Francesco Bellandi

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).

Early glycoprotein IIb–IIIa inhibitors in primary angioplasty (EGYPT) cooperation: an individual patient data meta-analysis

Background: Even though time-to-treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits from early pharmacological reperfusion by glycoprotein (Gp) IIb–IIIa inhibitors are still unclear. The aim of this meta-analysis was to combine individual data from all randomised trials conducted on facilitated primary angioplasty by the use of early Gp IIb–IIIa inhibitors. Methods and results: The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. All randomised trials on facilitation by the early administration of Gp IIb–IIIa inhibitors in ST-segment elevation myocardial infarction (STEMI) were examined. No language restrictions were enforced. Individual patient data were obtained from 11 out of 13 trials, including 1662 patients (840 patients (50.5%) randomly assigned to early and 822 patients (49.5%) to late Gp IIb–IIIa inhibitor administration). Preprocedural Thrombolysis in Myocardial Infarction Study (TIMI) grade 3 flow was more frequent with early Gp IIb–IIIa inhibitors. Postprocedural TIMI 3 flow and myocardial blush grade 3 were higher with early Gp IIb–IIIa inhibitors but did not reach statistical significance except for abciximab, whereas the rate of complete ST-segment resolution was significantly higher with early Gp IIb–IIIa inhibitors. Mortality was not significantly different between groups, although early abciximab demonstrated improved survival compared with late administration, even after adjustment for clinical and angiographic confounding factors. Conclusions: This meta-analysis shows that pharmacological facilitation with the early administration of Gp IIb–IIIa inhibitors in patients undergoing primary angioplasty for STEMI is associated with significant benefits in terms of preprocedural epicardial recanalisation and ST-segment resolution, which translated into non-significant mortality benefits except for abciximab.

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.

Early glycoprotein IIb-IIIa inhibitors in primary angioplasty-abciximab long-term results (EGYPT-ALT) cooperation: individual patient's data meta-analysis.

Summary.  Background: Even although time to treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits are still unclear from early pharmacological reperfusion by glycoprotein (Gp) IIb‐IIIa inhibitors. Therefore, the aim of this meta‐analysis was to combine individual data from all randomized trials conducted on upstream as compared with late peri‐procedural abciximab administration in primary angioplasty. Methods: The literature was scanned using formal searches of electronic databases (MEDLINE and EMBASE) from January 1990 to December 2010. All randomized trials on upstream abciximab administration in primary angioplasty were examined. No language restrictions were enforced. Results: We included a total of seven randomized trials enrolling 722 patients, who were randomized to early (n = 357, 49.4%) or late (n = 365, 50.6%) peri‐procedural abciximab administration. No difference in baseline characteristics was observed between the two groups. Follow‐up data were collected at a median (25th–75th percentiles) of 1095 days (720–1967). Early abciximab was associated with a significant reduction in mortality (primary endpoint) [20% vs. 24.6%; hazard ratio (HR) 95% confidence interval (CI) = 0.65 (0.42–0.98) P = 0.02, Phet = 0.6]. Furthermore, early abciximab administration was associated with a significant improvement in pre‐procedural thrombolysis in myocardial infarction (TIMI) 3 flow (21.6% vs. 10.1%, P < 0.0001), post‐procedural TIMI 3 flow (90% vs. 84.8%, P = 0.04), an improvement in myocardial perfusion as evaluated by post‐procedural myocardial blush grade (MBG) 3 (52.0% vs. 43.2%, P = 0.03) and ST‐segment resolution (58.4% vs. 43.5%, P < 0.0001) and significantly less distal embolization (10.1% vs. 16.2%, P = 0.02). No difference was observed in terms of major bleeding complications between early and late abciximab administration (3.3% vs. 2.3%, P = 0.4). Conclusions: This meta‐analysis shows that early upstream administration of abciximab in patients undergoing primary angioplasty for ST‐segment elevation myocardial infarction (STEMI) is associated with significant benefits in terms of pre‐procedural epicardial re‐canalization and ST‐segment resolution, which translates in to significant mortality benefits at long‐term follow‐up.

Increase of myocardial salvage and left ventricular function recovery with intracoronary abciximab downstream of the coronary occlusion in patients with acute myocardial infarction treated with primary coronary intervention

In this prospective randomized trial on patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI), we hypothesized that abciximab administered intracoronarily, downstream of the coronary occlusion, leads to a greater degree of myocardial salvage and better left ventricular function recovery compared with the usual abciximab administration. Forty‐five consecutive patients with first AMI and infarct‐related artery TIMI flow 0–1 undergoing primary PCI were enrolled. Twenty‐two patients were randomly assigned to the intracoronary treatment and 23 to the usual treatment. The initial perfusion defect, final infarct size, myocardial salvage, salvage index, and left ventricular function recovery were assessed by serial scintigraphic scans performed at admission and 7 days and 1 month after PCI. Angiographic myocardial blush grade, corrected TIMI frame count, and electrocardiographic ST segment elevation reduction were also assessed as markers of myocardial reperfusion. Final infarct size was significantly smaller (P = 0.043) and salvage index significantly higher (P = 0.003) in the intracoronary treatment group as a result of a greater degree of myocardial salvage (P = 0.0001). The increase of left ventricular ejection fraction at 1 month was significantly higher in the intracoronary treatment patients (P = 0.013). The markers of myocardial reperfusion were also significantly better in the intracoronary treatment group. In patients with AMI and occluded infarct‐related artery treated with primary PCI, intracoronary abciximab given just before PCI downstream of the occlusion is associated to a greater degree of myocardial salvage than the usual abciximab protocol. This benefit is mainly related to a substantial reduction in final infarct size, which leads to an improvement in left ventricular ejection fraction. Catheter Cardiovasc Interv 2004;62:186–192.

Persistent Renal Damage after Contrast-Induced Acute Kidney Injury: Incidence, Evolution, Risk Factors and Prognosis

Background— The temporal evolution of renal function in patients with acute kidney injury after contrast medium (CI-AKI) is not well known. The aim of this observational study was to evaluate the incidence, risk factors, and prognostic implications of persistent renal damage (RD) in patients with preexistent moderate-to-severe renal dysfunction. Methods and Results— From June 2003 to March 2008, 3986 patients underwent coronary angiography at our institution; 1490 of 3986 had an estimated creatinine clearance of <60 mL/min and were enrolled. CI-AKI was defined as an absolute increase ≥0.5 mg/dL over baseline serum creatinine within 3 days after the administration of contrast medium (iodixanol). In patients who developed CI-AKI, persistent RD was defined as a relative decrease of creatinine clearance ≥25% over baseline at 3 months. Patients whose creatinine clearance returned to baseline (or nearly) were classified as transient RD. The overall incidence of CI-AKI was 12.1%, and persistent RD occurred in 18.6% of CI-AKI patients. At Cox regression analysis, nephropathy risk score ≥17, left ventricular ejection fraction ⩽30%, and increased value of serum creatinine ≥1.5-fold from baseline within 5 days were found to be significant risk factors for persistent RD. At 5 years, the incidence of death was significantly higher in patients with persistent RD than in both patients with transient RD (P=0.015) and those without CI-AKI (P=0.0001). A similar trend was observed for the combined end point of death, dialysis and cardiovascular events. Conclusions— These results suggest that CI-AKI is not always a transient, benign creatininopathy, but rather a direct cause of worsening renal function. The occurrence of CI-AKI can identify patients at increased risk of cardiovascular events.Background— The temporal evolution of renal function in patients with acute kidney injury after contrast medium (CI-AKI) is not well known. The aim of this observational study was to evaluate the incidence, risk factors, and prognostic implications of persistent renal damage (RD) in patients with preexistent moderate-to-severe renal dysfunction. Methods and Results— From June 2003 to March 2008, 3986 patients underwent coronary angiography at our institution; 1490 of 3986 had an estimated creatinine clearance of <60 mL/min and were enrolled. CI-AKI was defined as an absolute increase ≥0.5 mg/dL over baseline serum creatinine within 3 days after the administration of contrast medium (iodixanol). In patients who developed CI-AKI, persistent RD was defined as a relative decrease of creatinine clearance ≥25% over baseline at 3 months. Patients whose creatinine clearance returned to baseline (or nearly) were classified as transient RD. The overall incidence of CI-AKI was 12.1%, and persistent RD occurred in 18.6% of CI-AKI patients. At Cox regression analysis, nephropathy risk score ≥17, left ventricular ejection fraction ≤30%, and increased value of serum creatinine ≥1.5-fold from baseline within 5 days were found to be significant risk factors for persistent RD. At 5 years, the incidence of death was significantly higher in patients with persistent RD than in both patients with transient RD ( P =0.015) and those without CI-AKI ( P =0.0001). A similar trend was observed for the combined end point of death, dialysis and cardiovascular events. Conclusions— These results suggest that CI-AKI is not always a transient, benign creatininopathy, but rather a direct cause of worsening renal function. The occurrence of CI-AKI can identify patients at increased risk of cardiovascular events. # Clinical Perspective {#article-title-35}

Effects of Hydration in Contrast-Induced Acute Kidney Injury After Primary Angioplasty A Randomized, Controlled Trial

Background— Intravascular volume expansion represents a beneficial measure against contrast-induced acute kidney injury (CI-AKI) in patients undergoing elective angiographic procedures. However, the efficacy of this preventive strategy has not yet been established for patients with ST-elevation–myocardial infarction (STEMI), who are at higher risk of this complication after primary percutaneous coronary intervention (PCI). In this randomized study we investigated the possible beneficial role of periprocedural intravenous volume expansion and we compared the efficacy of 2 different hydration strategies in patients with STEMI undergoing primary PCI. Methods and Results— We randomly assigned 450 STEMI patients to receive (1) preprocedure and postprocedure hydration of sodium bicarbonate (early hydration group), (2) postprocedure hydration of isotonic saline (late hydration group), or (3) no hydration (control group). The primary end point was the development of CI-AKI, defined as an increase in serum creatinine of ≥25% or 0.5 mg/dL over the baseline value within 3 days after administration of the contrast medium. Moreover, we evaluated a possible relationship between the occurrence of CI-AKI and total hydration volume administered. There were no significant differences in baseline clinical, biochemical, and procedural characteristics in the 3 groups. Overall, CI-AKI occurred in 93 patients (20.6%): the incidence was significantly lower in the early hydration group (12%) with respect to both the late hydration group (22.7%) and the control group (27.3%) (P for trend=0.001). In hydrated patients (early and late hydration groups), lower infused volumes were associated with a significant increase in CI-AKI incidence, and the optimal cutoff point of hydration volume that best discriminates patients at higher risk was ⩽960 mL. Conclusions— Adequate intravenous volume expansion may prevent CI-AKI in patients undergoing primary PCI. A regimen of preprocedure and postprocedure hydration therapy with sodium bicarbonate appears to be more efficacious than postprocedure hydration only with isotonic saline. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00770614.

Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation

This study was performed to evaluate, using a randomized double-blind, placebo-controlled protocol, the long-term efficacy and safety of propafenone and sotalol in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation (AF). The maintenance of sinus rhythm in patients with recurrent AF has several potential benefits, the most important being a reduced risk of thromboembolic events. Three hundred patients with recurrent AF (> or = 4 episodes in the last year) and AF at enrollment lasting < 48 hours were randomized to receive either propafenone (mean daily dose 13 +/- 1.5 mg/kg; 102 patients), sotalol (mean daily dose 3 +/- 0.4 mg/kg; 106 patients), or placebo (92 patients). After 1-year follow-up, Kaplan-Meier estimates of the proportion of patients remaining in sinus rhythm were comparable between propafenone (63%) and sotalol (73%) and superior to placebo (35%; p = 0.001 vs both drugs). Symptomatic recurrences occurred later with propafenone and sotalol than with placebo. Nine patients (9%) in the propafenone group, 11 (10%) in the sotalol group, and 3 (3%) in the placebo group discontinued therapy due to adverse effects. Malignant nonfatal arrhythmias due to proarrhythmic effects were documented with sotalol only, and occurred < 72 hours from the beginning of therapy in 4 patients (4%). During recurrences, the ventricular rate was significantly reduced in patients taking propafenone and sotalol (p = 0.001 for both drugs vs placebo). The likelihood of remaining in sinus rhythm during follow-up was higher in younger patients with smaller left atrial size and without concomitant heart disease. In patients with recurrent symptomatic AF, propafenone and sotalol are not significantly different from each other and are superior to placebo in maintaining sinus rhythm at 1 year. Recurrences occur later and tend to be less symptomatic with propafenone and sotalol compared with placebo.

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 ≥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 ≥ 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 (≤3) and very high (≥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 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.