Search

ObjectivesThis study sought to evaluate the feasibility and safety of autologous bone marrow–derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure.BackgroundIn pre-clinical heart failure models, cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodeling.MethodsThe C-CURE (Cardiopoietic stem Cell therapy in heart failURE) trial, a prospective, multicenter, randomized trial, was conducted in patients with heart failure of ischemic origin who received standard of care or standard of care plus lineage-specified stem cells. In the cell therapy arm, bone marrow was harvested and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail. Derived cardiopoietic stem cells, meeting release criteria under Good Manufacturing Practice, were delivered by endomyocardial injections guided by left ventricular electromechanical mapping. Data acquisition and analysis were performed in blinded fashion. The primary endpoint was feasibility/safety at 2-year follow-up. Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy.ResultsMesenchymal stem cell cocktail–based priming was achieved for each patient with the dose attained in 75% and delivery without complications in 100% of cases. There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy. Left ventricular ejection fraction was improved by cell therapy (from 27.5 ± 1.0% to 34.5 ± 1.1%) versus standard of care alone (from 27.8 ± 2.0% to 28.0 ± 1.8%, p < 0.0001) and was associated with a reduction in left ventricular end-systolic volume (−24.8 ± 3.0 ml vs. −8.8 ± 3.9 ml, p < 0.001). Cell therapy also improved the 6-min walk distance (+62 ± 18 m vs. −15 ± 20 m, p < 0.01) and provided a superior composite clinical score encompassing cardiac parameters in tandem with New York Heart Association functional class, quality of life, physical performance, hospitalization, and event-free survival.ConclusionsThe C-CURE trial implements the paradigm of lineage guidance in cell therapy. Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure, meriting definitive clinical evaluation. (C-Cure Clinical Trial; NCT00810238).

(1) Background: Stent underexpansion is the main cause of stent thrombosis and restenosis. Coronary angiography has limitations in the assessment of stent expansion. Enhanced stent imaging (ESI) methods allow a detailed visualization of stent deployment. We qualitatively compare image results from two ESI system vendors (StentBoost™ (SB) and CAAS StentEnhancer™ (SE)) and report quantitative results of deployed stents diameters by quantitative coronary angiography (QCA) and by SE. (2) Methods: The ESI systems from SB and SE were compared and graded by two blinded observers for different characteristics: 1 visualization of the proximal and distal edges of the stents; 2 visualization of the stent struts; 3 presence of underexpansion and 4 calcifications. Stent diameters were quantitatively measured using dedicated QCA and SE software and compared to chart diameters according to the pressure of implantation. (3) Results: A total of 249 ESI sequences were qualitatively compared. Inter-observer variability was noted for strut visibility and total scores. Inter-observer agreement was found for the assessment of proximal stent edge and stent underexpansion. The predicted chart diameters were 0.31 ± 0.30 mm larger than SE diameters (p < 0.05). Stent diameters by SE after post-dilatation were 0.47 ± 0.31 mm smaller than the post-dilation balloon diameter (p < 0.05). SE-derived diameters significantly differed from QCA; by Bland–Altman analysis the bias was −0.37 ± 0.42 mm (p < 0.001). (4) Conclusions: SE provides an enhanced visualization and allows precise quantitative assessment of stent expansion without the limitations of QCA when overlapping coronary side branches are present.

IntroductionAlthough recently published evidence favours transradial access (TRA) when using large-bore guiding catheters for percutaneous coronary intervention (PCI) of complex coronary lesions, the femoral artery will still be used in a considerate proportion of patients undergoing complex PCI, especially in PCI of chronic total occlusions (CTO). Ultrasound-guided puncture of the femoral artery may reduce clinically relevant access site complications, but robust evidence is lacking up to date.Methods and analysisA total of 542 patients undergoing complex PCI, defined as PCI of CTO, complex bifurcation, heavy calcified lesion or left main, in which the 7-F or 8-F transfemoral access is required, will be randomised to ultrasound-guided puncture or fluoroscopy-guided puncture. The primary outcome is the incidence of the composite end-point of clinically relevant access site related bleeding and/or vascular complications requiring intervention. Access site complications and major adverse cardiovascular events up to 1 month will also be compared between both groups.Ethics and disseminationEthical approval for the study was granted by the local Ethics Committee (‘Medisch Ethische Toetsing Commissie Isala Zwolle’) for all Dutch sites, ‘Comité Medische Ethiek Ziekenhuis Oost-Limburg’ for Hospital Oost-Limburg, ‘Comité d’éthique CHU-Charleroi—ISPPC’ for Centre Hospilatier Universitaire de Charleroi and ‘Ethik Kommission de Ärztekammer Nordrhein’ for Elisabeth-Krankenhaus). The trial outcomes will be published in peer-reviewed journals of the concerned literature. Theultrasound guidedtransfemoral access incomplexlarge bore PCI trial has been administered in the ClinicalTrials.gov database, reference number:NCT03846752.Registration detailsClinicalTrials.gov identifier:NCT03846752.

Objectives: To assess the safety and efficacy of everolimus-eluting bioresorbable scaffolds (BRS) in the treatment of chronic total occlusions (CTO) using noninvasive multislice computed tomography (MSCT) angiography at one-year follow-up. Background: Current evidence regarding the safety and efficacy of BRS for the percutaneous treatment of CTO is limited. Methods: Between September 2013 and January 2016, patients who received one or more ABSORB BRSs were included at three centers. MSCT (including quantitative analysis) and clinical follow-up were performed at one year. Results: Forty-one CTO patients were included. Mean age was 6011 years and the majority was male (83%). Average Japanese CTO (J-CTO) score was 0.9 +/- 0.9. Seventy-one BRS were implanted in total with, on average, 1.7 +/- 0.8 scaffolds/patient, and a total length of 43 +/- 20 mm and diameter of 3.1 +/- 0.4 mm. One noncardiac death took place. MSCT angiography was performed in 34 (83%) patients: all scaffolds were patent, except in one patient, in whom a patent target vessel was present on subsequent diagnostic angiography. MSCT quality was sufficient for quantitative analyses in 27 patients (46 scaffolds): median reference versus scaffold minimal lumen diameter and minimal lumen area were measured, and showed a small difference of 0.1 mm (-0.2-0.4) (lumen diameter stenosis = 3.0%) and 0.5 mm(2) (-1.0-2.0) (lumen area stenosis = 4.2%). Conclusions: The low number of events and high patency rate at 1 year are encouraging the further use of the ABSORB scaffold for CTOs with low J-CTO score. Noninvasive MSCT angiography is a valid tool to assess scaffold patency, although its image resolution limits the use for quantitative measurements. This research project is supported by an unrestricted research grant from ABBOTT Vascular (Santa Clara, California, USA). Joren Maeremans is researcher for the Limburg Clinical Research Program (LCRP) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk (LSM), Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital.

This study assessed the influence of the evolution in Transcatheter Aortic Valve Implantation technology on cerebral oxygenation. Cerebral oxygenation was measured continuously with Near-Infrared Spectroscopy and compared retrospectively between balloon-expandable, self-expandable and differential deployment valves which were implanted in 12 (34%), 17 (49%) and 6 patients (17%), respectively. Left and right SctO2 values were averaged at four time points and used for analysis (i.e. at baseline, balloon-aortic valvuloplasty, valve deployment, and at the end of the procedure). During balloon-aortic valvuloplasty and valve deployment, cerebral oxygenation decreased in patients treated with balloon or self-expandable valves (balloon-expandable: p = 0.003 and p = 0.002; self-expandable: p

Background: The aim of this study was to elucidate the possible role of cerebral saturation monitoring in the post-cardiac arrest setting. Methods: Cerebral tissue saturation (SctO(2)) was measured in 107 successfully resuscitated out-of-hospital cardiac arrest patients for 48 hours between 2011 and 2015. All patients were treated with targeted temperature management, 24 hours at 33 degrees C and rewarming at 0.3 degrees C per hour. A threshold analysis was performed as well as a linear mixed models analysis for continuous SctO(2) data to compare the relation between SctO(2) and favorable (cerebral performance category (CPC) 1-2) and unfavorable outcome (CPC 3-4-5) at 180 days post-cardiac arrest in OHCA patients. Results: Of the 107 patients, 50 (47 %) had a favorable neurological outcome at 180 days post-cardiac arrest. Mean SctO(2) over 48 hours was 68 % +/- 4 in patients with a favorable outcome compared to 66 % +/- 5 for patients with an unfavorable outcome (p = 0.035). No reliable SctO(2) threshold was able to predict favorable neurological outcome. A significant different course of SctO(2) was observed, represented by a logarithmic and linear course of SctO(2) in patients with favorable outcome and unfavorable outcome, respectively (p < 0.001). During the rewarming phase, significant higher SctO(2) values were observed in patients with a favorable neurological outcome (p = 0.046). Conclusions: This study represents the largest post-resuscitation cohort evaluated using NIRS technology, including a sizeable cohort of balloon-assisted patients. Although a significant difference was observed in the overall course of SctO(2) between OHCA patients with a favorable and unfavorable outcome, the margin was too small to likely represent functional outcome differentiation based on SctO(2) alone. As such, these results given such methodology as performed in this study suggest that NIRS is insufficient by itself to serve in outcome prognostication, but there may remain benefit when incorporated into a multi-neuromonitoring bedside assessment algorithm. This study is part of the Limburg Clinical Research Program (LCRP) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital.

Aims Antegrade wire escalation (AWE) remains the method of choice for tackling chronic total occlusions (CTOs), especially for lesions with low J-CTO score. To increase the number of operators which treat CTOs and increase AWE success rates, there is a need for a clear, algorithmic approach. We report the results of a simple AWE algorithm with new guidewire technology in coronary CTOs. Methods Hundred consecutive CTO lesions selected for AWE as the primary strategy were included in five Benelux centers. The algorithm follows a step-wise increase in guidewire tip load. Lesions were categorized according to the J-CTO score. Primary endpoint was successful guidewire crossing. Results No differences in baseline demographics were present between successful and unsuccessful procedures. Overall, in 75% of the lesions AWE resulted in successful crossing. AWE success rates in easy, intermediate, difficult and very difficult CTOs were 83, 86, 71 and 43%, respectively. 46% could be crossed using a soft guidewire only. An additional success of 34 and 60% could be reached with an intermediate and stiff guidewire, respectively. Adding additional techniques resulted in 88% overall success. Procedure and fluoroscopy times, radiation doses and use of contrast were within highly acceptable ranges (67 W 39 min, 27 W 19 min, 1.7 W 1.3 Gy, 264 W 123 ml). Conclusion The algorithm and new wire technologies led to high success rates. AWE as a standalone procedure is highly successful in J-CTO 0-1. Low- and intermediatevolume CTO operators should try to implement a systematic approach in their CTO procedures, especially for lesions with low J-CTO scores. Adding additional techniques further increases these success rates. No grants, contracts or other forms of financial support were given to support publication of this article.

Background: Post-cardiac arrest (CA) patients are at risk of secondary ischemic damage in the case of suboptimal brain oxygenation during an ICU stay. We hypothesized that elevated central venous pressures (CVP) would impair cerebral perfusion and oxygenation (venous cerebral congestion). The aim of the present study was to investigate the relationship between CVP, cerebral tissue oxygen saturation (SctO2) as assessed with near-infrared spectroscopy (NIRS) and outcome in post-CA patients. Methods: This was an observational study in 48 post-CA patients with continuous CVP and SctO2 monitoring during therapeutic hypothermia. Results: The relationship between CVP and mean SctO2 was best described by an S-shaped, third-degree polynomial regression curve (SctO2 = −0.002 × CVP3 + 0.08 × CVP2 – 1.07 × CVP + 69.78 %, R2 0.89, n = 1,949,108 data points) with high CVP (>20 mmHg) being associated with cerebral desaturation. Multivariate linear regression revealed CVP to be a more important determinant of SctO2 than mean arterial pressure (MAP) without important interaction between both (SctO2 = 0.01 × MAP – 0.20 × CVP + 0.001 × MAP × CVP + 65.55 %). CVP and cardiac output were independent determinants of SctO2 with some interaction between both (SctO2 = 1.86 × CO – 0.09 × CVP – 0.05 × CO × CVP + 60.04 %). Logistic regression revealed that a higher percentage of time with CVP above 5 mmHg was associated with lower chance of survival with a good neurological outcome (cerebral performance category (CPC) 1–2) at 180 days (OR 0.96, 95 % CI 0.92–1.00, p = 0.04). In a multivariate model, the negative association between CVP and outcome persisted after correction for hemodynamic variables, including ejection fraction and MAP. Conclusions: Elevated CVP results in lower brain saturation and is associated with worse outcome in post-CA patients. This pilot study provides support that venous cerebral congestion as indicated by high CVP may be detrimental for post-CA patients. The study is part of the Limburg Clinical Research Program (LRCP) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk, hasselt University, Ziekenhuis Oost-Limburg and Jessa hospital. There are no other financial disclosures.

BACKGROUND: Periprocedural myocardial injury (PMI) after percutaneous coronary intervention (PCI) might occur more frequently during challenging procedures such as PCI of chronic coronary total occlusion (CTO). The prognostic implication of PMI in CTO-PCI remains unclear. METHODS: From January 2006 to September 2012, a total of 715 consecutive patients undergoing CTO-PCI were screened at three centers. Only patients with available pre-PCI and post-PCI troponin (cTn) were included (n = 442). PMI was defined as an elevation of cTn >5x the upper reference limit (URL), or a rise of cTn >20% if baseline values were elevated. RESULTS: Patients were grouped into: (1) successful CTO-PCI and no-PMI (Group A; n = 195); (2) successful CTO-PCI with PMI (Group B; n = 133); failed CTO-PCI (Group C; n = 114). Occurrence of major adverse cardiovascular event (MACE) was assessed in 431 patients (97%), at a median follow-up of 25 months, and were significantly lower in patients successfully treated without PMI occurrence, while increased in cases of PMI or failed CTO-PCI (Group A, 9%; Group B, 15%; Group C, 28%; hazard ratio, 1.57 (95% confidence interval, 1.12-2.18); P

The brain is the most complex and fragile organ of our body: it exerts centralized control over the other organs of the body and forms the physical structure associated with the mind. Despite the brains’ vital role and fragility, it is one of the least monitored organs of our body. Standard monitoring or imaging technologies allows detecting brain injury after irreversible damage has occurred. Near infrared spectroscopy (NIRS) has the ability to detect regional cerebral tissue oxygen saturation in a continuous and non-invasive matter, allowing immediate detection of oxygenation disturbances and possible intervention when necessary. The technology is based on the ‘oxygen supply and demand’ physiology and could therefore be an indirect measurement of cerebral blood flow. We used the NIRS technology in several observational studies in different patient populations. In this way, we did an effort to determine in which patients or circumstances cerebral NIRS monitoring might be useful. ...