Indexed neutrophil gelatinase associated lipocalin: a novel biomarker for the assessment of acute kidney injury.

INTRODUCTION: Acute kidney injury (AKI) is a clinically relevant and common complication among patients with acute coronary syndrome. Neutrophil gelatinase-associated lipocalin (NGAL), secreted from different cells including renal tubules, has been widely studied as an early marker for kidney injury. However, chronic kidney disease (CKD) could impact NGAL levels and alter their predictive performance. Some studies attempted to address this issue by setting different cutoff values for patients with CKD, with limited success to date. Our aim was to evaluate a novel estimated glomerular filtration rate (eGFR)-adjusted "indexed NGAL" and its ability to predict in-hospital AKI among patients with ST elevation myocardial infarction. METHODS: We performed a prospective, observational, single center study involving patients with ST elevation myocardial infarction admitted to the coronary intensive care unit. Serum samples for baseline NGAL were collected within 24 h following hospital admission. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. In-hospital AKI was determined as occurring after ≥ 24 h from admission. To perform an individualized adjustment, we used the result of 24 h NGAL divided by the eGFR measured upon admission to the hospital (Indexed-NGAL; I-NGAL). RESULTS: Our cohort includes 311 patients, of whom 123 (40%) had CKD, and 66 (21%) suffered in-hospital AKI. NGAL levels as well as I-NGAL levels were significantly higher in patients with AKI (136 vs. 86, p < 0.01 and 3.13 VS. 1.06, p < 0.01, respectively). Multivariate analysis revealed I-NGAL to be independently associated with AKI (OR 1.34 (1.10-1.58), p < 0.01). I-NGAL had a higher predictive ability than simple NGAL results (AUC-ROC of 0.858 vs. 0.778, p < 0.001). CONCLUSION: Adjusting NGAL values according to eGFR yields a new indexed NGAL value that enables better prediction of AKI regardless of baseline kidney function.

Novel Biomarkers for the Assessment of the Cardio-Renal Syndrome-A Paradigm Shift.

Among patients admitted to medical wards, a growing number have various degrees of cardiac and renal dysfunction [...].

Predictive value of elevated neutrophil gelatinase-associated lipocalin levels for assessment of in-hospital adverse outcomes among myocardial infarction patients.

BACKGROUND: Inflammatory biomarkers are known to rise and have predictive value for adverse outcomes in patients with acute coronary ischemia. One of those biomarkers is neutrophil gelatinase-associated lipocalin (NGAL). To date, only very few studies have assessed the prognostic value of NGAL in this setting. We investigated the prognostic utility of elevated NGAL levels on clinical outcomes among ST-elevation myocardial infarction patients. METHODS: High NGAL was defined as values within the 4th quartile. Patients were assessed for major in-hospital adverse clinical events (MACE). Multivariable logistic regression and area under the receiver operating characteristic curve (AUC) were used to further evaluate NGAL association for MACE and discrimination ability. RESULTS: A total of 273 patients were included. patients with high NGAL were at increased risk for MACE (62% vs. 19%; odds ratio 6.88, 95% confidence interval, 3.77-12.54, P  < 0.001). After propensity score matching, the incidence of MACE was significantly higher in patients with high vs. low NGAL levels (69% vs. 6%, P  = 0.002). In multivariable regression, high NGAL level was independently associated with MACE. The discrimination ability of NGAL to identify MACE (AUC 0.823), is significantly better than that of other inflammatory markers. CONCLUSION: Among ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention, high NGAL levels are associated with adverse outcomes, independent of traditional inflammatory markers.

Serial Measurements of Neutrophil Gelatinase-Associated Lipocalin levels for Assessment of Contrast Induced Nephropathy among Chronic Kidney Disease Patients Who Underwent Elective Coronary Angiography.

BACKGROUND: Among chronic kidney disease (CKD) patients, baseline neutrophil gelatinase-associated lipocalin (NGAL) may reflect the severity of renal impairment. No data exists on serial changes in serum NGAL levels in CKD patients before and after percutaneous coronary intervention (PCI). OBJECTIVES: To evaluate serial serum NGAL levels relation to contrast induced acute kidney injury (CI-AKI) following PCI. METHODS: The study included 58 patients with CKD who underwent elective PCI. Plasma NGAL measurements were performed before (pre-NGAL) and 24 hours following (post-NGAL) PCI. Patients were followed for CI-AKI and changes in NGAL levels. Receiver operator characteristic identified the optimal sensitivity and specificity for pre-NGAL levels compared with post-NGAL for patients with CI-AKI. RESULTS: Overall CI-AKI incidence was 33%. Both pre-NGAL (172 vs. 119 ng/ml, P < 0.001) and post-NGAL (181 vs. 121 ng/ml, P < 0.001) levels were significantly higher in patients with CI-AKI, but no significant changes were detected. Pre-NGAL levels were similar to post-NGAL levels in predicting CI-AKI (area under the curve 0.753 vs. 0.745). Optimal cutoff value for pre-NGAL was 129 ng/ml (sensitivity of 73% and specificity of 72%, P < 0.001). Post-NGAL levels > 141 ng/ml were independently associated with CI-AKI (hazard ratio [HR] 4.86, 95% confidence interval [95%CI] 1.34-17.64, P = 0.02) with a strong trend for post-NGAL levels > 129 ng/ml (HR 3.46, 95%CI 1.23-12.81, P = 0.06). CONCLUSIONS: In high-risk patients, pre-NGAL levels may predict CI-AKI. Further studies on larger populations are needed to validate the use of NGAL measurements in CKD patients.

Biomarker-Guided Assessment of Acute Kidney Injury Phenotypes E among ST-Segment Elevation Myocardial Infarction Patients.

Recent practice guidelines recommended the use of new stress, functional, and damage biomarkers in clinical practice to prevent and manage acute kidney injury (AKI). Biomarkers are one of the tools used to define various AKI phenotypes and provide prognostic information regardless of an acute decline in renal function. We investigated the incidence and possible implications of AKI phenotypes among ST elevation myocardial infarction patient treated with primary coronary intervention. We included 281 patients with STEMI treated with PCI. Neutrophil gelatinase associated lipocalin (NGAL) was utilized to determine structural renal damage and functional AKI was determined using the KDIGO criteria. Patients were stratified into four AKI phenotypes: no AKI, subclinical AKI, hemodynamic AKI, and severe AKI. Patients were assessed for in-hospital adverse events (MACE). A total of 46 patients (44%) had subclinical AKI, 17 (16%) had hemodynamic AKI, and 42 (40%) had severe AKI. We observed a gradual and significant increase in the occurrence of MACE between the groups being highest among patients with severe AKI (10% vs. 19% vs. 29% vs. 43%; p < 0.001). In a multivariable regression model, any AKI phenotype was independently associated with MACE with an odds ratio of 4.15 (95% CI 2.1−8.3, p < 0.001,) for subclinical AKI, 4.51 (95% CI 1.61−12.69; p = 0.004) for hemodynamic AKI, and 12.9 (95% CI 5.59−30.1, p < 0.001) for severe AKI. In conclusion, among STEMI patients, AKI is a heterogeneous condition consisting of distinct phenotypes, addition of novel biomarkers may overcome the limitations of sCr-based AKI definitions to improve AKI phenotyping and direct potential therapies.

Predictive Value of Elevated Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels for Assessment of Cardio-Renal Interactions among ST-Segment Elevation Myocardial Infarction Patients.

Background: Elevated serum neutrophil gelatinase-associated lipocalin (NGAL) levels reflect both inflammatory reactions and renal tubular injury. Recently, associations with endothelial dysfunction and plaque instability were also proposed. We investigated the prognostic utility of elevated NGAL levels for renal and clinical outcomes among ST-segment elevation myocardial infarction (STEMI) patients treated with primary coronary intervention (PCI). Methods: We performed a prospective, observational, open-label trial. High NGAL was defined as values within the third tertile (>66 percentile). Results: A total of 267 patients were included (mean age 66 ± 14 years, 81% males). Short-term adverse outcomes were consistently increased in the high NGAL group with more acute kidney injury, lower mean left ventricular ejection fraction, higher 30-day mortality, and higher incidence for the composite outcome of major adverse cardiac events (MACE). In a multivariate logistic regression model, high NGAL emerged as a strong and independent predictor for MACE (OR 2.07, 95% CI 1.15−3.73, p = 0.014). Conclusions: Among STEMI patients undergoing primary PCI, elevated NGAL levels are associated with adverse renal and cardiovascular outcomes, independent of traditional inflammatory markers. Further studies are needed to assess the potentially unique role of NGAL in cardio−renal interactions.

Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Reversible versus Persistent Renal Tubular Damage in ST-Segment Myocardial Infarction Patients.

BACKGROUND: Most studies investigated the value of neutrophil gelatinase-associated lipocalin (NGAL) as a marker of renal tubular injury only at a single time point. We investigated the possible utilization of NGAL level dynamics for the identification of different renal injury patterns in ST-elevation myocardial infarction (STEMI) patients. METHODS: Blood samples for plasma NGAL in 132 STEMI patients were drawn immediately before and 24 h following primary coronary intervention. Abnormal elevation of NGAL levels was defined using the cardiac surgery-associated NGAL score with NGAL levels ≥100 ng/mL suggesting renal tubular damage. According to NGAL levels at 0 and 24 h, patients were stratified into 3 groups: no tubular damage (NGAL <100 ng/mL in both exams), reversible tubular damage (NGAL >100 ng/mL at 0 h but <100 ng/mL at 24 h), and persistent tubular damage (NGAL >100 ng/mL at both 0 and 24 h). RESULTS: Mean age was 62 ± 13 years, and 78% were men. Of these patients, 29/132 (22%) demonstrated reversible tubular damage, and 36/132 (27%) persistent tubular damage. Only 13/132 patients (10%) progressed to clinical acute kidney injury during hospitalization, all of whom had persistent tubular injury. In multivariate regression model, symptom duration was independently associated with persistent tubular damage, both as continues variable (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04; p = 0.04) and for symptom duration >360 min (OR 2.66, 95% CI 1.07-6.63; p = 0.03). CONCLUSIONS: Renal tubular damage is common among STEMI patients. Dynamic NGAL measurement may differentiate between reversible and persistent tubular damage. Further trials are needed in order to assess the complex cardiorenal interactions.

Re-Appraisal of Echocardiographic Assessment in Patients with Pulmonary Embolism: Prospective Blinded Long-Term Follow-Up.

BACKGROUND: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease. OBJECTIVES: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE. METHODS: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results. RESULTS: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function. CONCLUSIONS: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among -ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). METHODS: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(-) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(-) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. RESULTS: Of the study patients, 56 (42%) were NGAL(-)/sCr(-), 58 (44%) NGAL(+)/sCr(-), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(-) patients developed the composite endpoint when compared to NGAL(-)/sCr(-) patients (64 vs. 46%; OR 2.1, [95% CI 1.1-4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. CONCLUSIONS: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr.

Assessment of Respiratory Distress by the Roth Score.

INTRODUCTION: Health care demand is increasing due to greater longevity of patients with chronic comorbidities. This increasing demand is occurring in a setting of resource scarcity. To address these changes, high-value care initiatives, such as telemedicine, are valuable resource-preservation strategies. This study introduces the Roth score as a telemedicine tool that uses patient counting times to accurately risk-stratify dyspnea severity in terms of hypoxia. HYPOTHESIS: The Roth score has correlation with dyspnea severity. METHODS: This is a prospective, controlled-cohort study. Roth score index is measured by having the patient count from 1 to 30 in their native language, in a single breath, as rapidly as possible. The primary result of the Roth score is the duration of time and the highest number reached. RESULTS: There was a strongly positive correlation between pulse oximetry and both maximal count achieved in 1 breath (r = 0.67; P < 0.001) and counting time (r = 0.59; P < 0.001). For oxygen saturation <95%, the maximal count number area under the curve is 0.828 and counting time area under the curve is 0.764. Counting time >8 seconds had a sensitivity of 78% and specificity of 73% for pulse oximetry <95%. CONCLUSIONS: The Roth score has strong correlation with dyspnea severity as determined by hypoxia. This tool is reproducible, low resource-utilization, and amenable to telemedicine. It is not intended to replace full clinical workup and diagnosis of respiratory distress, but it is useful in risk-stratifying severity of dyspnea that warrants further clinical evaluation.

Serial Echocardiographic Assessment of Left Ventricular Filling Pressure and Remodeling among ST-Segment Elevation Myocardial Infarction Patients Treated by Primary Percutaneous Intervention.

BACKGROUND: Acute myocardial infarction and remodeling of the left ventricle is associated with significant changes in systolic and diastolic echocardiographic derived indices. The investigators have tried to determine whether persistence of increased ratio of transmitral flow velocity (E) to early mitral annulus velocity (e'), signifying increased cardiac filling pressure, is associated with left ventricular (LV) remodeling and increased chamber size among patients presenting with ST-segment elevation myocardial infarction, who underwent successful reperfusion with primary percutaneous coronary intervention. METHODS: Fifty-two patients (76% men; mean age, 61 ± 10 years) with first ST-segment elevation myocardial infarctions who underwent primary percutaneous coronary intervention were retrospectively studied. Echocardiography was performed at baseline (days 1-3) and after 178 ± 62 days. Patients were stratified according to E/septal e' ratio >15 and ≤15 in both examinations. All patients received optimal medical therapy according to guidelines and local practice. RESULTS: Patients with maintained or worsened E/septal e' ratios to >15 demonstrated on the second examination worse LV ejection fractions (mean, 45 ± 12% vs 52 ± 8%; P = .03) and higher indexed LV end-diastolic volumes (mean, 81.3 ± 22.9 vs 69.2 ± 13.4 mL/m(2); P = .01) and end-systolic volumes (mean, 33.0 ± 12.2 vs 23.7 ± 13.4 mL/m(2); P = .02) compared with the first examination, representing LV remodeling. Patients with E/septal e' ratios > 15 on the second examination demonstrated a positive correlation between the change in E/septal e' ratio and the change in indexed LV end-diastolic volume (linear R(2) = 0.344, P = .03). CONCLUSIONS: Among patients with ST-segment elevation myocardial infarctions undergoing primary percutaneous coronary intervention, early and persistent elevation of the E/septal e' ratio may be associated with LV remodeling.

Gender-related mortality and in-hospital complications following ST-segment elevation myocardial infarction: data from a primary percutaneous coronary intervention cohort.

BACKGROUND: The increased mortality related to female gender in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) has been reported from various patient cohorts and treatment strategies with controversial results. In the present work, we evaluated the impact of female gender on mortality and in-hospital complications among a specific subset of consecutive STEMI patients managed solely by PPCI. HYPOTHESIS: Female gender is not an independent predicor for mortality among STEMI patients. METHODS: We performed a retrospective, single-center observational study that included 1346 consecutive STEMI patients undergoing PPCI, of which 1075 (80%) were male. Patient's records were evaluated for 30-day mortality, in-hospital complications, and long-term mortality over a mean period of 2.7 ± 1.6 years. RESULTS: Compared with males, females were older (69 ± 13 vs 60 ± 13 years, P < 0.001), had a significantly higher rate of baseline risk factors, and had prolonged symptom duration (460 ± 815 minutes vs 367 ± 596 minutes, P = 0.03). Females suffered from more in-hospital complications and had higher 30-day mortality (5% vs 2%, P = 0.008) as well as higher overall mortality (12.5% vs 6%, P < 0.001). In spite of the significant mortality risk in unadjusted models, a multivariate adjusted Cox regression model did not demonstrate that female gender was an independent predictor for mortality among STEMI patients. CONCLUSIONS: Among patients with STEMI treated by PPCI, female gender is associated with a higher 30-day mortality and complications rates compared to males. Following multivariate analysis, female gender was not a significant predictor of long-term death following STEMI.