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Transcatheter closure of patent foramen ovale (PFO) is an effective strategy for preventing recurrence of paradoxical embolism. However, PFO closure is often associated with residual shunt, which is a risk of recurrent stroke. This study aimed to evaluate the relationship between the anatomical features of PFO and residual shunt. The degree of residual shunt and its relationship with the anatomical features of PFO were evaluated in 106 patients who underwent PFO closure at our institution between March 2011 and January 2022 and in whom contrast transthoracic echocardiography was performed 1 year later. The mean PFO tunnel length was 9.3 ± 3.6 mm and the mean PFO height was 3.2 ± 2.2 mm. Atrial septal aneurysm (ASA) was found in 37 patients. After PFO closure, residual shunt was observed in 28 patients (grade 1, n = 8; grade 2, n = 16; grade 3, n = 3; grade 4, n = 1). Univariate logistic analysis identified ASA to be associated with residual shunt (odds ratio 2.78, 95% confidence interval 1.14 to 6.79; p = 0.024). There was no association of residual shunt with the size of the PFO, the length of PFO tunnel, or the size of the device used for closure. Two of four patients with a large residual shunt of grade 3 or grade 4 were found to have device size mismatch. Residual shunt after PFO closure was observed in a quarter of patients and was related to the presence of ASA. A few patients had a large residual shunt due to the device size mismatch.

DOI： 10.1007/s12928-023-00979-y

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BACKGROUND: Patients with severe aortic stenosis (AS) frequently have concomitant aortic regurgitation (AR), but the association between aortic valvular calcification (AVC) and the severity of AR remains unclear. METHODS AND RESULTS: We retrospectively reviewed patients with severe AS who underwent transthoracic echocardiography and multidetector computed tomography (MDCT) within 1 month. The patients were divided into 3 groups according to the degree of concomitant AR. The association between AVC and the severity of concomitant AR was assessed in patients with severe AS. The study population consisted of 95 patients: 43 men and 52 women with a mean age of 82±7 years. Of the 95 patients with severe AS, 27 had no or trivial AR, 53 had mild AR, and 15 had moderate AR. The AVC score (AVCS) and AVC volume (AVCV) significantly increased as the severity of concomitant AR increased (P=0.014 for both), and similar findings were obtained for the AVCS and AVCV indexes (P=0.004 for both). CONCLUSIONS: The severity of AR correlated with AVCS and AVCV measured by MDCT in patients with severe AS. AVC may cause concomitant AR, leading to worsening of disease condition.

DOI： 10.1253/circj.CJ-22-0746

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OBJECTIVE: To investigate the diagnostic performance of a calcium-removal image reconstruction algorithm with photon-counting detector-computed tomography (PCD-CT), a technology that hides only the calcified plaque from the spectral data in coronary calcified lesions. METHODS: This retrospective study included 17 patients who underwent PCD-coronary CT angiography (CCTA) with at least one significant coronary stenosis (≥50 %) with calcified plaque by CCTA and invasive coronary angiography (ICA) performed within 60 days of CCTA. A total of 162 segments with calcified plaque were evaluated for subjective image quality using a 4-point scale. Their calcium-removal images were reconstructed from conventional images, and both images were compared with ICA images as the reference standard. The contrast-to noise ratios for both images were calculated. RESULTS: Conventional and calcium-removal images had a subjective image quality of 2.7 ± 0.5 and 3.2 ± 0.9, respectively (p < 0.001). The percentage of segments with a non-diagnostic image quality was 32.7 % for conventional images and 28.3 % for calcium-removal images (p < 0.001). The segment-based diagnostic accuracy revealed an area under the receiver operating characteristic curve of 0.87 for calcium-removal images and 0.79 for conventional images (p = 0.006). Regarding accuracy, the specificity and positive predictive value of calcium-removal images were significantly improved compared with those of conventional images (80.5 % vs. 69.5 %, p = 0.002 and 64.1 % vs. 52.0 %, p < 0.001, respectively). The objective image quality of the mean contrast-to-noise ratio did not differ between the images (13.9 ± 3.6 vs 13.3 ± 3.4, p = 0.356) CONCLUSIONS: Calcium-removal images with PCD-CT can potentially be used to evaluate diagnostic performance for calcified coronary artery lesions.

DOI： 10.1016/j.ejrad.2024.111354

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AIMS: Heart failure with a preserved ejection fraction (HFpEF) is associated with chronic inflammation. We aimed to investigate the association between pericoronary adipose tissue attenuation (PCATA) on coronary computed tomography angiography as a novel noninvasive marker of pericoronary inflammation and the presence of HFpEF. METHODS AND RESULTS: This retrospective study included 607 outpatients (median age, 65 years; 50% male) who underwent both echocardiography and coronary computed tomography angiography. Patients with obstructive coronary artery disease were excluded from this study. PCATA was compared between patients with and without HFpEF, which was diagnosed according to the Heart Failure Association (HFA)-PEFF score. PCATA was assessed at the proximal 40-mm segments of all three major coronary arteries on coronary computed tomography angiography. Patients with HFpEF had higher PCATA in all coronary arteries compared to the control participants: left anterior descending artery (LAD), -65.2 ± 6.9 Hounsfield units (HU) vs. -68.1 ± 6.7 HU; left circumflex artery (LCX), -62.7 ± 6.8 HU vs. -65.4 ± 6.6 HU; and right coronary artery (RCA), -63.6 ± 8.5 HU vs. -65.5 ± 7.7 HU (P < 0.01). Multivariate logistic regression analysis, including conventional risk factors, revealed that PCATA per standard deviation in the LAD (odds ratio [OR], 1.449; 95% confidence interval [CI], 1.152-1.823), LCX (OR, 1.634; 95% CI, 1.283-2.081), and RCA (OR, 1.388; 95% CI, 1.107-1.740) were independently associated with HFpEF. The association between PCATA and HFpEF was mostly consistent across various patient clinical characteristics. The left ventricular mass and left atrial volume index showed a mild correlation with LAD-PCATA (ρ = 0.13 [P < 0.01] and ρ = 0.24 [P < 0.01]) and LCX-PCATA (ρ = 0.16 [P < 0.01] and ρ = 0.23 [P < 0.01]). CONCLUSIONS: High PCATA score was significantly associated with the presence of HFpEF. Our results suggest that inflammation in the pericoronary artery adipose tissue is one of the underlying mechanisms of HFpEF.

DOI： 10.1002/ehf2.14419

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BACKGROUND: Patent foramen ovale (PFO) is associated with various diseases such as cryptogenic stroke, migraine, and platypnea-orthodeoxia syndrome. This study aimed to evaluate the diagnostic performance of cardiac computed tomography (CT) for PFO detection. MATERIALS AND METHODS: Consecutive patients diagnosed with atrial fibrillation and who underwent catheter ablation with pre-procedural cardiac CT and transesophageal echocardiography (TEE) were enrolled in this study. The presence of PFO was defined as (1) the confirmation of PFO using TEE and/or (2) the catheter crossing the interatrial septum (IAS) into the left atrium during ablation. CT findings indicative of PFO included (1) the presence of a channel-like appearance (CLA) on the IAS and (2) a CLA with a contrast jet flow from the left atrium to the right atrium. The diagnostic performance of both a CLA alone and a CLA with a jet flow was evaluated for PFO detection. RESULTS: Altogether, 151 patients were analyzed in the study (mean age, 68 years; men, 62%). Twenty-nine patients (19%) had PFO confirmed by TEE and/or catheterization. The diagnostic performance of a CLA alone was as follows: sensitivity, 72.4%; specificity, 79.5%; positive predictive value (PPV), 45.7%; negative predictive value (NPV), 92.4%. The diagnostic performance of a CLA with a jet flow was as follows: sensitivity, 65.5%; specificity, 98.4%; PPV, 90.5%; NPV, 92.3%. The diagnostic performance of a CLA with a jet flow was statistically superior to that of a CLA alone (p = 0.045), and the C-statistics were 0.76 and 0.82, respectively. CONCLUSION: A CLA with a contrast jet flow in cardiac CT has a high PPV for PFO detection, and its diagnostic performance is superior to that of a CLA alone.

DOI： 10.3390/jcdd10050193

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AIMS: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a noninvasive biomarker for pericoronary inflammation and is associated with cardiac mortality. We aimed to investigate the association between PCAT attenuation and endothelial dysfunction assessed using flow-mediated dilation (FMD). METHODS: A total of 119 outpatients who underwent both coronary CTA and FMD measurements were examined. PCAT attenuation values were assessed at the proximal 40-mm segments of all three major coronary arteries on coronary CTA. Endothelial function was assessed using FMD. Patients were then classified into two groups: those with endothelial dysfunction (FMD ＜4%, n=44) and those without endothelial dysfunction (FMD ≥ 4%, n=75). RESULTS: In all three coronary arteries, PCAT attenuation was significantly higher in patients with endothelial dysfunction than in those without endothelial dysfunction. Multivariate logistic regression analysis revealed that PCAT attenuation in the right coronary artery (odds ratio [OR]=1.543; 95% confidence interval [CI]=1.004-2.369, p=0.048) and left anterior descending artery (OR=1.525, 95% CI=1.004-2.369, p=0.049) was an independent predictor of endothelial dysfunction. Subgroup analysis of patients with adverse CTA findings (significant stenosis and/or high-risk plaque) and those with coronary artery calcium score ＞100 showed that high PCAT attenuation in all three coronary arteries was a significant predictor of endothelial dysfunction. CONCLUSION: High PCAT attenuation was significantly associated with FMD-assessed endothelial dysfunction in patients with suspected coronary artery disease. Our results suggest that endothelial dysfunction is one of the pathophysiological mechanisms linking pericoronary inflammation to cardiac mortality.

DOI： 10.5551/jat.63580

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DOI： 10.1007/s12928-022-00887-7

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UNLABELLED: A 46-year-old woman with a history of repeated thromboembolic stroke and anti-phospholipid antibody syndrome was referred to our hospital. Saline contrast transthoracic echocardiography showed that microbubbles appeared in the left atrium within 4 heartbeats. Thus, she was initially suspected as having a patent foramen ovale with associated paradoxical embolism. However, no evidence of patent foramen ovale or atrial septal defect could be found using transesophageal echocardiography. Saline contrast transesophageal echocardiography showed that microbubbles flowed into the left atrium through the left superior pulmonary vein. Ultimately, she was diagnosed as having a pulmonary arteriovenous malformation located at the upper left pulmonary lobe using contrast computed tomography and pulmonary artery angiography. Pulmonary arteriovenous malformations are typically located in the lower lobe of either lung and, in bubble studies, contrast appears in the left atrium after 4 heartbeats. Here, the pulmonary arteriovenous malformation was in the upper lobe, and contrast appeared in the left atrium at an earlier time point: one associated with patent foramen ovale. These findings made it difficult to differentiate the two diseases initially. This case suggests that pulmonary arteriovenous malformation should be carefully considered, even if microbubbles appear in the left atrium early on a saline contrast transthoracic echocardiograph. LEARNING OBJECTIVE: Pulmonary arteriovenous malformation occasionally appears in the upper lobe. In these cases, microbubbles may appear in the left atrium after detection in the right atrium with a time-course that is suggestive of a patent foramen ovale. Therefore, diagnosis should be carefully confirmed by using other multimodal imaging tests, such as transesophageal echocardiography, contrast computed tomography, or pulmonary artery angiography.

DOI： 10.1016/j.jccase.2022.11.005

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BACKGROUND: Atrial septal defect (ASD) closure can cause acute pulmonary edema. Before transcatheter closure is performed, temporary balloon occlusion test (BOT) is recommended in patients with left ventricular dysfunction to predict the risk of pulmonary edema. However, the accuracy of BOT has not been verified. This study aimed to compare hemodynamic differences between BOT and transcatheter closure. METHODS: A total of 42 patients with a single ASD over age 18 years who underwent BOT before transcatheter ASD closure between October 2010 and May 2020 were analyzed. Pulmonary capillary wedge pressure (PCWP) was measured using a Swan-Ganz catheter placed in the pulmonary artery at baseline, after 10 min of BOT, and after transcatheter closure. Amplatzer septal occluder was used for all transcatheter closures. RESULTS: Mean patient age was 64 ± 18 years (range, 18-78). Mean ASD diameter and pulmonary to systemic flow ratio were 18 ± 5 and 2.8 ± 1.0 mm, respectively. Mean PCWP at baseline, during BOT, and after transcatheter closure was 8.9 ± 2.9, 13.5 ± 4.2, and 9.5 ± 2.6 mmHg, respectively. The difference between BOT and after transcatheter closure values was significant (p < 0.001). During BOT, PCWP increased ≥18 mmHg in 7 patients, whereas after ASD closure, PCWP was <18 mmHg in all 7 and none developed acute pulmonary edema. CONCLUSION: Temporary balloon occlusion of an ASD and transcatheter ASD closure result in different hemodynamic change. BOT overestimates increase of PCWP after transcatheter ASD closure and requires careful interpretation. Well-designed, larger studies in higher-risk patients are warranted to verify the clinical implications of BOT in more detail.

DOI： 10.1002/ccd.30556

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Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) has been emerged as a marker of pericoronary inflammation. We aimed to investigate the prognostic value of PCAT attenuation in patients with non-alcoholic fatty liver disease (NAFLD). We enrolled 232 NAFLD patients with suspected coronary artery disease and underwent coronary CTA. NAFLD was defined by abdominal CT as the ratio of hepatic attenuation to spleen attenuation less than 1.0. PCAT attenuation values were assessed by the crude analysis of mean CT attenuation value of the left anterior descending artery (LAD) and right coronary artery (RCA). As coronary CTA findings, luminal stenosis and high-risk plaque features were examined. Primary outcome was the composite of cardiovascular (CV) death, nonfatal acute coronary syndrome, and hospitalization for heart failure. During a median follow-up of 4.9 years, 17 patients had CV events. LAD-PCAT attenuation in patients with CV events was higher than that without CV events (-66.9 ± 7.0 versus -70.5 ± 6.6; p = 0.032), while RCA-PCAT attenuation was not. LAD-PCAT attenuation and high-risk plaque features were independent predictors of CV events. The addition of LAD-PCAT attenuation to high-risk plaque features increased the C-statistics and global chi-square from 0.66 to 0.75 (p = 0.042) and 6.8 to 12.7 (p = 0.015), respectively. The net reclassification achieved by adding LAD-PCAT attenuation to high-risk plaque features was 0.494 (p = 0.041). High-LAD-PCAT attenuation was an independent predictor of CV events in NAFLD patients, regardless of CTA-verified high-risk plaque features. In addition, LAD-PCAT attenuation had an incremental prognostic value over high-risk plaque features.

DOI： 10.1007/s00380-022-02107-x

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The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is an independent risk index for cardiovascular events. This study aimed to evaluate the association between TG/HDL-C ratio and coronary plaque characteristics as seen on coronary computed tomography angiography (CCTA) and the corresponding increase in the likelihood of cardiovascular events. A total of 935 patients who underwent CCTA for suspected coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined based on three characteristics: positive remodeling, low-density plaques, and spotty calcification. Significant stenosis was defined as luminal narrowing of >70%. Patients with a higher TG/HDL-C ratio showed significantly greater prevalence of HRP and significant stenosis than patients with low TG/HDL-C ratios (p < 0.01). Multivariate logistic analysis demonstrated that the TG/HDL-C ratio was significantly associated with the presence of HRP (p < 0.01) but not with significant coronary stenosis (p = 0.24). During the median follow-up period of 4.1 years, 26 cardiovascular events including cardiovascular death and acute coronary syndrome occurred. The highest TG/HDL-C tertile was associated with cardiovascular events, with the lowest TG/HDL-C tertile as the reference (hazard ratio, 3.75; 95% confidence interval, 1.04−13.50). A high TG/HDL-C ratio is associated with the presence of CCTA-verified HRP, which can lead to cardiovascular events in patients with suspected CAD.

DOI： 10.3390/jcdd9100329

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The 86thAnnual Scientific Meeting of the Japanese Circulation Society was held in a web-based format on March 11-13, 2022. In accordance with the internationalization policy of the JCS, the meeting was held with the Asian Pacific Society of Cardiology Congress 2022. The main theme was "Cardiology Spreading its Wings". The number of patients with heart failure and other cardiovascular diseases is increasing dramatically, and the fields dealt with by cardiovascular medicine are also greatly expanding. This conference was both intellectually satisfying and exciting for all participants, who numbered over 14,900. The meeting was completed with great success, and the enormous amount of cooperation and support from all involved was greatly appreciated.

DOI： 10.1253/circj.CJ-22-0349

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Nonalcoholic fatty liver disease (NAFLD) is a risk factor for the development of atherosclerotic cardiovascular diseases (CVDs), and oxidative stress has been proposed as a shared pathophysiological condition. This study examined whether oxidized low-density lipoprotein (LDL) is involved in the underlying mechanism that links coronary atherosclerosis and NAFLD. This study included 631 patients who underwent coronary computed tomography angiography (CTA) for suspected coronary artery disease. NAFLD was defined on CT images as a liver-to-spleen attenuation ratio of <1.0. Serum-malondialdehyde-modified LDL (MDA-LDL) and coronary CTA findings were analyzed in a propensity-score-matched cohort of patients with NAFLD (n = 150) and those without NAFLD (n = 150). This study analyzed 300 patients (median age, 65 years; 64% men). Patients with NAFLD had higher MDA-LDL levels and a greater presence of CTA-verified high-risk plaques than those without NAFLD. In the multivariate linear regression analysis, MDA-LDL was independently associated with NAFLD (β = 11.337, p = 0.005) and high-risk plaques (β = 12.487, p = 0.007). Increased MDA-LDL may be a mediator between NAFLD and high-risk coronary plaque on coronary CTA. Increased oxidative stress in NAFLD, as assessed using MDA-LDL, may be involved in the development of CVDs.

DOI： 10.3390/jcm11102838

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BACKGROUND: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a non-invasive biomarker for pericoronary inflammation. We aimed to investigate the prognostic value of PCAT attenuation in patients with type 2 diabetes mellitus (T2DM). METHODS: We included 333 T2DM patients (mean age, 66 years; male patients, 211; mean body mass index, 25 kg/m2) who underwent clinically indicated coronary CTA and examined their CT findings, coronary artery calcium score, pericardial fat volume, stenosis (> 50% luminal narrowing), high-risk plaque features of low-attenuation plaque and/or positive remodelling and/or spotty calcification, and PCAT attenuation. We assessed PCAT attenuation in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery (LAD) and right coronary artery (RCA). Cardiovascular events were defined as cardiac death, hospitalisation for acute coronary syndrome, late coronary revascularisation, and hospitalisation for heart failure. RESULTS: During a median follow-up of 4.0 years, we observed 31 cardiovascular events. LAD-PCAT attenuation was significantly higher in patients with cardiovascular events than in those without (- 68.5 ± 6.5 HU vs - 70.8 ± 6.1 HU, p = 0.045), whereas RCA-PCAT attenuation was not (p = 0.089). High LAD-PCAT attenuation (> - 70.7 HU; median value) was significantly associated with cardiovascular events in a model that included adverse CTA findings, such as significant stenosis and/or high-risk plaque (hazard ratio; 2.69, 95% confidence interval; 1.17-0.20, p = 0.020). After adding LAD-PCAT attenuation to the adverse CTA findings, the C-statistic and global chi-square values increased significantly from 0.65 to 0.70 (p = 0.037) and 10.9-15.0 (p = 0.043), respectively. CONCLUSIONS: In T2DM patients undergoing clinically indicated coronary CTA, high LAD-PCAT attenuation could significantly predict cardiovascular events. This suggests that assessing LAD-PCAT attenuation can help physicians identify high-risk T2DM patients.

DOI： 10.1186/s12933-022-01478-9

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Transcatheter closure of patent foramen ovale (PFO) is an effective therapy for preventing recurrent stroke in very specific patient cohorts, such as cryptogenic stroke (CS). The identification of high-risk PFO, which is more likely to be linked to CS, is essential. This study aimed to assess the accuracy of saline contrast transthoracic echocardiography (TTE) for evaluating large right-to-left (RL) shunt. We enrolled 119 patients with or without CS who were confirmed to have PFO by transesophageal echocardiography (TEE) or catheterization. The severity of RL shunt evaluated by TTE and TEE was classified as follows: small (< 10 microbubbles), moderate (10-20 microbubbles), and large (> 20 microbubbles). With TTE, large RL shunt was observed in 94 (79%) of 119 patients, including 66 of 74 with CS and 28 of 45 without CS. With TEE, large RL shunt was observed in 33 (28 %) patients, including 26 with CS and 7 without CS. TTE showed large RL shunt more frequently than TEE (p < 0.01). Large RL shunt evaluated by TTE had a sensitivity of 89 % and an accuracy of 70 % for the association with CS, whereas large RL shunt evaluated by TEE had a sensitivity of 35% and an accuracy of 56 %. Accuracy was significantly greater in TTE than in TEE (p = 0.02). In conclusion, TTE identified large RL shunt associated with CS with higher sensitivity and accuracy compared to TEE. Our findings suggest that the decision for device closure should be made based on the severity of RL shunt by TTE.

DOI： 10.1007/s10554-021-02418-6

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AIMS: This study aimed to investigate additional risk stratification benefits of hepatic steatosis (HS) concurrently assessed during coronary computed tomography angiography (CTA) in a large patient cohort with suspected stable coronary artery disease (CAD). METHODS AND RESULTS: In this prospective study, 1148 Japanese outpatients without a history of CAD who underwent coronary CTA for suspected stable CAD (mean age 64 ± 14 years) were included. HS, defined on CT as a hepatic-to-spleen attenuation ratio of <1.0, was examined just before the evaluation of adverse CTA findings, defined as obstructive and/or high-risk plaque. The major adverse cardiac events (MACE) were the composite of cardiac death, acute coronary syndrome, and late revascularization. The incremental predictive value of HS was evaluated using the global χ2 test and C-statistic. HS was identified in 247 (22%) patients. During a median follow-up of 3.9 years, MACE was observed in 40 (3.5%) patients. HS was significantly associated with MACE in a model that included adverse CTA findings (hazard ratio 4.01, 95% confidence interval 2.12-7.59, P < 0.001). By adding HS to the Framingham risk score and adverse CTA findings, the global χ2 score and C-statistic significantly increased from 29.0 to 49.5 (P < 0.001) and 0.74 to 0.81 (P = 0.026), respectively. In subgroup analyses in patients with diabetes mellitus and metabolic syndrome, HS had significant additive predictive value for MACE over the Framingham risk score and adverse CTA findings. CONCLUSION: In patients with suspected stable CAD, concurrent evaluation of HS during coronary CTA enables more accurate detection of patients at higher risk of MACE.

DOI： 10.1093/eurjpc/zwab120

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BACKGROUND: Decreases in circulating CD34-positive cells are associated with increases in cardiovascular events. We investigated the association between the number of CD34-positive cells and the progression of coronary artery calcification (CAC), a marker of atherosclerosis, in patients with hypercholesteremia under statin therapy in a sub-analysis of a multicenter study. METHODS: In the principal study, patients with CAC scores of 1-999 were treated with pitavastatin. Measurement of CAC by non-enhanced computed tomography and a blood test were performed at baseline and at 1-year follow-up. Patients were divided into two groups: CAC progression (change in CAC score > 0) and non-progression. The number of circulating CD34-positive cells was counted using flow cytometry. RESULTS: A total of 156 patients (mean age 67 years, 55% men) were included in this sub-analysis. CD34 positive cell numbers at baseline as a continuous variable was inversely correlated with annual change in the log-transformed CAC score (r = -0.19, p = 0.02). When patients were divided into high and low CD34 groups based on the median value of 0.8 cells/μL, the adjusted change in CAC score in the low-CD34 group was significantly greater than that in the high-CD34 group (54.2% vs. 20.8%, respectively, p = 0.04). In multiple logistic analysis, a low CD34-positive cell number was an independent predictor of CAC progression, with an odds ratio of 2.88 (95% confidence interval 1.28-6.49, p = 0.01). CONCLUSIONS: Low numbers of CD34-positive cells are associated with CAC progression in patients with hypercholesterolemia under statin therapy. The number of CD34-positive cells may help to identify patients at increased cardiovascular risk.

DOI： 10.5603/CJ.a2021.0151

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DOI： 10.1016/j.jcct.2021.09.001

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BACKGROUND: Because transcatheter closure of patent foramen ovale (PFO) has become effective for preventing cryptogenic stroke (CS), it is necessary to determine high-risk PFO associated with CS. This study aimed to clarify the importance of direct right-to-left (RL) shunt through the PFO for identifying high-risk PFO. METHODS: We analyzed 137 patients with and without CS who were confirmed to have PFO. The timing of RL shunt through the PFO was evaluated by cardiac cycles after right atrium (RA) opacification on saline contrast transesophageal echocardiography. Direct RL shunt was defined as microbubbles crossing the PFO before and at the same time of RA opacification. RESULTS: Cardiac cycles of microbubbles crossing the PFO were shorter in patients with CS than in those without CS (2.0 ± 2.2 vs .5 ± 1.1, p < 0.01). Direct RL shunt was more frequently observed in patients with CS than in those without CS (77% vs 29%, p < 0.01), with a sensitivity of 79% and a specificity of 71% for the association with CS. Multivariate analysis revealed that direct RL shunt was related to atrial septal aneurysm and low-angle PFO. Regarding functional features of PFO, the detection rate of CS was 50% for large RL shunt alone, and was increased to 83% when direct RL shunt was added. CONCLUSION: Direct RL shunt was associated with CS and had the incremental value in detecting PFO associated with CS for large RL shunt. The timing of RL shunt can be valuable for identifying high-risk PFO.

DOI： 10.1111/echo.15234

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Non-alcoholic fatty liver disease (NAFLD) is a risk factor for cardiac mortality. Pericoronary adipose tissue (PCAT) attenuation, expressed by the fat attenuation index on coronary computed tomography angiography, reflects pericoronary inflammation. We aimed to investigate the association between PCAT attenuation and NAFLD.This is a single-center cohort study comprising of patients who underwent coronary computed tomography angiography for suspected stable coronary artery disease between January and December 2020. Patient characteristics and coronary computed tomography angiography findings were analyzed between patients with NAFLD (n = 78) and a propensity score-matched cohort of patients without NAFLD (n = 78). PCAT attenuation was assessed in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery (LAD) and right coronary artery.The mean PCAT attenuation in LAD and right coronary artery were significantly higher in patients with NAFLD than those without NAFLD. When patients were divided into 2 groups using the median LAD-PCAT attenuation of -72.5 HU, the high PCAT attenuation group had more males (82% vs 67%, P = .028) and NAFLD patients (63% vs 37%, P = .001) compared to the low PCAT attenuation group. No differences in age, body mass index, conventional cardiovascular risk factors, or the presence of high-risk plaque were observed between the 2 groups. In the multivariate logistic analysis, NAFLD was independently associated with high PCAT attenuation (odds ratio 2.912, 95% confidence interval 1.386 to 6.118, P = .005).NAFLD is associated with high PCAT attenuation on coronary computed tomography angiography. This finding suggests that pericoronary inflammation is involved in the increased cardiac mortality in NAFLD patients.

DOI： 10.1097/MD.0000000000027043

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• Identification of high-risk PFO associated with stroke is important. • Low-angle PFO is reported to be one of the high-risk PFO morphologies. • Low-angle PFO can allow venous blood to flow directly from the IVC to the LA. • The case showed direct blood flow from the IVC to LA through the low-angle PFO.

DOI： 10.1016/j.case.2021.02.008

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Few studies have reported the efficacy of Occlutech Figulla Flex II (FFII) device compared with Amplatzer Septal Occluder (ASO) device. The aim of this study was to examine the efficacy and safety of FFII compared with ASO for transcatheter atrial septal defect (ASD) closure. We retrospectively evaluated 190 patients using FFII and 190 patients using ASO who underwent transcatheter ASD closure. ASD characteristics were evaluated by transesophageal echocardiography. The prevalence of procedural complications, including erosion, device embolization, stroke, and new-onset atrial arrhythmia, and the presence of a residual shunt were evaluated between the two groups during 12-month follow-up. FFII was used more frequently than ASO in patients with a deficient aortic rim or septal malalignment (P = 0.02, P < 0.01, respectively). The procedural complications of erosion, device embolization, and stroke did not occur in any patients. New-onset atrial arrhythmia occurred in 3 patients of the FFII group and 4 patients of the ASO group, and the difference between the two groups was not significant (P = 0.70). A large residual shunt (≥ 3 mm) was observed in 6 patients of the FFII group and 5 patients of the ASO group, and the difference between the two groups was not significant (P = 0.76). FFII was used frequently in patients with high-risk ASD morphology; however, there was no difference in the prevalence of procedural complications or efficacy between patients using FFII and those using ASO.

DOI： 10.1007/s00380-020-01739-1

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OBJECTIVE: To evaluate the association of serum malondialdehyde low-density lipoprotein (MDA-LDL), an oxidatively modified LDL, with the prevalence of high-risk plaques (HRP) determined with coronary computed tomography angiography (CTA) in statin-treated patients. METHODS: This study was a single-center retrospective cohort comprising 268 patients (mean age 67 years, 58% men) with statin therapy and who underwent coronary CTA for suspected stable coronary artery disease. Patients were classified into two groups according to median MDA-LDL level or median LDL-C level. Coronary CTA-verified HRP was defined when two or more characteristics, including positive remodeling, low-density plaques, and spotty calcification, were present. RESULTS: Patients with HRP had higher MDA-LDL (p = 0.011), but not LDL-C (p = 0.867) than those without HRP. High MDA-LDL was independently associated with HRP (odds ratio 1.883, 95% confidential interval 1.082-3.279) after adjustment for traditional risk factors. Regarding incremental value of MDA-LDL for predicting CTA-verified HRP, addition of serum MDA-LDL levels to the baseline model significantly increased global chi-square score from 26.1 to 32.8 (p = 0.010). CONCLUSIONS: A high serum MDA-LDL level is an independent predictor of CTA-verified HRP, which can lead to cardiovascular events in statin-treated patients.

DOI： 10.3390/jcm10071480

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OBJECTIVES: This study aimed to assess the feasibility of transcatheter atrial septal defect (ASD) closure in patients with absent aortic rim. BACKGROUND: The indication of transcatheter closure for ASD with absent aortic rim is controversial. METHODS: We enrolled 547 patients with ASD who were scheduled for transcatheter closure. Morphologies of aortic rim were evaluated using transesophageal echocardiography (TEE). RESULTS: Aortic rim of <5 mm was observed in 396 (72%) patients; 128 (23%) had absent aortic rim of 0 mm, and 268 (49%) had deficient aortic rim of >0 to <5 mm. Patients with absent aortic rim frequently had aortic rim absence at an angle of 0° on TEE and septal malalignment. Of the 128 patients with absent aortic rim, 126 (98%) successfully underwent transcatheter closure, while 2 (2%) failed transcatheter closure due to a large defect with severe septal malalignment. The success rate of transcatheter closure was similar between patients with absent aortic rim and those with deficient aortic rim (98% vs. 99%, p = .45). After the procedure, no patients had erosion or device embolization during a median follow-up of 24 months. CONCLUSIONS: Transcatheter closure was successfully performed without adverse events in patients with absent aortic rim, as well as in those with deficient aortic rim. Our findings can be valuable to determine the indication of transcatheter closure in patients with ASD.

DOI： 10.1002/ccd.29457

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BACKGROUND: Oxidized high-density lipoprotein (oxHDL), unlike native HDL, is characterized by reduced cholesterol efflux capability and anti-inflammatory properties. The ratio of oxHDL to apolipoprotein A-I (oxHDL/apoAI) is a possible marker of dysfunctional HDL. The aim of this study was to evaluate the association between oxHDL/apoAI and coronary plaque characteristics that increase the likelihood of cardiovascular events as determined by coronary computed tomography (CT) angiography. METHODS: A total of 297 patients (mean age; 67 years, men; 63%) who underwent coronary CT angiography for suspected stable coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined by three characteristics: positive remodeling; low-density plaques; and spotty calcification. Significant stenosis was defined as a luminal narrowing of >70%. Serum concentrations of oxHDL were measured using an enzyme-linked immunosorbent assay. RESULTS: Patients with higher oxHDL/ApoAI showed significantly greater prevalence of HRP (p = 0.03) and significant stenosis (p < 0.01) compared with patients with low oxHDL/ ApoAI. The multivariate logistic analysis demonstrated that oxHDL/ApoAI significantly associated with the presence of HRP and significant coronary stenosis (p = 0.01 and < 0.01). In the follow-up study including 243 patients for a median period of 1.8 years, univariate cox regression analysis showed that oxHDL/ApoAI, HRP and significant stenosis were significant predictors of cardiovascular events. CONCLUSIONS: A high oxHDL/apoAI was associated with the presence of HRP and significant stenosis determined by coronary CT angiography, which can lead to cardiovascular events in patients with suspected stable CAD.

DOI： 10.1016/j.ijcard.2020.09.060

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BACKGROUND: Risk stratification of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) has not been established. Coronary artery calcium score (CACS) and non-alcoholic fatty liver disease (NAFLD) are independently associated with cardiovascular events in T2DM patients. This study examined the incremental prognostic value of NAFLD assessed by non-enhanced computed tomography (CT) in addition to CACS and Framingham risk score (FRS) for cardiovascular events in T2DM patients. METHODS: This prospective pilot study included 529 T2DM outpatients with no history of cardiovascular disease who underwent CACS measurement because of suspected coronary artery disease. NAFLD was defined on CT images as a liver:spleen attenuation ratio < 1.0. Cardiovascular events were defined as cardiovascular death, nonfatal myocardial infarction, late coronary revascularization, nonfatal stroke, or hospitalization for heart failure. RESULTS: Among 529 patients (61% men, mean age 65 years), NAFLD was identified in 143 (27%). Forty-four cardiovascular events were documented during a median follow-up of 4.4 years. In multivariate Cox regression analysis, NAFLD, CACS, and FRS were associated with cardiovascular events (hazard ratios and 95% confidence intervals 5.43, 2.82-10.44, p < 0.001; 1.56, 1.32-1.86, p < 0.001; 1.23, 1.08-1.39, p = 0.001, respectively). The global χ2 score for predicting cardiovascular events increased significantly from 27.0 to 49.7 by adding NAFLD to CACS and FRS (p < 0.001). The addition of NAFLD to a model including CACS and FRS significantly increased the C-statistic from 0.71 to 0.80 (p = 0.005). The net reclassification achieved by adding CACS and FRS was 0.551 (p < 0.001). CONCLUSIONS: NAFLD assessed by CT, in addition to CACS and FRS, could be useful for identifying T2DM patients at higher risk of cardiovascular events.

DOI： 10.1186/s12933-020-01192-4

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OBJECTIVES: This study aimed to determine morphological characteristics of deficient posterior-inferior rim for transcatheter atrial septal defect (ASD) closure success. BACKGROUND: The feasibility of transcatheter closure of ASD with deficient posterior-inferior rim remains unclear. METHODS: Of 869 patients with ASD who were scheduled transcatheter closure, 121 with posterior-inferior rim of <5 mm were included. Posterior-inferior rim morphologies were evaluated by transesophageal echocardiography. RESULTS: One hundred six patients successfully underwent transcatheter closure, while 15 patients failed. These 15 patients had complete deficient posterior-inferior rim of 0 mm and/or a large defect of ≥38 mm. Multivariate logistic regression analysis showed that transcatheter closure failure was independently related to complete deficient posterior-inferior rim and a large defect of ≥38 mm. Incomplete deficient posterior-inferior rim of >0 to <5 mm was observed in 84 patients. All these patients successfully underwent transcatheter closure, except two patients with a large defect of ≥38 mm. Complete deficient posterior-inferior rim was observed in 37 patients. The frequency of complete deficient posterior-inferior rim was higher in patients who failed transcatheter closure (87% vs. 23%, p < .01), but transcatheter closure was performed successfully if the range of complete deficient rim was ≤30°. After the procedure, no adverse events occurred during a median follow-up of 24 months. CONCLUSIONS: Most patients with deficient posterior-inferior rim successfully underwent transcatheter closure. Transcatheter closure could be performed even in patients with complete deficient posterior-inferior rim if the range was partial. Our findings can help to identify candidates for transcatheter closure.

DOI： 10.1002/ccd.29182

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Preoperative chemoradiation therapy (CRT) has been considered as an effective treatment for non-small cell lung cancer. However, there is concern that CRT progresses atherosclerosis in cancer survivors. This study sought to determine if preoperative CRT exacerbated thoracic aortic calcification (TAC) detected by computed tomography (CT) in patients with lung cancer. Among 473 patients who underwent surgery for lung cancer at Okayama University Hospital between 2011 and 2015, 34 patients undergoing preoperative CRT and surgery (CRT group) and 33 matched patients undergoing initial surgery (non-CRT group) were analyzed and compared. The volume of TAC between the 2nd and 12th thoracic vertebrae was quantitatively measured by CT at baseline and 1-year follow-up. Patients in the CRT group (62 ± 7 years old, 74% male) received cisplatin chemotherapy with docetaxel or vinorelbine and radiation therapy (mean 47.3 ± 4.0 Gy). The percent change in TAC volume was significantly greater in the CRT compared with the non-CRT group (58.7%, 95% confidence interval [CI] 41.7-75.7% vs. 27.2%, 95% CI 9.9-44.4%; p = 0.01). Multivariate logistic regression analysis identified CRT as an independent factor associated with greater TAC progression (> the median value) (odds ratio 3.63, 95% CI 1.19-11.08; p = 0.02). In conclusion, preoperative CRT for lung cancer exacerbates TAC. Follow-up of such patients should thus include careful longitudinal assessment for cardiovascular disease.

DOI： 10.1007/s00380-020-01611-2

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DOI： 10.1016/j.jcmg.2020.01.022

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Chronic-active Epstein-Barr virus infection (CAEBV) is a rare disease that can lead to pulmonary arterial hypertension (PAH). However, the treatment for CAEBV-associated PAH has not been established. We discuss a case of improved pulmonary hypertension after chemotherapy in a patient with CAEBV-associated PAH. A 44-year old man was admitted to our hospital because of an abnormal electrocardiogram and liver dysfunction detected by annual medical examination. Echocardiography showed a dilated right ventricle and an estimated right ventricular systolic pressure of 92 mmHg. Right heart catheterization revealed a mean pulmonary arterial pressure of 45 mmHg and pulmonary vascular resistance of 9.8 Wood units. Laboratory examination showed granular lymphocytes and 91% natural killer cells in lymphocyte subsets in peripheral blood. We diagnosed the patient as having CAEBV-associated PAH. After two cycles of chemotherapy without PAH-specific drugs, echocardiography showed improvement in the dilated right ventricle and an estimated right ventricular systolic pressure of 59 mmHg. Right heart catheterization revealed a mean pulmonary arterial pressure of 27 mmHg and pulmonary vascular resistance of 2.4 Wood units. Chemotherapy may improve pulmonary hypertension in patients with CAEBV-associated PAH.

DOI： 10.1536/ihj.19-419

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BACKGROUND: Septal malalignment is related to erosion and device embolization in transcatheter closure of atrial septal defect (ASD), but limited information is available. OBJECTIVES: This study aimed to assess clinical significance of septal malalignment and to determine appropriate evaluation of ASD diameter, including the selection of device size. METHODS: Four hundred and seventeen patients with ASD who underwent transcatheter closure were enrolled. Septal malalignment was defined as separation between the septum primum and the septum secundum on transesophageal echocardiography. RESULTS: One hundred and eighty-four patients had septal malalignment. The frequency of septal malalignment increased with age reaching around 50% in adult patients. Septal malalignment was related to aortic rim deficiency. The distance of separation between the septum primum and the septum secundum was 5 ± 2 mm (range, 1-11 mm). In patients with septal malalignment, the ASD diameter measured at the septum primum was 19 ± 6 mm, while the ASD diameter measured at the septum secundum was 16 ± 6 mm. There was a difference of 4 ± 2 mm (range, 0-8 mm) between the ASD diameter measured at the septum primum and that measured at the septum secundum. For transcatheter closure, the Amplatzer Septal Occluder device size 2-3 mm larger and the Occlutech Figulla Flex II device size 4-7 mm larger than the ASD diameter measured at the septum primum were frequently used. During the study period, erosion or device embolization did not occur in all of the patients. CONCLUSIONS: Septal malalignment is highly prevalent in adult patients with aortic rim deficiency. The measurement of ASD diameter at the septum primum can be valuable for the selection of device size in patients with septal malalignment.

DOI： 10.1155/2020/6090612

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Coronary artery calcification (CAC) as measured by computed tomography is a strong predictor of coronary artery disease. The brachial intima-media thickness (IMT) was recently reported to be associated with cardiovascular risk factors. This study investigated the association of brachial IMT with CAC, which is a marker of coronary artery atherosclerosis, in patients with diabetes. We enrolled 292 patients with diabetes (mean age, 65 ± 12 years; 59% men) who underwent both endothelial function testing and computed tomography for risk assessment of coronary artery disease. Flow-mediated dilation (FMD) and IMT in the brachial artery were measured with a specialized machine. FMD was lower and brachial IMT was thicker in patients with than without CAC. The CAC score was significantly correlated with both brachial IMT and FMD, while the multivariate logistic analysis demonstrated that brachial IMT (> 0.32 mm) but not FMD (< 5.1%) was significantly associated with the presence of CAC (odds ratio, 2.03; 95% confidence interval, 1.10-3.77; p = 0.02). The receiver operating characteristic curve analysis showed that the area under the curve for discriminating patients with CAC was 0.67 for IMT (p < 0.001) and 0.62 for FMD (p < 0.001). When patients were classified into four groups based on brachial IMT and FMD, the CAC score was higher in patients with thicker brachial IMT and lower FMD than in patients of the other groups (p < 0.001). Measurement of brachial IMT could be useful for the risk assessment of patients with diabetes.

DOI： 10.1007/s00380-019-01371-8

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PURPOSE OF REVIEW: To summarize the current status of coronary computed tomography angiography (CTA) in the assessment of coronary plaques and discuss the ability of serial coronary CTA to quantitatively measure changes in the plaque burden in response to lipid-lowering therapy. RECENT FINDINGS: Recent advances in coronary CTA have allowed identification of high-risk coronary features in acute coronary syndrome and measurement of changes in the coronary plaque burden with good reproducibility. Statin therapy may delay plaque progression and change some plaque features. However, the clinical relevance of quantitative changes in coronary plaques and the optimal methods to reduce the plaque burden remain unclear. Despite guideline-directed lipid-lowering therapy, adverse events still occur in substantial numbers of patients receiving statins. Coronary CTA is noninvasive and has high diagnostic performance in patients with coronary artery disease, making change in the plaque burden an applicable biomarker for individualized assessment of future risk.

DOI： 10.1007/s11886-019-1170-4

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BACKGROUND AND AIMS: Oxidized high-density lipoprotein (oxHDL) is characterized by reduced anti-inflammatory properties compared with HDL. However, the role of oxHDL in the pathogenesis of coronary artery calcification (CAC), a marker of subclinical atherosclerosis, remains unclear. We prospectively investigated the association between the change in oxHDL and progression of CAC in a substudy of a multicenter study. METHODS: In the principal study, patients with a CAC score of 1-999 were treated with pitavastatin with/without eicosapentaenoic acid. Measurement of CAC with multidetector-row computed tomography and a blood test were performed at baseline and at the 1-year follow-up. In the principal study, the increase in CAC did not differ among treatment groups. In this substudy, patients were divided into two groups: CAC progression (change in Agatston score of >0) and no CAC progression. RESULTS: In total, 140 patients were analyzed. The oxHDL level significantly decreased from 167 (132-246) at baseline to 122 (103-149) after treatment (median [25th-75th percentile], U/ml) (p < 0.001). The annual change in CAC was significantly positively associated with changes in oxHDL (r = 0.17, p = 0.04), triglycerides (r = 0.17, p = 0.04), and high-sensitivity C-reactive protein (r = 0.22, p = 0.01) but was not associated with changes in low-density lipoprotein cholesterol or HDL-cholesterol. Multiple logistic analysis demonstrated that the decrease in oxHDL per 10 U/ml was independently associated with CAC progression (odds ratio, 0.95; 95% confidence interval, 0.90-0.99; p = 0.04). CONCLUSIONS: The decrease in oxHDL is associated with the attenuation of CAC progression, suggesting that oxHDL is a potential target for atherosclerosis prevention.

DOI： 10.1016/j.atherosclerosis.2019.01.032

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DOI： 10.1016/j.jjcc.2018.03.005

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A right coronary artery of anomalous origin is rare congenital anatomy that can be fatal. CT angiography is an excellent tool for its anatomical assessment. Noninvasive CT-based fractional flow reserve measurement can additionally evaluate the functional severity of coronary stenosis and is potentially useful for evaluating coronary anomalies.

DOI： 10.1002/ccr3.1582

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Lipoprotein(a), or Lp(a), is a low-density lipoprotein-like particle largely independent of known risk factors for, and predictive of, cardiovascular disease (CVD). We investigated the association between baseline Lp(a) levels and the progression of coronary artery calcification (CAC) in patients with hypercholesterolemia undergoing statin therapy. This study was a sub-analysis of a multicenter prospective study that evaluated the annual progression of CAC under intensive and standard pitavastatin treatment with or without eicosapentaenoic acid in patients with an Agatston score of 1 to 999, and hypercholesterolemia treated with statins. We classified the patients into 3 groups according to CAC progression. A total of 147 patients (mean age, 67 years; men, 54%) were analyzed. The proportion of patients with Lp(a) > 30 mg/dL significantly increased as CAC progressed (non-progression; 5.4%, 0<CAC progression ≦100; 7.7%, and CAC progression >100; 23.6%). Logistic regression analysis showed that Lp(a) > 30 mg/dL was an independent predictor of the annual change in Agatston score > 100 (OR: 5.51; 95% CI: 1.28-23.68; p=0.02), even after adjusting for age, sex, hypertension, diabetes mellitus, current smoking, body mass index, and lipid-lowering medications. Baseline Lp(a) >30 mg/dL was a predictor of CAC progression in this population of patients with hypercholesterolemia undergoing statin therapy.

DOI： 10.18926/AMO/56067

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High diagnostic performance of noninvasive fractional flow reserve computed from CT (FFR-CT) was recently reported in prospective multicenter trials. The aims of this study were to evaluate the diagnostic accuracy of FFR-CT in clinical practice and to examine the lesion characteristics showing a mismatch between FFR-CT and invasive FFR. A total of 20 patients (29 vessels) with suspected coronary artery disease were included. All patients underwent invasive coronary angiography and invasive FFR according to coronary artery CT angiography (CCTA) findings. The same raw data used for CCTA were used to evaluate FFR-CT. Results from FFR-CT were compared with invasively measured FFR. A positive ischemia was defined as FFR <0.80. Analyses from three vessels in two patients were not evaluated because of severe calcification or motion artifacts. The diagnostic accuracy, sensitivity, and specificity of FFR-CT per-vessel basis were 81, 100, and 69 %, respectively. To find the reason for mismatch in positive ischemia, lesion characteristics determined with CCTA were compared between the matched group and the mismatched group. A significant difference in bifurcation lesions with positive remodeling was observed between the matched group and the mismatched group (p < 0.01). The high sensitivity of FFR-CT may provide an additional support to the use of CCTA, although particular attention should be paid when using FFR-CT in bifurcation lesions with positive remodeling.

DOI： 10.1007/s00380-016-0892-0

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BACKGROUND: The presence of coronary artery calcification (CAC) and its severity predict future cardiovascular events and is used for risk stratification. However, the association of CAC with heart failure (HF) in patients without a history of coronary artery disease (CAD) remains unclear. This study aimed to determine the correlations of CAC with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and HF events in patients without a history of CAD or HF. METHODS: From June 2010 to June 2013, a total of 487 patients without a history of CAD and HF were enrolled. All of the patients underwent plane multi-detector computed tomography. They were divided into four categories according to CAC scores: ≤10, 11-100, 101-400, and ≥401. RESULTS: The proportion of patients with high NT-proBNP levels increased with CAC categories (p<0.0001). The CAC score was associated with NT-proBNP levels ≥400pg/ml, with an odds ratio of 2.901 (95% confidence interval: 1.368-6.151, p=0.0055) for CAC scores ≥401 compared with CAC scores of 0-10 after adjustment for confounding factors. During the follow-up period of 497±315 days, nine patients were admitted for HF. Kaplan-Meier analysis showed that patients with CAC scores ≥401 had a lower rate of freedom from admission for HF with cumulative incidences of 0.4%, 1%, 2%, and 8% for CAC scores of 0-10, 11-100, 101-400, and ≥401, respectively (p<0.0001). Increasing CAC scores were associated with an increase in incidence of admission for HF, with a hazard ratio of 10.371 for CAC scores ≥401 (95% CI: 1.062-101.309, p=0.0443) compared with CAC scores of 0-10 after adjustment for risk factors. CONCLUSION: Severe CAC is an independent determinant of high NT-proBNP levels and a predictor of admission for HF in a population without a history of CAD or HF.

DOI： 10.1016/j.jjcc.2015.06.014

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Coronary computed tomography angiography (CCTA) in combination with first-pass CT myocardial perfusion imaging (MPI) has a better diagnostic performance than CCTA alone, compared with invasive coronary angiography as the reference standard. The aim of this study was to investigate the additional diagnostic value of first-pass CT-MPI without stress for detecting hemodynamic significance of coronary stenosis, compared with invasive fractional flow reserve (FFR). We recruited 53 patients with suspected coronary artery disease undergoing both CCTA and first-pass CT-MPI without stress and invasive FFR, and 75 vessels were analyzed. We used the same raw data for CCTA and CT-MPI. First-pass CT-MPI was reconstructed by examining the diastolic signal densities as a bull's eye map. Invasive FFR <0.8 was considered as positive. On per-vessel analysis, the area under the receiver operating characteristic curve for CCTA plus first-pass CT-MPI and CCTA alone was 0.81 (0.73-0.90) and 0.70 (0.61-0.81), respectively (P = 0.036). CCTA plus first-pass CT-MPI without stress showed 0.73 sensitivity, 0.74 specificity, 0.53 positive predictive value, and 0.87 negative predictive value for detecting hemodynamically significant coronary stenosis. First-pass CT-MPI without stress correctly reclassified 38% of CCTA false-positive vessels as true negative. First-pass CT-MPI without stress combined with CCTA demonstrated excellent diagnostic accuracy, compared with invasive FFR as the reference standard. This technique could complement CCTA for diagnosis of coronary artery disease.

DOI： 10.1371/journal.pone.0149170

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BACKGROUND: Cystatin C is an endogenous marker of kidney function that overcomes the limitations of serum creatinine. High serum cystatin C levels have been associated with increased cardiovascular mortality and morbidity. In this cross-sectional study, we aimed to determine the associations between serum cystatin C levels and structural and functional cardiac changes in patients with stage 2 or 3 chronic kidney disease (CKD). METHODS AND RESULTS: We enrolled 429 consecutive patients (aged 24-97 years) with CKD stage 2 or 3 and left ventricular (LV) ejection fraction (LVEF)>40%. Echocardiographic parameters, including LV mass index (LVMI), early diastolic mitral annulus velocity (e' velocity), left atrial volume index (LAVI), and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) were measured. Patients were categorized into quartiles according to serum cystatin C levels. Cystatin C was associated with LAVI (p=0.0055), LVEF (p=0.0432), LVMI (p=0.0409), e' (p=0.0051), E/e' (p=0.0027), and log-transformed NT-proBNP (p<0.0001) according to multivariate linear regression analysis, after adjustment for confounding factors including creatinine-based estimated glomerular filtration rate (eGFRcreat) and urinary albumin to creatinine ratio. Incidence of eccentric and concentric hypertrophy increased with increasing cystatin C (Q1, 38%; Q2 49%; Q3, 51%; Q4, 66%, p=0.0008), mainly because of increasing concentric hypertrophy (Q1, 30%; Q2, 39%; Q3, 39%; Q4, 51%, p=0.0187). CONCLUSION: A high serum cystatin C is strongly associated with structural cardiac abnormalities such as LVH and left atrial enlargement, impaired LV relaxation, and an increased NT-proBNP, independently of eGFRcreat in patients with stage 2 or 3 CKD.

DOI： 10.1016/j.ijcard.2015.04.189

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BACKGROUND: Distal embolization during percutaneous coronary intervention (PCI) may deteriorate microvascular reperfusion in patients with ST-elevation myocardial infarction (STEMI). Reperfusion at the coronary microvascular level is important for STEMI and culprit plaque is associated with distal embolization and microvascular reperfusion. ST-segment resolution (ST-R) in the electrocardiogram reflects microvascular reperfusion after primary PCI. Longitudinal extent of lipid pool assessed by optical coherence tomography (OCT) may predict the risk of failure of microvascular reperfusion after primary PCI. METHODS AND RESULTS: This study consisted of 39 patients with STEMI who underwent primary PCI within 24h after the onset of chest pain. Immediately after thrombectomy, OCT was performed and length of lipid pool was measured. Microvascular reperfusion after primary PCI was assessed by ST-R, which was defined as >50% decrease in ST elevation at 1h after primary PCI. There were 23 patients with ST-R and 16 patients without ST-R, with no significant difference in baseline clinical and angiographical variables between the 2 groups. Final thrombolysis in myocardial infarction 3 flow was obtained in all of the patients. Peak creatine kinase was significantly higher in the ST-R (-) group than in the ST-R (+) group (p=0.01). Length of lipid pool was 10.1 ± 2.8mm in the ST-R (-) group and 7.8 ± 3.2mm in the ST-R (+) group (p=0.02). In receiver operating characteristics curve assessing the ability of length of lipid pool to predict ST-R, area under the curve was 0.74 (p=0.02). Length of lipid pool >9.0mm best predicted the absence of ST-R with sensitivity 88% and specificity 78%. CONCLUSIONS: These findings suggest that length of lipid pool estimated by OCT may predict microvascular no-reflow after primary PCI.

DOI： 10.1016/j.jjcc.2013.03.005

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OBJECTIVES: We assessed angioscopic findings after everolimus-eluting stents (EES) implantation, compared with sirolimus-eluting stents (SES). BACKGROUND: Coronary angioscopy (CAS) provides an opportunity to assess neointimal coverage over stent struts, thrombus, and plaque color by direct visualization. CAS is a useful tool for evaluating stent struts after drug-eluting stent implantation. Angioscopic findings after EES implantation have not been reported before. METHODS: We performed CAS in 23 patients who were treated with EES and 41 patients with SES. CAS was performed 8.5 months after stent implantation. We assessed neointimal coverage, thrombus, and plaque color. We classified neointimal coverage in 4 grades: grade 0=struts were completely exposed; grade 1=struts were visible with dull light reflexion; grade 2=there was no light reflexion from slightly visible struts; grade 3=struts were completely covered. RESULTS: There was no significant difference in minimum, maximum, dominant grade of neointimal coverage, and heterogeneity index between EES and SES. Thrombus was less frequently observed in EES than SES (4% vs 29%, p=0.02). When we divided study patients into acute coronary syndrome (ACS) or stable angina pectoris (SAP), there was a tendency toward less thrombus in EES than SES, in both ACS and SAP. Maximum color grade of the plaques was less advanced in EES than SES (p<0.01). Yellow plaques of grade 2 or 3 were less frequent in EES than SES (35% vs 76%, p<0.01). CONCLUSIONS: This study suggested that EES were associated with lower risk of thrombus formation than SES.

DOI： 10.1016/j.jjcc.2012.08.011

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BACKGROUND: The long-term safety and efficacy of drug-eluting stents for patients with acute myocardial infarction (AMI) remain controversial. METHODS AND RESULTS: A total of 143 consecutive patients who presented between August 2004 and July 2006 with AMI and who underwent primary percutaneous coronary intervention (PCI) using sirolimus-eluting stents (SES), were compared with a historical control cohort of 129 consecutive patients who presented between August 2002 and July 2004 and who underwent primary PCI using bare metal stents (BMS). The rate of major adverse cardiovascular events at 3 years was significantly lower in the SES group than in the BMS group (20.3% vs. 33.1%, respectively; P=0.01). This reduction was mainly driven by a decrease in the rate of target vessel revascularization (12.3% vs. 22.4%, respectively; P=0.02). There was no significant difference in the rate of cardiovascular death (4.5% vs. 5.7%, respectively; P=0.67), non-fatal myocardial infarction (4.5% vs. 9.2%, respectively; P=0.16), coronary artery bypass grafting (2.3% vs. 2.5%, respectively; P=0.93), stroke (2.4% vs. 0.8%, respectively; P=0.35), and stent thrombosis (2.9% vs. 2.3%, respectively; P=0.80) between the 2 groups. CONCLUSIONS: SES can be used safely and effectively in patients with AMI.

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The aim of the present study was to investigate the gender-specific mortality after acute myocardial infarction in those aged < 70 years versus ≥ 70 years. The present study consisted of 2,677 consecutive patients with acute myocardial infarction who had undergone coronary angiography within 24 hours after the onset of symptoms. The patients were divided into 2 groups: 1,810 patients < 70 years old and 867 patients ≥ 70 years old. Women were older and had a greater incidence of hypertension and diabetes mellitus and a lower incidence of current smoking and previous myocardial infarction in both groups. The in-hospital mortality rate was significantly greater in women ≥ 70 years old age than in men ≥ 70 years old (16.2% vs 9.3%, respectively; p = 0.003) but was comparable between women and men in patients < 70 years old (5.7% vs 4.9%, respectively; p = 0.59). On multivariate analysis, the association between female gender and in-hospital mortality in patients ≥ 70 years old remained significant (odds ratio 1.78, 95% confidential interval 1.05 to 3.00), but the gender difference was not observed in patients < 70 years old (odds ratio 1.09, 95% confidence interval 0.53 to 2.24). In conclusion, female gender was associated with in-hospital mortality after acute myocardial infarction in patients ≥ 70 years old but not in patients < 70 years old.

DOI： 10.1016/j.amjcard.2011.04.030

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BACKGROUND: The serum lipoprotein (a) [Lp(a)] level is genetically determined and remains consistent during a person's life. Previous cohort studies have reported that subjects with a high Lp(a) level are at high risk of cardiac events. METHODS AND RESULTS: This study consisted of 410 patients who underwent primary percutaneous coronary intervention within 24h of the onset of acute myocardial infarction (AMI). Lp(a) was measured 1 week after AMI and patients were divided into 2 groups based: high Lp(a) group (>40mg/dl, n=95) and low Lp(a) group (≤40mg/dl, n=315). A major adverse cardiac event (MACE) was defined as cardiac death, myocardial infarction and/or revascularization for new lesions. The incidence of MACE during 5 years was significantly higher in the high Lp(a) group than in the low Lp(a) group (34.7% vs. 16.5%, P<0.001). This difference was primarily driven by a higher incidence of new lesions requiring revascularization in the high Lp(a) group (31.6% vs. 15.2%, P<0.001). Multivariate analysis showed that Lp(a) was an independent predictor for MACE (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.31-2.06, P<0.001) and revascularization of a new lesion (OR 1.61, 95%CI 1.32-2.13, P<0.001). CONCLUSIONS: Lp(a) levels could predict the progression of the non-culprit coronary lesions after AMI.

PubMed

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