Prognostic impact of abnormal sodium burden in heart failure patients with preserved ejection fraction.

BACKGROUND: Sodium abnormality is common in patients with heart failure (HF) and is associated with adverse clinical outcomes. The aim of this study is to determine the impact of abnormal sodium burden on long-term mortality and hospitalization in HF with preserved ejection fraction (HFpEF). METHODS: We analysed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline and follow-up data (n = 1717). Abnormal sodium burden was defined as the proportion of days with abnormal sodium plasma levels (either <135 mmol/L or > 145 mmol/L). To determine the independent prognostic impact of abnormal sodium burden on the long-term clinical adverse outcomes (The primary outcome was any cause death, the secondary outcomes include cardiovascular disease death, HF hospitalization, any cause hospitalization and the primary endpoint of the original study), a multivariable Cox proportional hazard model and time-updated Cox regression model were performed. RESULTS: Abnormal sodium burden occurred in 717 patients (41.76%). A high abnormal sodium burden was associated with 1.47 (95% CI, 1.15-1.89) higher risk with any cause mortality, 1.51 (95% CI, 1.08-2.09) higher risk with CVD death and 1.31 (95% CI, 1.02-1.69) higher risk with HF hospitalization when compared with no burden group. When sodium level changes over time were accounted for in time-updated models, abnormal sodium level was still associated with poor clinical outcomes. Diuretic and spironolactone usage did not show a statistical interaction effect on the prognostic significance. CONCLUSIONS: In HFpEF patients, abnormal sodium burden was an independent predictor long-term any-cause mortality and HF hospitalization.

Clinical Implication of N-Terminal Pro-Brain Natriuretic Peptide Burden in Heart Failure With Reduced Ejection Fraction: From the GUIDE-IT.

This study aimed to explore the prognostic implication of N-terminal pro-brain natriuretic peptide (NT-proBNP) burden on heart failure (HF) with reduced ejection fraction (HFrEF). We performed a post hoc analysis of the GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) trial. NT-proBNP burden was defined as the proportion of days with increased NT-proBNP (≥1,800 pg/ml) to the whole observation time. A Cox proportional hazards regression model was used to evaluate the association with NT-proBNP burden and prognosis. A total of 815 patients with HFrEF were analyzed in our study. Patients were categorized into 4 groups according to the degree of NT-proBNP burden. In the multivariate Cox analysis, NT-proBNP burden was significantly associated with all-cause mortality, cardiovascular mortality, and HF hospitalization. Compared with patients without NT-proBNP burden, the risk for the composite outcome increased by 210% (hazard ratio [HR] 3.10, 95% confidence interval [CI] 1.72 to 5.58, p <0.001) in NT-proBNP burden 1 (mild) group, 432% (HR 5.32, 95% CI 2.93 to 9.67, p <0.001) in NT-proBNP burden 2 (moderate) group, and over 12 times (HR 13.15, 95% CI 7.42 to 23.33, p <0.001) in NT-proBNP burden 3 (severe) group. The sensitivity analyses stratified by age and renal function yielded similar results. A higher NT-proBNP burden was associated with a significant increase in risks of all-cause mortality, cardiovascular mortality, HF hospitalization, and composite outcome. The results suggested that NT-proBNP burden could be an important predictor of the prognosis of patients with HFrEF.

Hemoglobin to red cell distribution width ratio: A predictor of clinical outcome and diuretic response in patients with acute heart failure.

BACKGROUND: Hemoglobin to Red Cell Distribution Width Ratio (HRR) is a novel inflammatory marker in the prognostic assessment of tumors. Nevertheless, its focus on the cardiovascular field is relatively limited, particularly regarding its correlation with diuretic responses and clinical outcomes. METHODS: This is a secondary analysis of the Renal Optimization Strategies Evaluation (ROSE AHF) clinical trial. The outcomes of interest included all-cause death, rehospitalization and diuretic responses. Multivariable Cox proportional hazard regression and linear regression models were performed, respectively. Prognostic outcomes and diuretic response were further evaluated in ejection fraction (EF) subgroups (preserved EF ≥ 50% and reduced EF<50%). RESULTS: A total of 351 patients were included in the present study and further categorized according to HRR median (0.7131) value at admission: low HRR group (n = 176) and high HRR group (n = 175). High HRR were found to be independently associated with decreased risk of all-cause death (HR = 0.51; 95% CI,0.30-0.87, P = 0.013), reduced risk of developing all-caused death or rehospitalization (HR = 0.62; 95% CI,0.39-0.98, P = 0.039). Furthermore, high HRR indicated lower cumulative urine output (OR: -992.33, P = 0.004) and less weight loss (OR: 3.08, P < 0.001) within 72 h after diuresis. Subgroup analysis revealed no significant interaction effect between EF and HRR in prognostic impact or diuretic responses, and HRR was negatively correlated with plasma volume. CONCLUSION: High HRR demonstrated a lower risk of developing adverse clinical outcomes and a poorer diuretic response that might be due to less volume overload in AHF patients.

Mean corpuscular haemoglobin concentration and outcomes in heart failure with preserved ejection fraction.

AIMS: This study aims to evaluate the prognostic value of mean corpuscular haemoglobin concentration (MCHC) on clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We analysed HFpEF participants from the Americas in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline data (n = 1747). Patients were grouped into hypochromia or non-hypochromia group according to a MCHC cut-off level of 330 g/L. Cox proportional hazard model was used to explore the prognostic value of hypochromia on the long-term clinical outcomes (the primary endpoint [composite of cardiovascular mortality, HF hospitalization and aborted cardiac arrest], any-cause and HF hospitalization, all-cause and cardiovascular mortality). Patients were further stratified according to baseline estimated glomerular filtration rate (eGFR) to explore the impact of renal dysfunction on the prognostic value of hypochromia. Baseline hypochromia was prevalent (n = 662, 37.9%) and strongly associated with worse clinical outcomes. In patients with worse renal function (eGFR < 60 mL/min per 1.73 m2 ), hypochromia was independently associated with primary endpoint (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.23-1.98; P < 0.001), any-cause hospitalization (HR, 1.43; 95% CI, 1.20-1.71, P < 0.001) and HF hospitalization (HR, 1.40; 95% CI, 1.07-1.84; P = 0.015), whereas no significant association between hypochromia and these outcomes was found in patients with better renal function. CONCLUSIONS: Among HFpEF patients, hypochromia (i.e. MCHC ≤ 330 g/L) is independently associated with adverse clinical outcomes, especially when in the presence of co-morbidity renal dysfunction.

Distinct implications of body mass index in different subgroups of nonobese patients with heart failure with preserved ejection fraction: a latent class analysis of data from the TOPCAT trial.

BACKGROUND: Obesity is a well-defined risk factor for heart failure with preserved ejection fraction (HFpEF), but it is associated with a better prognosis in patients with diagnosed HFpEF. The paradoxically poor prognosis in nonobese patients with HFpEF may be driven by a subset of high-risk patients, which suggests that the nonobese HFpEF subpopulation is heterogeneous. METHODS: Latent class analysis (LCA) was adopted to identify the potential subgroups of 623 nonobese patients enrolled in the TOPCAT trial. The baseline characteristics of the identified nonobese subgroups were compared with each other and with the obese patients. The risks of all-cause, cardiovascular, and noncardiovascular mortality, and an HF composite outcome were also compared. RESULTS: Two subgroups of nonobese patients with HFpEF (the physiological non-obesity and the pathological non-obesity) were identified. The obese patients were younger than both nonobese subgroups. The clinical profile of patients with pathological non-obesity was poorer than that of patients with physiological non-obesity. They had more comorbidities, more severe HF, poorer quality of life, and lower levels of physical activity. Patients with pathological non-obesity showed low serum hemoglobin and albumin levels. After 2 years of follow-up, more patients in the pathological group lost ≥ 10% of body weight compared with those in the physiological group (11.34% vs. 4.19%, P = 0.009). The prognostic implications of the two subgroups were opposite. Compared to patients with obesity, patients with physiological non-obesity had a 47% decrease in the risk of HF composite outcome (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.40-0.70, P<0.001) and a trend of decreased all-cause mortality risk (HR 0.75, 95% CI 0.55-1.01, P=0.06), while patients with pathological non-obesity had a 59% increase (HR 1.59, 95% CI 1.24-2.02, P<0.001) in all-cause mortality risk. CONCLUSIONS: Two subgroups of nonobese patients with HFpEF with distinct clinical profiles and prognostic implications were identified. The low BMI was likely physiological in one group but pathological in the other group. Using a data-driven approach, our study provided an alternative explanation for the "obesity paradox" that the poor prognosis of nonobese patients with HFpEF was driven by a pathological subgroup.

Worsening of Renal Function Among Hospitalized Patients With Acute Heart Failure: Phenotyping, Outcomes, and Predictors.

OBJECTIVE: To define clinical phenotyping and its associated outcome of worsening of renal function (WRF) in hospitalized acute heart failure (AHF) patients. PATIENTS AND METHODS: Latent class analysis was performed in 113 AHF patients who developed WRF within 72 hours in the DOSE (Diuretic Optimization Strategies Evaluation) trial (from March 2008 to November 2009) and ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure) trial (from September 2010 to March 2013) to identify potential WRF phenotypes. Clinical characteristics and outcome (in-hospital and post-discharge) were compared between different phenotypes. RESULTS: Two WRF phenotypes were identified by latent class analysis, which we named WRF minimally responsive to diuretics (WRF-MRD) and WRF responsive to diuretics (WRF-RD). Among the population, 58 (9.5%) developed WRF-MRD and 55 (9.0%) developed WRF-RD. Patients with WRF-MRD had more comorbidities than WRF-RD. In WRF-MRD, there were an early increase in serum creatinine, a smaller amount of net fluid loss and weight loss, and a higher rate of worsening or persistent heart failure over 72 hours. In contrast, for those with WRF-RD, they had faster in-hospital net fluid loss and weight loss and a better 60-day survival after discharge even compared with patients without WRF (P=.004). Furthermore, baseline chronic obstructive pulmonary disease, diabetes, and cystatin C were independent predictors of WRF-MRD, whereas serum hemoglobin and sodium predicted WRF-RD. CONCLUSIONS: Among hospitalized AHF patients, we identified two phenotypes of WRF with distinct response to heart failure treatment, predictors, and short-term prognosis after discharge. The results could help early differentiation of WRF phenotypes in clinical practice.

Prognostic significance of resting cardiac power to left ventricular mass and E/e' ratio in heart failure with preserved ejection fraction.

Background: Cardiac power-to-left ventricular mass (power/mass) is an index reflecting the muscular hydraulic pump capability of the heart, and the E/e' ratio is a specific indicator for identifying increased left ventricular filling pressure. Limited data exist regarding the prognostic value of incorporating power/mass and E/e' ratio in heart failure with preserved ejection fraction (HFpEF). Materials and methods: In total, 475 patients with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with complete baseline echocardiography data were included in our analysis. Patients were categorized into four groups according to power/mass and E/e' ratio. The risk of outcomes was examined using Cox proportional hazards models and competing risk models. Results: Patients with low power/mass and high E/e' were more likely to be males (60.5%), with higher waist circumference, and had a higher prevalence of diabetes (52.1%), atrial fibrillation (50.4%), and lower estimated glomerular filtration rate (eGFR). Combined resting power/mass and E/e' have graded correlations with left ventricular (LV) dysfunction and clinical outcomes in patients with HFpEF. After multivariable adjustments, an integrative approach combining power/mass and E/e' remained to be a powerful prognostic predictor, with the highest HRs of clinical outcomes observed in patients with low power/mass and high E/e' (all-cause mortality: HR 3.45; 95% CI: 1.69-7.05; P = 0.001; hospitalization for heart failure: HR 3.27; 95% CI: 1.60-6.67; P = 0.001; and primary endpoint: HR 3.07; 95% CI: 1.73-5.42; P < 0.001). Conclusion: In patients with HFpEF, an echo-derived integrated approach incorporating resting power/mass and E/e' ratio remained to be a powerful prognosis predictor and may be useful to risk-stratify patients with this heterogeneous syndrome. Clinical Trial Registration: [https://clinicaltrials.gov], identifier [NCT00094302].

Identification of a long noncoding RNA Gm17501 as a novel negative regulator of cardiac hypertrophy.

Pathological cardiac hypertrophy is an independent risk factor for the development of heart failure. Long noncoding RNAs (lncRNAs), an emerging class of non-protein-coding transcripts, are involved in regulation of multiple cardiac diseases through diverse molecular mechanism, whereas the role of cytoplasmic lncRNAs in regulating cardiac hypertrophy remains unclear. In this study, we identified a novel and functional long noncoding RNA Gm17501, which was predominantly expressed in the cytoplasm of cardiomyocytes. The expression level of lncRNA Gm17501 was altered in cardiac hypertrophy induced by pressure overload and phenylephrine treatment. Moreover, lncRNA Gm17501 expression was decreased in the heart tissue of patients with heart failure. Silencing lncRNA Gm17501 aggravated cardiac hypertrophy under pathological stress. Inhibition of lncRNA Gm17501 did not alter the expression of nearby genes but decreased mRNA level of calcium handling proteins which were involved in cardiac contraction. Therefore, the cytoplasmic lncRNA Gm17501 might protect cardiomyocytes against hypertrophy, possibly by maintaining calcium signaling pathway.

Modified Exosomes: a Good Transporter for miRNAs within Stem Cells to Treat Ischemic Heart Disease.

Stem cell-based therapy for ischemic heart disease (IHD) has become a promising but controversial strategy during the past two decades. The fate and effects of stem cells engrafted into ischemia myocardium are still not fully understood. Stem cell-derived exosomes, a subcategory of extracellular vesicles with nano size, have been considered as an efficient and safe transporter for microRNAs (miRNAs) and a central mediator of the cardioprotective potentials of the parental cells. Hypoxia, pharmacological intervention, and gene manipulation could alter the exosomal miRNAs cargos from stem cells and promote therapeutic potential. Furthermore, several bioengineering methods were also successfully applied to modify miRNAs content and components of exosomal membrane proteins recently. In this review, we outline relevant results about exosomal miRNAs from stem cells and focus on the current strategies to promote their therapeutic efficiency in IHD.

Prognostic significance of blood urea nitrogen/creatinine ratio in chronic HFpEF.

BACKGROUND: The prognostic significance of blood urea nitrogen (BUN)/creatinine ratio specifically in chronic heart failure with preserved ejection fraction (HFpEF) patients remained unclear. We aimed to evaluate the association of BUN/creatinine ratio (baseline level and visit-to-visit variation) with the risk of adverse clinical outcomes among patients with chronic HFpEF. METHODS AND RESULTS: This is a secondary analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Of the enrolled 3445 participants in the TOPCAT trial, associations between BUN/creatinine and clinical outcomes were examined in a subset of 1521 (baseline measurements level) and 1453 (visit-to-visit variation) participants. A multivariable Cox proportional hazard model was used to assess the prognostic significance of BUN/creatinine ratio and BUN/creatinine ratio variation for the prespecified clinical outcomes. A higher BUN/creatinine ratio was associated with a higher risk of all-cause mortality (hazard ratio [HR] = 1.52, 95%CI, 1.21-1.91; p < .001) as well as cardiovascular disease mortality (HR = 1.83, 95%CI, 1.35-2.49; p < .001) in the fully adjusted model. Greater visit-to-visit variability in BUN/creatinine ratio tended to be independently associated with a higher risk of heart failure hospitalization and primary endpoint (p < .001 for both outcomes). Furthermore, those findings were consistent across participants stratified by the presence of chronic kidney disease at baseline. CONCLUSIONS: Higher BUN/creatinine ratio and greater BUN/creatinine ratio variability are independently associated with adverse outcomes in HFpEF participants in the TOPCAT trial.

Role of N6-methyladenosine Modification in Cardiac Remodeling.

Cardiac remodeling is the critical process in heart failure due to many cardiovascular diseases including myocardial infarction, hypertension, cardiovascular disease and cardiomyopathy. However, treatments for heart failure focusing on cardiac remodeling show relatively limited effectiveness. In recent decades, epitranscriptomic modifications were found abundantly present throughout the progression of cardiac remodeling, and numerous types of biochemical modifications were identified. m6A modification is the methylation of the adenosine base at the nitrogen-6 position, and dysregulation of m6A modification has been implicated in a wide range of diseases. However, function of m6A modifications still remain largely unknown in cardiac diseases, especially cardiac remodeling. LncRNAs are also shown to play a vital role in the pathophysiology of cardiac remodeling and heart failure. The crosstalk between lncRNAs and m6A modification provides a novel prospective for exploring possible regulatory mechanism and therapeutic targets of cardiac remodeling. This review summarizes the role of m6A modification in cardiac remodeling in the current researches.

Clinical Significance of Mean and Pulse Pressure in Patients With Heart Failure With Preserved Ejection Fraction.

It remains debated whether pulse pressure is associated with left ventricular traits and adverse outcomes over and beyond mean arterial pressure (MAP) in patients with heart failure (HF) with preserved ejection fraction. We investigated these associations in 3428 patients with HF with preserved ejection fraction (51.5% women; mean age, 68.6 years) enrolled in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). We computed association sizes and hazards ratios with 1-SD increase in MAP and pulse pressure. In multivariable-adjusted analyses, association sizes (P≤0.039) for MAP were 0.016 cm and 0.014 cm for septal and posterior wall thickness, -0.15 for E/A ratio, -0.66 for E/e', and -0.64% for ejection fraction, independent of pulse pressure. With adjustment additionally applied for MAP, E/A ratio and longitudinal strain increased with higher pulse pressure with association sizes amounting to 0.067 (P=0.026) and 0.40% (P=0.023). In multivariable-adjusted analyses of both placebo and spironolactone groups, lower MAP and higher pulse pressure predicted the primary composite end point (P≤0.028) and hospitalized HF (P≤0.002), whereas MAP was also significantly associated with total mortality (P≤0.007). Sensitivity analyses stratified by sex, median age, and region generated confirmatory results with exception for the association of adverse outcomes with pulse pressure in patients with age ≥69 years. In conclusion, the clinical application of MAP and pulse pressure may refine risk estimates in patients with HF with preserved ejection fraction. This finding may help further investigation for the development of HF with preserved ejection fraction preventive strategies targeting pulsatility and blood pressure control.

Chest pain in a mid-aged woman, not simply myopericarditis: a case report of anti-Ku positive polymyositis.

BACKGROUND: Anti-Ku is a rare antibody which can be positive in some rheumatic diseases and it might be related to cardiac involvement. Polymyositis is an inflammatory myopathy, and its cardiac involvement seldom presents as myopericarditis and anti-Ku positive. CASE PRESENTATION: In this case, we report a mid-aged woman with chest pain, upper limbs weakness and fever unrelated with infection. The diagnosis of this case was unquestionably myopericarditis supported by ECG, cardiac MRI and negative findings in coronary arteries. Diagnosis of polymyositis was further clarified by the evidence of persistently increased CK, degeneration of proximal muscle in MRI, muscular dystrophy with lymphocytes infiltration in muscle biopsy. In the analysis of autoantibodies, we surprisingly discovered positive anti-Ku. Glucocorticoid and mycophenolate mofetil were then prescribed for polymyositis. Patient follow-up indicated remission of both myopericarditis and polymyositis. We finally clarified this rare case as a positive anti-Ku polymyositis with myopericarditis as cardiac involvement. CONCLUSION: This report presents a rare case with anti-Ku positive polymyositis and the cardiac involvement of polymyositis was manifested as myopericarditis. Therefore, positive anti-Ku might explain the myopericarditis as cardiac involvement in polymyositis. More cases and longer duration of follow-up is required for the comprehensive understanding of the disease.

Association of Body-Weight Fluctuation With Outcomes in Heart Failure With Preserved Ejection Fraction.

Aims: To investigate the relationship between body-weight fluctuation and risks of clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results:We measured intra-individual variations in body weight from baseline and follow-up visits in 1,691 participants with HFpEF from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. The primary endpoint was any cardiovascular events (a composite of death from cardiovascular disease, non-fatal myocardial infarction, aborted cardiac arrest, or hospitalization for HF). The body-weight fluctuation was measured according to average successive variability and high variability was defined as greater than or equal to the median. After adjustment for risk factors, mean body weight and weight change, each increase of 1 standard deviation in body-weight variability was significantly associated with increased risks of any cardiovascular events (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.15-1.33, P < 0.001). Patients with high variability had a 47% increased risk of any cardiovascular events and 27% increased risk of all-cause death compared with those with low variability. Such association was similar among patients with New York Heart Association functional class I/II vs. III/IV, obesity vs. non-obesity, and weight loss, gain vs. stability (the P-values for interaction were all insignificant). Conclusion: Among patients with HFpEF, body-weight fluctuation was associated with increased risks of cardiovascular events independent of traditional cardiovascular risk factors, and regardless of HF severity, baseline weight or weight change direction. Clinical Trial Registration: Aldosterone antagonist therapy for adults with heart failure and preserved systolic function (TOPCAT), https://clinicaltrials.gov, identifier [NCT00094302].

Effect of aggressive diuresis in acute heart failure with reduced and preserved ejection fraction.

AIMS: Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) had distinct haemodynamic characteristics in the setting of acute heart failure. The aim of our study is to evaluate the differential response to aggressive diuresis in HFrEF and HFpEF. METHODS AND RESULTS: Patients in the Diuretic Optimization Strategies Evaluation trial with left ventricular ejection fraction measurement were included (n = 300) and classified into HFrEF [left ventricular ejection fraction (LVEF) < 40%] (n = 193) and HFpEF (LVEF ≥ 40%) (n = 107). Effect of high-dose vs. low-dose furosemide strategy was compared separately in HFrEF and HFpEF. In HFrEF, high-dose strategy did not increase change in creatinine or cystatin C at 72 h [treatment difference: -0.05, 95% confidence interval (CI): -0.14 to 0.03 mg/dL; P = 0.23 for creatinine, and treatment difference: -0.06, 95% CI: -0.15 to 0.02 mg/dL; P = 0.15 for cystatin C] compared with low-dose strategy, but there were significantly more net fluid loss, weight loss, and congestion-free patients at 72 h in high-dose group. It was also associated with a significantly lower risk of composite clinical outcome of death, total hospitalizations, and unscheduled visits due to heart failure. In HFpEF, high-dose strategy significantly increased change in creatinine and cystatin C at 72 h (treatment difference: 0.16; 95% CI: 0.02-0.30 mg/dL; P = 0.03 for creatinine, and treatment difference: 0.26; 95% CI: 0.09-0.43 mg/dL; P = 0.003 for cystatin C), but did not significantly affect net fluid loss, weight loss, proportion of congestion-free patients at 72 h, and risk of the composite clinical outcome. CONCLUSIONS: Acute heart failure on the basis of HFrEF and HFpEF responded differently to aggressive diuresis. Future trials should be designed separately for HFrEF and HFpEF.

Prognostic Implication of Liver Function Tests in Heart Failure With Preserved Ejection Fraction Without Chronic Hepatic Diseases: Insight From TOPCAT Trial.

Background: Liver dysfunction is prevalent in patients with heart failure (HF), but the prognostic significance of liver function tests (LFTs) remains controversial. Heart failure with preserved ejection fraction (HFpEF) had been introduced for some time, but no previous study had focused on LFTs in HFpEF. Thus, we aim to evaluate the prognostic significance of LFTs in well-defined HFpEF patients. Methods and Results: We conveyed a post-hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). The primary outcome was the composite of cardiovascular mortality, HF hospitalization, and aborted cardiac arrest, and the secondary outcomes were cardiovascular mortality and HF hospitalization. In Cox proportional hazards models, aspartate transaminase (AST) and alanine transaminase (ALT) were not associated with any of the outcomes. On the contrary, increases in total bilirubin (TBIL) and alkaline phosphatase (ALP) were associated with increased risks of the primary outcome [TBIL: adjusted hazard ratio (HR), 1.17; 95% confidence interval (CI) 1.08-1.26; ALP: adjusted HR, 1.12; 95% CI 1.04-1.21], cardiovascular mortality (TBIL: adjusted HR, 1.16; 95% CI 1.02-1.31; ALP: adjusted HR, 1.16; 95% CI 1.05-1.28), and HF hospitalization (TBIL: adjusted HR, 1.22; 95% CI 1.12-1.33; ALP: adjusted HR, 1.12; 95% CI 1.03-1.23). Conclusion: Elevated serum cholestasis markers TBIL and ALP were significantly associated with a poor outcome in HFpEF patients without chronic hepatic diseases, while elevated ALT and AST were not.

Living Alone and Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: In patients with heart failure with preserved ejection fraction (HFpEF), whether living alone could contribute to a poor prognosis remains unknown. We sought to investigate the association of living alone with clinical outcomes in patients with HFpEF. METHODS: Symptomatic patients with HFpEF with a follow-up of 3.3 years (data collected from August 2006 to June 2013) in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial were classified as patients living alone and those living with others. The primary outcome was defined as a composite of cardiovascular death, aborted cardiac arrest, or HF hospitalization. RESULTS: A total of 3103 patients with HFpEF were included; 25.2% of them were living alone and were older, predominantly female, and less likely to be White and have more comorbidities compared with the other patients. After multivariate adjustment for confounders, living alone was associated with increased risks of HF hospitalization (hazard ratio [HR] = 1.29, 95% confidence interval [CI] = 1.03-1.61) and any hospitalization (HR = 1.26, 95% CI = 1.12-1.42). A significantly increased risk of any hospitalization (HR = 1.16, 95% CI = 1.01-1.34) was also observed in the Americas-based sample. In addition, each year increase in age, female sex, non-White race, New York Heart Association functional classes III and IV, dyslipidemia, and chronic obstructive pulmonary disease were independently associated with living alone. CONCLUSIONS: We assessed the effect of living arrangement status on clinical outcomes in patients with HFpEF and suggested that living alone was associated with an independent increase in any hospitalization.Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00094302.

Visit-to-Visit Blood Pressure Variability and Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

[Figure: see text].

Meta-analysis of metabolic syndrome and its individual components with risk of atrial fibrillation in different populations.

BACKGROUND: Recent studies have reported the effects of metabolic syndrome (MetS) and its components on atrial fibrillation (AF), but the results remain controversial. Therefore, we performed a meta-analysis to evaluate the relationship between MetS and AF risk. METHODS: Studies were searched from the Cochrane library, PubMed, and Embase databases through May 2020. Adjusted hazard ratios (HRs) and its corresponding 95% confidence intervals (CIs) were extracted and then pooled by using a random effects model. RESULTS: A total of 6 observational cohort studies were finally included. In the pooled analysis, MetS was associated with an increased risk of AF (HR 1.57; 95% CI 1.40-1.77; P < 0.01). And the components of MetS including abdominal obesity (HR 1.37; 95% CI 1.36-1.38; P < 0.01), elevated blood pressure (HR 1.56; 95% CI 1.46-1.66; P < 0.01), elevated fasting glucose (HR 1.18; 95% CI 1.15-1.21; P < 0.01) and low high density cholesterol (HDL) (HR 1.18; 95% CI 1.06-1.32; P < 0.01) was also associated with an increased risk of AF, while high triglyceride (HR 0.99; 95% CI 0.87-1.11, P = 0.82) was not. CONCLUSIONS: Our present meta-analysis suggested that MetS, as well as its components including abdominal obesity, elevated blood pressure, elevated fasting glucose and low HDL cholesterol were associated with an increase in the risk of AF.