procedural AR ≥ 2 could contribute to a mortality difference between women and men is not known. Methods Six hundred fifty-six patients, women (53.1%), men (46.9%), with aortic stenosis underwent TAVI with the CoreValve system (92.8%) or the Edwards SAPIEN valve system (7.2%). AR was graded semiquantitatively as 0 = none, 1 = trivial, 2 = mild, 3 = moderate, and 4 = severe. The incidence of post-procedural AR ≥ 2 was reported. Results Procedural success was similar in women as compared to men (97.9 vs 96.7%, P = 0.32). Post-procedural AR ≥ 2 occurred less frequently in women than in men (20.9 vs 29.6%, P = 0.01). After a median follow-up of 434 days, all-cause mortality tended to be lower in women than in men (20.7 vs 26.6%, logrank P = 0.10), and was significantly higher in patients with AR ≥ 2 than in those without (34.8 vs 19.7%, logrank P

Drug-coated balloons are a new tool for the treatment of patients with coronary artery disease. The main feature of this technology is a rapid and homogenous transfer of an antiproliferative drug (paclitaxel) to the vessel wall just at the time of balloon inflation, when neointimal proliferation, in response to angioplasty, is the highest. Moreover, drug-coated balloons share adjuntive advantages over stents: the absence of permanent scaffold and polymer, the respect of the original coronary anatomy, and limited inflammatory stimuli, thereby allowing for short-term dual antiplatelet therapy. To this day, a lot of devices are available in the market, with limited scientific data for the vast majority of them. Thus, the Italian scientific society of interventional cardiologists GISE decided to coordinate the efforts of a group of reknown experts on the field, in order to obtain a Position Paper on the correct use of drug-coated balloons in all the settings of coronary artery disease, giving a class of indication to each one, based on the clinical evidence. This Position Paper represents a quick reference for operators, investigators, and manufactures to promote the understanding and the correct use of the drug-coated balloon technology in everyday clinical practice. © 2013 Wiley Periodicals, Inc.

The neurotrophin system has a role in skeletal muscle biology. Conditional depletion of BDNF in mouse muscle precursor cells alters myogenesis and regeneration in vivo . However, the expression, localization and function of BDNF in human skeletal muscle tissue is not known, so the relevance of the rodent findings for human muscle are unknown. Here we address this by combining ex vivo histological investigations on human biopsies with in vitro analyses of human primary myocytes. We found that BDNF was expressed by precursor and differentiated cells both in vitro and in vivo . Differential analysis of BDNF receptors showed expression of p75NTR and not of TrkB in myocytes, suggesting that the BDNF–p75NTR axis is predominant in human skeletal muscle cells. Several in vitro functional experiments demonstrated that BDNF gene silencing or protein blockade in myoblast cultures hampered myogenesis. Finally, histological investigations of inflammatory myopathy biopsies revealed that infiltrating immune cells localized preferentially near p75NTR ‐positive regenerating fibres and that they produced BDNF . In conclusion, BDNF is an autocrine factor for skeletal muscle cells and may regulate human myogenesis. Furthermore, the preferential localization of BDNF ‐producing immune cells near p75NTR ‐positive regenerating myofibres suggests that immune cell‐derived BDNF may sustain tissue repair in inflamed muscle. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Transcatheter aortic valve implantation (TAVI) for failed surgical bioprostheses, or "valve-in-valve" implantation, is a therapeutic option for high-risk patients. While coronary occlusion during TAVI for native aortic stenosis has been described, in the setting of valve-in-valve implantation the bioprosthetic posts may be protective against this complication. We describe the first two cases of coronary occlusion following valve-in-valve therapy, both occurring during treatment of degenerated Mitroflow bioprostheses. Aortic root anatomy, coronary ostial position, and the specifics of the bioprosthetic valve type need to be considered in assessing and preventing this rare complication.

The TAXUS OLYMPIA registry is a prospective, global, post-approval program designed to collect clinical outcome data through 1 year from patients receiving the TAXUS Liberté paclitaxel-eluting stent in routine interventional cardiology practice.The thin-strut TAXUS Liberté stent has been studied in ongoing clinical trials with specific inclusion/exclusion criteria.Between September 2005 and April 2007, a total of 21,954 patients from 365 sites in 57 countries eligible to receive a TAXUS Liberté stent were enrolled in the TAXUS OLYMPIA registry. Baseline characteristics and procedure patterns were collected and clinical follow-up is available for 1 year. The primary endpoint was the composite cardiac event (cardiac death, MI, and reintervention of the target vessel) rate related to the TAXUS Liberté stent at 1 year. All cardiac events were monitored and all endpoints were independently adjudicated.Complex patients and lesions were prevalent, including: 27% medically-treated diabetes, 58% ACC/AHA type B2/C lesions, 32% multiple stenting, 13% long lesions (28 mm), and 10% small vessels (2.5 mm). At 1 year, the composite cardiac event rate was 4.4%, including 1.4% cardiac death, 1.0% MI, and 3.2% TVR. Stent thrombosis (ST, angiographically confirmed) occurred in 0.8% of patients, with 0.4% ST occurring30 days postprocedure. The composite cardiac event rate related to the TAXUS Liberté stent was 3.8% at 1 year.Low 1-year cardiac event rates were reported with TAXUS Liberté in a broad spectrum of patients, thereby confirming the technical and clinical performance of this stent in a "real-world" setting.

Prenatal stress represents a well-established experimental protocol resembling some features of schizophrenia, including deficits in social interactions, disruption of prepulse inhibition and enhanced response to psychomotor stimulants. In order to evaluate molecular changes that could participate in long-lasting effects on brain function, we analysed the effects of prenatal stress on the expression of brain-derived neurotrophic factor (BDNF), an important molecular determinant of synaptic plasticity and cellular homeostasis, in adult male rats under basal conditions as well as in response to a chronic stress. The main finding is that BDNF expression is reduced in the prefrontal cortex and striatum of prenatally stressed rats. Furthermore, when exposed to chronic stress in adulthood, these rats display an altered regulation of BDNF expression in these brain structures, implying that adverse life events during gestation may interfere with the expression and function of this neurotrophin at adulthood in a region-specific manner. The dysregulation of corticostriatal BDNF expression might thus contribute to permanent alterations in brain functions leading to heightened susceptibility to psychiatric disorders.

Brain-derived neurotrophic factor (BDNF) promotes a variety of neuromodulatory processes during development as well as in adulthood. This neurotrophin has been associated with synaptic plasticity, suggesting that its regulation may represent one of the mechanisms through which psychotropic drugs alter brain function. Because reduced glutamatergic function represents a major feature of schizophrenia, we investigated the effects of the concomitant administration of haloperidol or olanzapine with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on BDNF expression. MK-801 reduces the hippocampal expression of the neurotrophin; this effect was exacerbated by haloperidol, but it was normalized by olanzapine. Our data reveal a fine tuning of BDNF biosynthesis and a differential modulation by antipsychotic drugs when NMDA-mediated transmission is reduced, suggesting that haloperidol and olanzapine can produce different effects on brain plasticity through the modulation of BDNF expression.

We hereby present the case of a patient with severe aortic stenosis who underwent in her previous medical history a mitral valve replacement with a mechanical valve (Omnicarbon 27), and progressively developed a severe aortic stenosis. This patient was judged inoperable and then scheduled for CoreValve Revalving System implantation. Despite a good positioning of the CoreValve, an acute, severe mitral regurgitation developed soon after implantation as a consequence of the impaired movement of the mitral prosthesis leaflet. A condition of cardiogenic shock quickly developed. A good mitral prosthesis function was restored disengaging the CoreValve from the aortic annulus. After few months, the patients underwent successful Edwards-Sapien valve implantation through the Corevalve. This case strongly demonstrates how much a careful evaluation of the features of the mitral prosthesis and patient anatomy is crucial to select which specific transcatheter bioprosthesis would better perform.

The article reports the cases of two patients with severe coronary artery disease and associated recurrent sustained ventricular tachycardia successfully treated with radiofrequency catheter ablation. In the first patient, two different types of ventricular tachycardia (one incessant) were eliminated. In all procedures, an area of slow conduction critical for tachycardia maintenance was localized by endocardial mapping techniques. Radiofrequency energy delivered to this area could permanently modify the anatomical substrate of the arrhythmia. After single follow-ups of 19, 14, and 13 months regarding the arrhythmic entities, the patients are well and free from spontaneous recurrences.