Bruno Ricciardelli

Renal insufficiency following contrast media administration trial (REMEDIAL) : A randomized comparison of 3 preventive strategies

Background— Volume supplementation by saline infusion combined with N-acetylcysteine (NAC) represents an effective strategy to prevent contrast agent–induced nephrotoxicity (CIN). Preliminary data support the concept that sodium bicarbonate and ascorbic acid also may be effective in preventing CIN. Methods and Results— Three hundred twenty-six consecutive patients with chronic kidney disease, referred to our institutions for coronary and/or peripheral procedures, were randomly assigned to prophylactic administration of 0.9% saline infusion plus NAC (n=111), sodium bicarbonate infusion plus NAC (n=108), and 0.9% saline plus ascorbic acid plus NAC (n=107). All enrolled patients had serum creatinine ≥2.0 mg/dL and/or estimated glomerular filtration rate <40 mL · min−1 · 1.73 m−2. Contrast nephropathy risk score was calculated in each patient. In all cases, iodixanol (an iso-osmolar, nonionic contrast agent) was administered. The primary end point was an increase of ≥25% in the creatinine concentration 48 hours after the procedure (CIN). The amount of contrast media administered (179±102, 169±92, and 169±94 mL, respectively; P=0.69) and risk scores (9.1±3.4, 9.5±3.6, and 9.3±3.6; P=0.21) were similar in the 3 groups. CIN occurred in 11 of 111 patients (9.9%) in the saline plus NAC group, in 2 of 108 (1.9%) in the bicarbonate plus NAC group (P=0.019 by Fisher exact test versus saline plus NAC group), and in 11 of 107 (10.3%) in the saline plus ascorbic acid plus NAC group (P=1.00 versus saline plus NAC group). Conclusions— The strategy of volume supplementation by sodium bicarbonate plus NAC seems to be superior to the combination of normal saline with NAC alone or with the addition of ascorbic acid in preventing CIN in patients at medium to high risk.

Acetylcysteine and contrast agent-associated nephrotoxicity

OBJECTIVES Prophylactic acetylcysteine along with hydration seems to be better than hydration alone in preventing the reduction in renal function induced by a contrast dye. BACKGROUND Contrast media can lead to acute renal failure that may occasionally require hemodialysis. METHODS One hundred eighty-three consecutive patients with impairment of renal function, undergoing coronary and/or peripheral angiography and/or angioplasty, were randomly assigned to receive 0.45% saline intravenously and acetylcysteine (600 mg orally twice daily; group A, n = 92) or 0.45% saline intravenously alone (group B, n = 91) before and after nonionic, low-osmolality contrast dye administration. RESULTS The baseline serum creatinine concentrations were similar (1.5 +/- 0.4 mg/dl in group A vs. 1.5 +/- 0.4 mg/dl in group B; p = 0.37). An increase of > or =25% in the baseline creatinine level 48 h after the procedure occurred in 6 (6.5%) of 92 patients in group A and in 10 (11%) of 91 patients in group B (p = 0.22). In the subgroup with a low (<140 ml) contrast dose, renal function deterioration occurred in 5 (8.5%) of 60 patients in group B and in 0 of 60 patients in group A (p = 0.02; odds ratio [OR] 0.44, 95% confidence interval [CI] 0.35 to 0.54). In the subgroup with a high contrast dose, no difference was found (5/31 vs. 6/32 patients, p = 0.78). By multivariate analysis, the amount of contrast agent, but not the treatment strategy, was a predictor of the occurrence of contrast dye-associated nephrotoxicity (OR 2.58, 95% CI 1.1 to 4.9; p = 0.035). CONCLUSIONS In patients with reduced renal function undergoing angiography and/or angioplasty, the amount of contrast agent, but not the administration of prophylactic acetylcysteine, was a predictor of renal function deterioration. Prophylactic acetylcysteine might provide better protection than hydration alone, only when a small volume of contrast agent is used.

Novel Approaches for Preventing or Limiting Events (Naples) II Trial Impact of a Single High Loading Dose of Atorvastatin on Periprocedural Myocardial Infarction

OBJECTIVES Atorvastatin administered at least 7 days before the percutaneous coronary intervention (PCI) reduces the rate of periprocedural myocardial infarction (MI). It is unknown whether a single, high (80 mg) loading dose of atorvastatin may reduce the rate of periprocedural MI. BACKGROUND Periprocedural MI is a prognostically important complication of PCI. METHODS The day before the elective PCI, 668 statin-naive patients were randomly assigned to atorvastatin 80 mg (atorvastatin group; n = 338) or no statin treatment (control group; n = 330). Creatine kinase-myocardial isoenzyme (CK-MB) (upper limit of normal [ULN] 3.5 ng/ml) and cardiac troponin I (ULN 0.10 ng/ml) were assessed before and 6 and 12 h after the intervention. Periprocedural MI was defined as a CK-MB elevation >3x ULN alone or associated with chest pain or ST-segment or T-wave abnormalities. RESULTS The incidence of a periprocedural MI was 9.5% in the atorvastatin group and 15.8% in the control group (odds ratio: 0.56; 95% confidence interval: 0.35 to 0.89; p = 0.014). Median CK-MB peak after PCI was 2.10 ng/ml (interquartile range 1.00 to 12.50 ng/ml) in the atorvastatin group and 3.20 ng/ml (interquartile range 1.37 to 16.07 ng/ml) in the control group (p = 0.014). The incidence of cardiac troponin I elevation >3x ULN was 26.6% in the atorvastatin group and 39.1% in the control group (odds ratio: 0.56; 95% confidence interval: 0.40 to 0.78; p < 0.001). CONCLUSIONS A single, high (80 mg) loading (within 24 h) dose of atorvastatin reduces the incidence of periprocedural MI in elective PCI.

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 ≥0.3 mg/dL) occurred in 34 patients (8.2%). A CyC increase concentration ≥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 ≥10% and sCr ≥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 ≥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.

Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II) RenalGuard System in High-Risk Patients for Contrast-Induced Acute Kidney Injury

Background— The RenalGuard System, which creates high urine output and fluid balancing, may be beneficial in preventing contrast-induced acute kidney injury. Methods and Results— The Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II) trial is a randomized, multicenter, investigator-driven trial addressing the prevention of contrast-induced acute kidney injury in high-risk patients. Patients with an estimated glomerular filtration rate ≤30 mL · min−1 · 1.73 m−2 and/or a risk score ≥11 were randomly assigned to sodium bicarbonate solution and N-acetylcysteine (control group) or hydration with saline and N-acetylcysteine controlled by the RenalGuard System and furosemide (RenalGuard group). The primary end point was an increase of ≥0.3 mg/dL in the serum creatinine concentration at 48 hours after the procedure. The secondary end points included serum cystatin C kinetics and rate of in-hospital dialysis. Contrast-induced acute kidney injury occurred in 16 of 146 patients in the RenalGuard group (11%) and in 30 of 146 patients in the control group (20.5%; odds ratio, 0.47; 95% confidence interval, 0.24 to 0.92). There were 142 patients (48.5%) with an estimated glomerular filtration rate ≤30 mL · min−1 · 1.73 and 149 patients (51.5%) with only a risk score ≥11. Subgroup analysis according to inclusion criteria showed a similarly lower risk of adverse events (estimated glomerular filtration rate ≤30 mL · min−1 · 1.73 m−2: odds ratio, 0.44; risk score ≥11: odds ratio, 0.45; P for interaction=0.97). Changes in cystatin C at 24 hours (0.02±0.32 versus −0.08±0.26; P =0.002) and 48 hours (0.12±0.42 versus 0.03±0.31; P =0.001) and the rate of in-hospital dialysis (4.1% versus 0.7%; P =0.056) were higher in the control group. Conclusion— RenalGuard therapy is superior to sodium bicarbonate and N-acetylcysteine in preventing contrast-induced acute kidney injury in high-risk patients. Clinical Trial Registration— URL: [http://www.clinicaltrial.gov][1]. Unique identifier: [NCT01098032][2]. # Clinical Perspective {#article-title-39} [1]: http://www.clinicaltrial.gov. [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01098032&atom=%2Fcirculationaha%2F124%2F11%2F1260.atomBackground— The RenalGuard System, which creates high urine output and fluid balancing, may be beneficial in preventing contrast-induced acute kidney injury. Methods and Results— The Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II) trial is a randomized, multicenter, investigator-driven trial addressing the prevention of contrast-induced acute kidney injury in high-risk patients. Patients with an estimated glomerular filtration rate ⩽30 mL · min−1 · 1.73 m−2 and/or a risk score ≥11 were randomly assigned to sodium bicarbonate solution and N-acetylcysteine (control group) or hydration with saline and N-acetylcysteine controlled by the RenalGuard System and furosemide (RenalGuard group). The primary end point was an increase of ≥0.3 mg/dL in the serum creatinine concentration at 48 hours after the procedure. The secondary end points included serum cystatin C kinetics and rate of in-hospital dialysis. Contrast-induced acute kidney injury occurred in 16 of 146 patients in the RenalGuard group (11%) and in 30 of 146 patients in the control group (20.5%; odds ratio, 0.47; 95% confidence interval, 0.24 to 0.92). There were 142 patients (48.5%) with an estimated glomerular filtration rate ⩽30 mL · min−1 · 1.73 and 149 patients (51.5%) with only a risk score ≥11. Subgroup analysis according to inclusion criteria showed a similarly lower risk of adverse events (estimated glomerular filtration rate ⩽30 mL · min−1 · 1.73 m−2: odds ratio, 0.44; risk score ≥11: odds ratio, 0.45; P for interaction=0.97). Changes in cystatin C at 24 hours (0.02±0.32 versus −0.08±0.26; P=0.002) and 48 hours (0.12±0.42 versus 0.03±0.31; P=0.001) and the rate of in-hospital dialysis (4.1% versus 0.7%; P=0.056) were higher in the control group. Conclusion— RenalGuard therapy is superior to sodium bicarbonate and N-acetylcysteine in preventing contrast-induced acute kidney injury in high-risk patients. Clinical Trial Registration— URL: http://www.clinicaltrial.gov. Unique identifier: NCT01098032.

Failure of atrial natriuretic factor to increase with saline load in patients with dilated cardiomyopathy and mild heart failure.

To investigate whether the response of atrial natriuretic factor (ANF) to volume expansion is impaired in the early stages of dilated cardiomyopathy, the effects of saline load (SL; 0.25 ml/kg.min for 120 min) were assessed in 12 patients with dilated cardiomyopathy and asymptomatic to mildly symptomatic heart failure (HF) and in nine normal subjects (N). SL increased plasma ANF levels in N (from 14.3 +/- 2 to 19.5 +/- 3 and 26 +/- 4 pg/ml, at 60 and 120 min, respectively, P less than 0.001), but not in HF (from 42.9 +/- 9 to 45.9 +/- 9 and 43.9 +/- 8 pg/ml). Left ventricular end-diastolic volume (LVEDV) and stroke volume were increased (P less than 0.001) by SL in N but not in HF. Urinary sodium excretion (UNaV) increased in N more than in HF during SL, whereas forearm vascular resistance (FVR) did not change in N and increased in HF (P less than 0.001). In five HF patients SL was performed during ANF infusion (50 ng/kg, 5 ng/kg.min) that increased ANF levels from 37.1 +/- 10 to 146 +/- 22 pg/ml. In this group, SL raised both LVEDV (P less than 0.01) and ANF (P less than 0.05), whereas FVR did not rise. In addition, the UNaV increase and renin and aldosterone suppressions by SL were more marked than those observed in HF under control conditions. Thus, in patients with dilated cardiomyopathy and mild cardiac dysfunction, plasma ANF levels are not increased by volume expansion as observed in N. The lack of ANF response is related to the impaired cardiac adaptations. The absence of an adequate increase of ANF levels may contribute to the abnormal responses of HF patients to saline load.

Gadolinium-based contrast agents and nephrotoxicity in patients undergoing coronary artery procedures

Objective: We tested whether gadolinium‐based contrast agent is less nephrotoxic than iodinated‐contrast media. Background: Iodinated contrast agents are nephrotoxic. Some data suggest that gadolinium‐based contrast agent may be less nephrotoxic than iodinated‐contrast media. Methods: Twenty‐five consecutive patients with chronic renal insufficiency (creatinine concentration ≥2.0 mg/dl and/or clearance ≤40 ml/min), referred to our institution for coronary procedures, were assigned to receive gadolinium‐based contrast agents, a solution of gadolinium chelates diluted 3:1 by iso‐osmolality contrast media (Gadolinium‐based group). A control group of 32 patients with comparable clinical characteristics and treated with iodinated iso‐osmolality contrast agent alone (Iodinated‐based group) was selected from our database and compared with the Gadolinium‐based group. In all cases, prophylactic administration of 0.45% saline intravenously and NAC (1200 mg orally twice daily) was used. Results: Baseline creatinine levels and creatinine clearance were similar in the 2 groups (Gadolinium‐based group = 2.30 [IQR: 2.01–2.68] mg/dl and 33 ± 13 ml/min; Iodinated‐based group = 2.24 [IQR: 2.05–2.65] mg/dl and 30 ± 10 ml/min; P >0.05 for all). Increase of at least 0.5 mg/dl of the creatinine concentration 48 hr after the procedure occurred in 7/25 (28%) patients in the Gadolinium‐based group and in 2/32 (6.5%) patients in the Iodinated‐based group (P = 0.034; OR = 4.48; 95% CI = 1.01–19.17). Renal failure requiring temporary dialysis occurred in 2 (8%) patients in the Gadolinium‐based group and in none in the Iodinated‐based group (P = 0.19). Conclusions: The strategy of gadolinium‐based contrast agent administration does not seem to reduce the rate of CAN, as compared to the iodinated iso‐osmolality contrast agent in patients with chronic renal insufficiency.© 2006 Wiley‐Liss, Inc.

Cardiac function in systemic hypertension before and after reversal of left ventricular hypertrophy.

In 3 age- and sex-matched groups of subjects--15 normotensives, 15 hypertensives without left ventricular (LV) hypertrophy and 15 hypertensives with LV hypertrophy--the slopes of the regression line obtained by plotting the individual values of LV fractional shortening against the corresponding values of echocardiographic end-systolic stress were compared. The first 2 groups were studied only in control conditions while the third group was restudied after a 20% reduction in LV mass index induced by a long-term antihypertensive treatment and after a 3-week washout period. A significant relation between fractional shortening and end-systolic stress was found in all instances. The slope of this correlation was higher in normotensives (-0.251) and in hypertensives without LV hypertrophy (-0.232) (both p less than 0.01) than in hypertensives with ventricular hypertrophy (-0.079). In this latter group, the slope increased after the reversal of LV hypertrophy (-0.230, p less than 0.01) and remained unchanged (-0.202) at the end of the washout period. No difference was detectable between the slopes obtained in these patients after reversal of LV hypertrophy, both with the antihypertensive treatment on and off, and those of normotensives and hypertensives without LV hypertrophy. Thus, LV hypertrophy attenuates the influence of changes in afterload on LV function. Reversal of LV hypertrophy restores a fractional shortening end-systolic stress relation quite comparable to that found both in normotensives and in hypertensives before the development of LV hypertrophy.

Participation of endogenous catecholamines in the regulation of left ventricular mass in progeny of hypertensive parents.

To investigate whether adrenergic activity is a determinant of left ventricular hypertrophy in human hypertension, in each of 10 normotensive subjects with two hypertensive parents we have examined the relationship between changes in echocardiographic parameters of left ventricular anatomy and those in circulating catecholamine levels induced by three, 3 week periods of different sodium and potassium intakes. A high sodium-normal potassium regimen induced a significant reduction in upright plasma norepinephrine (from 599 +/- 89 to 379 +/- 45 pg/ml, p less than .01) and in posterior wall (PWT) and interventricular septal (IVST) thickness, as well as in the left ventricular mass index (LVMi). Changes in upright plasma norepinephrine concentrations correlated with those in IVST (r = .822, p less than .01) and in LVMi (r = .833, p less than .01). A low sodium-normal potassium diet resulted in increases in supine and upright plasma norepinephrine levels (from 356 +/- 44 to 488 +/- 89 pg/ml, p less than .001; and from 565 +/- 42 to 744 +/- 33 pg/ml, p less than .01) as well as increases in IVST and LVMi (from 97 +/- 7 to 107 +/- 7 g/m2, p less than .001). The changes in norepinephrine levels in supine and upright subjects correlated with changes in IVST (r = .836, p less than .01 and r = .796, p less than .01) and in LVMi (r = .931, p less than .001 and r = .947, p less than .001). No significant change in plasma catecholamine concentrations or in PWT, IVST, or LVMi was detected after a low sodium-high potassium regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intravenous verapamil administration on left ventricular diastolic function in systemic hypertension

The effects of intravenous verapamil administration (0.1 mg/kg as a bolus followed by an infusion of 0.007 mg/kg/min) were studied using high-temporal-resolution radionuclide angiography in 27 patients with hypertension. Verapamil administration increased heart rate from 69 +/- 11 to 75 +/- 12 beats/min (p less than 0.001) and decreased systolic, diastolic and mean blood pressures (BPs) from 155 +/- 21/102 +/- 12 mm Hg (mean 119 +/- 14) to 142 +/- 19/95 +/- 12 mm Hg (mean 109 +/- 13) (p less than 0.001 for all). Ejection fraction decreased significantly (from 65 +/- 10% to 60 +/- 11%, p less than 0.005); peak filling rate, however, increased significantly only in patients in whom it was subnormal in the basal study (from 2.2 +/- 0.4 to 3.0 +/- 0.6 end-diastolic counts/s, p less than 0.001). These latter patients had significantly higher values of left ventricular (LV) mass index than patients with normal or increased peak filling rate (129 +/- 22 vs 112 +/- 22 g/m2, respectively, p less than 0.05). The isovolumic relaxation period changes were inversely related to the baseline values (r = 0.83, p less than 0.001). In the subgroup of patients in whom isovolumic relaxation period lengthened, time to end systole decreased (from 360 +/- 31 to 329 +/- 30 ms, p less than 0.025) and time to onset of rapid filling increased (from 420 +/- 31 to 451 +/- 34 ms, p less than 0.025), whereas these 2 intervals had opposite patterns in patients in whom isovolumic relaxation period decreased or did not change.(ABSTRACT TRUNCATED AT 250 WORDS)