A streamlined pathway for transcatheter aortic valve implantation: the BENCHMARK study.

BACKGROUND AND AIMS: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries. METHODS: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety. RESULTS: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%). CONCLUSIONS: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety.

The PIGTAIL paradigm for a fast and safe transfemoral transcatheter aortic valve replacement.

Transfemoral transcatheter aortic valve replacement is the preferred primary access route whenever possible. Despite advancements in expertise and delivery system profiles, complications associated with the primary femoral access still significantly affect procedural morbidity and outcomes. The current standard for accurate main access planning involves proper preprocedural evaluation guided by computed tomography. Several baseline clinical and anatomical features serve as predictors for the risk of vascular injury occurring during or after transcatheter aortic valve replacement. In this paper, we aimed at reviewing the most up-to-date knowledge of the topic for a safe transfemoral access approach according to a paradigm we have called "PIGTAIL."

Treatment of late paravalvular regurgitation after transcatheter aortic valve implantation: prognostic implications.

AIMS: Paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI) is associated with increased morbidity and mortality. The effect of transcatheter interventions to treat PVR after the index TAVI was investigated. METHODS AND RESULTS: A registry of consecutive patients who underwent transcatheter intervention for ≥ moderate PVR after the index TAVI at 22 centers. The principal outcomes were residual aortic regurgitation (AR) and mortality at 1 year after PVR treatment. A total of 201 patients were identified: 87 (43%) underwent redo-TAVI, 79 (39%) plug closure, and 35 (18%) balloon valvuloplasty. Median TAVI-to-re-intervention time was 207 (35; 765) days. The failed valve was self-expanding in 129 (63.9%) patients. The most frequent devices utilized were a Sapien 3 valve for redo-TAVI (55, 64%), an AVP II as plug (33, 42%), and a True balloon for valvuloplasty (20, 56%). At 30 days, AR ≥ moderate persisted in 33 (17.4%) patients: 8 (9.9%) after redo-TAVI, 18 (25.9%) after plug, and 7 (21.9%) after valvuloplasty (P = 0.036). Overall mortality was 10 (5.0%) at 30 days and 29 (14.4%) at 1 year: 0, 8 (10.1%), and 2 (5.7%) at 30 days (P = 0.010) and 11 (12.6%), 14 (17.7%), and 4 (11.4%) at 1 year (P = 0.418), after redo-TAVI, plug, and valvuloplasty, respectively. Regardless of treatment strategy, patients in whom AR was reduced to ≤ mild had lower mortality at 1 year compared with those with AR persisting ≥ moderate [11 (8.0%) vs. 6 (21.4%); P = 0.007]. CONCLUSION: This study describes the efficacy of transcatheter treatments for PVR after TAVI. Patients in whom PVR was successfully reduced had better prognosis. The selection of patients and the optimal PVR treatment modality require further investigation.

Amulet or Watchman Device for Percutaneous Left Atrial Appendage Closure: Primary Results of the SWISS-APERO Randomized Clinical Trial.

BACKGROUND: No study has so far compared Amulet with the new Watchman FLX in terms of residual left atrial appendage (LAA) patency or clinical outcomes in patients undergoing percutaneous LAA closure. METHODS: In the investigator-initiated SWISS APERO trial (Comparison of Amulet Versus Watchman/FLX Device in Patients Undergoing Left Atrial Appendage Closure), patients undergoing LAA closure were randomly assigned (1:1) open label to receive Amulet or Watchman 2.5 or FLX (Watchman) across 8 European centers. The primary end point was the composite of justified crossover to a nonrandomized device during LAA closure procedure or residual LAA patency detected by cardiac computed tomography angiography (CCTA) at 45 days. The secondary end points included procedural complications, device-related thrombus, peridevice leak at transesophageal echocardiography, and clinical outcomes at 45 days. RESULTS: Between June 2018 and May 2021, 221 patients were randomly assigned to Amulet (111 [50.2%]) or Watchman (110 [49.8%]), of whom 25 (22.7%) patients included before October 2019 received Watchman 2.5, and 85 (77.3%) patients received Watchman FLX. The primary end point was assessable in 205 (92.8%) patients and occurred in 71 (67.6%) patients receiving Amulet and 70 (70.0%) patients receiving Watchman, respectively (risk ratio, 0.97 [95% CI, 0.80-1.16]; P=0.713). A single justified crossover occurred in a patient with Amulet who fulfilled LAA patency criteria at 45-day CCTA. Major procedure-related complications occurred more frequently in the Amulet group (9.0% versus 2.7%; P=0.047) because of more frequent bleeding (7.2% versus 1.8%). At 45 days, the peridevice leak rate at transesophageal echocardiography was higher with Watchman than with Amulet (27.5% versus 13.7%, P=0.020), albeit none was major (ie, >5 mm), whereas device-related thrombus was detected in 1 (0.9%) patient with Amulet and 3 (3.0%) patients with Watchman at CCTA and in 2 (2.1%) and 5 (5.5%) patients at transesophageal echocardiography, respectively. Clinical outcomes at 45 days did not differ between the groups. CONCLUSIONS: Amulet was not associated with a lower rate of the composite of crossover or residual LAA patency compared with Watchman at 45-day CCTA. Amulet, however, was associated with lower peridevice leak rates at transesophageal echocardiography, higher procedural complications, and similar clinical outcomes at 45 days compared with Watchman. The clinical relevance of CCTA-detected LAA patency requires further investigation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03399851.

Prosthesis-patient mismatch after transcatheter implantation of contemporary balloon-expandable and self-expandable valves in small aortic annuli.

BACKGROUND: Evidence of clinical impact of PPM after TAVI is conflicting and might vary according to the type of valve implanted. AIMS: To assess the clinical impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI) with balloon-expandable (BEV) and self-expandable valves (SEV) in patients with small annuli. METHODS: TAVI-SMALL 2 enrolled 628 patients in an international retrospective registry, which included patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm2 ) treated with transfemoral TAVI at 16 high-volume centers between 2011 and 2020. Analyses were performed comparing patients with less than moderate (n = 452), moderate (n = 138), and severe PPM (n = 38). Primary endpoint was incidence of all-cause mortality. Predictors of all-cause mortality and PPM were investigated. RESULTS: At a median follow-up of 380 days (interquartile range: 210-709 days), patients with severe PPM, but not moderate PPM, had an increased risk of all-cause mortality when compared with less than moderate PPM (log-rank p = 0.046). Severe PPM predicted all-cause mortality in patients with BEV (hazard ratio [HR]: 5.20, 95% confidence interval [CI]: 1.27-21.2) and intra-annular valves (IAVs, HR: 4.23, 95% CI: 1.28-14.02), and it did so with borderline significance in the overall population (HR: 2.89, 95% CI: 0.95-8.79). Supra-annular valve (SAV) implantation was the only predictor of severe PPM (odds ratio: 0.33, 95% CI: 0.13-0.83). CONCLUSIONS: Patients with small aortic annuli and severe PPM after TAVI have an increased risk of all-cause mortality at early term follow-up, especially after IAV or BEV implantation. TAVI with SAV protected from severe PPM.

Postprocedural trans-mitral gradient in patients with degenerative mitral regurgitation undergoing mitral valve transcatheter edge-to-edge repair.

BACKGROUND: The relationship between high postprocedural mean gradient (ppMG) and clinical events following mitral valve transcatheter edge-to-edge repair (MV-TEER) in patients with degenerative mitral regurgitation (DMR) is still debated. AIM: The purpose of this study was to evaluate the effect of elevated ppMG after MV-TEER on clinical events in patients with DMR at 1-year follow-up. METHODS: The study included 371 patients with DMR treated with MV-TEER enrolled in the "Multi-center Italian Society of Interventional Cardiology (GISE) registry of trans-catheter treatment of mitral valve regurgitation" (GIOTTO) registry. Patients were stratified in tertiles according to ppMG. Primary endpoint was a composite of all-cause death and hospitalization due to heart failure at 1-year follow-up. RESULTS: Patients were stratified as follows: 187 with a ppMG ≤ 3 mmHg, 77 with a ppMG > 3/=4 mmHg, and 107 with a ppMG > 4 mmHg. Clinical follow-up was available in all subjects. At multivariate analysis, neither a ppMG > 4 mmHg nor a ppMG ≥ 5 mmHg were independently associated with the outcome. Notably, the risk of elevated residual MR (rMR > 2+) was significantly higher in patients belonging to the highest tertile of ppMG (p = 0.009). The association of ppMG > 4 mmHg and rMR ≥ 2+ was strongly and independently associated with adverse events (hazard ratio: 1.98; 95% confidence interval: [1.10-3.58]). CONCLUSIONS: In a real-world cohort of patients suffering DMR and treated with MV-TEER, isolated ppMG was not associated with the outcome at 1-year follow-up. A high proportion of patients showed both elevated ppMG and rMR and their combination appeared to be a strong predictor of adverse events.

Predictors of optimal procedural result after transcatheter edge-to-edge mitral valve repair in secondary mitral regurgitation.

BACKGROUND: Procedural success after transcatheter edge-to-edge mitral valve repair (TEER) is defined as a reduction of mitral regurgitation (MR) degree to

Prognostic significance of right ventricle to pulmonary artery coupling in patients with mitral regurgitation treated with the MitraClip system.

OBJECTIVES: To evaluate the prognostic impact of baseline tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio, as an expression of the right ventricle-pulmonary artery (RV-PA) coupling, in patients with mitral regurgitation (MR) treated with the MitraClip. BACKGROUND: Impaired RV to PA coupling is considered a marker of RV dysfunction. METHODS: From February 2016 to February 2020, a total of 165 patients were evaluated and stratified in two groups according to a prespecified value of TAPSE/PASP ratio ≤ 0.36. RESULTS: The median patients' age was 79 (men: 62.4%). Sixty-three patients (38.1%) presented TAPSE/PASP ≤ 0.36 and were then compared with patients with TAPSE/PASP > 0.36. Functional MR etiology was more frequent in TAPSE/PASP ≤ 0.36 (71.4%; p = 0.046). Acute technical success was achieved in 92.7% of the population, without any significant difference between the two groups of study and with sustained results at 30-day (device success: 85.5%; procedural success: 84.8%). On multivariate Cox regression analysis, after correction for body mass index, chronic kidney disease and left ventricle ejection fraction ≥30% but <50%, TAPSE/PASP ≤ 0.36 remained a sustained predictor of mortality and hospitalization for heart failure at one year after MitraClip (hazard ratio: 3.87; 95% confidence interval: 1.83-8.22; p ≤ 0.001). Kaplan-Meier all-cause mortality and heart failure hospitalization rates at one year were consequently higher in patients with TAPSE/PASP ≤ 0.36 (39.4% vs. 14.8%; log-rank p ≤ 0.001). CONCLUSION: Baseline TAPSE/PASP ratio seems independently associated with all-cause mortality and heart failure hospitalization after MitraClip both in functional and degenerative MR.

Next-generation balloon-expandable Myval transcatheter heart valve in low-risk aortic stenosis patients.

OBJECTIVES: We aimed to describe hemodynamic performance and clinical outcomes at 30-day follow-up of the balloon-expandable (BE) Myval transcatheter heart valve (THV) in low-risk patients. BACKGROUND: The results of the next-generation BE Myval THV in low-risk aortic stenosis (AS) patients are still unknown. METHODS: Retrospective registry performed in nine European centers including patients with low predicted operative mortality risk according to Society of thoracic surgeons (STS) and European system for cardiac operative risk evaluation (EuroSCORE-II) scores. RESULTS: Between September 2019 and February 2021, a total of 100 patients (51% males, mean age 80 ± 6.5 years) were included. Mean STS score and EuroSCORE-II were 2.4 ± 0.8% and 2.2 ± 0.7%, respectively. Intermediate sizes were used in 39% (21.5 mm: 8%, 24.5 mm: 15%, 27.5 mm: 15%). There were no cases of valve embolization, coronary artery occlusion, annulus rupture, or procedural death. A definitive pacemaker implantation was needed in eight patients (8%). At 30-day follow-up aortic valve area (0.7 ± 0.2 vs. 2.1 ± 0.6 cm2 ) and mean aortic valve gradient (43.4 ± 11.1 vs. 9.0 ± 3.7 mmHg) improved significantly (p < 0.001). Moderate aortic regurgitation occurred in 4%. Endpoints of early safety and clinical efficacy were 3 and 1%, respectively. CONCLUSIONS: Hemodynamic performance and 30-day clinical outcomes of the BE Myval THV in low-risk AS patients were favorable. Longer-term follow-up is warranted.

A patient-specific algorithm to achieve commissural alignment with Acurate Neo: The sextant technique.

AIMS: The aim of this proof-of-concept study was to investigate safety and efficacy of a CT-scan based patient-specific algorithm to maximize coronary clearance and secondarily to achieve anatomically correct commissural alignment with the Acurate Neo device. METHOD AND RESULTS: A total of 45 consecutive patients undergoing TAVR with the Acurate Neo THV were prospectively enrolled in the study. Mean age was 81.6 ± 5.5 years, mean STS score was 6.1 ± 3.7. Device success rate was 100%. Aim of the technique was to rotationally deploy the TAVR device with a commissure lying on the bisector between the coronary ostia as calculated on the pre-procedural CT-scan. At post-TAVR CT-scan, coronary clearance was achieved in 98% of patients with no cases of severe coronary artery overlap. In 42 out of 45 patients, THV was aligned or, at most, mildly misaligned; there were 2 cases of moderate misalignment without any case of severe misalignment. Post-TAVR selective coronary artery engagement was attempted and succeeded in all patients (100%). CONCLUSION: Our CT-scan based patient-specific algorithm is safe and proven to be effective in avoiding coronary artery overlap and providing commissural alignment with Acurate Neo in all treated patients.

One-year safety and efficacy profile of transcatheter aortic valve-in-valve implantation with the portico system.

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 <21 mm in 71.4% of cases. Device success rate were 69.6% with 14 (25%) patients showing a residual gradient ≥20 mmHg, 2 (3.6%) a PVL ≥ moderate and 1 (1.8%) required a second THV implantation due to device embolization. At 1-year follow-up 5 patients (8.9%) died whereas moderate SVD was reported in 2 (3.6%). Patients with a post-procedural mean gradient ≥20 mmHg showed a significantly higher rate of CV hospitalization (21.4% vs. 2.4%, p = .02) whereas no differences in procedural and 1-year outcomes were noticed according to true ID diameter or degeneration mode. Chimney stenting (ChT) was performed in 23 (41%) patients without significant differences in procedural and 1-year outcomes compared to non-ChT group. CONCLUSIONS: TAVI-ViV with Portico valve was associated with good procedural and 1-year outcomes, even in patients with features of high procedural and anatomical complexity.

Impact of aortic angle on transcatheter aortic valve implantation outcome with Evolut-R, Portico, and Acurate-NEO.

OBJECTIVES: To investigate paravalvular leak (PVL) and devices success rates according to aortic angle (AA) in patients undergoing transcatheter aortic valve implantation (TAVI) with three new-generation self-expanding devices. BACKGROUND: The impact of aortic angle (AA) on TAVI device success and PVL rates is controversial. METHODS: This retrospective study included 392 patients submitted to TAVI for severe aortic stenosis with Portico, Evolut-R and Acurate-NEO, and available AA measurements at computed tomography (CT) angiography. AA was calculated from the implantation projection and was defined as the angle between the plane of aortic annulus and an ideal horizontal plane. Aorta was defined horizontal if AA>57° (75th percentile). RESULTS: In the horizontal group, the rates of moderate/severe PVL was higher in the Evolut-R group (20.8%), which was also characterized by a lower implant compared to that of Acurate-NEO, whereas device success was comparable among the three devices. AA was a significant predictor of moderate/severe PVLs (AUC 0.72, p = .002) only in the Evolut-R population. On multivariate analysis, calcium volume 850HU, bicuspid aortic valve, and implantation depth at the level of left coronary cusp were independent predictors of moderate/severe PVL. On univariate analysis in the horizontal aorta population, implantation depth was confirmed among the most significant predictors of moderate/severe PVL. CONCLUSIONS: Despite comparable device success rates, horizontal aorta represented a technical challenge only in the Evolut-R subgroup, which showed higher rates of moderate/severe PVL than Portico and Acurate-NEO, and was associated with a low implant.

Timing of Impella implantation and outcomes in cardiogenic shock or high-risk percutaneous coronary revascularization.

OBJECTIVE: To evaluate the role of the microaxial percutaneous mechanical circulatory support device (Impella® pump) implantation pre-percutaneous coronary intervention (PCI) versus during/after PCI in cardiogenic shock (CS) and high-risk PCI populations. BACKGROUND: A better understanding of the safety and effectiveness of the Impella and the role of timing of this support initiation in specific clinical settings is of utmost clinical relevance. METHODS: A total of 365 patients treated with Impella 2.5/CP in the 17 centers of the IMP-IT Registry were included. Through propensity-score weighting (PSW) analysis, 1-year clinical outcomes were assessed separately in CS and HR-PCI patients, stratified by timing of Impella support. RESULTS: Pre-procedural insertion was associated with an improvement in 1-year survival in patients with CS due to acute myocardial infarction (AMI) treated with PCI (p = .04 before PSW, p = .009 after PSW) and HR-PCI (p < .01 both before and after PSW). Among patients undergoing HR-PCI, early Impella support was also associated with a lower rate of the composite of mortality, re-hospitalization for heart failure, and need for left-ventricular assist device/heart transplantation at 1-year (p = .04 before PSW, p = .01 after PSW). Furthermore, Impella use during/after PCI was associated with an increased in-hospital life-threatening and severe bleeding among patients with AMI-CS receiving PCI (7 vs. 16%, p = .1) and HR-PCI (1 vs. 9%, p = .02). CONCLUSIONS: Our findings suggested a survival benefit and reduced rates of major bleeding when a pre-PCI Impella implantation instead of during-after procedure was used in the setting of HR-PCI and AMI-CS.

Long-term clinical outcome and performance of transcatheter aortic valve replacement with a self-expandable bioprosthesis.

AIMS: In the last decade, transcatheter aortic valve (TAV) replacement determined a paradigm shift in the treatment of patients with severe symptomatic aortic stenosis. Data on long-term TAV performance are still limited. We sought to evaluate the clinical and haemodynamic outcomes of the CoreValve self-expandable valve up to 8-year follow-up (FU). METHODS AND RESULTS: Nine hundred and ninety inoperable or high-risk patients were treated with the CoreValve TAV in eight Italian Centres from June 2007 to December 2011. The median FU was 4.4 years (interquartile range 1.4-6.7 years). Longest FU reached 11 years. A total of 728 died within 8-year FU (78.3% mortality from Kaplan-Meier curve analysis). A significant functional improvement was observed in the majority of patients and maintained over time, with 79.3% of surviving patients still classified New York Heart Association class ≤ II at 8 years. Echocardiographic data showed that the mean transprosthetic aortic gradient remained substantially unchanged (9 ± 4 mmHg at discharge, 9 ± 5 mmHg at 8 years, P = 0.495). The rate of Grade 0/1 paravalvular leak was consistent during FU with no significant change from post-procedure to FU ≥5 years in paired analysis (P = 0.164). Structural valve deterioration (SVD) and late bioprosthetic valve failure (BVF) were defined according to a modification of the 2017 EAPCI/ESC/EACTS criteria. In cumulative incidence functions at 8 years, moderate and severe SVD were 3.0% [95% confidence interval (CI) 2.1-4.3%] and 1.6% (95% CI 0.6-3.9%), respectively, while late BVF was 2.5% (95% CI 1.2-5%). CONCLUSION: While TAVs are questioned about long-term performance and durability, the results of the present research provide reassuring 8-year evidence on the CoreValve first-generation self-expandable bioprosthesis.

TFEB activation restores migration ability to Tsc1-deficient adult neural stem/progenitor cells.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). mTOR inhibitors are now considered the treatment of choice for TSC disease. A major pathological feature of TSC is the development of subependymal giant cell astrocytomas (SEGAs) in the brain. Nowadays, it is thought that SEGAs could be a consequence of aberrant aggregation and migration of neural stem/progenitor cells (NSPCs). Therefore, reactivation of cell migration of NSPCs might be the crucial step for the treatment of patients. In order to identify potential in vitro targets activating migration, we generated Tsc1-deficient NSPCs. These cells summarize most of the biochemical and morphological characteristics of TSC neural cells, such as the mTORC1 activation, the formation of abnormally enlarged astrocytes-like cells, the reduction of autophagy flux and the impairment of cell migration. Moreover, nuclear translocation, namely activation of the transcription factor EB (TFEB) was markedly impaired. Herein, we show that compounds such as everolimus, ionomycin and curcumin, which directly or indirectly stimulate TFEB nuclear translocation, restore Tsc1-deficient NSPC migration. Our data suggest that reduction of TFEB activation, caused by mTORC1 hyperactivation, contributes to the migration deficit characterizing Tsc1-deficient NSPCs. The present work highlights TFEB as a druggable protein target for SEGAs therapy, which can be additionally or alternatively exploited for the mTORC1-directed inhibitory approach.

Emergency trans-catheter coronary intervention for left main compression secondary to pulmonary hypertension in a 4-year-old child.

Here, we report on the case of a 4-year-old child with large atrial septal defect (ASD) and severe pulmonary hypertension presenting an ischemic cardiomyopathy secondary to left main (LM) compression by a dilated pulmonary artery trunk. Despite of surgical treatment consisting in ASD closure and coronary artery bypass grafting, the patient was not weanable from ECMO. Control coronarography showed a near-occlusion of the left mammary bypass. A rescue percutaneous LM angioplasty with drug-eluting stent implantation was performed.

Transfemoral aortic valve implantation following lithoplasty of iliac artery in a patient with poor vascular access.

Transfemoral approach is considered the preferred route to perform transcatheter aortic valve implantation (TAVI) by most operators due to the low invasiveness and good outcome, as compared to non-transfemoral approach. However, transfemoral access is not always feasible particularly in patients with small and calcific vessels. Recently, catheter-based lithoplasty has emerged as a new technique based on the use of circumferential pulse pressure waves to disrupt calcific plaques. This technology may help to expand eligibility for transfemoral TAVI to patients with calcific ileo-femoral vessels and at high risk for non-transfemoral approach. We present the case of an 87-year-old woman with poor vascular access who successfully underwent transfemoral TAVI following lithoplasty of iliac artery.

Temporal Trends in Adverse Events After Everolimus-Eluting Bioresorbable Vascular Scaffold Versus Everolimus-Eluting Metallic Stent Implantation: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Bioresorbable coronary stents have been introduced into clinical practice to improve the outcomes of patients treated with percutaneous coronary intervention. The everolimus-eluting bioresorbable vascular scaffold (BVS) is the most studied of these stent platforms; however, recent trials comparing BVS with everolimus-eluting metallic stents (EES) raised concerns about BVS safety. We aimed to assess the efficacy and safety of BVS versus EES in patients undergoing percutaneous coronary intervention. METHODS: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials, scientific sessions abstracts, and relevant Web sites for randomized trials with a follow-up of ≥2 years investigating percutaneous coronary interventions with BVS versus EES. The primary outcomes of our analysis were definite/probable stent thrombosis (ST) and target lesion failure (TLF; device-oriented composite end point of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization [TLR]). Secondary outcomes were target vessel myocardial infarction, TLR, and cardiac death. We calculated the risk estimates for main outcomes according to a fixed-effect model. RESULTS: We included 7 trials comprising data for 5583 patients randomized to receive either a BVS (n=3261) or an EES (n=2322). Median follow-up was 24 months (range, 24-36 months). Patients treated with BVS had a higher risk of definite/probable ST compared with patients treated with EES (odds ratio, 3.33; 95% confidence interval, 1.97-5.62; P<0.00001). In particular, patients with BVS had a higher risk of subacute, late, and very late ST, whereas the risk of acute ST was similar. Patients treated with BVS compared with EES had a higher risk at 2 years of TLF (odds ratio, 1.47; 95% confidence interval, 1.14-1.90; P=0.003), driven mainly by an increased risk of target vessel myocardial infarction (odds ratio, 1.73; 95% confidence interval, 1.31-2.28; P=0.0001; I2=0%) and of TLR (odds ratio, 1.27; 95% confidence interval, 1.00-1.62; P=0.05). Of importance, the risk of TLF and TLR for patients with BVS was higher between 1 and 2 years, whereas there was no difference in the first year. Risk of cardiac death was similar between the 2 groups. CONCLUSIONS: Our meta-analysis of randomized trials with a follow-up of ≥2 years demonstrated a higher risk of ST and of TLF in patients treated with BVS compared with EES. Of note, BVS had a higher risk of subacute, late, and very late ST, whereas the risk of TLF and TLR was higher between 1 and 2 years.

Redox control of viral carcinogenesis: The human papillomavirus paradigm.

BACKGROUND: Cervical cancer is the second most common neoplastic disease among women worldwide. The initiating event of such cancer is the infection with certain types of human papillomavirus (HPV), a very common condition in the general population. However, the majority of HPV infections is subclinical and transitory and is resolved spontaneously. Intriguingly, viral oncogene expression, although necessary, is not per se sufficient to promote cervical cancer and other factors are involved in the progression of infected cells to the full neoplastic phenotype. In this perspective it has been suggested that the redox balance and the oxidative stress (OS) may represent interesting and under-explored candidates as promoting factors in HPV-initiated carcinogenesis. SCOPE OF THE REVIEW: The current review discusses the possible interplay between the viral mechanisms modulating cell homeostasis and redox sensitive mechanisms. Experimental data and indirect evidences are presented on the activity of viral dependent functions on i) the regulation of enzymes and compounds involved in OS; ii) the protection from oxidation of detoxifying/antiapoptotic enzymes and redox-sensitive transcription factors; iii) the suppression of apoptosis; and iv) the modulation of host microRNAs regulating genes associated with antioxidant defense. MAJOR CONCLUSIONS: The resulting tangled scenario suggests that viral hosting cells adapt their metabolisms in order to support their growth and survival in the increasingly oxidant micro-environment associated with HPV tumor initiation and progression. GENERAL SIGNIFICANCE: HPV can modulate the host cell redox homeostasis in order to favor infection and possibly tumor transformation. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.