Abstract Background Since uric acid is associated with cardiovascular and renal disease, a treatment to maintain blood uric acid level may be required in patients with hyperuricemia. This study aims ...to evaluate preventive effects of febuxostat, a selective xanthine oxidase inhibitor, on cerebral, cardiovascular, and renal events in patients with hyperuricemia compared to conventional treatment. Methods and results This study is a prospective randomized open-label blinded endpoint study. Patient enrolment was started in November 2013 and was completed in October 2014. The patients will be followed for at least 3 years. The primary endpoint is a composite of cerebral, cardiovascular, and renal events, and all deaths including death due to cerebral, cardiovascular, and renal disease, new or recurring cerebrovascular disease, new or recurring non-fatal coronary artery disease, cardiac failure requiring hospitalization, arteriosclerotic disease requiring treatment, renal impairment, new atrial fibrillation, and all deaths other than cerebral or cardiovascular or renal disease. These events will be independently evaluated by the Event Assessment Committee under blinded information regarding the treatment group. The study was registered at ClinicalTrials.gov with the identifier NCT01984749.
Abstract Background The majority of patients who undergo coronary arteriography are discharged from the hospital on the day of the procedure or on the following day. The aim of this study is to ...investigate whether the change in serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) on the day following cardiac catheterization can predict the development of contrast-induced nephropathy (CIN). Methods This is a multicenter prospective observational study, which consists of 860 patients who underwent cardiac catheterization. We measured SCr and eGFR before cardiac catheterization, on the following day, and 48–72 h post-procedure. Definition of CIN is changes in SCr ≥0.5 mg/dL or ≥25% from baseline 48–72 h after contrast exposure. Results CIN occurred in 40 patients. SCr levels significantly increased from a baseline of 1.55 ± 1.08 mg/dL to 1.79 ± 1.26 mg/dL on the following day in patients with CIN ( p < 0.0001), but significantly decreased from a baseline of 1.21 ± 0.65 mg/dL to 1.18 ± 0.61 mg/dL on the following day in those without CIN ( p < 0.0001). eGFR significantly decreased from a baseline of 47.3 ± 28.3 mL/min/1.73 m2 to 40.6 ± 26.7 mL/min/1.73 m2 on the following day in patients with CIN ( p < 0.0001), but significantly increased from a baseline of 53.1 ± 22.0 mg/dL to 53.6 ± 21.2 mg/dL on the following day in those without CIN ( p = 0.0236). Receiver operating characteristic curve analysis indicated that SCr change ≥0.1 mg/dL area under the curve (AUC) = 0.852, sensitivity 72.5%, specificity 86.1% and eGFR change ≤−1.1 mL/min/1.73 m2 (AUC = 0.789, sensitivity 85.0%, specificity 64.9%) were the best cut-off values for predicting CIN. Multivariate logistic regression showed that a change in SCr ≥0.1 mg/dL odds ratio (OR), 29.3; 95% confidence interval (CI), 10.8–96.2 and change in eGFR ≤−1.1 mL/min/1.73 m2 (OR, 69.7; 95% CI, 13.3–952) were powerful independent predictors of CIN. Conclusions Changes in SCr and eGFR on the day following cardiac catheterization predict the development of CIN.
Abstract 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 48 h after symptom onset. AKI was diagnosed as increase in creatinine ≥0.3 mg/dl or ≥50% within any 48 h after admission. Patients were classified into 3 groups according to the occurrence and timing of AKI: no-AKI, early-AKI (within 48 h after admission) and late-AKI (>48 h). 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.
Abstract Background Several blood tests are commonly used to assess nutritional status, including serum albumin levels (SAL) and lymphocyte counts (LC). The aim of this study is to investigate ...whether nutritional screening on admission can be used to determine risk levels for adverse clinical events in acute heart failure syndrome (AHFS) patients. Methods In 432 consecutive AHFS patients, we measured SAL and LC and prospectively followed the patients for their combined clinical events (all-cause death and re-hospitalization for heart failure) for three years from admission. The classification and regression tree (CART) tool identified the cut-off criteria for SAL and LC to differentiate among patients with different risks of clinical events as 3.5 g/dl and 963/mm3 , respectively. Results The CART tool classified 15.5% patients as high risk, 15.7% as intermediate risk, and 68.8% as low risk. The CART for nutritional status (CART-NS) values were strongly correlated with combined clinical events hazard ratio of 2.13 (low vs high risk), 95% confidence interval of 1.42–3.16, p < 0.001, even after adjusting for plasma brain natriuretic peptide levels. The CART-NS analysis improved the specificity (89.5%) of predictions of clinical outcomes with the comparable sensitivity (36.3%) compared with the use of a single criterion (SAL <3.5 g/dl: 70.2, 42.4% or LC <963/mm3 : 73.4, 41.7%, respectively). Conclusion A substantial proportion of AHFS patients are at risk of malnutrition, and this risk is associated with poor clinical outcomes. We demonstrate that this algorithm for nutritional screening, even in emergency clinical settings, can determine risk levels for further adverse events in AHFS patients.
It remains unclear whether atrial fibrillation (AF) is maintained by the rotor.
We evaluated the role of the rotor and examined its mechanism.
Among 75 patients with AF (60 paroxysmal, 15 persistent ...AF) who underwent 3-dimensional noncontact left atrial mapping during AF, we examined the prevalence and location of rotor activation and elucidated its mechanism. Catheter ablation was performed in a stepwise fashion (linear roof lesion and complex fractionated atrial electrogram ablation after pulmonary vein PV) isolation) until AF termination.
Rotor activation was observed in 11 patients (14.7%; 10 paroxysmal and 1 persistent AF) (tachycardia cycle length 160.0 ± 19.8 ms). Rotors were observed transiently (duration 6128 ± 9094 ms) during AF at the roof (n = 5), septum (n = 3), and ostium of the left superior PV (n = 3). Five rotors circulated in clockwise and 6 in counterclockwise directions. The length of the block line at the center of the rotor was 15.2 ± 6.9 mm. The electrograms at the block line showed low-amplitude multiple deflections (n = 7) or double potentials (n = 4), and the amplitudes during rotor activation were significantly lower than those during sinus rhythm (0.27 ± 0.18 mV vs 1.22 ± 0.92 mV; P < .01). No conduction disturbances were found during sinus rhythm, suggesting that the central line of block was formed functionally. AF was terminated by PV isolation alone without additional lesions in patients with rotors.
Functionally formed rotor activation was observed during AF in a limited number of patients. These rotor activations may not be related to AF maintenance, but rather may reflect a transient organization of random propagation.
Abstract Background Although the positive association between achieved low-density lipoprotein cholesterol (LDL-C) level and the risk of coronary artery disease (CAD) has been confirmed by randomized ...studies with statins, many patients remain at high residual risk of events suggesting the necessity of novel pharmacologic strategies. The combination of ezetimibe/statin produces greater reductions in LDL-C compared to statin monotherapy. Purpose The Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS) trial was aimed at evaluating the effects of ezetimibe addition to atorvastatin, compared with atorvastatin monotherapy, on coronary plaque regression and change in lipid profile in patients with CAD. Methods The study is a prospective, randomized, controlled, multicenter study. The eligible patients undergoing IVUS-guided percutaneous coronary intervention will be randomly assigned to receive either atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily using a web-based randomization software. The dosage of atorvastatin will be increased by titration within the usual dose range with a treatment goal of lowering LDL-C below 70 mg/dL based on consecutive measures of LDL-C at follow-up visits. IVUS will be performed at baseline and 9–12 months follow-up time point at participating cardiovascular centers. The primary endpoint will be the nominal change in percent coronary atheroma volume measured by volumetric IVUS analysis. Conclusion PRECISE-IVUS will assess whether the efficacy of combination of ezetimibe/atorvastatin is noninferior to atorvastatin monotherapy for coronary plaque reduction, and will translate into increased clinical benefit of dual lipid-lowering strategy in a Japanese population.
Abstract Objective The purpose of this study was to examine the cardiovascular protective effects of candesartan in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting ...stents (DESs). Background Candesartan has been reported to reduce cardiovascular events when therapy was started 6 months after PCI with bare-metal stents in patients who survived restenosis. Candesartan started immediately after PCI with DESs was also effective in preventing cardiovascular events. Methods The 4C trial was a multicenter, prospective, randomized, open-label study. A total of 1145 patients at 39 centers in Japan were randomly assigned to receive candesartan plus standard medical treatment or standard medical treatment alone. The primary endpoints were all-cause death, and a composite of non-fatal myocardial infarction (MI), unstable angina pectoris (uAP), congestive heart failure (CHF), and non-fatal cerebrovascular events. The follow-up period was up to 3 years after the index PCI (ClinicalTrials.gov NCT00139386 ). Results The incidence of total death, one of the primary endpoints, was comparable between the two treatment groups (3.8% each, p = 0.9702). Another primary endpoint, non-fatal major cardiovascular events, tended to occur more often in the control group than in the candesartan group (9.2% vs. 12.5%, p = 0.0985). In contrast, candesartan significantly reduced one of the pre-specified secondary endpoints: cardiovascular events that included non-fatal MI, uAP, and CHF (4.4% vs. 6.7%, p = 0.0136). Furthermore, candesartan significantly reduced another secondary endpoint that included cardiovascular events and cardiovascular death (5.0% vs. 7.7%, p = 0.0493). Conclusions The 4C trial showed that candesartan administered immediately after PCI with DESs did not improve the prognosis after the index procedure, but did reduce some cardiac-related events for 3 years.
Abstract Background There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in patients receiving dual antiplatelet therapy (DAPT). Peripheral endothelial ...dysfunction has recently been reported to predict adverse cardiovascular events. We hypothesized that CYP2C19 loss-of-function (LOF) allele carriers with peripheral endothelial dysfunction had worse prognosis. The aim of this study was to evaluate an additive effect of peripheral endothelial dysfunction on clinical outcome following percutaneous coronary intervention (PCI) in patients with a CYP2C19 variant. Methods We enrolled 434 patients on DAPT following PCI. CYP2C19 genotype was examined, and we divided patients into two groups: carriers, who had at least one CYP2C19 LOF allele, and non-carriers. Peripheral endothelial dysfunction was examined using reactive hyperemia-peripheral arterial tonometry index (RHI), and we divided patients into low and high RHI. Thus, subjects were divided into four groups, and clinical events were followed up. Results A total of 55 patients had a cardiovascular event. Kaplan–Meier analysis demonstrated a significantly higher probability of cardiovascular events in carriers with low RHI (log-rank test: p = 0.007). Multivariate Cox proportional hazards analysis identified both CYP2C19 LOF allele possession (hazard ratio (HR): 1.94; 95% confidence interval (CI): 1.1–3.69; p = 0.045) and low RHI (HR: 2.15; 95% CI: 1.22–3.78; p = 0.008) as independent and significant predictors of future cardiovascular events. Conclusions CYP2C19 LOF allele carriers with peripheral endothelial dysfunction were significantly correlated with cardiovascular events. The additional evaluation of peripheral endothelial function along with CYP2C19 polymorphism might improve risk stratification after coronary stent implantation.
Abstract Background Stent thrombosis (ST) has emerged as a severe complication of percutaneous coronary intervention (PCI). Since the occurrence of ST is lower in Japan than Western countries, there ...are few data to predict ST after drug-eluting stent (DES) implantation in Japan. We examined the independent predictors of ST incidence after DES implantation in Japanese patients, including the use of calcium channel blockers (CCBs). Methods and results We used data from the Kumamoto Intervention Conference Study registry. There were 6286 consecutive patients enrolled from June 2008 to March 2011. Among them, we analyzed 3493 patients who underwent DES implantation. The incidence of definite/probable ST throughout a median follow-up period of 364 days was 0.57% (20 patients). There were 8 patients with early ST (within 30 days), 8 patients with late ST (between 31 and 365 days), and 4 patients with very late ST (after 1 year). The frequency of CCB use was significantly lower in ST than non-ST patients (25.0% versus 51.4%, respectively, p = 0.016). Multiple regression analysis showed that longer stent length ( p = 0.034), acute coronary syndrome ( p = 0.039), and the absence of CCB use ( p = 0.046) were significant and independent predictors of ST within 1 year. Conclusions These results suggest that CCB use may be associated with a decreased risk of ST after DES implantation within 1 year in Japanese patients.
Abstract Background Many large-scale clinical trials have confirmed that statins are effective in reducing low-density lipoprotein cholesterol (LDL-C) level, resulting in reducing cardiovascular ...events. Recent studies have focused on the effects of statins on high-density lipoprotein cholesterol (HDL-C). Here we compared the effects of two statins on lipid profile and other metabolic parameters. Methods The study population included 129 patients with stable coronary artery disease, hypercholesterolemia, and hypo-HDL-cholesterolemia (HDL-C < 50 mg/dl). They were randomly allocated to treatment by pitavastatin 2–4 mg/day or atorvastatin 10–20 mg/day and followed-up for 30 months. The primary endpoint was percent changes in HDL-C and adiponectin during the study. The secondary endpoints were percent and absolute changes in markers of glucose metabolism, serum lipids, and apolipoproteins. Results The effects of 30-month treatment with pitavastatin on HDL-C were significantly greater than those of atorvastatin (%change: pitavastatin: 20.1 ± 25.7%, atorvastatin: 6.3 ± 19.8%, p = 0.01; absolute change: pitavastatin: 7.3 ± 9.1 mg/dl, atorvastatin: 2.3 ± 8.0 mg/dl, p = 0.02). A similar trend was seen with regard to apolipoprotein-AI (ApoAI) (%change: pitavastatin: 20.8 ± 19.3%, atorvastatin: 11.4 ± 17.6%, p = 0.03; absolute change: pitavastatin: 23.1 ± 20.2 mg/dl, atorvastatin: 12.1 ± 19.4 mg/dl, p = 0.02). Treatment with pitavastatin, but not atorvastatin, significantly increased adiponectin levels. Neither statin had a significant effect on hemoglobin A1c. No severe adverse events were registered during the study. Conclusion Long-term treatment with pitavastatin resulted in significantly greater increases in serum HDL-C and ApoAI levels without adverse effects on glucose metabolism, compared with atorvastatin.
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