Josep Lupón

Head-to-head comparison of 2 myocardial fibrosis biomarkers for long-term heart failure risk stratification: ST2 versus galectin-3.

OBJECTIVES ST2 and galectin-3 (Gal-3) were compared head-to-head for long-term risk stratification in an ambulatory heart failure (HF) population on top of other risk factors including N-terminal pro-B-type natriuretic peptide. BACKGROUND ST2 and Gal-3 are promising biomarkers of myocardial fibrosis and remodeling in HF. METHODS This cohort study included 876 patients (median age: 70 years, median left ventricular ejection fraction: 34%). The 2 biomarkers were evaluated relative to conventional assessment (11 risk factors) plus N-terminal pro-B-type natriuretic peptide in terms of discrimination, calibration, and reclassification analysis. Endpoints were 5-year all-cause and cardiovascular mortality, and the combined all-cause death/HF hospitalization. RESULTS During a median follow-up of 4.2 years (5.9 for alive patients), 392 patients died. In bivariate analysis, Gal-3 and ST2 were independent variables for all endpoints. In multivariate analysis, only ST2 remained independently associated with cardiovascular mortality (hazard ratio: 1.27, 95% confidence interval [CI]: 1.05 to 1.53, p = 0.014). Incorporation of ST2 into a full-adjusted model for all-cause mortality (including clinical variables and N-terminal pro-B-type natriuretic peptide) improved discrimination (C-statistic: 0.77, p = 0.004) and calibration, and reclassified significantly better (integrated discrimination improvement: 1.5, 95% CI: 0.5 to 2.5, p = 0.003; net reclassification index: 9.4, 95% CI: 4.8 to 14.1, p < 0.001). Incorporation of Gal-3 showed no significant increase in discrimination or reclassification and worse calibration metrics. On direct model comparison, ST2 was superior to Gal-3. CONCLUSIONS Head-to-head comparison of fibrosis biomarkers ST2 and Gal-3 in chronic HF revealed superiority of ST2 over Gal-3 in risk stratification. The incremental predictive contribution of Gal-3 to existing clinical risk factors was trivial.

Combined use of high‐sensitivity ST2 and NTproBNP to improve the prediction of death in heart failure

To address the incremental usefulness of biomarkers from different disease pathways for predicting risk of death in heart failure (HF).

Estimated glomerular filtration rate and prognosis in heart failure: value of the Modification of Diet in Renal Disease Study-4, chronic kidney disease epidemiology collaboration, and cockroft-gault formulas.

OBJECTIVES The purpose of this study was to assess the value of estimated glomerular filtration rate (eGFR) calculated by different formulas for predicting the risk of death in heart failure (HF) outpatients. BACKGROUND Patients with both HF and renal insufficiency have a poor prognosis. Three formulas are mostly used to assess renal function: Cockroft-Gault formula, MDRD-4 (Modification of Diet in Renal Disease Study) formula, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The prognostic values of these formulas have not been adequately compared in HF patients. METHODS A total of 925 patients (72% men; age 69 years; interquartile range: 59 to 75.5 years) with a left ventricular ejection fraction of 31% (interquartile range: 23.5% to 39%) were studied. Follow-up was 1,202 days (interquartile range: 627.5 to 2,156.5 days). Measures of performance were evaluated using continuous data and by dividing patients into 4 subgroups according to the eGFR: ≥90, 89 to 60, <60 to 30, and <30 ml/min/1.73 m(2). RESULTS The 3 formulas correlated significantly, with the best correlation found between the MDRD-4 and CKD-EPI formulas. The 3 formulas afforded independent prognostic information over long-term follow-up. However, risk prediction was most accurate using the Cockroft-Gault formula as evaluated by Cox proportional hazards models (hazard ratio: 0.75 vs. 0.81 with the MDRD-4 formula and 0.80 with the CKD-EPI equation), area under the curve (0.67 vs. 0.62 and 0.64, respectively), and Bayesian information criterion (both analyzing eGFR as a continuous or categorical variable). Indeed, net reclassification improvement and integrated discrimination improvement using the Cockroft-Gault formula were 21% and 5.04, respectively, versus the MDRD-4 formula (the most used) and 13.1% and 3.77 respectively versus CKD-EPI equation (the more recent) (all p values <0.001). CONCLUSIONS In this ambulatory, real-life cohort of HF patients, the Cockroft-Gault formula was the most accurate of the 3 used eGFR formulas to improve the risk stratification for death.

Prognostic Implication of Frailty and Depressive Symptoms in an Outpatient Population With Heart Failure

INTRODUCTION AND OBJECTIVES Heart failure patients have high levels of frailty and dependence. Our aim was to determine the impact of frailty and depressive symptoms on the 1-year mortality rate and the rate of hospitalization for heart failure during a follow-up period of 1 year. METHODS All patients underwent geriatric evaluation, and frailty and depressive symptoms were identified. The study included 622 patients (72.5% male; median age, 68 years; 92% in New York Heart Association class II or III; and median ejection fraction, 30%). RESULTS During follow-up, 60 patients (9.5%) died and 101 (16.2%) were hospitalized for heart failure. Overall, 39.9% of patients exhibited frailty, while 25.2% had depressive symptoms. There were significant associations between mortality at 1 year and the presence of frailty (16.9% vs. 4.8%; P< .001) and depressive symptoms (15.3% vs. 7.7%; P=.006). There was also a significant relationship between heart failure hospitalization and the presence of frailty (20.5% vs. 13.3%; P=.01). No relationship was found between heart failure hospitalization and depressive symptoms. Frailty was an independent predictor of mortality but not of hospitalization. CONCLUSIONS Univariate analysis demonstrated significant relationships between frailty and depressive symptoms and mortality at 1 year. In addition, there was a significant relationship between frailty and the need for heart failure hospitalization. However, only frailty showed prognostic value to predict mortality, which was independent of other variables strongly associated to outcome.

Six-Month Outcome in Patients With Myocardial Infarction Initially Admitted to Tertiary and Nontertiary Hospitals

OBJECTIVES The aim of the present study was to ascertain whether the degree of accessibility to coronary angiography and revascularization results in differing usages or outcomes, or both, in the setting of a high coverage national health system. BACKGROUND The selective use of coronary angiography and revascularization procedures in the management of acute myocardial infarction (MI) remains controversial. METHODS A cohort of 1,460 consecutive patients with a first MI admitted to four referral teaching hospitals (one with tertiary facilities) were followed up for 6 months after admission. Only patients initially admitted to each of the study hospitals were retained for analysis in the original hospitals cohort. End points were 6-month mortality and readmission for reinfarction, unstable angina, heart failure or severe ventricular arrhythmia. RESULTS Patients admitted to the tertiary hospital were more likely to undergo coronary angiography (adjusted relative risk 4.22, 95% confidence interval [CI] 3.37 to 5.45) than those admitted to the nontertiary sites (use rate: 22.1% for nontertiary care, 55.5% for tertiary care). Revascularization procedures were performed in 21.2% of patients in the tertiary hospital and in 8.3% in the nontertiary hospitals (p < 0.0001). Median delay for emergency coronary angiography was shorter in the tertiary hospital (within 1 vs. 2 days, p < 0.0001). Six-month mortality or readmission rates were similar (23.7% and 24.7% for tertiary and nontertiary care, respectively). After adjustment for comorbidity and disease severity, the relative risk of death or readmission for the tertiary hospital was 1.03 (95% CI 0.69 to 1.53) times that of the nontertiary hospitals. CONCLUSIONS Selective use of coronary angiography and revascularization procedures may be as effective as less restricted use in the management of acute MI.

Development of a Novel Heart Failure Risk Tool: The Barcelona Bio-Heart Failure Risk Calculator (BCN Bio-HF Calculator)

Background A combination of clinical and routine laboratory data with biomarkers reflecting different pathophysiological pathways may help to refine risk stratification in heart failure (HF). A novel calculator (BCN Bio-HF calculator) incorporating N-terminal pro B-type natriuretic peptide (NT-proBNP, a marker of myocardial stretch), high-sensitivity cardiac troponin T (hs-cTnT, a marker of myocyte injury), and high-sensitivity soluble ST2 (ST2), (reflective of myocardial fibrosis and remodeling) was developed. Methods Model performance was evaluated using discrimination, calibration, and reclassification tools for 1-, 2-, and 3-year mortality. Ten-fold cross-validation with 1000 bootstrapping was used. Results The BCN Bio-HF calculator was derived from 864 consecutive outpatients (72% men) with mean age 68.2±12 years (73%/27% New York Heart Association (NYHA) class I-II/III-IV, LVEF 36%, ischemic etiology 52.2%) and followed for a median of 3.4 years (305 deaths). After an initial evaluation of 23 variables, eight independent models were developed. The variables included in these models were age, sex, NYHA functional class, left ventricular ejection fraction, serum sodium, estimated glomerular filtration rate, hemoglobin, loop diuretic dose, β-blocker, Angiotensin converting enzyme inhibitor/Angiotensin-2 receptor blocker and statin treatments, and hs-cTnT, ST2, and NT-proBNP levels. The calculator may run with the availability of none, one, two, or the three biomarkers. The calculated risk of death was significantly changed by additive biomarker data. The average C-statistic in cross-validation analysis was 0.79. Conclusions A new HF risk-calculator that incorporates available biomarkers reflecting different pathophysiological pathways better allowed individual prediction of death at 1, 2, and 3 years.

Combined use of high-sensitivity cardiac troponin T and N-terminal pro-B type natriuretic peptide improves measurements of performance over established mortality risk factors in chronic heart failure

BACKGROUND Heart failure still maintains a high mortality. Biomarkers reflecting different pathophysiological pathways are under evaluation to better stratify the mortality risk. The objective was to assess high-sensitivity cardiac troponin T (hs-cTnT) in combination with N-terminal pro-B type natriuretic peptide (NT-proBNP) for risk stratification in a real-life cohort of ambulatory heart failure patients. METHODS We analyzed 876 consecutive patients (median age 70.3 years, median left ventricular ejection fraction 34%) treated at a heart failure unit. A combination of biomarkers reflecting myocyte injury (hs-cTnT) and myocardial stretch (NT-proBNP) was used in addition to an assessment based on established mortality risk factors (age, sex, left ventricular ejection fraction, New York Heart Association functional class, diabetes, estimated glomerular filtration rate, ischemic etiology, sodium, hemoglobin, β-blocker treatment, and angiotensin converting enzyme inhibitor or angiotensin II receptor blocker treatment). RESULTS During a median follow-up of 41.4 months, 311 patients died. In the multivariable Cox proportional hazards model, hs-cTnT and NT-proBNP were independent prognosticators (P = .003 each). The combined elevation of both biomarkers above cut-off values significantly increased the risk of death (HR 7.42 [95% CI, 5.23-10.54], P < .001). When hs-cTnT and NT-proBNP were individually included in a model with established mortality risk factors, measurements of performance significantly improved. Results obtained for hs-cTnT compared with NT-proBNP were superior according to comprehensive discrimination, calibration, and reclassification analysis (net reclassification indices of 7.7% and 1.5%, respectively). CONCLUSIONS hs-cTnT provides significant prognostic information in a real-life cohort of patients with chronic heart failure. Simultaneous addition of hs-cTnT and NT-proBNP into a model that includes established risk factors improves mortality risk stratification.

Sex and age differences in fragility in a heart failure population.

Heart failure (HF) patients have a high degree of fragility and dependence from physical, cognitive and psychological points of view, and are a mainly geriatric population.

Statins in Heart Failure: The Paradox Between Large Randomized Clinical Trials and Real Life

OBJECTIVE To assess the relationship between statins and prognosis in ischemic and nonischemic patients with heart failure (HF) in a real-life cohort followed up for a long period. PATIENTS AND METHODS This prospective study included 960 patients with HF with preserved or depressed left ventricular ejection fraction (LVEF), irrespective of HF etiology, who were referred to the HF clinic of a university hospital between August 1, 2001, and December 31, 2008. The patients were followed up for a maximum of 9.1 years (median, 3.7 years), and survival in ischemic and nonischemic patients was determined. RESULTS Median age was 69 years, and median LVEF was 31%. Of the 960 patients, 532 (55.4%) had ischemic HF etiology, and most received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (846; 88.1%) and β-blockers (776; 80.8%). Patients with HF of ischemic origin were more often treated with statins (P<.001). During follow-up, 440 patients (45.8%) died. Statin therapy was associated with significantly improved survival (hazard ratio, 0.45 [95% confidence interval, 0.37-0.54]; P<.001). After adjustment for HF prognostic factors (age, sex, cholesterol level, New York Heart Association class, HF etiology, LVEF, body mass index, HF duration, atrial fibrillation, implantable cardioverter-defibrillator therapy, and medicines), statins remained significantly associated with lower mortality risk in both ischemic (P=.007) and nonischemic (P=.002) patients. CONCLUSION In contrast to results of large randomized trials, statins were independently and significantly associated with lower mortality risk in our real-life HF cohort, including patients with nonischemic HF etiology.

Significado pronóstico de los valores de hemoglobina en pacientes con insuficiencia cardíaca

Introduccion y objetivos Evaluar el valor pronostico de las concentraciones de hemoglobina (Hb) en relacion con la mortalidad y con los ingresos hospitalarios por insuficiencia cardiaca (IC) al ano de la primera visita a la Unidad de IC. Pacientes y metodo Conocemos la situacion vital y los ingresos por IC al ano en 337 pacientes admitidos entre agosto de 2001 y marzo de 2003. Las concentraciones de Hb se recogieron en la primera visita. Resultados Fallecieron 28 (8%) pacientes y hubo 158 ingresos por IC en 66 pacientes. Los valores de Hb se asociaron con la mortalidad a 1 ano (pacientes vivos, 13,0 ± 1,7 g/dl; pacientes fallecidos, 11,6 ± 1,7 g/dl; p Conclusiones Los valores de Hb se asocian inversamente con la mortalidad y los ingresos por IC en el primer ano de seguimiento. La prevalencia de anemia en nuestra poblacion con IC es elevada y tiene valor pronostico independiente.