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Impact of diabetes on mortality and rehospitalization in acute heart failure patients stratified by ejection fraction.

ABSTRACT: AIMS:The aim of this study is to determine the impact of diabetes mellitus on all-cause mortality and rehospitalization rates at 3 months and at 1 year in patients admitted with acute heart failure (AHF) stratified by left ventricular ejection fraction (EF). METHODS AND RESULTS:We analysed consecutive patients admitted to 47 hospitals in seven Middle Eastern countries (Saudi Arabia, Oman, Yemen, Kuwait, United Arab Emirates, Qatar, and Bahrain) with AHF from February to November 2012 with AHF who were enrolled in Gulf CARE, a multinational registry of patients with heart failure (HF). AHF patients were stratified into three groups: HF patients with reduced (EF) (HFrEF) (<40%), HF with mid-range EF (HFmrEF) (40-49%), and HF patients with preserved EF (HFpEF) (?50%). Analyses were performed using univariate and multivariate statistical techniques. The mean age of the cohort was 59 ± 15 years (ranging from 18 to 99 years), and 63% (n = 2887) of the patients were males. A total of 2258 (49%) AHF patients had diabetes mellitus. The mean EF was 37 ± 14%. A reduced EF was observed in 2683 patients (59%), whereas 962 patients (21%) had mid-range and 932 patients (20%) had preserved EF. Multivariable analyses demonstrated no significant differences in all-cause mortality between diabetics and non-diabetics in all the three types of HF; at 3 months follow-up: HFrEF [adjusted odds ratio (aOR), 1.30; 95% confidence interval (CI): 0.94-1.80; P = 0.119], HFmrEF (aOR, 0.98; 95% CI: 0.51-1.87; P = 0.952), and HFpEF (aOR, 0.69; 95% CI: 0.38-1.26; P = 0.225); and at 12-months follow-up: HFrEF (aOR, 1.25; 95% CI: 0.97-1.62; P = 0.080), HFmrEF (aOR, 1.07; 95% CI: 0.68-1.68; P = 0.783), and HFpEF (aOR, 1.07; 95% CI: 0.67-1.72; P = 0.779). There were also no significant differences in rehospitalization rates between diabetics and non-diabetics in all the three types of HF; at 3 months follow-up: HFrEF (aOR, 0.94; 95% CI: 0.74-1.19; P = 0.581), HFmrEF (aOR, 0.82; 95% CI: 0.53-1.26; P = 0.369), and HFpEF (aOR, 1.06; 95% CI: 0.64-1.78; P = 0.812); and at 12-months follow-up: HFrEF (aOR, 0.93; 95% CI: 0.73-1.17; P = 0.524), HFmrEF (aOR, 0.81; 95% CI: 0.56-1.17; P = 0.257), and HFpEF (aOR, 1.29; 95% CI: 0.82-2.05; P = 0.271). CONCLUSIONS:There were no significant differences in 3 and 12 months all-cause mortality as well as rehospitalization rates between diabetics and non-diabetic patients in all the three types of AHF patients stratified by left ventricular ejection fraction.

SUBMITTER: Al-Jarallah M

PROVIDER: S-EPMC7083462 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Impact of diabetes on mortality and rehospitalization in acute heart failure patients stratified by ejection fraction.

Al-Jarallah Mohammed M Rajan Rajesh R Al-Zakwani Ibrahim I Dashti Raja R Bulbanat Bassam B Ridha Mustafa M Sulaiman Kadhim K Alsheikh-Ali Alawi A AA Panduranga Prashanth P AlHabib Khalid F KF Al Suwaidi Jassim J Al-Mahmeed Wael W AlFaleh Hussam H Elasfar Abdelfatah A Al-Motarreb Ahmed A Bazargani Nooshin N Asaad Nidal N Amin Haitham H

ESC heart failure 20191211 1

<h4>Aims</h4>The aim of this study is to determine the impact of diabetes mellitus on all-cause mortality and rehospitalization rates at 3 months and at 1 year in patients admitted with acute heart failure (AHF) stratified by left ventricular ejection fraction (EF).<h4>Methods and results</h4>We analysed consecutive patients admitted to 47 hospitals in seven Middle Eastern countries (Saudi Arabia, Oman, Yemen, Kuwait, United Arab Emirates, Qatar, and Bahrain) with AHF from February to November 2 ...[more]

PMID: 31825180

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Project description:AIMS:This study aims to evaluate the incidence and impact of cardiorenal anaemia syndrome (CRAS) on all-cause mortality in acute heart failure (AHF) patients stratified by left ventricular ejection fraction (LVEF) status in the Middle East. METHODS AND RESULTS:Data were analysed from 4934 consecutive patients admitted to 47 hospitals in seven Middle Eastern countries (Saudi Arabia, Oman, Yemen, Kuwait, United Arab Emirates, Qatar, and Bahrain) with AHF from February to November 2012. CRAS was defined as AHF with estimated glomerular filtration rate of <60 mL/min and low haemoglobin (<13 g/dL for men or <12 g/dL for women). Analyses were performed using univariate and multivariate statistical techniques. The overall mean age of the cohort was 59 ± 15 years, 62% (n = 3081) were men, and 27% (n = 1319) had CRAS. Co-morbid conditions were common including hypertension (n = 3014; 61%), coronary artery disease (n = 2971; 60%), and diabetes mellitus (n = 2449; 50%). A total of 79% (n = 3576) of the patients had AHF with reduced ejection fraction (HFrEF) (LVEF < 50%). CRAS patients were associated with major bleeding (1.29% vs. 0.6%; P = 0.017), blood transfusion (10.1% vs. 3.0%; P < 0.001), higher re-admission rate for AHF at 3 months' follow-up (27.6% vs. 18.8%; P < 0.001) and at 12 months' follow-up (34.3% vs. 26.2%; P < 0.001). Multivariate logistic regression demonstrated that patients with CRAS were associated with higher odds of all-cause mortality during hospital admission [adjusted odds ratio (aOR), 2.10; 95% confidence interval (CI): 1.34-3.31; P = 0.001], at 3 months' follow-up (aOR, 1.48; 95% CI: 1.07-2.06; P = 0.018), and at 12 months' follow-up (aOR, 1.45; 95% CI: 1.12-1.87; P = 0.004). Stratified analyses showed that CRAS patients with HFrEF were associated with higher odds of all-cause mortality during hospital admission (aOR, 2.03; 95% CI: 1.20-3.45; P = 0.009) and at 12 months' follow-up (aOR, 1.42; 95% CI: 1.06-1.89; P = 0.019) but not at 3 months' follow-up (aOR, 1.43; 95% CI: 0.98-2.09; P = 0.063). However, in AHF patients with preserved ejection fraction (LVEF ? 50%), CRAS was not associated with higher odds of all-cause mortality not only during hospital admission (aOR, 2.15; 95% CI: 0.84-5.55; P = 0.113) but also at 3 months' follow-up (aOR, 1.87; 95% CI: 0.93-3.76; P = 0.078) and at 12 months' follow-up (aOR, 1.59; 95% CI: 0.91-2.76; P = 0.101). CONCLUSIONS:The incidence of CRAS was 27%. CRAS was associated with higher odds of all-cause mortality in AHF patients in the Middle East, especially in those with HFrEF.

Project description:BackgroundHeart failure with preserved ejection fraction (HFpEF) is a growing health problem without effective therapies. Epidemiological studies indicate that diabetes is a strong risk factor for HFpEF, and about 45% of patients with HFpEF are suffering from diabetes, yet the underlying mechanisms remain elusive.MethodsUsing a combination of echocardiography, hemodynamics, RNA-sequencing, molecular biology, in vitro and in vivo approaches, we investigated the roles of SIRT6 (sirtuin 6) in regulation of endothelial fatty acid (FA) transport and HFpEF in diabetes.ResultsWe first observed that endothelial SIRT6 expression was markedly diminished in cardiac tissues from heart failure patients with diabetes. We then established an experimental mouse model of HFpEF in diabetes induced by a combination of the long-term high-fat diet feeding and a low-dose streptozocin challenge. We also generated a unique humanized SIRT6 transgenic mouse model, in which a single copy of human SIRT6 transgene was engineered at mouse Rosa26 locus and conditionally induced with the Cre-loxP technology. We found that genetically restoring endothelial SIRT6 expression in the diabetic mice ameliorated diastolic dysfunction concurrently with decreased cardiac lipid accumulation. SIRT6 gain- or loss-of-function studies showed that SIRT6 downregulated endothelial FA uptake. Mechanistically, SIRT6 suppressed endothelial expression of PPARγ through SIRT6-dependent deacetylation of histone H3 lysine 9 around PPARγ promoter region; and PPARγ reduction mediated SIRT6-dependent inhibition of endothelial FA uptake. Importantly, oral administration of small molecule SIRT6 activator MDL-800 to diabetic mice mitigated cardiac lipid accumulation and diastolic dysfunction.ConclusionsThe impairment of endothelial SIRT6 expression links diabetes to HFpEF through the alteration of FA transport across the endothelial barrier. Genetic and pharmacological strategies that restored endothelial SIRT6 function in mice with diabetes alleviated experimental HFpEF by limiting FA uptake and improving cardiac metabolism, thus warranting further clinical evaluation.

Project description:BackgroundThe relationship between stress hyperglycemia and long-term prognosis in acute decompensated heart failure (ADHF) patients is unknown. This study investigated the associations of stress hyperglycemia with mortality and rehospitalization rates among ADHF patients with diabetes.MethodsWe consecutively enrolled 1904 ADHF patients. Among them, 780 were with diabetes. Stress hyperglycemia was estimated using the stress hyperglycemia ratio (SHR), which was calculated by the following formula: SHR = admission blood glucose/[(28.7 × HbA1c%) - 46.7]. All diabetic ADHF subjects were divided into quintiles according to the SHR. The primary endpoint was all-cause death at the 3-year follow-up. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization at the 3-year follow-up. A Cox proportional hazards model and restricted cubic spline analysis were used to elucidate the relationship between the SHR and the endpoints in diabetic ADHF patients. Further analyses were performed to examine the relationships between SHR and the outcomes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).ResultsA total of 169 all-cause deaths were recorded during a median follow-up of 3.24 years. Restricted cubic spline analysis suggested a U-shaped association between the SHR and the mortality and rehospitalization rates. Kaplan-Meier survival analysis showed the lowest mortality in the 2nd quintile (P = 0.0028). Patients categorized in the highest range (5th quintile) of SHR, compared to those in the 2nd quintile, exhibited the greatest susceptibility to all-cause death (with a hazard ratio [HR] of 2.76 and a 95% confidence interval [CI] of 1.63-4.68), CV death (HR 2.81 [95% CI 1.66-4.75]) and the highest rate of HF rehospitalization (HR 1.54 [95% CI 1.03-2.32]). Similarly, patients in the lowest range (1st quintile) of SHR also exhibited significantly increased risks of all-cause death (HR 2.33, 95% CI 1.35-4.02) and CV death (HR 2.32, 95% CI 1.35-4.00). Further analyses indicated that the U-shape association between the SHR and mortality remained significant in both HFpEF and HFrEF patients.ConclusionBoth elevated and reduced SHRs indicate an unfavorable long-term prognosis in patients with ADHF and diabetes.

Project description:Background The pathobiology of heart failure with preserved ejection fraction (HFpEF) is still poorly understood, and effective therapies remain limited. Diabetes and mineralocorticoid excess are common and important pathophysiological factors that may synergistically promote HFpEF. The authors aimed to develop a novel animal model of HFpEF that recapitulates key aspects of the complex human phenotype with multiorgan impairments. Methods and Results The authors created a novel HFpEF model combining leptin receptor-deficient db/db mice with a 4-week period of aldosterone infusion. The HFpEF phenotype was assessed using morphometry, echocardiography, Ca2+ handling, and electrophysiology. The sodium-glucose cotransporter-2 inhibitor empagliflozin was then tested for reversing the arrhythmogenic cardiomyocyte phenotype. Continuous aldosterone infusion for 4 weeks in db/db mice induced marked diastolic dysfunction with preserved ejection fraction, cardiac hypertrophy, high levels of B-type natriuretic peptide, and significant extracardiac comorbidities (including severe obesity, diabetes with marked hyperglycemia, pulmonary edema, and vascular dysfunction). Aldosterone or db/db alone induced only a mild diastolic dysfunction without congestion. At the cellular level, cardiomyocyte hypertrophy, prolonged Ca2+ transient decay, and arrhythmogenic action potential remodeling (prolongation, increased short-term variability, delayed afterdepolarizations), and enhanced late Na+ current were observed in aldosterone-treated db/db mice. All of these arrhythmogenic changes were reversed by empagliflozin pretreatment of HFpEF cardiomyocytes. Conclusions The authors conclude that the db/db+aldosterone model may represent a distinct clinical subgroup of HFpEF that has marked hyperglycemia, obesity, and increased arrhythmia risk. This novel HFpEF model can be useful in future therapeutic testing and should provide unique opportunities to better understand disease pathobiology.

Project description:AimThere is an association between heart failure with preserved ejection fraction (HFpEF) and insulin resistance, but less is known about the diabetic continuum, and in particular about pre-diabetes, in HFpEF. We examined characteristics and outcomes of participants with diabetes or pre-diabetes in PARAGON-HF.Methods and resultsPatients aged ≥50 years with left ventricular ejection fraction ≥45%, structural heart disease and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) were eligible. Patients were classified according to glycated haemoglobin (HbA1c): (i) normal HbA1c, <6.0%; (ii) pre-diabetes, 6.0%-6.4%; (iii) diabetes, ≥6.5% or history of diabetes. The primary outcome was a composite of cardiovascular (CV) death and total heart failure hospitalizations (HFH). Of 4796 patients, 50% had diabetes and 18% had pre-diabetes. Compared to patients with normal HbA1c, patients with pre-diabetes and diabetes more often were obese, had a history of myocardial infarction and had lower Kansas City Cardiomyopathy Questionnaire scores, while patients with diabetes had more clinical evidence of congestion, but similar NT-proBNP concentrations. The risks of the primary composite outcome (rate ratio [RR] 1.59, 95% confidence interval [CI] 1.35-1.88), total HFH (RR 1.67, 95% CI 1.39-2.02) and CV death (hazard ratio [HR] 1.35, 95% CI 1.07-1.71) were higher among patients with diabetes, compared to those with normal HbA1c. Patients with pre-diabetes had a higher risk (which was intermediate between that of patients with diabetes and those with normal HbA1c) of the primary outcome (HR 1.27, 95% CI 1.00-1.60) and HFH (HR 1.35, 95% CI 1.03-1.77), but not of CV death (HR 1.02, 95% CI 0.75-1.40). Patients with diabetes treated with insulin had worse outcomes than those not, and those with 'lean diabetes' had similar mortality rates to those with a higher body mass index, but lower rates of HFH.ConclusionPre-diabetes is common in patients with HFpEF and is associated with worse clinical status and greater risk of HFH.Clinical trial registrationClinicalTrials.gov Identifier NCT01920711.

Dataset Information

Impact of diabetes on mortality and rehospitalization in acute heart failure patients stratified by ejection fraction.

Publications

Impact of diabetes on mortality and rehospitalization in acute heart failure patients stratified by ejection fraction.

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