Evaluation of fractional flow reserve and atherosclerotic plaque characteristics on coronary non-contrast T1-weighted magnetic resonance imaging.

BACKGROUND AND AIMS: The relationship between high-risk coronary plaque characteristics regardless of the severity of lesion stenosis and myocardial ischemia remains unsettled. High-intensity plaques (HIPs) on non-contrast T1-weighted magnetic resonance imaging (T1WI) have been characterized as high-risk coronary plaques. We sought to elucidate whether the presence of coronary HIPs on T1WI influences fractional flow reserve (FFR) in the distal segment of the vessel. METHODS: We retrospectively analyzed 281 vessels in 231 patients with chronic coronary syndrome who underwent invasive FFR measurement and coronary T1WI using a multicenter registry. The plaque-to-myocardial signal intensity ratio (PMR) of the most stenotic lesion was evaluated; a coronary plaque with PMR ≥1.4 was defined as a HIP. RESULTS: The median PMR of coronary plaques on T1WI in vessels with FFR ≤0.80 was significantly higher than that of plaques with FFR >0.80 (1.17 [interquartile range (IQR): 0.99-1.44] vs. 0.97 [IQR: 0.85-1.09]; p < 0.001). Multivariable analysis showed that an increase in PMR of the most stenotic segment was associated with lower FFR (beta-coefficient, -0.050; p < 0.001). The presence of coronary HIPs was an independent predictor of FFR ≤0.80 (odds ratio (OR), 6.18; 95% confidence interval (CI), 1.93-19.77; p = 0.002). Even after adjusting for plaque composition characteristics based on computed tomography angiography, the presence of coronary HIPs was an independent predictor of FFR ≤0.80 (OR, 4.48; 95% CI, 1.19-16.80; p = 0.026). CONCLUSIONS: Coronary plaques with high PMR are associated with low FFR in the corresponding vessel, indicating that plaque morphology might influence myocardial ischemia severity.

Effect of Eicosapentaenoic Acid/Docosahexaenoic Acid on Coronary High-Intensity Plaques Detected Using Noncontrast T1-weighted Imaging: The AQUAMARINE EPA/DHA Randomized Study.

AIM: Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction. METHODS: The Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technic EPA/DHA study is a single-center, triple-arm, randomized, controlled, open-label trial used to investigate the effect of EPA/DHA on high-risk coronary plaques after 12 months of treatment, detected using cardiac magnetic resonance (CMR) in patients with CAD receiving statin therapy. Eligible patients were randomly assigned to no-treatment, 2-g/day, and 4-g/day EPA/DHA groups. The primary endpoint was the change in the plaque-to-myocardium signal intensity ratio (PMR) of coronary high-intensity plaques detected by CMR. Coronary plaque assessment using computed tomography angiography (CTA) was also investigated. RESULTS: Overall, 84 patients (mean age: 68.2 years, male: 85%) who achieved low-density lipoprotein cholesterol levels of ＜100 mg/dL were enrolled. The PMR was reduced in each group over 12 months. There were no significant differences in PMR changes among the three groups in the primary analysis or analysis including total lesions. The changes in CTA parameters, including indexes for detecting high-risk features, also did not differ. CONCLUSION: The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy.

Clinical impact of cardiac magnetic resonance in patients with suspected coronary artery disease associated with chronic kidney disease (AQUAMARINE-CKD study): study protocol for a randomized controlled trial.

BACKGROUND: Although screening for coronary artery disease (CAD) using computed tomography coronary angiography in patients with stable chest pain has been reported to be beneficial, patients with chronic kidney disease (CKD) might have limited benefit due to complications of contrast agent nephropathy and decreased diagnostic accuracy as a result of coronary artery calcifications. Cardiac magnetic resonance (CMR) has emerged as a novel imaging modality for detecting coronary stenosis and high-risk coronary plaques without contrast media that is not affected by coronary artery calcification. However, the clinical use of this technology has not been robustly evaluated. METHODS: AQUAMARINE-CKD is an open parallel-group prospective multicenter randomized controlled trial of 524 patients with CKD at high risk for CAD estimated based on risk factor categories for a Japanese urban population (Suita score) recruited from 6 institutions. Participants will be randomized 1:1 to receive a CMR examination that includes non-contrast T1-weighted imaging and coronary magnetic angiography (CMR group) or standard examinations that include stress myocardial scintigraphy (control group). Randomization will be conducted using a web-based system. The primary outcome is a composite of cardiovascular events at 1 year after study examinations: all-cause death, death from CAD, nonfatal myocardial infarction, nonfatal ischemic stroke, and ischemia-driven unplanned coronary intervention (percutaneous coronary intervention or coronary bypass surgery). DISCUSSION: If the combination of T1-weighted imaging and coronary magnetic angiography contributes to the risk assessment of CAD in patients with CKD, this study will have major clinical implications for the management of patients with CKD at high risk for CAD. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) 1,052,210,075. Registered on September 10, 2021.

Relationship between the serum GDF-15 concentration and muscle function in female patients receiving aortic valve replacement (TAVR, SAVR): Comparison with healthy elderly female subjects.

Purpose: Sarcopenia is closely associated with postoperative prognosis in patients undergoing cardiovascular surgery. Growth differentiation factor (GDF)-15 is involved in the pathogenesis of cardiovascular disease. We examined the relationship between the serum GDF-15 concentration and muscle function in patients receiving aortic valve replacement and healthy elderly subjects. Methods: Forty-three female patients undergoing aortic valve surgery (79.9 ± 6.4 years; transcatheter aortic valve replacement [TAVR] n = 19, conventional surgical aortic valve replacement [SAVR] n = 24) and 64 healthy elderly female subjects (75.9 ± 6.1 years) were included. Walking speed, grip strength, and skeletal muscle mass index (SMI) by a multifrequency bioelectrical impedance analyzer were measured to determine the presence of sarcopenia. Preoperative serum GDF-15 concentration was measured by enzyme-linked immunosorbent assay. Results: The GDF-15 level was higher in patients receiving aortic valve replacement than in healthy elderly subjects (aortic valve replacement: 1624 ± 1186 pg/mL vs. healthy: 955 ± 368 pg/mL, p < 0.001). Multivariate linear regression analysis showed that the serum GDF-15 level determined grip strength independently of the high-sensitivity C-reactive protein level and eGFR, even after adjusting for age (ß = -0.318, p = 0.025). Sarcopenia was found in 12.5% of healthy elderly subjects, 83.3% of patients with TAVR, and 64.3% of patients with SAVR. The GDF-15 concentration that defined sarcopenia was 1109 pg/mL in subjects including patients receiving aortic valve replacement. Conclusions: The preoperative serum GDF-15 concentration, which was higher in female patients receiving aortic valve replacement than in healthy elderly subjects, may be a serum marker of sarcopenia.

Mobilization of progenitor cells and vessel healing after implantation of SYNERGY in acute coronary syndrome.

This study was aimed to compare the vascular healing process of a SYNERGY stent with that of a PROMUS PREMIER stent in patients with acute coronary syndrome (ACS). In 71 patients with ACS, undergoing coronary stent implantation using the SYNERGY stent (n = 52) or PROMUS PREMIER stent (n = 19), we measured circulating CD34+/CD133+/CD45null cells and CD34+/KDR+ cells and observed vascular healing at the stented sites using optical coherence tomography (OCT) and coronary angioscopy. On the day 7, circulating CD34+/CD133+/CD45null cells increased in SYNERGY group (P < 0.0001), while it did not change in PROMUS group. The CD34+/KDR+ cells also increased in SYNERGY group (P < 0.0001) but less significantly in the PROMUS group (P < 0.05). The OCT-based neointimal thickness (P < 0.0005) and neointimal coverage rate (P < 0.05) at 12 months were greater in SYNERGY group, compared with PROMUS group. The coronary angioscopy-based neointimal coverage grade at 12 months was also greater in SYNERGY group (P < 0.001). In overall patients, the change in CD34+/KDR+ cells on the day 7 correlated with the OCT-based neointimal thickness at 12 months (R = 0.288, P < 0.05). SYNERGY stent seems to have potential advantages over PROMUS PREMIER stent for ACS patients in terms of vascular healing process at the stented sites.

The association between the extent of lipidic burden and delta-fractional flow reserve: analysis from coronary physiological and near-infrared spectroscopic measures.

BACKGROUND: Vulnerable plaque features including lipidic plaque have been shown to affect fractional flow reserve (FFR). Given that formation and propagation of lipid plaque is accompanied by endothelial dysfunction which impairs vascular tone, the degree of lipidic burden may affect vasoreactivity during hyperemia, potentially leading to reduced FFR. Our aim is to elucidate the relationship of the extent of lipidic plaque burden with coronary physiological vasoreactivity measure. METHODS: We analyzed 89 subjects requeuing PCI due to angiographically intermediate coronary stenosis with FFR ≤0.80. Near-infrared spectroscopy (NIRS) and intravascular ultrasound were used to evaluate lipid-core burden index (LCBI) and atheroma volume at both target lesion (maxLCBI4mm; maximum value of LCBI within any 4 mm segments) and entire target vessel (LCBIvessel: LCBI within entire vessel). In addition to FFR, delta-FFR was measured by difference of distal coronary artery pressure/aortic pressure (Pd/Pa) between baseline and hyperemic state. RESULTS: The averaged FFR and delta-FFR was 0.74 (0.69-0.77), and 0.17±0.05, respectively. On target lesion-based analysis, maxLCBI4mm was negatively correlated to FFR (ρ=-0.213, P=0.040), and it was positively correlated to delta-FFR (ρ=0.313, P=0.002). Furthermore, target vessel-based analysis demonstrated similar relationship of LCBIvessel with FFR (ρ=-0.302, P=0.003) and delta-FFR (ρ=0.369, P<0.001). Even after adjusting clinical characteristics and lesion/vessel features, delta-FFR (by 0.10 increase) was independently associated with maxLCBI4mm (ß=57.2, P=0.027) and LCBIvessel (ß=24.8, P=0.007) by mixed linear model analyses. CONCLUSIONS: A greater amount of lipidic plaque burden at not only "target lesion" alone but "entire target vessel" was associated with a greater delta-FFR. The accumulation of lipidic plaque materials at both local site and entire vessel may impair hyperemia-induced vasoreactivity, which causes a reduced FFR.

The feasibility and limitation of coronary computed tomographic angiography imaging to identify coronary lipid-rich atheroma in vivo: Findings from near-infrared spectroscopy analysis.

BACKGROUND: Coronary computed tomography angiography (CCTA) non-invasively visualizes lipid-rich plaque. However, this ability is not fully validated in vivo. The current study aimed to elucidate the association of CCTA features with near-infrared spectroscopy-derived lipidic plaque measure in patients with coronary artery disease. METHODS: 95 coronary lesions (culprit/non-culprit = 51/44) in 35 CAD subjects were evaluated by CCTA and NIRS imaging. CT density, positive remodeling, spotty calcification, napkin-ring sign and NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) were analyzed by two independent physicians. The association of CCTA-derived plaque features with maxLCBI4mm ≥ 400 was evaluated. RESULTS: The median CT density and maxLCBI4mm were 57.7 Hounsfield units (HU) and 304, respectively. CT density (r = -0.75, p < 0.001) and remodeling index (RI) (r = 0.58, p < 0.001) were significantly associated with maxLCBI4mm, respectively. Although napkin-ring sign (p < 0.001) showed higher prevalence of maxLCBI4mm ≥ 400 than those without it, spotty calcification did not (p = 0.13). On multivariable analysis, CT density [odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.93-0.97; p < 0.001] and positive remodeling [OR = 7.71, 95%CI = 1.37-43.41, p = 0.02] independently predicted maxLCBI4mm ≥ 400. Receiver operating characteristic curve analysis demonstrated CT density <32.9 HU (AUC = 0.92, sensitivity = 85.7%, specificity = 91.7%) and RI ≥ 1.08 (AUC = 0.83, sensitivity = 74.3%, specificity = 85.0%) as optimal cut-off values of maxLCBI4mm ≥ 400. Of note, only 52.6% at lesions with one of these plaque features exhibited maxLCBI4mm ≥ 400, whereas the frequency of maxLCBI4mm ≥ 400 was highest at those with both features (88.5%, p < 0.001 for trend). CONCLUSIONS: CT density <32.9 HU and RI ≥ 1.08 were associated with lipid-rich plaque on NIRS imaging. Our findings underscore the synergistic value of CT density and positive remodeling to detect lipid-rich plaque by CCTA.

Neointimal tissue characterization after implantation of drug-eluting stents by optical coherence tomography: quantitative analysis of optical density.

Normalized optical density (NOD) measured by optical coherence tomography represents neointimal maturity after coronary stent implantation and is correlated with morphologic information provided by both light and electron microscopy. We aimed to test the hypothesis that even second generation drug-eluting stents (DESs) are problematic in terms of neointimal maturity. We implanted bare-metal stents (BMS: n = 14), everolimus-eluting stents (EESs: n = 15) or zotarolimus-eluting stents (ZESs: n = 12) at 41 sites in 32 patients with stable coronary artery disease. OCT was performed at up to 12 months of follow-up, and the average optical density of neointima covering struts was evaluated. NOD was calculated as the optical density of stent-strut covering tissue divided by the optical density of the struts. We also measured circulating CD34+ /CD133+ /CD45low cells, and serum levels of stromal cell-derived factor (SDF)-1, interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 at baseline and follow-up. NOD was lower in the EES (0.70 ± 0.06) group than in the BMS (0.76 ± 0.07, P < 0.05) and ZES (0.76 ± 0.06, P < 0.05) groups. The mean neointimal area (R = 0.33, P < 0.05) and mean neointimal thickness (R = 0.37, P < 0.05) were correlated with NOD. Although NOD was not correlated with percent changes in circulating endothelial progenitor cells, and the levels of SDF-1 and IL-8, it was negatively correlated with the change in MMP-9 level (R = - 0.51, P < 0.01). Neointimal maturity might be lower at EES sites than BMS or ZES sites. This might lead to impaired neointimal tissue growth and matrix degradation. These results suggest a specific pathophysiology after DES implantation.

Patients With CONgestive Heart Failure Benefit From Long-Term Treatment Effects With Novel Treatment Using Azosemide Compared With Furosemide Derived From Existing Retrospective Study Data: CONTENTED.

A long-acting loop diuretic, azosemide, has been shown to improve long-term prognosis in patients with heart failure compared with a short-acting loop diuretic, furosemide. However, the therapeutic advantages of azosemide over furosemide have not been clearly established. In this study, we retrospectively analyzed clinical outcomes and laboratory data in patients with congestive heart failure treated with furosemide or azosemide, and the efficacy of these agents was compared. First, we screened 1900 patients and selected 124 (furosemide group: n = 40; azosemide group: n = 84) as the total study population. From these patients, we next selected 72 patients for the propensity score-matched analysis (furosemide group: n = 36; azosemide group: n = 36). The incidence of all-cause death and rehospitalization due to worsening heart failure during 24 months of follow-up was similar between the furosemide and azosemide groups in both the total study population and the propensity score-matched population. However, in the propensity score-matched analysis, the estimated glomerular filtration rate time-dependently decreased during 36 months of follow-up in the furosemide group (56.5 ± 19.5-43.2 ± 16.3 mL/min/1.73 m), whereas it did not change in the azosemide group (58.6 ± 22.0-50.3 ± 17.8 mL/min/1.73 m) (P = 0.032). Azosemide might have some potential advantage for renal protection over furosemide in patients with congestive heart failure.

Prediction of Acute-phase Complications in Patients with Infectious Endocarditis.

Objective Embolic events are frequent and life-threatening complications of infective endocarditis (IE). Recently, an embolic risk assessment at admission, based on the Embolic Risk (ER) French Calculator, was designed to predict the development of symptomatic emboli associated with IE. This study aimed to validate the ER French Calculator for the prediction of in-hospital events, including embolic events. Methods We retrospectively analyzed the clinical features of 52 consecutive patients with left-sided IE to identify possible predictors of in-hospital events within 30 days of admission. Results New embolic events were seen in 15 patients (29%), cardiac surgery was performed in 22 patients (42%), and 1 patient (2%) died within 30 days of admission. A composite endpoint of embolic complications, cardiac surgery, or death was observed in 28 patients (54%). The cumulative incidence of new embolic events was significantly higher in the high-risk group identified by the ER French Calculator than in the low-risk group (log-rank test; p=0.0004). The incidence of the composite endpoint was higher in the high-risk group than in the low-risk group (log-rank test; p<0.0001). A multivariate Cox proportional hazards model indicated that the high-risk designation on the ER French Calculator predicted embolic events (p=0.0410) and composite events (p=0.0371) independently of other candidate predictors. Conclusion The ER French Calculator may be a useful tool for predicting new in-hospital embolic events and other unfavorable in-hospital events in patients with IE.

Short-term Safety and Mid-term Efficacy of Prasugrel Versus Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention.

Objective Although several clinical trials have shown that the mid- and long-term safety and efficacy of prasugrel are better than those of clopidogrel after percutaneous coronary intervention (PCI), there are few data regarding the short-term safety. Methods In this study, we retrospectively analyzed the short-term (72 hours) PCI-related bleeding complications and mid-term (12 months) efficacy in 250 consecutive coronary artery disease patients who underwent PCI and received aspirin plus prasugrel (prasugrel group; 67.7±10.0 years, 200 men). Patients The comparison group consisted of 250 age- and gender-matched patients who received aspirin plus clopidogrel (clopidogrel group: 67.2±11.2 years, 199 men). Results The incidence of a composite of PCI-related bleeding complications in the acute phase post-PCI was significantly higher in the prasugrel group than in the clopidogrel group (22.4% vs. 13.2%, p=0.007), although the incidence of non-PCI-related bleeding complications over 12 months was comparable between the 2 groups. The cumulative incidence of major cardiovascular events (MACEs) was comparable between the prasugrel and clopidogrel groups (log-rank test; p=0.561). A multivariate logistic regression analysis of the 250 prasugrel-treated patients showed that acute coronary syndrome tended to be negatively associated with the incidence of PCI-related bleeding complications (p=0.061). Conclusion Prasugrel and clopidogrel may have similar efficacy for preventing cardiovascular events as the post-PCI antiplatelet regimen; however, prasugrel should be used cautiously because of the risk of PCI-related bleeding complications.

Optical coherence tomography-verified morphological correlates of high-intensity coronary plaques on non-contrast T1-weighted magnetic resonance imaging in patients with stable coronary artery disease.

Aims: Coronary high-intensity plaques (HIPs) with a high plaque-to-myocardial signal intensity ratio (PMR) on non-contrast T1-weighted imaging in patients with stable coronary artery disease (CAD) are associated with future coronary events. To characterize the morphological substrate of HIP, we performed a correlative optical coherence tomography (OCT) study. Methods and results: We examined 137 lesions in 105 patients with stable angina pectoris or silent myocardial ischaemia scheduled for percutaneous coronary intervention (PCI) using a 3 T magnetic resonance scanner. Pre-interventional OCT was performed for PCI target lesions. HIP was defined as PMR ≥ 1.4. Of the 137 lesions, 34% were HIP and 66% were non-HIP. The prevalence of lipid-rich plaque (96% vs. 70%, P < 0.001), macrophage accumulation (65% vs. 46%, P = 0.046), cholesterol crystals (46% vs. 22%, P = 0.006), and healed plaque rupture (multiple layers of different optical densities overlaying a large lipid accumulation, 72% vs. 18%, P < 0.001) was significantly higher in the HIP group than the non-HIP group; no significant differences were observed for the presence of thin cap fibroatheroma, intracoronary thrombus, and plaque rupture between the two groups. Multivariable stepwise logistic regression analysis showed that HIP was significantly associated with the presence of healed plaque rupture [odds ratio (OR) 9.32; 95% confidence interval (95% CI) 4.05-22.71; P < 0.001] and lipid-rich plaque (OR 4.38; 95% CI 1.08-29.77; P = 0.038). Conclusions: The significant association between HIP- and OCT-derived healed plaque rupture and large lipid core provides new insights into the characteristics of high-risk plaques, even in clinically stable CAD.

Procedural challenge of coronary catheterization for ST-segment elevation myocardial infarction in patient who underwent transcatheter aortic valve replacement using the CoreValveTM.

A 73-year-old man with severe aortic valve stenosis successfully underwent transcatheter aortic valve replacement (TAVR) using CoreValveTM (29 mm, Medtronic Inc., Minneapolis, MN, USA). Four years after the TAVR, he was hospitalized due to anterior ST-segment elevation myocardial infarction. Despite the need for prompt restoration of coronary flow in the infarct-related artery, the implanted CoreValveTM profoundly restricted the manipulation of diagnostic catheters during the coronary angiography. In particular, (I) guidewire easily migrated into the space between CoreValveTM and aorta vessel wall; (II) the nickel-titanium frame of CoreValveTM limited the space to manipulate catheters, making difficult to advance Judkins left (JL) 4, Judkins right (JR) 4 and Amplatz left 1 into coronary cusps; and (III) selecting specific spot within frame was required for cannulation. Left and right coronary arteries were barely engaged by JL3.5 and modified JR4, respectively. Percutaneous coronary intervention (PCI) for culprit lesion in the left-anterior descending artery was successfully completed by 6-French JL3.5 (BritetipTM, Cordis, Milpitas, CA, USA) with drug-eluting stent implantation. Meticulous strategies and understanding of the prosthetic valve geometry are warranted to conduct PCI in patients who underwent TAVR.

Clinical determinants of successful weaning from extracorporeal membrane oxygenation in patients with fulminant myocarditis.

AIMS: Patients with fulminant myocarditis (FM) often present with cardiogenic shock and require mechanical circulatory support, including extracorporeal membrane oxygenation (ECMO) and ventricular assist device (VAD) implantation. This study sought to clarify the determinants of successful weaning from ECMO in FM patients. METHODS AND RESULTS: We studied 37 consecutive FM patients supported by ECMO as the initial form of mechanical circulatory support between January 1995 and December 2014 in our hospital. Twenty-two (59%) patients were successfully weaned from ECMO, while 15 (41%) were not. There were significant differences in levels of peak creatine kinase and those of its MB isoform (CK-MB), left ventricular posterior wall thickness (LVPWT), and prevalence of cardiac rhythm disturbances. Receiver operating characteristic curve analysis revealed that a peak CK-MB level of 185 IU/L and LVPWT of 11 mm were the optimal cut-off values for predicting successful weaning from ECMO (areas under the curve, 0.89 and 0.85, respectively). During the follow-up [median 48 (interquartile range 8-147) months], 83% of FM patients who were weaned from ECMO survived, with preserved fractional shortening based on echocardiography. Of the 15 FM patients who were not weaned from ECMO, nine bridged to VAD, and only two were successfully weaned from VAD and survived. CONCLUSIONS: These results indicate that myocardial injury, as evidenced by CK-MB and LVPWT, and prolonged presence of cardiac rhythm disturbances are important clinical determinants of successful weaning from ECMO.

Effect of eicosapentaenoic acid/docosahexaenoic acid on coronary high-intensity plaques detected with non-contrast T1-weighted imaging (the AQUAMARINE EPA/DHA study): study protocol for a randomized controlled trial.

BACKGROUND: Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals. These high-intensity plaques (HIPs) are quantitatively assessed using the plaque-to-myocardium signal intensity ratio (PMR). Our goal is to assess the effect of EPA/DHA on coronary HIPs detected with T1WI in patients with CAD on statin treatment. METHODS/DESIGN: This prospective, controlled, randomized, open-label study examines the effect of 12 months of EPA/DHA therapy and statin treatment on PMR of HIPs detected with CMR and computed tomography angiography (CTA) in patients with CAD. The primary endpoint is the change in PMR after EPA/DHA treatment. Secondary endpoints include changes in Hounsfield units, plaque volume, vessel area, and plaque area measured using CTA. Subjects are randomly assigned to either of three groups: the 2 g/day EPA/DHA group, the 4 g/day EPA/DHA group, or the no-treatment group. DISCUSSION: This trial will help assess whether EPA/DHA has an anti-atherosclerotic effect using PMR of HIPs detected by CMR. The trial outcomes will provide novel insights into the effect of EPA/DHA on high-risk coronary plaques and may provide new strategies for lowering the residual risk in patients with CAD on statin therapy. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000015316 . Registered on 2 October 2014.

Coronary Artery Ectasia Predicts Future Cardiac Events in Patients With Acute Myocardial Infarction.

OBJECTIVE: Coronary artery ectasia (CAE) is an infrequently observed vascular phenotype characterized by abnormal vessel dilatation and disturbed coronary flow, which potentially promote thrombogenicity and inflammatory reactions. However, whether or not CAE influences cardiovascular outcomes remains unknown. APPROACH AND RESULTS: We investigated major adverse cardiac events (MACE; defined as cardiac death and nonfatal myocardial infarction [MI]) in 1698 patients with acute MI. The occurrence of MACE was compared in patients with and without CAE. CAE was identified in 3.0% of study subjects. During the 49-month observation period, CAE was associated with 3.25-, 2.71-, and 4.92-fold greater likelihoods of experiencing MACE (95% confidence interval [CI], 1.88-5.66; P<0.001), cardiac death (95% CI, 1.37-5.37; P=0.004), and nonfatal MI (95% CI, 2.20-11.0; P<0.001), respectively. These cardiac risks of CAE were consistently observed in a multivariate Cox proportional hazards model (MACE: hazard ratio, 4.94; 95% CI, 2.36-10.4; P<0.001) and in a propensity score-matched cohort (MACE: hazard ratio, 8.98; 95% CI, 1.14-71.0; P=0.03). Despite having a higher risk of CAE-related cardiac events, patients with CAE receiving anticoagulation therapy who achieved an optimal percent time in target therapeutic range, defined as ≥60%, did not experience the occurrence of MACE (P=0.03 versus patients with percent time in target therapeutic range <60% or without anticoagulation therapy). CONCLUSIONS: The presence of CAE predicted future cardiac events in patients with acute MI. Our findings suggest that acute MI patients with CAE are a high-risk subset who might benefit from a pharmacological approach to controlling the coagulation cascade.

Mature proprotein convertase subtilisin/kexin type 9, coronary atheroma burden, and vessel remodeling in heterozygous familial hypercholesterolemia.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), an important contributor to low-density lipoprotein metabolism in heterozygous familial hypercholesterolemia (HeFH), exhibits direct proatherogenic effects. PCSK9 circulates as mature and furin-cleaved forms, which differ in its biological activity. However, it remains to be elucidated whether each PCSK9 subtype has different atherogenic properties. OBJECTIVE: To investigate the association of each PCSK9 subtype with coronary atherosclerosis in HeFH. METHODS: About 204 nonculprit segments in 138 HeFH subjects with coronary artery disease were evaluated by using intravascular ultrasound. Mature, furin-cleaved PCSK9 and total concentration of PCSK9 subtypes were measured by using enzyme-linked immunosorbent assay (BML Inc., Tokyo, Japan). The relationship of these PCSK9 values with intravascular ultrasound measures was investigated. RESULTS: Mature PCSK9 level was positively associated with percent atheroma volume (PAV: r = 0.78, P = .003). Despite extensive atheroma under a higher mature PCSK9 level, vessel volume did not change across any mature PCSK9 levels (r = 0.05, P = .78). These responses resulted in smaller lumen volume, which was negatively correlated to mature PCSK9 level (r = 0.65, P = .009). By contrast, there were no significant relationships of PAV with furin-cleaved (r = 0.12, P = .45) and total PCSK9 (r = 0.37, P = .25) levels. On multivariate analysis, mature PCSK9 level independently contributed to PAV (odds ratio: 1.45, 95% confidence interval: 1.11-1.67, P = .01). Even in subjects with low-density lipoprotein cholesterol level <2.6 mmol/L, greater PAV was still observed in association with an elevated mature PCSK9 level (P = .003). CONCLUSIONS: Mature PCSK9 associated with atheroma volume and impaired vessel remodeling in HeFH patients with coronary artery disease. These findings suggest the potential role of mature PCSK9 in propagation of coronary atherosclerosis in HeFH.

Early development of acute kidney injury is an independent predictor of in-hospital mortality in patients with acute myocardial infarction.

BACKGROUND: Acute kidney injury (AKI) often occurs in patients with acute myocardial infarction (AMI), and is associated with adverse outcomes. However, it remains unclear how timing of AKI affects it. This study assessed impact of timing of AKI on prognosis after AMI. METHODS: This study consisted of 760 patients with AMI who were admitted within 48h after symptom onset. AKI was diagnosed as increase in creatinine ≥0.3mg/dl or ≥50% within any 48h after admission. Patients were classified into 3 groups according to the occurrence and timing of AKI: no-AKI, early-AKI (within 48h after admission) and late-AKI (>48h). Early-AKI was classified into transient early-AKI, defined as creatinine returning to the level below the criteria of AKI, and persistent early-AKI. RESULTS: Early-AKI occurred in 64 patients (9%) and late-AKI in 32 patients (4%). Patients with early-AKI had significantly higher mortality (35%) than those with late-AKI (7%, p<0.001) and no-AKI (3%, p<0.001). Multivariate analysis showed early-AKI was an independent predictor of in-hospital mortality (OR: 3.38, 95% CI: 1.30-8.76, p=0.013), but late-AKI was not. Among patients with early-AKI, mortality was significantly higher even if AKI was transient (23%, p<0.001). Patients with persistent early-AKI had the highest mortality (66%, p<0.001). CONCLUSIONS: Early-AKI was associated with worse outcome. Even if renal function once returned to baseline level, patients with early-AKI tended to be at high risk of mortality.