Designing a Person-Centred Integrated Care Programme for People with Complex Chronic Conditions: A Case Study from Catalonia.

INTRODUCTION: The prevalence of people with complex chronic conditions is increasing. This population's high social and health needs require person-centred integrated approaches to care. METHODS: To collect data about experiences with the health system and identify priorities for care, we conducted 2 focus groups and 15 semi-structured interviews involving patients with multimorbidity and advanced conditions, caregivers, and representatives of patients' associations. To design the programme, we combined this information with evidence-based recommendations from local healthcare and social care professionals. RESULTS: Patients' and caregivers' main priorities were to ensure (a) comprehension of information provided by healthcare professionals; (b) coordination between patients, caregivers, and professionals; (c) access to social services; (d) support to caregivers in managing situations; (e) perceived support throughout the healthcare process; (f) home care, when available; and (d) a patient-centred approach. These dimensions were included in 37 of 63 clinical actions of the programme to cover the whole care trajectory: identifying high needs, defining, and providing care plans, managing crises, and providing transitional care and end-of-life care. CONCLUSION: We developed an evidence-based integrated care programme tailored to high-need patients combining input from patients, caregivers, and healthcare and social care professionals.

Efecto de la vacunación en la prevención de gripe grave en adultos atendidos en un hospital de tercer nivel durante la temporada 2017-2018 / Effect of vaccination on the prevention of influenza-related severe illness in adults attended in a third level hospital during the 2017-2018 epidemic season

OBJETIVOS: El objetivo de este trabajo fue evaluar el efecto de la vacunación antigripal en la prevención de casos graves asociados a gripe en pacientes adultos atendidos en un hospital de tercer nivel durante la temporada epidémica 2017-2018. METODOLOGÍA: Se realizó un análisis descriptivo con toda la población de sujetos con gripe confirmada por laboratorio en la temporada 2017-2018. Se definió caso grave como el ingreso en unidades de críticos o muerte. El efecto de la vacuna en la población adulta se determinó mediante análisis de regresión logística multivariante. RESULTADOS: Entre las semanas epidemiológicas 44/2017 y 19/2018, el laboratorio del hospital detectó 706 muestras positivas de virus influenza. De los 551 pacientes confirmados de 18 años o más, cuarenta y tres fueron ingresados en alguna de las unidades de críticos del hospital y 26 fallecieron durante el ingreso. El modelo multivariante explicativo mostró la vacunación de la gripe durante la temporada de estudio como factor protector del desarrollo de gravedad [OR: 0,27 (0,11-0,65), p = 0,004], ajustada por edad [1,03 (1,01-1,06), p = 0,04], sexo, tipo de virus (H1N1-pdm09, H3N2 o B) y el estar clasificado como Paciente Crónico Complejo o Enfermedad Avanzada Crónica. CONCLUSIONES: La vacuna de la gripe se muestra como factor protector frente al desarrollo de complicaciones en una temporada en la que la vacuna no contiene el virus que más ha circulado entre la población. Se debe recomendar la vacuna antigripal con periodicidad anual a los grupos de riesgo establecidos por las autoridades sanitarias

OBJECTIVES: The objective of this research was to evaluate the effect of influenza vaccination on the prevention of influenza-related severe cases in adults treated in a third-level hospital during the 2017-2018 epidemic season. METHODOLOGY: A descriptive analysis was performed on the entire population of subjects with a laboratory-confirmed influenza test during the 2017-2018 season. A severe case was defined as a patient treated in one of the Intensive Care Units (ICUs) and/or death. The effect of the vaccine on the adult population was determined by multivariate logistic regression analysis. RESULTS: Between epidemiological weeks 44/2017 and 19/2018, the hospital's laboratory detected 706 positive samples for influenza virus. Of the 551 confirmed patients aged 18 years or older, forty-three were admitted to one of the ICUs, and 26 died during admission. The explanatory multivariate model has shown that flu vaccination prior to or during the epidemic season was a protective factor for the development of severity [OR:0.27 (0.11-0.65, p = 0.004)], adjusted by age [OR: 1.03 (1.01-1.06), p=.04], sex, type of virus (H1N1-pdm09, H3N2 or B virus), Chronic Complex Patient index or Advanced Chronic Disease index. Conclussions: Influenza vaccination is a protective factor against the development of severity associated with influenza infection in a season when vaccination did not contain the virus with higher epidemic circulation among the population. Flu vaccination should be recommended annually following the guidelines established by the health authorities

Effect of vaccination on the prevention of influenza-related severe illness in adults attended in a third level hospital during the 2017-2018 epidemic season. / Efecto de la vacunación en la prevención de gripe grave en adultos atendidos en un hospital de tercer nivel durante la temporada 2017-2018.

OBJECTIVES: The objective of this research was to evaluate the effect of influenza vaccination on the prevention of influenza-related severe cases in adults treated in a third-level hospital during the 2017-2018 epidemic season. METHODOLOGY: A descriptive analysis was performed on the entire population of subjects with a laboratory-confirmed influenza test during the 2017-2018 season. A severe case was defined as a patient treated in one of the Intensive Care Units (ICUs) and/or death. The effect of the vaccine on the adult population was determined by multivariate logistic regression analysis. RESULTS: Between epidemiological weeks 44/2017 and 19/2018, the hospital's laboratory detected 706 positive samples for influenza virus. Of the 551 confirmed patients aged 18 years or older, forty-three were admitted to one of the ICUs, and 26 died during admission. The explanatory multivariate model has shown that flu vaccination prior to or during the epidemic season was a protective factor for the development of severity [OR:0.27 (0.11-0.65, p=0.004)], adjusted by age [OR: 1.03 (1.01-1.06), p=.04], sex, type of virus (H1N1-pdm09, H3N2 or B virus), Chronic Complex Patient index or Advanced Chronic Disease index. CONCLUSSIONS: Influenza vaccination is a protective factor against the development of severity associated with influenza infection in a season when vaccination did not contain the virus with higher epidemic circulation among the population. Flu vaccination should be recommended annually following the guidelines established by the health authorities.

Adherence to reporting guidelines increases the number of citations: the argument for including a methodologist in the editorial process and peer-review.

BACKGROUND: From 2005 to 2010, we conducted 2 randomized studies on a journal (Medicina Clínica), where we took manuscripts received for publication and randomly assigned them to either the standard editorial process or to additional processes. Both studies were based on the use of methodological reviewers and reporting guidelines (RG). Those interventions slightly improved the items reported on the Manuscript Quality Assessment Instrument (MQAI), which assesses the quality of the research report. However, masked evaluators were able to guess the allocated group in 62% (56/90) of the papers, thus presenting a risk of detection bias. In this post-hoc study, we analyse whether those interventions that were originally designed for improving the completeness of manuscript reporting may have had an effect on the number of citations, which is the measured outcome that we used. METHODS: Masked to the intervention group, one of us used the Web of Science (WoS) to quantify the number of citations that the participating manuscripts received up December 2016. We calculated the mean citation ratio between intervention arms and then quantified the uncertainty of it by means of the Jackknife method, which avoids assumptions about the distribution shape. RESULTS: Our study included 191 articles (99 and 92, respectively) from the two previous studies, which all together received 1336 citations. In both studies, the groups subjected to additional processes showed higher averages, standard deviations and annual rates. The intervention effect was similar in both studies, with a combined estimate of a 43% (95% CI: 3 to 98%) increase in the number of citations. CONCLUSIONS: We interpret that those effects are driven mainly by introducing into the editorial process a senior methodologist to find missing RG items. Those results are promising, but not definitive due to the exploratory nature of the study and some important caveats such as: the limitations of using the number of citations as a measure of scientific impact; and the fact that our study is based on a single journal. We invite journals to perform their own studies to ascertain whether or not scientific repercussion is increased by adhering to reporting guidelines and further involving statisticians in the editorial process.

Biomarker-assist score for reverse remodeling prediction in heart failure: The ST2-R2 score.

BACKGROUND: Limited data exists regarding biomarker use to predict left ventricular (LV) reverse remodeling (R2). Our aim was to examine the value of soluble ST2 (ST2), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and galectin-3 relative to LV-R2 in systolic heart failure (HF), and to develop a clinical score for LV-R2 prediction. METHODS: R2 was defined as a) LV ejection fraction (LVEF) increase ≥15%, or b) LVEF increase ≥10% plus reduction of LV end-systolic diameter index ≥20% or LV end-systolic volume ≥40%, for 12 months. RESULTS: We studied 304 patients (79.6% men, mean age 66.1 ± 12.3 years) with baseline LVEF <40%. R2 was observed in 104 patients (34.2%). In univariable logistic regression, factors associated with R2 were age (p=0.02), non-ischemic etiology of HF (p<0.001), NYHA functional class (p=0.02), baseline LVEF (p=0.005), absence of left bundle branch block (LBBB; p=0.002), ST2 (p=0.004), NT-proBNP (p=0.005), and hs-cTnT (p<0.001); HF duration achieved borderline significance (p=0.08). In multivariable analysis, ST2 remained the only biomarker associated with LV-R2. We developed the ST2-R2 score for use in clinical practice for predicting R2; variables included were ST2 <48 ng/mL, non-ischemic etiology, absence of LBBB, HF duration <12 months, baseline LVEF <24%, and ß-blocker treatment. The score had an area under the curve of 0.79 in the derivation cohort and 0.73 in a separate validation cohort. CONCLUSIONS: The ST2-R2 score, which includes the novel biomarker ST2 and five clinical variables, reasonably predicts LV-R2 in systolic HF patients. ST2 was the only studied biomarker that was independently associated with R2.

Soluble neprilysin is predictive of cardiovascular death and heart failure hospitalization in heart failure patients.

BACKGROUND: Neprilysin is a membrane-bound enzyme that breaks down natriuretic peptides. The PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial showed that patients with heart failure (HF) treated with an angiotensin receptor neprilysin inhibitor lived longer without being hospitalized for HF than those receiving standard care with enalapril. OBJECTIVES: This study sought to assess the presence of circulating soluble neprilysin in a real-life cohort of HF patients and correlate neprilysin levels with outcomes. METHODS: Circulating soluble neprilysin was measured with a modified sandwich immunoassay in consecutive ambulatory patients with HF who were followed up for 4.1 years. Associations between neprilysin level and a composite endpoint that included cardiovascular death or HF hospitalization were explored. RESULTS: Median neprilysin concentration in 1,069 patients was 0.642 ng/ml (median quartile 1 to 3: 0.385 to 1.219). Neprilysin weakly but significantly correlated with age (rho = 0.16; p < 0.001). In age-adjusted Cox regression analyses, neprilysin concentrations were significantly associated with the composite endpoint (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.06 to 1.29; p = 0.001) and cardiovascular death (HR: 1.19; 95% CI: 1.06 to 1.32; p = 0.002). In comprehensive multivariable analyses, soluble neprilysin remained significantly associated with both the composite endpoint (HR: 1.18; 95% CI: 1.07 to 1.31; p = 0.001) and cardiovascular death (HR: 1.18; 95% CI: 1.05 to 1.32; p = 0.006). CONCLUSIONS: Identification of circulating neprilysin in HF patients and the positive association of neprilysin with cardiovascular mortality and morbidity further support the importance of NEP inhibition for augmenting natriuretic peptides as a therapeutic target.

Body mass index, body fat, and nutritional status of patients with heart failure: The PLICA study.

BACKGROUND & AIMS: Nutritional assessment may help to explain the incompletely understood obesity paradox in patients with heart failure (HF). Currently, obesity is usually identified by body mass index (BMI). Our objective was to assess the prognostic influence of undernourishment in HF outpatients. METHODS: Two published definitions of undernourishment were used to assess 214 ambulatory HF patients. Definition 1 included albumin, total lymphocyte count, tricipital skinfold (TS), subscapular skinfold, and arm muscle circumference (AMC) measurements (≥2 below normal considered undernourishment). Definition 2 included TS, AMC, and albumin (≥1 below normal considered undernourishment). Patients were also stratified by BMI and body fat percentage and followed for 2 years. All-cause death or HF hospitalization was the primary endpoint. RESULTS: Based on BMI strata, among underweight patients, 60% and 100% were undernourished by Definitions 1 and 2, respectively (31% and 44% among normal-weight, 4% and 11% among overweight, and 0% and 3% among obese patients, respectively, according to the two definitions). The most prevalent undernourishment type was marasmus-like (18% of the total cohort). Undernourishment by both definitions was significantly associated with lower event-free survival. Following multivariable analysis, age, NYHA functional class, NTproBNP, and undernourishment (hazard ratio [HR] 2.25 [1.11-4.56] and 2.24 [1.19-4.21] for Definitions 1 and 2, respectively) remained in the model. In this cohort, BMI and percentage of body fat did not independently predict 2-year event-free survival. CONCLUSIONS: Nutritional status is a key prognostic factor in HF above and beyond BMI and percentage of body fat. Patients in normal BMI range and even in overweight and obese groups showed undernourishment. The high mortality observed in undernourishment, infrequent in high BMI patients, may help to partly explain the obesity paradox. Proper undernourishment assessment should become routine in patients with HF.

ST2 pathogenetic profile in ambulatory heart failure patients.

BACKGROUND: Soluble ST2 is involved in multiple pathogenic pathways, including cardiac strain, inflammation, and myocardial necrosis with remodeling. The relative weight of ST2 and the point at which its prognostic value in heart failure (HF) is affected by different degrees of myocardial strain, inflammation, necrosis, and remodeling is unknown. METHODS AND RESULTS: We examined whether soluble ST2 levels improves HF risk stratification relative to other biomarkers representative of multiple pathogenic pathways-N-terminal pro-B-type natriuretic peptide (NT-proBNP; strain), high-sensitivity C-reactive protein (hsCRP; inflammation), and galectin-3 and high-sensitivity troponin T (hsTnT; necrosis and remodeling)-in 1,015 patients with mean left ventricular ejection fraction (LVEF) 33.5%. Mean follow-up was 4.2 ± 2.1 years. The correlation with soluble ST2 was highest with NT-proBNP (r = 0.32; P < .001) and lowest with galectin-3 (r = 0.15; P < .001). ST2 levels increased with increasing concentrations of the other biomarkers (P < .001 in all cases). During follow-up, 467 patients died. Soluble ST2 remained an independent prognosticator of risk at every tertile of each biomarker. This was observed even after adjusting for clinical parameters. CONCLUSIONS: Soluble ST2 may be regarded as a 3-in-1 prognosis biomarker in HF. ST2 provides valuable long-term risk stratification information in HF beyond that reported by other biomarkers of stretch, inflammation, necrosis, and remodeling.

Renal function largely influences Galectin-3 prognostic value in heart failure.

BACKGROUND: Galectin-3 (Gal-3) has been associated with cardiac remodeling and heart failure (HF) prognosis. Renal function is also a well known HF prognostic indicator. The link between renal insufficiency, HF, and Gal-3 is not completely elucidated. METHODS AND RESULTS: We explored the association between Gal-3 and renal function in a cohort of 876 consecutive ambulatory patients with HF (mean age: 68 years; mean left ventricular ejection fraction [LVEF]: 36%), 52.2% had HF etiology of ischemic heart disease. Circulating Gal-3 was highly correlated with estimated glomerular filtration rate (eGFR), calculated with either the chronic kidney disease-epidemiology (CKD-EPI) equation (r = -0.64) or the CKD-EPI-cystatin-C equation (r = -0.59) and with Cystatin-C levels (r = 0.70), after adjusting for age, sex, New York Heart Association (NYHA) functional class, LVEF, and HF etiology (all p<0.001). Patients were stratified by CKD-EPI-eGFR (ml/min/1.73 m(2)), as follows: ≥ 60 (n = 218), 30 to 59 (n = 434), and <30 (n = 224). In these strata, Gal-3 significantly increased (median [IQR]: 12.3 [10.4-15.6]; 16.1 [13-19.8]; and 24.5 [20-33.8] ng/ml, respectively; trend p < 0.001). This was independent of NYHA functional class (I-II and III-IV) and LVEF (<45% and ≥ 45%). Gal-3 was associated with mortality in univariate analyses, but after adjusting for CKD-EPI-eGFR, the hazard ratios were 1.10 (95% CI: 0.89-1.34, p = 0.39) for all cause death, and 0.90 (95% CI: 0.68-1.21, p = 0.50) for cardiovascular death. Similar results were obtained with eGFRs calculated with the CKD-EPI-cystatin-C equation. CONCLUSION: Circulating Gal-3 was highly associated with renal function in outpatients with HF. The value of Gal-3 for HF prognosis declined after adjusting for renal function.

[Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock]. / Formas de presentación de la insuficiencia cardíaca aguda: edema agudo de pulmón y shock cardiogénico.

Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2l/min/m(2). The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease.

Fragility is a key determinant of survival in heart failure patients.

BACKGROUND: Heart failure (HF) is a chronic condition with poor prognosis, and has a high prevalence among older adults. Due to older age, fragility is often present among HF patients. However, even young HF patients show a high degree of fragility. The effect of fragility on long-term prognosis in HF patients, irrespective of age, remains unexplored. The aim of this study was to assess the influence of fragility on long-term prognosis in outpatients with HF. METHODS AND RESULTS: At least one abnormal evaluation among four standardized geriatric scales was used to identify fragility. Predefined criteria for such scales were: Barthel Index, <90; OARS scale, <10 in women and <6 in men; Pfeiffer Test, >3 (± 1, depending on educational grade); and ≥ 1 positive response for depression on the abbreviated Geriatric Depression Scale (GDS). We assessed 1314 consecutive HF outpatients (27.8% women, mean age years 66.7 ± 12.4 years with different etiologies. Fragility was detected in 581 (44.2%) patients. 626 deaths occurred during follow-up; the median follow-up was 3.6 years [P25-P75: 1.8-6.7] for the total cohort, and 4.9 years [P25-P75: 2.5-8.4] for living patients. Fragility and its components were significantly associated with decreased survival by univariate analysis. In a comprehensive multivariable Cox regression analysis, fragility remained independently associated with survival in the entire cohort, and in age and left ventricular ejection fraction subgroups. CONCLUSION: Fragility is a key determinant of survival in ambulatory patients with HF across all age strata.

Formas de presentación de la insuficiencia cardíaca aguda: edema agudo de pulmón y shock cardiogénico / Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock

El edema agudo de pulmón y el shock cardiogénico son 2 de las formas principales de presentación de la insuficiencia cardíaca aguda. Ambos cuadros son graves, con alta mortalidad, y requieren de un diagnóstico precoz y de un manejo urgente y agresivo. El edema agudo de pulmón es consecuencia del paso de líquido a través de la membrana alveolocapilar, suele ser consecuencia de un episodio cardíaco agudo. En el manejo del edema agudo de pulmón es fundamental una correcta evaluación e identificación clínica del cuadro. En el tratamiento, el objetivo inicial es asegurar la situación hemodinámica y la corrección de la hipoxemia. Vasodilatadores como nitroglicerina, diuréticos de asa y, de forma puntual, opiáceos son otras de las armas terapéuticas a utilizar. El shock cardiogénico se caracteriza por una hipoperfusión mantenida, presión pulmonar enclavada > 18 mmHg y un índice cardíaco < 2,2 l/min/m2. De forma típica se presenta con hipotensión (presión arterial sistólica < 90 mmHg o un descenso de la presión arterial media > 30 mmHg) y una diuresis ausente o disminuida (< 0,5 ml/kg/h). La causa más frecuente es la insuficiencia ventricular izquierda secundaria a un infarto agudo de miocardio. El tratamiento consta de medidas generales para revertir la acidosis y la hipoxemia, así como el uso de fármacos vasopresores e inotrópicos. La revascularización coronaria precoz ha demostrado mejorar la supervivencia en el shock por cardiopatía isquémica (AU)

Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2 l/min/m2. The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease (AU)

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, ß-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.

Long-term prognostic value for patients with chronic heart failure of estimated glomerular filtration rate calculated with the new CKD-EPI equations containing cystatin C.

BACKGROUND: Correct estimation of renal function is crucial in assessing prognosis of patients with heart failure (HF). Recently, two new equations have been proposed to calculate estimated glomerular filtration rate (eGFR) with cystatin C alone or both creatinine and cystatin C. We assessed the prognostic value of eGFR estimated by these new equations in outpatients with HF. METHODS: The study included 879 patients with median age, 70.4 years; main etiology of HF ischemic heart disease, 52.7%; and median LVEF, 34%. RESULTS: eGFR estimates by the new equations correlated significantly with eGFR estimates from previous equations, with the best correlation observed between the 2 equations containing cystatin C [intraclass correlation coefficient 0.95 (95% confidence interval 0.94-0.95)]. During a median follow-up of 3.94 years, 371 patients died. The Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations containing cystatin C were found to be best for predicting death [area under the ROC curve 0.685 for CKD-EPI-cystatin C and 0.672 for CKD-EPI-creatinine-cystatin C vs 0.632 for simplified Modification of Diet in Renal Disease Study traceable to isotope dilution mass spectrometry and 0.643 for CKD-EPI (all P < 0.001)]. The CKD-EPI-cystatin C equations also showed significantly better calibration and reclassification measurements for both integrated discrimination improvement and net reclassification improvement in predicting death (P < 0.001). Reclassification with these new equations was particularly better in the subgroup with intermediate eGFR [45-74 mL · min(-1) · (1.73 m(2))(-1)]. CONCLUSIONS: The two new CKD-EPI equations containing cystatin C are useful for HF risk stratification and show better prognostic performance than creatinine-only based eGFR equations, mostly in patients with intermediate eGFR. These equations seem appropriate for assessing prognosis of HF patients with moderate renal insufficiency.

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.

Soluble ST2 serum concentration and renal function in heart failure.

BACKGROUND: Soluble ST2 (sST2) provides important prognostic information in patients with heart failure (HF). How sST2 serum concentration is related to renal function is uncertain. We evaluated the association between sST2 and renal function and compared its prognostic value in HF patients with renal insufficiency. METHODS AND RESULTS: Patients (n = 879; median age 70.4 years; 71.8% men) were divided into 3 subgroups according to estimated glomerular filtration rate (eGFR): ≥60 mL/min/1.73 m(2) (n = 337); 30-59 mL/min/1.73 m(2) (n = 352); and <30 mL/min/1.73 m(2) (n = 190). sST2 (rho = -0.16; P < .001), N-terminal pro-B-type natriuretic peptide (rho = -0.40; P < .001), and high-sensitivity cardiac troponin T (rho = -0.47; P < .001) inversely correlated with eGFR. All-cause mortality was the primary end point. During a median follow-up of 3.46 years, 312 patients (35%) died, 246 of them from the subgroup of 542 patients with eGFR <60 mL/min/1.73 m(2) (45%). Biomarker combination including sST2 showed best discrimination, calibration, and reclassification metrics in renal insufficiency patients (net reclassification improvement 16.6 [95% confidence interval (CI) 8.1-25; P < .001]; integrated discrimination improvement 4.2 [95% CI 2.2-6.2; P < .001]). Improvement in reclassification was higher in these patients than in the total cohort. CONCLUSIONS: The prognostic value of sST2 was not influenced by renal function. On top of other biomarkers, sST2 improved long-term prediction in patients with renal insufficiency even more than in the total cohort.