Suhas S. Lele

Serum catalytic iron as a novel biomarker of vascular injury in acute coronary syndromes.

AIMS Catalytic iron is associated with high oxidative stress during vascular injury. We measured catalytic iron in patients with suspected acute coronary syndromes (ACS) and healthy volunteers to evaluate its utility in early detection of patients with acute myocardial infarction (MI) and predicting major adverse cardiac events (MACE). METHODS AND RESULTS Catalytic iron was measured on admission and 24 hours later in 127 patients with acute MI, 51 patients with suspected ACS without MI, and 250 healthy volunteers. Descriptive and decision statistics were performed for catalytic iron and troponin I. Catalytic iron levels at presentation were 1.5+2.0 micromol/l, 0.2+0.16 micromol/l, and 0.1+0.06 micromol/l for acute MI, suspected ACS without MI, and normals, respectively p<0.0001. Catalytic iron was elevated in all patients with MI at presentation. At a cutpoint of 0.30 micromol/L, the sensitivity, specificity, and diagnostic accuracy for identifying MI was 84%, 95%, and 92%, respectively. Increase in catalytic iron at 24 hours compared to baseline was associated with MACE at 30 days. CONCLUSIONS Catalytic iron identified all patients with acute MI at presentation and serial elevation was independently associated with MACE. This biomarker of vascular injury is useful in the rapid serologic assessment of patients with suspected ACS.

Increased plasma catalytic iron in patients may mediate acute kidney injury and death following cardiac surgery

Catalytic iron, the chemical form of iron capable of participating in redox cycling, is a key mediator of acute kidney injury (AKI) in multiple animal models, but its role in human AKI has not been studied. Here we tested in a prospective cohort of 250 patients undergoing cardiac surgery whether plasma catalytic iron levels are elevated and associated with the composite outcome of AKI requiring renal replacement therapy or in-hospital mortality. Plasma catalytic iron, free hemoglobin, and other iron parameters were measured preoperatively, at the end of cardiopulmonary bypass, and on postoperative days 1 and 3. Plasma catalytic iron levels, but not other iron parameters, rose significantly at the end of cardiopulmonary bypass and were directly associated with bypass time and number of packed red blood cell transfusions. In multivariate analyses adjusting for age and preoperative eGFR, patients in the highest compared with the lowest quartile of catalytic iron on postoperative day 1 had a 6.71 greater odds of experiencing the primary outcome, and also had greater odds of AKI, hospital mortality, and postoperative myocardial injury. Thus, our data are consistent with and expand on findings from animal models demonstrating a pathologic role of catalytic iron in mediating adverse postoperative outcomes. Interventions aimed at reducing plasma catalytic iron levels as a strategy for preventing AKI in humans are warranted.

Prognostic Evaluation of Catalytic Iron in Patients With Acute Coronary Syndromes

The potential of iron to generate reactive oxygen species has motivated a long‐standing interest in whether excess iron is causally linked to atherosclerotic heart disease. Circulating catalytic iron (“free” iron) is that which is not bound to transferrin or ferritin and is available to generate reactive oxygen species that may have deleterious vascular effects.

Impact of catalytic iron on mortality in patients with acute coronary syndrome exposed to iodinated radiocontrast—The Iscom Study

BACKGROUND Catalytic iron (CI) mediates vascular injury by generating reactive oxygen species. We evaluated role of CI in predicting mortality in patients with acute coronary syndrome (ACS) and studied association of contrast nephropathy with CI levels. METHODS We investigated 806 patients with ACS undergoing contrast exposure for a cardiac procedure who were followed up for 30 days. RESULTS Overall mortality was 1.6% at 30 days. Catalytic iron at baseline predicted mortality with CI levels significantly higher in those who died, 0.45 μmol/L (0.37, 0.68) compared with survivors 0.31 μmol/L (0.21, 0.40); P = .004. Catalytic iron was associated with increased risk of death in the highest quartile compared with lower 3 quartiles (hazard ratio 7.88, P = .001) after adjustment for age, diabetes, ST deviation, Killip class, ejection fraction, baseline creatinine, hemoglobin level, and troponin. Fifty-five patients (6.8%) developed contrast nephropathy. Patients with contrast nephropathy had a 27% increase in median CI levels from baseline up to 48 hours compared with a marginal 2.9% increase in those without contrast nephropathy (0.37, 0.14 μmol/L to 0.47, 0.20 μmol/L versus 0.35, 0.12 μmol/L to 0.36, 0.14 μmol/L, P < .0001). Patients with contrast nephropathy had significantly higher mortality compared with those without contrast nephropathy (9.1% vs 1.1%, P = .001). CONCLUSION High baseline CI levels predicted mortality in patients with ACS. Occurrence of contrast nephropathy was associated with rise in CI levels and higher mortality. Therapeutic options to buffer or chelate CI may have beneficial effects on mortality in this setting.

Plasma Catalytic Iron, AKI, and Death among Critically Ill Patients

BACKGROUND AND OBJECTIVES Catalytic iron has been hypothesized to be a key mediator of AKI. However, the association between plasma catalytic iron levels and AKI has not been well studied in humans. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS A single-center, prospective, nonconsecutive cohort study of 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012 was performed. Plasma catalytic iron, free hemoglobin, and other iron markers were measured on ICU days 1 and 4. The primary end point was in-hospital mortality or AKI requiring RRT. Secondary end points included mortality (assessed during hospitalization, at 30 days, and 1 year) and incident AKI, defined by modified Kidney Disease Improving Global Outcomes criteria. RESULTS ICU day 1 plasma catalytic iron levels were higher among patients who reached the primary end point (median, 0.74 µmol/l [interquartile range, 0.31-3.65] versus 0.29 µmol/l [0.22-0.46]; P<0.01). ICU day 1 plasma catalytic iron levels were associated with number of packed red blood cell transfusions before ICU arrival (rs=0.29; P<0.001) and plasma free hemoglobin levels on ICU day 1 (rs=0.32; P<0.001). Plasma catalytic iron levels on ICU day 1 were significantly associated with in-hospital mortality or AKI requiring RRT, even after adjusting for age, enrollment eGFR, and number of packed red blood cell transfusions before ICU arrival (13 events; adjusted odds ratio per 1-SD higher ln[catalytic iron], 3.33; 95% confidence interval, 1.79 to 6.20). ICU day 1 plasma catalytic iron levels were also significantly associated with incident AKI, RRT, hospital mortality, and 30-day mortality. CONCLUSIONS Among critically ill patients, elevated plasma catalytic iron levels on arrival to the ICU are associated with a greater risk of incident AKI, RRT, and hospital mortality.

Percutaneous endovascular management of recurrent aneurysm of transplant renal artery anastomosed to internal iliac artery

Aneurysm formation constitutes 0.5 to 1% of all vascular complications in transplant patients. Aneurysms may result from infection, injury during procurement or preservation, faulty suture technique or trauma. Transplant renal artery aneurysm presents with hypertension, graft dysfunction and bleeding. We report a case of percutaneous covered stent-graft for recurrent aneurysm with stenosis of transplant renal artery. To our knowledge this is the first report of successful treatment of transplant renal artery aneurysm with covered stent-graft.

Catalytic iron in acute myocardial infarction complicated by cardiogenic shock — A biomarker substudy of the IABP-SHOCK II-trial

BACKGROUND Catalytic iron (CI) is unbound ferric iron with the potential to generate reactive oxygen species with further deleterious vascular effects. In acute coronary syndromes, high levels of CI are linked to all-cause mortality. The prognostic impact of CI and iron metabolism in cardiogenic shock (CS) is currently undetermined. Aims of this study were to investigate the prognostic impact of CI and to identify predictors of high CI levels in patients with CS complicating acute myocardial infarction. METHODS The Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial randomized 600 patients with CS to either therapy with intraaortic balloon pump or control. In 185 of these patients, blood samples were systematically collected at baseline and day 3. CI levels were measured using a modified bleomycin detectable iron assay. Furthermore, levels of free hemoglobin, total serum iron, transferrin, total iron binding capacity, ferritin, hepcidin, and transferrin saturation were assessed. RESULTS Patients with baseline CI levels in the highest quartile had a worse outcome in comparison to patients with lower CI (day 1: HR 1.91 [1.11-3.31], p=0.005; day 3: HR 2.15 [1.06-4.34], p=0.01). In multivariable Cox-regression analysis baseline CI remained an independent predictor of 30-day mortality (HR per 10LOG 2.08 [1.25-3.47], p=0.005). Predictors of CI levels on day 3 were baseline CI, bleeding events, and baseline troponin T. CONCLUSIONS CI levels were associated with increased short-term mortality in CS complicating acute myocardial infarction. High levels of CI at day 3 were associated with bleeding and high troponin levels.