A Pilot Study on Standardized In-hospital Education About Heart Failure Conducted During the First Days After Decompensation.

INTRODUCTION: Education addressed to heart failure (HF) patients constitutes an important element of modern comprehensive treatment programs. The present article demonstrates a novel method of standardized in-hospital education addressed to patients admitted due to decompensation in HF. METHODS: This pilot study was conducted among 20 patients [19 men, age 63 ± 16 years, NYHA (Classification according to New York Heart Association) on admission (II/III/IV): 5/25/70%]. Five-day education was based on individual sessions conducted using colorful boards demonstrating selected, highly practical elements of the knowledge about HF management, prepared by experts in HF management (medical doctors, a psychologist, and a dietician). The level of knowledge about HF was measured before and after education, based on a questionnaire prepared by the authors of the boards. RESULTS: All patients experienced an improvement of their clinical status (confirmed by reduced New York Heart Association class and body mass, both P < 0.05). Mini Mental State Exam (MMSE) confirmed that no one demonstrated cognitive impairment. The score reflecting the level of knowledge about HF improved significantly after 5 days of in-hospital treatment accompanied by education (P = 0.0001). CONCLUSIONS: We showed that the proposed model of education addressed to patients with decompensated HF, conducted using colorful boards demonstrating selected, highly practical elements of the knowledge about HF management, prepared by experts in HF management lead to significant increase of HF-related knowledge.

Effects of an outpatient intervention comprising nurse-led non-invasive assessments, telemedicine support and remote cardiologists' decisions in patients with heart failure (AMULET study): a randomised controlled trial.

AIM: Prevention of heart failure (HF) hospitalisations and deaths constitutes a major therapeutic aim in patients with HF. The role of telemedicine in this context remains equivocal. We investigated whether an outpatient telecare based on nurse-led non-invasive assessments supporting remote therapeutic decisions (AMULET telecare) could improve clinical outcomes in patients after an episode of acute HF during 12-month follow-up. METHODS AND RESULTS: In this prospective randomised controlled trial, patients with HF and left ventricular ejection fraction (LVEF) ≤49%, after an episode of acute HF within the last 6 months, were randomly assigned to receive either an outpatient telecare based on nurse-led non-invasive assessments (n = 300) (AMULET model) or standard care (n = 305). The primary composite outcome of unplanned HF hospitalisation or cardiovascular death occurred in 51 (17.1%) patients in the telecare group and 73 (23.9%) patients in the standard care group up to 12 months after randomization [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48-0.99; P = 0.044]. The implementation of AMULET telecare, as compared to standard care, reduced the risk of first unplanned HF hospitalisation (HR 0.62, 95% CI 0.42-0.91; P = 0.015) as well as the risk of total unplanned HF hospitalisations (HR 0.64, 95% CI 0.41-0.99; P = 0.044).There was no difference in cardiovascular mortality between the study groups (HR 1.03, 95% CI 0.54-1.67; P = 0.930). CONCLUSIONS: AMULET telecare as compared to standard care significantly reduced the risk of HF hospitalisation or cardiovascular death during 12-month follow-up among patients with HF and LVEF ≤49% after an episode of acute HF.

Rationale and design of the AMULET study: A new Model of telemedical care in patients with heart failure.

AIMS: Heart failure (HF) is characterized by high mortality and hospital readmission rates. Limited access to cardiologists restricts the application of guideline-directed, patient-tailored medical therapy. Some telemedicine solutions and novel non-invasive diagnostic tools may facilitate real-time detection of early HF decompensation symptoms, prompt initiation of appropriate treatment, and optimal management of medical resources. We describe the rationale and design of the AMULET trial, which investigates the effect of comprehensive outpatient intervention, based on individualized haemodynamic assessment and teleconsultations, on cardiovascular mortality and unplanned hospitalizations in HF patients. METHODS AND RESULTS: The AMULET trial is a multicentre, prospective, randomized, open-label, and controlled parallel group trial (ClinicalTrials.gov Identifier: NCT03476590). Six hundred and five eligible patients with HF (left ventricular ejection fraction ≤49%, at least one hospitalization due to acute HF decompensation within 6 months prior to enrolment) were randomly assigned in a 1:1 ratio to either an intervention group or a standard care group. The planned follow-up is 12 months. The AMULET interventions are performed in ambulatory care points operated by nurses, with the remote support of cardiologists. The comprehensive clinical evaluation comprises measurements of heart rate, blood pressure, body mass, thoracic fluid content, and total body water. A recommendation support module based on these objective parameters is implemented in remote therapeutic decision-making. The primary complex endpoints are cardiovascular mortality and unplanned HF hospitalization. CONCLUSIONS: The AMULET trial will provide a prospective assessment of the effect of comprehensive ambulatory intervention, based on telemedicine and haemodynamically guided therapy, on mortality and readmissions in HF patients.

Nurse-led ambulatory care supported by non-invasive haemodynamic assessment after acute heart failure decompensation.

Heart failure (HF) is characterized by frequent decompensation and an unpredictable trajectory. To prevent early hospital readmission, coordinated discharge planning and individual therapeutic approach are recommended. AIMS: We aimed to assess the effect of 1 month of ambulatory care, led by nurses and supported by non-invasive haemodynamic assessment, on the functional status, well-being, and haemodynamic status of patients post-acute HF decompensation. METHODS AND RESULTS: This study had a multicentre, prospective, and observational design and included patients with at least one hospitalization due to acute HF decompensation within 6 months prior to enrolment. The 1 month ambulatory care included three visits led by a nurse when the haemodynamic state of each patient was assessed non-invasively by impedance cardiography, including thoracic fluid content assessment. The pharmacotherapy was modified basing on haemodynamic assessment. Sixty eight of 73 recruited patients (median age = 67 years; median left ventricular ejection fraction = 30%) finished 1 month follow-up. A significant improvement was observed in both the patients' functional status as defined by New York Heart Association class (P = 0.013) and sense of well-being as evaluated by a visual analogue score (P = 0.002). The detailed patients' assessment on subsequent visits resulted in changes of pharmacotherapy in a significant percentage of patients (Visit 2 = 39% and Visit 3 = 44%). CONCLUSIONS: The proposed model of nurse-led ambulatory care for patients after acute HF decompensation, with consequent assessment of the haemodynamic profile, resulted in: (i) improvement in the functional status, (ii) improvement in the well-being, and (iii) high rate of pharmacotherapy modifications.

Elevated plasma endothelin-1 is related to low natriuresis, clinical signs of congestion, and poor outcome in acute heart failure.

AIMS: Endothelin-1 (ET-1) is a potent vasoconstrictor, which regulates renal and vascular function. We aimed to relate plasma levels of ET-1 with the clinical picture and outcomes in acute heart failure (AHF). METHODS AND RESULTS: We studied 113 patients with AHF [mean age 65 ± 13 (years), median (upper and lower quartiles) N-terminal pro-B-type natriuretic peptide, 5422 (2689; 8582) (pg/mL)], in whom plasma levels of ET-1 were serially measured at admission (10.8 ± 5.2), Day 1 (9.5 ± 3.4), and Day 2 (8.9 ± 3.8) (pg/mL). The population was divided into tertiles across baseline ET-1 levels. Patients in the highest ET-1 tertile had predominant clinical signs of peripheral congestion; however, no difference was observed in pulmonary congestion and severity of dyspnoea. They also presented lower spot urine sodium at admission (75 ± 35 vs. 99 ± 43 vs. 108 ± 30), 6 h (84 ± 34 vs. 106 ± 43 vs. 106 ± 35), and Day 1 (75 ± 38 vs. 96 ± 36 vs. 100 ± 35) (mmol/L), when compared with the second and first tertile, respectively (all P < 0.05); furthermore, they received higher doses of intravenous furosemide from Day 2 and had longer intravenous diuretics, as median switch to oral furosemide was 4 (3; 4) vs. 3 (2; 4) vs. 2 (2; 3) (days), respectively, P < 0.05. There was no difference in serum creatinine, urea, and renal injury biomarkers (kidney injury molecule-1, serum cystatin C, and urine neutrophil gelatinase-associated lipocalin) between the ET-1 tertiles. Higher values of ET-1 measured at each time point were related with a higher risk of 1 year mortality. CONCLUSIONS: Elevation of ET-1 is related to clinical signs of peripheral congestion, low urine sodium excretion, and poor outcome in AHF.

Distinct clinical phenotypes of congestion in acute heart failure: characteristics, treatment response, and outcomes.

AIMS: Patients with acute heart failure (AHF) are included into clinical trials regardless of differences in baseline clinical characteristics. The aim of this study was to assess patients with AHF according to the presence of central and/or peripheral congestion at hospital admission and evaluate treatment response and outcomes in studied phenotypes. METHODS AND RESULTS: We investigated retrospectively 352 patients (mean age: 68 ± 13 years, 77% men) hospitalized due to AHF with the signs of congestion on admission. Patients were divided according to the type of signs of congestion into three groups: A, isolated pulmonary congestion (n = 52, 15%); B, isolated peripheral congestion (n = 31, 9%); and C, signs of mixed (peripheral and central) congestion (n = 269, 76%). Patients from Group A had lower concentration of urea, bilirubin, and gamma-glutamyl transferase whereas higher level of haematocrit, albumin, and leukocytes on admission. The highest baseline N-terminal pro-B-type natriuretic peptide level (median: 4113 vs. 3634 vs. 6093 pg/mL) and percentage of patients with chronic heart failure (56 vs. 58 vs. 74%; A vs. B. vs. C, respectively, all P < 0.01) were observed in Group C. There were no differences in terms of demographics, co-morbidities, left ventricular ejection fraction, and applied treatment between studied groups. Patients from Group A had the highest systolic blood pressure on admission (145 ± 37 vs. 122 ± 20 vs. 130 ± 29 mmHg) and the biggest decrease in systolic blood pressure [-22 (-45 to -4) vs. -2 (-13 to 2) vs. -10 (-25 to 0) mmHg] and heart rate [-16 (-35 to -1.5) vs. -1 (-10 to 5) vs. -7 (-20 to 0) b.p.m.] with the lowest weight change [-1.0 (-1.0 to 0) vs. -2.9 (-3.8 to -0.9) vs. -2.0 (-3.0 to -1.0) kg; all P < 0.01] after 48 h of hospitalization. There were differences in short-term and long-term outcomes with favourable results in Group A. Group A experienced less frequent in-hospital heart failure worsening during the first 48 h (4 vs. 23 vs. 7%), had shorter length of hospital stay [6 (5-8) vs. 7 (5-11) vs. 7 (6-11) days], and had lower 1 year all-cause mortality (12 vs. 28 vs. 29%; all P < 0.05). Presence of peripheral congestion on admission was independent predictor for all-cause mortality within 1 year [hazard ratio (95% confidence interval): 2.68 (1.06-6.79); P = 0.04]. CONCLUSIONS: Patterns of congestion in AHF are associated with differences in clinical characteristics, treatment response, and outcomes. It needs to be considered once planning clinical trials in AHF.

Controlled decongestion by Reprieve therapy in acute heart failure: results of the TARGET-1 and TARGET-2 studies.

AIMS: Safe and effective decongestion is the main goal of therapy in acute heart failure (AHF). In the non-randomized, prospective TARGET-1 and TARGET-2 studies (NCT03897842), we investigated whether adding the Reprieve System® (which continuously monitors urine output and delivers a matched volume of hydration fluid sufficient to maintain the set fluid balance rate) to standard diuretic-based regimen improves decongestion in AHF. METHODS AND RESULTS: The population consisted of 19 patients hospitalized with AHF (mean age 67 ± 10 years, 18 male, ejection fraction 34 ± 15%, median N-terminal pro-B-type natriuretic peptide 4492 pg/mL). Patients served as their own controls: each patient underwent 24 h of standard diuretic therapy followed by 24 h of diuretics with Reprieve therapy (with normal saline used for matched volume replacement). The primary efficacy endpoint of actual fluid loss not exceeding the target fluid loss at the end of therapy was met in all 19 (100%) patients. The mean diuresis during Reprieve therapy was 6284 ± 2679 mL (vs. 1966 ± 1057 mL 24 h before therapy) and 2053 ± 888 mL (24 h after therapy) (both P < 0.0001). At the end of therapy, patient global assessment improved from 7.7 ± 1.1 to 3.0 ± 1.3 points (P < 0.001), central venous pressure decreased from 15.5 ± 5.3 mmHg to 12.8 ± 4.8 mmHg (P < 0.05) and the median urine sodium loss was 9.7 [3-13] mmol/h. The Reprieve therapy was safe, systolic blood pressure remained stable, mean creatinine dropped from 1.45 ± 0.4 mg/dL to 1.26 ± 0.4 mg/dL (P < 0.001) and biomarkers of renal injury did not change during treatment. CONCLUSIONS: The Reprieve System in conjunction with diuretic therapy supports safe and controlled decongestion in AHF.

Persistent hyperlactataemia is related to high rates of in-hospital adverse events and poor outcome in acute heart failure.

BACKGROUND: Although lactate is a well-established marker in intensive care, our understanding of its utility in acute heart failure (AHF) is modest and based on studies with a single measurement of this marker. AIM: We aimed to investigate whether persistent elevation of lactate during hospitalisation is related to a higher risk of ad- verse events. METHODS: We conducted a prospective study to assess AHF patients hospitalised in one cardiac centre. The diagnosis of persistent hyperlactataemia was based on two measurements of the marker (on admission and at 24 h of hospitalisation) and it was defined as lactate elevation (≥ 2 mmol/L) at both time points. RESULTS: The population consisted of 222 patients at a mean age of 70 ± 13 years. Mean ejection fraction and creatinine level on admission were 37% ± 16% and 1.36 ± 0.51 mg/dL, respectively. The percentage of patients with elevated lactates on admission, at 24 h of hospitalisation, and persistent hyperlactataemia were 47%, 35%, and 24%, respectively. The group with persistent hyperlactataemia did not differ in most clinical and laboratory variables from the rest of the population. Patients with persistent hyperlactataemia had higher rate of adverse events during hospitalisation: worsening of heart failure (22.6% vs. 6.5%, p < 0.05), inotrope use (22.6% vs. 5.3%, p < 0.05), and increase of N-terminal pro-B-type natriuretic peptide at 48 h of hospitalisation (30% vs. 18%, p < 0.05). Persistent hyperlactataemia was an independent predictor of one-year mortality (hazard ratio 2.5, 95% confidence interval 1.5-4.3, p < 0.001). CONCLUSIONS: Persistent hyperlactataemia within the first 24 h of hospitalisation is a predictor of a worse outcome in AHF and is related to higher rates of in-hospital adverse events and one-year mortality.

Patterns of dyspnoea onset in patients with acute heart failure: clinical and prognostic implications.

AIMS: Despite attempts to improve the management of patients with acute heart failure (HF), virtually all therapeutic agents investigated in large clinical trials failed to show any consistent reduction in mortality and morbidity. Complexity of the clinical syndrome of acute HF seems to be likely an underlying explanation. Traditionally, clinical trials studied mixed patient populations with acute HF, and only recently, better clinical characterization of patients has been proposed. Dyspnoea is the most common presenting symptom related to hospital admission for acute HF. Whether in patients with acute HF, the pattern of symptoms onset preceding hospital admission is associated with clinical characteristics, and the outcomes have not yet been established. METHODS AND RESULTS: We investigated 137 patients (mean age: 65 ± 13 years; 80% men) hospitalized due to acute HF with dyspnoea as major reported symptom, who were divided according to the time of its onset into those with acute (n = 98) vs. subacute (n = 39) onset (i.e. within 7 days vs. >7 days preceding hospital admission, respectively). On admission, the former group presented higher blood pressure (138 ± 33 vs. 121 ± 32 mmHg), more often moderate-severe pulmonary congestion (33 vs. 8%), and lower bilirubin level [1.07 (0.72-1.60) vs. 1.27 (0.87-2.06); P < 0.05 in all comparisons]. There were no other differences in baseline clinical characteristics and laboratory indices. Higher percentage of patients with an acute dyspnoea onset reported marked/moderate dyspnoea relief after 6 (18% vs. 7%), 24 (59% vs. 24%), and 48 h (80% vs. 46% assessed as an improvement of at least 5 points in self-reported 10-point Likert scale; P < 0.05 in all time points). In patients with an acute onset of dyspnoea after 48 h, a decrease of N-terminal pro BNP was more frequently observed (83% vs. 65%), and the levels of endothelin-1 were more reduced [-1.1 (-2.9-0.03) vs 0.4 (-2.2-1.4); all P < 0.05]. Patients with acute onset experienced less in-hospital HF worsening (13% vs. 40%, P = 0.001), and 1 year cardiovascular mortality was significantly lower (20% vs. 41%, P = 0.01). On the multivariable analysis, subacute pattern of dyspnoea was independent predictor of 12 month cardiovascular mortality in patients with acute HF after adjusting for other prognostic factors: systolic blood pressure, urea, and HF de novo [hazard ratio (95% confidence interval): 2.32 (1.13-4.75), P = 0.02]. CONCLUSIONS: In patients with acute HF, the pattern of symptoms onset is associated with baseline differences in clinical characteristics, biomarker profile, response to standard treatment, and the long-term outcomes. This is relevant information for planning future clinical trials.

Multi-organ dysfunction/injury on admission identifies acute heart failure patients at high risk of poor outcome.

BACKGROUND: Clinical consequences of an interplay between dysfunction/injury of different end-organs in acute heart failure (AHF) remain unknown. METHODS AND RESULTS: In 284 consecutive AHF patients, end-organ dysfunction/injury was defined as cardiac [troponin I level above the upper reference limit (URL, > 0.056 ng/mL)], kidney (estimated glomerular filtration rate < 60 mL/min/1.73 m2 ), and liver [at least one of the following: aspartate transaminase (AST)/alanine transaminase (ALT) > 3 times the URL (> 114 IU/L and > 105 IU/L for AST and ALT, respectively), bilirubin above the URL (> 1.3 mg/mL), albumin below the lower reference limit (< 3.5 mg/dL)]. The primary endpoints were early (within first 48 h) in-hospital worsening of heart failure and 1-year all-cause mortality. On admission, cardiac, kidney, liver dysfunction/injury were present in 38%, 50%, and 54% of patients, respectively. Patients were classified as having 0, 1, 2, or 3 organ injury/dysfunction (17%, 36%, 35%, and 12% of patients, respectively). Baseline clinical characteristics and co-morbidity profile were similar across groups. Patients with three organ dysfunction/injury had the worst 1-year survival rate [46%; hazard ratio (HR) with 95% confidence interval (CI) vs. patients without organ dysfunction: 6.75 (2.52-18.13), those with two (67%; HR 3.54, 95% CI 1.38-9.08), one (84%; HR 1.58, 95% CI 0.58-4.30), or no organ dysfunction/injury (90%); P < 0.01]. Worsening of heart failure was more frequent in patients with three and two vs. those with one or no organ dysfunction/injury (37% vs. 38% vs. 23% vs. 21%, P < 0.05). CONCLUSIONS: In patients with AHF, dysfunction/injury of > 1 end-organ dysfunction/injury identifies patients at the highest risk of poor outcomes.

Increased blood lactate is prevalent and identifies poor prognosis in patients with acute heart failure without overt peripheral hypoperfusion.

AIMS: Lactate is produced by anaerobic metabolism and may reflect inadequate tissue perfusion in conditions such as acute heart failure (AHF). We evaluated the prevalence and clinical significance of elevated blood lactate on admission in patients with AHF. METHODS AND RESULTS: We enrolled 237 patients with AHF (mean age 67 ± 12 years; 70% men) presenting without overt clinical evidence of peripheral hypoperfusion ('warm haemodynamic profile'). Median (upper and lower quartiles) blood lactate on admission was 1.8 (1.5; 2.4) mmol/L; 103 (43%) patients had an elevated blood lactate (≥2 mmol/L). Patients with an elevated lactate had higher blood high-sensitivity troponin I [15.4 (8.5; 26.1) vs. 9.9 (4.3; 19.6) pg/mL], aspartate aminotransferase [28 (20; 44) vs 24 (19; 36) IU/L] and endothelin-1 (12.1 ± 6.2 vs. 9.3 ± 3.9 pg/mL) (all P < 0.05). In this group plasma concentration of neutrophil gelatinase-associated lipocalin increased during the first 48 h, whereas values fell for those with normal baseline lactate [1.9 (-3.2; 9.7) vs. -1.3 (-13.9; 5.6) µg/dL; P < 0.05). One-year mortality was higher amongst patients with an elevated blood lactate (36% vs. 21%; P < 0.05). After adjustment for other well-established prognostic variables, blood lactate on admission predicted poor outcome (hazard ratio 1.24, 95% confidence interval 1.08-1.41; P < 0.05). CONCLUSIONS: An elevated blood lactate on admission is common in AHF patients without overt clinical evidence of peripheral hypoperfusion and is associated with markers of organ dysfunction/damage and a worse prognosis.

Urinary levels of novel kidney biomarkers and risk of true worsening renal function and mortality in patients with acute heart failure.

AIMS: Recent studies indicate the need to redefine worsening renal function (WRF) in acute heart failure (AHF), linking a rise in creatinine with clinical status to identify patients who develop 'true WRF'. We evaluated the usefulness of serial assessment of urinary levels of neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (uKIM-1), and cystatin C (uCysC) for prediction of 'true WRF'. METHODS AND RESULTS: In 132 patients with AHF, uNGAL, uKIM-1, and uCysC were measured using a highly sensitive immunoassay based on a single-molecule counting technology (Singulex, Alameda, CA, USA) at baseline, day 2, and day 3. Patients who developed WRF (a ≥0.3 mg/dL increase in serum creatinine or a >25% decrease in the estimated glomerular filtration rate from the baseline value) were differentiated into those 'true WRF' (presence of deterioration/no improvement in clinical status during hospitalization) vs. 'pseudo-WRF' (uneventful clinical course). 'True WRF' occurred in 13 (10%), 'pseudo-WRF' in 15 (11%), whereas the remaining 104 (79%) patients did not develop WRF. Patients with 'true WRF' were more often females, had higher levels of NT-proBNP, creatinine, and urea on admission, higher urine albumin to creatinine ratio at day 2, higher uNGAL at baseline, day 2, and day 3, and higher KIM-1 at day 2 (vs. pseudo-WRF vs. without WRF, all P < 0.05). Patients with pseudo-WRF did not differ from those without WRF. In the multivariable model, elevated uNGAL at all time points and uKIM-1 at day 2 remained independent predictors of 'true WRF'. CONCLUSION: Elevated levels of uNGAL and uKIM-1 may predict development of 'true WRF' in AHF.

Impaired hepato-renal function defined by the MELD XI score as prognosticator in acute heart failure.

AIM: Multi-organ dysfunction often complicates the natural course of acute heart failure (AHF) and identifies patients with poor prognosis. The MELD score (Model of End-Stage Liver Dysfunction) combines data reflecting liver and kidney function, which makes it a potentially useful tool for the assessment of patients with AHF. The aim of this study was to assess the prognostic utility of the MELD score in patients with AHF. METHODS AND RESULTS: The MELD score was calculated on admission and during hospital stay (days 2-3) using a formula that does not take into account the international normalized ratio (MELD XI). The study population consisted of 203 AHF patients (mean age 65 ± 12 years, 76% male). The mean MELD XI score was -14.8 ± 4.5 points on admission and 13.9 ± 4.3 points during hospitalization. Contributors of elevated MELD XI score at baseline and during hospital stay were isolated increase in creatinine in 22-25%, isolated increase in bilirubin in 17-19%, and abnormal values of both in 40-46% of patients. During 1-year follow-up, 67 (33%) patients died. After adjustment for well-established prognosticators, MELD XI score at baseline and during hospital stay were significant predictors of poor outcome [hazard ratio (95% confidence interval): 1.11 (1.05-1.2) and 1.14 (1.09-1.2), respectively, P < 0.001]. An increase in the MELD XI score during hospital stay occurred in 31% of patients and was related to increased risk of death at 1 year [1.97 (1.2-3.2), P < 0.005]. CONCLUSIONS: Impairment of hepato-renal function defined by the MELD XI score is common and carries unfavourable prognosis in AHF patients.

Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure.

AIM: Acute heart failure (AHF) critically deranges haemodynamic and metabolic homoeostasis. Iron is a key micronutrient for homoeostasis maintenance. We hypothesized that iron deficiency (ID) defined as depleted iron stores accompanied by unmet cellular iron requirements would in this setting predict the poor outcome. METHODS AND RESULTS: Among 165 AHF patients (age 65 ± 12 years, 81% men, 31% de novo HF), for ID diagnosis we prospectively applied: low serum hepcidin reflecting depleted iron stores (<14.5 ng/mL, the 5th percentile in healthy peers), and high-serum soluble transferrin receptor (sTfR) reflecting unmet cellular iron requirements (≥1.59 mg/L, the 95th percentile in healthy peers). Concomitance of low hepcidin and high sTfR (the most profound ID) was found in 37%, isolated either high sTfR or low hepcidin was found in 29 and 9% of patients, and 25% of subjects demonstrated preserved iron status. Patients with low hepcidin and high sTfR had peripheral oedema, high NT-proBNP, high uric acid, low haemoglobin (P < 0.05), and 5% in-hospital mortality (0% in remaining patients). During the 12-month follow-up, 33 (20%) patients died. Those with low hepcidin and high sTfR had the highest 12-month mortality [(41% (95% CI: 29-53%)] when compared with those with isolated high sTfR [15% (5-25%)], isolated low hepcidin [7% (0-19%)] and preserved iron status (0%) (P < 0.001). Analogous mortality patterns were seen separately in anaemics and non-anaemics. CONCLUSION: Iron deficiency defined as depleted body iron stores and unmet cellular iron requirements is common in AHF, and identifies those with the poor outcome. Its correction may be an attractive therapeutic approach.

Liver function tests in patients with acute heart failure.

INTRODUCTION: Acute heart failure (AHF) is associated with multiorgan dysfunction, which may unfavorably affect prognosis. OBJECTIVES: We investigated the prevalence, clinical determinants, and prognostic consequences of abnormal liver function tests (LFTs) in population with AHF. PATIENTS AND METHODS: We conducted a retrospective analysis of patients with AHF, in whom the following LFTs were performed on admission: serum bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), and albumin. Abnormal LFTs were defined as the elevation above the upper normal limit of bilirubin, AST, and ALT, or reduction below the lower normal limit of albumin. RESULTS: The study involved 189 patients (age, 68 ±11 years; men, 68%; de novo AHF, 25%). On admission, abnormal LFTs were observed in 46% of the patients for AST, 31% for ALT, 33% for bilirubin, and 44% for albumin. Only 29% of the patients had all LFTs within the normal ranges. The following variables were independently related to abnormal LFTs: high hemoglobin and N­terminal pro­B­type natriuretic peptide (NT­proBNP) levels for AST; high hemoglobin, bilirubin, and NT­proBNP levels for ALT; high hemoglobin, low sodium levels, and dilated right ventricle for bilirubin; and high NT­proBNP levels for albumin (all P <0.05). In 21 patients, hemodynamic monitoring was performed, which revealed that among LFTs only elevated bilirubin independently correlated with higher right atrial pressure (P <0.005). In a univariate Cox model, among LFTs, low albumin and markedly elevated AST and ALT (>3 times above the upper normal limit) were associated with increased mortality during 180­day follow­up. CONCLUSIONS: Abnormal LFTs are common in patients with AHF and may have prognostic relevance. Among them, only elevated bilirubin was correlated with impaired hemodynamic parameters.

Clinical characteristics and predictors of in-hospital mortality in 270 consecutive patients hospitalised due to acute heart failure in a single cardiology centre during one year.

BACKGROUND: Acute heart failure (HF) is an emerging problem in clinical practice, associated with high in-hospital mortality and a high short-term readmission rate. AIM: To describe the clinical characteristics and define predictors of in-hospital mortality in patients with acute HF. METHODS: We conducted a prospective registry of all consecutive patients hospitalised due to acute HF from October 2008 to November 2009 in a single cardiology centre. Clinical status and laboratory parameters were analysed on admission and after 48 h. RESULTS: We examined 270 patients (age 68 ± 13 years, 71% men, 27% with de novo acute HF, 55% with ischaemic aetiology, 56% with decompensated chronic HF, 80% with warm-wet haemodynamic profile). In-hospital mortality was 8.5% (n = 23). There were no differences between survivors vs non-survivors regarding age, gender, HF aetiology, prevalence of de novo acute HF, and baseline heart rate and body weight values and changes of these parameters during hospitalisation (p > 0.2 for all comparisons). Cardiogenic shock and isolated right-sided HF were more common in patients who died as compared to survivors (17% vs 1% and 22% vs 2%, respectively; p < 0.001), as were the cold-wet and cold-dry haemodynamic profiles (22% vs 2% and 17% vs 1%, respectively; p < 0.001). The most common factor precipitating decompensation in non-survivors was an acute coronary syndrome (17% vs 7%), while elevation of blood pressure and inadequate diuretic therapy were the most common causes of acute HF in survivors (26% vs 4% and 45% vs 22%, respectively; p < 0.05). Baseline mean blood pressure and serum Na(+) level were higher in survivors than in non-survivors (94 ± 20 vs 79 ± 19 mm Hg and 140 ± 4 vs 136 ± 5 mmol/L, respectively; p < 0.001) and both remained higher during follow-up. There were no differences in baseline haemoglobin and serum K(+) levels between these groups. Haemoglobin level decreased after 48 h of therapy only in patients who died (11.1 ± 2.4 vs 12.5 ± 2.1 g/dL; p < 0.01), whereas a reduction in serum K(+) level after 48 h was observed only in survivors (4.2 ± 0.6 vs 3.9 ± 0.5 mmol/L; p < 0.05), probably reflecting effective diuretic therapy. Baseline renal function was more impared in non-survivors (serum creatinine 1.7 [1, 2.5] vs 1.2 [1, 1.6] mg/dL, and blood urea nitrogen 40 [24, 65] vs 24 [19, 33] mg/dL; p < 0.05) and deteriorated further during hospitalisation (serum creatinine 2.0 [1.2, 2.5] vs 1.2 [0.9, 1.5] mg/dL, blood urea nitrogen 64 [45, 77] vs 27 [19, 36] mg/dL; p < 0.01). Baseline plasma N-terminal proB-type natriuretic peptide (NT-proBNP) level did not differentiate these two groups, but plasma NT-proBNP level measured after 48 h was lower in survivors compared to non- -survivors (3560 [1711, 6738] vs 11780 [5371, 18912] pg/mL; p < 0.01); data are shown as medians [lower, upper quartile]. CONCLUSIONS: In our registry, in-hospital mortality in patients admitted due to acute HF was slightly higher compared to other reports. Baseline values of some parameters (e.g. blood pressure, serum Na(+), renal function) as well as their changes during hospitalisation (e.g. serum K(+), renal function, plasma NT-proBNP) can help identify acute HF patients at a higher risk of in-hospital mortality.