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.

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.

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.

Bilateral diagonal earlobe crease

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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.

[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).

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.

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.

Prognostic Value of Osteoprotegerin in Acute Heart Failure.

BACKGROUND: Osteoprotegerin (OPG) is promising as a predictor of adverse prognosis in patients with acute coronary syndromes and chronic heart failure. Its prognostic value in acute heart failure (AHF) is unknown. The aim of this study was to assess the prognostic value provided by serum OPG levels at discharge after an admission for AHF. METHODS: In a prospective study, we enrolled 338 patients consecutively admitted with AHF to the internal medicine department of a tertiary care university hospital in Porto, Portugal between March 2009 and December 2010. OPG was measured using a commercial enzyme-linked immunosorbent assay and was both analyzed as a continuous variable and categorized by quartiles. Patients were followed for up to 6 months after discharge to ascertain the occurrence of all-cause death or hospital readmission resulting from AHF. RESULTS: During follow-up, 119 patients died or were readmitted for AHF. A graded increase in the risk of the combined end point was observed across quartiles of OPG. At 6 months, the cumulative risk of the end point was 25% for the first quartile and 50% for the fourth quartile. The multivariable adjusted risk of death or hospitalization for AHF increased progressively across categories of OPG up to a statistically significant 2.44-fold increase in risk in the highest category (P for linear trend = 0.002, ie, by 5% per 10 pg/mL increase in OPG). CONCLUSIONS: Serum OPG was directly associated with a higher probability of death or readmission for AHF within 6 months, irrespective of other known prognostic markers. This was true both when the ejection fraction was preserved and when it was reduced.

Prognostic value of sST2 added to BNP in acute heart failure with preserved or reduced ejection fraction.

BACKGROUND: Natriuretic peptides and suppression of tumorigenicity 2 (ST2) represent two different physiopathological pathways. We evaluated the prognostic accuracy and complementarity of B-type natriuretic peptide (BNP) and soluble ST2 (sST2) plasma levels at discharge from a hospital admission for acute heart failure, both in patients with preserved (HFpEF) and depressed (HFrEF) systolic function. METHODS AND RESULTS: We enrolled 195 consecutive patients discharged alive and followed them prospectively for 6 months. The endpoint was all-cause death or hospital readmission for heart failure. Seventy-six patients had HFpEF and 119 had HFrEF, of whom 23 (30.3%) and 43 (36.1%) reached the combined endpoint, respectively. In both HFpEF and HFrEF, having the two biomarkers into account added prognostic information, with the highest risk in patients with both biomarkers above the median in their group (approximately 40% hospitalization-free survival in both groups at 6 months). These associations translated into a significant fourfold increase in risk of the endpoint for one elevated biomarker and sevenfold for both biomarkers elevated in HFrEF, and no association for one elevated biomarker and fivefold increase in risk for both biomarkers elevated in HFpEF. Considering the reclassification of risk added to BNP by measurement of sST2, net reclassification index was 0.31 (p = 0.21) among patients with HFpEF and 0.70 (p < 0.001) among patients with HFrEF. CONCLUSIONS: sST2 provides robust prognostic information in acute heart failure with HFrEF, while this pattern was less clear in HFpEF. When sST2 was measured together with BNP, it improved prognostic accuracy in both groups, more clearly in HFrEF.

Medication adherence to specific drug classes in chronic heart failure.

BACKGROUND: Adherence to medication is crucial to improve clinical outcomes in patients with heart failure (HF). However, at least 1 out of 4 patients is nonadherent to his or her medication. Several studies have quantified medication adherence in HF patients, monitoring only 1 drug with the Medication Event Monitoring System (MEMS). Some authors have argued that monitoring 1 drug reflects the whole adherence behavior, although there is some evidence of important differences in adherence to distinct drug classes. Furthermore, medication characteristics could be a relevant predictor of adherence, and different drugs could pose different barriers to patients. OBJECTIVES: To (a) quantify medication adherence to angiotensin-converting enzyme inhibitors (ACEI), beta blockers, and loop diuretics and (b) compare the agreement in adherence among drug classes in chronic HF. METHODS: Medication adherence to 3 different drugs was monitored using MEMS in 63 patients (81% male, mean age 63.5 years). Medication adherence was measured as the percentage of prescribed doses effectively taken. Patients were considered to be adherent when at least 88% of prescribed doses were taken. Adherence agreement between drug classes was analyzed with Bland-Altman plots and Kappa coefficients.  RESULTS: The mean adherence was 97.3% for ACEI, 97.2% for beta blockers, and 96.0% for loop diuretics. Individual patients did not adhere equally to all drug classes, with differences within the same patient ranging from -35% to 33%. The proportion of patients classified as adherent was 77.8% to ACEI, 69.8% to beta blockers, and 69.8% to loop diuretics. The agreement between each of 2 drugs regarding adherence was substantial (beta blocker vs. ACEI: K = 0.72; beta blocker vs. diuretic: K = 0.62; ACEI vs. diuretic: K = 0.72). If patients were classified as adherent and nonadherent based only on 1 drug, 20% of patients would be misclassified regarding the other drugs.  CONCLUSIONS: Patients can adhere differently to medication used in HF treatment, with lowest adherence to loop diuretic and beta blockers and highest adherence to ACEI. Studies measuring medication adherence should always specify the drug class being analyzed and should not mix different drug classes to generalize about adherence behavior.

Prognostic value of worsening renal function in outpatients with chronic heart failure.

INTRODUCTION AND OBJECTIVES: Renal function impairment predicts poor survival in heart failure. Attention has recently shifted to worsening renal function, based mostly on serum creatinine and estimated glomerular filtration rate. We assessed the prognostic effect of worsening renal function in ambulatory heart failure patients. METHODS: Data from 306 ambulatory patients were abstracted from medical files. Worsening renal function was based on the change in estimated glomerular filtration rate, serum creatinine and urea within 6 months of referral. Prognosis was assessed by the composite endpoint all-cause death or heart failure hospitalization, censored at 2 years. Hazard ratios were estimated for worsening renal function, adjusted for sex, age, diabetes, New York Heart Association class, left ventricular systolic dysfunction, medications and baseline renal function. RESULTS: The agreement among definitions was fair, with kappa coefficients generally not surpassing 0.5. Worsening renal function was associated with poor outcome with adjusted hazard ratios (95% confidence interval) of 3.2 (1.8-5.9) for an increase of serum creatinine >0.3mg/dl; 2.2 (1.3-3.7) for an increase in serum urea >20mg/dl and 1.9 (1.1-3.3) for a decrease in estimated glomerular filtration rate >20%, independent of baseline renal function. The 2-year risk of death/heart failure hospitalization was approximately 50% in patients with an increase in serum creatinine or in serum urea; this positive predictive value was higher than for decreasing estimated glomerular filtration rate. CONCLUSIONS: In conclusion, worsening renal function was significantly associated with a worse outcome. Different definitions identified different patients at risk and increasing creatinine/urea performed better than decreasing estimated glomerular filtration rate.

Low prealbumin is strongly associated with adverse outcome in heart failure.

OBJECTIVE: Prealbumin is one of the best indicators of nutritional status. We previously showed that prealbumin predicted in-hospital mortality in heart failure (HF) patients. We evaluated if a low discharge prealbumin after admission with acute HF would predict morbidity and mortality. METHODS: We conducted a prospective observational study. Patients admitted with a primary diagnosis of HF were studied. Follow-up was up to 6 months. Endpoints analysed were: all-cause and HF-death; all-cause and worsening HF hospitalisation. Patients with discharge prealbumin ≤15.0 mg/dL and those with prealbumin >15 mg/dL were compared. A Cox-regression analysis was used to evaluate the prognostic impact of low prealbumin. RESULTS: We studied 514 patients. Mean age was 78 years and 45.7% were male. During follow-up, 101 patients died (78 for HF) and 209 patients were hospital readmitted (140 for worsening HF). Median prealbumin was 20.1 (15.3-25.3) mg/dL. Patients with lower prealbumin were more often women, older aged and with non-ischaemic HF; they had lower albumin, haemoglobin and total cholesterol; and higher glomerular filtration rate, C-reactive protein, B-type natriuretic peptide and length of hospital stay. Lower prealbumin associated with less ß-blocker and statin use. Patients with discharge prealbumin ≤15 mg/dL had a multivariate adjusted HR of 6-month all-cause and HF death of 1.67 (1.00 to 2.80) and 2.12 (1.19 to 3.79) respectively and of all-cause and HF readmission of 1.47 (1.01 to 2.14) and 1.58 (1.01 to 2.47). CONCLUSIONS: Patients with discharge prealbumin ≤15 mg/dL have an higher risk of 6 months morbidity and mortality. The unbalance between protein-energy demands and its availability predicts ominous HF outcome.