Juan Ignacio Pérez-Calvo

Predictive value of serum galectin-3 levels in patients with acute heart failure with preserved ejection fraction

AIMS This study was conducted to determine whether galectin-3 (Gal3), a β-galactoside-binding lectin, has usefulness to predict outcomes in patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF). METHODS AND RESULTS We measured Gal3, urea, creatinine and natriuretic peptides on admission in 419 selected patients with HF and LVEF over 45%. The primary endpoint was all-cause mortality and/or readmission at one-year follow-up. Multivariable Cox proportional hazards models were generated for Gal3 and classical risk factors. We also evaluated the reclassification of patients on the basis of the different score category after adding Gal3 levels. A total of 219 patients had combined adverse events, and 129 patients died during the follow-up. Kaplan-Meir survival curve showed significantly increased primary endpoint and all-cause mortality according to quartiles of Gal3 (log rank, P<0.001). Serum Gal3 levels above median (13.8 ng/ml) was a significant predictor of primary endpoint risk after adjustment for age, estimated glomerular filtration rate, anemia, diabetes, serum sodium, brain natriuretic peptide levels, NYHA class and urea, respectively (hazard ratio 1.43, 95% CI 1.07-1.91 P=0.015). The reclassification index increased significantly after addition of Gal3 (9.5%, P<0.001) and the integrated discrimination index was 0.022, (P=0.001). The clinical prediction model with Gal3 increased the c-statistic from 0.711 to 0.731 (difference of 0.020, P=0.001). CONCLUSIONS Serum Gal3 is a strong and independent predictor of unfavorable outcomes in patients with HF and preserved LVEF. We also demonstrated the improvement of adding the new biomarker to the model.

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 value of serum cystatin C and N-terminal pro b-type natriuretic peptide in patients with acute heart failure

BACKGROUND Cystatin C (CysC) is a good prognostic marker in heart failure. However, there is not much information of CysC combined with other biomarkers in acute heart failure (AHF). AIM To assess prognostic value of CysC and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients hospitalized for AHF with no apparent deterioration of renal function. DESIGN Prospective, multicenter, observational study. METHODS CysC and NTpro-BNP were measured in patients consecutively admitted with a diagnosis of AHF. Patients with, NTpro-BNP concentration above 900 pg/mL and serum creatinine below 1.3mg/dL, were included for statistical analysis. End-point of the study was all-cause mortality during a 12-month follow-up. RESULTS 526 patients with AHF and NTpro-BNP concentration above 900 pg/mL were included in the study. From this group, 367 patients (69.8%) had serum creatinine below 1.3mg/dL. Receiver operating characteristic (ROC) curves were used to determine the best cut-off value for CysC. Patients with a concentration of CsyC above 1.25mg/dL had a 37.8% mortality rate, vs. 13.6% for those below cut-off (p<0.001). After Cox proportional hazard model, age, CysC, low total cholesterol and HF with preserved ejection fraction remained significantly associated with all-cause mortality during one-year follow-up. CONCLUSIONS In AHF and normal or slightly impaired renal function, performance of CysC may be superior to NT-proBNP. Hence, CysC may be the preferred biomarker in the assessment of patients with AHF and slightly impaired renal function.

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.

Clinical characteristics and prognostic influence of renal dysfunction in heart failure patients with preserved ejection fraction

BACKGROUND Renal dysfunction is common in patients with heart failure (HF) and is associated with high mortality. This relationship is well established in HF and reduced ejection fraction (HFREF), however, it is not fully understood in HF and preserved ejection fraction (HFPEF). The aim of this study was to determine the impact of renal dysfunction on all-cause mortality in HFPEF patients and to evaluate the clinical characteristics of patients that deteriorate renal function in the first year of follow-up. METHODS We evaluated the patients with HFPEF included in the RICA registry. This is a multi-center and prospective cohort study that includes patients admitted for decompensated HF. Estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and plasma creatinine concentrations were used for renal function assessment at admission and after one year of follow up. RESULTS A total of 455 patients (mean age 78±8.1years; 62% women) were included, of whom 265 (58.2%) had eGFR<60mL/min/1.73m(2). After adjustment for covariates, only lower admission eGFR remained significantly predictive of all-cause mortality (HR 2.97; 95% CI 1.59-5.53). After one year of follow-up 16.6% of patients deteriorated at least 25% of eGFR. These patients were more likely to be diabetic (54.5% vs 42.6%; p=0.039) and had a higher rate of prescription of mineralcorticoid receptor antagonist (MRA) agents (47% vs 23.3%; p<0.001). CONCLUSION Renal dysfunction is frequently associated with HFPEF. eGFR below normal is strongly associated with mortality. Further decline of renal function is frequent especially among diabetic and patients treated with MRA agents.

Cystatin C–based CKD-EPI Equations and N-Terminal Pro-B-Type Natriuretic Peptide for Predicting Outcomes in Acutely Decompensated Heart Failure

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.

La cistatina C: una proteína para la insuficiencia cardíaca

Cystatin C (CysC) is an antiprotease useful for measuring kidney function. Beyond such property, it carries significant prognostic information in several fields of cardiovascular diseases. We review data that support CysC as a prognostic factor in cardiovascular diseases among healthy elderly, hypertensive and heart failure patients. In addition, it has been speculated that CysC may be an early marker of ventricular remodelling, primarily involved in its pathogenesis, as a local antiprotease. Its role in physiopathology and clinical issues of cardiovascular pathology is yet to be elucidated.

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.

Diagnosis of Heart Failure With Preserved Ejection Fraction: Still a Challenge

Campbell et al. ([1][1]) addressed a key issue of heart failure with preserved ejection fraction (HFPEF). Does it really exist? They concluded that it does, because of the differences in outcomes, comorbidities, and biomarkers between hypertensive and HFPEF patients in clinical trials. When these

Heart failure in elderly patients: it is time to add geriatric assessment.

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