Elevated urinary kidney injury molecule 1 at discharge strongly predicts early mortality following an episode of acute decompensated heart failure.

INTRODUCTION: Hospitalization for acute decompensation of heart failure (ADHF) is a frequent event associated with long­term adverse effects. Prognosis is even worse if acute kidney injury (AKI) occurs during hospitalization. OBJECTIVES: The study aimed to determine whether kidney damage biomarkers neutrophil gelatinase­associatedlipocalin (NGAL), kidney injury molecule 1 (KIM­1), and interleukin18 (IL­18) might predict AKI and have prognostic value in ADHF. PATIENTS AND METHODS: Serum NGAL on admission and urine NGAL, KIM­1, and IL­18 on discharge were determined in 187 ADHF patients enrolled in a prospective, observational, unblinded study. AKI was diagnosed using the Kidney Disease: Improving Global Outcomes criteria. Patients were followedfor 12 months to record all­cause mortality. RESULTS: A total of 22% patients died during the follow­up, with 52.5% dying within 4 months after discharge. Serum NGAL (P <0.001), urine NGAL (P = 0.047), and urinary KIM­1 (P = 0.014) levels were significantly higher in the deceased patients at discharge. After adjustment for estimated glomerular filtration rate (eGFR), only urinary KIM­1 independently predicted mortality at month 4 (hazard ratio [HR], 3.166; 95% CI, 1.203-8.334; P = 0.020) and month 12 (HR, 1.969; 95% CI, 1.123-3.454; P = 0.018) in Cox regression models. In receiver operating characteristic (ROC) analysis urinary KIM­1 (area under the ROC curve [AUC] = 0.830) outperformed other markers of renal function. The Kaplan-Meier survival analysis showed KIM­1 predictive value as additive to that of AKI incidence and admission eGFR. Admission serum NGAL was higher in AKI patients (P ≤0.001) with a modest diagnostic performance (AUC = 0.667), below that of urea (AUC = 0.732), creatinine (AUC = 0.696), or cystatin C (AUC = 0.676). CONCLUSIONS: Discharge urinary KIM­1 was a strong and independent predictor of mortality, particularly during the most vulnerable period shortly after hospitalization. Admission serum NGAL was inferior to conventional renal function parameters in predicting AKI during ADHF.

Prevalence, predictors and clinical outcome of residual congestion in acute decompensated heart failure.

BACKGROUND: Congestion is the main reason for hospital admission for acute decompensated heart failure (ADHF). A better understanding of the clinical course of congestion and factors associated with decongestion are therefore important. We studied the clinical course, predictors and prognostic value of congestion in a cohort of patients admitted for ADHF by including different indirect markers of congestion (residual clinical congestion, brain natriuretic peptides (BNP) trajectories, hemoconcentration or diuretic response). METHODS AND RESULTS: We studied the prognostic value of residual clinical congestion using an established composite congestion score (CCS) in 1572 ADHF patients. At baseline, 1528 (97.2%) patients were significantly congested (CCS ≥ 3), after 7 days of hospitalization or discharge (whichever came first), 451 (28.7%) patients were still significantly congested (CCS ≥ 3), 751 (47.8%) patients were mildly congested (CCS = 1 or 2) and 370 (23.5%) patients had no signs of residual congestion (CCS = 0). The presence of significant residual congestion at day 7 or discharge was independently associated with increased risk of re-admissions for heart failure by day 60 (HR [95%CI] = 1.88 [1.39-2.55]) and all-cause mortality by day 180 (HR [95%CI] = 1.54 [1.16-2.04]). Diuretic response provided added prognostic value on top of residual congestion and baseline predictors for both outcomes, yet gain in prognostic performance was modest. CONCLUSION: Most patients with acute decompensated heart failure still have residual congestion 7 days after hospitalization. This factor was associated with higher rates of re-hospitalization and death. Decongestion surrogates, such as diuretic response, added to residual congestion, are still significant predictors of outcomes, but they do not provide meaningful additive prognostic information.

Estrategia de tratamiento de la enfermedad de Fabry tras un ictus / Treatment strategy for Fabry's disease following a stroke

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Cystatin C-based CKD-EPI equations and N-terminal pro-B-type natriuretic peptide for predicting outcomes in acutely decompensated heart failure.

BACKGROUND: In patients with acute decompensated heart failure (ADHF), both natriuretic peptides and renal impairment predict adverse outcomes. Our aim was to evaluate the complementary prognosis role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the newly developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on cystatin C (CysC) for glomerular filtration rate (GFR) estimation in ADHF patients. HYPOTHESIS: Renal impairment assessed by CysC-based CKD-EPI equations and natriuretic peptides have complementary prognostic value in ADHF patients. METHODS: The study included 613 consecutive patients presenting with ADHF. At admission, plasma levels of NT-proBNP and CysC were determined. The GFR was estimated using CysC-based CKD-EPI equations. The primary endpoint was death from any cause and heart failure readmission. RESULTS: During the median follow-up of 365 days (interquartile range, 227-441 days), 323 patients (0.65 %patient-year) died or were readmitted for heart failure. After multivariate adjustment, estimated GFR <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL were independent predictors of adverse outcomes (P < 0.01). The combination of GFR <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL was associated with the highest risk of adverse outcomes. Furthermore, reclassification analyses demonstrated that use of both NT-proBNP and CysC-based CKD-EPI equations resulted in improving the accuracy for adverse outcomes prediction. CONCLUSIONS: In patients with ADHF, the combination of NT-proBNP with estimated GFR using CysC-based CKD-EPI equations better predicts outcomes than either parameter alone and adds valuable complementary prognosis information to other established risk factors.

Influence of gender on prognosis of acute coronary syndromes.

INTRODUCTION: Ischemic heart disease presents different features in men and women. We analyzed the relation between gender and prognosis in patients who had suffered a high-risk acute coronary syndrome (ACS). METHODS: This was a prospective analytical cohort study performed at Lozano Blesa University Hospital, Zaragoza, Spain, of 559 patients diagnosed with high-risk ACS with and without ST-segment elevation according to the American College of Cardiology/American Heart Association guidelines. The sample was divided into two groups by gender and differences in epidemiologic, laboratory, electrocardiographic and echocardiographic variables and treatment were recorded. A Cox's proportional hazard model was applied and 6-month mortality was analyzed as the main variable. RESULTS: The median age was 65.2±12.7 years, and 21.8% were women. Baseline characteristics in women were more unfavorable, with higher GRACE scores, older age, higher prevalence of hypertension, diabetes and heart failure, lower ejection fraction and more renal dysfunction at admission. Women suffered more adverse cardiovascular events (27.9% vs. 15.8%, p=0.002). Sixty-four patients died, 18.9% of the women vs. 9.4% of the men (p=0.004). After multivariate analysis, female gender did not present an independent relation with mortality. Hemoglobin level, renal function, ejection fraction and Killip class >1 presented significant differences. CONCLUSIONS: Acute syndrome coronary in women has a worse prognosis than in men. Their adverse course is due to their baseline characteristics and not to their gender.

Heart failure mortality according to acute variations in N-terminal pro B-type natriuretic peptide and cystatin C levels.

AIM: Changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels and cystatin C (CysC) are predictors of adverse outcomes in acute heart failure. This study assess whether NT-proBNP variations might provide independent information in addition to that obtained from CysC levels. METHODS: NT-proBNP levels were assessed in patients admitted due to acute heart failure using an observational study. Patients were classified as follows: group 1, those with a decrease in NT-proBNP levels of at least 30% from admission to 4 weeks after discharge; group 2, those with no significant changes in levels; and group 3, those who showed an increase in NT-proBNP of 30%. A multivariable Cox regression model and c-statistics were used. The primary end-point was all-cause mortality at 1-year follow-up. RESULTS: A total of 195 patients completed the follow-up. The mortality rate reached 20.5% (40 patients); 14 out of the 32 in group 3. The cumulative incidence of death, according to the change in NT-proBNP and Kaplan-Meier analysis, showed a significant increase in group 3 (log-rank P = 0.004). In the multivariable analysis, NT-proBNP variation for group 3 (hazard ratio 4.27; P <0.001) and for group 2 (hazard ratio 2.19; P = 0.043) in comparison with group 1 were independently associated with all-cause mortality, as well as anemia, hyponatremia, and admission CysC levels. Patients in group 3, and those with levels of serum CysC above the median, were also associated with slight increase in mortality. CONCLUSION: An increase of at least 30% in NT-proBNP levels after hospitalization is related to all-cause mortality in patients with acute heart failure and provides supplementary prognostic information in patients with high levels of CysC. A decrease in NT-proBNP of at least 30% is a desirable target to achieve.

Comparison of risk prediction with the CKD-EPI and MDRD equations in acute decompensated heart failure.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (eGFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. The aim of this study was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for adverse outcomes more accurately than the MDRD equation in a hospitalized cohort of patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: A total of 526 subjects with ADHF were studied. Blood was collected within 48 hours from admission. eGFR was calculated with the use of MDRD and CKD-EPI equations. The occurrences of mortality and heart failure (HF) hospitalization were recorded. Over the study period (median 365 days [interquartile range 238-370]), 305 patients (58%) died or were rehospitalized for HF. Areas under the receiver operator characteristic curves for CKD-EPI CysC and CKD-EPI creatinine-CysC equations were significantly higher than that for the MDRD equation, especially in patients with >60 mL min(-1) 1.73 m(-2). After multivariate adjustment, all eGFR equations were independent predictors of adverse outcomes (P < .001). However, only CKD-EPI CysC and CKD-EPI creatinine-CysC equations were associated with significant improvement in reclassification analyses (net reclassification improvements 10.8% and 12.5%, respectively). CONCLUSIONS: In patients with ADHF, CysC-based CKD-EPI equations were superior to the MDRD equation for predicting mortality and/or HF hospitalization especially in patients with >60 mL min(-1) 1.73 m(-2), and both CKD-EPI equations improved clinical risk stratification.

Prognostic utility of NT-proBNP in acute exacerbations of chronic pulmonary diseases.

BACKGROUND: The prognostic value of NT-proBNP levels in patients admitted to hospital due to acute exacerbations of chronic pulmonary diseases (CPDs) is unknown. SETTING: Internal Medicine units at two general hospitals. METHODS: NT-proBNP levels were obtained within 72 h after admission in 192 consecutive patients with acute exacerbations of CPDs and no history of heart failure or diuretic treatment. Clinical characteristics and main outcomes were assessed over a 12-month follow-up. NT-proBNP cut-points for outcomes were obtained by ROC (receiver operating characteristics) curve analysis. RESULTS: Chronic obstructive lung disease (69.3%) and chronic asthma (22.4%) were the most prevalent CPDs, and non-pneumonic acute respiratory infection (72.4%) and pneumonia (22.9%) were the most frequent causes of exacerbation. Atrial flutter or fibrillation rate was 11%. During the one-year follow-up period, 22 patients died, 42 were re-admitted, 46 received new long-term oxygen therapy, and 39 received new diuretic treatment. NT-proBNP values correlated with hospitalisation days. NT-proBNP values over 587.9 pg/ml were associated with significantly raised one-year mortality (OR=3.90; 95% IC 1.46-10.47; p=0.006) and over 782.2 pg/ml with cardio-pulmonary deaths (OR=6.38; 95% IC 1.91-21.3; p=0.002). That association persisted after adjustment for age, gender, creatinine levels and cardiac rhythm. NT-proBNP values over 628.7 pg/ml were associated with significantly higher probability of new diuretic treatment (OR=4.38; IC 95% 2.07-9.25; p<0.001). The negative predictive values for these cut-points ranged from 89% to 97%. CONCLUSION: NT-proBNP levels below 587.9 pg/ml in patients with acute exacerbations of CPD were associated with favourable one-year outcomes.

Differential prognostic utility of NTproBNP and Cystatin C in patients with acute exacerbation of chronic pulmonary disease.

OBJECTIVES: To determine whether serum Cystatin C (CysC) and NTproBNP have prognostic value among patients with long-standing chronic lung disease. DESIGN: Prospective, observational, non-interventional study. SETTING: CysC and NTproBNP are prognostic markers in several cardiac conditions. In addition, CysC acts as an antiprotease following Cathepsin activation, which has been involved in the pathogenesis of chronic obstructive pulmonary disease. PARTICIPANTS: Patients with a basal functional status of II-IV (NYHA), admitted for an acute exacerbation of chronic pulmonary diseases and no previous history of symptoms related to pulmonary hypertension or heart failure. MAIN OUTCOME MEASURES: NTproBNP and CysC were determined at admission in 107 patients with acute exacerbation of chronic lung disease. During 12-month follow-up, mortality, new hospital admissions and prescription of diuretics were recorded. RESULTS: During follow-up there were eight patient deaths (7.5%). Mean NTproBNP among the deceased was 1510.20 pg/mL (95% CI 498.44-4628.55) vs 502.70 pg/mL (95% CI 395.44-645.48) among survivors (p = 0.01). Twenty-seven patients (25%) were prescribed loop diuretics. Mean concentration of CysC was 1.45 mg/dL (95% CI 1.21-1.69 mg/dL) vs 1.17 mg/dL (95% IC 1.09-1.25 mg/dL) in those not prescribed (p = 0.004). NTproBNP concentration was 837.14 pg/mL (95% CI 555.57-1274.10 pg/mL) in patients prescribed diuretics vs 473.42 pg/mL (95% CI 357.80-632.70 pg/mL) in those not prescribed (p = 0.03). Kaplan-Meier analysis revealed a significant difference between death and diuretic prescription during follow-up when cut-off value for NTproBNP was 550 pg/mL (p = 0.03 and p = 0.02, respectively). For 1.16mg/dL of CsysC, a significant difference was only observed in diuretic prescription (p = 0.007). CONCLUSIONS: In patients with chronic respiratory diseases NTproBNP has predictive value in terms of mortality whereas CysC does not. However, it is still possible that both can contribute to the early identification of patients at risk of developing clinical ventricular dysfunction.

Valor pronóstico del NT-proBNP en pacientes con enfermedad pulmonar crónica reagudizada / Prognostic value of NT-proBNP in chronic pulmonary disease exacerbation

Fundamentos y objetivo: Los péptidos natriuréticos (PN) han demostrado su utilidad en la insuficiencia cardiaca (IC) y algunos trastornos de la circulación pulmonar. El presente trabajo tiene por objeto conocer la utilidad de la fracción aminoterminal del péptido natriurético cerebral (NT-proBNP) como marcador pronóstico en pacientes con enfermedad pulmonar crónica reagudizada, sin semiología clínica de IC. Pacientes y método: Estudio prospectivo y observacional. Se incluyeron de forma consecutiva 192 pacientes con enfermedad pulmonar crónica ingresados por descompensación de su enfermedad respiratoria. Se determinó la concentración sanguínea de NT-proBNP en todos ellos y se realizó posteriormente un seguimiento durante los 6 meses posteriores al ingreso para detectar reingresos, prescripción de diuréticos, oxigenoterapia o muerte.Resultados: El 6,3% de los pacientes fallecieron, en un 22,9% se prescribió oxigenoterapia, en un 18,2% diuréticos y el 21,9% reingresó al menos en una ocasión durante el período de seguimiento de 6 meses. La concentración media de NT-proBNP fue de 1180pg/ml. Concentraciones de NT-proBNP superiores a 500pg/ml (odds ratio [OR] 11,0, intervalo de confianza del 95% [IC 95%] 1,39–86,99) y de 350pg/ml fueron predictoras de mortalidad y prescripción de diurético (OR 2,83; IC 95% 1,16–6,86), respectivamente. Conclusiones: El NT-proBNP podría ser un marcador pronóstico en pacientes con enfermedad pulmonar crónica, identificando a aquellos con especial riesgo de fallecer o más probabilidad de desarrollar una disfunción ventricular sintomática (AU)

Background and objective: Brain natriuretic peptide (BNP) is produced and released mainly from ventricles. BNP has been shown to be useful in diagnosis and prognosis in heart failure and some pulmonary conditions. The aim of this study is to analyse whether NT-proBNP has a prognostic value in chronic pulmonary patients without overt heart failure. Patient and method: We conducted an observational and prospective study. We included 192 patients admitted to the Internal Medicine Departments of Hospital Clinico “Lozano Blesa” (Zaragoza, Spain) and “Virgen de la Luz” (Cuenca, Spain) with acute exacerbation of pulmonary disease. Blood samples were taken to determine NT-proBNP concentrations. All patients were followed for 6 months after admission.Results: 6,3% of patients died, 22,9% were prescribed with home oxygen-therapy, 18,2% received a diuretic prescription and 21,9% were re-admitted at least once during the follow-up period. Mean NT-proBNP was 1180pg/ml. A concentration above 500pg/ml and 350pg/ml of NT-proBNP was useful to predict mortality and diuretic prescription respectively.Conclusions: Among patients with acute exacerbations of chronic pulmonary disease, NT-proBNP could be a prognostic factor to identify those at risk of death or worst clinical development (AU)

[Prognostic value of NT-proBNP in chronic pulmonary disease exacerbation]. / Valor pronóstico del NT-proBNP en pacientes con enfermedad pulmonar crónica reagudizada.

BACKGROUND AND OBJECTIVE: Brain natriuretic peptide (BNP) is produced and released mainly from ventricles. BNP has been shown to be useful in diagnosis and prognosis in heart failure and some pulmonary conditions. The aim of this study is to analyse whether NT-proBNP has a prognostic value in chronic pulmonary patients without overt heart failure. PATIENT AND METHOD: We conducted an observational and prospective study. We included 192 patients admitted to the Internal Medicine Departments of Hospital Clinico "Lozano Blesa" (Zaragoza, Spain) and "Virgen de la Luz" (Cuenca, Spain) with acute exacerbation of pulmonary disease. Blood samples were taken to determine NT-proBNP concentrations. All patients were followed for 6 months after admission. RESULTS: 6,3% of patients died, 22,9% were prescribed with home oxygen-therapy, 18,2% received a diuretic prescription and 21,9% were re-admitted at least once during the follow-up period. Mean NT-proBNP was 1180pg/ml. A concentration above 500pg/ml and 350pg/ml of NT-proBNP was useful to predict mortality and diuretic prescription respectively. CONCLUSIONS: Among patients with acute exacerbations of chronic pulmonary disease, NT-proBNP could be a prognostic factor to identify those at risk of death or worst clinical development.

Valor pronóstico del filtrado glomerular en el síndrome coronario agudo: ¿índice de Cockcroft o ecuación MDRD? / Prognostic value of glomerular filtrate in acute coronary syndrome: Cockcroft's index or MDRD equation?

Fundamento y objetivo: La tercera parte de los pacientes con un episodio coronario agudo presenta insuficiencia renal. El objetivo es determinar la relación entre la insuficiencia renal y la mortalidad en pacientes que tienen un síndrome coronario agudo (SCA) mediante el índice de Cockcroft y la ecuación modification of diet in renal disease study group 4 (MDRD-4), y analizar cuál de las 2 es preferible como estratificación pronóstica. Pacientes y método: Estudio prospectivo de 455 pacientes ingresados de forma consecutiva entre 2006 y 2007 con SCA de alto riesgo mediante división de la muestra según su función renal al ingreso en <60ml/min/1,73m2 y ≥60ml/min/1,73m2 y mediante el índice de Cockcroft-Gault y la ecuación MDRD-4, junto con otras variables. Se realizó un análisis de regresión logística multivariante para cada uno de éstos y se analizó su relación con la mortalidad en los siguientes 6 meses al ingreso. Resultados: La insuficiencia renal (creatinina<1,1mg/dl) estaba presente en el 27,9%, en un 30,5% según el índice de Cockcroft-Gault y en un 22,6% según la ecuación MDRD-4. La media (desviación estándar) del filtrado glomerular (FG) fue de 81,6 (35,2)ml/min según el índice de Cockcroft-Gault y de 77,2 (26,1)ml/min/1,73m2 según la ecuación MDRD-4. Los pacientes con FG <60ml/min presentaron mayor mortalidad, con una odds ratio de 2,652 (intervalo de confianza [IC] del 95%: 1,140–6,166) (p=0,024) según el índice de Cockcroft-Gault y de 3,372 (IC del 95%: 1,637–6,954) (p=0,001) según la ecuación MDRD-4.Conclusión: La insuficiencia renal incrementa el riesgo de fallecer en los siguientes 6 meses tras un SCA. El cálculo del FG mediante el índice de Cockcroft-Gault o la ecuación MDRD-4 depende de las características de la población y es indiferente con filtrados entre 60 y 80ml/min (AU)

Background and objectives: One third of patients with a coronary event show kidney failure. Our aim is to establish the relationship between kidney failure and mortality in patients diagnosed of acute coronary syndrome (ACS) through Cockcroft Index (C-G) and MDRD-4 equation, analyzing which of them is better for prognostic stratification. Patients and method: Prospective study of 445 patients admitted consecutively between 2006 and 2007 with a high risk of ACS, dividing the sample depending on his kidney function at admission in <60mL/min/1,73m2 and ≥60mL/min/1,73m2 through C-G and modification of diet in renal disease study gruop 4 (MDRD-4) and other variables. We performed a multivariate logistic regression for both of them, analysing the relationship with mortality in the following six months after admission. Results: Renal failure was present in 27.9% (creatinine<1,1mg/dl); 30,5% (C-G) and 22,6% (MDRD-4). Glomerular filtration (GF) was 81,6±35,2mL/min (C-G) and 77,2±26,1mL/min/1,73m2 (MDRD-4). Patients with GF<60mL/min showed high mortality, Odds ratio 2,652; p=0,024 (IC 95%, 1,140–6,166) for C-G and 3,372; p=0,001 (IC 95%, 1,637–6,954) for MDRD-4. Conclusion: Renal failure increases the risk to die in the following six months after an ACS. The estimation through Cockcroft Index and/or MDRD-4 equation depends on the population characteristics and is indifferent with GF between 60 and 80mL/min (AU)

[Prognostic value of glomerular filtrate in acute coronary syndrome: Cockcroft's index or MDRD equation?]. / Valor pronóstico del filtrado glomerular en el síndrome coronario agudo: ¿índice de Cockcroft o ecuación MDRD?

BACKGROUND AND OBJECTIVES: One third of patients with a coronary event show kidney failure. Our aim is to establish the relationship between kidney failure and mortality in patients diagnosed of acute coronary syndrome (ACS) through Cockcroft Index (C-G) and MDRD-4 equation, analyzing which of them is better for prognostic stratification. PATIENTS AND METHOD: Prospective study of 445 patients admitted consecutively between 2006 and 2007 with a high risk of ACS, dividing the sample depending on his kidney function at admission in < 60 mL/min/1.73 m(2) and > or =60 mL/min/1.73 m(2) through C-G and Modification of Diet in Renal Disease study group 4 (MDRD-4) and other variables. We performed a multivariate logistic regression for both of them, analysing the relationship with mortality in the following six months after admission. RESULTS: Renal failure was present in 27.9% (creatinine < 1.1mg/dl); 30.5% (C-G) and 22.6% (MDRD-4). Glomerular filtration (GF) was 81.6+/-35.2 mL/min (C-G) and 77.2+/-26.1 mL/min/1.73 m(2) (MDRD-4). Patients with GF < 60 mL/min showed high mortality, Odds ratio 2.652; p=0.024 (IC 95%, 1.140-6.166) for C-G and 3.372; p=0.001 (IC 95%, 1.637-6.954) for MDRD-4. CONCLUSION: Renal failure increases the risk to die in the following six months after an ACS. The estimation through Cockcroft Index and/or MDRD-4 equation depends on the population characteristics and is indifferent with GF between 60 and 80 mL/min.