Mechanisms of gradual pressure drop in angiographically normal left anterior descending and right coronary artery: Insights from wave intensity analysis.

BACKGROUND: This study evaluated the mechanism of decline in coronary pressure from the proximal to the distal part of the coronary arteries in the left anterior descending (LAD) versus the right coronary artery (RCA) from the insight of coronary hemodynamics using wave intensity analysis (WIA). METHODS: Twelve patients with angiographically normal LAD and RCA were prospectively enrolled. Distal coronary pressure, mean aortic pressure, and average peak velocity were measured at 4 different positions: 9, 6, 3, and 0 cm distal from each coronary ostium. RESULTS: The distal-to-proximal coronary pressure ratio during maximum hyperemia gradually decreased in proportion to the distance from the ostium (0.92±0.03 and 0.98±0.03 at 9 cm distal to the LAD and RCA ostium). WIA showed the dominant forward-traveling compression wave gradually decreased and the backward-traveling suction wave gradually decreased in proportion to the decrease in coronary pressure through the length of the non-diseased LAD but not the RCA. CONCLUSIONS: The pushing wave and suction wave intensities on WIA were diminished in proportion to the distance from the ostium of the LAD despite the wave intensity not changing across the length of the RCA, which may lead to gradual intracoronary pressure drop in the angiographically normal LAD.

Impact of low tissue backscattering by optical coherence tomography on endothelial function after drug-eluting stent implantation.

This study evaluated the impact of optical coherence tomography (OCT)-derived low-backscattered tissue on mid-term coronary endothelial function after drug-eluting stent (DES) implantation. Although OCT enables detailed in vivo evaluation of neointimal tissue characterization after DES implantation, its association with physiological vascular healing response is unclear. Thirty-three stable angina pectoris patients underwent OCT examination and endothelial function testing with intracoronary infusion of incremental doses of acetylcholine 8-month after DES implantation in a single lesion of the left anterior descending artery. Neointimal tissue was classified into two patterns based on the predominant OCT light backscatter: high backscatter and low backscatter. Although the presence of uncovered or malapposed stent strut was not associated with the degree of vasoconstriction, the degree of vasoconstriction was significantly greater in the DES with low-backscattered neointima than in the DES without low-backscattered neointima (- 32.1 ± 25.7 vs. - 4.1 ± 20.1%, p = 0.003). Moreover, there was an inverse linear relationship between low backscatter tissue index and degree of vasoconstriction after acetylcholine infusion (r = 0.50 and p = 0.003). The endothelium-dependent vasomotor response after 8-month of DES was impaired in patients with low neointimal tissue backscatter on OCT imaging. OCT assessment of low-backscattered tissue may be used as surrogate markers for impairment of endothelial function after DES.

Atherosclerotic Component of the Yellow Segment After Drug-Eluting Stent Implantation on Coronary Angioscopy　- An Ex-Vivo Validation Study.

BACKGROUND: Coronary angioscopy (CAS) is used to comprehensively evaluate vascular responses after drug-eluting stent (DES) implantation. This study sought to evaluate the capability of CAS for evaluating DES strut coverage grade and color grade of the intima compared with histological images in coronary autopsy specimens. Methods and Results: A total of 23 DES extracted from 11 autopsy hearts were imaged by CAS. All stent segments were graded as white or yellow according to the luminal surface color, and thrombus was evaluated according to a previous report. Neointimal coverage over the DES was graded as 0 (stent struts fully visible) to grade 3 (stent struts fully embedded and invisible). Of 76 segments, neointimal coverage was graded as 0 in 35 (46%), 1 in 22 (29%), 2 in 8 (11%), and 3 in 11 (14%). The neointimal thickness increased significantly with increasing neointimal coverage grade on angioscopy. Neointimal color was graded as white in 40 (53%) and yellow in 36 segments (47%). Histological analysis revealed that yellow neointima contained fibroatheroma, foam cells accumulation or superficial calcium deposition. A thrombus was identified in 13 segments. Thrombi adherent around the stent strut were partly intimal erythrocyte accumulation around the strut. CONCLUSIONS: In-stent yellow segment had atherosclerotic components. CAS could evaluate vascular status comprehensively after DES implantation.

The distribution of calcified nodule and plaque rupture in patients with peripheral artery disease: an intravascular ultrasound analysis.

In addition to plaque rupture (PR), calcified nodule (CN) may also have the potential to develop into arterial thrombus in the peripheral arteries. This study evaluated the distribution of plaque ruptures and calcified nodules in the peripheral arteries and their impact on the outcome of endovascular therapy (EVT). Consecutive 159 patients who underwent EVT with intravascular ultrasound guidance were enrolled. The position of CNs and PRs were assigned to any of common iliac artery, external iliac artery, common femoral artery, and superficial femoral artery. Forty-six (29%) patients had calcified nodule and twenty-eight (18%) patients had plaque rupture somewhere in the lower limb arteries. Although calcified nodules were evenly distributed throughout the length of the arteries plaque ruptures were predominantly located in the proximal segment of the iliofemoral arteries. Stent expansion ratio was significantly smaller in the target arteries with calcified nodules than in those with plaque rupture. Multivariate logistic regression analysis identified hemodialysis as an independent clinical predictor of calcified nodule (odds ratio 8.15, 95% confidence interval 1.73-38.3; P = 0.008). CN definitely affects incomplete stent deployment in the peripheral artery contributing to adverse events, on the other hand, PR has more acceptable outcomes after stent implantation. In the clinical setting, it is important that we realize the features of peripheral artery disease and its patient characteristics which having CNs and PRs to make a strategy for revascularization.

Impact of stent diameter on vascular response after self-expanding paclitaxel-eluting stent implantation in the superficial femoral artery.

BACKGROUND: The optimal sizing of self-expanding paclitaxel-eluting stents (PES) in the treatment for superficial femoral artery (SFA) lesions is unclear. This study sought to investigate the influence of PES diameter on stent patency in SFA lesions using optical frequency domain imaging (OFDI). METHODS: A total of 20 de novo SFA lesions were randomized 1:1 to receive either self-expanding PES with a nominal diameter of 6mm or 8mm. Follow-up angiography and OFDI was scheduled six months after stent implantation, and volumetric OFDI analysis was performed to evaluate vascular response to the stents. Volume index (VI) was defined as the volume divided by the stent length. The primary end point was lumen VI at the 6-month follow-up. Secondary end point was minimum lumen diameter (MLD) by quantitative vascular angiography (QVA) at the follow-up. RESULTS: Stent length was 78.0±23.9mm in the 6-mm group and 70.0±23.6mm in the 8-mm group (p=0.46). Baseline QVA data were also similar between the two groups. MLD immediately after stent implantation was similar between the two groups (4.2±0.5mm in the 6-mm group and 3.9±0.5mm in the 8-mm group, p=NS). At the 6-month follow-up, MLD was greater in the 8-mm group compared to the 6-mm group (4.0±1.0mm vs. 3.2±0.4mm, p<0.05). Stent VI was larger in the 8-mm group (28.4±6.7mm3/mm vs. 22.2±1.2mm3/mm, p=0.01). Neointimal VI was similar between the two groups (5.8±2.9mm3/mm vs. 5.2±2.6mm3/mm, p=0.68). Lumen VI was greater in the 8-mm group (23.2±7.6mm3/mm vs. 17.3±2.6mm3/mm, p=0.04). CONCLUSIONS: Chronic stent enlargement resulted in greater lumen area after implantation of self-expanding PES with a large diameter at the mid-term follow-up. Stent diameter might be important for stent patency in procedure with PES for SFA lesions.

Impact of thermodilution-derived coronary blood flow patterns after percutaneous coronary intervention on mid-term left ventricular remodeling in patients with ST elevation myocardial infarction.

We recently reported the coronary thermodilution curve can be evaluated by analyzing the thermodilution curve obtained from a pressure sensor/thermistor-tipped guidewire, and presence of a bimodal-shaped thermodilution curve following primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients was associated with worse outcomes. This study evaluated whether the bimodal-shaped thermodilution curve predicts left ventricular (LV) remodeling after STEMI. The coronary thermodilution curve patterns were evaluated for 75 patients treated by pPCI for their first STEMI using a pressure sensor/thermistor-tipped guidewire, and classified into the three groups according to the thermodilution curve shape: narrow unimodal (n = 39), wide unimodal (n = 26), and bimodal pattern (n = 10). Echocardiography was performed at baseline and 6 months after STEMI. LV remodeling was defined as a >20 % increase in LV end-diastolic volumes (LVEDV). LVEDV at 6-month follow-up was greater in the bimodal group than in the other groups (p < 0.001). The prevalence of LV remodeling was highest in the bimodal group than in the narrow and wide unimodal groups (60, 12, and 15 %, respectively; p = 0.003). Multivariate analysis revealed a bimodal-shaped thermodilution curve as an independent predictor of the prevalence of LV remodeling. A bimodal-shaped thermodilution curve is associated with LV remodeling after STEMI. This easily assessable coronary thermodilution curve pattern is useful to predict mid-term LV remodeling for STEMI patients at the catheterization laboratory.

Impact of analysis interval size on the quality of optical frequency domain imaging assessments of stent implantation for lesions of the superficial femoral artery.

OBJECTIVES: This study aimed to investigate the influence of analysis interval size on optical frequency domain imaging (OFDI) assessment of stent therapy for lesions of the superficial femoral artery (SFA). BACKGROUND: No consensus or validating data are available with respect to the methodology of intravascular imaging analysis for the peripheral arteries. METHODS: OFDI was performed for 30 SFA lesions, during endovascular therapy and at the 6-month follow-up. Initially, lumen and stent borders were traced at 1-mm axial intervals. Volumes were calculated using a PC-based software, and the volume index (VI) was defined as the volume divided by the stent length. Two additional OFDI analyses were performed using 2-mm and 5-mm intervals, thereby reducing the number of cross-sectional image frames analyzed. RESULTS: The mean stent length was 89.7 ± 35.2 mm. The mean difference in baseline minimum lumen area (MLA) was 0.4 mm2 between MLA values from the 1-mm and 2-mm interval analyses, and 2.2 mm2 between MLA values from the 1-mm and 5-mm interval analyses. In volumetric analysis, there were excellent correlations and good agreements for stent, lumen, and neointimal VI measurements obtained on the basis of different analysis intervals. CONCLUSIONS: Using large intervals in OFDI analyses of SFA lesions resulted in few differences in measurement variability of volumetric parameters. However, planar analysis for MLA assessment can be susceptible to high variability when large intervals are applied. © 2016 Wiley Periodicals, Inc.

Histopathological validation of optical frequency domain imaging to quantify various types of coronary calcifications.

AIMS: This study evaluated whether optical frequency domain imaging (OFDI) could identify various coronary calcifications and accurately measure calcification thickness in comparison with histopathology. METHODS AND RESULTS: A total of 902 pathological cross-sections from 44 coronary artery specimens of human cadavers were examined to compare OFDI and histological images. Histological coronary calcification was classified into four different types: (i) superficial dense calcified plates, (ii) deep intimal calcification, (iii) scattered microcalcification, and (iv) calcified nodule. The thickness of calcification was measured when both the leading and trailing edges of calcification were visible on OFDI. Of the 902 histological cross-sections, 158 (18%) had calcification: 105 (66%) were classified as superficial dense calcified plates, 20 (13%) as deep intimal calcifications, 30 (19%) as scattered microcalcifications, and 3 (2%) as calcified nodules. Superficial dense calcified plates appeared as well-delineated heterogeneous signal-poor regions with sharp borders on OFDI. Deep intimal calcifications could not be identified on OFDI. Scattered microcalcification appeared as homogeneous low intensity areas with indiscriminant borders. Calcified nodule, a high-backscattering protruding mass with an irregular surface, also appeared as a low intensity area with a diffuse border. The ROC analysis identified calcium thicknesses <893 µm as cut points for the prediction of measurable calcification (72% sensitivity and 91% specificity, area under the curve = 0.893, P < 0.001). CONCLUSION: Our study demonstrated the potential capability of OFDI to characterize various types of coronary calcifications, which may contribute to the understanding of the pathogenesis of coronary atherosclerosis.

Ex vivo assessment of neointimal characteristics after drug-eluting stent implantation: Optical coherence tomography and histopathology validation study.

BACKGROUND: Optical coherence tomography (OCT) is one of the tools trying to distinguish neoatherosclerosis from other neointimal tissue but its role has to be still validated. This study evaluated the diagnostic accuracy of OCT for characterization of lipid-atherosclerotic neointima following drug-eluting stent (DES) implantation. METHODS: Twelve stented coronary arteries from the 7 autopsy hearts were imaged by OCT. These OCT images were compared with histology. By OCT, the morphological appearances of neointima were classified into three patterns: homogeneous pattern, heterogeneous pattern with visible strut, or heterogeneous pattern with invisible strut. RESULTS: Of 21 histological cross-sections, 6 were categorized as homogeneous patterns (29%), 11 as heterogeneous patterns with visible stent strut (52%), and 4 as heterogeneous patterns with invisible stent strut (19%). All homogeneous patterns were composed of smooth muscle cells with collagen fibers. The heterogeneous patterns with visible stent strut included proteoglycan-rich myxomatous matrix and calcium deposition. On the other hand, the heterogeneous patterns with invisible stent strut comprised atheromatous tissue, including a large amount of foam cell accumulation (25%) or large fibroatheroma/necrotic core (75%) inside the stent struts within neointima. The optical attenuation coefficient was highest in the heterogeneous pattern with invisible stent strut due to scattering of light by atheromatous tissue. CONCLUSION: The heterogeneous patterns with invisible stent strut on OCT imaging identify the presence of lipid-atherosclerotic tissue within neointima after DES. This may suggest the potential capability of OCT based on visualization of stent struts for discriminating atheromatous formation within neointima from other neointimal tissue.

Intravascular Ultrasound-Derived Stent Dimensions as Predictors of Angiographic Restenosis Following Nitinol Stent Implantation in the Superficial Femoral Artery.

PURPOSE: To identify intravascular ultrasound (IVUS) measurements that can predict angiographic in-stent restenosis (ISR) following nitinol stent implantation in superficial femoral artery (SFA) lesions. METHODS: A retrospective review was conducted of 97 patients (mean age 72.9±8.9 years; 63 men) who underwent IVUS examination during endovascular treatment of 112 de novo SFA lesions between July 2012 and December 2014. Self-expanding bare stents were implanted in 46 lesions and paclitaxel-eluting stents in 39 lesions. Six months after stenting, follow-up angiography was conducted to assess stent patency. The primary endpoint was angiographic ISR determined by quantitative vascular angiography analysis at the 6-month follow-up. Variables associated with restenosis were sought in multivariate analysis; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: At follow-up, 27 (31.8%) angiographic ISR lesions were recorded. The lesions treated with uncoated stents were more prevalent in the ISR group compared with the no restenosis group (74.1% vs 44.8%, p=0.02). Lesion length was longer (154.4±79.5 vs 109.0±89.3 mm, p=0.03) and postprocedure minimum stent area (MSA) measured by IVUS was smaller (13.9±2.8 vs 16.3±1.6 mm(2), p<0.001) in the ISR group. Multivariate analysis revealed that bare stent use (OR 7.11, 95% CI 1.70 to 29.80, p<0.01) and longer lesion length (OR 1.08, 95% CI 1.01 to 1.16, p=0.04) were predictors of ISR, while increasing postprocedure MSA (OR 0.58, 95% CI 0.41 to 0.82, p<0.01) was associated with lower risk of ISR. Receiver operating characteristic analysis identified a MSA of 15.5 mm(2) as the optimal cutpoint below which the incidence of restenosis increased (area under the curve 0.769). CONCLUSION: Postprocedure MSA can predict ISR in SFA lesions, which suggests that adequate stent enlargement during angioplasty might be required for superior patency.

Chronic vascular response after self-expanding nitinol stent implantation in superficial femoral arteries: a serial intravascular ultrasound analysis.

The mechanical properties of the self-expanding nitinol stents (SENS) and chronic biological stimulation on the wall from the SENS have not been fully investigated. This study evaluated the mechanical vascular response to SENS implantation in superficial femoral artery (SFA) lesions using serial volumetric intravascular ultrasound (IVUS). Twenty-five symptomatic patients due to de novo SFA lesions scheduled for SENS placement were prospectively enrolled. Serial IVUS studies were performed immediately after crossing with a guidewire, immediately after the procedure, and at a 8-month follow-up. Serial IVUS volumetric analysis was conducted after stent deployment and at follow-up. Mean stent, lumen and neointimal areas were calculated as the volume divided by the stent length, and the calcium arc was measured. At follow-up, SENS had increased 40.6 % in overall volume. The chronic stent expansion tended to be larger, and the mean neointimal area at the 8-month follow-up was significantly larger in less calcified lesions compared to heavily calcified lesions. As a result, the mean late lumen area loss was significantly larger in lesions with calcium arcs of 0° and in the first and second quadrants than in those with calcium arcs in the third and fourth quadrants (2.8 ± 7.2, 1.3 ± 5.6, 0.6 ± 5.9, 1.2 ± 5.4, -0.8 ± 5.2 mm(2), respectively; p < 0.001). SENSs continued to enlarge with intimal proliferation over 8 months in all lesions. Although arterial calcium affected the degree of chronic stent expansion during the follow-up period, neointimal proliferation was smaller in heavily calcified lesion compared to less calcified lesion following SENS implantation.

Impact of intravascular ultrasound findings on long-term patency after self-expanding nitinol stent implantation in the iliac artery lesion.

Although intravascular ultrasound (IVUS) predictors of stent patency for the coronary artery lesion have been established, little is known about IVUS predictors of stent patency for the aorto-iliac artery lesion. We analyzed 154 lesions of 122 patients who underwent stent implantation for iliac artery lesions. Quantitative and qualitative IVUS analyses were performed for pre- and post-procedural IVUS imaging in all lesions. Target lesion revascularization (TLR) was defined as clinically driven revascularization with >50 % angiographic stenosis of the target lesion. The mean follow-up period was 39 ± 16 months. TLRs were performed in 13 lesions (8.4 %). Post-procedural minimum stent area (MSA) was significantly smaller in the TLR group compared to the no-TLR group (16.0 ± 5.8 vs. 25.6 ± 8.5 mm(2), p < 0.001). Stent edge dissection was frequently observed in the TLR group compared to the no-TLR group (53.8 vs. 24.1 %, p = 0.04). Multivariate analysis revealed that post-procedural MSA (OR = 0.76, p < 0.01) and stent edge dissection (OR = 10.4, p < 0.01) were independent IVUS predictors of TLR. Receiver-operating characteristic analysis identified post-procedural MSA <17.8 mm(2) as the optimal cut-point for the prediction of TLR (AUC = 0.846). Post-procedural MSA and stent edge dissection could predict long-term stent patency in the iliac artery lesion. Our results propose that adequate stent enlargement without edge dissection might be important to reduce TLR in the iliac artery lesion.

Impact of spotty calcification on long-term prediction of future revascularization: a prospective three-vessel intravascular ultrasound study.

To date, there are no prospective studies on the relationship between plaque characteristics identified by 40 MHz IVUS and future adverse events. This prospective study evaluated the relationship between plaque morphology in nonculprit nonsignificant lesions, determined by 40 MHz IVUS, and long-term clinical outcomes. Consecutively, 45 patients who underwent 3-vessel intravascular ultrasound (IVUS) examinations were prospectively enrolled. Qualitative and quantitative IVUS analyses including scoring of echogenicity for assessment of plaque characterization were performed for each nonsignificant nonculprit lesion. The number, the length, the location (superficial or deep), and maximum arc were measured for each calcium deposit within plaques. Spotty calcification was defined as calcium deposits <90° and <6 mm in length. Primary end point was defined as nonsignificant nonculprit lesion-related revascularization (NNLR) during 6 years of follow-up. A total of 163 nonsignificant nonculprit lesions with mild to moderate stenosis were identified on baseline 3-vessel IVUS. Of those 163 lesions, six lesions required NNLR during the follow-up period. There were no differences in quantitative IVUS parameters including remodeling index, plaque burden, and echogenicity between lesions requiring and not requiring NNLR. However, deep spotty calcification was more frequently identified in lesions requiring NNLR than in those not requiring NNLR (33 vs. 8 %, P = 0.02). Spotty calcium deposits identified by 40 MHz IVUS predicted the need for NNLR during a 6-year follow-up period. This finding suggests that deep spotty calcium may be a surrogate marker for plaque progression and the subsequent need for revascularization in the future.

Recurrent coronary artery dissection of left main trunk initially presented with normal coronary angiography.

Although spontaneous coronary artery dissection (SCAD) is usually diagnosed by coronary angiography, diagnosis may be missed because of various presentations and imperfections of coronary angiography. We report a case of a 41-year-old female with pregnancy-related SCAD who presented with cardiac arrest. Initial coronary angiography was normal without intimal flap. Unexpectedly, 4 days after admission, SCAD in left main trunk was revealed with recurrent myocardial infarction. Intimal flap was sealed at the time of first angiography and this is an interesting point that made us report this case. SCAD is a rare but not negligible cause of not only acute myocardial infarction but also sudden cardiac arrest even if first coronary angiography is normal. .

Tissue Characterization of In-Stent Neointima Using Optical Coherence Tomography in the Late Phase After Bare-Metal Stent Implantation--An Ex Vivo Validation Study.

BACKGROUND: We performed an ex vivo study to investigate optical coherence tomography (OCT) imaging for differentiating several types of neointimal tissue during the later phases after bare-metal stent (BMS) implantation as compared with histologic results. METHODS AND RESULTS: OCT imaging was performed in 6 autopsy hearts for 10 BMS with implant duration >4 years. OCT qualitative neointimal tissue characterization was based on tissue structure and classified as homogeneous pattern, heterogeneous pattern with visible struts, or heterogeneous pattern with invisible struts. Corresponding histological analyses of each 2-mm cross-section of the entire BMS were performed. Of 81 cross-sections, histological analysis revealed that the homogeneous pattern of neointima on OCT (n=39) contained smooth muscle cells with collagen, indicating high neointimal maturity. The heterogeneous patterns with visible struts (n=35) contained different tissues, including a proteoglycan-rich myxomatous matrix or dense calcified plate deposition. The heterogeneous patterns with invisible struts (n=7) included neointimal lipid/necrotic core formation, accumulation of foam cells, or microcalcification scattering. Of the 66 cross-sections containing large microvessels within the neointima on histology, only 6 (9%) were visualized by OCT. CONCLUSIONS: The present study confirmed the potential use of OCT in differentiating several types of neointima after BMS implantation. The image interpretation of OCT, based on visualization of stent struts, enables identification of several types of neointimal tissues, including in-stent fibroatheroma formation, more accurately.

Vascular flow reserve immediately after infrapopliteal intervention as a predictor of wound healing in patients with foot tissue loss.

BACKGROUND: The purpose of this study was to verify whether the concept of coronary blood flow reserve can be applied to patients with critical limb ischemia who are undergoing endovascular treatment (EVT) for isolated infrapopliteal lesions. METHODS AND RESULTS: Forty patients diagnosed with critical limb ischemia (Rutherford category 5) who were undergoing EVT for isolated infrapopliteal lesions were prospectively enrolled. All lesions were treated with conventional balloon angioplasty without stent placement. After successful EVT, a pressure/temperature sensor-tipped guidewire was positioned in the proximal popliteal artery. Using the thermodilution technique, the mean transit time (Tmn) was determined after bolus injections of 3-mL saline at baseline and at the onset of intra-arterial papaverine induced maximum hyperemia. Vascular flow reserve (VFR) was calculated as resting Tmn divided by hyperemic Tmn. Complete epithelialization of the reference wound (wound healing) was completely closed by either surgical or secondary intervention within 3 months after EVT. Wound healing was achieved in 22 patients after EVT (healing group) but was not achieved in 18 patients (nonhealing group). Postprocedural VFR was significantly lower in the nonhealing group than in the healing group (2.40; interquartile range, 2.00-3.08 versus 4.05; interquartile range, 3.60-4.60; P<0.0001). Receiver operating characteristic analysis revealed postprocedural VFR >3.6 as the best threshold value for complete wound healing after EVT. Univariate analysis revealed that postprocedural VFR >3.6 was a predictor of wound healing (P=0.0002). CONCLUSIONS: Advanced lower limb clinical setting may be caused by a poor capability of microvasculature. VFR, which is easily assessable, is useful in clinical risk stratification for patients with critical limb ischemia after EVT in the catheterization laboratory. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN000009313.