Nutrients restriction upregulates adiponectin in epicardial or subcutaneous adipose tissue: impact in de novo heart failure patients.

Background: Hyperadiponectinemia is an indicator of worse outcomes in advanced heart failure (HF), its role in de novo HF is less clear. Objective: Because this protein is a hormone with starvation properties, we wanted to know its association with nutritional state and its regulator factors in de novo HF. Methods: Adiponectin circulating levels were determined by ELISA at discharge in patients admitted for de novo HF (n=74). Nutritional status was determined by CONUT score. Univariate and multivariate Cox regression analyses were employed to calculate the estimated hazard ratio (HR) with 95% confidence interval (CI) for death or all-cause readmission. Stromal vascular cells (SVC) of EAT and subcutaneous adipose tissue (SAT) from patients (n=5) underwent heart surgery were induced to adipogenesis for 18 days. Then, cells were cultured with complete or starved medium for 8 hours. At the end, adiponectin expression levels were analysed by real time polymerase chain reaction. Results: Patients were grouped regarding nutritional status. There was a strong association between high adiponectin levels and failing nutritional status. Those patients with worse nutritional state had the highest adiponectin and proBNP levels at discharge (p<0.01). Both proteins were slightly correlated (p<0.05). However, only high adiponectin levels were independently associated with death or all-cause readmission. Nutrients starvation upregulated adiponectin expression levels in adipogenesis-induced SVC from EAT or SAT. Conclusions: Worse nutritional state in de novo HF patients is associated with higher adiponectin plasma levels. Their levels were upregulated in adipose cells after being nutrients-starved. These results may help us to understand the adiponectin paradox in HF.

Prognostic value of the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio in cardiac amyloidosis.

INTRODUCTION AND OBJECTIVES: The tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/SPAP) ratio is a noninvasive surrogate of right ventricular to pulmonary circulation that has prognostic implications in patients with heart failure (HF) or pulmonary hypertension. Our purpose was to evaluate the prognostic value of the TAPSE/SPAP ratio in patients with cardiac amyloidosis. METHODS: We used the database of the AMIGAL study, a prospective, observational registry of patients with cardiac amyloidosis recruited in 7 hospitals of the Autonomous Community of Galicia, Spain, from January 1, 2018 to October 31, 2022. We selected patients whose baseline TAPSE/SPAP ratio was calculated with transthoracic echocardiography. Long-term survival and survival free of HF hospitalization were assessed by means of 5 different multivariable Cox regression models. Median follow-up was 680 days. RESULTS: We studied 233 patients with cardiac amyloidosis, among whom 209 (89.7%) had transthyretin type. The baseline TAPSE/SPAP ratio correlated significantly with clinical outcomes. Depending on the multivariable model considered, the adjusted hazard ratios estimated per 0.1mm/mmHg increase of baseline TAPSE/SPAP ratio ranged from 0.76 to 0.84 for all-cause mortality. Similarly, the ratios for all-cause mortality of HF hospitalization ranged from 0.79 to 0.84. The addition of the baseline TAPSE/SPAP ratio to the predictive model of the United Kingdom National Amyloidosis Centre resulted in an increase in Harrell's c-statistic from 0.662 to 0.705 for all-cause mortality and from 0.668 to 0.707 for all-cause mortality or HF hospitalization. CONCLUSIONS: Reduced TAPSE/SPAP ratio is an independent adverse prognostic marker in patients with cardiac amyloidosis.

[Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis]. / Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL).

INTRODUCTION AND OBJETIVES: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease. MATERIAL AND METHODS: One hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations. RESULTS: During a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2). AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). CONCLUSIONS: CA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions.

Intermittent inotropic support with levosimendan in advanced heart failure as destination therapy: The LEVO-D registry.

AIM: Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations in AHF in the short term. In this real-life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies. METHODS AND RESULTS: Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 [95% CI: 20.4-26.9] months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta-blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (-1.5) HF visit 1 year before levosimendan (-1.5) and heart rate >70 b.p.m. (-2). Patients with a score less than -1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO-D score performed well in the ROC analysis. CONCLUSION: In this large real-life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO-D Score could be of help when deciding about futile therapy in this population.

Influence of the medical treatment schedule in new diagnoses patients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) guidelines recommend treating all patients with HF and reduced ejection fraction (HFrEF) with quadruple therapy, although they do not establish how to start it. This study aimed to evaluate the implementation of these recommendations, analyzing the efficacy and safety of the different therapeutic schedules. METHODS AND RESULTS: Prospective, observational, and multicenter registry that evaluated the treatment initiated in patients with newly diagnosed HFrEF and its evolution at 3 months. Clinical and analytical data were collected, as well as adverse reactions and events during follow-up. Five hundred and thirty-three patients were included, selecting four hundred and ninety-seven, aged 65.5 ± 12.9 years (72% male). The most frequent etiologies were ischemic (25.5%) and idiopathic (21.1%), with a left ventricular ejection fraction of 28.7 ± 7.4%. Quadruple therapy was started in 314 (63.2%) patients, triple in 120 (24.1%), and double in 63 (12.7%). Follow-up was 112 days [IQI 91; 154], with 10 (2%) patients dying. At 3 months, 78.5% had quadruple therapy (p < 0.001). There were no differences in achieving maximum doses or reducing or withdrawing drugs (< 6%) depending on the starting scheme. Twenty-seven (5.7%) patients had any emergency room visits or admission for HF, less frequent in those with quadruple therapy (p = 0.02). CONCLUSION: It is possible to achieve quadruple therapy in patients with newly diagnosed HFrEF early. This strategy makes it possible to reduce admissions and visits to the emergency room for HF without associating a more significant reduction or withdrawal of drugs or significant difficulty in achieving the target doses.

Experience with the potassium binder patiromer in hyperkalaemia management in heart failure patients in real life.

AIMS: Hyperkalaemia (HK) is common in heart failure (HF) patients, related to renal dysfunction and medical treatment. It limits medical therapy optimization, which impacts prognosis. New potassium (K) binders help control HK, allowing better medical management of HF. METHODS AND RESULTS: A retrospective multicentre register included all outpatients with HF and HK (K ≥ 5.1 mEq/L) treated with patiromer according to current recommendations. We evaluated analytic and clinical parameters before starting the treatment and at 7, 30 and 90 days, as well as adverse events related to patiromer and treatment optimization. We included 74 patients (71.6% male) with a mean age of 70.8 years (SD 9.2). Sixty-seven patients (90.5%) presented HK in the previous year. Forty patients (54.1%) underwent down-titration of a renin-angiotensin-aldosterone inhibitor (RAASi) or a mineralocorticoid receptor antagonist (MRA), and 27 (36.5%) stopped any of them due to HK. Initial K was 5.5 mEq/L (SD 0.6), with a significantly reduction at 7 days (4.9 mEq/L (SD 0.8); P < 0.001), maintained at 90 days (4.9 mEq/L (SD 0.8); P < 0.001). There were no other electrolyte disturbances, with a slight improvement in renal function [glomerular filtration rate 39.6 mL/min (SD 20.4) to 42.7 mL/min (SD 23.2); P = 0.005]. Adverse events were reported in 33.9% of patients, the most common being hypomagnesaemia (16.3%), gastrointestinal disturbances (14.9%) and HK (2.8%). Withdrawal of patiromer was uncommon (12.2%) due to gastrointestinal disturbances in 66.7% of cases. Nine patients (12.2%) started on a RAASi, and 15 patients (20.3%) on an MRA during the follow-up. Forty-five patients (60.8%) increased the dose of RAASi or MRA, increasing to target doses in 5.4 and 10.8% of patients, respectively. At 90 days, NTproBNP values were reduced from 2509.5 pg/mL [IQR 1311-4,249] to 1396.0 pg/mL [IQR 804-4263]; P = 0.003, but the reduction was only observed in those who optimized HF medical treatment [NTproBNP from 1950.5 pg/mL (IQR 1208-3403) to 1349.0 pg/mL (IQR 804-2609); P < 0.01]. NYHA functional class only improved in 7.5% of patients, corresponding with those who optimized HF medical treatment. Compared with the previous 3 months before patiromer treatment, the rate of hospitalization was reduced from 28.4 to 10.9% (P < 0.01), and the emergency room visits from 18.9 to 5.4% (P < 0.01). CONCLUSIONS: In a real-life cohort of patients with HF, patiromer reduced and maintained K levels during 3 months of follow-up. The most common adverse events were hypomagnesaemia and gastrointestinal disturbances. Patiromer helps optimize medical treatment, increasing the percentage of patients treated with RAASi and MRA at target doses. At the end of follow-up, natriuretic peptides values and hospital visits were reduced, suggesting the benefit of optimizing HF medical treatment.

Cardiac amyloidosis: Description of a series of 143 cases. / Amiloidosis cardiaca: descripción de una serie de 143 casos.

INTRODUCTION AND OBJECTIVES: Recently, there have been important advances in the diagnosis and treatment of cardiac amyloidosis (CA). Our aim was to provide an updated description of its 2 most frequent types: the transthyretin CA (ATTR-CA) and the light chain CA (AL-CA). METHODS: Prospective registry of patients with CA diagnosed in 7 institutions in Galicia (Spain) between January 1, 2018 and June 30, 2020. Variables related to clinical characteristics, complementary tests, survival and causes of death were collected. RESULTS: One hundred and forty-three patients with CA were consecutively included, 128 ATTR-CA (89.5%) and 15 AL-CA (10.5%). Mean age was 79.6±7.7 years and 23.8% were women. Most patients with ATTR-CA were diagnosed non-invasively (87.5%). On physical examination, 35.7, 35 and 7% had Popeye's sign, Dupuytren's contracture and macroglossia, respectively. Twelve-month and 24-month survival was 92.1 and 76.2% in the ATTR-CA group, and 78.6 and 61.1% in the AL-CA group (P=.152). The cause of death was cardiovascular in 80.8% of the cohort. CONCLUSIONS: ATTR-CA can be diagnosed non-invasively in most cases and it is the most common type of CA in routine clinical practice. Furthermore, an increase in the short-term survival of CA appears to be observed, which could be due to advances related to its diagnosis and treatment.

Syncope in patients with transthyretin amyloid cardiomyopathy: clinical features and outcomes.

BACKGROUND: We aimed to describe the clinical characteristics, underlying causes and outcomes of syncope in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). METHODS: The clinical profile and underlying causes of syncopal episodes were reviewed in a cohort of 128 patients with ATTR-CM enrolled from January 2018 to June 2020 in a prospective multicentre registry in 7 hospitals of Galicia (Spain). After enrollment, patients were followed during a median period of 520 days. The effect of syncope on all-cause mortality was assessed by means of multivariate Cox´s regression. RESULTS: Thirty (23.4%) patients had a history of previous syncope as a clinical antecedent before being enrolled in the prospective phase of the registry, and 4 (3.1%) experienced a first episode of syncope thereafter. The estimated incidence density rate of syncope during the prospective follow-up period after registry enrollment was 71.9 episodes per 1000 patients-year (95% Confidence Interval (CI) 32.8-111.1). The estimated overall prevalence of syncope was 26.6% (95% CI 18.9%-34.2%). Cardiac arrhythmias (n = 11, 32.3%), structural diseases of the heart or great vessels (n = 5, 14.7%), a neurally mediated reflex (n = 6, 17.6%), and orthostatic hypotension (n = 4, 11.8%) were identified as probable underlying causes of syncope; in 8 (23.6%) patients, syncope remained unexplained. Patients with syncope had increased non-adjusted all-cause mortality than patients without it (univariate hazard-ratio 3.37; 95% CI 1.43-7.94). When other independent predictors of survival were added to the survival model, this association was no longer statistically significant (multivariate hazard-ratio 1.81, 95% CI 0.67-4.84). CONCLUSIONS: Syncope is frequent in patients with ATTR-CM. This study could not demonstrate an independent association between syncope and mortality in those individuals.Abbreviations: ATTR-CM: Transthyretin amyloid cardiomyopathy; CI: Confidence Interval; HF: Heart Failure; HR: Hazard Ratio; IQR: Interquartile rank; LVEF: Left Ventricular Ejection Fraction; NTproBNP: N-terminal pro-brain natriuretic peptide; SD: Standard Deviation; 99mTc-DPD: technetium-99m-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid.

Beta-Blocker Exposure and Survival in Patients With Transthyretin Amyloid Cardiomyopathy.

OBJECTIVE: To investigate a potential association between beta-blocker exposure and survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). METHODS: In this real-world prospective registry of 128 consecutive patients with ATTR-CM recruited in 7 institutions in Galicia (Spain), survival of 65 patients who received beta blockers on registry enrollment was compared with that of 63 untreated controls by means of both unweighted Cox regression and Cox regression with inverse probability of treatment weighting. Tolerance to and adverse effects of beta blockers were recorded. Median study follow-up was 520 days. RESULTS: Patients with ATTR-CM who received beta blockers showed statistically significant lower all-cause mortality than untreated controls as evaluated by either unweighted Cox regression (hazard ratio, 0.31; 95% CI, 0.12 to 0.79) or Cox regression with inverse probability of treatment weighting (hazard ratio, 0.18; 95% CI, 0.08 to 0.41; P<.001). Several sensitivity analyses confirmed the internal validity of these results. The overall frequency of beta-blocker suspension due to adverse effects was 25% (95% CI, 15.5% to 34.5%). CONCLUSION: In this real-world, prospective, multi-institutional registry, patients with ATTR-CM who received beta blockers had lower all-cause mortality than untreated controls.

Prevalence, Incidence, and Outcomes of Hyperkalaemia in Patients with Chronic Heart Failure and Reduced Ejection Fraction from a Spanish Multicentre Study: SPANIK-HF Design and Baseline Characteristics.

Hyperkalaemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) as it limits the use of some prognostic-modifying drugs and has a negative impact on prognosis. The objective of the present study was to estimate the prevalence of hyperkalaemia in outpatients with HFrEF and its impact on achieving optimal medical treatment. For this purpose, a multicentre, prospective, and observational study was carried out on consecutive HFrEF patients who were monitored as outpatients in heart failure (HF) units and who, in the opinion of their doctor, received optimal medical treatment. A total of 565 HFrEF patients were included from 16 specialised HF units. The mean age was 66 ± 12 years, 78% were male, 45% had an ischemic cause, 39% had atrial fibrillation, 43% were diabetic, 42% had a glomerular filtration rate < 60 mL/min/1.7 m2, and the mean left ventricular ejection fraction was 31 ± 7%. Treatment at the study entry included: 76% on diuretics, 13% on ivabradine, 7% on digoxin, 18.9% on angiotensin-conversing enzyme inhibitors (ACEi), 11.3% on angiotensin receptors blockers (ARBs), 63.8% on angiotensin-neprilysin inhibitors (ARNi), 78.5% on mineralocorticoid receptor antagonists (MRAs), and 92.9% on beta-blockers. Potassium levels in the baseline analysis were: ≤5 mEq/L = 80.5%, 5.1−5.4 mEq/L = 13.8%, 5.5−5.9 mEq/L = 4.6%, and ≥6 mEq/L = 1.06%. Hyperkalaemia was the reason for not prescribing or reaching the target dose of an MRAs in 34.8% and 12.5% of patients, respectively. The impact of hyperkalaemia on not prescribing or dropping below the target dose in relation to ACEi, ARBs, and ARNi was significantly less. In conclusion, hyperkalaemia is a frequent problem in the management of patients with HFrEF and a limiting factor in the optimisation of medical treatment.

Sex and Heart Failure Treatment Prescription and Adherence.

Heart disease is the leading cause of death in both men and women in developed countries. Heart failure (HF) contributes to significant morbidity and mortality and continues to remain on the rise. While advances in pharmacological therapies have improved its prognosis, there remain a number of unanswered questions regarding the impact of these therapies in women. Current HF guidelines recommend up-titration of neurohormonal blockade, to the same target doses in both men and women but several factors may impair achieving this goal in women: more adverse drug reactions, reduced adherence and even lack of evidence on the optimal drug dose. Systematic under-representation of women in cardiovascular drug trials hinders the identification of sex differences in the efficacy and safety of cardiovascular medications. Women are also under-represented in device therapy trials and are 30% less likely to receive a device in clinical practice. Despite presenting with fewer ventricular arrythmias and having an increased risk of implant complications, women show better response to resynchronization therapy, with lower mortality and HF hospitalizations. Fewer women receive advanced HF therapies. They have a better post-heart transplant survival compared to men, but an increased immunological risk needs to be acknowledged. Technological advances in mechanical circulatory support, with smaller and more hemocompatible devices, will likely increase their implantation in women. This review outlines current evidence regarding sex-related differences in prescription, adherence, adverse events, and prognostic impact of the main management strategies for HF.

A New Biomarker Tool for Risk Stratification in "de novo" Acute Heart Failure (OROME).

Background: Inflammation is one of the mechanisms involved in heart failure (HF) pathophysiology. Thus, the acute phase reactant protein, orosomucoid, was associated with a worse post-discharge prognosis in de novo acute HF (AHF). However, the presence of anti-inflammatory adipokine, omentin, might protect and reduce the severity of the disease. We wanted to evaluate the value of omentin and orosomucoid combination for stratifying the risk of these patients. Methods and Results: Two independent cohorts of patients admitted for de novo AHF in two centers were included in the study (n = 218). Orosomucoid and omentin circulating levels were determined by ELISA at discharge. Patients were followed-up for 317 (3-575) days. A predictive model was determined for the primary endpoint, death, and/or HF readmission. Differences in survival were evaluated using a Log-rank test. According to cut-off values of orosomucoid and omentin, patients were classified as UpDown (high orosomucoid and low omentin levels), equal (both proteins high or low), and DownUp (low orosomucoid and high omentin levels). The Kaplan Meier determined a worse prognosis for the UpDown group (Long-rank test p = 0.02). The predictive model that includes the combination of orosomucoid and omentin groups (OROME) + NT-proBNP values achieved a higher C-index = 0.84 than the predictive model with NT-proBNP (C-index = 0.80) or OROME (C-index = 0.79) or orosomucoid alone (C-index = 0.80). Conclusion: The orosomucoid and omentin determination stratifies de novo AHF patients into the high, mild, and low risk of rehospitalization and/or death for HF. Its combination with NT-proBNP improves its predictive value in this group of patients.

Changes in causes of death and influence of therapeutic improvement over time in patients with heart failure and reduced ejection fraction.

INTRODUCTION AND OBJECTIVES: In patients with heart failure and reduced ejection fraction (HFrEF), several therapies have been proven to reduce mortality in clinical trials. However, there are few data on the effect of the use of evidence-based therapies on causes of death in clinical practice. METHODS: This study included 2351 outpatients with HFrEF (< 40%) from 2 multicenter prospective registries: MUSIC (n=641, period: 2003-2004) and REDINSCOR I (n=1710, period: 2007-2011). Variables were recorded at inclusion and all patients were followed-up for 4 years. Causes of death were validated by an independent committee. RESULTS: Patients in REDINSCOR I more frequently received beta-blockers (85% vs 71%; P <.001), mineralocorticoid antagonists (64% vs 44%; P <.001), implantable cardioverter-defibrillators (19% vs 2%; P <.001), and resynchronization therapy (7.2% vs 4.8%; P=.04). In these patients, sudden cardiac death was less frequent than in those in MUSIC (6.8% vs 11.4%; P <.001). After propensity score matching, we obtained 2 comparable populations differing only in treatments (575 vs 575 patients). In patients in REDINSCOR I, we found a lower risk of total mortality (HR, 0.70; 95%CI, 0.57-0.87; P=.001) and sudden cardiac death (sHR, 0.46; 95%CI, 0.30-0.70; P <.001), and a trend toward lower mortality due to end-stage HF (sHR, 0.73; 95%CI, 0.53-1.01; P=.059), without differences in other causes of death (sHR, 1.17; 95%CI, 0.78-1.75; P=.445), regardless of functional class. CONCLUSIONS: In ambulatory patients with HFrEF, implementation of evidence-based therapies was associated with a lower risk of death, mainly due to a significant reduction in sudden cardiac death.

Long-Term Weight Gain Associated With High Omentin Levels at Hospital Discharge Improves Prognosis of Patients Following Acute Heart Failure.

A obesity paradox has been described following heart failure (HF). The aim of this study was to analyze the association between food intake-involved adipokines and long-term weight changes. Leptin, adiponectin, and omentin were analyzed in 92 acute HF (AHF) patients at discharge, classified on the basis of weight gains or losses > 6%. The mean follow-up was 256 ± 143 days. Leptin and adiponectin levels were similar among weight groups. However, omentin levels were higher in those patients who had gained weight (16 ± 5 ng/mL) than in those who had lost weight (12 ± 4 ng/mL) or showed no weight change (11 ± 5 ng/mL; p < 0.002). Omentin levels were the best independent predictors for patients with weight gain, who had less mortality and hospital readmission during the follow-up. The association between omentin levels and weight gain might explain part of the obesity paradox in HF.

Heart failure with recovered ejection fraction: Clinical characteristics, determinants and prognosis. CARDIOCHUS-CHOP registry.

BACKGROUND: The magnitude and the prognostic impact of recovering left ventricular ejection fraction (LVEF) in patients with heart failure (HF) and systolic dysfunction is unclear. The aim of this study was to evaluate the clinical characteristics and prognosis of patients with HFrecEF in an HF population. METHODS: 449 consecutive patients were selected with the diagnosis of HF and an evaluation of LVEF in the 6 months prior to selection who were referred to two HF units. Patients with systolic dysfunction were only considered if a second echocardiogram was performed during the follow-up. RESULTS: At the time of diagnosis, 207 patients had LVEF > 40% (HFpEF) and 242 had LVEF ≤ 40% (HFrEF). After 1 year, the LVEF was re-evaluated in all 242 patients with a LVEF ≤ 40%: in 126 (52%), the second LVEF was > 40% (HFrecEF), and the remaining 116 (48%) had LVEF ≤ 40% (HFrEF). After 1800 ± 900 days of follow-up patients with recovered LVEF had a significantly lower mortality rate (HFpEF vs. HFrecEF: hazard ratio [HR] = 2.286, 95% confidence interval [95% CI] 1.264-4.145, p = 0.019; HFrEF vs. HFrecEF: HR = 2.222, 95% CI 1.189-4.186, p < 0.001) and hospitalization rate (HFpEF vs. HFrecEF: HR = 1.411, 95% CI 1.046-1.903, p = 0.024; HFrEF vs. HFrecEF: HR = 1.388, 95% CI 1.002-1.924, p = 0.049). The following are predictors of LVEF recovery: younger age, lower functional class, treatment with renin-angiotensin-aldosterone system inhibitors and beta-blockers, absence of defibrillator use, and non-ischemic etiology. CONCLUSIONS: Patients with HF and reduced LVEF who were re-evaluated after 1 year, had significant improvement in their LVEF and had a more favourable prognosis than HF with preserved and reduced ejection fraction.

Determinants and Prognostic Impact of Heart Failure and Left Ventricular Ejection Fraction in Acute Coronary Syndrome Settings.

INTRODUCTION AND OBJECTIVES: Contemporary data on the incidence and prognosis of heart failure (HF) and the influence of left ventricular ejection fraction (LVEF) in the setting of acute coronary syndrome (ACS) are scant. The aim of this study was to examine the relationship between LVEF and HF with long-term prognosis in a cohort of patients with ACS. METHODS: This is a retrospective observational study of 6208 patients consecutively admitted for ACS to 2 different Spanish hospitals. Baseline characteristics were examined and a follow-up period was established for registration of death and HF rehospitalization as the primary endpoint. RESULTS: Among the study participants, 5064 had ACS without HF during hospitalization: 290 (5.8%) had LVEF<40%, 540 (10.6%) LVEF 40% to 49%, and 4234 (83.6%) LVEF ≥ 50%. The remaining 1144 patients developed HF in the acute phase: 395 (34.6%) had LVEF<40%, 251 (21.9%) LVEF 40% to 49%, and 498 (43.5%) LVEF ≥ 50%. Patients with LVEF 40% to 49% had a demographic and clinical profile with intermediate features between the LVEF <40% and LVEF ≥ 50% groups. Kaplan-Meier curves showed that mortality and HF readmissions were statistically different depending on LVEF in the non-HF group but not in the HF group. Left ventricular ejection fraction ≥ 50% was an independent prognostic factor in the non-HF group only. CONCLUSIONS: In ACS, long-term prognosis is considerably worse in patients who develop HF during hospitalization than in patients without HF, irrespective of LVEF. This parameter is a strong prognostic predictor only in patients without HF.

Mid-range Ejection Fraction Does Not Permit Risk Stratification Among Patients Hospitalized for Heart Failure.

INTRODUCTION AND OBJECTIVES: European Society of Cardiology heart failure guidelines include a new patient category with mid-range (40%-49%) left ventricular ejection fraction (HFmrEF). HFmrEF patient characteristics and prognosis are poorly defined. The aim of this study was to analyze the HFmrEF category in a cohort of hospitalized heart failure patients (REDINSCOR II Registry). METHODS: A prospective observational study was conducted with 1420 patients classified according to ejection fraction as follows: HFrEF, < 40%; HFmrEF, 40%-49%; and HFpEF, ≥ 50%. Baseline patient characteristics were examined, and outcome measures were mortality and readmission for heart failure at 1-, 6-, and 12-month follow-up. Propensity score matching was used to compare the HFmrEF group with the other ejection fraction groups. RESULTS: Among the study participants, 583 (41%) had HFrEF, 227 (16%) HFmrEF, and 610 (43%) HFpEF. HFmrEF patients had a clinical profile similar to that of HFpEF patients in terms of age, blood pressure, and atrial fibrillation prevalence, but shared with HFrEF patients a higher proportion of male participants and ischemic etiology, and use of class I drugs targeting HFrEF. All other features were intermediate, and comorbidities were similar among the 3 groups. There were no significant differences in all-cause mortality, cause of death, or heart failure readmission. The similar outcomes were confirmed in the propensity score matched cohorts. CONCLUSIONS: The HFmrEF patient group has characteristics between the HFrEF and HFpEF groups, with more similarities to the HFpEF group. No between-group differences were observed in total mortality, cause of death, or heart failure readmission.

Nutritional status is related to heart failure severity and hospital readmissions in acute heart failure.

BACKGROUND: Malnutrition is common in hospitalized heart failure (HF) patients and predicts adverse outcomes. The relationship between nutritional status and outcomes in HF has been partially studied. Our aim was to determine the relationship between the nutritional status and the long-term prognosis in patients hospitalized for acute HF. METHODS: We analyzed 145 patients admitted consecutively to a cardiology department for acute HF. Nutritional status was measured with the CONUT method, a validated scale based on laboratory testing (albumin; cholesterol; lymphocytes) during hospitalization. Patients were classified as normal, mildly, moderately or severely malnourished, and followed in a HF clinic. RESULTS: The mean aged of the population was 69.6years and 61% of patients were men, 54 had previous HF hospitalization (37%), 112 had hypertension (77%), 67 were diabetic (46%) and 135 had class III or IV NYHA (93%). Forty eight patients (33%) had normal nutritional status, 75 were mildly malnourished (52%), and 22 were moderately or severely malnourished (15%). Age, sex, hypertension, diabetes mellitus, or NYHA class among the three groups were not statistically different. ProBNP was directly correlated with the nutritional status. After a mean follow-up of 326days, 27 had a HF hospitalization (19%) and 61 (42,1%) had a hospitalization not related to HF. The analysis by Kaplan-Meier curves and log rank test showed that these differences were statistically significant. CONCLUSION: Malnutrition is common in patients hospitalized for HF. It seems to be a mediator of disease progression and determines a poor prognosis especially in advanced stages.

Mid-range left ventricular ejection fraction: Clinical profile and cause of death in ambulatory patients with chronic heart failure.

BACKGROUND: The intermediate group of patients with heart failure (HF) and mid-range left ventricular ejection fraction (HFmrEF) may constitute a specific phenotype, but a direct evidence is lacking. This study aimed to know whether this HF category is accompanied by a particular clinical phenotype and prognosis. METHODS AND RESULTS: This study includes 3446 ambulatory patients with chronic HF from two national registries. According to EF at enrollment, patients were classified as reduced (HFrEF, <40%), mid-range (HFmrEF, 40-49%) or preserved (HFpEF, ≥50%). Patients were followed-up for a median of 41months and the specific cause of death was prospectively registered. Patients with HFmrEF represented 13% of population and they exhibited a phenotype closer to HFrEF, except for a higher rate of coronary revascularization and diabetes, and a less advanced HF syndrome. The observed all-cause mortality was higher among HFrEF (33.0%), and similar between HFmrEF (27.8%) and HFpEF (28.0%) (p=0.012); however, the contribution of each cause of death differed significantly between categories (p<0.001). After propensity score matching, the risk of cardiovascular death, HF death or sudden cardiac death did not differ between HFmrEF and HFrEF in paired samples; however, patients with HFmrEF were at higher risk of cardiovascular death (sHR 1.71, 95% CI 1.13-2.57, p=0.011) and sudden cardiac death (sHR 2.73, 95% CI 1.07-6.98, p=0.036) than patients with HFpEF. CONCLUSIONS: Patients in the intermediate category of HFmrEF conform a phenotype closer to the clinical profile of HFrEF, and associated to higher risk of sudden cardiac death and cardiovascular death than patients with HFpEF.

[Renal failure is an independent predictor of mortality in hospitalized heart failure patients and is associated with a worse cardiovascular risk profile]. / La insuficiencia renal es un predictor independiente de la mortalidad en pacientes hospitalizados por insuficiencia cardíaca y se asocia con un peor perfil de riesgo cardiovascular.

INTRODUCTION AND OBJECTIVES: Most clinical trials that demonstrated the negative impact of renal failure on survival in patients with congestive heart failure (CHF) included a relatively small proportion of subjects with a high creatinine level and were performed in patients with depressed left ventricular systolic function. Our aim was to investigate the clinical characteristics and prognosis of hospitalized CHF patients with depressed or preserved systolic function and different degrees of renal dysfunction. PATIENTS AND METHOD: The study included 552 consecutive CHF patients admitted to a hospital department of cardiology between 2000-2002. Renal function was determined from the estimated glomerular filtration rate (GFR), and patients were divided into three groups: GFR>60, GFR 30-60, and GFR<30 mL.min per 1.73 m2 (severe renal failure), containing 56.5%, 35.5%, and 8.0% of patients, respectively. RESULTS: Patients with severe renal failure had the worst cardiovascular risk profile: older age, higher prevalence of cardiovascular risk factors, anemia, inflammatory markers in plasma, and less prescription of angiotensin-converting enzyme (ACE) inhibitors. Survival in this patient group was significantly poorer than in other groups (relative risk or RR=2.4; 95% CI, 1.3-4.4) in those with either depressed (RR=3.8; 95% CI, 1.4-10.6) or preserved (RR=2.9; 95% CI, 1.2-6.9) systolic function, independent of other prognostic factors. The negative impact of severe renal failure on prognosis was reduced by ACE inhibitor use. CONCLUSIONS: Renal failure is common and a strong predictor of mortality in hospitalized CHF patients with or without depressed systolic function. It is associated with a worse risk profile.