Contrast media volume reduction with the DyeVertTM system to prevent acute kidney injury in stable patients undergoing coronary procedures.

BACKGROUND: Contrast associated acute kidney injury (CA-AKI) can lead to an increased risk of adverse events. Contrast media (CM) volume reduction has been advocated as a pivotal strategy to prevent CA-AKI in stable patients undergoing percutaneous coronary procedures. AIMS: To compare the effectiveness of CM volume reduction with the DyeVertTM system versus conventional strategy in reducing the risk of CA-AKI. METHODS: We prospectively collected data from 136 patients with stable coronary artery disease at high risk of CA-AKI treated with left ventricular end diastolic pressure (LVEDP)- guided hydration and undergoing interventions with the use of the DyeVertTM (Osprey Medical Inc.) system. Patients previously enrolled in the LVEDP-guided hydration arm of the "Renal Insufficiency Following Contrast MEDIA Administration triaL III" (REMEDIAL III) were considered as controls. Propensity score was used to perform 1:1 matching to adjust for major confounders. The primary outcome was the occurrence of CA-AKI, as defined by an absolute increase of creatinine values ≥0.3 mg/dL at 48 h. RESULTS: Patients in the DyeVert group were treated with a significant lower CM volume (median: 47.5 vs. 84.0 mL, p < 0.001). The trend in creatinine increase was lower (p = 0.004) and the Δ of creatinine (0-48 h) showed a higher drop (-0.18 vs. -0.10 mg/dL, p = 0.036) in the DyeVert group. The risk of CA-AKI was significantly lower in DyeVert group compared to control group (5.1% vs. 16.8%; odds ratio 0.27, 95% confidence interval [0.12-0.61]). CONCLUSIONS: CM volume reduction with the DyeVertTM system seems to be superior to conventional strategies in reducing the occurrence of CA-AKI.

Urinary Dickkopf-3 and Contrast-Associated Kidney Damage.

BACKGROUND: Administration of iodinated contrast medium (CM) during invasive cardiovascular procedures may be associated with impairment of kidney function. OBJECTIVES: Urinary dickkopf-3 (DKK3), a stress-induced renal tubular epithelium-derived glycoprotein, has been identified as a biomarker predicting both acute kidney injury (AKI) and persistent kidney dysfunction. METHODS: Urinary DKK3/creatinine ratio (uDKK3/uCr), urine and serum neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) and serum cystatin C (sCyC) were assessed in 458 patients with chronic kidney disease scheduled for invasive cardiovascular procedures requiring CM administration with universal adoption of nephroprotective interventions. Contrast-associated AKI (CA-AKI) was defined as serum creatinine increase ≥0.3 mg/dl at 48 h after CM administration. Persistent kidney dysfunction was defined as persistent estimated glomerular filtration rate reduction ≥25% at 1 month compared with baseline. RESULTS: CA-AKI occurred in 64 or the 458 patients (14%), and baseline uDKK3/uCr ≥491 pg/mg was the best threshold for its prediction. Net reclassification improvement (NRI) was significantly increased by adding baseline uDKK3/uCr to the Mehran, Gurm, and National Cardiovascular Data Registry (NCDR) scores (all p < 0.05), and the same applied to integrated discrimination improvement (IDI) when adding uDKK3/uCr to the Gurm and NCDR scores (p < 0.001). Persistent kidney dysfunction occurred in 57 of the 458 patients (12%) and baseline uDKK3/uCr ≥322 pg/mg appeared as the best threshold for its prediction. Adding baseline uDKK3/uCr to the Mehran, Gurm, and NCDR scores significantly increased IDI and NRI (all p < 0.001). CONCLUSIONS: Baseline uDKK3/uCr seems to be a reliable marker for improving the identification of patients with chronic kidney disease undergoing invasive coronary and peripheral procedures at risk for AKI and persistent kidney dysfunction.

Impact of a contrast media volume control device on acute kidney injury rate in patients with acute coronary syndrome.

BACKGROUND: The DyeVert™ system (Osprey Medical Inc., Minnesota, MN) may reduce contrast media (CM) volume during coronary procedures while maintaining fluoroscopic image quality. Here, we assessed whether the use of the DyeVert system reduces acute kidney injury (AKI) rate in patients with acute coronary syndrome (ACS) undergoing invasive coronary procedures. METHODS: ACS patients scheduled for coronary procedure from January 2017 to December 2019 were included. Two groups were identified: (a) Control group (n = 339), including patients in which a conventional manual injection syringe was used; and (b) DyeVert group (n = 112), in which CM injection was handled by the DyeVert™ system. A propensity score matching was performed to reduce the effect of treatment selection bias and potential confounders. In all cases, a low-osmolar, nonionic CM was administered. The primary objective was the rate of AKI, defined as a serum creatinine increase ≥0.3 mg/dl within 72 hr after CM exposure. RESULTS: CM volume was higher in the Control group than in the DyeVert group (130 [120-188] ml vs. 99 [69-136] ml; p <.001). In the DyeVert group the mean percent CM volume saved was 38 ± 13%. AKI occurred in 7/90 patients (8%) in the DyeVert group and in 17/90 (19%) patients in the Control group (odds ratio = 0.37; 95% confidence interval 0.14-0.95; p =.047). CONCLUSIONS: This preliminary result suggests that CM volume reduction obtained by the DyeVert™ system is an effective strategy to prevent AKI in ACS patients undergoing invasive procedure.

Left Ventricular End-Diastolic Pressure Versus Urine Flow Rate-Guided Hydration in Preventing Contrast-Associated Acute Kidney Injury.

OBJECTIVES: This study compared left ventricular end-diastolic pressure (LVEDP)-guided and urine flow rate (UFR)-guided hydration. BACKGROUND: Tailored hydration regimens improve the prevention of contrast-associated acute kidney injury (CA-AKI). METHODS: Between July 15, 2015, and June 6, 2019, patients at high risk for CA-AKI scheduled for coronary and peripheral procedures were randomized to 2 groups: 1) normal saline infusion rate adjusted according to the LVEDP (LVEDP-guided group); and 2) hydration controlled by the RenalGuard System in order to reach UFR ≥300 ml/h (UFR-guided group). The primary endpoint was the composite of CA-AKI (i.e., serum creatinine increase ≥25% or ≥0.5 mg/dl at 48 h) and acute pulmonary edema (PE). Major adverse events (all-cause death, renal failure requiring dialysis, PE, and sustained kidney injury) at 1 month were assessed. RESULTS: The primary endpoint occurred in 20 of 351 (5.7%) patients in the UFR-guided group and in 36 of 351 (10.3%) patients in the LVEDP-guided group (relative risk [RR]: 0.560; 95% confidence interval [CI]: 0.390 to 0.790; p = 0.036). CA-AKI and PE rates in the UFR-guided group and LVEDP-guided group were 5.7% and 10.0% (RR: 0.570; 95% CI: 0.300 to 0.960; p = 0.048), and, respectively, 0.3% and 2.0% (RR: 0.070; 95% CI: 0.020 to 1.160; p = 0.069). Three patients in the UFR-guided group experienced complications related to the Foley catheter. Hypokalemia rate was 6.2% in the UFR-guided group and 2.3% in the LVEDP-guided group (p = 0.013). The 1-month major adverse events rate was 7.1% in the UFR-guided group and 12.0% in the LVEDP-guided group (p = 0.030). CONCLUSIONS: The study demonstrates that UFR-guided hydration is superior to LVEDP-guided hydration to prevent the composite of CA-AKI and PE.

miR-216a Acts as a Negative Regulator of Breast Cancer by Modulating Stemness Properties and Tumor Microenvironment.

Breast cancer is the most frequent malignancy in females in terms of both incidence and mortality. Underlying the high mortality rate is the presence of cancer stem cells, which divide indefinitely and are resistant to conventional chemotherapies, so causing tumor relapse. In the present study, we identify miR-216a-5p as a downregulated microRNA in breast cancer stem cells vs. the differentiated counterpart. We demonstrate that overexpression of miR-216a-5p impairs stemness markers, mammosphere formation, ALDH activity, and the level of Toll-like receptor 4 (TLR4), which plays a significant role in breast cancer progression and metastasis by leading to the release of pro-inflammatory molecules, such as interleukin 6 (IL-6). Indeed, miR-216a regulates the crosstalk between cancer cells and the cells of the microenvironment, in particular cancer-associated fibroblasts (CAFs), through regulation of the TLR4/IL6 pathway. Thus, miR-216a has an important role in the regulation of stem phenotype, decreasing stem-like properties and affecting the cross-talk between cancer cells and the tumor microenvironment.

Renal insufficiency following contrast media administration trial III: Urine flow rate-guided versus left-ventricular end-diastolic pressure-guided hydration in high-risk patients for contrast-induced acute kidney injury. Rationale and design.

BACKGROUND: Urine flow rate (UFR)-guided and left-ventricular end-diastolic pressure (LVEDP)-guided hydration regimens have been proposed to prevent contrast-induced acute kidney injury (CIAKI). The REnal Insufficiency Following Contrast MEDIA Administration triaL III (REMEDIAL III) is a randomized, multicenter, investigator-sponsored trial aiming to compare these two hydration strategies. METHODS: Patients at high risk for CIAKI (that is, those with estimated glomerular filtration rate ≤ 45 mL/min/1.73 m2 and/or with Mehran's score ≥11 and/or Gurm's score >7) will be enrolled. Patients will be randomly assigned to (a) LVEDP-guided hydration with normal saline (LVEDP-guided group) and (b) UFR-guided hydration carried out by the RenalGuard system (RenalGuard group). Seven-hundred patients (350 in each arm) will be enrolled. In the LVEDP-guided group the fluid infusion rate will be adjusted according to the LVEDP as follows: 5 mL kg-1 hr-1 for LVEDP ≤12 mmHg, 3 mL kg-1 hr-1 for LVEDP 13-18 mmHg, and 1.5 mL kg-1 hr-1 for LVEDP >18 mmHg. In the RenalGuard group hydration with normal saline plus low-dose of furosemide is controlled by the RenalGuard system, in order to reach and maintain a high (>300 mL/hr) UFR. In all cases, iobitridol (a low-osmolar, nonionic contrast agent) will be administered. RESULTS: The primary endpoint is the composite of CIAKI (i.e., serum creatinine increase ≥25% and/or ≥0.5 mg/dL from the baseline to 48 hr after contrast media exposure) and/or acute pulmonary edema. CONCLUSION: The REMEDIAL III will test the hypothesis that the UFR-guided hydration is superior to the LVEDP-guided hydration to prevent the composite of CIAKI and/or acute pulmonary edema.

Persistent serum creatinine increase following contrast-induced acute kidney injury.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) may led to both a transient and a persistent serum creatinine (sCr) increase. OBJECTIVES: To assess whether serum cystatin C (sCyC) and urine and serum neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) are useful in the early identification of persistent sCr increase following CI-AKI. METHODS: One hundred and eighteen patients who developed CI-AKI were included into the study. Persistent sCr elevation was defined as a persistent increase ≥0.3 mg dL-1 at 1 month after contrast media (CM) administration. RESULTS: sCr levels recovered in 87 patients (74%; Transient group), whereas a persistent elevation of sCr was observed in the remaining 31 patients (26%; Persistent group). By multivariable logistic regression analysis, independent predictors of persistent sCr increase were insulin therapy, uNGAL at 48 hr and absolute sCr difference between 48 and 72 hr. On the contrary, sCyC assessment did not help in the early identification of this subset of patients. By receiver operating curve analysis, the best cutoff values for predicting persistent sCr increase were uNGAL ≥0.50 ng dL-1 at 48 hr, and the absolute sCr increase ≥0.20 mg dL-1 between 48 and 72 hr. CONCLUSIONS: uNGAL ≥0.50 ng dL-1 at 48 hr and absolute sCr increase ≥0.20 mg dL-1 between 48 and 72 hr but not sCyC are useful in the early identification of patients developing persistent sCr increase after CM administration.

Impact of statin therapy intensity on endothelial progenitor cells after percutaneous coronary intervention in diabetic patients. The REMEDY-EPC late study.

BACKGROUND: A low number (that is, ≤0.0038 per 100 peripheral mononuclear cells) of circulating endothelial progenitor cells (EPC) is common in diabetic patients. Statins increase EPC levels. It is unclear whether intensity of statin therapy has a different impact on EPC levels. METHODS: Diabetic patients undergoing drug-eluting stent (DES) implantation were randomized to 1) High intensity statin therapy (atorvastatin 80mg/day; n=66) or 2) Moderate intensity statin therapy (atorvastatin 20mg/day; n=64). EPC levels were assessed at baseline, 24h and 3months. Endpoints assessed at 3months were 1) changes in the proportion of patients with low EPC levels, and 2) uncovered struts rate and neointima growth evaluated by optical coherence tomography. RESULTS: Low EPC levels rate significantly decreased in the High intensity statin therapy group (from 31.7% to 12.7%; p=0.017) but not in the Moderate intensity statin therapy group (from 25.5% to 21.8%; p=0.81). Uncovered struts rate was similar in the 2 groups (2.4±2.6% vs 2.3±2.2%; p=0.82), whereas mean neointima area and volume were lower in the High intensity statin therapy group (0.68±0.69 vs 1.22±1.29mm2; p=0.001; and, respectively, 13.10±5.77 vs 20.19±24.08mm3; p=0.042). CONCLUSIONS: In diabetic patients, a high intensity statin therapy 1) significantly increases EPC levels and decreases in-stent neointima area and volume, and 2) does not have an impact on the degree of stent re-endothelialization at 3months after DES implantation.

Performance of the XLIMUS Sirolimus-Eluting Coronary Stent in Very Complex Lesions.

INTRODUCTION: Stent delivery failure may occur especially when treating complex coronary artery stenosis. XLIMUS (CARDIONOVUM GmbH, Bonn, Germany) is a new sirolimus-eluting stent (SES) with the following features: 1) cobalt chromium stent platform, with low (73 µm) strut thickness, (2) biodegradable polymer, and 3) potent antiproliferative drug (Sirolimus). Preliminary data suggest that XLIMUS SES may be ideal for the treatment of complex lesions. METHODS: In this registry, we assessed the deliverability, safety, and efficacy of percutaneous coronary interventions (PCI) using the XLIMUS SES in patients undergoing elective PCI in native coronary vessels for complex de novo lesions, including severe calcification, severe tortuosity, and chronic total occlusion. The primary objective of the study is the delivery success of the XLIMUS SES. The secondary objective is the 1-year rate of major adverse cardiac events (MACE; including all-cause death, nonfatal myocardial infarction, and repeat revascularization). RESULTS: A total of 200 consecutive patients with 255 lesions were included. Delivery success was obtained in 196 (98%) patients and in 251 (98.4%) lesions. The XLIMUS SES was successfully implanted on the first attempt with a single guidewire in 176 (88%) patients and in 208 (81.6%) lesions. Additional techniques to facilitate stent delivery (i.e., buddy wire, anchoring-balloon, or GuideLiner catheter) were necessary in 47 (18.4%) lesions. Failure in XLIMUS SES implantation occurred in 4 (1.6%) lesions. MACE rate at 1 year was 9%. CONCLUSIONS: This registry supports the positive performance of the XLIMUS SES in the treatment of complex coronary artery lesions.

RenalGuard system in high-risk patients for contrast-induced acute kidney injury.

BACKGROUND: High urine flow rate (UFR) has been suggested as a target for effective prevention of contrast-induced acute kidney injury (CI-AKI). The RenalGuard therapy (saline infusion plus furosemide controlled by the RenalGuard system) facilitates the achievement of this target. METHODS: Four hundred consecutive patients with an estimated glomerular filtration rate ≤30 mL/min per 1.73 m(2) and/or a high predicted risk (according to the Mehran score ≥11 and/or the Gurm score >7%) treated by the RenalGuard therapy were analyzed. The primary end points were (1) the relationship between CI-AKI and UFR during preprocedural, intraprocedural, and postprocedural phases of the RenalGuard therapy and (2) the rate of acute pulmonary edema and impairment in electrolytes balance. RESULTS: Urine flow rate was significantly lower in the patients with CI-AKI in the preprocedural phase (208 ± 117 vs 283 ± 160 mL/h, P < .001) and in the intraprocedural phase (389 ± 198 vs 483 ± 225 mL/h, P = .009). The best threshold for CI-AKI prevention was a mean intraprocedural phase UFR ≥450 mL/h (area under curve 0.62, P = .009, sensitivity 80%, specificity 46%). Performance of percutaneous coronary intervention (hazard ratio [HR] 4.13, 95% CI 1.81-9.10, P < .001), the intraprocedural phase UFR <450 mL/h (HR 2.27, 95% CI 1.05-2.01, P = .012), and total furosemide dose >0.32 mg/kg (HR 5.03, 95% CI 2.33-10.87, P < .001) were independent predictors of CI-AKI. Pulmonary edema occurred in 4 patients (1%). Potassium replacement was required in 16 patients (4%). No patients developed severe hypomagnesemia, hyponatremia, or hypernatremia. CONCLUSIONS: RenalGuard therapy is safe and effective in reaching high UFR. Mean intraprocedural UFR ≥450 mL/h should be the target for optimal CI-AKI prevention.

Neutrophil Gelatinase-Associated Lipocalin and Contrast-Induced Acute Kidney Injury.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of acute kidney injury (AKI). METHODS AND RESULTS: Urine NGAL and serum NGAL (sNGAL) were assessed at 2, 6, 24, and 48 hours after contrast media (CM) exposure in 458 high-risk patients (development set). Optimal thresholds in predicting contrast-induced AKI (serum creatinine [sCr] increase ≥0.3 mg/dL at 48 hours after CM administration) were identified. Major adverse events (MAE; death, dialysis, nonfatal myocardial infarction, sustained kidney injury, and myocardial revascularization) at 1 year were assessed. In the development set, optimal thresholds for contrast-induced AKI occurred at 6 hours for both urine NGAL (≥20 ng/mL; 97% negative predictive value and 27% positive predictive value) and sNGAL (≥179 ng/mL; 93% negative predictive value and 20% positive predictive value). Furthermore, sNGAL ≥179 ng/mL at 6 hours was an independent predictor of 1-year MAE. 1-year MAE occurred in 27/198 patients (13.5%) with sNGAL <179 ng/mL and sCr <0.3 mg/dL, in 57/193 (29.5%) patients with only sNGAL ≥179 ng/mL, and in 37/67 (55%) patients with sCr ≥0.3 mg/dL. In additional 253 patients (validation set), no patient with urine NGAL <20 ng/mL or sNGAL <179 ng/mL at 6 hours developed contrast-induced AKI. Furthermore, 6/68 (9%) patients with sNGAL <179 ng/mL and sCr increase <0.3 mg/dL had 1-year MAE versus 17/57 (30%) patients with sNGAL ≥179 ng/mL and sCr increase <0.3 mg/dL and 8/16 (50%) patients with sCr increase ≥0.3 mg/dL. CONCLUSIONS: Urine NGAL <20 ng/mL and sNGAL <179 ng/mL at 6 hours are reliable markers for ruling out contrast-induced AKI. sNGAL ≥179 ng/mL at 6 hours predicts 1-year MAE. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098032.

Routine assessment of on-clopidogrel platelet reactivity and gene polymorphisms in predicting clinical outcome following drug-eluting stent implantation in patients with stable coronary artery disease.

OBJECTIVES: This study sought to assess the usefulness of clopidogrel-pathway genotyping and on-treatment platelet reactivity (OTR) testing in predicting major adverse cardiac events (MACE) in stable coronary artery disease (CAD) patients receiving drug-eluting stents (DES) under dual antiplatelet (clopidogrel plus aspirin) therapy. BACKGROUND: The role of pharmacogenetics and OTR in predicting MACE-death, myocardial infarction, or stent thrombosis-in stable CAD patients scheduled for DES implantation is still debated. METHODS: Patients with stable CAD treated by DES implantation (n = 1,432) were genotyped with a TaqMan OpenArray (Applied Biosystems, Carlsbad, California) and assessed for OTR with the VerifyNow P2Y12 test (Accumetrics Inc., San Diego, California). Genes tested were ABCB1, CYP1A2, CYP2B6*9, CYP2C8*3, CYP2C9*2, CYP2C19, CYP3A4, CYP3A5*3, P2RY12, and PON1CYP2C19. High OTR was defined as P2Y12 reaction units ≥230. The endpoint at 12-month follow-up was MACE occurring during antiplatelet therapy. RESULTS: All groups that were stratified for loss-of-function variants of the cytochrome P450 gene CYP2C19 had significant hazard ratios (HR) for MACE (genotypic HR: 1.41, 95% confidence interval [CI]: 1.06 to 1.89, p = 0.01; allelic HR: 1.56, 95% CI: 2.26 to 1.2, p = 0.01). Variants of other clopidogrel-pathway genes were not significantly associated with MACE. When OTR was assessed, clinical significance was found only in high-risk diabetic (HR: 2.11, 95% CI: 1.29 to 3.45, p < 0.001) and chronic kidney disease (HR: 2.03, 95% CI: 1.03 to 4.02, p = 0.04) patients. CONCLUSIONS: CYP2C19 metabolizer status is an independent predictor of MACE after DES implantation and can be used for prognostication in all stable CAD patients. High OTR, as assessed by the VerifyNow P2Y12 test, is an independent predictor of MACE only for high-risk subsets, that is, patients with diabetes or chronic kidney disease.

Assessment of the 9p21.3 locus in severity of coronary artery disease in the presence and absence of type 2 diabetes.

BACKGROUND: The 9p21.3 locus is strongly associated with the risk of coronary artery disease (CAD) and with type 2 diabetes (T2D). We investigated the association of 9p21.3 variants with severity of CAD (defined by the number of vessel diseased [VD]) in the presence and absence of T2D. METHODS: We tested 11 9p21.3-variants for association in a white Italian study (N = 2,908), and carried out replication in 2 independent white populations, a German study (N = 2,028) and a Canadian Study (N=950). SNP association and permutation analyses were conducted. RESULTS: We identified two 9p21.3-variants, rs4977574 (P < 4×10(-4)) and rs2383207 (P < 1.5×10(-3)) that were associated with severity of CAD in subjects without T2D. Association of rs4977574 with severity of CAD was confirmed in the Canadian Study. Results from subgroup analysis among patients with T2D showed an interaction between rs10738610 and T2D with P = 4.82×10(-2). Further investigation showed that rs10738610 (P < 1.99×10(-2)) was found to be significantly associated with severity of CAD in subjects with T2D. CONCLUSIONS: The 9p21.3 locus is significantly associated with severity of CAD. The number of associations of 9p21.3 variants with severity of CAD is variable to the presence and absence of T2D. In a CAD-susceptible region of 115 kb, there is only one variant associated with the severity of coronary vessel disease in the presence of type 2 diabetes.

Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury.

BACKGROUND: The role of statins in the prevention of contrast-induced acute kidney injury (CIAKI) is controversial. METHODS AND RESULTS: First, we investigated the in vivo effects of atorvastatin on CIAKI. Patients with chronic kidney disease enrolled in the Novel Approaches for Preventing or Limiting Events (NAPLES) II trial were randomly assigned to (1) the atorvastatin group (80 mg within 24 hours before contrast media [CM] exposure; n=202) or (2) the control group (n=208). All patients received a high dose of N-acetylcysteine and sodium bicarbonate solution. Second, we investigated the in vitro effects of atorvastatin pretreatment on CM-mediated modifications of intracellular pathways leading to apoptosis or survival in renal tubular cells. CIAKI (ie, an increase >10% of serum cystatin C concentration within 24 hours after CM exposure) occurred in 9 of 202 patients in the atorvastatin group (4.5%) and in 37 of 208 patients in the control group (17.8%) (P=0.005; odds ratio=0.22; 95% confidence interval, 0.07-0.69). CIAKI rate was lower in the atorvastatin group in both diabetics and nondiabetics and in patients with moderate chronic kidney disease (estimated glomerular filtration rate, 31-60 mL/min per 1.73 m(2)). In the in vitro model, pretreatment with atorvastatin (1) prevented CM-induced renal cell apoptosis by reducing stress kinases activation and (2) restored the survival signals (mediated by Akt and ERK pathways). CONCLUSIONS: A single high loading dose of atorvastatin administered within 24 hours before CM exposure is effective in reducing the rate of CIAKI. This beneficial effect is observed only in patients at low to medium risk.

The avantgarde carbostent in patients scheduled for undelayable noncardiac surgery.

Background. Treatment of patients who need coronary revascularization before undelayable non-cardiac surgery is challenging. Methods. We assessed the safety and efficacy of percutaneous coronary interventions (PCI) using the Avantgarde( TM) Carbostent (CID, Italy) in patients undergoing PCI before undelayable non-cardiac surgery. The Multiplate analyzer point-of-care was used to assess residual platelet reactivity. One major cardiac events (MACE, defined as death, myocardial infarction, and stent thrombosis and major bleeding) were assessed. Results. 42 consecutive patients were analyzed. Total stent length ≥25 mm was observed in 16 (37%) patients. Multivessel stenting was performed in 11 (31.5%) patients. Clopidogrel was interrupted 5 days before surgery in 35 patients, whereas it was stopped the day of the surgery in 7 patients. Surgery was performed after 27 ± 9 (7-42) days from PCI. MACE occurred in one patient (2.4%; 95% confidence interval: 0.01-13%), who had fatal acute myocardial infarction 3 days after abdominal aortic aneurysm surgery and 12 days after stent implantation. No case of major bleeding in the postoperative phase was observed. Conclusions. The present pilot study suggests that, although at least 10-14 days of dual antiplatelet therapy remain mandatory, the Avantgarde( TM) stent seems to have a role in patients requiring undelayable surgery.

Nephrotoxicity of contrast media and protective effects of acetylcysteine.

Contrast-induced acute kidney injury (CI-AKI) accounts for approximately 10% of all causes of hospital-acquired renal failure, causes a prolonged in-hospital stay, and represents a powerful predictor of poor early and late outcome. N-acetylcysteine (NAC) is a thiol compound classically known as a mucolytic agent, which is a potent antioxidant that scavenges a wide variety of oxygen-derived-free-radicals and may be capable of preventing acute kidney injury. In the present study, we will review (1) the pathophysiology of the CI-AKI and (2) the experimental and clinical data on the effects of NAC in preventing CI-AKI.

Cystatin C and contrast-induced acute kidney injury.

BACKGROUND: Cystatin C (CyC) is more sensitive than serum creatinine (sCr) to rapidly detect acute changes in renal function. METHODS AND RESULTS: We measured CyC together with sCr in 410 consecutive patients with chronic kidney disease undergoing either coronary and/or peripheral angiography and/or angioplasty. sCr was assessed at baseline and 24 and 48 hours after contrast media exposure. CyC was assessed at baseline and at 24 hours. Major adverse events (including death of any cause and dialysis) at 12 months were assessed. At 48 hours after contrast media exposure, contrast-induced acute kidney injury (defined as a sCr increase > or =0.3 mg/dL) occurred in 34 patients (8.2%). A CyC increase concentration > or =10% at 24 hours after contrast media exposure was detected in 87 patients (21.2%). This was the best CyC cutoff for the early identification of patients at risk for contrast-induced acute kidney injury (negative predictive value=100%; positive predictive value=39.1%). According to the defined cutoffs (that is, increase in CyC > or =10% and sCr > or =0.3 mg/dL), major adverse events occurred in 16 of 297 patients (5.4%) without any cutoffs satisfied (group 1), in 9 of 49 patients (18.4%) with only a CyC increase > or =10% (group 2), and in 9 of 31 patients (29%) with both cutoffs satisfied (group 3). By logistic regression analysis, the independent predictors of major adverse events at 1 year were group 2 (odds ratio=2.52; 95% confidence interval, 1.17 to 5.41; P=0.02), group 3 (odds ratio=4.45; 95% confidence interval, 1.72 to 11.54; P=0.002), and baseline glomerular filtration rate (odds ratio=0.91; 95% confidence interval, 0.88 to 0.95; P<0.001). CONCLUSIONS: In patients with chronic kidney disease, CyC seems to be a reliable marker for the early diagnosis and prognosis of contrast-induced acute kidney injury.

Correlations between progression of coronary artery disease and circulating endothelial progenitor cells.

The pathophysiology of coronary artery disease (CAD) progression is not well understood. Endothelial progenitor cells (EPCs) may have an important role. In the present observational cohort study we assessed the number of circulating EPCs in 136 patients undergoing elective percutaneous coronary intervention and who had at least one major epicardial vessel with a nonsignificant stenosis [<50% diameter stenosis (DS)], and the relationship between plasma EPC levels and the 24-mo progression of the nonsignificant coronary artery lesion. The following cell populations were analyzed: CD34(+), CD133(+), CD34(+)/KDR(+), CD34(+)/VE cadherin(+), and endothelial cell colony-forming units (CFU-ECs). Progression was defined as a >15% DS increase of the objective vessel at follow-up. At 24 mo, 57 patients (42%) experienced significant progression. Independent predictors of disease progression were LDL cholesterol > 100 mg/dl (OR=1.03; 95% CI 1.01-1.04; P=0.001), low plasma levels of CFU-ECs (OR=3.99; 95% CI 1.54-10.37; P=0.005), and male sex (OR=3.42; 95% CI 1.15-10.22; P=0.027). Circulating levels of EPCs are significantly lower in patients with angiographic CAD progression.