Mitochondrial Biomarkers in Patients with ST-Elevation Myocardial Infarction and Their Potential Prognostic Implications: A Prospective Observational Study.

BACKGROUND: Mitochondrial biomarkers have been investigated in different critical settings, including ST-elevation myocardial infarction (STEMI). Whether they provide prognostic information in STEMI, complementary to troponins, has not been fully elucidated. We prospectively explored the in-hospital and long-term prognostic implications of cytochrome c and cell-free mitochondrial DNA (mtDNA) in STEMI patients undergoing primary percutaneous coronary intervention. METHODS: We measured cytochrome c and mtDNA at admission in 466 patients. Patients were grouped according to mitochondrial biomarkers detection: group 1 (-/-; no biomarker detected; n = 28); group 2 (-/+; only one biomarker detected; n = 283); group 3 (+/+; both biomarkers detected; n = 155). A composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema was the primary endpoint. Four-year all-cause mortality was the secondary endpoint. RESULTS: Progressively lower left ventricular ejection fractions (52 ± 8%, 49 ± 8%, 47 ± 9%; p = 0.006) and higher troponin I peaks (54 ± 44, 73 ± 66, 106 ± 81 ng/mL; p = 0.001) were found across the groups. An increase in primary (4%, 14%, 19%; p = 0.03) and secondary (10%, 15%, 23%; p = 0.02) endpoint rate was observed going from group 1 to group 3. The adjusted odds ratio increment of the primary endpoint from one group to the next was 1.65 (95% CI 1.04-2.61; p = 0.03), while the adjusted hazard ratio increment of the secondary endpoint was 1.55 (95% CI 1.12-2.52; p = 0.03). The addition of study group allocation to admission troponin I reclassified 12% and 22% of patients for the primary and secondary endpoint, respectively. CONCLUSIONS: Detection of mitochondrial biomarkers is common in STEMI and seems to be associated with in-hospital and long-term outcome independently of troponin.

Impact of Glomerular Filtration Rate on the Incidence and Prognosis of New-Onset Atrial Fibrillation in Acute Myocardial Infarction.

BACKGROUND: Atrial fibrillation (AF) is a frequent complication of acute myocardial infarction (AMI) and is associated with a worse prognosis. Patients with chronic kidney disease are more likely to develop AF. Whether the association between AF and glomerular filtration rate (GFR) is also true in AMI has never been investigated. METHODS: We prospectively enrolled 2445 AMI patients. New-onset AF was recorded during hospitalization. Estimated GFR was estimated at admission, and patients were grouped according to their GFR (group 1 (n = 1887): GFR >60; group 2 (n = 492): GFR 60-30; group 3 (n = 66): GFR <30 mL/min/1.73 m2). The primary endpoint was AF incidence. In-hospital and long-term (median 5 years) mortality were secondary endpoints. RESULTS: The AF incidence in the population was 10%, and it was 8%, 16%, 24% in groups 1, 2, 3, respectively (p < 0.0001). In the overall population, AF was associated with a higher in-hospital (5% vs. 1%; p < 0.0001) and long-term (34% vs. 13%; p < 0.0001) mortality. In each study group, in-hospital mortality was higher in AF patients (3.5% vs. 0.5%, 6.5% vs. 3.0%, 19% vs. 8%, respectively; p < 0.0001). A similar trend was observed for long-term mortality in three groups (20% vs. 9%, 51% vs. 24%, 81% vs. 50%; p < 0.0001). The higher risk of in-hospital and long-term mortality associated with AF in each group was confirmed after adjustment for major confounders. CONCLUSIONS: This study demonstrates that new-onset AF incidence during AMI, as well as the associated in-hospital and long-term mortality, increases in parallel with GFR reduction assessed at admission.

Reduced Cardio-Renal Function Accounts for Most of the In-Hospital Morbidity and Mortality Risk Among Patients With Type 2 Diabetes Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: ST-segment elevation myocardial infarction (STEMI) patients with type 2 diabetes mellitus (DM) have higher in-hospital mortality than those without. Since cardiac and renal functions are the main variables associated with outcome in STEMI, we hypothesized that this prognostic disparity may depend on a higher rate of cardiac and renal dysfunction in DM patients. RESEARCH DESIGN AND METHODS: We retrospectively analyzed 5,152 STEMI patients treated with primary angioplasty. Left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were evaluated at hospital admission. The primary end point was in-hospital mortality. A composite of in-hospital mortality, cardiogenic shock, and acute kidney injury was the secondary end point. RESULTS: There were 879 patients (17%) with DM. The incidence of LVEF ≤40% (30% vs. 22%), eGFR ≤60 mL/min/1.73 m2 (27% vs. 18%), or both (12% vs. 6%) was higher (P < 0.001 for all comparisons) in DM patients. In-hospital mortality was higher in DM patients than in non-DM patients (6.1% vs. 3.5%; P = 0.002), with an unadjusted odds ratio (OR) of 1.81 (95% CI 1.31-2.49; P < 0.001). However, DM was no longer associated with an increased mortality risk after adjustment for cardiac and renal function (OR 1.03, 95% CI 0.68-1.56; P = 0.89). A similar behavior was observed for the secondary end point, with an unadjusted OR for DM of 1.52 (95% CI 1.25-1.85; P < 0.001) and an OR after adjustment for cardiac and renal function of 1.07 (95% CI 0.85-1.36; P = 0.53). CONCLUSIONS: The study indicates that the increased in-hospital mortality and morbidity of DM patients with STEMI is mainly driven by their underlying cardio-renal dysfunction.

Acute Kidney Injury in Diabetic Patients With Acute Myocardial Infarction: Role of Acute and Chronic Glycemia.

BACKGROUND: In acute myocardial infarction, acute hyperglycemia is a predictor of acute kidney injury (AKI), particularly in patients without diabetes mellitus. This emphasizes the importance of an acute glycemic rise rather than glycemia level at admission. We investigated whether, in diabetic patients with acute myocardial infarction, the combined evaluation of acute and chronic glycemic levels may have better prognostic value for AKI than admission glycemia. METHODS AND RESULTS: At admission, we prospectively measured glycemia and estimated average chronic glucose levels (mg/dL) using glycosylated hemoglobin (HbA1c), according to the following formula: 28.7×HbA1c (%)-46.7. We evaluated the association with AKI of the acute/chronic glycemic ratio and of the difference between acute and chronic glycemia (ΔA-C). We enrolled 474 diabetic patients with acute myocardial infarction. Of them, 77 (16%) experienced AKI. The incidence of AKI increased in parallel with the acute/chronic glycemic ratio (12%, 14%, 22%; P=0.02 for trend) and ΔA-C (13%, 13%, 23%; P=0.01) but not with admission glycemic tertiles (P=0.22). At receiver operating characteristic analysis, the acute/chronic glycemic ratio (area under the curve: 0.62 [95% confidence interval, 0.55-0.69]; P=0.001) and ΔA-C (area under the curve: 0.62 [95% confidence interval, 0.54-0.69]; P=0.002) accurately predicted AKI, without difference in the area under the curve between them (P=0.53). At reclassification analysis, the addition of the acute/chronic glycemic ratio and ΔA-C to acute glycemia allowed proper AKI risk prediction in 16% of patients. CONCLUSIONS: In diabetic patients with acute myocardial infarction, AKI is better predicted by the combined evaluation of acute and chronic glycemic values than by assessment of admission glycemia alone.

Impact of Chronic Antiplatelet Therapy on Infarct Size and Bleeding in Patients With Acute Myocardial Infarction.

BACKGROUND: Patients hospitalized with acute myocardial infarction (AMI) are often on prior single antiplatelet therapy (SAPT) or a dual antiplatelet therapy (DAPT). Whether chronic SAPT or DAPT is beneficial or associated with an increased risk in AMI is still controversial. METHODS AND RESULTS: We prospectively enrolled 1718 consecutive patients with AMI (798 ST-segment elevation myocardial infarction and 920 non-ST-segment elevation myocardial infarction) who were divided according to their chronic APT (no APT, SAPT, or DAPT). The study primary end point was the infarct size, as estimated by troponin I peak. Incidence of major bleeding was also evaluated. Five hundred thirty-six (31%) patients were on chronic SAPT and 215 (13%) on DAPT. A graded increase in Global Registry of Acute Coronary Events (GRACE) and Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) risk scores was found going from patients without APT to those with DAPT, while a progressive smaller troponin I peak was observed with the increasing number of chronic antiplatelet agents (11.2 [interquartile range: 2-45] ng/mL, 6.6 [1-33] ng/mL, and 4.1 [1-24] ng/mL; P < .001 for trend). This result was maintained after adjustment for baseline ischemic risk profile (GRACE score) and other major confounders ( P < .001). The incidence of bleeding was higher in patients on chronic APT than in those without APT (5.2% vs 2.4%; P = .002). However, when the bleeding risk was adjusted for the CRUSADE risk score, chronic SAPT (odds ratio [OR]: 1.40, 95% confidence interval [CI]: 0.77-2.53) and DAPT (OR: 0.70, 95% CI: 0.29-1.70) were not associated with an increased bleeding risk. CONCLUSION: In patients with AMI, chronic APT is associated with higher baseline ischemic and bleeding risks. Despite this and unexpectedly, they have a smaller infarct size and similar adjusted bleeding risk.

Prognostic Value of the Acute-to-Chronic Glycemic Ratio at Admission in Acute Myocardial Infarction: A Prospective Study.

OBJECTIVE: Acute hyperglycemia is a powerful predictor of poor prognosis in acute myocardial infarction (AMI), particularly in patients without diabetes. This emphasizes the importance of an acute glycemic rise rather than glycemia level at admission alone. We investigated in AMI whether the combined evaluation of acute and chronic glycemic levels, as compared with admission glycemia alone, may have a better prognostic value. RESEARCH DESIGN AND METHODS: We prospectively measured admission glycemia and estimated average chronic glucose levels (mg/dL) by the following formula: [(28.7 × glycosylated hemoglobin %) - 46.7], and calculated the acute-to-chronic (A/C) glycemic ratio in 1,553 consecutive AMI patients (mean ± SD age 67 ± 13 years). The primary end point was the combination of in-hospital mortality, acute pulmonary edema, and cardiogenic shock. RESULTS: The primary end point rate increased in parallel with A/C glycemic ratio tertiles (5%, 8%, and 20%, respectively; P for trend <0.0001). A parallel increase was observed in troponin I peak value (15 ± 34 ng/mL, 34 ± 66 ng/mL, and 68 ± 131 ng/mL; P < 0.0001). At multivariable analysis, A/C glycemic ratio remained an independent predictor of the primary end point and of troponin I peak value, even after adjustment for major confounders. At reclassification analyses, A/C glycemic ratio showed the best prognostic power in predicting the primary end point as compared with glycemia at admission in the entire population (net reclassification improvement 12% [95% CI 4-20]; P = 0.003) and, particularly, in patients with diabetes (27% [95% CI 14-40]; P < 0.0001). CONCLUSIONS: In AMI patients with diabetes, A/C glycemic ratio is a better predictor of in-hospital morbidity and mortality than glycemia at admission.

Renal replacement therapy in patients with acute myocardial infarction: Rate of use, clinical predictors and relationship with in-hospital mortality.

OBJECTIVES: We evaluated the rate of use, clinical predictors, and in-hospital outcome of renal replacement therapy (RRT) in acute myocardial infarction (AMI) patients. METHODS: All consecutive AMI patients admitted to the Coronary Care Unit between January 1st, 2005 and December 31st, 2015 were identified through a search of our prospectively collected clinical database. Patients were grouped according to whether they required RRT or not. RESULTS: Two-thousand-eight-hundred-thirty-nine AMI patients were included. Eighty-three (3%) AMI patients underwent RRT. Variables confirmed at cross validation analysis to be associated with RRT were: admission creatinine >1.5mg/dl (OR 16.9, 95% CI 10.4-27.3), cardiogenic shock (OR 23.0, 95% CI 14.4-36.8), atrial fibrillation (OR 8.6, 95% CI 5.5-13.4), mechanical ventilation (OR 22.6, 95% CI 14.2-36.0), diabetes mellitus (OR 4.8, 95% CI 3.1-7.4), and left ventricular ejection fraction <40% (OR 9.1, 95% CI 5.6-14.7). The AUC for RRT with the combination of these predictors was 0.96 (95% CI 0.94-0.97; P<0.001). In-hospital mortality was significantly higher in RRT patients (41% vs. 2.1%, P<0.001). Oligoanuria as indication for RRT (OR 5.1, 95% CI 1.7-15.4), atrial fibrillation (OR 4.3, 95% CI 1.6-11.5), mechanical ventilation (OR 20.8, 95% CI 6.1-70.4), and cardiogenic shock (OR 12.9, 95% CI 4.4-38.3) independently predicted mortality in RRT-treated patients. The AUC for in-hospital mortality prediction with the combination of these variables was 0.92 (95% CI 0.87-0.98; P<0.001). CONCLUSIONS: Patients with AMI undergoing RRT had strikingly high in-hospital mortality. Use of RRT and its associated mortality were accurately predicted by easily obtainable clinical variables.

Acute Kidney Injury Definition and In-Hospital Mortality in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Acute kidney injury (AKI) has been associated with increased mortality in ST-segment elevation myocardial infarction. We compared the mortality predictive accuracy of the 3 AKI definitions used most widely for patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: We included 3771 patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention at 2 Italian hospitals. AKI incidence was evaluated according to creatinine increases of ≥25% (AKI-25), ≥0.3 mg/dL (AKI-0.3), and ≥0.5 mg/dL (AKI-0.5). The primary end point was in-hospital mortality. Overall, 557 (15%), 522 (14%), and 270 (7%) patients developed AKI-25, AKI-0.3, and AKI-0.5, respectively (P<0.01). All AKI definitions independently predicted in-hospital mortality (adjusted odds ratio 4.9 [95% CI 3.1-7.8], 5.4 [95% CI 3.3-8.6], and 8.3 [95% CI 5.1-13.3], respectively; P<0.01 for all). At receiver operating characteristic analysis, the addition of each AKI definition to combined clinical predictors of mortality (age, sex, left ventricular ejection fraction, admission creatinine, creatine kinase-MB peak) found at stepwise analysis significantly improved mortality prognostication (area under the curve increased from 0.89 for clinical predictor combination alone to 0.92 for AKI-25, 0.92 for AKI-0.3, and 0.93 for AKI-0.5; P<0.01 for all). At reclassification analysis, AKI-0.5 added to clinical predictors, provided the highest score in mortality (net reclassification improvement +10% versus AKI-0.3 [P=0.01] and +8% versus AKI-25 [P=0.05]). CONCLUSIONS: Each AKI definition significantly improved the mortality prediction beyond major clinical variables. AKI-0.5 showed a mortality discrimination advantage, suggesting it should be the preferred definition in studies addressing ST-segment elevation myocardial infarction and focusing on short-term mortality.

B-type natriuretic peptide levels in patients with pericardial effusion undergoing pericardiocentesis.

OBJECTIVES: Pericardial effusion is characterized by progressive accumulation of fluid within the pericardial space, resulting in increased intra-pericardial pressure and compression of the heart. As B-type natriuretic peptide (BNP) is secreted by the ventricles in response to increased myocardial stretch, we hypothesized that pericardial effusion, as well as its resolution, might influence BNP plasma levels. METHODS: We prospectively measured, in 146 consecutive patients with pericardial effusion, BNP plasma levels at baseline, soon after, and 24h after pericardiocentesis. A scoring system based on 7 clinical and echocardiographic parameters was developed, and patients were classified according to the number of variables as having low (0-2), intermediate (3-4), or high (5-7) severity score. RESULTS: Out of the 146 patients, 42 (29%) had normal values (<100pg/ml), whereas 104 (71%) had high BNP values at baseline. In the whole population, baseline BNP levels significantly decreased as the severity score increased (r=-0.21; P=0.01). 24h after pericardiocentesis, a significant increase in BNP was observed in patients with intermediate (P=0.004) score and with high (P<0.001) severity score; no increase occurred in low score patients (P=0.56). The higher was the severity score, the steeper was the increase in BNP through the three time-points considered (P=0.04). CONCLUSIONS: The results of the present study show that BNP plasma levels are suppressed in the presence of severe pericardial effusion, and that they rise after pericardiocentesis. Future studies should investigate the role of BNP in assisting clinicians in the decision-making process of pericardial fluid drainage.

[Mild therapeutic hypothermia for the treatment of cardiac arrest and acute myocardial infarction]. / Ipotermia terapeutica moderata nel trattamento dell'arresto cardiocircolatorio e dell'infarto miocardico acuto.

Mild therapeutic hypothermia improves neurological outcomes after cardiac arrest by preserving brain function. It is currently under discussion the possibility that hypothermia may also provide a protective effect on cardiac function, in particular, by reducing the infarct size in patients with acute myocardial infarction complicated by cardiac arrest. Despite encouraging experimental and clinical data obtained so far may suggest a potential future indication in this population, routine use of therapeutic hypothermia in acute myocardial infarction patients needs further investigation and it is not currently recommended.

Incidence and relevance of acute kidney injury in patients hospitalized with acute coronary syndromes.

Acute kidney injury (AKI) occurs frequently in patients with acute coronary syndromes (ACS) and is associated with adverse short- and long-term outcomes. To date, however, no standardized definition of AKI has been used for patients with ACS. As a result, information on its true incidence and the clinical and prognostic relevance according to the severity of renal function deterioration are still lacking. We retrospectively studied 3,210 patients with ACS. AKI was identified on the basis of the changes in serum creatinine during hospitalization according to the AKI Network criteria. Overall, 409 patients (13%) developed AKI: 262 (64%) had stage 1, 25 (6%) stage 2, and 122 (30%) stage 3 AKI. In-hospital mortality was greater in patients with AKI than in those without AKI (21% vs 1%; p <0.001). The adjusted risk of death increased with increasing AKI severity. Compared to no AKI, the adjusted odds ratio for death was 3.5 (95% confidence interval 1.79 to 6.83) with stage 1 AKI and 31.2 (95% confidence interval 16.96 to 57.45) with stage 2 to 3 AKI. A significant parallel increase in major adverse cardiac events was also observed comparing patients without AKI and those with stage 2 to 3 AKI. In conclusion, in patients with ACS, AKI is a frequent complication, and the graded increase of its severity, as assessed using the AKI Network classification, is associated with a progressive increased risk of in-hospital morbidity and mortality.

Acute hyperglycemia and contrast-induced nephropathy in primary percutaneous coronary intervention.

BACKGROUND: Acute hyperglycemia and contrast-induced nephropathy (CIN) are frequently observed in ST-elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI), and both are associated with an increased mortality rate. We investigated the possible association between acute hyperglycemia and CIN in patients undergoing primary PCI. METHODS: We prospectively enrolled 780 STEMI patients undergoing primary PCI. For each patient, plasma glucose levels were assessed at hospital admission. Acute hyperglycemia was defined as glucose levels>198 mg/dL (11 mmol/L). Contrast-induced nephropathy was defined as an increase in serum creatinine>25% from baseline in the first 72 hours. RESULTS: Overall, 148 (19%) patients had acute hyperglycemia; and 113 (14.5%) patients developed CIN. Patients with acute hyperglycemia had a 2-fold higher incidence of CIN than those without acute hyperglycemia (27% vs 12%, P<.001). In-hospital mortality was higher in patients with acute hyperglycemia than in those without acute hyperglycemia (12% vs 3%, P<.001). Mortality rate was also higher in patients developing CIN than in those without this renal complication (27% vs 0.9%, P<.001). Patients with acute hyperglycemia that developed CIN had the highest mortality rate (38%). Acute hyperglycemia was an independent predictor of CIN and in-hospital mortality. CONCLUSIONS: In STEMI patients undergoing primary PCI, acute hyperglycemia is associated with an increased risk for CIN and with increased in-hospital mortality.

[Cardiogenic shock complicating acute myocardial infarction: trends in management and outcome]. / Terapia dello shock cardiogeno in corso di infarto miocardico acuto: attuali acquisizioni.

Despite emergency coronary revascularization coupled with medical stabilization, intra-aortic balloon pump and ventricular assist devices have significantly improved survival in patients with cardiogenic shock complicating acute myocardial infarction, mortality still remains excessively high, being actually about 30-40%. Future research should focus on new therapeutic strategies, aimed to further decrease mortality rate of these patients.

Contrast volume during primary percutaneous coronary intervention and subsequent contrast-induced nephropathy and mortality.

BACKGROUND: Contrast-induced nephropathy (CIN) frequently occurs in patients with acute ST-segment elevation myocardial infarction (STEMI) who are undergoing primary percutaneous coronary intervention, and CIN is associated with a more complicated clinical course and increased mortality. OBJECTIVE: To investigate the association between absolute and weight- and creatinine-adjusted contrast volume, CIN incidence, and clinical outcome in the era of mechanical reperfusion of STEMI. DESIGN: Prospective, observational study. SETTING: A university cardiology center in Milan, Italy. PATIENTS: 561 consecutive patients with STEMI who were undergoing primary percutaneous coronary intervention. MEASUREMENTS: For each patient, the maximum contrast dose was calculated, according to the formula (5 x body weight [kg])/serum creatinine, and the contrast ratio, defined as the ratio between the contrast volume administered and the maximum dose calculated, was assessed. An increase in serum creatinine of more than 25% from baseline was defined as CIN. RESULTS: 115 (20.5%) patients developed CIN. In-hospital mortality was higher among patients with CIN than those without CIN (21.4% vs. 0.9%; P < 0.001). The maximum contrast dose was exceeded in 130 (23%) patients. Patients who received more than the maximum contrast dose (contrast ratio >1) had a more complicated in-hospital clinical course and higher mortality rate (13% vs. 2.8%; P < 0.001) than did patients with a contrast ratio less than 1. Development of CIN was associated with both contrast volume and contrast ratio. LIMITATION: The association between contrast volume and outcomes was observed in a single center and could be due to comorbid conditions, disease severity, or an unknown factor. CONCLUSION: During primary percutaneous coronary intervention for STEMI, higher contrast volume is associated with higher rates of CIN and mortality; however, further study is needed to determine whether limiting contrast volume would improve patient outcome. FUNDING: Centro Cardiologico Monzino, Institute of Cardiology, University of Milan.

Impact of cardiac and renal dysfunction on inhospital morbidity and mortality of patients with acute myocardial infarction undergoing primary angioplasty.

BACKGROUND: Risk stratification of patients with ST-elevation myocardial infarction (STEMI) undergoing primary angioplasty is important in order to predict outcomes and to delineate targeted therapeutic strategies. Although the prognostic implications of reduced left ventricular ejection fraction (LVEF) and creatinine clearance (CrCl) have been recognized, the clinical and prognostic impact of their combination has never been prospectively evaluated. METHODS: We stratified 467 patients with STEMI undergoing primary angioplasty according to LVEF and CrCl values at admission: CrCl > 60 mL/min and LVEF > 40% (group 1, n = 261); CrCl < or = 60 mL/min and LVEF > 40% (group 2, n = 113); CrCl > 60 mL/min and LVEF < or = 40% (group 3, n = 60); CrCl < or = 60 mL/min and LVEF < or = 40% (group 4, n = 33). RESULTS: Inhospital mortality was different in the 4 groups (1% in group 1, 3% in group 2, 15% in group 3, 30% in group 4) (P < .001). The incidence of combined end point of death, acute pulmonary edema, cardiogenic shock, and acute renal failure requiring mechanical support increased progressively from group 1 to group 4 (5%, 17%, 33%, and 48%, respectively) (P < .001). We found a significant gradient of risk in terms of inhospital mortality and combined end point when patients outcome was evaluated according to the presence of both normal LVEF and CrCl (group 1), impairment in only 1 of these 2 parameters (group 2 and 3 pooled together), and combined LVEF and CrCl reductions (group 4). CONCLUSIONS: Reduced LVEF and CrCl are strong independent predictors of increased inhospital morbidity and mortality, and their combined evaluation provides a simple tool for early risk stratification in patients with STEMI treated with primary angioplasty.

N-acetylcysteine and contrast-induced nephropathy in primary angioplasty.

BACKGROUND: Patients with acute myocardial infarction undergoing primary angioplasty are at high risk for contrast-medium-induced nephropathy because of hemodynamic instability, the need for a high volume of contrast medium, and the lack of effective prophylaxis. We investigated the antioxidant N-acetylcysteine for the prevention of contrast-medium-induced nephropathy in patients undergoing primary angioplasty. METHODS: We randomly assigned 354 consecutive patients undergoing primary angioplasty to one of three groups: 116 patients were assigned to a standard dose of N-acetylcysteine (a 600-mg intravenous bolus before primary angioplasty and 600 mg orally twice daily for the 48 hours after angioplasty), 119 patients to a double dose of N-acetylcysteine (a 1200-mg intravenous bolus and 1200 mg orally twice daily for the 48 hours after intervention), and 119 patients to placebo. RESULTS: The serum creatinine concentration increased 25 percent or more from baseline after primary angioplasty in 39 of the control patients (33 percent), 17 of the patients receiving standard-dose N-acetylcysteine (15 percent), and 10 patients receiving high-dose N-acetylcysteine (8 percent, P<0.001). Overall in-hospital mortality was higher in patients with contrast-medium-induced nephropathy than in those without such nephropathy (26 percent vs. 1 percent, P<0.001). Thirteen patients (11 percent) in the control group died, as did five (4 percent) in the standard-dose N-acetylcysteine group and three (3 percent) in the high-dose N-acetylcysteine group (P=0.02). The rate for the composite end point of death, acute renal failure requiring temporary renal-replacement therapy, or the need for mechanical ventilation was 21 (18 percent), 8 (7 percent), and 6 (5 percent) in the three groups, respectively (P=0.002). CONCLUSIONS: Intravenous and oral N-acetylcysteine may prevent contrast-medium-induced nephropathy with a dose-dependent effect in patients treated with primary angioplasty and may improve hospital outcome. (ClinicalTrials.gov number, NCT00237614[ClinicalTrials.gov]).

Comparison of two hemofiltration protocols for prevention of contrast-induced nephropathy in high-risk patients.

PURPOSE: Contrast-induced nephropathy is a complication of contrast medium administration during diagnostic and interventional procedures, with important prognostic relevance. Patients with chronic kidney disease have a higher risk for contrast-induced nephropathy and poorer outcome. In patients with chronic kidney disease, hemofiltration reduces contrast-induced nephropathy incidence and improves long-term survival. We assessed the mechanisms involved in the prophylactic effect of hemofiltration and of the most effective hemofiltration protocol to prevent contrast-induced nephropathy in patients with chronic kidney disease. SUBJECTS AND METHODS: We randomized 92 patients with chronic kidney disease (creatinine clearance < or =30 mL/min) to three different prophylactic treatments: intravenous hydration with isotonic saline (1 mL x kg x h for 12 hours before and after contrast exposure, control group; n = 30); intravenous hydration for 12 hours before contrast exposure, followed by hemofiltration for 18 to 24 hours after contrast exposure (post-hemofiltration group; n = 31), and hemofiltration performed for 6 hours before and for 18 to 24 hours after contrast exposure (pre/post-hemofiltration group; n = 31). The incidence of contrast-induced nephropathy (>25% increase in creatinine) and the in-hospital clinical course were compared in the three groups. RESULTS: Twelve patients (40%) in the control group, 8 patients (26%) in the post-hemofiltration group, and 1 patient (3%) in the pre/post-hemofiltration group experienced contrast-induced nephropathy (P = .0013); hemodialysis was required in 9 (30%), three (10%), and zero (0%) patients, respectively (P = .002). In-hospital mortality was 20%, 10%, and 0%, respectively (P = .03). CONCLUSIONS: Hemofiltration is an effective strategy for contrast-induced nephropathy prevention in patients with chronic kidney disease who are undergoing cardiovascular procedures. Pre-hemofiltration is required to obtain the full clinical benefit, suggesting that, among different mechanisms possibly involved, high-volume controlled hydration before contrast media exposure plays a major role.

Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction.

OBJECTIVES: The aim of this research was to assess the incidence, clinical predictors, and outcome of contrast-induced nephropathy (CIN) after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: Contrast-induced nephropathy is associated with significant morbidity and mortality after PCI. Patients undergoing primary PCI may be at higher risk of CIN because of hemodynamic instability and unfeasibility of adequate prophylaxis. METHODS: In 208 consecutive AMI patients undergoing primary PCI, we measured serum creatinine concentration (Cr) at baseline and each day for the following three days. Contrast-induced nephropathy was defined as a rise in Cr >0.5 mg/dl. RESULTS: Overall, CIN occurred in 40 (19%) patients. Of the 160 patients with baseline Cr clearance >/=60 ml/min, only 21 (13%) developed CIN, whereas it occurred in 19 (40%) of those with Cr clearance <60 ml/min (p < 0.0001). In multivariate analysis, age >75 years (odds ratio [OR] 5.28, 95% confidence interval [CI] 1.98 to 14.05; p = 0.0009), anterior infarction (OR 2.17, 95% CI 0.88 to 5.34; p = 0.09), time-to-reperfusion >6 h (OR 2.51, 95% CI 1.01 to 6.16; p = 0.04), contrast agent volume >300 ml (OR 2.80, 95% CI 1.17 to 6.68; p = 0.02) and use of intraaortic balloon (OR 15.51, 95% CI 4.65 to 51.64; p < 0.0001) were independent correlates of CIN. Patients developing CIN had longer hospital stay (13 +/- 7 days vs. 8 +/- 3 days; p < 0.001), more complicated clinical course, and significantly higher mortality rate (31% vs. 0.6%; p < 0.001). CONCLUSIONS: Contrast-induced nephropathy frequently complicates primary PCI, even in patients with normal renal function. It is associated with higher in-hospital complication rate and mortality. Thus, preventive strategies are needed, particularly in high-risk patients.

The prevention of radiocontrast-agent-induced nephropathy by hemofiltration.

BACKGROUND: Nephropathy induced by exposure to radiocontrast agents, a possible complication of percutaneous coronary interventions, is associated with significant in-hospital and long-term morbidity and mortality. Patients with preexisting renal failure are at particularly high risk. We investigated the role of hemofiltration, as compared with isotonic-saline hydration, in preventing contrast-agent-induced nephropathy in patients with renal failure. METHODS: We studied 114 consecutive patients with chronic renal failure (serum creatinine concentration, >2 mg per deciliter [176.8 micromol per liter]) who were undergoing coronary interventions. We randomly assigned them to either hemofiltration in an intensive care unit (ICU) (58 patients, with a mean [+/-SD] serum creatinine concentration of 3.0+/-1.0 mg per deciliter [265.2+/-88.4 micromol per liter]) or isotonic-saline hydration at a rate of 1 ml per kilogram of body weight per hour given in a step-down unit (56 patients, with a mean serum creatinine concentration of 3.1+/-1.0 mg per deciliter [274.0+/-88.4 micromol per liter]). Hemofiltration (fluid replacement rate, 1000 ml per hour without weight loss) and saline hydration were initiated 4 to 8 hours before the coronary intervention and were continued for 18 to 24 hours after the procedure was completed. RESULTS: An increase in the serum creatinine concentration of more than 25 percent from the base-line value after the coronary intervention occurred less frequently among the patients in the hemofiltration group than among the control patients (5 percent vs. 50 percent, P<0.001). Temporary renal-replacement therapy (hemodialysis or hemofiltration) was required in 25 percent of the control patients and in 3 percent of the patients in the hemofiltration group. The rate of in-hospital events was 9 percent in the hemofiltration group and 52 percent in the control group (P<0.001). In-hospital mortality was 2 percent in the hemofiltration group and 14 percent in the control group (P=0.02), and the cumulative one-year mortality was 10 percent and 30 percent, respectively (P=0.01). CONCLUSIONS: In patients with chronic renal failure who are undergoing percutaneous coronary interventions, periprocedural hemofiltration given in an ICU setting appears to be effective in preventing the deterioration of renal function due to contrast-agent-induced nephropathy and is associated with improved in-hospital and long-term outcomes.