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Endomyocardial biopsy (EMB) is widely used for the diagnosis of unexplained ventricular dysfunction and for assessment of cardiac allograft rejection. But, the impact of vascular access site on procedural time of EMB is not well-known. From February 2014 to May 2016, consecutive patients requiring EMB were prospectively enrolled in this study. Vascular access, by either the jugular or femoral vein, was randomly assigned. EMB was randomly performed by 3 pre-identified physicians based on practical experience in EMB. Each case was required to obtain at least 3 samples. The primary endpoint was to compare the total time spent in acquiring EMB from the right ventricular septum between the jugular and femoral vein access groups. The secondary endpoints were evaluation of each set (1st to 3rd attempt) of EMB times and safety. In addition, factors affecting the EMB procedural times were evaluated. A total of 49 consecutive patients requiring EMB (3.9 attempts/patient) were enrolled (the jugular group: 23, the femoral group: 26), and 156 myocardial samples (3.2 samples/patient) were obtained. There were no significant differences in total biopsy procedural time between the 2 groups (16.3 ± 7.4 vs. 20.8 ± 9.9 min, p = 0.075). Independent predictors for longer procedural time of the 1st attempt included femoral access, non-expert operators, and larger right atrium according to multiple linear regression analysis. The complication rates were not significantly different between the 2 groups, except for catheter kinking as a technical factor. Total biopsy time was not significantly different between the jugular and femoral venous access groups. However, the 1st attempt EMB procedural time by non-expert operators was longer when using the femoral approach, especially in cases involving a larger right atrium diameter.

Background: There is no echocardiographic predictor of the effectiveness of tolvaptan in patients with heart failure (HF). The aim of this study was to investigate the echocardiographic predictor of responders to tolvaptan in patients with HF., Methods: This observational study consisted of 62 consecutive in-hospital patients with HF who received tolvaptan with volume overload despite standard therapies. The echocardiography data were obtained within 1 week before the administration of tolvaptan. Tolvaptan responders were defined as those having a body weight decrease from baseline >1 kg on the morning of day 8., Results: The mean age of the 62 patients was 75.1 ± 13.9 years, and 45 patients (72.6%) were considered to be responders. Tricuspid annular plane systolic excursion (TAPSE) was significantly higher (17.1 ± 3.8 vs. 13.0 ± 3.9 mm; p = 0.0004) and the tricuspid valve regurgitation pressure gradient (33.3 ± 14.6 vs. 44.9 ± 12.2 mmHg; p = 0.007) and estimated right atrium pressure (7.8 ± 4.2 vs. 10.3 ± 4.5 mmHg; p = 0.043) were significantly lower in the Responder group than in the Non-responder group. In a multivariate logistic regression analysis, TAPSE was found to be an independent predictor of response (odds ratio 1.28; 95% confidence interval 1.03-1.60). According to the receiver operating characteristics analysis, the area under the curve of TAPSE was the largest among the parameters measured by echocardiography. The cut-off value for TAPSE to predict responders was determined to be 17.0 mm (sensitivity = 56.8%, specificity = 94.1%)., Conclusions: TAPSE is a simple predictor of the effectiveness of tolvaptan in patients with HF.

Although late restenosis is one of the long-term complications of stent implantation, its pathogenesis has not been fully elucidated. For consecutive patients who developed in-stent restenosis (ISR) after stent implantation, integrated backscatter (IB) intravascular ultrasound was performed for ISR lesions. The tissue characteristics of neointima within the stented segment were compared between lesions with early restenosis and those with late restenosis. Of 73 ISR lesions arising after sirolimus-eluting stent (SES; n = 25) or bare-metal stent (BMS; n = 48) implantation, early and late restenosis were documented in 52 and 21 lesions, respectively. A higher prevalence of late restenosis was observed after SES implantation than after BMS implantation (60.0 vs. 12.5 %; p < 0.001). The duration between stent implantation and late restenosis was significantly shorter after SES implantation than after BMS implantation (57.0 ± 22.1 vs. 124.4 ± 19.6 months; p < 0.001). Percent low-IB volume was significantly higher in the neointima of late restenosis than in that of early restenosis (29.9 ± 9.9 vs. 19.8 ± 11.3 %; p < 0.001). Significantly more low-IB tissue was observed in the neointima of late restenosis than in that of early restenosis, suggesting atherosclerotic progression in late phase after stent implantation as a possible mechanism of late restenosis.

Background and Aims: Disruption of atherosclerotic plaque and distal embolism often cause peri-procedural myocardial injury during percutaneous coronary intervention (PCI). In the present study, we evaluate the association between the characteristics of the target lesion and the amount of debris captured by the filter-type distal protection device., Methods: We enrolled 120 consecutive patients with acute coronary syndrome, who underwent coronary stent implantation with a filter-type distal protection device after integrated backscatter intravascular ultrasound (IB-IVUS) analysis. The amount of debris captured by the protection filter was measured through microscopic evaluation., Results: The lipid and fibrous volume evaluated with IB-IVUS was significantly correlated with the amount of the captured debris (r = 0.657, p < 0.01), (r = 0.322, p < 0.01). The lipid plaque fraction showed a positive correlation (r = 0.335, p < 0.01), while the fibrous plaque fraction was found to be inversely correlated (r = -0.375, p < 0.01) with the amount of captured debris. Multivariate regression analysis showed that lipid volume correlated independently with the amount of captured debris., Conclusion: The volume of the lipid-rich plaque was associated with the amount of procedure-related debris released and captured by the filter-type distal protection device., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study was to determine the correlation between the fractional flow reserve (FFR) values and volumetric intravascular ultrasound (IVUS) parameters derived from classic gray-scale IVUS and integrated backscatter (IB)-IVUS, taking into account known confounding factors. Patients with unstable angina pectoris with the frequent development of vulnerable plaques often showed the discrepancy between the FFR value and the quantitative coronary angiography findings. Our target population was 107 consecutive subjects with 114 isolated lesions who were scheduled for elective coronary angiography. The FFR was calculated as the mean distal coronary pressure divided by the mean aortic pressure during maximal hyperemia. Various volumetric parameters such as lipid plaque volume (LPV) and percentage of LPV (%LPV) were measured using IB-IVUS. Simple and multivariate linear regression analysis was employed to evaluate the correlation between FFR values and various classic gray-scale IVUS and IB-IVUS parameters. The Akaike information criterion (AIC) was used to compare the goodness of fit in an each model. Both the %LPV (r = -0.24; p = 0.01) and LPV (r = -0.40; p < 0.01) were significantly correlated with the FFR value. Only the LPV (AIC = -147.0; p = 0.006) and %LPV (AIC = -152.9; p = 0.005) proved to be independent predictors for the FFR value even after the adjustment of known confounding factors. The volumetric assessment by IB-IVUS could provide better information in terms of the relationship between plaque morphology and the FFR values as compared to the classic IVUS 2-dimensional gray-scale analysis.

Fractional flow reserve (FFR) is a useful modality to assess the functional significance of coronary stenoses. Although adenosine triphosphate (ATP) is generally used as the hyperemic stimulus, we sometimes encounter adverse events like hypotension during FFR measurement. Nicorandil, an ATP-sensitive potassium channel opener, recognized as an epicardial and resistance vessel dilator, has not been fully evaluated as a possible alternative hyperemic agent. The aim of this study was to evaluate the feasibility and safety of intracoronary nicorandil infusion compared to intravenous ATP for FFR measurement in patients with coronary artery disease. A total of 102 patients with 124 intermediate lesions (diameter stenosis >40 and <70% by visual assessment) were enrolled. All vessels underwent FFR measurements with both ATP (150 μg/kg/min) and nicorandil (2.0 mg) stimulus. FFR, hemodynamic values, and periprocedural adverse events between the two groups were evaluated. A strong correlation was observed between FFR with ATP and FFR with nicorandil (r = 0.954, p < 0.001). The agreement between the two sets of measurements was also high, with a mean difference of 0.01 ± 0.03. The mean aortic pressure drop during pharmacological stimulus was significantly larger with ATP compared to nicorandil (9.6 ± 9.6 vs. 5.5 ± 5.8 mmHg, p < 0.001). During FFR measurement, transient atrioventricular block was frequently observed with ATP compared to nicorandil (4.0 vs. 0%, p = 0.024). This study suggests that intracoronary nicorandil infusion is associated with clinical utility and safety compared to ATP as an alternative hyperemic agent for FFR measurement.

Objectives: The aim of this study was to evaluate the relationship between the multifunction cardiogram (MCG), and SYNTAX score (SS) and functional SYNTAX score (FSS) in detecting the presence of intermediate to obstructive coronary lesions., Background: Performing coronary angiography (CAG) and measuring fractional flow reserve (FFR) to calculate the SS and FSS is inherently invasive and adds complexity., Methods: The MCG was obtained and analyzed before performing CAG in 87 consecutive subjects with suspected coronary artery disease who were scheduled for elective CAG. The patients were divided into three groups according to risk based on high, borderline, and low MCG scores. The SS was determined, as well as FSS but only by counting lesions prone to functional ischemia (FFR ≤ 0.8). The relationship between the MCG and the SS and FSS was evaluated., Results: The MCG was the only test significantly associated with the SS (odds ratio, 2.92 [1.60 - 5.31], P < 0.001) and FSS (odds ratio, 3.66 [1.95 - 6.87], P < 0.001). A high MCG score had a specificity of 92.6% (89.0-96.2%) and 92.3% (89.0-95.6%), and a predictive accuracy of 72.4% (67.6-77.2%) and 82.8% (78.7-86.8%) for the prediction of SS and FSS, respectively., Conclusions: The MCG showed high specificity and predictive accuracy especially for the FSS, suggesting that it is useful not only in identifying functionally significant ischemia but also in reducing unnecessary CAGs., (© 2015 Wiley Periodicals, Inc.)

We sought to determine the morphologic predictors of major adverse cardiac events (MACEs) after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES), using integrated backscatter intravascular ultrasound (IB-IVUS). Conventional IVUS and IB-IVUS were performed in 260 consecutive patients who underwent PCI with DES. Three-dimensional analyses were performed to determine plaque volume and the volume of each plaque component (lipid, fibrous, and calcification). Patients were divided into two groups according to the median lipid volume (LV) in the target lesion. MACEs were defined as death, nonfatal myocardial infarction, and any repeat revascularization. The median follow-up interval was 1285 days. MACEs were observed in 64 patients (24.6 %). Patients having a larger LV compared with their counterparts had worse long-term clinical outcomes regarding mortality (3.8 vs. 0 %, P = 0.02) and MACEs (31.5 vs. 17.7 %, P = 0.008) by log-rank test. After adjustment for confounders, large LV (odds ratio 1.95, 95 % confidence interval 1.14-3.33, P = 0.02) was significantly and independently associated with MACEs. The assessment of coronary plaque characteristics in the target lesion may be useful to predict long-term outcome following successful coronary intervention.

Eicosapentaenoic acid (EPA), a member of the omega-3 polyunsaturated fatty acid family, prevents cardiovascular disease. C-reactive protein (CRP) is a marker of inflammation, which promotes atherosclerosis. The aim of this study was to investigate the relationship among EPA, CRP, and the prevalence of peripheral artery disease (PAD), which is a manifestation of systemic atherosclerosis. A cross-sectional study was performed on 238 patients with coronary artery disease (CAD). Blood EPA and CRP levels and ankle-brachial pressure indices were measured. Cut-off values for plasma EPA levels and serum CRP levels were determined using receiver operating characteristic (ROC) analysis. Patients with ABIs ≤0.9 were defined as having PAD. EPA levels were significantly lower and CRP levels were significantly higher in patients with PAD than in those without [48 (26-77) vs. 58 (41-83) μg/ml, p = 0.026 and 3.3 (0.64-14.0) vs. 0.70 (0.32, 2.4) mg/l, p = 0.004]. Multivariate analysis for PAD revealed that high CRP levels and low EPA levels were significant and independent predictors of PAD [odds ratio 3.1 (95 % CI 1.4-6.9), p = 0.006 and odds ratio 4.9 (95 % CI 1.5-9.7), p = 0.004]. Furthermore, to predict PAD, adding high CRP levels and low EPA levels to the established risk factors significantly improved the area under the ROC curves, from 0.66 to 0.78, of the PAD prediction model (p = 0.004). A significant relationship among EPA, CRP, and PAD was confirmed in patients with CAD.

Aims: The pathogenesis of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains unclear. The purpose of this study is to analyse tissue characterizations of neointima in restenosis lesions after sirolimus-eluting stent (SES), comparing with those after bare metal stent (BMS) using integrated backscatter intravascular ultrasound (IB-IVUS)., Methods and Results: A total of 54 consecutive patients who had ISR lesions after SES (n = 20) or BMS (n = 34) implantation were enrolled. For tissue characterization of neointima, IB-IVUS was performed by cross-sectional (at the minimum lumen area) and volumetric (within the stented segment) analyses. In addition, angiographic patterns of restenosis were evaluated with division into focal and diffuse. The focal angiographic pattern of restenosis was predominantly observed in the SES group (SES vs. BMS; 80.0 vs. 26.5%; P = 0.0001), whereas the diffuse pattern was more common in the BMS group (SES vs. BMS; 20.0 vs. 73.5%; P = 0.0001). On both cross-sectional and volumetric IB-IVUS analyses, the neointimal tissue in restenosis lesions after SES implantation had a significantly larger percentage of lipid tissue (cross-sectional: 23.3 ± 12.7 vs. 15.7 ± 11.9%; P = 0.033; volumetric: 22.8 ± 10.4 vs. 16.3 ± 7.0%; P = 0.008) and a significantly smaller percentage of fibrous tissue compared with that after BMS implantation (cross-sectional: 73.6 ± 11.6 vs. 82.0 ± 11.2%; P = 0.011, volumetric: 73.8 ± 9.5 vs. 80.5 ± 6.7%; P = 0.004)., Conclusion: This IB-IVUS study indicates that larger amounts of lipid tissue are present in neointima of SES when compared with BMS, suggesting that neoatherosclerosis may in part be responsible for ISR after SES implantation.

We evaluated the association between inflammatory markers and coronary artery plaque assessed by 64-slice multidetector computed tomography. Coronary computed tomography angiography was performed in patients with chest discomfort suggestive of coronary artery disease (CAD). Individuals with an acute coronary syndrome were excluded from the study. Coronary plaque morphology, the number of artery segments exhibiting plaque, and the number of vessels with >50% stenosis were evaluated. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), plasminogen activator inhibitor-1, and vascular endothelial growth factor were measured. Among the 178 patients studied (age 65 ± 10 years; 70% men), 125 were diagnosed with CAD. Hs-CRP and IL-6 concentrations were significantly higher in patients with CAD than in patients without (2.73 ± 4.7 vs. 1.32 ± 2.6 mg/L, P = 0.018, and 3.06 ± 3.3 vs. 2.19 ± 2.4 pg/mL, P = 0.036). The IL-6 level was high in patients with predominantly calcified plaque, and was significantly higher in patients with 4-9 plaque segments than in those with no or 1-3 plaque segments (4.07 ± 5.3 vs. 2.19 ± 2.4 pg/mL and 2.43 ± 2.0 pg/mL, respectively, P = 0.025). The number of stenotic vessels was not significantly related to inflammatory markers. Multivariate logistic analysis revealed that plasma levels of hs-CRP but not IL-6 were associated with the presence of coronary plaque with calcification (OR 3.37, P = 0.026). This study supports the usefulness of inflammatory markers for the evaluation of coronary plaque in patients with stable CAD.

Background: It is well known that chronic kidney disease is a strong independent predictor of adverse outcomes after percutaneous coronary intervention in patients with ischemic heart disease. Recently, peri-procedural myocardial injury has been associated with adverse cardiac events. The aim of this study was to investigate the relationship between renal function and peri-procedural myocardial injury in patients undergoing elective stent implantation., Methods: This study comprised 273 consecutive patients who underwent elective stent implantation. They were divided into two groups: estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m(2) and eGFR ≥60 mL/min/1.73m(2). Peri-procedural TnT levels higher than three times the normal limit were defined as peri-procedural myocardial injury., Results: Patients with eGFR <60 mL/min/1.73m(2) showed a higher incidence of peri-procedural myocardial injury compared to patients with eGFR ≥60 mL/min/1.73m(2) (4.3 versus 20.9%, P < 0.0001). Even after a multivariate adjustment, the eGFR level predicted peri-procedural myocardial injury [odds ratio 0.92, 95% confidence interval (CI): 0.89-0.95, P < 0.0001]. Total stent length was also an independent predictor of peri-procedural myocardial injury (odds ratio 1.09, 95% CI: 1.02-1.16, P = 0.009). Using a receiver-operating curve analysis, eGFR level of 62.1 mL/min/1.73m(2) (sensitivity 93.3%, specificity 57.2%) was the best value (area under the curve = 0.803) to maximize the power of eGFR levels in predicting peri-procedural myocardial injury., Conclusions: Patients with eGFR <60 mL/min/1.73m(2) were strongly associated with peri-procedural myocardial injury after elective stent implantation. Therefore, eGFR may be a simple and convenient predictor of peri-procedural myocardial injury.

Background: An increase in cystatin C (CyC) of ≥10% for 24 hours may predict contrast-induced nephropathy and worse outcomes in patients with renal dysfunction undergoing invasive coronary angiography., Objective: We investigated the changes in CyC in patients with preserved renal function referred for contrast-enhanced coronary computed tomography angiography (CTA)., Methods: We studied 151 patients undergoing CTA with 70 mL of iopamidol. Serum creatinine and CyC, a sensitive measure of renal dysfunction, shown to be associated with adverse outcomes, were measured 1 day and 1 week after CTA, respectively. The percentage change in CyC (%CyC) was determined and evaluated in comparison to fluid intake., Results: The patients were dichotomized into 2 groups: 47 patients had ≥10% increase in CyC 1 day after CTA (group A) and 104 did not (group B). The percentage of diabetic patients, hemoglobin A1c (HbA1c), and the CyC levels at 1 week were significantly greater, and the oral fluid volume was significantly lower in group A than in group B. The %CyC inversely correlated with oral fluid volume (r = -0.80, P < 0.0001) and positively with HbA1c (r = 0.38, P < 0.001). Multiple regression analysis showed that oral fluid intake (β = -0.796, P < 0.0001) and HbA1c (β = 0.128, P = 0.007) are independent predictors for %CyC of ≥10%., Conclusion: Frequency of CyC elevation was strongly related to hydration after the study and also weakly related to HbA1c. Sufficient oral fluid intake (oral fluid volume/kg ≥ 20 mL/kg) is crucial, particularly for poorly controlled diabetic patients referred for CTA even though they show preserved renal function., (Copyright © 2012 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objective: Eicosapentaenoic acid (EPA) of the omega-3 polyunsaturated fatty acids (ω-3 PUFA) family plays important roles in the prevention of cardiovascular disease (CVD), while, arachidonic acid (AA) of the ω-6 PUFA family promotes inflammatory and prothrombotic influences. The complexity of coronary lesions represents the vulnerability of patients. The aim of this study was to investigate the association between the plasma EPA/AA ratio and the prevalence of complex coronary lesion morphology., Methods: This study consisted of 206 consecutive patients with stable angina pectoris (sAP). Each coronary lesion was determined either as complex or simple based on angiographic findings. To examine the plasma fatty acid level, blood samples were obtained. Patients were divided into three groups according to the obtained plasma EPA/AA ratio: the highest tertile, n=67, the 2nd tertile, n=70, or the lowest tertile, n=69., Results: A higher incidence of complex coronary lesion was obtained from patients with a lower plasma EPA/AA ratio [43 (62%) vs. 31 (44%) vs. 25 (37%), p=0.011]. High-sensitivity CRP levels and a low plasma EPA/AA ratio could independently predict the prevalence of complex coronary lesions on multivariate logistic regression analysis [odds ratio 1.83 (95%CI 1.03-3.25), p=0.038 and odds ratio 2.10 (95%CI 1.11-3.94), p=0.02)]., Conclusion: In patients with sAP, a low plasma EPA/AA ratio was significantly associated with a high prevalence of complex coronary lesions.

Objectives: With an intracoronary electrocardiogram (IcECG) recording with insulated polymer-coated guidewire without balloon catheter, we sought to examine the association between ST-segment elevation in the IcECG after elective stenting and myocardial injury., Background: An IcECG is a sensitive method to detect local myocardial ischemia. Occasionally, persistent ST-segment elevation in the IcECG was recorded after successful coronary intervention. Conventionally IcECG was recorded with a guidewire and over-the-wire system., Methods: Patients who underwent elective stenting were enrolled (n = 339). The IcECG both at baseline and after procedure were obtained with a guidewire with an insulating coated shaft suitable for IcECG recording. The presence of chest pain after percutaneous coronary intervention was recorded. Cardiac biomarkers were examined 18 h after the procedure., Results: The ST-segment elevation in the IcECG after procedure was recorded in 65 patients, and no change was recorded in 274 patients. Troponin-T, creatine phosphokinase, and creatine kinase MB isoform after the procedure were significantly higher in patients with post-procedural ST-segment elevation in the IcECG than patients without ST-segment elevation. Multivariate analysis demonstrated that ST-segment elevation in the IcECG is an independent predictor of post-procedural myocardial injury. The incidence of ST-segment elevation in the IcECG was significantly higher in patients with post-procedural chest pain than patients without chest pain (p < 0.001)., Conclusions: We demonstrated a facile method to record IcECG with a guidewire with a polymer-coated shaft. The IcECG is a useful method for predicting post-procedural myocardial injuries.

Objectives: We assessed the impact of metabolic syndrome (MetS) on the tissue characteristics of coronary plaques using integrated backscatter intravascular ultrasound (IB-IVUS)., Background: Metabolic syndrome is associated with the increasing risk of cardiovascular disease., Methods: We identified MetS by the definition of the National Cholesterol Education Program in Adult Treatment Panel III criterion. Non-target coronary lesions with mild to moderate stenosis were measured by conventional and IB-IVUS parameters using 40-MHz (motorized pullback 0.5 mm/s) intravascular catheter. A total of 20 IB-IVUS images were recorded at an interval of 0.5 mm for 10 mm length in each plaque. The 3-dimensional analyses were performed using commercially available software., Results: The prevalence of MetS was 61 patients (50%) with 73 lesions (49%) among 122 patients with 148 lesions. Patients with MetS showed a significant increase in percentage lipid area (38 +/- 19% vs. 30 +/- 19%, p = 0.02) and percentage lipid volume (39 +/- 17% vs. 33 +/- 17%, p = 0.03), and they also showed a significant decrease in percentage of fibrous volume (57 +/- 14% vs. 61 +/- 13%, p = 0.03). Multivariate regression analysis after adjustment for potentially confounding risk factors showed that MetS remains correlated independently with the percentage of lipid volume (r = 0.223, p = 0.01). Logistic regression analysis after adjusting for confounding and non-MetS coronary risk factors showed that MetS (odds ratio 4.00, 95% confidence interval 1.33 to 12.0, p = 0.01) is proved to be an independent predictor of the lipid-rich plaque., Conclusions: Metabolic syndrome is associated with lipid-rich plaques, contributing to the increasing risk of plaque vulnerability.