Response of conductance and resistance coronary vessels to scalar concentrations of acetylcholine: Assessment with quantitative angiography and intracoronary Doppler echography in 29 patients with coronary artery disease

Abnormal vasoreactivity of the large conductance arteries has been observed in the presence of impaired endothelial function. More recently, experimental and clinical reports have shown that in early coronary atherosclerosis the impairment of the endothelium-mediated vasodilatation also involves the resistance arteries. The aim of this study is the correlation of endothelium-dependent vasodilatation of conductance and resistance vessels in coronary arteries without significant stenoses. In 29 patients (aged 57 +/- 9 years, 24 men and 5 women) undergoing coronary angioplasty, a Doppler guide wire and a perfusion catheter were introduced into the proximal segment of an artery with less than 30% diameter stenosis. Selective infusions of papaverine (bolus of 7 mg), acetylcholine (continuous infusion of 0.036, 0.36, and 3.6 micrograms/ml at a flow rate of 2 ml/min), and isosorbide dinitrate (bolus of 3 mg) were sequentially performed. Heart rate, aortic blood pressure, and blood flow velocity were continuously measured. Mean cross-sectional areas of a proximal and a distal arterial segment were measured in baseline conditions, at the end of each infusion of acetylcholine, and at the peak effect of isosorbide dinitrate with quantitative angiography (CAAS System; Pie Medical Data, Maastricht, The Netherlands). Coronary blood flow was calculated from the time-averaged flow velocity and the cross-sectional area at the site of the Doppler sample volume. Coronary flow resistance was calculated as mean aortic pressure divided by coronary flow. All of the concentrations of acetylcholine induced a significant vasoconstriction of the studied artery. At the maximal concentration of acetylcholine all but three patients (90%) showed a reduction of cross-sectional area (-24% +/- 20% and -22% +/- 20% for the proximal and distal segments, respectively, p < 0.00001). Flow velocity showed a significant increase only with the two highest concentrations of acetylcholine. The maximal concentration induce

901-21 Percutaneous Vascular Surgery: Suture Mediated Percutaneous Closure of Femoral Artery Access Site Following Coronary Intervention

A new device (prostarTm, Perclose, Inc.) was developed to close femoral artery access sites percutaneously following coronary interventions in fully anticoagulated patients. The catheter deploys four needles with two pairs of sutures around the hole of femoral artery access sites. The sutures are then tied to close the arteriotomy site mechanically to achieve immediate hemostasis. As a pilot phase, the device was tested in six centers. The device was used immediately following coronary intervention in 91 access sites. Despite an average ACT at the time of the procedure of &gt;300 seconds, immediate complete hemostasis was achieved in 82 sites (90%). The devices were not appropriately positioned in 8 cases and procedures were aborted followed by reinsertion of a sheath or manual compression. Two patients (2.2%) required surgical repair of the femoral artery; one with device mechanical failure and one with bleeding from the initial puncture site in the posterior wall despite successful closure of the sheath site in the front wall. There were no AV fistulae or pseudoaneurysms requiring surgery and no infection, distal embolism or need for blood transfusion.In conclusion, this pilot study suggests that this suture mediated closure device appears to provide safe and effective hemostasis at the femoral access site in fully anticoagulated patients following coronary interventions

OCT assessment of the long-term vascular healing response 5 years after everolimus-eluting bioresorbable vascular scaffold

AbstractBackgroundAlthough recent observations suggest a favorable initial healing process of the everolimus-eluting bioresorbable vascular scaffold (BVS), little is known regarding long-term healing response.ObjectivesThis study assessed the in vivo vascular healing response using optical coherence tomography (OCT) 5 years after elective first-in-man BVS implantation.MethodsOf the 14 living patients enrolled in the Thoraxcenter Rotterdam cohort of the ABSORB A study, 8 patients underwent invasive follow-up, including OCT, 5 years after implantation. Advanced OCT image analysis included luminal morphometry, assessment of the adluminal signal-rich layer separating the lumen from other plaque components, visual and quantitative tissue characterization, and assessment of side-branch ostia “jailed” at baseline.ResultsIn all patients, BVS struts were integrated in the vessel and were not discernible. Both minimum and mean luminal area increased from 2 to 5 years, whereas lumen eccentricity decreased over time. In most patients, plaques were covered by a signal-rich, low-attenuating layer. Minimum cap thickness over necrotic core was 155 ± 90 μm. One patient showed plaque progression and discontinuity of this layer. Side-branch ostia were preserved with tissue bridge thinning that had developed in the place of side-branch struts, creating a neo-carina.ConclusionsAt long-term BVS follow-up, we observed a favorable tissue response, with late luminal enlargement, side-branch patency, and development of a signal-rich, low-attenuating tissue layer that covered thrombogenic plaque components. The small size of the study and the observation of a different tissue response in 1 patient warrant judicious interpretation of our results and confirmation in larger studies

Antithrombotic therapy in patients undergoing TAVI: an overview of Dutch hospitals

To assess current antithrombotic treatment strategies in the Netherlands in patients undergoing transcatheter aortic valve implantation (TAVI). For every Dutch hospital performing TAVI (n = 14) an interventional cardiologist experienced in performing TAVI was interviewed concerning heparin, aspirin, thienopyridine and oral anticoagulation treatment in patients undergoing TAVI. The response rate was 100 %. In every centre, a protocol for antithrombotic treatment after TAVI was available. Aspirin was prescribed in all centres, concomitant clopidogrel was prescribed 13 of the 14 centres. Duration of concomitant clopidogrel was 3 months in over two-thirds of cases. In 2 centres, duration of concomitant clopidogrel was based upon type of prosthesis: 6 months versus 3 months for supra-annular and intra-annular prostheses, respectively. Leaning on a small basis of evidence and recommendations, the antithrombotic policy for patients undergoing TAVI is highly variable in the Netherlands. As a standardised regimen might further reduce haemorrhagic complications, large randomised clinical trials may help to establish the most appropriate approac

ABCA4-associated disease as a model for missing heritability in autosomal recessive disorders: novel noncoding splice, cis-regulatory, structural, and recurrent hypomorphic variants

PURPOSE: ABCA4-associated disease, a recessive retinal dystrophy, is hallmarked by a large proportion of patients with only one pathogenic ABCA4 variant, suggestive for missing heritability. METHODS: By locus-specific analysis of ABCA4, combined with extensive functional studies, we aimed to unravel the missing alleles in a cohort of 67 patients (p), with one (p = 64) or no (p = 3) identified coding pathogenic variants of ABCA4. RESULTS: We identified eight pathogenic (deep-)intronic ABCA4 splice variants, of which five are novel and six structural variants, four of which are novel, including two duplications. Together, these variants account for the missing alleles in 40.3% of patients. Furthermore, two novel variants with a putative cis-regulatory effect were identified. The common hypomorphic variant c.5603A>T p.(Asn1868Ile) was found as a candidate second allele in 43.3% of patients. Overall, we have elucidated the missing heritability in 83.6% of our cohort. In addition, we successfully rescued three deep-intronic variants using antisense oligonucleotide (AON)-mediated treatment in HEK 293-T cells and in patient-derived fibroblast cells. CONCLUSION: Noncoding pathogenic variants, novel structural variants, and a common hypomorphic allele of the ABCA4 gene explain the majority of unsolved cases with ABCA4-associated disease, rendering this retinopathy a model for missing heritability in autosomal recessive disorders

Dedicated plug based closure for large bore access -The MARVEL prospective registry

Objectives To study safety and performance of the MANTA Vascular closure device (VCD) under real world conditions in 10 centers.Background The MANTA is a novel plug-based device for large bore arteriotomy closure.Methods We included all eligible patients who underwent transfemoral large bore percutaneous procedures. Exclusion criteria were per operator's discretion and included severe calcification or marked tortuosity of the access vessel, presence of marked obesity/cachexia or a systolic blood pressure above 180 mmHg. The primary performance endpoint was time to hemostasis. Primary and secondary safety endpoints were major and minor access site related vascular complications up to 30 days, respectively. Vascular complications were adjudicated by an independent clinical event committee according to VARC-2 criteria. We performed multivariable logistic regression to estimate the effect of baseline and procedural characteristics on any and major vascular complications.Results Between February 2018 and July 2019 500 patients were enrolled undergoing Transcatheter aortic valve replacement (TAVR, N = 496), Balloon aortic valvuloplasty (BAV, N = 2), Mechanical circulatory support (MCS, N = 1) or Endovascular aneurysm repair (EVAR, N = 1). Mean age was 80.8 +/- 6.6 years with a median STS-score of 2.7 [IQR 2.0-4.3] %. MANTA access site complications were major in 20 (4%) and minor in 28 patients (5.6%). Median time to hemostasis was 50 [IQR 20-120] sec. Severe femoral artery calcification, scar presence in groin, longer procedure duration, female gender and history of hypertension were independent predictors for vascular complications.Conclusion In this study, MANTA appeared to be a safe and effective device for large bore access closure under real-world conditions