Microvascular endoglin (CD105) expression correlates with tissue markers for atherosclerotic plaque vulnerability in an ageing population with multivessel coronary artery disease.

AIMS: Vulnerable atherosclerotic plaques are lesions with a high propensity to develop plaque disruption and superimposed thrombosis. No systematic studies have been carried out on tissue markers for plaque vulnerability throughout the entire coronary artery system at the end stages of coronary atherosclerosis. METHODS AND RESULTS: Nine autopsied patients (mean age 77 years) with angiographically severe trivascular coronary atherosclerosis were selected for this study. All visible lesions in postmortem coronary angiograms (n = 125) were histologically and immunohistochemically screened for the presence of intraplaque haemorrhages (activated) microvessels and inflammatory infiltrates. Intraplaque haemorrhages were observed in 76/125 plaques (61%). Chronic inflammation was found superficially in 59/125 plaques (47%) and deeply inside the plaque tissue in 103/125 plaques (83%). Microvessels were found in 100/125 lesions (80%), of which 58% showed endothelial expression of the vascular activation marker CD105. Moreover, microvascular CD105 positivity correlated positively with plaque haemorrhage and deeply seated plaque inflammation. CONCLUSIONS: Plaque inflammation and haemorrhages can be found at a high frequency throughout the coronary artery system of elderly patients with multivessel coronary atherosclerosis. Microvascular expression of endoglin (CD105), which correlates positively with both of these features of plaque vulnerability, can serve as a marker of the risk of developing coronary thrombotic complications.

Association of Pulse Pressure With Clinical Outcomes in Patients Under Different Antiplatelet Strategies After Percutaneous Coronary Intervention: Analysis of GLOBAL LEADERS.

BACKGROUND: We evaluated the association of pulse pressure (PP) and different antiplatelet regimes with clinical and safety outcomes in an all-comers percutaneous coronary intervention (PCI) population. METHODS: In this analysis of GLOBAL LEADERS (n = 15,936) we compared the experimental therapy of 23 months of ticagrelor after 1 month of dual-antiplatelet therapy (DAPT) vs standard DAPT for 12 months followed by aspirin monotherapy in subjects who underwent PCI and were divided into 2 groups according to the median PP (60 mm Hg). The primary end point (all-cause death or new Q-wave myocardial infarction) and the composite end points: patient-oriented composite end points (POCE), Bleeding Academic Research Consortium (BARC) 3 or 5, and net adverse clinical events (NACE) were evaluated. RESULTS: At 2 years, subjects in the high-PP group (n = 7971) had similar rates of the primary end point (4.3% vs 3.9%; P = 0.058), POCE (14.9% vs 12.7%; P = 0.051), and BARC 3 or 5 (2.5% vs 1.7%; P = 0.355) and higher rates of NACE (16.4% vs 13.7%; P = 0.037) compared with the low-PP group (n = 7965). Among patients with PP < 60 mm Hg, the primary end point (3.4% vs 4.4%, adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.96), POCE (11.8% vs 13.5%, aHR 0.86, 95% CI 0.76-0.98), NACE (12.8% vs 14.7%, aHR 0.85, 95% CI 0.76-0.96), and BARC 3 or 5 (1.4% vs 2.1%, aHR 0.69, 95% CI 0.49-0.97) were lower with ticagrelor monotherapy compared with DAPT. The only significant interaction was for BARC 3 or 5 (P = 0.008). CONCLUSIONS: After contemporary PCI, subjects with high PP levels experienced high rates of NACE at 2 years. In those with low PP, ticagrelor monotherapy led to a lower risk of bleeding events compared with standard DAPT.

Transcatheter and minimally invasive surgical left ventricular reconstruction for the treatment of ischaemic cardiomyopathy: preliminary results†.

OBJECTIVES: Adverse remodelling of the left ventricle (LV) after myocardial infarction (MI) results in a pathological increase in LV volume and reduction in LV ejection fraction (EF). We describe the preliminary results of a novel, multicentre, combined transcatheter and minimally invasive technique to reconstruct the remodelled LV by plication and exclusion of the scar, and to reduce the excess volume, resulting in decreased wall stress and increased EF. METHODS: A novel hybrid transcatheter technique that relies on microanchoring technology (Revivent TC™ System, BioVentrix Inc., San Ramon, CA, USA) was used. The LV is reconstructed without the use of extracorporeal circulation by plication of the fibrous scar. This is achieved by implantation of a series of internal and external microanchors brought together over a PEEK (poly-ether-ether-ketone) tether to form a longitudinal line of apposition between the LV free wall and the anterior septum. Internal anchors are deployed by a transcatheter technique on the right side of the ventricular septum through the right internal jugular vein. Paired external anchors are advanced through a left-sided minithoracotomy and deployed on the LV epicardium. A specialized force gauge is used to bring these 'right ventricle (RV)-LV' anchors together under measured compression forces. LV-LV' anchor pairs through the LV apex beyond the distal tip of the RV complete the reconstruction. Patients who were considered eligible for the procedure presented with symptomatic heart failure (New York Heart Association class ≥II) and ischaemic cardiomyopathy (EF <40%) after anteroseptal MI. All patients had a dilated LV with either an a- or dys-kinetic scar in the anteroseptal wall and apex of ≥50% transmurality. RESULTS: Between October 2016 and April 2017, 9 patients (8 men, 1 woman; mean age 60 ± 8 years) were operated on in 2 Dutch centres. Procedural success was 100%. On average, 2.6 anchor pairs were used to reconstruct the LV. Comparing echocardiographic data preoperatively and directly postoperatively, LV ejection fraction increased from 28 ± 8% to 40 ± 10% (change +43%, P < 0.001) and LV volumes decreased LV end-systolic volume index 53 ± 8 ml/m2 to 30 ± 11 ml/m2 (change -43%, P < 0.001) and LVEDVI 75 ± 23 ml/m2 to 45 ± 6 ml/m2 (change -40%, P = 0.001). In 1 patient, an RV perforation occurred which necessitated conversion to full sternotomy. One patient underwent a postoperative revision because of RV restriction. After the removal of 1 'RV-LV' anchor pair, the patient recovered completely. Hospital mortality was 0%. The median duration of intensive care unit stay was 2 days [interquartile range (IQR) 1-46 days], and the median length of hospital stay was 9 days (IQR 3-57 days). CONCLUSIONS: Hybrid transcatheter LV reconstruction is a promising novel treatment option for patients with symptomatic heart failure and ischaemic cardiomyopathy after anteroseptal MI. The early results demonstrate that the procedure is safe and results in a significant improvement in EF and reduction in LV volumes in the early postoperative period.

Electrical remodeling after percutaneous atrial septal defect closure in pediatric and adult patients.

BACKGROUND: Several studies have reported changes in electrocardiographic variables after atrial septal defect (ASD) closure. However no temporal electro-and vectorcardiographic changes have been described from acute to long-term follow-up at different ages. We aimed to study electrical remodeling after percutaneous ASD closure in pediatric and adult patients. METHODS: ECGs of 69 children and 75 adults (median age 6 [IQR 4-11] years and 45 [IQR 33-54] years, respectively) were retrospectively selected before percutaneous ASD closure and at acute (1-7 days), intermediate (4-14 weeks) and late (6-18 months) follow-up. Apart from electrocardiographic variables, spatial QRS-T angle and ventricular gradient (VG) were derived from mathematically-synthesized vectorcardiograms. RESULTS: In both pediatric and adult patients, the heart rate decreased immediately post-closure, which persisted to late follow-up. The P-wave amplitude also decreased acutely post-closure, but remained unchanged at later follow-up. The PQ duration shortened immediately in children and at intermediate follow-up in adults. The QRS duration and QTc interval decreased at intermediate-term follow-up in both children and adults. In both groups the spatial QRS-T angle decreased at late follow-up. The VG magnitude increased at intermediate follow-up in children and at late follow-up in adults, after an initial decrease in children. CONCLUSION: In both pediatric and adult ASD patients, electrocardiographic changes mainly occurred directly after ASD closure except for shortening of QRS duration and QTc interval, which occurred at later follow-up. Adults also showed late changes in PQ duration. At 6-to-18 month post-closure, the spatial QRS-T angle decreased, reflecting increased electrocardiographic concordance. The initial acute decrease in VG in children, which was followed by a significant increase, may be the effect of action potential duration dynamics directly after percutaneous ASD closure.

Procedural Outcome and Midterm Survival of Lower Risk Transfemoral Transcatheter Aortic Valve Implantation Patients Treated With the SAPIEN XT or SAPIEN 3 Device.

Over the years increasing experience and technical device improvements in transcatheter aortic valve implantation (TAVI) have led to treatment of patients with lower surgical risks. Specifically for this population, device performance and longer term outcome are of great importance. In this single center, we performed a retrospective analysis of 515 consecutive patients with low- to intermediate surgical risk (STS-PROM ≤8), who underwent transfemoral TAVI between January 2009 and February 2017 with the SXT and ES3 prostheses, and we assessed procedural outcome and procedural and 3-year survival. Mean age (82 years in both groups, p = 0.344) and STS-PROM risk score (3.862 vs 3.992, p = 0.154) did not differ between the ES3 and SXT group. ES3-treated patients showed favorable procedural outcomes, with significantly higher device success (90% vs 73%, p <0.0001) and less paravalvular leakage (7% vs 13%, p <0.0001). Procedural mortality (0.87% vs 1.45%, p = 0.245) and the very low rate of permanent pacemaker implantations (7.4% vs 6.1%, p = 0.234) did not differ significantly. Three-year survival was 87% in the ES3 vs 80% in the SXT group (log-rank p = 0.385). In conclusion, we showed excellent survival and procedural outcomes in patients receiving a transfemoral TAVI with either the SAPIEN 3 or the SAPIEN XT device. The newer SAPIEN 3 even outperforms the SAPIEN XT in terms of less major bleeding complications, substantially higher device success rates, and less paravalvular leakage, with the permanent pacemaker implantation rate being very low in both groups. Survival curves show a nonsignificant trend toward better midterm survival in the ES3 group.

Incidence, Predictors, and Impact of Vascular Complications After Transfemoral Transcatheter Aortic Valve Implantation With the SAPIEN 3 Prosthesis.

Vascular complications (VCs) after transfemoral transcatheter aortic valve implantation (TAVI) have always been reported to occur frequently. Studies addressing VCs have been conducted with older-generation prostheses. We aimed to evaluate the incidence, predictors, and impact of VCs after transfemoral TAVI with the balloon-expandable SAPIEN 3. We report a single-center retrospective analysis of 400 consecutive patients of a prospectively acquired cohort. All patients underwent transfemoral TAVI with SAPIEN 3 between January 2014 and December 2016. VC was defined according to the Valve Academic Research Consortium. In this cohort 83 patients had VCs (20.8%), 5.8% major and 15.0% minor. Sheath-to-iliofemoral artery ratio was the only predictor of major VCs (odds ratio 7.51, 95% confidence interval 1.61 to 34.95, p = 0.010). The area under the receiver-operator characteristic curve for sheath-to-iliofemoral artery ratio was 0.63 (poor accuracy). Thirty-day mortality rates were 17.4%, 1.7%, and 0.6% for major, minor, and no VCs, respectively (log-rank p ≤0.001). After adjustment, only major VCs were associated with 30-day mortality (adjusted hazard ratio 48.31, 95% confidence interval 7.80 to 299.24). Mortality from 30 days until 1 year did not differ between patients with and without VCs (log-rank p = 0.61). In conclusion we report that VCs remain an issue of transfemoral TAVI with the SAPIEN 3, and their prediction continues to be difficult, albeit the low-incidence, major VCs were associated with higher 30-day mortality. However, after these first 30 days, they were not of influence on survival anymore.

Restenosis after percutaneous coronary intervention is associated with the angiotensin-II type-1 receptor 1166A/C polymorphism but not with polymorphisms of angiotensin-converting enzyme, angiotensin-II receptor, angiotensinogen or heme oxygenase-1.

OBJECTIVES: The renin-angiotensin system (RAS) is thought to play a major role in the pathophysiology of de-novo restenotic lesions and in-stent restenosis after percutaneous coronary intervention (PCI). Heme oxygenase-1 (HO-1), is thought to beneficially influence these processes. We examined the effect of pharmacologic as well as genetic RAS interactions on restenosis in a large population of consecutive patients undergoing PCI, and evaluated possible gene-gene interactions in both systems. METHODS: The GENDER project is a multicenter prospective follow-up study, including 3146 patients after successful PCI. Genotyping in these patients was performed for the ACE gene insertion/deletion, the angiotensinogen 235Met/Thr, T174M and A(-6)G, the angiotensin-II type 1 receptor (AT1R) 1166A/C and T810A, the angiotensin-II type 2 receptor (AT2R) 1675G/A and 3123A polymorphisms and the length polymorphism in the HO-1 promoter region. RESULTS: A total of 3104 patients were followed for 10 months. In 2975 patients at least one of the nine genotypes could be determined. The AT1R 1166 CC genotype showed a significant association with TVR; the other polymorphisms did not. RAS-inhibitory drugs were not associated with the incidence of TVR, nor did they interact with any of the investigated polymorphisms. Patients with the ACE I/I polymorphism showed a trend towards a better outcome if they had a short number of repeats in the HO-1 promoter. This relationship was inversely present in carriers of the ACE D/D polymorphism. CONCLUSION: We could only establish a role for the AT1R 1166A/C polymorphism in restenosis after PCI. However, significant gene-gene interaction was suggested for the ACE gene and the HO-1 promotor. The RAS and HO-1 relation in restenosis merits further investigation.