Impact of Chronic Kidney Disease on In-Hospital and 3-Year Clinical Outcomes in Patients With Acute Myocardial Infarction Treated by Contemporary Percutaneous Coronary Intervention and Optimal Medical Therapy　- Insights From the J-MINUET Study.

BACKGROUND: The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in debate.Methods and Results:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m2); moderate CKD (60>eGFR≥30 mL/min/1.73 m2); and severe CKD (eGFR <30 mL/min/1.73 m2). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788-0.841) to 0.831 (0.806-0.857), as well as 0.731 (0.708-0.755) to 0.740 (0.717-0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement [NRI] 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively. CONCLUSIONS: CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.

Adding coronary computed tomography angiography to invasive coronary angiography improves prediction of cardiac events.

BACKGROUND: The additive value of plaque characteristics determined by computed tomography angiography (CTA) in patients undergoing invasive coronary angiography (ICA) has not been established. METHODS AND RESULTS: We studied 676 patients undergoing ICA and CTA within 3 months. The luminal diameter narrowing based on ICA and the presence of high risk plaque (HRP) based on CTA were assessed in all coronary artery segments except for those after or before scheduled treatment. We followed their cardiac events including cardiac death, acute coronary syndrome (ACS), and revascularization for de novo lesions ≥3 months after ICA. The incidence of coronary events was higher in the segments including >25% luminal narrowing than in those without (2.94% vs. 0.31%, P<0.0001), and higher in the segments containing HRP than in those without (12.6 vs. 0.46%, P<0.0001). Greater than 25% residual luminal narrowing and the presence of HRP were identified as independent predictors of cardiac events after risk adjustment for age, gender, and history of ACS (hazard ratio [HR], 3.22; 95% confidence interval [CI]: 1.29-10.76; P=0.0092, HR, 2.64; 95% CI: 1.59-4.35; P=0.0002, respectively). Adding the presence of HRP to a model including age, gender, ACS history, and >25% residual stenosis improved the prediction of cardiac events. CONCLUSIONS: Assessment of coronary plaque characteristics on CTA improves the prediction of cardiac events in patients undergoing ICA.

Characteristics of plaque progression detected by serial coronary computed tomography angiography.

We previously reported that serial coronary computed tomography angiography (CTA) had a potential to evaluate the interval change of plaque morphology of coronary arteries. The aim of this study was to evaluate variables associated with the plaque progression by serial CTA. We included 148 patients (age 66.3 ± 9.8 years, male 81.1 %, median scan interval 12 months) with coronary artery disease undergoing serial CTA. Each coronary artery was compared visually between baseline and follow-up CTA to detect plaque progression. Baseline characteristics between progression and nonprogression patients did not demonstrate any significant differences. Logistic analysis revealed that only low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dl at follow-up was associated with plaque progression (odds ratio 2.59, 95 % confidence interval 1.12-6.34, P = 0.0263). Cutoff value of LDL-C for plaque progression at follow-up was 103.0 mg/dl based on receiver-operator characteristic curves analyses. Of the 36 progressive lesions in 32 patients, plaque composition at baseline included 13 lesions (36.1 %) of noncalcified plaque, 1 lesion (2.8 %) of calcified plaque, 12 lesions (33.3 %) of partially calcified plaque, and the remaining 10 lesions (27.8 %) had no plaque at baseline and revealed de novo plaques at follow-up. There were 9 lesions (25 %) with high-risk plaque (HRP) characteristics at baseline and 18 lesions (50 %) with HRP at follow-up. Plaque progression of coronary arteries by serial CTA was associated with LDL-C ≥100 mg/dl at follow-up regardless of baseline LDL-C level. There was no specific finding to predict plaque progression on the baseline plaque characteristics.

The fate of incomplete stent apposition with drug-eluting stents: an optical coherence tomography-based natural history study.

AIMS: To assess the fate of incomplete stent apposition (ISA) after deployment of sirolimus-eluting stents (SESs). METHODS AND RESULTS: Thirty-two patients having intravascular ultrasound (IVUS)-guided PCI with SESs underwent assessment of stent deployment with quantitative coronary angiography, IVUS, and optical coherence tomography (OCT) pre-procedure, post-procedure, and at 10 months follow-up. Incomplete stent apposition was defined as separation of a stent strut from the inner vessel wall by >160 microm. At follow-up, 4.67% of struts with ISA at deployment failed to heal and 7.59% which were well apposed did not develop neointimal hyperplasia even after 10 months. Lesion remodelling was responsible for the development of late ISA in only 0.37% of struts. Failure of adequate neointimal hyperplasia was quantitatively the most important mechanism responsible for persistent acute ISA, classified in previous studies, which relied only on follow-up OCT, as late ISA. Thrombus was visualized in 20.6% of struts with ISA at follow-up and in 2.0% of struts with a good apposition (P < 0.001). CONCLUSION: In patients with SESs, ISA can fail to heal and even complete apposition can be associated with no neointimal hyperplasia. Incomplete stent apposition without neointimal hyperplasia was significantly associated with the presence of OCT-detected thrombus at follow-up, and may constitute a potent substrate for late stent thrombosis.

Plaque Characterization by Coronary Computed Tomography Angiography and the Likelihood of Acute Coronary Events in Mid-Term Follow-Up.

BACKGROUND: Coronary computed tomography angiography (CTA)-verified positive remodeling and low attenuation plaques are considered morphological characteristics of high-risk plaque (HRP) and predict short-term risk of acute coronary syndrome (ACS). OBJECTIVES: This study evaluated whether plaque characteristics by CTA predict mid-term likelihood of ACS. METHODS: The presence of HRP and significant stenosis (SS) of ≥70% were evaluated in 3,158 patients undergoing CTA. Serial CTA was performed in 449 patients, and plaque progression (PP) was evaluated. Outcomes (fatal and nonfatal ACS) were recorded during follow-up (mean 3.9 ± 2.4 years). RESULTS: ACS occurred in 88 (2.8%) patients: 48 (16.3%) of 294 HRP(+) and 40 (1.4%) of 2,864 HRP(-) patients. ACS was also significantly more frequent in SS(+) (36 of 659; 5.5%) than SS(-) patients (52 of 2,499; 2.1%). HRP(+)/SS(+) (19%) and HRP(+)/SS(-) (15%) had higher rates of ACS compared with no-plaque patients (0.6%). Although ACS incidence was relatively low in HRP(-) patients, the cumulative number of patients with ACS developing from HRP(-) lesions (n = 43) was similar to ACS patients with HRP(+) lesions (n = 45). In patients with serial CTA, PP also was an independent predictor of ACS, with HRP (27%; p < 0.0001) and without HRP (10%) compared with HRP(-)/PP(-) patients (0.3%). CONCLUSIONS: CTA-verified HRP was an independent predictor of ACS. However, the cumulative number of ACS patients with HRP(-) was similar to patients with HRP(+). Additionally, plaque progression detected by serial CTA was an independent predictor of ACS.

Major bleeding complications related to combined antithrombotic therapy in atrial fibrillation patients 12 months after coronary artery stenting.

BACKGROUND AND PURPOSE: Many patients with atrial fibrillation (AF) and coronary artery stent deployment are given both antiplatelet drug and warfarin. Little information is available as to the relationship between the antithrombotic therapies in the late phase after stenting and the clinical outcomes of these patients. We examined the clinical outcomes of AF patients 12 months after coronary artery stenting. METHODS: We retrospectively examined 146 patients and classified them into three groups according to the antithrombotic therapies [dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT) plus warfarin, and DAPT plus warfarin] 12 months after stenting. We defined the primary endpoint as Thrombolysis in Myocardial Infarction major bleeding and the secondary endpoint as a composite of adverse events (CAE: all-cause death, nonfatal myocardial infarction, intracranial bleeding, and cerebral infarction). RESULTS: During a median follow-up of 37 months, major bleeding and CAE were observed in 14 (9.6%) and 46 (31.5%) patients, respectively. DAPT plus warfarin was an independent risk factor for major bleeding in a multivariate Cox hazard regression model after adjustment for age, gender, and the type of AF (hazard ratio: 4.20; 95% confidence interval: 1.13-17.27; p=0.033). No significant clinical variables were found for CAE. CONCLUSIONS: Prolonged use of DAPT with warfarin significantly increases the risk of major bleeding in AF patients after coronary artery stenting. Individualized antithrombotic treatment is required in these patients to prevent major bleeding.

Impact of statin therapy on plaque characteristics as assessed by serial OCT, grayscale and integrated backscatter-IVUS.

OBJECTIVES: The purpose of this study was to evaluate the effect of statin treatment on coronary plaque composition and morphology by optical coherence tomography (OCT), grayscale and integrated backscatter (IB) intravascular ultrasound (IVUS) imaging. BACKGROUND: Although previous studies have demonstrated that statins substantially improve cardiac mortality, their precise effect on the lipid content and fibrous cap thickness of atherosclerotic coronary lesions is less clear. While IVUS lacks the spatial resolution to accurately assess fibrous cap thickness, OCT lacks the penetration of IVUS. We used a combination of OCT, grayscale and IB-IVUS to comprehensively assess the impact of pitavastatin on plaque characteristics. METHODS: Prospective serial OCT, grayscale and IB-IVUS of nontarget lesions was performed in 42 stable angina patients undergoing elective coronary intervention. Of these, 26 received 4 mg pitavastatin after the baseline study; 16 subjects who refused statin treatment were followed with dietary modification alone. Follow-up imaging was performed after a median interval of 9 months. RESULTS: Grayscale IVUS revealed that in the statin-treated patients, percent plaque volume index was significantly reduced over time (48.5 ± 10.4%, 42.0 ± 11.1%; p = 0.033), whereas no change was observed in the diet-only patients (48.7 ± 10.4%, 50.4 ± 11.8%; p = NS). IB-IVUS identified significant reductions in the percentage lipid volume index over time (34.9 ± 12.2%, 28.2 ± 7.5%; p = 0.020); no change was observed in the diet-treated group (31.0 ± 10.7%, 33.8 ± 12.4%; p = NS). While OCT demonstrated a significant increase in fibrous cap thickness (140 ± 42 µm, 189 ± 46 µm; p = 0.001), such changes were not observed in the diet-only group (140 ± 35 µm, 142 ± 36 µm; p = NS). Differences in the changes in the percentage lipid volume index (-6.8 ± 8.0% vs. 2.8 ± 9.9%, p = 0.031) and fibrous cap thickness (52 ± 32 µm vs. 2 ± 22 µm, p < 0.001) over time between the pitavastatin and diet groups were highly significant. CONCLUSIONS: Statin treatment induces favorable plaque morphologic changes with an increase in fibrous cap thickness, and decreases in both percentage plaque and lipid volume indexes.

Do drug elution components increase the risk of fracture of sirolimus-eluting stents?

OBJECTIVES: Stent fracture (SF) of sirolimus-eluting stents (SES) has emerged recently in the literature and shown to be associated with an increased risk of restenosis; however, little is known regarding SF after bare-metal stent implantation. We sought to assess whether the use of SES was associated with an increased risk of SF compared with its bare-metal platform, the Bx-velocity stent (BX-BMS). METHODS: A total of 478 lesions in 416 patients undergoing SES implantation and subsequent angiography 6-9 months after the index procedure were compared with 152 lesions in 142 consecutive patients treated with BX-BMS. Stented lesions with total stent-length greater than 40 mm were excluded. RESULTS: There were no significant differences in overall baseline clinical and anatomic features between the SES and BX-BMS groups, or in SF frequencies at 6-9 month follow-up (4.4% for SES and 1.3% for BX-BMS, P= 0.078). In-stent restenosis was observed more often in SF lesions versus non-SF lesions (34.8 vs. 7.7%, P< 0.001) in association with a higher 3-year adverse events rate (27.3 vs. 13.6%, P = 0.076). The risk of SF at 6-9 months was independently associated with total stent length [odds ratio (OR), 2.13; 95% confidence interval (CI), 1.18-3.83; P = 0.012], angulated lesions (OR, 4.25; 95% CI, 1.80-10.00; P = 0.001), and right coronary artery lesions (OR, 3.55; 95% CI, 1.46-8.62; P = 0.005) but not with SES use. CONCLUSION: Stent implantation in right coronary artery lesions, tortuous lesions, and/or longer lesions covered with longer stents, and not SES versus BX-BMS use, may be associated with increased likelihood of SF.

Pentraxin 3 in unstable angina and non-ST-segment elevation myocardial infarction.

PURPOSE: We prospectively investigated the prognostic value of pentraxin 3 (PTX3) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). BACKGROUND: PTX3 may be a useful marker for localized vascular inflammation and damage to the cardiovascular system. Recent studies have shown that plasma PTX3 is elevated in patients with UA/NSTEMI; however, its prognostic value in UA/NSTEMI remains unclear. METHODS: PTX3, high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac troponin I were measured on admission in 204 consecutive patients (mean age of 69 years; 144 males) hospitalized for UA/NSTEMI within 24h (mean of 7.5h) after the onset of chest symptoms. A cardiac event, which was defined as cardiac death, rehospitalization for acute coronary syndrome (ACS), or rehospitalization for worsening heart failure, was monitored for 6 months after admission. RESULTS: A total of 26 (13%) cardiac events occurred during the 6-month follow-up period. In a stepwise Cox regression analysis including 18 well-known clinical and biochemical predictors of ACS outcome, both PTX3 (relative risk 3.86 per 10-fold increment, P=0.01) and NT-proBNP (relative risk 2.16 per 10-fold increment, P=0.02), but not hsCRP, were independently associated with the 6-month cardiac event. The cardiac event rate was higher in patients with increased PTX3 (> or = 3.1ng/mL of median value) than those without (20% vs. 5.8%, P=0.003). A Kaplan-Meier analysis revealed that patients with increased PTX3 had a higher risk for cardiac events than those without (P=0.002). CONCLUSION: PTX3 and NT-proBNP may be potent and independent predictors for 6-month cardiac events in patients hospitalized for UA/NSTEMI within 24h after the onset. Measurement of plasma PTX3 may substantially improve the early risk stratification of patients with UA/NSTEMI.

Cystatin C in acute heart failure without advanced renal impairment.

BACKGROUND: The prognostic value of cystatin C relative to glomerular filtration rate (GFR) estimated by the Modification of Diet in Renal Disease Study (MDRD) equation modified for Japan has not been investigated in acute heart failure patients with normal to moderately impaired renal function. More accurate detection of mild renal impairment might improve the risk stratification of heart failure patients, especially patients with normal to moderately impaired renal function. METHODS: Cystatin C and creatinine levels were measured on admission in 328 consecutive patients hospitalized for worsening chronic heart failure with a GFR estimated by MDRD equation modified for Japan >or=30 mL/min/1.73 m(2). RESULTS: During a median follow-up period of 915 days, there were 52 (16%) cardiac deaths. In stepwise Cox regression analyses including cystatin C and GFR estimated by MDRD equation modified for Japan (either as continuous variables or as variables categorized into quartiles), cystatin C (P <.0001), but not GFR estimated by MDRD equation modified for Japan, was independently associated with cardiac mortality. Adjusted relative risk according to the quartiles of these markers and Kaplan-Meier analyses revealed that the cystatin C was a better marker to separate low-risk from high-risk patients. Furthermore, receiver-operating characteristic curve analyses of these markers revealed that cystatin C showed a higher precision in predicting cardiac mortality. CONCLUSION: Measurements of cystatin C might improve early risk stratification compared with GFR estimated by MDRD equation modified for Japan in acute heart failure patients with normal to moderately impaired renal function.

Restenosis and stent fracture following sirolimus-eluting stent (SES) implantation.

BACKGROUND: Restenosis still occurs, even with the sirolimus-eluting stent (SES), and the precise mechanisms and the impact of stent fracture on restensosis have not yet been elucidated. METHODS AND RESULTS: Intravascular ultrasound (IVUS)-guided SES implantation was performed in 184 lesions in 151 patients with stable and unstable angina. Serial (pre-, post- and follow-up) quantitative coronary angiography analysis was obtained in 169 lesions in 138 patients (angiographic follow-up rate: 91%) and 12-month clinical follow-up was done in all patients. Restenosis occurred in 13 (7.7%) of 169 lesions. Stent fracture occurred in 4 (2.4%) of 169 lesions at follow-up. Of the 13 restenotic lesions, 8 had intimal hyperplasia, 4 had stent fracture, and 1 had late stent thrombosis at 7 months. Although multivariate logistic regression analysis revealed that minimal lumen area (min-LA) post (p=0.027), total stent length (p=0.003) and diabetes (p=0.032) were significant independent predictors of restenosis, univariate analysis showed that stent fracture was more common in the restenosis than in the non-restenosis groups (p=0.001). CONCLUSIONS: Although min-LA post by IVUS, total stent length by QCA and diabetes are independent predictors for angiographic restenosis, stent fracture occurred in 4 lesions (2.4%) and all of them resulted in restenosis (31% of the restenosis). The impact of stent fracture and its potential role in the development of restenosis deserves further study.