Plaque characteristics and slow flow during percutaneous coronary intervention of irregular protrusion by optical coherence tomography.

Irregular protrusion on optical coherence tomography (OCT) is associated with clinical events and target lesion revascularization. We investigated clinical and procedure characteristics, plaque characteristics, slow flow after stent implantation, and clinical outcomes with irregular protrusion using OCT. Eighty-four lesions in 76 patients undergoing OCT before percutaneous coronary intervention were evaluated. Irregular protrusion was defined as protrusion of material with an irregular surface into the lumen between stent struts with a maximum height of ≥100 µm. Lesions with irregular protrusion were found in 56% (47/84). Compared with lesions without irregular protrusion, those with irregular protrusion had significantly higher low-density lipoprotein cholesterol (LDL-C) levels (108 ± 31 mg/dl vs. 95 ± 25 mg/dl, P = 0.044); a tendency toward decreased use of statins [44% (19/43) vs. 67% (22/33), P = 0.065]; significantly larger reference vessel diameter (3.12 ± 0.53 mm vs. 2.74 ± 0.63 mm, P = 0.004); more frequent slow flow after stent implantation [38% (18/47) vs. 11% (4/37), P = 0.006]; higher incidence of thin-cap fibroatheromas [TCFAs; 49% (23/47) vs. 5% (2/37), P < 0.001]; plaque rupture [40% (19/47) vs. 16% (6/37), P = 0.018]; and a tendency higher incidence of 1-year adverse clinical outcomes (death, acute myocardial infarction, acute coronary syndrome, or target lesion revascularization) [12% (5/43) vs. 0% (0/33), P = 0.075]. In conclusion, irregular protrusion on OCT was associated with high plaque vulnerability, higher LDL-C, less frequent use of statin, larger vessel diameter, slow flow after stent implantation, and 1-year adverse clinical outcomes.

Prognostic Significance of Serum Indoxyl Sulfate and Albumin for Patients with Cardiovascular Disease.

The progression of renal dysfunction reduces serum albumin and deteriorates the binding capacity of protein-bound uremic toxins. We evaluated the prognostic implications of serum indoxyl sulfate (IS) and albumin levels in patients with cardiovascular disease.We prospectively enrolled 351 consecutive patients undergoing percutaneous revascularization for coronary artery disease or peripheral artery disease. The primary endpoint was all-cause mortality. Patients were assigned to four groups according to the median levels of serum IS (0.1 mg/dL) and albumin (3.9 g/dL).During the median follow-up time of 575 days, 16 patients died. The IS level was significantly higher in nonsurvivors (0.33 versus 0.85 mg/dL, P < 0.05). On the Kaplan-Meier curve, the high IS/low albumin group presented the highest mortality rate (log-rank test, P < 0.01). Cox proportional hazard analysis revealed that high IS/low albumin (hazard ratio (HR): 5.33; 95% confidence interval (CI): 1.71-16.5; P < 0.01), diastolic pressure (HR: 0.94; 95% CI: 0.91-0.98; P < 0.01), prior stroke (HR: 4.54; 95% CI: 1.33-15.4; P = 0.01), and left ventricular ejection fraction (LVEF) (HR: 0.92; 95% CI: 0.88-0.96; P < 0.001) were associated with increased mortality. Furthermore, the combination of IS and albumin levels significantly conferred an additive value to LVEF for predicting mortality (C-statistic: 0.69 versus 0.80; P < 0.001; net reclassification improvement: 0.83; P < 0.001; integrated discrimination improvement: 0.02; P = 0.02).A lower albumin level adds potentiating effects on IS as a prognostic factor for cardiovascular disease.

Combined assessment of left ventricular end-diastolic pressure and ejection fraction by left ventriculography predicts long-term outcomes of patients with ST-segment elevation myocardial infarction.

In patients with ST-segment elevation myocardial infarction (STEMI), it is unclear if combined assessment of left ventricular end-diastolic pressure (LVEDP) and left ventricular ejection fraction (LVEF) improves prediction of major adverse cardiac events (MACE). We analyzed data from 266 STEMI patients who underwent successful percutaneous coronary intervention and subsequent left ventriculography (LVG). Patients were divided into 4 groups, as follows: Group 1, LVEDP < 21 mmHg and LVEF ≥ 55%; Group 2, LVEDP < 21 mmHg and LVEF < 55%; Group 3, LVEDP ≥ 21 mmHg and LVEF ≥ 55%; and Group 4, LVEDP ≥ 21 mmHg and LVEF < 55%. Multivariate Cox proportional hazards analysis was used to determine if LVEDP and LVEF were associated with MACE (including cardiac death, non-fatal myocardial infarction, and heart failure requiring hospitalization). Change in LV parameters was assessed in the subset of 183 patients who underwent serial LVG (mean interval 6.3 ± 1.6 months). During a mean follow-up of 43 ± 31 months, 29 patients (10.9%) had a MACE. As compared to Group 1, MACE risk was significantly higher in Group 3 [hazard ratio (HR) 3.26; 95% confidence interval (CI) 1.05-10.0] and Group 4 (HR 3.99; 95% CI 1.44-11.0), but not in Group 2 (HR 0.46, 95% CI 0.54-3.96). In sub-analyses, LV end-systolic volume index after PCI was significantly higher in Group 4 than in the other groups and remained higher during follow-up. Combined LVEDP/LVEF assessment was useful in predicting MACE after successful PCI for STEMI patients and could facilitate risk stratification, as it predicts LV remodeling.

Pericoronary adipose tissue ratio is a stronger associated factor of plaque vulnerability than epicardial adipose tissue on coronary computed tomography angiography.

This study was designed to clarify the influence of pericoronary adipose tissue (PAT) on plaque vulnerability using coronary computed tomography angiography (CCTA). A total of 103 consecutive patients who underwent CCTA and subsequent percutaneous coronary intervention (PCI) using intravascular ultrasound (IVUS) for coronary artery disease were enrolled. The PAT ratio was calculated as the sum of the perpendicular thickness of the visceral layer between the coronary artery and the pericardium, or the coronary artery and the surface of the heart at the PCI site, divided by the PAT thickness without a plaque in the same vessel. PAT ratios were divided into low, mid and high tertile groups. Epicardial adipose tissue (EAT) thickness was measured at the eight points surrounding the heart. Multivariate logistic analysis was performed to determine whether the PAT ratio is predictive of vulnerable plaques (positive remodeling, low attenuation and/or spotty calcification) on CCTA or echo-attenuated plaque on IVUS. The Hounsfield unit of obstructive plaques >50% was lower in the high PAT group than in the mid and low PAT groups (47.5 ± 28.8 vs. 53.1 ± 29.7 vs. 64.7 ± 27.0, p = 0.04). In multivariate logistic analysis, a high PAT ratio was an independent, associated factor of vulnerable plaques on CCTA (OR: 3.55, 95% CI: 1.20-10.49), whereas mean EAT thickness was not (OR: 1.22, 95% CI: 0.82-1.83). We observed a similar result in predicting echo-attenuated plaque on IVUS. PAT ratio on CCTA was an associated factor of vulnerable plaques, while EAT was not. These results support the important concept of local effects of cardiac adipose tissue on plaque vulnerability.

Efficacy and Safety of Triple Therapy and Dual Therapy With Direct Oral Anticoagulants Compared to Warfarin.

The efficacy and safety of direct oral anticoagulants (DOAC) with antiplatelet therapy compared to warfarin are unclear. The subjects were 280 patients who received antiplatelet therapy with oral anticoagulation (OAC) for the treatment of or protection from thromboembolism between January 2012 and September 2015. Among the 280 subjects, 79 (28.2%) received dual therapy (OAC plus aspirin or P2Y12 inhibitor) with DOAC, 75 (26.8%) dual therapy with warfarin, 46 (16.4%) triple therapy (OAC plus aspirin and P2Y12 inhibitor) with DOAC, and 80 (28.6%) triple therapy with warfarin.Compared to triple therapy with warfarin, triple therapy with DOAC had slightly lower bleeding (3.5 versus 12.0/100 persons-years, HR: 0.24, 95%CI: 0.03 to 1.96, P = 0.183), and similar benefit outcomes (cardiac death, acute myocardial infarction or stroke) and thromboembolism (7.0 versus 10.5, HR: 0.53, 95%CI: 0.10 to 2.75, P = 0.453; 7.0 versus 7.5, HR: 0.96, 95%CI: 0.18 to 5.22, P = 0.964, respectively). Compared to dual therapy with warfarin, dual therapy with DOAC had slightly lower bleeding (3.0 versus 8.4, HR: 0.38, 95%CI: 0.07 to 2.18, P = 0.279), and similar benefit outcomes and thromboembolism (4.6 versus 4.2, HR: 1.66, 95%CI: 0.30 to 9.25, P = 0.565; 4.6 versus 1.4, HR: 3.11, 95%CI: 0.23 to 42.84, P = 0.397, respectively). Bleeding mainly occurred after 3 months (16/17, 94.1%).Triple therapy and dual therapy with DOAC were not inferior to triple therapy and dual therapy with warfarin in terms of major bleeding, benefit outcomes, and thromboembolism. Bleeding mainly occurred in the late phase.

Same or Different Drug-Eluting Stent Re-Implantation for Drug-Eluting Stent Restenosis: An Assessment Including Second-Generation Drug-Eluting Stents.

OBJECTIVES: We examined the long-term outcomes of implanting a different type of drug-eluting stent (DES), including second-generation DES, for treatment of DES-in stent restenosis (ISR). BACKGROUND: Treatment for DES-ISR has not been standardized. METHODS: The subjects were 80 patients with 89 lesions underwent DES implantation for DES-ISR. The patients were divided into the group of patients receiving the same DES for DES-ISR (Homo-stent: 24 patients, 25 lesions) and a different DES for DES-ISR (Hetero-stent: 56 patients, 64 lesions). The primary endpoint was survival free of major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, and target vessel revascularization (TVR). The secondary endpoint was late loss at 8-12 months follow-up. In the subgroup of patients who were treated with second-generation DES for DES-ISR, we also assessed the survival free of MACE. RESULTS: During a mean follow-up of 45.1 ± 21.2 months, 26 patients experienced MACE. There was no significant difference in the survival free of MACE (Log rank P = 0.17). In the sub-analysis of second generation DES, MACE was significantly higher in the Homo-stent group compared to the Hetero-stent group (Log rank P = 0.04). Late loss was significantly higher in the Homo-stent group than in the Hetero-stent group (0.86 ± 1.03 vs. 0.38 ± 0.74 mm, P = 0.03). This trend was prominent in the first-generation DES group. CONCLUSIONS: Although there was no significant difference in MACE between the Hetero-stent and the Homo-stent groups including both first and second-generation DES, the sub-analysis demonstrated different DES implantation for DES-ISR significantly improved the MACE rate among patients treated with second-generation DES. (J Interven Cardiol 2016;29:311-318).

Plaque Composition and No-Reflow Phenomenon During Percutaneous Coronary Intervention of Low-Echoic Structures in Grayscale Intravascular Ultrasound.

It has been reported that coronary vasa vasorum is associated with plaque vulnerability, and low-echoic structures in grayscale intravascular ultrasound (IVUS) are consistent pathologically with vasa vasorum. However, the association of low-echoic structures with plaque composition and no-reflow phenomenon during percutaneous coronary intervention (PCI) is unclear. We investigated plaque composition in virtual histology IVUS (VH-IVUS) and no-reflow phenomenon during PCI of low-echoic structures.A total of 106 lesions being treated by VH-IVUS before PCI were included in this study. Low-echoic structure was defined as a small tubular structure exterior to media without a connection to the vessel lumen in ≥ 3 consecutive crosssectional IVUS images. Lesions with low-echoic structures were found in 42% (45/106).Lesions with low-echoic structures were more prevalent in acute coronary syndrome (ACS) patients (53% [24/45] versus 20% [12/61], P < 0.001), had more positive remodeling (49% [22/45] versus 21% [13/61], P = 0.003), a larger number of VH-IVUS derived thin-cap fibroatheromas (VH-TCFAs) (0.64 ± 0.53 versus 0.05 ± 0.22, P < 0.001), more VH-TCFAs with a baseline plaque burden of 70% or more and minimal luminal area of 4.0 mm(2) or less (29% [13/45] versus 2% [1/61], P < 0.001), and more frequent no-reflow phenomenon after stent implantation and more final TIMI flow grade 0/1/2 (38% [17/45] versus 5% [3/61], P < 0.001; 9% [4/45] versus 0% [0/61], P = 0.03) than lesions without low-echo structures.Lesions with low-echoic structures in grayscale IVUS had high plaque vulnerability and were more prevalent in ACS patients, positive remolding, and VH-TCFAs, and they had more frequent no-reflow phenomenon during PCI than lesions without low-echoic structures.

Assessment of angiographic coronary calcification and plaque composition in virtual histology intravascular ultrasound.

OBJECTIVES: We assessed the relation between coronary plaque composition and angiographic calcification by using virtual histology intravascular ultrasound (VH-IVUS). BACKGROUND: The plaque vulnerability according to angiographic calcification is unclear. METHODS: Subjects were 140 consecutive patients (145 lesions) undergoing VH-IVUS before percutaneous coronary intervention. Subjects were divided into 4 groups: no calcification group (n = 27), spotty group (n = 65) that had calcium deposits under 90° in grayscale IVUS, intermediate group (n = 37) had calcium deposits with 90° or more and under 180°, and extensive group (n = 16) had calcium deposits with 180° or more. RESULTS: The number of VH thin-cap fibroatheromas in spotty group was significantly larger than no calcification group, intermediate group, and extensive group (0.66 ± 0.71 vs 0.22 ± 0.42 [P < 0.01], 0.32 ± 0.48 [P < 0.05], 0.13 ± 0.34 [P < 0.01], respectively). Spotty group without angiographic calcification had significantly larger %necrotic core than with angiographic calcification (24.5 ± 6.7% vs 19.9 ± 7.2%, P < 0.05). Intermediate group without angiographic calcification had significantly larger necrotic core area than with angiographic calcification (2.5 ± 0.9 mm(2) vs 1.7 ± 0.9 mm(2) , P < 0.05). Extensive group with angiographic calcification had significantly larger %dense calcium than without angiographic calcification (18.3 ± 4.0% vs 13.4 ± 4.4%, P < 0.05). CONCLUSIONS: Lesions with spotty calcification was highly vulnerable in VH-IVUS. Spotty or intermediate plaque calcification without angiographic calcification was more vulnerable than those with angiographic calcification. Extensive plaque calcification with angiographic calcification had more dense calcium than those without angiographic calcification.

Measurement of left ventricular end-diastolic pressure improves the prognostic utility of the Global Registry of Acute Coronary Events score in patients with ST-segment elevation myocardial infarction.

Aims: This study aimed to evaluate the clinical significance of measuring left ventricular end-diastolic pressure (LVEDP) in patients with ST-segment elevation myocardial infarction (STEMI). Methods and results: We retrospectively analysed clinical data from 277 patients with STEMI between October 2006 and June 2014. LVEDP and left ventricular ejection fraction (LVEF) were perioperatively measured during percutaneous coronary intervention (PCI). The primary endpoint was a major adverse cardiac event (MACE) such as cardiac death, non-fatal myocardial infarction, or hospitalisation due to heart failure during the observation period. The independent predictors were identified by Cox proportional hazards regression analysis. Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) were conducted to assess the incremental prognostic value of adding cardiovascular parameters, including LVEDP, to the Global Registry of Acute Coronary Events (GRACE) score. The mean follow-up period was 44±31 months. A MACE occurred in 33 patients (12.0%). In the Cox proportional hazards regression model, after adjusting for confounding factors, LVEDP was an independent predictor of a MACE (hazard ratio [HR] 1.11, 95% confidence interval [CI]: 1.06-1.17, p<0.001). In addition, the predictive value of the GRACE score for a MACE was significantly improved by LVEDP (NRI 0.66, 95% CI: 0.32-1.01, p<0.001; IDI 0.06, 95% CI: 0.02-0.11, p=0.001), but not by LVEF (NRI 0.14, 95% CI: -0.22-0.50, p=0.44; IDI 0.01, 95% CI: 0.00-0.03, p=0.11). Conclusions: The results of this study demonstrated that evaluating LVEDP provides an additive prognostic value over conventional risks estimated by the GRACE score among STEMI patients.

Prognostic Utility of Indoxyl Sulfate for Patients with Acute Coronary Syndrome.

AIM: We investigated whether indoxyl sulfate (IS), a protein-bound uremic toxin, predicts prognosis after acute coronary syndrome (ACS). METHODS: Serum IS level was determined prospectively in 98 patients who underwent successful primary percutaneous coronary intervention for ACS. Patients on hemodialysis were excluded. The endpoint of this study was six-month composite events including death, nonfatal myocardial infarction, heart failure requiring hospitalization, and adverse bleeding events. RESULTS: During the mean follow-up period of 168 days, composite events occurred in 13.3% of cases. Serum IS level was significantly higher in subjects who developed composite events than in those without events (0.14±0.11 mg/dl vs. 0.06±0.04 mg/dl; p＜0.001). After adjusting for confounding factors, a Cox proportional hazard analysis revealed that the IS level (hazard ratio (HR): 10.6; 95% confidence interval (CI): 1.63-69.3, p=0.01), hemoglobin level (HR: 0.61; 95% CI: 0.43-0.87; p＜0.01), and left ventricular ejection fraction (LVEF) (HR: 0.95; 95% CI: 0.91-0.99; p=0.03) were independent predictive factors of composite events. Furthermore, IS level significantly conferred additional value to the combined established risks of LVEF and hemoglobin level for predicting the incidence of composite events (area under the curve: 0.82 vs. 0.88, p=0.01; net reclassification improvement: 0.67, p=0.01; and integrated discrimination improvement: 0.15, p＜0.01). CONCLUSIONS: The assessment of serum IS level has prognostic utility for the management of ACS.

Clinical outcome of treatment with or without a final kissing balloon technique for bifurcation in-stent restenosis lesions.

BACKGROUND: The treatment strategy for in-stent restenosis (ISR) with bifurcation lesions has not been well explored. We examined the clinical outcomes between final kissing balloon technique (FKBT) after stent implantation and single-stent implantation without FKBT for bifurcation ISR lesions. METHODS: We identified 115 consecutive ISR with bifurcation lesions among 108 patients who underwent drug-eluting stent implantation. The patients were divided into the FKBT group (34 patients, 35 lesions) and the non-FKBT group (74 patients, 80 lesions). RESULTS: Thrombolysis in myocardial infarction flow grade of side branch was significantly greater in the patients with FKBT than those without FKBT after coronary intervention (2.80±0.46 vs. 2.65±0.68, p=0.04), but this difference was attenuated and was no longer statistically significant at the time of follow-up (2.80±0.48 vs. 2.80±0.60, p=0.97). During a mean follow-up of 47.8±23.6 months, there were no significant differences in the incidence of major adverse cardiac events (MACE). In multivariate analysis, estimated glomerular filtration rate (hazard ratio: 0.96, 95% confidence interval: 0.92-0.99, p=0.02) was an independent predictor of MACE. Contrast volume (170.71±47.17ml vs. 136.46±55.56ml, p=0.002) and radiation dose (1.44±1.65Gy vs. 0.96±0.46Gy, p=0.02) were significantly higher in the FKBT group than in the non-FKBT group. CONCLUSIONS: Single-stent implantation without FKBT may be a sufficient treatment strategy for bifurcation ISR lesions.

Comparison of Coronary Intimal Plaques by Optical Coherence Tomography in Arteries With Versus Without Internal Running Vasa Vasorum.

It has been reported that the internal running vasa vasorum (VV) was associated with plaque vulnerability, and microchannels in optical coherence tomography (OCT) are consistent pathologically with VV. We investigated plaque vulnerability and incidence of slow flow during percutaneous coronary intervention of the internal longitudinal running VV. Subjects were 71 lesions that underwent OCT before percutaneous coronary intervention. Internal running VV was defined as intraplaque neovessels running from the adventitia to plaque. Lesions with internal running VV were found in 47% (33 of 71). Compared with lesions without internal running VV, lesions with internal running VV showed significantly higher incidence of intimal laceration (64% [21 of 33] vs 16% [6 of 38], p <0.001), lipid-rich plaque (79% [26 of 33] vs 26% [10 of 38], p <0.001), plaque rupture (52% [17 of 33] vs 13% [5 of 38], p <0.001), thin-cap fibroatheroma (58% [19 of 33] vs 11% [4 of 38], p <0.001), macrophage accumulation (61% [20 of 33] vs 26% [10 of 38], p = 0.004), intraluminal thrombus (36% [12 of 33] vs 3% [1 of 38], p <0.001), and slow flow after stent implantation (42% [14 of 33] vs 13% [5 of 38], p = 0.007). The multivariable analysis showed that internal running VV was an independent predictor of slow flow after stent implantation (odds ratio 4.23, 95% confidence interval 1.05 to 17.01, p = 0.042). In conclusion, compared with those without, plaques with internal running VV in OCT had high plaque vulnerability with more intimal laceration, lipid-rich plaque, plaque rupture, thin-cap fibroatheroma, macrophage accumulation, and intraluminal thrombus, and they had high incidence of slow flow after stent implantation.