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The use of stem cells as carriers for therapeutic agents is an appealing modality for targeting tissues or organs of interest. Combined delivery of cells together with various information molecules as therapeutic agents has the potential to enhance, modulate or even initiate local or systemic repair processes, increasing stem cell efficiency for regenerative medicine applications. Stem-cell-mediated delivery of genes, proteins or small molecules takes advantage of the innate capability of stem cells to migrate and home to injury sites. As the native migratory properties are affected by in vitro expansion, the existent methods for enhancing stem cell targeting capabilities (modified culture methods, genetic modification, cell surface engineering) are described. The role of various nanoparticles in equipping stem cells with therapeutic small molecules is revised together with their class-specific advantages and shortcomings. Modalities to circumvent common challenges when designing a stem-cell-mediated targeted delivery system are described as well as future prospects in using this approach for regenerative medicine applications., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.

During recent years, equipment and techniques for percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) have improved significantly. The retrograde approach remains critical to the improved success of CTO PCI. Currently, the reverse controlled antegrade and retrograde tracking (CART) technique has become the dominant retrograde wire crossing technique. In this article, we propose a standardised terminology and classification for this technique divided into three subtypes: a) conventional reverse CART, usually involving the use of large balloons on the antegrade wire to achieve re-entry within the CTO segment; b) "directed" reverse CART, which is characterised by small antegrade balloon size and more active, intentional vessel tracking and penetration with a controllable retrograde wire, still within the CTO segment; and c) "extended" reverse CART, in which the intimal/subintimal dissection is extended proximal or distal to the CTO segment, achieving re-entry outside the CTO segment. The proposed standardised terminology will facilitate the communication, teaching and adoption of the reverse CART techniques.

Aims: Periprocedural myocardial injury (PMI) is frequently observed after percutaneous coronary interventions (PCI) for chronic total occlusion (CTO). We aimed to investigate the prognostic impact of PMI with the antegrade as compared to the retrograde crossing technique., Methods and Results: A total of 1,909 patients undergoing CTO PCI were stratified according to the presence/absence of PMI (elevation of cardiac troponin T [cTnT] >5x99th percentile of normal), and divided according to tertiles of the difference between peak and baseline cTnT within 24 hours (∆cTnT). The primary endpoint was all-cause mortality at a median follow-up of 3.1 (interquartile range 3.0-4.4) years. PMI occurred in 19.4% and 25.4% after antegrade (n=1,447) and retrograde (n=462) procedures (p<0.001). PMI was significantly associated with mortality after antegrade (adjusted HR 1.39, 95% CI: 1.02-1.88, p=0.04), but not retrograde CTO PCI (adjusted HR 0.93, 95% CI: 0.53-1.63, p=0.80, pint=0.02). With the antegrade, but not with the retrograde approach, mortality also increased with tertiles of ∆cTnT (T1: 11.0%, T2: 18.6%, T3: 21.6%, log-rank p<0.001)., Conclusions: Periprocedural myocardial injury was significantly associated with all-cause mortality following antegrade, but not retrograde CTO PCI. Hence, the higher risk of PMI following retrograde procedures did not translate into worse survival.

Patients with non-valvular atrial fibrillation (AF) and a high risk for oral anticoagulation can be treated by percutaneous implantation of left atrial appendage occlusion devices (LAAC) to reduce the risk of cardio-embolic stroke. This study evaluates whether LAAC may influence lipid metabolism, which has never been investigated before. Patients with successful LAAC were included consecutively. Venous peripheral blood samples of patients were collected immediately before (T0, baseline) and 6 months after (T1, mid-term) LAAC. A targeted metabolomics approach based on electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements was performed. A total of 34 lipids revealed a significant change from baseline to mid-term follow-up after successful LAAC. Subgroup analysis revealed confounding influence by gender, age, diabetes mellitus type II, body mass index, left ventricular ejection fraction, creatinine and NT-proBNP. After multivariable adjustment within logistic regression models, these 34 lipids were still significantly altered after LAAC. Successful percutaneous LAAC may affect lipid metabolism and thereby may potentially affect pro-atherogenic and cardio-toxic effects.

Percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) has been rapidly evolving during recent years. With improvement in equipment and techniques, high success rates can be achieved at experienced centers, although overall success rates remain low. Prospective, randomized-controlled data regarding optimal use and indications for CTO PCI remain limited. CTO PCI should be performed when the anticipated benefit exceeds the potential risk. New high-quality studies of the clinical outcomes and techniques of CTO PCI are needed, as is the expansion of expert centers and operators that can achieve excellent clinical outcomes in this challenging patient and lesion subgroup. In the current review the authors summarize the latest publications in CTO PCI and provide an overview of the current state of the field., (Copyright © 2018 American College of Cardiology Foundation. All rights reserved.)

Aim: The prognostic value of coronary artery dominance pattern in patients with chronic total occlusions (CTO) is unknown. The aim of this study was to assess the influence of coronary vessel dominance on short and long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) for CTO., Methods and Results: Our study population consisted of 2002 consecutive patients (17% females, mean age 65.2 ± 10.7 years) who underwent PCI of at least one coronary CTO lesion at our center between 01/2005 and 12/2013. Based on the origin of the posterior descending coronary artery, coronary circulation was categorised into left, right, and balanced coronary dominance. Right coronary dominance (RD) was present in 88% (n = 1759), left coronary dominance (LD) in 7% (n = 136), and balanced coronary dominance (BD) in 5% (n = 107) of the study population. After a median follow-up duration of 2.6 years [interquartile range 1.1-3.1 years] all-cause mortality was significantly higher in patients with LD as compared with RD and BD (log rank = 0.001). Accordingly, the presence of a LD system was identified as a significant predictor for all-cause mortality (adjusted HR 1.7, 95% CI: 1.2-2.6, P = .007) and major adverse cardiac events (MACE) (adjusted HR 1.4, 95% CI: 1.1-1.8, P = 0.02)., Conclusion: Our data suggest that LD is an independent predictor of increased all-cause death and MACE in patients with CTO. Therefore, assessment of coronary vessel dominance by angiography may contribute to risk stratification in these patients., (© 2017 Wiley Periodicals, Inc.)

Background: Chronic kidney disease (CKD) adversely affects outcomes in patients with coronary artery disease. Data on the impact of renal impairment on prognosis of patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) are scarce., Methods: A total of 2002 patients undergoing CTO PCI were stratified according to baseline renal function (group 1: estimated glomerular filtration rate [eGFR] ≥ 90 ml/min/1.73 m 2 , group 2: 60 to 89 ml/min/1.73 m 2 , group 3: 30 to 59 ml/min/1.73 m 2 , and group 4: <30 ml/min/1.73 m 2 ). The primary outcome measure was all-cause mortality at a median follow-up of 2.6 (interquartile range 1.1-3.1) years., Results: All-cause mortality increased with decreasing renal function (group 1: 5.0%, group 2: 9.5%, group 3: 26.4%, and group 4: 38.7%, log rank p < 0.001). Continuous eGFR values were significantly related with all-cause mortality (adjusted HR 0.98, 95% CI 0.98-0.99, p < 0.001). Procedural failure was associated with all-cause mortality both in patients with an eGFR < 60 ml/min/1.73 m 2 (42.6 vs. 23.7%, adjusted HR 1.59, 95% CI 1.08-2.32, p = 0.02) and in those with an eGFR ≥ 60 ml/min/1.73 m 2 (14.6 vs. 6.5%, adjusted HR 1.73, 95% CI 1.15-2.60, p = 0.009, interaction p = 0.47)., Conclusions: Although renal impairment is associated with all-cause mortality in patients undergoing CTO PCI, successful CTO recanalization is related to improved survival irrespective of renal function.

Background: Left atrial appendage closure (LAAC) represents the interventional alternative to oral anticoagulation for stroke prevention in atrial fibrillation (AF). The metabolism of acylcarnitines was shown to affect cardiovascular diseases. This study evaluates the influence of successful LAAC on the metabolism of acylcarnitines., Methods: Patients undergoing successful LAAC were enrolled prospectively. Peripheral blood samples for metabolomics measurements were collected immediately before (i.e., index) and six months after LAAC (i.e., mid-term). A targeted metabolomics analysis based on electrospray ionization-liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements was performed., Results: 44 patients with non-valvular AF (median CHA₂DS₂-VASc score 4, median HAS-BLED score 4) and successful LAAC were included. Significant changes in acylcarnitine levels were found in the total cohort, which were mainly attributed to patients with impaired left ventricular and renal function, elevated amino-terminal pro-brain natriuretic peptide (NT-proBNP) and diabetes mellitus. Adjusted multivariable regression models revealed significant changes of five metabolites over mid-term follow-up: C2, C14:1, C16, and C18:1 decreased significantly (each p < 0.05); short-chain C5 acylcarnitine plasma levels increased significantly ( p < 0.05)., Conclusion: This study demonstrates that successful LAAC affects the metabolism of acylcarnitines at mid-term follow-up., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02985463., Competing Interests: The authors declare no conflict of interest.

Objectives: We sought to examine contemporary perspectives and practices on chronic total occlusion (CTO) percutaneous coronary intervention (PCI)., Background: The frequency and success of CTO-PCI have been increasing in recent years., Methods: An online questionnaire was created and distributed to cardiologists within the United States and internationally., Results: A total of 1149 responses were obtained. The United States (n = 845; 73.5%), Asia (n = 98; 8.5%), Europe (n = 88; 7.7%), South America (n = 42; 3.7%), and Canada (n = 33; 2.9%) accounted for most responses. Mean practice duration of the respondents was 16.4 ± 11.5 years and 66.9% were interventional cardiologists. Most respondents agreed that CTO-PCI results in an improvement of patient symptoms (90.7%), left ventricular function (79.3%), arrhythmia risk (69.2%), and overall survival (63.1%). Interventional cardiologists had a more favorable view of the benefits of CTO-PCI as compared with non-interventional cardiologists (P<.001). Most respondents estimated the procedural success rates of contemporary CTO-PCI to be between 51%-75% (34.2%) and 76%-85% (30.2%), with interventional cardiologists estimating higher success rates than non-interventionalists (P<.001). Perforation, mortality, and tamponade were the three most concerning complications. Time and procedure complexity were reported to be the most significant barriers to the development of a CTO-PCI program., Conclusions: Most cardiologists believe that CTO-PCI can provide significant clinical benefits and can be accomplished with moderate to high success rates. Interventional cardiologists have a more favorable view of CTO-PCI as compared with non-invasive cardiologists.

Objectives: A single-centre, observational study was performed in order to investigate the relationship between anemia and outcomes after percutaneous coronary intervention (PCI) for chronic total occlusion (CTO)., Background: Anemia has been identified as adverse predictor in patients with coronary artery disease undergoing coronary revascularization. Data on the impact of anemia on outcomes in patients undergoing PCI for CTO lesions are lacking., Methods: A total of 1,964 patients undergoing CTO PCI were stratified according to the presence/absence of anemia (hemoglobin of <13 g/dl for men and <12 g/dl for women). The primary endpoint was all-cause mortality. Median follow-up was 2.6 (interquartile range 1.1-3.1) years., Results: Of the 1,964 patients, 297 (15.1%) had anemia. Anemic as compared to nonanemic patients had and an increased all-cause mortality (27.9% versus 9.1%, P < 0.001), and associations remained significant after multivariable adjustments (adjusted HR 2.26, 95% CI 1.71-2.98, P < 0.001). All-cause mortality decreased with increasing hemoglobin tertiles (T1: 18.6%, T2: 8.6%, T3: 8.2%, log rank P < 0.001). Procedural success was associated with reduced all-cause mortality both in anemic (21.8% versus 47.2%, adjusted HR 0.59, 95% CI 0.37-0.93, P = 0.02) and nonanemic patients (7.8% versus 16.3%, adjusted HR 0.64, 95% CI 0.42-0.98, P = 0.02, interaction P = 0.69)., Conclusions: Although anemia is associated with an increased all-cause mortality in patients undergoing CTO PCI, the survival benefit associated with successful CTO recanalization is maintained., (© 2017 Wiley Periodicals, Inc.)

Background: Reticulated platelets are associated with impaired antiplatelet response to irreversibly acting P2Y 12 -receptor inhibitors. However, the impact of reticluated platelets (RP) on the reversibly acting injectable P2Y 12 -receptor inhibitor cangrelor is unknown. Thus, this study sought to investigate the influence of RP on cangrelor and transitioning strategies to oral P2Y 12 -receptor inhibitors., Methods: This study randomized 110 patients undergoing elective percutaneous coronary intervention with use of cangrelor to different oral transitioning strategies loading with prasugrel 60 mg or ticagrelor 180 mg at the start of cangrelor ( n  = 45 each) or loading with clopidogrel 600 mg after discontinuation of cangrelor ( n  = 20). ADP-induced platelet reactivity was assessed by impedance aggregometry. Reticulated platelets were analysed by an automated whole blood flow cytometry and described as immature platelet count., Results: There was no correlation of reticulated platelets and ADP-induced platelet reactivity in patients under treatment with cangrelor ( r  = 0.06, p  = 0.47). This finding was consistent in all three transitioning strategies. On day 1 following treatment with cangrelor, the correlation of reticulated platelets and platelet reactivity was detectable again in patients receiving thienopyridines but not ticagrelor (all patients r  = 0.37, p  < 0.001; clopidogrel: r  = 0.59, p  = 0.01; prasugrel: r  = 0.47, p  < 0.001; ticagrelor r  = 0.22, p  = 0.13)., Conclusion: Platelet inhibition is not influenced by levels of reticulated platelets during infusion of cangrelor independent of oral P2Y 12 -receptor inhibitor transitioning strategy. These findings underline the potency of cangrelor as immediate and reversibly acting P2Y 12 -receptor inhibitor., Competing Interests: Dr. Hochholzer reports receiving consulting and lecture fees from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo and The Medicines Company. Dr. Stratz reports receiving lecture fees or travel expense from Eli Lilly, Daiichi Sankyo and Bayer. Dr. Trenk reports receiving consulting and lecture fees from AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, MSD, Otsuka and Sanofi. All other authors report no conflict of interests., (Schattauer GmbH Stuttgart.)

A standardized imaging algorithm by cardiac computed tomography angiography (cCTA) (LOVE-view) was used in 30 patients to evaluate the influence of different left atrial appendage (LAA) morphologies on development of thrombosis in the LAA 6 months after implantation of an occlusion device (Watchman or Amplatzer-Cardiac-Plug) in patients with non-valvular atrial fibrillation, CHA 2 DS 2 -VASc-Score >1 and a contraindication for oral anticoagulation. The distribution of different LAA morphologies was 40% windsock, 17% broccoli and 43% chicken wing type. There was no significant difference in the level of thrombosis regarding LAA morphology or the type of chosen occlusion device. The rates of complete LAA thrombosis was 40% in broccoli type, 33% in windsock and 15% in chicken wing type. Independently of LAA type, 13% had none and 60% incomplete thrombosis. The ratio of density (LA/LAA) was 0.14 in patients with complete thrombosis and 0.67 in those with none or incomplete thrombosis. cCTA and the LOVE-view-imaging-algorithm were shown to be a valuable method for standardized imaging in clinical routine in a greater set of patients. Surprisingly thrombosis of the occluded LAA was still in progress in most cases at 6 months, whereas further studies are needed defining its clinical consequences, especially for the selection of the optimal post-procedural antithrombotic treatment strategy.

The article Occlusion of left atrial appendage aff ects metabolomic profile:focus on glycolysis, tricarboxylic acid and urea metabolism, written by K. Sattler, M. Behnes, C. Barth, A. Wenke, B. Sartorius, I. El-Battrawy, K. Mashayekhi, J. Kuschyk, U. Hoffmann, T. Papavasiliu, C. Fastner, S. Baumann, S. Lang, X. Zhou, G. Yücel, M. BorggrefeI, Akin, was originally published Online First without open access.

Background: The optimal strategy to treat bifurcation lesions (BFLs) in a percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) remains unknown., Aims: We sought to assess whether T-provisional or mini-crush is appropriate for BFLs within CTO vessels., Patients and Methods: From January 2011 to December 2013, patients who underwent successful CTO guidewire crossing and with a BFL within the CTO target vessel were enrolled prospectively and assigned randomly to either T-provisional stenting or the mini-crush technique for BFL treatment. One-year clinical follow-up was performed. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of cardiovascular death, myocardial infarction, target vessel revascularization, and stroke., Results: The prevalence of BFLs was 54.3%. A total of 146 patients with BFLs within CTO vessel were enrolled prospectively and assigned randomly to either T-provisional stenting (N=73) or the mini-crush technique (N=73). Angiographic and clinical success rates were similar in the two groups: 91.8 versus 97.2% (P=0.27) and 91.8 versus 94.5% (P=0.67), respectively.Although T-provisional stenting was associated with a nonsignificantly lower incidence of MACCE in case of BFLs located far from the CTO (9.3 vs. 22.2%; P=0.426), the mini-crush technique resulted in higher MACCE-free survival at 1 year in the presence of BFLs within the CTO body or close to the proximal or the distal cap (89.1 vs. 64.9%; P=0.007)., Conclusion: The mini-crush technique appeared to be associated with improved 1-year clinical and angiographic outcomes, particularly when used to treat BFLs located within the CTO body or close to the proximal or the distal cap.

Background: Iatrogenic aorto-coronary dissections following percutaneous coronary interventions (PCI) represent a rare but potentially life threatening complication. This restrospective and observational study aims to describe our in-house experience for timely diagnostics and therapy including cardiovascular imaging to follow-up securely high-risk patients with Dunning dissections., Methods: Dunning dissections (DD) occurred during clinical routine PCIs, which were indicated according to current ESC guidelines. Diagnostic assessment, treatment and follow-up were based on coronary angiography with PCI or conservative treatment and cardiac computed tomography (cCTA) imaging., Results: A total of eight patients with iatrogenic DD were included. Median age was 69 years (IQR 65.8-74.5). Patients revealed a coronary multi-vessel-disease in 75% with a median SYNTAX-II-score of 35.3 (IQR 30.2-41.2). The most common type of DD was type III (50%), followed by type I (38%) and type II (13%). In most patients (88%) the DD involved the right coronary arterial ostium. 63% were treated by PCI, the remaining patients were treated conservatively. 88% of patients received at least one cCTA within 2 days, 50% were additionally followed-up by cCTA within a median of 6 months (range: 4-8 months) without any residual., Conclusion: Independently of the type of DD (I-III) it was demonstrated that cCTA represents a valuable imaging modality for detection and follow-up of patients with DDs.

Background: Successful CTO recanalization has been associated with clinical benefit. Outcomes of patients with atrial fibrillation undergoing CTO PCI have not been investigated, yet., Aims: This study sought to evaluate the association between atrial fibrillation and outcomes after percutaneous coronary intervention (PCI) for chronic total occlusions (CTO)., Methods: Consecutive patients undergoing CTO PCI between January 2005 and December 2013 were divided into patients with and without atrial fibrillation, and propensity-matched models used to adjust for baseline differences between groups. The primary outcome was all-cause mortality at a median follow-up of 3.2 (interquartile range 3.1-4.5) years., Results: Of 2002 patients undergoing CTO PCI, atrial fibrillation was present in 169 (8.4%) patients. Patients with atrial fibrillation were older, and more frequently had hypertension, left ventricular systolic dysfunction, and chronic kidney disease. Before matching, all-cause mortality was 39.6 and 14.5% in the atrial fibrillation and the sinus rhythm groups (HR 2.92, 95% CI 2.23-3.82, p < 0.001). In the propensity-matched model, atrial fibrillation remained associated with an increased risk of mortality (HR 1.62, 95% CI 1.06-2.47, p = 0.03). In the unmatched patient cohort, all-cause mortality was significantly reduced in patients with procedural success, both in the atrial fibrillation (34.9 versus 55.0%, adjusted HR 0.99, 95% CI 0.97-1.00, p = 0.02) and the sinus rhythm groups (12.8 versus 23.0%, adjusted HR 0.70, 95% CI 0.53-0.92, p = 0.01)., Conclusions: Although atrial fibrillation is independently associated with mortality after CTO PCI, substantial survival benefit of successful CTO recanalization is observed in both patients with and without atrial fibrillation.

Successful recanalization of chronic total occlusions (CTO) has been associated with improved survival. Data on outcomes in patients with left ventricular (LV) systolic dysfunction undergoing percutaneous coronary intervention for CTO, however, are scarce. Between January 2005 and December 2013, a total of 2,002 consecutive patients undergoing elective CTO percutaneous coronary intervention at a tertiary care center were divided into patients with (LV ejection fraction ≤ 40%) and without (LV ejection fraction > 40%) LV systolic dysfunction as defined by transthoracic echocardiography. The primary end point was all-cause mortality. Median follow-up was 2.6 (1.1 to 3.1) years. A total of 348 (17.4%) patients had LV dysfunction. All-cause mortality was higher in patients with LV dysfunction (30.2%) than in those with normal LV function (8.2%, p <0.001), and associations remained significant after adjustment for baseline differences (adjusted hazard ratio [HR] 3.39, 95% confidence interval [CI] 2.57 to 4.47, p <0.001). Successful CTO recanalization was independently associated with reduced all-cause mortality, with similar relative risk reductions in both the preserved (6.6% vs 16.9%, adjusted HR 0.48, 95% CI 0.34 to 0.70, p <0.001) and the reduced LV function groups (26.2% vs 45.2%, adjusted HR 0.63, 95% CI 0.41 to 0.98, p = 0.04, interaction p = 0.28). In conclusion, irrespective of LV function, successful CTO recanalization is associated with a clear survival benefit., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The study sought to assess the outcome of percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) in patients with low left ventricular ejection fraction (LVEF) (≤35%)., Background: Data regarding the outcome of PCI in patients with low LVEF affected by CTO are scarcely reported., Methods: The authors performed a prospective longitudinal multicenter study including consecutive patients undergoing elective PCI of CTOs. Patients were subdivided into 3 groups: group 1 (LVEF ≥50%), group 2 (LVEF 35% to 50%), and group 3 (LVEF ≤35%)., Results: A total of 839 patients (mean 64.6 ± 10.5 years of age, 87.7% men) underwent CTO PCI attempts. Baseline LVEF ≤35% was present in 72 (8.6%) patients. The angiographic success was high (overall 93.6%) and similar among the 3 groups (93.5% vs. 94.4% vs. 91.7%, respectively; all p = NS). In group 3, no periprocedural complications of CTO PCI were observed. Mean clinical follow-up of 16.3 ± 8.2 months duration was available in 781 (93.1%) patients including those with LVEF ≤35%. At 2 years, major cardiac and cerebrovascular events (MACCE) free survival was similar in the 3 groups (86% vs. 82.8% vs. 75.2%; all p = NS). In patients with LVEF ≤35%, LVEF improved significantly in the presence of a successful CTO PCI from 29.1 ± 3.4% to 41.6 ± 7.9% (p < 0.001)., Conclusions: In CTO patients with low LVEF, PCI could represent a safe and effective revascularization strategy achieving good midterm outcome and LVEF improvement., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background  As technologies of percutaneous coronary intervention (PCI) for coronary chronic total occlusions (CTO) have improved, great uncertainty exists regarding patient selection and long-term benefit of CTO-PCI. Given that white blood cell (WBC) count has been associated with cardiovascular risk, we hypothesized that the latter might provide incremental prognostic value in patients undergoing CTO-PCI. Methods and Results  Our study population consisted of 1,262 consecutive patients (76.3% males, mean age of 67.7 ± 10.3 years) who underwent elective PCI at our centre between January 2002 and December 2008. Four hundred seventy-five patients had at least one CTO, while 787 patients with non-occlusive coronary lesions served as controls. Baseline WBC count was higher in CTO patients as compared with controls (8,072 ± 3,459/μL vs. 7,469 ± 2,668/μL, p  = 0.001) and independently predicted the occurrence of a CTO lesion (odds ratio: 1.8; 95% confidence interval [CI]: 1.3-2.4; p  < 0.001). After a median follow-up of 3.1 years (interquartile range: 2.1-4.2 years), CTO patients with WBC counts ranging in the highest tertile had significantly worse outcomes than CTO patients with lower WBC counts (log-rank = 0.009 for all-cause mortality and log-rank = 0.01 for major adverse cardiac events). These associations were not seen in controls. Accordingly, elevated WBC count was identified as a significant predictor for all-cause mortality (adjusted hazard ratio: 3.1; 95% CI: 1.6-6.2; p  = 0.001) in CTO patients but not in patients with non-occlusive coronary artery disease ( p int  = 0.088). Conclusion  Assessment of the inflammatory status of CTO patients may be an important element in selecting CTO patients at low risk who may be referred to CTO-PCI., Competing Interests: Conflict of Interest: None., (Schattauer GmbH Stuttgart.)

Objectives: The aim of this study was to describe the procedural aspects and outcomes of retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) through ipsilateral collateral channels (ILCs)., Background: Retrograde CTO PCI via ILCs is rarely performed, usually when no other retrograde options exist, and available evidence derives mostly from case reports., Methods: A large retrospective multinational registry was compiled, including all consecutive patients undergoing retrograde CTO PCI through ILCs at 6 centers between September 2011 and October 2016. Success rates, as well as procedural complications and in-hospital outcomes, were studied., Results: A total of 126 patients (17% of all retrograde CTO PCIs) were included. The mean age was 65.7 ± 11.2 years, and the mean J-CTO (Multicenter CTO Registry in Japan) score was 2.36 ± 1.13. The target vessel was the circumflex coronary artery in 42%, the left anterior descending coronary artery in 39%, and the right coronary artery in 19%. The ILCs used were epicardial in 76% and septal in 24%. ILC anatomy was very heterogeneous. One guiding catheter was used in 80%, whereas the ping-pong technique was used in 20%. A retrograde wire could be advanced to the distal cap in 81%. Technical and procedural success rates were 87% and 82%, respectively. ILC perforation with need for intervention was observed in 5.6% and tamponade due to ILC perforation in 2.4%. One patient (0.8%) died., Conclusions: Retrograde CTO PCI through ILCs is a challenging intervention that can be performed in difficult occlusions with high success rates and reasonable rates of complications by experienced operators., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Conflicting evidence exists on gender differences in outcomes after coronary stenting, and gender-based data in patients with chronic total occlusions (CTO) who underwent percutaneous coronary intervention (PCI) are scarce. Consecutive patients who underwent CTO PCI from January 2005 to December 2013 were included in the analysis and stratified according to gender. The primary outcome measure was all-cause mortality. Median follow-up was 2.6 years (interquartile range 1.1 to 3.1). Of 2002 patients, 332 (17%) were women. Procedural success was achieved in 82% and 83% of women and men (p = 0.31). All-cause mortality was 15% and 11% in women and men (log-rank p = 0.17) with an adjusted hazard ratio of 0.85 (95% confidence interval [CI] 0.61 to 1.17, p = 0.31). All-cause mortality was significantly reduced in patients with procedural success, both in women (12% vs 32%, adjusted hazard ratio 0.44, 95% CI 0.24 to 0.79, p = 0.006) and men (9% vs 21%, adjusted hazard ratio 0.64, 95% CI 0.47 to 0.88, p = 0.006), with similar mortality benefits associated with successful revascularization in both groups (interaction p = 0.35). In conclusion, recanalization of coronary arterial CTO is equally successful in both women and men., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Previous research has shown that a subpopulation of cells within cultured human dermal fibroblasts, termed multilineage-differentiating stress enduring (Muse) cells, are preferentially reprogrammed into induced pluripotent stem cells. However, controversy exists over whether these cells are the only cells capable of being reprogrammed from a heterogeneous population of fibroblasts. Similarly, there is little research to suggest such cells may exist in embryonic tissues or other species. To address if such a cell population exists in pigs, we investigated porcine embryonic fibroblast populations (pEFs) and identified heterogeneous expression of several key cell surface markers. Strikingly, we discovered a small population of stage-specific embryonic antigen 1 positive cells (SSEA-1+) in Danish Landrace and Göttingen minipig pEFs, which were absent in the Yucatan pEFs. Furthermore, reprogramming of SSEA-1+ sorted pEFs led to higher reprogramming efficiency. Subsequent transcriptome profiling of the SSEA-1+ vs. the SSEA-1neg cell fraction revealed highly comparable gene signatures. However several genes that were found to be upregulated in the SSEA-1+ cells were similarly expressed in mesenchymal stem cells (MSCs). We therefore termed these cells SSEA-1 Expressing Enhanced Reprogramming (SEER) cells. Interestingly, SEER cells were more effective at differentiating into osteocytes and chondrocytes in vitro. We conclude that SEER cells are more amenable for reprogramming and that the expression of mesenchymal stem cell genes is advantageous in the reprogramming process. This data provides evidence supporting the elite theory and helps to delineate which cell types and specific genes are important for reprogramming in the pig.

Aims: Few data are available on outcomes of percutaneous coronary intervention (PCI) for coronary chronic total occlusions (CTO) in very elderly patients in the drug-eluting stent (DES) era. We aimed to investigate long-term survival in a single-centre cohort of elderly patients following CTO PCI using DES., Methods and Results: A total of 2,002 consecutive patients who underwent PCI of a CTO at our centre between January 2005 and December 2013 were followed for a median of 2.6 years (interquartile range 1.1-3.1 years). Four hundred and nine (409) patients were older than 75 years. The absolute reduction in all-cause mortality by successful CTO PCI was numerically greater in elderly patients as compared to younger patients (22.1% vs. 7.2% at three years). In multivariate models, successful CTO PCI was significantly associated with improved survival in both elderly (adjusted hazard ratio [HR] 0.58, 95% confidence interval [CI]: 0.39 to 0.87; p=0.009) and younger patients (adjusted HR 0.59, 95% CI: 0.40 to 0.86; p=0.006)., Conclusions: In the DES era, elderly patients (≥75 years) derive a similar survival benefit from successful CTO PCI to younger patients. These findings suggest that CTO PCI, when indicated, should not be withheld from the elderly.

Background: Successful chronic total occlusion (CTO) revascularization has been associated with prognostic benefits. Whether the extent of coronary artery disease interferes with these benefits has not been investigated yet., Aims: We sought to compare the survival after percutaneous coronary intervention (PCI) for CTO between patients with multi- (MVD) and single-vessel disease (SVD)., Methods: A total of 2002 consecutive patients undergoing CTO PCI between 01/2005 and 12/2013 were identified and stratified according to the presence/absence of MVD. The primary endpoint was all-cause mortality. Median follow-up was 2.6 (interquartile range 1.1-3.1) years., Results: A total of 1634 (81.6%) patients had MVD. Procedural success rates were 81.5 and 89.7% in the MVD and SVD groups (p < 0.001). All-cause mortality during entire follow-up was higher in MVD as compared to SVD patients (13.5 versus 5.7%, p < 0.001), and differences were attenuated after multivariable adjustment for baseline characteristics [adjusted hazard ratio (HR) 1.51, 95% CI 0.98-2.33, p = 0.06]. The effect of successful CTO PCI on all-cause mortality was consistent among patients with MVD [11.0 versus 24.5%; adjusted HR 0.60, 95% CI 0.45-0.80, p < 0.001] and SVD [5.2 versus 10.5%; adjusted HR 0.74, 95% CI 0.24-2.26, p = 0.59, P int  = 0.65]. However, due to the greater baseline risk in the former group, the absolute survival benefit after successful CTO PCI was higher., Conclusions: Successful recanalization of a CTO is a strong independent predictor for reduced long-term mortality. Due a higher baseline risk, the absolute benefit in patients with MVD is substantially larger than in patients with SVD.

This study aims to compare prospectively the differences of clinical outcomes being associated with a specific femoral closure (FC) compared to a radial compression (RC) device following percutaneous coronary interventions (PCI). This single-center, prospective observational study included consecutively 400 patients either treated by a specific FC (Angio-Seal™, St. Jude Medical, Inc., St. Paul, MN) or RC (TR Band ® , Terumo Corporation, Tokyo, Japan) device following PCI. The primary outcome was to evaluate overall, access site and non-access site bleedings, the secondary outcome was major adverse cardiac events (MACE) occurring within 30 days of follow-up. 200 patients in each group (FC and RC group) were enrolled following PCI. The prevalence of overall bleedings was 56% in FC and 37% in RC group (p = 0.001). Access site bleedings were significantly higher in the FC (50%) compared to the RC (30%) group (p = 0.001). Most common type of access site bleeding consisted of hematomas (FC 45% vs. RC 27%, p = 0.001). Of these, intermediate and large hematomas were significantly higher in the FC group (p < 0.05). Surgical interventions following device-related bleedings were uncommon in both groups. No significant differences of MACE were observed in both treatment groups. Despite the use of a vascular closure device, the femoral arterial access is still associated with a higher rate of access site bleedings, consisting mostly of intermediate to large hematomas. No differences of MACE were found between FC versus RC following PCI at 30 days., Trial Registry: ClinicalTrials.gov ( https://clinicaltrials.gov/ct2/show/NCT02455661 ).

Coronary artery disease (CAD) represents a common structural cause for developing cardiac arrest in older patients, whereas in young adults cardiac arrest is more often caused by cardiomyopathies and cardiac channelopathies. A structural heart disease is known in almost 50% of patients prior to cardiac arrest. The present review outlines current interventional and operative therapeutic options for patients surviving cardiac arrest. The focus is on associations between epidemiological data on the incidence of malignant arrhythmias causing cardiac arrest depending on the presence or absence of CAD. Furthermore, the potential benefits of an early coronary revascularization as well as of a prompt complete coronary revascularization compared to the individual treatment of the so-called culprit lesion only are described. Finally, the advantages of invasive therapies for patients surviving cardiac arrest, such as targeted temperature management and mechanical cardiac assist devices, are elucidated. Cardiac assist devices comprise the use of the intra-aortic balloon pump (IABP) and devices for extracorporeal life support (ECLS) for peripheral and central support of the right and left heart chambers.

The aim of the present study was to determine the analysis of virulence genes and antimicrobial profile of diarrheagenic Escherichia coli isolated from diseased lambs. Two hundred ninety E. coli isolates were recovered from 300 rectal swabs of diarrheic lambs and were confirmed by biochemical tests. The pathotype determination was done according to the presence of genes including f5, f41, LTI, STI, bfp, ipaH, stx 1 , stx 2 , eae, ehlyA, cnf 1 , cnf 2 , cdIII, cdIV, and f17 by PCR method. Sixty-six isolates (23.72%) possessed the STI gene and categorized into entrotoxigenic E. coli (ETEC). Nine isolates (3.1%) and five isolates (1.72%) were positive for the cnf1 and cnf2 genes which categorized into necrotoxic E. coli (NTEC). Hundred and seventeen isolates (40.34%) harbored stx 1 and/or stx 2 and classified as Shiga toxin-producing E. coli (STEC). Thirteen isolates (4.48%) were assigned to atypical entropathogenic E. coli (aEPEC) and possessed eae gene. Two isolates (0.68%) were positive for ipaH gene and were assigned to entroinvasive E. coli (EIEC). Statistical analysis showed a specific association between eae gene and STEC pathotype (P < 0.0001). The most prevalent resistance was observed against lincomycin (96.5%) and the lowest resistance was against kanamycine (56.02%), respectively. The high prevalence of STEC and ETEC indicates that diarrheic lambs represent an important reservoir for humans. ETEC may play an important role for frequent occurrence of diarrhea in lambs observed in this region. Due to high antibiotic resistance, appropriate control should be implemented in veterinary medicine to curb the development of novel resistant isolates.

Derivation and stable maintenance of porcine induced pluripotent stem cells (piPSCs) is challenging. We herein systematically analyzed two piPSC lines, derived by lentiviral transduction and cultured under either leukemia inhibitory factor (LIF) or fibroblast growth factor (FGF) conditions, to shed more light on the underlying biological mechanisms of porcine pluripotency. LIF-derived piPSCs were more successful than their FGF-derived counterparts in the generation of in vitro chimeras and in teratoma formation. When LIF piPSCs chimeras were transferred into surrogate sows and allowed to develop, only their prescence within the embryonic membranes could be detected. Whole-transcriptome analysis of the piPSCs and porcine neonatal fibroblasts showed that they clustered together, but apart from the two pluripotent cell populations of early porcine embryos, indicating incomplete reprogramming. Indeed, bioinformatic analysis of the pluripotency-related gene network of the LIF- versus FGF-derived piPSCs revealed that ZFP42 (REX1) expression was absent in both piPSC-like cells, whereas it was expressed in the porcine inner cell mass at Day 7/8. A second striking difference was the expression of ATOH1 in piPSC-like cells, which was absent in the inner cell mass. Moreover, our gene expression analyses plus correlation analyses of known pluripotency genes identified unique relationships between pluripotency genes in the inner cell mass, which are to some extent, in the piPSC-like cells. This deficiency in downstream gene activation and divergent gene expression may be underlie the inability to derive germ line-transmitting piPSCs, and provides unique insight into which genes are necessary to achieve fully reprogrammed piPSCs. 84: 229-245, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Retrograde recanalization of coronary chronic total occlusions (CTO) via contralateral (CL) collateral connections (CCs) is successful in 60-70% of patients in whom conventional antegrade approach fails or is unpromising. This study describes our experience with retrograde CTO-PCI via ipsi-lateral (IL) CCs in patients with unfavorable CL CCs., Methods: Between January 2013 and September 2015, 392 consecutive CTO procedures were performed by two high volume CTO-operators and the relevant data were fed into an online registry (ERCTO® EuroCTO-club). Most patients (222/392; 57%) were approached antegradely, whereas 43% were attempted retrogradely (170/392). After exclusion of all procedures performed via bypass-grafts (n = 12), PCI via CL CCs, the CL-group (n = 114/158; 72%), was compared with the IL-group that was attempted via IL CCs (n = 44/158; 28%)., Results: Both groups were similar with respect to risk factors and morphologic criteria of CTO-severity. The initial primary strategy was successful in 78% in the CL-group and in 68% in the IL-group. In both patient groups, the initial strategy had to be switched in five patients from CL toward IL (4.4%, n = 5/114) and from IL to CL (11.3% n = 5/44). The rate of major complications was 7% (CL) and 5% (IL), respectively (n.s.). After retrograde failure and cross-over to an antegrade controlled re-entry strategy the overall success rates increased to 92% (CL) and 93% (IL)., Conclusions: In experienced hands retrograde CTO-PCI via IL CCs appears as safe and successful as the CL approach. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: To analyze differences of access-site complications related to the height of femoral arterial puncture and the use of a vascular closure device (VCD) following percutaneous coronary intervention (PCI)., Methods: A subgroup of the FERARI study being treated by femoral arterial access and valuable inguinal angiography before implantation of a VCD were included. Inguinal angiographies were systematically reviewed by two independent cardiologists to determine the correct height of femoral arterial puncture. Bleeding complications were documented within 30 days after PCI and were categorized according to BARC, TIMI, GUSTO and FERARI classifications., Results: Femoral access point imaging was available in 95 patients compared to 105 patients without. The common femoral artery (CFA) was the most accessed artery in 41%, followed by the femoral arterial bifurcation (39%) and lower access sites distally from the femoral arterial bifurcation (low puncture: 20%). No differences were observed regarding indication of PCI, procedural data and anticoagulation therapies in relation to the heights of femoral arterial access (p > 0.05). Despite using VCD, arterial puncture at the CFA resulted in numerically highest numbers of overall bleedings (62%) compared to femoral arterial bifurcation (41%) (p = 0.059). 58% of bleedings occurred after arterial puncture below the femoral bifurcation (low puncture). Though no significant differences of bleedings regarding classifications of BARC, GUSTO, TIMI and FERARI as well as other vascular endpoints were observed regarding puncture height., Conclusions: The present analysis demonstrates no significant differences of bleeding complications in relation to the height of femoral arterial puncture and subsequent use of a VCD.

Background: Coronary Artery Disease (CAD) is the most common reason for death in the western hemisphere. Therefore, a well-functioning risk-management has been established over the past decades with uprising interest in 'novel' biomarkers to predict adverse coronary events and detect patients with subclinical CAD. This review will focus on selected biomarkers belonging to the family of inflammatory markers (fibrinogen or hs-CRP) or to the family of lipid-associated markers (Lipoprotein associated PA2 or Lipoprotein a) and organ-specific biomarkers (hs-troponin, Cystatin C or NTproBNP)., Methods: This review is based on a pubmed search focusing on the biomarkers fibrinogen, hs-CRP, Lipoprotein associated PA2, Lipoprotein a, hs-troponin, NT-proBNP and Cystatin C., Results: The search retrieved 149 references containing meta-analysis, prospective and retrospective studies concerning the usage of the selected biomarkers in risk prediction and detection of CAD. Despite clinical studies, current guidelines of the European Society of Cardiology (ESC), the American Heart Association (AHA) and the Canadian Cardiovascular Society (CCS) were analyzed regarding their recommendation of the implementation of biomarkers in clinical routine. The review identified promising stand-alone biomarkers and multi-marker risk models for CAD patients., Conclusion: Novel biomarkers detect patients at risk beyond established risk scores. However, an ideal biomarker fulfilling all necessary criteria does still not exist., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: This study evaluates the association between high sensitivity troponin I (hsTnI) and T (hsTnT) in patients with suspected stable Coronary Artery Disease (CAD) undergoing Coronary Computed Tomography Angiography (CCTA)., Methods: Patients undergoing CCTA were enrolled prospectively. CCTA was indicated in patients with angina and a low to intermediate pre-test probability for CAD during routine clinical care. Blood samples were taken at the time of CCTA to measure cardiac biomarkers., Results: A total of 99 patients were enrolled with 43 % revealing no CAD, 30 % with non-obstructive and 26 % with obstructive CAD. Out of these, 61 % had single-vessel and 39 % had multi-vessel CAD. Both hsTnI and hsTnT levels increased significantly according to the presence and extent of CAD (p = 0.0001) and were able to discriminate the presence of both obstructive (AUC range: 0.775 - 0.785; p = 0.0001) and multi-vessel CAD (AUC range: 0.740 - 0.749; p = 0.01). In multivariate logistic regression models adjusted for cardiovascular risk factors and NT-proBNP, both hsTn were still associated significantly with obstructive CAD (range of odds ratios (OR): 8.3-32.3; p < 0.02)., Discussion: This study shows that high sensitivity troponin I and T reflect the presence and extent of CAD being diagnosed by CCTA in patients with a low to intermediate pretest probability for CAD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet., Objectives: We aimed to study the effects of interventional LAAC on systemic metabolism., Methods: Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ™ p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1)., Results: During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta -0.19, p < 0.01) and the increase of sarcosine (beta 0.16, p < 0.01)., Conclusions: Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future., Competing Interests: Compliance with Ethical StandardsEach of the authors declares that she or he has no conflict of interest.All procedures performed in this study were approved by the medical ethics committee II of the Faculty of Medicine Mannheim, University of Heidelberg, Germany, and were in accordance with the 1964 Helsinki declaration and its later amendments.Written informed consent was obtained from all participants or their respective legal representative.

Successful revascularization of chronic total occlusions (CTOs) has been associated with clinical benefit. Data on outcomes in patients with previous coronary artery bypass grafting (CABG) undergoing percutaneous coronary intervention (PCI) for CTO, however, are scarce. A total of 2,002 consecutive patients undergoing PCI for CTO from January 2005 to December 2013 were divided into patients with and without previous CABG, and outcomes were retrospectively assessed. The primary outcome measure was all-cause mortality. Median follow-up was 2.6 years (interquartile range 1.1 to 3.1). A total of 292 patients (15%) had previous CABG; they were older and had a greater prevalence of comorbidities. Procedural success was achieved in 75% and 84% of patients in the previous CABG and the non-CABG groups (p <0.001), respectively. All-cause mortality was 16% and 11% in the previous CABG and the non-CABG groups (p = 0.002), and differences were mitigated after adjustment for baseline characteristics (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.86 to 1.74, p = 0.27). All-cause death was significantly reduced in patients with procedural success, both in the previous CABG (11% vs 32%, adjusted HR 0.43, 95% CI 0.24 to 0.77, p = 0.005) and the non-CABG groups (10% vs 20%, adjusted HR 0.63, 95% CI 0.45 to 0.86, p = 0.004), with similar mortality benefits associated with successful revascularization in both groups (interaction p = 0.24). In conclusion, the relative survival benefit of successful recanalization of CTO is independent of previous CABG. However, owing to a greater baseline risk, the absolute survival benefit of successful CTO procedures is more pronounced in patients with previous CABG than in non-CABG patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The obesity paradox has been described in different patient populations. Data on the relation between obesity and outcomes in patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) are lacking. Therefore, long-term mortality in patients undergoing CTO PCI was assessed according to different body mass index (BMI) categories., Methods: A total of 1993 patients undergoing CTO PCI at a tertiary care center between January 2005 and December 2013 were divided into five different BMI categories: underweight, <18.5kg/m 2 ; normal BMI, 18.5-24.9kg/m 2 ; overweight, 25.0-29.9kg/m 2 ; obese, 30.0-34.9kg/m 2 ; and very obese, ≥35.0kg/m 2 . The primary endpoint was all-cause mortality., Results: Median follow-up was 2.6 (interquartile range 1.1-3.1) years. Of the 1993 patients, 461 (23.1%) were of normal weight, 985 (49.4%) overweight, 396 (19.9%) obese, and 144 (7.2%) very obese. Compared with normal weight BMI patients (16.3%), overweight patients had a lower all-cause mortality (10.2%, Log Rank p=0.001), while obese (11.1%, Log Rank p=0.08) and severely obese (13.2%, Log Rank p=0.39) patients had similar mortality rates. Being overweight was significantly associated with a lower all-cause mortality (HR 0.69, 95% CI 0.53-0.89, p=0.005), and associations remained significant after multivariable adjustments for confounding factors (HR 0.73, 95% CI 0.56-0.95, p=0.02). While being overweight was linked with a reduced all-cause mortality in men (HR 0.65, 95% CI 0.48-0.88, p=0.005), it was not in women (HR 1.25, 95% CI 0.60-2.52, p=0.58)., Conclusions: Overweight is associated with an improved survival in patients undergoing PCI for CTO, particularly in men., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Data regarding radiation exposure related to radial versus femoral arterial access in patients undergoing percutaneous coronary intervention (PCI) remain controversial. This study aims to evaluate patients enrolled in the FERARI study regarding radiation exposure, fluoroscopy time and contrast agent use., Methods: The Femoral Closure versus Radial Compression Devices Related to Percutaneous Coronary Interventions (FERARI) study evaluated prospectively 400 patients between February 2014 and May 2015 undergoing PCI either using the radial or femoral access. In these 400 patients, baseline characteristics, procedural data such as procedural duration, fluoroscopy time, dose-area product (DAP) as well as the amount of contrast agent used were documented and analyzed., Results: Median fluoroscopy time was not significantly different in patients undergoing radial versus femoral access (12.2 vs. 9.8min, p=0.507). Furthermore, median DAP (54.5 vs. 52.0 Gycm2, p=0.826), procedural duration (46.0 vs. 45.0min, p=0.363) and contrast agent use (185.5 vs. 199.5ml, p=0.742) were also similar in radial and femoral PCI., Conclusion: There was no difference regarding median fluoroscopy time, procedural duration, radiation dose or contrast agent use between radial versus femoral arterial access in PCI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This case report describes a successful percutaneous coronary intervention (PCI) of a severely calcified aorto-ostial chronic total occlusion (CTO) of the right coronary artery (RCA). The lesion was treated by a retrograde approach implementing long spiral subintimal wire tracking and final coronary stenting creating a subintimal neo-luminal helix around the natively occluded RCA. After 6 months of follow-up valuable angiographic results were proven., Competing Interests: The authors have no conflicts of interest to declare.

Objectives: The treatment of mild-to-moderate aortic dilatation at the time of aortic valve replacement (AVR) in patients with bicuspid aortic valve (BAV) disease is still controversial. We aimed to estimate late progression of aortopathy in patients who underwent isolated AVR for BAV stenosis with concomitant proximal aortic dilatation of ≥40 mm., Methods: The review of our institutional BAV database (n = 510) revealed a subgroup of 96 consecutive BAV patients (57 ± 10 years, 78% male) with BAV stenosis and concomitant ascending aortic dilatation of ≥40 mm [i.e. as defined by magnetic resonance imaging (MRI)/computed tomography (CT)], who underwent isolated AVR from 1995 to 2006. Aortic diameters were quantified by preoperative MRI/CT in all patients (i.e. all cases without MRI/CT were excluded). Moreover, we excluded all cases of simultaneous aortic surgery. MRI/CT follow-up (855 patient-years) was obtained in 83 (87%) patients. Study end-points were progression of proximal aortic diameters (mm/patient-year) and prevalence of aortic events (sudden death, aortic dissection and aortic surgery)., Results: MRI/CT follow-up (mean 10.3 ± 3.8 years post-AVR) revealed no significant progress of maximal cross-sectional aortic diameters (i.e. 46.4 ± 4.4 mm pre-AVR vs 46.9 ± 4.6 mm post-AVR, P = 0.1). Aortic diameters were identical in 54 (65%) patients. The mean progression rate of maximal cross-sectional aortic diameter was 0.09 mm/patient-year for the whole study cohort, whereas diameter increase of ≥5 mm was revealed in 1 (1%) patient. No aortic dissection occurred. Five (5%) patients underwent redo aortic surgery for aneurysm, whereas 3 of them had aortic diameters identical to pre-AVR., Conclusions: Mild-to-moderate ascending aortic dilatation remains stable in most BAV patients who underwent isolated AVR surgery for aortic valve stenosis at least 10-year post-AVR., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The efficiency of various assisted reproductive techniques can be improved by preconditioning the gametes and embryos with sublethal hydrostatic pressure treatment. However, the underlying molecular mechanism responsible for this protective effect remains unknown and requires further investigation. Here, we studied the effect of optimised hydrostatic pressure treatment on the global gene expression of mouse oocytes after embryonic genome activation. Based on a gene expression microarray analysis, a significant effect of treatment was observed in 4-cell embryos derived from treated oocytes, revealing a transcriptional footprint of hydrostatic pressure-affected genes. Functional analysis identified numerous genes involved in protein synthesis that were downregulated in 4-cell embryos in response to hydrostatic pressure treatment, suggesting that regulation of translation has a major role in optimised hydrostatic pressure-induced stress tolerance. We present a comprehensive microarray analysis and further delineate a potential mechanism responsible for the protective effect of hydrostatic pressure treatment.

Aims: A systematic description of the percutaneous treatment of chronic total occlusions (CTOs) of the right coronary artery (RCA) using ipsilateral collateral connections (CCs) for the retrograde approach has never been carried out. Our aim was to investigate this issue systematically., Methods and Results: Based on the experiences of a European high-volume CTO centre: 1) a generalised scheme of the varying anatomic courses of ipsilateral CCs bridging CTOs of the RCA was developed; 2) important stepwise technical advice for the ipsilateral retrograde approach was formulated; and 3) a supportive clinical case series was assessed. Of a total of 158 patients with CTOs of the RCA, 30% (n=47) revealed ipsilateral CCs of the RCA. Five different types (A-E) of ipsilateral CCs were assessed. The retrograde ipsilateral approach was attempted in nine patients, and was completed successfully in 89% (8/9 patients). Median left ventricular ejection fraction was 56% (interquartile range [IQR]: 50-60%) and mean J-CTO score was 2.9 (standard error of mean [SEM]: ±0.3). Median procedural duration time was 150 min (IQR 117-160 min), with a median applied amount of contrast of 360 ml (IQR 270-400 ml). No relevant complications, such as acute renal failure or severe bleedings, occurred., Conclusions: The percutaneous treatment of CTOs of the RCA using ipsilateral CCs for the retrograde approach might provide a novel treatment alternative for patients with CTOs of the RCA in specific clinical situations.

Gastric cancer (GC) is the second cause of cancer-related death worldwide. Interleukin (IL)-16 has a vital role in the development and homeostasis of the immune system. In the present study, we evaluated an exon variant rs4072111 C/T polymorphism and 3' UTR variant rs1131445 C/T within the miRNA binding with gastric cancer susceptibility in Iranian population. Genomic DNA was isolated from peripheral blood samples according to phenol chloroform extraction. The genotypes of IL-16 polymorphisms rs1131445 T/C and rs4072111 T/C were determined by polymerase chain reaction-restriction fragment length polymorphism method. In this case control study, a total of 256 patients with gastric cancer (238 cases (92.9 %) non-cardia and 18 cases (7.1 %) cardia) and 300 healthy control subjects were evaluated. In the present study, we found a significant association between rs4072111 of IL-16 gene and risk of GC in Iranian population. Individuals with CT genotype showed a significant association with 1.79-fold increased risk of GC (P = 0.008; adjusted OR 1.792; 95 % CI 1.164-2.759). The significant association was also detected for T allele of rs4072111 and increased risk of GC (P < 0.001; adjusted OR 1.981; 95 % CI 1.354-2.900). We also observed statistically a significant relationship between rs1131445 of IL-16 CT genotype and GC risk. Carriers of IL-16 CT genotype compared with TT genotype had 1.44 times higher increased likelihood of GC (P = 0.048; adjusted OR 1.445; 95 % CI 1.003-2.084). After stratification according to gender, we observed that in rs1131445, CT and CC male carriers had a higher risk of GC than females (P = 0.08; adjusted OR 1.608; 95 % CI 0.945-2.737 and P = 0.08; adjusted OR 2.186; 95 % CI 0.897-5.325, respectively). We also observed that for male carriers with C allele in rs1131445, there was a 1.53-fold higher risk of GC risk than female subjects (P = 0.029; adjusted OR 1.53; 95 % CI 1.04.4-2.248). We found that the rs1131445 T/C and rs4072111 T/C variants of IL-16 were significantly associated with increased risk of GC in Iranian population.

Background: Implantation of left atrial appendage (LAA) occlusion devices was shown to be a feasible and effective alternative to oral anticoagulation in patients with non-valvular atrial fibrillation. However, only few data about in-hospital and peri-procedural data are currently available. This study aims to report about echocardiographic, procedural and in-hospital data of patients receiving LAA occlusion devices., Methods: This single-center, prospective and observational study includes consecutively patients being eligible for percutaneous implantation of LAA occlusion devices (either Watchman™ or Amplatzer™ Cardiac Plug 2). Data on pre- and peri-procedural transesophageal echocardiography (TEE), implantation and procedure related in-hospital complications were collected. The primary efficacy outcome measure was a successful device implantation without relevant peri-device leaks (i.e., < 5 mm)., Results: In total, 37 patients were included, 22 receiving the Watchman™ and 15 ACP 2 device. Baseline characteristics did not differ significantly in both patient groups. The primary efficacy outcome measure was reached in 91.9% of patients (90.9% for the Watchman™, 93.3 % for the ACP 2 group). One device embolization (Watchman™ group) with successful retrieval occurred (2.7% of patients). No thromboembolism or device thrombosis were present. The majority of bleedings was caused by access site bleedings (88.3% of all bleedings), consisting mostly of mild hematomas corresponding to a BARC type 1 bleeding (80.0% of all access-site complications). One patient died due to septic shock (non-procedure related)., Conclusions: In daily real-life practice, percutaneous treatment with LAA occlusion devices appears to be an effective and safe.

A transcriptomic analysis of cultured human uterine smooth muscle cells (hUtSMCs) was performed to examine gene expression profiles in smooth muscle in an environment containing the two major steroid hormones that regulate the human myometrium in physiological states associated with estrous, pregnancy, labor, and pathophysiological states such as leiomyoma and endometrial cancer. hUtSMCs were treated with progesterone (P4) and 17β-estradiol (E2) individually and in combination, in the presence and absence of RU486 (mifepristone). Transcription of many genes was modulated in the presence of P4 or E2 alone, but almost six times more genes were transcriptionally modulated in the presence of the P4/E2 hormone combination. In total 796 annotated genes were significantly differentially expressed in the presence of both P4 and E2 relative to their expression in untreated cells. Functional withdrawal of P4 by addition of RU486 effectively reversed almost all transcriptional changes caused by P4/E2 treatment. Gene ontology analysis of differentially expressed genes revealed a strong association between P4/E2 treatment and downregulated expression of genes involved in cell communication, signal transduction, channel activity, inflammatory response, and differentiation. Upregulated processes included cell survival, gene transcription, steroid hormone biosynthesis, muscle development, insulin receptor signaling, and cell growth., (Copyright © 2016 the American Physiological Society.)

Background: Bleeding events after percutaneous coronary interventions (PCI) are associated with patients' age, gender, and the presence of chronic kidney disease, antithrombotic treatment, as well as arterial access site. Patients being treated by PCI using radial access site are associated with an improved prognosis. However, the safety of femoral closure devices has never been compared to radial compression devices following PCI. Therefore, the aim of this study is to evaluate the safety of femoral closure compared to radial compression devices in patients treated by PCI envisaging access site bleedings as well as short- and long-term prognostic outcomes., Methods: The Femoral Closure versus Radial Compression Devices Related to Percutaneous Coronary Interventions (FERARI) study is a single-center observational study comparing 400 consecutive patients undergoing PCI either using radial compression devices (TR Band™) or femoral closure devices (Angio-Seal™) at the corresponding access site. The primary outcome consists of the occurrence of vascular complications at the arterial access site, including major bleedings as defined by common classification systems. Secondary outcomes consist of the occurrence of adverse cardiac events, including all-cause mortality, target lesion revascularization, and target vessel revascularization during 30 days and 12 months of follow-up., Results: Study enrollment was initiated in February 2014. The enrollment phase is expected to last until May 2015., Conclusions: The FERARI study intends to comparatively evaluate the safety and prognostic outcome of patients being treated by radial or femoral arterial closure devices following PCI during daily clinical practice.

Changes in carbohydrates, enzymes, and pigments were investigated in the Red Garlic (Allium sativum L.) cv. Azarshahr bulbs in storage from harvest to sprouting. For storage period, garlic cloves of the same diameter with 3-4 g weight were arranged in dark condition and exposed to 4 and 21°C, separately. Soluble sugar, total sugar, glucose, sucrose, fructose, starch, chlorophyll a, b, ab, carotenoid, anthocyanin, lipase, α-amylase, and protease were measured every 2 weeks up to sprouting time. Result revealed that starch, lipase, and protease levels declined at the end of storage when clove sprouting started at both 4 and 21°C storage temperature. Starch, glucose, chlorophyll a, b, ab, and carotenoid content during the first 14 days and sucrose at 42 days showed a decreasing trend. Anthocyanin showed an increasing trend 14 and 42 days after harvesting and then decreased at the end of storage (when sprouting began) at both 4 and 21°C storage periods. Finally, starch, glucose, and sucrose measurement can be used as a criterion to predict sprouting time of garlic, due to the decrease in the levels of starch, lipase, and protease, and increase in the levels of α-amylase, glucose, and sucrose in garlic cloves under storage.