Noriyuki Takeyasu

Association of contrast-induced acute kidney injury with long-term cardiovascular events in acute coronary syndrome patients with chronic kidney disease undergoing emergent percutaneous coronary intervention☆

BACKGROUND The association between contrast-induced acute kidney injury (CI-AKI) and chronic kidney disease (CKD) in patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI) has not been fully reported. We evaluated the association of CI-AKI on cardiovascular events in ACS patients with CKD. METHODS A total of 1059 ACS patients who underwent emergent PCI in our multicenter registry were enrolled (69±12 years, 804 men, 604 STEMI patients). CKD was defined as at least stage 3 CKD, and CI-AKI was defined as an increase of at least 0.5 mg/dL and/or an increase of at least 25% of pre-PCI to post-PCI serum creatinine levels within 1 week after the procedure. Primary endpoints included cardiovascular death, myocardial infarction, and cerebrovascular disorder (stroke or transient ischemic attack). RESULTS In our study, 368 (34.7%) patients had CKD. During follow-up periods (435±330 days), CI-AKI and primary endpoints occurred in 164 (15.5%) patients and 106 (10.0%) patients, respectively. Multivariate Cox proportional hazards model revealed that age, female gender, peak creatinine kinase>4000, IABP use, CI-AKI (hazard ratio [HR], 2.17; 95% confidential interval [CI], 1.52 to 4.00; P<0.001), and CKD (HR, 1.66; 95% CI, 1.01 to 2.72; P=0.046) were independent predictors of primary endpoints. Kaplan-Meier analysis showed that occurrence of primary endpoints increased significantly with an increase in CKD stage, and CI-AKI yielded worse long-term prognosis at every stage of CKD (P<0.001). CONCLUSIONS CI-AKI was revealed to be a significant incremental predictor of cardiovascular events at each stage of CKD in ACS patients.

Association of Sleep-Disordered Breathing and Ventricular Arrhythmias in Patients Without Heart Failure

The prevalence and characteristics of sleep-disordered breathing (SDB) in patients with ventricular arrhythmias, such as premature ventricular complexes and ventricular tachycardia, are unknown. Therefore, this study was conducted to evaluate the prevalence of SDB in patients with severe ventricular arrhythmias and normal left ventricular (LV) function. Thirty-five patients (63% men, mean age 57.4 +/- 13.8 years) underwent a sleep study. All patients had ventricular tachycardia or frequent premature ventricular complexes (>or=300/hour) and had been referred to the cardiology department for medication, catheter ablation therapy, or the implantation of a cardioverter-defibrillator. Patients with heart failure with LV ejection fractions <50% were excluded; in the remaining patients, the mean LV ejection fraction was 63.9 +/- 8.0%. Twenty-one patients (60%) had SDB with apnea-hypopnea indexes >or=5/hour, and the average apnea-hypopnea index was 22.7 +/- 17.9/hour. Twelve patients (34%) had moderate to severe SDB, with an average apnea-hypopnea index of 33.6 +/- 16.6/hour. Central dominant sleep apnea was evident in 3 patients with SDB. The average age and body mass index were significantly higher in patients with SDB than in those without SDB (age 62.0 +/- 12.8 vs 50.6 +/- 12.7 years, body mass index 26.3 +/- 4.0 vs 21.2 +/- 2.0 kg/m2). In conclusion, this study found a high prevalence of SDB in patients with ventricular arrhythmias and normal LV function.

Preventive effect of statin pretreatment on contrast-induced acute kidney injury in patients undergoing coronary angioplasty: Propensity score analysis from a multicenter registry

BACKGROUND The prophylactic benefit of statins in reducing the incidence of contrast-induced acute kidney injury (CI-AKI) has been investigated in several studies with conflicting results. We sought to investigate whether statin pretreatment prevents CI-AKI in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). METHODS A total of 2198 CAD patients who underwent PCI, except for those undergoing dialysis or who died within 7 days after angioplasty, were analyzed from the ICAS (Ibaraki Cardiovascular Assessment Study) multicenter registry. Analyzed subjects were divided into 2 groups according to statin pretreatment: statin pretreatment (n=839) and non-statin pretreatment (n=1359). Selection bias of statin pretreatment was adjusted by propensity score-matching method: pretreatment statin (n=565) and non-statin pretreatment (n=565). CI-AKI was defined as an increase in serum creatinine of ≥ 25% or 0.5mg/dl from baseline within 1 week of contrast medium exposure. RESULTS A total of 192 (8.7%) patients developed CI-AKI. No significant differences were observed in baseline patient characteristics between the statin and non-statin pretreatment groups after propensity score matching. In the propensity score-matched groups, the incidence of CI-AKI was significantly lower in patients with statin pretreatment than in those without statin pretreatment (3.5% vs.10.6%, odds ratio [OR]: 0.31, 95% confidence interval [CI]: 0.18-0.52, P<0.001). Multivariate logistic regression analysis showed that statin pretreatment remained an independent negative predictor of CI-AKI (OR: 0.31, 95% CI: 0.18-0.53, P<0.001) among propensity score-matched subjects. CONCLUSIONS Statin pretreatment was associated with a significant decrease in the risk of CI-AKI in CAD patients undergoing PCI in the ICAS Registry.

Triple Antithrombotic Therapy Is the Independent Predictor for the Occurrence of Major Bleeding Complications Analysis of Percent Time in Therapeutic Range

Background—Triple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention. However, it remains unclear whether good control of percent time in therapeutic range is associated with reduced occurrence of bleeding complications in patients undergoing triple antithrombotic therapy. Methods and Results—This study included 2648 patients (70±11 years; 2037 men) who underwent percutaneous coronary intervention with stent in the Ibaraki Cardiovascular Assessment Study registry and received dual antiplatelet therapy with or without warfarin. Clinical end points were defined as the occurrence of major bleeding complications (MBC), major adverse cardiac and cerebrovascular event, and all-cause death. Among these 2648 patients, 182 (7%) patients received warfarin. After a median follow-up period of 25 months (interquartile range, 15–35 months), MBC had occurred in 48 (2%) patients, major adverse cardiac and cerebrovascular event in 484 (18%) patients, and all-cause death in 206 (8%) patients. Multivariable Cox regression analysis revealed that triple antithrombotic therapy was the independent predictor for the occurrence of MBC (hazard ratio, 7.25; 95% confidence interval, 3.05–17.21; P<0.001). The time in therapeutic range value did not differ between the patients with and without MBC occurrence (83% [interquartile range, 50%–90%] versus 75% [interquartile range, 58%–87%]; P=0.7). However, the mean international normalized ratio of prothrombin time at the time of MBC occurrence was 3.3±2.1. Triple antithrombotic therapy did not have a predictive value for the occurrence of all-cause death (P=0.1) and stroke (P=0.2). Conclusions—Triple antithrombotic therapy predisposes patients to an increased risk of MBC regardless of the time in therapeutic range.

Effect of individual proton pump inhibitors on cardiovascular events in patients treated with clopidogrel following coronary stenting: results from the Ibaraki Cardiac Assessment Study Registry.

Objectives: The aim of this study was to evaluate whether combination therapy of clopidogrel and proton pump inhibitors (PPIs) causes higher numbers of cardiovascular events than clopidogrel alone in Japanese patients. Background: PPIs are often prescribed in combination with clopidogrel following coronary stenting. PPIs are reported to diminish the effect of clopidogrel because both are metabolized by CYP2C19. However, no reports address the effects of PPIs on cardiovascular events following coronary stenting in the Japanese population. Methods: A total of 1,887 patients treated with clopidogrel following coronary stenting were enrolled in the Ibaraki Cardiac Assessment Study (ICAS) registry. All subjects were classified into two groups according to treatment without (n = 819) or with (n = 1,068) PPI. Propensity score analysis matched 1:1 according to treatment without PPI (n = 500) or with PPI (n = 500). Primary endpoint was the composite of all‐cause death or myocardial infarction. Results: No significant difference was observed in the primary endpoint between the group without PPI and the group with PPI (4.6% vs. 4.6%, P = 0.77). In contrast, a significant difference was found between the group without PPI and with PPI in regard to the incidence of gastrointestinal bleeding at the end of the follow‐up period and the specific PPI prescribed (2.4% vs. 0.8%, adjusted HR = 0.30, 95% Confidence interval 0.08‐0.87, P = 0.026) after propensity score matching. Conclusions: No significant association between PPI use and primary endpoint was observed in the Japanese population, whereas PPI use resulted in a significant reduction in the rate of gastrointestinal bleeding.

Gender differences in the association between serum uric acid and prognosis in patients with acute coronary syndrome

BACKGROUND Increased levels of uric acid (UA) have been associated with cardiovascular disease. This association is generally stronger in women than men. However, gender differences in the prognostic value of UA in patients with acute coronary syndrome (ACS) are unknown. We investigated gender differences in the relationship between UA level and the prognosis in patients with ACS. METHOD This was an observational analysis of patients with ACS undergoing percutaneous coronary intervention enrolled in the Ibaraki Cardiac Assessment Study (ICAS) registry. We analyzed 1380 patients (330 women, 1050 men) with ACS who had information on UA. We assessed the association between UA and the incidence of major cardiovascular adverse events (MACE), defined as all-cause death, congestive heart failure, reinfarction, and stroke. Patients were divided according to gender-specific UA quartile. RESULTS The mean UA level in women was significantly lower than that in men (4.9mg/dl vs 5.9mg/dl, p<0.001). After a median duration of follow-up period of 437 days (interquartile range 222-801 days), MACE had occurred in 186 (13%) patients [56 (17%) events in women; 130 (12%) events in men]. Kaplan-Meier analysis for MACE-free survival demonstrated that a higher quartile of UA was associated with MACE in both women and men (p<0.001, p=0.002, respectively). Multivariate Cox regression analysis revealed that the highest quartile of UA, as compared with the lowest quartile of UA, was an independent predictor of MACE in women [hazard ratio (HR), 2.84; 95% CI, 1.19-6.77; p=0.018] but not in men (HR, 1.32; 95% CI, 0.66-2.64; p=0.422). CONCLUSIONS An increased level of UA was associated with MACE more strongly in women than in men with ACS. These results suggest that there are gender differences in the association of UA level with the prognosis in patients with ACS.

Troponin elevation after radiofrequency catheter ablation of atrial fibrillation: Relevance to AF substrate, procedural outcomes, and reverse structural remodeling

BACKGROUND Although radiofrequency ablation creates myocardial necrosis leading to troponin T (TnT) release into the systemic circulation, the significance of TnT elevation after atrial fibrillation (AF) ablation is unknown. OBJECTIVE To demonstrate a possible mechanism of reverse structural remodeling in the left atrium (LA) by evaluating postprocedural TnT elevation. METHODS This study included 106 patients with an enlarged LA (paroxysmal AF, n = 43; persistent AF, n = 63). All patients underwent pulmonary vein isolation alone in the index procedure. Left atrial volume indexed to body surface area (LAVi) was measured by echocardiography before ablation and 6 months after sinus rhythm restoration. Patients were divided into responders (n = 53) and nonresponders (n = 53) based on a cutoff value of 23% reduction in LAVi. The TnT level was measured 12 hours postprocedure. RESULTS LAVi decreased from 43 ± 13 to 33 ± 12 mL/m(2) (P < .0001). The TnT level was higher in responders than in nonresponders (1.31 ± 0.34 μg/L vs 0.88 ± 0.29 μg/L; P < .0001) and correlated linearly with percent reduction in LAVi (R = .54; P < .0001). Also in multivariate analysis, the TnT level was the only independent predictor for responders (odds ratio 90.1; 95% confidence interval 14.95-543.3; P < .0001). The TnT level in patients who required a repeat procedure (n = 30) was lower than that in patients who did not require a repeat procedure only in the persistent AF group (0.92 ± 0.38 μg/L vs 1.16 ± 0.37 μg/L; P = .01). CONCLUSION Greater elevation of the TnT level was related both to favorable outcomes after ablation and to greater reversal of structural remodeling. Postprocedural TnT level may be reflective of the preservation of healthy LA myocardium.

Effect of the Mehran risk score for the prediction of clinical outcomes after percutaneous coronary intervention.

BACKGROUND The association of Mehran risk score (MRS) with long-term prognosis in patients treated with percutaneous coronary intervention (PCI) has not been fully reported. We investigated the association between MRS and clinical outcomes in patients who underwent PCI. METHODS Study subjects comprised 2198 patients treated with PCI from the Ibaraki Cardiovascular Assessment Study multicenter registry, excluding patients receiving hemodialysis or who died within 7 days. We categorized them into 4 groups according to MRS (low-risk: ≤5; medium-risk: 6-10; high-risk: 11-16; and very high-risk: ≥16). Contrast-induced acute kidney injury (CI-AKI) was defined as an increase of 0.5mg/dL or 25% in pre-PCI serum creatinine within 1-week post procedure. We evaluated CI-AKI and major adverse cardiac and cerebrovascular events (MACCE), and defined as all-cause death, myocardial infarction, congestive heart failure, or cerebrovascular disorder (stroke or transient ischemic attack). RESULTS A total of 192 (8.7%) patients developed CI-AKI. At multivariate analysis, odds ratio for CI-AKI was 4.09 (95% CI: 1.72-9.17, p=0.002) in the very high-risk group, 1.49 (95% CI: 0.89-2.42, p=0.120) in the high-risk group, and 1.08 (95% CI: 0.74-1.54, p=0.693) in the medium-risk group, as compared with the low-risk group. MACCE in the very high-risk group was more than 5-fold higher [hazard ratio (HR) 5.40, 95% CI: 2.96-9.28, p<0.001] compared with the low-risk group and was also increased in the high-risk (HR 3.72, CI: 2.59-5.32, p<0.001) and medium-risk groups (HR 1.97, CI: 1.45-2.69, p<0.001). Kaplan-Meier analysis showed that increasing risk for MACCE was seen across the groups as MRS increased (p<0.001). CONCLUSION MRS might provide potentially useful information for prediction of CI-AKI and clinical outcomes after PCI.

Elevated plasma norepinephrine level and sick sinus syndrome in patients with lone atrial fibrillation

Objective Plasma norepinephrine (NE) level can be a guide to mortality in patients with heart failure. This study aimed to evaluate the significance of plasma NE level compared with plasma natriuretic peptides (atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)) levels in patients with atrial fibrillation (AF). Methods Included in this study were 137 consecutive patients referred for catheter ablation of lone AF (paroxysmal in 90 and persistent in 47 patients). Blood samples for measurements of ANP, BNP and NE were drawn in the supine position before the procedure. Results ANP, BNP and NE levels were greater in patients with persistent AF than in patients with paroxysmal AF (median (25th–75th centile)=28 (18–49) vs 69 (36–106), p<0.0001; 28 (15–50) vs 94 (39–156), p<0.0001; and 315 (223–502) vs 382 (299–517) pg/mL, p=0.04, respectively). NE level correlated weakly with ANP and BNP levels (r=0.28 and r=0.23, respectively, p<0.01 for both). BNP and NE levels differed between patients with and without recurrence of AF (55 (26–135) vs 35 (18–64), p=0.005 and 431 (323–560) vs 302 (225–436) pg/mL, p<0.001, respectively). Of note, only NE level was significantly greater in patients with symptomatic sick sinus syndrome (SSS) (n=21) than in those without SSS (560 (466–632) vs 321 (242–437) pg/mL, p<0.0001). Logistic regression analysis showed NE level to be the only independent discriminator for SSS (OR 1.006, 95% CI 1.002 to 1.010, p=0.001). Conclusions An increase in plasma NE level was observed in patients with AF and SSS. Although this implies a pathophysiological link between clinical manifestation of SSS and the autonomic nervous dysfunction, further studies are needed to clarify the mechanisms for this novel finding.

Drug-eluting versus bare-metal stents in large coronary arteries of patients with ST-segment elevation myocardial infarction: Findings from the ICAS registry

BACKGROUND AND PURPOSE There are a few retrospective subgroup analyses or registries of large-vessel (≥ 3.5mm) stenting. We investigated clinical outcomes of patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and bare-metal stents (BMS) in large coronary vessels. METHODS AND SUBJECTS Of 1100 STEMI patients registered in the Ibaraki Cardiovascular Assessment Study (ICAS) multicenter registry from April 2007 to June 2012 who underwent PCI, we enrolled 454 patients (65.8 ± 12.7 years old, 81% male) with ≥ 3.5-mm stents. We excluded 53 patients with cardiogenic shock or left main trunk lesions. The remaining 401 patients were divided into Group-D, PCI with DES (n = 184), and Group-B, PCI with BMS (n = 217). Propensity score analysis matched 1:1 according to treatment with DES (n = 101) or with BMS (n = 101). We evaluated major adverse cardiac and cerebrovascular events (MACCE) and incidence of stent thrombosis (ST). MACCE was defined as all-cause death, myocardial infarction (MI), target-vessel revascularization (TVR), or cerebrovascular accident (CVA). ESSENTIAL RESULTS During a mean follow-up period of 526 days, all-cause death, MI, CVA, MACCE, and ST were not significantly different in Group-D versus Group-B (all-cause death: 4.35% vs. 4.61%, p = 0.90; MI: 0% vs. 0%; CVA: 2.72% vs. 3.23%, p = 0.76; MACCE: 15.2% vs. 20.3%, p = 0.19; and ST: 0.0% vs. 1.38%, p = 0.11). After adjusting for age, insulin use, multivessel disease, intra-aortic balloon pump use, culprit lesions, and estimated glomerular filtration rate <60 ml/min/1.73 m(2), MACCE was not significantly different between the groups (odds ratio: 0.69; 95% CI: 0.40-1.23; p = 0.21). However, TVR was significantly lower in Group-D than Group-B in Kaplan-Meier analysis (p = 0.048) after propensity score matching. PRINCIPAL CONCLUSION There was no advantage to using a DES in large vessels for preventing a hard endpoint, whereas DES use resulted in a significant reduction in TVR in the patients with STEMI in this registry.