Heart Failure with Recovered Ejection Fraction in a Cohort of Elderly Patients with Chronic Heart Failure.

OBJECTIVE: The aim of this study was to determine whether patients with heart failure (HF) who recover left ventricular ejection fraction (LVEF), termed here as 'Rec-HF', have a distinct clinical profile and prognosis compared with patients with HF and reduced LVEF (HF-REF) or HF and preserved LVEF (HF-PEF). METHODS: We evaluated and classified patients from the Spanish Heart Failure Registry into three categories based on enrollment/follow-up echocardiograms: HF-PEF (LVEF ≥50%), HF-REF (LVEF persistently <50%) and Rec-HF (LVEF on enrollment <50% but normalized during follow-up). RESULTS: A total of 1,202 patients were included, 1,094 with HF-PEF, 81 with HF-REF and 27 with Rec-HF. The three groups included patients of advanced age (mean age 75 years) with comorbidities. Rec-HF patients were younger, with a better functional status, lower prevalence of diabetes mellitus, dementia and cerebrovascular disease, and higher prevalence of COPD. The etiology of HF was more frequently ischemic and alcoholic and less frequently hypertensive. After a median follow-up of 367 days, the unadjusted hazard ratios for death in the Rec-HF versus HF-PEF and HF-REF groups were 0.11 (95% CI 0.02-080; p = 0.029) and 0.31 (95% CI 0.04-2.5; p = 0.274). Results were statistically nonsignificant in multivariate-adjusted models. CONCLUSION: Rec-HF is also present in elderly patients with HF but it is necessary to further investigate the natural history and optimal pharmacologic management of this 'new HF syndrome'.

Cancer Impacts Prognosis on Mortality in Patients with Acute Heart Failure: Analysis of the EPICTER Study.

INTRODUCTION: Heart failure (HF) and cancer are currently the leading causes of death worldwide, with an increasing incidence with age. Little is known about the treatment received and the prognosis of patients with acute HF and a prior cancer diagnosis. OBJECTIVE: to determine the clinical characteristics, palliative treatment received, and prognostic impact of patients with acute HF and a history of solid tumor. METHODS: The EPICTER study ("Epidemiological survey of advanced heart failure") is a cross-sectional, multicenter project that consecutively collected patients admitted for acute HF in 74 Spanish hospitals. Patients were classified into two groups according to whether they met criteria for acute HF with and without solid cancer, and the groups were subsequently compared. A multivariable logistic regression analysis was conducted, using the forward stepwise method. A Kaplan-Meier survival analysis was performed to evaluate the impact of solid tumor on prognosis in patients with acute HF. RESULTS: A total of 3127 patients were included, of which 394 patients (13%) had a prior diagnosis of some type of solid cancer. Patients with a history of cancer presented a greater frequency of weight loss at admission: 18% vs. 12% (p = 0.030). In the cancer group, functional impairment was noted more frequently: 43% vs. 35%, p = 0.039). Patients with a history of solid cancer more frequently presented with acute HF with preserved ejection fraction (65% vs. 58%, p = 0.048) than reduced or mildly reduced. In-hospital and 6-month follow-up mortality was 31% (110/357) in patients with solid cancer vs. 26% (637/2466), p = 0.046. CONCLUSION: Our investigation demonstrates that in-hospital mortality and mortality during 6-month follow-up in patients with acute HF were higher in those subjects with a history of concomitant solid tumor cancer diagnosis.

Modes of death in heart failure according to age, sex and left ventricular ejection fraction.

Modes of death in patients with heart failure (HF) have been well characterized in randomized studies, but data from real-life are scarce, especially in the elderly, women and in HF with mid-range or preserved left ventricular ejection fraction (LVEF). Our purpose was to examine modes of death in HF patients according to age, sex and LVEF. We analysed the mode of death of HF patients from two prospective multicentre contemporary Spanish registries conducted by cardiologists (REDINSCOR, n = 2150) and by internists (RICA, n = 1396). Mode of death was pre-specified. Out of 3546 patients, 485 (13.7%) died during the 9-month follow-up. Cardiovascular (CV) causes were the most frequent, regardless of the age, sex and LVEF. More than half of patients died due to worsening HF in both groups of patients, followed by other non-CV causes in those attended by internists, and sudden cardiac death in those cared by cardiologists. Stroke was more common among elderly patients, women and HF with preserved LVEF. Non-CV causes, particularly infectious diseases, accounted for a remarkable proportion of deaths, especially in the elderly and in HF patients with preserved LVEF. Functional class, age and anaemia had a strong influence on both CV and non-CV death. CV death due to refractory HF was the most prevalent among our population, irrespective of age, sex or LVEF. However, a significant proportion of HF patients died from non-CV causes, particularly elderly with mid-range and preserved LVEF. These patients could benefit significantly from a multidisciplinary follow-up.

Prevalence of advanced heart failure and use of palliative care in admitted patients: Findings from the EPICTER study.

INTRODUCTION AND AIM: Palliative care in patients with advanced heart failure is strongly recommended by Clinical Practice Guidelines. We aimed to calculate the prevalence of advanced heart failure in admitted patients, to describe their management, and to analyse the factors that influence their referral to specialised palliative care. PATIENTS AND METHODS: Cross-sectional, multicentre study that consecutively included patients admitted for heart failure in 74 Spanish hospitals. If they met criteria for advanced heart failure, their treatment, complications and procedures were recorded. RESULTS: A total of 3153 patients were included. Of them, 739 (23%) met criteria for advanced heart failure. They were more likely to be women, older and to have a history of anaemia, chronic kidney disease and cognitive impairment. For their management, furosemide infusions (30%) and vasodilators (21%) were used. Refractory symptoms were treated with opioids (47%) and benzodiazepines (44%). Palliative care was only provided in the last hours of life in 48% of them. A multidisciplinary approach, involving palliative care specialists was sought in 15% of these patients. Treatment with furosemide infusions, an advanced New York Heart Association functional class, to meet advanced HF criteria and the presence of cancer were associated with the referral to specialised palliative care. CONCLUSIONS: Almost one in four patients admitted with HF met criteria of advanced disease. They were older and had more comorbidities. Specialist palliative care services were involved in only a minority of patients, mainly those who were highly symptomatic or had cancer.

[Etiology and clinical management of anemia in heart failure. GESAIC Study]. / Etiología y tratamiento de la anemia en la insuficiencia cardíaca. Estudio GESAIC.

BACKGROUND AND OBJECTIVE: Studies about anemia in heart failure (HF) tend to link the anemia to a cardio-renal dysfunction, and its syndromic value is seldom evaluated. Our objective was to assess the etiology and clinical management of anemia in HF patients in a hospital setting. PATIENTS AND METHOD: Initial cross-sectional analysis of a multi-center and prospective cohort of patients with HF and anemia. Anemia was defined according to the WHO criteria; the Modification of Diet in Renal Disease equation was used to assess glomerular filtration and the etiology of anemia was defined according to common criteria. RESULTS: We evaluated 228 patients, with a median age of 79.1 years and 59.65% women. Iron deficiency anemia was present in 36,8% of patients and anemia of chronic disease in 30.3%. Of note, 12.7% cases did not meet any etiological criteria. The main factor associated with iron deficiency was anti-platelet therapy (OR=1.99; 95% CI, 1.16-1.68) and the main factors associated with anemia of chronic disease were the use of angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (ARA-II) (OR=3.29; 95% CI, 1.36-7.94). The main factor associated with undefined anemia was initial heart failure (OR=5.41; 95% CI, 1.65-17.65). On the other hand, 8.1% of patients required transfusion, 6% were treated with erythropoietin and 25.3% were treated with iron. Both age (OR=1.04; 95% CI, 1-1.08) and hemoglobin level at admission (OR=1.81; 95% CI, 1.46-2.25) were associated with active treatment for anemia. CONCLUSIONS: A clinical study of anemia in patients with HF can establish an etiological diagnosis in 70% of cases, resulting in a more effective treatment.

Heart failure with mid-range ejection fraction in patients admitted to internal medicine departments: Findings from the RICA Registry.

AIM: To improve the knowledge on characteristics, treatment and prognosis in patients with heart failure (HF) and mid-range ejection fraction discharged after an acute HF episode. METHODS: We prospectively included and followed 2753 patients admitted with HF to Internal Medicine units. Patients were classified according to ejection fraction (EF) into three strata: reduced, EF <40% (HFrEF); mid-range EF 40-49% (HFmrEF); and preserved EF ≥50% (HFpEF). Clinical, echocardiographic, laboratory data and treatment at discharge were recorded and the groups were compared. A multivariable analysis was performed to evaluate the association of EF with outcomes in these three groups. RESULTS: A total of 10.2% of patients had HFmrEF. They were more likely to be men and to have a history of chronic kidney disease and higher levels of NT-proBNP than those with HFpEF. Compared to patients with HFrEF, these patients had less frequently ischaemic aetiology and chronic obstructive pulmonary disease, and a higher proportion of atrial fibrillation and hypertension. In HFmrEF, the use of beta-blockers, aldosterone antagonists and antiplatelet drugs was lower than in HFrEF, but the use of calcium channel blockers and anticoagulants was higher. There were no differences between groups in 30-day and 1-year readmission rates. However, patients with HFrEF had significantly higher 1-year mortality (28%) than patients with HFmrEF and HFpEF (20% and 22%, p<0.001). CONCLUSIONS: Clinical characteristics and treatment among patients with HF differ depending on EF strata. Prognosis of patients with HFmrEF is closer to that of HFpEF, being medium term survival better than in HFrEF.

Ontogeny of digestive enzymes in larvae of the Clown Anemonefish, Amphiprion ocellaris (Perciformes: Pomacentridae)

Introduction: The Clown anemonefish (Amphiprion ocellaris) is the most popular fish species in the marine aquarium trade; however, there is a lack of information on their digestive physiology during larval ontogeny, valuable information needed for diet design and management protocols. Objective: To characterize the early digestive enzymes of A. ocellaris larvae. Methods: We used three pools (10 larvae each) and extracted 10 samples per tank, from just before hatching to the 38th day. We analyzed the specific activity of acid and alkaline proteases, trypsin, chymotrypsin, leucine aminopeptidase and lipase; and did acid and alkaline protease zymograms. Results: We detected all measured enzymes at hatching. Acid proteases increased in activity until the 38th day. Alkaline proteases, trypsin, chymotrypsin, and leucine aminopeptidase had the same pattern, and maximum activity on the 8th day, decreasing at the 38th day. Lipase activity peaked on the 8th and 30th day. The acid zymogram had a single band, appearing on the 8th day. A total of eight alkaline proteases were revealed (154.2, 128.1, 104.0, 59.8, 53.5, 41.9, 36.5 and 25.1 KDa), with seven bands on the 1st day and all bands from the 3rd to 8th day, decreasing at two bands (41.9 and 25.1 KDa) in the 38th day. Conclusion: A. ocellaris has a functional stomach on the 8th day, and, on the 38th day, a digestive omnivore pattern with a tendency to carnivory.

Introducción: El pez payaso (Amphiprion ocellaris) es la especie de pez más popular en el comercio de acuarios marinos; sin embargo, falta información sobre su fisiología digestiva durante la ontogenia larval, información valiosa necesaria para protocolos de diseño y manejo dietético. Objetivo: Caracterizar las enzimas digestivas tempranas de larvas de A. ocellaris. Métodos: Usamos tres homogenados (con 10 larvas cada uno) y extrajimos 10 muestras por tanque, justo antes de la eclosión hasta el día 38. Analizamos la actividad específica de proteasas ácidas y alcalinas, tripsina, quimotripsina, leucina aminopeptidasa y lipasa; e hicimos zimogramas de proteasas ácidas y alcalinas. Resultados: Detectamos todas las enzimas medidas en la eclosión. La actividad de proteasas ácidas incrementó hasta el día 38. Proteasas alcalinas, tripsina, quimotripsina, y leucina aminopeptidasa tuvieron el mismo patrón, con actividad máxima en el octavo día, decreciendo en el día 38. Hubo picos en la actividad lipasa a los ocho y 30 días. El zimograma ácido tuvo una banda única, apareciendo al octavo día. Se hallaron ocho proteasas alcalinas (154.2, 128.1, 104.0, 59.8, 53.5, 41.9, 36.5 y 25.1 KDa), con siete bandas al primer día, y todas las bandas entre el tercer y octavo día, bajando a dos bandas (41.9 y 25.1 KDa) al día 38. Conclusión: A. ocellaris tiene un estómago funcional al octavo día, y, al día 38, un patrón digestivo omnívoro con tendencias carnívoras.

Ambulatory blood pressure monitoring in heart failure and serum sodium levels.

AIMS: To determine whether there are differences in blood pressure profile on dynamic assessment by ambulatory blood pressure monitoring (ABPM) according to serum sodium levels in stable heart failure patients. METHODS: Data were collected from the Spanish National Registry on Ambulatory Blood Pressure Monitoring in Heart Failure (DICUMAP). Patients underwent ABPM by the oscillometric principle using a Spacelabs 90121 monitor. The sample was divided into three groups according to sodium levels and their clinical and laboratory data and echocardiographic findings were analyzed. Robust statistical methods were used to compare the groups in univariate and multivariate models. RESULTS: A total of 175 patients (44.57% male) were analyzed. We found a predominance of anomalous circadian blood pressure profiles in all three groups, with a significantly higher percentage of risers in the lowest serum sodium group (p=0.05). In addition, in this group there were significant differences in mean 24-hour systolic blood pressure (SBP) (24-h SBP, p=0.05) and in mean daytime SBP (dSBP, p=0.008), with significant differences in nocturnal fall in SBP (p=0.05) and in diastolic blood pressure (p=0.005). In multivariate analysis a significant relationship was found between sodium levels and 24-h SBP (OR 0.97, 95% CI 0.95-0.99, p=0.01) and dSBP (OR 0.96, 95% CI 0.94-0.99, p=0.004). CONCLUSION: A relationship was found between lower sodium levels and lower systolic blood pressure, especially during waking hours, with a lower decline between daytime and night-time blood pressure.

Prognostic Impact of Physician Specialty on the Prognosis of Outpatients With Heart Failure: Propensity Matched Analysis of the REDINSCOR and RICA Registries.

INTRODUCTION AND OBJECTIVES: The specialty treating patients with heart failure (HF) has a prognostic impact in the hospital setting but this issue remains under debate in the ambulatory environment. We aimed to compare the clinical profile and outcomes of outpatients with HF treated by cardiologists or internists. METHODS: We analyzed the clinical, electrocardiogram, laboratory, and echocardiographic data of 2 prospective multicenter Spanish cohorts of outpatients with HF treated by cardiologists (REDINSCOR, n=2150) or by internists (RICA, n=1396). Propensity score matching analysis was used to test the influence of physician specialty on outcome. RESULTS: Cardiologist-treated patients were often men, were younger, and had ischemic etiology and reduced left ventricular ejection fraction (LVEF). Patients followed up by internists were predominantly women, were older, and a higher percentage had preserved LVEF and associated comorbidities. The 9-month mortality was lower in the REDINSCOR cohort (11.6% vs 16.9%; P<.001), but the 9-month HF-readmission rates were similar (15.7% vs 16.9%; P=.349). The propensity matching analysis selected 558 pairs of comparable patients and continued to show significantly lower 9-month mortality in the cardiology cohort (12.0% vs 18.8%; RR, 0.64; 95% confidence interval [95%CI], 0.48-0.85; P=.002), with no relevant differences in the 9-month HF-readmission rate (18.1% vs 17.2%; RR, 0.95; 95%CI, 0.74-1.22; P=.695). CONCLUSIONS: Age, sex, LVEF and comorbidities were major determinants of specialty-related referral in HF outpatients. An in-depth propensity matched analysis showed significantly lower 9-month mortality in the cardiologist cohort.

Relationship between osteoprotegerin and mortality in decompensated heart failure with preserved ejection fraction.

AIM: The aim of this study was to evaluate whether osteoprotegerin - an emerging inflammatory biomarker in cardiovascular diseases - predicts outcomes in patients with acute heart failure and preserved ejection fraction. METHODS: We measured urea, creatinine, hemoglobin, high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide and osteoprotegerin on admission in 177 patients admitted with decompensated heart failure and left ventricular ejection fraction at least 45%. The population was divided according to the median values of osteoprotegerin (158.6 ng/l). Primary and secondary endpoints were all-cause mortality and death/readmission at 1-year follow-up, respectively. Multivariable Cox models were generated for osteoprotegerin and common risk factors. We also evaluated the reclassification of patients into risk categories after adding this biomarker to the model. RESULTS: A total of 43 patients died during the follow-up and 84 had a combined event. Kaplan-Meier curves showed significantly increased primary and secondary endpoints according to the median of osteoprotegerin (log-rank, P < 0.0001 and 0.001, respectively). After adjustment for age, estimated glomerular filtration rate, hemoglobin, N-terminal pro-B-type natriuretic peptide, BMI and New York Heart Association III-IV, osteoprotegerin was a significant predictor of primary endpoint evaluated as continuous and categorized variable (relative risk 2.49, 95% confidence interval 1.18-5.24, P = 0.016 and relative risk 2.35, 95% confidence interval 1.11-4.96, P = 0.025, respectively). The clinical prediction model with osteoprotegerin evaluated with Net Reclassification Index was not significant. CONCLUSION: Osteoprotegerin is independently associated with all-cause mortality in patients hospitalized for heart failure with preserved ejection fraction. However, adding this biomarker into a risk model does not improve its prediction value.

Troponin T in acute heart failure: clinical implications and prognosis in the Spanish National Registry on Heart Failure.

BACKGROUND: Elevated troponin in heart failure has been associated with worse prognosis, but there are differences in the design and results of published studies. Our objective was to determine the association of troponin T with mortality and readmissions in patients with acute heart failure in clinical practice conditions. METHODS: We included patients from the RICA registry who were hospitalized for acute heart failure. They were classified into 3 groups according to troponin T levels: normal, intermediate and high (<0.02, 0.02-0.049 and ≥ 0.05 ng/mL, respectively). Survival was studied by Kaplan-Meier curves and the association of variables was tested by Cox regression analysis. RESULTS: A total of 406 patients was included. Average age was 76.9 (76.0-77.7) years. Hypertensive heart disease was the most common etiology. Left ventricular ejection fraction was <45% in 22.1% of the patients. The group with elevated troponin T had higher proportions of women, systolic dysfunction, renal failure and anemia, a lower body mass index and longer hospital stay. At one year, patients with elevated troponin T had higher mortality than patients with normal troponin (35.5 vs. 13.9%, p<0.001). The composite event (mortality and readmissions) was also more frequent (51.6 vs. 30.9%, p<0.001), but there were no differences in readmissions alone. Troponin T ≥ 0.02 ng/mL was independently associated with mortality. CONCLUSIONS: Elevated troponin T levels are common in patients with heart failure in clinical practice and are associated with increased mortality and events after one year of follow-up.

Predictive value of serum galectin-3 levels in patients with acute heart failure with preserved ejection fraction.

AIMS: This study was conducted to determine whether galectin-3 (Gal3), a ß-galactoside-binding lectin, has usefulness to predict outcomes in patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We measured Gal3, urea, creatinine and natriuretic peptides on admission in 419 selected patients with HF and LVEF over 45%. The primary endpoint was all-cause mortality and/or readmission at one-year follow-up. Multivariable Cox proportional hazards models were generated for Gal3 and classical risk factors. We also evaluated the reclassification of patients on the basis of the different score category after adding Gal3 levels. A total of 219 patients had combined adverse events, and 129 patients died during the follow-up. Kaplan-Meir survival curve showed significantly increased primary endpoint and all-cause mortality according to quartiles of Gal3 (log rank, P<0.001). Serum Gal3 levels above median (13.8 ng/ml) was a significant predictor of primary endpoint risk after adjustment for age, estimated glomerular filtration rate, anemia, diabetes, serum sodium, brain natriuretic peptide levels, NYHA class and urea, respectively (hazard ratio 1.43, 95% CI 1.07-1.91 P=0.015). The reclassification index increased significantly after addition of Gal3 (9.5%, P<0.001) and the integrated discrimination index was 0.022, (P=0.001). The clinical prediction model with Gal3 increased the c-statistic from 0.711 to 0.731 (difference of 0.020, P=0.001). CONCLUSIONS: Serum Gal3 is a strong and independent predictor of unfavorable outcomes in patients with HF and preserved LVEF. We also demonstrated the improvement of adding the new biomarker to the model.