Mechanisms of Medial Wall Thinning in Chronic Total Occlusion.

BACKGROUND: The success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is lower and the risk for complications higher compared with other non-CTO PCI. Although interventionalists focus on intimal plaque characteristics, the coronary media is an important (especially for techniques involving antegrade dissection and re-entry) but poorly understood structure in CTO PCI. OBJECTIVES: The aim of the present study was to investigate coronary medial wall thinning in CTO lesions and determine how this thinning might affect CTO PCI. METHODS: A total of 2,586 sections were investigated, from arteries with evidence of CTO from 54 subjects (n = 1,383 sections) and arteries without evidence of CTO from 54 subjects with non-coronary-related deaths (n = 1,203 sections) after matching for age, gender, body weight, and body height. RESULTS: The medial thickness in subjects with CTO was lower than that in those with non-coronary-related death (P < 0.001). In subjects with CTO, CTO lesions had thinner medial walls compared with those with lower luminal narrowing (P < 0.001). At the CTO distal segments, the 6- to 12-mm distal segment from the distal end of the CTO had significantly less luminal narrowing (P < 0.001), and similar medial thickness, compared with the distal end of the CTO. Immunohistochemical analysis revealed that short-duration CTO had more cleaved caspase-3-positive cells in media and had significantly more CD3+, CD4+, CD8+, and CD4+CD28null T cells compared with long-duration CTO. CONCLUSIONS: CTO lesions demonstrated coronary medial thinning compared with non-CTO lesions. Further investigation of the cause-and-effect relationship among inflammation, apoptosis, and coronary medial wall thinning is warranted in future mechanistic studies.

Randomized comparison between 2-link cell design biolimus A9-eluting stent and 3-link cell design everolimus-eluting stent in patients with de novo true coronary bifurcation lesions: the BEGIN trial.

The appropriate stent platform for treating coronary bifurcation lesions (CBLs) remains controversial. Previous bench tests have demonstrated the superiority of a 2-link cell design to 3-link cell design for creating inter-strut dilation at the side branch ostium. This randomized multicenter prospective BEGIN trial compared the biodegradable polymer-based biolimus A9-eluting stent (2-link BES) with the durable polymer-based cobalt chromium everolimus-eluting stent (3-link EES) in 226 patients with de novo CBLs. Patients with true bifurcations, defined as > 50% stenosis in the main vessel and side branch (SB) and an SB diameter > 2.25 mm, were enrolled. Guide wire re-crossing to the distal cell (near the carina) in the jailed SB and final kissing inflation were recommended. The SB angiographic endpoint was < 50% stenosis diameter. Left-main CBLs (13.5% vs. 13.0%) and 2-stent technique (30.6% vs. 22.6%) rates were similar. The primary endpoints (minimum lumen diameter at the SB ostium measured at an independent core laboratory at the 8-month follow-up) were comparable (1.64 ± 0.50 mm vs. 1.63 ± 0.51 mm, p = 0.976). There was no significant difference in composite outcomes of cardiac death, myocardial infarction, or target vascular revascularization at 12 months (7.4% vs. 8.0%, p = 0.894). Two-link BES and 3-link EES showed similar 8-month angiographic and 1-year clinical outcomes for true CBLs.

Efficacy of lacrosse NSE using the "leopard-crawl" technique on severely calcified lesions.

Calcified lesions often encounter difficulties associated with stent delivery and underexpansion. Lesion preparation of calcified lesions prior to stent implantation is important to facilitate stent delivery and provide concentric stent expansion. The Lacrosse NSE, a balloon catheter with 3 nylon elements, provides an efficacious scoring effect when used for predilatation of calcified lesions. Although bench testing on a calcified model verified that Lacrosse NSE and other scoring catheters provide a greater scoring effect compared to conventional plain old balloon angioplasty, delivery to target lesion location using standard delivery techniques for severely calcified lesions is typically more problematic. One method for overcoming the obstacles faced by difficult delivery is use of the "leopard-crawl" technique. This technique uses a low inflation pressure to create a wedge into the calcification and then subsequently advances the catheter during balloon deflation to facilitate catheter delivery across the stenosis. This technique is well suited for the Lacrosse NSE due to the unique catheter design. We hereby report on the initial clinical use of the leopard-crawl technique for facilitating catheter delivery in cases of severely calcified lesions in which standard delivery was unsuccessful, while creating an efficacious scoring effect into the calcified lesion that reflects the results of bench testing.

Virtual histology intravascular ultrasound comparison of coronary chronic total occlusions versus non-occlusive lesions.

To use virtual histology intravascular ultrasound (VH-IVUS) to assess the differences in tissue composition between chronic total occlusions (CTO) and non-occlusive lesions, especially in vivo. We compared 50 CTOs (49 patients) after guidewire crossing with 41 non-occlusive lesions (41 patients, 25 with unstable angina and 16 with stable angina). Overall, the percentage of necrotic core in the CTO segments was similar to non-occlusive lesions (35.6 vs. 38.7 %, p = 0.18 at the maximum necrotic core site; 24.2 vs. 23.7 %, p = 0.8 in mean analysis over the entire segment length). However, the percentage of dense calcium in CTO segments was less than in non-occlusive lesions (10.6 vs. 14.8 %, p = 0.025 at the maximum necrotic core site; 7.6 vs. 11.4 %, p = 0.036 in mean analysis over the entire segment length). Finally, the necrotic core/dense calcium ratio tended to be larger in the CTO segment than in non-occlusive lesions (2.94 vs. 2.35, p = 0.082 at the maximum necrotic core site; 3.05 vs. 2.03, p = 0.005 in mean analysis over the entire segment length). Overall, 42 (84 %) CTOs contained a fibroatheroma compared to 40 (97 %) of non-occulsive stenoses. The percentage of necrotic core in CTOs with a fibroathroma (39.0 %) was less than non-occlusive stenoses with a VH-thin cap fibroathroma (44.4 %, p = 0.017) and greater than non-occlusive stenoses with a VH-thick cap fibroathroma (33.5 %, p = 0.022) at maximum necrotic core site. These findings suggest that the morphological characteristics of most CTOs were similar as compared with non-CTO lesions and CTOs evolved from fibroatheromas.

A virtual histology intravascular ultrasound analysis of coronary chronic total occlusions.

OBJECTIVES: We used virtual histology intravascular ultrasound (VH-IVUS) to investigate plaque composition of chronic total occlusions (CTO). BACKGROUND: There are limited data on the composition of CTOs, especially in vivo. METHODS: VH-IVUS was performed in 50 CTO lesions (49 patients) after guidewire crossing or pre-dilation using a 1.5-2 mm balloon. Plaque composition in the proximal reference, distal reference, and CTO segment (subsequently divided into proximal, middle, and distal subsegments) was analyzed and reported as median and interquartile range. VH-IVUS phenotype was also assessed. The definition of a fibroatheroma was >10% confluent necrotic core (NC) in more than three consecutive frames. RESULTS: Overall, the maximum NC within the CTO [35.5% (28.7, 44.3%)] was similar to the proximal reference [35.6% (24.1, 42.1%)] and greater than the distal reference [31.5% (22.6, 35.2%), P < 0.01]. There was no difference in maximum NC observed among proximal [31.4% (25.2, 10.4%)], middle [31.0% (23.3, 38.3%)], and distal CTO subsegments [30.4% (22.0, 39.5%)]. Overall, 42/50 CTOs contained a VH-fibroathroma; and 8/50 did not. CTOs containing a VH-fibroatheroma had more NC and dense calcium while CTOs not containing a fibroatheroma had more fibrotic and fibrofatty plaque. Importantly, 60.5% of VH-fibroatheroma-containing CTOs had a thin-cap fibroatheroma (NC abutted to the lumen) in the proximal reference. CONCLUSIONS: Using VH-IVUS, CTO morphology can be divided into two patterns: (1) CTO with VH-fibroatheroma or (2) CTO without VH-fibroatheroma. This suggests two mechanisms of CTO formation-the majority evolving from acute coronary syndrome and thrombosis and the minority from atherosclerosis progression.

Magnetic resonance evaluation of the associations of thoracic and abdominal aortic plaques with the presence and extent of coronary artery stenosis.

The association between coronary artery disease (CAD) and thoracic aortic plaques has often been reported using transesophageal echocardiography. However, studies showing the association between CAD and abdominal aortic plaques are scarce. CMR can visualize plaques in both the thoracic and abdominal aortas. Using CMR, we investigated the associations of thoracic and abdominal aortic plaques with the presence and extent of coronary artery stenosis in 146 patients undergoing coronary angiography, of whom 108 had CAD. The prevalence of thoracic and abdominal aortic plaques was higher in patients with CAD than in those without CAD (73% and 94% vs. 32% and 79%, p < 0.025). Stepwise increases in the prevalence and extents of both thoracic and abdominal plaques were found depending on the number of stenotic coronary vessels. Plaque extent in the thoracic aorta correlated with the numbers of > 50% and > 25% stenotic coronary segments (rs = 0.30 and 0.41). Plaque extent in the abdominal aorta also correlated with the numbers of > 50% and > 25% stenotic segments (rs = 0.40 and 0.44). Notably, the total plaque extent in the aortas correlated best with the numbers of > 50% and > 25% stenotic coronary segments (rs = 0.41 and 0.49, p < 0.001), and this factor was found to be the best predictor for the presence of CAD by the receiver-operating-characteristics curve analysis. Thus, the total plaque extent in the aortas was found to be more closely associated with the presence and extent of coronary stenosis than the thoracic or abdominal aortic plaque extent.

Procedural implications of intravascular ultrasound morphologic features of chronic total coronary occlusions.

Although the success rates of percutaneous coronary intervention of chronic total occlusions (CTOs) have improved, morphologic features are not well known. We analyzed experience at 4 centers where intravascular ultrasound (IVUS) was performed in 67 native artery CTO lesions (mean CTO duration 6.3 months) just after the lesion was crossed with a guidewire (n = 7) or after dilatation with a 1.5-mm (n = 46) or 2.0-mm (n = 14) balloon. IVUS detected calcium somewhere in the CTO in 96%; however, only 68% had mild calcium. IVUS identified a proximal end of the CTO in all lesions, but a distal end of the CTO in only 50%. An intramural hematoma was observed in 34% of CTOs, suggesting that the guidewire frequently entered the medial space during successful recanalization. CTOs were longer, vessel area was smaller, and total calcium index was greater in lesions with hematomas (p = 0.003, 0.05, and 0.03, respectively). Inadequate reflow after the procedure was observed in 9% and was associated with longer lesions and intralesional calcium. CTO length as measured with angiography was shorter than the length as measured with IVUS (p = 0.02). Calcium was detected on the angiogram in 61% (p = 0.054 vs IVUS). Most typical angiographic findings associated with a low rate of procedural success were not associated with different IVUS morphologies. In conclusion, CTO lesions had multiple small calcium deposits, intramural hematomas were common and were indicative of guidewire penetration into the medial space during the CTO procedure, especially in long calcified lesions in smaller vessels, and inadequate reflow after the procedure was correlated with more complex CTO morphology.

Intravascular ultrasound guided wiring for chronic total occlusions.

The success of percutaneous intervention for chronic total occlusion depends mainly on crossing the lesion with a wire. This report deals with the principles and the technical tips of intravascular ultrasound-guided wiring for chronic total occlusion, which can be divided into two trategies.The first is "identification of the site of entry." When the abrupt type chronic total occlusion with a side branch is treated, it is possible to identify the occlusion and the entry point by pulling back the intravascular ultrasound catheter from the distal part of the side branch.The second is "returning to the true lumen after entering a false lumen." If hematoma is caused by manipulating a wire in the false lumen that impairs visualization of the distal true lumen, an intravascular ultrasound catheter can be advanced into the false lumen.An attempt to make a successful re-entry into the true lumen can be achieved under intravascular ultrasound guidance.

The latest wire technique for chronic total occlusion.

If patency is restored after chronic total occlusion (CTO), it can be maintained over the long term by implanting drug-eluting stents. The cause of unsuccessful percutaneous coronary intervention is usually failure of the wire to cross the site of CTO. The objective of this article is to describe the latest wire techniques for CTO. As for wire selection, CTO should generally be treated with hard-tipped spring wires, preferably Conquest Pro series (Asahi Intec). According to the penetrating strategy, the course of a blood vessel with CTO is established preoperatively and the wire is advanced based on the imaging data with minimum rotation (a torque of +/- 90 degrees or less). If the operator encounters divergence between the preoperative CTO image and the actual course of the coronary artery, the parallel wire technique should be used. With this method, a wire which enters the subintimal space is left there, and a second wire is inserted along it to find a new channel. When this technique is successful, the following findings are often noted: 1) the second wire crosses over the first one in the CTO; 2) the second wire shows more acute curve than the first wire; 3) the second wire penetrates the lesion from the outer curvature of the coronary artery and then is advanced along the same curvature of the vessel. Indeed, the second wire should be operated intentionally to achieve these findings so that the probability of success increases and the duration of the procedure is shortened.

Characterization of the expression of TLR2 (toll-like receptor 2) and TLR4 on circulating monocytes in coronary artery disease.

TLRs are receptors involved in the recognition of pathogens by the innate immune system, and TLR2 and TLR4 play important roles in the activation of monocytes. A total of 105 consecutive patients who underwent coronary angiography comprised of 46 with stable effort angina (SA), 41 with unstable angina (UA), and 18 with no significant CAD (CNT) were enrolled. The baseline expression levels of TLR2 and TLR4 on monocytes in peripheral blood mononuclear cells (PBMCs) were determined by flow-cytometric analysis. Since TLR2 expression has been reported to be regulated by TLR4 signaling, we cultured PBMCs with or without lipopolysaccharide (LPS, 1 microg/ml). At baseline, TLR4 levels (mean of fluorescence intensity ) in SA (145 +/- 58, p < 0.05) and UA (164 +/- 65, p < 0.01) were higher than those in CNT (107 +/- 37). As for TLR2, levels were higher in UA (108 +/- 36, p < 0.05) than in SA (94 +/- 18) and CNT (87 +/- 22). After stimulation with LPS, TLR2 levels increased in SA but decreased in UA. In conclusions, TLR4 levels increased in both SA and UA. Monocytes in UA were characterized by elevated TLR2 levels and unresponsiveness of the TLR2 levels to TLR4 stimulation.

In vivo magnetic resonance evaluation of associations between aortic atherosclerosis and both risk factors and coronary artery disease in patients referred for coronary angiography.

BACKGROUND: Magnetic resonance imaging was recently reported to detect atherosclerotic plaques in thoracic and abdominal aortas. METHODS: Using magnetic resonance imaging, we investigated associations of risk factors and plasma inflammatory markers with plaques in both thoracic and abdominal aortas in 102 patients undergoing coronary angiography. Associations between coronary artery disease (CAD) and aortic plaques were also evaluated. RESULTS: Plaques in thoracic and abdominal aortas were detected in 61% and 90% of patients, respectively. Age and systolic blood pressure correlated with plaque extents in both the aortas. Serum LDL cholesterol level correlated with plaque extent in the thoracic aorta (r(s) = 0.42). The degree of smoking correlated with plaque extent in the abdominal aorta (r(s) = 0.43). In multivariate analysis, age and systolic blood pressure were associated with plaques in both the aortas. The LDL cholesterol and smoking were characteristically associated with plaques in the thoracic and abdominal aortas, respectively. Regarding inflammatory markers, fibrinogen and C-reactive protein levels correlated with total plaque extent in the aortas (r(s) = 0.50 and r(s) = 0.51). Compared with 24 patients without CAD, 78 with CAD more often had plaques in the thoracic (71% vs 29%) and abdominal (95% vs 75%) aortas. Although plaque extents in both the aortas correlated with the severity of CAD, only thoracic plaques were independently associated with CAD. CONCLUSIONS: The thoracic and abdominal aortas may have different susceptibilities to risk factors. However, plasma inflammatory markers appear to reflect total extent of aortic atherosclerosis. Although aortic plaques are common in patients with CAD, only thoracic plaques are an independent factor for CAD.

Sarpogrelate, a specific 5HT2-receptor antagonist, improves the coronary microcirculation in coronary artery disease.

BACKGROUND: Serotonin (5-hydroxytryptamine: 5-HT) reduces the coronary blood flow (CBF) as a product of aggregating platelets. Sarpogrelate, a specific 5HT2-receptor antagonist, has been reported to increase the coronary collateral flow in humans: however, its effect on the microcirculation is still not fully understood. HYPOTHESIS: This study was undertaken to determine whether sarpogrelate might improve the microcirculation in coronary artery disease (CAD). METHODS: To investigate the effect of sarpogrelate on the microcirculation in CAD, we measured CBF in 15 patients with CAD but no significant stenosis in the left anterior descending artery (LAD). The patients were randomly allocated to two groups, including those receiving oral administration of 200 mg of sarpogrelate (SPG, 8 patients, age 61 +/- 6 years) and those receiving no medication (controls, 7 patients, age 57 +/- 8 years). Prior to and 1 h after the administration of sarpogrelate, or in controls at 1-h intervals, the average peak velocity (APV) at baseline and hyperemia was measured by an intracoronary Doppler guidewire. Systemic blood pressure (SBP) and cardiac output (CO) were also measured. RESULTS: In the patients receiving SPG, the medication significantly increased the baseline (18 +/- 9 to 19 +/- 10 cm/s, p < 0.05) and maximal APV (55 +/- 9 to 64 +/- 31 cm/s, p<0.05). However, no significant changes were observed in SBP and CO after the administration of SPG. In the control group, there were no significant differences in baseline and hyperemic APV. CONCLUSION: Sarpogrelate increased both baseline and maximal CBF without changing the systemic hemodynamics. These findings thus support that SPG improves the microcirculation by antagonizing the vasoconstrictive products of the aggregating platelets in CAD.