Margarida Alvelos

The effect of dietary sodium restriction on neurohumoral activity and renal dopaminergic response in patients with heart failure

This work evaluates the effect of a low‐sodium diet on clinical and neurohumoral parameters and on renal dopaminergic system activity in heart failure (HF) patients.

Neutrophil Gelatinase-Associated Lipocalin in the Diagnosis of Type 1 Cardio-Renal Syndrome in the General Ward

BACKGROUND AND OBJECTIVES The early identification of acute heart failure (HF) patients with type 1 cardio-renal syndrome should be the first step for developing prevention and treatment strategies for these patients. This study aimed to assess the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C in the early detection of type 1 cardio-renal syndrome in patients with acute HF. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS One-hundred nineteen patients admitted with acute HF were studied. NGAL and creatinine were measured in the first hospitalization morning; creatinine was also measured at least after 48 to 72 hours. Physicians were blinded to NGAL and cystatin C levels. Type 1 cardio-renal syndrome was defined as an increase in the creatinine level of at least 0.3 mg/dl or 50% of basal creatinine. RESULTS Type 1 cardio-renal syndrome developed within 48 to 72 hours in 14 patients (11.8%). Admission NGAL levels were higher in these patients: 212 versus 83 ng/dl. At a cutoff value of 170 ng/L, NGAL determined type 1 cardio-renal syndrome with a sensitivity of 100% and a specificity of 86.7%. The area under the receiver-operating characteristic curve of NGAL was 0.93 and that of cystatin C was 0.68. CONCLUSIONS Above a cutoff value of 170 ng/L, NGAL predicts 48- to 72-hour development of type 1 cardio-renal syndrome with a negative predictive value of 100% and a positive predictive value of 50%. NGAL independently associates with type 1 cardio-renal syndrome and might be a useful biomarker in the early recognition of these patients.

Prognostic value of neutrophil gelatinase-associated lipocalin in acute heart failure

BACKGROUND The identification of patients at risk for worse outcome is still a challenge. We hypothesized that cystatin C, a marker of renal function, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute renal injury, would have a role in the prognostic stratification of these patients. METHODS We prospectively evaluated 121 patients admitted for acute HF. Serum NGAL and cystatin C levels were measured on the first morning after admission. The outcome measures used were the occurrence of death from all causes, and the combined endpoint defined as the first occurrence of either death or hospital admission. Patients were followed for up to 3 months. RESULTS The variables associated with a higher occurrence of death in a univariate approach were older age and higher levels of BNP, cystatin C and NGAL, and those associated with the occurrence of the combined endpoint were older age, Diabetes mellitus, lower GFR, type 1 cardio-renal syndrome, BNP, cystatin C and NGAL. BNP and NGAL remained independent predictors of the occurrence of both all-cause death and the combined endpoint. NGAL levels in the 75th percentile (>167.5 ng/mL) were associated with a 2.7-fold increase in the risk of death and a 2.9-fold increase in the risk of the first occurrence of either death or hospitalization. CONCLUSIONS Serum NGAL, a marker of acute renal injury, is an independent predictor of worse short term prognosis in patients with acute HF. This suggests a role of renal damage, apart from renal function, in the prognosis of these patients.

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 β-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.

Depressive Symptoms and Heart Failure Stages

The authors measured depressive symptoms cross-sectionally, across evolving stages of heart failure as defined by the American College of Cardiology, from low risk, through high risk for heart failure (Stage A), asymptomatic cardiac dysfunction (Stage B), up to symptomatic heart failure (Stage C), in a community sample of 338 noninstitutionalized adults age >or=45 years. Depressive symptoms were measured with the Beck Depression Inventory (BDI). Women scored significantly higher on the BDI. Adjusted BDI scores increased linearly with heart failure stages in women, whereas, in men, only Stage C was associated with a significantly higher score.

Diagnostic value of patterns of symptoms and signs of heart failure: application of latent class analysis with concomitant variables in a cross-sectional study

Objective The diagnosis of heart failure (HF) requires a compatible clinical syndrome and demonstration of cardiac dysfunction by imaging or functional tests. Since individual symptoms and signs are generally unreliable and have limited value for diagnosing HF, the authors aimed to identify patterns of symptoms and signs, based on findings routinely collected in current clinical practice, and to evaluate their diagnostic value, taking into account the a priori likelihood of HF. Design Cross-sectional evaluation. Participants 1115 community participants aged ≥45 years from Porto, Portugal, in 2006–2008. Main outcomes measures Patterns were identified by latent class analysis, using concomitant variables to predict class membership. Patterns used 11 symptoms/signs, covering dimensions of congestion and hypoperfusion. Sex, age, education, obesity, diabetes and history of myocardial infarction or HF were included as concomitants. Results Bayesian information criteria supported a solution with three patterns: 10.1% of participants followed a pattern with symptoms of troubled breathing and signs of congestion (pattern 1), 27.8% a pattern characterised mainly by signs of congestion (pattern 2) and 62.1% were essentially asymptomatic (pattern 3); model fit was best when including concomitant variables. The likelihood ratio of patterns 1, 2 and 3 for left ventricular systolic dysfunction was 3.4, 1.1 and 0.6, and for left ventricular diastolic dysfunction 3.5, 1.4 and 0.5, respectively. Conclusions The use of concomitant variables can improve the diagnostic value of the symptoms and signs patterns and, consequently, improve the usefulness of the symptoms and signs for diagnosis and as an outcome measure. The potential for application in other settings of complex diagnoses is very high. These models were shown to be useful to standardise and quantify the probabilistic reasoning in clinical diagnosis, upon which decisions of further investigation and even treatment need to be made.

Effect of saline load and metoclopramide on the renal dopaminergic system in patients with heart failure and healthy controls.

Dopamine of renal origin has natriuretic/diuretic actions by activating D1-like receptors of the nephron. Saline load increases renal dopamine production and natriuresis in healthy subjects, and, under these conditions, the activation of D2-like receptors also produces natriuresis/diuresis. Metoclopramide is a D2-like receptor antagonist. Patients with heart failure (HF) have an increased renal dopamine-synthesizing efficiency. However, the effect of salt loading was not explored in HF. We hypothesized that HF patients respond to salt loading with increased production of renal dopamine and that metoclopramide antagonizes this response. This was a randomized, controlled, crossover study exploring the effect of NaCl and metoclopramide on renal dopaminergic, sympathetic, renin-angiotensin-aldosterone, and arginine-vasopressin (AVP) systems activity on sodium handling in 9 HF patients and 9 controls. NaCl markedly increased renal dopamine production and natriuresis in both groups. Metoclopramide blunted these responses in HF patients but not in controls. NaCl decreased renin and aldosterone plasma levels in controls but not in HF patients. In these patients B-type natriuretic peptide (BNP) levels increased, but AVP was not affected. HF patients respond to salt loading with increased natriuresis. However, the mechanisms for this response are different from those found in healthy subjects. Metoclopramide has antinatriuretic effects only in HF patients.

Does pre-albumin predict in-hospital mortality in heart failure?

Does pre-albumin predict in-hospital mortality in heart failure?☆ Patricia Lourenco ⁎, Sergio Silva , Fernando Frioes , Margarida Alvelos , Marta Amorim , Paulo Torres-Ramalho , Maria Jose Teles , Joao Tiago Guimaraes , Paulo Bettencourt a a Servico de Medicina Interna, Centro Hospitalar Sao Joao, Faculdade de Medicina da Universidade do Porto, Unidade I&D Cardiovascular do Porto, Portugal b Servico de Patologia Clinica, Centro Hospitalar Sao Joao, Faculdade de Medicina da Universidade do Porto, Portugal c Departamento de Bioquimica, Faculdade de Medicina da Universidade do Porto, Portugal

Hypocalcaemia as a Reversible Cause of Acute Heart Failure in a Long-Term Survivor of Childhood Cancer

Hypocalcaemia is known for its neuromuscular symptoms, which are rapidly alleviated by intravenous supplementation. Calcium is also essential for both cardiac cell excitability and contraction. We present a case of acute heart failure due to hypocalcaemia in a young male with a complex medical history. LEARNING POINTS Hypocalcaemia is a rare cause of acute heart failure. All clinical decisions, although correct and necessary, may have grave consequences in the short and long term. Childhood cancer survivors have an excess risk of developing multiple complications, namely heart failure and lung fibrosis.

692 Prognosis in elderly patients with heart failure

Introduction: Patients with heart failure (HF) are getting older and prognosis in these cases should be assessed since prognostic markers may differ from those previously identified in younger patient populations. Objective: To evaluate the prognostic information provided by some clinical, haemodynamic, analytical and therapeutic variables in elderly (>70 years) HF patients in comparison with younger ones. Material and Methods: We reviewed the clinical records of 127 patients consecutively admitted to our HF Clinic, with an established diagnosis of HF according to the ESC criteria and left ventricular systolic dysfunction. At the first visit patients were submitted to complete physical examination, blood analysis and echocardiography, and therapy was instituted according to the state of the art towards individualised optimisation. Cox regression was used to evaluate the association between baseline characteristics and prognosis. The outcome under study was the composite endpoint all-cause mortality or hospitalisation Results: Sixty-three patients were older than 70 years. Overall, higher NYHA class, lower pulse pressure, lower creatinine, lower sodium, higher uric acid, higher B-type natriuretic peptide (BNP) and not being treated with a beta-blocker (BB) and a statin were significantly associated with worse prognosis on univariate analysis. In multivariate analysis, only BNP (HR=1.05 for the increase in each 100pg/ml; p=0.08) and the use of BB (HR=0.31; p<0.001) maintained prognostic value. Among the 64 younger patients, lower sodium, higher uric acid, higher BNP and not being treated with a BB were significantly related with worse prognosis on univariate analysis. In multivariate analysis, only BNP (HR=1.10 for the increase in each 100pg/ml; p=0.02) and the use of BB (HR=0.17; p<0.001) remained statistically significant. The characteristics of older patients related with prognosis on univariate analysis were higher NYHA class, lower pulse pressure, and not using a BB and a statin. All of these factors except for the use of BB, retained their statistical significance on multivariate analysis (HR=2.00, p=0.02 for NYHA class; HR=0.65, p=0.002 for the increase in each 10mmHg in pulse pressure; and HR=0.46, p=0.04 for the use of a statin). Conclusions: This study suggests that among elderly patients, who have largely been left out of experimental studies, prognostic markers are different from those in younger ones. Further studies in larger samples are needed to clarify this issue.