Reduction of Cerebral Emboli: In vitro Study with a Novel Cerebral Embolic Protection Device.

AIM: To assess the efficacy of the TriGUARD 3™, a novel cerebral embolic protection (CEP) device in reducing cerebral embolization by deflecting embolic debris away from the cerebral circulation using a quantitative in vitro model. METHODS AND RESULTS: This in vitro study assessed the ability of a cerebral embolic protection device to deflect embolic debris, by measuring the percent of particles and air bubbles, 200 µm and 300 µm in size, from entering the cerebral circulation compared to unprotected controls. A 3D printed silicone model of the ascending aorta, the aortic arch with its three major cerebral arteries and the descending aorta was connected to a custom-made simulator that mimics physiological pulsatile flow patterns of the left ventricle. Comparative analyses were used to assess the efficacy of the cerebral embolic protection device to deflect particles and air bubbles away from the major cerebral arteries. The percent of particles and air bubbles entering the major cerebral arteries was significantly lower with cerebral embolic protection compared to unprotected controls (p<0.0001). Cerebral protection resulted in 97.4-100% reduction in air bubble counts, and 97.4-97.8% reduction in particle counts compared to unprotected controls. CONCLUSION: This in vitro study used simulated physiologic flow conditions in an aortic arch model to demonstrate >97% efficacy of the TriGUARD 3 CEP device, in reducing cerebral embolization of particulate and air bubbles of 200 µm to 300 µm in size.

Neurologic Complications of Unprotected Transcatheter Aortic Valve Implantation (from the Neuro-TAVI Trial).

Cerebral embolization during transcatheter aortic valve implantation (TAVI) can lead to a spectrum of clinically relevant manifestations, ranging from overt stroke to mild neurologic or cognitive deficits and subclinical cerebral infarcts. This study sought to determine the frequency of neurologic injury, cerebral ischemic lesions, and cognitive dysfunction in subjects undergoing contemporary commercial TAVI in the United States. Neuro-TAVR is the first prospective, multicenter study to use serial systematic neurologic and cognitive assessments and diffusion-weighted magnetic resonance imaging (at 4 ± 2 days after procedure) to investigate the incidence and severity of neurologic injury after contemporary unprotected TAVI in the United States. A total of 44 consecutive patients underwent TAVI at 5 US sites. Diffusion-weighted magnetic resonance imaging lesions were detected in 94%, with a mean of 10.4 ± 15.3 lesions per subject and a median total lesion volume of 295 mm3 (interquartile range 71.6 to 799.6 mm3). New neurologic impairment (worsening in National Institutes of Health Stroke Scale score from baseline with new cerebral lesions) occurred in 22.6% (7 of 31) of subjects at discharge and 14.8% (4 of 27) at 30 days. In addition, cognitive decrements from baseline were identified by the Montreal Cognitive Assessment in 33% (12 of 36) of subjects at discharge and 41% (13 of 32) at 30 days. In conclusion, this contemporary cohort of US patients confirms that TAVI results in cerebral infarction in most patients and that 1 in 5 patients have measurable neurologic impairment and 1 in 3 patients have decrease in cognitive measures by Montreal Cognitive Assessment score after TAVI, reinforcing the need for methods to mitigate the risk of brain injury during TAVI.

A prospective randomized evaluation of the TriGuard™ HDH embolic DEFLECTion device during transcatheter aortic valve implantation: results from the DEFLECT III trial.

AIMS: To evaluate the safety, efficacy, and performance of the TriGuard™ HDH Embolic Deflection Device (TriGuard) compared with no cerebral protection in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: From February 2014 to March 2015, 85 subjects undergoing TAVI at 13 centres in Europe and Israel were randomized to TriGuard protection vs. no protection. Subjects underwent neurologic and cognitive evaluation at baseline, pre-discharge and 30 days; cerebral diffusion-weighted magnetic resonance imaging was performed at 4 ± 2 days post-procedure and at 30 days. Technical success, which included complete 3-vessel cerebral coverage, was achieved in 88.9% (40/45) of cases. The primary in-hospital procedural safety endpoint (death, stroke, life-threatening or disabling bleeding, stage 2 or 3 acute kidney injury, or major vascular complications) occurred in 21.7% of TriGuard and 30.8% of control subjects (P = 0.34). In the Per Treatment population (subjects with complete three-vessel cerebral coverage), TriGuard use was associated with greater freedom from new ischaemic brain lesions (26.9 vs. 11.5%), fewer new neurologic deficits detected by the National Institutes of Health Stroke Scale (3.1 vs. 15.4%), improved Montreal Cognitive Assessment (MoCA) scores, better performance on a delayed memory task (P = 0.028) at discharge, and a >2-fold increase in recovery of normal cognitive function (MoCA score >26) at 30 days. CONCLUSION: TriGuard cerebral protection during TAVI is safe and complete cerebral vessel coverage was achieved in 89% of subjects. In this exploratory study, subjects undergoing protected TAVI had more freedom from ischaemic brain lesions, fewer neurologic deficits, and improved cognitive function in some domains at discharge and 30 days compared with controls.

Safety and performance of a novel embolic deflection device in patients undergoing transcatheter aortic valve replacement: results from the DEFLECT I study.

AIMS: This study aimed to evaluate the safety and performance of the TriGuard™ Embolic Deflection Device (EDD), a nitinol mesh filter positioned in the aortic arch across all three major cerebral artery take-offs to deflect emboli away from the cerebral circulation, in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: The prospective, multicentre DEFLECT I study (NCT01448421) enrolled 37 consecutive subjects undergoing TAVR with the TriGuard EDD. Subjects underwent clinical and cognitive follow-up to 30 days; cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) was performed pre-procedure and at 4±2 days post procedure. The device performed as intended with successful cerebral coverage in 80% (28/35) of cases. The primary safety endpoint (in-hospital EDD device- or EDD procedure-related cardiovascular mortality, major stroke disability, life-threatening bleeding, distal embolisation, major vascular complications, or need for acute cardiac surgery) occurred in 8.1% of subjects (VARC-defined two life-threatening bleeds and one vascular complication). The presence of new cerebral ischaemic lesions on post-procedure DW-MRI (n=28) was similar to historical controls (82% vs. 76%, p=NS). However, an exploratory analysis found that per-patient total lesion volume was 34% lower than reported historical data (0.2 vs. 0.3 cm3), and 89% lower in patients with complete (n=17) versus incomplete (n=10) cerebral vessel coverage (0.05 vs. 0.45 cm3, p=0.016). CONCLUSIONS: Use of the first-generation TriGuard EDD during TAVR is safe, and device performance was successful in 80% of cases during the highest embolic-risk portions of the TAVR procedure. The potential of the TriGuard EDD to reduce total cerebral ischaemic burden merits further randomised investigation.

Radiofrequency-intravascular ultrasound assessment of lesion coverage after angiography-guided emergent percutaneous coronary intervention in patients with non-ST elevation myocardial infarction.

Using radiofrequency-intravascular ultrasound (VH-IVUS), we have previously demonstrated that in 50% of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention with optimal angiographic result, the stent does not fully cover the whole VH-IVUS-derived thin-cap fibroatheroma (VH-TCFA) related to the culprit lesion. Presently, we set out to extend these findings to 20 patients with non-STEMI with Thrombolysis In Myocardial Infarction flow 3 in the infarct-related artery before intervention who were then treated with angiography-guided direct stent implantation. The lesion was imaged with VH-IVUS before and after intervention, but the results were blinded to the operator. Plaque rupture site was identified in 8 lesions (40%), all proximal to the minimum lumen area (MLA) site. The maximum necrotic core site was found proximal to MLA in 18 lesions and at the MLA in 2 lesions. Although the plaque rupture site was fully covered with the stent in all lesions, an uncovered VH-TCFA was found in 7 lesions (35%), 4 in the proximal reference segment, 1 in the distal reference segment, and 2 in both the proximal and distal reference segments. In conclusion, in 35% of patients with non-STEMI undergoing angiography-guided emergent percutaneous coronary intervention, the stent does not fully cover a VH-TCFA related to the culprit lesion.

Virtual histology-intravascular ultrasound assessment of lesion coverage after angiographically-guided stent implantation in patients with ST Elevation myocardial infarction undergoing primary percutaneous coronary intervention.

An occlusion or severe stenosis (angiographic culprit lesion) of the infarct-related artery is frequently located at the site of the maximum thrombus burden, whereas the origin of the plaque rupture (the true culprit) can be situated proximal or distal to it. The aim of this study was to examine stent coverage of true culprit lesions in 20 patients who underwent primary percutaneous coronary intervention and had Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow restored in the infarct-related artery by angiographically guided direct stenting. Images of lesions were obtained using virtual histology-intravascular ultrasound before and after intervention (blinded to the operator). Plaque rupture sites were identified by intravascular ultrasound in 12 lesions (60%), 11 proximal and 1 distal to the minimum luminal area (MLA). Maximum necrotic core sites were found proximal to the MLA in 16 lesions, at the MLA in 3 lesions, and distal to the MLA in 1 lesion. Plaque rupture sites were fully covered by stents in 11 lesions. Virtual histology-intravascular ultrasound-derived thin-cap fibroatheroma longitudinal geographic misses were found in 10 lesions, 7 in the proximal reference segment and in 3 patients in the proximal and distal reference segments. In conclusion, in about 50% of patients who undergo primary percutaneous coronary intervention for ST-segment elevation myocardial infarction with optimal angiographic results, the stent does not fully cover the maximum necrotic core site related to the culprit lesion.

Tissue characterisation of atherosclerotic plaque in coronary artery bifurcations: an intravascular ultrasound radiofrequency data analysis in humans.

AIMS: To investigate tissue characteristics of atherosclerotic plaques in coronary artery bifurcations. METHODS AND RESULTS: Using a global virtual histology registry, geometric and compositional characteristics of plaque in three segments (proximal, distal, and at the bifurcation) of coronary bifurcation sites were analysed with intravascular ultrasound radiofrequency data (RFD) analysis. A total of 256 bifurcation sites were analysed: left main (LM)-left anterior descending artery (LAD), 41; LAD-diagonal artery, 128; left circumflex artery-obtuse marginal artery, 34; and right coronary artery-acute marginal artery, 53. The plaque+media (P+M) burden was larger in the distal segments of LM-LAD bifurcation sites than in the proximal and at the bifurcation segments (46.55±12.08% vs. 40.40±11.76%, 41.15±11.01%, p<0.001). The % necrotic core (NC) and % dense calcium (DC) at the bifurcation and distal segments of LM-LAD bifurcation sites was significantly greater than in the proximal segments (6.75±5.09%, 7.36±6.01% vs. 4.89±4.78%, p<0.05, and 3.31±2.87%, 3.73±3.28% vs. 1.89±2.10%, p<0.001). In contrast, P+M burden, % NC and % DC in the proximal segments of non-LM bifurcation sites was significantly greater than at the bifurcation and distal segments (49.41±12.12% vs. 45.34±11.21%, 46.80±10.68% / 8.08±6.21% vs. 6.47±5.11%, 6.28±5.05% / 4.57±4.67% vs. 3.38±3.44%, 3.55±3.74%, all p<0.001). CONCLUSIONS: The results demonstrate that heterogeneous nature of coronary atherosclerosis at coronary bifurcations according to their segments and anatomical locations (LM-LAD vs. non-LM bifurcations). The further investigation for the clinical efficacy of the RFD analysis on bifurcation sites are warranted.

Diabetes mellitus is associated with plaque classified as thin cap fibroatheroma: an intravascular ultrasound study.

We compared measures of ID coronary atherosclerosis between diabetic and non-diabetic patients enrolled in a prospective multinational IVUS registry. The region of interest was the most diseased 10 mm segment of a single coronary artery. Coronary plaque was quantified using greyscale IVUS and further classified by phenotype (ID-adaptive intimal thickening, ID-pathological intimal thickening, ID-TCFA, ID-fibroatheroma, or ID-fibrocalcific) using VH-IVUS. There was a non-significant trend for greater total plaque volume in diabetic (n=191) compared with non-diabetic (n=584) patients (94.8 vs. 88.1 mm(3), p=0.36, adjusted for multiple comparisons). There was a greater proportion of ID-TCFA among diabetic patients (21.6 vs. 13.6%, p=0.01 after adjustment for multiple comparisons; p=0.08 following multivariable adjustment for age and clinical demographics), while differences in pathological intimal thickening, fibroatheroma and fibrocalcific plaque were not significant between groups. ID-TCFA was more common in the most diseased 10 mm segment of diabetic than in non-diabetic coronary arteries. Multivariable adjustment demonstrated age and possibly the presence of diabetes to be independent predictors of ID-TCFA.

Synergistic effect of cardiovascular risk factors on necrotic core in coronary arteries: a report from the global intravascular radiofrequency data analysis registry.

OBJECTIVES: This study explored whether an individual or a cluster of risk factors affects the extent of necrotic core (NC) assessed by intravascular ultrasound (IVUS) radiofrequency data (RFD) analysis. BACKGROUND: Several systemic diseases contribute to the development of coronary artery disease. METHODS: The Global Intravascular Radiofrequency Data Analysis Registry was a prospective, multicenter, nonrandomized database that enrolled 990 patients with coronary artery disease in whom 1 major coronary artery was imaged by IVUS-RFD. For the multivariable analysis, the population was divided into 4 classes: young women, young men (both 62 years). Mean NC area was categorized as 1: top quartile (>or=0.62 mm(2)) or as 0: lower 3 quartiles. RESULTS: Young patients had less NC compared with older patients (0.40 +/- 0.36 mm(2) of NC vs. 0.50 +/- 0.46 mm(2) in old patients, p = 0.0007). Nondiabetic patients had less NC than diabetic patients (0.43 +/- 0.41 mm(2) of NC vs. 0.51 +/- 0.44 mm(2) in diabetic patients, p = 0.02). The NC area was lower in normotensive patients (0.40 +/- 0.36 mm(2)) than in hypertensive patients (0.48 +/- 0.44 mm(2)) (p = 0.02). In the bivariate analysis, age, hypertension, diabetes, and prior coronary artery bypass graft were statistically significant, however in logistic regression analysis, only age (odds ratio [OR]: 1.023, 95% confidence interval [CI]: 1.009 to 1.037, p = 0.001) and diabetes (OR: 1.636, 95% CI: 1.174 to 2.279, p = 0.004) remained statistically significant. In a per-class logistic regression analyses including only diabetes as covariate, the OR in young women was 2.1 (95% CI: 0.77 to 6.0, p = 0.14), in young men the OR was 1.6 (95% CI: 0.90 to 2.7, p = 0.11), in old women the OR was 2.3 (95% CI: 1.09 to 4.9, p = 0.03), and in old men the OR was 1.6 (95% CI: 0.96 to 2.7, p = 0.07). Further, when only patients with diabetes and hypertension were included, young men (OR: 2.0, p = 0.041), old women (OR: 3.04, p = 0.046), and old men (OR: 2.2, p = 0.025) were significant. CONCLUSIONS: Individually and collectively, age and diabetes mellitus are associated with an increase in NC by IVUS-RFD analysis.

Multicenter assessment of coronary allograft vasculopathy by intravascular ultrasound-derived analysis of plaque composition.

BACKGROUND: Coronary allograft vasculopathy is a severe complication of heart transplantation. We used virtual histology intravascular ultrasound to characterize plaque burden and tissue composition over time in heart transplant recipients. METHODS: We recruited patients undergoing heart transplantation in four centers in Europe and the US between 2004 and 2006. We used intravascular ultrasound to obtain morphological plaque measurements and to perform virtual histology in the left anterior descending coronary artery. Data were characterized according to the duration between transplantation and intravascular ultrasound assessment: 24-60, >60-120 and >120-192 months. RESULTS: We assessed vessels from 152 patients (mean age 58 +/- 12 years) a mean of 70 +/- 53 months (range 1 week to 16 years) after transplantation. Plaque burden of >40% was observed in 26% of vessels analyzed, with increases from baseline being seen in all time categories. If assessed >24 months after transplantation, necrotic core and dense calcified volumes were significantly greater than at baseline (P = 0.0005 and P = 0.01, respectively). Time since heart transplantation and donor age and recipient age were independent predictive factors of increased necrotic core content. Necrotic core volume >2.01 mm(3), diabetes mellitus, donor age older than 40 years, follow-up from transplantation longer than 5 years and recipient age older than 58 years were associated with the need for revascularization. CONCLUSIONS: In coronary allograft vasculopathy, plaque burden and composition change over time and seem to affect clinical outcome. This relationship might facilitate identification of high-risk patients in whom the value of more aggressive medical therapy should be tested.

Intravascular ultrasound measures of coronary atherosclerosis are associated with the Framingham risk score: an analysis from a global IVUS registry.

AIMS: In addition to an adjunctive imaging platform during coronary angiography, intravascular ultrasound (IVUS) with Virtual Histology (VH) is increasingly being used to quantify coronary atherosclerosis. The relationship between VH-IVUS measures of coronary atherosclerosis and traditional cardiovascular risk factors has not been completely described. The objective of this study was to determine if an association exists between VH-IVUS measures of coronary atherosclerosis and the Framingham risk score in a prospective, multinational registry. METHODS AND RESULTS: Patients enrolled from 2004-2006 at 37 multinational centres in the prospective VHIVUS Global Registry were analysed. All subjects underwent diagnostic coronary angiography followed by IVUS. A Framingham risk score (FRS) was calculated for each subject, then stratified into three exclusive estimates (<10%, 10-19%, or >or= 20%) for future coronary heart disease (CHD) event risk over 10 years. Among 531 patients, plaque volume of the most diseased 10 mm segment increased with increasing FRS (P=0.006, adjusted for multiple comparisons). Patients with higher FRS estimates of CHD risk had a higher proportion of plaque classified as thin cap fibroatheroma compared with patients in the middle and lower risk score categories (21.4% vs 15.2% and 11.3%, respectively, P=0.008, adjusted for multiple comparisons). CONCLUSIONS: Using data from a large, multinational VH-IVUS registry we describe an association between the Framingham risk score and VH-IVUS measures of atherosclerosis within the most diseased 10 mm segment, namely plaque volume and the proportion of thin cap fibroatheroma.

Impact of intramural thrombus in coronary arteries on the accuracy of tissue characterization by in vivo intravascular ultrasound radiofrequency data analysis.

Virtual Histology (VH) intravascular ultrasound (IVUS) allows differentiation between 4 different tissue phenotypes. However, the current classification tree for analysis cannot differentiate the presence of intramural thrombus. The aim of this study was to evaluate the impact of intramural thrombus for correlative accuracy between in vitro histopathology of coronary atherosclerotic plaque obtained by directional coronary atherectomy and corresponding in vivo tissue characterization obtained by VH IVUS. Coronary IVUS imaging of 30 coronary artery lesions was obtained using a 20-MHz phased-array IVUS catheter with a motorized pull-back system at set 0.5 mm/s. The debulking region of the in vivo histologic image was predicted from comparison between pre- and post-first debulking VH IVUS images. Cross-sectional histologic slices were cut every 0.5 mm starting from the most proximal part of the formalin-fixed debulking tissue. Histologic slices were divided into 2 groups by the presence or absence of pathologic thrombus. A total of 259 in vitro histologic slices were obtained, and pathologic thrombus was detected in 81 slices. Correlation was favorable, with high sensitivity for all plaque components, but specificities for fibrous (thrombus slices vs nonthrombus slices 36% vs 94%) and fibrofatty (9% vs 60%) tissue were lower in thrombus slices. Therefore, predictive accuracies for the 2 plaque components were lower in thrombus slices (fibrous tissue 78% vs 99%, fibrofatty tissue 68% vs 83%, respectively). In conclusion, intramural thrombus was colored as fibrous or fibrofatty by VH IVUS, reducing VH accuracy in these kinds of lesions.