Rationale and design of COLchicine On-admission to Reduce inflammation in Acute Coronary Syndrome (COLOR-ACS) study.

AIMS: The aim of the colchicine on-admission to reduce inflammation in acute coronary syndrome (COLOR-ACS) study is to evaluate the effects of the addition of short-term, low-dose colchicine to high-dose atorvastatin in limiting levels of inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: The COLOR-ACS study is a multicenter, randomized, open-label, two-arm trial. Statin-naive patients with NSTE-ACS, scheduled for an early invasive strategy, are randomized on admission to receive standard treatment of atorvastatin 80 mg or standard treatment plus colchicine (1 mg loading dose followed by 0.5 mg/day until discharge). The main exclusion criteria are prior statin and/or colchicine treatment, current treatment with potent inhibitors of CYP3A4, P-glycoprotein or immunosuppressive drugs, known active malignancy, severe kidney, cardiac, liver disease. There is clinical and biochemical follow-up at 30 days after discharge and telephone interview at 6 months. The primary end point is the change in hs-CRP from admission to discharge. Secondary end points include: incidence of acute kidney injury; MB fraction of creatine kinase peak value; glomerular filtration rate change from baseline to 30 days; persistence of hs-CRP ≥2 mg/dl at 30 days; adverse clinical events within 30 days; tolerance to colchicine. CONCLUSION: The COLOR-ACS study will provide evidence on the efficacy of early short-term treatment with colchicine in addition to high-dose atorvastatin compared to atorvastatin alone in ACS patients. The potential anti-inflammatory action of colchicine plus atorvastatin is expected to limit hs-CRP increase with resultant clinical benefits. TRIAL REGISTRATION: ClinicalTrials.gov; NCT05250596.

Bioimpedance-Guided Hydration for the Prevention of Contrast-Induced Kidney Injury: The HYDRA Study.

BACKGROUND: Intravascular volume expansion plays a major role in the prevention of contrast-induced acute kidney injury (CI-AKI). Recommended standard amounts of fluid infusion before procedures do not produce homogeneous responses in subjects with different initial hydration status. OBJECTIVES: The goal of this study was to compare the effect of standard and double intravenous (IV) infusion volumes in patients with low body fluid level, assessed by using bioimpedance vector analysis (BIVA), on the incidence of CI-AKI after elective coronary angiographic procedures. METHODS: A total of 303 patients with low BIVA level on admission were randomized to receive standard volume saline (1 ml/kg/h for 12 h before and after the procedure) or double volume saline (2 ml/kg/h). Patients (n = 715) with an optimal BIVA level received standard volume saline and were included in a prospective registry. The saline infusion was halved in all patients with an ejection fraction <40%. BIVA was repeated immediately before the angiographic procedure in all patients. CI-AKI was defined as an increase in levels of cystatin C ≥10% above baseline at 24 h after contrast administration. RESULTS: The incidence of CI-AKI was significantly lower (11.5% vs. 22.3%; p = 0.015) in patients receiving double volume saline than in those receiving standard volume saline, respectively. Before the angiographic procedure, 50% of the double volume patients achieved the optimal BIVA level compared with only 27.7% in the standard group (p = 0.0001). The findings were consistent in all the pre-specified subgroups excluding patients with a left ventricular ejection fraction <40% (p for interaction = 0.01). CONCLUSIONS: Evaluation of BIVA levels on admission in patients with stable coronary artery disease allows adjustment of intravascular volume expansion, resulting in lower CI-AKI occurrence after angiographic procedures. (Personalized Versus Standard Hydration for Prevention of CI-AKI: A Randomized Trial With Bioimpedance Analysis; NCT02225431).

Impact of time from symptom onset to drug administration on outcome in patients undergoing glycoprotein IIb-IIIa facilitated primary angioplasty (from the EGYPT cooperation).

Contrasting data have been so far reported on facilitation with glycoprotein IIb-IIIa inhibitors (GpIIbIIIa) in patients who underwent primary percutaneous coronary intervention. However, it has been demonstrated a time-dependent composition of coronary thrombus in ST-segment elevation myocardial infarction, with more platelets in the first hours. Subsequently, the benefits of early administration of GpIIbIIIa may be affected by the time from symptoms onset to GpIIbIIIa, that therefore is the aim of this study. Our population is represented by 814 patients who underwent GpIIbIIIa facilitated primary angioplasty included in the Early glycoprotein IIb-IIIa inhibitors in primary angioplasty database. Patients were divided according to quartiles of time from symptom onset to GpIIbIIIa administration (≤65 minutes; 65 to 100 minutes; 101 to 178 minutes; and >178 minutes). Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Time from symptoms onset to GpIIbIIIa was linearly associated with hypertension, diabetes, hypercholesterolemia, and previous myocardial infarction but inversely associated with smoking. Abciximab was more often administrated later from symptoms onset. Time from symptoms onset to GpIIbIIIa was significantly associated with the rate of preprocedural recanalization (thrombolysis in myocardial infarction [TIMI] 2 to 3; p <0.001), postprocedural TIMI 3 flow (p <0.001), the rate of complete ST-segment resolution (p <0.001), and the rate of myocardial blush grade 2 to 3 (p <0.001) and inversely associated with the occurrence of distal embolization (p <0.001). Follow-up data were collected at a median (twenty-fifth to seventy-fifth) of 360 (30 to 1,095) days. A total of 52 patients had died. Time to GpIIbIIIa had a significant impact on mortality (hazard ratio [95% confidence interval] 1.46 [1.11 to 1.92], p = 0.007) that was confirmed after correction for baseline confounding factors (adjusted hazard ratio [95% confidence interval] 1.41 [1.02 to 2.21], p = 0.042). In conclusion, this study showed that in patients who underwent primary angioplasty with upstream GpIIbIIIa, time from symptoms onset to GpIIbIIIa strongly impacts on preprocedural recanalization, distal embolization, myocardial perfusion, and long-term survival.

Impact of advanced age on myocardial perfusion, distal embolization, and mortality patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb-IIIa inhibitors.

Despite mechanical reperfusion, the outcome is still unsatisfactory in elderly patients with ST-segment elevation myocardial infarction (STEMI). The vast majority of studies have been conducted without extensive use of glycoprotein (Gp) IIb-IIIa inhibitors, which have been associated with improved perfusion and survival. Thus the aim of the current study was to evaluate the impact of age on the angiographic and clinical outcome patients with STEMI undergoing primary angioplasty with Gp IIb-IIIa inhibitors. Our population is represented by a total of 1,662 patients undergoing primary angioplasty for STEMI included in 11 randomized trials comparing early versus late administration of Gp IIb-IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. A total of 231 (13.9 %) patients were older than 75 years. Elderly patients showed a larger prevalence of female gender, hypertension, and diabetes, more advanced Killip class at presentation and longer time to treatment, but a smaller prevalence of smoking. All patients were treated with GP IIb-IIIa inhibitors. Elderly patients showed a significantly impaired postprocedural thrombolysis in myocardial infarction (TIMI) flow (TIMI 0-2: 17.7 vs 10.3 %, P = 0.002) and myocardial perfusion (myocardial blush grade 0-1: 38.3 vs 26.5 %, P = 0.001), and higher prevalence of distal embolization (19.2 vs 9.8 %, P < 0.001), whereas no difference was observed in terms of ST-segment resolution. At follow-up, elderly patients showed a significantly higher mortality (3.2 vs 11.0 %, hazard ratio (HR) (95 % confidence interval (CI)) = 3.78 (2.31-6.16), P < 0.001), which was confirmed after adjustment for baseline confounding factors (HR (95 % CI) = 5.01 (2.63-9.55), P < 0.0001). This study showed that among patients with STEMI undergoing primary angioplasty, advanced age is an independent predictor of mortality after primary angioplasty. Higher rates of distal embolization and poor myocardial perfusion, in addition to the worse risk profile, contribute toward explaining the impact of aging on mortality.

[Statin and clopidogrel pharmacological interaction]. / Interazione farmacologica fra statine e clopidogrel.

Antiplatelet therapy with clopidogrel should be administered to patients with acute coronary syndromes and those submitted to percutaneous coronary intervention (PCI) (secondary prevention). Clopidogrel is a pro-drug which requires hepatic cytochrome P450 (CYP) metabolic activation to produce the active metabolite that inhibits platelet aggregation. CYP2C19 and CYP3A4/5 are the principal contributors in the two-step hepatic oxidation of clopidgrel. However, the response to clopidogrel is not uniform; it varies from patients platelet reactivity on standard-dose clopidogrel are at increased risk of recurrence of adverse cardiovascular events. Also drug-drug interactions that influence the function of CYP isoenzymes may affect the response to clopidogrel. Lipophilic statins, such as atorvastatin, are predominantly metabolized by CYP3A4 and may interfere with CYP activation of clopidogrel, contrary to what happens with hydrophilic statins, such as rosuvastin or pravastatin. Recently, it has been shown that in patients who presented post-PCI high on-treatment platelet reactivity on standard-dose clopidogrel during chronic treatment with clopidogrel and low-dose atorvastatin (10 mg), switching to a non-CYP3A4-metabolized statin, such as rosuvastatin or pravastatin, resulted in a significant decrease in platelet reactivity. The clinical benefit of statins is attributed to mulitple mechanisms which go beyond their lipid-lowering effects and include also antithrombotic properties. In particular, atorvastatin inhibits adenosine diphospate and thrombin-induced platelet aggregation. Moreover, pharmacodynamic studies appear to show some synergy between clopidogrel and atorvastatin: the enhancement of clopidogrel effects due to atorvastatin seems to be dose-related and independent of LDL cholesterol reduction. A recent study shows that the addition of high-dose atorvastatin (80mg) for 30 days significantly improves the pharmacodynamic effects of double-dose clopidogrel, reducing platelet reactivity and improving optimal clopidogrel response in statin naïve patients with high-on treatment platelet reactivity on standard-dose clopidogrel. These pharmacodynamic studies suggest that switching to a no CYP3A4-metabolized statin in patients with high on-treatment platelet reactivity on standard-dose clopidogre on chronic treatment with low-dose atorvastatin or administration of high-dose atorvastatin maybe two alternative strategies to avoid possible negative drug-drug interactions and to improve individual patient response to clopidogrel.

Impact of time-to-treatment on myocardial perfusion after primary percutaneous coronary intervention with Gp IIb-IIIa inhibitors.

BACKGROUND: Primary angioplasty has been shown to be superior to thrombolysis. However, previous reports have shown a negative impact of longer time-to-treatment on myocardial perfusion and survival even with mechanical reperfusion. However, these deleterious effects might potentially be overcome by an extensive use of glycoprotein (Gp) IIb-IIIa inhibitors. Thus, the aim of the current study was to evaluate the prognostic role of the interval from symptoms onset to reperfusion in a large cohort of patients undergoing primary angioplasty with Gp IIb-IIIa inhibitors. METHODS: Our population is represented by 1560 patients undergoing primary angioplasty for ST-segment elevation myocardial infarction (STEMI) included in the EGYPT (Early Glycoprotein IIb-IIIa Inhibitors in Primary Angiography) database. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak creatine kinase and creatine kinase-MB (CK-MB). Follow-up data were collected between 30 days and 1 year after primary angioplasty. RESULTS: Time-to-treatment was significantly associated with age and female sex, diabetes and previous myocardial infarction (MI), but inversely related to smoking. Time-to-treatment affected the rate of postprocedural thrombolysis in myocardial infarction (TIMI) 3 flow (P < 0.0001), myocardial blush grade 2-3 (P = 0.052), complete ST-resolution (P < 0.0001) and distal embolization (P = 0.038). This relationship was confirmed after correction for baseline confounding factors for postprocedural TIMI 3 flow (P = 0.008) and complete ST-segment resolution (P = 0.003). Furthermore, time-to-treatment significantly affected enzymatic infarct size, even after correction for baseline confounding factors [odds ratio (OR) 95% confidence interval (95% CI) = 1.002 (1.001-1.003), P = 0.004]. At 208 ±â€Š160 days follow-up, time-to-treatment was associated with a significantly higher mortality (P = 0.006). The impact was confirmed when time-to-treatment was evaluated as a continuous variable (P < 0.001), even after correction for baseline confounding factors [age, sex, diabetes, smoking, hypertension, previous myocardial infarction (MI), preprocedural TIMI 3 flow, multivessel disease, coronary stenting and early Gp IIb-IIIa inhibitors] (P = 0.001). CONCLUSION: This study showed that time-to-treatment is a major determinant of mortality in ST-segment elevation myocardial infarction patients undergoing primary angioplasty. Impaired epicardial and myocardial perfusion and larger infarct size associated with longer ischemia time contribute to explain this finding.

High-dose atorvastatin on the pharmacodynamic effects of double-dose clopidogrel in patients undergoing percutaneous coronary interventions: The ACHIDO (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity) study.

OBJECTIVES: The goal of this study was to investigate the impact of high-dose atorvastatin on the pharmacodynamic (PD) effects of double-dose clopidogrel in statin-naive patients with stable coronary artery disease (CAD) and high-on-treatment platelet reactivity (HTPR) while on standard-dose clopidogrel before percutaneous coronary intervention (PCI). BACKGROUND: Patients with HTPR are at increased risk of adverse cardiovascular events after PCI. High-dose statins improve prognosis in high-risk patients by lipid- and nonlipid-related mechanisms, including antithrombotic effects. METHODS: The ACHIDO (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity) study was a randomized PD study of high-dose (80 mg) atorvastatin in addition to double-dose (150 mg) clopidogrel (atorvastatin group, n = 38) versus double-dose clopidogrel alone (control group, n = 38) in patients with HTPR. HTPR was defined as P2Y(12) reaction units (PRU) ≥235 by the VerifyNow P2Y12 assay. Platelet reactivity was evaluated immediately before PCI and at 10 and 30 days. RESULTS: Patients randomized to atorvastatin had lower PRU values (188 ± 48 vs. 223 ± 53 PRU, p < 0.01; primary endpoint) and HTPR rates (16% vs. 42%, p < 0.01) at 30 days than patients in the control group. Statin treatment (odds ratio [OR]: 3.8, p = 0.011), baseline PRU <298 (OR: 10.7, p = 0.0001), noncarrier status of CYP2C19*2 loss-of-function allele (OR: 2.9, p = 0.043), and age (OR: 0.94, p = 0.032) were variables significantly associated with optimal PD response (PRU <235) at 30 days. No correlations were found between PRU and lipid fractions. CONCLUSIONS: High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in our stable CAD patients with HTPR undergoing PCI (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity [ACHIDO]; NCT01335048).

Impact of preprocedural TIMI flow on myocardial perfusion, distal embolization and mortality in patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb/IIIa inhibitors.

BACKGROUND: Despite optimal epicardial recanalization, primary angioplasty for ST-elevation myocardial infarction (STEMI) is still associated with suboptimal reperfusion in a relatively large proportion of patients. The aim of the current study was to evaluate the impact of preprocedural TIMI flow on myocardial perfusion, distal embolization, and survival among STEMI patients undergoing primary angioplasty with glycoprotein (GP) IIb/IIIa inhibitors. METHODS: Our population is represented by a total of 1637 patients undergoing primary angioplasty for STEMI treated with GP IIb/IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. RESULTS: Poor preprocedural TIMI flow (TIMI 0-1) was observed in 1039 patients (63.5%), and was associated with higher Killip class at presentation (P=.006), longer time-to-treatment (P=.03), less often with early administration of GP IIb/IIIa inhibitors (P<.001), impaired postprocedural epicardial (P=.001) and myocardial perfusion (determined by myocardial blush grade, P<.001 and/or ST-segment resolution (P<.001), and distal embolization (P=.041). At 206 ± 158 days follow-up, poor preprocedural recanalization was associated with a significantly higher mortality (adjusted odds ratio, 0.58; 95% CI, 0.34-0.96; P=.034). CONCLUSION: This study shows that among patients with STEMI undergoing primary angioplasty with GP IIb/IIIa inhibitors, poor preprocedural TIMI flow is associated with higher incidence of distal embolization and impaired epicardial and myocardial perfusion, and significantly higher mortality.

[Contrast-induced nephropathy: the VIKISAFE study group statement]. / Nefropatia da mezzo di contrasto: risoluzioni del gruppo di studio VIKISAFE (VIsipaque KIdney SAfety efFEct).

Contrast-induced nephropathy (CIN) has undergone a significant evolution over the years in terms of epidemiology and diagnostic criteria. At present it is defined as CI-AKI (contrast-induced acute kidney injury) and represents a pathologically relevant event for different disciplines. Thus, a multidisciplinary approach is needed to propose and deploy a common strategy to reduce the incidence of CI-AKI. It seems that the use of isoosmolar non-ionic contrast media such as iodixanol can reduce the nephrotoxic effects. However, since these - still controversial - results have been obtained using various diagnostic criteria, they are difficult to compare and pool together. Common criteria are therefore required. The term acute renal failure has been replaced by acute kidney injury (AKI). Thanks to consensus groups such as ADQI (Acute Dialysis Quality Initiative) and AKIN (Acute Kidney Injury Network) and the development of guidelines by KDIGO, the diagnostic criteria for AKI are well defined. Nevertheless, the possibility to utilize new biomarkers of structural kidney damage such as neutrophil gelatinase-associated lipocalin (NGAL) or cystatin C has introduced the concept that AKI may be diagnosed even in the absence of creatinine elevation or decreased urine output. A re-evaluation of the epidemiology of CI-AKI based on new diagnostic criteria is required. In this paper the results of a collaborative multidisciplinary study group are reported from the perspective of different disciplines including nephrology, cardiology, radiology and pharmacology. The findings in a cohort of cardiac patients undergoing imaging procedures using exclusively the isoosmolar non-ionic contrast medium iodixanol are evaluated according to the RIFLE/AKIN criteria.

Short-term high-dose atorvastatin for periprocedural myocardial infarction prevention in patients with renal dysfunction.

OBJECTIVES: Short-term high-dose atorvastatin administered before percutaneous coronary intervention (PCI) reduces the rate of periprocedural myocardial infarction (pMI) in high-risk patients, such as those with acute coronary syndromes and those with elevated high-sensitivity C-reactive protein. It is unknown whether short-term high-dose administration reduces the rate of pMI in patients with chronic kidney disease. Recently, we observed that in 304 patients with estimated creatinine clearance less than 60 ml/min randomized to receive 80 mg/day of atorvastatin or placebo for 48 h before elective coronary angiography and/or angioplasty, statin administration did not reduce contrast-induced nephropathy (CIN). In this post-hoc analysis, we evaluate the pMI in the subgroup of 161 patients who underwent PCI. METHODS: In all patients, creatine kinase myocardial isoenzyme (CK-MB) [upper reference limit (URL) 5 ng/ml] was assessed before and at 12 and 24 h after PCI. The pMI, defined as CK-MB elevation more than three times the URL, occurred in 27 (17%) patients. RESULTS: The incidence of pMI was 10.4% (of 77 patients) in the atorvastatin and 23% (of 84 patients) in the placebo group (P < 0.05). Multivariate analysis identified the pretreatment with high-dose atorvastatin as an independent predictor of reduced risk of pMI [odds ratio 0.39, 95% confidence interval 0.16-0.96, P < 0.05]. CONCLUSION: This post-hoc analysis shows that short-term high-dose atorvastatin administration reduced pMI in patients with renal dysfunction submitted to elective PCI, but without benefit regarding CIN prevention.

Preprocedural score for risk of contrast-induced nephropathy in elective coronary angiography and intervention.

OBJECTIVES: To develop a simplified scoring system based on preprocedure clinical characteristics to predict contrast-induced nephropathy (CIN) before elective coronary angiography and percutaneous coronary intervention (PCI). BACKGROUND: CIN is associated with increased mortality and morbidity following coronary angiography and PCI and accounts for increased hospital costs. METHODS: Several baseline clinical characteristics of 1218 patients were considered as candidate univariate predictors of CIN (increase > or =0.5 mg/dl in serum creatinine within 5 days after contrast exposure). On the basis of the odds ratio at multivariate logistic regression, seven markers (with weighted scores) were identified as independent correlates of CIN: age at least 73 years (1), diabetes mellitus (2), left ventricular ejection fraction 45% or less (2), baseline serum creatinine value at least 1.5 mg/dl (2), baseline creatinine clearance 44 ml/min or less (2), posthydration creatinine > or = prehydration creatinine value (2) and one procedure effected within the past 72 h (3). RESULTS: CIN occurred in 114 (9.4%) patients [range 1.1-52.1% for a low (< or =3) and very high (> or =9) risk score, respectively]; the odds of CIN increased significantly with each class (Cochran-Armitage chi-square, P < 0.0001) and the risk score allowed us to determine patients with low and high risk for postprocedure CIN (c-statistic = 0.86). These results were reproduced in a validation set. CONCLUSION: Preprocedural clinical risk factors have different influences on the likelihood of CIN. Risk classification based on the most significant parameters can be used to predict CIN before contrast exposure. The simple scoring system proposed here provides a good estimate of the risk of CIN, allowing the interventional team to make adequate adjustment to the procedures.

Usefulness of atorvastatin (80 mg) in prevention of contrast-induced nephropathy in patients with chronic renal disease.

We investigated the efficacy of short-term high-dose atorvastatin in decreasing the risk of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) subjected to coronary angiography and/or angioplasty. CIN occurs in up to 15% of patients with pre-existing CKD and affects clinical outcome. The protective effect of statin therapy against CIN is still controversial. A prospective, single-center study of 304 patients with baseline estimated creatinine clearance <60 ml/min were randomized to receive atorvastatin 80 mg/day or placebo for 48 hours before and 48 hours after contrast medium administration. All patients received intravenous saline hydration and oral N-acetylcysteine 1,200 mg 2 times/day. Iso-osmolar contrast medium was used. CIN was defined as an absolute increase of serum creatinine > or = 0.5 mg/dl within 5 days after the procedure. CIN occurred in 31 patients (10%), 16 (11%) in the placebo group and 15 (10%) in the atorvastatin group (p = 0.86). Mean increase in creatinine was not significantly different in the 2 groups (0.59 + or - 0.17 in placebo group vs 0.72 + or - 0.26 mg/dl in atorvastatin group, p = 0.31). Persistent kidney injury, defined as 1-month increase from baseline creatinine value > or = 25%, was observed in 30% in the placebo group and in 31% in the atorvastatin group (p = 0.58). In conclusion, a short-term administration of high doses of atorvastatin before and after contrast exposure, in addition to standard intravenous hydration and oral N-acetylcysteine, does not decrease CIN occurrence in patients with pre-existing CKD.

Impact of distal embolization on myocardial perfusion and survival among patients undergoing primary angioplasty with glycoprotein IIb-IIIa inhibitors: insights from the EGYPT cooperation.

Even though primary angioplasty is able to obtain TIMI 3 flow in the vast majority of STEMI patients, epicardial recanalization does not guarantee optimal myocardial perfusion, that remain suboptimal in a relatively large proportion of patients. Large interest has been focused in recent years on the role of distal embolization as major determinant of impaired reperfusion. The aim of the current study was to investigate in a large cohort of STEMI undergoing primary angioplasty with Gp IIb-IIIa inhibitors the impact of distal embolization on myocardial perfusion and survival. Our population is represented by patients undergoing primary angioplasty for STEMI included in the EGYPT database. Distal embolization was defined as an abrupt ''cutoff'' in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak CK and CK-MB. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Data on distal embolization were available in a total of 1182 patients (71% of total population). Distal embolization was observed in 132 patients (11.1%). Patients with distal embolization were older (P < 0.001), with larger prevalence of diabetes (P = 0.01), previous MI (P = 0.048) and advanced Killip class at presentation (P = 0.018), abciximab administration (P < 0.001), with a lower prevalence of smoking (P = 0.04). Patients with distal embolization had more often poor preprocedural recanalization (P = 0.061), less often postprocedural TIMI 3 flow (P < 0.001), postprocedural MBG 2-3 (P < 0.001), complete ST-segment resolution (P = 0.021) and larger infarct size (CK-MB: 328 +/- 356 U/l vs. 259 +/- 226 U/l, P = 0.012). The impact of distal embolization on myocardial perfusion was confirmed after correction for baseline confounding factors as evaluated by MBG 2-3 (adjusted OR [95% CI] = 3.14 [2.06-4.77], P < 0.0001) but not complete ST-segment resolution (adjusted OR [95% CI] = 1.23 [0.84-1.92], P = 0.26). At 208 +/- 160 days follow-up, distal embolization was associated with a significantly higher mortality (9.2% vs. 2.7%, HR [95% CI] = 3.41 [1.73-6.71], P < 0.0001), that was confirmed after correction for baseline confounding factors (adjusted HR [95% CI] = 2.23 [1.1-4.7], P = 0.026). This study showed among STEMI patients treated with Gp IIb-IIIa inhibitors, that distal embolization is independently associated with impaired myocardial perfusion and survival.

Sodium bicarbonate versus saline for the prevention of contrast-induced nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention.

OBJECTIVES: The purpose of this study was to compare the efficacy of sodium bicarbonate versus isotonic saline in addition to N-acetylcysteine (NAC) to prevent contrast-induced nephropathy (CIN) in a larger population of patients with renal dysfunction undergoing coronary angiography or intervention. BACKGROUND: Contrast-induced nephropathy accounts for more than 10% of hospital-acquired renal failure. Recent studies suggest that hydration with sodium bicarbonate is more protective than isotonic saline in the prevention of CIN. METHODS: The prospective, single center study included 502 patients with estimated creatinine clearance <60 ml/min, randomized to receive infusion of either saline or sodium bicarbonate before and after iso-osmolar contrast medium administration. All patients received oral NAC 600 mg twice a day. Contrast-induced nephropathy was defined as an absolute increase of serum creatinine > or =0.5 mg/dl measured within 5 days. RESULTS: Contrast-induced nephropathy occurred in 54 patients (10.8%); 25 (10%) were treated with sodium bicarbonate and 29 (11.5%) with saline (p = 0.60). In patients with CIN, the mean increase in creatinine was not significantly different in the 2 study groups (0.9 +/- 0.6 mg/dl vs. 0.7 +/- 0.2 mg/dl, respectively; p = 0.15). Only 2 patients needed temporary hemofiltration. CONCLUSIONS: Hydration with sodium bicarbonate plus NAC before contrast medium exposure is not more effective than hydration with isotonic saline plus NAC for prophylaxis of CIN in patients with moderate-to-severe renal dysfunction. (Sodium Bicarbonate Versus Saline for the Prevention of Contrast-Induced Nephropathy; NCT00606827).

Usefulness of dobutamine Tc-99m sestamibi-gated single-photon emission computed tomography for prediction of left ventricular ejection fraction outcome after coronary revascularization for ischemic cardiomyopathy.

Gated single-photon emission computed tomography (SPECT) imaging allows analysis of myocardial perfusion and assessment of baseline global and regional left ventricular (LV) function and their changes during low-dose dobutamine infusion. The study examined whether the changes in LV ejection fraction induced by dobutamine and evaluated using technetium-99m sestamibi- gated SPECT predict the evolution of ejection fraction after revascularization in patients with ischemic cardiomyopathy. Thirty-seven patients underwent resting and dobutamine nitrate-enhanced sestamibi-gated SPECT before revascularization and baseline-resting sestamibi gated SPECT after intervention to assess global functional changes. A postrevascularization improvement in ejection fraction > or =5 U was defined as significant. At follow-up, ejection fraction increased significantly in 19 patients. According to receiver-operating characteristic curve analysis, an increase in ejection fraction > or =5 U during dobutamine was the optimal cutoff value for predicting a significant postrevascularization improvement, with 79% sensitivity, 78% specificity, and 78% accuracy. A significant correlation was found between dobutamine and postrevascularization ejection fraction (r = 0.85; p <0.0001). The increase in ejection fraction during dobutamine is a good predictor of an improvement in ejection fraction after revascularization. This represents another important diagnostic contribution obtained using gated SPECT imaging for the assessment of myocardial viability in patients with ischemic cardiomyopathy.