Hack-Lyoung Kim

N-acetylcysteine versus AScorbic acid for preventing contrast-induced nephropathy in patients with renal insufficiency undergoing coronary angiography: NASPI study - a prospective randomized controlled trial.

BACKGROUND Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired renal failure and affects mortality and morbidity. There has been no study comparing the efficacy of N-acetylcysteine (NAC) and ascorbic acid that have potential for CIN prevention in patients with renal insufficiency. METHODS We conducted a prospective randomized controlled trial. A total of 212 patients who had pre-existing renal impairment with basal creatinine clearance < or =60 mL/min and/or serum creatinine (SCr) level of > or =1.1 mg/dL, were randomized to have either high-dose NAC (1,200 mg orally twice a day before and on the day of coronary catheterization, n = 106) or ascorbic acid (3 g and 2 g orally before, and 2 g twice after coronary catheterization with a 12-hour interval, n = 106). The primary end point was the maximum increase of SCr level, and the secondary end point was the incidence of CIN. RESULTS The maximum increase of SCr level was significantly lower in NAC group than in ascorbic acid group as follows: -0.03 +/- 0.18 mg/dL versus 0.04 +/- 0.20 mg/mL, respectively (P = .026). Patients with diabetes or who had received a high dose of contrast media experienced significantly less rise of SCr level with NAC than ascorbic acid; in diabetic subgroup, -0.05 +/- 0.22 mg/dL versus 0.09 +/- 0.29 mg/mL, respectively (P = .020); in patients with high dose of dye, -0.03 +/- 0.17 mg/dL versus 0.04 +/- 0.21 mg/mL, respectively (P = .032). The incidence of CIN, the secondary end point, tended to be in favor of NAC rather than ascorbic acid, 1.2% versus 4.4%, respectively (P = .370). Notably, among the diabetes patients, the NAC significantly lowered CIN rate than ascorbic acid, 0% (0/38) versus 12.5% (4/32), respectively (P = .039). CONCLUSION High-dose NAC seems more beneficial than ascorbic acid in preventing contrast-induced renal function deterioration in patients, especially diabetic patients, with renal insufficiency undergoing coronary angiography.

Clinical and Physiological Outcomes of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients With Serial Stenoses Within One Coronary Artery

OBJECTIVES This study was performed to evaluate the physiological and clinical outcomes of fractional flow reserve (FFR)-guided revascularization strategy with drug-eluting stents in serial stenoses within the same coronary artery. BACKGROUND Identifying a functionally significant stenosis is difficult when several stenoses exist within 1 coronary artery. METHODS A total of 131 patients (141 vessels and 298 lesions) with multiple intermediate stenoses within the same coronary artery were assessed by FFR with pullback pressure tracings. In vessels with an FFR <0.8, the stenosis that caused the largest pressure step-up was stented first. Major adverse cardiac events were assessed during follow-up. RESULTS FFR was measured 239 times and there were no procedure-related complications. There was a weak negative correlation between FFR and angiographic percent diameter stenosis (r = -0.282, p < 0.001). In total, 116 stents were implanted and revascularization was deferred in 61.1% (182 of 298) of lesions. When the vessels with an initial FFR <0.8 were divided into 2 groups according to FFR after first stenting (FFR ≥0.8 vs. FFR <0.8), there were no differences in baseline angiographic and physiological parameters between the 2 groups. During the mean follow-up of 501 ± 311 days, there was only 1 target vessel revascularization due to in-stent restenosis. There were no events related to deferred lesions. CONCLUSIONS FFR-guided revascularization strategy using pullback pressure tracing in serial stenoses was safe and effective. This strategy can reduce unnecessary intervention and maximize the benefit of percutaneous coronary intervention with drug-eluting stents in patients with multiple stenoses within 1 coronary artery.

Comparison Among Drug-Eluting Balloon, Drug-Eluting Stent, and Plain Balloon Angioplasty for the Treatment of In-Stent Restenosis : A Network Meta-Analysis of 11 Randomized, Controlled Trials

OBJECTIVES A Bayesian network meta-analysis was performed comparing the efficacy and safety of drug-eluting balloons (DEB), drug-eluting stents (DES), or plain old balloon angioplasty (POBA) for treatment of in-stent restenosis (ISR). BACKGROUND Optimal treatment options for ISR have not been well established. METHODS Randomized, controlled trials comparing DEB, DES, and POBA for the treatment of ISR after percutaneous coronary intervention with bare metal stent or DES were included. The primary outcome was target lesion revascularization (TLR). The pairwise posterior median odds ratio (OR) with 95% credible interval (CrI) was the effect measure. RESULTS This analysis included 2,059 patients from 11 RCTs. The risk of TLR was markedly lower in patients treated with DEB (OR: 0.22, 95% CrI: 0.10 to 0.42) or DES (OR: 0.24, 95% CrI: 0.11 to 0.47) than in those treated with POBA in a random-effects model. In a comparison of DEB and DES, the risk of TLR (OR: 0.92, 95% CrI: 0.43 to 1.90) was similar. The risk of MI or all-cause mortality was lowest in the DEB group compared with the DES and POBA groups, which did not meet statistical significance. The risk of major adverse cardiac events, which was mainly driven by TLR, was also significantly lower in the DEB or and DES group (OR: 0.28, 95% CrI: 0.14 to 0.53) than in the POBA group, but it was similar between the DEB and DES groups (OR: 0.84, 95% CrI: 0.45 to 1.50). The probability of being ranked as the best treatment was 59.9% (DEB), 40.1% (DES), and 0.1% (POBA) in terms of TLR, whereas it was 63.0% (DEB), 35.3% (POBA), and 1.7% (DES) in terms of MI. CONCLUSIONS Local drug delivery by DEB or DES for ISR lesions was markedly better than POBA in preventing TLR, but not for MI or mortality. Among the 2 different strategies of drug delivery for ISR lesions, treatment with DEB showed a trend of less development of MI than did treatment with DES.

Helicobacter pylori Infection is Associated with Elevated Low Density Lipoprotein Cholesterol Levels in Elderly Koreans

This study was conducted to investigate the association between Helicobacter pylori (H. pylori) infection and the lipid profile among elderly Koreans. A total of 462 subjects (mean age 66.2 ± 7.6 yr, 84% males) who underwent health check-up were investigated. Each subject underwent gastroduodenoscopy with gastric mucosal biopsy, and H. pylori infection was determined by histopathological examination using the updated Sydney System score. The presence of H. pylori infection was significantly associated with the elevated serum levels of total cholesterol and low density lipoprotein (LDL) cholesterol (P < 0.05 for each) in univariate analysis. H. pylori infection was not associated with triglyceride and high density lipoprotein (HDL) cholesterol levels (P > 0.05 for each). After controlling confounders, multiple logistic regression analysis showed that the odds ratio of H. pylori infection for high LDL cholesterol level (> 140 mg/dL) was 3.113 (95% confidence interval, 1.364-7.018; P = 0.007). There were no significant associations between the presence of H. pylori infection and elevated total cholesterol levels (> 200 mg/dL) in this model (P = 0.586). The results of this study demonstrate that H. pylori infection is associated with the elevated serum LDL cholesterol levels in elderly Koreans, supporting the hypothesis that H. pylori plays a role in promoting atherosclerosis by modifying lipid metabolism.

Peroxisome proliferator-activated receptor-δ activates endothelial progenitor cells to induce angio-myogenesis through matrix metallo-proteinase-9-mediated insulin-like growth factor-1 paracrine networks

AIMS The roles of peroxisome proliferator-activated receptor (PPAR)-δ in vascular biology are mainly unknown. We investigated the effects of PPAR-δ activation on the paracrine networks between endothelial progenitor cells (EPCs) and endothelial cells (ECs)/skeletal muscle. METHODS AND RESULTS Treatment of EPCs with GW501516, a PPAR-δ agonist, induced specifically matrix metallo-proteinase (MMP)-9 by direct transcriptional activation. Subsequently, this increased-MMP-9 broke down insulin-like growth factor-binding protein (IGFBP)-3, resulting in IGF-1 receptor (IGF-1R) activation in surrounding target cells. Treatment of conditioned medium from GW501516-stimulated EPCs enhanced the number and functions of human umbilical vein ECs and C2C12 myoblasts via MMP-9-mediated IGF-1R activation. Systemic administration of GW501516 in mice increased MMP-9 expression in EPCs, and augmented IGFBP-3 degradation in serum. In a mouse hindlimb ischaemia model, systemic treatment of GW501516 or local transplantation of GW501516-treated EPCs induced IGF-1R phosphorylation in ECs and skeletal muscle in the ischaemic limbs, leading to augmented angiogenesis and skeletal muscle regeneration. It also enhanced wound healing with increased angiogenesis in a mouse skin punch wound model. These pro-angiogenic and muscle-regenerating effects were abolished by MMP-9 knock-out. CONCLUSION Our results suggest that PPAR-δ is a crucial modulator of angio-myogenesis via the paracrine effects of EPCs, and its agonist is a good candidate as a therapeutic drug for patients with peripheral vascular diseases.

The association between arterial stiffness and left ventricular filling pressure in an apparently healthy Korean population

BackgroundThe aim of this study is to investigate the association between arterial stiffness and left ventricular filling pressure in an apparently healthy Korean population.MethodsA total of 115 healthy subjects without known cardiovascular risk factors or overt heart disease who underwent both transthoracic echocardiography and brachial-ankle pulse wave velocity (baPWV) measurement at the same day during their routine check-ups were analyzed.ResultsThe mean age of study subjects was 52.8 ± 8.4 years, and 78 (67.8%) were men. The mean baPWV value was 1,325 ± 185 cm/s. Study subjects were divided into 3 groups according to E/E’ value: subjects with E/E’ < 8, 8–12.9 and E/E’ ≥ 13. As E/E’ increased, baPWV value increased gradually: baPWV in subjects with E/E’ < 8, E/E’ 8–12.9 and E/E’ ≥ 13, were 1,261 ± 163, 1,345 ± 169, 1,569 ± 232 cm/s, respectively (p < 0.001). In multiple linear regression analyses, baPWV was significantly associated with E/E’ (β = 0.371, p < 0.001) after controlling confounders including age, sex and body mass index. In receiver-operating characteristic (ROC) curve analysis, the sensitivity and specificity for detection of E/E’ ≥ 10 were 78.6% and 59.8%, respectively with mean baPWV of 1,282 cm/s as the cut off value. The discriminatory capacity for predicting E/E’ ≥ 10 was improved from an area under the ROC curve of 0.646 with age alone to 0.734 when baPWV was added (p < 0.001).ConclusionsThere is a significant association between baPWV and E/E’ in an apparently healthy Korean population. BaPWV is useful as a simple and non-invasive method for early detection of increased LV filling pressure among these people.

Efficacy of Short-Term High-Dose Statin Pretreatment in Prevention of Contrast-Induced Acute Kidney Injury: Updated Study-Level Meta-Analysis of 13 Randomized Controlled Trials

Background There have been conflicting results across the trials that evaluated prophylactic efficacy of short-term high-dose statin pre-treatment for prevention of contrast-induced acute kidney injury (CIAKI) in patients undergoing coronary angiography (CAG). The aim of the study was to perform an up-to-date meta-analysis regarding the efficacy of high-dose statin pre-treatment in preventing CIAKI. Methods and Results Randomized-controlled trials comparing high-dose statin versus low-dose statin or placebo pre-treatment for prevention of CIAKI in patients undergoing CAG were included. The primary endpoint was the incidence of CIAKI within 2–5days after CAG. The relative risk (RR) with 95% CI was the effect measure. This analysis included 13 RCTs with 5,825 total patients; about half of them (n = 2,889) were pre-treated with high-dose statin (at least 40 mg of atorvastatin) before CAG, and the remainders (n = 2,936) pretreated with low-dose statin or placebo. In random-effects model, high-dose statin pre-treatment significantly reduced the incidence of CIAKI (RR 0.45, 95% CI 0.35–0.57, p<0.001, I2 = 8.2%, NNT 16), compared with low-dose statin or placebo. The benefit of high-dose statin was consistent in both comparisons with low-dose statin (RR 0.47, 95% CI 0.34–0.65, p<0.001, I2 = 28.4%, NNT 19) or placebo (RR 0.34, 95% CI 0.21–0.58, p<0.001, I2 = 0.0%, NNT 16). In addition, high-dose statin showed significant reduction of CIAKI across various subgroups of chronic kidney disease, acute coronary syndrome, and old age (≥60years), regardless of osmolality of contrast or administration of N-acetylcystein. Conclusions High-dose statin pre-treatment significantly reduced overall incidence of CIAKI in patients undergoing CAG, and emerges as an effective prophylactic measure to prevent CIAKI.

SYSTEMIC INFLAMMATION IS ASSOCIATED WITH CORONARY ARTERY CALCIFICATION AND ALL-CAUSE MORTALITY IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Systemic inflammation in chronic kidney disease (CKD) is associated with advanced coronary artery calcification (CAC). However, the prognostic significance of such association is unknown. We assessed if the associations between CAC, estimated glomerular filtration rate (eGFR) and all-cause mortality

Incremental prognostic value of sequential imaging of single-photon emission computed tomography and coronary computed tomography angiography in patients with suspected coronary artery disease

AIMS This study was conducted to investigate the incremental prognostic value of sequential use of single-photon emission computed tomography (SPECT) and coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS A total of 1295 patients with suspected CAD who underwent both CCTA and SPECT within 90 days was retrospectively reviewed in three cardiac centres. Cardiovascular events including cardiac death, non-fatal myocardial infarction, unstable angina, and late (> 90 days of imaging tests) revascularization were assessed. During the mean follow-up period of 795 ± 566 days (median, 735 days), there were 109 events (8.4%). Perfusion defect on SPECT and significant stenosis (≥ 50%) on CCTA were independent predictors for events. Sequential use of both imaging tests significantly improved prediction of the cardiovascular events. The incremental prognostic value of SPECT was significant in patients with stenosis of <90% but not in patients with stenosis of ≥ 90% on CCTA. Similarly, the incremental prognostic value of CCTA was significant in patients with the summed stress score (SSS) <4 but not in patients with SSS ≥ 4 on SPECT. CONCLUSIONS Sequential use of SPECT and CCTA showed an incremental prognostic value in patients with suspected CAD. However, additional benefits were not significant when CCTA revealed stenosis of ≥ 90% or SPECT revealed SSS ≥ 4. These results suggest an effective risk stratification strategy for sequential use of SPECT and CCTA, and maximizing the benefits in these patients.

Chronic Kidney Disease in the Second-Generation Drug-Eluting Stent Era : Pooled Analysis of the Korean Multicenter Drug-Eluting Stent Registry

OBJECTIVES The purpose of this study was to evaluate the clinical impact of chronic kidney disease (CKD) on clinical outcomes in contemporary practice of percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DES). BACKGROUND Although second-generation DES have improved the safety and efficacy issues in PCI, data regarding the performance of second-generation DES in patients with CKD are still limited. METHODS We performed a patient-level pooled analysis on 12,426 patients undergoing PCI using second-generation DES from the Korean Multicenter Drug-Eluting Stent Registry. Endpoints were stent-oriented outcomes (target lesion failure [TLF]) and patient-oriented composite outcomes (POCO) during a median follow-up of 35 months. CKD patients were stratified by the estimated glomerular filtration rate (eGFR) from mild CKD to end-stage renal disease patients, and by the coexistence of diabetes mellitus (DM). RESULTS A total of 2,927 patients had CKD (23.6%), who showed a significantly higher risk of TLF (adjusted hazard ratio [HRadjust]: 1.50; 95% confidence interval [CI]: 1.21 to 1.86) and POCO (HRadjust 1.34; 95% CI: 1.17 to 1.55) compared to patients with preserved renal function. Stratified analysis by eGFR showed that TLF was not increased in the mild to moderate CKD, whereas severe CKD and dialysis-dependent patients showed significantly higher risk of TLF (HRadjust 2.44; 95% CI: 1.54 to 3.86; HRadjust 3.58; 95% CI: 2.52 to 5.08, respectively). The eGFR threshold of increased clinical events was 40 to 45 ml/min/1.73 m2. Among CKD patients, DM CKD patients showed a higher incidence of TLF compared to non-DM CKD patients (HRadjust: 1.82; 95% CI: 1.32 to 2.52), driven by the increase in target vessel-related events. CONCLUSIONS In the era of second-generation DES, CKD patients were at a significantly higher risk of clinical outcomes only in severe CKD and end-stage renal disease patients.