Angiography-based superficial wall strain of de novo stenotic coronary arteries:serial assessment of vessels treated with bioresorbable scaffold or drug-eluting stent

Objectives: This study sought to present an angiography-based computational model for serial assessment of superficial wall strain (SWS, dimensionless) of de-novo coronary stenoses treated with either bioresorbable scaffold (BRS) or drug-eluting stent (DES). Background: A novel method for SWS allows the assessment of the mechanical status of arteries in-vivo, which may help for predicting cardiovascular outcomes. Methods: Patients with arterial stenosis treated with BRS (n = 21) or DES (n = 21) were included from ABSORB Cohort B1 and AIDA trials. The SWS analyses were performed along with quantitative coronary angiography (QCA) at pre-PCI, post-PCI, and 5-year follow-up. Measurements of QCA and SWS parameters were quantified at the treated segment and adjacent 5-mm proximal and distal edges. Results: Before PCI, the peak SWS on the ‘to be treated’ segment (0.79 ± 0.36) was significantly higher than at both virtual edges (0.44 ± 0.14 and 0.45 ± 0.21; both p &lt; 0.001). The peak SWS in the treated segment significantly decreased by 0.44 ± 0.13 (p &lt; 0.001). The surface area of high SWS decreased from 69.97mm2 to 40.08mm2 (p = 0.002). The peak SWS in BRS group decreased to a similar extent (p = 0.775) from 0.81 ± 0.36 to 0.41 ± 0.14 (p &lt; 0.001), compared with DES group from 0.77 ± 0.39 to 0.47 ± 0.13 (p = 0.001). Relocation of high SWS to device edges was often observed in both groups after PCI (35 of 82 cases, 41.7 %). At follow-up of BRS, the peak SWS remained unchanged compared to post-PCI (0.40 ± 0.12 versus 0.36 ± 0.09, p = 0.319). Conclusion: Angiography-based SWS provided valuable information about the mechanical status of coronary arteries. Device implantation led to a significant decrease of SWS to a similar extent with either polymer-based scaffolds or permanent metallic stents.</p

Intracoronary physiology-guided percutaneous coronary intervention in patients with diabetes

Objective: The risk of vessel-oriented cardiac adverse events (VOCE) in patients with diabetes mellitus (DM) undergoing intracoronary physiology-guided coronary revascularization is poorly defined. The purpose of this work is to evaluate the risk of VOCE in patients with and without DM in whom percutaneous coronary intervention (PCI) was performed or deferred based on pressure-wire functional assessment. Methods: This is a retrospective analysis of a multicenter registry of patients evaluated with fractional flow reserve (FFR) and/or non-hyperaemic pressure ratio (NHPR). Primary endpoint was a composite of VOCE including cardiac death, vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR). Results: A large cohort of 2828 patients with 3353 coronary lesions was analysed to assess the risk of VOCE at long-term follow-up (23 [14-36] months). Non-insulin-dependent-DM (NIDDM) was not associated with the primary endpoint in the overall cohort (adjusted Hazard Ratio [aHR] 1.18, 95% CI 0.87-1.59, P = 0.276) or in patients with coronary lesions treated with PCI (aHR = 1.30, 95% CI 0.78-2.16, P = 0.314). Conversely, insulin-dependent diabetes mellitus (IDDM) demonstrated an increased risk of VOCE in the overall cohort (aHR 1.76, 95% CI 1.07-2.91, P = 0.027), but not in coronary lesions undergoing PCI (aHR 1.26, 95% CI 0.50-3.16, P = 0.621). Importantly, in coronary lesions deferred after functional assessment IDDM (aHR 2.77, 95% CI 1.11-6.93, P = 0.029) but not NIDDM (aHR = 0.94, 95% CI 0.61-1.44, P = 0.776) was significantly associated with the risk of VOCE. IDDM caused a significant effect modification of FFR-based risk stratification (P for interaction &lt; 0.001). Conclusion: Overall, DM was not associated with an increased risk of VOCE in patients undergoing physiology-guided coronary revascularization. However, IDDM represents a phenotype at high risk of VOCE

Clinical outcomes of transcatheter aortic valve implantation: from learning curve to proficiency

Objective: The use of transcatheter aortic valve implantation (TAVI) is growing rapidly in countries with a predominantly elderly population, posing a huge challenge to healthcare systems worldwide. The increment of human and economic resource consumption imposes a careful monitoring of clinical outcomes and cost-benefit balance, and this article is aimed at analysing clinical outcomes related to the TAVI learning curve.Methods: Outcomes of 177 consecutive transfemoral TAVI procedures performed in 5 years by a single team were analysed by the Cumulative Sum of failures method (CUSUM) according to the clinical events comprised in the Valve Academic Research Consortium (VARC-2) safety end point and the VARC-2 definition of device success. Margins for events acceptance were extrapolated from landmark trials that tested both balloon or self-expandable percutaneous valves.Results: 30-day and 1-year survival rates were 97.2% and 89.9%, respectively. Achievement of the primary end point (number of cases needed to provide the acceptable margin of the composite end point of any death, stroke, myocardial infarction, life-threatening bleeding, major vascular complications, stage 2-3 acute kidney injury and valve-related dysfunction requiring a repeat procedure) required the performance of 54 cases, while the learning curve to achieve 'device success' identified 32 cases to reach the expected proficiency. In this experience, the baseline clinical risk as assessed by the Society of Thoracic Surgeons (STS) score determined the long-term survival rather than the adverse events related to the learning curve.Conclusions: A relatively large number of cases are required to achieve clinical outcomes comparable to those reported in high-volume centres and controlled trials. According to our national workload standards, this represents more than 2 years of continuous activity

ETS-related gene (ERG) undermines genome stability in mouse prostate progenitors via Gsk3β dependent Nkx3.1 degradation.

21q22.2-3 deletion is the most common copy number alteration in prostate cancer (PCa). The genomic rearrangement results in the androgen-dependent de novo expression of ETS-related gene (ERG) in prostate cancer cells, a condition promoting tumor progression to advanced stages of the disease. Interestingly, ERG expression characterizes 5-30% of tumor precursor lesions - High Grade Prostatic Intraepithelial Neoplasia (HGPIN) - where its role remains unclear. Here, by combining organoids technology with Click-chemistry coupled Mass Spectrometry, we demonstrate a prominent role of ERG in remodeling the protein secretome of prostate progenitors. Functionally, by lowering autocrine Wnt-4 signaling, ERG represses canonical Wnt pathway in prostate progenitors, and, in turn, promotes the accumulation of DNA double strand breaks via Gsk3β-dependent degradation of the tumor suppressor Nkx3.1. On the other hand, by shaping extracellular paracrine signals, ERG strengthens the pro-oxidative transcriptional signature of inflammatory macrophages, which we demonstrate to infiltrate pre-malignant ERG positive prostate lesions. These findings highlight previously unrecognized functions of ERG in undermining adult prostate progenitor niche through cell autonomous and non-autonomous mechanisms. Overall, by supporting the survival and proliferation of prostate progenitors in the absence of growth stimuli and promoting the accumulation of DNA damage through destabilization of Nkx3.1, ERG could orchestrate the prelude to neoplastic transformation

Long-term variations of FFR and iFR after transcatheter aortic valve implantation

Long-term variations of fractional flow reserve (FFR) and instantaneous wave-free-ratio (iFR) after transcatheter aortic valve implantation (TAVI) have not been previously assessed. A total of 23 coronary lesions in 14 patients with aortic stenosis (AS) underwent physiology assessment at baseline, immediately after TAVI and at 14(7-29) months of follow-up. The angiographic severity of the lesions did not progress at follow-up (54[45-64] vs 54[49-63], p&nbsp;=&nbsp;.53). Overall, FFR (0.87[0.85-0.92] vs 0.88[0.82-0.92], p&nbsp;=&nbsp;.45) and iFR (0.88[0.85-0.96] vs 0.91[0.86-0.97], p&nbsp;=&nbsp;.30) did not change significantly compared with the baseline. FFR decreased in 3(13%) lesions with abnormal baseline value, whereas it remained stable in lesions with FFR&nbsp;&gt;&nbsp;0.80. Conversely, iFR did not show a systematic trend at long-term after TAVI. However, iFR demonstrated a higher reclassification rate at follow-up compared with FFR (p&nbsp;=&nbsp;.02). In conclusions, in this exploratory study, only minor variations of coronary physiology indices were observed at long-term after TAVI. Nevertheless, caution should be exercised in the interpretation of borderline FFR and iFR values in severe AS

Coronary Catheterization and Percutaneous Interventions After Transcatheter Aortic Valve Implantation

Coronary artery disease (CAD) is often present in patients with severe aortic valve stenosis candidates to transcatheter aortic valve implantation (TAVI). Mild CAD may also worsen and need treatment years after TAVI. The implantation of a transcatheter valve may interfere with the capability of reengaging the coronary arteries. We prospectively assessed the feasibility of performing coronary angiography (CA), fractional flow reserve, and, where indicated, percutaneous coronary intervention after valve implantation in a consecutive series of patients with CAD undergoing TAVI. Valve type and size were decided according to accurate computed tomography scan and angiographic measurement of the aortic root structures. We analyzed 66 consecutive patients undergoing TAVI, 41 with balloon expandable, and 25 with self-expandable transcatheter valves. Right and left coronary catheterization (132 vessels) was successful in all cases except in 1 left coronary artery after a high implantation of a self-expandable valve (unsuccess rate, 1 in 50 vessels). In 6 of 132 vessels (4%), CA was initially nonselective, but after positioning the 0.014 '' intracoronary guidevvire, selective injections were obtained in all these cases. Percutaneous coronary intervention was performed successfully in 19 coronary vessels (17 patients) as indicated by fractional flow reserve measurements: In conclusion, catheterization of the coronary ostia after transfemoral TAVI with balloon or self-expandable valves is safe and feasible in almost all cases. Accurate imaging of the aortic root and procedural planning may help to avoid too high implantation of supra-annular self-expandable valves to obviate difficulties in accessing coronary ostia. Use of intracoronary guidewires facilitates selective CA in cases with difficult access. (C) 2016 Elsevier Inc. All rights reserved