Quantification and characterisation of released plaque material during bioresorbable vascular scaffold implantation into right coronary artery lesions by multimodality intracoronary imaging.

AIMS: We aimed to compare intravascular ultrasound with virtual histology (VH-IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS) for their ability to quantify the true amount and characterise the nature of released plaque material during bioresorbable vascular scaffold (BVS) implantation into right coronary artery (RCA) lesions using a distal occlusion and aspiration device. METHODS AND RESULTS: Seventeen patients underwent BVS implantation into the right coronary artery under distal protection with intracoronary imaging using VH-IVUS, OCT and NIRS. The amount of released plaque material and its lipid content (LC) were determined. Necrotic core volume and minimal fibrous cap thickness correlated with the amount of released plaque material (r=0.80 and r=-0.65, respectively) and its LC (r=0.75 and r=-0.78, respectively), but not maximal lipid core burden index (LCBI). OCT-identified thin-cap fibroatheromata (TCFA) were associated with the greatest amount of released plaque material compared to non-TCFA (46.8 [29.0;49.2] mg vs. 14.2 [11.3;19.4] mg; p=0.003) and LC (4.4 [4.0;4.8] mg vs. 2.0 [1.8;2.5] mg; p=0.000). CONCLUSIONS: VH-IVUS and OCT but not NIRS parameters quantify and characterise the amount of released plaque material. TCFA is associated with the highest amount of released plaque material and may therefore benefit from the use of protection devices.

Kinetics and Signal Activation Properties of Circulating Factor(s) From Healthy Volunteers Undergoing Remote Ischemic Pre-Conditioning.

Although remote ischemic pre-conditioning (RIPC) reduced infarct size in animal experiments and proof-of-concept clinical trials, recent phase III trials failed to confirm cardioprotection during cardiac surgery. Here, we characterized the kinetic properties of humoral factors that are released after RIPC, as well as the signal transduction pathways that were responsible for cardioprotection in an ex vivo model of global ischemia reperfusion injury. Venous blood from 20 healthy volunteers was collected at baseline and 5 min, 30 min, 1 h, 6 h, and daily from 1 to 7 days after RIPC (3 × 5/5 min upper-limb ischemia/reperfusion). Plasma-dialysates (cut-off: 12 to 14 kDa; dilution: 1:20) were infused into Langendorff-perfused mouse hearts subjected to 20/120 min global ischemia/reperfusion. Infarct size and phosphorylation of signal transducer and activator of transcription (STAT)3, STAT5, extracellular-regulated kinase 1/2 and protein kinase B were determined. In a subgroup of plasma-dialysates, an inhibitor of STAT3 (Stattic) was used in mouse hearts. Perfusion with baseline-dialysate resulted in an infarct size of 39% of ventricular mass (interquartile range: 36% to 42%). Perfusion with dialysates obtained 5 min to 6 days after RIPC significantly reduced infarct size by ∼50% and increased STAT3 phosphorylation beyond that with baseline-dialysate. Inhibition of STAT3 abrogated these effects. These results suggest that RIPC induces the release of cardioprotective, dialyzable factor(s) within 5 min, and that circulate for up to 6 days. STAT3 is activated in murine myocardium by RIPC-induced human humoral factors and is causally involved in cardioprotection.

Silent cerebral ischemia after thoracic endovascular aortic repair: a neuroimaging study.

BACKGROUND: The risk of clinically apparent, periprocedural stroke after thoracic endovascular aortic repair (TEVAR) due to dislodgement and embolization of aortic debris from intravascular manipulation of guidewires, catheters, and large-bore delivery systems ranges between 2% and 6% and has been associated with increased postoperative mortality. The rate of clinically silent cerebral ischemia is yet unknown, but may be even higher. METHODS: Nineteen patients (13 male, 6 female) who underwent TEVAR were included into this descriptive study. Periprocedural apparent and silent cerebral ischemia was assessed by daily clinical neurologic assessment and serial cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) at baseline and 5 days (median, interquartile range: 3.5) after the procedure. RESULTS: The TEVAR was successful in all patients without immediate clinically apparent neurologic deficits. Postinterventional cerebral DW-MRI detected a total of 29 new foci of restricted diffusion in 12 of 19 TEVAR patients (63%). Lesions were usually multiple (1 to 6 lesions per patient) and ranged in size between 15 mm3 and 300 mm3; 16 lesions were found in the left hemisphere, 13 lesions in the right hemisphere. Overstenting of the left subclavian artery was performed in 8 cases, but was not associated with lateralization of lesions. There were no additional apparent neurologic events during the in-hospital period. CONCLUSIONS: Thoracic endovascular aortic repair resulted in a high incidence of new foci of restricted diffusion on cerebral DW-MRI in a pattern suggestive of periprocedural embolization. Although multiple lesions per patients were found, these lesions were not associated with apparent neurologic deficits during the in-hospital period. Further developments in TEVAR should be directed toward reducing the risk of periprocedural cerebral embolization.

Preparatory balloon aortic valvuloplasty during transcatheter aortic valve implantation for improved valve sizing.

OBJECTIVES: This study sought to evaluate whether supra-aortic angiography during preparatory balloon aortic valvuloplasty (BAV) improves valve sizing. BACKGROUND: Current recommendations for valve size selection are based on annular measurements by transesophageal echocardiography and computed tomography, but paravalvular aortic regurgitation (PAR) is a frequent problem. METHODS: Data of 270 consecutive patients with either conventional sizing (group 1, n = 167) or balloon aortic valvuloplasty-based sizing (group 2, n = 103) were compared. PAR was graded angiographically and quantitatively using several hemodynamic indices. RESULTS: PAR was observed in 113 patients of group 1 and 41 patients of group 2 (67.7% vs. 39.8%, p < 0.001). More than mild PAR was found in 24 (14.4%) patients of group 1 and 8 (7.8%) patients of group 2. According to pre-interventional imaging, 40 (39%) patients had a borderline annulus size, raising uncertainty regarding valve size selection. Balloon sizing resulted in selection of the bigger prosthesis in 30 (29%) and the smaller prosthesis in the remaining patients, and only 1 of these 40 patients had more than mild PAR. As predicted by the hemodynamic indices of PAR, mortality at 30 days and 1 year was less in group 2 than in group 1 (5.8% vs. 9%, p = 0.2 and 10.6% vs. 20%, p = 0.01). CONCLUSIONS: Preparatory balloon aortic valvuloplasty during transcatheter aortic valve implantation improves valve size selection, reduces the associated PAR, and increases survival in borderline cases.

Hemodynamic assessment of paravalvular aortic regurgitation after TAVI: estimated myocardial supply-demand ratio and cardiovascular mortality.

A relevant (at least moderate) paravalvular regurgitation (PAR) after transcatheter aortic valve implantation (TAVI) is found in up to 20% of cases and associated with increased mortality. The ratio of the diastolic over the systolic pressure time integral (DPTI:SPTI) has been proposed to reflect an estimate of myocardial oxygen supply versus demand and the propensity for myocardial ischemia. We have now evaluated the potential of this ratio to predict PAR-associated cardiovascular mortality after TAVI, retrospectively analyzing data from 167 consecutive TAVI patients. PAR was graded angiographically, and the myocardial supply-demand ratio was estimated from the planimetric integration of the diastolic and systolic pressure-time area (DPTI and SPTI), respectively. PAR was observed in 113 patients (67%) and angiographically graded as mild in 89 (78.8%), moderate in 21 (18.6%) or moderate to severe in 3 (2.7%) cases. The DPTI:SPTI ratio decreased with increasing Sellers grade of PAR (P < 0.001). A DPTI:SPTI of ≤0.7 predicted cardiovascular mortality (area under the curve = 0.96). Cardiovascular mortality at 30 days and 1 yr was increased in patients with DPTI:SPTI ≤ 0.7 over those with DPTI:SPTI > 0.7 (42 vs. 2% and 63 vs. 3%, respectively; P < 0.001). In conclusion, DPTI:SPTI provides an excellent cutoff value of ≤0.7 for the prediction of PAR-associated mortality.

Segmental heterogeneity of vasa vasorum neovascularization in human coronary atherosclerosis.

OBJECTIVES: Our aim was to investigate the role of coronary vasa vasorum (VV) neovascularization in the progression and complications of human coronary atherosclerotic plaques. BACKGROUND: Accumulating evidence supports an important role of VV neovascularization in atherogenesis and lesion location determination in coronary artery disease. VV neovascularization can lead to intraplaque hemorrhage, which has been identified as a promoter of plaque progression and complications like plaque rupture. We hypothesized that distinctive patterns of VV neovascularization and associated plaque complications can be found in different stages of human coronary atherosclerosis. METHODS: Hearts from 15 patients (age 52+/-5 years, mean+/-SEM) were obtained at autopsy, perfused with Microfil (Flow Tech, Inc., Carver, Massachusetts), and subsequently scanned with micro-computed tomography (CT). The 2-cm segments (n=50) were histologically classified as either normal (n=12), nonstenotic plaque (<50% stenosis, n=18), calcified (n=10) or noncalcified (n=10) stenotic plaque. Micro-CT images were analyzed for VV density (number/mm2), VV vascular area fraction (mm2/mm2), and VV endothelial surface fraction (mm2/mm3). Histological sections were stained for Mallory's (iron), von Kossa (calcium), and glycophorin-A (erythrocyte fragments) as well as endothelial nitric oxide synthase, vascular endothelial growth factor, and tumor necrosis factor-alpha. RESULTS: VV density was higher in segments with nonstenotic and noncalcified stenotic plaques as compared with normal segments (3.36+/-0.45, 3.72+/-1.03 vs. 1.16+/-0.21, p<0.01). In calcified stenotic plaques, VV spatial density was lowest (0.95+/-0.21, p<0.05 vs. nonstenotic and noncalcified stenotic plaque). The amount of iron and glycophorin A was significantly higher in nonstenotic and stenotic plaques as compared with normal segments, and correlated with VV density (Kendall-Tau correlation coefficient 0.65 and 0.58, respectively, p<0.01). Moreover, relatively high amounts of iron and glycophorin A were found in calcified plaques. Further immunohistochemical characterization of VV revealed positive staining for endothelial nitric oxide synthase and tumor necrosis factor-alpha but not vascular endothelial growth factor. CONCLUSIONS: Our results support a possible role of VV neovascularization, VV rupture, and intraplaque hemorrhage in the progression and complications of human coronary atherosclerosis.

Differential distribution of vasa vasorum in different vascular beds in humans.

OBJECTIVE: Vasa vasorum (VV) have been implicated to play a role in the pathogenesis of atherosclerosis. This study was designed to describe the distribution of VV density in different vascular beds in humans and to investigate the association between VV density and the known distribution of atherosclerosis in human arteries. METHODS: Forty-two human arteries, harvested at autopsy or after explantation, were analyzed by three-dimensional microscopic-computed tomography (micro-CT). VV density, endothelial-surface-fraction (Sigma VV endothelial-surface-area/vessel-wall-volume) and vascular-area-fraction (Sigma VV area/vessel-wall-area) were calculated for coronary, renal and femoral arteries. Representatively five coronary, renal and femoral arteries were stained for endothelial cells (von Willebrand-Factor), macrophages (CD68), vascular endothelial growth factor (VEGF) and collagen (Sirius Red). RESULTS: Coronary arteries showed a higher VV density compared to renal and femoral arteries (2.12+/-0.26 n/mm(2) versus 0.61+/-0.06 n/mm(2) and 0.66+/-0.11 n/mm(2); P<0.05 for both) as well as a higher endothelial-surface-fraction and vascular-area-fraction. Histology showed a positive correlation between histologically derived VV density and CD68-positive cells/area (r=0.54, P<0.01), VEGF-immunoreactivity/area (r=0.55, P<0.01) and a negative correlation between VV density and collagen I content (r=0.66, P<0.05). CONCLUSION: This micro-CT study highlights a higher VV density in coronary than in peripheral arteries, supporting the relation between VV density and the susceptibility to atherosclerosis in different vascular beds in humans.