Jeness Campodonico

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

Context Contrast-induced nephropathy (CIN) can complicate percutaneous coronary intervention (PCI). A better understanding of the relationship among contrast volume, patient characteristics, and CIN could help to reduce this complication. Contribution Of 561 patients who underwent primary PCI in the setting of ST-segment elevation myocardial infarction, 20% developed CIN, and those with CIN were more likely than those without CIN to die in hospital. Higher contrast volume and contrast ratio (volume administered/volume calculated) were associated with CIN and in-hospital death. Caution It is unclear whether the worse outcomes were due to the contrast or whether unmeasured aspects of disease severity led to both the need for more contrast and the worse outcomes. The Editors Primary percutaneous coronary intervention (PCI), defined as intervention in the culprit vessel within 12 hours after the onset of chest pain without previous thrombolytic or other clot-dissolving therapy, is the best available strategy for treatment of ST-segment elevation acute myocardial infarction (STEMI) (1). Patients having primary PCI, however, are at higher risk for contrast-induced nephropathy (CIN), although most of them do not have preprocedural renal dysfunction (2). Contrast-induced nephropathy is associated with a marked increase in in-hospital morbidity and mortality rates, which may partially thwart the survival benefit of primary PCI in patients who develop this serious renal complication (2, 3). Effective CIN prevention may further improve the clinical outcome of patients with STEMI who receive primary PCI. Potential preventive strategies include protecting the kidney from contrast- or ischemic-induced injury and limiting the amount of contrast administered. Studies of the antioxidant agent N-acetylcysteine (4) have yielded promising results for kidney protection. N-acetylcysteine has been shown to be effective in reducing CIN incidence and in improving clinical outcomes after emergency or primary PCI, particularly when administered as a high-dose intravenous bolus or with sodium bicarbonate (4, 5). Conversely, because few previous studies have reported the amount of contrast used, data on the effect of contrast volume limitation during primary PCI are lacking. Moreover, investigators disagree on the relation between the volume of contrast administered during interventional procedures and the risk for CIN. Some studies have reported no relationship, whereas others have suggested an independent correlation (614). ST-segment elevation myocardial infarction further complicates the issue. Patients with STEMI who are not undergoing primary PCI may also have acute worsening of renal function with the same prognostic implications as for CIN (15), which suggests that acute kidney injury may result from hemodynamic compromise rather than from CIN per se. In addition, primary PCI success, a major determinant of clinical outcome in patients with STEMI (1618), may require larger amounts of contrast. Thus, an optimal procedural result should be carefully weighed against risk for CIN. The association of contrast volume, as an absolute and a weight- and creatinine-adjusted value (19); CIN incidence; and clinical outcome in the setting of primary PCI remains unknown. As a result, evidence-based recommendations to guide best procedural strategies during primary PCI are still lacking. We sought to prospectively assess the possible association between contrast volume and CIN incidence and in-hospital clinical outcome in patients with STEMI who undergo primary PCI. Methods Study Population We conducted our prospective observational study at the Centro Cardiologico Monzino, University of Milan, between 1 January 2002 and 30 September 2007. We enrolled all consecutive patients with STEMI who were undergoing primary PCI. According to our institute protocol, we included patients who presented within 12 hours (18 hours for STEMI complicated by cardiogenic shock) of the onset of symptoms (characteristic pain lasting for at least 30 minutes, not responsive to nitrates, with electrocardiographic ST-segment elevation of at least 0.2 mV in 2 or more contiguous leads, or left bundle-branch block). We excluded patients receiving long-term peritoneal or hemodialysis treatment. We also excluded patients if they had cardiac surgery for emergency coronary revascularization or STEMI-related mechanical complications, died during PCI, or had been treated with an intravenous bolus of N-acetylcysteine before PCI. The Ethics Committee of the Centro Cardiologico Monzino approved the study, and all patients gave written, informed consent. PCI Procedure A 24-hour on-call interventional team performed primary PCI according to standard clinical practice by using standard guide catheters (6 French), guide wires, and balloon catheters via the femoral approach. Patients received a 5000-U bolus of heparin, followed by additional boluses during the procedure to maintain an activated clotting time longer than 300 seconds (between 200 and 250 seconds when abciximab was used). Coronary stenting was performed with standard technique. Contrast dose was left to the discretion of the interventional cardiologist. All patients received nonionic, low-osmolar contrast agents (iomeprol or iohexol). After contrast exposure, patients received isotonic (0.9%) saline intravenously at a rate of 1 mL/kg per hour for 12 hours. In patients with a left ventricular ejection fraction (LVEF) lower than 40% or overt heart failure, the hydration rate was reduced to 0.5 mL/kg per hour. Poststenting antithrombotic treatment consisted of aspirin and either clopidogrel or ticlopidine at standard dosages. Data Collection We measured serum creatinine concentration in all patients at hospital admission (before primary PCI), every day for the following 3 days, at discharge from the coronary care unit, and at hospital discharge. We estimated creatinine clearance by applying the CockcroftGault formula to the serum creatinine concentration (20). We defined preprocedural renal insufficiency as a creatinine clearance less than 1 mL/s (60 mL/min) (21). We calculated the maximum contrast dose (MCD) for each patient by using the formula proposed by Cigarroa and colleagues (19): MCD (mL) = (5body weight [kg]) divided by serum creatinine (mg/dL). From this contrast limit, we determined the contrast ratio by dividing the administered contrast amount by the calculated MCD. We left the use of -adrenergic blocking agents, angiotensin-converting enzyme inhibitors, platelet glycoprotein IIb/IIIa receptor inhibitors (abciximab), diuretics, intra-aortic balloon pump, or inotropic drug support to the discretion of the interventional and coronary care unit cardiologists, on the basis of the current standards of care recommended by published guidelines (22). During hospitalization, medications were changed as needed at the discretion of the cardiologist responsible for the patient. The primary end point of the study was the occurrence of CIN, defined as a greater than 25% increase in creatinine concentration from the baseline value in the 72 hours after primary PCI (23). In-hospital mortality rate and other major adverse clinical events were also evaluated as secondary end points. Statistical Analysis On the basis of our previous study (2), we calculated a sample size of 550 patients, assuming a 30% incidence of patients exceeding the MCD and a 10% incidence of CIN in patients with a contrast ratio less than 1. This sample size allowed 84% statistical power to assess a significantly higher ( error of 0.05) CIN incidence of 20% (odds ratio, 2) in the group with a contrast ratio greater than 1. We present continuous variables as means (SDs); we compared them by using the t test for independent samples or one-way analysis of variance, as appropriate. We compared categorical data by using the chi-square test or the Fisher exact test, as appropriate. The P values reported in Table 1 were not adjusted for multiple comparisons. Table 1. Patient and Procedure Characteristics We explored the relationship between contrast ratio and maximum percentage increase in creatinine concentration after primary PCI by using linear regression analysis. Both variables were log-transformed before analysis. We estimated predicted probabilities of CIN and mortality from the logistic models with the covariates set to the population average values. We assessed the association among contrast volume, contrast ratio, and clinical outcomes (CIN and in-hospital mortality) through logistic regression analysis. First, we included only contrast volume or contrast ratio (model 1). To adjust for potential confounders selected among recognized clinical predictors of the 2 outcomes (age, body weight, infarct location, LVEF, time to reperfusion, and baseline creatinine level), we developed 2 multivariable logistic regression models: model 2, which adjusted for the 2 major predictors (LVEF and creatinine level), and model 3, which adjusted for the 6 considered variables. Because contrast ratio is a calculated variable that includes both body weight and creatinine, we did not include those 2 variables in the models when we tested the association with contrast ratio. Thus, model 2 included LVEF and time to reperfusion, whereas model 3 included age, infarction location, LVEF, and time to reperfusion. Because of the relatively small number of events, we only considered mortality models with 2 or fewer covariates. To assess whether the effect of contrast volume on CIN differed in patients with renal insufficiency, we stratified our sample according to creatinine clearance (1 or <1 mL/s [60 or <60 mL/min]) and tested the appropriate interaction terms by using logistic regression, adjusting with model 2. All tests were 2-sided. We performed all calculations by using SAS, version 9.13 (SAS Institute, Cary, North Carolina). Role of the Funding Source The Centro Cardiologico Monz

Circulatory response to fluid overload removal by extracorporeal ultrafiltration in refractory congestive heart failure

OBJECTIVES The goal of this study was to investigate the hemodynamic and circulatory adjustments to extracorporeal ultrafiltration (UF) in refractory congestive heart failure (rCHF). BACKGROUND In rCHF, UF allows clinical improvement and restores diuretic efficacy. However, in the course of a UF session, patients are exposed to rapid variations of body fluid composition so that, as fluid is withdrawn from the intravascular compartment, hypotension or even shock could occur. METHODS In 24 patients with rCHF undergoing UF, we measured, after every liter of plasma water removed, hemodynamics, blood gas analysis (in both systemic and pulmonary arteries), plasma volume changes (PV) and plasma refilling rate (PRR). The PV and PRR were calculated by considering hematocrit and ultrafiltrate volume. RESULTS In all patients, UF was performed safely, without side effects or hemodynamic instability (ultrafiltrate = 4,880 +/- 896 ml). Mean right atrial, pulmonary artery and wedge pressures progressively reduced during the procedure. Cardiac output increased at the end of the procedure and, to a greater extent, 24 h later, in relation to the increase of stroke volume. Heart rate and systemic vascular resistance did not increase, and other peripheral biochemical parameters did not worsen during UF. Intravascular volume remained stable throughout the entire duration of the procedure, indicating that a proportional volume of fluid was refilled from the congested parenchyma. CONCLUSIONS In patients with rCHF, subtraction of plasma water by UF is associated with hemodynamic improvement. Fluid refilling from the overhydrated interstitium is the major compensatory mechanism for intravascular fluid removal, and hypotension does not occur when plasma refilling rate is adequate to prevent hypovolemia.

Acute kidney injury in ST-segment elevation acute myocardial infarction complicated by cardiogenic shock at admission

Objective: To evaluate the clinical and prognostic relevance of acute kidney injury (AKI) in the setting of ST-elevation acute myocardial infarction (STEMI) complicated by cardiogenic shock (CS). Design: Prospective study. Setting: Single-center study, 13-bed intensive cardiac care unit at a University Cardiological Center. Patients: Ninety-seven consecutive STEMI patients with CS at admission, undergoing intra-aortic balloon pump (IABP) support and primary percutaneous coronary intervention (PCI). Interventions: None. Measurements and Main Results: We measured serum creatinine at baseline and each day for the following 3 days. Acute kidney injury was defined as a rise in creatinine >25% from baseline. Overall, AKI occurred in 52 (55%) patients, and in 12 of these patients, a renal replacement therapy was required. In multivariate analysis, age >75 yrs (p = .005), left ventricular ejection fraction ≤40% (p = .009), and use of mechanical ventilation (p = .01) were independent predictors of AKI. Patients developing AKI had a longer hospital stay, a more complicated clinical course, and significantly higher mortality rate (50% vs. 2.2%; p <.001) than patients without AKI. In our population, AKI was the strongest independent predictor of in-hospital mortality (relative risk 12.3, 95% confidence intervals 1.78 to 84.9; p <.001). Conclusions: In patients with STEMI complicated by CS, AKI represents a frequent clinical complication associated with a poor prognosis.

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.

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.

Continuous veno-venous hemofiltration for the treatment of contrast-induced acute renal failure after percutaneous coronary interventions

Acute renal failure (ARF) requiring hemodialysis after percutaneous coronary interventions (PCI) is a serious complication with poor prognosis. Hemodialysis‐induced hypotension may have deleterious cardiovascular effects, especially in high‐risk patients. Ultrafiltrate removal and simultaneous fluid replacement with a solution similar to plasma for high‐volume controlled hydration can be obtained with hemodynamic stability by continuous veno‐venous hemofiltration (CVVH). We prospectively assessed the safety and effectiveness of percutaneous CVVH (Y‐shaped double‐lumen catheter, circuit originating from and terminating in the femoral vein) in 33 consecutive patients (23 men and 10 women; mean age, 69 ± 9 years) who, after PCI, developed oligo‐anuric ARF, associated in 20 of them with congestive heart failure. All patients received a concomitant infusion of furosemide (500–1,000 mg/day) and dopamine (2 μg/kg/min). During CVVH, the average fluid volume replacement and body fluid net reduction were 1,000 ± 247 and 75 ± 48 ml/hr, respectively. Treatment with CVVH continued for 4.7 ± 2.7 days and corrected fluid overload in all cases. No patient experienced systemic hypotension or hypovolemia. Diuresis recovered in 32 (97%) patients, who showed a parallel improvement of renal function parameters. One patient required chronic dialysis. In‐hospital and 1‐year mortality was 9.1% and 27.3%, respectively. In conclusion, our data indicate that CVVH is a safe and effective therapy of radiocontrast‐induced ARF following PCI. It temporarily replaces renal function without deleterious cardiovascular effects, allowing the kidney to recover from the nephrotoxic injury. However, despite promising early results, large randomized trials are required to define the role of CVVH in ARF after PCI. Cathet Cardiovasc Intervent 2003;58:59–64.

Vitamin D plasma levels and in-hospital and 1-year outcomes in acute coronary syndromes: a prospective study.

AbstractDeficiency in 25-hydroxyvitamin D (25[OH]D), the main circulating form of vitamin D in blood, could be involved in the pathogenesis of acute coronary syndromes (ACS). To date, however, the possible prognostic relevance of 25 (OH)D deficiency in ACS patients remains poorly defined. The purpose of this prospective study was to assess the association between 25 (OH)D levels, at hospital admission, with in-hospital and 1-year morbidity and mortality in an unselected cohort of ACS patients.We measured 25 (OH)D in 814 ACS patients at hospital presentation. Vitamin D serum levels >30 ng/mL were considered as normal; levels between 29 and 21 ng/mL were classified as insufficiency, and levels < 20 ng/mL as deficiency. In-hospital and 1-year outcomes were evaluated according to 25 (OH)D level quartiles, using the lowest quartile as a reference.Ninety-three (11%) patients had normal 25 (OH)D levels, whereas 155 (19%) and 566 (70%) had vitamin D insufficiency and deficiency, respectively. The median 25 (OH)D level was similar in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) patients (14.1 [IQR 9.0–21.9] ng/mL and 14.05 [IQR 9.1–22.05] ng/mL, respectively; P = .88). The lowest quartile of 25 (OH)D was associated with a higher risk for several in-hospital complications, including mortality. At a median follow-up of 366 (IQR 364–379) days, the lowest quartile of 25 (OH)D, after adjustment for the main confounding factors, remained significantly associated to 1-year mortality (P < .01). Similar results were obtained when STEMI and NSTEMI patients were considered separately.In ACS patients, severe vitamin D deficiency is independently associated with poor in-hospital and 1-year outcomes. Whether low vitamin D levels represent a risk marker or a risk factor in ACS remains to be elucidated.

Serum to urinary sodium concentration ratio is an estimate of plasma renin activity in congestive heart failure

We investigated the relationship between plasma renin activity (PRA) and serum ([sNa+]) and urinary ([uNa+]) sodium concentrations in 124 congestive heart failure (CHF) patients (II–IV NYHA class) and 20 healthy subjects. According to PRA (> or <3 ng ml−1 h−1) and [sNa+] (> or <135 mEq l−1), patients were classified as Group A (normal PRA and normal [sNa+], n=39), Group B (increased PRA and normal [sNa+], n=62) and Group C (low [sNa+], n=23). Measurements were performed at rest and, in 26 cases, after extracorporeal ultrafiltration (UF). At rest, [sNa+] and [uNa+], and their difference ([sNa+]−[uNa+]), were linearly correlated with PRA, but the values did not allow differentiation of control subjects from patients or differentiation of patients with from those without renin–angiotensin system (RAS) activation. Conversely, the [sNa+]/[uNa+] ratio showed the best correlation with PRA (r=0.79, P<0.0001). UF‐induced PRA changes were linearly correlated with [sNa+]/[uNa+] ratio changes (r=0.67, P=0.002), but not with those of [sNa+], [uNa+] and [sNa+]−[uNa+]. In CHF, the [sNa+]/[uNa+] ratio best correlates with PRA and reflects the basal activity as well as the rapid changes (as those induced by UF) of the RAS. Therefore, it can be considered a strong and easily available marker of PRA.

Clinical Presentation and Outcome in a Contemporary Cohort of Patients with Acute Myocarditis: The Multicenter Lombardy Registry

Background: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. Methods: A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. Results: At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). &bgr;-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation. Conclusions: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.

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.