Interleukin-6, infection and cardiovascular outcomes in acute heart failure: Findings from the EDIFICA registry.

AIMS: Interleukin-6 (IL-6) is upregulated in response to infectious and inflammatory triggers and independently predicts all-cause mortality in acute heart failure (AHF). However, the association of IL-6 with cardiovascular outcomes and its interplay with C-reactive protein and infection, a major precipitating factor in AHF, remains poorly understood. METHODS AND RESULTS: The association between IL-6 and clinical outcomes (180 days) in AHF was evaluated using a cohort of 164 patients from the EDIFICA registry. Median IL-6 levels at admission were 17.4 pg/mL. Patients in the higher admission IL-6 tertile presented with lower blood pressure and more congestion, were diagnosed more frequently with infection, and had a longer hospital stay. Higher IL-6 levels were associated with increased risk of HF rehospitalization (hazard ratio per log2 3.69, 95% confidence interval (CI) 1.26-10.8, p =.017) and the composite of HF rehospitalization or cardiovascular death (hazard ratio per log2 3.50; 95% CI 1.28-9.57; p =.014), independently of major AHF prognosticators, including B-type natriuretic peptide and renal function. However, no independent associations were found for all-cause rehospitalization or mortality. Despite a moderate correlation of IL-6 with C-reactive protein (CRP) levels (R = .51), the latter were not associated with clinical outcomes in this population. CONCLUSIONS: IL-6 levels associate with higher rate of cardiovascular events in AHF, independently of classical prognosticators and evidence of infection, outperforming CRP as an inflammatory outcome biomarker.

Prognostic Effect of the Dose of Loop Diuretic Over 5 Years in Chronic Heart Failure.

BACKGROUND: High diuretic doses in chronic heart failure (HF) are potentially deleterious. We assessed the effect of dynamic furosemide dose on all-cause mortality among HF ambulatory patients. METHODS AND RESULTS: A cohort of 560 ambulatory patients from an outpatient clinic specialized in HF, with median age 70 years, 67% male, and 89% with moderate-severely reduced ejection fraction, was retrospectively followed for up to 5 years. Dynamic furosamide exposure was categorized as low (0-59 mg/d), medium (60-119 mg/d), high (120-159 mg/d), and very high (≥160 mg/d). Extended Cox models were used to estimate the association between time-varying diuretic dose and mortality. A dose-dependent crude association between higher doses of furosemide and death (hazard ratio [HR] = 1.34, 95% confidence interval (CI): 1.06-2.16; HR = 2.09, 95% CI: 1.54-2.84, for high and very high dose, respectively) was totally explained by patients' characteristics and disease severity indicators (adjusted HR = 0.94, 95% CI: 0.63-1.38; HR = 1.10, 95% CI: 0.79-1.55, for high and very high dose, respectively). CONCLUSION: In this context, higher doses of diuretic did not impair survival, but rather indicated greater severity of the patient's condition.

Office- versus home-based evaluation of quality of life in heart failure with reduced ejection fraction: A randomized study.

BACKGROUND: Heart failure (HF) patients often experience poor health-related quality-of-life (HR-QoL). The Kansas City Cardiomyopathy Questionnaire (KCCQ) is frequently used for assessing HR-QoL in HF. Whether KCCQ scores vary in a clinical meaningful manner according to the setting (home vs office) where patients respond to the questionnaire is currently unknown. AIMS: Assess the differences in the responses to KCCQ-23 questionnaire when completed at home or office. METHODS: Randomized parallel-group study, including patients with HF with reduced ejection fraction (HFrEF). Primary outcome was home vs office comparison of overall summary score (KCCQ-OSS). Main secondary outcomes were clinical summary score (KCCQ-CSS) and total symptom score (KCCQ-TSS). RESULTS: A total of 100 patients were included in the study: 50 home vs 50 office. Mean age was 71 yrs. Most baseline characteristics were well balanced between groups, except male sex, MRA use, and prior HF hospitalizations which were more frequent in the home group. No statistically-significant between-group differences were found regarding KCCQ-OSS (median [percentile25-75]) scores: home 69.1 (42.0-86.5) vs office 63.1 (44.3-82.3) points, P-value = 0.59, or main secondary outcomes: KCCQ-CSS home 62.2 (46.5-79.9) vs office 68.1 (51.9-79.2) points, P-value = 0.69, and KCCQ-TSS home 84.7 (59.7-97.2) vs office 76.4 (66.7-94.4) points, P-value = 0.85. Results remained similar after adjustment for differences in baseline characteristics and using non-parametric regressions. CONCLUSIONS: No major differences were found in KCCQ-23 scores regardless of whether the questionnaire was completed at home or office. These findings can be useful to make HR-QoL more accessible, allowing patients to respond at home using email or cell-phone applications.

Dipeptidyl peptidase IV and mortality after an acute heart failure episode.

BACKGROUND: Dipeptidyl peptidase IV (DPP IV) is a key enzyme in B-type natriuretic peptide processing. DPP IV was never studied in human heart failure (HF). We aimed to measure DPP IV concentration in acute HF and determine its association with mortality. METHODS AND RESULTS: Patients hospitalized with acute HF were eligible. We excluded patients with acute coronary syndromes. A discharge blood sample was collected from all patients and they were followed for a 6-month period. Outcome was HF death. Patients were compared across DPP IV quartiles. A Cox regression analysis was used to assess the prognostic power of DPP IV. We studied 164 patients. Median age was 78 years, 48.8% were men, and 63 had type 2 diabetes and 59.1% had left ventricular systolic dysfunction. Quartiles of DPP IV were <215.2; ≥ 215.2 and <269.3; ≥ 269.3 and <348.6; and ≥ 348.6 ng/mL; groups were homogenous between them. Seventeen patients died. Patients with DPP IV in the last quartile had a hazard ratio of HF death up to 6 months of 2.89, 95% confidence interval, 1.11-7.46. Association was B-type natriuretic peptide independent. CONCLUSIONS: Discharge DPP IV ≥ 348.6 ng/mL conferred an approximately 3-fold higher risk of 6-month HF death. Further studies would be important to understand the role of DPP IV in HF.

Erythropoietic response after intravenous iron in patients with heart failure and reduced ejection fraction with and without background treatment with sodium-glucose cotransporter 2 inhibitors.

AIMS: Intravenous (IV) iron increases haemoglobin/haematocrit and improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) also increase haemoglobin/haematocrit and improve outcomes in heart failure by mechanisms linked to nutrient deprivation signalling and reduction of inflammation and oxidative stress. The effect of IV iron among patients using SGLT2i has not yet been studied. The aim of this study was to evaluate the changes in haemoglobin, haematocrit, and iron biomarkers in HFrEF patients treated with IV iron with and without background SGLT2i treatment. Secondary outcomes included changes in natriuretic peptides, kidney function and heart failure-associated outcomes. METHODS AND RESULTS: Retrospective, single-centre analysis of HFrEF patients with iron deficiency treated with IV iron using (n = 60) and not using (n = 60) SGLT2i, matched for age and sex. Mean age was 73 ± 12 years, 48% were men, with more than 65% of patients having chronic kidney disease and anaemia. After adjustment for all baseline differences, SGLT2i users experienced a greater increase in haemoglobin and haematocrit compared to SGLT2i non-users: haemoglobin +0.57 g/dl (95% confidence interval [CI] 0.04-1.10, p = 0.036) and haematocrit +1.64% (95% CI 0.18-3.11, p = 0.029). No significant differences were noted for iron biomarkers or any of the secondary outcomes. CONCLUSION: Combined treatment with IV iron and background SGLT2i was associated with a greater increase in haemoglobin and haematocrit than IV iron without background SGLT2i. These results suggest that in HFrEF patients treated with IV iron, SGLT2i may increase the erythropoietic response. Further studies are needed to ascertain the potential benefit or harm of combining these two treatments in heart failure patients.

Door-to-furosemide time and clinical outcomes in acute heart failure.

BACKGROUND AND IMPORTANCE: Acute heart failure (AHF) is one of the main causes of unplanned hospitalization in patients >65 years of age and is associated with adverse outcomes in this population. Observational studies suggest that intravenous diuretic therapy given in the first hour of presentation for AHF was associated with favorable outcomes. OBJECTIVES: To study the short-term prognostic associations of the timing of intravenous diuretic therapy in patients admitted to the emergency department (ED) for acute AHF. DESIGN, SETTINGS AND PARTICIPANTS: Patients treated in the ED with intravenous diuretics were selected from the Estratificação de Doentes com InsuFIciência Cardíaca Aguda (EDIFICA) registry, a prospective study including AHF hospitalized patients. Early and non-early furosemide treatment groups were considered using the 1-h cutoff: door-to-furosemide ≤1 h and >1 h. OUTCOMES MEASURE AND ANALYSIS: Primary outcomes were a composite of heart failure re-hospitalizations or cardiovascular death at 30- and 90-days. MAIN RESULTS: Four-hundred ninety-three patients were included in the analysis. The median (interquartile range) door-to-furosemide time was 85 (41-220) min, and 210 (43%) patients had diuretics in the first hour. Patients in the ≤1 h group had higher evaluation priority according to the Manchester Triage System, presented more often with acute pulmonary edema, warm-wet clinical profile, higher blood pressure, and signs of left-side heart failure, while >1 h group had higher Get With the Guidelines-heart failure risk score, more frequent signs of right-side heart failure, higher circulating B-type natriuretic peptides and lower albumin. Door-to-furosemide ≤ 1 h was independently associated with lower 30-day heart failure hospitalizations and composite of heart failure hospitalizations or cardiovascular death (adjusted analysis Heart Failure Hospitalizations: odds ratios (OR) 3.65; 95% confidence interval (CI), 1.22-10.9; P = 0.020; heart failure hospitalizations or cardiovascular death: OR 3.15; 95% CI, 1.49-6.64; P < 0.001). These independent associations lost significance at 90 days. CONCLUSION: Door-to-furosemide ≤1 h was associated with a lower short-term risk of heart failure hospitalizations or cardiovascular death in AHF patients. Our findings add to the existing evidence that early identification and intravenous diuretic therapy of AHF patients may improve outcomes.

Platypnea-Orthodeoxia Syndrome: A Rare Cause of Positional Respiratory Failure.

Platypnea-orthodeoxia syndrome (POS) is a rare clinical entity characterized by dyspnea and arterial desaturation in the upright position. Hypoxia in POS has been attributed to the mixing of deoxygenated venous with oxygenated arterial blood via a shunt, with patent foramen ovale being the most commonly reported abnormality. A systematic evaluation is necessary to identify the underlying cause and promote an appropriate intervention. Here, we present the case of a 79-year-old female with a new diagnosis of POS during the workup of hypoxemic respiratory failure.

Prognostic value of high-sensitivity C-reactive protein in heart failure: a systematic review.

BACKGROUND: Several studies have suggested that high-sensitivity C-reactive protein (hsCRP) is a strong independent predictor of acute myocardial infarction and cardiovascular death. In the specific heart failure (HF) context, a low-grade inflammatory state can contribute to HF progression. AIMS: To perform a systematic review on the current knowledge about low-grade inflammation, as assessed by hsCRP, in the prediction of HF in general and in high-risk populations as well as its prognostic value in established HF. METHODS: We used a computerized literature search in the Medline database using the following key words: C-Reactive Protein, Heart Failure, Cardiomyopathy, Cardiac Failure, Prognosis, and Death. Articles were selected if they had measurements of hsCRP in different patient samples and reference to outcomes in terms of morbidity and mortality. RESULTS: hsCRP is associated with incident HF in general and high-risk populations and provides prognostic information in HF patients. In almost all studies, the association of hsCRP with clinical events was independent of other baseline variables known to influence morbidity and mortality. Very different cutoffs have been proposed in each context across studies. CONCLUSIONS: The prognostic power of hsCRP, whether we consider incident HF or adverse outcomes in established HF, is consistent in different patient populations.

Proteus mirabilis endocarditis.

A 62-year-old man was admitted to the emergency department due to fever and acute heart failure. A transthoracic echocardiogram revealed severe aortic valve obstruction. He was an hepatic transplant recipient and was medicated with everolimus. He underwent mitral and aortic valve replacement with prosthetic valves 4 years ago. Due to his medical background, therapy and clinical presentation, empirical therapy for infective endocarditis was started. Transoesophageal echocardiogram showed severe aortic valve regurgitation but no other findings suggestive of endocarditis. Computed tomography (CT) revealed pulmonary infiltrates compatible with infection and no evidence of septic embolisation. Multiple sets of blood cultures were negative. Proteus mirabilis was isolated in bronchial lavage and antibiotic therapy was adjusted. The patient underwent aortic valve replacement, with no macroscopic findings suggestive of endocarditis. P. mirabilis was isolated in the surgically removed valve. Dual antibiotic therapy was successfully administered for 6 weeks.

Seronegative neuromyelitis optica spectrum disorder: severe polysymptomatic presentation with successful treatment response.

We report the case of a 50-year-old caucasian man presenting with lumbar pain, bilateral ataxia, central facial palsy, ophthalmoparesis and urinary retention. Cerebral MRI hinted a hyperintensity of the medulla oblongata and cervical medulla suggestive of myelitis. Cerebrospinal fluid displayed lymphocytic pleocytosis and elevated protein concentration. Without the possibility to rule out an infectious or inflammatory aetiology, antibiotics and corticosteroids were started. Nevertheless, neurological status deteriorated with loss of muscle strength and left eye amaurosis. A neuroaxis MRI exhibited encephalomyelitis with signal abnormalities involving the pons, medulla oblongata, left optic nerve and cervicodorsal medulla. Although negative for aquaporin-4-IgG antibodies, the patient fulfilled criteria for seronegative neuromyelitis optica spectrum disorder with the presence of multiple core clinical characteristics. Through early institution of corticosteroids, plasma exchange and rituximab, good functional recovery was achieved (Expanded Disability Status Scale score of 2). However, left eye amaurosis persisted despite salvage therapy with intravenous immunoglobulin.

Prognostic Effect of Renal Function in Ambulatory Patients With Heart Failure and Reduced Ejection Fraction: The Kidney Is a Marker of Cardiac Function.

BACKGROUND: Chronic kidney disease is a frequent comorbidity in heart failure (HF), associated with increased mortality. The impact of temporal evolution of kidney function in HF prognosis is largely unknown. We evaluated the effect of renal function over time in all-cause mortality among ambulatory patients with HF. METHODS: We retrospectively analyzed data from 560 patients with HF with left ventricular systolic dysfunction followed for a median of 25.1 months at an outpatient clinic. Demographics and comorbidities were collected at baseline. Creatinine values were abstracted from records at each clinical visit. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and was categorized into 3 classes. Extended Cox models were performed to study the association between time-varying eGFR and death. RESULTS: Patients' mean age was 67.5 ± 13.9 years, 67.0% were men, 46.1% had ischemic etiology, the majority had moderate-to-severe left ventricular systolic dysfunction, and 45.9% had chronic kidney disease at baseline. The eGFR declined approximately 9.0 mL/min/1.73 m2 over 5 years. In crude analysis, time-varying eGFR had a significant dose-dependent association with death (hazard ratio [HR] = 1.34, 95% confidence interval [CI]: 1.03-1.75 for eGFR between 30 and 60 mL/min/1.73 m2; HR = 1.55, 95% CI: 1.11-2.17 for <30 mL/min/1.73 m2). The prognostic value of time-varying eGFR was totally explained by baseline comorbidities, indicators of HF severity and drugs (adjusted HR = 1.11, 95% CI: 0.83-1.48; HR = 1.19, 95% CI: 0.79-1.80, for eGFR 30-60 and <30 mL/min/m2, respectively). CONCLUSIONS: Time-varying kidney function is not independently related to poor prognosis in HF. Rather than directly affecting survival, renal impairment is probably a surrogate marker of HF severity.

Boerhaave Syndrome in an Elderly Man.

Boerhaave syndrome is rare, has an non-specific clinical presentation and most commonly develops after persistent vomiting. Septic shock dominates the clinical picture as a result of extensive infection of the mediastinum and pleural and abdominal cavities. The current management of Boerhaave syndrome includes conservative, endoscopic and surgical treatments. The authors present the case of a 94-year-old man admitted to hospital with community-acquired pneumonia with mild respiratory insufficiency complicated by oesophageal perforation after an episode of vomiting and the development of a large left pleural effusion. An endoscopic approach with the placement of an oesophageal prosthesis was chosen given the advanced age of the patient. The hospital stay was complicated by pleural effusion infection requiring broad-spectrum antibiotics and prosthesis substitution. The patient was discharged after 60 days of hospitalization, without the need for oxygen supplementation, and scoring 80% on the Karnofsky Performance Status Scale. The increase in average life expectancy requires a case-by-case approach, where the benefits of invasive manoeuvres and likelihood of discharge are weighed against an acceptable quality of life, aiming to prevent futile medical treatment. LEARNING POINTS: Boerhaave syndrome is a complete rupture of the oesophageal wall secondary to a sudden increase in intraluminal oesophageal pressure, often in the lower third and left lateral position of the oesophagus.The management of Boerhaave syndrome depends on the time of diagnosis and clinical presentation and includes conservative, endoscopic and surgical approaches.Curative, aggressive approaches focused on the treatment of disease are often not appropriate for an aging population, hence the need for a case-by-case approach, where the benefits of invasive manoeuvres and likelihood of discharge are weighed against an acceptable quality of life, aiming to prevent futile medical treatment.

Prognosis and risk stratification in patients with decompensated heart failure receiving inotropic therapy.

Objectives: The prognostic significance of transient use of inotropes has been sufficiently studied in recent heart failure (HF) populations. We hypothesised that risk stratification in these patients could contribute to patient selection for advanced therapies. Methods: We analysed a prospective cohort of adult patients admitted with decompensated HF and ejection fraction (left ventricular ejection fraction (LVEF)) less than 50%. We explored the outcomes of patients requiring inotropic therapy during hospital admission and after discharge. Results: The study included 737 patients, (64.0% male), with a median age of 58 years (IQR 48-66 years). Main aetiologies were dilated cardiomyopathy in 273 (37.0%) patients, ischaemic heart disease in 195 (26.5%) patients and Chagas disease in 163 (22.1%) patients. Median LVEF was 26 % (IQR 22%-35%). Inotropes were used in 518 (70.3%) patients. In 431 (83.2%) patients, a single inotrope was administered. Inotropic therapy was associated with higher risk of in-hospital death/urgent heart transplant (OR=10.628, 95% CI 5.055 to 22.344, p<0.001). At 180-day follow-up, of the 431 patients discharged home, 39 (9.0%) died, 21 (4.9%) underwent transplantation and 183 (42.4%) were readmitted. Inotropes were not associated with outcome (death, transplant and rehospitalisation) after discharge. Conclusions: Inotropic drugs are still widely used in patients with advanced decompensated HF and are associated with a worse in-hospital prognosis. In contrast with previous results, intermittent use of inotropes during hospitalisation did not determine a worse prognosis at 180-day follow-up. These data may add to prognostic evaluation in patients with advanced HF in centres where mechanical circulatory support is not broadly available.

Amino terminal B-type natriuretic peptide, renal function, and prognosis in acute heart failure: a hospital cohort study.

BACKGROUND: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable diagnostic and prognostic test in heart failure (HF). Limited information is available concerning its use in patients with renal failure, in whom dependence on renal clearance may negatively affect its performance. METHODS AND RESULTS: We evaluated influence of renal function on NT-proBNP levels and on its prognostic value after hospital discharge in 283 acute HF patients. Admission and discharge NT-proBNP levels were higher in patients with decreased estimated glomerular filtration rate (eGFR). In these patients discharge NT-proBNP above median was associated to occurrence of death or readmission at 6 months (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.27-5.03); in patients with normal eGFR, a trend to this association was found (HR 1.64, CI 0.98-2.76). Decrease in NT-proBNP less than 30% of baseline was associated to outcome in patients with normal eGFR (HR 2.68, CI 1.54-4.68) and decreased eGFR (HR 2.54, CI 1.49-4.33). CONCLUSIONS: Acute HF patients with renal failure have higher NT-proBNP levels than those with normal renal function. Discharge NT-proBNP has long-term prognostic value in HF patients with renal dysfunction. NT-proBNP variations during hospitalization provide additional prognostic information either in patients with normal or reduced eGFR.

Clinical syndrome suggestive of heart failure is frequently attributable to non-cardiac disorders--population-based study.

AIM: To assess how often the clinical syndrome (CS) of heart failure is attributable to alternative, including non-cardiac, explanations. METHODS AND RESULTS: Cross-sectional evaluation of 739 community participants aged>or=45 years. Subjects with >or=2 symptoms or signs (dyspnoea or fatigue, orthopnoea, nocturnal paroxysmal dyspnoea, third heart sound, jugular venous distension, rales and lower limb oedema) or who were receiving loop diuretics were considered to have the clinical syndrome of heart failure. Attributable fractions were derived based on adjusted odds ratios and the prevalence of underlying disorders among cases. CS was present in 28.0% of women and in 15.2% of men, p<0.001. The multivariate-adjusted fraction of CS attributable to female gender was 40.6%, to age>or=65 years 28.5%, left ventricular systolic dysfunction, left ventricular dilatation or moderate-severe valvular disease 4.9%, diastolic dysfunction or atrial fibrillation 13.0%, obesity 22.6%, coronary heart disease 7.2% and chronic lung disease 6.9%. When additionally adjusting for depressive symptoms, the association with gender and age became much weaker, and 32% of cases were attributable to depressive symptoms. Forty-two percent of subjects with CS had cardiac abnormalities. CONCLUSION: In less than half of subjects with CS was systolic or diastolic heart failure confirmed. Female gender, older age, obesity and depressive symptoms accounted for the largest fraction of CS.

[Syndrome of Irreversible Lithium-Effectuated NeuroToxicity]. / Síndrome de Neurotoxicidade Irreversível Causada por Lítio.

Lithium has a narrow therapeutic window. Frequent monitoring of both serum levels and clinical signs of toxicity is warranted because toxicity may be present even when concentrations are within the therapeutic range. We report the case of a man with lithium poisoning, with persistent neurologic signs and symptoms even after removal of lithium from circulation - a diagnosis of syndrome of irreversible lithium-effectuated neurotoxicity (SILENT) was made.

O lítio é um fármaco com janela terapêutica estreita, exigindo monitorização frequente dos seus níveis séricos e da clínica, pois a toxicidade pode surgir mesmo com níveis terapêuticos. Apresentamos o caso de um homem com intoxicação por lítio, com persistência de alterações neurológicas mesmo após normalização dos seus níveis séricos, permitindo-nos fazer o diagnóstico de síndrome de neurotoxicidade irreversível causada pelo lítio (SILENT).

Pericardial mesothelioma presenting as a suspected ST-elevation myocardial infarction.

Primary cardiac and pericardial tumors are rare entities with an autopsy frequency of 0.001-0.03%. Metastases to the heart and pericardium are much more common than primary tumors. Malignant pericardial mesotheliomas account for up to 50% of primary pericardial tumors. We report the case of a 75-year-old woman with hypertension, dyslipidemia and atrial fibrillation who went to the emergency department due to nonspecific thoracic discomfort of over six hours duration associated with syncope. Physical examination revealed a low-amplitude arrhythmic pulse, no heart murmurs and no signs of pulmonary congestion. The ECG revealed atrial fibrillation with ST-segment elevation in V2-V6, I and aVL. The patient was transferred for emergent coronary angiography, which revealed a long stenosis in the mid-distal portion of the left anterior descending artery. The echocardiogram showed a large pericardial effusion with diffuse thickening of the myocardium. Due to worsening hemodynamics, cardiac rupture was suspected and the patient underwent urgent sternotomy and pericardiotomy with drainage of a large quantity of hematic fluid. The surgeons then identified a large, unresectable tumor occupying the distal half of the anterior portion of the heart. This is, to our knowledge, the first case report of primary pericardial mesothelioma presenting with suspected ST-elevation myocardial infarction. In this case, direct observation of the tumor led to biopsy and the final diagnosis. These are highly malignant tumors and when diagnosed are usually already at an advanced stage.

Validity of the Seattle Heart Failure Model for prognosis in a population at low coronary heart disease risk.

AIM: Validation of the Seattle Heart Failure Model (SHFM) for predicting the risk of death in a population different than the derivation cohort. METHODS: In a retrospective analysis of a cohort of chronic heart failure patients with left ventricular systolic dysfunction, consecutively referred between 2000 and 2011, we computed the score, according to characteristics at referral. We compared the observed risk of death with that predicted by the model, using receiver operating characteristic (ROC) curves to assess discrimination and a goodness-of-fit test for the comparison of predicted and observed risks. RESULTS: In 565 patients, 68.5% were men, the median age was 70 years, 46.0% had ischemic cause, 89.7% moderate-severe left ventricular systolic dysfunction and 61.2% New York Heart Association class II. The risk of death increased progressively with the model's score, with an area under the ROC curve between 0.69 and 0.72 when considering different follow-up periods. The model underestimated the risk of death (observed vs. predicted: 12.2 vs. 10.4%, P < 0.001; 28.1 vs. 25.1%, P < 0.001; and 43.4 vs. 35.7%, P < 0.001 at 1, 3 and 5 years, respectively). Accurate predictions, with nonsignificant differences between observed and predicted risks in a goodness-of-fit test, were obtained after recalibration. CONCLUSION: In this study, the SHFM substantially underestimated the absolute risk of death in ambulatory chronic heart failure patients, mostly nonischemic and elderly. After adjustment for sample-specific circumstances, the recalibrated model demonstrated to be credible in clinical practice and may provide useful information to physicians.

N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients.

BACKGROUND: Heart failure (HF) is responsible for a huge burden in hospital care. Our goal was to evaluate the value of N-terminal-pro-brain natriuretic peptide (NT-proBNP) in predicting death or hospital readmission after discharge of HF patients. METHODS AND RESULTS: We included 182 patients consecutively admitted to hospital because of decompensated HF. Patients were followed up for 6 months. The primary end point was death or readmission. Twenty-six patients died in hospital. The median admission NT-proBNP level was 6778.5 pg/mL, and the median level at discharge was 4137.0 pg/mL (P<0.001). Patients were classified into 3 groups: (1) decreasing NT-proBNP levels by at least 30% (n=82), (2) no significant modifications on NT-proBNP levels (n=49), and (3) increasing NT-proBNP levels by at least 30% (n=25). The primary end point was observed in 42.9% patients. Variables associated with an increased hazard of death and/or hospital readmission in univariate analysis were length of hospitalization, heart rate, signs of volume overload, no use of ACE inhibitors, higher NYHA class at discharge, admission and discharge NT-proBNP, and the change in NT-proBNP levels. The variation in NT-proBNP was the strongest predictor of an adverse outcome. Independent variables associated with an increased risk of readmission or death were signs of volume overload and the change in NT-proBNP levels. CONCLUSIONS: Variations in NT-proBNP levels are related to hospital readmission and death within 6 months. NT-proBNP levels are potentially useful in the evaluation of treatment efficacy and might help clinicians in planning discharge of HF patients. Whether therapeutic strategies aimed to lower NT-proBNP levels modify prognosis warrants future investigation.